Flow coefficients v_{n} for n=2, 3, 4, characterizing the anisotropic collective flow in Au+Au collisions at sqrt[s_{NN}]=200  GeV, are measured relative to event planes Ψ_{n}, determined at large rapidity. We report v_{n} as a function of transverse momentum and collision centrality, and study the correlations among the event planes of different order n. The v_{n} are well described by hydrodynamic models which employ a Glauber Monte Carlo initial state geometry with fluctuations, providing additional constraining power on the interplay between initial conditions and the effects of viscosity as the system evolves. This new constraint can serve to improve the precision of the extracted shear viscosity to entropy density ratio η/s.

Back-to-back hadron pair yields in d+Au and p+p collisions at √s(NN)=200 GeV were measured with the PHENIX detector at the Relativistic Heavy Ion Collider. Rapidity separated hadron pairs were detected with the trigger hadron at pseudorapidity |η|<0.35 and the associated hadron at forward rapidity (deuteron direction, 3.0<η<3.8). Pairs were also detected with both hadrons measured at forward rapidity; in this case, the yield of back-to-back hadron pairs in d+Au collisions with small impact parameters is observed to be suppressed by a factor of 10 relative to p+p collisions. The kinematics of these pairs is expected to probe partons in the Au nucleus with a low fraction x of the nucleon momenta, where the gluon densities rise sharply. The observed suppression as a function of nuclear thickness, p(T), and η points to cold nuclear matter effects arising at high parton densities.

We present measurements of J/ψ yields in d+Au collisions at sqrt[s(NN)]=200  GeV recorded by the PHENIX experiment and compare them with yields in p+p collisions at the same energy per nucleon-nucleon collision. The measurements cover a large kinematic range in J/ψ rapidity (-2.2<y<2.4) with high statistical precision and are compared with two theoretical models: one with nuclear shadowing combined with final state breakup and one with coherent gluon saturation effects. In order to remove model dependent systematic uncertainties we also compare the data to a simple geometric model. The forward rapidity data are inconsistent with nuclear modifications that are linear or exponential in the density weighted longitudinal thickness, such as those from the final state breakup of the bound state.

Pictorial representations of three-dimensional objects are often used to investigate animal cognitive abilities; however, investigators rarely evaluate whether the animals conceptualize the two-dimensional image as the object it is intended to represent. We tested for picture recognition in lion-tailed macaques by presenting five monkeys with digitized images of familiar foods on a touch screen. Monkeys viewed images of two different foods and learned that they would receive a piece of the one they touched first. After demonstrating that they would reliably select images of their preferred foods on one set of foods, animals were transferred to images of a second set of familiar foods. We assumed that if the monkeys recognized the images, they would spontaneously select images of their preferred foods on the second set of foods. Three monkeys selected images of their preferred foods significantly more often than chance on their first transfer session. In an additional test of the monkeys' picture recognition abilities, animals were presented with pairs of food images containing a medium-preference food paired with either a high-preference food or a low-preference food. The same three monkeys selected the medium-preference foods significantly more often when they were paired with low-preference foods and significantly less often when those same foods were paired with high-preference foods. Our novel design provided convincing evidence that macaques recognized the content of two-dimensional images on a touch screen. Results also suggested that the animals understood the connection between the two-dimensional images and the three-dimensional objects they represented.

Loss of xanthine oxidoreductase (XOR) has been linked to aggressive breast cancer in vivo and to breast cancer cell aggressiveness in vitro. In the present study, we hypothesized that the contribution of XOR to the development of the normal mammary gland may underlie its capacity to modulate breast cancer. We contrasted in vitro and in vivo developmental systems by differentiation marker and microarray analyses. Human breast cancer microarray was used for clinical outcome studies. The role of XOR in differentiation and proliferation was examined in human breast cancer cells and in a mouse xenograft model. Our data show that XOR was required for functional differentiation of mammary epithelial cells both in vitro and in vivo. Poor XOR expression was observed in a mouse ErbB2 breast cancer model, and pharmacologic inhibition of XOR increased breast cancer tumor burden in mouse xenograft. mRNA microarray analysis of human breast cancer revealed that low XOR expression was significantly associated with time to tumor relapse. The opposing expression of XOR and inhibitor of differentiation-1 (Id1) during HC11 differentiation and mammary gland development suggested a potential functional relationship. While overexpression of Id1 inhibited HC11 differentiation and XOR expression, XOR itself modulated expression of Id1 in differentiating HC11 cells. Overexpression of XOR both inhibited Id1-induced proliferation and -stimulated differentiation of Heregulin-β1-treated human breast cancer cells. These results show that XOR is an important functional component of differentiation whose diminished expression contributes to breast cancer aggressiveness, and they support XOR as both a breast cancer biomarker and a target for pharmacologic activation in therapeutic management of aggressive breast cancer.

Computational models are often used as tools to study traumatic brain injury. The fidelity of such models depends on the incorporation of an appropriate level of structural detail, the accurate representation of the material behavior, and the use of an appropriate measure of injury. In this study, an axonal strain injury criterion is used to estimate the probability of diffuse axonal injury (DAI), which accounts for a large percentage of deaths due to brain trauma and is characterized by damage to neural axons in the deep white matter regions of the brain. We present an analytical and computational model that treats the white matter as an anisotropic, hyperelastic material. Diffusion tensor imaging is used to incorporate the structural orientation of the neural axons into the model. It is shown that the degree of injury that is predicted in a computational model of DAI is highly dependent on the incorporation of the axonal orientation information and the inclusion of anisotropy into the constitutive model for white matter.

Large parity-violating longitudinal single-spin asymmetries A(L)(e+)=-0.86(-0.14)(+0.30) and A(L)(e-)= 0.88(-0.71)(+0.12) are observed for inclusive high transverse momentum electrons and positrons in polarized p+p collisions at a center-of-mass energy of sqrt[s]= 500 GeV with the PHENIX detector at RHIC. These e± come mainly from the decay of W± and Z0 bosons, and their asymmetries directly demonstrate parity violation in the couplings of the W± to the light quarks. The observed electron and positron yields were used to estimate W± boson production cross sections for the e± channels of σ(pp → W+ X) × BR(W+ → e+ ν(e))= 144.1 ± 21.2(stat)(-10.3)(+3.4)(syst) ± 21.6(norm)  pb, and σ(pp → W- X) × BR(W- → e- ν[over ¯](e))= 31.7 ± 12.1(stat)(-8.2)(+10.1)(syst) ± 4.8(norm)  pb.

Background: Medication underutilization, or the omission of a potentially beneficial medication indicated for disease management, is common among older adults but poorly understood. Objectives: The aims of this work were to assess the prevalence of medication underuse and to determine whether polypharmacy or comorbidity was associated with medication underuse among physically frail older veterans transitioning from the hospital to the community. Methods: This was a cross-sectional analysis of patients who were discharged from 11 US veterans' hospitals to outpatient care, based on data from the Geriatric Evaluation and Management Drug Study, a substudy of the Veterans Affairs Cooperative Study of geriatric evaluation and management. Patients were enrolled between August 31, 1995, and January 31, 1999. To qualify for the study, patients had to be aged >/=65 years, hospitalized in a medical or surgical ward for >48 hours, and meet >/=2 of the following criteria: moderate functional disability; recent cerebrovascular accident with residual neurological deficit; history of >/=1 fall in the previous 3 months; documented difficulty with walking (ie, requiring personal assistance or equipment), not including preadmission use of a wheelchair with ability to transfer to and from chair independently; malnutrition (admission serum albumin of 3.5 g/dL,<80% of ideal body weight, or recent >/=15-lb weight loss reported in admission history); dementia; depression; documented diagnosis of new fracture or revision needed of older fracture; unplanned admission within 3 months of previous admission; and prolonged bed rest. Clinical pharmacist/physician pairs reviewed medical records and medication lists and independently applied the Assessment of Underutilization (AOU) index to determine omissions of indicated medications. Discordances in index ratings were resolved during clinical consensus conferences. The primary outcome measure was the percentage of patients with >/=1 medication omission detected by the AOU. Multivariable logistic regression analyses identified factors associated with underuse. Results: A total of 384 patients were included in the study. The majority (53.6%) were between the ages of 65 and 74 years, and the mean (SD) Charlson comorbidity index was 2.44 (1.93). Overall, 374 patients (97.4%) were men and 274 (71.4%) were white. Medication undertreatment occurred in 238 participants (62.0%). Diseases of the Accepted for publication October 26, 2009. circulatory, endocrine/nutritional, musculoskeletal, and respiratory systems were the most commonly undertreated conditions. The indicated medications most likely to be omitted were nitrates for those with a history of myocardial infarction, multivitamins in those with malnutrition, and inhaled anticholinergics for chronic obstructive airways disease. Statistically significant factors associated with medication underuse included limitations in activities of daily living (adjusted odds ratio [AOR], 2.17 [95% CI, 1.27-3.71]; P = 0.01), being white (AOR, 1.70 [95% CI, 1.06-2.71]; P = 0.03), and Charlson comorbidity index (AOR, 1.13 for each 1-point increase [95% CI, 1.00-1.27]; P = 0.04). Discharge from a general medicine service as opposed to a surgical service was associated with lower risk of medication underuse (AOR, 0.61 [95% CI, 0.38-0.98]; P = 0.04). Conclusions: Medication underuse was relatively common in this study. Patients with greater comorbidity, but not polypharmacy, had increased odds of undertreatment.

PURPOSE: To evaluate whether CNS medication use in older adults was associated with a higher risk of future incident mobility limitation. METHODS: This 5-year longitudinal cohort study included 3055 participants from the health, aging and body composition (Health ABC) study who were well-functioning at baseline. CNS medication use (benzodiazepine and opioid receptor agonists, antipsychotics, and antidepressants) was determined yearly (except year 4) during in-home or in-clinic interviews. Summated standardized daily doses (low, medium, and high) and duration of CNS drug use were computed. Incident mobility limitation was operationalized as two consecutive self-reports of having any difficulty walking 1/4 mile or climbing 10 steps without resting every 6 months after baseline. Multivariable Cox proportional hazard analyses were conducted adjusting for demographics, health behaviors, health status, and common indications for CNS medications. RESULTS: Each year at least 13.9% of participants used a CNS medication. By year 6, overall 49% had developed incident mobility limitation. In multivariable models, CNS medication users compared to never users showed a higher risk for incident mobility limitation (adjusted hazard ratio (Adj. HR) 1.28; 95% confidence interval (CI) 1.12-1.47). Similar findings of increased risk were seen in analyses examining dose- and duration-response relationships. CONCLUSIONS: CNS medication use is independently associated with an increased risk of future incident mobility limitation in community dwelling elderly. Further studies are needed to determine the impact of reducing CNS medication exposure on mobility problems. Copyright (c) 2009 John Wiley & Sons, Ltd.

OBJECTIVES: To evaluate whether combined use of multiple central nervous system (CNS) medications over time is associated with cognitive change. DESIGN: Longitudinal cohort study. SETTING: Pittsburgh, Pennsylvania, and Memphis, Tennessee. PARTICIPANTS: Two thousand seven hundred thirty-seven healthy adults (aged > or =65) enrolled in the Health, Aging and Body Composition study without baseline cognitive impairment (modified Mini-Mental State Examination (3MS) score > or =80). MEASUREMENTS: CNS medication (benzodiazepine- and opioid-receptor agonists, antipsychotics, antidepressants) use, duration, and dose were determined at baseline (Year 1) and Years 3 and 5. Cognitive function was measured using the 3MS at baseline and Years 3 and 5. The outcome variables were incident cognitive impairment (3MS score <80) and cognitive decline (> or =5-point decline on 3MS). Multivariable interval-censored survival analyses were conducted. RESULTS: By Year 5, 7.7% of subjects had incident cognitive impairment; 25.2% demonstrated cognitive decline. CNS medication use increased from 13.9% at baseline to 15.3% and 17.1% at Years 3 and 5, respectively. It was not associated with incident cognitive impairment (adjusted hazard ratio (adj HR)=1.11, 95% confidence interval (CI)=0.73-1.69) but was associated with cognitive decline (adj HR 1.37, 95% CI=1.11-1.70). Longer duration (adj HR=1.39, CI=1.08-1.79) and higher doses (>3 standardized daily doses)(adj HR=1.87, 95% CI=1.25-2.79) of CNS medications suggested greater risk of cognitive decline than with nonuse. CONCLUSION: Combined use of CNS medications, especially at higher doses, appears to be associated with cognitive decline in older adults. Future studies must explore the effect of combined CNS medication use on vulnerable older adults.