Predictors of ADL Disability in Culturally Diverse Older Adults

The purpose of this study was to utilize the disablement pathway model to examine the contribution of physical function, dyspnea, and pain to disability in activities-of-daily-living (ADL) in culturally diverse older adults. Participants were 51 older adults (age = 69.0 years ± 9.7; 76.5% African-American, 51.0% \u3c high school education, 52.9% \u3c $20,000 annual income) from an urban community center and an independent living housing facility for seniors. Participants completed the Functional Status Index (FSI), which provides ratings of need for assistance (FSIA) and pain (FSIP) with ADL, the Continuous Scale Physical Functional Performance 10-item Test (CS-PFP10), and an analog dyspnea scale. Hierarchical multiple regression analyses revealed that facility, physical function, pain, and dyspnea accounted for 50.5% of the variance in disability and that pain (β = .43, p \u3c .01) and physical function (β = -.39, p \u3c .01) were the only significant predictors. In the second model, facility, dyspnea, and pain explained 27.6% of the variance in physical function, and facility (β = .39, p \u3c .01) and dyspnea (β = -.26, p = .05) were the only significant predictors. Based on the disablement pathway model, physical functional improvement and pain prevention and management should be targeted when designing culturally appropriate strategies for delaying disability and maintaining independent life

Maternal Cadmium Levels during Pregnancy Associated with Lower Birth Weight in Infants in a North Carolina Cohort

Cadmium (Cd) is a ubiquitous environmental contaminant, a known carcinogen, and understudied as a developmental toxicant. In the present study, we examined the relationships between Cd levels during pregnancy and infant birth outcomes in a prospective pregnancy cohort in Durham, North Carolina. The study participants (n = 1027) had a mean Cd level of 0.46 µg/L with a range of <0.08 to 2.52 µg/L. Multivariable models were used to establish relationships between blood Cd tertiles and fetal growth parameters, namely birth weight, low birth weight, birth weight percentile by gestational age, small for gestational age, pre-term birth, length, and head circumference. In multivariable models, high maternal blood Cd levels (≥0.50 µg/L) during pregnancy were inversely associated with birth weight percentile by gestational age (p = 0.007) and associated with increased odds of infants being born small for gestational age (p<0.001). These observed effects were independent of cotinine-defined smoking status. The results from this study provide further evidence of health risks associated with early life exposure to Cd among a large pregnancy cohort

Direct versus indirect detection in mSUGRA with self-consistent halo models

We perform a detailed analysis of the detection prospects of neutralino dark matter in the mSUGRA framework. We focus on models with a thermal relic density, estimated with high accuracy using the DarkSUSY package, in the range favored by current precision cosmological measurements. Direct and indirect detection rates are computed implementing two models for the dark matter halo, tracing opposite regimes for the phase of baryon infall, with fully consistent density profiles and velocity distribution functions. This has allowed, for the first time, a fully consistent comparison between direct and indirect detection prospects. We discuss all relevant regimes in the mSUGRA parameter space, underlining relevant effects, and providing the basis for extending the discussion to alternative frameworks. In general, we find that direct detection and searches for antideuterons in the cosmic rays seems to be the most promising ways to search for neutralinos in these scenarios.Comment: 26 pages, 9 figure

The Carnegie Supernova Project: First Near-Infrared Hubble Diagram to z~0.7

The Carnegie Supernova Project (CSP) is designed to measure the luminosity distance for Type Ia supernovae (SNe Ia) as a function of redshift, and to set observational constraints on the dark energy contribution to the total energy content of the Universe. The CSP differs from other projects to date in its goal of providing an I-band {rest-frame} Hubble diagram. Here we present the first results from near-infrared (NIR) observations obtained using the Magellan Baade telescope for SNe Ia with 0.1 < z < 0.7. We combine these results with those from the low-redshift CSP at z <0.1 (Folatelli et al. 2009). We present light curves and an I-band Hubble diagram for this first sample of 35 SNe Ia and we compare these data to 21 new SNe Ia at low redshift. These data support the conclusion that the expansion of the Universe is accelerating. When combined with independent results from baryon acoustic oscillations (Eisenstein et al. 2005), these data yield Omega_m = 0.27 +/- 0.0 (statistical), and Omega_DE = 0.76 +/- 0.13 (statistical) +/- 0.09 (systematic), for the matter and dark energy densities, respectively. If we parameterize the data in terms of an equation of state, w, assume a flat geometry, and combine with baryon acoustic oscillations, we find that w = -1.05 +/- 0.13 (statistical) +/- 0.09 (systematic). The largest source of systematic uncertainty on w arises from uncertainties in the photometric calibration, signaling the importance of securing more accurate photometric calibrations for future supernova cosmology programs. Finally, we conclude that either the dust affecting the luminosities of SNe Ia has a different extinction law (R_V = 1.8) than that in the Milky Way (where R_V = 3.1), or that there is an additional intrinsic color term with luminosity for SNe Ia independent of the decline rate.Comment: 44 pages, 23 figures, 9 tables; Accepted for publication in the Astrophysical Journa

Yukawa Unified Supersymmetric SO(10) Model: Cosmology, Rare Decays and Collider Searches

It has recently been pointed out that viable sparticle mass spectra can be generated in Yukawa unified SO(10) supersymmetric grand unified models consistent with radiative breaking of electroweak symmetry. Model solutions are obtained only if $\tan\beta \sim 50$, $\mu <0$ and positive $D$-term contributions to scalar masses from SO(10) gauge symmetry breaking are used. In this paper, we attempt to systematize the parameter space regions where solutions are obtained. We go on to calculate the relic density of neutralinos as a function of parameter space. No regions of the parameter space explored were actually cosmologically excluded, and very reasonable relic densities were found in much of parameter space. Direct neutralino detection rates could exceed 1 event/kg/day for a $^{73}$Ge detector, for low values of GUT scale gaugino mass $m_{1/2}$. We also calculate the branching fraction for $b\to s \gamma$ decays, and find that it is beyond the 95% CL experimental limits in much, but not all, of the parameter space regions explored. However, recent claims have been made that NLO effects can reverse the signs of certain amplitudes in the $b\to s\gamma$ calculation, leading to agreement between theory and experiment in Yukawa unified SUSY models. For the Fermilab Tevatron collider, significant regions of parameter space can be explored via $b\bar{b}A$ and $b\bar{b}H$ searches. There also exist some limited regions of parameter space where a trilepton signal can be seen at TeV33. Finally, there exist significant regions of parameter space where direct detection of bottom squark pair production can be made, especially for large negative values of the GUT parameter $A_0$.Comment: Added comparison to Blazek/Raby results and added Comments on de Boer et al. b->s gamma result

BRCA2 polymorphic stop codon K3326X and the risk of breast, prostate, and ovarian cancers

Background: The K3326X variant in BRCA2 (BRCA2*c.9976A&gt;T; p.Lys3326*; rs11571833) has been found to be associated with small increased risks of breast cancer. However, it is not clear to what extent linkage disequilibrium with fully pathogenic mutations might account for this association. There is scant information about the effect of K3326X in other hormone-related cancers. Methods: Using weighted logistic regression, we analyzed data from the large iCOGS study including 76 637 cancer case patients and 83 796 control patients to estimate odds ratios (ORw) and 95% confidence intervals (CIs) for K3326X variant carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a pathogenic BRCA2 variant. Using Cox proportional hazards modeling, we also examined the associations of K3326X with breast and ovarian cancer risks among 7183 BRCA1 variant carriers. All statistical tests were two-sided. Results: The K3326X variant was associated with breast (ORw = 1.28, 95% CI = 1.17 to 1.40, P = 5.9x10- 6) and invasive ovarian cancer (ORw = 1.26, 95% CI = 1.10 to 1.43, P = 3.8x10-3). These associations were stronger for serous ovarian cancer and for estrogen receptor–negative breast cancer (ORw = 1.46, 95% CI = 1.2 to 1.70, P = 3.4x10-5 and ORw = 1.50, 95% CI = 1.28 to 1.76, P = 4.1x10-5, respectively). For BRCA1 mutation carriers, there was a statistically significant inverse association of the K3326X variant with risk of ovarian cancer (HR = 0.43, 95% CI = 0.22 to 0.84, P = .013) but no association with breast cancer. No association with prostate cancer was observed. Conclusions: Our study provides evidence that the K3326X variant is associated with risk of developing breast and ovarian cancers independent of other pathogenic variants in BRCA2. Further studies are needed to determine the biological mechanism of action responsible for these associations

The Reach of Fermilab Tevatron Upgrades for SU(5) Supergravity Models with Non-universal Gaugino Masses

We explore the reach of luminosity upgrades of the Fermilab Tevatron collider for SU(5) supergravity models in which non-universal GUT-scale gaugino masses arise via a vacuum expectation value for the auxiliary component of a superfield that transforms as a 24, 75 or 200 dimensional representation of SU(5). This results in a different pattern of sparticle masses and mixing angles from what is expected in the minimal supergravity model (mSUGRA) with universal GUT scale gaugino masses. We find that the resulting signal cross sections, and hence the reach of the Tevatron, are sensitive to the gaugino masses at the GUT scale. In the 24 model, the large splitting amongst the two lightest neutralinos leads to SUSY events containing many isolated leptons, including events with a real leptonic Z boson plus jets plus missing energy signal which is visible over much of parameter space. In contrast, in the 75 and 200 models, the reach via leptonic SUSY signals is greatly reduced relative to mSUGRA, and the signal is usually visible only via the canonical \eslt +jets channel.Comment: 38 page REVTEX file including 21 PS figure

Meta-analysis of pharmacogenetic interactions in amyotrophic lateral sclerosis clinical trials

OBJECTIVE: To assess whether genetic subgroups in recent amyotrophic lateral sclerosis (ALS) trials responded to treatment with lithium carbonate, but that the treatment effect was lost in a large cohort of nonresponders. METHODS: Individual participant data were obtained from 3 randomized trials investigating the efficacy of lithium carbonate. We matched clinical data with data regarding the UNC13A and C9orf72 genotype. Our primary outcome was survival at 12 months. On an exploratory basis, we assessed whether the effect of lithium depended on the genotype. RESULTS: Clinical data were available for 518 of the 606 participants. Overall, treatment with lithium carbonate did not improve 12-month survival (hazard ratio [HR] 1.0, 95% confidence interval [CI] 0.7-1.4; p = 0.96). Both the UNC13A and C9orf72 genotype were independent predictors of survival (HR 2.4, 95% CI 1.3-4.3; p = 0.006 and HR 2.5, 95% CI 1.1-5.2; p = 0.032, respectively). The effect of lithium was different for UNC13A carriers (p = 0.027), but not for C9orf72 carriers (p = 0.22). The 12-month survival probability for UNC13A carriers treated with lithium carbonate improved from 40.1% (95% CI 23.2-69.1) to 69.7% (95% CI 50.4-96.3). CONCLUSIONS: This study incorporated genetic data into past ALS trials to determine treatment effects in a genetic post hoc analysis. Our results suggest that we should reorient our strategies toward finding treatments for ALS, start focusing on genotype-targeted treatments, and standardize genotyping in order to optimize randomization and analysis for future clinical trials