Trends in the Health of Older Californians: Data From the 2001, 2003 and 2005 California Health Interview Surveys

Analyzes trends in the health status and use of preventive services among Californians age 65 and over by race/ethnicity, insurance type, and region. Reports rises in doctor visits and in cancer, diabetes, high cholesterol, obesity, and other illnesses

Chondrocyte response to in vitro mechanical injury and co-culture with joint capsule tissue

Thesis (Ph. D.)--Massachusetts Institute of Technology, Biological Engineering Division, 2005.Includes bibliographical references.Acute traumatic joint injury in young adults leads to an increased risk for the development of osteoarthritis (OA) later in life irrespective of surgical intervention to stabilize the injured joint. Although the mechanism by which injury leads to joint degeneration remains to be elucidated, several injury-related factors may contribute to the development of OA. These factors include but are not limited to altered mechanical loading and initiation of a cellular response in cartilage or other joint tissues at the time of the injury. Three in vitro models of joint injury were investigated to separately evaluate the effects on cartilage of mechanical overloading and damage to joint capsule and synovial lining. Models of injury included (1) mechanical injury lto cartilage explants alone, (2) co-culture of normal cartilage explants with an excised specimen of joint capsule tissue, and (3) co-culture of mechanically injured cartilage explants with excised joint capsule tissue. These models have been shown previously to result in matrix damage and decreased biosynthesis by the chondrocytes. We measured gene expression levels of matrix molecules and matrix proteases and found them to be expressed in control cartilage at levels ranging over five orders of magnitude, and to be differentially regulated in these three models of joint injury.(cont.) Expression of matrix molecules including collagen II and aggrecan were unaffected by injurious compression or co-culture with joint capsule tissue during the first 24 hours; however, the combination of injurious compression followed by co-culture resulted in a -50% decrease in expression by 24 hours. Matrix proteases aggrecanase-2 (ADAMTS-5) and stromelysin (MMP-3) showed increased expression of 40-250-fold by 12 hours following injurious compression and 6-12-fold during 24 hours of co-culture with joint capsule tissue. Aggrecanase-1 (ADAMTS-4) and collagenase-3 (MMP-13) showed larger magnitude increases in expression during co-culture (6-8-fold; 6-24 hours) compared to injurious compression (2-4-fold; 6-24 hours). Expression of transcription factors, c-fos and c-jun, was rapidly increased by injurious compression (40-100-fold within one hour) but was less affected by co-culture with joint capsule tissue (increased 3-5-fold; 1-24 hours). Expression level results displayed a general trend toward matrix degradation in the models of joint injury with specific differences apparent between the models. Analysis of matrix protein fragments in the same injury models showed cleavage of aggrecan at the aggrecanase site in the interglobular domain by 16 days following injurious compression and during co-culture with joint capsule tissue.(cont.) Equilibrium and dynamic stiffness of cartilage explants were decreased by 30-35% immediately after injurious compression but were unaffected through 16 days of co-culture with joint capsule tissue. Specific changes in gene expression and activity of matrix proteases observed in these injury models may be indicative of some of the molecules responsible in the initial phase of cartilage degradation observed clinically following joint injury.Jennifer H. Lee.Ph.D

Metformin as a Therapeutic Target in Endometrial Cancers.

Endometrial cancer is the most common gynecologic malignancy in developed countries. Its increasing incidence is thought to be related in part to the rise of metabolic syndrome, which has been shown to be a risk factor for the development of hyperestrogenic and hyperinsulinemic states. This has consequently lead to an increase in other hormone-responsive cancers as well e.g., breast and ovarian cancer. The correlation between obesity, hyperglycemia, and endometrial cancer has highlighted the important role of metabolism in cancer establishment and persistence. Tumor-mediated reprogramming of the microenvironment and macroenvironment can range from induction of cytokines and growth factors to stimulation of surrounding stromal cells to produce energy-rich catabolites, fueling the growth, and survival of cancer cells. Such mechanisms raise the prospect of the metabolic microenvironment itself as a viable target for treatment of malignancies. Metformin is a biguanide drug that is a first-line treatment for type 2 diabetes that has beneficial effects on various markers of the metabolic syndrome. Many studies suggest that metformin shows potential as an adjuvant treatment for uterine and other cancers. Here, we review the evidence for metformin as a treatment for cancers of the endometrium. We discuss the available clinical data and the molecular mechanisms by which it may exert its effects, with a focus on how it may alter the tumor microenvironment. The pleiotropic effects of metformin on cellular energy production and usage as well as intercellular and hormone-based interactions make it a promising candidate for reprogramming of the cancer ecosystem. This, along with other treatments aimed at targeting tumor metabolic pathways, may lead to novel treatment strategies for endometrial cancer

Latent Class Analysis of Children with Math Difficulties and/or Math Learning Disabilities: Are There Cognitive Differences?

This study investigated whether a latent class of children with math difficulties (MD) or math learning disabilities (MLD) emerged within a heterogeneous sample of learners. A latent class analysis was computed on children (N = 447) in Grade 3 who were administered a battery of math, reading, and cognitive measures. The analysis yielded four important findings. First, a discrete latent class of children with MD (15% of the sample) or MLD (10% of the sample) emerged when setting cut-off scores at or below the 25th and 11th percentile, respectively. Second, model testing yielded a high probability of finding children with MD or MLD with reading problems as well as a latent class of low problem solvers with average reading and calculation scores. Third, knowledge of problem solving component processes, estimation and the executive component of WM were significant and unique correlates of latent classes at both cut-off points. Finally, children defined as MD at 25th percentile cut-off but not 11th percentile cut-off yielded high effect sizes on measures of reading, but not on cognitive measures, when compared with children identified at risk at both cut-off points. The results suggest that a statistically distinct latent class of children at risk for MD or MLD can be separated from a heterogeneous sample of children who vary in math, reading and fluid intelligence

The Stellar Metallicity Distribution Function of the Galactic Halo from SDSS Photometry

We explore the stellar metallicity distribution function of the Galactic halo based on SDSS ugriz photometry. A set of stellar isochrones is calibrated using observations of several star clusters and validated by comparisons with medium-resolution spectroscopic values over a wide range of metal abundance. We estimate distances and metallicities for individual main-sequence stars in the multiply scanned SDSS Stripe 82, at heliocentric distances in the range 5 - 8 kpc and |b| > 35 deg, and find that the in situ photometric metallicity distribution has a shape that matches that of the kinematically-selected local halo stars from Ryan & Norris. We also examine independent kinematic information from proper-motion measurements for high Galactic latitude stars in our sample. We find that stars with retrograde rotation in the rest frame of the Galaxy are generally more metal poor than those exhibiting prograde rotation, which is consistent with earlier arguments by Carollo et al. that the halo system comprises at least two spatially overlapping components with differing metallicity, kinematics, and spatial distributions. The observed photometric metallicity distribution and that of Ryan & Norris can be described by a simple chemical evolution model by Hartwick (or by a single Gaussian distribution); however, the suggestive metallicity-kinematic correlation contradicts the basic assumption in this model that the Milky Way halo consists primarily of a single stellar population. When the observed metallicity distribution is deconvolved using two Gaussian components with peaks at [Fe/H] ~ -1.7 and -2.3, the metal-poor component accounts for ~20% - 35% of the entire halo population in this distance range.Comment: Accepted for publication in Ap

Spatially dependent Rabi oscillations: an approach to sub-diffraction-limited CARS microscopy

We present a theoretical investigation of coherent anti-Stokes Raman scattering (CARS) that is modulated by periodically depleting the ground state population through Rabi oscillations driven by an additional control laser. We find that such a process generates optical sidebands in the CARS spectrum and that the frequency of the sidebands depends on the intensity of the control laser light field. We show that analyzing the sideband frequency upon scanning the beams across the sample allows one to spatially resolve emitter positions where a spatial resolution of 65 nm, which is well below the diffraction-limit, can be obtained

Word-Problem-Solving Interventions for Elementary Students With Learning Disabilities: A Selective Meta-Analysis of the Literature

This meta-analysis assessed the effect of word-problem-solving interventions on the word-problem-solving accuracy of students identified as having a learning disability (LD) or at risk for an LD in kindergarten to the sixth grade. Eighteen randomized control group designed studies met the inclusion criteria. Overall, word-problem-solving interventions yielded a significant positive effect on the word-problem-solving accuracy of students in elementary grades with LD (effect size [ES] = 1.08). Instructional components that underlie effective studies were also identified. Results suggest that peer interaction and transfer instructions yielded large effects on treatment outcomes. Results also suggested that intensive interventions (50-min sessions, 34 total sessions) in Grade 3 regardless of instructional setting yielded the largest ESs. These findings support the need to develop and implement quality evidence-based instruction in classroom settings (Tier 1 instruction) prior to utilizing additional resources for more intensive and individualized intervention

Metallicity Mapping with gri Photometry: The Virgo Overdensity and the Halos of the Galaxy

We describe the methodology required for estimation of photometric estimates of metallicity based on the SDSS gri passbands, which can be used to probe the properties of main-sequence stars beyond ~ 10 kpc, complementing studies of nearby stars from more metallicity-sensitive color indices that involve the u passband. As a first application of this approach, we determine photometric metal abundance estimates for individual main-sequence stars in the Virgo Overdensity, which covers almost 1000 square degrees on the sky, based on a calibration of the metallicity sensitivity of stellar isochrones in the gri filter passbands using field stars with well-determined spectroscopic metal abundances. Despite the low precision of the method for individual stars, internal errors of in [Fe/H] ~ +/- 0.1 dex can be achieved for bulk stellar populations. The global metal abundance of the Virgo Overdensity determined in this way is = -2.0 +/- 0.1 (internal) +/- 0.5 (systematic), from photometric measurements of 0.7 million stars with heliocentric distances from ~ 10 kpc to ~ 20 kpc. A preliminary metallicity map, based on results for 2.9 million stars in the northern SDSS DR-7 footprint, exhibits a shift to lower metallicities as one proceeds from the inner- to the outer-halo population, consistent with recent interpretation of the kinematics of local samples of stars with spectroscopically available metallicity estimates and full space motions.Comment: 4 pages, 2 figures, to appear in IAU Symp. 26

Functional muscle hypertrophy by increased insulin-like growth factor 1 does not require dysferlin.

IntroductionDysferlin loss-of-function mutations cause muscular dystrophy, accompanied by impaired membrane repair and muscle weakness. Growth promoting strategies including insulin-like growth factor 1 (IGF-1) could provide benefit but may cause strength loss or be ineffective. The objective of this study was to determine whether locally increased IGF-1 promotes functional muscle hypertrophy in dysferlin-null (Dysf-/- ) mice.MethodsMuscle-specific transgenic expression and postnatal viral delivery of Igf1 were used in Dysf-/- and control mice. Increased IGF-1 levels were confirmed by enzyme-linked immunosorbent assay. Testing for skeletal muscle mass and function was performed in male and female mice.ResultsMuscle hypertrophy occurred in response to increased IGF-1 in mice with and without dysferlin. Male mice showed a more robust response compared with females. Increased IGF-1 did not cause loss of force per cross-sectional area in Dysf-/- muscles.DiscussionWe conclude that increased local IGF-1 promotes functional hypertrophy when dysferlin is absent and reestablishes IGF-1 as a potential therapeutic for dysferlinopathies