MAMOT: hidden Markov modeling tool.

Hidden Markov models (HMMs) are probabilistic models that are well adapted to many tasks in bioinformatics, for example, for predicting the occurrence of specific motifs in biological sequences. MAMOT is a command-line program for Unix-like operating systems, including MacOS X, that we developed to allow scientists to apply HMMs more easily in their research. One can define the architecture and initial parameters of the model in a text file and then use MAMOT for parameter optimization on example data, decoding (like predicting motif occurrence in sequences) and the production of stochastic sequences generated according to the probabilistic model. Two examples for which models are provided are coiled-coil domains in protein sequences and protein binding sites in DNA. A wealth of useful features include the use of pseudocounts, state tying and fixing of selected parameters in learning, and the inclusion of prior probabilities in decoding. AVAILABILITY: MAMOT is implemented in C++, and is distributed under the GNU General Public Licence (GPL). The software, documentation, and example model files can be found at http://bcf.isb-sib.ch/mamot

AssociationViewer: a scalable and integrated software tool for visualization of large-scale variation data in genomic context.

SUMMARY: We present a tool designed for visualization of large-scale genetic and genomic data exemplified by results from genome-wide association studies. This software provides an integrated framework to facilitate the interpretation of SNP association studies in genomic context. Gene annotations can be retrieved from Ensembl, linkage disequilibrium data downloaded from HapMap and custom data imported in BED or WIG format. AssociationViewer integrates functionalities that enable the aggregation or intersection of data tracks. It implements an efficient cache system and allows the display of several, very large-scale genomic datasets. AVAILABILITY: The Java code for AssociationViewer is distributed under the GNU General Public Licence and has been tested on Microsoft Windows XP, MacOSX and GNU/Linux operating systems. It is available from the SourceForge repository. This also includes Java webstart, documentation and example datafiles.

Three essays on major trends in a slow clockspeed industry : the case of industrial automation

The motivation for this research initiated from the abrupt rise and fall of minicomputers which were initially used both for industrial automation and business applications due to their significantly lower cost than their predecessors, the mainframes. Later industrial automation developed its own vertically integrated hardware and software to address the application needs of uninterrupted operations, real-time control and resilience to harsh environmental conditions. This has led to the creation of an independent industry, namely industrial automation used in PLC, DCS, SCADA and robot control systems. This industry employs today over 200'000 people in a profitable slow clockspeed context in contrast to the two mainstream computing industries of information technology (IT) focused on business applications and telecommunications focused on communications networks and hand-held devices. Already in 1990s it was foreseen that IT and communication would merge into one Information and communication industry (ICT). The fundamental question of the thesis is: Could industrial automation leverage a common technology platform with the newly formed ICT industry? Computer systems dominated by complex instruction set computers (CISC) were challenged during 1990s with higher performance reduced instruction set computers (RISC). RISC started to evolve parallel to the constant advancement of Moore's law. These developments created the high performance and low energy consumption System-on-Chip architecture (SoC). Unlike to the CISC processors RISC processor architecture is a separate industry from the RISC chip manufacturing industry. It also has several hardware independent software platforms consisting of integrated operating system, development environment, user interface and application market which enables customers to have more choices due to hardware independent real time capable software applications. An architecture disruption merged and the smartphone and tablet market were formed with new rules and new key players in the ICT industry. Today there are more RISC computer systems running Linux (or other Unix variants) than any other computer system. The astonishing rise of SoC based technologies and related software platforms in smartphones created in unit terms the largest installed base ever seen in the history of computers and is now being further extended by tablets. An underlying additional element of this transition is the increasing role of open source technologies both in software and hardware. This has driven the microprocessor based personal computer industry with few dominating closed operating system platforms into a steep decline. A significant factor in this process has been the separation of processor architecture and processor chip production and operating systems and application development platforms merger into integrated software platforms with proprietary application markets. Furthermore the pay-by-click marketing has changed the way applications development is compensated: Three essays on major trends in a slow clockspeed industry: The case of industrial automation 2014 freeware, ad based or licensed - all at a lower price and used by a wider customer base than ever before. Moreover, the concept of software maintenance contract is very remote in the app world. However, as a slow clockspeed industry, industrial automation has remained intact during the disruptions based on SoC and related software platforms in the ICT industries. Industrial automation incumbents continue to supply systems based on vertically integrated systems consisting of proprietary software and proprietary mainly microprocessor based hardware. They enjoy admirable profitability levels on a very narrow customer base due to strong technology-enabled customer lock-in and customers' high risk leverage as their production is dependent on fault-free operation of the industrial automation systems. When will this balance of power be disrupted? The thesis suggests how industrial automation could join the mainstream ICT industry and create an information, communication and automation (ICAT) industry. Lately the Internet of Things (loT) and weightless networks, a new standard leveraging frequency channels earlier occupied by TV broadcasting, have gradually started to change the rigid world of Machine to Machine (M2M) interaction. It is foreseeable that enough momentum will be created that the industrial automation market will in due course face an architecture disruption empowered by these new trends. This thesis examines the current state of industrial automation subject to the competition between the incumbents firstly through a research on cost competitiveness efforts in captive outsourcing of engineering, research and development and secondly researching process re- engineering in the case of complex system global software support. Thirdly we investigate the industry actors', namely customers, incumbents and newcomers, views on the future direction of industrial automation and conclude with our assessments of the possible routes industrial automation could advance taking into account the looming rise of the Internet of Things (loT) and weightless networks. Industrial automation is an industry dominated by a handful of global players each of them focusing on maintaining their own proprietary solutions. The rise of de facto standards like IBM PC, Unix and Linux and SoC leveraged by IBM, Compaq, Dell, HP, ARM, Apple, Google, Samsung and others have created new markets of personal computers, smartphone and tablets and will eventually also impact industrial automation through game changing commoditization and related control point and business model changes. This trend will inevitably continue, but the transition to a commoditized industrial automation will not happen in the near future.

Computer-assisted cup placement techniques in total hip arthroplasty improve accuracy of placement.

Malposition of the acetabular component during hip arthroplasty increases the occurrence of impingement, reduces range of motion, and increases the risk of dislocation and long-term wear. To prevent malpositioned hip implants, an increasing number of computer-assisted orthopaedic systems have been described, but their accuracy is not well established. The purpose of this study was to determine the reproducibility and accuracy of conventional versus computer-assisted techniques for positioning the acetabular component in total hip arthroplasty. Using a lateral approach, 150 cups were placed by 10 surgeons in 10 identical plastic pelvis models (freehand, with a mechanical guide, using computer assistance). Conditions for cup implantations were made to mimic the operating room situation. Preoperative planning was done from a computed tomography scan. The accuracy of cup abduction and anteversion was assessed with an electromagnetic system. Freehand placement revealed a mean accuracy of cup anteversion and abduction of 10 degrees and 3.5 degrees, respectively (maximum error, 35 degrees). With the cup positioner, these angles measured 8 degrees and 4 degrees (maximum error, 29.8 degrees), respectively, and using computer assistance, 1.5 degrees and 2.5 degrees degrees (maximum error, 8 degrees), respectively. Computer-assisted cup placement was an accurate and reproducible technique for total hip arthroplasty. It was more accurate than traditional methods of cup positioning.

Benchmarking therapeutic drug monitoring software: A review of available computer tools

Therapeutic drug monitoring (TDM) aims to optimize treatments by individualizing dosage regimens based on the measurement of blood concentrations. Dosage individualization to maintain concentrations within a target range requires pharmacokinetic and clinical capabilities. Bayesian calculations currently represent the gold standard TDM approach but require computation assistance. In recent decades computer programs have been developed to assist clinicians in this assignment. The aim of this survey was to assess and compare computer tools designed to support TDM clinical activities. The literature and the Internet were searched to identify software. All programs were tested on personal computers. Each program was scored against a standardized grid covering pharmacokinetic relevance, user friendliness, computing aspects, interfacing and storage. A weighting factor was applied to each criterion of the grid to account for its relative importance. To assess the robustness of the software, six representative clinical vignettes were processed through each of them. Altogether, 12 software tools were identified, tested and ranked, representing a comprehensive review of the available software. Numbers of drugs handled by the software vary widely (from two to 180), and eight programs offer users the possibility of adding new drug models based on population pharmacokinetic analyses. Bayesian computation to predict dosage adaptation from blood concentration (a posteriori adjustment) is performed by ten tools, while nine are also able to propose a priori dosage regimens, based only on individual patient covariates such as age, sex and bodyweight. Among those applying Bayesian calculation, MM-USC*PACK© uses the non-parametric approach. The top two programs emerging from this benchmark were MwPharm© and TCIWorks. Most other programs evaluated had good potential while being less sophisticated or less user friendly. Programs vary in complexity and might not fit all healthcare settings. Each software tool must therefore be regarded with respect to the individual needs of hospitals or clinicians. Programs should be easy and fast for routine activities, including for non-experienced users. Computer-assisted TDM is gaining growing interest and should further improve, especially in terms of information system interfacing, user friendliness, data storage capability and report generation.

Computer-assisted placement technique in hip resurfacing arthroplasty: improvement in accuracy?

Freehand positioning of the femoral drill guide is difficult during hip resurfacing and the surgeon is often unsure of the implant position achieved peroperatively. The purpose of this study was to find out whether, by using a navigation system, acetabular and femoral component positioning could be made easier and more precise. Eighteen patients operated on by the same surgeon were matched by sex, age, BMI, diagnosis and ASA score (nine patients with computer assistance, nine with the regular ancillary). Pre-operative planning was done on standard AP and axial radiographs with CT scan views for the computer-assisted operations. The final position of implants was evaluated by the same radiographs for all patients. The follow-up was at least 1 year. No difference between both groups in terms of femoral component position was observed (p > 0.05). There was also no difference in femoral notching. A trend for a better cup position was observed for the navigated hips, especially for cup anteversion. There was no additional operating time for the navigated hips. Hip navigation for resurfacing surgery may allow improved visualisation and hip implant positioning, but its advantage probably will be more obvious with mini-incisions than with regular incision surgery.

An image quality comparison of standard and dual-side read CR systems for pediatric radiology.

An objective analysis of image quality parameters was performed for a computed radiography (CR) system using both standard single-side and prototype dual-side read plates. The pre-sampled modulation transfer function (MTF), noise power spectrum (NPS), and detective quantum efficiency (DQE) for the systems were determined at three different beam qualities representative of pediatric chest radiography, at an entrance detector air kerma of 5 microGy. The NPS and DQE measurements were realized under clinically relevant x-ray spectra for pediatric radiology, including x-ray scatter radiations. Compared to the standard single-side read system, the MTF for the dual-side read system is reduced, but this is offset by a significant decrease in image noise, resulting in a marked increase in DQE (+40%) in the low spatial frequency range. Thus, for the same image quality, the new technology permits the CR system to be used at a reduced dose level.

A hierarchical approach to model parameter optimization for developmental systems.

In the context of Systems Biology, computer simulations of gene regulatory networks provide a powerful tool to validate hypotheses and to explore possible system behaviors. Nevertheless, modeling a system poses some challenges of its own: especially the step of model calibration is often difficult due to insufficient data. For example when considering developmental systems, mostly qualitative data describing the developmental trajectory is available while common calibration techniques rely on high-resolution quantitative data. Focusing on the calibration of differential equation models for developmental systems, this study investigates different approaches to utilize the available data to overcome these difficulties. More specifically, the fact that developmental processes are hierarchically organized is exploited to increase convergence rates of the calibration process as well as to save computation time. Using a gene regulatory network model for stem cell homeostasis in Arabidopsis thaliana the performance of the different investigated approaches is evaluated, documenting considerable gains provided by the proposed hierarchical approach.

Computer-generated reminders delivered on paper to healthcare professionals; effects on professional practice and health care outcomes.

BACKGROUND: Clinical practice does not always reflect best practice and evidence, partly because of unconscious acts of omission, information overload, or inaccessible information. Reminders may help clinicians overcome these problems by prompting the doctor to recall information that they already know or would be expected to know and by providing information or guidance in a more accessible and relevant format, at a particularly appropriate time. OBJECTIVES: To evaluate the effects of reminders automatically generated through a computerized system and delivered on paper to healthcare professionals on processes of care (related to healthcare professionals' practice) and outcomes of care (related to patients' health condition). SEARCH METHODS: For this update the EPOC Trials Search Co-ordinator searched the following databases between June 11-19, 2012: The Cochrane Central Register of Controlled Trials (CENTRAL) and Cochrane Library (Economics, Methods, and Health Technology Assessment sections), Issue 6, 2012; MEDLINE, OVID (1946- ), Daily Update, and In-process; EMBASE, Ovid (1947- ); CINAHL, EbscoHost (1980- ); EPOC Specialised Register, Reference Manager, and INSPEC, Engineering Village. The authors reviewed reference lists of related reviews and studies.  SELECTION CRITERIA: We included individual or cluster-randomized controlled trials (RCTs) and non-randomized controlled trials (NRCTs) that evaluated the impact of computer-generated reminders delivered on paper to healthcare professionals on processes and/or outcomes of care. DATA COLLECTION AND ANALYSIS: Review authors working in pairs independently screened studies for eligibility and abstracted data. We contacted authors to obtain important missing information for studies that were published within the last 10 years. For each study, we extracted the primary outcome when it was defined or calculated the median effect size across all reported outcomes. We then calculated the median absolute improvement and interquartile range (IQR) in process adherence across included studies using the primary outcome or median outcome as representative outcome. MAIN RESULTS: In the 32 included studies, computer-generated reminders delivered on paper to healthcare professionals achieved moderate improvement in professional practices, with a median improvement of processes of care of 7.0% (IQR: 3.9% to 16.4%). Implementing reminders alone improved care by 11.2% (IQR 6.5% to 19.6%) compared with usual care, while implementing reminders in addition to another intervention improved care by 4.0% only (IQR 3.0% to 6.0%) compared with the other intervention. The quality of evidence for these comparisons was rated as moderate according to the GRADE approach. Two reminder features were associated with larger effect sizes: providing space on the reminder for provider to enter a response (median 13.7% versus 4.3% for no response, P value = 0.01) and providing an explanation of the content or advice on the reminder (median 12.0% versus 4.2% for no explanation, P value = 0.02). Median improvement in processes of care also differed according to the behaviour the reminder targeted: for instance, reminders to vaccinate improved processes of care by 13.1% (IQR 12.2% to 20.7%) compared with other targeted behaviours. In the only study that had sufficient power to detect a clinically significant effect on outcomes of care, reminders were not associated with significant improvements. AUTHORS' CONCLUSIONS: There is moderate quality evidence that computer-generated reminders delivered on paper to healthcare professionals achieve moderate improvement in process of care. Two characteristics emerged as significant predictors of improvement: providing space on the reminder for a response from the clinician and providing an explanation of the reminder's content or advice. The heterogeneity of the reminder interventions included in this review also suggests that reminders can improve care in various settings under various conditions.

Influence of cassette type on the DQE of CR systems.

In our recent paper by Monnin et al. [Med. Phys. 33, 411-420 (2006)], an objective analysis of the relative performance of a computed radiography (CR) system using both standard single-side (ST-VI) and prototype dual-side read (ST-BD) plates was reported. The presampled modulation transfer function (MTF), noise power spectrum (NPS), and detective quantum efficiency (DQE) for the systems were determined at three different beam qualities representative of paediatric chest radiography, at an entrance detector air kerma of 5 microGy. Experiments demonstrated that, compared to the standard single-side read system, the MTF for the dual-side read system was slightly reduced, but a significant decrease in image noise resulted in a marked increase in DQE (+40%) in the low spatial frequency range. However, the DQE improvement for the ST-BD plate decreased with increasing spatial frequency, and, at spatial frequencies above 2.2 mm(-1), the DQE of the dual-side read system was lower than that of the single-side one.

Apprentissage automatique de la morphologie : le cas des structures racine-schème

RÉSUMÉ Cette thèse porte sur le développement de méthodes algorithmiques pour découvrir automatiquement la structure morphologique des mots d'un corpus. On considère en particulier le cas des langues s'approchant du type introflexionnel, comme l'arabe ou l'hébreu. La tradition linguistique décrit la morphologie de ces langues en termes d'unités discontinues : les racines consonantiques et les schèmes vocaliques. Ce genre de structure constitue un défi pour les systèmes actuels d'apprentissage automatique, qui opèrent généralement avec des unités continues. La stratégie adoptée ici consiste à traiter le problème comme une séquence de deux sous-problèmes. Le premier est d'ordre phonologique : il s'agit de diviser les symboles (phonèmes, lettres) du corpus en deux groupes correspondant autant que possible aux consonnes et voyelles phonétiques. Le second est de nature morphologique et repose sur les résultats du premier : il s'agit d'établir l'inventaire des racines et schèmes du corpus et de déterminer leurs règles de combinaison. On examine la portée et les limites d'une approche basée sur deux hypothèses : (i) la distinction entre consonnes et voyelles peut être inférée sur la base de leur tendance à alterner dans la chaîne parlée; (ii) les racines et les schèmes peuvent être identifiés respectivement aux séquences de consonnes et voyelles découvertes précédemment. L'algorithme proposé utilise une méthode purement distributionnelle pour partitionner les symboles du corpus. Puis il applique des principes analogiques pour identifier un ensemble de candidats sérieux au titre de racine ou de schème, et pour élargir progressivement cet ensemble. Cette extension est soumise à une procédure d'évaluation basée sur le principe de la longueur de description minimale, dans- l'esprit de LINGUISTICA (Goldsmith, 2001). L'algorithme est implémenté sous la forme d'un programme informatique nommé ARABICA, et évalué sur un corpus de noms arabes, du point de vue de sa capacité à décrire le système du pluriel. Cette étude montre que des structures linguistiques complexes peuvent être découvertes en ne faisant qu'un minimum d'hypothèses a priori sur les phénomènes considérés. Elle illustre la synergie possible entre des mécanismes d'apprentissage portant sur des niveaux de description linguistique distincts, et cherche à déterminer quand et pourquoi cette coopération échoue. Elle conclut que la tension entre l'universalité de la distinction consonnes-voyelles et la spécificité de la structuration racine-schème est cruciale pour expliquer les forces et les faiblesses d'une telle approche. ABSTRACT This dissertation is concerned with the development of algorithmic methods for the unsupervised learning of natural language morphology, using a symbolically transcribed wordlist. It focuses on the case of languages approaching the introflectional type, such as Arabic or Hebrew. The morphology of such languages is traditionally described in terms of discontinuous units: consonantal roots and vocalic patterns. Inferring this kind of structure is a challenging task for current unsupervised learning systems, which generally operate with continuous units. In this study, the problem of learning root-and-pattern morphology is divided into a phonological and a morphological subproblem. The phonological component of the analysis seeks to partition the symbols of a corpus (phonemes, letters) into two subsets that correspond well with the phonetic definition of consonants and vowels; building around this result, the morphological component attempts to establish the list of roots and patterns in the corpus, and to infer the rules that govern their combinations. We assess the extent to which this can be done on the basis of two hypotheses: (i) the distinction between consonants and vowels can be learned by observing their tendency to alternate in speech; (ii) roots and patterns can be identified as sequences of the previously discovered consonants and vowels respectively. The proposed algorithm uses a purely distributional method for partitioning symbols. Then it applies analogical principles to identify a preliminary set of reliable roots and patterns, and gradually enlarge it. This extension process is guided by an evaluation procedure based on the minimum description length principle, in line with the approach to morphological learning embodied in LINGUISTICA (Goldsmith, 2001). The algorithm is implemented as a computer program named ARABICA; it is evaluated with regard to its ability to account for the system of plural formation in a corpus of Arabic nouns. This thesis shows that complex linguistic structures can be discovered without recourse to a rich set of a priori hypotheses about the phenomena under consideration. It illustrates the possible synergy between learning mechanisms operating at distinct levels of linguistic description, and attempts to determine where and why such a cooperation fails. It concludes that the tension between the universality of the consonant-vowel distinction and the specificity of root-and-pattern structure is crucial for understanding the advantages and weaknesses of this approach.

A comparison of the performance of modern screen-film and digital mammography systems.

This work compares the detector performance and image quality of the new Kodak Min-R EV mammography screen-film system with the Fuji CR Profect detector and with other current mammography screen-film systems from Agfa, Fuji and Kodak. Basic image quality parameters (MTF, NPS, NEQ and DQE) were evaluated for a 28 kV Mo/Mo (HVL = 0.646 mm Al) beam using different mAs exposure settings. Compared with other screen-film systems, the new Kodak Min-R EV detector has the highest contrast and a low intrinsic noise level, giving better NEQ and DQE results, especially at high optical density. Thus, the properties of the new mammography film approach those of a fine mammography detector, especially at low frequency range. Screen-film systems provide the best resolution. The presampling MTF of the digital detector has a value of 15% at the Nyquist frequency and, due to the spread size of the laser beam, the use of a smaller pixel size would not permit a significant improvement of the detector resolution. The dual collection reading technology increases significantly the low frequency DQE of the Fuji CR system that can at present compete with the most efficient mammography screen-film systems.

A Small World Perspective on Urban Systems

The theory of small-world networks as initiated by Watts and Strogatz (1998) has drawn new insights in spatial analysis as well as systems theory. The theoryâeuro?s concepts and methods are particularly relevant to geography, where spatial interaction is mainstream and where interactions can be described and studied using large numbers of exchanges or similarity matrices. Networks are organized through direct links or by indirect paths, inducing topological proximities that simultaneously involve spatial, social, cultural or organizational dimensions. Network synergies build over similarities and are fed by complementarities between or inside cities, with the two effects potentially amplifying each other according to the âeurooepreferential attachmentâeuro hypothesis that has been explored in a number of different scientific fields (Barabási, Albert 1999; Barabási A-L 2002; Newman M, Watts D, Barabàsi A-L). In fact, according to Barabási and Albert (1999), the high level of hierarchy observed in âeurooescale-free networksâeuro results from âeurooepreferential attachmentâeuro, which characterizes the development of networks: new connections appear preferentially close to nodes that already have the largest number of connections because in this way, the improvement in the network accessibility of the new connection will likely be greater. However, at the same time, network regions gathering dense and numerous weak links (Granovetter, 1985) or network entities acting as bridges between several components (Burt 2005) offer a higher capacity for urban communities to benefit from opportunities and create future synergies. Several methodologies have been suggested to identify such denser and more coherent regions (also called communities or clusters) in terms of links (Watts, Strogatz 1998; Watts 1999; Barabási, Albert 1999; Barabási 2002; Auber 2003; Newman 2006). These communities not only possess a high level of dependency among their member entities but also show a low level of âeurooevulnerabilityâeuro, allowing for numerous redundancies (Burt 2000; Burt 2005). The SPANGEO project 2005âeuro"2008 (SPAtial Networks in GEOgraphy), gathering a team of geographers and computer scientists, has included empirical studies to survey concepts and measures developed in other related fields, such as physics, sociology and communication science. The relevancy and potential interpretation of weighted or non-weighted measures on edges and nodes were examined and analyzed at different scales (intra-urban, inter-urban or both). New classification and clustering schemes based on the relative local density of subgraphs were developed. The present article describes how these notions and methods contribute on a conceptual level, in terms of measures, delineations, explanatory analyses and visualization of geographical phenomena.

The establishment of communication systems depends on the scale of competition

How communication systems emerge and remain stable is an important question in both cognitive science and evolutionary biology. For communication to arise, not only must individuals cooperate by signaling reliable information, but they must also coordinate and perpetuate signals. Most studies on the emergence of communication in humans typically consider scenarios where individuals implicitly share the same interests. Likewise, most studies on human cooperation consider scenarios where shared conventions of signals and meanings cannot be developed de novo. Here, we combined both approaches with an economic experiment where participants could develop a common language, but under different conditions fostering or hindering cooperation. Participants endeavored to acquire a resource through a learning task in a computer-based environment. After this task, participants had the option to transmit a signal (a color) to a fellow group member, who would subsequently play the same learning task. We varied the way participants competed with each other (either global scale or local scale) and the cost of transmitting a signal (either costly or noncostly) and tracked the way in which signals were used as communication among players. Under global competition, players signaled more often and more consistently, scored higher individual payoffs, and established shared associations of signals and meanings. In addition, costly signals were also more likely to be used under global competition; whereas under local competition, fewer signals were sent and no effective communication system was developed. Our results demonstrate that communication involves both a coordination and a cooperative dilemma and show the importance of studying language evolution under different conditions influencing human cooperation.