Placing Arrows in Directed Graph Drawings

We consider the problem of placing arrow heads in directed graph drawings without them overlapping other drawn objects. This gives drawings where edge directions can be deduced unambiguously. We show hardness of the problem, present exact and heuristic algorithms, and report on a practical study.Comment: Appears in the Proceedings of the 24th International Symposium on Graph Drawing and Network Visualization (GD 2016

High fludarabine exposure and relationship with treatment-related mortality after nonmyeloablative hematopoietic cell transplantation.

Despite its common use in nonmyeloablative preparative regimens, the pharmacokinetics of fludarabine are poorly characterized in hematopoietic cell transplantation (HCT) recipients and exposure-response relationships remain undefined. The objective of this study was to evaluate the association between plasma F-ara-A exposure, the systemically circulating moiety of fludarabine, and engraftment, acute GVHD, TRM and OS after HCT. The preparative regimen consisted of CY 50 mg/kg/day i.v. day -6; plus fludarabine 30-40 mg/m²/day i.v. on days -6 to -2 and TBI 200 cGy on day -1. F-ara-A pharmacokinetics were carried out with the first dose of fludarabine in 87 adult patients. Median (range) F-ara-A area-under-the-curve (AUC((0-∞))) was 5.0 μg h/mL (2.0-11.0), clearance 15.3 L/h (6.2-36.6), C(min) 55 ng/mL (17-166) and concentration on day(zero) 16.0 ng/mL (0.1-144.1). Despite dose reductions, patients with renal insufficiency had higher F-ara-A exposures. There was strong association between high plasma concentrations of F-ara-A and increased risk of TRM and reduced OS. Patients with an AUC((0-∞)) greater than 6.5 μg h/mL had 4.56 greater risk of TRM and significantly lower OS. These data suggest that clinical strategies are needed to optimize dosing of fludarabine to prevent overexposure and toxicity in HCT

The sequential trauma score - a new instrument for the sequential mortality prediction in major trauma*

<p>Abstract</p> <p>Background</p> <p>There are several well established scores for the assessment of the prognosis of major trauma patients that all have in common that they can be calculated at the earliest during intensive care unit stay. We intended to develop a sequential trauma score (STS) that allows prognosis at several early stages based on the information that is available at a particular time.</p> <p>Study design</p> <p>In a retrospective, multicenter study using data derived from the Trauma Registry of the German Trauma Society (2002-2006), we identified the most relevant prognostic factors from the patients basic data (P), prehospital phase (A), early (B1), and late (B2) trauma room phase. Univariate and logistic regression models as well as score quality criteria and the explanatory power have been calculated.</p> <p>Results</p> <p>A total of 2,354 patients with complete data were identified. From the patients basic data (P), logistic regression showed that age was a significant predictor of survival (AUC_{model p}, area under the curve = 0.63). Logistic regression of the prehospital data (A) showed that blood pressure, pulse rate, Glasgow coma scale (GCS), and anisocoria were significant predictors (AUC_{model A}= 0.76; AUC_{model P + A}= 0.82). Logistic regression of the early trauma room phase (B1) showed that peripheral oxygen saturation, GCS, anisocoria, base excess, and thromboplastin time to be significant predictors of survival (AUC_{model B1}= 0.78; AUC_{model P +A + B1}= 0.85). Multivariate analysis of the late trauma room phase (B2) detected cardiac massage, abbreviated injury score (AIS) of the head ≥ 3, the maximum AIS, the need for transfusion or massive blood transfusion, to be the most important predictors (AUCmodel B2 = 0.84; AUCfinal model P + A + B1 + B2 = 0.90). The explanatory power - a tool for the assessment of the relative impact of each segment to mortality - is 25% for P, 7% for A, 17% for B1 and 51% for B2. A spreadsheet for the easy calculation of the sequential trauma score is available at: <url>http://www.sequential-trauma-score.com</url></p> <p>Conclusions</p> <p>This score is the first sequential, dynamic score to provide a prognosis for patients with blunt major trauma at several points in time. With every additional piece of information the precision increases. The medical team has a simple, useful tool to identify patients at high risk and to predict the prognosis of an individual patient with major trauma very early, quickly and precisely.</p

Surface electrons at plasma walls

In this chapter we introduce a microscopic modelling of the surplus electrons on the plasma wall which complements the classical description of the plasma sheath. First we introduce a model for the electron surface layer to study the quasistationary electron distribution and the potential at an unbiased plasma wall. Then we calculate sticking coefficients and desorption times for electron trapping in the image states. Finally we study how surplus electrons affect light scattering and how charge signatures offer the possibility of a novel charge measurement for dust grains.Comment: To appear in Complex Plasmas: Scientific Challenges and Technological Opportunities, Editors: M. Bonitz, K. Becker, J. Lopez and H. Thomse

A four phase development model for integrated care services in the Netherlands

Background. Multidisciplinary and interorganizational arrangements for the delivery of coherent integrated care are being developed in a large number of countries. Although there are many integrated care programs worldwide, the process of developing these programs and interorganizational collaboration is described in the literature only to a limited extent. The purpose of this study is to explore how local integrated care services are developed in the Netherlands, and to conceptualize and operationalize a development model of integrated care. Methods. The research is based on an expert panel study followed by a two-part questionnaire, designed to identify the development process of integrated care. Essential elements of integrated care, which were developed in a previous Delphi and Concept Mapping Study, were analyzed in relation to development process of integrated care. Results. Integrated care development can be characterized by four developmental phases: the initiative and design phase; the experimental and execution phase; the expansion and monitoring phase; and the consolidation and transformation phase. Different elements of integrated care have been identified in the various developmental phases. Conclusion. The findings provide a descriptive model of the development process that integrated care services can undergo in the Netherlands. The findings have important implications for integrated care services, which can use the model as an instrument to reflect on their current practices. The model can be used to help to identify improvement areas in practice. The model provides a framework for developing evaluation designs for integrated care arrangements. Further research is recommended to test the developed model in practice and to add international experiences

Short- and long-term effects of a quality improvement collaborative on diabetes management

Introduction: This study examined the short- and long-term effects of a quality improvement collaborative on patient outcomes, professional performance, and structural aspects of chronic care management of type 2 diabetes in an integrated care setting.Methods: Controlled pre- and post-intervention study assessing patient outcomes (hemoglobin A1c, cholesterol, blood pressure, weight, blood lipid levels, and smoking status), professional performance (guideline adherence), and structural aspects of chronic care management from baseline up to 24 months. Analyses were based on 1,861 patients with diabetes in six intervention and nine control regions representing 37 general practices and 13 outpatient clinics.Results: Modest but significant improvement was seen in mean systolic blood pressure (decrease by 4.0 mm Hg versus 1.6 mm Hg) and mean high density lipoprotein levels (increase by 0.12 versus 0.03 points) at two-year follow up. Positive but insignificant differences were found in hemoglobin A1c (0.3%), cholesterol, and blood lipid levels. The intervention group showed significant improvement in the percentage of patients receiving advice and instruction to examine feet, and smaller reductions in the percentage of patients receiving instruction to monitor blood glucose and visiting a dietician annually. Structural aspects of self-management and decision support also improved significantly.Conclusions: At a time of heightened national attention toward diabetes care, our results demonstrate a modest benefit of participation in a multi-institutional quality improvement collaborative focusing on integrated, patient-centered care. The effects persisted for at least 12 months after the intervention was completed.Trial number: http://clinicaltrials.gov Identifier: NCT 00160017

Molecular Variation at a Candidate Gene Implicated in the Regulation of Fire Ant Social Behavior

The fire ant Solenopsis invicta and its close relatives display an important social polymorphism involving differences in colony queen number. Colonies are headed by either a single reproductive queen (monogyne form) or multiple queens (polygyne form). This variation in social organization is associated with variation at the gene Gp-9, with monogyne colonies harboring only B-like allelic variants and polygyne colonies always containing b-like variants as well. We describe naturally occurring variation at Gp-9 in fire ants based on 185 full-length sequences, 136 of which were obtained from S. invicta collected over much of its native range. While there is little overall differentiation between most of the numerous alleles observed, a surprising amount is found in the coding regions of the gene, with such substitutions usually causing amino acid replacements. This elevated coding-region variation may result from a lack of negative selection acting to constrain amino acid replacements over much of the protein, different mutation rates or biases in coding and non-coding sequences, negative selection acting with greater strength on non-coding than coding regions, and/or positive selection acting on the protein. Formal selection analyses provide evidence that the latter force played an important role in the basal b-like lineages coincident with the emergence of polygyny. While our data set reveals considerable paraphyly and polyphyly of S. invicta sequences with respect to those of other fire ant species, the b-like alleles of the socially polymorphic species are monophyletic. An expanded analysis of colonies containing alleles of this clade confirmed the invariant link between their presence and expression of polygyny. Finally, our discovery of several unique alleles bearing various combinations of b-like and B-like codons allows us to conclude that no single b-like residue is completely predictive of polygyne behavior and, thus, potentially causally involved in its expression. Rather, all three typical b-like residues appear to be necessary

Who Is at Risk for Diagnostic Discrepancies? Comparison of Pre- and Postmortal Diagnoses in 1800 Patients of 3 Medical Decades in East and West Berlin

<div><h3>Background</h3><p>Autopsy rates in Western countries consistently decline to an average of <5%, although clinical autopsies represent a reasonable tool for quality control in hospitals, medically and economically. Comparing pre- and postmortal diagnoses, diagnostic discrepancies as uncovered by clinical autopsies supply crucial information on how to improve clinical treatment. The study aimed at analyzing current diagnostic discrepancy rates, investigating their influencing factors and identifying risk profiles of patients that could be affected by a diagnostic discrepancy.</p> <h3>Methods and Findings</h3><p>Of all adult autopsy cases of the Charité Institute of Pathology from the years 1988, 1993, 1998, 2003 and 2008, the pre- and postmortal diagnoses and all demographic data were analyzed retrospectively. Based on power analysis, 1,800 cases were randomly selected to perform discrepancy classification (class I-VI) according to modified Goldman criteria. The rate of discrepancies in major diagnoses (class I) was 10.7% (95% CI: 7.7%–14.7%) in 2008 representing a reduction by 15.1%. Subgroup analysis revealed several influencing factors to significantly correlate with the discrepancy rate. Cardiovascular diseases had the highest frequency among class-I-discrepancies. Comparing the 1988-data of East- and West-Berlin, no significant differences were found in diagnostic discrepancies despite an autopsy rate differing by nearly 50%. A risk profile analysis visualized by intuitive heatmaps revealed a significantly high discrepancy rate in patients treated in low or intermediate care units at community hospitals. In this collective, patients with genitourinary/renal or infectious diseases were at particularly high risk.</p> <h3>Conclusions</h3><p>This is the current largest and most comprehensive study on diagnostic discrepancies worldwide. Our well-powered analysis revealed a significant rate of class-I-discrepancies indicating that autopsies are still of value. The identified risk profiles may aid both pathologists and clinicians to identify patients at increased risk for a discrepant diagnosis and possibly suboptimal treatment intra vitam.</p> </div