Semiparametric Methods for Semi-competing Risks Problem with Censoring and Truncation

Studies of chronic life-threatening diseases often involve both mortality and morbidity. In observational studies, the data may also be subject to administrative left truncation and right censoring. Since mortality and morbidity may be correlated and mortality may censor morbidity, the Lynden-Bell estimator for left truncated and right censored data may be biased for estimating the marginal survival function of the non-terminal event. We propose a semiparametric estimator for this survival function based on a joint model for the two time-to-event variables, which utilizes the gamma frailty specification in the region of the observable data. Firstly, we develop a novel estimator for the gamma frailty parameter under left truncation. Using this estimator, we then derive a closed form estimator for the marginal distribution of the non-terminal event. The large sample properties of the estimators are established via asymptotic theory. The methodology performs well with moderate sample sizes, both in simulations and in an analysis of data from a diabetes registry.

Non-photorealistic rendering of virtual implant models for computer-assisted fluoroscopy-based surgical procedures

Surgical navigation systems visualize the positions and orientations of surgical instruments and implants as graphical overlays onto a medical image of the operated anatomy on a computer monitor. The orthopaedic surgical navigation systems could be categorized according to the image modalities that are used for the visualization of surgical action. In the so-called CT-based systems or 'surgeon-defined anatomy' based systems, where a 3D volume or surface representation of the operated anatomy could be constructed from the preoperatively acquired tomographic data or through intraoperatively digitized anatomy landmarks, a photorealistic rendering of the surgical action has been identified to greatly improve usability of these navigation systems. However, this may not hold true when the virtual representation of surgical instruments and implants is superimposed onto 2D projection images in a fluoroscopy-based navigation system due to the so-called image occlusion problem. Image occlusion occurs when the field of view of the fluoroscopic image is occupied by the virtual representation of surgical implants or instruments. In these situations, the surgeon may miss part of the image details, even if transparency and/or wire-frame rendering is used. In this paper, we propose to use non-photorealistic rendering to overcome this difficulty. Laboratory testing results on foamed plastic bones during various computer-assisted fluoroscopybased surgical procedures including total hip arthroplasty and long bone fracture reduction and osteosynthesis are shown.

On the modeling of drug induced respiratory depression in the non-steady-state

The ability of anesthetic agents to provide adequate analgesia and sedation is limited by the ventilatory depression associated with overdosing in spontaneously breathing patients. Therefore, quantitation of drug induced ventilatory depression is a pharmacokinetic-pharmacodynamic problem relevant to the practice of anesthesia. Although several studies describe the effect of respiratory depressant drugs on isolated endpoints, an integrated description of drug induced respiratory depression with parameters identifiable from clinically available data is not available. This study proposes a physiological model of CO2 disposition, ventilatory regulation, and the effects of anesthetic agents on the control of breathing. The predictive performance of the model is evaluated through simulations aimed at reproducing experimental observations of drug induced hypercarbia and hypoventilation associated with intravenous administration of a fast-onset, highly potent anesthetic mu agonist (including previously unpublished experimental data determined after administration of 1 mg alfentanil bolus). The proposed model structure has substantial descriptive capability and can provide clinically relevant predictions of respiratory inhibition in the non-steady-state to enhance safety of drug delivery in the anesthetic practice.

Free abdominal fluid without obvious solid organ injury upon CT imaging: an actual problem or simply over-diagnosing?

Whereas a non-operative approach for hemodynamically stable patients with free intraabdominal fluid in the presence of solid organ injury is generally accepted, the presence of free fluid in the abdomen without evidence of solid organ injury not only presents a challenge for the treating emergency physician but also for the surgeon in charge. Despite recent advances in imaging modalities, with multi-detector computed tomography (CT) (with or without contrast agent) usually the imaging method of choice, diagnosis and interpretation of the results remains difficult. While some studies conclude that CT is highly accurate and relatively specific at diagnosing mesenteric and hollow viscus injury, others studies deem CT to be unreliable. These differences may in part be due to the experience and the interpretation of the radiologist and/or the treating physician or surgeon.A search of the literature has made it apparent that there is no straightforward answer to the question what to do with patients with free intraabdominal fluid on CT scanning but without signs of solid organ injury. In hemodynamically unstable patients, free intraabdominal fluid in the absence of solid organ injury usually mandates immediate surgical intervention. For patients with blunt abdominal trauma and more than just a trace of free intraabdominal fluid or for patients with signs of peritonitis, the threshold for a surgical exploration - preferably by a laparoscopic approach - should be low. Based on the available information, we aim to provide the reader with an overview of the current literature with specific emphasis on diagnostic and therapeutic approaches to this problem and suggest a possible algorithm, which might help with the adequate treatment of such patients.

Non-ignorable loss to follow-up: correcting mortality estimates based on additional outcome ascertainment

Loss to follow-up (LTFU) is a common problem in many epidemiological studies. In antiretroviral treatment (ART) programs for patients with human immunodeficiency virus (HIV), mortality estimates can be biased if the LTFU mechanism is non-ignorable, that is, mortality differs between lost and retained patients. In this setting, routine procedures for handling missing data may lead to biased estimates. To appropriately deal with non-ignorable LTFU, explicit modeling of the missing data mechanism is needed. This can be based on additional outcome ascertainment for a sample of patients LTFU, for example, through linkage to national registries or through survey-based methods. In this paper, we demonstrate how this additional information can be used to construct estimators based on inverse probability weights (IPW) or multiple imputation. We use simulations to contrast the performance of the proposed estimators with methods widely used in HIV cohort research for dealing with missing data. The practical implications of our approach are illustrated using South African ART data, which are partially linkable to South African national vital registration data. Our results demonstrate that while IPWs and proper imputation procedures can be easily constructed from additional outcome ascertainment to obtain valid overall estimates, neglecting non-ignorable LTFU can result in substantial bias. We believe the proposed estimators are readily applicable to a growing number of studies where LTFU is appreciable, but additional outcome data are available through linkage or surveys of patients LTFU. Copyright © 2013 John Wiley & Sons, Ltd.

Dilution of non-reactive tracers in variably saturated sandy structures

Based on a dye tracer experiment in a sand tank we addressed the problem of local dispersion of conservative tracers in the unsaturated zone. The sand bedding was designed to have a defined spatial heterogeneity with a strong anisotropy. We estimated the parameters that characterize the local dispersion and dilution from concentration maps of a high spatial and temporal resolution obtained by image analysis. The plume spreading and mixing behavior was quantified on the basis of the coefficient of variation of the concentration and of the dilution index. The heterogeneous structure modified the flow pattern depending on water saturation. The shape of the tracer plumes revealed the structural signature of the sand bedding at low saturation only. In this case pronounced preferential flow was observed. At higher flow rates the structure remained hidden by a spatially almost homogeneous behavior of the plumes. In this context, we mainly discuss the mechanism of re-distributing a finite mass of inert solutes over a large volume, due to macro- and micro-heterogeneities of the structure. (C) 2001 Elsevier Science Ltd. AU rights reserved.

Dirichlet-Neumann inverse spectral problem for a star graph of Stieltjes strings

We solve two inverse spectral problems for star graphs of Stieltjes strings with Dirichlet and Neumann boundary conditions, respectively, at a selected vertex called root. The root is either the central vertex or, in the more challenging problem, a pendant vertex of the star graph. At all other pendant vertices Dirichlet conditions are imposed; at the central vertex, at which a mass may be placed, continuity and Kirchhoff conditions are assumed. We derive conditions on two sets of real numbers to be the spectra of the above Dirichlet and Neumann problems. Our solution for the inverse problems is constructive: we establish algorithms to recover the mass distribution on the star graph (i.e. the point masses and lengths of subintervals between them) from these two spectra and from the lengths of the separate strings. If the root is a pendant vertex, the two spectra uniquely determine the parameters on the main string (i.e. the string incident to the root) if the length of the main string is known. The mass distribution on the other edges need not be unique; the reason for this is the non-uniqueness caused by the non-strict interlacing of the given data in the case when the root is the central vertex. Finally, we relate of our results to tree-patterned matrix inverse problems.

On the similarity of Sturm-Liouville operators with non-Hermitian boundary conditions to self-adjoint and normal operators

We consider one-dimensional Schrödinger-type operators in a bounded interval with non-self-adjoint Robin-type boundary conditions. It is well known that such operators are generically conjugate to normal operators via a similarity transformation. Motivated by recent interests in quasi-Hermitian Hamiltonians in quantum mechanics, we study properties of the transformations and similar operators in detail. In the case of parity and time reversal boundary conditions, we establish closed integral-type formulae for the similarity transformations, derive a non-local self-adjoint operator similar to the Schrödinger operator and also find the associated “charge conjugation” operator, which plays the role of fundamental symmetry in a Krein-space reformulation of the problem.

The inverse problem for Schwinger pair production

The production of electron–positron pairs in time-dependent electric fields (Schwinger mechanism) depends non-linearly on the applied field profile. Accordingly, the resulting momentum spectrum is extremely sensitive to small variations of the field parameters. Owing to this non-linear dependence it is so far unpredictable how to choose a field configuration such that a predetermined momentum distribution is generated. We show that quantum kinetic theory along with optimal control theory can be used to approximately solve this inverse problem for Schwinger pair production. We exemplify this by studying the superposition of a small number of harmonic components resulting in predetermined signatures in the asymptotic momentum spectrum. In the long run, our results could facilitate the observation of this yet unobserved pair production mechanism in quantum electrodynamics by providing suggestions for tailored field configurations.

On an Application of Microsoft Excel’s Evolutionary Solver to the Resource-Constrained Project Scheduling Problem RCPSP

The Solver Add-in of Microsoft Excel is widely used in courses on Operations Research and in industrial applications. Since the 2010 version of Microsoft Excel, the Solver Add-in comprises a so-called evolutionary solver. We analyze how this metaheuristic can be applied to the resource-constrained project scheduling problem (RCPSP). We present an implementation of a schedule-generation scheme in a spreadsheet, which combined with the evolutionary solver can be used for devising good feasible schedules. Our computational results indicate that using this approach, non-trivial instances of the RCPSP can be (approximately) solved to optimality.

Linguista sum... sed lingua non definio. Absence de définition de la langue et circularité de la construction structurale

This article analyzes the Jakobsonian classification of aphasias. It aims to show on the one hand the non-linguistic character of this classification and on the other hand its asymmetry, in spite of the fact that its author had conceived his structural construction as symmetrical. The non-linguistic character of Jakobson’s formulation is due to the absence of any definition of language, this absence being the main characteristic of Jakobsonian linguistics: concerning the aphasia problem, the Jakobsonian formulation is linguistic solely by virtue of its object, aphasia, which is already considered as a linguistic concern because it belongs to the field of « language », but which is not defined as such (as linguistic). As for asymmetry, it demonstrates first the circularity of the Jakobsonian representation of language (the duality between structure and functioning), and secondly the non-linguistic character – in the Saussurean sense of the term – of the aphasia problem. Thus it appears that breaking (in the sense of Gaston Bachelard) with idiom is the prerequisite of a scientific apprehension of language, and therefore of any interdisciplinarity, this being one of Jakobson’s favorite topics but one that this linguist failed to render fruitful because he did not offer a real definition of language.

The Complexity of Non-Iterated Probabilistic Justification Logic

The logic PJ is a probabilistic logic defined by adding (noniterated) probability operators to the basic justification logic J. In this paper we establish upper and lower bounds for the complexity of the derivability problem in the logic PJ. The main result of the paper is that the complexity of the derivability problem in PJ remains the same as the complexity of the derivability problem in the underlying logic J, which is π[p/2] -complete. This implies that the probability operators do not increase the complexity of the logic, although they arguably enrich the expressiveness of the language.

The winner takes it all? Characteristics of adolescents at-risk/problem gamblers in Switzerland

Background: Gambling has and still entertains people in almost all societies throughout the world. Western societies have faced considerable changes in the amount and accessibility of gambling possibilities during the last decades, and the rates of both adolescent gamblers and problem gamblers have increased significantly. Objective: To determine the characteristics of at-risk and problem adolescent gamblers in Switzerland. Subjects: The study population consisted of 3134 students (1669 females) attending post-mandatory education in 15 randomly chosen centres. Participants were divided into non- (n=2207), non-problematic (n=754) and at-risk/ problematic gamblers (n=176). Methods: Both gambling groups were compared to non-gamblers on socio-demographic measures, substance use and Internet use. Overall, 29.6% had gambled during the past year and 5.6% had gambled in a risky or problematic way. Compared to non-gamblers and after controlling for potential confounders, non-problem gamblers were significantly more likely to be male, apprentices and to misuse alcohol. At-risk/problematic gamblers were additionally more likely to smoke cannabis, to be problematic Internet users and to be non-Swiss than non-gamblers. Conclusion: At-risk and problematic adolescent gambling is associated with other health risk behaviours. Health practitioners should include gambling in the psycho-social screening and preventive counselling of adolescents.

A cross-sectional study of disparities in suicide ideation between Hispanic and non-Hispanic white female adolescents

Suicide is recognized as a major public health and clinical problem in the United States. One fifth of adolescents in the United States seriously consider suicide each year, and about 8% of high school students attempt suicide at least once. Hispanic ethnicity constitutes a risk factor for suicidal ideation and suicide attempts, with Hispanic females at highest risk. Nevertheless, published studies on suicidal behavior in Hispanic female adolescents are extremely limited and focus on suicidal ideation in school samples. Given the severity of the problem and the paucity of information on this topic, more research on ethnic differences in suicidal ideation in community samples of high-risk children is urgently needed. This cross-sectional study delineated differences in suicide ideation between Hispanic female adolescents and non-Hispanic white female adolescents attending a mental health clinic and examined the association of ethnicity with suicide ideation independent of other known risk factors. Data were accrued between June 2004 and December 2008 in a Harris County Mental Health and Mental Retardation Association (MHMRA) clinic. Data were limited to adolescents who were Harris County Residents between the ages of 10 to 17 years when they were admitted to the clinic. The objective of this study was to determine whether differences in socio-demographic and clinical variables play a significant role in ethnic disparities in suicide ideation. A series of logistic regressions were performed to estimate the association between ethnicity and suicide ideation after controlling for potentially confounding factors. ^ Results showed an interaction between Hispanic ethnicity and having a history of treatment: Hispanic girls having history of treatment had lower odds of having suicide ideation than Hispanic girls without such a history. After adjusting for treatment history, family problems, substance use, juvenile justice involvement, current treatment, and age, Hispanic girls had 1.86 times the odds of having suicide ideation than non Hispanic girls (OR=1.86, 95% CI=0.88-1.46). Although additional studies on community samples of high risk adolescents are needed to verify these findings, our study highlights the fact that Hispanic girls are at significantly higher risk and need to be targeted for prevention and treatment efforts. ^

Non-nutritive sucking and the preterm infant

Background. Preterm birth is major public health problem. Preterm infants face a post-natal environment that their under developed systems are inapt to manage. Developmentally supportive individualized care has demonstrated positive outcomes in minimizing resulting negative effects. Non-nutritive sucking (NNS) interventions are thought to promote the development of the suck-swallow-breathe mechanism and a calming tool. It is hypothesized that growth and development is maintained by strengthened sucking skills and stable behavioral states.^ Objective. To determine the importance of non-nutritive sucking (NNS) on outcomes that are clinically relevant to the preterm infant population.^ Methods. A computerized search of MEDLINE and PUBMED databases during the period of 1975 and May 2011 was conducted. Relevant articles were selected using published criteria for detecting clinically validated studies. The search yielded 10 randomized controlled studies relative to the outcomes of interest: weight gain, time to full feeds, time to discharge from hospital, and pain response.^ Results. NNS was found to decrease significantly the length of hospitalization in preterm infants. Although positive results were reported in some of the studies, the results did not show a consistent benefit of NNS with respect to other major clinical variables. NNS was shown to reduce distress following painful stimuli.^ Conclusion. Although NNS shows promise for the development of preterm infants, there is lack of agreement concerning some of the outcomes of interest. Evidence does support NNS's positive contribution to early hospital discharge and pain relief. Future research should focus on long-term, comparable outcomes. ^