A Change-Point Regression Approach for Efficacy Evaluation of Dietary Supplements

In clinical trials for dietary supplements and functional foods, the study population tends to be a mixture of healthy subjects and those who are not so healthy but are not definitely diseased (called “borderline subjects”). For such heterogeneous populations, the t-test and ANCOVA method often fail to provide the desired treatment efficacy. We propose an alternative approach for the efficacy evaluation of dietary supplements and functional foods based on a change-point linear regression model. The model does not require the assumption of a constant treatment effect and provides clinically interpretable results. By employing the AIC-based profile likelihood method, inferences can be made easily using standard statistical software. The proposed method was applied to the Garcinia study data, and the merit of the method was demonstrated by comparing it with traditional methods

Energy level statistics of the two-dimensional Hubbard model at low filling

The energy level statistics of the Hubbard model for $L \times L$ square lattices (L=3,4,5,6) at low filling (four electrons) is studied numerically for a wide range of the coupling strength. All known symmetries of the model (space, spin and pseudospin symmetry) have been taken into account explicitly from the beginning of the calculation by projecting into symmetry invariant subspaces. The details of this group theoretical treatment are presented with special attention to the nongeneric case of L=4, where a particular complicated space group appears. For all the lattices studied, a significant amount of levels within each symmetry invariant subspaces remains degenerated, but except for L=4 the ground state is nondegenerate. We explain the remaining degeneracies, which occur only for very specific interaction independent states, and we disregard these states in the statistical spectral analysis. The intricate structure of the Hubbard spectra necessitates a careful unfolding procedure, which is thoroughly discussed. Finally, we present our results for the level spacing distribution, the number variance $\Sigma^2$, and the spectral rigidity $\Delta_3$, which essentially all are close to the corresponding statistics for random matrices of the Gaussian ensemble independent of the lattice size and the coupling strength. Even very small coupling strengths approaching the integrable zero coupling limit lead to the Gaussian ensemble statistics stressing the nonperturbative nature of the Hubbard model.Comment: 31 pages (1 Revtex file and 10 postscript figures

An Improved Measurement of Mixing-induced CP Violation in the Neutral B Meson System

We present an improved measurement of the standard model CP violation parameter sin2phi_1 (also known as sin2beta) based on a sample of 85 times 10^6 B Bbar pairs collected at the Upsilon(4S) resonance with the Belle detector at the KEKB asymmetric-energy e+e- collider. One neutral B meson is reconstructed in a J/psi K_S, psi(2S) K_S, chi_{c1} K_S, eta_c K_S, J/psi K^{*0}, or J/psi K_L CP-eigenstate decay channel and the flavor of accompanying B meson is identified from itsdecay products. From the asymmetry in the distribution of the time intervals between the two B meson decay points, we obtain sin2phi_1 = 0.719 +/- 0.074(stat) +/- 0.035(syst). We also report measurements of CP violation parameters for the related B^0 -> J/psi pi^0 decay mode and the penguin-dominated processes B^0 -> eta' K_S, phi K_S and K^+K^- K_S.Comment: 11 pages, 4 figures, 4 tables, contributed to ICHEP200

Myeloablative vs Reduced-Intensity Conditioning Allogeneic Hematopoietic Cell Transplantation for Chronic Myeloid Leukemia

Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative treatment of chronic myeloid leukemia (CML). Optimal conditioning intensity for allo-HCT for CML in the era of tyrosine kinase inhibitors (TKIs) is unknown. Using the Center for International Blood and Marrow Transplant Research database, we sought to determine whether reduced-intensity/nonmyeloablative conditioning (RIC) allo-HCT and myeloablative conditioning (MAC) result in similar outcomes in CML patients. We evaluated 1395 CML allo-HCT recipients between the ages of 18 and 60 years. The disease status at transplant was divided into the following categories: chronic phase 1, chronic phase 2 or greater, and accelerated phase. Patients in blast phase at transplant and alternative donor transplants were excluded. The primary outcome was overall survival (OS) after allo-HCT. MAC (n = 1204) and RIC allo-HCT recipients (n = 191) from 2007 to 2014 were included. Patient, disease, and transplantation characteristics were similar, with a few exceptions. Multivariable analysis showed no significant difference in OS between MAC and RIC groups. In addition, leukemia-free survival and nonrelapse mortality did not differ significantly between the 2 groups. Compared with MAC, the RIC group had a higher risk of early relapse after allo-HCT (hazard ratio [HR], 1.85; P = .001). The cumulative incidence of chronic graft-versus-host disease (cGVHD) was lower with RIC than with MAC (HR, 0.77; P = .02). RIC provides similar survival and lower cGVHD compared with MAC and therefore may be a reasonable alternative to MAC for CML patients in the TKI era

Clinically Actionable Hypercholesterolemia and Hypertriglyceridemia in Children with Nonalcoholic Fatty Liver Disease

OBJECTIVE: To determine the percentage of children with nonalcoholic fatty liver disease (NAFLD) in whom intervention for low-density lipoprotein cholesterol or triglycerides was indicated based on National Heart, Lung, and Blood Institute guidelines. STUDY DESIGN: This multicenter, longitudinal cohort study included children with NAFLD enrolled in the National Institute of Diabetes and Digestive and Kidney Diseases Nonalcoholic Steatohepatitis Clinical Research Network. Fasting lipid profiles were obtained at diagnosis. Standardized dietary recommendations were provided. After 1 year, lipid profiles were repeated and interpreted according to National Heart, Lung, and Blood Institute Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction. Main outcomes were meeting criteria for clinically actionable dyslipidemia at baseline, and either achieving lipid goal at follow-up or meeting criteria for ongoing intervention. RESULTS: There were 585 participants, with a mean age of 12.8 years. The prevalence of children warranting intervention for low-density lipoprotein cholesterol at baseline was 14%. After 1 year of recommended dietary changes, 51% achieved goal low-density lipoprotein cholesterol, 27% qualified for enhanced dietary and lifestyle modifications, and 22% met criteria for pharmacologic intervention. Elevated triglycerides were more prevalent, with 51% meeting criteria for intervention. At 1 year, 25% achieved goal triglycerides with diet and lifestyle changes, 38% met criteria for advanced dietary modifications, and 37% qualified for antihyperlipidemic medications. CONCLUSIONS: More than one-half of children with NAFLD met intervention thresholds for dyslipidemia. Based on the burden of clinically relevant dyslipidemia, lipid screening in children with NAFLD is warranted. Clinicians caring for children with NAFLD should be familiar with lipid management

Atmospheric metallicity and C/O of HD 189733 b from high-resolution spectroscopy

We present high-resolution $K$-band emission spectra of the quintessential hot Jupiter HD 189733 b from the Keck Planet Imager and Characterizer (KPIC). Using a Bayesian retrieval framework, we fit the dayside pressure-temperature profile, orbital kinematics, mass-mixing ratios of H$_2$O, CO, CH$_4$, NH$_3$, HCN, and H$_2$S, and the $\rm ^{13}CO/^{12}CO$ ratio. We measure mass fractions of $\rm \log H_2O = -2.0^{+0.4}_{-0.4}$ and $\rm \log CO = -2.2^{+0.5}_{-0.5}$, and place upper limits on the remaining species. Notably, we find $\rm \log CH_4 < -4.5$ at 99\% confidence, despite its anticipated presence at the equilibrium temperature of HD 189733 b assuming local thermal equilibrium. We make a tentative ($\sim3\sigma$) detection of $\rm ^{13}CO$, and the retrieved posteriors suggest a $\rm ^{12}C/^{13}C$ ratio similar to or substantially less than the local interstellar value. The possible $\rm ^{13}C$ enrichment would be consistent with accretion of fractionated material in ices or in the protoplanetary disk midplane. The retrieved abundances correspond to a substantially sub-stellar atmospheric $\rm C/O = 0.3\pm0.1$, while the carbon and oxygen abundances are stellar to slightly super-stellar, consistent with core-accretion models which predict an inverse correlation between C/O and metallicity. The specific combination of low C/O and high metallicity suggests significant accretion of solid material may have occurred late in the formation process of HD 189733 b.Comment: 17 pages, 7 figures, 2 tables, accepted in A

Allele-Specific Gene Expression Is Widespread Across the Genome and Biological Processes

Allelic specific gene expression (ASGE) appears to be an important factor in human phenotypic variability and as a consequence, for the development of complex traits and diseases. In order to study ASGE across the human genome, we have performed a study in which genotyping was coupled with an analysis of ASGE by screening 11,500 SNPs using the Mapping 10 K Array to identify differential allelic expression. We found that from the 5,133 SNPs that were suitable for analysis (heterozygous in our sample and expressed in peripheral blood mononuclear cells), 2,934 (57%) SNPs had differential allelic expression. Such SNPs were equally distributed along human chromosomes and biological processes. We validated the presence or absence of ASGE in 18 out 20 SNPs (90%) randomly selected by real time PCR in 48 human subjects. In addition, we observed that SNPs close to -but not included in- segmental duplications had increased levels of ASGE. Finally, we found that transcripts of unknown function or non-coding RNAs, also display ASGE: from a total of 2,308 intronic SNPs, 1510 (65%) SNPs underwent differential allelic expression. In summary, ASGE is a widespread mechanism in the human genome whose regulation seems to be far more complex than expected

SLC11A1 (NRAMP1) Polymorphisms and Tuberculosis Susceptibility: Updated Systematic Review and Meta-Analysis

Background: Natural resistance associated macrophage protein 1 (NRAMP1), encoded by the SLC11A1 gene, has been described to regulate macrophage activation and be associated with infectious and autoimmune diseases. The relation between SLC11A1 polymorphisms and tuberculosis susceptibility has been studied in different populations. Methods: We systematically reviewed published studies on SLC11A1 polymorphisms and tuberculosis susceptibility until September 15, 2010 and quantitatively summarized associations of the most widely studied polymorphisms using metaanalysis. Results: In total, 36 eligible articles were included in this review. In Meta-analysis, significant associations were observed between tuberculosis risk and widely studied SLC11A1 polymorphisms with summarized odds ratio of 1.35 (95%CI, 1.17– 1.54), 1.25 (95 % CI, 1.04–1.50), 1.23 (95 % CI, 1.04–1.44), 1.31 (95%CI, 1.08–1.59) for 39 UTR, D543N, INT4, and 59 (GT)n, respectively. Heterogeneity between studies was not pronounced, and the associations did not remarkably vary in the stratified analysis with respect to study population and study base. Conclusions: The association between SLC11A1 polymorphisms and tuberculosis susceptibility observed in our analyses supports the hypothesis that NRAMP1 might play an important role in the host defense to the development of tuberculosis

Validation of elemental and isotopic abundances in late-M spectral types with the benchmark HIP 55507 AB system

M dwarfs are common host stars to exoplanets but often lack atmospheric abundance measurements. Late-M dwarfs are also good analogs to the youngest substellar companions, which share similar $T_{\rm eff}\sim2300-2800~K$. We present atmospheric analyses for the M7.5 companion HIP 55507 B and its K6V primary star with Keck/KPIC high-resolution ($R\sim35,000$) $K$ band spectroscopy. First, by including KPIC relative radial velocities between the primary and secondary in the orbit fit, we improve the dynamical mass precision by 60% and find $M_B=88.0_{-3.2}^{+3.4}$ $M_{\rm Jup}$, putting HIP 55507 B above the stellar-substellar boundary. We also find that HIP 55507 B orbits its K6V primary star with $a=38^{+4}_{-3}$ AU and $e=0.40\pm0.04$. From atmospheric retrievals of HIP 55507 B, we measure $\rm [C/H]=0.24\pm0.13$, $\rm [O/H]=0.15\pm0.13$, and $\rm C/O=0.67\pm0.04$. Moreover, we strongly detect $\rm ^{13}CO$ ($7.8\sigma$ significance) and tentatively detect $\rm H_2^{18}O$ ($3.7\sigma$ significance) in companion's atmosphere, and measure $\rm ^{12}CO/^{13}CO=98_{-22}^{+28}$ and $\rm H_2^{16}O/H_2^{18}O=240_{-80}^{+145}$ after accounting for systematic errors. From a simplified retrieval analysis of HIP 55507 A, we measure $\rm ^{12}CO/^{13}CO=79_{-16}^{+21}$ and $\rm C^{16}O/C^{18}O=288_{-70}^{+125}$ for the primary star. These results demonstrate that HIP 55507 A and B have consistent $\rm ^{12} C/^{13}C$ and $\rm ^{16}O/^{18}O$ to the $<1\sigma$ level, as expected for a chemically homogeneous binary system. Given the similar flux ratios and separations between HIP 55507 AB and systems with young, substellar companions, our results open the door to systematically measuring $\rm ^{13}CO$ and $\rm H_2^{18}O$ abundances in the atmospheres of substellar or even planetary-mass companions with similar spectral types.Comment: Accepted to ApJ, 28 pages, 14 figure

Electromagnetic Wave Theory and Applications

Contains table of contents for Section 3 and reports on five research projects.U.S. Department of Transportation Contract DTRS-57-88-C-00078TTD13U.S. Department of Transportation Contract DTRS-57-88-C-00078TTD30Defense Advanced Research Projects Agency Contract MDA972-90-C-0021Digital Equipment CorporationIBM CorporationJoint Services Electronics Program Contract DAAL03-89-C-0001Joint Services Electronics Program Contract DAAL03-92-C-0001Schlumberger-Doll ResearchU.S. Navy - Office of Naval Research Grant N00014-90-J-1002U.S. Navy - Office of Naval Research Grant N00014-89-J-1019National Aeronautics and Space Administration Grant NAGW-1617National Aeronautics and Space Administration Grant 958461National Aeronautics and Space Administration Grant NAGW-1272U.S. Army Corp of Engineers Contract DACA39-87-K-0022U.S. Navy - Office of Naval Research Grant N00014-89-J-110