Sufficient Covariate, Propensity Variable and Doubly Robust Estimation

Statistical causal inference from observational studies often requires adjustment for a possibly multi-dimensional variable, where dimension reduction is crucial. The propensity score, first introduced by Rosenbaum and Rubin, is a popular approach to such reduction. We address causal inference within Dawid's decision-theoretic framework, where it is essential to pay attention to sufficient covariates and their properties. We examine the role of a propensity variable in a normal linear model. We investigate both population-based and sample-based linear regressions, with adjustments for a multivariate covariate and for a propensity variable. In addition, we study the augmented inverse probability weighted estimator, involving a combination of a response model and a propensity model. In a linear regression with homoscedasticity, a propensity variable is proved to provide the same estimated causal effect as multivariate adjustment. An estimated propensity variable may, but need not, yield better precision than the true propensity variable. The augmented inverse probability weighted estimator is doubly robust and can improve precision if the propensity model is correctly specified

The cell cycle regulatory DREAM complex is disrupted by high expression of oncogenic B-Myb.

Overexpression of the oncogene MYBL2 (B-Myb) is associated with increased cell proliferation and serves as a marker of poor prognosis in cancer. However, the mechanism by which B-Myb alters the cell cycle is not fully understood. In proliferating cells, B-Myb interacts with the MuvB core complex including LIN9, LIN37, LIN52, RBBP4, and LIN54, forming the MMB (Myb-MuvB) complex, and promotes transcription of genes required for mitosis. Alternatively, the MuvB core interacts with Rb-like protein p130 and E2F4-DP1 to form the DREAM complex that mediates global repression of cell cycle genes in G0/G1, including a subset of MMB target genes. Here, we show that overexpression of B-Myb disrupts the DREAM complex in human cells, and this activity depends on the intact MuvB-binding domain in B-Myb. Furthermore, we found that B-Myb regulates the protein expression levels of the MuvB core subunit LIN52, a key adapter for assembly of both the DREAM and MMB complexes, by a mechanism that requires S28 phosphorylation site in LIN52. Given that high expression of B-Myb correlates with global loss of repression of DREAM target genes in breast and ovarian cancer, our findings offer mechanistic insights for aggressiveness of cancers with MYBL2 amplification, and establish the rationale for targeting B-Myb to restore cell cycle control

Anomalous thermal conductivity and local temperature distribution on harmonic Fibonacci chains

The harmonic Fibonacci chain, which is one of a quasiperiodic chain constructed with a recursion relation, has a singular continuous frequency-spectrum and critical eigenstates. The validity of the Fourier law is examined for the harmonic Fibonacci chain with stochastic heat baths at both ends by investigating the system size N dependence of the heat current J and the local temperature distribution. It is shown that J asymptotically behaves as (ln N)^{-1} and the local temperature strongly oscillates along the chain. These results indicate that the Fourier law does not hold on the harmonic Fibonacci chain. Furthermore the local temperature exhibits two different distribution according to the generation of the Fibonacci chain, i.e., the local temperature distribution does not have a definite form in the thermodynamic limit. The relations between N-dependence of J and the frequency-spectrum, and between the local temperature and critical eigenstates are discussed.Comment: 10 pages, 4 figures, submitted to J. Phys.: Cond. Ma

Clinical impact of double protease inhibitor boosting with Lopinavir/Ritonavir and Amprenavir as part of salvage antiretroviral therapy

Purpose: Double protease inhibitor (PI) boosting is being explored as a new strategy in salvage antiretroviral (ARV) therapy. However, if a negative drug interaction leads to decreased drug levels of either or both PIs, double PI boosting could lead to decreased virologic response. A negative drug interaction has been described between amprenavir (APV) and lopinavir/ritonavir (LPV/r). This observational cohort study assessed the virologic impact of the addition of APV to a salvage ARV regimen, which also contains LPV/r, compared to a regimen containing LPV/r alone. Method: Patients initiated on a salvage ARV regimen that included LPV/r obtained from the expanded access program in Toronto, Canada, were evaluated. APV (600-1,200 mg bid) was added at the discretion of the treating physician. Results: Using multivariate Cox proportional hazards models, we found that the addition of APV to a LPV/r-containing salvage regimen was not significantly associated with time to virologic suppression (< 50 copies/mL; adjusted hazard ratio [HR] = 0.75, p = .12) or with time to virologic rebound (adjusted HR = 1.46, p = .34). Those patients who received higher doses of APV had an increased chance of virologic suppression (p = .03). In a subset of 27 patients, the median LPV Ctrough was significantly lower in patients receiving APV (p = .04), and the median APV Ctrough was reduced compared to reported controls. Conclusion: Our data do not support an additional benefit in virologic reduction of double boosting with APV and LPV/r relative to LPV/r alone in salvage ARV therapy. Our study's limitations include its retrospective nature and the imbalance between the two groups potentially confounding the results. Although these factors were adjusted for in the multivariate analysis, a prospective randomized controlled trial is warranted to confirm our findings

Ariel - Volume 9 Number 6

Executive Editor Seth B. Paul Associate Editor Warren J. Ventriglia Business Manager Fredric Jay Matlin University News John Patrick Welch World News George Robert Coar Editorials Editor Steve Levine Features Mark Rubin Sports Editor Eli Saleeby Photo Editor Ken Buckwalter Circulation Victor Onufreiczuk Lee Wugofski Graphics and Art Steve Hulkower Commons Editor Brenda Peterso

Zircon dissolution in a ductile shear zone, Monte Rosa granite gneiss, northern Italy

The sizes, distributions and shapes of zircon grains within variably deformed granite gneiss from the western Alps have been studied. Zircon shows numerous indicators of a metamorphic response in both the host gneiss and a 5 cm wide continuous ductile shear zone, within which the zircon grain sizes range from &#60;1 µm to &#62;50 µm. However, the very fine grain sizes are virtually absent from grain boundaries. Within this zone, zircons consistently have more rounded and embayed margins, which are interpreted as evidence of dissolution in response to fluid influx during shearing. Zircons are preferentially located near metamorphic muscovite in both the host gneiss and the shear zone and tend to show the poorest crystal shape, indicating that fluids linked to the formation and presence of muscovite may enhance both the crystallization of zircon and its subsequent dissolution. Larger zircon crystals typically show a brittle response to deformation when adjacent to phyllosilicates, with fractures consistently perpendicular to the (001) mica cleavage. The variety of metamorphic behaviour observed for zircon indicates that it may be highly reactive in sub-solidus mid-crustal metamorphic environments

Structural mechanisms of DREAM complex assembly and regulation

The DREAM complex represses cell cycle genes during quiescence through scaffolding MuvB proteins with E2F4/5 and the Rb tumor suppressor paralog p107 or p130. Upon cell cycle entry, MuvB dissociates from p107/p130 and recruits B-Myb and FoxM1 for up-regulating mitotic gene expression. To understand the biochemical mechanisms underpinning DREAM function and regulation, we investigated the structural basis for DREAM assembly. We identified a sequence in the MuvB component LIN52 that binds directly to the pocket domains of p107 and p130 when phosphorylated on the DYRK1A kinase site S28. A crystal structure of the LIN52–p107 complex reveals that LIN52 uses a suboptimal LxSxExL sequence together with the phosphate at nearby S28 to bind the LxCxE cleft of the pocket domain with high affinity. The structure explains the specificity for p107/p130 over Rb in the DREAM complex and how the complex is disrupted by viral oncoproteins. Based on insights from the structure, we addressed how DREAM is disassembled upon cell cycle entry. We found that p130 and B-Myb can both bind the core MuvB complex simultaneously but that cyclin-dependent kinase phosphorylation of p130 weakens its association. Together, our data inform a novel target interface for studying MuvB and p130 function and the design of inhibitors that prevent tumor escape in quiescence

On the classification of conditionally integrable evolution systems in (1+1) dimensions

We generalize earlier results of Fokas and Liu and find all locally analytic (1+1)-dimensional evolution equations of order $n$ that admit an $N$-shock type solution with $N\leq n+1$. To this end we develop a refinement of the technique from our earlier work (A. Sergyeyev, J. Phys. A: Math. Gen, 35 (2002), 7653--7660), where we completely characterized all (1+1)-dimensional evolution systems \bi{u}_t=\bi{F}(x,t,\bi{u},\p\bi{u}/\p x,...,\p^n\bi{u}/\p x^n) that are conditionally invariant under a given generalized (Lie--B\"acklund) vector field \bi{Q}(x,t,\bi{u},\p\bi{u}/\p x,...,\p^k\bi{u}/\p x^k)\p/\p\bi{u} under the assumption that the system of ODEs \bi{Q}=0 is totally nondegenerate. Every such conditionally invariant evolution system admits a reduction to a system of ODEs in $t$, thus being a nonlinear counterpart to quasi-exactly solvable models in quantum mechanics. Keywords: Exact solutions, nonlinear evolution equations, conditional integrability, generalized symmetries, reduction, generalized conditional symmetries MSC 2000: 35A30, 35G25, 81U15, 35N10, 37K35, 58J70, 58J72, 34A34Comment: 8 pages, LaTeX 2e, now uses hyperre

Correlations and scaling in one-dimensional heat conduction

We examine numerically the full spatio-temporal correlation functions for all hydrodynamic quantities for the random collision model introduced recently. The autocorrelation function of the heat current, through the Kubo formula, gives a thermal conductivity exponent of 1/3 in agreement with the analytical prediction and previous numerical work. Remarkably, this result depends crucially on the choice of boundary conditions: for periodic boundary conditions (as opposed to open boundary conditions with heat baths) the exponent is approximately 1/2. This is expected to be a generic feature of systems with singular transport coefficients. All primitive hydrodynamic quantities scale with the dynamic critical exponent predicted analytically.Comment: 7 pages, 11 figure

Hall Effect in the coma of 67P/Churyumov-Gerasimenko

Magnetohydrodynamics simulations have been carried out in studying the solar wind and cometary plasma interactions for decades. Various plasma boundaries have been simulated and compared well with observations for comet 1P/Halley. The Rosetta mission, which studies comet 67P/Churyumov-Gerasimenko, challenges our understanding of the solar wind and comet interactions. The Rosetta Plasma Consortium observed regions of very weak magnetic field outside the predicted diamagnetic cavity. In this paper, we simulate the inner coma with the Hall magnetohydrodynamics equations and show that the Hall effect is important in the inner coma environment. The magnetic field topology becomes complex and magnetic reconnection occurs on the dayside when the Hall effect is taken into account. The magnetic reconnection on the dayside can generate weak magnetic filed regions outside the global diamagnetic cavity, which may explain the Rosetta Plasma Consortium observations. We conclude that the substantial change in the inner coma environment is due to the fact that the ion inertial length (or gyro radius) is not much smaller than the size of the diamagnetic cavity.Comment: 23 pages, 6 figur