Application of methods for central statistical monitoring in clinical trials

Background On-site source data verification is a common and expensive activity, with little evidence that it is worthwhile. Central statistical monitoring (CSM) is a cheaper alternative, where data checks are performed by the coordinating centre, avoiding the need to visit all sites. Several publications have suggested methods for CSM; however, few have described their use in real trials. Methods R-programs were created to check data at either the subject level (7 tests within 3 programs) or site level (9 tests within 8 programs) using previously described methods or new ones we developed. These aimed to find possible data errors such as outliers, incorrect dates, or anomalous data patterns; digit preference, values too close or too far from the means, unusual correlation structures, extreme variances which may indicate fraud or procedural errors and under-reporting of adverse events. The methods were applied to three trials, one of which had closed and has been published, one in follow-up, and a third to which fabricated data were added. We examined how well the methods work, discussing their strengths and limitations. Results The R-programs produced simple tables or easy-to-read figures. Few data errors were found in the first two trials, and those added to the third were easily detected. The programs were able to identify patients with outliers based on single or multiple variables. They also detected (1) fabricated patients, generated to have values too close to the multivariate mean, or with too low variances in repeated measurements, and (2) sites which had unusual correlation structures or too few adverse events. Some methods were unreliable if applied to centres with few patients or if data were fabricated in a way which did not fit the assumptions used to create the programs. Outputs from the R-programs are interpreted using examples. Limitations Detecting data errors is relatively straightforward; however, there are several limitations in the detection of fraud: some programs cannot be applied to small trials or to centres with few patients (<10) and data falsified in a manner which does not fit the program’s assumptions may not be detected. In addition, many tests require a visual assessment of the output (showing flagged participants or sites), before data queries are made or on-site visits performed. Conclusions CSM is a worthwhile alternative to on-site data checking and may be used to limit the number of site visits by targeting only sites which are picked up by the programs. We summarise the methods, show how they are implemented and that they can be easy to interpret. The methods can identify incorrect or unusual data for a trial subject, or centres where the data considered together are too different to other centres and therefore should be reviewed, possibly through an on-site visit

Coverage, Matching, and Beyond: New Results on Budgeted Mechanism Design

We study a type of reverse (procurement) auction problems in the presence of budget constraints. The general algorithmic problem is to purchase a set of resources, which come at a cost, so as not to exceed a given budget and at the same time maximize a given valuation function. This framework captures the budgeted version of several well known optimization problems, and when the resources are owned by strategic agents the goal is to design truthful and budget feasible mechanisms, i.e. elicit the true cost of the resources and ensure the payments of the mechanism do not exceed the budget. Budget feasibility introduces more challenges in mechanism design, and we study instantiations of this problem for certain classes of submodular and XOS valuation functions. We first obtain mechanisms with an improved approximation ratio for weighted coverage valuations, a special class of submodular functions that has already attracted attention in previous works. We then provide a general scheme for designing randomized and deterministic polynomial time mechanisms for a class of XOS problems. This class contains problems whose feasible set forms an independence system (a more general structure than matroids), and some representative problems include, among others, finding maximum weighted matchings, maximum weighted matroid members, and maximum weighted 3D-matchings. For most of these problems, only randomized mechanisms with very high approximation ratios were known prior to our results

Realizing Innovations in Service Firms: new organizational forms and supporting processes

This paper describes a number of innovation forms that are of special relevance to firms in the service industry. Not only technological innovations but also organizational innovations have been distinguished. In the service industry organizational innovations seem to play a significant role. The literature on innovations makes little mention of new organizational arrangements in services. Based on the service management literature a scheme with three forms of organizational innovation and one form of technological innovation is developed. This scheme is illustrated and elaborated in ten case studies of firms in various service industries. The case studies shed some light on innovations in multi-unit forms, combinations of services and co-operation with customers. On a basis of the service management literature and the case studies some of the main processes supporting the (organizational) innovations are analysed.client as co-producer;multi-unit organization;supporting processes;technological innovations

Macroevolutionary patterns in cranial and lower jaw shape of ceratopsian dinosaurs (dinosauria, ornithischia). phylogeny, morphological integration, and evolutionary rates

Organisms: Ceratopsians were herbivorous, beaked dinosaurs, ranging from 1 m to 9 m in body length, usually four-footed, and with a bony frill that extended backwards from the cranium over the nape of the neck. Known from Asia, Europe, and North America, they appeared in the Late Jurassic and persisted until the end of the Late Cretaceous. Questions: Which evolutionary processes drive the phenotypic evolution of skulls and lower jaws within Ceratopsia? What is the degree of morphological integration between the skull and lower jaw, and between the snout and frill among clades? Finally, are there any morphological evolution rate shifts across the ceratopsian phylogeny? Data: Photographs from 121 ceratopsian skulls and 122 lower jaws in lateral view, both from original photos and published pictures. Fifty-five ceratopsian species are represented in the sample. Methods: We investigated cranial and lower jaw shape changes across ceratopsians applying two-dimensional geometric morphometrics. We also investigated the morphological variation of the snout and the frill. Using phylogenetic generalized least squares regression, we estimated the degree of phylogenetic signal in size and shape data, as well as in the shape-size relationship. We performed phenotypic evolutionary rate analysis on shape data to describe phenotypic shifts across the phylogeny. Using a rarefied version of Escoufier's RV coefficient, we tested morphological integration between skulls and lower jaws, and between snouts and frills. Finally, we explored the potential link between cranial and frill shape evolution in ceratopsians and the radiation of angiosperms using a linear regression model. Results: Skull, snout, and frill shapes differ among clades (with the exception of leptoceratopsids and protoceratopsids). Lower jaws show distinct morphologies among groups. Size and shape changes are phylogenetically structured. The frill drives the morphological variation of the skull, co-varying much more with the lower jaw than with the snout. The frill appears to evolve to co-vary better with the lower jaw in the more morphologically derived clades than in basal ones. A significant linear relationship does exist between cranial shape and angiosperm occurrences, suggesting the hypothesis that the frill evolved in response to changes in dietary compositions associated with the turnover between gymnosperms and angiosperms during the Cretaceous. Significant negative shifts in evolutionary rates characterize skull, snout, frill, and lower jaw shapes, corresponding to nodes where psittacosaurids diverge from other taxa. In contrast, a significant positive shift in skull and snout shape rate of evolution characterizes the clade Ceratopsoidea. Conclusion: The frill is the main driving force in the overall cranial shape within Ceratopsia and evolved secondarily to better co-vary with the lower jaw to produce a more efficient masticatory apparatus. The changes in frill shape are correlated with the angiosperm diversification that occurred in the Cretaceous and thus correlated with changes in diet. Ceratopsians exhibit a slowdown in the phenotypic evolutionary rate in the Early Cretaceous and an acceleration of the phenotypic rate in the Late Cretaceous

An enhanced artificial neural network with a shuffled complex evolutionary global optimization with principal component analysis

The classical Back-Propagation (BP) scheme with gradient-based optimization in training Artificial Neural Networks (ANNs) suffers from many drawbacks, such as the premature convergence, and the tendency of being trapped in local optimums. Therefore, as an alternative for the BP and gradient-based optimization schemes, various Evolutionary Algorithms (EAs), i.e., Particle Swarm Optimization (PSO), Genetic Algorithm (GA), Simulated Annealing (SA), and Differential Evolution (DE), have gained popularity in the field of ANN weight training. This study applied a new efficient and effective Shuffled Complex Evolutionary Global Optimization Algorithm with Principal Component Analysis – University of California Irvine (SP-UCI) to the weight training process of a three-layer feed-forward ANN. A large-scale numerical comparison is conducted among the SP-UCI-, PSO-, GA-, SA-, and DE-based ANNs on 17 benchmark, complex, and real-world datasets. Results show that SP-UCI-based ANN outperforms other EA-based ANNs in the context of convergence and generalization. Results suggest that the SP-UCI algorithm possesses good potential in support of the weight training of ANN in real-word problems. In addition, the suitability of different kinds of EAs on training ANN is discussed. The large-scale comparison experiments conducted in this paper are fundamental references for selecting proper ANN weight training algorithms in practice

Algebraic Properties of Valued Constraint Satisfaction Problem

The paper presents an algebraic framework for optimization problems expressible as Valued Constraint Satisfaction Problems. Our results generalize the algebraic framework for the decision version (CSPs) provided by Bulatov et al. [SICOMP 2005]. We introduce the notions of weighted algebras and varieties and use the Galois connection due to Cohen et al. [SICOMP 2013] to link VCSP languages to weighted algebras. We show that the difficulty of VCSP depends only on the weighted variety generated by the associated weighted algebra. Paralleling the results for CSPs we exhibit a reduction to cores and rigid cores which allows us to focus on idempotent weighted varieties. Further, we propose an analogue of the Algebraic CSP Dichotomy Conjecture; prove the hardness direction and verify that it agrees with known results for VCSPs on two-element sets [Cohen et al. 2006], finite-valued VCSPs [Thapper and Zivny 2013] and conservative VCSPs [Kolmogorov and Zivny 2013].Comment: arXiv admin note: text overlap with arXiv:1207.6692 by other author

Evaluating e-Government services from a citizens' prespective: A reference process model

Evaluating and optimizing e-government services is imperative for governments especially due to the capacity of e-services to transform public administrations and assist the interactions of governments with citizens, businesses and other government agencies. Existing widely applied evaluation approaches neglect to incorporate citizens’ satisfaction measures. Several citizen satisfaction models and indicators have been suggested in academia; however a reference process model that can assist practitioners to apply these performance measures is missing. In this paper we draw upon the evaluation approach proposed by the EU funded project CEES and propose a reference process model that captures re-usable practices for e-government evaluation from a citizens’ perspective. The novelty of the proposed approach is that using DEA for evaluating the e-services the assessment results in suggestions for strategic improvement of the e-services.EU FP7 Marie Curie People Project “CEES - Citizen oriented Evaluation of E-Government Systems” (reference IAPP-2008-230658

Invariances and Equations of Motion in Double Field Theory

We investigate the full set of equations of motion in double field theory and discuss their O(D,D) symmetry and gauge transformation properties. We obtain a Ricci-like tensor, its associated Bianchi identities, and relate our results to those with a generalized metric formulation.Comment: 24 page