Bayes linear spaces

Linear spaces consisting of σ-finite probability measures and infinite measures (improper priors and likelihood functions) are defined. The commutative group operation, called perturbation, is the updating given by Bayes theorem; the inverse operation is the Radon-Nikodym derivative. Bayes spaces of measures are sets of classes of proportional measures. In this framework, basic notions of mathematical statistics get a simple algebraic interpretation. For example, exponential families appear as affine subspaces with their sufficient statistics as a basis. Bayesian statistics, in particular some well-known properties of conjugated priors and likelihood functions, are revisited and slightly extended

Life designing: A paradigm for career construction in the 21st century

At the beginning of the 21st century, a new social arrangement of work poses a series of questions and challenges to scholars who aim to help people develop their working lives. Given the globalization of career counseling, we decided to address these issues and then to formulate potentially innovative responses in an international forum. We used this approach to avoid the difficulties of creating models and methods in one country and then trying to export them to other countries where they would be adapted for use. This article presents the initial outcome of this collaboration, a counseling model and methods. The life-designing model for career intervention endorses five presuppositions about people and their work lives: contextual possibilities, dynamic processes, non-linear progression, multiple perspectives, and personal patterns. Thinking from these five presuppositions, we have crafted a contextualized model based on the epistemology of social constructionism, particularly recognizing that an individual's knowledge and identity are the product of social interaction and that meaning is co-constructed through discourse. The life-design framework for counseling implements the theories of self-constructing [Guichard, J. (2005). Life-long self-construction. International Journal for Educational and Vocational Guidance, 5, 111-124] and career construction [Savickas, M. L. (2005). The theory and practice of career construction. In S. D. Brown & R. W. Lent (Eds.), Career development and counselling: putting theory and research to work (pp. 42-70). Hoboken, NJ: Wiley] that describe vocational behavior and its development. Thus, the framework is structured to be life-long, holistic, contextual, and preventive.

Effects of sample size on the performance of species distribution models

A wide range of modelling algorithms is used by ecologists, conservation practitioners, and others to predict species ranges from point locality data. Unfortunately, the amount of data available is limited for many taxa and regions, making it essential to quantify the sensitivity of these algorithms to sample size. This is the first study to address this need by rigorously evaluating a broad suite of algorithms with independent presence-absence data from multiple species and regions. We evaluated predictions from 12 algorithms for 46 species (from six different regions of the world) at three sample sizes (100, 30, and 10 records). We used data from natural history collections to run the models, and evaluated the quality of model predictions with area under the receiver operating characteristic curve (AUC). With decreasing sample size, model accuracy decreased and variability increased across species and between models. Novel modelling methods that incorporate both interactions between predictor variables and complex response shapes (i.e. GBM, MARS-INT, BRUTO) performed better than most methods at large sample sizes but not at the smallest sample sizes. Other algorithms were much less sensitive to sample size, including an algorithm based on maximum entropy (MAXENT) that had among the best predictive power across all sample sizes. Relative to other algorithms, a distance metric algorithm (DOMAIN) and a genetic algorithm (OM-GARP) had intermediate performance at the largest sample size and among the best performance at the lowest sample size. No algorithm predicted consistently well with small sample size (n < 30) and this should encourage highly conservative use of predictions based on small sample size and restrict their use to exploratory modelling.

Test automation in Basic Acceptance Testing of S60 platform

Perushyväksymistestaus on oleellinen osa S60 alustan julkaisukandidaatin maturiteetin seurannassa. Perushyväksymistestausta tehdään myös ohjelmiston julkistamiskelpoisuuden varmistamiseksi. Testaustulokset halutaan aina mahdollisimman nopeasti. Lisäksi testaustiimin työmäärä on hiljalleen kasvanut, koska projekteja onenemmän ja korjauksia sisältäviä ja räätälöityjä settejä testataan enemmän. Tässä diplomityössä tutkitaan lyhentäisikö testisetin osan automatisointi testien ajoaikaa ja helpottaisiko se testaajien työtaakkaa. Tarkastelu toteutetaan automatisoimalla osa testisetistä ja kokemuksia esitellään tässä lopputyössä.

Delayed delivery of second twin: a multicentre study of 35 cases.

OBJECTIVE: The aim of this study was to conduct a statistical analysis to determine the outcome of conservative treatment after delivery of a first fetus in multiple pregnancy and thus define new prognostic factors. STUDY DESIGN: Multicentre retrospective study involving 12 centers over a 10-year period. RESULTS: Twenty-eight twin pregnancies and seven triplet pregnancies which were managed conservatively. In twin pregnancies, 79% of the delayed-delivery fetuses survived; only 7% of the first delivered fetuses survived. The mean interval between deliveries was 47 days. No statistical difference was found concerning cerclage, antibiotic therapy, tocolysis and hospitalization. Earlier delivery of the first twin and premature rupture of membranes for the second twin were significantly related to a longer interval between deliveries. CONCLUSION: Delayed delivery in multifetal pregnancies can be successful if there are no contraindications and these pregnancies are managed in a tertiary perinatal center. Publications limited to successful cases have undoubtedly introduced some bias in assessment.

Teknologiat ja toteutustavat palvelukeskeiseen arkkitehtuuriin perustuvassa Internet-pohjaisessajärjestelmässä

Palvelukeskeiseen arkkitehtuuriin perustuvia järjestelmiä voidaan kehittää käyttämällä useita vaihtoehtoisia teknologioita. Toteuttamiseen parhaiten soveltuvia teknologioita ovat erilaiset standardikokoelmat, jotka tukevat useiden toisistaan toteutustavaltaan poikkeavien järjestelmien yhdistämistä käyttämällä standardeihin perustuvia rajapintoja. Täten kyseiset kokoelmat tukevat laajojen, useista erillisistä osista koostuvien palvelujärjestelmien kehittämistä. Tässä työssä selvitetään mikä palvelukeskeinen arkkitehtuuri on sekä millaisia komponentteja ja teknologioita kyseiseen arkkitehtuuriin perustuvan palvelujärjestelmän toteuttamiseen tarvitaan. Tavoitteena on esitellä palvelukeskeinen arkkitehtuuri ja siihen liittyvät teknologiat sekä suunnitella korkealla tasolla kyseisiä teknologioita hyödyntävä integraatioalusta käyttäjien ja useiden palvelun tarjoajien yhdistämiseksi. Työn tuloksena syntyvän teknologiaselvitysraportin selvitysluonteen vuoksi työssä ei suunnitella tarkasti toteutettavaa järjestelmää vaan ainoastaanpohjustetaan järjestelmän suunnittelua sekä esitellään siihen liittyviä arkkitehtuuri- ja toteutusmahdollisuuksia. Internet-pohjainen palvelukeskeiseen arkkitehtuuriin perustuva järjestelmä voi perustua suoriinverkon välisiin yhteyksiin tai vaihtoehtoisesti erityyppisiin välitason sovelluksiin. Välitason sovellukset mahdollistavat niiden tyypistä riippuen järjestelmän erilaisten lisäominaisuuksien toteuttamisen ja tukevat useita yleisimpiä palvelukeskeisiä teknologioita. Työn tuloksena syntyneen teknologiaselvityksen perusteella näistä teknologioista Web-palvelu -arkkitehtuuri ja siihen liittyvät menetelmät soveltuvat parhaiten suunniteltavan järjestelmän rakenneosiksi. Järjestelmän tarkemmat toteutustavat riippuvat myöhemmin määriteltävistä yksityiskohtaisista vaatimuksista sekä valittavasta välitason ohjelmiston toteutuksesta.

Predicting prognosis using molecular profiling in estrogen receptor-positive breast cancer treated with tamoxifen.

Background: Estrogen receptor positive (ER+) breast cancers (BC) are heterogeneous with regard to their clinical behavior and response to therapies. The ER is currently the best predictor of response to the anti-estrogen agent tamoxifen, yet up to 30-40% of ER+ BC will relapse despite tamoxifen treatment. New prognostic biomarkers and further biological understanding of tamoxifen resistance are required. We used gene expression profiling to develop an outcome-based predictor using a training set of 255 ER+ BC samples from women treated with adjuvant tamoxifen monotherapy. We used clusters of highly correlated genes to develop our predictor to facilitate both signature stability and biological interpretation. Independent validation was performed using 362 tamoxifen-treated ER+ BC samples obtained from multiple institutions and treated with tamoxifen only in the adjuvant and metastatic settings.Results: We developed a gene classifier consisting of 181 genes belonging to 13 biological clusters. In the independent set of adjuvantly-treated samples, it was able to define two distinct prognostic groups (HR 2.01 95% CI: 1.29-3.13; p = 0.002). Six of the 13 gene clusters represented pathways involved in cell cycle and proliferation. In 112 metastatic breast cancer patients treated with tamoxifen, one of the classifier components suggesting a cellular inflammatory mechanism was significantly predictive of response.Conclusion: We have developed a gene classifier that can predict clinical outcome in tamoxifen-treated ER+ BC patients. Whilst our study emphasizes the important role of proliferation genes in prognosis, our approach proposes other genes and pathways that may elucidate further mechanisms that influence clinical outcome and prediction of response to tamoxifen.

Structural connectomics in brain diseases.

Imaging the connectome in vivo has become feasible through the integration of several rapidly developing fields of science and engineering, namely magnetic resonance imaging and in particular diffusion MRI on one side, image processing and network theory on the other side. This framework brings in vivo brain imaging closer to the real topology of the brain, contributing to narrow the existing gap between our understanding of brain structural organization on one side and of human behavior and cognition on the other side. Given the seminal technical progresses achieved in the last few years, it may be ready to tackle even greater challenges, namely exploring disease mechanisms. In this review we analyze the current situation from the technical and biological perspectives. First, we critically review the technical solutions proposed in the literature to perform clinical studies. We analyze for each step (i.e. MRI acquisition, network building and network statistical analysis) the advantages and potential limitations. In the second part we review the current literature available on a selected subset of diseases, namely, dementia, schizophrenia, multiple sclerosis and others, and try to extract for each disease the common findings and main differences between reports.

Cultures en contacte a Catalunya

En el actual escenario mundial, interconectado en el circuito de la mundialización cultural, con poblaciones cada vez más heterogéneas a causa de los desplazamientos internos y extracomunitarios, el contacto de civilizaciones provoca tensiones y efectos múltiples y conectados en cadena en el ámbito económico, social, político y cultural. En este sentido, la cuestión que centra los debates es la problemática resultante de la vida, en común o en paralelo, en un mismo territorio, de las culturas que historicamente están ya asentadas con las que van llegando, que son (muy) diferentes. En nuestro estado multinacional, Cataluña tiene unas condiciones óptimas para ser observada como un paradigma, porque forma parte de este circuito mundializado; porque es un punto de llegada de una parte importante de la actual inmigración comunitaria y extracomunitaria; porque, además, tiene ya como bagaje una experiencia, no tan lejana, de recepción de emigrantes culturalmente distantes, de la que se desprenden tendencias interesantes para orientar el presente y consolidar en el futuro el escenario multicultural que ya se empieza a vertebrar.

Konttipaikannuksen toteutus konttitrukkiin

Diplomityössä perehdytään konttipaikannustekniikkaan, historiaan ja useisiin tekniikoihin joilla järjestelmiä voidaan toteuttaa. Huomiota on kiinnitetty erityisesti GPS paikannukseen ja satelliittien hyödyntämiseen merkintälaskussa. Lisäksi huomiota on kiinnitetty eri anturi tyyppeihin joita tullaan tarvitsemaan. Käytännön sovelluksena työssä on toteutettu konttipaikannus järjestelmä konttitrukkiin. Työssä on tarkasteltu eri teknisiä mahdollisuuksia ja niiden yhdistämistä niin, että saadaan toimiva sovellus.

Dynamic single cell measurements of kinase activity by synthetic kinase activity relocation sensors.

BACKGROUND: Mitogen activated protein kinases (MAPK) play an essential role in integrating extra-cellular signals and intra-cellular cues to allow cells to grow, adapt to stresses, or undergo apoptosis. Budding yeast serves as a powerful system to understand the fundamental regulatory mechanisms that allow these pathways to combine multiple signals and deliver an appropriate response. To fully comprehend the variability and dynamics of these signaling cascades, dynamic and quantitative single cell measurements are required. Microscopy is an ideal technique to obtain these data; however, novel assays have to be developed to measure the activity of these cascades. RESULTS: We have generated fluorescent biosensors that allow the real-time measurement of kinase activity at the single cell level. Here, synthetic MAPK substrates were engineered to undergo nuclear-to-cytoplasmic relocation upon phosphorylation of a nuclear localization sequence. Combination of fluorescence microscopy and automated image analysis allows the quantification of the dynamics of kinase activity in hundreds of single cells. A large heterogeneity in the dynamics of MAPK activity between individual cells was measured. The variability in the mating pathway can be accounted for by differences in cell cycle stage, while, in the cell wall integrity pathway, the response to cell wall stress is independent of cell cycle stage. CONCLUSIONS: These synthetic kinase activity relocation sensors allow the quantification of kinase activity in live single cells. The modularity of the architecture of these reporters will allow their application in many other signaling cascades. These measurements will allow to uncover new dynamic behaviour that previously could not be observed in population level measurements.

Protein homology reveals new targets for bioactive small molecules.

MOTIVATION: The functional impact of small molecules is increasingly being assessed in different eukaryotic species through large-scale phenotypic screening initiatives. Identifying the targets of these molecules is crucial to mechanistically understand their function and uncover new therapeutically relevant modes of action. However, despite extensive work carried out in model organisms and human, it is still unclear to what extent one can use information obtained in one species to make predictions in other species. RESULTS: Here, for the first time, we explore and validate at a large scale the use of protein homology relationships to predict the targets of small molecules across different species. Our results show that exploiting target homology can significantly improve the predictions, especially for molecules experimentally tested in other species. Interestingly, when considering separately orthology and paralogy relationships, we observe that mapping small molecule interactions among orthologs improves prediction accuracy, while including paralogs does not improve and even sometimes worsens the prediction accuracy. Overall, our results provide a novel approach to integrate chemical screening results across multiple species and highlight the promises and remaining challenges of using protein homology for small molecule target identification. AVAILABILITY AND IMPLEMENTATION: Homology-based predictions can be tested on our website http://www.swisstargetprediction.ch. CONTACT: david.gfeller@unil.ch or vincent.zoete@isb-sib.ch. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Septic Tenosynovitis of the Hand: Factors Predicting Need for Subsequent Débridement.

BACKGROUND: Treatment of septic hand tenosynovitis is complex, and often requires multiple débridements and prolonged antibiotic therapy. The authors undertook this study to identify factors that might be associated with the need for subsequent débridement (after the initial one) because of persistence or secondary worsening of infection. METHODS: In this retrospective single-center study, the authors included all adult patients who presented to their emergency department from 2007 to 2010 with septic tenosynovitis of the hand. RESULTS: The authors identified 126 adult patients (55 men; median age, 45 years), nine of whom were immunosuppressed. All had community-acquired infection; 34 (27 percent) had a subcutaneous abscess and eight (6 percent) were febrile. All underwent at least one surgical débridement and had concomitant antibiotic therapy (median, 15 days; range, 7 to 82 days). At least one additional surgical intervention was required in 18 cases (median, 1.13 interventions; range, one to five interventions). All but four episodes (97 percent) were cured of infection on the first attempt after a median follow-up of 27 months. By multivariate analysis, only two factors were significantly associated with the outcome "subsequent surgical débridement": abscess (OR, 4.6; 95 percent CI, 1.5 to 14.0) and longer duration of antibiotic therapy (OR, 1.2; 95 percent CI, 1.1 to 1.2). CONCLUSION: In septic tenosynovitis of the hand, the only presenting factor that was statistically predictive of an increased risk of needing a second débridement was the presence of a subcutaneous abscess. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

Explorer les intersections entre la science forensique et la criminologie au travers de la temporalité de trois types d'actions de contrôle social

Our contribution aims to explore some intersections between forensic science and criminology through the notion of time. The two disciplines analyse the vestiges of illicit activities in order to reconstruct and understand the past, and occasionally to prevent future harms. While forensic science study the material and digital traces as signs of criminal activities and repetitions, criminology contributes to the acquisition of knowledge through its analysis of crime, its authors and victims, as well as social (re)actions to harmful behaviours. Exploratory, our contribution proposes a conceptual delimitation of the notion of time considering its importance in the study of criminality and harms. Through examples, we propose a "crimino-forensic" analysis of three types of actions of social control - prevention, investigation and intelligence - through their respective temporality (before, near or during and after the criminal activity or harm). The temporal issues of the different methodologies developed to appreciate the efficiency of these actions are also addressed to highlight the connections between forensic science and criminology. This attempt to classify the relations between different times and actions of social control are discussed through the multiple benefits and challenges carried out by the formalisation of fusing those two sciences. Notre contribution vise à explorer quelques intersections entre la science forensique (ou criminalistique) et la criminologie au travers de la notion de temps. En effet, les deux disciplines ont en commun qu'elles analysent les vestiges du phénomène criminel pour tenter de reconstruire et comprendre le passé et parfois prévenir de futurs incidents. Alors que la science forensique étudie les traces matérielles et numériques comme signe d'activités et de répétitions criminelles, la criminologie contribue à l'avancée des connaissances en ce domaine par son analyse des comportements contraires aux normes, de leurs auteurs et de leurs victimes, ainsi que des (ré)actions sociales à ces comportements. A but exploratoire, notre contribution propose une délimitation conceptuelle de la notion de temps en regard de l'importance que revêtent ses différentes manifestations dans l'étude de la criminalité. A l'appui d'exemples, nous proposons une analyse « crimino-forensique » de trois types d'action de contrôle social - la prévention, l'investigation et le renseignement - en fonction de leur temporalité respective (avant, proche voire pendant et après l'activité criminelle). Les enjeux temporels entourant les différentes stratégies méthodologiques développées pour apprécier l'efficacité de ces actions sont aussi abordés pour mettre en évidence des pistes d'intégration entre la science forensique et la criminologie. Cet essai de classification des relations entre les temps et ces trois actions de contrôle social est discuté sous l'angle des bénéfices, multiples, mais aussi des défis, que pose la formalisation des liens entre ces deux disciplines des sciences criminelles.

A multistep process of cancer associated fibroblasts determination under CSL-p53 control

Stromal fibroblast senescence has been linked to the aging-associated increase of tumors. However, in epithelial cancer, density and proliferation of cancer associated fibroblasts (CAF) are frequently increased, rather than decreased. We previously showed that genetic deletion or down-modulation of the canonical Notch effector CSL/RBP-JK in dermal fibroblasts is sufficient for CAF activation with consequent development of keratinocyte-derived tumors. We show here that CSL silencing induces senescence of primary fibroblasts from dermis, oral mucosa, breast and lung. CSL functions in these cells as direct repressor of multiple senescence- and CAF-effector genes. It also physically interacts with p53, repressing its activity. CSL is down-modulated in stromal fibroblasts of premalignant skin actinic keratosis lesions and squamous cell carcinomas (SCC), while p53 gene expression and function is down-modulated only in the latter, with paracrine influences of incipient cancer cells as a likely culprit. Concomitant loss of CSL and p53 overcomes fibroblast senescence, enhances CAF effector gene expression and promotes stromal and cancer cell expansion. The findings support a CAF activation/stromal co-evolution model under convergent CSL/p53 control of likely clinical relevance.