A mixed-integer linear programming approach to the optimization of event-bus schedules: a scheduling application in the tourism sector

This paper deals with “The Enchanted Journey,” which is a daily event tour booked by Bollywood-film fans. During the tour, the participants visit original sites of famous Bollywood films at various locations in Switzerland; moreover, the tour includes stops for lunch and shopping. Each day, up to five buses operate the tour. For operational reasons, however, two or more buses cannot stay at the same location simultaneously. Further operative constraints include time windows for all activities and precedence constraints between some activities. The planning problem is how to compute a feasible schedule for each bus. We implement a two-step hierarchical approach. In the first step, we minimize the total waiting time; in the second step, we minimize the total travel time of all buses. We present a basic formulation of this problem as a mixed-integer linear program. We enhance this basic formulation by symmetry-breaking constraints, which reduces the search space without loss of generality. We report on computational results obtained with the Gurobi Solver. Our numerical results show that all relevant problem instances can be solved using the basic formulation within reasonable CPU time, and that the symmetry-breaking constraints reduce that CPU time considerably.

German Total Ankle Replacement Register of the German Foot and Ankle Society (D. A. F.) - presentation of design and reliability of the data as well as first results

INTRODUCTION Even though arthroplasty of the ankle joint is considered to be an established procedure, only about 1,300 endoprostheses are implanted in Germany annually. Arthrodeses of the ankle joint are performed almost three times more often. This may be due to the availability of the procedure - more than twice as many providers perform arthrodesis - as well as the postulated high frequency of revision procedures of arthroplasties in the literature. In those publications, however, there is often no clear differentiation between revision surgery with exchange of components, subsequent interventions due to complications and subsequent surgery not associated with complications. The German Orthopaedic Foot and Ankle Association's (D. A. F.) registry for total ankle replacement collects data pertaining to perioperative complications as well as cause, nature and extent of the subsequent interventions, and postoperative patient satisfaction. MATERIAL AND METHODS The D. A. F.'s total ankle replacement register is a nation-wide, voluntary registry. After giving written informed consent, the patients can be added to the database by participating providers. Data are collected during hospital stay for surgical treatment, during routine follow-up inspections and in the context of revision surgery. The information can be submitted in paper-based or online formats. The survey instruments are available as minimum data sets or scientific questionnaires which include patient-reported outcome measures (PROMs). The pseudonymous clinical data are collected and evaluated at the Institute for Evaluative Research in Medicine, University of Bern/Switzerland (IEFM). The patient-related data remain on the register's module server in North Rhine-Westphalia, Germany. The registry's methodology as well as the results of the revisions and patient satisfaction for 115 patients with a two year follow-up period are presented. Statistical analyses are performed with SAS™ (Version 9.4, SAS Institute, Inc., Cary, NC, USA). RESULTS About 2½ years after the register was launched there are 621 datasets on primary implantations, 1,427 on follow-ups and 121 records on re-operation available. 49 % of the patients received their implants due to post-traumatic osteoarthritis, 27 % because of a primary osteoarthritis and 15 % of patients suffered from a rheumatic disease. More than 90 % of the primary interventions proceeded without complications. Subsequent interventions were recorded for 84 patients, which corresponds to a rate of 13.5 % with respect to the primary implantations. It should be noted that these secondary procedures also include two-stage procedures not due to a complication. "True revisions" are interventions with exchange of components due to mechanical complications and/or infection and were present in 7.6 % of patients. 415 of the patients commented on their satisfaction with the operative result during the last follow-up: 89.9 % of patients evaluate their outcome as excellent or good, 9.4 % as moderate and only 0.7 % (3 patients) as poor. In these three cases a component loosening or symptomatic USG osteoarthritis was present. Two-year follow-up data using the American Orthopedic Foot and Ankle Society Ankle and Hindfoot Scale (AOFAS-AHS) are already available for 115 patients. The median AOFAS-AHS score increased from 33 points preoperatively to more than 80 points three to six months postoperatively. This increase remained nearly constant over the entire two-year follow-up period. CONCLUSION Covering less than 10 % of the approximately 240 providers in Germany and approximately 12 % of the annually implanted total ankle-replacements, the D. A. F.-register is still far from being seen as a national registry. Nevertheless, geographical coverage and inclusion of "high-" (more than 100 total ankle replacements a year) and "low-volume surgeons" (less than 5 total ankle replacements a year) make the register representative for Germany. The registry data show that the number of subsequent interventions and in particular the "true revision" procedures are markedly lower than the 20 % often postulated in the literature. In addition, a high level of patient satisfaction over the short and medium term is recorded. From the perspective of the authors, these results indicate that total ankle arthroplasty - given a correct indication and appropriate selection of patients - is not inferior to an ankle arthrodesis concerning patients' satisfaction and function. First valid survival rates can be expected about 10 years after the register's start.

Metabolomics reveals herbivore-induced metabolites of resistance and susceptibility in maize leaves and roots

Plants respond to herbivory by reprogramming their metabolism. Most research in this context has focused on locally induced compounds that function as toxins or feeding deterrents. We developed an ultra-high-pressure liquid chromatography time-of-flight mass spectrometry (UHPLC-TOF-MS)-based metabolomics approach to evaluate local and systemic herbivore-induced changes in maize leaves, sap, roots and root exudates without any prior assumptions about their function. Thirty-two differentially regulated compounds were identified from Spodoptera littoralis-infested maize seedlings and isolated for structure assignment by microflow nuclear magnetic resonance (CapNMR). Nine compounds were quantified by a high throughput direct nano-infusion tandem mass spectrometry/mass spectrometry (MS/MS) method. Leaf infestation led to a marked local increase of 1,3-benzoxazin-4-ones, phospholipids, N-hydroxycinnamoyltyramines, azealic acid and tryptophan. Only few changes were found in the root metabolome, but 1,3-benzoxazin-4-ones increased in the vascular sap and root exudates. The role of N-hydroxycinnamoyltyramines in plant–herbivore interactions is unknown, and we therefore tested the effect of the dominating p-coumaroyltyramine on S. littoralis. Unexpectedly, p-coumaroyltyramine was metabolized by the larvae and increased larval growth, possibly by providing additional nitrogen to the insect. Taken together, this study illustrates that herbivore attack leads to the induction of metabolites that can have contrasting effects on herbivore resistance in the leaves and roots.

Speciation in Freshwater Fishes

The extraordinary species richness of freshwater fishes has attracted much research on mechanisms and modes of speciation. We here review research on speciation in freshwater fishes in light of speciation theory, and place this in a context of broad-scale diversity patterns in freshwater fishes. We discuss several major repeated themes in freshwater fish speciation and the speciation mechanisms they are frequently associated with. These include transitions between marine and freshwater habitats, transitions between discrete freshwater habitats, and ecological transitions within habitats, as well as speciation without distinct niche shifts. Major research directions in the years to come include understanding the transition from extrinsic environment-dependent to intrinsic reproductive isolation and its influences on species persistence and understanding the extrinsic and intrinsic constraints to speciation and how these relate to broad-scale diversification patterns through time.

Geological map of the Scalaro Valley – Sesia Zone (Italian Western Alps)

In the Sesia Zone (Italian Western Alps), slivers of continental crust characterised by an Alpine high-pressure imprint are intermingled with abundant mafic rocks and Mesozoic metasediments. An extensive study of the central Sesia Zone was undertaken to identify and reconstruct the lithological setting of the mono-cyclic sediments of the Scalaro Unit. A new geological map (1:5000) and schematic cross sections across the Scalaro Unit and the adjoining Eclogitic Micaschist Complex are presented here. In order to delimit the size and shape of the mono-metamorphic unit and understand its internal geometry with respect to the poly-metamorphic basement, an integrated approach was used. Linking observations and data across a range of scales, from kilometres in the field down to petrological and chronological data obtained at micrometre scale, we define for the first time the real size and internal geometry of the Scalaro Unit, as well as its large-scale structural context.

Fate of accidental symmetries of the relativistic hydrogen atom in a spherical cavity

The non-relativistic hydrogen atom enjoys an accidental SO(4) symmetry, that enlarges the rotational SO(3) symmetry, by extending the angular momentum algebra with the Runge–Lenz vector. In the relativistic hydrogen atom the accidental symmetry is partially lifted. Due to the Johnson–Lippmann operator, which commutes with the Dirac Hamiltonian, some degeneracy remains. When the non-relativistic hydrogen atom is put in a spherical cavity of radius R with perfectly reflecting Robin boundary conditions, characterized by a self-adjoint extension parameter γ, in general the accidental SO(4) symmetry is lifted. However, for R=(l+1)(l+2)a (where a is the Bohr radius and l is the orbital angular momentum) some degeneracy remains when γ=∞ or γ = 2/R. In the relativistic case, we consider the most general spherically and parity invariant boundary condition, which is characterized by a self-adjoint extension parameter. In this case, the remnant accidental symmetry is always lifted in a finite volume. We also investigate the accidental symmetry in the context of the Pauli equation, which sheds light on the proper non-relativistic treatment including spin. In that case, again some degeneracy remains for specific values of R and γ.

Loss of tapasin correlates with diminished CD8(+) T-cell immunity and prognosis in colorectal cancer.

BACKGROUND Tapasin is a crucial component of the major histocompatibility (MHC) class I antigen presentation pathway. Defects in this pathway can lead to tumor immune evasion. The aim of this study was to test whether tapasin expression correlates with CD8(+) cytotoxic T lymphocyte (CTL) infiltration of colorectal cancer (CRC) and overall survival. METHODS A next-generation tissue microarray (ngTMA) of 198 CRC patients with full clinicopathological information was included in this study. TMA slides were immunostained for tapasin, MHC I and CD8. Marker expression was analyzed with immune-cell infiltration, patient survival and TNM-staging. RESULTS A reduction of tapasin expression strongly correlated with venous invasion (AUC 0.682, OR 2.7, p = 0.002; 95% CI 1.7-5.0), lymphatic invasion (AUC 0.620, OR 2.0, p = 0.005; 95 % CI 1.3-3.3), distant metastasis (AUC 0.727, OR 2.9, p = 0.004; 95% CI 1.4-5.9) and an infiltrative tumor border configuration (AUC 0.621, OR 2.2, p = 0.017; 95% CI 1.2-4.4). Further, tapasin expression was associated with CD8(+) CTL infiltration (AUC 0.729, OR 5.4, p < 0.001; 95% CI 2.6-11), and favorable overall survival (p = 0.004, HR 0.6, 95% CI 0.42-0.85). CONCLUSIONS Consistent with published functional data showing that tapasin promotes antigen presentation, as well as tumor immune recognition and destruction by CD8(+) CTLs, a reduction in tapasin expression is associated with tumor progression in CRC.

Prediction of Trabecular Bone Anisotropy from Quantitative Computed Tomography using Supervised Learning and a Novel Morphometric Feature Descriptor

Patient-specific biomechanical models including local bone mineral density and anisotropy have gained importance for assessing musculoskeletal disorders. However the trabecular bone anisotropy captured by high-resolution imaging is only available at the peripheral skeleton in clinical practice. In this work, we propose a supervised learning approach to predict trabecular bone anisotropy that builds on a novel set of pose invariant feature descriptors. The statistical relationship between trabecular bone anisotropy and feature descriptors were learned from a database of pairs of high resolution QCT and clinical QCT reconstructions. On a set of leave-one-out experiments, we compared the accuracy of the proposed approach to previous ones, and report a mean prediction error of 6% for the tensor norm, 6% for the degree of anisotropy and 19◦ for the principal tensor direction. These findings show the potential of the proposed approach to predict trabecular bone anisotropy from clinically available QCT images.

Stimulant medication and psychotic symptoms in offspring of parents with mental illness

BACKGROUND: Stimulants, such as methylphenidate, are among the most commonly used medications in children and adolescents. Psychotic symptoms have been reported as rare adverse reactions to stimulants but have not been systematically inquired about in most previous studies. Family history of mental illness may increase the vulnerability to drug-induced psychotic symptoms. We examined the association between stimulant use and psychotic symptoms in sons and daughters of parents with major mood and psychotic disorders. METHODS: We assessed psychotic symptoms, psychotic-like experiences, and basic symptoms in 141 children and youth (mean ± SD age: 11.8 ± 4.0 years; range: 6–21 years), who had 1 or both parents with major depressive disorder, bipolar disorder, or schizophrenia, and of whom 24 (17.0%) had taken stimulant medication. RESULTS: Psychotic symptoms were present in 62.5% of youth who had taken stimulants compared with 27.4% of participants who had never taken stimulants. The association between stimulant use and psychotic experiences remained significant after adjustment for potential confounders (odds ratio: 4.41; 95% confidence interval: 1.82–10.69; P = .001) and was driven by hallucinations occurring during the use of stimulant medication. A temporal relationship between use of stimulants and psychotic symptoms was supported by an association between current stimulant use and current psychotic symptoms and co-occurrence in cases that were assessed on and off stimulants. CONCLUSIONS: Psychotic symptoms should be monitored during the use of stimulants in children and adolescents. Family history of mood and psychotic disorders may need to be taken into account when considering the prescription of stimulants.

Erosive tooth wear and wedge-shaped defects in 1996 and 2006: cross- sectional surveys of Swiss army recruits.

The purpose of this study was to determine the prevalence and possible etiological factors of erosive tooth wear and wedge-shaped defects in Swiss Army recruits and compare the findings with those of an analogous study conducted in 1996. In 2006, 621 recruits between 18 and 25 years of age (1996: 417 recruits; ages 19 to 25) were examined for erosive tooth wear and wedge-shaped defects. Additional data was acquired using a questionnaire about personal details, education, dentitions subjective condition, oral hygiene, eating and drinking habits, medications used, and general medical problems. In 2006, 60.1% of those examined exhibited occlusal erosive tooth wear not involving the dentin (1996: 82.0%) and 23.0% involving the dentin (1996: 30.7%). Vestibular erosive tooth wear without dentin involvement was seen in 7.7% in 2006 vs. 14.4% in 1996. Vestibular erosive tooth wear with dentin involvement was rare in both years (0.5%). Oral erosive tooth wear lacking exposed dentin was also rare in those years, although more teeth were affected in 2006 (2.1%) than in 1996 (0.7%). The examinations in 2006 found one or more initial wedge-shaped lesions in 8.5% of the recruits, while 20.4% of the study participants exhibited such in 1996. In 1996, 53% consumed acidic foods and beverages more than 5 times/day; in 2006, 83.9% did so. In neither study did multivariate regression analyses show any significant correlations between occurrence and location of erosive tooth wear and wedge-shaped defects and various other parameters, e.g., eating and hygiene habits, or dentin hyper-sensitivity. Despite a significant increase in consumption of acidic products between 1996 and 2006, the latter study found both fewer erosive tooth wear and fewer wedge-shaped defects (i.e., fewer non-carious lesions.).

Time-dependent supraimplant mucosa changes: short communication

PURPOSE The aim of this short communication was to analyze time-dependent changes of the supraimplant mucosa architecture in the esthetic zone. MATERIALS AND METHODS Five patients underwent single-tooth replacement with implant crowns in the anterior maxilla. The supraimplant soft tissue was conditioned with fixed provisional crowns. Quadrantlike digital impressions were taken with an intraoral optical scanning device at three time points: t0, immediately after removal of the provisional (baseline); t1, after 5 minutes; and t2, after 10 minutes. To analyze time-dependent mucosal changes, the corresponding digital files were superimposed for each patient, and baseline (t0) scans were compared with t1 and t2 scans, respectively. Wilcoxon rank sum tests were used for statistical calculations with a strict level of significance at P < .01. RESULTS Mean values for supraimplant soft tissue changes were statistically significantly different after 5 minutes (5.5%; standard deviation ± 0.3%) in comparison to the results after 10 minutes (21.7%; standard deviation ± 1.8%). The direction of mucosa shrinkage showed a trend toward palatal sites. CONCLUSION Based on the findings of this analysis, changes in supraimplant mucosa architecture seem to be affected only slightly during the first 5 minutes after removal of soft tissue support.

Na 50 Nachlass Arthur Schopenhauer - 'Schopenhauer-Archiv', 149 - Bericht über negative Rezensionen von Veröffentlichungen Schopenhauers

u.a.: kritische Auseinandersetzung mit den Publikationen von Schopenhauer "Über den Willen der Natur", "Die beiden Grundprobleme der Ethik"; Immanuel Kant; Friedrich Schleiermacher, Andreas Ludwig;