The Traveling k-Median Problem: Approximating optimal network coverage

We introduce the Traveling k-Median Problem (TkMP) as a natural extension of the k-Median Problem, where k agents (medians) can move through a graph of n nodes over a discrete time horizon of ω steps. The agents start and end at designated nodes, and in each step can hop to an adjacent node to improve coverage. At each time step, we evaluate the coverage cost as the total connection cost of each node to its closest median. Our goal is to minimize the sum of the coverage costs over the entire time horizon. In this paper, we initiate the study of this problem by focusing on the uniform case, i.e., when all edge costs are uniform and all agents share the same start and end locations. We show that this problem is NP-hard in general and can be solved optimally in time O(ω2n2 k). We obtain a 5-approximation algorithm if the number of agents is large (i.e., k≥ n/ 2 ). The more challenging case emerges if the number of agents is small (i.e., k< n/ 2 ). Our main contribution is a novel rounding scheme that allows us to round an (approximate) solution to the ‘continuous movement’ relaxation of the problem to a discrete one (incurring a bounded loss). Using our scheme, we derive constant-factor approximation algorithms on path and cycle graphs. For general graphs, we use a different (more direct) approach and derive an O(min{ω,n}) -approximation algorithm if d(s,t)≤2ω, and an O(d(s,t)+ω) -approximation algorithm if d(s,t)>2ω, where d(s, t) is the distance between the start and end point

The median routing problem for simultaneous planning of emergency response and non-emergency jobs

This paper studies a setting in emergency logistics where emergency responders must also perform a set of known, non-emergency jobs in the network when there are no active emergencies going on. These jobs typically have a preventive function, and allow the responders to use their idle time much more productively than in the current standard. When an emergency occurs, the nearest responder must abandon whatever job he or she is doing and go to the emergency. This leads to the optimisation problem of timetabling jobs and moving responders over a discrete network such that the expected emergency response time remains minimal. Our model, the Median Routing Problem, addresses this complex problem by minimising the expected response time to the next emergency and allowing for re-solving after this. We describe a mixed-integer linear program and a number of increasingly refined heuristics for this problem. We created a large set of benchmark instances, both from real-life case study data and from a generator. On the real-life case study instances, the best performing heuristic finds on average a solution only 3.4% away from optimal in a few seconds. We propose an explanation for the success of this heuristic, with the most pivotal conclusion being the importance of solving the underlying p-Medians Problem

Two Novel Mutations Identified in an African-American Child with Chediak-Higashi Syndrome

Background. Chediak-Higashi syndrome (CHS) is a rare, autosomal recessive disorder characterized by oculocutaneous albinism, immunodeficiency, coagulopathy and late-onset, progressive neurological dysfunction. It also has an “accelerated phase” characterized by hemophagocytic lymphohistiocytosis (HLH). The disease is caused by mutations in the CHS1/LYST gene located on chromosome 1, which affects lysosome morphology and function. We report the case of an African-American child with CHS in Case. This 16-month old African-American girl presented with fever and lethargy. The proband had pale skin compared to her parents, with light brown eyes, silvery hair and massive hepatosplenomegaly. Her laboratory evaluation was remarkable for pancytopenia, high serum ferritin and an elevated LDH. Bone marrow aspirate revealed large inclusions in granulocytes and erythrophagocytosis consistent with HLH. Genetic evaluation revealed two novel nonsense mutations in the CHS1 gene: c.3622C > T (p.Q1208X) and c.11002G > T (p.E3668X). Conclusions. Our patient is one of the few cases of CHS reported in the African American population. We identified 2 nonsense mutations in the CHS1 gene, the first mutation analysis published of an African-American child with Chediak-Higashi Syndrome. These two mutations predict a severe phenotype and thus identification of these mutations has an important clinical significance in CHS

Association between the p.Thr1406Asn polymorphism of the carbamoyl-phosphate synthetase 1 gene and necrotizing enterocolitis: A prospective multicenter study

The p.Thr1406Asn (rs1047891) polymorphism of the carbamoyl-phosphate synthetase 1 (CPS1) gene has been linked to functional consequences affecting the downstream availability of the nitric oxide precursor L-arginine. L-arginine concentrations are decreased in preterm infants with necrotizing enterocolitis (NEC). In this multicenter prospective study, we investigated the association of the p.Thr1406Asn polymorphism with NEC in 477 preterm infants (36 cases of NEC) from 4 European neonatal intensive care units (Maastricht, Las Palmas de Gran Canaria, Mantova, and Milan). Allele and genotype frequencies of the p.Thr1406Asn polymorphism did not significantly differ between the infants with and without NEC. In contrast, the minor A-allele was significantly less frequent in the group of 64 infants with the combined outcome NEC or death before 34 weeks of corrected gestational age than in the infants without the outcome (0.20 vs. 0.31, P = 0.03). In addition, a significant negative association of the A-allele with the combined outcome NEC or death was found using the dominant (adjusted odds ratio, aOR: 0.54, 95% CI 0.29-0.99) and the additive (aOR 0.58, 95% CI 0.36-0.93) genetic models. In conclusion, our study provides further evidence that a functional variant of the CPS1 gene may contribute to NEC susceptibility

Solving discrete logarithms on a 170-bit MNT curve by pairing reduction

Pairing based cryptography is in a dangerous position following the breakthroughs on discrete logarithms computations in finite fields of small characteristic. Remaining instances are built over finite fields of large characteristic and their security relies on the fact that the embedding field of the underlying curve is relatively large. How large is debatable. The aim of our work is to sustain the claim that the combination of degree 3 embedding and too small finite fields obviously does not provide enough security. As a computational example, we solve the DLP on a 170-bit MNT curve, by exploiting the pairing embedding to a 508-bit, degree-3 extension of the base field.Comment: to appear in the Lecture Notes in Computer Science (LNCS

The enriched median routing problem and its usefulness in practice

Emergency response fleets often have to simultaneously perform two types of tasks: (1) urgent tasks requiring immediate action, and (2) non-urgent preventive maintenance tasks that can be scheduled upfront. In Huizing et al. (2020), Huizing et al. proposed the Median Routing Problem (MRP) to optimally schedule agents to a given set of non-urgent tasks, such that the response time for urgent tasks remains minimal. They proposed both an exact MILP-solution and a fast, scalable and accurate heuristic. However, when implementing the MRP-solution in a real-life pilot with a Dutch railway provider, we found that the model needed to be extended by including additional practical objectives and constraints. Therefore, in this paper, we extend the MRP to the so-called Enriched Median Routing Problem (E-MRP), making the model much better aligned with considerations from practice. Accordingly, we extend the MRP-based solutions to the E-MRP. This allows us to compare the performance of our proposed E-MRP solutions to performance obtained in the current operational practice of our partnering railway infrastructure company. We conclude that the E-MRP solution leads to a strong reduction in emergency response times compared to current practice by smartly scheduling the same volumes of non-urgent tasks

Belt restraint reduction in nursing homes: design of a quasi-experimental study

<p>Abstract</p> <p>Background</p> <p>The use of physical restraints still is common practice in the nursing home care. Since physical restraints have been shown to be an ineffective and sometimes even hazardous measure, interventions are needed to reduce their usage. Several attempts have been made to reduce the use of physical restraints. Most studies used educational approaches and introduced a nurse specialist as a consultant. However, the success rate of these interventions has been inconsistent. We developed a new multi-component intervention (EXBELT) comprising an educational intervention for nursing home staff in combination with a policy change (belt use is prohibited by the nursing home management), availability of a nurse specialist and nursing home manager as consultants, and availability of alternative interventions. The first aim of this study is to further develop and test the effectiveness of EXBELT on belt restraint reduction in Dutch psychogeriatric nursing homes. However, the reduction of belts should not result in an increase of other restrictive restraints (such as a chair with locked tray table) or psychoactive drug use. The overall aim is an effective and feasible intervention that can be employed on a large scale in Dutch nursing homes.</p> <p>Methods and design</p> <p>Effects of EXBELT will be studied in a quasi-experimental longitudinal study design. Alongside the effect evaluation, a process evaluation will be carried out in order to further develop EXBELT. Data regarding age, gender, use of physical restraints, the number of falls and fall related injuries, psychoactive drug use, and the use of alternative interventions will be collected at baseline and after four and eight months of follow-up. Data regarding the process evaluation will be gathered in a period of eight months between baseline and the last measurement. Furthermore, changing attitudes will become an important addition to the educational part of EXBELT.</p> <p>Discussion</p> <p>A quasi-experimental study is presented to investigate the effects of EXBELT on the use of belts on wards in psychogeriatric nursing homes. The study will be conducted in 26 wards in 13 psychogeriatric nursing homes. We selected the wards in a manner that contamination between control- and intervention group is prevented.</p> <p>Trial registration</p> <p>(NTR2140)</p

Paclitaxel in self-micro emulsifying formulations: oral bioavailability study in mice

The anticancer drug paclitaxel is formulated for i.v. administration in a mixture of Cremophor EL and ethanol. Its oral bioavailability is very low due to the action of P-glycoprotein in the gut wall and CYP450 in gut wall and liver. However, proof-of-concept studies using the i.v. formulation diluted in drinking water have demonstrated the feasibility of the oral route as an alternative when given in combination with inhibitors of P-glycoprotein and CYP450. Because of the unacceptable pharmaceutical properties of the drinking solution, a better formulation for oral application is needed. We have evaluated the suitability of various self-micro emulsifying oily formulations (SMEOF’s) of paclitaxel for oral application using wild-type and P-glycoprotein knockout mice and cyclosporin A (CsA) as P-glycoprotein and CYP450 inhibitor. The oral bioavailability of paclitaxel in all SMEOF’s without concomitant CsA was low in wild-type mice, showing that this vehicle does not enhance intestinal uptake by itself. Paclitaxel (10 mg/kg) in SMEOF#3 given with CsA resulted in plasma levels that were comparable to the Cremophor EL-ethanol containing drinking solution plus CsA. Whereas the AUC increased linearly with the oral paclitaxel dose in P-glycoprotein knockout mice, it increased less than proportional in wild-type mice given with CsA. In both strains more unchanged paclitaxel was recovered in the feces at higher doses. This observation most likely reflects more profound precipitation of paclitaxel within the gastro-intestinal tract at higher doses. The resulting absolute reduction in absorption of paclitaxel from the gut was possibly concealed by partial saturation of first-pass metabolism when P-glycoprotein was absent. In conclusion, SMEOF’s maybe a useful vehicle for oral delivery of paclitaxel in combination with CsA, although the physical stability within the gastro-intestinal tract remains a critical issue, especially when applied at higher dose levels