Multi-objective Analysis of Approaches to Dynamic Routing of a Vehicle

We consider a routing problem for a single vehicle serving customer Locations in the course of time. A subset of these customers must necessarily be served, while the complement of this subset contains dynamic customers which request for service over time, and which do not necessarily need to be served. The decision maker’s conflicting goals are serving as many customers as possible as well as minimizing total travel distance. We solve this bi-objective Problem with an evolutionary multi-objective algorithm in order to provide an a-posteriori evaluation tool for enabling decision makers to assess the single objective solution strategies that they actually use in real-time. We present the modifications to be applied to the evolutionary multi-objective algorithm NSGA2 in order to solve the routing problem, we describe a number of real-time single-objective solution strategies, and we finally use the gained efficient trade-off solutions of NSGA2 to exemplarily evaluate the real-time strategies. Our results show that the evolutionary multi-objective approach is well-suited to generate benchmarks for assessing dynamic heuristic strategies. Our findings point into future directions for designing dynamic multi-objective approaches for the vehicle routing problem with time windows

Acute porphyrias – A neurological perspective

Acute hepatic porphyrias (AHP) can cause severe neurological symptoms involving the central, autonomic, and peripheral nervous system. Due to their relative rarity and their chameleon-like presentation, delayed diagnosis and misdiagnosis are common. AHPs are genetically inherited disorders that result from heme biosynthesis enzyme deficiencies and comprise four forms: acute intermittent porphyria (AIP), variegate porphyria (VP), hereditary coproporphyria (HCP), and ALA-dehydratase porphyria (ALADP). Depending on the clinical presentation, the main differential diagnoses are Guillain-Barré syndrome and autoimmune encephalitis. Red flags that could raise the suspicion of acute porphyria are neurological symptoms starting after severe (abdominal) pain, in association with reddish urine, hyponatremia or photodermatitis, and the presence of encephalopathy and/or axonal neuropathy. We highlight the diagnostic difficulties by presenting three cases from our neurological intensive care unit and give a comprehensive overview about the diagnostic findings in imaging, electrophysiology, and neuropathology

Drug reaction with eosinophilia and systemic symptoms after daclizumab therapy in MS

Currently, 12 cases (including our patient) of autoimmune encephalitis/encephalopathy after daclizumab therapy in MS are known worldwide and led to voluntary withdrawal of marketing authorization for daclizumab by the manufacturer Biogen (press release from European Medicines Agency, 07.03.2018). Our findings suggest that early recognition of DRESS even with CNS manifestations and swift treatment with steroids and/or plasma exchange are essential to improve the longterm outcome

Drug reaction with eosinophilia and systemic symptoms after daclizumab therapy in MS

Currently, 12 cases (including our patient) of autoimmune encephalitis/encephalopathy after daclizumab therapy in MS are known worldwide and led to voluntary withdrawal of marketing authorization for daclizumab by the manufacturer Biogen (press release from European Medicines Agency, 07.03.2018). Our findings suggest that early recognition of DRESS even with CNS manifestations and swift treatment with steroids and/or plasma exchange are essential to improve the longterm outcome

Physical Fitness Training in Patients with Subacute Stroke (PHYS-STROKE): multicentre, randomised controlled, endpoint blinded trial

OBJECTIVE: To determine the safety and efficacy of aerobic exercise on activities of daily living in the subacute phase after stroke. DESIGN: Multicentre, randomised controlled, endpoint blinded trial. SETTING: Seven inpatient rehabilitation sites in Germany (2013-17). PARTICIPANTS: 200 adults with subacute stroke (days 5-45 after stroke) with a median National Institutes of Health stroke scale (NIHSS, range 0-42 points, higher values indicating more severe strokes) score of 8 (interquartile range 5-12) were randomly assigned (1:1) to aerobic physical fitness training (n=105) or relaxation sessions (n=95, control group) in addition to standard care. INTERVENTION: Participants received either aerobic, bodyweight supported, treadmill based physical fitness training or relaxation sessions, each for 25 minutes, five times weekly for four weeks, in addition to standard rehabilitation therapy. Investigators and endpoint assessors were masked to treatment assignment. MAIN OUTCOME MEASURES: The primary outcomes were change in maximal walking speed (m/s) in the 10 m walking test and change in Barthel index scores (range 0-100 points, higher scores indicating less disability) three months after stroke compared with baseline. Safety outcomes were recurrent cardiovascular events, including stroke, hospital readmissions, and death within three months after stroke. Efficacy was tested with analysis of covariance for each primary outcome in the full analysis set. Multiple imputation was used to account for missing values. RESULTS: Compared with relaxation, aerobic physical fitness training did not result in a significantly higher mean change in maximal walking speed (adjusted treatment effect 0.1 m/s (95% confidence interval 0.0 to 0.2 m/s), P=0.23) or mean change in Barthel index score (0 (-5 to 5), P=0.99) at three months after stroke. A higher rate of serious adverse events was observed in the aerobic group compared with relaxation group (incidence rate ratio 1.81, 95% confidence interval 0.97 to 3.36). CONCLUSIONS: Among moderately to severely affected adults with subacute stroke, aerobic bodyweight supported, treadmill based physical fitness training was not superior to relaxation sessions for maximal walking speed and Barthel index score but did suggest higher rates of adverse events. These results do not appear to support the use of aerobic bodyweight supported fitness training in people with subacute stroke to improve activities of daily living or maximal walking speed and should be considered in future guidelines. TRIAL REGISTRATION: ClinicalTrials.gov NCT01953549

PATH PLANNING FOR NON-PLANAR ROBOTIC ADDITIVE MANUFACTURING

As material extrusion additive manufacturing continues to mature, there is increasing need for an extrusion path planning (“slicing”) method that takes full advantage of the abilities of manydegree-of-freedom systems like those used in Robotic Material Extrusion (RoMEX). These systems can create engineering parts with complex geometries and improved mechanical properties by utilizing non-planar curved layers, part-region-specific extrusion parameters, and support-free printing. This paper explores the application of 3D surfaces (demonstrated here with an upward pointing cone) as the basis of non-planar layer generation without the need to decompose the object into regions. Creation of these toolpaths incorporates key principles from planar, multi-planar, and active-Z path generation methods with attention paid to variable layer thickness, extrusion angle control, and overhang angle. The primary result of this work is a method for the generation of curved extrusion paths forming layers of arbitrary shape for arbitrary part geometry, based on a novel combination of existing best practices present throughout the available literature.Mechanical Engineerin

Re-Os isotope and platinum group elements of a FOcal ZOne mantle source, Louisville Seamounts Chain, Pacific ocean

The Louisville Seamount Chain (LSC) is, besides the Hawaiian-Emperor Chain, one of the longest-lived hotspot traces. We report here the first Re-Os isotope and platinum group element (PGE) data for Canopus, Rigil, and Burton Guyots along the chain, which were drilled during IODP Expedition 330. The LSC basalts possess (187Os/188Os)i = 0.1245–0.1314 that are remarkably homogeneous and do not vary with age. A Re-Os isochron age of 64.9 ± 3.2 Ma was obtained for Burton seamount (the youngest of the three seamounts drilled), consistent with 40Ar-39Ar data. Isochron-derived initial 187Os/188Os ratio of 0.1272 ± 0.0008, together with data for olivines (0.1271–0.1275), are within the estimated primitive mantle values. This (187Os/188Os)i range is similar to those of Rarotonga (0.124–0.139) and Samoan shield (0.1276–0.1313) basalts and lower than those of Cook-Austral (0.136–0.155) and Hawaiian shield (0.1283–0.1578) basalts, suggesting little or no recycled component in the LSC mantle source. The PGE data of LSC basalts are distinct from those of oceanic lower crust. Variation in PGE patterns can be largely explained by different low degrees of melting under sulfide-saturated conditions of the same relatively fertile mantle source, consistent with their primitive mantle-like Os and primordial Ne isotope signatures. The PGE patterns and the low 187Os/188Os composition of LSC basalts contrast with those of Ontong Java Plateau (OJP) tholeiites. We conclude that the Re-Os isotope and PGE composition of LSC basalts reflect a relatively pure deep-sourced common mantle sampled by some ocean island basalts but is not discernible in the composition of OJP tholeiites

Concomitant statin use does not impair the clinical outcome of patients with diffuse large B cell lymphoma treated with rituximab-CHOP

Preclinical data indicated a detrimental effect of statins on the anti-lymphoma activity of rituximab. We evaluated the impact of concomitant statin medication on the response and survival of patients with diffuse large B cell lymphoma (DLBCL) receiving rituximab-cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP) as first-line therapy. Medical histories of patients with DLBCL who were treated with R-CHOP as first-line therapy were assessed for concomitant statin use, response after completion of chemotherapy, event-free survival (EFS), and overall survival (OS). Furthermore, 2-[18F]fluor-2-deoxyglucose (FDG)-PET/CT results after completion of first-line therapy were compared between the groups. Overall, 145 patients with DLBCL treated with R-CHOP from January 2001 to December 2009 were analyzed. Twenty-one (15%) patients received statins throughout therapy. Five-year EFS was 67.3% in patients without statins compared with 79% in patients receiving statins during R-CHOP (HR, 0.47; 95% CI, 0.15-1.54, p = 0.2). Five-year OS was 81.4% for patients without statins compared with 93.3% for patients taking statins (HR, 0.58; 95% CI 0.07-4.55, p = 0.6). There were no statistically significant differences in the rates of complete remissions between the two groups (75% in the non-statin group versus 86% in the statin group, p = 0.45). A trend toward a lower rate of complete metabolic responses in FDG-PET/CT after chemotherapy was seen in patients without statin medication compared with the patients taking statins (84% versus 92%, p = 0.068). Concomitant statin use had no adverse impact on response to chemotherapy, EFS, and OS in patients treated with R-CHOP for DLBC