pGQL: A probabilistic graphical query language for gene expression time courses

<p>Abstract</p> <p>Background</p> <p>Timeboxes are graphical user interface widgets that were proposed to specify queries on time course data. As queries can be very easily defined, an exploratory analysis of time course data is greatly facilitated. While timeboxes are effective, they have no provisions for dealing with noisy data or data with fluctuations along the time axis, which is very common in many applications. In particular, this is true for the analysis of gene expression time courses, which are mostly derived from noisy microarray measurements at few unevenly sampled time points. From a data mining point of view the robust handling of data through a sound statistical model is of great importance.</p> <p>Results</p> <p>We propose probabilistic timeboxes, which correspond to a specific class of Hidden Markov Models, that constitutes an established method in data mining. Since HMMs are a particular class of probabilistic graphical models we call our method Probabilistic Graphical Query Language. Its implementation was realized in the free software package pGQL. We evaluate its effectiveness in exploratory analysis on a yeast sporulation data set.</p> <p>Conclusions</p> <p>We introduce a new approach to define dynamic, statistical queries on time course data. It supports an interactive exploration of reasonably large amounts of data and enables users without expert knowledge to specify fairly complex statistical models with ease. The expressivity of our approach is by its statistical nature greater and more robust with respect to amplitude and frequency fluctuation than the prior, deterministic timeboxes.</p

Superform formulation for vector-tensor multiplets in conformal supergravity

The recent papers arXiv:1110.0971 and arXiv:1201.5431 have provided a superfield description for vector-tensor multiplets and their Chern-Simons couplings in 4D N = 2 conformal supergravity. Here we develop a superform formulation for these theories. Furthermore an alternative means of gauging the central charge is given, making use of a deformed vector multiplet, which may be thought of as a variant vector-tensor multiplet. Its Chern-Simons couplings to additional vector multiplets are also constructed. This multiplet together with its Chern-Simons couplings are new results not considered by de Wit et al. in hep-th/9710212.Comment: 28 pages. V2: Typos corrected and references updated; V3: References updated and typo correcte

Epstein-Barr Virus Reactivation After Paediatric Haematopoietic Stem Cell Transplantation: Risk Factors and Sensitivity Analysis of Mathematical Model

Epstein-Barr virus (EBV) establishes a lifelong latent infection in healthy humans, kept under immune control by cytotoxic T cells (CTLs). Following paediatric haematopoetic stem cell transplantation (HSCT), a loss of immune surveillance leads to opportunistic outgrowth of EBV-infected cells, resulting in EBV reactivation, which can ultimately progress to post-transplant lymphoproliferative disorder (PTLD). The aims of this study were to identify risk factors for EBV reactivation in children in the first 100 days post-HSCT and to assess the suitability of a previously reported mathematical model to mechanistically model EBV reactivation kinetics in this cohort. Retrospective electronic data were collected from 56 children who underwent HSCT at Great Ormond Street Hospital (GOSH) between 2005 and 2016. Using EBV viral load (VL) measurements from weekly quantitative PCR (qPCR) monitoring post-HSCT, a multivariable Cox proportional hazards (Cox-PH) model was developed to assess time to first EBV reactivation event in the first 100 days post-HSCT. Sensitivity analysis of a previously reported mathematical model was performed to identify key parameters affecting EBV VL. Cox-PH modelling revealed EBV seropositivity of the HSCT recipient and administration of anti-thymocyte globulin (ATG) pre-HSCT to be significantly associated with an increased risk of EBV reactivation in the first 100 days post-HSCT (adjusted hazard ratio (AHR) = 2.32, P = 0.02; AHR = 2.55, P = 0.04). Five parameters were found to affect EBV VL in sensitivity analysis of the previously reported mathematical model. In conclusion, we have assessed the effect of multiple covariates on EBV reactivation in the first 100 days post-HSCT in children and have identified key parameters in a previously reported mechanistic mathematical model that affect EBV VL. Future work will aim to fit this model to patient EBV VLs, develop the model to account for interindividual variability and model the effect of clinically relevant covariates such as rituximab therapy and ATG on EBV VL

Childhood leukemia: electric and magnetic fields as possible risk factors.

Numerous epidemiologic studies have reported associations between measures of power-line electric or magnetic fields (EMFs) and childhood leukemia. The basis for such associations remains unexplained. In children, acute lymphoblastic leukemia represents approximately three-quarters of all U.S. leukemia types. Some risk factors for childhood leukemia have been established, and others are suspected. Pathogenesis, as investigated in animal models, is consistent with the multistep model of acute leukemia development. Studies of carcinogenicity in animals, however, are overwhelmingly negative and do not support the hypothesis that EMF exposure is a significant risk factor for hematopoietic neoplasia. We may fail to observe effects from EMFs because, from a mechanistic perspective, the effects of EMFs on biology are very weak. Cells and organs function despite many sources of chemical "noise" (e.g., stochastic, temperature, concentration, mechanical, and electrical noise), which exceed the induced EMF "signal" by a large factor. However, the inability to detect EMF effects in bioassay systems may be caused by the choice made for "EMF exposure." "Contact currents" or "contact voltages" have been proposed as a novel exposure metric, because their magnitude is related to measured power-line magnetic fields. A contact current occurs when a person touches two conductive surfaces at different voltages. Modeled analyses support contact currents as a plausible metric because of correlations with residential magnetic fields and opportunity for exposure. The possible role of contact currents as an explanatory variable in the reported associations between EMFs and childhood leukemia will need to be clarified by further measurements, biophysical analyses, bioassay studies, and epidemiology

A cluster randomized controlled trial of the effectiveness and cost-effectiveness of Intermediate Care Clinics for Diabetes (ICCD) : study protocol for a randomized controlled trial

Background World-wide healthcare systems are faced with an epidemic of type 2 diabetes. In the United Kingdom, clinical care is primarily provided by general practitioners (GPs) rather than hospital specialists. Intermediate care clinics for diabetes (ICCD) potentially provide a model for supporting GPs in their care of people with poorly controlled type 2 diabetes and in their management of cardiovascular risk factors. This study aims to (1) compare patients with type 2 diabetes registered with practices that have access to an ICCD service with those that have access only to usual hospital care; (2) assess the cost-effectiveness of the intervention; and (3) explore the views and experiences of patients, health professionals and other stakeholders. Methods/Design This two-arm cluster randomized controlled trial (with integral economic evaluation and qualitative study) is set in general practices in three UK Primary Care Trusts. Practices are randomized to one of two groups with patients referred to either an ICCD (intervention) or to hospital care (control). Intervention group: GP practices in the intervention arm have the opportunity to refer patients to an ICCD - a multidisciplinary team led by a specialist nurse and a diabetologist. Patients are reviewed and managed in the ICCD for a short period with a goal of improving diabetes and cardiovascular risk factor control and are then referred back to practice. or Control group: Standard GP care, with referral to secondary care as required, but no access to ICCD. Participants are adults aged 18 years or older who have type 2 diabetes that is difficult for their GPs to control. The primary outcome is the proportion of participants reaching three risk factor targets: HbA1c (≤7.0%); blood pressure (<140/80); and cholesterol (<4 mmol/l), at the end of the 18-month intervention period. The main secondary outcomes are the proportion of participants reaching individual risk factor targets and the overall 10-year risks for coronary heart disease(CHD) and stroke assessed by the United Kingdom Prospective Diabetes Study (UKPDS) risk engine. Other secondary outcomes include body mass index and waist circumference, use of medication, reported smoking, emotional adjustment, patient satisfaction and views on continuity, costs and health related quality of life. We aimed to randomize 50 practices and recruit 2,555 patients

Semi-Holographic Fermi Liquids

We show that the universal physics of recent holographic non-Fermi liquid models is captured by a semi-holographic description, in which a dynamical boundary field is coupled to a strongly coupled conformal sector having a gravity dual. This allows various generalizations, such as a dynamical exponent and lattice and impurity effects. We examine possible relevant deformations, including multi-trace terms and spin-orbit effects. We discuss the matching onto the UV theory of the earlier work, and an alternate description in which the boundary field is integrated out.Comment: 26 pages, 4 figures; v2: typos corrected and report number adde

The linear multiplet and ectoplasm

In the framework of the superconformal tensor calculus for 4D N=2 supergravity, locally supersymmetric actions are often constructed using the linear multiplet. We provide a superform formulation for the linear multiplet and derive the corresponding action functional using the ectoplasm method (also known as the superform approach to the construction of supersymmetric invariants). We propose a new locally supersymmetric action which makes use of a deformed linear multiplet. The novel feature of this multiplet is that it corresponds to the case of a gauged central charge using a one-form potential not annihilated by the central charge (unlike the standard N=2 vector multiplet). Such a gauge one-form can be chosen to describe a variant nonlinear vector-tensor multiplet. As a byproduct of our construction, we also find a variant realization of the tensor multiplet in supergravity where one of the auxiliaries is replaced by the field strength of a gauge three-form.Comment: 31 pages; v3: minor corrections and typos fixed, version to appear in JHE