The impact of adjusting for baseline in pharmacogenomic genome-wide association studies of quantitative change.

In pharmacogenomic studies of quantitative change, any association between genetic variants and the pretreatment (baseline) measurement can bias the estimate of effect between those variants and drug response. A putative solution is to adjust for baseline. We conducted a series of genome-wide association studies (GWASs) for low-density lipoprotein cholesterol (LDL-C) response to statin therapy in 34,874 participants of the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort as a case study to investigate the impact of baseline adjustment on results generated from pharmacogenomic studies of quantitative change. Across phenotypes of statin-induced LDL-C change, baseline adjustment identified variants from six loci meeting genome-wide significance (SORT/CELSR2/PSRC1, LPA, SLCO1B1, APOE, APOB, and SMARCA4/LDLR). In contrast, baseline-unadjusted analyses yielded variants from three loci meeting the criteria for genome-wide significance (LPA, APOE, and SLCO1B1). A genome-wide heterogeneity test of baseline versus statin on-treatment LDL-C levels was performed as the definitive test for the true effect of genetic variants on statin-induced LDL-C change. These findings were generally consistent with the models not adjusting for baseline signifying that genome-wide significant hits generated only from baseline-adjusted analyses (SORT/CELSR2/PSRC1, APOB, SMARCA4/LDLR) were likely biased. We then comprehensively reviewed published GWASs of drug-induced quantitative change and discovered that more than half (59%) inappropriately adjusted for baseline. Altogether, we demonstrate that (1) baseline adjustment introduces bias in pharmacogenomic studies of quantitative change and (2) this erroneous methodology is highly prevalent. We conclude that it is critical to avoid this common statistical approach in future pharmacogenomic studies of quantitative change

Digital technologies and youth mobility in rural Zimbabwe

The adoption and use of digital technologies (DTs) in rural communities have an impact on several aspects of the society. Using empirical evidence from selected villages of Beitbridge district in Zimbabwe, this study examines the relationship between DTs and youth mobility. The different types, causes, and motifs associated with youth mobilities are explored using qualitative research methods including focus group discussions and community visioning workshops. Study findings reveal challenges facing youths in trying to be mobile including social (mainly gender) inequalities. Thus, women were found to be less mobile. Lack of infrastructure was found to be another key challenge impacting youth mobility. The study however found that DTs are being adopted and this has led to virtual mobilities, which is redefining youth mobility. The opportunities and challenges of integrating virtual mobilities and physical mobilities were explored. The study findings are critical to various actors including ICT, education, and other sectors in that they show opportunities that need to be expropriated to enhance youth mobility, which is key to socio‐economic well‐being of youths, as well as the challenges that can be faced through the ubiquity of DTs

Astrophysical factors:Zero energy vs. Most effective energy

Effective astrophysical factors for non-resonant astrophysical nuclear reaction are invariably calculated with respect to a zero energy limit. In the present work that limit is shown to be very disadvantageous compared to the more natural effective energy limit. The latter is used in order to modify the thermonuclear reaction rate formula so that it takes into account both plasma and laboratory screening effects.Comment: 7 RevTex pages. Accepted for publication in Phys.Rev.

Experimental scheme for quantum teleportation of a single-photon packet

Both complete protocol and optical setup for experimental realization of quantum teleportation of unknown single-photon wave packet are proposed.Comment: 7 pages, 1 figure (under request

New Mechanism for Electronic Energy Relaxation in Nanocrystals

The low-frequency vibrational spectrum of an isolated nanometer-scale solid differs dramatically from that of a bulk crystal, causing the decay of a localized electronic state by phonon emission to be inhibited. We show, however, that an electron can also interact with the rigid translational motion of a nanocrystal. The form of the coupling is dictated by the equivalence principle and is independent of the ordinary electron-phonon interaction. We calculate the rate of nonradiative energy relaxation provided by this mechanism and establish its experimental observability.Comment: 4 pages, Submitted to Physical Review

Model-Independent Comparison of Direct vs. Indirect Detection of Supersymmetric Dark Matter

We compare the rate for elastic scattering of neutralinos from various nuclei with the flux of upward muons induced by energetic neutrinos from neutralino annihilation in the Sun and Earth. We consider both scalar and axial-vector interactions of neutralinos with nuclei. We find that the event rate in a kg of germanium is roughly equivalent to that in a $10^5$- to $10^7$-m$^2$ muon detector for a neutralino with primarily scalar coupling to nuclei. For an axially coupled neutralino, the event rate in a 50-gram hydrogen detector is roughly the same as that in a 10- to 500-m$^2$ muon detector. Expected experimental backgrounds favor forthcoming elastic-scattering detectors for scalar couplings while the neutrino detectors have the advantage for axial-vector couplings.Comment: 10 pages, self-unpacking uuencoded PostScript fil

LIGHT PHOTINOS AS DARK MATTER

There are good reasons to consider models of low-energy supersymmetry with very light photinos and gluinos. In a wide class of models the lightest $R$-odd, color-singlet state containing a gluino, the $\r0$, has a mass in the 1-2 GeV range and the slightly lighter photino, \pho, would survive as the relic $R$-odd species. For the light photino masses considered here, previous calculations resulted in an unacceptable photino relic abundance. But we point out that processes other than photino self-annihilation determine the relic abundance when the photino and $R^0$ are close in mass. Including \r0\longleftrightarrow\pho processes, we find that the photino relic abundance is most sensitive to the $\r0$-to-\pho mass ratio, and within model uncertainties, a critical density in photinos may be obtained for an $\r0$-to-\pho mass ratio in the range 1.2 to 2.2. We propose photinos in the mass range of 500 MeV to 1.6 GeV as a dark matter candidate, and discuss a strategy to test the hypothesis.Comment: uuencoded compressed tar file containing 32 page LaTeX file and eight postscript figure

Indirect Detection of a Light Higgsino Motivated by Collider Data

Kane and Wells recently argued that collider data point to a Higgsino-like lightest supersymmetric partner which would explain the dark matter in our Galactic halo. They discuss direct detection of such dark-matter particles in laboratory detectors. Here, we argue that such a particle, if it is indeed the dark matter, might alternatively be accessible in experiments which search for energetic neutrinos from dark-matter annihilation in the Sun. We provide accurate analytic estimates for the rates which take into account all relevant physical effects. Currently, the predicted signal falls roughly one to three orders of magnitude below experimental bounds, depending on the mass and coupling of the particle; however, detectors such as MACRO, super-Kamiokande, and AMANDA will continue to take data and should be able to rule out or confirm an interesting portion of the possible mass range for such a dark-matter particle within the next five years.Comment: 10 pages, RevTe

On the direct search for spin-dependent WIMP interactions

We examine the current directions in the search for spin-dependent dark matter. We discover that, with few exceptions, the search activity is concentrated towards constraints on the WIMP-neutron spin coupling, with significantly less impact in the WIMP-proton sector. We review the situation of those experiments with WIMP-proton spin sensitivity, toward identifying those capable of reestablishing the balance.Comment: 7 pages, 4 figure