Potential short-term use of oral cladribine in treatment of relapsing-remitting multiple sclerosis

Multiple sclerosis (MS) is a chronic, immune-mediated disorder of the central nervous system. The clinical course of MS varies among patients. Currently, interferon (IFN) products, including IFN β-1a administered intramuscularly or subcutaneously and IFN β-1b subcutaneously, glatiramer acetate, natalizumab, and mitoxantrone are approved disease-modifying therapies for the treatment of relapsing-remitting MS. Cladribine, also known as 2-chlorodeoxyadenosine, is a synthetic adenosine deaminase-resistant purine nucleoside analog that preferentially depletes lymphocyte subpopulations. This sustained effect on lymphocytes is advantageous for patients with MS. CLARITY (CLAdRIbine Tablets Treating MS OrallY), a Phase III trial, has demonstrated that short-term oral cladribine decreases relapse rates and risk of disability progression in comparison with placebo. Cladribine was well tolerated in the study, with the most common adverse effects being headache, nausea, upper respiratory tract infections, and lymphocytopenia. An ongoing study is evaluating the efficacy and safety of the combination of oral cladribine and IFN-β products. A further ongoing study is examining the use of oral cladribine in clinically isolated syndrome and time to conversion to MS. Although the results of CLARITY are promising, the exact role of oral cladribine may be better defined with the completion of ongoing studies

A Framework for Establishing Restoration Goals for Contaminated Ecosystems

This article represents 1 of 6 articles in the special series “Restoration of Impaired Ecosystems: An Ounce of Prevention or a Pound of Cure?” The articles result from a Technical Workshop organized by SETAC and the Society for Ecological Restoration, held June 2014 in Jackson, Wyoming, that focused on advancing the practice of restoring ecosystems that have been contaminated or impaired from industrial activities.As natural resources become increasingly limited, the value of restoring contaminated sites, both terrestrial and aquatic, becomes increasingly apparent. Traditionally, goals for remediation have been set before any consideration of goals for ecological restoration. The goals for remediation have focused on removing or limiting contamination whereas restoration goals have targeted the ultimate end use. Here, we present a framework for developing a comprehensive set of achievable goals for ecological restoration of contaminated sites to be used in concert with determining goals for remediation. This framework was developed during a Society of Environmental Toxicology and Chemistry (SETAC) and Society of Ecological Restoration (SER) cosponsored workshop that brought together experts from multiple countries. Although most members were from North America, this framework is designed for use internationally. We discuss the integration of establishing goals for both contaminant remediation and overall restoration, and the need to include both the restoration of ecological and socio-cultural-economic value in the context of contaminated sites. Although recognizing that in some countries there may be regulatory issues associated with contaminants and clean up, landscape setting and social drivers can inform the restoration goals. We provide a decision tree support tool to guide the establishment of restoration goals for contaminated ecosystems. The overall intent of this decision tree is to provide a framework for goal setting and to identify outcomes achievable given the contamination present at a site. Integr Environ Assess Manag 2016;12:264–272. 2015 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals, Inc. on behalf of Society of Environmental Toxicology & Chemistry (SETAC

Gender and Health Behavior Clustering among U.S. Young Adults

U.S. trends in population health suggest alarming disparities among young adults who are less healthy across most measureable domains than their counterparts in other high-income countries; these international comparisons are particularly troubling for women. To deepen our understanding of gender disparities in health and underlying behavioral contributions, we document gender-specific clusters of health behavior among U.S. young adults using nationally representative data from the National Longitudinal Study of Adolescent to Adult Health. We find high levels of poor health behavior, but especially among men; 40 percent of men clustered into a group characterized by unhealthy behavior (e.g., poor diet, no exercise, substance use), compared to only 22 percent of women. Additionally, women tend to age out of unhealthy behaviors in young adulthood more than men. Further, we uncover gender differences in the extent to which sociodemographic position and adolescent contexts inform health behavior clustering. For example, college education was more protective for men, whereas marital status was equally protective across gender. Parental drinking mattered for health behavior clustering among men, whereas peer drinking mattered for clustering among women. We discuss these results in the context of declining female advantage in U.S. health and changing young adult social and health contexts

The reliability of pseudoneglect is task dependent

Funding: This work was supported by the University of St. Andrews and by Wellcome Trust Institutional Strategic Support Funds (105621/Z/14/Z).Bisection tasks that require individuals to identify the midpoint of a line are often used to assess the presence of biases to spatial attention in both healthy and patient populations. These tasks have helped to uncover a phenomenon called pseudoneglect, a bias towards the left-side of space in healthy individuals. First identified in the tactile domain, pseudoneglect has been subsequently demonstrated in other sensory modalities such as vision. Despite this, the specific reliability of pseudoneglect within individuals across tasks and time has been investigated very little. In this study, we investigated the reliability of response bias within individuals across four separate testing sessions and during three line bisection tasks: landmark, line bisection and tactile rod bisection. Strong reliability was expected within individuals across task and session. Pseudoneglect was found when response bias was averaged across all tasks, for the entire sample. However, individual data showed biases to both left and right, with some participants showing no clear bias, demonstrating individual differences in bias. Significant, cross-session within-individual reliability was found for the landmark and tactile rod bisection tasks respectively, but no significant reliability was observed for the line bisection task. Alongside this, no significant cross-task within-individual reliability was observed. These results highlight the inconsistent nature of pseudoneglect within individuals, particularly across sensory modality. They also provide strong support for the use of the landmark task as the most reliable measure of pseudoneglect.Publisher PDFPeer reviewe

Core Beliefs, Self-Perception, and Cognitive Organization in Depressed Adolescents

The relationships between cognitive products (e.g., self-perception) and cognitive structure (or organization) in clinically depressed adolescents and nonpsychiatric controls (average age = 14.68) were examined. Adolescents with major depressive disorder showed significantly higher scores than did controls on the Young Schema Questionnaire domains of Disconnection, Impaired Autonomy, and Impaired Limits. These individuals also demonstrated poorer self-concept than controls on scholastic abilities, social acceptance, athletic competence, physical appearance, job competence, behavioral conduct, and global self-worth, as well as perceptions of limited social networks. The organization of self-referent adjectives was more tightly interconnected for negative content and less interconnected for positive content in depressed adolescents than in nonpsychiatric controls. Specificity of cognitive organization to themes of interpersonal and achievement beliefs/self-perceptions was also found, particularly for positive content. Implications of the findings for the cognitive vulnerability model of depression and future directions are discussed

Inspection of the Math Model Tools for On-Orbit Assessment of Impact Damage Report

In Spring of 2005, the NASA Engineering Safety Center (NESC) was engaged by the Space Shuttle Program (SSP) to peer review the suite of analytical tools being developed to support the determination of impact and damage tolerance of the Orbiter Thermal Protection Systems (TPS). The NESC formed an independent review team with the core disciplines of materials, flight sciences, structures, mechanical analysis and thermal analysis. The Math Model Tools reviewed included damage prediction and stress analysis, aeroheating analysis, and thermal analysis tools. Some tools are physics-based and other tools are empirically-derived. Each tool was created for a specific use and timeframe, including certification, real-time pre-launch assessments. In addition, the tools are used together in an integrated strategy for assessing the ramifications of impact damage to tile and RCC. The NESC teams conducted a peer review of the engineering data package for each Math Model Tool. This report contains the summary of the team observations and recommendations from these reviews

VarSight: prioritizing clinically reported variants with binary classification algorithms.

BackgroundWhen applying genomic medicine to a rare disease patient, the primary goal is to identify one or more genomic variants that may explain the patient's phenotypes. Typically, this is done through annotation, filtering, and then prioritization of variants for manual curation. However, prioritization of variants in rare disease patients remains a challenging task due to the high degree of variability in phenotype presentation and molecular source of disease. Thus, methods that can identify and/or prioritize variants to be clinically reported in the presence of such variability are of critical importance.MethodsWe tested the application of classification algorithms that ingest variant annotations along with phenotype information for predicting whether a variant will ultimately be clinically reported and returned to a patient. To test the classifiers, we performed a retrospective study on variants that were clinically reported to 237 patients in the Undiagnosed Diseases Network.ResultsWe treated the classifiers as variant prioritization systems and compared them to four variant prioritization algorithms and two single-measure controls. We showed that the trained classifiers outperformed all other tested methods with the best classifiers ranking 72% of all reported variants and 94% of reported pathogenic variants in the top 20.ConclusionsWe demonstrated how freely available binary classification algorithms can be used to prioritize variants even in the presence of real-world variability. Furthermore, these classifiers outperformed all other tested methods, suggesting that they may be well suited for working with real rare disease patient datasets

Planning and establishment of a high throughput screening site

In 1996 and 1997, Glaxo Wellcome's US Research division planned and established their second generation research strategy. An important aspect of the strategy entailed development of two automated screening sites in Biochemistry in Research Triangle Park, NC. Development of the new operations required many decisions to be made very quickly, including automated process design, system selection and site preparation. Descriptions of the decision made in the development of one of the screening sites are presented in this paper

Inspection of the Math Model Tools for On-Orbit Assessment of Impact Damage Report

In Spring of 2005, the NASA Engineering Safety Center (NESC) was engaged by the Space Shuttle Program (SSP) to peer review the suite of analytical tools being developed to support the determination of impact and damage tolerance of the Orbiter Thermal Protection Systems (TPS). The NESC formed an independent review team with the core disciplines of materials, flight sciences, structures, mechanical analysis and thermal analysis. The Math Model Tools reviewed included damage prediction and stress analysis, aeroheating analysis, and thermal analysis tools. Some tools are physics-based and other tools are empirically-derived. Each tool was created for a specific use and timeframe, including certification, real-time pre-launch assessments, and real-time on-orbit assessments. The tools are used together in an integrated strategy for assessing the ramifications of impact damage to tile and RCC. The NESC teams conducted a peer review of the engineering data package for each Math Model Tool. This report contains the summary of the team observations and recommendations from these reviews

Cardiorespiratory profile and performance demands of elite hip-hop dancers: Breaking and new style

Dancers need to constantly maintain and develop their physiological capabilities to support their performances. Previously these physiological demands have been investigated only in traditional dance styles such as ballet and modern. The aim of this study was to examine the physiological demands of two types of hip-hop: new style and break dance. Nine female new style dancers (age 20±6 yrs, height 163.5±1.4 cm, mass 55.8±22 kg) and 9 male break dancers (age 23±4.2 yrs, height 178.2±5.7 cm, mass 62.1±7.7 kg) volunteered for the study. Each subject completed a maximal graded treadmill test and a dance performance routine, either new style (approx 1:45-2:30 min) or breaking (2 min). Breathe-by-breathe gas analysis and heart rate (HR) were collected by a portable gas analyser, and blood lactate (BLa) was measured at the end of the treadmill test and each routine. The male breaker dancers had significantly higher VO2 peak than other equivalent dancers in other genres, whilst the female new style dancers were similar to that previously reported for female dancers. Performance data showed significant differences between the two styles for VO2, HR, and BLa (p<0.001) and for VO2 and HR relative to individual maximal treadmill data (p<0.05). New style is more comparable to other theatrical dance genres, with a lower relative mean VO2 demand, whilst break dance is shorter in duration, allowing a higher cardiorespiratory demand and generating significant levels of blood lactate. This difference is also reflected in the dancers' cardiorespiratory profiles