The nested dirichlet distribution and incomplete categorical data analysis

The nested Dirichlet distribution (NDD) is an important distribution defined on the closed n-dimensional simplex. It includes the classical Dirichlet distribution and is useful in incomplete categorical data (ICD) analysis. In this article, we develop the distributional properties of NDD. New large-sample likelihood and small-sample Bayesian approaches for analyzing ICD are proposed and compared with existing likelihood/Bayesian strategies. We show that the new approaches have at least three advantages over existing approaches based on the traditional Dirichlet distribution in both frequentist and conjugate Bayesian inference for ICD. The new methods possess closed-form expressions for both the maximum likelihood and Bayes estimates when the likelihood function is in NDD form; produce computationally efficient EM and data augmentation algorithms when the likelihood is not in NDD form; and provide exact sampling procedures for some special cases. The methodologies are illustrated with simulated and real data.published_or_final_versio

Further properties and new applications of the nested Dirichlet distribution

Recently, Ng et al. (2009) studied a new family of distributions, namely the nested Dirichlet distributions. This family includes the traditional Dirichlet distribution as a special member and can be adopted to analyze incomplete categorical data. However, other important aspects of the family, such as marginal and conditional distributions and related properties are not yet available in the literature. Moreover, diverse applications of the family to the real world need to be further explored. In this paper, we first obtain the marginal and conditional distributions and other related properties of the nested Dirichlet distribution. We then present new applications of the family in fitting competing-risks model, analyzing incomplete categorical data and evaluating cancer diagnosis tests. Three real data involving failure times of radio transmitter receivers, attitude toward the death penalty and ultrasound ratings for breast cancer metastasis are provided. © 2009 Elsevier B.V. All rights reserved.postprin

Efficacy of High Dose Vitamin D Supplements for Elite Athletes.

PURPOSE: Supplementation with dietary forms of vitamin D is commonplace in clinical medicine, elite athletic cohorts and the general population, yet the response of all major vitamin D metabolites to high doses of vitamin D is poorly characterized. We aimed to identify the responses of all major vitamin D metabolites to moderate and high dose supplemental vitamin D3. METHODS: A repeated measures design was implemented in which 46 elite professional European athletes were block randomized based on their basal 25[OH]D concentration into two treatment groups. Athletes received either 35,000 or 70,000 IU.week vitamin D3 for 12 weeks and 42 athletes completed the trial. Blood samples were collected over 18 weeks to monitor the response to supplementation and withdrawal from supplementation. RESULTS: Both doses led to significant increases in serum 25[OH]D and 1,25[OH]2D3. 70,000 IU.week also resulted in a significant increase of the metabolite 24,25[OH]2D at weeks 6 and 12 that persisted following supplementation withdrawal at week 18, despite a marked decrease in 1,25[OH]2D3. Intact PTH was decreased in both groups by week 6 and remained suppressed throughout the trial. CONCLUSIONS: High dose vitamin D3 supplementation (70,000 IU.week) may be detrimental for its intended purposes due to increased 24,25[OH]2D production. Rapid withdrawal from high dose supplementation may inhibit the bioactivity of 1,25[OH]2D3 as a consequence of sustained increases in 24,25[OH]2D that persist as 25[OH]D and 1,25[OH]2D concentrations decrease. These data imply that lower doses of vitamin D3 ingested frequently may be most appropriate and gradual withdrawal from supplementation as opposed to rapid withdrawal may be favorable

Evidence for reversible control of magnetization in a ferromagnetic material via spin-orbit magnetic field

Conventional computer electronics creates a dichotomy between how information is processed and how it is stored. Silicon chips process information by controlling the flow of charge through a network of logic gates. This information is then stored, most commonly, by encoding it in the orientation of magnetic domains of a computer hard disk. The key obstacle to a more intimate integration of magnetic materials into devices and circuit processing information is a lack of efficient means to control their magnetization. This is usually achieved with an external magnetic field or by the injection of spin-polarized currents. The latter can be significantly enhanced in materials whose ferromagnetic properties are mediated by charge carriers. Among these materials, conductors lacking spatial inversion symmetry couple charge currents to spin by intrinsic spin-orbit (SO) interactions, inducing nonequilibrium spin polarization tunable by local electric fields. Here we show that magnetization of a ferromagnet can be reversibly manipulated by the SO-induced polarization of carrier spins generated by unpolarized currents. Specifically, we demonstrate domain rotation and hysteretic switching of magnetization between two orthogonal easy axes in a model ferromagnetic semiconductor.Comment: 10 pages including supplemental materia

Comparison of DC Bead-irinotecan and DC Bead-topotecan drug eluting beads for use in locoregional drug delivery to treat pancreatic cancer

DC Bead is a drug delivery embolisation system that can be loaded with doxorubicin or irinotecan for the treatment of a variety of liver cancers. In this study we demonstrate that the topoisomerase I inhibitor topotecan hydrochloride can be successfully loaded into the DC Bead sulfonate-modified polyvinyl alcohol hydrogel matrix, resulting in a sustained-release drug eluting bead (DEBTOP) useful for therapeutic purposes. The in vitro drug loading capacity, elution characteristics and the effects on mechanical properties of the beads are described with reference to our previous work with irinotecan hydrochloride (DEBIRI). Results showed that drug loading was faster when the solution was agitated compared to static loading and a maximum loading of ca. 40–45 mg topotecan in 1 ml hydrated beads was achievable. Loading the drug into the beads altered the size, compressibility moduli and colour of the bead. Elution was shown to be reliant on the presence of ions to perform the necessary exchange with the electrostatically bound topotecan molecules. Topotecan was shown by MTS assay to have an IC50 for human pancreatic adenocarcinoma cells (PSN-1) of 0.22 and 0.27 lM compared to 28.1 and 19.2 lM for irinotecan at 48 and 72 h, respectively. The cytotoxic efficacy of DEBTOP on PSN-1 was compared to DEBIRI. DEPTOP loaded at 6 & 30 mg ml-1, like its free drug form, was shown to be more potent than DEBIRI of comparable doses at 24, 48 & 72 h using a slightly modified MTS assay. Using a PSN-1 mouse xenograft model, DEBIRI doses of 3.3–6.6 mg were shown to be well tolerated (even with repeat administration) and effective in reducing the tumour size. DEBTOP however, was lethal after 6 days at doses of 0.83–1.2 mg but demonstrated reasonable efficacy and tolerability (again with repeat injection possible) at 0.2–0.4 mg doses. Care must therefore be taken when selecting the dose of topotecan to be loaded into DC Bead given its greater potency and potential toxicity

Vitamin D status in chronic fatigue syndrome/myalgic encephalomyelitis: a cohort study from the North-West of England

Objective Severe vitamin D deficiency is a recognised cause of skeletal muscle fatigue and myopathy. The aim of this study was to examine whether chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is associated with altered circulating vitamin D metabolites. Design Cohort study. Setting UK university hospital, recruiting from April 2014 to April 2015. Participants Ninety-two patients with CFS/ME and 94 age-matched healthy controls (HCs). Main outcome measures The presence of a significant association between CFS/ME, fatigue and vitamin D measures. Results No evidence of a deficiency in serum total 25(OH) vitamin D (25(OH)D2 and 25(OH)D3 metabolites) was evident in individuals with CFS/ME. Liquid chromatography tandem mass spectrometry (LC–MS/MS) analysis revealed that total 25(OH)D was significantly higher (p=0.001) in serum of patients with CFS/ME compared with HCs (60.2 and 47.3 nmol/L, respectively). Analysis of food/ supplement diaries with WinDiets revealed that the higher total 25(OH) vitamin D concentrations observed in the CFS/ ME group were associated with increased vitamin D intake through use of supplements compared with the control group. Analysis of Chalder Fatigue Questionnaire data revealed no association between perceived fatigue and vitamin D levels. Conclusions Low serum concentrations of total 25(OH) D do not appear to b

Sub-Sets of Cancer Stem Cells Differ Intrinsically in Their Patterns of Oxygen Metabolism

PMCID: PMC3640080This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Health services research in the public healthcare system in Hong Kong: An analysis of over 1 million antihypertensive prescriptions between 2004-2007 as an example of the potential and pitfalls of using routinely collected electronic patient data

<b>Objectives</b> Increasing use is being made of routinely collected electronic patient data in health services research. The aim of the present study was to evaluate the potential usefulness of a comprehensive database used routinely in the public healthcare system in Hong Kong, using antihypertensive drug prescriptions in primary care as an example.<p></p> <b>Methods</b> Data on antihypertensive drug prescriptions were retrieved from the electronic Clinical Management System (e-CMS) of all primary care clinics run by the Health Authority (HA) in the New Territory East (NTE) cluster of Hong Kong between January 2004 and June 2007. Information was also retrieved on patients’ demographic and socioeconomic characteristics, visit type (new or follow-up), and relevant diseases (International Classification of Primary Care, ICPC codes). <p></p> <b>Results</b> 1,096,282 visit episodes were accessed, representing 93,450 patients. Patients’ demographic and socio-economic details were recorded in all cases. Prescription details for anti-hypertensive drugs were missing in only 18 patients (0.02%). However, ICPC-code was missing for 36,409 patients (39%). Significant independent predictors of whether disease codes were applied included patient age > 70 years (OR 2.18), female gender (OR 1.20), district of residence (range of ORs in more rural districts; 0.32-0.41), type of clinic (OR in Family Medicine Specialist Clinics; 1.45) and type of visit (OR follow-up visit; 2.39). <p></p> In the 57,041 patients with an ICPC-code, uncomplicated hypertension (ICPC K86) was recorded in 45,859 patients (82.1%). The characteristics of these patients were very similar to those of the non-coded group, suggesting that most non-coded patients on antihypertensive drugs are likely to have uncomplicated hypertension. <p></p> <b>Conclusion</b> The e-CMS database of the HA in Hong Kong varies in quality in terms of recorded information. Potential future health services research using demographic and prescription information is highly feasible but for disease-specific research dependant on ICPC codes some caution is warranted. In the case of uncomplicated hypertension, future research on pharmaco-epidemiology (such as prescription patterns) and clinical issues (such as side-effects of medications on metabolic parameters) seems feasible given the large size of the data set and the comparability of coded and non-coded patients

Modeling recursive RNA interference.

An important application of the RNA interference (RNAi) pathway is its use as a small RNA-based regulatory system commonly exploited to suppress expression of target genes to test their function in vivo. In several published experiments, RNAi has been used to inactivate components of the RNAi pathway itself, a procedure termed recursive RNAi in this report. The theoretical basis of recursive RNAi is unclear since the procedure could potentially be self-defeating, and in practice the effectiveness of recursive RNAi in published experiments is highly variable. A mathematical model for recursive RNAi was developed and used to investigate the range of conditions under which the procedure should be effective. The model predicts that the effectiveness of recursive RNAi is strongly dependent on the efficacy of RNAi at knocking down target gene expression. This efficacy is known to vary highly between different cell types, and comparison of the model predictions to published experimental data suggests that variation in RNAi efficacy may be the main cause of discrepancies between published recursive RNAi experiments in different organisms. The model suggests potential ways to optimize the effectiveness of recursive RNAi both for screening of RNAi components as well as for improved temporal control of gene expression in switch off-switch on experiments

Theories for influencer identification in complex networks

In social and biological systems, the structural heterogeneity of interaction networks gives rise to the emergence of a small set of influential nodes, or influencers, in a series of dynamical processes. Although much smaller than the entire network, these influencers were observed to be able to shape the collective dynamics of large populations in different contexts. As such, the successful identification of influencers should have profound implications in various real-world spreading dynamics such as viral marketing, epidemic outbreaks and cascading failure. In this chapter, we first summarize the centrality-based approach in finding single influencers in complex networks, and then discuss the more complicated problem of locating multiple influencers from a collective point of view. Progress rooted in collective influence theory, belief-propagation and computer science will be presented. Finally, we present some applications of influencer identification in diverse real-world systems, including online social platforms, scientific publication, brain networks and socioeconomic systems.Comment: 24 pages, 6 figure