Deterministic Approximation Algorithms for Ranking and Clustering Problems

Deterministic Approximation Algorithms for Ranking and Clustering Problem

Maximizing Influence in a Competitive Social Network: A Follower's Perspective

Maximizing Influence in a Competitive Social Network: A Follower's Perspectiv

Prevalence, Impact, and Treatment of Death Rattle

Context: Death rattle, or respiratory tract secretion in the dying patient, is a common and potentially distressing symptom in dying patients. Health care professionals often struggle with this symptom because of the uncertainty about management. Objectives: To give an overview of the current evidence on the prevalence of death rattle in dying patients, its impact on patients, relatives, and professional caregivers, and the effectiveness of interventions. Methods: We systematically searched the databases PubMed, EMBASE, CINAHL, PsychINFO, and Web of Science. English-language articles containing original data on the prevalence or impact of death rattle or on the effects of interventions were included. Results: We identified 39 articles, of which 29 reported on the prevalence of death rattle, eight on its impact, and 11 on the effectiveness of interventions. There is a wide variation in reported prevalence rates (12%-92%; weighted mean, 35%). Death rattle leads to distress in both relatives and professional caregivers, but its impact on patients is unclear. Different medication regimens have been studied, that is, scopolamine, glycopyrronium, hyoscine butylbromide, atropine, and/or octreotide. Only one study used a placebo group. There is no evidence that the use of any antimuscarinic drug is superior to no treatment. Conclusion: Death rattle is a rather common symptom in dying patients, but it is doubtful if patients suffer from this symptom. Current literature does not support the standard use of antimuscarinic drugs in the treatment of death rattle

A Duality Based 2-Approximation Algorithm for Maximum Agreement Forest

We give a 2-approximation algorithm for the Maximum Agreement Forest problem on two rooted binary trees. This NP-hard problem has been studied extensively in the past two decades, since it can be used to compute the rooted Subtree Prune-and-Regraft (rSPR) distance between two phylogenetic trees. Our algorithm is combinatorial and its running time is quadratic in the input size. To prove the approximation guarantee, we construct a feasible dual solution for a novel linear programming formulation. In addition, we show this linear program is stronger than previously known formulations, and we give a compact formulation, showing that it can be solved in polynomial tim

Improving the quality of palliative and terminal care in the hospital by a network of palliative care nurse champions: The study protocol of the PalTeC-H project

Background: The quality of care of patients dying in the hospital is often judged as insufficient. This article describes the protocol of a study to assess the quality of care of the dying patient and the contribution of an intervention targeted on staff nurses of inpatient wards of a large university hospital in the Netherlands. Methods/Design. We designed a controlled before and after study. The intervention is the establishment of a network for palliative care nurse champions, aiming to improve the quality of hospital end-of-life care. Assessments are performed among bereaved relatives, nurses and physicians on seven wards before and after introduction of the intervention and on 11 control wards where the intervention is not applied. We focus on care provided during the last three days of life, covered in global ratings of the quality of life in the last three days of life and the quality of dying, and various secondary endpoints of treatment and care affecting quality of life and dying. Discussion. With this study we aim to improve the understanding of and attention for patients' needs, and the quality of care in the dying phase in the hospital and measure the impact of a quality improvement intervention targeted at nurses

Ten-year experience of a national multidisciplinary tumour board for cancer and pregnancy in the Netherlands

Background: Most physicians encounter pregnant women with cancer incidentally, leading to a lack of expertise or confidence to inform and treat these patients based on the most recent guidelines and expert opinions. In the Netherlands, a national multidisciplinary tumour board for cancer, infertility and pregnancy (CIP-MDT) was founded in December 2012, including 35 specialists from a variety of disciplines. This study evaluates the frequency of consultation of the CIP-MDT, the types of questions asked and the satisfaction of consulting physicians with its existence. Methodology: Of all requests to the CIP-MDT between December 2012 and June 2021, tumour type, stage, gestational age at diagnosis and recommendations were collected and analysed. For evaluating the methods of the CIP-MDT, a survey with questions regarding experiences with the CIP-MDT and its impact on treatment decisions was sent out to physicians that consulted the CIP-MDT. Results: Recommendations (n = 213) concerned preferred and safest options for imaging, treatment options during pregnancy, possible effects on the child and fertility preserving options. Most frequently discussed malignancies were breast cancer (n = 66), cervical cancer (n = 34), haematological malignancies (n = 32) and melanoma (n = 21). The questionnaire was completed by 54% of the physicians (n = 50). Satisfaction with the recommendations of the CIP-MDT was high, and 94% of the physicians informed their patients about consulting the CIP-MDT and felt supported by the received recommendations. Discussion: The national Dutch CIP-MDT contributes to a high level of satisfaction among physicians requesting advice. Further research should be executed to confirm that a CIP-MDT improves the outcomes for pregnant women and their children

Split scheduling with uniform setup times

We study a scheduling problem in which jobs may be split into parts, where the parts of a split job may be processed simultaneously on more than one machine. Each part of a job requires a setup time, however, on the machine where the job part is processed. During setup, a machine cannot process or set up any other job. We concentrate on the basic case in which setup times are job-, machine- and sequence-independent. Problems of this kind were encountered when modelling practical problems in planning dis- aster relief operations. Our main algorithmic result is a polynomial-time algorithm for minimising total completion time on two parallel identical machines. We argue, why the same problem with threemachines is not an easy extension of the two-machine case, leaving the complexity of this case as a tantalising open problem. We give a constant-factor approximation algorithm for the general case with any number of machines and a polynomial-time approximation scheme for a fixed number of machines. For the version with the objective to minimise total weighted completion time, we prove NP-hardness. Finally, we conclude with an overview of the state of the art for other split scheduling problems with job-, machine- and sequence-independent setup times

On the (non-)existence of polynomial kernels for Pl-free edge modification problems

Given a graph G = (V,E) and an integer k, an edge modification problem for a graph property P consists in deciding whether there exists a set of edges F of size at most k such that the graph H = (V,E \vartriangle F) satisfies the property P. In the P edge-completion problem, the set F of edges is constrained to be disjoint from E; in the P edge-deletion problem, F is a subset of E; no constraint is imposed on F in the P edge-edition problem. A number of optimization problems can be expressed in terms of graph modification problems which have been extensively studied in the context of parameterized complexity. When parameterized by the size k of the edge set F, it has been proved that if P is an hereditary property characterized by a finite set of forbidden induced subgraphs, then the three P edge-modification problems are FPT. It was then natural to ask whether these problems also admit a polynomial size kernel. Using recent lower bound techniques, Kratsch and Wahlstrom answered this question negatively. However, the problem remains open on many natural graph classes characterized by forbidden induced subgraphs. Kratsch and Wahlstrom asked whether the result holds when the forbidden subgraphs are paths or cycles and pointed out that the problem is already open in the case of P4-free graphs (i.e. cographs). This paper provides positive and negative results in that line of research. We prove that parameterized cograph edge modification problems have cubic vertex kernels whereas polynomial kernels are unlikely to exist for the Pl-free and Cl-free edge-deletion problems for large enough l

The orally administered P-glycoprotein inhibitor R101933 does not alter the plasma pharmacokinetics of docetaxel

This Phase I study was performed to assess the feasibility of combining docetaxel with the new P-glycoprotein inhibitor R101933 and to determine the dose limiting toxicity of this combination. Fifteen patients received oral R101933 alone at a dose escalated from 200 to 300 mg twice daily (b.i.d.; cycle 0), an escalating i.v. dose of docetaxel (60, 75, and 100 mg/m2) as a 1-h infusion (cycle 1), and the combination (cycle 2 and further). Dose limiting toxicity consisting of mucositis and neutropenic fever was reached at the combination of docetaxel, 100 mg/m2, and R101933, 300 mg b.i.d., and the maximum tolerated dose was established at docetaxel, 100 mg/m2, and R101933, 200 mg b.i.d. Plasma concentrations of R101933 achieved in patients were in the same range as required in preclinical rodent models to overcome paclitaxel resistance. The plasma pharmacokinetics of docetaxel were not influenced by the R101933 regimen at any dose level tested, as indicated by plasma clearance values of 26.5 +/- 7.78 liters/h/m2 and 23.4 +/- 4.52 liters/h/m2 (P = 0.15) in cycles 1 and 2, respectively. These findings indicate that the contribution of a P-glycoprotein inhibitor to the activity of anticancer chemotherapy can now be assessed in patients for the first time independent of its effect on drug pharmacokinetics

Role of intestinal P-glycoprotein in the plasma and fecal disposition of docetaxel in humans

Multidrug resistance (MDR)-1-P-glycoprotein (P-gp) is a drug-transporting protein that is abundantly present in biliary ductal cells and epithelial cells lining the gastrointestinal tract. Here, we have determined the role of P-gp in the metabolic disposition of the antineoplastic agent docetaxel (Taxotere) in humans. Pharmacokinetic profiles were evaluated in five cancer patients receiving treatment cycles with docetaxel alone (100 mg/m2 i.v. over a 1-h period) and in combination with a new potent inhibitor of P-gp activity, R101933 (200-300 mg b.i.d.). The terminal disposition half-life and total plasma clearance of docetaxel were not altered by treatment with oral R101933 (P > or = 0.27). The cumulative fecal excretion of docetaxel, however, was markedly reduced from 8.47 +/- 2.14% (mean +/- SD) of the dose with the single agent to less than 0.5% in the presence of R101933 (P = 0.0016). Levels of the major cytochrome P450 3A4-mediated metabolites of docetaxel in feces were significantly increased after combination treatment with R101933 (P = 0.010), indicating very prominent and efficient detoxification of reabsorbed docetaxel into hydroxylated compounds before reaching the systemic circulation. It is concluded that intestinal P-gp plays a principal role in the fecal elimination of docetaxel by modulating reabsorption of the drug after hepatobiliary secretion. In addition, the results indicate that inhibition of P-gp activity in normal tissues by effective modulators, and the physiological and pharmacological consequences of this treatment, cannot be predicted based on plasma drug monitoring alone