Identification of independent association signals and putative functional variants for breast cancer risk through fine-scale mapping of the 12p11 locus

BACKGROUND: Multiple recent genome-wide association studies (GWAS) have identified a single nucleotide polymorphism (SNP), rs10771399, at 12p11 that is associated with breast cancer risk. METHOD: We performed a fine-scale mapping study of a 700 kb region including 441 genotyped and more than 1300 imputed genetic variants in 48,155 cases and 43,612 controls of European descent, 6269 cases and 6624 controls of East Asian descent and 1116 cases and 932 controls of African descent in the Breast Cancer Association Consortium (BCAC; http://bcac.ccge.medschl.cam.ac.uk/ ), and in 15,252 BRCA1 mutation carriers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Stepwise regression analyses were performed to identify independent association signals. Data from the Encyclopedia of DNA Elements project (ENCODE) and the Cancer Genome Atlas (TCGA) were used for functional annotation. RESULTS: Analysis of data from European descendants found evidence for four independent association signals at 12p11, represented by rs7297051 (odds ratio (OR) = 1.09, 95 % confidence interval (CI) = 1.06-1.12; P = 3 × 10(-9)), rs805510 (OR = 1.08, 95 % CI = 1.04-1.12, P = 2 × 10(-5)), and rs1871152 (OR = 1.04, 95 % CI = 1.02-1.06; P = 2 × 10(-4)) identified in the general populations, and rs113824616 (P = 7 × 10(-5)) identified in the meta-analysis of BCAC ER-negative cases and BRCA1 mutation carriers. SNPs rs7297051, rs805510 and rs113824616 were also associated with breast cancer risk at P < 0.05 in East Asians, but none of the associations were statistically significant in African descendants. Multiple candidate functional variants are located in putative enhancer sequences. Chromatin interaction data suggested that PTHLH was the likely target gene of these enhancers. Of the six variants with the strongest evidence of potential functionality, rs11049453 was statistically significantly associated with the expression of PTHLH and its nearby gene CCDC91 at P < 0.05. CONCLUSION: This study identified four independent association signals at 12p11 and revealed potentially functional variants, providing additional insights into the underlying biological mechanism(s) for the association observed between variants at 12p11 and breast cancer risk

Unraveling networked learning initiatives: an analytic framework

Networked learning happens naturally within the social systems of which we are all part. However, in certain circumstances individuals may want to actively take initiative to initiate interaction with others they are not yet regularly in exchange with. This may be the case when external influences and societal changes require innovation of existing practices. This paper proposes a framework with relevant dimensions providing insight into precipitated characteristics of designed as well as ‘fostered or grown’ networked learning initiatives. Networked learning initiatives are characterized as “goal-directed, interest-, or needs based activities of a group of (at least three) individuals that initiate interaction across the boundaries of their regular social systems”. The proposed framework is based on two existing research traditions, namely 'networked learning' and 'learning networks', comparing, integrating and building upon knowledge from both perspectives. We uncover some interesting differences between definitions, but also similarities in the way they describe what ‘networked’ means and how learning is conceptualized. We think it is productive to combine both research perspectives, since they both study the process of learning in networks extensively, albeit from different points of view, and their combination can provide valuable insights in networked learning initiatives. We uncover important features of networked learning initiatives, characterize actors and connections of which they are comprised and conditions which facilitate and support them. The resulting framework could be used both for analytic purposes and (partly) as a design framework. In this framework it is acknowledged that not all successful networks have the same characteristics: there is no standard ‘constellation’ of people, roles, rules, tools and artefacts, although there are indications that some network structures work better than others. Interactions of individuals can only be designed and fostered till a certain degree: the type of network and its ‘growth’ (e.g. in terms of the quantity of people involved, or the quality and relevance of co-created concepts, ideas, artefacts and solutions to its ‘inhabitants’) is in the hand of the people involved. Therefore, the framework consists of dimensions on a sliding scale. It introduces a structured and analytic way to look at the precipitation of networked learning initiatives: learning networks. Successive research on the application of this framework and feedback from the networked learning community is needed to further validate it’s usability and value to both research as well as practice.

Unraveling networked learning initiatives: an analytic framework

Networked learning happens naturally within the social systems of which we are all part. However, in certain circumstances individuals may want to actively take initiative to initiate interaction with others they are not yet regularly in exchange with. This may be the case when external influences and societal changes require innovation of existing practices. This paper proposes a framework with relevant dimensions providing insight into precipitated characteristics of designed as well as ‘fostered or grown’ networked learning initiatives. Networked learning initiatives are characterized as “goal-directed, interest-, or needs based activities of a group of (at least three) individuals that initiate interaction across the boundaries of their regular social systems”. The proposed framework is based on two existing research traditions, namely 'networked learning' and 'learning networks', comparing, integrating and building upon knowledge from both perspectives. We uncover some interesting differences between definitions, but also similarities in the way they describe what ‘networked’ means and how learning is conceptualized. We think it is productive to combine both research perspectives, since they both study the process of learning in networks extensively, albeit from different points of view, and their combination can provide valuable insights in networked learning initiatives. We uncover important features of networked learning initiatives, characterize actors and connections of which they are comprised and conditions which facilitate and support them. The resulting framework could be used both for analytic purposes and (partly) as a design framework. In this framework it is acknowledged that not all successful networks have the same characteristics: there is no standard ‘constellation’ of people, roles, rules, tools and artefacts, although there are indications that some network structures work better than others. Interactions of individuals can only be designed and fostered till a certain degree: the type of network and its ‘growth’ (e.g. in terms of the quantity of people involved, or the quality and relevance of co-created concepts, ideas, artefacts and solutions to its ‘inhabitants’) is in the hand of the people involved. Therefore, the framework consists of dimensions on a sliding scale. It introduces a structured and analytic way to look at the precipitation of networked learning initiatives: learning networks. Successive research on the application of this framework and feedback from the networked learning community is needed to further validate it’s usability and value to both research as well as practice.

Back to the failure: an analytic narrative of the De Lorean debacle

There has been a recent identification of a need for a New Business History. This discussion connects with the analytic narrative approach. By following this approach, the study of business history provides important implications for the conduct and institutional design of contemporary industrial policy. The approach also allows us to solve historical puzzles. The failure of the De Lorean Motor Company Limited (DMCL) is one specific puzzle. Journalistic accounts that focus on John De Lorean's alleged personality defects as an explanation for this failure miss the crucial institutional component. Moreover, distortions in the rewards associated with industrial policy, and the fact that the objectives of the institutions implementing the policy were not solely efficiency-based, led to increased opportunities for rent-seeking. Political economy solves the specific puzzle; by considering institutional dimensions, we can also solve the more general puzzle of why activist industrial policy was relatively unsuccessful in Northern Ireland.

Paradigms that guide the models of attention to the health in Brazil: an analytic essay

SILVA, Flávio César Bezerra da ; COSTA, Francisca Marta de Lima; ANDRADE, Hamilton Leandro Pinto de; FREIRE, Lúcia de Fátima; MACIEL, Patrícia Suerda de Oliveira; ENDERS, Bertha Cruz ; MENEZES, Rejane Maria Paiva de. Paradigms that guide the models of attention to the health in Brazil: an analytic essay. Revista de Enfermagem UFPE On Line., Recife, v.3,n.4, p.460-65. out/dez. 2009. Disponível em < http://www.ufpe.br/revistaenfermagem/index.php/revista/search/results >.

Production of Gaseous Tracer I2 from the Sodiumiodide Salt

Found in the nature in form different, the iodine has been used in diverse works in the area of the industry and health. The iodine is very unstable and volatile in the ambient temperature and the I2 is one of the diverse gaseous forms found. In this work was developed methodology for production of gaseous tracer from the sodium iodide (NaI) 0,1 M marked with 123I. The synthesis was processed with in chlorine acid (HCl) 1M and sodium iodate salt (NaIO3). The production of gas I2 initially was carried through in unit of glass with the inert material and the purpose was to study the kinetic of reaction. The synthesis occurs in the reaction bottle and the produced gas is stored in the collect bottle that contains a starch solution (5 g/100 mL water). To determine the efficiency of production of gas I2, analytic tests had been carried through, where the consumption of iodide ions of the bottle of reaction is measured. The optimization of production of the gaseous tracer was studied varying parameters as: concentration of iodide and iodate, concentration of acid and temperature. Then, the synthesis of the radiotracer was realized in the compact unit, being utilized as main reagent the salt radiated of sodium iodide, Na123I. The transportation of elementary iodine was studied by a scintillation detector NaI (2 x 2)” placed in the reaction bottle. To acquire the data, the detector use a set of electronic modules for the acquisition of signals generated.

Analytic modelling of the galactic fountain in the Milky Way potential

Le galassie a spirale, come la Via Lattea, sono caratterizzate dalla presenza di gas freddo e formazione stellare e vengono perciò chiamate star-forming. Per creare nuove stelle è necessaria una sufficiente riserva di gas, la cui disponibilità governa l’evoluzione della galassia stessa. Finora, non è stato individuato con certezza un meccanismo che possa alimentare la formazione di nuove stelle nelle galassie star-forming. Una delle possibili sorgenti di tale gas è l’alone galattico caldo (corona galattica) il cui raffreddamento e successivo accrescimento possono essere stimolati dal processo di fontana galattica. L’esplosione di supernovae porta nubi di gas freddo in orbita al di sopra del disco stellare; queste nubi raggiungono altezze dell’ordine del kiloparsec, interagendo con la corona di gas caldo. Il moto delle nubi all’interno di un mezzo meno denso comporta l’instaurarsi dell’instabilità di Kelvin-Helmholtz, che ’strappa’ gas dalle nubi e causa la condensazione di materia coronale. Quest’ultima viene quindi accresciuta e, ricadendo sul disco, trasferisce nuovo materiale alla galassia e ne alimenta la formazione stellare. Lo scopo di questa tesi è derivare un modello analitico di fontana galattica che consenta di ottenere una formulazione analitica per il tempo orbitale, cioè il tempo richiesto alle nubi per ricadere sul disco galattico. Infatti, più u tempo le nubi impiegano per attraversare il materiale coronale caldo e ricadere sul disco, più materiale viene accresciuto durante l’orbita. Conoscendo i tempi orbitali sarebbe possibile calcolare il tasso di accrescimento legato al fenomeno di fontana e studiarne l’andamento con il raggio del disco. Questo modello potrebbe rivelarsi utile per lo studio dell’impatto della fontana nell’evoluzione globale del disco galattico e della chimica dell’intera galassia.

A Reliable Downscaling of ECG Signals for the Detection of T wave Heterogeneity Features

In cardiovascular disease the definition and the detection of the ECG parameters related to repolarization dynamics in post MI patients is still a crucial unmet need. In addition, the use of a 3D sensor in the implantable medical devices would be a crucial mean in the assessment or prediction of Heart Failure status, but the inclusion of such feature is limited by hardware and firmware constraints. The aim of this thesis is the definition of a reliable surrogate of the 500 Hz ECG signal to reach the aforementioned objective. To evaluate the worsening of reliability due to sampling frequency reduction on delineation performance, the signals have been consecutively down sampled by a factor 2, 4, 8 thus obtaining the ECG signals sampled at 250, 125 and 62.5 Hz, respectively. The final goal is the feasibility assessment of the detection of the fiducial points in order to translate those parameters into meaningful clinical parameter for Heart Failure prediction, such as T waves intervals heterogeneity and variability of areas under T waves. An experimental setting for data collection on healthy volunteers has been set up at the Bakken Research Center in Maastricht. A 16 – channel ambulatory system, provided by TMSI, has recorded the standard 12 – Leads ECG, two 3D accelerometers and a respiration sensor. The collection platform has been set up by the TMSI property software Polybench, the data analysis of such signals has been performed with Matlab. The main results of this study show that the 125 Hz sampling rate has demonstrated to be a good candidate for a reliable detection of fiducial points. T wave intervals proved to be consistently stable, even at 62.5 Hz. Further studies would be needed to provide a better comparison between sampling at 250 Hz and 125 Hz for areas under the T waves.

Entropy feature extraction of EEG signals for automatic person identification

The use of human brain electroencephalography (EEG) signals for automatic person identi cation has been investigated for a decade. It has been found that the performance of an EEG-based person identication system highly depends on what feature to be extracted from multi-channel EEG signals. Linear methods such as Power Spectral Density and Autoregressive Model have been used to extract EEG features. However these methods assumed that EEG signals are stationary. In fact, EEG signals are complex, non-linear, non-stationary, and random in nature. In addition, other factors such as brain condition or human characteristics may have impacts on the performance, however these factors have not been investigated and evaluated in previous studies. It has been found in the literature that entropy is used to measure the randomness of non-linear time series data. Entropy is also used to measure the level of chaos of braincomputer interface systems. Therefore, this thesis proposes to study the role of entropy in non-linear analysis of EEG signals to discover new features for EEG-based person identi- cation. Five dierent entropy methods including Shannon Entropy, Approximate Entropy, Sample Entropy, Spectral Entropy, and Conditional Entropy have been proposed to extract entropy features that are used to evaluate the performance of EEG-based person identication systems and the impacts of epilepsy, alcohol, age and gender characteristics on these systems. Experiments were performed on the Australian EEG and Alcoholism datasets. Experimental results have shown that, in most cases, the proposed entropy features yield very fast person identication, yet with compatible accuracy because the feature dimension is low. In real life security operation, timely response is critical. The experimental results have also shown that epilepsy, alcohol, age and gender characteristics have impacts on the EEG-based person identication systems.

Using electroencephalography signals to control acoustical processing

Current hearing-assistive technology performs poorly in noisy multi-talker conditions. The goal of this thesis was to establish the feasibility of using EEG to guide acoustic processing in such conditions. To attain this goal, this research developed a model via the constructive research method, relying on literature review. Several approaches have revealed improvements in the performance of hearing-assistive devices under multi-talker conditions, namely beamforming spatial filtering, model-based sparse coding shrinkage, and onset enhancement of the speech signal. Prior research has shown that electroencephalography (EEG) signals contain information that concerns whether the person is actively listening, what the listener is listening to, and where the attended sound source is. This thesis constructed a model for using EEG information to control beamforming, model-based sparse coding shrinkage, and onset enhancement of the speech signal. The purpose of this model is to propose a framework for using EEG signals to control sound processing to select a single talker in a noisy environment containing multiple talkers speaking simultaneously. On a theoretical level, the model showed that EEG can control acoustical processing. An analysis of the model identified a requirement for real-time processing and that the model inherits the computationally intensive properties of acoustical processing, although the model itself is low complexity placing a relatively small load on computational resources. A research priority is to develop a prototype that controls hearing-assistive devices with EEG. This thesis concludes highlighting challenges for future research.

An approach to emotion recognition in single-channel EEG signals: a mother child interaction

In this work, we perform a first approach to emotion recognition from EEG single channel signals extracted in four (4) mother-child dyads experiment in developmental psychology -- Single channel EEG signals are analyzed and processed using several window sizes by performing a statistical analysis over features in the time and frequency domains -- Finally, a neural network obtained an average accuracy rate of 99% of classification in two emotional states such as happiness and sadness

Second-order cyclostationarity-based detection and classification of LTE SC-FDMA signals for cognitive radio

Cognitive radio (CR) was developed for utilizing the spectrum bands efficiently. Spectrum sensing and awareness represent main tasks of a CR, providing the possibility of exploiting the unused bands. In this thesis, we investigate the detection and classification of Long Term Evolution (LTE) single carrier-frequency division multiple access (SC-FDMA) signals, which are used in uplink LTE, with applications to cognitive radio. We explore the second-order cyclostationarity of the LTE SC-FDMA signals, and apply results obtained for the cyclic autocorrelation function to signal detection and classification (in other words, to spectrum sensing and awareness). The proposed detection and classification algorithms provide a very good performance under various channel conditions, with a short observation time and at low signal-to-noise ratios, with reduced complexity. The validity of the proposed algorithms is verified using signals generated and acquired by laboratory instrumentation, and the experimental results show a good match with computer simulation results.