Semi-parametric estimation of the hazard function in a model with covariate measurement error

We consider a model where the failure hazard function, conditional on a covariate $Z$ is given by $R(t,\theta^0|Z)=\eta\_{\gamma^0}(t)f\_{\beta^0}(Z)$, with $\theta^0=(\beta^0,\gamma^0)^\top\in \mathbb{R}^{m+p}$. The baseline hazard function $\eta\_{\gamma^0}$ and relative risk $f\_{\beta^0}$ belong both to parametric families. The covariate $Z$ is measured through the error model $U=Z+\epsilon$ where $\epsilon$ is independent from $Z$, with known density $f\_\epsilon$. We observe a $n$-sample $(X\_i, D\_i, U\_i)$, $i=1,...,n$, where $X\_i$ is the minimum between the failure time and the censoring time, and $D\_i$ is the censoring indicator. We aim at estimating $\theta^0$ in presence of the unknown density $g$. Our estimation procedure based on least squares criterion provide two estimators. The first one minimizes an estimation of the least squares criterion where $g$ is estimated by density deconvolution. Its rate depends on the smoothnesses of $f\_\epsilon$ and $f\_\beta(z)$ as a function of $z$,. We derive sufficient conditions that ensure the $\sqrt{n}$-consistency. The second estimator is constructed under conditions ensuring that the least squares criterion can be directly estimated with the parametric rate. These estimators, deeply studied through examples are in particular $\sqrt{n}$-consistent and asymptotically Gaussian in the Cox model and in the excess risk model, whatever is $f\_\epsilon$

Estimation of the hazard function in a semiparametric model with covariate measurement error

International audienceWe consider a failure hazard function, conditional on a time-independent covariate , given by . The baseline hazard function and the relative risk both belong to parametric families with . The covariate has an unknown density and is measured with an error through an additive error model where is a random variable, independent from , with known density . We observe a -sample , = 1, ..., , where is the minimum between the failure time and the censoring time, and is the censoring indicator. Using least square criterion and deconvolution methods, we propose a consistent estimator of using the observations , = 1, ..., .
We give an upper bound for its risk which depends on the smoothness properties of and as a function of , and we derive sufficient conditions for the -consistency. We give detailed examples considering various type of relative risks and various types of error density . In particular, in the Cox model and in the excess risk model, the estimator of is -consistent and asymptotically Gaussian regardless of the form of

Feasibility of a randomized controlled trial of functional strength training for people between six months and five years after stroke: FeSTivaLS trial

Background: Functional Strength Training (FST) could enhance recovery late after stroke. The aim of this study was to evaluate the feasibility of a subsequent fully powered, randomized controlled trial. Methods: The study was designed as a randomized, observer-blind trial. Both interventions were provided for up to one hour a day, four days a week, for six weeks. Evaluation points were before randomization (baseline), after six weeks intervention (outcome), and six weeks thereafter (follow-up). The study took place in participants’ own homes. Participants (n = 52) were a mean of 24.4 months after stroke with a mean age of 68.3 years with 67.3% male. All had difficulty using their paretic upper (UL) and lower limb (LL). Participants were allocated to FST-UL or FST-LL by an independent randomization service. The outcome measures were recruitment rate, attrition rate, practicality of recruitment strategies, occurrence of adverse reactions, acceptability of FST, and estimation of sample size for a subsequent trial. Primary clinical efficacy outcomes were the Action Research Arm Test (ARAT) and the Functional Ambulation Categories (FAC). Analysis was conducted using descriptive statistics and thematic analysis of participants’ views of FST. A power calculation used estimates of clinical efficacy variance to estimate sample size for a subsequent trial. Results: The screening process identified 1,127 stroke survivors of whom 52 (4.6%) were recruited. The recruitment rate was higher for referral from community therapists than for systematic identification of people discharged from an acute stroke unit. The attrition rate was 15.5% at the outcome and follow-up time-points. None of the participants experienced an adverse reaction. The participants who remained in the study at outcome had received 68% of the total possible amount of therapy. Participants reported that their experience of FST provided a sense of purpose and involvement and increased their confidence in performing activities. The power calculation provides estimation that 150 participants in each group will be required for a subsequent clinical trial. Conclusions: This study found that a subsequent clinical trial was feasible with modifications to the recruitment strategy to be used

Can 3D synthesized views be reliably assessed through usual subjective and objective evaluation protocols?

International audienceThis paper addresses the problem of evaluating virtual view synthesized images in the multi-view video context. As a matter of fact, view synthesis brings new types of distortion. The question refers to the ability of the traditional used objective metrics to assess synthesized views quality, considering the new types of artifacts. The experiments conducted to determine their reliability consist in assessing seven different view synthesis algorithms. Subjective and objective measurements have been performed. Results show that the most commonly used objective metrics can be far from human judgment depending on the artifact to deal with

Perceived quality of DIBR-based synthesized views

International audienceThis paper considers the reliability of usual assessment methods when evaluating virtual synthesized views in the multi-view video context. Virtual views are generated from Depth Image Based Rendering (DIBR) algorithms. Because DIBR algorithms involve geometric transformations, new types of artifacts come up. The question regards the ability of commonly used methods to deal with such artifacts. This paper investigates how correlated usual metrics are to human judgment. The experiments consist in assessing seven different view synthesis algorithms by subjective and objective methods. Three different 3D video sequences are used in the tests. Resulting virtual synthesized sequences are assessed through objective metrics and subjective protocols. Results show that usual objective metrics can fail assessing synthesized views, in the sense of human judgment

Forschungsexzellenz in der Architektur: Standards zur Bewertung und Förderung der Forschung in den Architekturfachbereichen der Technischen Universitäten in Deutschland (TU9)

Vor dem Hintergrund großer gesellschaftlicher Herausforderungen ist die Profession und akademische Forschungsdisziplin Architektur aufgerufen, eine wesentliche Rolle im ökologi-schen Umbau des Bausektors und für eine nachhaltige Entwicklung lebenswerter gebauter Umwelten einzunehmen. Es besteht dabei großer Bedarf an grundlegender Forschung und an Innovation, die interdisziplinäre Zusammenarbeit und gesellschaftliche Wirkung im Einklang mit den Zielen für nachhaltige Entwicklung (SDGs) stärken können. Dieser Artikel zielt auf eine aggregierte Grundlage - vorderhand für die Architektur- fachbereiche der Technischen Universitäten (TU9) -, um innovative Forschungsleistungen in der Architektur fachbezogen und evidenzbasiert beurteilen zu können und um die Qualität und Exzellenz der Forschung in der Disziplin zu fördern. Ausgehend von der Analyse aktueller internationaler wissenschaftli-cher Debatten zu Forschung in der Architektur, erarbeitet die Studie Evidenz für Bewertungs-standards durch einen Vergleich von Praktiken in anderen großen europäischen Ländern und prominenten deutschen Förderorganisationen. Auf diese Weise können die gemeinsamen Herausforderungen der TU9-Architekturfachbereiche bei der Förderung von Forschung, für die allgemeine strategische Entwicklung und für das Argumentieren von Forschungsstärken innerhalb und außerhalb ihrer Universitäten auf einer soliden Bewertung aufgebaut werden. Die im Artikel dafür vorgeschlagenen Standards sind qualitative Peer-Review-Verfahren, in-formiert durch fachspezifische Aktivitätsindikatoren (activity indicators) und aufbauend auf einer Qualifizierung der für die Architektur charakteristischen großen Bandbreite an For-schungsoutputs (wie Ausstellungen, Performances, materielle/digitale Artefakte und Designs) und Publikationspraktiken. Die in der Fachkultur angelegte Ausrichtung auf kreative, experi-mentelle und kooperative Innovationsprozesse auch mit außeruniversitären Akteuren sowie die Fokussierung auf gesellschaftliche Herausforderungen und Kultur legen nahe, sowohl wissenschaftliche Qualität als auch gesellschaftlichen Impact als Kategorien in der Evaluie-rung anzusprechen. Darüber hinaus wird in dem Artikel argumentiert, dass zur Steigerung der Forschungsexzellenz in der Architektur verbesserte nationale und europäische Förder-schemen erforderlich sind. Angepasste Bewertungen und spezielle Programme für die Archi-tektur, die eine Brücke zwischen Ingenieurwesen, Design und Kunst schlagen, müssen mit der Förderung der Grundlagenforschung verbunden werden. Der Artikel fordert, dass innova-tive Forschungsbereiche in der Architektur als problemorientierte Grundlagenforschung zu betrachten sind, die im deutschen akademischen Umfeld noch nicht positioniert, strategisch entwickelt und angemessen evaluiert worden sind. Problemorientierte Grundlagenforschung in der Architektur erreicht Innovation durch die methodische Verbindung von erkenntnisorien-tierter, transferfähiger und praxisbezogener Forschung. In diesem Zusammenhang fordert der Beitrag auch eine Neujustierung der bestehenden Fächersystematik in der Forschungs-förderung. Der Artikel soll auch als Statement in der Diskussion für eine Reform der For-schungsbewertung in Europa dienen, die die Europäische Kommission 2021 angestoßen hat

Reactivity of neodymium carriers in deep sea sediments: Implications for boundary exchange and paleoceanography

The dissolved neodymium (Nd) isotopic distribution in the deep oceans is determined by continental weathering inputs, water mass advection, and boundary exchange between particulate and dissolved fractions. Reconstructions of past Nd isotopic variability may therefore provide evidence on temporal changes in continental weathering inputs and/or ocean circulation patterns over a range of timescales. However, such an approach is limited by uncertainty in the mechanisms and importance of the boundary exchange process, and the challenge in reliably recovering past seawater Nd isotopic composition (εNd) from deep sea sediments. This study addresses these questions by investigating the processes involved in particulate–solution interactions and their impact on Nd isotopes. A better understanding of boundary exchange also has wider implications for the oceanic cycling and budgets of other particle-reactive elements. Sequential acid-reductive leaching experiments at pH ∼2–5 on deep sea sediments from the western Indian Ocean enable us to investigate natural boundary exchange processes over a timescale appropriate to laboratory experiments. We provide evidence that both the dissolution of solid phases and exchange processes influence the εNd of leachates, which suggests that both processes may contribute to boundary exchange. We use major element and rare earth element (REE) data to investigate the pools of Nd that are accessed and demonstrate that sediment leachate εNd values cannot always be explained by admixture between an authigenic component and the bulk detrital component. For example, in core WIND 24B, acid-reductive leaching generates εNd values between −11 and −6 as a function of solution/solid ratios and leaching times, whereas the authigenic components have εNd ≈ −11 and the bulk detrital component has εNd ≈ −15. We infer that leaching in the Mascarene Basin accesses authigenic components and a minor radiogenic volcanic component that is more reactive than Madagascan-derived clays. The preferential mobilisation of such a minor component demonstrates that the Nd released by boundary exchange could often have a significantly different εNd composition than the bulk detrital sediment. These experiments further demonstrate certain limitations on the use of acid-reductive leaching to extract the εNd composition of the authigenic fraction of bulk deep sea sediments. For example, the detrital component may contain a reactive fraction which is also acid-extractible, while the incongruent nature of this dissolution suggests that it is often inappropriate to use the bulk detrital sediment elemental chemistry and/or εNd composition when assessing possible detrital contamination of leachates. Based on the highly systematic controls observed, and evidence from REE patterns on the phases extracted, we suggest two approaches that lead to the most reliable extraction of the authigenic εNd component and good agreement with foraminiferal-based approaches; either (i) leaching of sediments without a prior decarbonation step, or (ii) the use of short leaching times and low solution/solid ratios throughout

Predicate learning in neural systems:Using oscillations to discover latent structure

Humans learn to represent complex structures (e.g. natural language, music, mathematics) from experience with their environments. Often such structures are latent, hidden, or not encoded in statistics about sensory representations alone. Accounts of human cognition have long emphasized the importance of structured representations, yet the majority of contemporary neural networks do not learn structure from experience. Here, we describe one way that structured, functionally symbolic representations can be instantiated in an artificial neural network. Then, we describe how such latent structures (viz. predicates) can be learned from experience with unstructured data. Our approach exploits two principles from psychology and neuroscience: comparison of representations, and the naturally occurring dynamic properties of distributed computing across neuronal assemblies (viz. neural oscillations). We discuss how the ability to learn predicates from experience, to represent information compositionally, and to extrapolate knowledge to unseen data is core to understanding and modeling the most complex human behaviors (e.g. relational reasoning, analogy, language processing, game play)

Trends in measles incidence and measles vaccination coverage in Nigeria, 2008-2018

INTRODUCTION: All WHO regions have set measles elimination objective for 2020. To address the specific needs of achieving measles elimination, Nigeria is using a strategy focusing on improving vaccination coverage with the first routine dose of (monovalent) measles (MCV1) at 9 months, providing measles vaccine through supplemental immunization activities (children 9-59 months), and intensified measles case-based surveillance system. METHODS: We reviewed measles immunization coverage from population-based surveys conducted in 2010, 2013 and 2017-18. Additionally, we analyzed measles case-based surveillance reports from 2008-2018 to determine annual, regional and age-specific incidence rates. FINDINGS: Survey results indicated low MCV1 coverage (54.0% in 2018); with lower coverage in the North (mean 45.5%). Of the 153,097 confirmed cases reported over the studied period, 85.5% (130,871) were from the North. Moreover, 70.8% (108,310) of the confirmed cases were unvaccinated. Annual measles incidence varied from a high of 320.39 per 1,000,000 population in 2013 to a low of 9.80 per 1,000,000 in 2009. The incidence rate is higher among the 9-11 months (524.0 per million) and 12-59 months (376.0 per million). Between 2008 and 2018, the incidence rate had showed geographical variation, with higher incidence in the North (70.6 per million) compare to the South (17.8 per million). CONCLUSION: The aim of this study was to provide a descriptive analysis of measles vaccine coverage and incidence in Nigeria from 2008 to 2018 to assess country progress towards measles elimination. Although the total numbers of confirmed measles cases had decreased over the time period, measles routine coverage remains sub-optimal, and the incidence rates are critically high. The high burden of measles in the North highlight the need for region-specific interventions. The measles program relies heavily on polio resources. As the polio program winds down, strong commitments will be required to achieve elimination goals

Dystrophinopathy patients with non-contiguous molecular alterations: diagnosis and characterization of the genetic mechanisms involved

Introduction: Dystrophinopathies are neuromuscular X-linked recessive diseases caused by DMD mutations. Molecular alterations in this gene are large deletions/duplications in 80% of cases and small mutations in the remaining. Several authors reported the occurrence of non-contiguous rearrangements within the same DMD allele, with frequencies up to 4%. The present work aims to characterize the incidence of complex rearrangements in an Argentinian dystrophinopathy cohort and unravel the causing molecular mechanisms.Materials and Methods: We analyzed 437 boys with clinical diagnosis of Dystrophinopathy. The following techniques were implemented: MLPA, WES, WGS, PCR-Sanger Sequencing, CGH Array and HUMARA assay. In 2 cases, breakpoints were precisely determined, so we performed a bioinformatic screening of microhomologies, interspersed repeats, secondary structures and recombinogenic motifs 50pb surrounding each breakpoint. Results: We detected 6 patients carrying complex rearrangements in DMD: 2 deletions-duplications, 3 non-contiguous duplications and 1 large deletion plus a 20pb insertion. These accounted for 1.4% of our cohort. In a deletion-duplication case, familial segregation and bioinformatics analysis suggested that the duplication was the first mutagenic event caused by Fork Stalling and Template Switching (FoSTeS), while the deletion occurred secondly by Non-homologous end joining. Furthermore, bioinformatic screening of the deletion plus insertion propose that the deletion was due to Microhomology-mediated end joining, while the insertion arose by FoSTeS. Conclusions: Our findings widen the understanding of the molecular events that may take place in DMD and characterize the occurrence of complex rearrangements in our dystrophinopathy cohort.This study was supported by PTC Therapeutics and University of Buenos Aires.Fil: Luce, Leonela Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Genética y Biología Molecular; ArgentinaFil: Carcione, María Micaela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Genética y Biología Molecular; ArgentinaFil: Mazzanti, Chiara. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Genética y Biología Molecular; ArgentinaFil: Szijan, Irena. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Genética y Biología Molecular; ArgentinaFil: Menazzi, Sebastian. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Francipane, Liliana. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Nevado, Julian. No especifíca;Fil: Lapunzina, Pablo. No especifíca;Fil: Rossetti, Liliana Carmen. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Radic, Claudia Pamela. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Abelleyro, Miguel Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: de Brasi, Carlos Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Giliberto, Florencia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Genética y Biología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina53rd European Society of Human Genetics ConferenceViennaAlemaniaWiener Medizinische AkademieEuropean Society of Human Genetic