On singular Lagrangians affine in velocities

The properties of Lagrangians affine in velocities are analyzed in a geometric way. These systems are necessarily singular and exhibit, in general, gauge invariance. The analysis of constraint functions and gauge symmetry leads us to a complete classification of such Lagrangians.Comment: AMSTeX, 22 page

Two-stage model-based design of cancer phase I dose escalation trials: evaluation using the phase I program of barasertib (AZD1152)

Introduction Modeling and simulation of pharmacokinetics and pharmacodynamics has previously been shown to be potentially useful in designing Phase I programs of novel anti-cancer agents that show hematological toxicity. In this analysis, a two-stage model-based trial design was evaluated retrospectively using data from the Phase I program with the aurora kinase inhibitor barasertib. Methods Data from two Phase I trials and four regimens were used (n = 79). Using barasertib-hydroxy QPA plasma concentrations and neutrophil count data from only study 1A, a PKPD model was developed and subsequently used to predict the MTD and a safe starting dose for the other trials. Results The PKPD model based on data from the first study adequately described the time course of neutrophil count fluctuation. The two-stage model-based design provided safe starting doses for subsequent phase I trials for barasertib. Predicted safe starting dose levels were higher than those used in two subsequent trials, but lower than used in the other trial. Discussion The two-stage approach could have been applied safely to define starting doses for alternative dosing strategies with barasertib. The limited improvement in efficiency for the phase I program of barasertib may have been due to the fact that starting doses for the studied phase I trials were already nearly optimal. Conclusion Application of the two-stage model-based trial design in Phase I programs with novel anti-cancer drugs that cause haematological toxicity is feasible, safe, and may lead to a reduction in the number of patient treated at sub-therapeutic dose-levels

Expressiveness modulo Bisimilarity of Regular Expressions with Parallel Composition (Extended Abstract)

The languages accepted by finite automata are precisely the languages denoted by regular expressions. In contrast, finite automata may exhibit behaviours that cannot be described by regular expressions up to bisimilarity. In this paper, we consider extensions of the theory of regular expressions with various forms of parallel composition and study the effect on expressiveness. First we prove that adding pure interleaving to the theory of regular expressions strictly increases its expressiveness up to bisimilarity. Then, we prove that replacing the operation for pure interleaving by ACP-style parallel composition gives a further increase in expressiveness. Finally, we prove that the theory of regular expressions with ACP-style parallel composition and encapsulation is expressive enough to express all finite automata up to bisimilarity. Our results extend the expressiveness results obtained by Bergstra, Bethke and Ponse for process algebras with (the binary variant of) Kleene's star operation.Comment: In Proceedings EXPRESS'10, arXiv:1011.601

Spin dynamics for bosons in an optical lattice

We study the internal dynamics of bosonic atoms in an optical lattice. Within the regime in which the atomic crystal is a Mott insulator with one atom per well, the atoms behave as localized spins which interact according to some spin Hamiltonian. The type of Hamiltonian (Heisenberg, Ising), and the sign of interactions may be tuned by changing the properties of the optical lattice, or applying external magnetic fields. When, on the other hand, the number of atoms per lattice site is unknown, we can still use the bosons to perform general quantum computation

Numerical modelling of hip fracture patterns in human femur

[EN] Background and Objective: Hip fracture morphology is an important factor determining the ulterior surgical repair and treatment, because of the dependence of the treatment on fracture morphology. Although numerical modelling can be a valuable tool for fracture prediction, the simulation of femur fracture is not simple due to the complexity of bone architecture and the numerical techniques required for simulation of crack propagation. Numerical models assuming homogeneous fracture mechanical properties commonly fail in the prediction of fracture patterns. This paper focuses on the prediction of femur fracture based on the development of a finite element model able to simulate the generation of long crack paths. Methods: The finite element model developed in this work demonstrates the capability of predicting fracture patterns under stance loading configuration, allowing the distinction between the main fracture paths: intracapsular and extracapsular fractures. It is worth noting the prediction of different fracture patterns for the same loading conditions, as observed during experimental tests. Results and conclusions: The internal distribution of bone mineral density and femur geometry strongly influences the femur fracture morphology and fracture load. Experimental fracture paths have been analysed by means of micro-computed tomography allowing the comparison of predicted and experimental crack surfaces, confirming the good accuracy of the numerical model.The authors are indebted to University Complutense of Madrid and to the radiological team of the Hospital Universitario Infanta Leonor for supporting the experimental work on human bones included in this paper. The micro-CTs were performed in the Micro-Computed Tomography laboratory at CENIEH facilities with the collaboration of CENIEH staff. The authors gratefully acknowledge the funding support received from the Spanish Ministry of Economy and Competitiveness and the FEDER operation program for funding the projects DPI2013-46641-R, DPI2017-89197-C2-1-R, DPI2017-89197-C2-2-R, RTC-2015-3887-8 and the Generalitat Valenciana through theproject Prometeo/2016/007. The authors also acknowledge the funding support received from the Fundacion Espanola de Investigacion Osea y del Metabolismo Mineral through the 2018 research fellowship program.Marco, M.; Giner Maravilla, E.; Caeiro-Rey, JR.; Miguélez, MH.; Larrainzar-Garijo, R. (2019). Numerical modelling of hip fracture patterns in human femur. Computer Methods and Programs in Biomedicine. 173:67-75. https://doi.org/10.1016/j.cmpb.2019.03.010S677517

Pharmacological interventions for sleepiness and sleep disturbances caused by shift work

BACKGROUND: Shift work results in sleep-wake disturbances, which cause sleepiness during night shifts and reduce sleep length and quality in daytime sleep after the night shift. In its serious form it is also called shift work sleep disorder. Various pharmacological products are used to ameliorate symptoms of sleepiness or poor sleep length and quality. OBJECTIVES: To evaluate the effects of pharmacological interventions to reduce sleepiness or to improve alertness at work and decrease sleep disturbances whilst of work, or both, in workers undertaking shift work. METHODS: Search methods: We searched CENTRAL, MEDLINE, EMBASE, PubMed and PsycINFO up to 20 September 2013 and ClinicalTrials.gov up to July 2013. We also screened reference lists of included trials and relevant reviews. Selection criteria: We included all eligible randomised controlled trials (RCTs), including cross-over RCTs, of pharmacological products among workers who were engaged in shift work (including night shifts) in their present jobs and who may or may not have had sleep problems. Primary outcomes were sleep length and sleep quality while of work, alertness and sleepiness, or fatigue at work. Data collection and analysis: Two authors independently selected studies, extracted data and assessed risk of bias in included trials. We performed meta-analyses where appropriate. MAIN RESULTS: We included 15 randomised placebo-controlled trials with 718 participants. Nine trials evaluated the effect of melatonin and two the effect of hypnotics for improving sleep problems. One trial assessed the effect of modafinil, two of armodafinil and one examined cafeine plus naps to decrease sleepiness or to increase alertness

Dutch and American waterway development: identification and classification of tools for value creation

Waterways can serve society in a variety of ways. However, authorities responsible for maintenance and development of waterways often have a sectoral focus. They strive for cost efficient solutions within their restricted scope; broader development of socio-economic value receives little attention. This can be seen in e.g. the Netherlands and the USA. Both countries have strong national authorities responsible for the navigation function of waterways. The societal call for broader optimization is recognized, but a systemized response to this call is lacking. Nevertheless both authorities make attempts towards increasing the socio-economic value of their capital waterway projects by deploying tools for broader optimization. Six recent cases, in which such attempts were made, are studied with the aim of identifying and classifying the tools deployed. Identification and classification is needed to evaluate where gaps and opportunities lie for more systemized responses. From these cases a total of 15 tools are identified which stimulated broad optimization. These tools are classified by identifying the transaction characteristics associated with these tools. These characteristics can relate to cost, benefits or value capturing and can be of informative, coordinative or legislative nature. The results show overlaps and voids in the domains these tools address. For practitioners the results can be helpful to navigate through the planning and implementation phase of waterway projects. More broadly the study shows that in the waterway sector, a sector in need for adaptation and renewal, the application of a variety of mixes of governance is an emerging issue

LION/web:a web-based ontology enrichment tool for lipidomic data analysis

Background: A major challenge for lipidomic analyses is the handling of the large amounts of data and the translation of results to interpret the involvement of lipids in biological systems. Results: We built a new lipid ontology (LION) that associates &gt; 50,000 lipid species to biophysical, chemical, and cell biological features. By making use of enrichment algorithms, we used LION to develop a web-based interface (LION/web, www.lipidontology.com) that allows identification of lipid-associated terms in lipidomes. LION/web was validated by analyzing a lipidomic dataset derived from well-characterized sub-cellular fractions of RAW 264.7 macrophages. Comparison of isolated plasma membranes with the microsomal fraction showed a significant enrichment of relevant LION-terms including "plasma membrane", "headgroup with negative charge", "glycerophosphoserines", "above average bilayer thickness", and "below average lateral diffusion". A second validation was performed by analyzing the membrane fluidity of Chinese hamster ovary cells incubated with arachidonic acid. An increase in membrane fluidity was observed both experimentally by using pyrene decanoic acid and by using LION/web, showing significant enrichment of terms associated with high membrane fluidity ("above average", "very high", and "high lateral diffusion" and "below average transition temperature"). Conclusions: The results demonstrate the functionality of LION/web, which is freely accessible in a platform-independent way.</p

Psychosocial work characteristics associated with distress and intention to leave nursing education; a one-year follow-up study

Background: Dropout in later years of the nursing degree programme involves lost investment and is a particular problem for both students and educators. Reasons for late dropout seem to be related to the work and learning environment of the clinical placement. Objectives: The aim of this study was to investigate associations between psychosocial work characteristics and distress and intention to leave nursing education among third-year nursing students. Design: A prospective cohort study. Setting A Bachelor of Nursing programme of a University of Applied Sciences in [name country]. Participants: 363 third-year nursing students. Methods: Baseline and one-year follow-up measurements were used from a prospective cohort study. Third-year nursing students were invited annually in May between 2016 and 2018. Psychosocial work characteristics were psychological demands, supervisor and co-worker support, and acts of offensive behaviour. Logistic regression analyses were used to build multivariate models. Results: Frequent exposure to violence (OR = 2.52, 95% CI: 1.29-4.92) was univariately associated with distress. In the multivariate model for distress, psychological demands (OR = 1.63, 95% CI: 1.05-2.52) and frequent exposure to violence (OR = 3.02, 95% CI: 1.48-6.19) were associated with distress. Supervisor support (OR = 0.54, 95% CI: 0.36-0.80) and co-worker support (OR = 0.41, 95% CI: 0.24-0.72) were negatively associated with intention to leave (i.e. were protective) in the univariate model. In the adjusted multivariate model, only co-worker support (OR = 0.50, 95% CI: 0.25-0.97) was a protective factor for an intention to leave. Conclusion: Psychological demands and frequent exposure to violence are risk factors for distress, and co-worker support is a protective factor reducing the intention to leave nursing education in the last stage of the programme. Improving the psychosocial working climate of nursing students may reduce the intention to leave at a late stage in nursing education, and hence actual late dropout