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

Reliability of light microscopy and a computer-assisted replica measurement technique for evaluating the fit of dental copings

Abstract The aim of this in vitro study was to assess the reliability of two measurement systems for evaluating the marginal and internal fit of dental copings. Material and Methods: Sixteen CAD/CAM titanium copings were produced for a prepared maxillary canine. To modify the CAD surface model using different parameters (data density; enlargement in different directions), varying fit was created. Five light-body silicone replicas representing the gap between the canine and the coping were made for each coping and for each measurement method: (1) light microscopy measurements (LMMs); and (2) computer-assisted measurements (CASMs) using an optical digitizing system. Two investigators independently measured the marginal and internal fit using both methods. The inter-rater reliability [intraclass correlation coefficient (ICC)] and agreement [Bland-Altman (bias) analyses]: mean of the differences (bias) between two measurements [the closer to zero the mean (bias) is, the higher the agreement between the two measurements] were calculated for several measurement points (marginal-distal, marginal-buccal, axial-buccal, incisal). For the LMM technique, one investigator repeated the measurements to determine repeatability (intra-rater reliability and agreement). Results: For inter-rater reliability, the ICC was 0.848-0.998 for LMMs and 0.945-0.999 for CASMs, depending on the measurement point. Bland-Altman bias was −15.7 to 3.5 μm for LMMs and −3.0 to 1.9 μm for CASMs. For LMMs, the marginal-distal and marginal-buccal measurement points showed the lowest ICC (0.848/0.978) and the highest bias (-15.7 μm/-7.6 μm). With the intra-rater reliability and agreement (repeatability) for LMMs, the ICC was 0.970-0.998 and bias was −1.3 to 2.3 μm. Conclusion: LMMs showed lower interrater reliability and agreement at the marginal measurement points than CASMs, which indicates a more subjective influence with LMMs at these measurement points. The values, however, were still clinically acceptable. LMMs showed very high intra-rater reliability and agreement for all measurement points, indicating high repeatability

Accuracy of intraoral and extraoral digital data acquisition for dental restorations

The computer-aided design (CAD) and computer-aided manufacturing (CAM) process chain for dental restorations starts with taking an impression of the clinical situation. For this purpose, either extraoral digitization of gypsum models or intraoral digitization can be used. Despite the increasing use of dental digitizing systems, there are only few studies on their accuracy. Objective This study compared the accuracy of various intraoral and extraoral digitizing systems for dental CAD/CAM technology. Material and Methods An experimental setup for three-dimensional analysis based on 2 prepared ceramic master dies and their corresponding virtual CAD-models was used to assess the accuracy of 10 extraoral and 4 intraoral optical non-contact dental digitizing systems. Depending on the clinical procedure, 10 optical measurements of either 10 duplicate gypsum dies (extraoral digitizing) or directly of the ceramic master dies (intraoral digitizing) were made and compared with the corresponding CAD-models. Results The digitizing systems showed differences in accuracy. However, all topical systems were well within the benchmark of ±20 µm. These results apply to single tooth measurements. Conclusions Study results are limited, since only single teeth were used for comparison. The different preparations represent various angles and steep and parallel opposing tooth surfaces (incisors). For most digitizing systems, the latter are generally the most difficult to capture. Using CAD/CAM technologies, the preparation angles should not be too steep to reduce digitizing errors. Older systems might be limited to a certain height or taper of the prepared tooth, whereas newer systems (extraoral as well as intraoral digitization) do not have these limitations

Nestin Modulates Glucocorticoid Receptor Function by Cytoplasmic Anchoring

Nestin is the characteristic intermediate filament (IF) protein of rapidly proliferating progenitor cells and regenerating tissue. Nestin copolymerizes with class III IF-proteins, mostly vimentin, into heteromeric filaments. Its expression is downregulated with differentiation. Here we show that a strong nestin expression in mouse embryo tissue coincides with a strong accumulation of the glucocorticoid receptor (GR), a key regulator of growth and differentiation in embryonic development. Microscopic studies on cultured cells show an association of GR with IFs composed of vimentin and nestin. Cells lacking nestin, but expressing vimentin, or cells expressing vimentin, but lacking nestin accumulate GR in the nucleus. Completing these networks with an exogenous nestin, respectively an exogenous vimentin restores cytoplasmic anchoring of GR to the IF system. Thus, heteromeric filaments provide the basis for anchoring of GR. The reaction pattern with phospho-GR specific antibodies and the presence of the chaperone HSC70 suggest that specifically the unliganded receptor is anchored to the IF system. Ligand addition releases GR from IFs and shifts the receptor into the nucleus. Suppression of nestin by specific shRNA abolishes anchoring of GR, induces its accumulation in the nucleus and provokes an irreversible G1/S cell cycle arrest. Suppression of GR prior to that of nestin prevents entry into the arrest. The data give evidence that nestin/vimentin specific anchoring modulates growth suppression by GR. We hypothesize that expression of nestin is a major determinant in suppression of anti-proliferative activity of GR in undifferentiated tissue and facilitates activation of this growth control in a precise tissue and differentiation dependent manner

Onset of pain to surgery time in acute aortic dissections type A: a mandatory factor for evaluating surgical results?

ObjectiveAn acute aortic dissection type A (AADA) is a rare but life-threatening event. The mortality rate ranges between 18% to 28% and mortality is often within the first 24 h and up to 1%–2% per hour. Although the onset of pain to surgery time has not been a relevant factor in terms of research in the field of AADA, we hypothesize that a patient's preoperative conditions depend on the length of this time.MethodsBetween January 2000 and January 2018, 430 patients received surgical treatment for acute aortic dissection DeBakey type I at our tertiary referral hospital. In 11 patients, the exact time point of initial onset of pain was retrospectively not detectable. Accordingly, a total of 419 patients were included in the study. The cohort was categorized into two groups: Group A with an onset of pain to surgery time < 6 h (n = 211) and Group B > 6 h (n = 208), respectively.ResultsMedian age was 63.5 years (y) ((IQR: 53.3–71.4 y); (67.5% male)). Preoperative conditions differed significantly between the cohorts. Differences were detected in terms of malperfusion (A: 39.3%; B: 23.6%; P: 0.001), neurological symptoms (A: 24.2%; B: 15.4%; P: 0.024), and the dissection of supra-aortic arteries (A: 25.1%; B: 16.8%; P: 0.037). In particular, cerebral malperfusion (A 15.2%: B: 8.2%; P: 0.026) and limb malperfusion (A: 18%, B: 10.1%; P: 0.020) were significantly increased in Group A. Furthermore, Group A showed a decreased median survival time (A: 1,359.0 d; B: 2,247.5 d; P: 0.001), extended ventilation time (A: 53.0 h; B: 44.0 h; P: 0.249) and higher 30-day mortality rate (A: 25.1%; B: 17.3%; P: 0.051).ConclusionsPatients with a short onset of pain to surgery time in cases of AADA present themselves not only with more severe preoperative symptoms but are also the more compromised cohort. Despite early presentation and emergency aortic repair, these patients show increased chances of early mortality. The “onset of pain to surgery time” should become a mandatory factor when making comparable surgical evaluations in the field of AADA

Large-scale mapping of mutations affecting zebrafish development

BACKGROUND: Large-scale mutagenesis screens in the zebrafish employing the mutagen ENU have isolated several hundred mutant loci that represent putative developmental control genes. In order to realize the potential of such screens, systematic genetic mapping of the mutations is necessary. Here we report on a large-scale effort to map the mutations generated in mutagenesis screening at the Max Planck Institute for Developmental Biology by genome scanning with microsatellite markers. RESULTS: We have selected a set of microsatellite markers and developed methods and scoring criteria suitable for efficient, high-throughput genome scanning. We have used these methods to successfully obtain a rough map position for 319 mutant loci from the Tübingen I mutagenesis screen and subsequent screening of the mutant collection. For 277 of these the corresponding gene is not yet identified. Mapping was successful for 80 % of the tested loci. By comparing 21 mutation and gene positions of cloned mutations we have validated the correctness of our linkage group assignments and estimated the standard error of our map positions to be approximately 6 cM. CONCLUSION: By obtaining rough map positions for over 300 zebrafish loci with developmental phenotypes, we have generated a dataset that will be useful not only for cloning of the affected genes, but also to suggest allelism of mutations with similar phenotypes that will be identified in future screens. Furthermore this work validates the usefulness of our methodology for rapid, systematic and inexpensive microsatellite mapping of zebrafish mutations

Reasons for (Non)Participating in a Telephone-Based Intervention Program for Families with Overweight Children

Willingness to participate in obesity prevention programs is low; underlying reasons are poorly understood. We evaluated reasons for (non)participating in a novel telephone-based obesity prevention program for overweight children and their families. percentile) aged 3.5–17.4 years were screened via the CrescNet database, a representative cohort of German children, and program participation (repetitive computer aided telephone counseling) was offered by their local pediatrician. Identical questionnaires to collect baseline data on anthropometrics, lifestyle, eating habits, sociodemographic and psychosocial parameters were analyzed from 433 families (241 participants, 192 nonparticipants). Univariate analyses and binary logistic regression were used to identify factors associated with nonparticipation. percentile) was higher in participants (58.9% vs.38%,p<0.001). Participating girls were younger than boys (8.8 vs.10.4 years, p<0.001). 87.3% and 40% of participants, but only 72.2% and 24.7% of nonparticipants, respectively, reported to have regular breakfasts (p = 0.008) and 5 regular daily meals (p = 0.003). Nonparticipants had a lower household-net-income (p<0.001), but higher subjective physical wellbeing than participants (p = 0.018) and believed that changes in lifestyle can be made easily (p = 0.05).An important reason for nonparticipation was non-awareness of their child's weight status by parents. Nonparticipants, who were often low-income families, believed that they already perform a healthy lifestyle and had a higher subjective wellbeing. We hypothesize that even a low-threshold intervention program does not reach the families who really need it

Replication of Lung Cancer Susceptibility Loci at Chromosomes 15q25, 5p15, and 6p21: A Pooled Analysis From the International Lung Cancer Consortium

Background Genome-wide association studies have identified three chromosomal regions at 15q25, 5p15, and 6p21 as being associated with the risk of lung cancer. To confirm these associations in independent studies and investigate heterogeneity of these associations within specific subgroups, we conducted a coordinated genotyping study within the International Lung Cancer Consortium based on independent studies that were not included in previous genome-wide association studies. Methods Genotype data for single-nucleotide polymorphisms at chromosomes 15q25 (rs16969968, rs8034191), 5p15 (rs2736100, rs402710), and 6p21 (rs2256543, rs4324798) from 21 case-control studies for 11 645 lung cancer case patients and 14 954 control subjects, of whom 85% were white and 15% were Asian, were pooled. Associations between the variants and the risk of lung cancer were estimated by logistic regression models. All statistical tests were two-sided. Results Associations between 15q25 and the risk of lung cancer were replicated in white ever-smokers (rs16969968: odds ratio [OR] = 1.26, 95% confidence interval [CI] = 1.21 to 1.32, Ptrend = 2 × 10−26), and this association was stronger for those diagnosed at younger ages. There was no association in never-smokers or in Asians between either of the 15q25 variants and the risk of lung cancer. For the chromosome 5p15 region, we confirmed statistically significant associations in whites for both rs2736100 (OR = 1.15, 95% CI = 1.10 to 1.20, Ptrend = 1 × 10−10) and rs402710 (OR = 1.14, 95% CI = 1.09 to 1.19, Ptrend = 5 × 10−8) and identified similar associations in Asians (rs2736100: OR = 1.23, 95% CI = 1.12 to 1.35, Ptrend = 2 × 10−5; rs402710: OR = 1.15, 95% CI = 1.04 to 1.27, Ptrend = .007). The associations between the 5p15 variants and lung cancer differed by histology; odds ratios for rs2736100 were highest in adenocarcinoma and for rs402710 were highest in adenocarcinoma and squamous cell carcinomas. This pattern was observed in both ethnic groups. Neither of the two variants on chromosome 6p21 was associated with the risk of lung cancer. Conclusions In this international genetic association study of lung cancer, previous associations found in white populations were replicated and new associations were identified in Asian populations. Future genetic studies of lung cancer should include detailed stratification by histolog

The German MultiCare-study: Patterns of multimorbidity in primary health care – protocol of a prospective cohort study

Background Multimorbidity is a highly frequent condition in older people, but well designed longitudinal studies on the impact of multimorbidity on patients and the health care system have been remarkably scarce in numbers until today. Little is known about the long term impact of multimorbidity on the patients' life expectancy, functional status and quality of life as well as health care utilization over time. As a consequence, there is little help for GPs in adjusting care for these patients, even though studies suggest that adhering to present clinical practice guidelines in the care of patients with multimorbidity may have adverse effects. Methods The study is designed as a multicentre prospective, observational cohort study of 3.050 patients aged 65 to 85 at baseline with at least three different diagnoses out of a list of 29 illnesses and syndromes. The patients will be recruited in approx. 120 to 150 GP surgeries in 8 study centres distributed across Germany. Information about the patients' morbidity will be collected mainly in GP interviews and from chart reviews. Functional status, resources/risk factors, health care utilization and additional morbidity data will be assessed in patient interviews, in which a multitude of well established standardized questionnaires and tests will be performed. Discussion The main aim of the cohort study is to monitor the course of the illness process and to analyse for which reasons medical conditions are stable, deteriorating or only temporarily present. First, clusters of combinations of diseases/disorders (multimorbidity patterns) with a comparable impact (e.g. on quality of life and/or functional status) will be identified. Then the development of these clusters over time will be analysed, especially with regard to prognostic variables and the somatic, psychological and social consequences as well as the utilization of health care resources. The results will allow the development of an instrument for prediction of the deterioration of the illness process and point at possibilities of prevention. The practical consequences of the study results for primary care will be analysed in expert focus groups in order to develop strategies for the inclusion of the aspects of multimorbidity in primary care guidelines