Modeling the dynamics of biomarkers during primary HIV infection taking into account the uncertainty of infection date

During primary HIV infection, the kinetics of plasma virus concentrations and CD4+ cell counts is very complex. Parametric and nonparametric models have been suggested for fitting repeated measurements of these markers. Alternatively, mechanistic approaches based on ordinary differential equations have also been proposed. These latter models are constructed according to biological knowledge and take into account the complex nonlinear interactions between viruses and cells. However, estimating the parameters of these models is difficult. A main difficulty in the context of primary HIV infection is that the date of infection is generally unknown. For some patients, the date of last negative HIV test is available in addition to the date of first positive HIV test (seroconverters). In this paper we propose a likelihood-based method for estimating the parameters of dynamical models using a population approach and taking into account the uncertainty of the infection date. We applied this method to a sample of 761 HIV-infected patients from the Concerted Action on SeroConversion to AIDS and Death in Europe (CASCADE).Comment: Published in at http://dx.doi.org/10.1214/10-AOAS364 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

HIV in hiding: methods and data requirements for the estimation of the number of people living with undiagnosed HIV

Many people who are HIV positive are unaware of their infection status. Estimation of the number of people with undiagnosed HIV within a country or region is vital for understanding future need for treatment and for motivating testing programs. We review the available estimation approaches which are in current use. They can be broadly classified into those based on prevalence surveys and those based on reported HIV and AIDS cases. Estimation based on prevalence data requires data from regular prevalence surveys in different population groups together with estimates of the size of these groups. The recommended minimal case reporting data needed to estimate the number of patients with undiagnosed HIV are HIV diagnoses, including CD4 count at diagnosis and whether there has been an AIDS diagnosis in the 3 months before or after HIV diagnosis, and data on deaths in people with HIV. We would encourage all countries to implement several methods that will help develop our understanding of strengths and weaknesses of the various methods

Likelihood for generally coarsened observations from multi-state or counting process models

We consider first the mixed discrete-continuous scheme of observation in multistate models; this is a classical pattern in epidemiology because very often clinical status is assessed at discrete visit times while times of death or other events are observed exactly. A heuristic likelihood can be written for such models, at least for Markov models; however, a formal proof is not easy and has not been given yet. We present a general class of possibly non-Markov multistate models which can be represented naturally as multivariate counting processes. We give a rigorous derivation of the likelihood based on applying Jacod's formula for the full likelihood and taking conditional expectation for the observed likelihood. A local description of the likelihood allows us to extend the result to a more general coarsening observation scheme proposed by Commenges & G\'egout-Petit. The approach is illustrated by considering models for dementia, institutionalization and death

Empowering open science with reflexive and spatialised indicators

Bibliometrics have become commonplace and widely used by authors and journals to monitor, to evaluate and to identify their readership in an ever-increasingly publishing scientific world. This contribution introduces a multi-method corpus analysis tool, specifically conceived for scientific corpuses with spatialised content. We propose a dedicated interactive application that integrates three strategies for building semantic networks, using keywords (self-declared themes), citations (areas of research using the papers) and full-texts (themes derived from the words used in writing). The networks can be studied with respect to their temporal evolution as well as to their spatial expressions, by considering the countries studied in the papers under inquiry. The tool is applied as a proof-of-concept on the papers published in the online open access geography journal Cybergeo since its creation in 1996. Finally, we compare the three methods and conclude that their complementarity can help go beyond simple statistics to better understand the epistemological evolution of a scientific community and the readership target of the journal. Our tool can be applied by any journal on its own corpus, fostering thus open science and reflexivity

Unraveling the performance of dispersion-corrected functionals for the accurate description of weakly bound natural polyphenols

Long-range non-covalent interactions play a key role in the chemistry of natural polyphenols. We have previously proposed a description of supramolecular polyphenol complexes by the B3P86 density functional coupled with some corrections for dispersion. We couple here the B3P86 functional with the D3 correction for dispersion, assessing systematically the accuracy of the new B3P86-D3 model using for that the well-known S66, HB23, NCCE31, and S12L datasets for non-covalent interactions. Furthermore, the association energies of these complexes were carefully compared to those obtained by other dispersion-corrected functionals, such as B(3)LYP-D3, BP86-D3 or B3P86-NL. Finally, this set of models were also applied to a database composed of seven non-covalent polyphenol complexes of the most interest.FDM acknowledges financial support from the Swedish Research Council (Grant No. 621-2014-4646) and SNIC (Swedish National Infrastructure for Computing) for providing computer resources. The work in Limoges (IB and PT) is supported by the “Conseil Régional du Limousin”. PT gratefully acknowledges the support by the Operational Program Research and Development Fund (project CZ.1.05/2.1.00/03.0058 of the Ministry of Education, Youth and Sports of the Czech Republic). IB gratefully acknowledges financial support from “Association Djerbienne en France”

Multi-state models and arthroplasty histories after unilateral total hip arthroplasties: Introducing the Summary Notation for Arthroplasty Histories

Background and purpose: An increasing number of patients have several joint replacement procedures during their lifetime. We investigated the use and suitability of multi-state model techniques in providing a more comprehensive analysis and description of complex arthroplasty histories held in arthroplasty registries than are allowed for with traditional survival methods. Patients and methods: We obtained data from the Australian Orthopaedic Association National Joint Replacement Registry on patients (n = 84,759) who had undergone a total hip arthroplasty for osteoarthritis in the period 2002–2008. We set up a multi-state model where patients were followed from their first recorded arthroplasty to several possible states: revision of first arthroplasty, either a hip or knee as second arthroplasty, revision of the second arthroplasty, and death. The Summary Notation for Arthroplasty Histories (SNAH) was developed in order to help to manage and analyze this type of data. Results: At the end of the study period, 12% of the 84,759 patients had received a second hip, 3 times as many as had received a knee. The estimated probabilities of having received a second arthroplasty decreased with age. Males had a lower transition rate for receiving a second arthroplasty, but a higher mortality rate. Interpretation: Multi-state models in combination with SNAH codes are well suited to the management and analysis of arthroplasty registry data on patients who experience multiple joint procedures over time. We found differences in the progression of joint replacement procedures after the initial total hip arthroplasty regarding type of joint, age, and sex.Marianne H Gillam, Philip Ryan, Amy Salter, Stephen E Grave

Alcohol use disorders and risk of Parkinson’s disease: findings from a Swedish national cohort study 1972–2008

BACKGROUND: Alcohol has been suggested to be either protective of, or not associated with Parkinson’s disease (PD). However, experimental animal studies indicate that chronic heavy alcohol consumption may have dopamine neurotoxic effects relevant for PD. We studied the association between diagnosed alcohol use disorders and PD. METHODS: All individuals in Sweden admitted with a diagnosis of an alcohol use disorder or appendicitis (reference group) between January 1, 1972 and December 31, 2008 were identified through the Swedish National Inpatient Register, and followed for up to 37 years for a diagnosis of PD. We estimated hazard ratios (HR) with 95% confidence intervals (CI) and adjusted for age and sex. RESULTS: We found 1,741 (0.3%) cases of PD in the cohort of 602,930 individuals, 1,083 (0.4%) among those admitted with an alcohol use disorder and 658 (0.2%) of the individuals admitted with appendicitis. The mean follow-up time was 13.6 and 17.1 years, respectively. The HR for PD associated with an alcohol use disorder was 1.38 (CI 1.25-1.53) adjusted for age and sex. When the risk was estimated in age groups for first hospital admission with PD the highest risk was observed in the lowest age group, ≤44, HR 2.39 (0.96-5.93), adjusted for age at exposure and sex. CONCLUSIONS: A history of an alcohol use disorder conferred an increased risk of admission with a diagnosis of Parkinson’s disease in both women and men. In particular, the risk seemed higher at lower ages of first admission with Parkinson’s disease