A Canonical Genetic Algorithm for Blind Inversion of Linear Channels

It is well known the relationship between source separation and blind deconvolution: If a filtered version of an unknown i.i.d. signal is observed, temporal independence between samples can be used to retrieve the original signal, in the same manner as spatial independence is used for source separation. In this paper we propose the use of a Genetic Algorithm (GA) to blindly invert linear channels. The use of GA is justified in the case of small number of samples, where other gradient-like methods fails because of poor estimation of statistics.

GWAS of 126,559 individuals identifies genetic variants associated with educational attainment.

A genome-wide association study (GWAS) of educational attainment was conducted in a discovery sample of 101,069 individuals and a replication sample of 25,490. Three independent single-nucleotide polymorphisms (SNPs) are genome-wide significant (rs9320913, rs11584700, rs4851266), and all three replicate. Estimated effects sizes are small (coefficient of determination R(2) ≈ 0.02%), approximately 1 month of schooling per allele. A linear polygenic score from all measured SNPs accounts for ≈2% of the variance in both educational attainment and cognitive function. Genes in the region of the loci have previously been associated with health, cognitive, and central nervous system phenotypes, and bioinformatics analyses suggest the involvement of the anterior caudate nucleus. These findings provide promising candidate SNPs for follow-up work, and our effect size estimates can anchor power analyses in social-science genetics.

Typing less common ovarian tumors: A training tool based on a pattern-based algorithm applied to a set of 20 virtual slides.

Context: Ovarian tumors (OT) typing is a competency expected from pathologists, with significant clinical implications. OT however come in numerous different types, some rather rare, with the consequence of few opportunities for practice in some departments. Aim: Our aim was to design a tool for pathologists to train in less common OT typing. Method and Results: Representative slides of 20 less common OT were scanned (Nano Zoomer Digital Hamamatsu®) and the diagnostic algorithm proposed by Young and Scully applied to each case (Young RH and Scully RE, Seminars in Diagnostic Pathology 2001, 18: 161-235) to include: recognition of morphological pattern(s); shortlisting of differential diagnosis; proposition of relevant immunohistochemical markers. The next steps of this project will be: evaluation of the tool in several post-graduate training centers in Europe and Québec; improvement of its design based on evaluation results; diffusion to a larger public. Discussion: In clinical medicine, solving many cases is recognized as of utmost importance for a novice to become an expert. This project relies on the virtual slides technology to provide pathologists with a learning tool aimed at increasing their skills in OT typing. After due evaluation, this model might be extended to other uncommon tumors.

Audit report on the Office of Treasurer of State, Iowa Educational Savings Plan Trust (Trust) for the year ended June 30, 2015

Audit report on the Office of Treasurer of State, Iowa Educational Savings Plan Trust (Trust) for the year ended June 30, 2015

A hybrid algorithm combining metaheuristic with Monte Carlo simulation for solving the Stochastic Flow Shop problem

In this paper, a hybrid simulation-based algorithm is proposed for the StochasticFlow Shop Problem. The main idea of the methodology is to transform the stochastic problem into a deterministic problem and then apply simulation to the latter. In order to achieve this goal, we rely on Monte Carlo Simulation and an adapted version of a deterministic heuristic. This approach aims to provide flexibility and simplicity due to the fact that it is not constrained by any previous assumption and relies in well-tested heuristics.

EADock : design of a new molecular docking algorithm and some of its applications

3 Summary 3. 1 English The pharmaceutical industry has been facing several challenges during the last years, and the optimization of their drug discovery pipeline is believed to be the only viable solution. High-throughput techniques do participate actively to this optimization, especially when complemented by computational approaches aiming at rationalizing the enormous amount of information that they can produce. In siiico techniques, such as virtual screening or rational drug design, are now routinely used to guide drug discovery. Both heavily rely on the prediction of the molecular interaction (docking) occurring between drug-like molecules and a therapeutically relevant target. Several softwares are available to this end, but despite the very promising picture drawn in most benchmarks, they still hold several hidden weaknesses. As pointed out in several recent reviews, the docking problem is far from being solved, and there is now a need for methods able to identify binding modes with a high accuracy, which is essential to reliably compute the binding free energy of the ligand. This quantity is directly linked to its affinity and can be related to its biological activity. Accurate docking algorithms are thus critical for both the discovery and the rational optimization of new drugs. In this thesis, a new docking software aiming at this goal is presented, EADock. It uses a hybrid evolutionary algorithm with two fitness functions, in combination with a sophisticated management of the diversity. EADock is interfaced with .the CHARMM package for energy calculations and coordinate handling. A validation was carried out on 37 crystallized protein-ligand complexes featuring 11 different proteins. The search space was defined as a sphere of 15 R around the center of mass of the ligand position in the crystal structure, and conversely to other benchmarks, our algorithms was fed with optimized ligand positions up to 10 A root mean square deviation 2MSD) from the crystal structure. This validation illustrates the efficiency of our sampling heuristic, as correct binding modes, defined by a RMSD to the crystal structure lower than 2 A, were identified and ranked first for 68% of the complexes. The success rate increases to 78% when considering the five best-ranked clusters, and 92% when all clusters present in the last generation are taken into account. Most failures in this benchmark could be explained by the presence of crystal contacts in the experimental structure. EADock has been used to understand molecular interactions involved in the regulation of the Na,K ATPase, and in the activation of the nuclear hormone peroxisome proliferatoractivated receptors a (PPARa). It also helped to understand the action of common pollutants (phthalates) on PPARy, and the impact of biotransformations of the anticancer drug Imatinib (Gleevec®) on its binding mode to the Bcr-Abl tyrosine kinase. Finally, a fragment-based rational drug design approach using EADock was developed, and led to the successful design of new peptidic ligands for the a5ß1 integrin, and for the human PPARa. In both cases, the designed peptides presented activities comparable to that of well-established ligands such as the anticancer drug Cilengitide and Wy14,643, respectively. 3.2 French Les récentes difficultés de l'industrie pharmaceutique ne semblent pouvoir se résoudre que par l'optimisation de leur processus de développement de médicaments. Cette dernière implique de plus en plus. de techniques dites "haut-débit", particulièrement efficaces lorsqu'elles sont couplées aux outils informatiques permettant de gérer la masse de données produite. Désormais, les approches in silico telles que le criblage virtuel ou la conception rationnelle de nouvelles molécules sont utilisées couramment. Toutes deux reposent sur la capacité à prédire les détails de l'interaction moléculaire entre une molécule ressemblant à un principe actif (PA) et une protéine cible ayant un intérêt thérapeutique. Les comparatifs de logiciels s'attaquant à cette prédiction sont flatteurs, mais plusieurs problèmes subsistent. La littérature récente tend à remettre en cause leur fiabilité, affirmant l'émergence .d'un besoin pour des approches plus précises du mode d'interaction. Cette précision est essentielle au calcul de l'énergie libre de liaison, qui est directement liée à l'affinité du PA potentiel pour la protéine cible, et indirectement liée à son activité biologique. Une prédiction précise est d'une importance toute particulière pour la découverte et l'optimisation de nouvelles molécules actives. Cette thèse présente un nouveau logiciel, EADock, mettant en avant une telle précision. Cet algorithme évolutionnaire hybride utilise deux pressions de sélections, combinées à une gestion de la diversité sophistiquée. EADock repose sur CHARMM pour les calculs d'énergie et la gestion des coordonnées atomiques. Sa validation a été effectuée sur 37 complexes protéine-ligand cristallisés, incluant 11 protéines différentes. L'espace de recherche a été étendu à une sphère de 151 de rayon autour du centre de masse du ligand cristallisé, et contrairement aux comparatifs habituels, l'algorithme est parti de solutions optimisées présentant un RMSD jusqu'à 10 R par rapport à la structure cristalline. Cette validation a permis de mettre en évidence l'efficacité de notre heuristique de recherche car des modes d'interactions présentant un RMSD inférieur à 2 R par rapport à la structure cristalline ont été classés premier pour 68% des complexes. Lorsque les cinq meilleures solutions sont prises en compte, le taux de succès grimpe à 78%, et 92% lorsque la totalité de la dernière génération est prise en compte. La plupart des erreurs de prédiction sont imputables à la présence de contacts cristallins. Depuis, EADock a été utilisé pour comprendre les mécanismes moléculaires impliqués dans la régulation de la Na,K ATPase et dans l'activation du peroxisome proliferatoractivated receptor a (PPARa). Il a également permis de décrire l'interaction de polluants couramment rencontrés sur PPARy, ainsi que l'influence de la métabolisation de l'Imatinib (PA anticancéreux) sur la fixation à la kinase Bcr-Abl. Une approche basée sur la prédiction des interactions de fragments moléculaires avec protéine cible est également proposée. Elle a permis la découverte de nouveaux ligands peptidiques de PPARa et de l'intégrine a5ß1. Dans les deux cas, l'activité de ces nouveaux peptides est comparable à celles de ligands bien établis, comme le Wy14,643 pour le premier, et le Cilengitide (PA anticancéreux) pour la seconde.

A hybrid algorithm combining metaheuristic with Monte Carlo simulation for solving the Stochastic Flow Shop problem

In this paper, a hybrid simulation-based algorithm is proposed for the StochasticFlow Shop Problem. The main idea of the methodology is to transform the stochastic problem into a deterministic problem and then apply simulation to the latter. In order to achieve this goal, we rely on Monte Carlo Simulation and an adapted version of a deterministic heuristic. This approach aims to provide flexibility and simplicity due to the fact that it is not constrained by any previous assumption and relies in well-tested heuristics.

Educational achievement in Swiss childhood cancer survivors compared with the general population.

BACKGROUND: The objective of this study was to describe educational achievements of childhood cancer survivors in Switzerland compared with the general population. In particular, the authors investigated educational problems during childhood, final educational achievement in adulthood, and its predictors. METHODS: Childhood cancer survivors who were aged <16 years at diagnosis from 1976 to 2003 who had survived for ≥5 years and were currently ages 20 to 40 years received a postal questionnaire during 2007 to 2009. Controls were respondents of the Swiss Health Survey ages 20 to 40 years. Educational achievement included compulsory schooling, vocational training, upper secondary schooling, and university degree. The analysis was weighted to optimize comparability of the populations. The authors analyzed the association between demographic and clinical predictors and educational achievement using multivariable logistic regression. Subgroup analyses focused on survivors aged ≥27 years. RESULTS: One-third of survivors encountered educational problems during schooling (30% repeated 1 year, and 35% received supportive tutoring). In the total sample, more survivors than controls achieved compulsory schooling only (8.7% vs 5.2%) and fewer acquired a university degree (7.3% vs 11%), but more survivors than controls achieved an upper secondary education (36.1 vs 24.1%). In those aged ≥27 years, differences in compulsory schooling and university education largely disappeared. In survivors and controls, sex, nationality, language region, and migration background were strong predictors of achievement. Survivors of central nervous system tumors or those who had a relapse had poorer outcomes (P < .05). CONCLUSIONS: Childhood cancer survivors encountered problems during schooling and completed professional education with some delay. However, with the exception of patients who had central nervous system tumors and those who experienced a relapse, the final educational achievement in survivors of child cancer was comparable to that of the general population.

Educational Opportunity through The Advocate

This communication tool comes from the Office of the State Long-Term Care Ombudsman to long-term care facilities administrators and directors. The Office's objective is to share information regarding various topics of long term care.

Management of Pharyngeal Fistulas After Anterior Cervical Spine Surgery: A Treatment Algorithm for Severe Complications.

STUDY DESIGN:: Retrospective database- query to identify all anterior spinal approaches. OBJECTIVES:: To assess all patients with pharyngo-cutaneous fistulas after anterior cervical spine surgery. SUMMARY OF BACKGROUND DATA:: Patients treated in University of Heidelberg Spine Medical Center, Spinal Cord Injury Unit and Department of Otolaryngology (Germany), between 2005 and 2011 with the diagnosis of pharyngo-cutaneous fistulas. METHODS:: We conducted a retrospective study on 5 patients between 2005 and 2011 with PCF after ACSS, their therapy management and outcome according to radiologic data and patient charts. RESULTS:: Upon presentation 4 patients were paraplegic. 2 had PCF arising from one piriform sinus, two patients from the posterior pharyngeal wall and piriform sinus combined and one patient only from the posterior pharyngeal wall. 2 had previous unsuccessful surgical repair elsewhere and 1 had prior radiation therapy. In 3 patients speech and swallowing could be completely restored, 2 patients died. Both were paraplegic. The patients needed an average of 2-3 procedures for complete functional recovery consisting of primary closure with various vascularised regional flaps and refining laser procedures supplemented with negative pressure wound therapy where needed. CONCLUSION:: Based on our experience we are able to provide a treatment algorithm that indicates that chronic as opposed to acute fistulas require a primary surgical closure combined with a vascularised flap that should be accompanied by the immediate application of a negative pressure wound therapy. We also conclude that particularly in paraplegic patients suffering this complication the risk for a fatal outcome is substantial.

Learning in the working place: the educational potential of a multihead microscope in pathology postgraduate training.

Training future pathologists is an important mission of many hospital anatomic pathology departments. Apprenticeship-a process in which learning and teaching tightly intertwine with daily work, is one of the main educational methods in use in postgraduate medical training. However, patient care, including pathological diagnosis, often comes first, diagnostic priorities prevailing over educational ones. Recognition of the unique educational opportunities is a prerequisite for enhancing the postgraduate learning experience. The aim of this paper is to draw attention of senior pathologists with a role as supervisor in postgraduate training on the potential educational value of a multihead microscope, a common setting in pathology departments. After reporting on an informal observation of senior and junior pathologists' meetings around the multihead microscope in our department, we review the literature on current theories of learning to provide support to the high potential educational value of these meetings for postgraduate training in pathology. We also draw from the literature on learner-centered teaching some recommendations to better support learning in this particular context. Finally, we propose clues for further studies and effective instruction during meetings around a multihead microscope.

Approche éducationnelle des patients à risque cardiovasculaire [Educational approach to patients with cardiovascular risk factors]

In the outpatient setting, the long-term management of cardiovascular risk factors is essential to prevent recurrent cardiovascular disease. Recent studies have shown an additional benefit of beginning cardiovascular secondary prevention during the hospital stay. Early, in-hospital initiation of proven beneficial medications, such as aspirin or blood lipid lowering drugs and therapeutic lifestyle change counseling, improves patients' long-term outcome, as long as there is continuity of care in the outpatient setting. A recent hospitalization may be a teachable moment, when patients are more likely to modify their health behaviors. The continuity of care between in-hospital medicine and the outpatient setting helps patients in the long-term management of their cardiovascular disease.

Safety of a new algorithm for the management of childhood illness (Almanach) to improve quality of care and rational use of drugs

Introduction New evidence from randomized controlled and etiology of fever studies, the availability of reliable RDT for malaria, and novel technologies call for revision of the IMCI strategy. We developed a new algorithm based on (i) a systematic review of published studies assessing the safety and appropriateness of RDT and antibiotic prescription, (ii) results from a clinical and microbiological investigation of febrile children aged <5 years, (iii) international expert IMCI opinions. The aim of this study was to assess the safety of the new algorithm among patients in urban and rural areas of Tanzania.Materials and Methods The design was a controlled noninferiority study. Enrolled children aged 2-59 months with any illness were managed either by a study clinician using the new Almanach algorithm (two intervention health facilities), or clinicians using standard practice, including RDT (two control HF). At day 7 and day 14, all patients were reassessed. Patients who were ill in between or not cured at day 14 were followed until recovery or death. Primary outcome was rate of complications, secondary outcome rate of antibiotic prescriptions.Results 1062 children were recruited. Main diagnoses were URTI 26%, pneumonia 19% and gastroenteritis (9.4%). 98% (531/541) were cured at D14 in the Almanach arm and 99.6% (519/521) in controls. Rate of secondary hospitalization was 0.2% in each. One death occurred in controls. None of the complications was due to withdrawal of antibiotics or antimalarials at day 0. Rate of antibiotic use was 19% in the Almanach arm and 84% in controls.Conclusion Evidence suggests that the new algorithm, primarily aimed at the rational use of drugs, is as safe as standard practice and leads to a drastic reduction of antibiotic use. The Almanach is currently being tested for clinician adherence to proposed procedures when used on paper or a mobile phone

Technology educational affordance: Bridging the gap between patterns of interaction and technology usage

Peer-reviewed

Open Educational Resources: an opportunity for virtual learning institutions

The Universitat Oberta de Catalunya (UOC, Open University of Catalonia) is involved inseveral research projects and educational activities related to the use of Open Educational Resources (OER). Some of the discussed issues in the concept of OER are research issues which are being tackled in two EC projects (OLCOS and SELF). Besides the research part, the UOC aims at developing a virtual centre for analysing and promoting the concept of OERin Europe in the sector of Higher and Further Education. The objectives are to makeinformation and learning services available to provide university management staff,eLearning support centres, faculty and learners with practical information required to create, share and re-use such interoperable digital content, tools and licensing schemes. In the realisation of these objectives, the main activities are the following: to provide organisationaland individual e-learning end-users with orientation; to develop perspectives and useful recommendations in the form of a medium-term Roadmap 2010 for OER in Higher and Further Education in Europe; to offer practical information and support services about how to create, share and re-use open educational content by means of tutorials, guidelines, best practices, and specimen of exemplary open e-learning content; to establish a larger group ofcommitted experts throughout Europe and other continents who not only share theirexpertise but also steer networking, workshops, and clustering efforts; and to foster and support a community of practice in open e-learning content know-how and experiences.