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

Clusters of Exceptional Points for a Laser Control of Selective Vibrational Transfer

When a molecule is exposed to a laser field, all field-free vibrational states become resonances, with complex quasi energies calculated using Floquet theory. There are many ways to produce the coalescences of pairs of such quasi energies, with appropriate wavelength-intensity choices which define Exceptional Points (EP) in the laser parameter plane. We dress for the molecular ion H$_2^+$ an exhaustive map of these exceptional points which appear in clusters. Such clusters can be used to define several vibrational transfer scenarios implying more than a single exceptional point, exchanging single or multiple vibrational quanta. The ultimate goal is molecular vibrational cooling by transferring an initial (thermal, for instance) population on a final (ground, for instance) single vibrational state. When a molecule is exposed to a laser field, all field-free vibrational states become resonances, with complex quasi energies calculated using Floquet theory. There are many ways to produce the coalescences of pairs of such quasi energies, with appropriate wavelength-intensity choices which define Exceptional Points (EP) in the laser parameter plane. We dress for the molecular ion H$_2^+$ an exhaustive map of these exceptional points which appear in clusters. Such clusters can be used to define several vibrational transfer scenarios implying more than a single exceptional point, exchanging single or multiple vibrational quanta. The ultimate goal is molecular vibrational cooling by transferring an initial (thermal, for instance) population on a final (ground, for instance) single vibrational state.Comment: 16 pages, 7 figures, 1 tabl

Class Size for the Basic Communication Course: A Recommendation for the Dean

Authors were asked to prepare an essay as if they were writing a letter to their dean (whose academic training was in another discipline) who (1) asked that enrollment in each basic course section be increased to a level that compromises the pedagogy of the basic course or (2) proposed that the required basic communication course be eliminated from the university’s general education program

Observation of Feshbach resonances in an ultracold gas of 52{}^{52}Cr

We have observed Feshbach resonances in elastic collisions between ultracold ${}^{52}$Cr atoms. This is the first observation of collisional Feshbach resonances in an atomic species with more than one valence electron. The zero nuclear spin of ${}^{52}$Cr and thus the absence of a Fermi-contact interaction leads to regularly-spaced resonance sequences. By comparing resonance positions with multi-channel scattering calculations we determine the s-wave scattering length of the lowest $^{2S+1}\Sigma_{g}^{+}$ potentials to be \unit[112(14)]{a_0}, \unit[58(6)]{a_0} and -\unit[7(20)]{a_0} for S=6, 4, and 2, respectively, where a_{0}=\unit[0.0529]{nm}.Comment: 4 pages, 2 figures, 1 tabl

Fourier transform spectroscopy and coupled-channel deperturbation treatment of the A1Sigma+ ~ b3Pi complex of KCs molecule

The laser induced fluorescence (LIF) spectra A1Sigma ~ b3Pi --> X1Sigma+ of KCs dimer were recorded in near infrared region by Fourier Transform Spectrometer with a resolution of 0.03 cm-1. Overall more than 200 LIF spectra were rotationally assigned to 39K133Cs and 41K133Cs isotopomers yielding with the uncertainty of 0.003-0.01 cm-1 more than 3400 rovibronic term values of the strongly mixed singlet A1Sigma+ and triplet b3Pi states. Experimental data massive starts from the lowest vibrational level v_A=0 of the singlet and nonuniformly cover the energy range from 10040 to 13250 cm-1 with rotational quantum numbers J from 7 to 225. Besides of the dominating regular A1Sigma+ ~ b3P Omega=0 interactions the weak and local heterogenous A1S+ ~ b3P Omega=1 perturbations have been discovered and analyzed. Coupled-channel deperturbation analysis of the experimental 39K133Cs e-parity termvalues of the A1S+ ~ b3P complex was accomplished in the framework of the phenomenological 4 x 4 Hamiltonian accounting implicitly for regular interactions with the remote states manifold. The resulting diabatic potential energy curves of the interacting states and relevant spin-orbit coupling matrix elements defined analytically by Expanded Morse Oscillators model reproduce 95% of experimental data field of the 39K133Cs isotopomer with a standard deviation of 0.004 cm-1 which is consistent with the uncertainty of the experiment. Reliability of the derived parameters was additionally confirmed by a good agreement between the predicted and experimental termvalues of 41K133Cs isotopomer. Calculated intensity distributions in the A ~ b --> X LIF progressions are also consistent with their experimental counterparts.Comment: 17 pages, 14 figure

Why us? Perceived injustice is associated with more sexual and psychological distress in couples coping with genito-pelvic pain

Introduction Provoked vestibulodynia (PVD) is the most frequent cause of genito-pelvic pain/penetration disorder (GPPPD) and is associated with negative psychological and sexual consequences for affected women and their partners. PVD is often misdiagnosed or ignored and many couples may experience a sense of injustice, due to the loss of their ability to have a normal sexual life. Perceiving injustice has been documented to have important consequences in individuals with chronic pain. However, no quantitative research has investigated the experience of injustice in this population. Aim The aim of this study was to investigate the associations between perceived injustice and pain, sexual satisfaction, sexual distress, and depression among women with PVD and their partners. Methods Women diagnosed with PVD (N = 50) and their partners completed questionnaires of perceived injustice, pain, sexual satisfaction, sexual distress, and depression. Main Outcome Measures (1) Global Measure of Sexual Satisfaction Scale; (2) Female Sexual Distress Scale; (3) Beck Depression Inventory-II; and (4) McGill-Melzack Pain Questionnaire. Results After controlling for partners' age, women's higher level of perceived injustice was associated with their own greater sexual distress, and the same pattern was found for partners. Women's higher level of perceived injustice was associated with their own greater depression, and the same pattern was found for partners. Women's higher perceived injustice was not associated with their own lower sexual satisfaction but partners' higher perceived injustice was associated with their own lower sexual satisfaction. Perceived injustice was not associated with women's pain intensity. Conclusion Results suggest that perceiving injustice may have negative consequences for the couple's sexual and psychological outcomes. However, the effects of perceived injustice appear to be intra-individual. Targeting perceived injustice could enhance the efficacy of psychological interventions for women with PVD and their partners

Basal lamina remodeling at the skeletal muscle stem cell niche mediates stem cell self-renewal

A central question in stem cell biology is the relationship between stem cells and their niche. Although previous reports have uncovered how signaling molecules released by niche cells support stem cell function, the role of the extra-cellular matrix (ECM) within the niche is unclear. Here, we show that upon activation, skeletal muscle stem cells (satellite cells) induce local remodeling of the ECM and the deposition of laminin-α1 and laminin-α5 into the basal lamina of the satellite cell niche. Genetic ablation of laminin-α1, disruption of integrin-α6 signaling or blocking matrix metalloproteinase activity impairs satellite cell expansion and self-renewal. Collectively, our findings establish that remodeling of the ECM is an integral process of stem cell activity to support propagation and self-renewal, and may explain the effect laminin-α1-containing supports have on embryonic and adult stem cells, as well as the regenerative activity of exogenous laminin-111 therapy

adiabatic versus nonadiabatic dressed-state dynamics

We discuss how a recent pump-probe study [Kelkensberg et al., Phys. Rev. Lett. 103, 123005 (2009)] of the dissociative ionization of H2, under the combined effect of a single extreme ultraviolet attosecond pulse and an intense near- infrared pulse, actually represents a transition-state spectroscopy of the strong-field dissociation step, i.e., of the (probe-pulse-)dressed H2+ molecular ion. The way the dissociation dynamics is influenced by the duration of the near-infrared probe pulse, and by the time delay between the two pulses, is discussed in terms of adiabatic versus nonadiabatic preparation and transport of time-parametrized Floquet resonances associated with the dissociating molecular ion. Under a long probe pulse, the field-free vibrational states of the initial wave packet are transported, in a one-to-one manner, onto the Floquet resonances defined by the field intensity of the probe pulse and propagated adiabatically under the pulse. As the probe pulse duration shortens, nonadiabatic transitions between the Floquet resonances become important and manifest themselves in two respects: first, as a vibrational shake-up effect occurring near the peak of the short pulse, and second, through strong interference patterns in the fragment's kinetic energy spectrum, viewed as a function of the time delay between the pump and the probe pulses

A systematic review of non-pharmacological interventions for primary Sjögren’s syndrome

The objective of this systematic review was to assess the efficacy of non-pharmacological interventions for the management of primary Sjögren’s syndrome. We searched the following databases from inception to September 2014; Cochrane Database of Systematic Reviews; Medline; Embase; PsychINFO; Cinahl and clinical trials registers. We included randomised controlled trials of any non-pharmacological interventions. Two review authors independently reviewed titles and abstracts against the inclusion/exclusion criteria and independently assessed trial quality and extracted data. 1463 studies were identified of which 17 full text articles were screened and 5 studies were included in the review with a total of 130 participants randomised. The included studies investigated effectiveness of an oral lubricating device for dry mouth, acupuncture for dry mouth, lacrimal punctum plugs for dry eyes and psychodynamic group therapy for coping with symptoms. Overall the studies were of low quality and at high risk of bias. Although one study showed punctum plugs to improve dry eyes it was too small for the findings to be conclusive. Overall we identified no evidence to support any non-pharmacological interventions to improve PSS. The area needs quality large randomised controlled trials that are reported according to CONSORT guidelines and address important issues to patients