Characteristics of ADHD symptom response/remission in a clinical trial of methylphenidate extended release

Clinical trials in attention-deficit/hyperactivity disorder (ADHD) have typically measured outcome using clinician ratings on the Attention-Deficit/Hyperactivity Disorder Rating Scale, Fourth Edition (ADHD-RS-IV) and the Clinical Global Impression-Improvement (CGI-I) scale. Remission has been defined as an endpoint score of less than or equal to 18 on the ADHD-RS-IV (or a mean score of 1). Responders have been defined as patients who achieve a CGI-I score of much or very much improved (1 or 2). There is a lack of agreement in the literature on what percent change in symptoms on the ADHD-RS-IV should be used to define improvement or remission. This study uses data from a clinical trial of a methylphenidate extended release (MPH-MLR; Aptensio XR®) phase III clinical trial to attempt to determine the percent change of symptoms that best corresponds with improvement and remission. Symptom remission at endpoint (ADHD-RS-IV total score ≤18) was most closely aligned with a ≥46% reduction in ADHD-RS-IV total score. Clinical improvement was most closely aligned with a ≥40% reduction in ADHD-RS-IV total score. The three different measures of outcome were strongly aligned during double blind and open label treatment, and were independent of subtype status. Our data suggest that at least 40% improvement in symptoms is needed to achieve a robust response at endpoint

A molecular insight into algal-oomycete warfare: cDNA analysis of <i>Ectocarpus siliculosus</i> infected with the basal oomycete <i>Eurychasma dicksonii</i>

Brown algae are the predominant primary producers in coastal habitats, and like land plants are subject to disease and parasitism. Eurychasma dicksonii is an abundant, and probably cosmopolitan, obligate biotrophic oomycete pathogen of marine brown algae. Oomycetes (or water moulds) are pathogenic or saprophytic non-photosynthetic Stramenopiles, mostly known for causing devastating agricultural and aquacultural diseases. Whilst molecular knowledge is restricted to crop pathogens, pathogenic oomycetes actually infect hosts from most eukaryotic lineages. Molecular evidence indicates that Eu. dicksonii belongs to the most early-branching oomycete clade known so far. Therefore Eu. dicksonii is of considerable interest due to its presumed environmental impact and phylogenetic position. Here we report the first large scale functional molecular data acquired on the most basal oomycete to date. 9873 unigenes, totalling over 3.5Mb of sequence data, were produced from Sanger-sequenced and pyrosequenced EST libraries of infected Ectocarpus siliculosus. 6787 unigenes (70%) were of algal origin, and 3086 (30%) oomycete origin. 57% of Eu. dicksonii sequences had no similarity to published sequence data, indicating that this dataset is largely unique. We were unable to positively identify sequences belonging to the RXLR and CRN groups of oomycete effectors identified in higher oomycetes, however we uncovered other unique pathogenicity factors. These included putative algal cell wall degrading enzymes, cell surface proteins, and cyclophilin-like proteins. A first look at the host response to infection has also revealed movement of the host nucleus to the site of infection as well as expression of genes responsible for strengthening the cell wall, and secretion of proteins such as protease inhibitors. We also found evidence of transcriptional reprogramming of E. siliculosus transposable elements and of a viral gene inserted in the host genome

Effect of tissue fit on corneal shape after transplantation

Postkeratoplasty astigmatism is now a major problem preventing visual recovery. Certain postopertive topographic characteristics are felt to be dictated by the fit of the donor corneal button in its recipient bed. Deficient tissue at the wound is predicted to contribute to the location of the steep meridian and excess tissue to the location of the flat meridian. In an eight-cat sample using our Fit Assessment Method and Photogrammetric Index Method, the authors tested the relationship between button fit in recipient bed and resulting corneal curvature at approximately 42, 161, and 289 postoperative days. Corneal symmetry improved between the first and second postoperative periods. Deficient tissue led to steepened curvature and ample tissue to flattened curvature in the first measurement period. When buttons fit poorly, deficient tissue led to steepness in the first postoperative period, but led to flattened curvature 90 deg away from the deficient tissue meridian in the second and third periods. The relationship between ample tissue and flattest postoperative curvature did not depend on the magnitude of button-bed disparity in any period. Corneal elasticity appeared to influence the way tissue disparity affected postoperative topography. Our findings support Troutman's balloon mode. When there was a large amount of uncompensated tissue disparity, the tissue deficiency exerted a force that shortened the translimbal chord. This produced both steepened curvature parallel to this chord soon after surgery and flattened curvature at 90 deg to the chord in the stable postoperative cornea

A new photogrammetric method for quantifying corneal topography

Attempts to describe normal corneal shape and to represent corneal topography by an array of discrete points have limited usefulness. A quantitative photogrammetric method that produces indices to describe corneal shape was developed. Four indices depict the departure of keratographic rings from circularity, and two indices express the trends and consistencies of all the rings from one keratograph. This photogrammetric index method (PIM) was evaluated against established measurement techniques. Values for the six indices were computed for groups (10 corneas each) of symmetrical, regularly astigmatic, and keratoconic corneas that had been defined by keratometry and clinical criteria. Predictions of the differences among groups were formulated for each index based on group descriptions and anticipated manual tracing and/or digitization error. Parametric and nonparametric tests of significance supported most predictions. The asymmetry of irregularly astigmatic keratoconic corneas, the variability of their orthogonal principal meridians, and an increasing symmetry toward their peripheries were documented clearly. The circularity of symmetrical group rings and the ellipticity of regularly astigmatic group rings were also evident. Preliminary norms are offered to illustrate the usefulness of the PIM in defining groups of corneas with the same histories and in classifying individual corneas

Approximate and Pseudo-Likelihood Analysis for Logistic Regression Using External Validation Data to Model Log Exposure

A common goal in environmental epidemiologic studies is to undertake logistic regression modeling to associate a continuous measure of exposure with binary disease status, adjusting for covariates. A frequent complication is that exposure may only be measurable indirectly, through a collection of subject-specific variables assumed associated with it. Motivated by a specific study to investigate the association between lung function and exposure to metal working fluids, we focus on a multiplicative-lognormal structural measurement error scenario and approaches to address it when external validation data are available. Conceptually, we emphasize the case in which true untransformed exposure is of interest in modeling disease status, but measurement error is additive on the log scale and thus multiplicative on the raw scale. Methodologically, we favor a pseudo-likelihood (PL) approach that exhibits fewer computational problems than direct full maximum likelihood (ML) yet maintains consistency under the assumed models without necessitating small exposure effects and/or small measurement error assumptions. Such assumptions are required by computationally convenient alternative methods like regression calibration (RC) and ML based on probit approximations. We summarize simulations demonstrating considerable potential for bias in the latter two approaches, while supporting the use of PL across a variety of scenarios. We also provide accessible strategies for obtaining adjusted standard errors to accompany RC and PL estimates

Correlates of antioxidant nutrients and oxidative DNA damage differ by race in a cross-sectional study of healthy African American and white adults

Although antioxidant nutrients and oxidative DNA damage have been associated with carcinogenesis, few studies have investigated the factors that influence antioxidant intake and oxidative DNA damage in racially diverse populations. Demographic, behavioral, and diet-related psychosocial correlates of plasma antioxidant (carotenoids, vitamin C, and vitamin E) concentrations and oxidative DNA damage were examined using data from a cross-sectional study of 147 generally healthy, non-smoking African American and White adults in North Carolina, age 20 to 45 years. All participants completed self-administered demographic, diet, and health questionnaires and provided semi-fasting (≥ 6 hours) blood samples. Multivariate regression analyses were computed separately for each race to determine associations between the potential correlates with plasma antioxidant concentrations and oxidative DNA damage, separately. Our findings suggest appreciable differences by race. Only a few factors (age, supplement use, and several psychosocial factors) were associated with antioxidant concentrations in African Americans, whereas these and additional factors, including physical activity, waist circumference, and passive smoke exposure, were associated with antioxidant concentrations in Whites. For oxidative DNA damage, passive smoke exposure was significantly associated with oxidative DNA damage in African Americans, and age and alcohol were significant in Whites. In addition, the regression models generally explained more of the variance in plasma antioxidant concentrations and oxidative DNA damage in Whites than in African Americans. Considering the salient correlates differed by race, this work has important implications for the design and implementation of future research studies investigating antioxidant nutrients and/or oxidative stress, especially those in racially diverse populations

Dermal Exposure to Jet Fuel JP-8 Significantly Contributes to the Production of Urinary Naphthols in Fuel-Cell Maintenance Workers

Jet propulsion fuel 8 (JP-8) is the major jet fuel used worldwide and has been recognized as a major source of chemical exposure, both inhalation and dermal, for fuel-cell maintenance workers. We investigated the contributions of dermal and inhalation exposure to JP-8 to the total body dose of U.S. Air Force fuel-cell maintenance workers using naphthalene as a surrogate for JP-8 exposure. Dermal, breathing zone, and exhaled breath measurements of naphthalene were obtained using tape-strip sampling, passive monitoring, and glass bulbs, respectively. Levels of urinary 1- and 2-naphthols were determined in urine samples and used as biomarkers of JP-8 exposure. Multiple linear regression analyses were conducted to investigate the relative contributions of dermal and inhalation exposure to JP-8, and demographic and work-related covariates, to the levels of urinary naphthols. Our results show that both inhalation exposure and smoking significantly contributed to urinary 1-naphthol levels. The contribution of dermal exposure was significantly associated with levels of urinary 2-naphthol but not with urinary 1-naphthol among fuel-cell maintenance workers who wore supplied-air respirators. We conclude that dermal exposure to JP-8 significantly contributes to the systemic dose and affects the levels of urinary naphthalene metabolites. Future work on dermal xenobiotic metabolism and toxicokinetic studies are warranted in order to gain additional knowledge on naphthalene metabolism in the skin and the contribution to systemic exposure

Patterns of Intimate Partner Violence Victimization from Adolescence to Young Adulthood in a Nationally Representative Sample

To determine the prevalence of patterns of intimate partner violence (IPV) victimization from adolescence to young adulthood, and document associations with selected sociodemographic and experiential factors