Stability aspects of the traveling salesman problem based on k-best solutions

AbstractThis paper discusses stability analysis for the Traveling Salesman Problem (TSP). For a traveling salesman tour which is known to be optimal with respect to a given instance (length vector) we are interested in determining the stability region, i.e. the set of all length vectors for which the tour is optimal. The following three subsets of the stability region are of special interest: 1.(1) tolerances, i.e. the maximum perturbations of single edges;2.(2) tolerance regions which are subsets of the stability region that can be constructed from the tolerances; and3.(3) the largest ball contained in the stability region centered at the given length vector (the corresponding radius is known as the stability radius). It is well known that the problems of determining tolerances and the stability radius for the TSP are NP-hard so that in general it is not possible to obtain the above-mentioned three subsets without spending a lot of computation time. The question addressed in this paper is the following: assume that not only an optimal tour is known, but also a set of k shortest tours (k ⩾2) is given. Then to which extent does this allow us to determine the three subsets in polynomial time? It will be shown in this paper that having k-best solutions can give the desired information only partially. More precisely, it will be shown that only some of the tolerances can be determined exactly and for the other ones as well as for the stability radius only lower and/or upper bounds can be derived. Since the amount of information that can be derived from the set of k-best solutions is dependent on both the value of k as well as on the specific length vector, we present numerical experiments on instances from the TSPLIB library to analyze the effectiveness of our approach

Nature 2000 in Nederland : juridische ruimte, natuurdoelen en beheersplanprocessen

De Natura 2000-gebieden in Nederland bevatten natuur van Europese betekenis, met een groot aantal Europees beschermde soorten en habitats. De zogenoemde staat van instandhouding van veel van deze soorten en habitats is echter ongunstig en Nederland heeft de plicht die te verbeteren. Het beschermingsregime in en rond de Natura 2000-gebieden brengt activiteiten als landbouw, recreatie en wonen regelmatig in conflict met de te beschermen natuurwaarden. Onzekerheid over de verplichtingen in en rond de Natura 2000-gebieden voedt de maatschappelijke weerstand tegen het beschermingsregime

An instrument for broadened risk assessment in antenatal health care including non-medical issues.

Growing evidence on the risk contributing role of non-medical factors on pregnancy outcomes urged for a new approach in early antenatal risk selection. The evidence invites to more integration, in particular between the clinical working area and the public health domain. We developed a non-invasive, standardized instrument for comprehensive antenatal risk assessment. The current study presents the application-oriented development of a risk screening instrument for early antenatal detection of risk factors and tailored prevention in an integrated care setting. A review of published instruments complemented with evidence from cohort studies. Selection and standardization of risk factors associated with small for gestational age, preterm birth, congenital anomalies and perinatal mortality. Risk factors were weighted to obtain a cumulative risk score. Responses were then connected to corresponding care pathways. A cumulative risk threshold was defined, which can be adapted to the population and the availability of preventive facilities. A score above the threshold implies multidisciplinary consultation between caregivers. The resulting digital score card consisted of 70 items, subdivided into four non-medical and two medical domains. Weighing of risk factors was based on existing evidence. Pilot-evidence from a cohort of 218 pregnancies in a multi-practice urban setting showed a cut-off of 16 points would imply 20% of all pregnant women to be assessed in a multidisciplinary setting. A total of 28 care pathways were defined. The resulting score card is a universal risk screening instrument which incorporates recent evidence on non-medical risk factors for adverse pregnancy outcomes and enables systematic risk management in an integrated antenatal health care setting

Distal Versus Total D2-Gastrectomy for Gastric Cancer:a Secondary Analysis of Surgical and Oncological Outcomes Including Quality of Life in the Multicenter Randomized LOGICA-Trial

Background: Distal gastrectomy (DG) for gastric cancer can cause less morbidity than total gastrectomy (TG), but may compromise radicality. No prospective studies administered neoadjuvant chemotherapy, and few assessed quality of life (QoL). Methods: The multicenter LOGICA-trial randomized laparoscopic versus open D2-gastrectomy for resectable gastric adenocarcinoma (cT1–4aN0–3bM0) in 10 Dutch hospitals. This secondary LOGICA-analysis compared surgical and oncological outcomes after DG versus TG. DG was performed for non-proximal tumors if R0-resection was deemed achievable, TG for other tumors. Postoperative complications, mortality, hospitalization, radicality, nodal yield, 1-year survival, and EORTC-QoL-questionnaires were analyzed using Χ 2-/Fisher’s exact tests and regression analyses. Results: Between 2015 and 2018, 211 patients underwent DG (n = 122) or TG (n = 89), and 75% of patients underwent neoadjuvant chemotherapy. DG-patients were older, had more comorbidities, less diffuse type tumors, and lower cT-stage than TG-patients (p &lt; 0.05). DG-patients experienced fewer overall complications (34% versus 57%; p &lt; 0.001), also after correcting for baseline differences, lower anastomotic leakage (3% versus 19%), pneumonia (4% versus 22%), atrial fibrillation (3% versus 14%), and Clavien-Dindo grading compared to TG-patients (p &lt; 0.05), and demonstrated shorter median hospital stay (6 versus 8 days; p &lt; 0.001). QoL was better after DG (statistically significant and clinically relevant) in most 1-year postoperative time points. DG-patients showed 98% R0-resections, and similar 30-/90-day mortality, nodal yield (28 versus 30 nodes; p = 0.490), and 1-year survival after correcting for baseline differences (p = 0.084) compared to TG-patients. Conclusions: If oncologically feasible, DG should be preferred over TG due to less complications, faster postoperative recovery, and better QoL while achieving equivalent oncological effectiveness. Mini-abstract: Distal D2-gastrectomy for gastric cancer resulted in less complications, shorter hospitalization, quicker recovery and better quality of life compared to total D2-gastrectomy, whereas radicality, nodal yield and survival were similar.</p

Distal Versus Total D2-Gastrectomy for Gastric Cancer:a Secondary Analysis of Surgical and Oncological Outcomes Including Quality of Life in the Multicenter Randomized LOGICA-Trial

Background: Distal gastrectomy (DG) for gastric cancer can cause less morbidity than total gastrectomy (TG), but may compromise radicality. No prospective studies administered neoadjuvant chemotherapy, and few assessed quality of life (QoL). Methods: The multicenter LOGICA-trial randomized laparoscopic versus open D2-gastrectomy for resectable gastric adenocarcinoma (cT1–4aN0–3bM0) in 10 Dutch hospitals. This secondary LOGICA-analysis compared surgical and oncological outcomes after DG versus TG. DG was performed for non-proximal tumors if R0-resection was deemed achievable, TG for other tumors. Postoperative complications, mortality, hospitalization, radicality, nodal yield, 1-year survival, and EORTC-QoL-questionnaires were analyzed using Χ 2-/Fisher’s exact tests and regression analyses. Results: Between 2015 and 2018, 211 patients underwent DG (n = 122) or TG (n = 89), and 75% of patients underwent neoadjuvant chemotherapy. DG-patients were older, had more comorbidities, less diffuse type tumors, and lower cT-stage than TG-patients (p &lt; 0.05). DG-patients experienced fewer overall complications (34% versus 57%; p &lt; 0.001), also after correcting for baseline differences, lower anastomotic leakage (3% versus 19%), pneumonia (4% versus 22%), atrial fibrillation (3% versus 14%), and Clavien-Dindo grading compared to TG-patients (p &lt; 0.05), and demonstrated shorter median hospital stay (6 versus 8 days; p &lt; 0.001). QoL was better after DG (statistically significant and clinically relevant) in most 1-year postoperative time points. DG-patients showed 98% R0-resections, and similar 30-/90-day mortality, nodal yield (28 versus 30 nodes; p = 0.490), and 1-year survival after correcting for baseline differences (p = 0.084) compared to TG-patients. Conclusions: If oncologically feasible, DG should be preferred over TG due to less complications, faster postoperative recovery, and better QoL while achieving equivalent oncological effectiveness. Mini-abstract: Distal D2-gastrectomy for gastric cancer resulted in less complications, shorter hospitalization, quicker recovery and better quality of life compared to total D2-gastrectomy, whereas radicality, nodal yield and survival were similar.</p

Translation controls the expression level of a chimaeric reporter gene

Transcriptional and translational fusions between the reading frame of the β-D-glucuronidase gene (gusA) and the 2′ as well as the 1′ promoter of mannopine synthase (mas), a TR locus of Agrobacterium tumefaciens, were made. The expression of these constructs was studied in the transgenic F1 offspring of independent tobacco transformants at the protein level by assaying for GUS activity and western blot analysis of the GUS protein and at the steady-state mRNA level. In leaves, stems and roots no correlation was found between steady-state levels of GUS mRNA and enzyme activity. In older tissues significantly higher GUS activities were found. This is explained by the stable character of the GUS protein together with an accumulation of protein upon ageing. Three to ten times higher GUS activities were found for in vitro grown plants than for greenhouse-grown plants of the same offspring, despite similar levels of GUS mRNA. Roots from in vitro grown plants display three to ten times higher GUS activities than stems and leaves. In transgenic plants grown in vitro, containing a translational fusion with two AUGs in phase, the initiation of translation in leaf material occurred at both AUGs. Initiation of translation at the first AUG, however, was ten times more frequent. In contrast, initiation in roots from in vitro grown plants occurred exclusively at the second AUG

Around the Tables – Contextual Factors in Healthcare Coverage Decisions Across Western Europe

Background: Across Western Europe, procedures and formalised criteria for taking decisions on the coverage (inclusion in the benefits basket or equivalent) of healthcare technologies vary substantially. In the decision documents, which display the justification of, the rationale for, these decisions, national healthcare institutes may employ ‘contextual factors,’ defined here as situation-specific considerations. Little is known about how the use of such contextual factors compares across countries. We describe and compare contextual factors as used in coverage decisions generally and 4 decision documents specifically in Belgium, England, Germany, and the Netherlands. Methods: Four group interviews with 3 experts from the national healthcare institute of each country, document and web site analysis, and a workshop with 1 to 2 of these experts per country were followed by the examination of the documents of 4 specific decisions taken in each of the 4 countries, sampled to vary widely in type of technology and decision outcome. Results: From the available decision documents, we conclude that in every country studied, contextual factors are established ‘around the table,’ ie, in deliberation. All documents examined feature contextual factors, with similar contextual factor patterns leading to similar decisions in different countries. The Dutch decisions employ the widest variety of factors, with the exception of the societal functioning of the patient, which is relatively common in Belgium, England, and Germany. Half of the final decisions were taken in another setting, with the consequence that no documentation was retrievable for 2 decisions. Conclusion: First, we conclude that in these countries, contextual factors are actively integrated in the decision document, and that this is achieved in deliberation. Conceptualising contextual factors as both situation-specific and actively-integrated affords insight into practices of contextualisation and provides an encouragement for exchange between decision-makers on more qualitative aspects of decisions. Second, the decisions that lacked a publicly acc

Supplementary data for: Missed Diagnoses and Health Problems in Adults With Prader-Willi Syndrome: Recommendations for Screening and Treatment

Context: Prader-Willi syndrome (PWS) is a complex hypothalamic disorder, combining hyperphagia, hypotonia, intellectual disability, and pituitary hormone deficiencies. Annual mortality of patients with PWS is high (3%). In half of the patients, the cause of death is obesity related and/or of cardiopulmonary origin. Health problems leading to this increased mortality often remain undetected due to the complexity and rareness of the syndrome. Objective: To assess the prevalence of health problems in adults with PWS retrospectively. Patients, Design, and Setting: We systematically screened 115 PWS adults for undiagnosed health problems. All patients visited the multidisciplinary outpatient clinic for rare endocrine syndromes at the Erasmus University Medical Center, Rotterdam, Netherlands. We collected the results of medical questionnaires, interviews, physical xaminations, biochemical measurements, polygraphy, polysomnography, and radiology. Main outcome measures: Presence or absence of endocrine and nonendocrine comorbidities in relation to living situation, body mass index, genotype, and demographic factors. Results: Seventy patients (61%) had undiagnosed health problems, while 1 in every 4 patients had multiple undiagnosed health problems simultaneously. All males and 93% of females had hypogonadism, 74% had scoliosis, 18% had hypertension, 19% had hypercholesterolemia, 17% had type 2 diabetes mellitus, and 17% had hypothyroidism. Unfavorable lifestyles were common: 22% exercised too little (according to PWS criteria) and 37% did not see a dietitian. Conclusions: Systematic screening revealed many undiagnosed health problems in PWS adults. Based on patient characteristics, we provide an algorithm for diagnostics and treatment, with the aim to prevent early complications and reduce mortality in this vulnerable patient group

Short salsalate administration affects cell proliferation, metabolism, and inflammation in polycystic kidney disease

Metabolic reprogramming is a driver of autosomal dominant polycystic kidney disease (ADPKD) progression and a potential therapeutic intervention route. We showed before that the AMP-associated protein kinase (AMPK) activator salsalate attenuates cystic disease progression. Here, we aim to study the early, direct effects of short salsalate treatment in adult-onset conditional Pkd1 deletion mice. Cystic mice were treated with salsalate for two weeks, after which NMR metabolomics and RNA sequencing analyses were performed. Pkd1 deletion resulted in clear metabolomic dysregulation. Short salsalate treatment has small, but significant, effects, reverting acetylcarnitine and phosphocholine concentrations back to wild type levels, and showing associations with altered purine metabolism. RNA sequencing revealed that short salsalate treatment, next to restoring energy metabolism toward wildtype levels, also affects cell proliferation and inflammation, in PKD. We show that salsalate positively affects major dysregulated processes in ADPKD: energy metabolism, cell proliferation, and inflammation, providing more insights into its working mechanisms.Functional Genomics of Systemic Disorder