Signalling paediatric side effects using an ensemble of simple study designs

Background: Children are frequently prescribed medication `o-label', meaning there has not been sucient testing of the medication to determine its safety or eectiveness. The main reason this safety knowledge is lacking is due to ethical restrictions that prevent children from being included in the majority of clinical trials. Methods: Multiple measures of association are calculated for each drug and medical event pair and these are used as features that are fed into a classifier to determine the likelihood of the drug and medical event pair corresponding to an adverse drug reaction. The classier is trained using known adverse drug reactions or known non-adverse drug reaction relationships. Results: The novel ensemble framework obtained a false positive rate of 0:149, a sensitivity of 0:547 and a specificity of 0:851 when implemented on a reference set of drug and medical event pairs. The novel framework consistently outperformed each individual simple study design. Conclusion: This research shows that it is possible to exploit the mechanism of causality and presents a framework for signalling adverse drug reactions eectively

A novel semi-supervised algorithm for rare prescription side effect discovery

Drugs are frequently prescribed to patients with the aim of improving each patient's medical state, but an unfortunate consequence of most prescription drugs is the occurrence of undesirable side effects. Side effects that occur in more than one in a thousand patients are likely to be signalled efficiently by current drug surveillance methods, however, these same methods may take decades before generating signals for rarer side effects, risking medical morbidity or mortality in patients prescribed the drug while the rare side effect is undiscovered. In this paper we propose a novel computational meta-analysis framework for signalling rare side effects that integrates existing methods, knowledge from the web, metric learning and semi-supervised clustering. The novel framework was able to signal many known rare and serious side effects for the selection of drugs investigated, such as tendon rupture when prescribed Ciprofloxacin or Levofloxacin, renal failure with Naproxen and depression associated with Rimonabant. Furthermore, for the majority of the drug investigated it generated signals for rare side effects at a more stringent signalling threshold than existing methods and shows the potential to become a fundamental part of post marketing surveillance to detect rare side effects

The Atomic Limit of the Boson-Fermion Model

The Boson-Fermion model, describing a mixture of hybridized localized Bosons and itinerant Fermions on a lattice, is known to exhibit spectral properties for the Fermions which upon lowering the temperature develop into a three pole structure in the vicinity of the Fermi level. These spectral features go hand in hand with the opening of a pseudogap in the density of states upon approaching the critical temperature Tc when superconductivity sets in. In the present work we study this model, in the atomic limit where the three pole structure arises naturally from the local bonding, anti-bonding and non-bonding states between the Bosons and Fermions.Comment: revtex, 9 pages and 6 eps figures. Submitted to Europhysics Letter

Magnetic Field induced Dimensional Crossover Phenomena in Cuprate Superconductors and their Implications

We discuss the occurrence of crossing points in the magnetization - temperature $(m,T$) plane within the framework of critical phenomena. It is shown that in a two-dimensional superconducting slab of thickness $d_{s}$ $m_{z}(\delta)$ versus temperature $T$ curves measured in different fields $\mathbf{H} = H(0,\sin (\delta) ,\cos (\delta))$ will cross at the critical temperature T_c of the slab. In contrast, in a 3D anisotropic bulk superconductor the crossing point occurs in the plot $m_{z}(\delta) /H_{z}^{1/2}$ versus $T$. The experimental facts that 2D crossing point features have been observed in ceramics and in single crystals for $\mathbf{H}$ close to $\mathbf{H} = H(0,0,1)$, but not for $\mathbf{H} = H(0,1,0)$, is explained in terms of an angle-dependent crossover field separating the regions where 2D or 3D thermal fluctuations dominate. The measured 2D-crossing point data are used to estimate one of the fundamental parameters of cuprate superconductors, the minimum thickness of the slab $(d_{s})$, which remains superconducting. Our estimates, based on experimental 2D-crossing point data for single crystals, reveal that this length adopts material dependent values. Therefore, experimental data for T_c and $\lambda_{\Vert}^{2}(T=0)$, plotted in terms of T_c versus $1/\lambda_{\Vert}^{2}(T=0)$ will not tend to a straight line with universal slope as the underdoped limit is approached. Implications for magnetic torque measurements are also worked out

Glacial isostatic adjustment associated with the Barents Sea ice sheet: a modelling inter-comparison

The 3D geometrical evolution of the Barents Sea Ice Sheet (BSIS), particularly during its late-glacial retreat phase, remains largely ambiguous due to the paucity of direct marine- and terrestrial-based evidence constraining its horizontal and vertical extent and chronology. One way of validating the numerous BSIS reconstructions previously proposed is to collate and apply them under a wide range of Earth models and to compare prognostic (isostatic) output through time with known relative sea-level (RSL) data. Here we compare six contrasting BSIS load scenarios via a spherical Earth system model and derive a best-fit, χ2 parameter using RSL data from the four main terrestrial regions within the domain: Svalbard, Franz Josef Land, Novaya Zemlya and northern Norway. Poor χ2 values allow two load scenarios to be dismissed, leaving four that agree well with RSL observations. The remaining four scenarios optimally fit the RSL data when combined with Earth models that have an upper mantle viscosity of 0.2–2 × 1021 Pa s, while there is less sensitivity to the lithosphere thickness (ranging from 71 to 120 km) and lower mantle viscosity (spanning 1–50 × 1021 Pa s). GPS observations are also compared with predictions of present-day uplift across the Barents Sea. Key locations where relative sea-level and GPS data would prove critical in constraining future ice-sheet modelling efforts are also identified

A local families index formula for d-bar operators on punctured Riemann surfaces

Using heat kernel methods developed by Vaillant, a local index formula is obtained for families of d-bar operators on the Teichmuller universal curve of Riemann surfaces of genus g with n punctures. The formula also holds on the moduli space M{g,n} in the sense of orbifolds where it can be written in terms of Mumford-Morita-Miller classes. The degree two part of the formula gives the curvature of the corresponding determinant line bundle equipped with the Quillen connection, a result originally obtained by Takhtajan and Zograf.Comment: 47 page

A planar diagram approach to the correlation problem

We transpose an idea of 't Hooft from its context of Yang and Mills' theory of strongly interacting quarks to that of strongly correlated electrons in transition metal oxides and show that a Hubbard model of N interacting electron species reduces, to leading orders in N, to a sum of almost planar diagrams. The resulting generating functional and integral equations are very similar to those of the FLEX approximation of Bickers and Scalapino. This adds the Hubbard model at large N to the list of solvable models of strongly correlated electrons. PACS Numbers: 71.27.+a 71.10.-w 71.10.FdComment: revtex, 5 pages, with 3 eps figure

D-XY Critical Behavior in Cuprate Superconductors

We outline the universal and finite temperature critical properties of the 3D-XY model, extended to anisotropic extreme type-II superconductors, as well as the universal quantum critical properties in 2D. On this basis we review: (i) the mounting evidence for 3D-XY behavior in optimally doped cuprate superconductors and the 3D to 2D crossover in the underdoped regime; (ii) the finite size limitations imposed by inhomogeneities; (iii) the experimental evidence for a 2D-XY quantum critical point in the underdoped limit, where the superconductor to insulator transition occurs; (iv) the emerging implications and constraints for microscopic models.Comment: 5 pages, 6 figure

A physical activity intervention to improve the quality of life of patients with a stoma:a feasibility study protocol

Background: Physical activity (PA) is positively associated with quality of life. People with a stoma are less likely to engage in PA than those without a stoma. Methods: In this feasibility intervention study, we will perform the following: (1) Develop a PA intervention for people with a stoma. An Expert Working Group of behavioural scientists, exercise scientists, clinicians and a Patient Advisory Group of people with a bowel stoma will meet with the research team to inform the development of a PA intervention for people with a stoma. A manual of the intervention will be the main output. (2) Explore PA instructors' experiences of delivering the PA intervention. PA instructors will record on paper the number of PA consultations with each patient and a researcher will interview the PA instructors about their experiences of delivering the intervention. (3) Assess the level of patient (bowel cancer or inflammatory bowel disease (IBD) patients with a stoma between 6 weeks and 24 months postsurgery) engagement with the PA intervention and their views on intervention acceptability and usefulness. Patients will keep a PA diary to record daily pedometer recorded step count and type and duration of activities. A researcher will interview patients about their experiences of the PA intervention. (4) Assess screening, eligibility, consent, data completion, loss to follow up, and missing data rates, representativeness of participants and potential treatment effects. A researcher will record on paper all study procedure parameters. Quality of life (stoma-quality of life; Functional Assessment of Cancer Therapy, Short IBD questionnaire), fatigue (FACIT fatigue scale) and PA (accelerometer) will be measured pre- and post-intervention in patients. For IBD patients only, blood will be taken to measure systemic inflammation. Discussion: We hypothesise that a PA intervention will be an effective means of improving the quality of life of people with a stoma. Before embarking on a full randomised controlled trial to test this hypothesis, a PA intervention needs to be developed and a feasibility study of the proposed PA intervention conducted.</p

Stability and reproducibility of co-electrospun brain-mimicking phantoms for quality assurance of diffusion MRI sequences

Grey and white matter mimicking phantoms are important for assessing variations in diffusion MR measures at a single time point and over an extended period of time. This work investigates the stability of brain-mimicking microfibre phantoms and reproducibility of their MR derived diffusion parameters. The microfibres were produced by co-electrospinning and characterized by scanning electron microscopy (SEM). Grey matter and white matter phantoms were constructed from random and aligned microfibres, respectively. MR data were acquired from these phantoms over a period of 33 months. SEM images revealed that only small changes in fibre microstructure occurred over 30 months. The coefficient of variation in MR measurements across all time-points was between 1.6% and 3.4% for MD across all phantoms and FA in white matter phantoms. This was within the limits expected for intra-scanner variability, thereby confirming phantom stability over 33 months. These specialised diffusion phantoms may be used in a clinical environment for intra and inter-site quality assurance purposes, and for validation of quantitative diffusion biomarkers