Dynamic test results for the CASES ground experiment

The Controls, Astrophysics, and Structures Experiment in Space (CASES) Ground Test Facility (GTF) has been developed at Marshall Space Flight Center (MSFC) to provide a facility for the investigation of Controls/Structures Interaction (CSI) phenomena, to support ground testing of a potential shuttle-based CASES flight experiment, and to perform limited boom deployment and retraction dynamics studies. The primary objectives of the ground experiment are to investigate CSI on a test article representative of a Large Space Structure (LSS); provide a platform for Guest Investigators (GI's) to conduct CSI studies; to test and evaluate LSS control methodologies, system identification (ID) techniques, failure mode analysis; and to compare ground test predictions and flight results. The proposed CASES flight experiment consists of a 32 meter deployable/retractable boom at the end of which is an occulting plate. The control objective of the experiment is to maintain alignment of the tip plate (occulter) with a detector located at the base of the boom in the orbiter bay. The tip plate is pointed towards a star, the sun, or the galactic center to collect high-energy X-rays emitted by these sources. The tip plate, boom, and detector comprise a Fourier telescope. The occulting holes in the tip plate are approximately one millimeter in diameter making the alignment requirements quite stringent. Control authority is provided by bidirectional linear thrusters located at the boom tip and Angular Momentum Exchange Devices (AMED's) located at mid-boom and at the tip. The experiment embodies a number of CSI control problems including vibration suppression, pointing a long flexible structure, and disturbance rejection. The CASES GTF is representative of the proposed flight experiment with identical control objectives

The VEGF receptor Flt-1 spatially modulates Flk-1 signaling and blood vessel branching

Blood vessel formation requires the integrated regulation of endothelial cell proliferation and branching morphogenesis, but how this coordinated regulation is achieved is not well understood. Flt-1 (vascular endothelial growth factor [VEGF] receptor 1) is a high affinity VEGF-A receptor whose loss leads to vessel overgrowth and dysmorphogenesis. We examined the ability of Flt-1 isoform transgenes to rescue the vascular development of embryonic stem cell–derived flt-1−/− mutant vessels. Endothelial proliferation was equivalently rescued by both soluble (sFlt-1) and membrane-tethered (mFlt-1) isoforms, but only sFlt-1 rescued vessel branching. Flk-1 Tyr-1173 phosphorylation was increased in flt-1−/− mutant vessels and partially rescued by the Flt-1 isoform transgenes. sFlt-1–rescued vessels exhibited more heterogeneous levels of pFlk than did mFlt-1–rescued vessels, and reporter gene expression from the flt-1 locus was also heterogeneous in developing vessels. Our data support a model whereby sFlt-1 protein is more efficient than mFlt-1 at amplifying initial expression differences, and these amplified differences set up local discontinuities in VEGF-A ligand availability that are important for proper vessel branching

Leveraging population admixture to characterize the heritability of complex traits.

Despite recent progress on estimating the heritability explained by genotyped SNPs (h(2)g), a large gap between h(2)g and estimates of total narrow-sense heritability (h(2)) remains. Explanations for this gap include rare variants or upward bias in family-based estimates of h(2) due to shared environment or epistasis. We estimate h(2) from unrelated individuals in admixed populations by first estimating the heritability explained by local ancestry (h(2)γ). We show that h(2)γ = 2FSTCθ(1 - θ)h(2), where FSTC measures frequency differences between populations at causal loci and θ is the genome-wide ancestry proportion. Our approach is not susceptible to biases caused by epistasis or shared environment. We applied this approach to the analysis of 13 phenotypes in 21,497 African-American individuals from 3 cohorts. For height and body mass index (BMI), we obtained h(2) estimates of 0.55 ± 0.09 and 0.23 ± 0.06, respectively, which are larger than estimates of h(2)g in these and other data but smaller than family-based estimates of h(2)

Reducing harm from HIV/AIDS misconceptions among female sex workers in Tijuana and Ciudad Juarez, Mexico: A cross sectional analysis

Abstract Background HIV prevalence is increasing among female sex workers (FSWs) in Mexico’s Northern border region, who experience multiple occupational risks. Improving vulnerable populations’ education, empowerment, and access to preventive services are important components of harm reduction strategies. Given the increasing interest in adapting harm reduction principles from drug use to sex work and other public health responses to the HIV epidemic, we used a sex work harm reduction framework to guide our investigation of FSWs’ HIV knowledge. Methods From 2004–2006, FSWs aged ≥18 years in Tijuana and Ciudad Juarez participated in a behavioral intervention study and completed structured interviews. Measures included HIV knowledge assessment and factors within each domain of our theoretical framework for sex work harms: (1) socio-demographic factors that may lead to sex work, (2) sex work characteristics and behaviors that may lead to harm, and (3) mutually reinforcing harms that lead to sex work and result from it (e.g., drug abuse). Negative binomial regression identified factors independently associated with suboptimal HIV knowledge (i.e., incorrect responses during the HIV knowledge assessment). Results Among 924 FSWs, the median proportion of incorrect responses was nearly one third (28% incorrect). Examination of item responses revealed misconceptions regarding specific transmission and prevention mechanisms, including prevention of mother to child transmission. Suboptimal HIV knowledge was independently associated with older age, lower education, living in Tijuana (vs. Ciudad Juarez), inconsistent condom use for vaginal sex with male clients, and lacking prior HIV testing. Conclusions Our application of a sex work harm reduction framework to the study of FSWs’ HIV knowledge is an important first step in enhancing HIV prevention efforts in Northern Mexican border cities. Our findings imply that interventions should identify and discredit local HIV misconceptions to improve knowledge of specific HIV transmission routes and self-protective strategies (e.g., condom negotiation). Interventions will require materials appropriate for women from diverse socio-economic backgrounds and may benefit from innovative harm reduction approaches such as peer education and outreach

The VEGF receptor Flt-1 spatially modulates Flk-1 signaling and blood vessel branching

Blood vessel formation requires the integrated regulation of endothelial cell proliferation and branching morphogenesis, but how this coordinated regulation is achieved is not well understood. Flt-1 (vascular endothelial growth factor [VEGF] receptor 1) is a high affinity VEGF-A receptor whose loss leads to vessel overgrowth and dysmorphogenesis. We examined the ability of Flt-1 isoform transgenes to rescue the vascular development of embryonic stem cell–derived flt-1−/− mutant vessels. Endothelial proliferation was equivalently rescued by both soluble (sFlt-1) and membrane-tethered (mFlt-1) isoforms, but only sFlt-1 rescued vessel branching. Flk-1 Tyr-1173 phosphorylation was increased in flt-1−/− mutant vessels and partially rescued by the Flt-1 isoform transgenes. sFlt-1–rescued vessels exhibited more heterogeneous levels of pFlk than did mFlt-1–rescued vessels, and reporter gene expression from the flt-1 locus was also heterogeneous in developing vessels. Our data support a model whereby sFlt-1 protein is more efficient than mFlt-1 at amplifying initial expression differences, and these amplified differences set up local discontinuities in VEGF-A ligand availability that are important for proper vessel branching

A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci.

We conducted a multi-stage, genome-wide association study of bladder cancer with a primary scan of 591,637 SNPs in 3,532 affected individuals (cases) and 5,120 controls of European descent from five studies followed by a replication strategy, which included 8,382 cases and 48,275 controls from 16 studies. In a combined analysis, we identified three new regions associated with bladder cancer on chromosomes 22q13.1, 19q12 and 2q37.1: rs1014971, (P = 8 × 10⁻¹²) maps to a non-genic region of chromosome 22q13.1, rs8102137 (P = 2 × 10⁻¹¹) on 19q12 maps to CCNE1 and rs11892031 (P = 1 × 10⁻⁷) maps to the UGT1A cluster on 2q37.1. We confirmed four previously identified genome-wide associations on chromosomes 3q28, 4p16.3, 8q24.21 and 8q24.3, validated previous candidate associations for the GSTM1 deletion (P = 4 × 10⁻¹¹) and a tag SNP for NAT2 acetylation status (P = 4 × 10⁻¹¹), and found interactions with smoking in both regions. Our findings on common variants associated with bladder cancer risk should provide new insights into the mechanisms of carcinogenesis

Differential Effects of Migration and Deportation on HIV Infection among Male and Female Injection Drug Users in Tijuana, Mexico

HIV prevalence is rising, especially among high risk females in Tijuana, Baja California, a Mexico-US border city situated on major migration and drug trafficking routes. We compared factors associated with HIV infection among male and female injection drug users (IDUs) in Tijuana in an effort to inform HIV prevention and treatment programs. IDUs aged ≥18 years were recruited using respondent-driven sampling and underwent testing for HIV, syphilis and structured interviews. Logistic regression identified correlates of HIV infection, stratified by gender. Among 1056 IDUs, most were Mexican-born but 67% were born outside Tijuana. Reasons for moving to Tijuana included deportation from the US (56% for males, 29% for females), and looking for work/better life (34% for females, 15% for males). HIV prevalence was higher in females versus males (10.2% vs. 3.5%, p = 0.001). Among females (N = 158), factors independently associated with higher HIV prevalence included younger age, lifetime syphilis infection and living in Tijuana for longer durations. Among males (N = 898), factors independently associated with higher HIV prevalence were syphilis titers consistent with active infection, being arrested for having ‘track-marks’, having larger numbers of recent injection partners and living in Tijuana for shorter durations. An interaction between gender and number of years lived in Tijuana regressed on HIV infection was significant (p = 0.03). Upon further analysis, deportation from the U.S. explained the association between shorter duration lived in Tijuana and HIV infection among males; odds of HIV infection were four-fold higher among male injectors deported from the US, compared to other males, adjusting for all other significant correlates (p = 0.002). Geographic mobility has a profound influence on Tijuana's evolving HIV epidemic, and its impact is significantly modified by gender. Future studies are needed to elucidate the context of mobility and HIV acquisition in this region, and whether US immigration policies adversely affect HIV risk

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Thromboxane biosynthesis in cancer patients and its inhibition by aspirin: a sub-study of the Add-Aspirin trial

BACKGROUND: Pre-clinical models demonstrate that platelet activation is involved in the spread of malignancy. Ongoing clinical trials are assessing whether aspirin, which inhibits platelet activation, can prevent or delay metastases. METHODS: Urinary 11-dehydro-thromboxane B2 (U-TXM), a biomarker of in vivo platelet activation, was measured after radical cancer therapy and correlated with patient demographics, tumour type, recent treatment, and aspirin use (100 mg, 300 mg or placebo daily) using multivariable linear regression models with log-transformed values. RESULTS: In total, 716 patients (breast 260, colorectal 192, gastro-oesophageal 53, prostate 211) median age 61 years, 50% male were studied. Baseline median U-TXM were breast 782; colorectal 1060; gastro-oesophageal 1675 and prostate 826 pg/mg creatinine; higher than healthy individuals (~500 pg/mg creatinine). Higher levels were associated with raised body mass index, inflammatory markers, and in the colorectal and gastro-oesophageal participants compared to breast participants (P < 0.001) independent of other baseline characteristics. Aspirin 100 mg daily decreased U-TXM similarly across all tumour types (median reductions: 77-82%). Aspirin 300 mg daily provided no additional suppression of U-TXM compared with 100 mg. CONCLUSIONS: Persistently increased thromboxane biosynthesis was detected after radical cancer therapy, particularly in colorectal and gastro-oesophageal patients. Thromboxane biosynthesis should be explored further as a biomarker of active malignancy and may identify patients likely to benefit from aspirin