Estimating Discrete Markov Models From Various Incomplete Data Schemes

The parameters of a discrete stationary Markov model are transition probabilities between states. Traditionally, data consist in sequences of observed states for a given number of individuals over the whole observation period. In such a case, the estimation of transition probabilities is straightforwardly made by counting one-step moves from a given state to another. In many real-life problems, however, the inference is much more difficult as state sequences are not fully observed, namely the state of each individual is known only for some given values of the time variable. A review of the problem is given, focusing on Monte Carlo Markov Chain (MCMC) algorithms to perform Bayesian inference and evaluate posterior distributions of the transition probabilities in this missing-data framework. Leaning on the dependence between the rows of the transition matrix, an adaptive MCMC mechanism accelerating the classical Metropolis-Hastings algorithm is then proposed and empirically studied.Comment: 26 pages - preprint accepted in 20th February 2012 for publication in Computational Statistics and Data Analysis (please cite the journal's paper

Head and neck squamous cell carcinoma of unknown primary: Neck dissection and radiotherapy or definitive radiotherapy

Background Management of head and neck carcinoma from unknown primary (HNCUP) remains controversial, with neck dissection and radiotherapy (RT) or definitive RT both commonly used. The purpose of this study was to characterize HNCUP and retrospectively compare outcomes for patients treated with neck dissection + RT versus definitive RT. Methods From 1994 to 2009, 41 patients with HNCUP underwent either neck dissection + RT ( n  = 22) or definitive RT ± concurrent chemotherapy ( n  = 19) at our institution. Treatment outcomes were compared using Kaplan–Meier methods and log‐rank test. Results There were no differences between patients treated with neck dissection + RT and definitive RT in overall survival (OS), progression‐free survival (PFS), locoregional relapse‐free survival (LRFS), freedom from locoregional failure (FFLRG), or freedom from distant failure (FFDF). Among 17 patients who underwent neck dissection + RT for whom human papillomavirus (HPV) status could be determined, HPV(+) patients trended toward improved OS ( p  = .06) and PFS ( p  = .15). Conclusion Neck dissection and postoperative RT resulted in similar outcomes as definitive RT. The prognostic implications of HPV(+) nodes in HNCUP are similar to those in oropharyngeal primary cancers. © 2013 Wiley Periodicals, Inc. Head Neck 36: 1589–1595, 2014Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109313/1/hed23479.pd

Biomimetic apatite deposition on polymeric microspheres treated with a calcium silicate solution

Bioactive polymeric microspheres can be prepared by means of coating them with a calcium silicate solution and subsequently soaking in a simulated body fluid (SBF). Such combination should allow for the development of bioactive microspheres for several applications in the medical field including tissue engineering carriers. Four types of polymeric microspheres, with different sizes, were used in this work: (i) ethylene-vinyl alcohol copolymer (20–30 µm), (ii) polyamide 12 with 10% magnetite (100 µm), (iii) polyamide 12 (10–30 µm) and (iv) polyamide 12 (300 µm). These microspheres were soaked in a calcium silicate solution at 36.58C for various periods of time under different conditions. Afterwards, they were dried in air at 60 and 100ºC for 24 hr. Then, the samples were soaked in SBF for 1, 3, and 7 days. Fourier transformed infrared spectroscopy, thin-film X-ray diffraction, and scanning electron microscopy showed that after the calcium silicate treatment and the subsequent soaking in SBF, the microspheres successfully formed an apatite layer on their surfaces in SBF within 7 days due to the formation of silanol groups, which are effective for apatite formation.Contract grant sponsor: European NoE EXPERTISSUES; Contract grant number: NMP3-CT-2004-50028

Recognition of nonkeratinizing morphology in oropharyngeal squamous cell carcinoma – a prospective cohort and interobserver variability study *

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90168/1/j.1365-2559.2011.04092.x.pd

Vacuolating cytotoxin and variants in Atg16L1 that disrupt autophagy promote Helicobacter pylori infection in humans

Peer reviewedPreprin

Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition

An evaluation of emerging vaccines for childhood pneumococcal pneumonia

<p>Abstract</p> <p>Background</p> <p>Pneumonia is the leading cause of child mortality worldwide. <it>Streptococcus pneumoniae</it> (SP) or <it>pneumococcus</it> is estimated to cause 821,000 child deaths each year. It has over 90 serotypes, of which 7 to 13 serotypes are included in current formulations of pneumococcal conjugate vaccines that are efficacious in young children. To further reduce the burden from SP pneumonia, a vaccine is required that could protect children from a greater diversity of serotypes. Two different types of vaccines against pneumococcal pneumonia are currently at varying stages of development: a multivalent pneumococcal conjugate vaccine covering additional SP serotypes; and a conserved common pneumococcal protein antigen (PPA) vaccine offering protection for all serotypes.</p> <p>Methods</p> <p>We used a modified CHNRI methodology for setting priorities in health research investments. This was done in two stages. In Stage I, we systematically reviewed the literature related to emerging SP vaccines relevant to several criteria of interest: answerability; efficacy and effectiveness; cost of development, production and implementation; deliverability, affordability and sustainability; maximum potential for disease burden reduction; acceptability to the end users and health workers; and effect on equity. In Stage II, we conducted an expert opinion exercise by inviting 20 experts (leading basic scientists, international public health researchers, international policy makers and representatives of pharmaceutical companies). The policy makers and industry representatives accepted our invitation on the condition of anonymity, due to sensitive nature of their involvement in such exercises. They answered questions from CHNRI framework and their “collective optimism” towards each criterion was documented on a scale from 0 to 100%.</p> <p>Results</p> <p>The experts expressed very high level of optimism (over 80%) that low-cost polysaccharide conjugate SP vaccines would satisfy each of the 9 relevant CHNRI criteria. The median potential effectiveness of conjugate SP vaccines in reduction of overall childhood pneumonia mortality was predicted to be about 25% (interquartile range 20-38%, min. 15%, max 45%). For low cost, cross-protective common protein vaccines for SP the experts expressed concerns over answerability (72%) and the level of development costs (50%), while the scores for all other criteria were over 80%. The median potential effectiveness of common protein vaccines in reduction of overall childhood pneumonia mortality was predicted to be about 30% (interquartile range 26-40%, min. 20%, max 45%).</p> <p>Conclusions</p> <p>Improved SP vaccines are a very promising investment that could substantially contribute to reduction of child mortality world-wide.</p

State history and economic development: evidence from six millennia

The presence of a state is one of the most reliable historical predictors of social and economic development. In this article, we complete the coding of an extant indicator of state presence from 3500 BCE forward for almost all but the smallest countries of the world today. We outline a theoretical framework where accumulated state experience increases aggregate productivity in individual countries but where newer or relatively inexperienced states can reach a higher productivity maximum by learning from the experience of older states. The predicted pattern of comparative development is tested in an empirical analysis where we introduce our extended state history variable. Our key finding is that the current level of economic development across countries has a hump-shaped relationship with accumulated state history

Synthesis, characterization, DNA-binding and biological activity of Zn(II) complexes of sulfadiazine with different amino acids

New Zn(II) complexes (ZnII-VS, ZnII-LS, ZnII-SS, ZnII-CS and ZnII-MS) of the sulfonamide antibiotic sulfadiazine with different amino acids were prepared and fully characterized by elemental analyses, thermal analysis and IR, UV/Vis and 1H NMR spectroscopy. The IR and 1H NMR spectral data show that the ligands behave in a dibasic bidentate fashion coordinating to zinc ion. Interactions of these complexes with DNA were investigated by spectrophotometric method. Moreover, the antibacterial and antifungal activities were evaluated for five ligands and their complexes. The computational study for prediction of absorption, distribution, metabolism, elimination and toxic factors (ADMET) properties were performed for the prepared ligands

Constraints on the χ_(c1) versus χ_(c2) polarizations in proton-proton collisions at √s = 8 TeV

The polarizations of promptly produced χ_(c1) and χ_(c2) mesons are studied using data collected by the CMS experiment at the LHC, in proton-proton collisions at √s=8  TeV. The χ_c states are reconstructed via their radiative decays χ_c → J/ψγ, with the photons being measured through conversions to e⁺e⁻, which allows the two states to be well resolved. The polarizations are measured in the helicity frame, through the analysis of the χ_(c2) to χ_(c1) yield ratio as a function of the polar or azimuthal angle of the positive muon emitted in the J/ψ → μ⁺μ⁻ decay, in three bins of J/ψ transverse momentum. While no differences are seen between the two states in terms of azimuthal decay angle distributions, they are observed to have significantly different polar anisotropies. The measurement favors a scenario where at least one of the two states is strongly polarized along the helicity quantization axis, in agreement with nonrelativistic quantum chromodynamics predictions. This is the first measurement of significantly polarized quarkonia produced at high transverse momentum