Chromosome 5p Region SNPs Are Associated with Risk of NSCLC among Women

In a population-based case-control study, we explored the associations between 42 polymorphisms in seven genes in this region and non-small cell lung cancer (NSCLC) risk among Caucasian (364 cases; 380 controls) and African American (95 cases; 103 controls) women. Two TERT region SNPs, rs2075786 and rs2853677, conferred an increased risk of developing NSCLC, especially among African American women, and TERT-rs2735940 was associated with a decreased risk of lung cancer among African Americans. Five of the 20 GHR polymorphisms and SEPP1-rs6413428 were associated with a marginally increased risk of NSCLC among Caucasians. Random forest analysis reinforced the importance of GHR among Caucasians and identified AMACR, TERT, and GHR among African Americans, which were also significant using gene-based risk scores. Smoking-SNP interactions were explored, and haplotypes in TERT and GHR associated with NSCLC risk were identified. The roles of TERT, GHR, AMACR and SEPP1 genes in lung carcinogenesis warrant further exploration

Interactive computer-based interventions for weight loss or weight maintenance in overweight or obese people

BACKGROUND: The World Health Organization (WHO) estimates that the number of obese or overweight individuals worldwide will increase to 1.5 billion by 2015. Chronic diseases associated with overweight or obesity include diabetes, heart disease, hypertension and stroke. OBJECTIVES: To assess the effects of interactive computer-based interventions for weight loss or weight maintenance in overweight or obese people. SEARCH METHODS: We searched several electronic databases, including CENTRAL, MEDLINE, EMBASE, CINAHL, LILACS and PsycINFO, through 25 May 2011. We also searched clinical trials registries to identify studies. We scanned reference lists of included studies and relevant systematic reviews. SELECTION CRITERIA: Studies were included if they were randomized controlled trials or quasi-randomized controlled trials that evaluated interactive computer-based weight loss or weight maintenance programs in adults with overweight or obesity. We excluded trials if the duration of the intervention was less than four weeks or the loss to follow-up was greater than 20% overall. DATA COLLECTION AND ANALYSIS: Two authors independently extracted study data and assessed risk of bias. Where interventions, control conditions, outcomes and time frames were similar between studies, we combined study data using meta-analysis. MAIN RESULTS: We included 14 weight loss studies with a total of 2537 participants, and four weight maintenance studies with a total of 1603 participants. Treatment duration was between four weeks and 30 months. At six months, computer-based interventions led to greater weight loss than minimal interventions (mean difference (MD) -1.5 kg; 95% confidence interval (CI) -2.1 to -0.9; two trials) but less weight loss than in-person treatment (MD 2.1 kg; 95% CI 0.8 to 3.4; one trial). At six months, computer-based interventions were superior to a minimal control intervention in limiting weight regain (MD -0.7 kg; 95% CI -1.2 to -0.2; two trials), but not superior to infrequent in-person treatment (MD 0.5 kg; 95% -0.5 to 1.6; two trials). We did not observe consistent differences in dietary or physical activity behaviors between intervention and control groups in either weight loss or weight maintenance trials. Three weight loss studies estimated the costs of computer-based interventions compared to usual care, however two of the studies were 11 and 28 years old, and recent advances in technology render these estimates unlikely to be applicable to current or future interventions, while the third study was conducted in active duty military personnel, and it is unclear whether the costs are relevant to other settings. One weight loss study reported the cost-effectiveness ratio for a weekly in-person weight loss intervention relative to a computer-based intervention as USD 7177 (EUR 5678) per life year gained (80% CI USD 3055 to USD 60,291 (EUR 2417 to EUR 47,702)). It is unclear whether this could be extrapolated to other studies. No data were identified on adverse events, morbidity, complications or health-related quality of life. AUTHORS' CONCLUSIONS: Compared to no intervention or minimal interventions (pamphlets, usual care), interactive computer-based interventions are an effective intervention for weight loss and weight maintenance. Compared to in-person interventions, interactive computer-based interventions result in smaller weight losses and lower levels of weight maintenance. The amount of additional weight loss, however, is relatively small and of brief duration, making the clinical significance of these differences unclear

Converging identities: dimensions of acculturation and personal identity status among immigrant college students

The present study was designed to ascertain the extent to which dimensions of acculturation would differ across personal identity statuses in a sample of 2,411, first and second generation immigrant college‐attending emerging adults. Participants from 30 colleges and universities around the United States completed measures of personal identity processes as well as of heritage and American cultural practices, values, and identifications. Cluster‐analytic procedures were used to classify participants into personal identity statuses based on the personal identity processes. Results indicated that, across ethnic groups, individuals in the achieved and searching moratorium statuses reported the greatest endorsement of heritage and American cultural practices, values, and identifications; and individuals in the carefree diffusion status reported the lowest endorsement of all the cultural variables under study. These results are discussed in terms of the convergence between personal identity and cultural identity processes

Contralateral Cruciate Survival in Dogs with Unilateral Non-Contact Cranial Cruciate Ligament Rupture

BACKGROUND: Non-contact cranial cruciate ligament rupture (CrCLR) is an important cause of lameness in client-owned dogs and typically occurs without obvious injury. There is a high incidence of bilateral rupture at presentation or subsequent contralateral rupture in affected dogs. Although stifle synovitis increases risk of contralateral CrCLR, relatively little is known about risk factors for subsequent contralateral rupture, or whether therapeutic intervention may modify this risk. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a longitudinal study examining survival of the contralateral CrCL in client-owned dogs with unilateral CrCLR in a large baseline control population (n = 380), and a group of dogs that received disease-modifying therapy with arthroscopic lavage, intra-articular hyaluronic acid and oral doxycycline (n = 16), and were followed for one year. Follow-up in treated dogs included analysis of mobility, radiographic evaluation of stifle effusion and arthritis, and quantification of biomarkers of synovial inflammation. We found that median survival of the contralateral CrCL was 947 days. Increasing tibial plateau angle decreased contralateral ligament survival, whereas increasing age at diagnosis increased survival. Contralateral ligament survival was reduced in neutered dogs. Our disease-modifying therapy did not significantly influence contralateral ligament survival. Correlative analysis of clinical and biomarker variables with development of subsequent contralateral rupture revealed few significant results. However, increased expression of T lymphocyte-associated genes in the index unstable stifle at diagnosis was significantly related to development of subsequent non-contact contralateral CrCLR. CONCLUSION: Subsequent contralateral CrCLR is common in client-owned dogs, with a median ligament survival time of 947 days. In this naturally occurring model of non-contact cruciate ligament rupture, cranial tibial translation is preceded by development of synovial inflammation. However, treatment with arthroscopic lavage, intra-articular hyaluronic acid and oral doxycycline does not significantly influence contralateral CrCL survival

Effect of analgesic therapy on clinical outcome measures in a randomized controlled trial using client-owned dogs with hip osteoarthritis

BACKGROUND: Pain and impaired mobility because of osteoarthritis (OA) is common in dogs and humans. Efficacy studies of analgesic drug treatment of dogs with naturally occurring OA may be challenging, as a caregiver placebo effect is typically evident. However, little is known about effect sizes of common outcome-measures in canine clinical trials evaluating treatment of OA pain. Forty-nine client-owned dogs with hip OA were enrolled in a randomized, double-blinded placebo-controlled prospective trial. After a 1 week baseline period, dogs were randomly assigned to a treatment (ABT-116 – transient receptor potential vanilloid 1 (TRPV1) antagonist, Carprofen – non-steroidal anti-inflammatory drug (NSAID), Tramadol - synthetic opiate, or Placebo) for 2 weeks. Outcome-measures included physical examination parameters, owner questionnaire, activity monitoring, gait analysis, and use of rescue medication. RESULTS: Acute hyperthermia developed after ABT-116 treatment (P < 0.001). Treatment with carprofen (P ≤ 0.01) and tramadol (P ≤ 0.001) led to improved mobility assessed by owner questionnaire. Nighttime activity was increased after ABT-116 treatment (P = 0.01). Kinetic gait analysis did not reveal significant treatment effects. Use of rescue treatment decreased with treatment in the ABT-116 and Carprofen groups (P < 0.001). Questionnaire score and activity count at the end of treatment were correlated with age, clinical severity at trial entry, and outcome measure baseline status (S(R) ≥ ±0.40, P ≤ 0.005). Placebo treatment effects were evident with all variables studied. CONCLUSION: Treatment of hip OA in client-owned dogs is associated with a placebo effect for all variables that are commonly used for efficacy studies of analgesic drugs. This likely reflects caregiver bias or the phenomenon of regression to the mean. In the present study, outcome measures with significant effects also varied between groups, highlighting the value of using multiple outcome measures, as well as an a priori analysis of effect size associated with each measure. Effect size data from the present study could be used to inform design of future trials studying analgesic treatment of canine OA. Our results suggest that analgesic treatment with ABT-116 is not as effective as carprofen or tramadol for treatment of hip arthritis pain in client-owned dogs

Folate Network Genetic Variation, Plasma Homocysteine, and Global Genomic Methylation Content: A Genetic Association Study

Background: Sequence variants in genes functioning in folate-mediated one-carbon metabolism are hypothesized to lead to changes in levels of homocysteine and DNA methylation, which, in turn, are associated with risk of cardiovascular disease. Methods: 330 SNPs in 52 genes were studied in relation to plasma homocysteine and global genomic DNA methylation. SNPs were selected based on functional effects and gene coverage, and assays were completed on the Illumina Goldengate platform. Age-, smoking-, and nutrient-adjusted genotype--phenotype associations were estimated in regression models. Results: Using a nominal P $\leq$ 0.005 threshold for statistical significance, 20 SNPs were associated with plasma homocysteine, 8 with Alu methylation, and 1 with LINE-1 methylation. Using a more stringent false discovery rate threshold, SNPs in FTCD, SLC19A1, and SLC19A3 genes remained associated with plasma homocysteine. Gene by vitamin B-6 interactions were identified for both Alu and LINE-1 methylation, and epistatic interactions with the MTHFR rs1801133 SNP were identified for the plasma homocysteine phenotype. Pleiotropy involving the MTHFD1L and SARDH genes for both plasma homocysteine and Alu methylation phenotypes was identified. Conclusions: No single gene was associated with all three phenotypes, and the set of the most statistically significant SNPs predictive of homocysteine or Alu or LINE-1 methylation was unique to each phenotype. Genetic variation in folate-mediated one-carbon metabolism, other than the well-known effects of the MTHFR c.665C>T (known as c.677 C>T, rs1801133, p.Ala222Val), is predictive of cardiovascular disease biomarkers

Development Status of Adjustable Grazing Incidence Optics for 0.5 Arcsecond X-Ray Imaging

We describe progress in the development of adjustable grazing incidence X-ray optics for 0.5 arcsec resolution cosmic X-ray imaging. To date, no optics technology is available to blend high resolution imaging like the Chandra X-ray Observatory, with square meter collecting area. Our approach to achieve these goals simultaneously is to directly deposit thin film piezoelectric actuators on the back surface of thin, lightweight Wolter-I or Wolter- Schwarschild mirror segments. The actuators are used to correct mirror figure errors due to fabrication, mounting and alignment, using calibration and a one-time figure adjustment on the ground. If necessary, it will also be possible to correct for residual gravity release and thermal effects on-orbit. In this paper we discuss our most recent results measuring influence functions of the piezoelectric actuators using a Shack-Hartmann wavefront sensor. We describe accelerated and real-time lifetime testing of the piezoelectric material, and we also discuss changes to, and recent results of, our simulations of mirror correction

Folate network genetic variation, plasma homocysteine, and global genomic methylation content: a genetic association study

BACKGROUND: Sequence variants in genes functioning in folate-mediated one-carbon metabolism are hypothesized to lead to changes in levels of homocysteine and DNA methylation, which, in turn, are associated with risk of cardiovascular disease. METHODS: 330 SNPs in 52 genes were studied in relation to plasma homocysteine and global genomic DNA methylation. SNPs were selected based on functional effects and gene coverage, and assays were completed on the Illumina Goldengate platform. Age-, smoking-, and nutrient-adjusted genotype--phenotype associations were estimated in regression models. RESULTS: Using a nominal P 64 0.005 threshold for statistical significance, 20 SNPs were associated with plasma homocysteine, 8 with Alu methylation, and 1 with LINE-1 methylation. Using a more stringent false discovery rate threshold, SNPs in FTCD, SLC19A1, and SLC19A3 genes remained associated with plasma homocysteine. Gene by vitamin B-6 interactions were identified for both Alu and LINE-1 methylation, and epistatic interactions with the MTHFR rs1801133 SNP were identified for the plasma homocysteine phenotype. Pleiotropy involving the MTHFD1L and SARDH genes for both plasma homocysteine and Alu methylation phenotypes was identified. CONCLUSIONS: No single gene was associated with all three phenotypes, and the set of the most statistically significant SNPs predictive of homocysteine or Alu or LINE-1 methylation was unique to each phenotype. Genetic variation in folate-mediated one-carbon metabolism, other than the well-known effects of the MTHFR c.665C>T (known as c.677 C>T, rs1801133, p.Ala222Val), is predictive of cardiovascular disease biomarkers