Genetically engineered mesenchymal stem cells as a proposed therapeutic for Huntington's disease.

There is much interest in the use of mesenchymal stem cells/marrow stromal cells (MSC) to treat neurodegenerative disorders, in particular those that are fatal and difficult to treat, such as Huntington's disease. MSC present a promising tool for cell therapy and are currently being tested in FDA-approved phase I-III clinical trials for many disorders. In preclinical studies of neurodegenerative disorders, MSC have demonstrated efficacy, when used as delivery vehicles for neural growth factors. A number of investigators have examined the potential benefits of innate MSC-secreted trophic support and augmented growth factors to support injured neurons. These include overexpression of brain-derived neurotrophic factor and glial-derived neurotrophic factor, using genetically engineered MSC as a vehicle to deliver the cytokines directly into the microenvironment. Proposed regenerative approaches to neurological diseases using MSC include cell therapies in which cells are delivered via intracerebral or intrathecal injection. Upon transplantation, MSC in the brain promote endogenous neuronal growth, encourage synaptic connection from damaged neurons, decrease apoptosis, reduce levels of free radicals, and regulate inflammation. These abilities are primarily modulated through paracrine actions. Clinical trials for MSC injection into the central nervous system to treat amyotrophic lateral sclerosis, traumatic brain injury, and stroke are currently ongoing. The current data in support of applying MSC-based cellular therapies to the treatment of Huntington's disease is discussed

Prevention of smoking in Middle School Students: Psychometric assessment of the Temptations to Try Smoking Scale

Establishment of psychometrically sound measures is critical to the development of effective interventions. The current study examined the psychometric properties, including factorial invariance, of a six item Temptations to Try Smoking Scale on a sample of middle school students. The sample of 6th grade students (N = 3527) was from 20 Rhode Island middle schools and was 52% male and 84% white. The Temptations to Try Smoking Scale consisted of two correlated subscales: Positive Social and Curiosity/Stress. Structural equation modeling was implemented to evaluate the factorial invariance across four different subgroups defined by gender (male/female), race (white/black), ethnicity (Hispanic/Non-Hispanic), and school size (\u3c 200/ \u3e 200 6th graders). A model is factorially invariant when the measurement model is the same in each of the subgroups. Three levels of invariance were examined in sequential order: 1) Configural Invariance (unconstrained nonzero factor loadings); 2) Pattern Identity Invariance (equal factor loadings); and 3) Strong Factorial Invariance (equal factor loadings and measurement errors). Strong Factorial Invariance provided a good fit to the model across gender (CFI = .96), race (CFI = .96), ethnicity (CFI = .94), and school size (CFI = .97). Coefficient Alphas for the two subscales, Positive Social and Curiosity/Stress, were .87 and .86, respectively. These findings provide empirical support for the construct validity of the Temptations to Try Smoking Scale in middle school students

Psychometric assessment of the Temptations to Try Alcohol Scale

Effective interventions require an understanding of the behaviors and cognitions that facilitate positive change as well as the development of psychometrically sound measures. This paper reports on the psychometric properties of the Temptations to Try Alcohol Scale (TTAS), including factorial invariance across different subgroups. Data were collected from 3565 6th grade RI middle school students. Structural equation modeling was used to determine the appropriate factorial invariance model for the 9-item TTAS. The measure consists of three correlated subscales: Social Pressure, Social Anxiety, and Opportunity. Three levels of invariance, ranging from the least to the most restrictive, were examined: Configural Invariance, which constrains only the factor structure and zero loadings; Pattern Identity Invariance, which requires factor loadings to be equal across the groups; and Strong Factorial Invariance, which requires factor loadings and error variances to be constrained. Separate analyses evaluated the invariance across two levels of gender (males vs. females), race (white vs. black) ethnicity (Hispanic vs. Non-Hispanic) and school size (small, meaning \u3c 200 6th graders, or large). The highest level of invariance, Strong Factorial Invariance, provided a good fit to the model for gender (CFI: .95), race (CFI: .94), ethnicity (CFI: .94), and school size (CFI: .97). Coefficient Alpha was .90 for Social Pressure, .81 for Social Anxiety, and .82 for Opportunity. These results provide strong empirical support for the psychometric structure and construct validity of the TTAS in middle school students

Prevention of alcohol use in middle school students: Psychometric assessment of the decisional balance inventory

A measurement model should be equivalent across the different subgroups of a target population. The Decisional Balance Inventory for the Prevention of Alcohol Use is a 2-factor correlated model with 3 items for Pros of alcohol use and 3 items for Cons. The measure is part of a tailored intervention for middle school students. This study evaluated the important psychometric assumptions of factorial invariance and scale reliability with a large sample of sixth grade students (N = 3565) from 20 schools. A measure is factorially invariant when the model is the same across subgroups. Three levels of invariance were assessed, from least restrictive to most restrictive: 1) Configural Invariance (unconstrained nonzero factor loadings); 2) Pattern Identity Invariance (equal factor loadings); and 3) Strong Factorial Invariance (equal factor loadings and measurement errors). Structural equation modeling was used to assess invariance over two levels of gender (male and female), race (white and black), ethnicity (Hispanic and non-Hispanic), and school size (large, indicating \u3e 200 students per grade, or small). The strongest level of invariance, Strong Factorial Invariance, was a good fit for the model across all of the subgroups: gender (CFI: 0.94), race (CFI: 0.96), ethnicity (CFI: 0.93), and school size (CFI: 0.97). Coefficient alpha was 0.61 for the Pros and 0.67 for Cons. Together, invariance and reliability provide strong empirical support for the validity of the measure

Treated individuals who progress to action or maintenance for one behavior are more likely to make similar progress on another behavior: Coaction results of a pooled data analysis of three trials

Objective: This study compared, in treatment and control groups, the phenomena of coaction, which is the probability that taking effective action on one behavior is related to taking effective action on a second behavior. Methods: Pooled data from three randomized trials of Transtheoretical Model (TTM) tailored interventions (n = 9461), completed in the U.S. in 1999, were analyzed to assess coaction in three behavior pairs (diet and sun protection, diet and smoking, and sun protection and smoking). Odds ratios (ORs) compared the likelihood of taking action on a second behavior compared to taking action on only one behavior. Results: Across behavior pairs, at 12 and 24 months, the ORs for the treatment group were greater on an absolute basis than for the control group, with two being significant. The combined ORs at 12 and 24 months, respectively, were 1.63 and 1.85 for treatment and 1.20 and 1.10 for control. Conclusions: The results of this study with addictive, energy balance and appearance-related behaviors were consistent with results found in three studies applying TTM tailoring to energy balance behaviors. Across studies, there was more coaction within the treatment group. Future research should identify predictors of coaction in more multiple behavior change interventions

Visually assessed breast density, breast cancer risk and the importance of the craniocaudal view

Contains fulltext : 69403.pdf (publisher's version ) (Open Access)INTRODUCTION: Mammographic density is known to be a strong risk factor for breast cancer. A particularly strong association with risk has been observed when density is measured using interactive threshold software. This, however, is a labour-intensive process for large-scale studies. METHODS: Our aim was to determine the performance of visually assessed percent breast density as an indicator of breast cancer risk. We compared the effect on risk of density as measured with the mediolateral oblique view only versus that estimated as the average density from the mediolateral oblique view and the craniocaudal view. Density was assessed using a visual analogue scale in 10,048 screening mammograms, including 311 breast cancer cases diagnosed at that screening episode or within the following 6 years. RESULTS: Where only the mediolateral oblique view was available, there was a modest effect of breast density on risk with an odds ratio for the 76% to 100% density relative to 0% to 25% of 1.51 (95% confidence interval 0.71 to 3.18). When two views were available, there was a considerably stronger association, with the corresponding odds ratio being 6.77 (95% confidence interval 2.75 to 16.67). CONCLUSION: This indicates that a substantial amount of information on risk from percentage breast density is contained in the second view. It also suggests that visually assessed breast density has predictive potential for breast cancer risk comparable to that of density measured using the interactive threshold software when two views are available. This observation needs to be confirmed by studies applying the different measurement methods to the same individuals

The N2K Consortium. III. Short-Period Planets Orbiting HD 149143 and HD 109749

We report the detection of two short-period planets discovered at Keck Observatory. HD 149143 is a metal-rich G0 IV star with a planet of M sin i = 1.33M_J and an orbital radius of 0.053 AU. The best-fit Keplerian model has an orbital period, P = 4.072 days, semivelocity amplitude, K = 149.6 m s^(-1), and eccentricity, e = 0.016 ± 0.01. The host star is chromospherically inactive and metal-rich, with [Fe/H] = 0.26. Based on the T_(eff) and stellar luminosity, we derive a stellar radius of 1.49 R_☉. Photometric observations of HD 149143 were carried out using the automated photometric telescopes at Fairborn Observatory. HD 149143 is photometrically constant over the radial velocity period to 0.0003 ± 0.0002 mag, supporting the existence of the planetary companion. No transits were detected down to a photometric limit of approximately 0.02%, eliminating transiting planets with a variety of compositions and constraining the orbital inclination to less than 83°. A short-period planet was also detected around HD 109749, a G3 IV star. HD 109749 is chromospherically inactive, with [Fe/H] = 0.25 and a stellar radius of 1.24. The radial velocities for HD 109749 are modeled by a Keplerian with P = 5.24 days and K = 28.7 m s^(-1). The inferred planet mass is M sin i = 0.28M_J and the semimajor axis of this orbit is 0.0635 AU. Photometry of HD 109749 was obtained with the SMARTS consortium telescope, the PROMPT telescope, and by transitsearch.org observers in Adelaide and Pretoria. These observations did not detect a decrement in the brightness of the host star at the predicted ephemeris time, and they constrain the orbital inclination to less than 85° for gas giant planets with radii down to 0.7R_J

A detailed clinical and molecular survey of subjects with nonsyndromic USH2A retinopathy reveals an allelic hierarchy of disease-causing variants.

Defects in USH2A cause both isolated retinal disease and Usher syndrome (ie, retinal disease and deafness). To gain insights into isolated/nonsyndromic USH2A retinopathy, we screened USH2A in 186 probands with recessive retinal disease and no hearing complaint in childhood (discovery cohort) and in 84 probands with recessive retinal disease (replication cohort). Detailed phenotyping, including retinal imaging and audiological assessment, was performed in individuals with two likely disease-causing USH2A variants. Further genetic testing, including screening for a deep-intronic disease-causing variant and large deletions/duplications, was performed in those with one likely disease-causing change. Overall, 23 of 186 probands (discovery cohort) were found to harbour two likely disease-causing variants in USH2A. Some of these variants were predominantly associated with nonsyndromic retinal degeneration ('retinal disease-specific'); these included the common c.2276 G>T, p.(Cys759Phe) mutation and five additional variants: c.2802 T>G, p.(Cys934Trp); c.10073 G>A, p.(Cys3358Tyr); c.11156 G>A, p.(Arg3719His); c.12295-3 T>A; and c.12575 G>A, p.(Arg4192His). An allelic hierarchy was observed in the discovery cohort and confirmed in the replication cohort. In nonsyndromic USH2A disease, retinopathy was consistent with retinitis pigmentosa and the audiological phenotype was variable. USH2A retinopathy is a common cause of nonsyndromic recessive retinal degeneration and has a different mutational spectrum to that observed in Usher syndrome. The following model is proposed: the presence of at least one 'retinal disease-specific' USH2A allele in a patient with USH2A-related disease results in the preservation of normal hearing. Careful genotype-phenotype studies such as this will become increasingly important, especially now that high-throughput sequencing is widely used in the clinical setting.European Journal of Human Genetics advance online publication, 4 February 2015; doi:10.1038/ejhg.2014.283