Estimation with Interval Censored Data in Longitudinal Studies

In biostatistical applications interest often focuses on the estimation of the distribution of a time-until-event variable T. If one observes whether or not T exceeds an observed monitoring time at a random number of monitoring times, then the data structure is called interval censored data. We extend this data structure by allowing the presence of a possibly time-dependent covariate process that is observed until end of follow up. If one only assumes that the censoring mechanism satisfies coarsening at random, then, by the curve of dimensionality, typically no regular estimators will exist. To fight the curse of dimensionality we follow the approach of Robins and Rotnitzky (1992) by modeling parameters of the censoring mechanism. We model the right-censoring mechanism by modeling the hazard of the follow up time, conditional on T and the covariate process. For the monitoring mechanism we avoid modeling the joint distribution of the monitoring times by only modeling a univariate hazard of the pooled monitoring times, conditional on the follow up time, T, and the covariates process, which can be estimated by treating the pooled sample of monitoring times as i.i.d. In particular, it is assumed that the monitoring times and the right-censoring times only depend on T through the observed covariate process. We introduce inverse probability of censoring weighted (IPCW) estimator of the distribution of T and of smooth functionals thereof which are guaranteed to be consistent and asymptotically normal if we have available correctly specified semiparametric models for the two hazards of the censoring process. Furthermore, given such correctly specified models for these hazards of the censoring process, we propose a one-step estimator which will improve on the IPCW estimator if we correctly specify a lower-dimensional working model for the conditional distribution of T, given the covariate process, that remains consistent and asymptotically normal if this latter working model is misspecified. It is shown that the one-step estimator is efficient if each subject is at most monitored once and the working model contains the truth. In general, it is shown that the one-step estimator optimally uses the surrogate information if the working model contains the truth. It is not optimal in using the interval information provided by the current status indicators at the monitoring times, but simulations in Peterson, van der Laan (1997) show that the efficiency loss is small.

Assessing Decision Making Strategies In Construction Management By Using A Schedule-Based Simulation Framework

During the project, managers encounter numerous contingencies and are faced with the challenging task of making decisions that will effectively keep the project on track. This task is very challenging because construction projects are non-prototypical and the processes are irreversible. Therefore, it is critical to apply a methodological approach to develop a few alternative management decision strategies during the planning phase, which can be deployed to manage alternative scenarios resulting from expected and unexpected disruptions in the as-planned schedule. Such a methodology should have the following features but are missing in the existing research: (1) looking at the effects of local decisions on the global project outcomes, (2) studying how a schedule responds to decisions and disruptive events because the risk in a schedule is a function of the decisions made, (3) establishing a method to assess and improve the management decision strategies, and (4) developing project specific decision strategies because each construction project is unique and the lessons from a particular project cannot be easily applied to projects that have different contexts. The objective of this dissertation is to develop a schedule-based simulation framework to design, assess, and improve sequences of decisions for the execution stage. The contribution of this research is the introduction of applying decision strategies to manage a project and the establishment of iterative methodology to continuously assess and improve decision strategies and schedules. The project managers or schedulers can implement the methodology to develop and identify schedules accompanied by suitable decision strategies to manage a project at the planning stage. The developed methodology also lays the foundation for an algorithm towards continuously automatically generating satisfactory schedule and strategies through the construction life of a project. Different from studying isolated daily decisions, the proposed framework introduces the notion of {em decision strategies} to manage construction process. A decision strategy is a sequence of interdependent decisions determined by resource allocation policies such as labor, material, equipment, and space policies. The schedule-based simulation framework consists of two parts, experiment design and result assessment. The core of the experiment design is the establishment of an iterative method to test and improve decision strategies and schedules, which is based on the introduction of decision strategies and the development of a schedule-based simulation testbed. The simulation testbed used is Interactive Construction Decision Making Aid (ICDMA). ICDMA has an emulator to duplicate the construction process that has been previously developed and a random event generator that allows the decision-maker to respond to disruptions in the emulation. It is used to study how the schedule responds to these disruptions and the corresponding decisions made over the duration of the project while accounting for cascading impacts and dependencies between activities. The dissertation is organized into two parts. The first part presents the existing research, identifies the departure points of this work, and develops a schedule-based simulation framework to design, assess, and improve decision strategies. In the second part, the proposed schedule-based simulation framework is applied to investigate specific research problems.

Reporting quality of abstracts of randomized controlled trials published in dental specialty journals

OBJECTIVES A widespread assessment of the reporting of RCT abstracts published in dental journals is lacking. Our aim was to investigate the quality of reporting of abstracts published in leading dental specialty journals using, as a guide, the CONSORT for abstracts checklist. METHODS Electronic and supplementary hand searching were undertaken to identify RCTs published in seven dental specialty journals. The quality of abstract reporting was evaluated using a modified checklist based on the CONSORT for abstracts checklist. Descriptive statistics followed by univariate and multivariate analyses were conducted. RESULTS 228 RCT abstracts were identified. Reporting of interventions, objectives and conclusions within abstracts were adequate. Inadequately reported items included: title, participants, outcomes, random number generation, numbers randomized and effect size estimate. Randomization restrictions, allocation concealment, blinding, numbers analyzed, confidence intervals, intention-to-treat analysis, harms, registration and funding were rarely described. CONCLUSIONS The mean overall reporting quality score was suboptimal at 62.5% (95% CI: 61.9, 63.0). Significantly better abstract reporting was noted in certain specialty journals and in multicenter trials.

Implicit task sequence learning in patients with Parkinson's disease, frontal lesions and amnesia: The critical role of fronto–striatal loops

The purpose of this study was to investigate the role of the fronto–striatal system for implicit task sequence learning. We tested performance of patients with compromised functioning of the fronto–striatal loops, that is, patients with Parkinson's disease and patients with lesions in the ventromedial or dorsolateral prefrontal cortex. We also tested amnesic patients with lesions either to the basal forebrain/orbitofrontal cortex or to thalamic/medio-temporal regions. We used a task sequence learning paradigm involving the presentation of a sequence of categorical binary-choice decision tasks. After several blocks of training, the sequence, hidden in the order of tasks, was replaced by a pseudo-random sequence. Learning (i.e., sensitivity to the ordering) was assessed by measuring whether this change disrupted performance. Although all the patients were able to perform the decision tasks quite easily, those with lesions to the fronto–striatal loops (i.e., patients with Parkinson's disease, with lesions in the ventromedial or dorsolateral prefrontal cortex and those amnesic patients with lesions to the basal forebrain/orbitofrontal cortex) did not show any evidence of implicit task sequence learning. In contrast, those amnesic patients with lesions to thalamic/medio-temporal regions showed intact sequence learning. Together, these results indicate that the integrity of the fronto–striatal system is a prerequisite for implicit task sequence learning.

Suppressing versus releasing a habit: frequency-dependent effects of prefrontal transcranial magnetic stimulation.

When subjects are required to generate a random sequence of numbers they typically produce too many forward and backward 'counts' (e.g. 5-6, 4-3). This counting bias is interpreted as the consequence of an interference by overlearned tendencies to arrange numbers according to their natural order. Inhibition of such well-learned routines is known to rely on frontal lobe functioning. We examined differential effects of slow (1 Hz) and fast (10 Hz) repetitive transcranial magnetic stimulation (rTMS) over the left or right dorsolateral prefrontal cortex (DLPFC) on random number generation (RNG) performance. Eighteen healthy men performed an RNG task. Those subjects stimulated over the left DLPFC showed a frequency-dependent rTMS effect: counting bias was significantly reduced after the 1 Hz stimulation compared with baseline, but significantly exaggerated after the 10 Hz stimulation compared with 1 Hz stimulation. In contrast, the sequences of the subjects stimulated over the right DLPFC showed the well-known excess of counting in all conditions (i.e. baseline, 1 Hz and 10 Hz). These findings confirm the functional importance of specifically the left DLPFC in sequential response production and show, for the first time, that rTMS affects cognitive processing in a frequency-dependent manner.

Modeling the survival of T-cell lymphocytes using compound branching processes

Radiotherapy has been a method of choice in cancer treatment for a number of years. Mathematical modeling is an important tool in studying the survival behavior of any cell as well as its radiosensitivity. One particular cell under investigation is the normal T-cell, the radiosensitivity of which may be indicative to the patient's tolerance to radiation doses.^ The model derived is a compound branching process with a random initial population of T-cells that is assumed to have compound distribution. T-cells in any generation are assumed to double or die at random lengths of time. This population is assumed to undergo a random number of generations within a period of time. The model is then used to obtain an estimate for the survival probability of T-cells for the data under investigation. This estimate is derived iteratively by applying the likelihood principle. Further assessment of the validity of the model is performed by simulating a number of subjects under this model.^ This study shows that there is a great deal of variation in T-cells survival from one individual to another. These variations can be observed under normal conditions as well as under radiotherapy. The findings are in agreement with a recent study and show that genetic diversity plays a role in determining the survival of T-cells. ^

Photovoltaic LiNbO3particles: Applications to Biomedicine/Biophotonics

Recently, a novel method to trap and pattern ensembles of nanoparticles has been proposed and tested. It relies on the photovoltaic (PV) properties of certain ferroelectric crystals such as LiNbO3 [1,2]. These crystals, when suitably doped, develop very high electric fields in response to illumination with light of suitable wavelength. The PV effect lies in the asymmetrical excitation of electrons giving rise to PV currents and associated space-charge fields (photorefractive effect). The field generated in the bulk of the sample propagates to the surrounding medium as evanescent fields. When dielectric or metal nanoparticles are deposited on the surface of the sample the evanescent fields give rise to either electrophoretic or dielectrophoretic forces, depending on the charge state of the particles, that induce the trapping and patterning effects [3,4]. The purpose of this work has been to explore the effects of such PV fields in the biology and biomedical areas. A first work was able to show the necrotic effects induced by such fields on He-La tumour cells grown on the surface of an illuminated iron-doped LiNbO3 crystal [5]. In principle, it is conceived that LiNbO3 nanoparticles may be advantageously used for such biomedical purposes considering the possibility of such nanoparticles being incorporated into the cells. Previous experiments using microparticles have been performed [5] with similar results to those achieved with the substrate. Therefore, the purpose of this work has been to fabricate and characterize the LiNbO3 nanoparticles and assess their necrotic effects when they are incorporated on a culture of tumour cells. Two different preparation methods have been used: 1) mechanical grinding from crystals, and 2) bottom-up sol-gel chemical synthesis from metal-ethoxide precursors. This later method leads to a more uniform size distribution of smaller particles (down to around 50 nm). Fig. 1(a) and 1(b) shows SEM images of the nanoparticles obtained with both method. An ad hoc software taking into account the physical properties of the crystal, particullarly donor and aceptor concentrations has been developped in order to estimate the electric field generated in noparticles. In a first stage simulations of the electric current of nanoparticles, in a conductive media, due to the PV effect have been carried out by MonteCarlo simulations using the Kutharev 1-centre transport model equations [6] . Special attention has been paid to the dependence on particle size and [Fe2+]/[Fe3+]. First results on cubic particles shows large dispersion for small sizes due to the random number of donors and its effective concentration (Fig 2). The necrotic (toxicity) effect of nanoparticles incorporated into a tumour cell culture subjected to 30 min. illumination with a blue LED is shown in Fig.3. For each type of nanoparticle the percent of cell survival in dark and illumination conditions has been plot as a function of the particle dilution factor. Fig. 1a corresponds to mechanical grinding particles whereas 1b and 1c refer to chemically synthesized particles with two oxidation states. The light effect is larger with mechanical grinding nanoparticles, but dark toxicity is also higher. For chemically synthesized nanoparticles dark toxicity is low but only in oxidized samples, where the PV effect is known to be larger, the light effect is appreciable. These preliminary results demonstrate that Fe:LiNbO· nanoparticles have a biological damaging effect on cells, although there are many points that should be clarified and much space for PV nanoparticles optimization. In particular, it appears necessary to determine the fraction of nanoparticles that become incorporated into the cells and the possible existence of threshold size effects. This work has been supported by MINECO under grant MAT2011-28379-C03.

Contexto, criptoanálisis y propuesta de solución de la inscripción de la talla (original) de la Virgen de Candelaria de Tenerife (Canarias, España)

Esta investigación es un ejemplo de simbiosis entre criptoanálisis y desciframiento de lenguas. Es la búsqueda del sentido de una inscripción, un conjunto de casi doscientas letras latinas, en una talla de la Virgen María que estaba en la isla de Tenerife, en la localidad hoy de Candelaria, en las islas Canarias. La imagen desapareció en un temporal en el año 1826. No obstante, es posible lograr una gran certeza sobre qué letras tenía, acudiendo a las fuentes documentales textuales y artísticas. El conocimiento del significado, si lo hubiera, de la inscripción mariana, creemos que no puede lograrse sin la adecuada comprensión del contexto. Esto significa indagar en la historia de la misma talla, que se remonta hasta el siglo XIV o XV, en el estudio de la población autóctona canaria, así como de los pueblos que allí llegaron en sus diferentes momentos históricos. Además, es necesario conocer el redescubrimiento del archipiélago canario y sus procesos de conquista y evangelización. Todos estos datos irán ofreciendo un panorama nuevo y sorprendente para comprender no sólo las letras sino la misma imagen escultórica en madera. A partir de este momento la indagación se moverá en ver si las letras corresponden a alguna lengua posible, lo que nos ha llevado a analizar un amplísimo conjunto de textos lo más cercanos a la época bajo estudio, pertenecientes a alrededor de un centenar de lenguas. Tras el examen lingüístico se ha procedido a un estudio de las posibles formas criptográficas que se hubieran utilizado para generar el texto de la inscripción. Se ofrece un detallado y minucioso elenco de técnicas posibles que pudieran haberse adoptado y se criptoanaliza con exhaustividad las letras de la talla mariana. Al mismo tiempo se ofrece un nuevo marco criptológico de métodos y sistemas más ordenado y completo que el que hasta ahora venía considerándose, en especial desde el surgimiento de la criptografía de clave asimétrica. Continuamos la investigación sopesando la posible generación pseudo-aleatoria del texto, un texto que pudiera no tener sentido alguno. En este momento, y habiendo completado todas las posibilidades e hipótesis, habiéndose negado todas, volvemos a reconsiderar el cuerpo de conjeturas y supuestos. Desde ahí analizamos en profundidad el ámbito etnográfico y lingüístico bereber como hipótesis más plausible y probable. Tras la profundización en esta lengua y la corrección de los errores que nos llevaron a no detectarla en nuestro análisis precedente, llegamos a la conclusión de encontrarnos ante una lengua arcaica bereber, un conjunto de letras pertenecientes a una lengua y familia hoy no desaparecida, si bien muy modelada y difuminada por otras lenguas, en especial el árabe. Esto nos llevará a rescatar aspectos léxicos, morfológicos, sintácticos y fonéticos de este habla arcaica. Con todos estos datos realizamos un amplio estudio semántico de la talla tanto desde la perspectiva aborigen autóctona como cristiana. Finalmente, desde las voces lexicales y sus raíces de las lenguas bereberes e insulares amazigh, ofrecemos el significado de las letras inscritas en la talla mariana de Candelaria. ABSTRACT This research is an example of symbiosis between cryptanalysis and deciphering of languages. It is the search for meaning in an inscription, a group of about two hundred latin letters on a carving of the Virgin Mary that was on the island of Tenerife, in the town of Candelaria today, in the Canary islands. The image disappeared in a storm in 1826. However, it is possible to achieve a great certainty about what letters had, going to the textual and artistic documentary sources. The knowledge of the meaning, if any, of the marian inscription, can not be achieved without an adequate knowledge of the context. This means researching into the history of the same carving, which dates back to the fourteenth and fifteen century; the study of the canarian indigenous people and of the people who came there at different historical moments. Furthermore, it is necessary to know the rediscovery of the Canary islands and their processes of conquest and evangelization. All these data will offer a new and surprising outlook to understanding not only the letters but the same wood sculpture. From this moment the inquiry will move to see if the letters correspond to any possible language, which has led us to analyze a very large set of texts as close to the time under study, in a hundred languages. After the language examination, has been carried out a study of possible cryptographic forms used to generate the text of the inscription. A detailed and thorough list of possible techniques that could be adopted is offered. Then exhaustively we cryptanalyze the letters of the marian carving. At the same time a new crypto framework of methods and systems more orderly and complete, especially since the emergence of asymmetric key cryptography, is provided. We continue researching the possible pseudo-random generation of the text, a text that would not make any sense. At this time, and having completed all the possibilities and hypotheses, all having refused, we return to rethink our assumptions. From there we analyze in depth the ethnographic and linguistic berber sphere as the most likely hypothesis. Following the deepening of this language and correcting the mistakes that led us not to detect it in our analysis above, we conclude that this is an archaic berber language, a set of letters belonging to a language and family not extinct today but very modeled and influenced by other languages, primarily arabic. This will lead us to rescue lexical, morphological, syntactic and phonetic aspects of this archaic speech. With all this data we make a wide semantic study of the carving from the indigenous and christian perspective. Finally, from the lexical voices and roots of the berber languages amazigh and island-amazigh, we give the meaning of the letters inscribed in the marian carving of Candelaria.

Randomness and degrees of irregularity.

The fundamental question "Are sequential data random?" arises in myriad contexts, often with severe data length constraints. Furthermore, there is frequently a critical need to delineate nonrandom sequences in terms of closeness to randomness--e.g., to evaluate the efficacy of therapy in medicine. We address both these issues from a computable framework via a quantification of regularity. ApEn (approximate entropy), defining maximal randomness for sequences of arbitrary length, indicating the applicability to sequences as short as N = 5 points. An infinite sequence formulation of randomness is introduced that retains the operational (and computable) features of the finite case. In the infinite sequence setting, we indicate how the "foundational" definition of independence in probability theory, and the definition of normality in number theory, reduce to limit theorems without rates of convergence, from which we utilize ApEn to address rates of convergence (of a deficit from maximal randomness), refining the aforementioned concepts in a computationally essential manner. Representative applications among many are indicated to assess (i) random number generation output; (ii) well-shuffled arrangements; and (iii) (the quality of) bootstrap replicates.

Comparative analysis of the visual performance and aberrometric outcomes with a new hybrid and two silicone hydrogel multifocal contact lenses: a pilot study

Background: The aim was to evaluate the visual performance achieved with a new multifocal hybrid contact lens and to compare it with that obtained with two other currently available multifocal soft contact lenses. Methods: This pilot prospective comparative study comprised a total of 16 presbyopic eyes of eight patients ranging in age from 43 to 58 years. All patients were fitted with three different models of multifocal contact lens: Duette multifocal (SynergEyes), Air Optix AQUA multifocal (Alcon) and Biofinity multifocal (CooperVision). Fittings were performed randomly in each patient according to a random number sequence, with a wash-out period between fittings of seven days. At two weeks post-fitting, visual, photopic contrast sensitivity and ocular aberrometry were evaluated. Results: No statistically significant differences were found in distance and near visual acuity achieved with the three different types of multifocal contact lens (p ≥ 0.05). Likewise, no significant differences between lenses were found in the monocular and binocular defocus curve (p ≥ 0.10). Concerning contrast sensitivity, better monocular contrast sensitivities for 6, 12 and 18 cycles per degree were found with the Duette and Air Optix multifocal compared to Biofinity (p = 0.02). Binocularly, differences between lenses were not significant (p ≥ 0.27). Furthermore, trefoil aberration was significantly higher with Biofinity multifocal (p < 0.01) and Air Optix (p = 0.01) multifocal compared to Duette. Conclusions: The Duette multifocal hybrid contact lens seems to provide similar visual quality outcomes in presbyopic patients with low corneal astigmatism, when compared with other soft multifocal contact lenses. This preliminary result should be confirmed in studies with larger samples.

The experimental evaluation of the dynamics of fluid-loaded microplates

An experimental testing system for the study of the dynamic behavior of fluid-loaded rectangular micromachined silicon plates is designed and presented in this paper. In this experimental system, the base-excitation technique combined with pseudo-random signal and cross-correlation analysis is applied to test fluid-loaded microstructures. Theoretical model is also derived to reveal the mechanism of such an experimental system in the application of testing fluid-loaded microstructures. The dynamic experiments cover a series of testings of various microplates with different boundary conditions and dimensions, both in air and immersed in water. This paper is the first that demonstrates the ability and performances of base excitation in the application of dynamic testing of microstructures that involves a natural fluid environment. Traditional modal analysis approaches are used to evaluate natural frequencies, modal damping and mode shapes from the experimental data. The obtained experimental results are discussed and compared with theoretical predictions. This research experimentally determines the dynamic characteristics of the fluid-loaded silicon microplates, which can contribute to the design of plate-based microsystems. The experimental system and testing approaches presented in this paper can be widely applied to the investigation of the dynamics of microstructures and nanostructures.

A Limit Theorem for Multi-Type Subcritical Age-Dependent Branching Processes with two Types of Immigration

Марусия Н. Славчова-Божкова - В настоящата работа се обобщава една гранична теорема за докритичен многомерен разклоняващ се процес, зависещ от възрастта на частиците с два типа имиграция. Целта е да се обобщи аналогичен резултат в едномерния случай като се прилагат “coupling” метода, теория на възстановяването и регенериращи процеси.

Offspring Mean Estimators in Branching Processes with Immigration

2000 Mathematics Subject Classification: 60J80.

Functional Transfer Theorems for Maxima of Stationary Processes

2000 Mathematics Subject Classification: 60G70, 60F12, 60G10.

Estimators in Branching Processes with Immigration

2000 Mathematics Subject Classi cation: 60J80.