A Quantile Variant of the EM Algorithm and Its Applications to Parameter Estimation with Interval Data

The expectation-maximization (EM) algorithm is a powerful computational technique for finding the maximum likelihood estimates for parametric models when the data are not fully observed. The EM is best suited for situations where the expectation in each E-step and the maximization in each M-step are straightforward. A difficulty with the implementation of the EM algorithm is that each E-step requires the integration of the log-likelihood function in closed form. The explicit integration can be avoided by using what is known as the Monte Carlo EM (MCEM) algorithm. The MCEM uses a random sample to estimate the integral at each E-step. However, the problem with the MCEM is that it often converges to the integral quite slowly and the convergence behavior can also be unstable, which causes a computational burden. In this paper, we propose what we refer to as the quantile variant of the EM (QEM) algorithm. We prove that the proposed QEM method has an accuracy of $O(1/K^2)$ while the MCEM method has an accuracy of $O_p(1/\sqrt{K})$. Thus, the proposed QEM method possesses faster and more stable convergence properties when compared with the MCEM algorithm. The improved performance is illustrated through the numerical studies. Several practical examples illustrating its use in interval-censored data problems are also provided

Methods for estimating the case fatality ratio for a novel, emerging infectious disease.

During the course of an epidemic of a potentially fatal disease, it is important that the case fatality ratio be well estimated. The authors propose a novel method for doing so based on the Kaplan-Meier survival procedure, jointly considering two outcomes (death and recovery), and evaluate its performance by using data from the 2003 epidemic of severe acute respiratory syndrome in Hong Kong, People's Republic of China. They compare this estimate obtained at various points in the epidemic with the case fatality ratio eventually observed; with two commonly quoted, naïve estimates derived from cumulative incidence and mortality statistics at single time points; and with estimates in which a parametric mixture model is used. They demonstrate the importance of patient characteristics regarding outcome by analyzing subgroups defined by age at admission to the hospital

Nutrition Strategies for Triathlon

Contemporary sports nutrition guidelines recommend that each athlete develop a personalised, periodised and practical approach to eating that allows him or her to train hard, recover and adapt optimally, stay free of illness and injury and compete at their best at peak races. Competitive triathletes undertake a heavy training programme to prepare for three different sports while undertaking races varying in duration from 20 min to 10 h. The everyday diet should be adequate in energy availability, provide CHO in varying amounts and timing around workouts according to the benefits of training with low or high CHO availability and spread high-quality protein over the day to maximise the adaptive response to each session. Race nutrition requires a targeted and well-practised plan that maintains fuel and hydration goals over the duration of the specific event, according to the opportunities provided by the race and other challenges, such as a hot environment. Supplements and sports foods can make a small contribution to a sports nutrition plan, when medical supplements are used under supervision to prevent/treat nutrient deficiencies (e.g. iron or vitamin D) or when sports foods provide a convenient source of nutrients when it is impractical to eat whole foods. Finally, a few evidence-based performance supplements may contribute to optimal race performance when used according to best practice protocols to suit the triathlete’s goals and individual responsiveness

A study of blood contamination of Siqveland matrix bands

AIMS To use a sensitive forensic test to measure blood contamination of used Siqveland matrix bands following routine cleaning and sterilisation procedures in general dental practice. MATERIALS AND METHODS: Sixteen general dental practices in the West of Scotland participated. Details of instrument cleaning procedures were recorded for each practice. A total of 133 Siqveland matrix bands were recovered following cleaning and sterilisation and were examined for residual blood contamination by the Kastle-Meyer test, a well-recognised forensic technique. RESULTS: Ultrasonic baths were used for the cleaning of 62 (47%) bands and retainers and the remainder (53%) were hand scrubbed prior to autoclaving. Overall, 21% of the matrix bands and 19% of the retainers gave a positive Kastle-Meyer test, indicative of residual blood contamination, following cleaning and sterilisation. In relation to cleaning method, 34% of hand-scrubbed bands and 32% of hand-scrubbed retainers were positive for residual blood by the Kastle-Meyer test compared with 6% and 3% respectively of ultrasonically cleaned bands and retainers (P less than 0.001). CONCLUSIONS: If Siqveland matrix bands are re-processed in the assembled state, then adequate pre-sterilisation cleaning cannot be achieved reliably. Ultrasonic baths are significantly more effective than hand cleaning for these items of equipment

High-dimensional simplexes for supermetric search

In a metric space, triangle inequality implies that, for any three objects, a triangle with edge lengths corresponding to their pairwise distances can be formed. The n-point property is a generalisation of this where, for any (n+1) objects in the space, there exists an n-dimensional simplex whose edge lengths correspond to the distances among the objects. In general, metric spaces do not have this property; however in 1953, Blumenthal showed that any semi-metric space which is isometrically embeddable in a Hilbert space also has the n-point property. We have previously called such spaces supermetric spaces, and have shown that many metric spaces are also supermetric, including Euclidean, Cosine, Jensen-Shannon and Triangular spaces of any dimension. Here we show how such simplexes can be constructed from only their edge lengths, and we show how the geometry of the simplexes can be used to determine lower and upper bounds on unknown distances within the original space. By increasing the number of dimensions, these bounds converge to the true distance. Finally we show that for any Hilbert-embeddable space, it is possible to construct Euclidean spaces of arbitrary dimensions, from which these lower and upper bounds of the original space can be determined. These spaces may be much cheaper to query than the original. For similarity search, the engineering tradeoffs are good: we show significant reductions in data size and metric cost with little loss of accuracy, leading to a significant overall improvement in exact search performance

The Fusion Loops of the Initial Prefusion Conformation of Herpes Simplex Virus 1 Fusion Protein Point Toward the Membrane

All enveloped viruses, including herpesviruses, must fuse their envelope with the host membrane to deliver their genomes into target cells, making this essential step subject to interference by antibodies and drugs. Viral fusion is mediated by a viral surface protein that transits from an initial prefusion conformation to a final postfusion conformation. Strikingly, the prefusion conformation of the herpesvirus fusion protein, gB, is poorly understood. Herpes simplex virus (HSV), a model system for herpesviruses, causes diseases ranging from mild skin lesions to serious encephalitis and neonatal infections. Using cryo-electron tomography and subtomogram averaging, we have characterized the structure of the prefusion conformation and fusion intermediates of HSV-1 gB. To this end, we have set up a system that generates microvesicles displaying full-length gB on their envelope. We confirmed proper folding of gB by nondenaturing electrophoresis-Western blotting with a panel of monoclonal antibodies (MAbs) covering all gB domains. To elucidate the arrangement of gB domains, we labeled them by using (i) mutagenesis to insert fluorescent proteins at specific positions, (ii) coexpression of gB with Fabs for a neutralizing MAb with known binding sites, and (iii) incubation of gB with an antibody directed against the fusion loops. Our results show that gB starts in a compact prefusion conformation with the fusion loops pointing toward the viral membrane and suggest, for the first time, a model for gB’s conformational rearrangements during fusion. These experiments further illustrate how neutralizing antibodies can interfere with the essential gB structural transitions that mediate viral entry and therefore infectivity

Impacts of climate extremes in Brazil the development of a web platform for understanding long-term sustainability of ecosystems and human health in amazonia (pulse-Brazil)

This is the final version of the article. Available from the American Meteorological Society via the DOI in this record.This work was funded by the joint FAPESP 2011/51843-2 and NERC NE/J016276/1 International Opportunities Fund. PULSE-Brazil development is also funded by the FAPESP grant (2012/51876-0) under the Belmont Forum Cooperation Agreement. Marengo and Aragão thank the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) for their Research Productivity Fellowship

CDH1 mutation distribution and type suggests genetic differences between the etiology of orofacial clefting and gastric cancer

Pathogenic variants in CDH1, encoding epithelial cadherin (E-cadherin), have been implicated in hereditary diffuse gastric cancer (HDGC), lobular breast cancer, and both syndromic and non-syndromic cleft lip/palate (CL/P). Despite the large number of CDH1 mutations described, the nature of the phenotypic consequence of such mutations is currently not able to be predicted, creating significant challenges for genetic counselling. This study collates the phenotype and molecular data for available CDH1 variants that have been classified, using the American College of Medical Genetics and Genomics criteria, as at least ‘likely pathogenic’, and correlates their molecular and structural characteristics to phenotype. We demonstrate that CDH1 variant type and location differ between HDGC and CL/P, and that there is clustering of CL/P variants within linker regions between the extracellular domains of the cadherin protein. While these differences do not provide for exact prediction of the phenotype for a given mutation, they may contribute to more accurate assessments of risk for HDGC or CL/P for individuals with specific CDH1 variants