Computing Individual Risks based on Family History in Genetic Disease in the Presence of Competing Risks

When considering a genetic disease with variable age at onset (ex: diabetes , familial amyloid neuropathy, cancers, etc.), computing the individual risk of the disease based on family history (FH) is of critical interest both for clinicians and patients. Such a risk is very challenging to compute because: 1) the genotype X of the individual of interest is in general unknown; 2) the posterior distribution P(X|FH, T > t) changes with t (T is the age at disease onset for the targeted individual); 3) the competing risk of death is not negligible. In this work, we present a modeling of this problem using a Bayesian network mixed with (right-censored) survival outcomes where hazard rates only depend on the genotype of each individual. We explain how belief propagation can be used to obtain posterior distribution of genotypes given the FH, and how to obtain a time-dependent posterior hazard rate for any individual in the pedigree. Finally, we use this posterior hazard rate to compute individual risk, with or without the competing risk of death. Our method is illustrated using the Claus-Easton model for breast cancer (BC). This model assumes an autosomal dominant genetic risk factor such as non-carriers (genotype 00) have a BC hazard rate $\lambda$ 0 (t) while carriers (genotypes 01, 10 and 11) have a (much greater) hazard rate $\lambda$ 1 (t). Both hazard rates are assumed to be piecewise constant with known values (cuts at 20, 30,. .. , 80 years). The competing risk of death is derived from the national French registry

Fully representable and *-semisimple topological partial *-algebras

We continue our study of topological partial *-algebras, focusing our attention to *-semisimple partial *-algebras, that is, those that possess a {multiplication core} and sufficiently many *-representations. We discuss the respective roles of invariant positive sesquilinear (ips) forms and representable continuous linear functionals and focus on the case where the two notions are completely interchangeable (fully representable partial *-algebras) with the scope of characterizing a *-semisimple partial *-algebra. Finally we describe various notions of bounded elements in such a partial *-algebra, in particular, those defined in terms of a positive cone (order bounded elements). The outcome is that, for an appropriate order relation, one recovers the \M-bounded elements introduced in previous works.Comment: 26 pages, Studia Mathematica (2012) to appea

Achieving the Millennium Development Goals: What’s wrong with existing analytical models?

This study critically evaluates analytical models presently used to estimate the cost of achieving the Millennium Development Goals (MDGs) from sources including the UN Millennium Project, the UN Development Programme, the World Bank and the Zedillo Commission. Effective strategic choices for achieving the MDGs must be based on sound assessments of the costs and benefits of alternative policies. However, the existing approaches are unreliable. They derive from implausible and restrictive assumptions, depend on poor quality data, and are undermined by the presence of large uncertainties concerning the future. An alternative and less technocratic approach to planning is required.poverty, development, Millennium Development Goals

A limit for large RR-charge correlators in N=2\mathcal{N}=2 theories

Using supersymmetric localization, we study the sector of chiral primary operators $({\rm Tr} \, \phi^2 )^n$ with large $R$-charge $4n$ in $\mathcal{N}=2$ four-dimensional superconformal theories in the weak coupling regime $g\rightarrow 0$, where $\lambda\equiv g^2n$ is kept fixed as $n\to\infty$, $g$ representing the gauge theory coupling(s). In this limit, correlation functions $G_{2n}$ of these operators behave in a simple way, with an asymptotic behavior of the form $G_{2n}\approx F_{\infty}(\lambda) \left(\frac{\lambda}{2\pi e}\right)^{2n}\ n^\alpha$, modulo $O(1/n)$ corrections, with $\alpha=\frac{1}{2} \mathrm{dim}(\mathfrak{g})$ for a gauge algebra $\mathfrak{g}$ and a universal function $F_{\infty}(\lambda)$. As a by-product we find several new formulas both for the partition function as well as for perturbative correlators in ${\cal N}=2$ $\mathfrak{su}(N)$ gauge theory with $2N$ fundamental hypermultiplets

Family history in the Aetiology of Gestational Diabetes Mellitus and Type 2 Diabetes

The aetiology of Type 2 diabetes [NIDDM] is assumed to involve a multiplicity of causal factors involving both genetic and environmental, including intrauterine, components. Aim: To identify the relationship of various aspects of family history and hence the possible role of genetic influence in the development of Type 2 DM in the Maltese population. Methods: The family history details of a study population undergoing an oGTT during pregnancy was assessed during pregnancy and at follow-up eight years postpartum. The findings were related to previous national epidemiological studies. Results: The study showed a definite statistical correlation between a maternal and sibling family history of diabetes with the onset of GDM/GIGT and later Type 2 DM. No such correlation was shown with a paternal or grandparent family history. Conclusions: The findings suggest that genetic factors are poor determinants for adult-onset GDM or Type 2 DM, the major role player being apparently alterations in the intrauterine environment of the fetus.peer-reviewe

Study and interpretation of the millimeter-wave spectrum of Venus

The effects of the Venus atmospheric constituents on its millimeter wavelength emission are investigated. Specifically, this research describes the methodology and the results of laboratory measurements which are used to calculate the opacity of some of the major absorbers in the Venus atmosphere. The pressure broadened absorption of gaseous SO2/CO2 and gaseous H2SO4/CO2 has been measured at millimeter wavelengths. We have also developed new formalisms for computing the absorptivities of these gases based on our laboratory work. The complex dielectric constant of liquid sulfuric acid has been measured and the expected opacity from the liquid sulfuric acid cloud layer found in the atmosphere of Venus has been evaluated. The partial pressure of gaseous H2SO4 has been measured which results in a more accurate estimate of the dissociation factor of H2SO4. A radiative transfer model has been developed in order to understand how each atmospheric constituent affects the millimeter wave emissions from Venus. Our results from the radiative transfer model are compared with recent observations of the micro-wave and millimeter wave emissions from Venus. Our main conclusion from this work is that gaseous H2SO4 is the most likely cause of the variation in the observed emission from Venus at 112 GHz

Understanding the variation in the millimeter-wave emission of Venus

Recent observations of the millimeter-wave emission from Venus at 112 GHz (2.6 mm) have shown significant variations in the continuum flux emission that may be attributed to the variability in the abundances of absorbing constituents in the Venus atmosphere. Such constituents include gaseous H2SO4, SO2, and liquid sulfuric acid (cloud condensates). Recently, Fahd and Steffes have shown that the effects of liquid H, SO4, and gaseous SO2 cannot completely account for this measured variability in the millimeter-wave emission of Venus. Thus, it is necessary to study the effect of gaseous H2SO4 on the millimeter-wave emission of Venus. This requires knowledge of the millimeter-wavelength (MMW) opacity of gaseous H2SO4, which unfortunately has never been determined for Venus-like conditions. We have measured the opacity of gaseous H2SO4 in a CO2 atmosphere at 550, 570, and 590 K, at 1 and 2 atm total pressure, and at a frequency of 94.1 GHz. Our results, in addition to previous centimeter-wavelength results are used to verify a modeling formalism for calculating the expected opacity of this gaseous mixture at other frequencies. This formalism is incorporated into a radiative transfer model to study the effect of gaseous H2SO4 on the MMW emission of Venus

Geological indicators for impact: The anomalous case of the Vredefort structure, South Africa

The Vredefort Dome is located within and almost central to the Witwatersrand basin in its presently known extent. It exposes a central Archean granite core which is surrounded by a collar of supracrustal rocks. These collar rocks outline a strong polygonal geometry. The Archean core is comprised of two concentric zones, the Outer Granite Gneiss (OGG), and the core central Inlandsee Leucogranofels (ILG). The rocks of the inner core display granulite facies metamorphism, while the OGG is in amphibolite facies. The inner core is believed from recent drill hole information to be underlain by mafic and ultramafic gneisses, the extent of which cannot be assessed at present. A fairly broad zone of charnockites separates the OGG and ILG domains. This zone is characterized by a high concentration of pseudotachylite and ductile shearing. Whereas a number of other domical structures are located within or surrounding the Witwatersrand basin, the Vredefort structure is anomalous, in that it has: a partly polygonal geometry; extensive alkali intrusives in the northwestern sector; granophyre dykes (ring-dykes peripheral to the contact collar-basement and NW-SE or NE-SW trending dykes within the Archean basement); contact metamorphism of the collar supracrustal rocks; the overturning of collar supracrustals in the northern sectors; deformation phenomena widely regarded as representing shock metamorphism (pseudotachylite, (sub)planar microdeformation features in quartz, shatter cones and occurrences of high-P quartz polymorphs); a positive 30 mgal gravity anomaly; and high amplitude magnetic anomalies. Recent geophysical, structural and petrological evidence pertinent for the identification of the processes that led to the formation of the Vredefort structure are summarized

Fuels characterization studies

Current analytical techniques used in the characterization of broadened properties fuels are briefly described. Included are liquid chromatography, gas chromatography, and nuclear magnetic resonance spectroscopy. High performance liquid chromatographic ground-type methods development is being approached from several directions, including aromatic fraction standards development and the elimination of standards through removal or partial removal of the alkene and aromatic fractions or through the use of whole fuel refractive index values. More sensitive methods for alkene determinations using an ultraviolet-visible detector are also being pursued. Some of the more successful gas chromatographic physical property determinations for petroleum derived fuels are the distillation curve (simulated distillation), heat of combustion, hydrogen content, API gravity, viscosity, flash point, and (to a lesser extent) freezing point