An independent randomized clinical trial of multisystemic therapy with non-court-referred adolescents with serious conduct problems.

PubMed

Weiss, Bahr; Han, Susan; Harris, Vicki; Catron, Thomas; Ngo, Victoria K; Caron, Annalise; Gallop, Robert; Guth, Carol

2013-12-01

Adolescent conduct problems exact serious social as well as personal costs, and effective treatments are essential. One of the most widely disseminated and effective programs for the treatment of serious conduct problems in adolescents is Multisystemic Therapy (MST). However, most evaluations of MST have involved the developers of MST. The purpose of the present study was to conduct an independent evaluation of MST, with non-court-referred adolescents with conduct problems. Participants were 164 adolescents ages 11-18 years who were recruited from self-contained behavior intervention classrooms in public schools. Adolescents and their families were randomly assigned to receive MST or services as usual. Outcome measures assessed conduct problems, school functioning, and court records of criminal behavior. Participants were followed for 18 months after baseline using parent, adolescent, and teacher reports; arrest data were collected for 2.5 years postbaseline. Two of 4 primary outcome measures focused on externalizing problems showed significant treatment effects favoring MST. Several secondary and intervention targets pertaining to family functioning and parent psychopathology showed positive effects of MST, and no negative effects were identified. Results provide some further support for the effectiveness of MST, although smaller effect sizes than previous studies also suggest the complexity of successful dissemination, particularly to non-court-referred populations.

An Evaluation of Multisystemic Therapy with Australian Families.

PubMed

Porter, Mark; Nuntavisit, Leartluk

2016-12-01

This study aims to evaluate the effectiveness of the Multisystemic Therapy (MST) intervention for Australian families invloved with the Specialist Child and Adolescent Mental Health Service (CAMHS). This program was implemented within the Western Australian Department of Health in 2005, and has continually operated two small clinical teams within the Perth metropolitan area since then. This intervention was specifically chosen to improve service access, engagement, and intervention with vulnerable families having young persons with a history of significant and enduring behavioural problems. The study reports on data collected from July 2007 to July 2013 which includes baseline, post-treatment, 6-month, and 12-month follow-up. There were 153 MST families participating in the research at all time points (71% male; 11% Australian Aboriginal; average youth age was 13.6 years). Caregivers completed a set of questionnaires including Child Behaviour Checklist, Parenting Styles and Dimensions Questionnaire, and Depression, Anxiety and Stress Scale. One-way repeated measure ANOVA were used to measure changes over time. Significant caregiver-reported improvements in all measures were reported at post-treatment, and most improvements were maintained at the follow-up periods of 6 and 12 months post-intervention. These preliminary outcomes demonstrate that the 4-5 month MST intervention significantly reduces behavioural problems and emotional difficulties in young Australians and these improvements are generally maintained by caregivers over time. Primary caregivers reported improved skills and mental health functioning that were also maintained over the follow-up period. A proposed randomised controlled trial of the program will address potential placebo and selection bias effects.

Changes in Maternal Depression Are Associated with MST Outcomes for Adolescents with Co-Occurring Externalizing and Internalizing Problems

ERIC Educational Resources Information Center

Grimbos, Teresa; Granic, Isabela

2009-01-01

The efficacy of Multisystemic therapy (MST) in treating adolescent aggression has been established, however, not all youth and their families benefit from MST. One reason for this treatment variability could be the failure to distinguish between different aggressive subtypes with different risk factors, developmental prognoses and treatment needs.…

Economic evaluation of multisystemic therapy for young people at risk for continuing criminal activity in the UK.

PubMed

Cary, Maria; Butler, Stephen; Baruch, Geoffrey; Hickey, Nicole; Byford, Sarah

2013-01-01

To evaluate whether multisystemic therapy (MST) is more cost-effective than statutory interventions that are currently available for young offenders in England. A cost-offset evaluation of MST based on data from a randomised controlled trial conducted in North London, England, comparing MST with usual services provided by two youth offending teams (YOT). Service costs were compared to cost savings in terms of rates of criminal re-offending. 108 adolescents, aged 11-17 years, were randomly allocated to MST+YOT (n = 56) or YOT alone (n = 52). Reductions in offending were evident in both groups, but were higher in the MST+YOT group. At 18-month follow-up, the MST+YOT group cost less in terms of criminal activity (£9,425 versus £11,715, p = 0.456). The MST+YOT group were significantly cheaper in terms of YOT services than the YOT group (£3,402 versus £4,619, p = 0.006), but more expensive including the cost of MST, although not significantly so (£5,687 versus £4,619, p = 0.195). The net benefit per young person for the 18-month follow-up was estimated to be £1,222 (95% CI -£5,838 to £8,283). The results reported in this study support the finding that MST+YOT has scope for cost-savings when compared to YOT alone. However, the limitations of the study in terms of method of economic evaluation, outcome measures used and data quality support the need for further research.

Efficacy of multisystemic therapy in youths aged 10-17 with severe antisocial behaviour and emotional disorders: systematic review.

PubMed

Tan, Jia Xuan; Fajardo, Maria Lourdes Restrepo

2017-11-01

Antisocial behaviour and conduct disorders are the most common behavioural and mental health problems in children and young people globally. An efficacious intervention is needed to manage these antisocial behaviours that have costly consequences. Multisystemic Therapy (MST), an intensive home-based intervention for youths with psychosocial and behavioural problems, is recommended under National Institute for Health and Clinical Excellence guidelines for conduct disorder. However, reviews on the efficacy of MST are mixed. To review randomised controlled trials (RCTs) reporting efficacy of MST among youths presenting with antisocial behaviour and emotional disorder respectively. A systematic map term to subject heading search was conducted in PsycINFO, Embase, and Ovid Medline databases for articles up to November 2015. RCTs comparing MST vs.treatment as usual (TAU) in youths presenting with antisocial behaviour and emotional disorder were included. 12 RCTs ( n  = 1425) reported efficacy of MST vs. TAU in youths presenting with antisocial behaviour and emotional disorder. Clinically significant treatment effects of MST showed a reduction of antisocial behaviour which includes delinquency. MST, vs. psychiatric hospitalisation, was associated with a reduction of suicidal attempts in youths presenting with psychiatric emergencies. 4 studies showed that MST was less costly than TAU in the short term, with further analysis required for long-term cost-effectiveness. MST is an efficacious intervention for severe antisocial behaviours in reduction of delinquency and should be included in clinical practices. MST was shown to have a positive effect on emotional disorder but further research is needed to evaluate the efficacy of MST with emotional disorder. Further analysis is required to assess the services utilized for long-term cost effectiveness.

Placement and Delinquency Outcomes Among System-Involved Youth Referred to Multisystemic Therapy: A Propensity Score Matching Analysis.

PubMed

Vidal, Sarah; Steeger, Christine M; Caron, Colleen; Lasher, Leanne; Connell, Christian M

2017-11-01

Multisystemic therapy (MST) was developed to help youth with serious social, emotional, and behavioral problems. Research on the efficacy and effectiveness of MST has shown positive outcomes in different domains of development and functioning among various populations of youth. Nonetheless, even with a large body of literature investigating the treatment effects of MST, few studies have focused on the effectiveness of MST through large-scale dissemination efforts. Utilizing a large sample of youth involved in a statewide dissemination of MST (n = 740; 43% females; 14% Black; 29% Hispanic; 49% White; M age  = 14.9 years), propensity score matching was employed to account for baseline differences between the treatment (n = 577) and comparison (n = 163) groups. Treatment effects were examined based on three outcomes: out-of-home placement, adjudication, and placement in a juvenile training school over a 6-year period. Significant group differences remained after adjusting for baseline differences, with youth who received MST experiencing better outcomes in offending rates than youth who did not have an opportunity to complete MST due to non-clinical or administrative reasons. Survival analyses revealed rates of all three outcomes were approximately 40% lower among the treatment group. Overall, this study adds to the body of literature supporting the long-term effectiveness of MST in reducing offending among high-risk youth. The findings underscore the potential benefits of taking evidence-based programs such as MST to scale to improve the well-being and functioning of high-risk youth. However, strategies to effectively deliver the program in mental health service settings, and to address the specific needs of high-risk youth are necessary.

Psychopathy as predictor and moderator of multisystemic therapy outcomes among adolescents treated for antisocial behavior.

PubMed

Manders, Willeke A; Deković, Maja; Asscher, Jessica J; van der Laan, Peter H; Prins, Pier J M

2013-10-01

The aim of the present study was to determine whether psychopathic traits act as a predictor and/or moderator of the effectiveness of Multisystemic Therapy (MST). The sample included N = 256 adolescents (188 boys and 68 girls) referred for conduct problems, randomized to MST or Treatment As Usual (TAU). The mean age was 16 years (SD = 1.31). Assessments were carried out before and immediately after treatment (6 months later). Three psychopathic traits (callous/unemotional traits, narcissism, and impulsiveness) were assessed with parent reports. Adolescents and parents were informants on externalizing problems. MST was more effective than TAU in decreasing externalizing problems for the "lower callous/unemotional" and "lower narcissism" group, but not for the "high callous/unemotional" and "high narcissism" group (moderators). Impulsiveness was found to predict more post-treatment externalizing problems rated by adolescents (predictor), but not more post-treatment externalizing problems rated by parents. These findings point out the clinical relevance of adequately assessing psychopathic traits in adolescents referred for treatment of antisocial behaviour, and identifying those adolescents who show high levels of these traits. It is important to tailor MST specifically to meet the needs of juveniles with high levels of callous/unemotional traits and high levels of narcissism to obtain the same level of effectiveness as with juveniles scoring lower on these traits.

Common and Specific Factors Approaches to Home-Based Treatment: I-FAST and MST

ERIC Educational Resources Information Center

Lee, Mo Yee; Greene, Gilbert J.; Fraser, J. Scott; Edwards, Shivani G.; Grove, David; Solovey, Andrew D.; Scott, Pamela

2013-01-01

Objectives: This study examined the treatment outcomes of integrated families and systems treatment (I-FAST), a moderated common factors approach, in reference to multisystemic therapy (MST), an established specific factor approach, for treating at risk children and adolescents and their families in an intensive community-based setting. Method:…

Economic Impact of the Statewide Implementation of an Evidence-Based Treatment: Multisystemic Therapy in New Mexico.

PubMed

Dopp, Alex R; Coen, Anita Saranga; Smith, Allison B; Reno, Jessica; Bernstein, David H; Kerns, Suzanne E U; Altschul, Deborah

2018-07-01

Several states have made considerable investments into large-scale implementation of evidence-based treatments (EBTs), yet little is known about key success indicators for these implementation efforts such as cost and sustainability. To that end, the present study examined the economic impact of statewide implementation of multisystemic therapy (MST; Henggeler, Schoenwald, Borduin, Rowland, & Cuningham, 2009), a family- and community-based behavioral EBT for serious juvenile offenders in New Mexico. Participants were 1,869 youth who received MST across 23 teams during the study period. We conducted a cost-benefit analysis using metrics from state data sources that compared the cost of MST to its benefits (i.e., avoided expenses from pre- to posttreatment) in two domains: (a) behavioral health services (i.e., Medicaid claims) and (b) juvenile crime (i.e., taxpayer expenses, tangible and intangible expenses to crime victims). MST costs were based on Medicaid claims, which were reimbursed at an enhanced billing rate that was intended to cover expenses for both clinical and implementation (e.g., training, quality assurance) activities. Results suggest that implementation of MST in New Mexico over the 7-year study period may have produced net benefits, through 2 years posttreatment, of more than $4,643 per youth in avoided behavioral health claims and $15,019 per youth through reductions in juvenile crime. Stated differently, every dollar that New Mexico spent on MST appeared to have returned $3.34 for a total benefit of $64.2 million over the course of the study. We discuss implications of these findings for policymakers, administrators, and researchers who are interested in increasing the sustainability of complex EBTs in community settings. Copyright © 2018. Published by Elsevier Ltd.

Multisystemic Therapy for social, emotional, and behavioral problems in youth aged 10-17.

PubMed

Littell, J H; Popa, M; Forsythe, B

2005-10-19

Multisystemic Therapy (MST) is an intensive, home-based intervention for families of youth with social, emotional, and behavioral problems. Masters-level therapists engage family members in identifying and changing individual, family, and environmental factors thought to contribute to problem behavior. Intervention may include efforts to improve communication, parenting skills, peer relations, school performance, and social networks. Most MST trials were conducted by program developers in the USA; results of one independent trial are available and others are in progress. To provide unbiased estimates of the impacts of MST on restrictive out-of-home living arrangements, crime and delinquency, and other behavioral and psychosocial outcomes for youth and families. Electronic searches were made of bibliographic databases (including the Cochrane Library, C2-SPECTR, PsycINFO, Science Direct and Sociological Abstracts) as well as government and professional websites, from 1985 to January 2003. Reference lists of articles were examined, and experts were contacted. Studies where youth (age 10-17) with social, emotional, and/or behavioral problems were randomised to licensed MST programs or other conditions (usual services or alternative treatments). Two reviewers independently reviewed 266 titles and abstracts; 95 full-text reports were retrieved, and 35 unique studies were identified. Two reviewers independently read all study reports for inclusion. Eight studies were eligible for inclusion. Two reviewers independently assessed study quality and extracted data from these studies. Significant heterogeneity among studies was identified (assessed using Chi-square and I(2)), hence random effects models were used to pool data across studies. Odds ratios were used in analyses of dichotomous outcomes; standardised mean differences were used with continuous outcomes. Adjustments were made for small sample sizes (using Hedges g). Pooled estimates were weighted with inverse variance

Implementation of Evidence-Based Models in Social Work Practice: Practitioners' Perspectives on an MST Trial in Sweden

ERIC Educational Resources Information Center

Gustle, Lars-Henry; Hansson, Kjell; Sundell, Knut; Andree-Lofholm, Cecilia

2008-01-01

The implementation of new treatment methods in social work practice is warranted. Moreover, little is known about professionals' attitudes toward the introduction of evidence-based practices into their communities. Therefore, this article reports on the implementation of a Swedish research project that evaluated Multisystemic Therapy (MST). All…

Bridging the Gap between Science and Practice: The Effective Nationwide Transport of MST Programs in Norway

ERIC Educational Resources Information Center

Ogden, Terje; Christensen, Bernadette; Sheidow, Ashli J.; Holth, Per

2008-01-01

The successful nationwide transport and evaluation of Multisystemic Therapy (MST) programs in Norway is described. This description is provided within the context of the nation's movement towards the adoption of evidence-based practices (EBPs) during the past decade, the conduct of a multisite randomized clinical trial to examine the effectiveness…

Multisystemic Therapy for social, emotional, and behavioral problems in youth aged 10-17.

PubMed

Littell, J H; Popa, M; Forsythe, B

2005-07-20

Multisystemic Therapy (MST) is an intensive, home-based intervention for families of youth with social, emotional, and behavioral problems. Masters-level therapists engage family members in identifying and changing individual, family, and environmental factors thought to contribute to problem behavior. Intervention may include efforts to improve communication, parenting skills, peer relations, school performance, and social networks. Most MST trials were conducted by program developers in the USA; results of one independent trial are available and others are in progress. To provide unbiased estimates of the impacts of MST on restrictive out-of-home living placements, crime and delinquency, and other behavioral and psychosocial outcomes for youth and families. Electronic searches were made of bibliographic databases including the Cochrane Library, C2-SPECTR, PsycINFO, Science Direct and Sociological Abstracts) as well as government and professional websites, from 1985 to January 2003. Reference lists of articles were examined, and experts were contacted. Studies where youth (age 10-17) with social, emotional, and/or behavioral problems were randomised to licensed MST programs or other conditions (usual services or alternative treatments). Two reviewers independently reviewed 266 titles and abstracts; 95 full-text reports were retrieved, and 35 unique studies were identified. Two reviewers independently read all study reports for inclusion. Eight studies were eligible for inclusion. Two reviewers independently assessed study quality and extracted data from these studies.Significant heterogeneity among studies was identified (assessed using Chi-square and I(2)), hence random effects models were used to pool data across studies. Odds ratios were used in analyses of dichotomous outcomes; standardised mean differences were used with continuous outcomes. Adjustments were made for small sample sizes (using Hedges g). Pooled estimates were weighted with inverse variance

Mediators of Treatment Effects in a Randomized Clinical Trial of Multisystemic Therapy-Health Care in Adolescents With Poorly Controlled Asthma: Disease Knowledge and Device Use Skills.

PubMed

Ellis, Deborah A; King, Pamela; Naar-King, Sylvie

2016-06-01

Determine whether Multisystemic Therapy-Health Care (MST-HC) improved asthma knowledge and controller device use skills among African-American youth with poorly controlled asthma and whether any improvements mediated changes in illness management. A randomized controlled trial was conducted with 170 adolescents with moderate to severe asthma. Families were randomized to MST-HC or attention control. Data were collected at baseline and 6 and 12 months after intervention completion. In linear mixed models, adolescents in the MST-HC group had increases in asthma knowledge; asthma knowledge was unchanged for attention control. Controller device use skills increased for adolescents in the MST-HC group, while skills declined for attention control. Both knowledge and skills mediated the relationship between intervention condition and changes in illness management. Tailored, home-based interventions that include knowledge and skills building components are one means by which illness management in African-American youth with poorly controlled asthma can be improved. © The Author 2015. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Adolescent Physiological and Behavioral Patterns of Emotion Dysregulation Predict Multisystemic Therapy Response.

PubMed

Winiarski, D Anne; Schechter, Julia C; Brennan, Patricia A; Foster, Sharon L; Cunningham, Phillippe B; Whitmore, Elizabeth A

2017-09-01

This study examined whether physiological and behavioral indicators of emotion dysregulation assessed over the course of Multisystemic Therapy (MST) were related to treatment response. Participants were 180 ethnically diverse adolescents ( n =120 males), ranging in age from 12 to 17 years. Treatment response was assessed through therapist report and official arrest records. Changes in cortisol reactivity and changes in scores on a behavioral dysregulation subscale of the Child Behavior Checklist were used as indicators of emotion dysregulation. Hierarchical linear modeling analyses examined whether a less favorable treatment response was associated with cortisol reactivity measures (a) collected early in treatment and (b) over the course of treatment, as well as with behavioral reports of emotion dysregulation reported (c) early in treatment, and (d) over the course of treatment. Sex was explored as a moderator of these associations. Results indicated that both cortisol and behavioral indices of emotion dysregulation early in treatment and over the course of therapy predicted treatment responsiveness. This relationship was moderated by sex: girls were more likely to evidence a pattern of increasing emotion regulation prior to successful therapy response. The results lend further support to the notion of incorporating emotion regulation techniques into treatment protocols for delinquent behavior.

Effectiveness of a Multisystem Aquatic Therapy for Children with Autism Spectrum Disorders.

PubMed

Caputo, Giovanni; Ippolito, Giovanni; Mazzotta, Marina; Sentenza, Luigi; Muzio, Mara Rosaria; Salzano, Sara; Conson, Massimiliano

2018-06-01

Aquatic therapy improves motor skills of persons with Autism Spectrum Disorders (ASD), but its usefulness for treating functional difficulties needs to be verified yet. We tested effectiveness of a multisystem aquatic therapy on behavioural, emotional, social and swimming skills of children with ASD. Multisystem aquatic therapy was divided in three phases (emotional adaptation, swimming adaptation and social integration) implemented in a 10-months-programme. At post-treatment, the aquatic therapy group showed significant improvements relative to controls on functional adaptation (Vineland Adaptive Behavior Scales), emotional response, adaptation to change and on activity level (Childhood Autism Rating Scale). Swimming skills learning was also demonstrated. Multisystem aquatic therapy is useful for ameliorating functional impairments of children with ASD, going well beyond a swimming training.

Test of “Facilitation” vs. “Proximal Process” Moderator Models for the Effects of Multisystemic Therapy on Adolescents with Severe Conduct Problem

PubMed Central

Weiss, Bahr; Han, Susan S.; Tran, Nam T.; Gallop, Robert; Ngo, Victoria K.

2014-01-01

The present study identified moderators of Multisystemic Therapy’s (MST) effects on adolescent conduct problems, considering “facilitation” and “proximal process” moderation models. The sample included 164 adolescents (mean age=14.6 years; 83% male) randomly assigned to receive MST or services as usual; parent, youth, and teacher reports of adolescent functioning were obtained. A number of significant moderators were identified. Proximal process moderation patterns were identified (e.g., families with parents with lower levels of adaptive child discipline skills gained more from MST), but the majority of significant interactions showed a facilitation moderation pattern with, for instance, higher levels of adaptive functioning in families and parents appearing to facilitate MST (i.e., greater benefits from MST were found for these families). This facilitation pattern may reflect such families being more capable of and/or more motivated to use the resources provided by MST. It is suggested that factors consistently identified as facilitation moderators may serve as useful foci for MST’s strength-based levers of change approach. Other implications of these findings for individualized treatment also are discussed. PMID:25387903

Evaluation of multisystemic therapy pilot services in Services for Teens Engaging in Problem Sexual Behaviour (STEPS-B): study protocol for a randomized controlled trial.

PubMed

Fonagy, Peter; Butler, Stephen; Baruch, Geoffrey; Byford, Sarah; Seto, Michael C; Wason, James; Wells, Charles; Greisbach, Jessie; Ellison, Rachel; Simes, Elizabeth

2015-11-02

Clinically effective and cost-effective methods for managing problematic sexual behaviour in adolescents are urgently needed. Adolescents who show problematic sexual behaviour have a range of negative psychosocial outcomes, and they and their parents can experience stigma, hostility and rejection from their community. Multisystemic therapy (MST) shows some evidence for helping to reduce adolescent sexual reoffending and is one of the few promising interventions available to young people who show problematic sexual behaviour. This paper describes the protocol for Services for Teens Engaging in Problem Sexual Behaviour (STEPS-B), a feasibility trial of MST for problem sexual behaviour (MST-PSB) in antisocial adolescents at high risk of out-of-home placement due to problematic sexual behaviour. Eighty participants and their families recruited from five London boroughs will be randomized to MST-PSB or management as usual with follow-up to 20 months post-randomization. The primary outcome is out-of-home placement at 20 months. Secondary outcomes include sexual and non-sexual offending rates and antisocial behaviours, participant well-being, educational outcomes and total service and criminal justice sector costs. Feasibility outcomes include mapping the clinical service pathways needed to recruit adolescents displaying problematic sexual behaviour, acceptability of a randomized controlled trial to the key systems involved in managing these adolescents, and acceptability of the research protocol to young people and their families. Data will be gathered from police computer records, the National Pupil Database and interviews and self-report measures administered to adolescents and parents and will be analysed on an intention-to-treat basis. The STEPS-B feasibility trial aims to inform policymakers, commissioners of services and professionals about the potential for implementing MST-PSB as an intervention for adolescents showing problem sexual behaviour. Should MST

Differential neurophysiological effects of magnetic seizure therapy (MST) and electroconvulsive shock (ECS) in non-human primates.

PubMed

Cycowicz, Yael M; Luber, Bruce; Spellman, Timothy; Lisanby, Sarah H

2008-07-01

Magnetic seizure therapy (MST) is under development as a means of reducing the side effects of electroconvulsive therapy (ECT) through enhanced control over patterns of seizure induction and spread. We previously reported that chronic treatment with MST resulted in less impairment in cognitive function than electroconvulsive shock (ECS) in a non-human primate model of convulsive therapy. Here we present quantitative analyses of ictal expression and post-ictal suppression following ECS, MST, and anesthesia-alone sham in the same model to test whether differential neurophysiological characteristics of the seizures could be identified. Rhesus monkeys received 4 weeks of daily treatment with ECS, MST, and anesthesia-alone sham in a counterbalanced order separated by a recovery period. Both ECS and MST were given bilaterally at 2.5 x seizure threshold. Neurophysiological characteristics were derived from two scalp EEG electrode recording sites during and immediately following the ictal period, and were compared to sham treatment. EEG power within four frequencies (delta, theta, alpha and beta) was calculated. Our results support earlier findings from intracerebral electrode recordings demonstrating that MST- and ECS- induced seizures elicit differential patterns of EEG activation. Specifically, we found that ECS shows significantly more marked ictal expression, and more intense post-ictal suppression than MST in the theta, alpha, and beta frequency bands (Ps < .05). However, the ECS and MST were indistinguishable in the delta frequency band during both ictal and post-ictal periods. These results demonstrate that magnetic seizure induction can result in seizures that differ in some neurophysiological respects compared with ECS, but that these modalities share some aspects of seizure expression. The clinical significance of these similarities and differences awaits clinical correlation.

Differential Effects of High Dose Magnetic Seizure Therapy (MST) and Electroconvulsive Shock (ECS) on Cognitive Function

PubMed Central

Spellman, Timothy; McClintock, Shawn M.; Terrace, Herbert; Luber, Bruce; Husain, Mustafa M.; Lisanby, Sarah H.

2008-01-01

Background Magnetic seizure therapy (MST) is under investigation as an alternative form of convulsive therapy that induces more focal seizures and spares cortical regions involved in memory. Using a newly expanded version of the Columbia University Primate Cognitive Profile, we compared the cognitive effects of high-dose MST delivered at 100 Hz (6X seizure threshold) with electroconvulsive shock (ECS) delivered at 2.5X seizure threshold. Methods Daily high-dose MST, ECS, and Sham (anesthesia-only) were administered for 4 weeks each in a within-subject cross-over design. Rhesus macaques (n = 3) were trained on five cognitive tasks assessing automatic memory, anterograde learning and memory, combined anterograde and retrograde simultaneous chaining, and spatial and serial working memory. Acutely following each intervention, monkeys were tested on the cognitive battery twice daily, separated by a 3-hour retention interval. Results Subjects were slower to complete criterion tasks (p’s<0.0001) following ECS, compared to sham and high-dose MST. Moreover, time to task-completion following high-dose MST did not differ from sham. Out of 6 measures of accuracy, treatment effects were found in 4; in all of these, ECS, but not MST, fared worse than Sham. On all accuracy and time to completion measurements, subjects performed as well as following high-dose MST as did subjects from a previous study on moderate-dose MST. Conclusion These findings provide evidence that high-dose MST results in benign acute cognitive side-effect profile relative to ECS, and are in line with our previous studies. PMID:18262171

Ethnic Similarity, Therapist Adherence, and Long-Term Multisystemic Therapy Outcomes

ERIC Educational Resources Information Center

Chapman, Jason E.; Schoenwald, Sonja K.

2011-01-01

The current study investigated relations among ethnic similarity in caregiver-therapist pairs of youth participating in Multisystemic Therapy, therapist adherence, and youth long-term behavioral and criminal outcomes. Participants were 1,979 youth and families treated by 429 therapists across provider organizations in 45 sites. Relations were…

Randomized controlled trial of the cognitive side-effects of magnetic seizure therapy (MST) and electroconvulsive shock (ECS).

PubMed

Moscrip, Tammy D; Terrace, Herbert S; Sackeim, Harold A; Lisanby, Sarah H

2006-02-01

Magnetic seizure therapy (MST) is under development as a means of improving the cognitive side-effect profile of electroconvulsive therapy (ECT) by inducing more spatially delimited seizures that spare cortical regions involved in memory. We tested whether MST had a cognitive side-effect profile distinct from electroconvulsive shock (ECS) in a non-human primate model, using the Columbia University Primate Cognitive Profile, which has been shown to be sensitive to the cognitive effects of ECS. Using a within-subject cross-over design, daily ECS, MST, and sham (anaesthesia-only) interventions were administered in 5-wk blocks. Rhesus macaques (n = 2) were trained on a long-term memory task, an anterograde learning and memory task, and a combined anterograde and retrograde task where learning and memory were evaluated for new and previously learned 3-item lists. Acutely following each intervention, monkeys were tested on the cognitive battery twice daily, separated by a 3-h retention interval. Overall, monkeys were least accurate following ECS (p's < 0.05) compared to sham and MST. This effect was most marked for long-term memory of a constant target, short-term memory of a variable target and recall of previously learned 3-item lists. Monkeys were slowest to complete all tasks following ECS (p's = 0.0001). Time to task completion following MST did not differ from sham. These findings suggest that MST results in a more benign acute cognitive side-effect profile than ECS in this model, consistent with initial observations with human MST.

Evaluation of multisystemic therapy pilot services in the Systemic Therapy for At Risk Teens (START) trial: study protocol for a randomised controlled trial

PubMed Central

2013-01-01

Background There is an urgent need for clinically effective and cost-effective methods to manage antisocial and criminal behaviour in adolescents. Youth conduct disorder is increasingly prevalent in the UK and is associated with a range of negative outcomes. Quantitative systematic reviews carried out for the National Institute for Health and Clinical Excellence have identified multisystemic therapy, an intensive, multimodal, home-based, family intervention for youth with serious antisocial behaviour, as one of the most promising interventions for reducing antisocial or offending behaviour and improving individual and family functioning. Previous international trials of multisystemic therapy have yielded mixed outcomes, and it is questionable to what extent positive US findings can be generalised to a wider UK mental health and juvenile justice context. This paper describes the protocol for the Systemic Therapy for At Risk Teens (START) trial, a multicentre UK-wide randomised controlled trial of multisystemic therapy in antisocial adolescents at high risk of out-of-home placement. Methods/Design The trial is being conducted at 10 sites across the UK. Seven hundred participants and their families will be recruited and randomised on a 1:1 basis to multisystemic therapy or management as usual. Treatments are offered over a period of 3 to 5 months, with follow-up to 18 months post-randomisation. The primary outcome is out-of-home placement at 18 months. Secondary outcomes include offending rates, total service and criminal justice sector costs, and participant well-being and educational outcomes. Data will be gathered from police computer records, the National Pupil Database, and interview and self-report measures administered to adolescents, parents and teachers. Outcomes will be analysed on an intention-to-treat basis, using a logistic regression with random effects for the primary outcome and Cox regressions and linear mixed-effects models for secondary outcomes

Evaluation of multisystemic therapy pilot services in the Systemic Therapy for At Risk Teens (START) trial: study protocol for a randomised controlled trial.

PubMed

Fonagy, Peter; Butler, Stephen; Goodyer, Ian; Cottrell, David; Scott, Stephen; Pilling, Stephen; Eisler, Ivan; Fuggle, Peter; Kraam, Abdullah; Byford, Sarah; Wason, James; Haley, Rachel

2013-08-20

There is an urgent need for clinically effective and cost-effective methods to manage antisocial and criminal behaviour in adolescents. Youth conduct disorder is increasingly prevalent in the UK and is associated with a range of negative outcomes. Quantitative systematic reviews carried out for the National Institute for Health and Clinical Excellence have identified multisystemic therapy, an intensive, multimodal, home-based, family intervention for youth with serious antisocial behaviour, as one of the most promising interventions for reducing antisocial or offending behaviour and improving individual and family functioning. Previous international trials of multisystemic therapy have yielded mixed outcomes, and it is questionable to what extent positive US findings can be generalised to a wider UK mental health and juvenile justice context. This paper describes the protocol for the Systemic Therapy for At Risk Teens (START) trial, a multicentre UK-wide randomised controlled trial of multisystemic therapy in antisocial adolescents at high risk of out-of-home placement. The trial is being conducted at 10 sites across the UK. Seven hundred participants and their families will be recruited and randomised on a 1:1 basis to multisystemic therapy or management as usual. Treatments are offered over a period of 3 to 5 months, with follow-up to 18 months post-randomisation. The primary outcome is out-of-home placement at 18 months. Secondary outcomes include offending rates, total service and criminal justice sector costs, and participant well-being and educational outcomes. Data will be gathered from police computer records, the National Pupil Database, and interview and self-report measures administered to adolescents, parents and teachers. Outcomes will be analysed on an intention-to-treat basis, using a logistic regression with random effects for the primary outcome and Cox regressions and linear mixed-effects models for secondary outcomes depending on whether the

The use of ECT and MST in treating depression.

PubMed

Allan, Charlotte L; Ebmeier, Klaus P

2011-10-01

Electroconvulsive therapy (ECT) has been used clinically since 1938. Its most common use is in the treatment of depression: first line treatment where rapid recovery is a priority, but more frequently as an effective treatment for patients who do not respond to pharmacological and psychological approaches. Whilst it is widely hailed as an effective treatment, concerns about its effect on cognition remain. The development of magnetic seizure therapy (MST) over the past decade has attempted to devise a therapy with comparable efficacy to ECT, but without the associated cognitive side effects. The rationale for this is that MST uses magnetic fields to induce seizures in the cortex, without electrical stimulation of brain structures involved with memory. MST has been used successfully in the treatment of depression, yet there is a dearth of literature in comparison with ECT. We present a systematic review of the literature on ECT (from 2009-2011) and MST (from 2001-2011).

New directions in the rational design of electrical and magnetic seizure therapies: individualized Low Amplitude Seizure Therapy (iLAST) and Magnetic Seizure Therapy (MST).

PubMed

Radman, Thomas; Lisanby, Sarah H

2017-04-01

Electroconvulsive therapy remains a key treatment option for severe cases of depression, but undesirable side-effects continue to limit its use. Innovations in the design of novel seizure therapies seek to improve its risk benefit ratio through enhanced control of the focality of stimulation. The design of seizure therapies with increased spatial precision is motivated by avoiding stimulation of deep brain structures implicated in memory retention, including the hippocampus. The development of two innovations in seizure therapy-individualized low-amplitude seizure therapy (iLAST) and magnetic seizure therapy (MST), are detailed. iLAST is a method of seizure titration involving reducing current spread in the brain by titrating current amplitude from the traditional fixed amplitudes. MST, which can be used in conjunction with iLAST dosing methods, involves the use of magnetic stimulation to reduce shunting and spreading of current by the scalp occurring during electrical stimulation. Evidence is presented on the rationale for increasing the focality of ECT in hopes of preserving its effectiveness, while reducing cognitive side-effects. Finally, the value of electric field and neural modelling is illustrated to explain observed clinical effects of modifications to ECT technique, and their utility in the rational design of the next generation of seizure therapies.

A review of “music and movement” therapies for children with autism: embodied interventions for multisystem development

PubMed Central

Srinivasan, Sudha M.; Bhat, Anjana N.

2013-01-01

The rising incidence of Autism Spectrum Disorders (ASDs) has led to a surge in the number of children needing autism interventions. This paper is a call to clinicians to diversify autism interventions and to promote the use of embodied music-based approaches to facilitate multisystem development. Approximately 12% of all autism interventions and 45% of all alternative treatment strategies in schools involve music-based activities. Musical training impacts various forms of development including communication, social-emotional, and motor development in children with ASDs and other developmental disorders as well as typically developing children. In this review, we will highlight the multisystem impairments of ASDs, explain why music and movement therapies are a powerful clinical tool, as well as describe mechanisms and offer evidence in support of music therapies for children with ASDs. We will support our claims by reviewing results from brain imaging studies reporting on music therapy effects in children with autism. We will also discuss the critical elements and the different types of music therapy approaches commonly used in pediatric neurological populations including autism. We provide strong arguments for the use of music and movement interventions as a multisystem treatment tool for children with ASDs. Finally, we also make recommendations for assessment and treatment of children with ASDs, and provide directions for future research. PMID:23576962

Do Extremely Violent Juveniles Respond Differently to Treatment?

PubMed Central

Asscher, Jessica J.; Deković, M.; Van den Akker, Alithe L.; Prins, Pier J. M.; Van der Laan, Peter H.

2016-01-01

This study increases knowledge on effectiveness of treatment for extremely violent (EV) youth by investigating their response to multisystemic therapy (MST). Using data of a randomized controlled trial on effectiveness of MST, we investigated differences in treatment response between EV youth and not extremely violent (NEV) youth. Pre- to post-treatment comparison indicated MST was equally effective for EV and NEV youth, whereas treatment as usual was not effective for either group. Growth curves of within-treatment changes indicated EV youth responded differently to MST than NEV youth. The within-treatment change was for EV youth non-linear: Initially, they show a deterioration; however, after one month, EV juveniles respond positively to MST, indicating longer lasting, intensive programs may be effective in treating extreme violence. PMID:27794135

MST1 is a key regulator of beta cell apoptosis and dysfunction in diabetes.

PubMed

Ardestani, Amin; Paroni, Federico; Azizi, Zahra; Kaur, Supreet; Khobragade, Vrushali; Yuan, Ting; Frogne, Thomas; Tao, Wufan; Oberholzer, Jose; Pattou, Francois; Conte, Julie Kerr; Maedler, Kathrin

2014-04-01

Apoptotic cell death is a hallmark of the loss of insulin-producing beta cells in all forms of diabetes mellitus. Current treatments fail to halt the decline in functional beta cell mass, and strategies to prevent beta cell apoptosis and dysfunction are urgently needed. Here, we identified mammalian sterile 20-like kinase-1 (MST1) as a critical regulator of apoptotic beta cell death and function. Under diabetogenic conditions, MST1 was strongly activated in beta cells in human and mouse islets and specifically induced the mitochondrial-dependent pathway of apoptosis through upregulation of the BCL-2 homology-3 (BH3)-only protein BIM. MST1 directly phosphorylated the beta cell transcription factor PDX1 at T11, resulting in the latter's ubiquitination and degradation and thus in impaired insulin secretion. MST1 deficiency completely restored normoglycemia, beta cell function and survival in vitro and in vivo. We show MST1 as a proapoptotic kinase and key mediator of apoptotic signaling and beta cell dysfunction and suggest that it may serve as target for the development of new therapies for diabetes.

Music-supported therapy (MST) in improving post-stroke patients' upper-limb motor function: a randomised controlled pilot study.

PubMed

Tong, Yanna; Forreider, Brian; Sun, Xinting; Geng, Xiaokun; Zhang, Weidong; Du, Huishan; Zhang, Tong; Ding, Yuchuan

2015-05-01

Music-supported therapy (MST) is a new approach for motor rehabilitation of stroke patients. Recently, many studies have demonstrated that MST improved the motor functions of post-stroke patients. However, the underlying mechanism for this effect is still unclear. It may result from repeated practice or repeated practice combined with musical stimulation. Currently, few studies have been designed to clarify this discrepancy. In this study, the application of "mute" musical instruments allowed for the study of music as an independent factor. Thirty-three post-stroke patients with no substantial previous musical training were included. Participants were assigned to either audible music group (MG) or mute music group (CG), permitting observation of music's independent effect. All subjects received the conventional rehabilitation treatments. Patients in MG (n = 15) received 20 extra sessions of audible musical instrument training over 4 weeks. Patients in CG (n = 18) received "mute" musical instrument training of the same protocol as that of MG. Wolf motor function test (WMFT) and Fugl-Meyer assessment (FMA) for upper limbs were utilised to evaluate motor functions of patients in both groups before and after the treatment. Three patients in CG dropped out. All participants in both groups showed significant improvements in motor functions of upper limbs after 4  weeks' treatment. However, significant differences in the WMFT were found between the two groups (WMFT-quality: P = 0.025; WMFT-time: P = 0.037), but not in the FMA (P = 0.448). In short, all participants showed significant improvement after 4 weeks' treatment, but subjects in MG demonstrated greater improvement than those in CG. This study supports that MST, when combined with conventional treatment, is effective for the recovery of motor skills in post-stroke patients. Additionally, it suggests that apart from the repetitive practices of MST, music may play a unique role in improving

The efficacy of Life Review Therapy combined with Memory Specificity Training (LRT-MST) targeting cancer patients in palliative care: A randomized controlled trial.

PubMed

Kleijn, Gitta; Lissenberg-Witte, Birgit I; Bohlmeijer, Ernst T; Steunenberg, Bas; Knipscheer-Kuijpers, Kitty; Willemsen, Vincent; Becker, Annemarie; Smit, Egbert F; Eeltink, Corien M; Bruynzeel, Anna M E; van der Vorst, Maurice; de Bree, Remco; Leemans, C René; van den Brekel, Michiel W M; Cuijpers, Pim; Verdonck-de Leeuw, Irma M

2018-01-01

The aim of this study was to evaluate the efficacy of an intervention combining Life Review Therapy (LRT) and Memory Specificity Training (MST) (LRT-MST) to improve ego-integrity and despair among cancer patients in palliative care. In this multicentre randomized controlled trial, cancer patients in palliative care were randomized to the intervention group (LRT-MST; n = 55) or waiting-list control group (n = 52). LRT-MST is a 4-session home-based psychological intervention that aims to retrieve specific positive memories, to re-evaluate life events and to reconstruct the story of a patient's life, including the diagnosis of incurable cancer. Outcome measures were ego-integrity and despair (NEIS), psychological distress, anxiety and depression (HADS), quality of life (EORTC QLQ-C15-PAL), and specificity of the autobiographical memory (AMT). NEIS, HADS and EORTC QLQ-C15-PAL were assessed at baseline (T0), 1 month later (post-treatment; T1), and at 1 month follow-up (T2). AMT was assessed at T0 and T1. Linear mixed models (intention to treat) were used to assess group differences in changes over time. Independent samples t-tests were used to assess group differences at T0, T1, and T2, and effect sizes (ES) were calculated at T1 and T2. The course of ego-integrity (not despair) improved significantly over time (p = .007) in the intervention group compared to the waiting-list control group, with moderate, but insignificant, effect sizes at T1 (ES = .42) and T2 (ES = .48). Compliance rate was 69% and total dropout rate was 28%, both primarily related to disease progression and death. LRT-MST seems effective among cancer patients in palliative care to improve the course of ego-integrity.

MST Filterability Tests

DOE Office of Scientific and Technical Information (OSTI.GOV)

Poirier, M. R.; Burket, P. R.; Duignan, M. R.

2015-03-12

The Savannah River Site (SRS) is currently treating radioactive liquid waste with the Actinide Removal Process (ARP) and the Modular Caustic Side Solvent Extraction Unit (MCU). The low filter flux through the ARP has limited the rate at which radioactive liquid waste can be treated. Recent filter flux has averaged approximately 5 gallons per minute (gpm). Salt Batch 6 has had a lower processing rate and required frequent filter cleaning. Savannah River Remediation (SRR) has a desire to understand the causes of the low filter flux and to increase ARP/MCU throughput. In addition, at the time the testing started, SRRmore » was assessing the impact of replacing the 0.1 micron filter with a 0.5 micron filter. This report describes testing of MST filterability to investigate the impact of filter pore size and MST particle size on filter flux and testing of filter enhancers to attempt to increase filter flux. The authors constructed a laboratory-scale crossflow filter apparatus with two crossflow filters operating in parallel. One filter was a 0.1 micron Mott sintered SS filter and the other was a 0.5 micron Mott sintered SS filter. The authors also constructed a dead-end filtration apparatus to conduct screening tests with potential filter aids and body feeds, referred to as filter enhancers. The original baseline for ARP was 5.6 M sodium salt solution with a free hydroxide concentration of approximately 1.7 M.3 ARP has been operating with a sodium concentration of approximately 6.4 M and a free hydroxide concentration of approximately 2.5 M. SRNL conducted tests varying the concentration of sodium and free hydroxide to determine whether those changes had a significant effect on filter flux. The feed slurries for the MST filterability tests were composed of simple salts (NaOH, NaNO 2, and NaNO 3) and MST (0.2 – 4.8 g/L). The feed slurry for the filter enhancer tests contained simulated salt batch 6 supernate, MST, and filter enhancers.« less

Intensive Quality Assurance of Therapist Adherence to Behavioral Interventions for Adolescent Substance Use Problems

ERIC Educational Resources Information Center

Holth, Per; Torsheim, Torbjorn; Sheidow, Ashli J.; Ogden, Terje; Henggeler, Scott W.

2011-01-01

This study was a cross-cultural replication of a study that investigated therapist adherence to behavioral interventions as a result of an intensive quality assurance system which was integrated into Multisystemic Therapy (MST). Thirty-three therapists and eight supervisors were block randomized to either an Intensive Quality Assurance or a…

Overview of MST Research

NASA Astrophysics Data System (ADS)

Chapman, B. E.

2017-10-01

MST progress in advancing the RFP for (1) fusion plasma confinement with ohmic heating and minimal external magnetization, (2) predictive capability in toroidal confinement physics, and (3) basic plasma physics is summarized. Validation of key plasma models is a program priority, which is enhanced by programmable power supplies (PPS) to maximize inductive capability. The existing PPS enables access to very low plasma current, down to Ip =0.02 MA. This greatly expands the Lundquist number range S =104 -108 and allows nonlinear, 3D MHD computation using NIMROD and DEBS with dimensionless parameters that overlap those of MST plasmas. A new, second PPS will allow simultaneous PPS control of the Bp and Bt circuits. The PPS also enables MST tokamak operation, thus far focused on disruptions and RMP suppression of runaway electrons. Gyrokinetic modeling with GENE predicts unstable TEM in improved-confinement RFP plasmas. Measured fluctuations have TEM properties including a density-gradient threshold larger than for tokamak plasmas. Turbulent energization of an electron tail occurs during sawtooth reconnection. Probe measurements hint that drift waves are also excited via the turbulent cascade in standard RFP plasmas. Exploration of basic plasma science frontiers in MST RFP and tokamak plasmas is proposed as part of WiPPL, a basic science user facility. Work supported by USDoE.

Dendritic cell MST1 inhibits Th17 differentiation

PubMed Central

Li, Chunxiao; Bi, Yujing; Li, Yan; Yang, Hui; Yu, Qing; Wang, Jian; Wang, Yu; Su, Huilin; Jia, Anna; Hu, Ying; Han, Linian; Zhang, Jiangyuan; Li, Simin; Tao, Wufan; Liu, Guangwei

2017-01-01

Although the differentiation of CD4+T cells is widely studied, the mechanisms of antigen-presenting cell-dependent T-cell modulation are unclear. Here, we investigate the role of dendritic cell (DC)-dependent T-cell differentiation in autoimmune and antifungal inflammation and find that mammalian sterile 20-like kinase 1 (MST1) signalling from DCs negatively regulates IL-17 producing-CD4+T helper cell (Th17) differentiation. MST1 deficiency in DCs increases IL-17 production by CD4+T cells, whereas ectopic MST1 expression in DCs inhibits it. Notably, MST1-mediated DC-dependent Th17 differentiation regulates experimental autoimmune encephalomyelitis and antifungal immunity. Mechanistically, MST1-deficient DCs promote IL-6 secretion and regulate the activation of IL-6 receptor α/β and STAT3 in CD4+T cells in the course of inducing Th17 differentiation. Activation of the p38 MAPK signal is responsible for IL-6 production in MST1-deficient DCs. Thus, our results define the DC MST1–p38MAPK signalling pathway in directing Th17 differentiation. PMID:28145433

Outcomes from Wraparound and Multisystemic Therapy in a Center for Mental Health Services System-of-Care Demonstration Site

ERIC Educational Resources Information Center

Stambaugh, Leyla Faw; Mustillo, Sarah A.; Burns, Barbara J.; Stephens, Robert L.; Baxter, Beth; Edwards, Dan; DeKraai, Mark

2007-01-01

This study examined outcomes for 320 youth in a Center for Mental Health Services system-of-care demonstration site. Youth received wraparound-only (n = 213), MST-only (n = 54), or wraparound + MST (n = 53). Participants were 12 years old on average and mostly White (90%), and 75% were Medicaid-eligible. Service use and functional and clinical…

Genetic characterization drives personalized therapy for early-stage non-small-cell lung cancer (NSCLC) patients and survivors with metachronous second primary tumor (MST): A case report.

PubMed

Ding, Xingchen; Wang, Linlin; Liu, Xijun; Sun, Xindong; Yu, Jinming; Meng, Xue

2017-03-01

The pathogenesis and progression of lung cancer is a complicated process in which many genes take part. But molecular gene testing is typically only performed in advanced-stage non-squamous non-small-cell lung cancer (NSCLC). The value of tyrosine kinase inhibitors (TKI) administration is not widely recognized with respect to early-stage NSCLC. Here, we present a case of a man, heavy smoker who initially presented with stage IA lung adenocarcinoma (LADC). Three years after a lung lobectomy, he was diagnosed with advanced lung squamous cell carcinoma (SCC), according to laboratory, imaging, and pathological examinations. The case initially had an early-stage LADC with an L858R epidermal growth factor receptor (EGFR) mutation. A subsequent advanced SCC bearing EGFR L858R/T790M mutations occurred 3 years after surgery. The comprehensive therapy we utilized, including surgical resection for the early-stage lesion and GP chemotherapy and local radiotherapy as the first line therapy along with gefitinib maintenance treatment for the advanced metachronous second primary tumors (MST). The synthetical therapy, have resulted in our patient with remaining alive and progression free for 4.5 years. This case suggests that changes in molecular pathology should be monitored closely throughout cancer progression to guide personalized therapy and improve prognosis. We further review administration of TKI to early-stage NSCLC and to the metachronous second primary tumors (MST) in survivors.

Therapists' and Clients' Perceptions of Bonding as Predictors of Outcome in Multisystemic Therapy®.

PubMed

Glebova, Tatiana; Foster, Sharon L; Cunningham, Phillippe B; Brennan, Patricia A; Whitmore, Elizabeth A

2017-12-08

This longitudinal study examined whether strength of and balance in self-reported caregiver, youth, and therapist emotional bonds in mid- and late treatment predicted outcomes in Multisystemic Therapy of adolescent behavior problems in a sample of 164 caregiver-youth dyads. Strength of and balance in bonds related to outcome in different ways, depending on the source of the report and time. Results showed a limited association between family members' emotional connection with the therapist and treatment outcome, whereas therapists' perceptions of bond with the caregiver showed highly significant associations across time. Caregiver-therapist agreement on emotional connection at both time points predicted therapist evaluation of treatment success and successful termination, but this was largely explained by therapists' level of alliance. Balance in bonds with the therapist between caregiver and youth had no significant associations with any outcome. The study major limitations such as examining only one component of alliance and possible implications are discussed. © 2017 Family Process Institute.

Bravemind: Advancing the Virtual Iraq/Afghanistan PTSD Exposure Therapy for MST

DTIC Science & Technology

2015-06-01

threatened death, serious injury or sexual violation. Military Sexual Trauma (MST) has been recognized as a significant risk factor for the...development of PTSD. This has become an issue of grave concern within the military, as reports of sexual violations and assaults have been on the rise over the...far, the system was built and delivered and the RCT has commenced. 15. SUBJECT TERMS PTSD, Virtual Reality, Prolonged Exposure, Military Sexual

We Are, Therefore I Am: A Multisystems Approach with Families in Poverty.

ERIC Educational Resources Information Center

Brown, Shunda L.

2002-01-01

Although many individuals living in poverty are referred for family counseling services via schools, court systems, and social service agencies, theories have failed to provide an adequate framework for treatment. This article addresses the common principles of the multisystems approach and feminist family therapies and how they can be applied in…

AWIWPCA STATES HELPING STATES CLL ON MST

EPA Science Inventory

Several Microbial Source Tracking (MST) tools are now being applied in the development of TMDL plans and in the evaluation of best management practices. However, due to the relatively recent development of MST most environmental managers and scientists have little training and ...

Antidepressant effects, of magnetic seizure therapy and electroconvulsive therapy, in treatment-resistant depression.

PubMed

Kayser, Sarah; Bewernick, Bettina H; Grubert, Christiane; Hadrysiewicz, Barbara L; Axmacher, Nikolai; Schlaepfer, Thomas E

2011-05-01

Major depression is a common mental health problem and associated with significant morbidity and mortality, including impaired social and physical functioning and increased risk for suicide. Electroconvulsive therapy (ECT) is highly efficacious in treatment-resistant depressive disorders, but cognitive side effects are frequently associated with the treatment. Magnetic seizure therapy (MST) is a form of convulsive therapy, using magnetic fields in order to induce therapeutic seizures. First studies suggested that cognitive side effects of MST, including postictal recovery time, are more benign than those resulting from ECT treatment. In this open-label study we tested the hypothesis that MST is associated with clinically significant antidepressant effects in treatment-resistant depression (TRD) as an add-on therapy to a controlled pharmacotherapy. Twenty patients suffering from TRD were randomly assigned to receive either MST or ECT starting from July 2006 until November 2008. Primary outcome measure was antidepressant response assessed by Montgomery Åsberg Depression Scale. Secondary outcome measures included Hamilton Depression Rating Scale, Hamilton Anxiety Scale, Beck Depression Inventory and 90-Item Symptom Checklist. Antidepressant response (improvement of 50% in MADRS ratings) was statistically significant and of similar size in both treatment groups. Cognitive side effects were observed in neither group. Characteristics in MST- and ECT-induced seizures were comparable, especially regarding ictal activity and postictal suppression. Thus, MST may be a potential alternative to ECT if efficacy and safety are validated in larger clinical trials. Copyright © 2010 Elsevier Ltd. All rights reserved.

Taking Effective Treatments to Scale: Organizational Effects on Outcomes of Multisystemic Therapy for Youth with Co-occurring Substance Use

PubMed Central

Schoenwald, Sonja K.; Chapman, Jason E.; Henry, David B.; Sheidow, Ashli J.

2012-01-01

A prospective multi-site study examined organizational climate and structure effects on the behavior and functioning of delinquent youth with and without co-occurring substance treated with an evidence-based treatment for serious antisocial behavior (i.e., Multisystemic Therapy). Participants were 1979 youth treated by 429 therapists across 45 provider organizations in North America. Results of Mixed Effects Regression Models showed some aspects of climate and structure had no effects, some had similar effects, and some had slightly differential and sometimes counter-intuitive effects on the outcomes of these youth. Implications are considered for research to increase the array and availability of effective treatments for youth with co-occurring substance use across service sectors. PMID:22844190

The Telomerase Inhibitor MST-312 Interferes with Multiple Steps in the Herpes Simplex Virus Life Cycle.

PubMed

Haberichter, Jarod; Roberts, Scott; Abbasi, Imran; Dedthanou, Phonphanh; Pradhan, Prajakta; Nguyen, Marie L

2015-10-01

The life cycle of herpes simplex virus (HSV) has the potential to be further manipulated to yield novel, more effective therapeutic treatments. Recent research has demonstrated that HSV-1 can increase telomerase activity and that expression of the catalytic component of telomerase, telomerase reverse transcriptase (TERT), alters sensitivity to HSV-dependent apoptosis. Telomerase is a cellular enzyme that synthesizes nucleotide repeats at the ends of chromosomes (telomeres), which prevents shortening of the 3' ends of DNA with each cell division. Once telomeres reach a critical length, cells undergo senescence and apoptosis. Here, we used a cell-permeable, reversible inhibitor of the telomerase enzyme, MST-312, to investigate telomerase activity during HSV infection. Human mammary epithelial cells immortalized through TERT expression and human carcinoma HEp-2 cells were infected with the KOS1.1 strain of HSV-1 in the presence of MST-312. MST-312 treatment reduced the number of cells displaying a cytopathic effect and the accumulation of immediate early and late viral proteins. Moreover, the presence of 20 μM to 100 μM MST-312 during infection led to a 2.5- to 5.5-log10 decrease in viral titers. MST-312 also inhibited the replication of HSV-2 and a recent clinical isolate of HSV-1. Additionally, we determined that MST-312 has the largest impact on viral events that take place prior to 5 h postinfection (hpi). Furthermore, MST-312 treatment inhibited virus replication, as measured by adsorption assays and quantification of genome replication. Together, these findings demonstrate that MST-312 interferes with the HSV life cycle. Further investigation into the mechanism for MST-312 is warranted and may provide novel targets for HSV therapies. Herpes simplex virus (HSV) infections can lead to cold sores, blindness, and brain damage. Identification of host factors that are important for the virus life cycle may provide novel targets for HSV antivirals. One such factor

Electric field strength and focality in electroconvulsive therapy and magnetic seizure therapy: a finite element simulation study

NASA Astrophysics Data System (ADS)

Deng, Zhi-De; Lisanby, Sarah H.; Peterchev, Angel V.

2011-02-01

We present the first computational study comparing the electric field induced by various electroconvulsive therapy (ECT) and magnetic seizure therapy (MST) paradigms. Four ECT electrode configurations (bilateral, bifrontal, right unilateral, and focal electrically administered seizure therapy) and three MST coil configurations (circular, cap, and double cone) were modeled. The model incorporated a modality-specific neural activation threshold. ECT (0.3 ms pulse width) and MST induced the maximum electric field of 2.1-2.5 V cm-1 and 1.1-2.2 V cm-1 in the brain, corresponding to 6.2-7.2 times and 1.2-2.3 times the neural activation threshold, respectively. The MST electric field is more confined to the superficial cortex compared to ECT. The brain volume stimulated was much larger with ECT (up to 100%) than with MST (up to 8.2%). MST with the double-cone coil was the most focal, and bilateral ECT was the least focal. Our results suggest a possible biophysical explanation of the reduced side effects of MST compared to ECT. Our results also indicate that the conventional ECT pulse amplitude (800-900 mA) is much higher than necessary for seizure induction. Reducing the ECT pulse amplitude should be explored as a potential means of diminishing side effects.

Electric field strength and focality in electroconvulsive therapy and magnetic seizure therapy: A finite element simulation study

PubMed Central

Deng, Zhi-De; Lisanby, Sarah H.; Peterchev, Angel V.

2014-01-01

We present the first computational study comparing the electric field induced by various electroconvulsive therapy (ECT) and magnetic seizure therapy (MST) paradigms. Four ECT electrode configurations (bilateral, bifrontal, right unilateral, and focal electrically administered seizure therapy) and three MST coil configurations (circular, cap, and double cone) were modeled. The model incorporated a modality-specific neural activation threshold. ECT (0.3 ms pulse width) and MST induced maximum electric field in the brain of 2.1–2.5 V/cm and 1.1–2.2 V/cm, corresponding to 6.2–7.2 times and 1.2–2.3 times the neural activation threshold, respectively. The MST electric field is more confined to the superficial cortex compared to ECT. The brain volume stimulated was much higher with ECT (up to 100%) than MST (up to 8.2%). MST with the double cone coil was the most focal and bilateral ECT was the least focal. Our results suggest a possible biophysical explanation of the reduced side effects of MST compared to ECT. Our results also indicate that the conventional ECT pulse amplitude (800–900 mA) is much higher than necessary for seizure induction. Reducing the ECT pulse amplitude should be explored as a potential means of diminishing side effects. PMID:21248385

Effects of electroconvulsive therapy and magnetic seizure therapy on acute memory retrieval.

PubMed

Polster, Julia D; Kayser, Sarah; Bewernick, Bettina H; Hurlemann, René; Schlaepfer, Thomas E

2015-03-01

Electroconvulsive therapy (ECT) is currently the most effective treatment for severe depression. However, it is frequently associated with negative cognitive side effects. Magnetic seizure therapy (MST) depicts an alternative, although experimental, convulsive treatment for major depression. Initial results suggest comparable antidepressant effects accompanied by a better side effect profile. However, no studies up to now have addressed acute retrieval disruption after MST in comparison to ECT. Therefore, we intended to broaden insight into the side effect profile of MST compared to ECT by examining the disruption of acute verbal memory processes after treatment. Twenty depressed patients were randomly assigned to either MST (10 patients) or ECT (10 patients) treatment. On 2 treatment days and 2 treatment-free days, the patients memorized words using a controlled learning paradigm derived from the Batchelder and Riefer storage retrieval model. Four hours after memorization, the patients were asked to retrieve words freely (delayed recall) and a second time with the help of an additional cue constructed out of a hypernymic category (cued recall). By comparing memory performance on treatment days to control days, treatment-induced memory disruption was evaluated. After ECT, delayed recall was disturbed, whereas after MST, it was not. However, this difference in performance was no longer apparent upon cue application (cued recall). This study demonstrates that ECT-induced acute memory disruption measured by delayed recall is absent after MST, confirming its superior side effect profile. We hope that confirming advantages of MST over ECT will improve therapy options for patients with severe depression.

MST1, a key player, in enhancing fast skeletal muscle atrophy

PubMed Central

2013-01-01

Background Skeletal muscle undergoes rapid atrophy upon denervation and the underlying mechanisms are complicated. FOXO3a has been implicated as a major mediator of muscle atrophy, but how its subcellular location and activity is controlled during the pathogenesis of muscle atrophy remains largely unknown. MST1 (Mammalian Sterile 20-like kinase 1) is identified as a central component of the Hippo signaling pathway. MST1 has been shown to mediate phosphorylation of FOXO3a at Ser207. Whether this MST1-FOXO signaling cascade exerts any functional consequence on cellular homeostasis remains to be investigated. Result We identified that MST1 kinase was expressed widely in skeletal muscles and was dramatically up-regulated in fast- but not slow-dominant skeletal muscles immediately following denervation. The results of our histological and biochemical studies demonstrated that deletion of MST1 significantly attenuated denervation-induced skeletal muscle wasting and decreased expression of Atrogin-1 and LC3 genes in fast-dominant skeletal muscles from three- to five-month-old adult mice. Further studies indicated that MST1, but not MST2, remarkably increased FOXO3a phosphorylation level at Ser207 and promoted its nuclear translocation in atrophic fast-dominant muscles. Conclusions We have established that MST1 kinase plays an important role in regulating denervation-induced skeletal muscle atrophy. During the early stage of muscle atrophy, the up-regulated MST1 kinase promoted progression of neurogenic atrophy in fast-dominant skeletal muscles through activation of FOXO3a transcription factors. PMID:23374633

Reducing recidivism and symptoms in emerging adults with serious mental health conditions and justice system involvement.

PubMed

Davis, Maryann; Sheidow, Ashli J; McCart, Michael R

2015-04-01

The peak years of offending in the general population and among those with serious mental health conditions (SMHC) are during emerging adulthood. There currently are no evidence-based interventions for reducing offending behavior among 18-21 year olds, with or without SMHC. This open trial examined outcomes from an adaptation of Multisystemic Therapy (MST), an effective juvenile recidivism reduction intervention, modified for use with emerging adults with SMHC and recent justice system involvement. MST for emerging adults (MST-EA) targets MH symptoms, recidivism, problem substance use, and young adult functional capacities. All study participants (n = 41) were aged 17-20 and had a MH diagnosis and recent arrest or incarceration. Implementation outcomes indicated that MST-EA was delivered with strong fidelity, client satisfaction was high, and the majority of participants successfully completed the intervention. Research retention rates also were high. Pre-post-analyses revealed significant reductions in participants' MH symptoms, justice system involvement, and associations with antisocial peers.

Reducing Recidivism and Symptoms in Emerging Adults with Serious Mental Health Conditions and Justice System Involvement

PubMed Central

Davis, Maryann; Sheidow, Ashli J.; McCart, Michael R.

2014-01-01

The peak years of offending in the general population and among those with serious mental health conditions (SMHC) are during emerging adulthood. There currently are no evidence-based interventions for reducing offending behavior among 18–21 year olds, with or without SMHC. This open trial examined outcomes from an adaptation of Multisystemic Therapy (MST), an effective juvenile recidivism reduction intervention, modified for use with emerging adults with SMHC and recent justice system involvement. MST for emerging adults (MST-EA) targets MH symptoms, recidivism, problem substance use, and young adult functional capacities. All study participants (n=41) were aged 17–20 and had a MH diagnosis and recent arrest or incarceration. Implementation outcomes indicated that MST-EA was delivered with strong fidelity, client satisfaction was high, and the majority of participants successfully completed the intervention. Research retention rates also were high. Pre-post analyses revealed significant reductions in participants’ MH symptoms, justice-system involvement, and associations with antisocial peers. PMID:25023764

Mst1 shuts off cytosolic antiviral defense through IRF3 phosphorylation

PubMed Central

Meng, Fansen; Zhou, Ruyuan; Wu, Shiying; Zhang, Qian; Jin, Qiuheng; Zhou, Yao; Plouffe, Steven W.; Liu, Shengduo; Song, Hai; Xia, Zongping; Zhao, Bin; Ye, Sheng; Feng, Xin-Hua; Guan, Kun-Liang; Zou, Jian

2016-01-01

Cytosolic RNA/DNA sensing elicits primary defense against viral pathogens. Interferon regulatory factor 3 (IRF3), a key signal mediator/transcriptional factor of the antiviral-sensing pathway, is indispensible for interferon production and antiviral defense. However, how the status of IRF3 activation is controlled remains elusive. Through a functional screen of the human kinome, we found that mammalian sterile 20-like kinase 1 (Mst1), but not Mst2, profoundly inhibited cytosolic nucleic acid sensing. Mst1 associated with IRF3 and directly phosphorylated IRF3 at Thr75 and Thr253. This Mst1-mediated phosphorylation abolished activated IRF3 homodimerization, its occupancy on chromatin, and subsequent IRF3-mediated transcriptional responses. In addition, Mst1 also impeded virus-induced activation of TANK-binding kinase 1 (TBK1), further attenuating IRF3 activation. As a result, Mst1 depletion or ablation enabled an enhanced antiviral response and defense in cells and mice. Therefore, the identification of Mst1 as a novel physiological negative regulator of IRF3 activation provides mechanistic insights into innate antiviral defense and potential antiviral prevention strategies. PMID:27125670

Examining Therapist Comfort in Delivering Family Therapy in Home and Community Settings: Development and Evaluation of the Therapist Comfort Scale

PubMed Central

Glebova, Tatiana; Foster, Sharon L.; Cunningham, Phillippe B.; Brennan, Patricia A.; Whitmore, Elizabeth

2015-01-01

This study reports on the development and psychometric properties of a new measure assessing therapist comfort in the home treatment context, and the relationship between therapist comfort, related process variables, and therapist characteristics. Data were drawn from a longitudinal evaluation of 185 families treated by 51 therapists using Multisystemic Therapy (MST). Therapist comfort was measured at four time points. Psychometric evaluation indicated that the measure was internally and temporally consistent. Examination of the measure’s validity indicated that therapists’ feelings of safety and comfort during the provision of home-based treatment were associated with family neighborhood characteristics and family socioeconomic factors. Furthermore, the therapist’s reported level of alliance (as measured by the Emotional Bonding subscale of the Working Alliance Inventory) was related to her/his feeling of comfort. Analyses also indicated that therapists with greater belief in the clinical utility of the MST model felt more comfortable when delivering MST. Together the results suggest that economically disadvantaged families treated in home and community settings may be most at risk for erosions in the therapeutic relationship over time as a function of lower therapist comfort. Because therapist comfort was associated with therapeutic alliance - a factor found to be associated with clinical outcomes across studies and treatment models - findings imply that psychotherapists should regularly examine their own level of comfort, especially when providing services in non-traditional settings, and that therapist comfort should be routinely assessed as part of clinical supervision and training. PMID:22181024

LEACHING OF TITANIUM FROM MONOSODIUM TITANATE AND MODIFIED MST

DOE Office of Scientific and Technical Information (OSTI.GOV)

Taylor-Pashow, K.; Fondeur, F.; Fink, S.

2012-08-01

Analysis of a fouled coalescer and pre-filters from Actinide Removal Process/Modular Caustic Side Solvent Extraction Unit (ARP/MCU) operations showed evidence of Ti containing solids. Based on these results a series of tests were planned to examine the extent of Ti leaching from monosodium titanate (MST) and modified monosodium titanate (mMST) in various solutions. The solutions tested included a series of salt solutions with varying free hydroxide concentrations, two sodium hydroxide concentrations, 9 wt % and 15 wt %, nitric and oxalic acid solutions. Overall, the amount of Ti leached from the MST and mMST was much greater in the acidmore » solutions compared to the sodium hydroxide or salt solutions, which is consistent with the expected trend. The leaching data also showed that increasing hydroxide concentration, whether pure NaOH solution used for filter cleaning in ARP or the waste salt solution, increased the amount of Ti leached from both the MST and mMST. For the respective nominal contact times with the MST solids - for filter cleaning or the normal filter operation, the dissolved Ti concentrations are comparable suggesting either cause may contribute to the increased Ti fouling on the MCU coalescers. Tests showed that Ti containing solids could be precipitated from solution after the addition of scrub acid and a decrease in temperature similar to expected in MCU operations. FTIR analysis of these solids showed some similarity to the solids observed on the fouled coalescer and pre-filters. Although only a cursory study, this information suggests that the practice of increasing free hydroxide in feed solutions to MCU as a mitigation to aluminosilicate formation may be offset by the impact of formation of Ti solids in the overall process. Additional consideration of this finding from MCU and SWPF operation is warranted.« less

Individualized Low-Amplitude Seizure Therapy: Minimizing Current for Electroconvulsive Therapy and Magnetic Seizure Therapy.

PubMed

Peterchev, Angel V; Krystal, Andrew D; Rosa, Moacyr A; Lisanby, Sarah H

2015-08-01

Electroconvulsive therapy (ECT) at conventional current amplitudes (800-900 mA) is highly effective but carries the risk of cognitive side effects. Lowering and individualizing the current amplitude may reduce side effects by virtue of a less intense and more focal electric field exposure in the brain, but this aspect of ECT dosing is largely unexplored. Magnetic seizure therapy (MST) induces a weaker and more focal electric field than ECT; however, the pulse amplitude is not individualized and the minimum amplitude required to induce a seizure is unknown. We titrated the amplitude of long stimulus trains (500 pulses) as a means of determining the minimum current amplitude required to induce a seizure with ECT (bilateral, right unilateral, bifrontal, and frontomedial electrode placements) and MST (round coil on vertex) in nonhuman primates. Furthermore, we investigated a novel method of predicting this amplitude-titrated seizure threshold (ST) by a non-convulsive measurement of motor threshold (MT) using single pulses delivered through the ECT electrodes or MST coil. Average STs were substantially lower than conventional pulse amplitudes (112-174 mA for ECT and 37.4% of maximum device amplitude for MST). ST was more variable in ECT than in MST. MT explained 63% of the ST variance and is hence the strongest known predictor of ST. These results indicate that seizures can be induced with less intense electric fields than conventional ECT that may be safer; efficacy and side effects should be evaluated in clinical studies. MT measurement could be a faster and safer alternative to empirical ST titration for ECT and MST.

Involvement of Mst1 in tumor necrosis factor-{alpha}-induced apoptosis of endothelial cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ohtsubo, Hideki; Ichiki, Toshihiro; Imayama, Ikuyo

2008-03-07

Mammalian sterile 20-kinase 1 (Mst1), a member of the sterile-20 family protein kinase, plays an important role in the induction of apoptosis. However, little is know about the physiological activator of Mst1 and the role of Mst1 in endothelial cells (ECs). We examined whether Mst1 is involved in the tumor necrosis factor (TNF)-{alpha}-induced apoptosis of ECs. Western blot analysis revealed that TNF-{alpha} induced activation of caspase 3 and Mst1 in a time- and dose-dependent manner. TNF-{alpha}-induced Mst1 activation is almost completely prevented by pretreatment with Z-DEVD-FMK, a caspase 3 inhibitor. Nuclear staining with Hoechst 33258 and fluorescence-activated cell sorting ofmore » propidium iodide-stained cells showed that TNF-{alpha} induced apoptosis of EC. Diphenyleneiodonium, an inhibitor of NADPH oxidase, and N-acetylcysteine, a potent antioxidant, also inhibited TNF-{alpha}-induced activation of Mst1 and caspase 3, as well as apoptosis. Knockdown of Mst1 expression by short interfering RNA attenuated TNF-{alpha}-induced apoptosis but not cleavage of caspase 3. These results suggest that Mst1 plays an important role in the induction of TNF-{alpha}-induced apoptosis of EC. However, positive feedback mechanism between Mst1 and caspase 3, which was shown in the previous studies, was not observed. Inhibition of Mst1 function may be beneficial for maintaining the endothelial integrity and inhibition of atherogenesis.« less

Hypermethylation of MST1 in IgG4-related autoimmune pancreatitis and rheumatoid arthritis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fukuhara, Takataro; Tomiyama, Takashi; Yasuda, Kaneki

The serine/threonine kinase Mst1 plays important roles in the control of immune cell trafficking, proliferation, and differentiation. Previously, we reported that Mst1 was required for thymocyte selection and regulatory T-cell functions, thereby the prevention of autoimmunity in mice. In humans, MST1 null mutations cause T-cell immunodeficiency and hypergammaglobulinemia with autoantibody production. RASSF5C(RAPL) is an activator of MST1 and it is frequently methylated in some tumors. Herein, we investigated methylation of the promoter regions of MST1 and RASSF5C(RAPL) in leukocytes from patients with IgG4-related autoimmune pancreatitis (AIP) and rheumatoid arthritis (RA). Increased number of CpG methylation in the 5′ region ofmore » MST1 was detected in AIP patients with extrapancreatic lesions, whereas AIP patients without extrapancreatic lesions were similar to controls. In RA patients, we detected a slight increased CpG methylation in MST1, although the overall number of methylation sites was lower than that of AIP patients with extrapancreatic lesions. There were no significant changes of the methylation levels of the CpG islands in the 5′ region of RASSF5C(RAPL) in leukocytes from AIP and RA patients. Consistently, we found a significantly down-regulated expression of MST1 in regulatory T cells of AIP patients. Our results suggest that the decreased expression of MST1 in regulatory T cells due to hypermethylation of the promoter contributes to the pathogenesis of IgG4-related AIP. - Highlights: • Mst1 controls immune cells trafficking, cell proliferation and differentiation. • Autoimmune pancreatitis (AIP) is an idiopathic pancreatitis affecting multiple organs. • Decreased MST1 expression and increased CpG methylation of promoter of MST1 in AIP. • Slight increased CpG methylation of MST1 in rheumatoid arthritis patients. • MST1 contributes pathogenesis of IgG4-related AIP.« less

MST radar data-base management

NASA Technical Reports Server (NTRS)

Wickwar, V. B.

1983-01-01

Data management for Mesospheric-Stratospheric-Tropospheric, (MST) radars is addressed. An incoherent-scatter radar data base is discussed in terms of purpose, centralization, scope, and nature of the data base management system.

Individualized Low-Amplitude Seizure Therapy: Minimizing Current for Electroconvulsive Therapy and Magnetic Seizure Therapy

PubMed Central

Peterchev, Angel V; Krystal, Andrew D; Rosa, Moacyr A; Lisanby, Sarah H

2015-01-01

Electroconvulsive therapy (ECT) at conventional current amplitudes (800–900 mA) is highly effective but carries the risk of cognitive side effects. Lowering and individualizing the current amplitude may reduce side effects by virtue of a less intense and more focal electric field exposure in the brain, but this aspect of ECT dosing is largely unexplored. Magnetic seizure therapy (MST) induces a weaker and more focal electric field than ECT; however, the pulse amplitude is not individualized and the minimum amplitude required to induce a seizure is unknown. We titrated the amplitude of long stimulus trains (500 pulses) as a means of determining the minimum current amplitude required to induce a seizure with ECT (bilateral, right unilateral, bifrontal, and frontomedial electrode placements) and MST (round coil on vertex) in nonhuman primates. Furthermore, we investigated a novel method of predicting this amplitude-titrated seizure threshold (ST) by a non-convulsive measurement of motor threshold (MT) using single pulses delivered through the ECT electrodes or MST coil. Average STs were substantially lower than conventional pulse amplitudes (112–174 mA for ECT and 37.4% of maximum device amplitude for MST). ST was more variable in ECT than in MST. MT explained 63% of the ST variance and is hence the strongest known predictor of ST. These results indicate that seizures can be induced with less intense electric fields than conventional ECT that may be safer; efficacy and side effects should be evaluated in clinical studies. MT measurement could be a faster and safer alternative to empirical ST titration for ECT and MST. PMID:25920013

21. DETAIL OF AIR HANDLER 1 (MST AIRCONDITIONING SYSTEM) INTERIOR, ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

21. DETAIL OF AIR HANDLER 1 (MST AIR-CONDITIONING SYSTEM) INTERIOR, SOUTHEAST CORNER, STATION 30, SLC-3W MST - Vandenberg Air Force Base, Space Launch Complex 3, Launch Pad 3 West, Napa & Alden Roads, Lompoc, Santa Barbara County, CA

22. DETAIL OF CHILLERS 1 AND 2 (MST AIRCONDITIONING SYSTEM) ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

22. DETAIL OF CHILLERS 1 AND 2 (MST AIR-CONDITIONING SYSTEM) INTERIOR, NORTHEAST CORNER, STATION 30, SLC-3W MST - Vandenberg Air Force Base, Space Launch Complex 3, Launch Pad 3 West, Napa & Alden Roads, Lompoc, Santa Barbara County, CA

Differences in Seizure Expression Between Magnetic Seizure Therapy and Electroconvulsive Shock.

PubMed

Cycowicz, Yael M; Rowny, Stefan B; Luber, Bruce; Lisanby, Sarah H

2018-06-01

Evidence suggests that magnetic seizure therapy (MST) results in fewer side effects than electroconvulsive treatment, both in humans treated with electroconvulsive therapy (ECT) as well as in the animal preclinical model that uses electroconvulsive shock (ECS). Evidence suggests that MST results in fewer cognitive side effects than ECT. Although MST offers enhanced control over seizure induction and spread, little is known about how MST and ECT seizures differ. Seizure characteristics are associated with treatment effect. This study presents quantitative analyses of electroencephalogram (EEG) power after electrical and magnetic seizure induction and anesthesia-alone sham in an animal model. The aim was to test whether differential neurophysiological characteristics of the seizures could be identified that support earlier observations that the powers of theta, alpha, and beta but not delta frequency bands were lower after MST when compared with those after ECS. In a randomized, sham-controlled trial, 24 macaca mulatte received 6 weeks of daily sessions while scalp EEG was recorded. Electroencephalogram power was quantified within delta, theta, alpha, and beta frequency bands. Magnetic seizure therapy induced lower ictal expression in the theta, alpha and beta frequencies than ECS, but MST and ECS were indistinguishable in the delta band. Magnetic seizure therapy showed less postictal suppression than ECS. Increasing electrical dosage increased ictal power, whereas increasing MST dosage had no effect on EEG expression. Magnetic seizure therapy seizures have less robust electrophysiological expression than ECS, and these differences are largest in the alpha and beta bands. The relevance of these differences in higher frequency bands to clinical outcomes deserves further exploration. Contrasting EEG in ECS and MST may lead to insights on the physiological underpinnings of seizure-induced amnesia and to finding ways to reduce cognitive side effects.

Magnetic Seizure Therapy for Unipolar and Bipolar Depression: A Systematic Review

PubMed Central

Cretaz, Eric; Brunoni, André R.

2015-01-01

Objective. Magnetic seizure therapy (MST) is a novel, experimental therapeutic intervention, which combines therapeutic aspects of electroconvulsive therapy (ECT) and transcranial magnetic stimulation, in order to achieve the efficacy of the former with the safety of the latter. MST might prove to be a valuable tool in the treatment of mood disorders, such as major depressive disorder (MDD) and bipolar disorder. Our aim is to review current literature on MST. Methods. OVID and MEDLINE databases were used to systematically search for clinical studies on MST. The terms “magnetic seizure therapy,” “depression,” and “bipolar” were employed. Results. Out of 74 studies, 8 met eligibility criteria. There was considerable variability in the methods employed and samples sizes were small, limiting the generalization of the results. All studies focused on depressive episodes, but few included patients with bipolar disorder. The studies found reported significant antidepressant effects, with remission rates ranging from 30% to 40%. No significant cognitive side effects related to MST were found, with a better cognitive profile when compared to ECT. Conclusion. MST was effective in reducing depressive symptoms in mood disorders, with generally less side effects than ECT. No study focused on comparing MST to ECT on bipolar depression specifically. PMID:26075100

17. VIEW OF INTERIOR, EAST SIDE, DECK LEVEL OF MST. ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

17. VIEW OF INTERIOR, EAST SIDE, DECK LEVEL OF MST. NOTE CANVAS CURTAIN (RIGHT) USED TO COVER SOUTH SIDE OF MST BELOW LOWEST ENVIRONMENTAL DOORS. - Vandenberg Air Force Base, Space Launch Complex 3, Launch Pad 3 West, Napa & Alden Roads, Lompoc, Santa Barbara County, CA

73. LIQUID NITROGEN PUMPING STATION ON WEST SIDE OF MST; ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

73. LIQUID NITROGEN PUMPING STATION ON WEST SIDE OF MST; NITROGEN EXCHANGERS ON RIGHT. SOUTHWEST CORNER OF MST VISIBLE; ENVIRONMENTAL CURTAIN SWING AND PLATFORM EXTENDED. - Vandenberg Air Force Base, Space Launch Complex 3, Launch Pad 3 East, Napa & Alden Roads, Lompoc, Santa Barbara County, CA

1. VIEW OF SOUTHEAST CORNER OF MOBILE SERVICE TOWER (MST). ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

1. VIEW OF SOUTHEAST CORNER OF MOBILE SERVICE TOWER (MST). CABLE TRAY SHED IN FOREGROUND. MICROWAVE ANTENNAS AND AIR-CONDITIONING PORCH ON EAST SIDE OF MST. - Vandenberg Air Force Base, Space Launch Complex 3, Launch Pad 3 East, Napa & Alden Roads, Lompoc, Santa Barbara County, CA

Pervanadate induces Mammalian Ste20 Kinase 3 (MST3) tyrosine phosphorylation but not activation.

PubMed

Kan, Wei-Chih; Lu, Te-Ling; Ling, Pin; Lee, Te-Hsiu; Cho, Chien-Yu; Huang, Chi-Ying F; Jeng, Wen-Yih; Weng, Yui-Ping; Chiang, Chun-Yen; Wu, Jin Bin; Lu, Te-Jung

2016-07-01

The yeast Ste20 (sterile) protein kinase, which is a serine/threonine kinase, responds to the stimulation of the G proteincoupled receptor (GPCR) pheromone receptor. Ste20 protein kinase serves as the critical component that links signaling from the GPCR/G proteins to the mitogen-activated protein kinase (MAPK) cascade in yeast. The yeast Ste20p functions as a MAP kinase kinase kinase kinase (MAP4K) in the pheromone response. Ste20-like kinases are structurally conserved from yeast to mammals. The mechanism by which MAP4K links GPCR to the MAPK pathway is less clearly defined in vertebrates. In addition to MAP4K, the tyrosine kinase cascade bridges G proteins and the MAPK pathway in vertebrate cells. Mammalian Ste20 Kinase 3 (MST3) has been categorized into the Ste20 family and has been reported to function in the regulation of cell polarity and migration. However, whether MST3 tyrosine phosphorylation regulates diverse signaling pathways is unknown. In this study, the tyrosine phosphatase inhibitor pervanadate was found to induce MST3 tyrosine phosphorylation in intact cells, and the activity of tyrosine-phosphorylated MST3 was measured. This tyrosine-directed phosphorylation was independent of MST3 activity. Parameters including protein conformation, Triton concentration and ionic concentration influenced the sensitivity of MST3 activity. Taken together, our data suggests that the serine/threonine kinase MST3 undergoes tyrosinedirected phosphorylation. The tyrosine-phosphorylated MST3 may create a docking site for the structurally conserved SH2/SH3 (Src Homology 2 and 3) domains within the Src oncoprotein. The unusual tyrosinephosphorylated MST3 may recruit MST3 to various signaling components. Copyright © 2016. Published by Elsevier Inc.

MST1 activation by curcumin mediates JNK activation, Foxo3a nuclear translocation and apoptosis in melanoma cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yu, Teng, E-mail: tengyu33@yahoo.com; Ji, Jiang; Guo, Yong-li

2013-11-08

Highlights: •Curcumin activates MST1 in melanoma cells. •MST1 mediates curcumin-induced apoptosis of melanoma cells. •ROS production is involved in curcumin-induced MST1 activation. •MST1 mediates curcumin-induced JNK activation in melanoma cells. •MST1 mediates curcumin-induced Foxo3a nuclear translocation and Bim expression. -- Abstract: Different groups including ours have shown that curcumin induces melanoma cell apoptosis, here we focused the role of mammalian Sterile 20-like kinase 1 (MST1) in it. We observed that curcumin activated MST1-dependent apoptosis in cultured melanoma cells. MST1 silencing by RNA interference (RNAi) suppressed curcumin-induced cell apoptosis, while MST1 over-expressing increased curcumin sensitivity. Meanwhile, curcumin induced reactive oxygen speciesmore » (ROS) production in melanoma cells, and the ROS scavenger, N-acetyl-cysteine (NAC), almost blocked MST1 activation to suggest that ROS might be required for MST1 activation by curcumin. c-Jun N-terminal protein kinase (JNK) activation by curcumin was dependent on MST1, since MST1 inhibition by RNAi or NAC largely inhibited curcumin-induced JNK activation. Further, curcumin induced Foxo3 nuclear translocation and Bim-1 (Foxo3 target gene) expression in melanoma cells, such an effect by curcumin was inhibited by MST1 RNAi. In conclusion, we suggested that MST1 activation by curcumin mediates JNK activation, Foxo3a nuclear translocation and apoptosis in melanoma cells.« less

29. DETAIL OF OUTLET DUCTS FOR MST AIRCONDITIONING SYSTEM IN ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

29. DETAIL OF OUTLET DUCTS FOR MST AIR-CONDITIONING SYSTEM IN NORTHWEST CORNER OF SLC-3W MST STATION 70.5 (LOWEST PAYLOAD SERVICE STATION). NOTE RING ATTACHMENT FOR PERSONNEL SAFETY HARNESS IN LEFT FOREGROUND. - Vandenberg Air Force Base, Space Launch Complex 3, Launch Pad 3 West, Napa & Alden Roads, Lompoc, Santa Barbara County, CA

14. VIEW OF MST, FACING SOUTHEAST, AND LAUNCH PAD TAKEN ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

14. VIEW OF MST, FACING SOUTHEAST, AND LAUNCH PAD TAKEN FROM NORTHEAST PHOTO TOWER WITH WINDOW OPEN. FEATURES LEFT TO RIGHT: SOUTH TELEVISION CAMERA TOWER, SOUTHWEST PHOTO TOWER, LAUNCHER, UMBILICAL MAST, MST, AND OXIDIZER APRON. - Vandenberg Air Force Base, Space Launch Complex 3, Launch Pad 3 East, Napa & Alden Roads, Lompoc, Santa Barbara County, CA

Long-Term Youth Criminal Outcomes in MST Transport: The Impact of Therapist Adherence and Organizational Climate and Structure

ERIC Educational Resources Information Center

Schoenwald, Sonja K.; Chapman, Jason E.; Sheidow, Ashli J.; Carter, Rickey E.

2009-01-01

This study investigated relations among therapist adherence to an evidence-based treatment for youth with serious antisocial behavior (i.e., Multisystemic Therapy), organizational climate and structure, and youth criminal charges on average 4 years posttreatment. Participants were 1,979 youth and families treated by 429 therapists across 45…

Comparison of electric field strength and spatial distribution of electroconvulsive therapy and magnetic seizure therapy in a realistic human head model

PubMed Central

Lee, Won Hee; Lisanby, Sarah H.; Laine, Andrew F.; Peterchev, Angel V.

2017-01-01

Background This study examines the strength and spatial distribution of the electric field induced in the brain by electroconvulsive therapy (ECT) and magnetic seizure therapy (MST). Methods The electric field induced by standard (bilateral, right unilateral, and bifrontal) and experimental (focal electrically administered seizure therapy and frontomedial) ECT electrode configurations as well as a circular MST coil configuration was simulated in an anatomically realistic finite element model of the human head. Maps of the electric field strength relative to an estimated neural activation threshold were used to evaluate the stimulation strength and focality in specific brain regions of interest for these ECT and MST paradigms and various stimulus current amplitudes. Results The standard ECT configurations and current amplitude of 800–900 mA produced the strongest overall stimulation with median of 1.8–2.9 times neural activation threshold and more than 94% of the brain volume stimulated at suprathreshold level. All standard ECT electrode placements exposed the hippocampi to suprathreshold electric field, although there were differences across modalities with bilateral and right unilateral producing respectively the strongest and weakest hippocampal stimulation. MST stimulation is up to 9 times weaker compared to conventional ECT, resulting in direct activation of only 21% of the brain. Reducing the stimulus current amplitude can make ECT as focal as MST. Conclusions The relative differences in electric field strength may be a contributing factor for the cognitive sparing observed with right unilateral compared to bilateral ECT, and MST compared to right unilateral ECT. These simulations could help understand the mechanisms of seizure therapies and develop interventions with superior risk/benefit ratio. PMID:27318858

System aspects of the Indian MST radar facility

NASA Technical Reports Server (NTRS)

Viswanathan, G.

1986-01-01

One of the major objectives of the Indian Middle Atmosphere Program is to investigate the motions of the middle atmosphere on temporal and spatial scales and the interaction between the three height regions of the middle atmosphere. Realizing the fact that radar technique has proven to be a very powerful tool for the study of Earth atmosphere, the Indian Middle Atmosphere Program has recommended establishing a mesosphere-stratosphere-troposphere (MST) radar as a national facility for atmospheric research. The major landmarks in this attempt to setup the MST radar as a national facility are described.

Maximizing MST's inductive capability with a Bp programmable power supply

NASA Astrophysics Data System (ADS)

Chapman, B. E.; Holly, D. J.; Jacobson, C. M.; McCollam, K. J.; Morin, J. C.; Sarff, J. S.; Squitieri, A.

2016-10-01

A major goal of the MST program is the advancement of inductive control for the development of both the RFP's fusion potential and, synergistically, the predictive capability of fusion science. This entails programmable power supplies (PPS's) for the Bt and Bp circuits. A Bt PPS is already in place, allowing advanced RFP operation and the production of tokamak plasmas, and a Bp PPS prototype is under construction. To explore some of the new capabilities to be provided by the Bp PPS, the existing Bt PPS has been temporarily connected to the Bp circuit. One key result is new-found access to very low Ip (20 kA) and very low Lundquist number, S (104). At this low S, simulation of RFP plasmas with the MHD code NIMROD is readily achievable, and work toward validation of extended MHD models using NIMROD is underway with direct comparisons to these MST plasmas. The full Bp PPS will also provide higher Ip and S than presently possible, allowing MST to produce plasmas with S spanning as much as five orders of magnitude, a dramatic extension of MST's capability. In these initial tests, the PPS has also increased five-fold MST's Ip flattop duration, to about 100 ms. This, coupled with the recently demonstrated PPS ability to drive large-amplitude sinusoidal oscillations in Ip, will allow tests of extended-duration oscillating field current drive, the goal of which is ac sustainment of a quasi-dc plasma current. Work supported by US DOE.

Structural basis of the heterodimerization of the MST and RASSF SARAH domains in the Hippo signalling pathway

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hwang, Eunha; Korea University, Seoul 136-701; Cheong, Hae-Kap

2014-07-01

The heterodimeric structure of the MST1 and RASSF5 SARAH domains is presented. A comparison of homodimeric and heterodimeric interactions provides a structural basis for the preferential association of the SARAH heterodimer. Despite recent progress in research on the Hippo signalling pathway, the structural information available in this area is extremely limited. Intriguingly, the homodimeric and heterodimeric interactions of mammalian sterile 20-like (MST) kinases through the so-called ‘SARAH’ (SAV/RASSF/HPO) domains play a critical role in cellular homeostasis, dictating the fate of the cell regarding cell proliferation or apoptosis. To understand the mechanism of the heterodimerization of SARAH domains, the three-dimensional structuresmore » of an MST1–RASSF5 SARAH heterodimer and an MST2 SARAH homodimer were determined by X-ray crystallography and were analysed together with that previously determined for the MST1 SARAH homodimer. While the structure of the MST2 homodimer resembled that of the MST1 homodimer, the MST1–RASSF5 heterodimer showed distinct structural features. Firstly, the six N-terminal residues (Asp432–Lys437), which correspond to the short N-terminal 3{sub 10}-helix h1 kinked from the h2 helix in the MST1 homodimer, were disordered. Furthermore, the MST1 SARAH domain in the MST1–RASSF5 complex showed a longer helical structure (Ser438–Lys480) than that in the MST1 homodimer (Val441–Lys480). Moreover, extensive polar and nonpolar contacts in the MST1–RASSF5 SARAH domain were identified which strengthen the interactions in the heterodimer in comparison to the interactions in the homodimer. Denaturation experiments performed using urea also indicated that the MST–RASSF heterodimers are substantially more stable than the MST homodimers. These findings provide structural insights into the role of the MST1–RASSF5 SARAH domain in apoptosis signalling.« less

A pilot study of the comparative efficacy of 100 Hz magnetic seizure therapy and electroconvulsive therapy in persistent depression.

PubMed

Fitzgerald, Paul B; Hoy, Kate E; Elliot, David; McQueen, Susan; Wambeek, Lenore E; Chen, Leo; Clinton, Anne Maree; Downey, Glenn; Daskalakis, Zafiris J

2018-05-01

Magnetic seizure therapy (MST) is a novel brain stimulation technique that uses a high-powered transcranial magnetic stimulation device to produce therapeutic seizures. Preliminary MST studies have found antidepressant effects in the absence of cognitive side effects but its efficacy compared to electroconvulsive therapy (ECT) remains unclear. The aim of this study was to investigate the therapeutic efficacy and cognitive profile of MST compared to standard right unilateral ECT treatment. Thirty-seven patients completed a course of at least nine ECT or MST treatments in a randomized double-blind protocol. Assessments of depression severity and cognition were performed before and after treatment. No difference in the antidepressant effectiveness between the treatments was seen across any of the clinical outcome measures, although the overall response rates in both groups were quite low. In regards to cognition, following MST there were significant improvements in tests of psychomotor speed, verbal memory, and cognitive inhibition, with no reductions in cognitive performance. Following ECT there was significant improvement in only one of the cognitive inhibition tasks. With respect to the between-group comparisons, the MST group showed a significantly greater improvement on psychomotor speed than ECT. MST showed similar efficacy to right unilateral ECT in patients with treatment-resistant depression without cognitive side effects but in a sample that was only of sufficient size to demonstrate relatively large differences in response between the two groups. Future research should aim to optimize the methods of MST administration and compare its efficacy to ECT in large randomized controlled trials. © 2018 Wiley Periodicals, Inc.

Effects of family treatment on parenting beliefs among caregivers of youth with poorly controlled asthma.

PubMed

Ellis, Deborah A; King, Pamela; Naar-King, Sylvie; Lam, Phebe; Cunningham, Phillippe B; Secord, Elizabeth

2014-10-01

Caregiver involvement is critical in ensuring optimal adolescent asthma management. The study investigated whether multisystemic therapy (MST), an intensive home-based family therapy, was superior to family support for changing beliefs regarding asthma-related positive parenting among caregivers of African-American youth with poorly controlled asthma. The relationship between parenting beliefs and asthma management at the conclusion of the intervention was also assessed. A randomized controlled trial was conducted with 167 adolescents with moderate-to-severe, persistent, poorly controlled asthma and their primary caregivers. Families were randomly assigned to MST or family support (FS), a home-based family support condition. Data were collected at baseline and 7-month posttest. Changes in caregiver ratings of importance and confidence for engaging in asthma-related positive parenting were assessed through questionnaire. Illness management was assessed by the Family Asthma Management System Scale. Participation in MST was associated with more change in caregiver beliefs as compared with FS for both importance (t = 2.39, p = .02) and confidence (t = 2.04, p = .04). Caregiver beliefs were also significantly related to youth controller medication adherence at the conclusion of treatment (importance: r = .21, p = .01; confidence: r = .23, p = .004). Results support the effectiveness of MST for increasing parental beliefs in the value of asthma-related positive parenting behaviors and parental self-efficacy for these behaviors among families of minority adolescents with poorly controlled asthma.

Antenna induced range smearing in MST radars

NASA Technical Reports Server (NTRS)

Watkins, B. J.; Johnston, P. E.

1984-01-01

There is considerable interest in developing stratosphere troposphere (ST) and mesosphere stratosphere troposphere (MST) radars for higher resolution to study small-scale turbulent structures and waves. At present most ST and MST radars have resolutions of 150 meters or larger, and are not able to distinguish the thin (40 - 100 m) turbulent layers that are known to occur in the troposphere and stratosphere, and possibly in the mesosphere. However the antenna beam width and sidelobe level become important considerations for radars with superior height resolution. The objective of this paper is to point out that for radars with range resolutions of about 150 meters or less, there may be significant range smearing of the signals from mesospheric altitudes due to the finite beam width of the radar antenna. At both stratospheric and mesospheric heights the antenna sidelobe level for lear equally spaced phased arrays may also produce range aliased signals. To illustrate this effect the range smearing functions for two vertically directed antennas have been calculated, (1) an array of 32 coaxial-collinear strings each with 48 elements that simulates the vertical beam of the Poker Flat, Glaska, MST radar; and (2) a similar, but smaller, array of 16 coaxial-collinear strings each with 24 elements.

MST's Programmable Power Supplies: Bt Update, Bp Prototype

NASA Astrophysics Data System (ADS)

Holly, D. J.; Chapman, B. E.; McCollam, K. J.; Morin, J. C.; Thomas, M. A.

2013-10-01

MST's toroidal field programmable power supply (Bt PPS) has now been in operation for several years and has provided important new capabilities. One of the primary goals for the Bt PPS is the partial optimization of inductive current profile control, involving control of the poloidal electric field. The Bt PPS has achieved fluctuation reduction over MST's entire range of Ip. At the largest Ip, the Bt PPS achieves fluctuation reduction with a smaller poloidal electric field than the previous passive system, implying that substantially longer periods of current profile control may be possible. The Bt PPS has also been used to produce Ohmic tokamak plasmas in MST. With an applied toroidal field of 0.135 T, and q(a) > 2, the estimated energy confinement time is roughly consistent with neo-Alcator scaling. Driving q(a) < 2 with larger Ip, the confinement time degrades, but the discharge duration does not terminate prematurely. To fully optimize current profile control and to test MST operational limits, a PPS is also needed for the Bp circuit. Currently in prototype stage, the Bp PPS will feature a number of innovations to increase its flexibility and performance. Isolated charging, control, and monitor systems will eliminate charging relays, reduce coupling between modules, and minimize capacitor heating. Seven-level pulse width modulation will reduce output ripple and switching losses. Solid state shorting bars will eliminate shorting relays and minimize wiring. A balanced switching algorithm will minimize capacitive noise generation. Work supported by U. S. D. o. E.

Assessment of performing an MST strike in Tank 21H

DOE Office of Scientific and Technical Information (OSTI.GOV)

Poirier, Michael R.

2014-09-29

Previous Savannah River National Laboratory (SRNL) tank mixing studies performed for the Small Column Ion Exchange (SCIX) project have shown that 3 Submersible Mixer Pumps (SMPs) installed in Tank 41 are sufficient to support actinide removal by MST sorption as well as subsequent resuspension and removal of settled solids. Savannah River Remediation (SRR) is pursuing MST addition into Tank 21 as part of the Large Tank Strike (LTS) project. The preliminary scope for LTS involves the use of three standard slurry pumps (installed in N, SE, and SW risers) in a Type IV tank. Due to the differences in tankmore » size, internal interferences, and pump design, a separate mixing evaluation is required to determine if the proposed configuration will allow for MST suspension and strontium and actinide sorption. The author performed the analysis by reviewing drawings for Tank 21 [W231023] and determining the required cleaning radius or zone of influence for the pumps. This requirement was compared with previous pilot-scale MST suspension data collected for SCIX that determined the cleaning radius, or zone of influence, as a function of pump operating parameters. The author also reviewed a previous Tank 50 mixing analysis that examined the ability of standard slurry pumps to suspend sludge particles. Based on a review of the pilot-scale SCIX mixing tests and Tank 50 pump operating experience, three standard slurry pumps should be able to suspend sludge and MST to effectively sorb strontium and actinides onto the MST. Using the SCIX data requires an assumption about the impact of cooling coils on slurry pump mixing. The basis for this assumption is described in this report. Using the Tank 50 operating experience shows three standard slurry pumps should be able to suspend solids if the shear strength of the settled solids is less than 160 Pa. Because Tank 21 does not contain cooling coils, the shear strength could be larger.« less

MST4 kinase phosphorylates ACAP4 protein to orchestrate apical membrane remodeling during gastric acid secretion.

PubMed

Yuan, Xiao; Yao, Phil Y; Jiang, Jiying; Zhang, Yin; Su, Zeqi; Yao, Wendy; Wang, Xueying; Gui, Ping; Mullen, McKay; Henry, Calmour; Ward, Tarsha; Wang, Wenwen; Brako, Larry; Tian, Ruijun; Zhao, Xuannv; Wang, Fengsong; Cao, Xinwang; Wang, Dongmei; Liu, Xing; Ding, Xia; Yao, Xuebiao

2017-09-29

Digestion in the stomach depends on acidification of the lumen. Histamine-elicited acid secretion is triggered by activation of the PKA cascade, which ultimately results in the insertion of gastric H,K-ATPases into the apical plasma membranes of parietal cells. Our recent study revealed the functional role of PKA-MST4-ezrin signaling axis in histamine-elicited acid secretion. However, it remains uncharacterized how the PKA-MST4-ezrin signaling axis operates the insertion of H,K-ATPases into the apical plasma membranes of gastric parietal cells. Here we show that MST4 phosphorylates ACAP4, an ARF6 GTPase-activating protein, at Thr 545 Histamine stimulation activates MST4 and promotes MST4 interaction with ACAP4. ACAP4 physically interacts with MST4 and is a cognate substrate of MST4 during parietal cell activation. The phosphorylation site of ACAP4 by MST4 was mapped to Thr 545 by mass spectrometric analyses. Importantly, phosphorylation of Thr 545 is essential for acid secretion in parietal cells because either suppression of ACAP4 or overexpression of non-phosphorylatable ACAP4 prevents the apical membrane reorganization and proton pump translocation elicited by histamine stimulation. In addition, persistent overexpression of MST4 phosphorylation-deficient ACAP4 results in inhibition of gastric acid secretion and blockage of tubulovesicle fusion to the apical membranes. Significantly, phosphorylation of Thr 545 enables ACAP4 to interact with ezrin. Given the location of Thr 545 between the GTPase-activating protein domain and the first ankyrin repeat, we reason that MST4 phosphorylation elicits a conformational change that enables ezrin-ACAP4 interaction. Taken together, these results define a novel molecular mechanism linking the PKA-MST4-ACAP4 signaling cascade to polarized acid secretion in gastric parietal cells. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Minimum Electric Field Exposure for Seizure Induction with Electroconvulsive Therapy and Magnetic Seizure Therapy.

PubMed

Lee, Won H; Lisanby, Sarah H; Laine, Andrew F; Peterchev, Angel V

2017-05-01

Lowering and individualizing the current amplitude in electroconvulsive therapy (ECT) has been proposed as a means to produce stimulation closer to the neural activation threshold and more focal seizure induction, which could potentially reduce cognitive side effects. However, the effect of current amplitude on the electric field (E-field) in the brain has not been previously linked to the current amplitude threshold for seizure induction. We coupled MRI-based E-field models with amplitude titrations of motor threshold (MT) and seizure threshold (ST) in four nonhuman primates (NHPs) to determine the strength, distribution, and focality of stimulation in the brain for four ECT electrode configurations (bilateral, bifrontal, right-unilateral, and frontomedial) and magnetic seizure therapy (MST) with cap coil on vertex. At the amplitude-titrated ST, the stimulated brain subvolume (23-63%) was significantly less than for conventional ECT with high, fixed current (94-99%). The focality of amplitude-titrated right-unilateral ECT (25%) was comparable to cap coil MST (23%), demonstrating that ECT with a low current amplitude and focal electrode placement can induce seizures with E-field as focal as MST, although these electrode and coil configurations affect differently specific brain regions. Individualizing the current amplitude reduced interindividual variation in the stimulation focality by 40-53% for ECT and 26% for MST, supporting amplitude individualization as a means of dosing especially for ECT. There was an overall significant correlation between the measured amplitude-titrated ST and the prediction of the E-field models, supporting a potential role of these models in dosing of ECT and MST. These findings may guide the development of seizure therapy dosing paradigms with improved risk/benefit ratio.

Overview of MST Research

NASA Astrophysics Data System (ADS)

Sarff, J. S.

2016-10-01

MST progress in advancing the RFP for (1) fusion plasma confinement with ohmic heating and minimal external magnetization, (2) predictive capability in toroidal confinement physics, and (3) basic plasma physics is summarized. Validation of key plasma models is a program priority. Programmable power supplies (PPS) are being developed to maximize inductive capability. Well-controlled flattops with current as low as 0.02 MA are produced with an existing PPS, and Ip <= 0.8 MA is anticipated with a second PPS under construction. The Lundquist number spans S =10(4 - 9) for 0.02-0.8 MA, allowing nonlinear MHD validation using NIMROD and DEBS at low S to be connected to highest S experiments. The PPS also enables MST tokamak operation for studying transients and runaway electron suppression with RMPs. Gyrokinetic modeling with GENE predicts unstable TEM in improved-confinement plasmas. Fluctuations are measured with TEM properties including a density-gradient threshold larger than for tokamak plasmas. Probe measurements hint that drift waves are also excited via the turbulent cascade in standard RFP plasmas. Turbulent energization of an electron tail occurs during sawtooth reconnection. New diagnostics are being developed to measure the energetic ion profile and transport from EP instabilities with NBI. Supported by US DoE and NSF.

The Development of MST Test Information for the Prediction of Test Performances

ERIC Educational Resources Information Center

Park, Ryoungsun; Kim, Jiseon; Chung, Hyewon; Dodd, Barbara G.

2017-01-01

The current study proposes novel methods to predict multistage testing (MST) performance without conducting simulations. This method, called MST test information, is based on analytic derivation of standard errors of ability estimates across theta levels. We compared standard errors derived analytically to the simulation results to demonstrate the…

Music-supported therapy in the rehabilitation of subacute stroke patients: a randomized controlled trial.

PubMed

Grau-Sánchez, Jennifer; Duarte, Esther; Ramos-Escobar, Neus; Sierpowska, Joanna; Rueda, Nohora; Redón, Susana; Veciana de Las Heras, Misericordia; Pedro, Jordi; Särkämö, Teppo; Rodríguez-Fornells, Antoni

2018-04-01

The effect of music-supported therapy (MST) as a tool to restore hemiparesis of the upper extremity after a stroke has not been appropriately contrasted with conventional therapy. The aim of this trial was to test the effectiveness of adding MST to a standard rehabilitation program in subacute stroke patients. A randomized controlled trial was conducted in which patients were randomized to MST or conventional therapy in addition to the rehabilitation program. The intensity and duration of the interventions were equated in both groups. Before and after 4 weeks of treatment, motor and cognitive functions, mood, and quality of life (QoL) of participants were evaluated. A follow-up at 3 months was conducted to examine the retention of motor gains. Both groups significantly improved their motor function, and no differences between groups were found. The only difference between groups was observed in the language domain for QoL. Importantly, an association was encountered between the capacity to experience pleasure from music activities and the motor improvement in the MST group. MST as an add-on treatment showed no superiority to conventional therapies for motor recovery. Importantly, patient's intrinsic motivation to engage in musical activities was associated with better motor improvement. © 2018 New York Academy of Sciences.

Controlling stimulation strength and focality in electroconvulsive therapy via current amplitude and electrode size and spacing: comparison with magnetic seizure therapy.

PubMed

Deng, Zhi-De; Lisanby, Sarah H; Peterchev, Angel V

2013-12-01

Understanding the relationship between the stimulus parameters of electroconvulsive therapy (ECT) and the electric field characteristics could guide studies on improving risk/benefit ratio. We aimed to determine the effect of current amplitude and electrode size and spacing on the ECT electric field characteristics, compare ECT focality with magnetic seizure therapy (MST), and evaluate stimulus individualization by current amplitude adjustment. Electroconvulsive therapy and double-cone-coil MST electric field was simulated in a 5-shell spherical human head model. A range of ECT electrode diameters (2-5 cm), spacing (1-25 cm), and current amplitudes (0-900 mA) was explored. The head model parameters were varied to examine the stimulus current adjustment required to compensate for interindividual anatomical differences. By reducing the electrode size, spacing, and current, the ECT electric field can be more focal and superficial without increasing scalp current density. By appropriately adjusting the electrode configuration and current, the ECT electric field characteristics can be made to approximate those of MST within 15%. Most electric field characteristics in ECT are more sensitive to head anatomy variation than in MST, especially for close electrode spacing. Nevertheless, ECT current amplitude adjustment of less than 70% can compensate for interindividual anatomical variability. The strength and focality of ECT can be varied over a wide range by adjusting the electrode size, spacing, and current. If desirable, ECT can be made as focal as MST while using simpler stimulation equipment. Current amplitude individualization can compensate for interindividual anatomical variability.

Multisystemic Sarcoidosis Presenting as Pretibial Leg Ulcers.

PubMed

Wollina, Uwe; Baunacke, Anja; Hansel, Gesina

2016-09-01

Sarcoidosis is a multisystemic disease of unknown etiology. Up to 30% of patients develop cutaneous manifestations, either specific or nonspecific. Ulcerating sarcoidosis leading to leg ulcers is a rare observation that may lead to confusions with other, more common types of chronic leg ulcers. We report the case of a 45-year-old female patient with chronic multisystemic sarcoidosis presenting with pretibial leg ulcers. Other etiology could be excluded. Histology revealed nonspecific findings. Therefore, the diagnosis of nonspecific leg ulcers in sarcoidosis was confirmed. Treatment consisted of oral prednisolone and good ulcer care. Complete healing was achieved within 6 months. Sarcoidosis is a rare cause of leg ulcers and usually sarcoid granulomas can be found. Our patient illustrates that even in the absence of sarcoid granulomas, leg ulcers can be due to sarcoidosis. © The Author(s) 2016.

Hydrogen sulfide ameliorates subarachnoid hemorrhage-induced neuronal apoptosis via the ROS-MST1 pathway

PubMed Central

Shi, Ligen; Lei, Jianwei; Xu, Hangzhe; Zheng, Jingwei; Wang, Yan; Peng, Yucong; Yu, Jun; Zhang, Jianmin

2017-01-01

Background Hydrogen sulfide (H2S) has shown a neuroprotective role in several cerebrovascular diseases. This study aimed to explore the underlying mechanisms of H2S in early brain injury after subarachnoid hemorrhage (SAH). Methods One hundred seventy-seven male Sprague-Dawley rats were employed in this study. Sodium hydrosulfide (NaHS), a donor of H2S, was injected intraperitoneally at 60 min after SAH was induced by endovascular perforation. Western blot analysis determined the expression of several proteins of interest, and an immunofluorescence assay was used to examine neuronal apoptosis. Results Exogenous NaHS markedly improved neurological scores, attenuated brain edema, and ameliorated neuronal apoptosis at 24 h after SAH induction. The underlying mechanisms of H2S in ameliorating neuronal apoptosis might be executed through inhibition of the activity of mammalian sterile 20-like kinase 1 (MST1) protein. Western blot analysis demonstrated that exogenous NaHS decreased cleaved MST1 (cl-MST1) while increasing full-length MST1 expression. This anti-apoptotic effect of H2S could be reversed by chelerythrine, which could activate MST1 via caspase-dependent cleavage. Conclusions Exogenous NaHS, as a donor of H2S, could ameliorate early brain injury after SAH by inhibiting neuronal apoptosis by reducing the activity of the MST1 protein. PMID:29088725

Electron Thermal Transport due to Magnetic Diffusion in the MST RFP

NASA Astrophysics Data System (ADS)

Reusch, J. A.; Anderson, J. K.; den Hartog, D. J.; Forest, C. B.; Kasten, C. P.; Schnack, D. D.; Stephens, H. D.

2011-10-01

Comparison of measurements made in the MST RFP to the results from extensive nonlinear resistive MHD simulations has provided two key observations. First, trapped particles reduce electron thermal diffusion; inclusion of this effect is required for quantitative agreement of simulation to measurement. Second, the structure and evolution of long-wavelength temperature fluctuations measured in MST shows remarkable qualitative similarity to fluctuations appearing in a finite-pressure simulation. These simulations were run at parameters matching those of 400 kA discharges in MST (S ~ 4 ×106). In a zero β simulation, the measured χe is compared to the thermal diffusion due to parallel losses along diffusing magnetic field lines, χst =v∥Dmag . Agreement is only found if the reduction in χst due to trapped particles is taken into account. In a second simulation, the pressure field was evolved self consistently assuming Ohmic heating and anisotropic thermal conduction. Fluctuations in the simulated temperature are very similar in character and time evolution to temperature fluctuations measured in MST. This includes m = 1 , n = 6 fluctuations that flatten the temperature profile as well as m = 1 , n = 5 fluctuations that generate hot island structures near the core shortly after sawtooth crashes. This work supported by the US DOE and NSF.

Overview of results from the MST reversed field pinch experiment

NASA Astrophysics Data System (ADS)

Sarff, J. S.; Almagri, A. F.; Anderson, J. K.; Borchardt, M.; Carmody, D.; Caspary, K.; Chapman, B. E.; Den Hartog, D. J.; Duff, J.; Eilerman, S.; Falkowski, A.; Forest, C. B.; Goetz, J. A.; Holly, D. J.; Kim, J.-H.; King, J.; Ko, J.; Koliner, J.; Kumar, S.; Lee, J. D.; Liu, D.; Magee, R.; McCollam, K. J.; McGarry, M.; Mirnov, V. V.; Nornberg, M. D.; Nonn, P. D.; Oliva, S. P.; Parke, E.; Reusch, J. A.; Sauppe, J. P.; Seltzman, A.; Sovinec, C. R.; Stephens, H.; Stone, D.; Theucks, D.; Thomas, M.; Triana, J.; Terry, P. W.; Waksman, J.; Bergerson, W. F.; Brower, D. L.; Ding, W. X.; Lin, L.; Demers, D. R.; Fimognari, P.; Titus, J.; Auriemma, F.; Cappello, S.; Franz, P.; Innocente, P.; Lorenzini, R.; Martines, E.; Momo, B.; Piovesan, P.; Puiatti, M.; Spolaore, M.; Terranova, D.; Zanca, P.; Belykh, V.; Davydenko, V. I.; Deichuli, P.; Ivanov, A. A.; Polosatkin, S.; Stupishin, N. V.; Spong, D.; Craig, D.; Harvey, R. W.; Cianciosa, M.; Hanson, J. D.

2013-10-01

An overview of recent results from the MST programme on physics important for the advancement of the reversed field pinch (RFP) as well as for improved understanding of toroidal magnetic confinement more generally is reported. Evidence for the classical confinement of ions in the RFP is provided by analysis of impurity ions and energetic ions created by 1 MW neutral beam injection (NBI). The first appearance of energetic-particle-driven modes by NBI in a RFP plasma is described. MST plasmas robustly access the quasi-single-helicity state that has commonalities to the stellarator and ‘snake’ formation in tokamaks. In MST the dominant mode grows to 8% of the axisymmetric field strength, while the remaining modes are reduced. Predictive capability for tearing mode behaviour has been improved through nonlinear, 3D, resistive magnetohydrodynamic computation using the measured resistivity profile and Lundquist number, which reproduces the sawtooth cycle dynamics. Experimental evidence and computational analysis indicates two-fluid effects, e.g., Hall physics and gyro-viscosity, are needed to understand the coupling of parallel momentum transport and current profile relaxation. Large Reynolds and Maxwell stresses, plus separately measured kinetic stress, indicate an intricate momentum balance and a possible origin for MST's intrinsic plasma rotation. Gyrokinetic analysis indicates that micro-tearing modes can be unstable at high beta, with a critical gradient for the electron temperature that is larger than for tokamak plasmas by roughly the aspect ratio.

Robust MST-Based Clustering Algorithm.

PubMed

Liu, Qidong; Zhang, Ruisheng; Zhao, Zhili; Wang, Zhenghai; Jiao, Mengyao; Wang, Guangjing

2018-06-01

Minimax similarity stresses the connectedness of points via mediating elements rather than favoring high mutual similarity. The grouping principle yields superior clustering results when mining arbitrarily-shaped clusters in data. However, it is not robust against noises and outliers in the data. There are two main problems with the grouping principle: first, a single object that is far away from all other objects defines a separate cluster, and second, two connected clusters would be regarded as two parts of one cluster. In order to solve such problems, we propose robust minimum spanning tree (MST)-based clustering algorithm in this letter. First, we separate the connected objects by applying a density-based coarsening phase, resulting in a low-rank matrix in which the element denotes the supernode by combining a set of nodes. Then a greedy method is presented to partition those supernodes through working on the low-rank matrix. Instead of removing the longest edges from MST, our algorithm groups the data set based on the minimax similarity. Finally, the assignment of all data points can be achieved through their corresponding supernodes. Experimental results on many synthetic and real-world data sets show that our algorithm consistently outperforms compared clustering algorithms.

Shikonin regulates C-MYC and GLUT1 expression through the MST1-YAP1-TEAD1 axis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vališ, Karel, E-mail: karel.valis@biomed.cas.cz; Faculty of Science, Charles University, Prague; Talacko, Pavel

The general mechanism underlying the tumor suppressor activity of the Hippo signaling pathway remains unclear. In this study, we explore the molecular mechanisms connecting the Hippo signaling pathway with glucose metabolism. We have found that two key regulators of glycolysis, C-MYC and GLUT1, are targets of the Hippo signaling pathway in human leukemia cells. Our results revealed that activation of MST1 by the natural compound shikonin inhibited the expression of GLUT1 and C-MYC. Furthermore, RNAi experiments confirmed the regulation of GLUT1 and C-MYC expression via the MST1-YAP1-TEAD1 axis. Surprisingly, YAP1 was found to positively regulate C-MYC mRNA levels in complexmore » with TEAD1, while it negatively regulates C-MYC levels in cooperation with MST1. Hence, YAP1 serves as a rheostat for C-MYC, which is regulated by MST1. In addition, depletion of MST1 stimulates lactate production, whereas the specific depletion of TEAD1 has an opposite effect. The inhibition of lactate production and cellular proliferation induced by shikonin also depends on the Hippo pathway activity. Finally, a bioinformatic analysis revealed conserved TEAD-binding motifs in the C-MYC and GLUT1 promoters providing another molecular data supporting our observations. In summary, regulation of glucose metabolism could serve as a new tumor suppressor mechanism orchestrated by the Hippo signaling pathway. - Highlights: • Shikonin inhibits C-MYC and GLUT1 expression in MST1 and YAP1 dependent manner. • YAP1-TEAD1 interaction activates C-MYC and GLUT1 expression. • MST1 in cooperation with YAP1 inhibits C-MYC and GLUT1 expression. • MST1-YAP1-TEAD1 axis regulates lactate production by leukemic cells. • MST1 and YAP1 proteins block proliferation of leukemic cells.« less

The MST/Hippo Pathway and Cell Death: A Non-Canonical Affair

PubMed Central

Fallahi, Emma; O’Driscoll, Niamh A.; Matallanas, David

2016-01-01

The MST/Hippo signalling pathway was first described over a decade ago in Drosophila melanogaster and the core of the pathway is evolutionary conserved in mammals. The mammalian MST/Hippo pathway regulates organ size, cell proliferation and cell death. In addition, it has been shown to play a central role in the regulation of cellular homeostasis and it is commonly deregulated in human tumours. The delineation of the canonical pathway resembles the behaviour of the Hippo pathway in the fly where the activation of the core kinases of the pathway prevents the proliferative signal mediated by the key effector of the pathway YAP. Nevertheless, several lines of evidence support the idea that the mammalian MST/Hippo pathway has acquired new features during evolution, including different regulators and effectors, crosstalk with other essential signalling pathways involved in cellular homeostasis and the ability to actively trigger cell death. Here we describe the current knowledge of the mechanisms that mediate MST/Hippo dependent cell death, especially apoptosis. We include evidence for the existence of complex signalling networks where the core proteins of the pathway play a central role in controlling the balance between survival and cell death. Finally, we discuss the possible involvement of these signalling networks in several human diseases such as cancer, diabetes and neurodegenerative disorders. PMID:27322327

PHLPP1 regulates contact inhibition by dephosphorylating Mst1 at the inhibitory site

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jung, Sujin; Kang, Jeong Gu; Lee, Ju Hee

2014-01-24

Highlights: • PHLPP1 regulates contact inhibition by dephosphorylating Mst1 at Thr{sup 387}. • Overexpression of PHLPP1 sensitizes contact inhibition. • Tumor cells with suppressed PHLPP1 expression are refractory to apoptosis and highly proliferative. • Loss or down-regulation of PHLPP1 may drive tumor development and progression. - Abstract: Contact inhibition has been largely elusive despite that a loss of contact inhibition is a critical event for cancer development and progression. Here, we report that PHLPP1 is a binding protein for Mst1 and it modulates the Hippo pathway by dephosphorylating Mst1 at the inhibitory Thr{sup 387} of Mst1. Yap1 was localized predominantlymore » in the nucleus but marginally in the cytoplasm in HeLa cells under sparse conditions, whereas the functional protein was more directed to sequestration in the cytoplasm under dense environments. Furthermore, loss of PHLPP1 resulted in a failure of the apoptotic control. It is interesting that down-regulated expression of PHLPP1 appears to mimic the loss of contact inhibition, a hallmark of cancer.« less

Simulation of MST tokamak discharges with resonant magnetic perturbations

NASA Astrophysics Data System (ADS)

Cornille, B. S.; Sovinec, C. R.; Chapman, B. E.; Dubois, A.; McCollam, K. J.; Munaretto, S.

2016-10-01

Nonlinear MHD modeling of MST tokamak plasmas with an applied resonant magnetic perturbation (RMP) reveals degradation of flux surfaces that may account for the experimentally observed suppression of runaway electrons with the RMP. Runaway electrons are routinely generated in MST tokamak discharges with low plasma density. When an m = 3 RMP is applied these electrons are strongly suppressed, while an m = 1 RMP of comparable amplitude has little effect. The computations are performed using the NIMROD code and use reconstructed equilibrium states of MST tokamak plasmas with q (0) < 1 and q (a) = 2.2 . Linear computations show that the (1 , 1) -kink and (2 , 2) -tearing modes are unstable, and nonlinear simulations produce sawtoothing with a period of approximately 0.5 ms, which is comparable to the period of MHD activity observed experimentally. Adding an m = 3 RMP in the computation degrades flux surfaces in the outer region of the plasma, while no degradation occurs with an m = 1 RMP. The outer flux surface degradation with the m = 3 RMP, combined with the sawtooth-induced distortion of flux surfaces in the core, may account for the observed suppression of runaway electrons. Work supported by DOE Grant DE-FC02-08ER54975.

Long-Read Single Molecule Sequencing to Resolve Tandem Gene Copies: The Mst77Y Region on the Drosophila melanogaster Y Chromosome

PubMed Central

Krsticevic, Flavia J.; Schrago, Carlos G.; Carvalho, A. Bernardo

2015-01-01

The autosomal gene Mst77F of Drosophila melanogaster is essential for male fertility. In 2010, Krsticevic et al. (Genetics 184: 295−307) found 18 Y-linked copies of Mst77F (“Mst77Y”), which collectively account for 20% of the functional Mst77F-like mRNA. The Mst77Y genes were severely misassembled in the then-available genome assembly and were identified by cloning and sequencing polymerase chain reaction products. The genomic structure of the Mst77Y region and the possible existence of additional copies remained unknown. The recent publication of two long-read assemblies of D. melanogaster prompted us to reinvestigate this challenging region of the Y chromosome. We found that the Illumina Synthetic Long Reads assembly failed in the Mst77Y region, most likely because of its tandem duplication structure. The PacBio MHAP assembly of the Mst77Y region seems to be very accurate, as revealed by comparisons with the previously found Mst77Y genes, a bacterial artificial chromosome sequence, and Illumina reads of the same strain. We found that the Mst77Y region spans 96 kb and originated from a 3.4-kb transposition from chromosome 3L to the Y chromosome, followed by tandem duplications inside the Y chromosome and invasion of transposable elements, which account for 48% of its length. Twelve of the 18 Mst77Y genes found in 2010 were confirmed in the PacBio assembly, the remaining six being polymerase chain reaction−induced artifacts. There are several identical copies of some Mst77Y genes, coincidentally bringing the total copy number to 18. Besides providing a detailed picture of the Mst77Y region, our results highlight the utility of PacBio technology in assembling difficult genomic regions such as tandemly repeated genes. PMID:25858959

Inherited MST1 deficiency underlies susceptibility to EV-HPV infections.

PubMed

Crequer, Amandine; Picard, Capucine; Patin, Etienne; D'Amico, Aurelia; Abhyankar, Avinash; Munzer, Martine; Debré, Marianne; Zhang, Shen-Ying; de Saint-Basile, Geneviève; Fischer, Alain; Abel, Laurent; Orth, Gérard; Casanova, Jean-Laurent; Jouanguy, Emmanuelle

2012-01-01

Epidermodysplasia verruciformis (EV) is characterized by persistent cutaneous lesions caused by a specific group of related human papillomavirus genotypes (EV-HPVs) in otherwise healthy individuals. Autosomal recessive (AR) EVER1 and EVER2 deficiencies account for two thirds of known cases of EV. AR RHOH deficiency has recently been described in two siblings with EV-HPV infections as well as other infectious and tumoral manifestations. We report here the whole-exome based discovery of AR MST1 deficiency in a 19-year-old patient with a T-cell deficiency associated with EV-HPV, bacterial and fungal infections. MST1 deficiency has recently been described in seven patients from three unrelated kindreds with profound T-cell deficiency and various viral and bacterial infections. The patient was also homozygous for a rare ERCC3 variation. Our findings broaden the clinical range of infections seen in MST1 deficiency and provide a new genetic etiology of susceptibility to EV-HPV infections. Together with the recent discovery of RHOH deficiency, they suggest that T cells are involved in the control of EV-HPVs, at least in some individuals.

Inherited MST1 Deficiency Underlies Susceptibility to EV-HPV Infections

PubMed Central

Crequer, Amandine; Picard, Capucine; Patin, Etienne; D’Amico, Aurelia; Abhyankar, Avinash; Munzer, Martine; Debré, Marianne; Zhang, Shen-Ying; de Saint-Basile, Geneviève; Fischer, Alain

2012-01-01

Epidermodysplasia verruciformis (EV) is characterized by persistent cutaneous lesions caused by a specific group of related human papillomavirus genotypes (EV-HPVs) in otherwise healthy individuals. Autosomal recessive (AR) EVER1 and EVER2 deficiencies account for two thirds of known cases of EV. AR RHOH deficiency has recently been described in two siblings with EV-HPV infections as well as other infectious and tumoral manifestations. We report here the whole-exome based discovery of AR MST1 deficiency in a 19-year-old patient with a T-cell deficiency associated with EV-HPV, bacterial and fungal infections. MST1 deficiency has recently been described in seven patients from three unrelated kindreds with profound T-cell deficiency and various viral and bacterial infections. The patient was also homozygous for a rare ERCC3 variation. Our findings broaden the clinical range of infections seen in MST1 deficiency and provide a new genetic etiology of susceptibility to EV-HPV infections. Together with the recent discovery of RHOH deficiency, they suggest that T cells are involved in the control of EV-HPVs, at least in some individuals. PMID:22952854

Cell Polarity Kinase MST4 Cooperates with cAMP-dependent Kinase to Orchestrate Histamine-stimulated Acid Secretion in Gastric Parietal Cells*

PubMed Central

Jiang, Hao; Wang, Wenwen; Zhang, Yin; Yao, William W.; Jiang, Jiying; Qin, Bo; Yao, Wendy Y.; Liu, Fusheng; Wu, Huihui; Ward, Tarsha L.; Chen, Chun Wei; Liu, Lifang; Ding, Xia; Liu, Xing; Yao, Xuebiao

2015-01-01

The digestive function of the stomach depends on acidification of the gastric lumen. Acid secretion into the lumen is triggered by activation of the PKA cascade, which ultimately results in the insertion of gastric H,K-ATPases into the apical plasma membranes of parietal cells. A coupling protein is ezrin, whose phosphorylation at Ser-66 by PKA is required for parietal cell activation. However, little is known regarding the molecular mechanism(s) by which this signaling pathway operates in gastric acid secretion. Here we show that PKA cooperates with MST4 to orchestrate histamine-elicited acid secretion by phosphorylating ezrin at Ser-66 and Thr-567. Histamine stimulation activates PKA, which phosphorylates MST4 at Thr-178 and then promotes MST4 kinase activity. Interestingly, activated MST4 then phosphorylates ezrin prephosphorylated by PKA. Importantly, MST4 is important for acid secretion in parietal cells because either suppression of MST4 or overexpression of non-phosphorylatable MST4 prevents the apical membrane reorganization and proton pump translocation elicited by histamine stimulation. In addition, overexpressing MST4 phosphorylation-deficient ezrin results in an inhibition of gastric acid secretion. Taken together, these results define a novel molecular mechanism linking the PKA-MST4-ezrin signaling cascade to polarized epithelial secretion in gastric parietal cells. PMID:26405038

Studying Filamentary Currents with Thomson Scattering on MST

NASA Astrophysics Data System (ADS)

den Hartog, D. J.; Young, W. C.; Kubala, S. Z.

2016-10-01

The MST reversed-field pinch plasma generates bursts of toroidally localized magnetic activity associated with m = 0 modes resonant at the reversal surface near the plasma edge. Previously, using data from an array of edge magnetic probes, these bursts were connected to poloidal current filaments. Now the MST Thomson scattering diagnostic is being used to measure the net drift in the electron distribution due to these currents. An additional long-wavelength spectral bin has been added to several Thomson scattering polychromators, in addition to 5-7 pre-existing short wavelength spectral bins, to improve discrimination between shifted vs. broadened spectra. The bursts are examined in plasma conditions that display spontaneous periods of low tearing-mode activity, with higher confinement and higher temperatures that improve Thomson scattering measurement performance. This work is supported by the U.S. Department of Energy and the National Science Foundation.

28. VIEW SOUTH FROM SLC3W MST STATION 63. FOREGROUND LEFT: ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

28. VIEW SOUTH FROM SLC-3W MST STATION 63. FOREGROUND LEFT: THEODOLITE SHELTER (BLDG. 786) CENTER LEFT TO RIGHT: GLOBAL POSITIONING SYSTEM AZIMUTH STATION (BLDG. 775), PYROTECHNIC SHED (BLDG. 757), PORTABLE GUARD SHED, METEOROLOGICAL SHED (BLDG. 756), METEOROLOGICAL TOWER. BACKGROUND CENTER TO RIGHT: STORAGE SHED (BLDG. 776), LIQUID OXYGEN APRON, SLC-3E MST, TOP OF SLC-3E FUEL STORAGE TANK. - Vandenberg Air Force Base, Space Launch Complex 3, Launch Pad 3 West, Napa & Alden Roads, Lompoc, Santa Barbara County, CA

Emulating the Visual Receptive Field Properties of MST Neurons with a Template Model of Heading Estimation

NASA Technical Reports Server (NTRS)

Perrone, John A.; Stone, Leland S.

1997-01-01

We have previously proposed a computational neural-network model by which the complex patterns of retinal image motion generated during locomotion (optic flow) can be processed by specialized detectors acting as templates for specific instances of self-motion. The detectors in this template model respond to global optic flow by sampling image motion over a large portion of the visual field through networks of local motion sensors with properties similar to neurons found in the middle temporal (MT) area of primate extrastriate visual cortex. The model detectors were designed to extract self-translation (heading), self-rotation, as well as the scene layout (relative distances) ahead of a moving observer, and are arranged in cortical-like heading maps to perform this function. Heading estimation from optic flow has been postulated by some to be implemented within the medial superior temporal (MST) area. Others have questioned whether MST neurons can fulfill this role because some of their receptive-field properties appear inconsistent with a role in heading estimation. To resolve this issue, we systematically compared MST single-unit responses with the outputs of model detectors under matched stimulus conditions. We found that the basic physiological properties of MST neurons can be explained by the template model. We conclude that MST neurons are well suited to support heading estimation and that the template model provides an explicit set of testable hypotheses which can guide future exploration of MST and adjacent areas within the primate superior temporal sulcus.

A Role for MST Neurons in Heading Estimation

NASA Technical Reports Server (NTRS)

Stone, L. S.; Perrone, J. A.

1994-01-01

A template model of human visual self-motion perception, which uses neurophysiologically realistic "heading detectors", is consistent with numerous human psychophysical results including the failure of humans to estimate their heading (direction of forward translation) accurately under certain visual conditions. We tested the model detectors with stimuli used by others in single-unit studies. The detectors showed emergent properties similar to those of MST neurons: (1) Sensitivity to non-preferred flow; Each detector is tuned to a specific combination of flow components and its response is systematically reduced by the addition of nonpreferred flow, and (2) Position invariance; The detectors maintain their apparent preference for particular flow components over large regions of their receptive fields. It has been argued that this latter property is incompatible with MST playing a role in heading perception. The model however demonstrates how neurons with the above response properties could still support accurate heading estimation within extrastriate cortical maps.

Emulating the visual receptive-field properties of MST neurons with a template model of heading estimation

NASA Technical Reports Server (NTRS)

Perrone, J. A.; Stone, L. S.

1998-01-01

We have proposed previously a computational neural-network model by which the complex patterns of retinal image motion generated during locomotion (optic flow) can be processed by specialized detectors acting as templates for specific instances of self-motion. The detectors in this template model respond to global optic flow by sampling image motion over a large portion of the visual field through networks of local motion sensors with properties similar to those of neurons found in the middle temporal (MT) area of primate extrastriate visual cortex. These detectors, arranged within cortical-like maps, were designed to extract self-translation (heading) and self-rotation, as well as the scene layout (relative distances) ahead of a moving observer. We then postulated that heading from optic flow is directly encoded by individual neurons acting as heading detectors within the medial superior temporal (MST) area. Others have questioned whether individual MST neurons can perform this function because some of their receptive-field properties seem inconsistent with this role. To resolve this issue, we systematically compared MST responses with those of detectors from two different configurations of the model under matched stimulus conditions. We found that the characteristic physiological properties of MST neurons can be explained by the template model. We conclude that MST neurons are well suited to support self-motion estimation via a direct encoding of heading and that the template model provides an explicit set of testable hypotheses that can guide future exploration of MST and adjacent areas within the superior temporal sulcus.

The involvement of audio-motor coupling in the music-supported therapy applied to stroke patients.

PubMed

Rodriguez-Fornells, Antoni; Rojo, Nuria; Amengual, Julià L; Ripollés, Pablo; Altenmüller, Eckart; Münte, Thomas F

2012-04-01

Music-supported therapy (MST) has been developed recently to improve the use of the affected upper extremity after stroke. MST uses musical instruments, an electronic piano and an electronic drum set emitting piano sounds, to retrain fine and gross movements of the paretic upper extremity. In this paper, we first describe the rationale underlying MST, and we review the previous studies conducted on acute and chronic stroke patients using this new neurorehabilitation approach. Second, we address the neural mechanisms involved in the motor movement improvements observed in acute and chronic stroke patients. Third, we provide some recent studies on the involvement of auditory-motor coupling in the MST in chronic stroke patients using functional neuroimaging. Finally, these ideas are discussed and focused on understanding the dynamics involved in the neural circuit underlying audio-motor coupling and how functional connectivity could help to explain the neuroplastic changes observed after therapy in stroke patients. © 2012 New York Academy of Sciences.

Measuring power loss due to radiation and charge exchange in MST

NASA Astrophysics Data System (ADS)

Waksman, Jeff; Chapman, Brett; Fiksel, Gennady; Nonn, Paul

2008-11-01

An array of photodiode-pyrobolometer pairs will be placed on MST to measure the spatial structure of the radiated power and charge exchange. Photodiodes (XUV detectors) measure photonic radiated power from about 10eV to 10keV, while pyrobolometers (thermal detectors) measure both photonic radiated power and power carried by charge-exchange neutrals. Compared to other thermal detectors, pyrobolometers have very good time resolution. To accurately calibrate the individual detectors, an electron gun producing a modulated square wave output has been set up to carefully calibrate each new pyrobolometer to be placed on MST. When viewing the MST plasma, subtraction of the data from the photodiode-pyrobolometer pairs allows one to determine the net power loss due to charge-exchange neutrals. These measurements are important in the calculation of ion energy balance, and it is potentially important in understanding the difference in the temperatures reached by majority and impurity ions during magnetic-reconnection ion-heating events. Since toroidal and poloidal asymmetries in charge exchange are possible, a distributed array of detector pairs will facilitate a better estimate of global power loss. Work supported by the U.S.D.O.E. .

Electron Bernstein Wave Studies in MST

NASA Astrophysics Data System (ADS)

Seltzman, Andrew; Anderson, Jay; Forest, Cary; Nonn, Paul; Thomas, Mark; Almagri, Abdulgader; Chapman, Brett; Dubois, Ami; Goetz, John; McCollam, Karsten

2015-11-01

The RFP plasma is inaccessible to ECRH, requiring the electron Bernstein wave (EBW) for edge localized heating and current drive. MST is capable of generating RFPs or overdense tokamaks with Bt(0) ~ 0.08-0.14T in which a 5.55 GHz RF source (450kW, 2ms pulse) can heat at fundamental and harmonic EC resonances. The design of a suitable antenna is challenging in the RFP due to a magnetic field geometry that requires a low-field-side launch. The small vacuum gap between the close-fitting conducting shell and plasma leads to substantial antenna-plasma interaction. A minimized port hole size is required to limit error fields. Even so the port hole induced magnetic field perturbation in the antenna near-field that affects the mode conversion process and introduces EC resonances. A 5cm diameter cylindrical antenna centered in 5cm and 11cm diameter portholes is used. A multi-chord time-resolved x-ray detector and GENRAY ray tracing verifies EBW heating at higher harmonics in an MST tokamak with 10-40keV detected x-ray energies. Evidence of RF-induced emission from absorption at higher harmonics (4th / 5th) in low current RFP discharges has been observed. Simultaneous reflected power changes correspond to termination of x-ray emission indicating power limits. Work supported by USDOE.

Suppression of high-energy electrons generated in both disrupting and sustained MST tokamak plasmas

NASA Astrophysics Data System (ADS)

Pandya, M. D.; Chapman, B. E.; Munaretto, S.; Cornille, B. S.; McCollam, K. J.; Sovinec, C. R.; Dubois, A. M.; Almagri, A. F.; Goetz, J. A.

2017-10-01

High-energy electrons appearing during MST tokamak plasma disruptions are rapidly lost from the plasma due apparently to internal MHD activity. Work has just recently begun on generating and diagnosing disruptions in MST tokamak plasmas. Initial measurements show the characteristic drop in central temperature and density preceding a quench of the plasma current. This corresponds to a burst of dominantly n=1 MHD activity, which is accompanied by a short-lived burst of high-energy electrons. The short-lived nature of these electrons is suspected to be due to stochastic transport associated with the increased MHD. Earlier work shows that runaway electrons generated in low density, sustained plasmas are suppressed by a sufficiently large m=3 RMP in plasmas with q(a) <3. RMPs of various poloidal mode number can be generated with an array of saddle coils wound around the vertical insulated gap in MST's thick conducting shell. With an m=3 RMP, the degree of runaway suppression increases with RMP amplitude, while an m=1 RMP has little effect on the runaways. Nonlinear MHD modeling with NIMROD of these MST plasmas indicates increased stochasticity with an m=3 RMP, while no such increase in stochasticity is observed with an m=1 RMP. Work supported by US DOE.

Program of the Antarctic Syowa MST/IS radar (PANSY)

NASA Astrophysics Data System (ADS)

Sato, K.; Tsutsumi, M.; Sato, T.; Saito, A.; Tomikawa, Y.; Aso, T.; Yamanouchi, T.; Ejiri, M.

We have been promoting a project to introduce the first MST Mesosphere-Stratosphere-Troposphere IS Incoherent Scatter radar which is a VHF pulse Doppler radar in the Antarctic to Syowa Station 39E 69S Program of the Antarctic Syowa MST IS Radar PANSY as an important station observing the earth s environment with the aim to catch the climate change signals that the Antarctic atmosphere shows This radar consists of about 1000 crossed Yagi antennas having a peak power of 500kW which allows us to observe the Antarctic atmosphere with fine resolution and good accuracy in a wide height range of 1-500 km The interaction of the neutral atmosphere with the ionosphere and magnetosphere as well as the global-scale atmospheric circulation including the low and middle latitude regions are also targets of PANSY The observation data with high resolution and good accuracy obtained by the PANSY radar are also valuable from the viewpoint of certification of the reality of phenomena simulated by high-resolution numerical models The scientific importance of PANSY is discussed and resolved by international research organizations of IUGG URSI SCAR SCOSTEP and SPARC and documented in a report by Council of Science and Technology Policy in Japan One major issue for the operation of the MST IS radar at an isolated place such as Syowa Station is the reduction of power consumption We have developed a new power-efficient transmitter class-E amplifier and successfully reduced the needed power consumption to an acceptable

Can bipolar disorder be viewed as a multi-system inflammatory disease?

PubMed Central

Leboyer, Marion; Soreca, Isabella; Scott, Jan; Frye, Mark; Henry, Chantal; Tamouza, Ryad; Kupfer, David J.

2012-01-01

Background Patients with bipolar disorder are known to be at high risk of premature death. Comorbid cardio-vascular diseases are a leading cause of excess mortality, well above the risk associated with suicide. In this review, we explore comorbid medical disorders, highlighting evidence that bipolar disorder can be effectively conceptualized as a multi-systemic inflammatory disease. Methods We conducted a systematic PubMed search of all English-language articles recently published with bipolar disorder cross-referenced with the following terms: mortality and morbidity, cardio-vascular, diabetes, obesity, metabolic syndrome, inflammation, auto-antibody, retro-virus, stress, sleep and circadian rhythm. Results Evidence gathered so far suggests that the multi-system involvement is present from the early stages, and therefore requires proactive screening and diagnostic procedures, as well as comprehensive treatment to reduce progression and premature mortality. Exploring the biological pathways that could account for the observed link show that dysregulated inflammatory background could be a common factor underlying cardio-vascular and bipolar disorders. Viewing bipolar disorder as a multi-system disorder should help us to re-conceptualize disorders of the mind as “disorders of the brain and the body”. Limitations The current literature substantially lacks longitudinal and mechanistic studies, as well as comparison studies to explore the magnitude of the medical burden in bipolar disorder compared to major mood disorders as well as psychotic disorders. It is also necessary to look for subgroups of bipolar disorder based on their rates of comorbid disorders. Conclusions Comorbid medical illnesses in bipolar disorder might be viewed not only as the consequence of health behaviors and of psychotropic medications, but rather as an early manifestation of a multi-systemic disorder. Medical monitoring is thus a critical component of case assessment. Exploring common

Pheochromocytoma Multisystem Crisis Behaving Like Interstitial Pneumonia: An Autopsy Case

PubMed Central

Nomoto, Yohta; Kawano, Kiyoshi; Fujisawa, Naoki; Yoshida, Keiko; Yamashita, Tomoko; Makita, Naoki; Takeshita, Hiroaki; Kamimori, Kimio; Yanagi, Shiro; Yoshiyama, Minoru

2017-01-01

Pheochromocytoma multisystem crisis is a rare and life-threatening disease that is associated with numerous symptoms and which is also difficult to diagnose. We herein report an autopsy case of a 61-year-old man who died due to pheochromocytoma multisystem crisis. The patient complained of vomiting and breathlessness. Computed tomography showed a shadow-like region with a similar appearance to interstitial pneumonia. The patient was diagnosed with takotsubo cardiomyopathy induced by severe lung disease based on the results of echocardiography and coronary angiography. The patient was treated for interstitial pneumonia. However, his condition rapidly deteriorated and he died 6 hours after arrival. We were later informed of his extremely high catecholamine serum levels. We found pheochromocytoma with hemorrhage at autopsy. The patient's lungs showed acute passive congestion with edema and extravasation. PMID:28090043

10. PARTIAL VIEW OF SOUTH FACE OF MST AND BRIDGE ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

10. PARTIAL VIEW OF SOUTH FACE OF MST AND BRIDGE CRANE MOVED TO ITS SOUTHERN LIMIT - Vandenberg Air Force Base, Space Launch Complex 3, Launch Pad 3 West, Napa & Alden Roads, Lompoc, Santa Barbara County, CA

11. PARTIAL VIEW OF NORTH FACE OF MST AND BRIDGE ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

11. PARTIAL VIEW OF NORTH FACE OF MST AND BRIDGE CRANE MOVED TO ITS NORTHERN LIMIT - Vandenberg Air Force Base, Space Launch Complex 3, Launch Pad 3 West, Napa & Alden Roads, Lompoc, Santa Barbara County, CA

Plasmodium coatneyi in Rhesus Macaques Replicates the Multisystemic Dysfunction of Severe Malaria in Humans

PubMed Central

Cabrera-Mora, Monica; Garcia, AnaPatricia; Orkin, Jack; Strobert, Elizabeth; Barnwell, John W.; Galinski, Mary R.

2013-01-01

Severe malaria, a leading cause of mortality among children and nonimmune adults, is a multisystemic disorder characterized by complex clinical syndromes that are mechanistically poorly understood. The interplay of various parasite and host factors is critical in the pathophysiology of severe malaria. However, knowledge regarding the pathophysiological mechanisms and pathways leading to the multisystemic disorders of severe malaria in humans is limited. Here, we systematically investigate infections with Plasmodium coatneyi, a simian malaria parasite that closely mimics the biological characteristics of P. falciparum, and develop baseline data and protocols for studying erythrocyte turnover and severe malaria in greater depth. We show that rhesus macaques (Macaca mulatta) experimentally infected with P. coatneyi develop anemia, coagulopathy, and renal and metabolic dysfunction. The clinical course of acute infections required suppressive antimalaria chemotherapy, fluid support, and whole-blood transfusion, mimicking the standard of care for the management of severe malaria cases in humans. Subsequent infections in the same animals progressed with a mild illness in comparison, suggesting that immunity played a role in reducing the severity of the disease. Our results demonstrate that P. coatneyi infection in rhesus macaques can serve as a highly relevant model to investigate the physiological pathways and molecular mechanisms of malaria pathogenesis in naïve and immune individuals. Together with high-throughput postgenomic technologies, such investigations hold promise for the identification of new clinical interventions and adjunctive therapies. PMID:23509137

Multisystem altruistic metadynamics—Well-tempered variant

NASA Astrophysics Data System (ADS)

Hošek, Petr; Kříž, Pavel; Toulcová, Daniela; Spiwok, Vojtěch

2017-03-01

Metadynamics method has been widely used to enhance sampling in molecular simulations. Its original form suffers two major drawbacks, poor convergence in complex (especially biomolecular) systems and its serial nature. The first drawback has been addressed by introduction of a convergent variant known as well-tempered metadynamics. The second was addressed by introduction of a parallel multisystem metadynamics referred to as altruistic metadynamics. Here, we combine both approaches into well-tempered altruistic metadynamics. We provide mathematical arguments and trial simulations to show that it accurately predicts free energy surfaces.

Multisystem altruistic metadynamics-Well-tempered variant.

PubMed

Hošek, Petr; Kříž, Pavel; Toulcová, Daniela; Spiwok, Vojtěch

2017-03-28

Metadynamics method has been widely used to enhance sampling in molecular simulations. Its original form suffers two major drawbacks, poor convergence in complex (especially biomolecular) systems and its serial nature. The first drawback has been addressed by introduction of a convergent variant known as well-tempered metadynamics. The second was addressed by introduction of a parallel multisystem metadynamics referred to as altruistic metadynamics. Here, we combine both approaches into well-tempered altruistic metadynamics. We provide mathematical arguments and trial simulations to show that it accurately predicts free energy surfaces.

Transtracheal oxygen therapy.

PubMed

Christopher, Kent L; Schwartz, Michael D

2011-02-01

Transtracheal oxygen therapy (TTO) has been used for long-term oxygen therapy for nearly 30 years. Numerous investigators have explored the potential benefits of TTO. Those results are reviewed in this article. TTO is best viewed not as a catheter but as a program for care. This article discusses patient selection for TTO. Publications evaluating complications are reviewed. In the past, a modified Seldinger technique (MST) was used for the creation of the tracheocutaneous fistula. The rather long program required for tract maturation with MST was labor-intensive and required substantial patient education and monitoring, particularly during the immature tract phase. Minor complications were not infrequent. More recently, the Lipkin method has been used to create a surgical tract under conscious sedation with topical anesthesia. The procedure is safe and well tolerated. Transtracheal oxygen is initiated the day following the procedure. Similarly, the tract matures in 7 to 10 days rather than the 6 to 8 weeks with MST. More rapid healing time and superior tract characteristics substantially reduce complications. The TTO program tailored for the Lipkin procedure is shortened, streamlined, and much less labor-intensive. Optimal outcomes with the TTO program require a committed pulmonologist, respiratory therapist, nurse, and surgeon (for the Lipkin procedure). This article discusses new directions in the use of transtracheal gas delivery, including the management of obstructive sleep apnea. Preliminary investigations regarding transtracheal augmented ventilation are presented. These include nocturnal use in severe chronic lung disease and liberation from prolonged mechanical ventilation.

Music-supported therapy induces plasticity in the sensorimotor cortex in chronic stroke: a single-case study using multimodal imaging (fMRI-TMS).

PubMed

Rojo, Nuria; Amengual, Julian; Juncadella, Montserrat; Rubio, Francisco; Camara, Estela; Marco-Pallares, Josep; Schneider, Sabine; Veciana, Misericordia; Montero, Jordi; Mohammadi, Bahram; Altenmüller, Eckart; Grau, Carles; Münte, Thomas F; Rodriguez-Fornells, Antoni

2011-01-01

Music-Supported Therapy (MST) has been developed recently in order to improve the use of the affected upper extremity after stroke. This study investigated the neuroplastic mechanisms underlying effectiveness in a patient with chronic stroke. MST uses musical instruments, a midi piano and an electronic drum set emitting piano sounds, to retrain fine and gross movements of the paretic upper extremity. Data are presented from a patient with a chronic stroke (20 months post-stroke) with residual right-sided hemiparesis who took part in 20 MST sessions over the course of 4 weeks. Post-therapy, a marked improvement of movement quality, assessed by 3D movement analysis, was observed. Moreover, functional magnetic resonance imaging (fMRI) of a sequential hand movement revealed distinct therapy-related changes in the form of a reduction of excess contralateral and ipsilateral activations. This was accompanied by changes in cortical excitability evidenced by transcranial magnetic stimulation (TMS). Functional MRI in a music listening task suggests that one of the effects of MST is the task-dependent coupling of auditory and motor cortical areas. The MST appears to be a useful neurorehabilitation tool in patients with chronic stroke and leads to neural reorganization in the sensorimotor cortex.

All Might Have Won, But Not All Have the Prize: Optimal Treatment for Substance Abuse Among Adolescents with Conduct Problems

PubMed Central

Spas, Jayson; Ramsey, Susan; Paiva, Andrea L.; Stein, L.A.R.

2012-01-01

Considerable evidence from the literature on treatment outcomes indicates that substance abuse treatment among adolescents with conduct problems varies widely. Treatments commonly used among this population are cognitive-behavioral therapy (CBT), 12-step facilitation, multisystemic therapy (MST), psychoeducation (PE), and motivational interviewing (MI). This manuscript thoroughly and systematically reviews the available literature to determine which treatment is optimal for substance-abusing adolescents with conduct problems. Results suggest that although there are several evidence-based and empirically supported treatments, those that incorporate family-based intervention consistently provide the most positive treatment outcomes. In particular, this review further reveals that although many interventions have gained empirical support over the years, only one holds the prize as being the optimal treatment of choice for substance abuse treatment among adolescents with conduct problems. PMID:23170066

4. VIEW OF NORTH FACE OF MST. NOTE: ENVIRONMENTAL DOOR ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

4. VIEW OF NORTH FACE OF MST. NOTE: ENVIRONMENTAL DOOR ON THE LOWER EAST SIDE OF THE NORTH FACE IS MISSING. - Vandenberg Air Force Base, Space Launch Complex 3, Launch Pad 3 East, Napa & Alden Roads, Lompoc, Santa Barbara County, CA

Effect of local therapy on locoregional recurrence in postmenopausal women with breast cancer in the Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial.

PubMed

van Hezewijk, Marjan; Bastiaannet, Esther; Putter, Hein; Scholten, Astrid N; Liefers, Gerrit-Jan; Rea, Daniel; Hasenburg, Annette; Paridaens, Robert; Hozumi, Yasuo; Markopoulos, Christos; Seynaeve, Caroline; Jones, Stephen E; Marijnen, Corrie A M; van de Velde, Cornelis J H

2013-08-01

The TEAM trial investigated the efficacy and safety of adjuvant endocrine therapy consisting of either exemestane or the sequence of tamoxifen followed by exemestane in postmenopausal hormone-sensitive breast cancer. The present analyses explored the association between locoregional therapy and recurrence (LRR) in this population. Between 2001 and 2006, 9779 patients were randomized. Local treatment was breast conserving surgery plus radiotherapy (BCS+RT), mastectomy without radiotherapy (MST-only), or mastectomy plus radiotherapy (MST+RT). Patients with unknown data on surgery, radiotherapy, tumor or nodal stage (n=199), and patients treated by lumpectomy without radiotherapy (n=349) were excluded. After a median follow-up of 5.2 years, 270 LRRs occurred (2.9%) among 9231 patients. The 5-years actuarial incidence of LRR was 4.2% (95% CI 3.3-4.9%) for MST-only, 3.4% (95% CI 2.4-4.2%) for MST+RT and 1.9% (95% CI 1.5-2.3%) for BCS+RT. After adjustment for prognostic factors, the hazard ratio (HR, reference BCS+RT) for LRR remained significantly higher for MST-only (HR 1.53; 95% CI 1.10-2.11), not for MST+RT (HR 0.78; 95% CI 0.50-1.22). This explorative analysis showed a higher LRR risk after MST-only than after BCS+RT, even after adjustment for prognostic factors. As this effect was not seen for MST+RT versus BCS+RT, it might be explained by the beneficial effects of radiation treatment. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

A Role for MST Neurons in Heading Estimation

NASA Technical Reports Server (NTRS)

Stone, Leland Scott; Perrone, J. A.; Wade, Charles E. (Technical Monitor)

1994-01-01

A template model of human visual self-motion perception (Perrone, JOSA, 1992; Perrone & Stone, Vis. Res., in press), which uses neurophysiologically realistic "heading detectors", is consistent with numerous human psychophysical results (Warren & Hannon, Nature, 1988; Stone & Perrone, Neuro. Abstr., 1991) including the failure of humans to estimate their heading (direction of forward translation) accurately under certain visual conditions (Royden et al., Nature, 1992). We tested the model detectors with stimuli used by others in- single-unit studies. The detectors showed emergent properties similar to those of MST neurons: 1) Sensitivity to non-preferred flow. Each detector is tuned to a specific combination of flow components and its response is systematically reduced by the addition of nonpreferred flow (Orban et al., PNAS, 1992), and 2) Position invariance. The detectors maintain their apparent preference for particular flow components over large regions of their receptive fields (e.g. Duffy & Wurtz, J. Neurophys., 1991; Graziano et al., J. Neurosci., 1994). It has been argued that this latter property is incompatible with MST playing a role in heading perception. The model however demonstrates how neurons with the above response properties could still support accurate heading estimation within extrastriate cortical maps.

Measuring viscosity with a resonant magnetic perturbation in the MST RFP

NASA Astrophysics Data System (ADS)

Fridström, Richard; Munaretto, Stefano; Frassinetti, Lorenzo; Chapman, Brett; Brunsell, Per; Sarff, John; MST Team

2016-10-01

Application of an m = 1 resonant magnetic perturbation (RMP) causes braking and locking of naturally rotating m = 1 tearing modes (TMs) in the MST RFP. The experimental TM dynamics are replicated by a theoretical model including the interaction between the RMP and multiple TMs [Fridström PoP 23, 062504 (2016)]. The viscosity is the only free parameter in the model, and it is chosen such that model TM velocity evolution matches that of the experiment. The model does not depend on the means by which the natural rotation is generated. The chosen value of the viscosity, about 40 m2/s, is consistent with separate measurements in MST using a biased probe to temporarily spin up the plasma. This viscosity is about 100 times larger than the classical prediction, likely due to magnetic stochasticity in the core of these plasmas. Viscosity is a key parameter in visco-resistive MHD codes like NIMROD. The validation of these codes requires measurement of the viscosity over a broad parameter range, which will now be possible with the RMP technique that, unlike the biased probe, is not limited to low-energy-density plasmas. Estimation with the RMP technique of the viscosity in several MST discharges suggests that the viscosity decreases as the electron beta increases. Work supported by USDOE.

Heart failure: not a single organ disease but a multisystem syndrome.

PubMed

Warriner, David; Sheridan, Paul; Lawford, Patricia

2015-06-01

Heart failure is not simply a single organ disease; rather it is a complex multi-system clinical syndrome, with impairment of endocrine, haematological, musculoskeletal, renal, respiratory and vascular systems, which influence morbidity and mortality.

Morin impedes Yap nuclear translocation and fosters apoptosis through suppression of Wnt/β-catenin and NF-κB signaling in Mst1 overexpressed HepG2 cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Perumal, NaveenKumar; Perumal, MadanKumar; Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, Texas 75390

Recent clinical and experimental evidences strongly acclaim Yes-associated protein (Yap), a key oncogenic driver in liver carcinogenesis, as a therapeutic target. Of the known multiple schemes to inhibit Yap activity, activation of Mammalian Sterile 20-like Kinase 1 (Mst1), an upstream regulator of Yap, appears to be a promising one. In this study, we hypothesize that morin, a bioflavonoid, mediates its anti-cancer effect through the activation of Mst1/hippo signaling in liver cancer cells. To test this hypothesis, both full length Mst1 (F-Mst1) and kinase active N-terminal Mst1 (N-Mst1)-overexpressed HepG2 cells were used. Exposure of F-Mst1 overexpressed HepG2 cells to morin activatedmore » Mst1 by caspase-3 cleavage and thereby inhibited Yap nuclear translocation and fostered apoptosis. Morin suppressed NF-κB p65 and Wnt/β-catenin signaling through Mst1 activation via cleavage and phosphorylation, leading to cell death. Annexin-V/PI staining further confirmed the induction of apoptosis in morin treated F-Mst1 overexpressed cells. The present study shows that morin targets cell survival molecules such as NF-κB p65 and β-catenin through activation of hippo signaling. Therefore, morin could be considered as a potential anti-cancer agent against liver cancer. - Highlights: • Morin induced cytotoxicity in cultured HepG2 cells. • Morin activated hippo pathway via Mst1 activation in transfected HepG2 cells. • Morin suppressed Wnt/β-catenin signaling and induced G0/G1 cell cycle arrest. • Morin inhibited NF-κB signaling through Mst1 activation in transfected HepG2 cells. • Morin potentiates apoptosis through Mst1-JNK-caspase mediated mechanism in HepG2 cells.« less

42. VIEW OF UMBILICAL MAST AND LAUNCH PAD FROM MST ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

42. VIEW OF UMBILICAL MAST AND LAUNCH PAD FROM MST BASE. LAUNCHER IS BEHIND UMBILICAL MAST AND RAIL SYSTEM IS PARALLEL TO MAST ON RIGHT AND LEFT. - Vandenberg Air Force Base, Space Launch Complex 3, Launch Pad 3 East, Napa & Alden Roads, Lompoc, Santa Barbara County, CA

3. VIEW OF NORTHEAST CORNER OF MST. NOTE: ENVIRONMENTAL DOOR ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

3. VIEW OF NORTHEAST CORNER OF MST. NOTE: ENVIRONMENTAL DOOR ON THE LOWER EAST SIDE OF THE NORTH FACE IS MISSING. NORTH CAMERA TOWER IN FOREGROUND. - Vandenberg Air Force Base, Space Launch Complex 3, Launch Pad 3 East, Napa & Alden Roads, Lompoc, Santa Barbara County, CA

The Effects of Family Therapies for Adolescent Delinquency and Substance Abuse: A Meta-Analysis

ERIC Educational Resources Information Center

Baldwin, Scott A.; Christian, Sarah; Berkeljon, Arjan; Shadish, William R.

2012-01-01

This meta-analysis summarizes results from k = 24 studies comparing either Brief Strategic Family Therapy, Functional Family Therapy, Multidimensional Family Therapy, or Multisystemic Therapy to either treatment-as-usual, an alternative therapy, or a control group in the treatment of adolescent substance abuse and delinquency. Additionally, the…

Multistimulation group therapy in Alzheimer's disease promotes changes in brain functioning.

PubMed

Baglio, Francesca; Griffanti, Ludovica; Saibene, Francesca Lea; Ricci, Cristian; Alberoni, Margherita; Critelli, Raffaella; Villanelli, Fabiana; Fioravanti, Raffaella; Mantovani, Federica; D'amico, Alessandra; Cabinio, Monia; Preti, Maria Giulia; Nemni, Raffaello; Farina, Elisabetta

2015-01-01

Background. The growing social emergency represented by Alzheimer's disease (AD) and the lack of medical treatments able to modify the disease course have kindled the interest in nonpharmacological therapies. Objective. We introduced a novel nonpharmacological approach for people with AD (PWA) named Multidimensional Stimulation group Therapy (MST) to improve PWA condition in different disease domains: cognition, behavior, and motor functioning. Methods. Enrolling 60 PWA in a mild to moderate stage of the disease, we evaluated the efficacy of MST with a randomized-controlled study. Neuropsychological and neurobehavioral measures and functional magnetic resonance imaging (fMRI) data were considered as outcome measures. Results. The following significant intervention-related changes were observed: reduction in Neuropsychiatric Inventory scale score, improvement in language and memory subscales of Alzheimer's Disease Assessment Scale-Cognitive subscale, and increased fMRI activations in temporal brain areas, right insular cortex, and thalamus. Conclusions. Cognitive-behavioral and fMRI results support the notion that MST has significant effects in improving PWA cognitive-behavioral status by restoring neural functioning. © The Author(s) 2014.

Validation of MHD Models using MST RFP Plasmas

NASA Astrophysics Data System (ADS)

Jacobson, C. M.; Chapman, B. E.; den Hartog, D. J.; McCollam, K. J.; Sarff, J. S.; Sovinec, C. R.

2017-10-01

Rigorous validation of computational models used in fusion energy sciences over a large parameter space and across multiple magnetic configurations can increase confidence in their ability to predict the performance of future devices. MST is a well diagnosed reversed-field pinch (RFP) capable of operation with plasma current ranging from 60 kA to 500 kA. The resulting Lundquist number S, a key parameter in resistive magnetohydrodynamics (MHD), ranges from 4 ×104 to 8 ×106 for standard RFP plasmas and provides substantial overlap with MHD RFP simulations. MST RFP plasmas are simulated using both DEBS, a nonlinear single-fluid visco-resistive MHD code, and NIMROD, a nonlinear extended MHD code, with S ranging from 104 to 105 for single-fluid runs, and the magnetic Prandtl number Pm = 1 . Validation metric comparisons are presented, focusing on how normalized magnetic fluctuations at the edge b scale with S. Preliminary results for the dominant n = 6 mode are b S - 0 . 20 +/- 0 . 02 for single-fluid NIMROD, b S - 0 . 25 +/- 0 . 05 for DEBS, and b S - 0 . 20 +/- 0 . 02 for experimental measurements, however there is a significant discrepancy in mode amplitudes. Preliminary two-fluid NIMROD results are also presented. Work supported by US DOE.

21. STATION 70.5 OF MST, WEST SIDE. AIRCONDITIONING DUCT AT ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

21. STATION 70.5 OF MST, WEST SIDE. AIR-CONDITIONING DUCT AT TOP; POWER BOX ON RIGHT; WINCH ON LEFT. - Vandenberg Air Force Base, Space Launch Complex 3, Launch Pad 3 East, Napa & Alden Roads, Lompoc, Santa Barbara County, CA

22. DOOR CONTROL BOX AT STATION 70.5 OF MST FOR ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

22. DOOR CONTROL BOX AT STATION 70.5 OF MST FOR CONTROL OF SOUTH DOORS. NITROGEN PRESSURE REGULATOR ON LEFT. - Vandenberg Air Force Base, Space Launch Complex 3, Launch Pad 3 East, Napa & Alden Roads, Lompoc, Santa Barbara County, CA

Gaseous signalling molecule SO2 via Hippo-MST pathway to improve myocardial fibrosis of diabetic rats

PubMed Central

Liu, Maojun; Liu, Shengquan; Tan, Wenting; Tang, Fen; Long, Junrong; Li, Zining; Liang, Biao; Chu, Chun; Yang, Jun

2017-01-01

Recent studies have indicated the existence of an endogenous sulfur dioxide (SO2)-generating system in the cardiovascular system. The present study aimed to discuss the function and regulatory mechanism of gaseous signal molecule SO2 in inhibiting apoptosis and endoplasmic reticulum stress (ERS) via the Hippo-MST signaling pathway to improve myocardial fibrosis of diabetic rats. A total of 40 male Sprague-Dawley rats were randomly divided into four groups (10 rats per group): Normal control group (control group), diabetic rats group [streptozotocin (STZ) group], SO2 intervention group (STZ+SO2 group) and diabetes mellitus rats treated with L-Aspartic acid β-hydroxamate (HDX) group (HDX group). Diabetic rats models were established by intra-peritoneal injection of STZ (40 mg/kg) Following model establishment, intra-peritoneal injection of Na2SO3/NaHSO3 solution (0.54 mmol/kg) was administered in the STZ+SO2 group, and HDX solution (25 mg/kg/week) was administered in the HDX group. A total of 4 weeks later, echocardiography was performed to evaluate rats' cardiac function; Masson staining, terminal deoxynucleotidyl transferase dUTP nick end labeling staining and transmission electron microscopy examinations were performed to observe myocardial morphological changes. ELISA was employed to determine the SO2 content. Western blot analysis was performed to detect the expression of proteins associated with apoptosis, ERS and the Hippo-MST signalling pathway. Compared with the control group, the STZ group and HDX group had a disordered arrangement of myocardial cells with apparent myocardial fibrosis, and echocardiography indicated that the cardiac function was lowered, there was an obvious increase of apoptosis in myocardial tissue, the expression levels of apoptosis-associated protein B-cell lymphoma associated protein X, caspase-3 and caspase-9 were upregulated, and Bcl-2 expression was downregulated. The expression of ERS and Hippo-MST pathway-associated proteins

Gaseous signalling molecule SO2 via Hippo‑MST pathway to improve myocardial fibrosis of diabetic rats.

PubMed

Liu, Maojun; Liu, Shengquan; Tan, Wenting; Tang, Fen; Long, Junrong; Li, Zining; Liang, Biao; Chu, Chun; Yang, Jun

2017-12-01

Recent studies have indicated the existence of an endogenous sulfur dioxide (SO2)‑generating system in the cardiovascular system. The present study aimed to discuss the function and regulatory mechanism of gaseous signal molecule SO2 in inhibiting apoptosis and endoplasmic reticulum stress (ERS) via the Hippo‑MST signaling pathway to improve myocardial fibrosis of diabetic rats. A total of 40 male Sprague‑Dawley rats were randomly divided into four groups (10 rats per group): Normal control group (control group), diabetic rats group [streptozotocin (STZ) group], SO2 intervention group (STZ+SO2 group) and diabetes mellitus rats treated with L‑Aspartic acid β‑hydroxamate (HDX) group (HDX group). Diabetic rats models were established by intra‑peritoneal injection of STZ (40 mg/kg) Following model establishment, intra‑peritoneal injection of Na2SO3/NaHSO3 solution (0.54 mmol/kg) was administered in the STZ+SO2 group, and HDX solution (25 mg/kg/week) was administered in the HDX group. A total of 4 weeks later, echocardiography was performed to evaluate rats' cardiac function; Masson staining, terminal deoxynucleotidyl transferase dUTP nick end labeling staining and transmission electron microscopy examinations were performed to observe myocardial morphological changes. ELISA was employed to determine the SO2 content. Western blot analysis was performed to detect the expression of proteins associated with apoptosis, ERS and the Hippo‑MST signalling pathway. Compared with the control group, the STZ group and HDX group had a disordered arrangement of myocardial cells with apparent myocardial fibrosis, and echocardiography indicated that the cardiac function was lowered, there was an obvious increase of apoptosis in myocardial tissue, the expression levels of apoptosis‑associated protein B‑cell lymphoma associated protein X, caspase‑3 and caspase‑9 were upregulated, and Bcl‑2 expression was downregulated. The expression of ERS and Hippo‑MST

Neutral dynamics and ion energy transport in MST plasma

NASA Astrophysics Data System (ADS)

Xing, Zichuan; Nornberg, Mark; den Hartog, Daniel; Kumar, Santosh; Anderson, Jay

2015-11-01

Neutral dynamics can have a significant effect on ion energy transport through charge exchange collisions. Whereas previously charge exchange was considered a direct loss mechanism in MST plasmas, new analysis indicates that significant thermal charge exchange neutrals are reionized. Further, the temperatures of the neutral species in the core of the plasma are suspected to be much higher than room temperature, which has a large effect on ion energy losses due to charge exchange. The DEGAS2 Monte Carlo simulation code is applied to the MST reversed field pinch experiment to estimate the density and temperature profile of the neutral species. The result is then used to further examine the effect of the neutral species on ion energy transport in improved confinement plasmas. This enables the development of a model that accounts for collisional equilibration between species, classical convective and conductive energy transport, and energy loss due to charge exchange collisions. The goal is to quantify classical, stochastic, and anomalous ion heating and transport in RFP plasmas. Work supported by the US DOE. DEGAS2 is provided by PPPL and STRAHL is provided by Ralph Dux of the Max-Planck-Institut fur Plasmaphysik.

Terminology and global standardization of endoscopic information: Minimal Standard Terminology (MST).

PubMed

Fujino, Masayuki A; Bito, Shigeru; Takei, Kazuko; Mizuno, Shigeto; Yokoi, Hideto

2006-01-01

Since 1994, following the leading efforts by the European Society for Gastrointestinal Endoscopy, Organisation Mondiale d'Endoscopie Digestive (OMED) has succeeded in compiling minimal number of terms required for computer generation of digestive endoscopy reports nicknamed MST (Minimal Standard Terminology). Though with some insufficiencies, and though developed only for digestive endoscopy, MST has been the only available terminology that is globally standardized in medicine. By utilizing the merits of a unified, structured terminology that can be used in multiple languages we can utilize the data stored in different languages as a common database. For this purpose, a standing, terminology-managing organization that manages and maintains and, when required, expands the terminology on a global level, is absolutely necessary. Unfortunately, however, the organization that performs version control of MST (OMED terminology, standardization and data processing committee) is currently suspending its activity. Medical practice of the world demands more and more specialization, with resultant needs for information exchange among specialized territories. As the cooperation between endoscopy and pathology has become currently the most important problem in the Endoscopy Working Group of Integrating Healthcare Enterprise-Japan (IHE-J,) the cooperation among different specialties is essential. There are DICOM or HL7 standards as the protocols for storage, and exchange (communication) of the data, but there is yet no organization that manages the terminology itself astride different specialties. We hereby propose to establish, within IEEE, for example, a system that promotes standardization of the terminology that can transversely describe a patient, and that can control different societies and groups, as far as the terminology is concerned.

Ion Heating Anisotropy during Dynamo Activity in the MST RFP

NASA Astrophysics Data System (ADS)

den Hartog, D. J.; Chapman, J. T.; Craig, D.; Fiksel, G.; Fontana, P. W.

1999-11-01

MHD dynamo activity is large in the MST Reversed-Field Pinch during sawtooth crashes, and small otherwise. During a sawtooth crash, ion temperature increases rapidly to a level several times as high as the temperature between sawteeth, which itself can be larger than the electron temperature. Several theories have been developed to explain this ion heating, some indicating a possible asymmetry in perpendicular to parallel heating [C. G. Gimblett, Europhys. Lett. 11, 541 (1990); Z. Yoshida, Nucl. Fusion 31, 386 (1991); N. Mattor, P. W. Terry, and S. C. Prager, Comments Plasma Phys. Controlled Fusion 15, 65 (1992)]. In standard MST discharges, impurity ion temperature measured perpendicular to the magnetic field (T_⊥) is higher than impurity ion temperature parallel to the magnetic field (T_allel) during a sawtooth crash. Throughout the rest of the sawtooth cycle, T_⊥ <= T_allel. This is in contrast to results obtained on the EXTRAP-T2 RFP which showed T_⊥ < T_allel throughout the discharge [K. Sasaki et al., Plasma Phys. Control. Fusion 39, 333 (1997)

DLG5 connects cell polarity and Hippo signaling protein networks by linking PAR-1 with MST1/2

PubMed Central

Kwan, Julian; Sczaniecka, Anna; Heidary Arash, Emad; Nguyen, Liem; Chen, Chia-Chun; Ratkovic, Srdjana; Klezovitch, Olga; Attisano, Liliana; McNeill, Helen; Emili, Andrew; Vasioukhin, Valeri

2016-01-01

Disruption of apical–basal polarity is implicated in developmental disorders and cancer; however, the mechanisms connecting cell polarity proteins with intracellular signaling pathways are largely unknown. We determined previously that membrane-associated guanylate kinase (MAGUK) protein discs large homolog 5 (DLG5) functions in cell polarity and regulates cellular proliferation and differentiation via undefined mechanisms. We report here that DLG5 functions as an evolutionarily conserved scaffold and negative regulator of Hippo signaling, which controls organ size through the modulation of cell proliferation and differentiation. Affinity purification/mass spectrometry revealed a critical role of DLG5 in the formation of protein assemblies containing core Hippo kinases mammalian ste20 homologs 1/2 (MST1/2) and Par-1 polarity proteins microtubule affinity-regulating kinases 1/2/3 (MARK1/2/3). Consistent with this finding, Hippo signaling is markedly hyperactive in mammalian Dlg5−/− tissues and cells in vivo and ex vivo and in Drosophila upon dlg5 knockdown. Conditional deletion of Mst1/2 fully rescued the phenotypes of brain-specific Dlg5 knockout mice. Dlg5 also interacts genetically with Hippo effectors Yap1/Taz. Mechanistically, we show that DLG5 inhibits the association between MST1/2 and large tumor suppressor homologs 1/2 (LATS1/2), uses its scaffolding function to link MST1/2 with MARK3, and inhibits MST1/2 kinase activity. These data reveal a direct connection between cell polarity proteins and Hippo, which is essential for proper development of multicellular organisms. PMID:28087714

The economics of data acquisition computers for ST and MST radars

NASA Technical Reports Server (NTRS)

Watkins, B. J.

1983-01-01

Some low cost options for data acquisition computers for ST (stratosphere, troposphere) and MST (mesosphere, stratosphere, troposphere) are presented. The particular equipment discussed reflects choices made by the University of Alaska group but of course many other options exist. The low cost microprocessor and array processor approach presented here has several advantages because of its modularity. An inexpensive system may be configured for a minimum performance ST radar, whereas a multiprocessor and/or a multiarray processor system may be used for a higher performance MST radar. This modularity is important for a network of radars because the initial cost is minimized while future upgrades will still be possible at minimal expense. This modularity also aids in lowering the cost of software development because system expansions should rquire little software changes. The functions of the radar computer will be to obtain Doppler spectra in near real time with some minor analysis such as vector wind determination.

Probing RFP Density Limits and the Interaction of Pellet Fueling and NBI Heating on MST

NASA Astrophysics Data System (ADS)

Caspary, K. J.; Chapman, B. E.; Anderson, J. K.; Limbach, S. T.; Oliva, S. P.; Sarff, J. S.; Waksman, J.; Combs, S. K.; Foust, C. R.

2013-10-01

Pellet fueling on MST has previously achieved Greenwald fractions of up to 1.5 in 200 kA improved confinement discharges. Additionally, pellet fueling to densities above the Greenwald limit in 200 kA standard discharges resulted in early termination of the plasma, but pellet size was insufficient to exceed the limit for higher current discharges. To this end, the pellet injector on MST has been upgraded to increase the maximum fueling capability by increasing the size of the pellet guide tubes, which constrain the lateral motion of the pellet in flight, to accommodate pellets of up to 4.0 mm in diameter. These 4.0 mm pellets are capable of triggering density limit terminations for MST's peak current of 600 kA. An unexpected improvement in the pellet speed and mass control was also observed compared to the smaller diameter pellets. Exploring the effect of increased density on NBI particle and heat deposition shows that for MST's 1 MW tangential NBI, core deposition of 25 keV neutrals is optimized for densities of 2-3 × 1019 m-3. This is key for beta limit studies in pellet fueled discharges with improved confinement where maximum NBI heating is desired. An observed toroidal deflection of pellets injected into NBI heated discharges is consistent with asymmetric ablation due to the fast ion population. In 200 kA improved confinement plasmas with NBI heating, pellet fueling has achieved a Greenwald fraction of 2.0. Work supported by US DoE.

Unary and binary multisystems; topologic classification of phase diagrams and relation to Euler's theorem on polyhedra.

USGS Publications Warehouse

Roseboom, E.H.; Zen, E.-A.

1982-01-01

A representation polyhedron summarizing the topology of a large number of possible nets previously devised by Zen (M.A. 18-167) is extended from n + 3 unary to n + 6 phase unary systems. A general way for constructing n + 4 phase nets is outlined. With the technique described, 62 multisystems are recognized, of which 26 contain all 16 possible divariant fields and represent the most nearly complete closed nets possible for a binary six-phase (n + 4) multisystem.-M.S.

36. 1,000POUND CHAIN HOIST AT STATION 124 OF MST, WEST ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

36. 1,000-POUND CHAIN HOIST AT STATION 124 OF MST, WEST SIDE. (ITS ONLY USE WAS INSTALLATION OF ELEVATOR MOTOR.) - Vandenberg Air Force Base, Space Launch Complex 3, Launch Pad 3 East, Napa & Alden Roads, Lompoc, Santa Barbara County, CA

Suppression of runaway electrons with a resonant magnetic perturbation in MST tokamak plasmas

NASA Astrophysics Data System (ADS)

Munaretto, Stefano; Chapman, B. E.; Almagri, A. F.; Cornille, B. S.; Dubois, A. M.; Goetz, J. A.; McCollam, K. J.; Sovinec, C. R.

2016-10-01

Runaway electrons generated in MST tokamak plasmas are now being probed with resonant magnetic perturbations (RMP's). An RMP with m =3 strongly suppresses the runaway electrons. Initial modeling of these plasmas with NIMROD shows the degradation of flux surfaces with an m =3 RMP, which may account for the runaway electron suppression. These MST tokamak plasmas have Bt =0.14 T, Ip =50kA, and q(a) =2.2, with a bulk electron density and temperature of 5x1017 m-3 and 150 eV. Runaway electrons are detected via x-ray emission. The RMP is produced by a poloidal array of 32 saddle coils at the narrow vertical insulated cut in MST's thick conducting shell. Each RMP has a single m but a broad n spectrum. A sufficiently strong m =3 RMP completely suppresses the runaway electrons, while a comparable m =1 RMP has little effect. The impact of the RMP's on the magnetic topology of these plasmas is being studied with the nonlinear MHD code, NIMROD. With an m =3 RMP, stochasticity is introduced in the outer third of the plasma. No such change is observed with the m =1 RMP. NIMROD also predicts regularly occurring sawtooth oscillations with a period comparable to MHD activity observed in the experiment. Work supported by USDOE.

Validation of Extended MHD Models using MST RFP Plasmas

NASA Astrophysics Data System (ADS)

Jacobson, C. M.; Chapman, B. E.; Craig, D.; McCollam, K. J.; Sovinec, C. R.

2016-10-01

Significant effort has been devoted to improvement of computational models used in fusion energy sciences. Rigorous validation of these models is necessary in order to increase confidence in their ability to predict the performance of future devices. MST is a well diagnosed reversed-field pinch (RFP) capable of operation over a wide range of parameters. In particular, the Lundquist number S, a key parameter in resistive magnetohydrodynamics (MHD), can be varied over a wide range and provide substantial overlap with MHD RFP simulations. MST RFP plasmas are simulated using both DEBS, a nonlinear single-fluid visco-resistive MHD code, and NIMROD, a nonlinear extended MHD code, with S ranging from 104 to 5 ×104 for single-fluid runs, with the magnetic Prandtl number Pm = 1 . Experiments with plasma current IP ranging from 60 kA to 500 kA result in S from 4 ×104 to 8 ×106 . Validation metric comparisons are presented, focusing on how magnetic fluctuations b scale with S. Single-fluid NIMROD results give S b - 0.21 , and experiments give S b - 0.28 for the dominant m = 1 , n = 6 mode. Preliminary two-fluid NIMROD results are also presented. Work supported by US DOE.

Further developments of EISCAT as an MST radar

NASA Technical Reports Server (NTRS)

Rottger, J.

1984-01-01

The principal capabilities of EISCAT as an MST radar were described. Since the VHF transmitter of the EISCAT system is not yet delivered, only the UHF system could be used for radar experiments. Considerable developments in the year 1983 have now strongly improved the reliability of the operations. Most of the experiments were and will be done to investigate the high latitude ionosphere and thermosphere, but some time was also devoted to observations of the lower and middle atmosphere, particularly during the MAP/WINE compaign.

18. VIEW OF EAST SIDE INTERIOR OF MST AT STATIONS ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

18. VIEW OF EAST SIDE INTERIOR OF MST AT STATIONS 3 AND 12, FACING WEST. COMPRESSED AIR TANK AND GENERATOR AT STATION 3. CURTAIN FOR NORTH ENVIRONMENTAL DOOR VISIBLE ON LEFT SIDE OF PHOTOGRAPH; RAIL VISIBLE AT BOTTOM OF PHOTOGRAPH. - Vandenberg Air Force Base, Space Launch Complex 3, Launch Pad 3 East, Napa & Alden Roads, Lompoc, Santa Barbara County, CA

Thyrotoxic and pheochromocytoma multisystem crisis: a case report.

PubMed

Suzuki, Kodai; Miyake, Takahito; Okada, Hideshi; Yamaji, Fuminori; Kitagawa, Yuichiro; Fukuta, Tetsuya; Yasuda, Ryu; Tanaka, Yoshihito; Okamoto, Haruka; Nachi, Sho; Doi, Tomoaki; Yoshida, Takahiro; Kumada, Keisuke; Yoshida, Shozo; Ushikoshi, Hiroaki; Toyoda, Izumi; Ogura, Shinji

2017-06-23

Thyrotoxic crisis and pheochromocytoma multisystem crisis are rare, life-threatening, emergency endocrine diseases with various clinical manifestations. Here we report a case of a patient who simultaneously developed thyrotoxic crisis and pheochromocytoma multisystem crisis and required intensive cardiovascular management. A 60-year-old Asian man experienced nausea and vomiting, and subsequently developed dyspnea and cold sweats while farming. His serum free thyroxine, free triiodothyronine, and thyrotropin receptor antibody levels were elevated at 2.9 ng/dL, 7.2 pg/dL, and 4.7 IU/L, respectively. Serum thyrotropin levels were suppressed at less than 0.01 μIU/mL. Thyroid echography demonstrated no thyroid swelling (23 × 43 mm). A whole body computed tomography was performed for systemic evaluation. This revealed exophthalmos and a mass of size 57 × 64 mm in the anterior pararenal space. Based on these findings, we made an initial diagnosis of thyrotoxic crisis secondary to exacerbation of Grave's hyperthyroidism. Treatment was begun with an iodine agent at a dose of 36 mg/day, thiamazole at a dose of 30 mg/day, and hydrocortisone at a dose of 300 mg daily for 3 consecutive days. To control tachycardia, continuous intravenously administered propranolol and diltiazem infusions were given. At the same time, small doses of doxazosin and carvedilol were used for both alpha and beta adrenergic blockade. On hospital day 5, his blood pressure and serum catecholamine concentrations (adrenalin 42,365 pg/mL, dopamine 6409 pg/mL, noradrenalin 72,212 pg/mL) were still high despite higher beta blocker and calcium channel blocker doses. These findings contributed to the diagnosis of pheochromocytoma multisystem crisis with simultaneous thyrotoxic crisis. We increased the doses of doxazosin and carvedilol, which stabilized his hemodynamic status. On hospital day 16, metaiodobenzylguanidine scintigraphy showed high accumulation in the right adrenal gland tumor

A Progress Report on a Multi-Systems Theory of Communication Behavior.

ERIC Educational Resources Information Center

Grunig, James E.

Previous research is reviewed in which a multi-systems theory of communication behavior has been used to explain communication behavior of individuals and of several organization-related systems and subsystems. Recent research is then summarized which sought to develop conditional probabilities that communication behavior will occur in each of 16…

Discovery and Mechanistic Characterization of Selective Inhibitors of H2S-producing Enzyme: 3-Mercaptopyruvate Sulfurtransferase (3MST) Targeting Active-site Cysteine Persulfide

PubMed Central

Hanaoka, Kenjiro; Sasakura, Kiyoshi; Suwanai, Yusuke; Toma-Fukai, Sachiko; Shimamoto, Kazuhito; Takano, Yoko; Shibuya, Norihiro; Terai, Takuya; Komatsu, Toru; Ueno, Tasuku; Ogasawara, Yuki; Tsuchiya, Yukihiro; Watanabe, Yasuo; Kimura, Hideo; Wang, Chao; Uchiyama, Masanobu; Kojima, Hirotatsu; Okabe, Takayoshi; Urano, Yasuteru; Shimizu, Toshiyuki; Nagano, Tetsuo

2017-01-01

Very recent studies indicate that sulfur atoms with oxidation state 0 or −1, called sulfane sulfurs, are the actual mediators of some physiological processes previously considered to be regulated by hydrogen sulfide (H2S). 3-Mercaptopyruvate sulfurtransferase (3MST), one of three H2S-producing enzymes, was also recently shown to produce sulfane sulfur (H2Sn). Here, we report the discovery of several potent 3MST inhibitors by means of high-throughput screening (HTS) of a large chemical library (174,118 compounds) with our H2S-selective fluorescent probe, HSip-1. Most of the identified inhibitors had similar aromatic ring-carbonyl-S-pyrimidone structures. Among them, compound 3 showed very high selectivity for 3MST over other H2S/sulfane sulfur-producing enzymes and rhodanese. The X-ray crystal structures of 3MST complexes with two of the inhibitors revealed that their target is a persulfurated cysteine residue located in the active site of 3MST. Precise theoretical calculations indicated the presence of a strong long-range electrostatic interaction between the persulfur anion of the persulfurated cysteine residue and the positively charged carbonyl carbon of the pyrimidone moiety of the inhibitor. Our results also provide the experimental support for the idea that the 3MST-catalyzed reaction with 3-mercaptopyruvate proceeds via a ping-pong mechanism. PMID:28079151

Manipulating the content of dynamic natural scenes to characterize response in human MT/MST.

PubMed

Durant, Szonya; Wall, Matthew B; Zanker, Johannes M

2011-09-09

Optic flow is one of the most important sources of information for enabling human navigation through the world. A striking finding from single-cell studies in monkeys is the rapid saturation of response of MT/MST areas with the density of optic flow type motion information. These results are reflected psychophysically in human perception in the saturation of motion aftereffects. We began by comparing responses to natural optic flow scenes in human visual brain areas to responses to the same scenes with inverted contrast (photo negative). This changes scene familiarity while preserving local motion signals. This manipulation had no effect; however, the response was only correlated with the density of local motion (calculated by a motion correlation model) in V1, not in MT/MST. To further investigate this, we manipulated the visible proportion of natural dynamic scenes and found that areas MT and MST did not increase in response over a 16-fold increase in the amount of information presented, i.e., response had saturated. This makes sense in light of the sparseness of motion information in natural scenes, suggesting that the human brain is well adapted to exploit a small amount of dynamic signal and extract information important for survival.

Time course of motor gains induced by music-supported therapy after stroke: An exploratory case study.

PubMed

Grau-Sánchez, Jennifer; Ramos, Neus; Duarte, Esther; Särkämö, Teppo; Rodríguez-Fornells, Antoni

2017-09-01

Previous studies have shown that Music-Supported Therapy (MST) can improve the motor function and promote functional neuroplastic changes in motor areas; however, the time course of motor gains across MST sessions and treatment periods remain unknown. The aim of this study was to explore the progression of the rehabilitation of motor deficits in a chronic stroke patient for a period of 7 months. A reversal design (ABAB) was implemented in a chronic stroke patient where no treatment was provided in the A periods and MST was applied in the B periods. Each period comprised of 4 weeks and an extensive evaluation of the motor function using clinical motor tests and 3D movement analysis was performed weekly. During the MST periods, a keyboard task was recorded daily. A follow-up evaluation was performed 3 months after the second MST treatment. Improvements were observed during the first sessions in the keyboard task but clinical gains were noticeable only at the end of the first treatment and during the second treatment period. These gains were maintained in the follow-up evaluation. This is the first study examining the pattern of motor recovery progression in MST, evidencing that gradual and continuous motor improvements are possible with the repeated application of MST training. Fast-acquisition in specific motor abilities was observed at the beginning of the MST training but generalization of these improvements to other motor tasks took place at the end or when another treatment period was provided. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

MiR-183 regulates milk fat metabolism via MST1 in goat mammary epithelial cells.

PubMed

Chen, Zhi; Shi, HuaiPing; Sun, Shuang; Luo, Jun; Zhang, Wei; Hou, Yu; Loor, Juan J

2018-03-10

The nutritional value of goat milk largely depends on its fatty acid content and composition. MicroRNAs (miRNAs) are a class of RNA molecules 18-25nt in length that regulate gene expression and play crucial roles in several biological processes, including fatty acid metabolism. In this study, we analyzed the correlation between differentially expressed miRNAs in goat mammary tissue and the fatty acid composition of goat milk by using Pearson correlations. Results revealed that levels of miR-183 were highly and positively correlated with the fatty acid content in the milk. In addition, we demonstrated that overexpression of miR-183 inhibits milk fat metabolism and inhibition of miR-183 promotes milk fat metabolism. Using Western blot, we demonstrate that MST1, one of the major elements of the Hippo signaling pathway, is a target of miR-183. Immunofluorescence assays revealed that miR-183 targets MST1 in the cytoplasm. In summary, data indicate that miR-183 inhibits the metabolism of milk fat by targeting the MST1 gene in the cytoplasm in goat mammary epithelial cells. Copyright © 2017 Elsevier B.V. All rights reserved.

Increase in MST activity correlates with visual motion learning: A functional MRI study of perceptual learning

PubMed Central

Larcombe, Stephanie J.; Kennard, Chris

2017-01-01

Abstract Repeated practice of a specific task can improve visual performance, but the neural mechanisms underlying this improvement in performance are not yet well understood. Here we trained healthy participants on a visual motion task daily for 5 days in one visual hemifield. Before and after training, we used functional magnetic resonance imaging (fMRI) to measure the change in neural activity. We also imaged a control group of participants on two occasions who did not receive any task training. While in the MRI scanner, all participants completed the motion task in the trained and untrained visual hemifields separately. Following training, participants improved their ability to discriminate motion direction in the trained hemifield and, to a lesser extent, in the untrained hemifield. The amount of task learning correlated positively with the change in activity in the medial superior temporal (MST) area. MST is the anterior portion of the human motion complex (hMT+). MST changes were localized to the hemisphere contralateral to the region of the visual field, where perceptual training was delivered. Visual areas V2 and V3a showed an increase in activity between the first and second scan in the training group, but this was not correlated with performance. The contralateral anterior hippocampus and bilateral dorsolateral prefrontal cortex (DLPFC) and frontal pole showed changes in neural activity that also correlated with the amount of task learning. These findings emphasize the importance of MST in perceptual learning of a visual motion task. Hum Brain Mapp 39:145–156, 2018. © 2017 Wiley Periodicals, Inc. PMID:28963815

EDITORIAL: MST Best Paper Award for 2003

NASA Astrophysics Data System (ADS)

Gill, Patrick

2004-09-01

For the last 12 years, Measurement Science and Technology has awarded a Best Paper prize. The Editorial Board of the journal believes that such a prize is an opportunity to thank authors for submitting their work, and serves as an integral part of the on-going quality review of the journal. An Editorial Board working party, comprising Patrick Gill (Chairman), Ralph Tatam and David Birch, was convened to determine a single contributed paper describing new and significant work, well aligned with the measurement scope of the journal, and presented in clear and rigorous form. They received a number of recommendations from the Editorial and International Advisory Board Members, and they would like to record their thanks to the Members for these recommendations, as they form an all-important first stage in the assessment process. There were responses from some 12 Board Members. In total, there were 31 papers nominated. To aid the process, additional information in the form of the 2003 MST papers top rated by referees, and the top papers ranked by most electronic accesses, was accessed. Reviews, and papers which included a Board Member as an author, were automatically excluded. From the totality of nominations and working party deliberations, there emerged a clear winner. Thus the paper recommended by the working party for the MST Best Paper Award for 2003 is: 'Extension of the torsional crystal viscometer to measurements in the time domain' by Richard F Hafer and Arno Laesecke, 14 663-673 (2003) This paper describes a significant advance in viscosity measurement using torsional vibration in piezoelectric rods. The method reported here demonstrates the use of free-decay time-domain measurements as opposed to the more established steady-state forced-mode resonance technique. The time domain technique is faster and more sensitive, with the potential for improved accuracy due to the lack of large time constants necessary for the interpretation of forced mode data. It offers

Increase in MST activity correlates with visual motion learning: A functional MRI study of perceptual learning.

PubMed

Larcombe, Stephanie J; Kennard, Chris; Bridge, Holly

2018-01-01

Repeated practice of a specific task can improve visual performance, but the neural mechanisms underlying this improvement in performance are not yet well understood. Here we trained healthy participants on a visual motion task daily for 5 days in one visual hemifield. Before and after training, we used functional magnetic resonance imaging (fMRI) to measure the change in neural activity. We also imaged a control group of participants on two occasions who did not receive any task training. While in the MRI scanner, all participants completed the motion task in the trained and untrained visual hemifields separately. Following training, participants improved their ability to discriminate motion direction in the trained hemifield and, to a lesser extent, in the untrained hemifield. The amount of task learning correlated positively with the change in activity in the medial superior temporal (MST) area. MST is the anterior portion of the human motion complex (hMT+). MST changes were localized to the hemisphere contralateral to the region of the visual field, where perceptual training was delivered. Visual areas V2 and V3a showed an increase in activity between the first and second scan in the training group, but this was not correlated with performance. The contralateral anterior hippocampus and bilateral dorsolateral prefrontal cortex (DLPFC) and frontal pole showed changes in neural activity that also correlated with the amount of task learning. These findings emphasize the importance of MST in perceptual learning of a visual motion task. Hum Brain Mapp 39:145-156, 2018. © 2017 Wiley Periodicals, Inc. © 2017 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

Spatial Attention Reduces Burstiness in Macaque Visual Cortical Area MST

PubMed Central

Xue, Cheng; Kaping, Daniel; Ray, Sonia Baloni; Krishna, B. Suresh; Treue, Stefan

2017-01-01

Abstract Visual attention modulates the firing rate of neurons in many primate cortical areas. In V4, a cortical area in the ventral visual pathway, spatial attention has also been shown to reduce the tendency of neurons to fire closely separated spikes (burstiness). A recent model proposes that a single mechanism accounts for both the firing rate enhancement and the burstiness reduction in V4, but this has not been empirically tested. It is also unclear if the burstiness reduction by spatial attention is found in other visual areas and for other attentional types. We therefore recorded from single neurons in the medial superior temporal area (MST), a key motion-processing area along the dorsal visual pathway, of two rhesus monkeys while they performed a task engaging both spatial and feature-based attention. We show that in MST, spatial attention is associated with a clear reduction in burstiness that is independent of the concurrent enhancement of firing rate. In contrast, feature-based attention enhances firing rate but is not associated with a significant reduction in burstiness. These results establish burstiness reduction as a widespread effect of spatial attention. They also suggest that in contrast to the recently proposed model, the effects of spatial attention on burstiness and firing rate emerge from different mechanisms. PMID:28365773

Overview of MST Research

NASA Astrophysics Data System (ADS)

Sarff, J. S.; MST Team

2011-10-01

MST progress in advancing the RFP for (1) fusion plasma confinement with minimal external magnetization, (2) toroidal confinement physics, and (3) basic plasma physics is summarized. New tools and diagnostics are accessing physics barely studied in the RFP. Several diagnostic advances are important for ITER/burning plasma. A 1 MW neutral beam injector operates routinely for fast ion, heating, and transport investigations. Energetic ions are also created spontaneously by tearing mode reconnection, reminiscent of astrophysical plasmas. Classical confinement of impurity ions is measured in reduced-tearing plasmas. Fast ion slowing-down is also classical. Alfven-eigenmode-like activity occurs with NBI, but apparently not TAE. Stellarator-like helical structure appears in the core of high current plasmas, with improved confinement characteristics. FIR interferometry, Thomson scattering, and HIBP diagnostics are beginning to explore microturbulence scales, an opportunity to exploit the RFP's high beta and strong magnetic shear parameter space. A programmable power supply for the toroidal field flexibly explores scenarios from advanced inductive profile control to low current tokamak operation. A 1 MW 5.5 GHz source for electron Bernstein wave injection is nearly complete to investigate heating and current drive in over-dense plasmas. Supported by DOE and NSF.

Long-term youth criminal outcomes in MST transport: the impact of therapist adherence and organizational climate and structure.

PubMed

Schoenwald, Sonja K; Chapman, Jason E; Sheidow, Ashli J; Carter, Rickey E

2009-01-01

This study investigated relations among therapist adherence to an evidence-based treatment for youth with serious antisocial behavior (i.e., Multisystemic Therapy), organizational climate and structure, and youth criminal charges on average 4 years posttreatment. Participants were 1,979 youth and families treated by 429 therapists across 45 provider organizations. Results showed therapist adherence predicted significantly lower rates of youth criminal charges independently and in the presence of organizational variables. Therapist perceptions of job satisfaction and opportunities for growth and advancement relative to the organizational average predicted youth criminal charges, as did organizational average levels of participation in decision making. These associations washed out in the presence of adherence, despite the fact that job satisfaction and growth and advancement were associated with adherence.

Long-Term Youth Criminal Outcomes in MST Transport: The Impact of Therapist Adherence and Organizational Climate and Structure

PubMed Central

Schoenwald, Sonja K.; Chapman, Jason E.; Sheidow, Ashli J.; Carter, Rickey E.

2010-01-01

The current study investigated relations among therapist adherence to an evidence-based treatment for youth with serious antisocial behavior (i.e., Multisystemic Therapy), organizational climate and structure, and youth criminal charges on average 4 years post-treatment. Participants were 1979 youth and families treated by 429 therapists across 45 provider organizations. Results showed therapist adherence predicted significantly lower rates of youth criminal charges independently and in the presence of organizational variables. Therapist perceptions of job satisfaction and opportunities for growth and advancement relative to the organizational average predicted youth criminal charges, as did organizational average levels of participation in decision-making. These associations washed out in the presence of adherence, despite the fact that job satisfaction and growth and advancement were associated with adherence. PMID:19130360

Music supported therapy promotes motor plasticity in individuals with chronic stroke.

PubMed

Ripollés, P; Rojo, N; Grau-Sánchez, J; Amengual, J L; Càmara, E; Marco-Pallarés, J; Juncadella, M; Vaquero, L; Rubio, F; Duarte, E; Garrido, C; Altenmüller, E; Münte, T F; Rodríguez-Fornells, A

2016-12-01

Novel rehabilitation interventions have improved motor recovery by induction of neural plasticity in individuals with stroke. Of these, Music-supported therapy (MST) is based on music training designed to restore motor deficits. Music training requires multimodal processing, involving the integration and co-operation of visual, motor, auditory, affective and cognitive systems. The main objective of this study was to assess, in a group of 20 individuals suffering from chronic stroke, the motor, cognitive, emotional and neuroplastic effects of MST. Using functional magnetic resonance imaging (fMRI) we observed a clear restitution of both activity and connectivity among auditory-motor regions of the affected hemisphere. Importantly, no differences were observed in this functional network in a healthy control group, ruling out possible confounds such as repeated imaging testing. Moreover, this increase in activity and connectivity between auditory and motor regions was accompanied by a functional improvement of the paretic hand. The present results confirm MST as a viable intervention to improve motor function in chronic stroke individuals.

Multisystemic Disease Modeling of Liver-Derived Protein Folding Disorders Using Induced Pluripotent Stem Cells (iPSCs).

PubMed

Leung, Amy; Murphy, George J

2016-01-01

Familial transthyretin amyloidosis (ATTR) is an autosomal dominant protein-folding disorder caused by over 100 distinct mutations in the transthyretin (TTR) gene. In ATTR, protein secreted from the liver aggregates and forms fibrils in target organs, chiefly the heart and peripheral nervous system, highlighting the need for a model capable of recapitulating the multisystem complexity of this clinically variable disease. Here, we describe detailed methodologies for the directed differentiation of protein folding disease-specific iPSCs into hepatocytes that produce mutant protein, and neural-lineage cells often targeted in disease. Methodologies are also described for the construction of multisystem models and drug screening using iPSCs.

The ARC organizational and community intervention strategy for implementing evidence-based children's mental health treatments.

PubMed

Glisson, Charles; Schoenwald, Sonja K

2005-12-01

This paper reviews the implications of organizational and community intervention research for the implementation of effective mental health treatments in usual community practice settings. The paper describes an organizational and community intervention model named ARC for Availability, Responsiveness and Continuity, that was designed to support the improvement of social and mental health services for children. The ARC model incorporates intervention components from organizational development, interorganizational domain development, the diffusion of innovation, and technology transfer that target social, strategic, and technological factors in effective children's services. This paper also describes a current NIMH-funded study that is using the ARC intervention model to support the implementation of an evidence-based treatment, Multisystemic Therapy (MST), for delinquent youth in extremely rural, impoverished communities in the Appalachian Mountains of East Tennessee.

MST Pellet Injector Upgrades to Probe Beta and Density Limits and Impurity Particle Transport

NASA Astrophysics Data System (ADS)

Caspary, K. J.; Chapman, B. E.; Anderson, J. K.; Kumar, S. T. A.; Limbach, S. T.; Oliva, S. P.; Sarff, J. S.; Waksman, J.; Combs, S. K.; Foust, C. R.

2012-10-01

Upgrades to the pellet injector on MST will allow for significantly increased fueling capability enabling density limit studies for previously unavailable density regimes. Thus far, Greenwald fractions of 1.2 and 1.5 have been achieved in 500 kA and 200 kA improved confinement plasmas, respectively. The size of the pellet guide tubes, which constrain the lateral motion of the pellet in flight, was increased to accommodate pellets of up to 4.0 mm in diameter, capable of fueling to Greenwald fractions > 2.0 for MST's peak current of 600 kA. Exploring the effect of increased density on NBI deposition shows that for MST's NBI, core deposition of 25 keV neutrals is optimized for densities of 2 -- 3 x 10^19 m-3. This is key for beta limit studies in pellet fueled discharges with improved confinement where maximum NBI heating is desired. In addition, a modification to the injector has allowed operation using alternative pellet fuels with triple points significantly higher than that of deuterium (18.7 K). A small flow of helium into the pellet formation vacuum chamber introduces a controllable heat source capable of elevating the operating temperature of the injector. Injection of methane pellets with a triple point of 90.7 K results in a 12-fold increase in the core carbon impurity density. The flow rate is easily adjusted to optimize injector operating temperature for other fuel gases as well. Work supported by US DoE.

An Open and Shut Case: The Interaction of Magnesium with MST Enzymes

PubMed Central

2016-01-01

The shikimate pathway of bacteria, fungi, and plants generates chorismate, which is drawn into biosynthetic pathways that form aromatic amino acids and other important metabolites, including folates, menaquinone, and siderophores. Many of the pathways initiated at this branch point transform chorismate using an MST enzyme. The MST enzymes (menaquinone, siderophore, and tryptophan biosynthetic enzymes) are structurally homologous and magnesium-dependent, and all perform similar chemical permutations to chorismate by nucleophilic addition (hydroxyl or amine) at the 2-position of the ring, inducing displacement of the 4-hydroxyl. The isomerase enzymes release isochorismate or aminodeoxychorismate as the product, while the synthase enzymes also have lyase activity that displaces pyruvate to form either salicylate or anthranilate. This has led to the hypothesis that the isomerase and lyase activities performed by the MST enzymes are functionally conserved. Here we have developed tailored pre-steady-state approaches to establish the kinetic mechanisms of the isochorismate and salicylate synthase enzymes of siderophore biosynthesis. Our data are centered on the role of magnesium ions, which inhibit the isochorismate synthase enzymes but not the salicylate synthase enzymes. Prior structural data have suggested that binding of the metal ion occludes access or egress of substrates. Our kinetic data indicate that for the production of isochorismate, a high magnesium ion concentration suppresses the rate of release of product, accounting for the observed inhibition and establishing the basis of the ordered-addition kinetic mechanism. Moreover, we show that isochorismate is channeled through the synthase reaction as an intermediate that is retained in the active site by the magnesium ion. Indeed, the lyase-active enzyme has 3 orders of magnitude higher affinity for the isochorismate complex relative to the chorismate complex. Apparent negative-feedback inhibition by ferrous

Transfusion-transmitted malaria masquerading as sickle cell crisis with multisystem organ failure.

PubMed

Maier, Cheryl L; Gross, Phillip J; Dean, Christina L; Chonat, Satheesh; Ip, Andrew; McLemore, Morgan; El Rassi, Fuad; Stowell, Sean R; Josephson, Cassandra D; Fasano, Ross M

2018-06-01

Fever accompanying vaso-occlusive crisis is a common presentation in patients with sickle cell disease (SCD) and carries a broad differential diagnosis. Here, we report a case of transfusion-transmitted malaria in a patient with SCD presenting with acute vaso-occlusive crisis and rapidly decompensating to multisystem organ failure (MSOF). An 18-year-old African American male with SCD was admitted after multiple days of fever and severe generalized body pain. He received monthly blood transfusions as stroke prophylaxis. A source of infection was not readily identified, but treatment was initiated with continuous intravenous fluids and empiric antibiotics. The patient developed acute renal failure, acute hypoxic respiratory failure, and shock. He underwent red blood cell (RBC) exchange transfusion followed by therapeutic plasma exchange and continuous veno-venous hemodialysis. A manual peripheral blood smear revealed intraerythrocytic inclusions suggestive of Plasmodium, and molecular studies confirmed Plasmodium falciparum infection. Intravenous artesunate was given daily for 1 week. A look-back investigation involving two hospitals, multiple blood suppliers, and state and federal public health departments identified the source of malaria as a unit of RBCs transfused 2 weeks prior to admission. Clinical suspicion for transfusion-related adverse events, including hemolytic transfusion reactions and transfusion-transmitted infections, should be high in typically and atypically immunocompromised patient populations (like SCD), especially those on chronic transfusion protocols. Manual blood smear review aids in the evaluation of patients with SCD presenting with severe vaso-occlusive crisis and MSOF and can alert clinicians to the need for initiating aggressive therapy like RBC exchange and artesunate therapy. © 2018 AABB.

Fluctuation reduction and enhanced confinement in the MST reversed-field pinch

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chapman, Brett Edward

1997-10-01

Plasmas with a factor of ≥3 improvement in energy confinement have been achieved in the MST reversed-field pinch (RFP). These plasmas occur spontaneously, following sawtooth crashes, subject to constraints on, eg, toroidal magnetic field reversal and wall conditioning. Possible contributors to the improved confinement include a reduction of core-resonant, global magnetic fluctuations and a reduction of electrostatic fluctuations over the entire plasma edge. One feature of these plasmas is a region of strong ExB flow shear in the edge. Never before observed in conjunction with enhanced confinement in the RFP, such shear is common in enhanced confinement discharges in tokamaks and stellarators. Another feature of these plasmas is a new type of discrete dynamo event. Like sawtooth crashes, a common form of discrete dynamo, these events correspond to bursts of edge parallel current. The reduction of electrostatic fluctuations in these plasmas occurs within and beyond the region of strong ExB flow shear, similar to what is observed in tokamaks and stellarators. However, the reductions in the MST include fluctuations whose correlation lengths are larger than the width of the shear region. The reduction of the global magnetic fluctuations is most likely due to flattening of the μ=μ 0more » $$\\vec{J}$$∙$$\\vec{B}$$/B 2 profile. Flattening can occur, eg, due to the new type of discrete dynamo event and reduced edge resistivity. Enhanced confinement plasmas are also achieved in the MST when auxiliary current is applied to flatten the μ profile and reduce magnetic fluctuations. Unexpectedly, these plasmas also exhibit a region (broader than in the case above) of strong ExB flow shear in the edge, an edge-wide reduction of electrostatic fluctuations, and the new type of discrete dynamo event. Auxiliary current drive has historically been viewed as the principal route to fusion reactor viability for the RFP.« less

RON (MST1R) is a novel prognostic marker and therapeutic target for gastroesophageal adenocarcinoma

PubMed Central

Catenacci, Daniel VT; Cervantes, Gustavo; Yala, Soheil; Nelson, Erik A; El-Hashani, Essam; Kanteti, Rajani; El Dinali, Mohamed; Hasina, Rifat; Brägelmann, Johannes; Seiwert, Tanguy; Sanicola, Michele; Henderson, Les; Grushko, Tatyana A; Olopade, Olufunmilayo; Karrison, Theodore; Bang, Yung-Jue; Ho Kim, Woo; Tretiakova, Maria; Vokes, Everett; Frank, David A; Kindler, Hedy L; Huet, Heather

2011-01-01

RON (MST1R) is one of two members of the MET receptor tyrosine kinase family, along with parent receptor MET. RON has a putative role in several cancers, but its expression and function is poorly characterized in gastroesophageal adenocarcinoma. A recognized functional role of MET tyrosine kinase in gastroesophageal cancer has led to early phase clinical trials using MET inhibitors, with unimpressive results. Therefore, the role of RON in gastroesophageal cancer, as well as its role in cooperative signaling with MET and as a mechanism of resistance to MET inhibition, was studied in gastroesophageal tissues and cell lines. By IHC, RON was highly overexpressed in 74% of gastroesophageal samples (n = 94) and overexpression was prognostic of poor survival (p = 0.008); RON and MET co-expression occurred in 43% of samples and was prognostic of worst survival (p = 0.03). High MST1R gene copy number by quantitative polymerase chain reaction and confirmed by fluorescence in situ hybridization and/or array comparative genomic hybridization, was seen in 35.5% (16/45) of cases. High MST1R gene copy number correlated with poor survival (p = 0.01), and was associated with high MET and ERBB2 gene copy number. a novel somatic MST1R juxtamembrane mutation R1018G was found in 11% of samples. RON signaling was functional in cell lines, activating downstream effector STAT3, and resulted in increased viability over controls. RON and MET co-stimulation assays led to enhanced malignant phenotypes over stimulation of either receptor alone. Growth inhibition as evidenced by viability and apoptosis assays was optimal using novel blocking monoclonal antibodies to both ROn and MET, versus either alone. SU11274, a classic MET small molecule tyrosine kinase inhibitor, blocked signaling of both receptors and proved synergistic when combined with STAT3 inhibition (combination index <1). These preclinical studies define RON as an important novel prognostic marker and therapeutic target for

Spatial Attention Reduces Burstiness in Macaque Visual Cortical Area MST.

PubMed

Xue, Cheng; Kaping, Daniel; Ray, Sonia Baloni; Krishna, B Suresh; Treue, Stefan

2017-01-01

Visual attention modulates the firing rate of neurons in many primate cortical areas. In V4, a cortical area in the ventral visual pathway, spatial attention has also been shown to reduce the tendency of neurons to fire closely separated spikes (burstiness). A recent model proposes that a single mechanism accounts for both the firing rate enhancement and the burstiness reduction in V4, but this has not been empirically tested. It is also unclear if the burstiness reduction by spatial attention is found in other visual areas and for other attentional types. We therefore recorded from single neurons in the medial superior temporal area (MST), a key motion-processing area along the dorsal visual pathway, of two rhesus monkeys while they performed a task engaging both spatial and feature-based attention. We show that in MST, spatial attention is associated with a clear reduction in burstiness that is independent of the concurrent enhancement of firing rate. In contrast, feature-based attention enhances firing rate but is not associated with a significant reduction in burstiness. These results establish burstiness reduction as a widespread effect of spatial attention. They also suggest that in contrast to the recently proposed model, the effects of spatial attention on burstiness and firing rate emerge from different mechanisms. © The Author 2016. Published by Oxford University Press.

Two-fluid Magnetic Relaxation in the MST Reversed Field Pinch

NASA Astrophysics Data System (ADS)

Triana, Joseph; Almagri, Af; McCollam, Kj; Sarff, Js; Sovinec, Cr

2016-10-01

Recent measurements and extended MHD simulations expose the importance of two-fluid physics in the relaxation and self-organization of the current and momentum profiles in RFP plasmas. A hallmark of relaxation is that the inductive electric field is not balanced by resistive dissipation, prompting the study of fluctuation-induced emfs in the generalized Ohm's law, E- ηJ =- +/ne, the two terms on the right known as the MHD and Hall dynamo terms, respectively. The Hall emf is measured in the outer half of the MST plasma minor radius using an armored deep-insertion probe. The emf matches previous measurements in the edge (r/a>0.8) but in the new region examined (0.8>r/a>0.6) it is much larger than E- ηJ, implying the MHD dynamo must also be large and oppositely directed. Recent nonlinear simulations that include two-fluid effects using the extended-MHD NIMROD code show complex radial structure for the emf terms, but the size of the measured Hall emf is much larger than predicted by the simulations. In the two-fluid model, the Hall dynamo couples to the parallel momentum as the mean-field Maxwell stress. The simulations predict relaxation of the parallel flow profiles that is also qualitatively consistent with measurements in MST plasmas. Work supported by US DoE and NSF.

Mammalian Sterile 20-like Kinase 1 (Mst1) Enhances the Stability of Forkhead Box P3 (Foxp3) and the Function of Regulatory T Cells by Modulating Foxp3 Acetylation.

PubMed

Li, Jiang; Du, Xingrong; Shi, Hao; Deng, Kejing; Chi, Hongbo; Tao, Wufan

2015-12-25

Regulatory T cells (Tregs) play crucial roles in maintaining immune tolerance. The transcription factor Foxp3 is a critical regulator of Treg development and function, and its expression is regulated at both transcriptional and post-translational levels. Acetylation by lysine acetyl transferases/lysine deacetylases is one of the main post-translational modifications of Foxp3, which regulate Foxp3's stability and transcriptional activity. However, the mechanism(s) by which the activities of these lysine acetyl transferases/lysine deacetylases are regulated to preserve proper Foxp3 acetylation during Treg development and maintenance of Treg function remains to be determined. Here we report that Mst1 can enhance Foxp3 stability, its transcriptional activity, and Treg function by modulating the Foxp3 protein at the post-translational level. We discovered that Mst1 could increase the acetylation of Foxp3 by inhibiting Sirt1 activity, which requires the Mst1 kinase activity. We also found that Mst1 could attenuate Sirt1-mediated deacetylation of Foxp3 through directly interacting with Foxp3 to prevent or interfere the interaction between Sirt1 and Foxp3. Therefore, Mst1 can regulate Foxp3 stability in kinase-dependent and kinase-independent manners. Finally, we showed that treatment of Mst1(-/-) Tregs with Ex-527, a Sirt1-specific inhibitor, partially restored the suppressive function of Mst1(-/-) Tregs. Our studies reveal a novel mechanism by which Mst1 enhances Foxp3 expression and Treg function at the post-translational level. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

The effects of music-supported therapy on motor, cognitive, and psychosocial functions in chronic stroke.

PubMed

Fujioka, Takako; Dawson, Deirdre R; Wright, Rebecca; Honjo, Kie; Chen, Joyce L; Chen, J Jean; Black, Sandra E; Stuss, Donald T; Ross, Bernhard

2018-05-24

Neuroplasticity accompanying learning is a key mediator of stroke rehabilitation. Training in playing music in healthy populations and patients with movement disorders requires resources within motor, sensory, cognitive, and affective systems, and coordination among these systems. We investigated effects of music-supported therapy (MST) in chronic stroke on motor, cognitive, and psychosocial functions compared to conventional physical training (GRASP). Twenty-eight adults with unilateral arm and hand impairment were randomly assigned to MST (n = 14) and GRASP (n = 14) and received 30 h of training over a 10-week period. The assessment was conducted at four time points: before intervention, after 5 weeks, after 10 weeks, and 3 months after training completion. As for two of our three primary outcome measures concerning motor function, all patients slightly improved in Chedoke-McMaster Stroke Assessment hand score, while the time to complete Action Research Arm Test became shorter in the MST group. The third primary outcome measure for well-being, Stroke Impact Scale, was improved for emotion and social communication earlier in MST and coincided with the improved executive function for task switching and music rhythm perception. The results confirmed previous findings and expanded the potential usage of MST for enhancing quality of life in community-dwelling chronic-stage survivors. © 2018 New York Academy of Sciences.

Anti-proliferative effects, cell cycle G2/M phase arrest and blocking of chromosome segregation by probimane and MST-16 in human tumor cell lines

PubMed Central

Lu, Da Yong; Huang, Min; Xu, Cheng Hui; Yang, Wei Yi; Hu, Chao Xin; Lin, Li Ping; Tong, Lin Jiang; Li, Mei Hong; Lu, Wei; Zhang, Xiong Wen; Ding, Jian

2005-01-01

Background Anticancer bisdioxopiperazines, including ICRF-154, razoxane (Raz, ICRF-159) and ICRF-193, are a family of anticancer agents developed in the UK, especially targeting metastases of neoplasms. Two other bisdioxopiperazine derivatives, probimane (Pro) and MST-16, were synthesized at the Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China. Cytotoxic activities and mechanisms of Raz (+)-steroisomer (ICRF-187, dexrazoxane), Pro and MST-16 against tumor cells were evaluated by MTT colorimetry, flow cytometry and karyotyping. Results Pro was cytotoxic to human tumor cell lines in vitro (IC50<50 μM for 48 h). Four human tumor cell lines (SCG-7901, K562, A549 and HL60) were susceptible to Pro at low inhibitory concentrations (IC50 values < 10 μM for 48 h). Although the IC50 against HeLa cell line of vincristine (VCR, 4.56 μM), doxorubicin (Dox, 1.12 μM) and 5-fluoruouracil (5-Fu, 0.232 μM) are lower than Pro (5.12 μM), ICRF-187 (129 μM) and MST-16 (26.4 μM), VCR, Dox and 5-Fu shows a low dose-related – high cytotoxic activity. Time-response studies showed that the cytotoxic effects of Pro are increased for 3 days in human tumor cells, whereas VCR, Dox and 5-Fu showed decreased cytotoxic action after 24 h. Cell cycle G2/M phase arrest and chromosome segregation blocking by Pro and MST-16 were noted. Although there was similar effects of Pro and MST-16 on chromosome segregation blocking action and cell cycle G2/M phase arrest at 1- 4 μM, cytotoxicity of Pro against tumor cells was higher than that of MST-16 in vitro by a factor of 3- 10 folds. Our data show that Pro may be more effective against lung cancer and leukemia while ICRF-187 and MST-16 shows similar IC50 values only against leukemia. Conclusion It suggests that Pro has a wider spectrum of cytotoxic effects against human tumor cells than other bisdioxopiperazines, especially against solid tumors, and with a single cytotoxic pathway of Pro and MST-16 affecting

Runaway electrons and mitigation studies in MST tokamak plasmas

NASA Astrophysics Data System (ADS)

Goetz, J. A.; Chapman, B. E.; Almagri, A. F.; Cornille, B. S.; Dubois, A.; McCollam, K. J.; Munaretto, S.; Sovinec, C. R.

2016-10-01

Studies of runaway electrons generated in low-density MST tokamak plasmas are being undertaken. The plasmas have Bt <= 0.14 T, Ip <= 50 kA, q (a) = 2.2 , and an electron density and temperature of about 5 ×1017m-3 and 150 eV. Runaway electrons are detected via x-ray bremsstrahlung emission. The density and electric field thresholds for production and suppression have been previously explored with variations in gas puffing for density control. Runaway electrons are now being probed with resonant magnetic perturbations (RMP's). An m = 3 RMP strongly suppresses the runaway electrons and initial NIMROD modeling shows that this may be due to degradation of flux surfaces. The RMP is produced by a poloidal array of 32 saddle coils at the narrow vertical insulated cut in MST's thick conducting shell, with each RMP having a single m but a broad n spectrum. While a sufficiently strong m = 3 RMP suppresses the runaway electrons, an RMP with m = 1 and comparable amplitude has little effect. The impact of the RMP's on the magnetic topology of these plasmas is being studied with the nonlinear MHD code NIMROD. With an m = 3 RMP, stochasticity is introduced in the outer third of the plasma but no such flux surface degradation is observed with an m = 1 RMP. NIMROD also predicts regularly occurring MHD activity similar to that observed in the experiment. These studies have also been done in q (a) = 2.7 plasmas and analysis and modeling is ongoing. This work supported by USDoE.

Quantitative Simulations of MST Visual Receptive Field Properties Using a Template Model of Heading Estimation

NASA Technical Reports Server (NTRS)

Stone, Leland S.; Perrone, J. A.

1997-01-01

We previously developed a template model of primate visual self-motion processing that proposes a specific set of projections from MT-like local motion sensors onto output units to estimate heading and relative depth from optic flow. At the time, we showed that that the model output units have emergent properties similar to those of MSTd neurons, although there was little physiological evidence to test the model more directly. We have now systematically examined the properties of the model using stimulus paradigms used by others in recent single-unit studies of MST: 1) 2-D bell-shaped heading tuning. Most MSTd neurons and model output units show bell-shaped heading tuning. Furthermore, we found that most model output units and the finely-sampled example neuron in the Duffy-Wurtz study are well fit by a 2D gaussian (sigma approx. 35deg, r approx. 0.9). The bandwidth of model and real units can explain why Lappe et al. found apparent sigmoidal tuning using a restricted range of stimuli (+/-40deg). 2) Spiral Tuning and Invariance. Graziano et al. found that many MST neurons appear tuned to a specific combination of rotation and expansion (spiral flow) and that this tuning changes little for approx. 10deg shifts in stimulus placement. Simulations of model output units under the same conditions quantitatively replicate this result. We conclude that a template architecture may underlie MT inputs to MST.

Childhood abuse, parental warmth, and adult multisystem biological risk in the Coronary Artery Risk Development in Young Adults study.

PubMed

Carroll, Judith E; Gruenewald, Tara L; Taylor, Shelley E; Janicki-Deverts, Denise; Matthews, Karen A; Seeman, Teresa E

2013-10-15

Childhood abuse increases adult risk for morbidity and mortality. Less clear is how this "toxic" stress becomes embedded to influence health decades later, and whether protective factors guard against these effects. Early biological embedding is hypothesized to occur through programming of the neural circuitry that influences physiological response patterns to subsequent stress, causing wear and tear across multiple regulatory systems. To examine this hypothesis, we related reports of childhood abuse to a comprehensive 18-biomarker measure of multisystem risk and also examined whether presence of a loving parental figure buffers against the impact of childhood abuse on adult risk. A total of 756 subjects (45.8% white, 42.7% male) participated in this ancillary substudy of the Coronary Artery Risk Development in Young Adults Study. Childhood stress was determined by using the Risky Families Questionnaire, a well-validated retrospective self-report scale. Linear regression models adjusting for age, sex, race, parental education, and oral contraceptive use found a significant positive relationship between reports of childhood abuse and multisystem health risks [B (SE) = 0.68 (0.16); P < 0.001]. Inversely, higher amounts of reported parental warmth and affection during childhood was associated with lower multisystem health risks [B (SE) = -0.40 (0.14); P < 0.005]. A significant interaction of abuse and warmth (P < 0.05) was found, such that individuals reporting low levels of love and affection and high levels of abuse in childhood had the highest multisystem risk in adulthood.

Measurements of Impurity Particle Transport Associated with Drift-Wave Turbulence in MST

NASA Astrophysics Data System (ADS)

Nishizawa, Takashi; Nornberg, Mark; Boguski, John; Craig, Darren; den Hartog, Daniel; Pueschel, M. J.; Sarff, John; Terry, Paul; Williams, Zach; Xing, Zichuan

2017-10-01

Understanding and controlling impurity transport in a toroidal magnetized plasma is one of the critical issues that need to be addressed in order to achieve controlled fusion. Gyrokinetic modeling shows turbulence can drive impurity transport, but direct measurements of the turbulent flux have not been made. Particle balance is typically used to infer the presence of turbulent impurity transport. We report, for the first time in a toroidal plasma, direct measurements of turbulence-driven impurity transport. Trapped electron mode (TEM) turbulence appears in MST plasmas when MHD tearing fluctuations are suppressed. Impurity ion-Doppler spectroscopy is used to correlate impurity density and radial velocity fluctuations associated with TEM. Small Doppler shifts associated with the radial velocity fluctuations (rms 1km/s) are resolved with the use of a new linearized spectrum correlation analysis method, which improves the rejection of Poisson noise. The method employs frequency-domain correlation analysis to expose the fluctuation and transport spectrum. The C+ 2 impurity transport velocity driven by turbulence is found to be 48m/s (inward), which is sufficiently large to impact an impurity flux balance in MST improved-confinement plasmas. This work is supported by the US DOE.

Observation of Electron Bernstein Wave Heating in the MST Reversed Field Pinch

NASA Astrophysics Data System (ADS)

Seltzman, Andrew; Anderson, Jay; Dubois, Ami; Almagri, Abdulgader; Nonn, Paul; McCollam, Karsten; Chapman, Brett; Goetz, John; Forest, Cary

2016-10-01

We report the first observation of electron Bernstein wave heating in the MST RFP. Similar to a high density stellarator, the RFP is inaccessible to electromagnetic ECRH. The plasma current and |B|operating range of MST allows a 5.5 GHz RF source (100kW, 4ms pulse) to heat on the fundamental and up to 4th harmonic EC resonances. With an x-ray diagnostic most sensitive to edge electrons located +12 degrees toroidally from the antenna, the measured emission is a strong function of predicted heating inside versus outside the Bt =0 reversal layer of the RFP. Measured during a scan of plasma current, distinct edges in a plot of emissivity versus predicted deposition layer align with the deposition layers crossing of this reversal layer and confirm EBW heating on the fundamental through 4th EC harmonic. Additional confirmation of the absorption location has been demonstrated by using auxiliary poloidal current drive to reduce electron diffusion rates and sweep the location of the Bt =0 surface across a static RF absorption location in RFP discharges. In these discharges EBW enhancement of the 15-40keV x-ray energies has been observed. Work supported by USDOE.

Amyotrophic Lateral Sclerosis, a Multisystem Pathology: Insights into the Role of TNFα

PubMed Central

Tortarolo, Massimo; Lo Coco, Daniele; Veglianese, Pietro; Vallarola, Antonio; Giordana, Maria Teresa; Marcon, Gabriella; Beghi, Ettore; Poloni, Marco; Strong, Michael J.; Iyer, Anand M.; Aronica, Eleonora

2017-01-01

Amyotrophic lateral sclerosis (ALS) is considered a multifactorial, multisystem disease in which inflammation and the immune system play important roles in development and progression. The pleiotropic cytokine TNFα is one of the major players governing the inflammation in the central nervous system and peripheral districts such as the neuromuscular and immune system. Changes in TNFα levels are reported in blood, cerebrospinal fluid, and nerve tissues of ALS patients and animal models. However, whether they play a detrimental or protective role on the disease progression is still not clear. Our group and others have recently reported opposite involvements of TNFR1 and TNFR2 in motor neuron death. TNFR2 mediates TNFα toxic effects on these neurons presumably through the activation of MAP kinase-related pathways. On the other hand, TNFR2 regulates the function and proliferation of regulatory T cells (Treg) whose expression is inversely correlated with the disease progression rate in ALS patients. In addition, TNFα is considered a procachectic factor with a direct catabolic effect on skeletal muscles, causing wasting. We review and discuss the role of TNFα in ALS in the light of its multisystem nature. PMID:29081600

Recessive mutations in EPG5 cause Vici syndrome, a multisystem disorder with defective autophagy

PubMed Central

Cullup, Thomas; Kho, Ay L.; Dionisi-Vici, Carlo; Brandmeier, Birgit; Smith, Frances; Urry, Zoe; Simpson, Michael A.; Yau, Shu; Bertini, Enrico; McClelland, Verity; Al-Owain, Mohammed; Koelker, Stefan; Koerner, Christian; Hoffmann, Georg F.; Wijburg, Frits A.; Hoedt, Amber E. ten; Rogers, Curtis; Manchester, David; Miyata, Rie; Hayashi, Masaharu; Said, Elizabeth; Soler, Doriette; Kroisel, Peter M.; Windpassinger, Christian; Filloux, Francis M.; Al-Kaabi, Salwa; Hertecant, Jozef; Del Campo, Miguel; Buk, Stefan; Bodi, Istvan; Goebel, Hans-Hilmar; Sewry, Caroline A.; Abbs, Stephen; Mohammed, Shehla; Josifova, Dragana; Gautel, Mathias; Jungbluth, Heinz

2012-01-01

Vici syndrome is a recessively inherited multisystem disorder characterized by callosal agenesis, cataracts, cardiomyopathy, combined immunodeficiency and hypopigmentation. To investigate the molecular basis of Vici syndrome, we carried out exome and Sanger sequence analysis in a cohort of 18 patients. We identified recessive mutations in EPG5 (previously KIAA1632), indicating a causative role in Vici syndrome. EPG5 is the human homologue of the metazoan-specific autophagy gene epg-5, encoding a key autophagy regulator (ectopic P-granules autophagy protein 5) implicated in the formation of autolysosomes. Further studies demonstrated a severe block of autophagosomal clearance in muscle and fibroblasts from EPG5 mutant patients, resulting in autophagic cargo accumulation in autophagosomes. These findings indicate Vici syndrome as a paradigm of a human multisystem disorder associated with defective autophagy, and suggest a fundamental role of the autophagy pathway in the anatomical and functional formation of organs such as the brain, the heart and the immune system. PMID:23222957

36. GENERAL VIEW OF SLC3W MST STATION 85.5 FROM SOUTHEAST ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

36. GENERAL VIEW OF SLC-3W MST STATION 85.5 FROM SOUTHEAST CORNER SHOWING REMOVABLE SAFETY RAILS AROUND CENTRAL OPENING, STRETCH SLING CYLINDER, AND PULLEY ON WEST SIDE, AIR-CONDITIONING DUCTING IN NORTHWEST CORNER, PLATFORM SEGMENTS AND HINGES - Vandenberg Air Force Base, Space Launch Complex 3, Launch Pad 3 West, Napa & Alden Roads, Lompoc, Santa Barbara County, CA

a New Multi-Spectral Threshold Normalized Difference Water Index Mst-Ndwi Water Extraction Method - a Case Study in Yanhe Watershed

NASA Astrophysics Data System (ADS)

Zhou, Y.; Zhao, H.; Hao, H.; Wang, C.

2018-05-01

Accurate remote sensing water extraction is one of the primary tasks of watershed ecological environment study. Since the Yanhe water system has typical characteristics of a small water volume and narrow river channel, which leads to the difficulty for conventional water extraction methods such as Normalized Difference Water Index (NDWI). A new Multi-Spectral Threshold segmentation of the NDWI (MST-NDWI) water extraction method is proposed to achieve the accurate water extraction in Yanhe watershed. In the MST-NDWI method, the spectral characteristics of water bodies and typical backgrounds on the Landsat/TM images have been evaluated in Yanhe watershed. The multi-spectral thresholds (TM1, TM4, TM5) based on maximum-likelihood have been utilized before NDWI water extraction to realize segmentation for a division of built-up lands and small linear rivers. With the proposed method, a water map is extracted from the Landsat/TM images in 2010 in China. An accuracy assessment is conducted to compare the proposed method with the conventional water indexes such as NDWI, Modified NDWI (MNDWI), Enhanced Water Index (EWI), and Automated Water Extraction Index (AWEI). The result shows that the MST-NDWI method generates better water extraction accuracy in Yanhe watershed and can effectively diminish the confusing background objects compared to the conventional water indexes. The MST-NDWI method integrates NDWI and Multi-Spectral Threshold segmentation algorithms, with richer valuable information and remarkable results in accurate water extraction in Yanhe watershed.

Cytomegalovirus Retinitis as a Presenting Feature of Multisystem Disorder: Dyskeratosis Congenita.

PubMed

Parchand, Swapnil; Barwad, Adarsh

2017-01-01

Cytomegalovirus (CMV) retinitis is an opportunistic infection commonly seen in disorders that affect the immune system of the body such as acquired immunodeficiency syndrome and hematological malignancies such as leukemia/lymphoma or organ transplantation. The occurrence of CMV retinitis in the absence of such condition should be thoroughly investigated, as it is a strong indicator of poor immune competence. We here report an interesting case of CMV retinitis as a presenting feature of rare multisystem disorde r "Dyskeratosis congenita."

37. GENERAL VIEW OF SLC3W MST STATION 85.5 FROM NORTHEAST ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

37. GENERAL VIEW OF SLC-3W MST STATION 85.5 FROM NORTHEAST CORNER SHOWING PLATFORM CONTROLS IN SOUTHWEST CORNER, COMMUNICATION STATION AND ELEVATOR ON WEST SIDE. STRETCH SLING CYLINDER PRESSURE GAUGE IN SOUTHWEST CORNER OF STATION 78 VISIBLE THROUGH CENTRAL OPENING. - Vandenberg Air Force Base, Space Launch Complex 3, Launch Pad 3 West, Napa & Alden Roads, Lompoc, Santa Barbara County, CA

Sawtooth-cycle variation of electron temperature in MST, and prospects for improvement of fast Thomson scattering measurements

NASA Astrophysics Data System (ADS)

den Hartog, D. J.

2005-10-01

Initial measurements with the new Thomson scattering diagnostic on MST show a flattening of the Te profile during a sawtooth crash. These measurements were made in standard sawtoothing reversed-field pinch discharges, and show the core temperature dropping from 400 to approximately 150 eV, while the edge rises several-fold. Measurement of Te time dynamics in MST will be advanced by further development of the Thomson scattering diagnostic. In the near term, two independently triggerable lasers will be used to make two Te profile measurements separated by greater than or equal to 100 ns. By varying this separation time over the course of a data ensemble, an initial Te fluctuation spectrum will be produced. In the longer term, a third ``pulse-burst'' laser will be added to the diagnostic system. This laser will produce a burst of 10-30 approximately 1 J Q-switched pulses at repetition frequencies 5-250 kHz. The planned laser system will operate at 1064 nm and is based on existing Nd:YAG systems used to study fluid dynamics [Brian Thurow et al., Appl. Opt. 43, 5064 (2004)]. The burst train of laser pulses will enable the study of Te and ne dynamics in a single MST shot, and with ensembling, will enable correlation of Te and ne fluctuations with other fluctuating quantities.

Acute pancreatitis: a multisystem disease.

PubMed

Agarwal, N; Pitchumoni, C S

1993-06-01

Proteolytic enzymes, lipase, kinins, and other active peptides liberated from the inflamed pancreas convert inflammation of the pancreas, a single-organ disease of the retroperitoneum, to a multisystem disease. Adult respiratory distress syndrome, in addition to being secondary to microvascular thrombosis, may be the result of active phospholipase A (lecithinase), which digests lecithin, a major component of surfactant. Myocardial depression and shock are suspected to be secondary to vasoactive peptides and a myocardial depressant factor. Coagulation abnormalities may range from scattered intravascular thrombosis to severe disseminated intravascular coagulation. Acute renal failure has been explained on the basis of hypovolemia and hypotension. The renin-angiotensin alterations in acute pancreatitis (AP) as mediators of renal failure need to be studied. Metabolic complications include hypocalcemia, hyperlipemia, hyperglycemia, hypoglycemia, and diabetic ketoacidosis, of which hypocalcemia has been long recognized as an indicator of poor prognosis. The pathogenesis of hypocalcemia is multifactorial and includes calcium-soap formation, hormonal imbalances (e.g., parathyroid hormone, calcitonin, glucagon), binding of calcium by free fatty acid-albumin complexes, and intracellular translocation of calcium. Subcutaneous fat necrosis, arthritis, and Purtscher's retinopathy are rare. The various prognostic criteria of AP and other associated laboratory abnormalities are manifestations of systemic effects. Early recognition and appropriated management of these complications have resulted in improved prognosis of severe AP.

Multi-system influences on adolescent risky sexual behavior.

PubMed

Chen, Angela Chia-Chen; Thompson, Elaine Adams; Morrison-Beedy, Dianne

2010-12-01

We examined multi-system influences on risky sexual behavior measured by cumulative sexual risk index and number of nonromantic sexual partners among 4,465 single, sexually experienced adolescents. Hierarchical Poisson regression analyses were conducted with Wave I-II data from the National Longitudinal Study of Adolescent Health. Individual and family factors predicted both outcome measures. Neighborhood set predicted cumulative sexual risk index only, and peer factors predicted the number of nonromantic sexual partners only. School set did not predict either outcome. There were significant associations among risky sexual behavior, drug use, and delinquent behaviors. The results highlight the need for multifaceted prevention programs that address relevant factors related to family, peer and neighborhood influence as well as individual factors among sexually active adolescents. Copyright © 2010 Wiley Periodicals, Inc.

Multisystemic Eosinophilia Resembling Hypereosinophilic Syndrome in a Colony-Bred Owl Monkey (Aotus vociferans)

PubMed Central

Gozalo, Alfonso S; Rosenberg, Helene F; Elkins, William R; Montoya, Enrique J; Weller, Richard E

2009-01-01

In animals, multisystemic eosinophilic disease is a rare condition characterized by eosinophilic and lymphoplasmacytic infiltrates in various organs. This disorder resembles the human disease known as hypereosinophilic syndrome, a condition defined by prolonged peripheral eosinophilia in the absence of recognizable etiology and associated with end-organ damage. In this report we describe a research-naïve, colony-born, juvenile female owl monkey (Aotus vociferans) who presented clinically with severe respiratory distress and histologically with multiple end-organ infiltration with phenotypically mature eosinophils, plasma cells, and lymphocytes. No tumors or infectious agents were noted either macroscopically or microscopically. Cultures from lung samples revealed no bacteria or fungi. Histologic examination of lung, heart, thymus, liver, spleen, kidney, adrenal, pancreas, stomach, small intestine, and colon revealed no migrating nematode larvae, other parasites, or foreign material that might trigger eosinophilia, nor was there any evidence of or history consistent with an allergic etiology. Given that we ruled out most exogenous and endogenous triggers of eosinophilia, the signs, symptoms, and pathologic findings support the diagnosis of multisystemic eosinophilic disease. To our knowledge, this report is the first description of presumptive hypereosinophilic syndrome in a nonhuman primate. PMID:19476722

MS&T'13 Symposium Preview: Metal and Polymer Matrix Composites

NASA Astrophysics Data System (ADS)

Gupta, Nikhil; Paramsothy, Muralidharan

2013-08-01

The Metal and Polymer Matrix Composites symposium at Materials Science & Technology 2013 (MS&T'13) conference is planned to provide a platform to researchers working on various aspects of composite materials and capture the state of the art in this area. The dialogue among leading researchers is expected to provide insight into the future of this field and identify the future directions in terms of research, development, and applications of composite materials. In the 2 day program, the symposium includes 34 presentations, including 10 invited presentations. The contributions have come from 16 different countries including USA, Mexico, Switzerland, India, Egypt, and Singapore.

Advances in Heavy Ion Beam Probe Technology and Operation on MST

NASA Astrophysics Data System (ADS)

Demers, D. R.; Connor, K. A.; Schoch, P. M.; Radke, R. J.; Anderson, J. K.; Craig, D.; den Hartog, D. J.

2003-10-01

A technique to map the magnetic field of a plasma via spectral imaging is being developed with the Heavy Ion Beam Probe on the Madison Symmetric Torus. The technique will utilize two-dimensional images of the ion beam in the plasma, acquired by two CCD cameras, to generate a three-dimensional reconstruction of the beam trajectory. This trajectory, and the known beam ion mass, energy and charge-state, will be used to determine the magnetic field of the plasma. A suitable emission line has not yet been observed since radiation from the MST plasma is both broadband and intense. An effort to raise the emission intensity from the ion beam by increasing beam focus and current has been undertaken. Simulations of the accelerator ion optics and beam characteristics led to a technique, confirmed by experiment, that achieves a narrower beam and marked increase in ion current near the plasma surface. The improvements arising from these simulations will be discussed. Realization of the magnetic field mapping technique is contingent upon accurate reconstruction of the beam trajectory from the camera images. Simulations of two camera CCD images, including the interior of MST, its various landmarks and beam trajectories have been developed. These simulations accept user input such as camera locations, resolution via pixellization and noise. The quality of the images simulated with these and other variables will help guide the selection of viewing port pairs, image size and camera specifications. The results of these simulations will be presented.

Amyotrophic lateral sclerosis with sensory neuropathy: part of a multisystem disorder?

PubMed Central

Isaacs, Jeremy D; Dean, Andrew F; Shaw, Christopher E; Al‐Chalabi, Ammar; Mills, Kerry R; Leigh, P Nigel

2007-01-01

Sensory involvement is thought not to be a feature of amyotrophic lateral sclerosis (ALS). However, in the setting of a specialist motor neuron disease clinic, we have identified five patients with sporadic ALS and a sensory neuropathy for which an alternative cause could not be identified. In three individuals, sensory nerve biopsy was performed, demonstrating axonal loss without features of an alternative aetiology. These findings support the hypothesis that ALS is a multisystem neurodegenerative disorder that may occasionally include sensory neuropathy among its non‐motor features. PMID:17575021

Hippo signaling pathway in liver and pancreas: the potential drug target for tumor therapy.

PubMed

Kong, Delin; Zhao, Yicheng; Men, Tong; Teng, Chun-Bo

2015-02-01

Cell behaviors, including proliferation, differentiation and apoptosis, are intricately controlled during organ development and tissue regeneration. In the past 9 years, the Hippo signaling pathway has been delineated to play critical roles in organ size control, tissue regeneration and tumorigenesis through regulating cell behaviors. In mammals, the core modules of the Hippo signaling pathway include the MST1/2-LATS1/2 kinase cascade and the transcriptional co-activators YAP/TAZ. The activity of YAP/TAZ is suppressed by cytoplasmic retention due to phosphorylation in the canonical MST1/2-LATS1/2 kinase cascade-dependent manner or the non-canonical MST1/2- and/or LATS1/2-independent manner. Hippo signaling pathway, which can be activated or inactivated by cell polarity, contact inhibition, mechanical stretch and extracellular factors, has been demonstrated to be involved in development and tumorigenesis of liver and pancreas. In addition, we have summarized several small molecules currently available that can target Hippo-YAP pathway for potential treatment of hepatic and pancreatic cancers, providing clues for other YAP initiated cancers therapy as well.

On the morphology of the scattering medium as seen by MST/ST radars

NASA Technical Reports Server (NTRS)

Gage, K. S.

1983-01-01

Much is learned about the morphology of the small scale structures of the atmosphere from analysis of echoes observed by MST radars. The use of physical models enables a synthesis of diverse observations. Each model contains an implicit assumption about the nature of the irregularity structure of the medium. A comparison is made between the irregularity structure implicit in several models and what is known about the structure of the medium.

Optimum coding techniques for MST radars

NASA Technical Reports Server (NTRS)

Sulzer, M. P.; Woodman, R. F.

1986-01-01

The optimum coding technique for MST (mesosphere stratosphere troposphere) radars is that which gives the lowest possible sidelobes in practice and can be implemented without too much computing power. Coding techniques are described in Farley (1985). A technique mentioned briefly there but not fully developed and not in general use is discussed here. This is decoding by means of a filter which is not matched to the transmitted waveform, in order to reduce sidelobes below the level obtained with a matched filter. This is the first part of the technique discussed here; the second part consists of measuring the transmitted waveform and using it as the basis for the decoding filter, thus reducing errors due to imperfections in the transmitter. There are two limitations to this technique. The first is a small loss in signal to noise ratio (SNR), which usually is not significant. The second problem is related to incomplete information received at the lowest ranges. An appendix shows a technique for handling this problem. Finally, it is shown that the use of complementary codes on transmission and nonmatched decoding gives the lowest possible sidelobe level and the minimum loss in SNR due to mismatch.

An introduction to the multisystem model of knowledge integration and translation.

PubMed

Palmer, Debra; Kramlich, Debra

2011-01-01

Many nurse researchers have designed strategies to assist health care practitioners to move evidence into practice. While many have been identified as "models," most do not have a conceptual framework. They are unidirectional, complex, and difficult for novice research users to understand. These models have focused on empirical knowledge and ignored the importance of practitioners' tacit knowledge. The Communities of Practice conceptual framework allows for the integration of tacit and explicit knowledge into practice. This article describes the development of a new translation model, the Multisystem Model of Knowledge Integration and Translation, supported by the Communities of Practice conceptual framework.

'"My Land, Your Social Transformation": Conflicts within the Landless People Movement (MST), Rio De Janeiro, Brazil

ERIC Educational Resources Information Center

Caldeira, Rute

2008-01-01

The Brazilian "Movimento dos Trabalhadores Rurais Sem-Terra" (MST) is one of the best-known and most prominent rural social movements. The unequal distribution of land in Brazil, and the neglect of this problem by successive Brazilian governments contributed greatly to the organisation of rural movements striving for the implementation…

[BIPOLAR DISORDER AS A MULTI-SYSTEM ILLNESS].

PubMed

Fenchel, Daphna; Levkovitz, Yechiel; Kotler, Moshe

2017-12-01

Bipolar disorder is a chronic condition, characterized by high distress in patients and high suicide rates (30%). Most patients suffer from medical and other psychiatric comorbidities, which worsen the psychiatric symptoms and decrease the likelihood of remission. More than 70% of bipolar patients have cardio-metabolic symptoms, with higher rates compared to other psychiatric disorders. Cardiovascular disease is the major cause of high mortality rates in these patients, with 1.5-2 fold increased risk of mortality, compared to the general population without psychiatric symptoms. The rates of cardiovascular risk factors and their resulting increased mortality rates are similar to those found in schizophrenia. In addition to cardio-metabolic conditions, 50% of patients with bipolar disorder suffer from other medical symptoms, which are also associated with worse outcomes. Therefore, the current perspective is that bipolar disorder is not only a psychiatric disorder, but rather a multi-system illness, affecting the entire body. The optimal treatment for these patients should include diagnosis, monitoring and treatment of both psychiatric and physical symptoms, which would improve their prognosis.

Reframing the Public in Public Education: The Landless Workers Movement (MST) and Adult Education in Brazil

ERIC Educational Resources Information Center

Thapliyal, Nisha

2013-01-01

Education for rural Brazilians has historically been dominated by two imperatives: human capital and political patronage. For the last four decades, the Landless Workers Movement (MST) have maintained a struggle to democratise public education and democracy itself. In this article, I make a situated analysis of the educational politics of the MST…

Use of low density lipoprotein particle number levels as an aid in statin treatment decisions for intermediate risk patients: a cost-effectiveness analysis.

PubMed

Shiffman, Dov; Arellano, Andre R; Caulfield, Michael P; Louie, Judy Z; Bare, Lance A; Devlin, James J; Melander, Olle

2016-12-07

The 2013 ACC/AHA guideline recommended either no statin therapy or moderate-intensity statin therapy (MST) for intermediate risk patients-those with 5-7.5% 10-year risk and without cardiovascular disease (CVD), hypercholesterolemia or diabetes. The guideline further suggested that the therapy choice be based on patient-clinician discussions of risks and benefits. Since low-density lipoprotein particle (LDL-P) levels were reported to be associated with CVD independently of traditional risk factors in intermediate and low risk patients, we investigated the cost-effectiveness of using LDL-P levels to identify intermediate risk patients likely to benefit from initiating or intensifying statin therapy. We evaluated 5 care strategies for intermediate risk patients. These included the strategies suggested by the guideline: no-statin therapy and MST. We compared each of these strategies to a related strategy that incorporated LDL-P testing. No-statin therapy was compared with the strategy of MST for those with high LDL-P levels and no statin therapy for all other patients (test-and-MST). MST was compared with the strategy of high-intensity statin therapy (HST) for those with high LDL-P levels and MST for all other patients (test-and-HST). We also evaluated the strategy of HST for all. Costs (payer perspective) and utilities were assessed over a 5-year time horizon in a Markov model of 100,000 hypothetical intermediate risk patients. HST dominated all other strategies, costing less and-despite causing 739 more cases of diabetes than did MST-resulting in more quality adjusted life-years (QALYs). For patient-clinician discussions that would otherwise lead to the MST strategy, we found the test-and-HST strategy reduced costs by $4.67 MM and resulted in 134 fewer CVD events and 115 additional QALYs. For patient-clinician discussions that would otherwise lead to no statin therapy, we found that the test-and-MST strategy reduced costs by $3.25 MM, resulted in 97 fewer CVD events

Artificial Gravity as a Multi-System Countermeasure for Exploration Class Space Flight Missions

NASA Technical Reports Server (NTRS)

Paloski, William H.; Dawson, David L. (Technical Monitor)

2000-01-01

NASA's vision for space exploration includes missions of unprecedented distance and duration. However, during 30 years of human space flight experience, including numerous long-duration missions, research has not produced any single countermeasure or combination of countermeasures that is completely effective. Current countermeasures do not fully protect crews in low-Earth orbit, and certainly will not be appropriate for crews journeying to Mars and back over a three-year period. The urgency for exploration-class countermeasures is compounded by continued technical and scientific successes that make exploration class missions increasingly attractive. The critical and possibly fatal problems of bone loss, cardiovascular deconditioning, muscle weakening, neurovestibular disturbance, space anemia, and immune compromise may be alleviated by the appropriate application of artificial gravity (AG). However, despite a manifest need for new countermeasure approaches, concepts for applying AG as a countermeasure have not developed apace. To explore the utility of AG as a multi-system countermeasure during long-duration, exploration-class space flight, eighty-three members of the international space life science and space flight community met earlier this year. They concluded unanimously that the potential of AG as a multi-system countermeasure is indeed worth pursuing, and that the requisite AG research needs to be supported more systematically by NASA. This presentation will review the issues discussed and recommendations made.

Plasticity in the sensorimotor cortex induced by Music-supported therapy in stroke patients: a TMS study.

PubMed

Grau-Sánchez, Jennifer; Amengual, Julià L; Rojo, Nuria; Veciana de Las Heras, Misericordia; Montero, Jordi; Rubio, Francisco; Altenmüller, Eckart; Münte, Thomas F; Rodríguez-Fornells, Antoni

2013-01-01

Playing a musical instrument demands the engagement of different neural systems. Recent studies about the musician's brain and musical training highlight that this activity requires the close interaction between motor and somatosensory systems. Moreover, neuroplastic changes have been reported in motor-related areas after short and long-term musical training. Because of its capacity to promote neuroplastic changes, music has been used in the context of stroke neurorehabilitation. The majority of patients suffering from a stroke have motor impairments, preventing them to live independently. Thus, there is an increasing demand for effective restorative interventions for neurological deficits. Music-supported Therapy (MST) has been recently developed to restore motor deficits. We report data of a selected sample of stroke patients who have been enrolled in a MST program (1 month intense music learning). Prior to and after the therapy, patients were evaluated with different behavioral motor tests. Transcranial Magnetic Stimulation (TMS) was applied to evaluate changes in the sensorimotor representations underlying the motor gains observed. Several parameters of excitability of the motor cortex were assessed as well as the cortical somatotopic representation of a muscle in the affected hand. Our results revealed that participants obtained significant motor improvements in the paretic hand and those changes were accompanied by changes in the excitability of the motor cortex. Thus, MST leads to neuroplastic changes in the motor cortex of stroke patients which may explain its efficacy.

Plasticity in the sensorimotor cortex induced by Music-supported therapy in stroke patients: a TMS study

PubMed Central

Grau-Sánchez, Jennifer; Amengual, Julià L.; Rojo, Nuria; Veciana de las Heras, Misericordia; Montero, Jordi; Rubio, Francisco; Altenmüller, Eckart; Münte, Thomas F.; Rodríguez-Fornells, Antoni

2013-01-01

Playing a musical instrument demands the engagement of different neural systems. Recent studies about the musician's brain and musical training highlight that this activity requires the close interaction between motor and somatosensory systems. Moreover, neuroplastic changes have been reported in motor-related areas after short and long-term musical training. Because of its capacity to promote neuroplastic changes, music has been used in the context of stroke neurorehabilitation. The majority of patients suffering from a stroke have motor impairments, preventing them to live independently. Thus, there is an increasing demand for effective restorative interventions for neurological deficits. Music-supported Therapy (MST) has been recently developed to restore motor deficits. We report data of a selected sample of stroke patients who have been enrolled in a MST program (1 month intense music learning). Prior to and after the therapy, patients were evaluated with different behavioral motor tests. Transcranial Magnetic Stimulation (TMS) was applied to evaluate changes in the sensorimotor representations underlying the motor gains observed. Several parameters of excitability of the motor cortex were assessed as well as the cortical somatotopic representation of a muscle in the affected hand. Our results revealed that participants obtained significant motor improvements in the paretic hand and those changes were accompanied by changes in the excitability of the motor cortex. Thus, MST leads to neuroplastic changes in the motor cortex of stroke patients which may explain its efficacy. PMID:24027507

Identification and mitigation of stray laser light in the Thomson scattering system on the Madison Symmetric Torus (MST).

PubMed

Jacobson, C M; Borchardt, M T; Den Hartog, D J; Falkowski, A F; Morton, L A; Thomas, M A

2016-11-01

The Thomson scattering diagnostic on the Madison Symmetric Torus (MST) records excessive levels of stray Nd:YAG laser light. Stray light saturates the 1064 nm spectral channel in all polychromators, which prevents absolute electron density measurements via Rayleigh scattering calibration. Furthermore, stray light contaminates adjacent spectral channels for r/a ≥ 0.75, which renders the diagnostic unable to make electron temperature measurements at these radii. In situ measurements of stray light levels during a vacuum vessel vent are used to identify stray light sources and strategies for reduction of stray light levels. Numerical modeling using Zemax OpticStudio supports these measurements. The model of the vacuum vessel and diagnostic includes synthetic collection optics to enable direct comparison of measured and simulated stray light levels. Modeling produces qualitatively similar stray light distributions to MST measurements, and quantifies the mitigation effects of stray light mitigation strategies prior to implementation.

Identification and mitigation of stray laser light in the Thomson scattering system on the Madison Symmetric Torus (MST)

NASA Astrophysics Data System (ADS)

Jacobson, C. M.; Borchardt, M. T.; Den Hartog, D. J.; Falkowski, A. F.; Morton, L. A.; Thomas, M. A.

2016-11-01

The Thomson scattering diagnostic on the Madison Symmetric Torus (MST) records excessive levels of stray Nd:YAG laser light. Stray light saturates the 1064 nm spectral channel in all polychromators, which prevents absolute electron density measurements via Rayleigh scattering calibration. Furthermore, stray light contaminates adjacent spectral channels for r/a ≥ 0.75, which renders the diagnostic unable to make electron temperature measurements at these radii. In situ measurements of stray light levels during a vacuum vessel vent are used to identify stray light sources and strategies for reduction of stray light levels. Numerical modeling using Zemax OpticStudio supports these measurements. The model of the vacuum vessel and diagnostic includes synthetic collection optics to enable direct comparison of measured and simulated stray light levels. Modeling produces qualitatively similar stray light distributions to MST measurements, and quantifies the mitigation effects of stray light mitigation strategies prior to implementation.

Elevated basal serum tryptase identifies a multisystem disorder associated with increased TPSAB1 copy number.

PubMed

Lyons, Jonathan J; Yu, Xiaomin; Hughes, Jason D; Le, Quang T; Jamil, Ali; Bai, Yun; Ho, Nancy; Zhao, Ming; Liu, Yihui; O'Connell, Michael P; Trivedi, Neil N; Nelson, Celeste; DiMaggio, Thomas; Jones, Nina; Matthews, Helen; Lewis, Katie L; Oler, Andrew J; Carlson, Ryan J; Arkwright, Peter D; Hong, Celine; Agama, Sherene; Wilson, Todd M; Tucker, Sofie; Zhang, Yu; McElwee, Joshua J; Pao, Maryland; Glover, Sarah C; Rothenberg, Marc E; Hohman, Robert J; Stone, Kelly D; Caughey, George H; Heller, Theo; Metcalfe, Dean D; Biesecker, Leslie G; Schwartz, Lawrence B; Milner, Joshua D

2016-12-01

Elevated basal serum tryptase levels are present in 4-6% of the general population, but the cause and relevance of such increases are unknown. Previously, we described subjects with dominantly inherited elevated basal serum tryptase levels associated with multisystem complaints including cutaneous flushing and pruritus, dysautonomia, functional gastrointestinal symptoms, chronic pain, and connective tissue abnormalities, including joint hypermobility. Here we report the identification of germline duplications and triplications in the TPSAB1 gene encoding α-tryptase that segregate with inherited increases in basal serum tryptase levels in 35 families presenting with associated multisystem complaints. Individuals harboring alleles encoding three copies of α-tryptase had higher basal serum levels of tryptase and were more symptomatic than those with alleles encoding two copies, suggesting a gene-dose effect. Further, we found in two additional cohorts (172 individuals) that elevated basal serum tryptase levels were exclusively associated with duplication of α-tryptase-encoding sequence in TPSAB1, and affected individuals reported symptom complexes seen in our initial familial cohort. Thus, our findings link duplications in TPSAB1 with irritable bowel syndrome, cutaneous complaints, connective tissue abnormalities, and dysautonomia.

MST radar observations of Perseid meteor shower 2004

NASA Astrophysics Data System (ADS)

Venkata Phani Kumar, D.; Reddy, K. Chenna; Yellaiah, G.

2006-09-01

There was a special attention for Perseid meteor shower observations in view of the predictions of an intense activity on 11th August 2004 caused by a filament of dust drifting across the Earth's orbit. Results of a systematic study of Perseid meteor shower observations, carried out during 12-15 August 2004 using Indian MST radar are presented. Based on over 27 hours of observing time, we detected 2260 meteor echoes occurring between 80 km and 120 km with a mean height of 103 km. For our observations, the peak activity of the shower occured on 12/13 August, corresponding to solar longitude lambdao = 140.565± 0.16 with an average rate of 250 meteor echoes per hour. The SNR distribution of the echoes observed during the shower indicates that the smaller size meteoroids are more compared to larger size meteoroids in the perseid meteor stream. The three distinct peaks observed in the shower activity is presented and discussed.

Ross filter development for absolute measurement of Al line radiation on MST

NASA Astrophysics Data System (ADS)

Lauersdorf, N.; Reusch, L. M.; den Hartog, D. J.; Goetz, J. A.; Franz, P.; Vanmeter, P.

2017-10-01

The MST has a two-color soft x-ray tomography (SXT) diagnostic that, using the double-filter technique, measures electron temperature (Te) from the slope of the soft x-ray (SXR) continuum. Because MST has an aluminum plasma-facing surface, bright Al line radiation occurs in the SXR spectrum. In past application of the double-filter technique, these lines have been filtered out using thick Be filters ( 400 μm and 800 μm), restricting the measurement temperature range to >=1 keV due to the signal strength having a positive correlation with Te. Another way to deal with the line radiation is to explicitly include it into the SXR spectrum analysis from which Te is derived. A Ross filter set has been designed to measure this line radiation, and will enable the absolute intensities of the aluminum lines to be quantified and incorporated into the analysis. The Ross filter will be used to measure Al+11 and Al+12 lines, occurring between 1.59 and 2.04 keV. By using multiple detectors with filters made of varying element concentrations, we create spectral bins in which the dominant transmission is the line radiation. Absolute measurement of Al line intensities will enable use of thinner filters in the SXT diagnostic and accurate measurement of Te < 1 keV. This material is based upon work supported by the U.S. Department of Energy Office of Science, Office of Fusion Energy Sciences program under Award Numbers DE-FC02-05ER54814 and DE-SC0015474.

Mesospheric momentum fluxes observed by the MST radar at Poker Flat, Alaska

NASA Technical Reports Server (NTRS)

Wang, Ding-Yi; Fritts, David C.

1990-01-01

An analysis of the wave motions observed with the Poker Flat MST radar during the winter, summer, and fall of 1986 is presented. Monthly and daily mean winds, momentum fluxes, and velocity variances are investigated in detail. While several features are in agreement with previous measurements, some significant differences also are found to exist in the observations. Monthly mean horizontal winds between 82 and 89 km have amplitudes of 20-40 m/s westward and 10-25 m/s southward in July and August. In fall and winter, the horizontal winds between 58 and 75 km are weaker and essentially eastward.

Heterogeneous nuclear ribonucleoprotein H Blocks MST2-Dependent Apoptosis in Cancer Cells via Regulation of A-Raf transcription

PubMed Central

Rauch, Jens; O'Neill, Eric; Mack, Brigitte; Matthias, Christoph; Munz, Markus; Kolch, Walter; Gires, Olivier

2010-01-01

Summary A-Raf belongs to the family of oncogenic Raf kinases that are involved in mitogenic signalling by activating the MEK-ERK pathway. Low kinase activity of A-Raf towards MEK suggested that A-Raf might have alternative functions. We show that A-Raf prevents cancer cell apoptosis contingent on the expression of the hnRNP H splice factor, which is required for the correct transcription and expression of A-Raf. A-Raf prevented apoptosis by sequestering and inactivating the pro-apoptotic MST2 kinase. Knock-down of hnRNP H or A-Raf resulted in MST2-dependent apoptosis, while enforced expression of either one partially counteracted apoptosis induced by etoposide. In vivo expression studies in colon specimens corroborated the over-expression of hnRNP H in malignant tissues and its correlation with A-Raf levels. In summary, we present a novel route that is usurped by tumor cells to escape naturally imposed apoptotic signals. PMID:20145135

Identification and mitigation of stray laser light in the Thomson scattering system on the Madison Symmetric Torus (MST)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jacobson, C. M., E-mail: cjacobson@wisc.edu; Borchardt, M. T.; Den Hartog, D. J.

The Thomson scattering diagnostic on the Madison Symmetric Torus (MST) records excessive levels of stray Nd:YAG laser light. Stray light saturates the 1064 nm spectral channel in all polychromators, which prevents absolute electron density measurements via Rayleigh scattering calibration. Furthermore, stray light contaminates adjacent spectral channels for r/a ≥ 0.75, which renders the diagnostic unable to make electron temperature measurements at these radii. In situ measurements of stray light levels during a vacuum vessel vent are used to identify stray light sources and strategies for reduction of stray light levels. Numerical modeling using Zemax OpticStudio supports these measurements. The modelmore » of the vacuum vessel and diagnostic includes synthetic collection optics to enable direct comparison of measured and simulated stray light levels. Modeling produces qualitatively similar stray light distributions to MST measurements, and quantifies the mitigation effects of stray light mitigation strategies prior to implementation.« less

Novel large-range mitochondrial DNA deletions and fatal multisystemic disorder with prominent hepatopathy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bianchi, Marzia; Rizza, Teresa; Verrigni, Daniela

2011-11-18

Highlights: Black-Right-Pointing-Pointer Expanded array of mtDNA deletions. Black-Right-Pointing-Pointer Pearson syndrome with prominent hepatopathy associated with single mtDNA deletions. Black-Right-Pointing-Pointer Detection of deletions in fibroblasts and blood avoids muscle and liver biopsy. Black-Right-Pointing-Pointer Look for mtDNA deletions before to study nuclear genes related to mtDNA depletion. -- Abstract: Hepatic involvement in mitochondrial cytopathies rarely manifests in adulthood, but is a common feature in children. Multiple OXPHOS enzyme defects in children with liver involvement are often associated with dramatically reduced amounts of mtDNA. We investigated two novel large scale deletions in two infants with a multisystem disorder and prominent hepatopathy. Amount ofmore » mtDNA deletions and protein content were measured in different post-mortem tissues. The highest levels of deleted mtDNA were in liver, kidney, pancreas of both patients. Moreover, mtDNA deletions were detected in cultured skin fibroblasts in both patients and in blood of one during life. Biochemical analysis showed impairment of mainly complex I enzyme activity. Patients manifesting multisystem disorders in childhood may harbour rare mtDNA deletions in multiple tissues. For these patients, less invasive blood specimens or cultured fibroblasts can be used for molecular diagnosis. Our data further expand the array of deletions in the mitochondrial genomes in association with liver failure. Thus analysis of mtDNA should be considered in the diagnosis of childhood-onset hepatopathies.« less

ApoE and SNAP-25 Polymorphisms Predict the Outcome of Multidimensional Stimulation Therapy Rehabilitation in Alzheimer's Disease.

PubMed

Guerini, Franca Rosa; Farina, Elisabetta; Costa, Andrea Saul; Baglio, Francesca; Saibene, Francesca Lea; Margaritella, Nicolò; Calabrese, Elena; Zanzottera, Milena; Bolognesi, Elisabetta; Nemni, Raffaello; Clerici, Mario

2016-10-01

Alzheimer's disease (AD) is a highly prevalent neurodegenerative disorder. Rate of decline and functional restoration in AD greatly depend on the capacity for neural plasticity within residual neural tissues; this is at least partially influenced by polymorphisms in genes that determine neural plasticity, including Apolipoprotein E4 (ApoE4) and synaptosomal-associated protein of 25 kDa (SNAP-25). We investigated whether correlations could be detected between polymorphisms of ApoE4 and SNAP-25 and the outcome of a multidimensional rehabilitative approach, based on cognitive stimulation, behavioral, and functional therapy (multidimensional stimulation therapy [MST]). Fifty-eight individuals with mild-to-moderate AD underwent MST for 10 weeks. Neuro-psychological functional and behavioral evaluations were performed blindly by a neuropsychologist at baseline and after 10 weeks of therapy using Mini-Mental State Examination (MMSE), Functional Living Skill Assessment (FLSA), and Neuropsychiatric Inventory (NPI) scales. Molecular genotyping of ApoE4 and SNAP-25 rs363050, rs363039, rs363043 was performed. Results were correlated with ΔMMSE, ΔNPI and ΔFLSA scores by multinomial logistic regression analysis. Polymorphisms in both genes correlated with the outcome of MST for MMSE and NPI scores. Thus, higher overall MMSE scores after rehabilitation were detected in ApoE4 negative compared to ApoE4 positive patients, whereas the SNAP-25 rs363050(G) and rs363039(A) alleles correlated with significant improvements in behavioural parameters. Polymorphisms in genes known to modulate neural plasticity might predict the outcome of a multistructured rehabilitation protocol in patients with AD. These data, although needing confirmation on larger case studies, could help optimizing the clinical management of individuals with AD, for example defining a more intensive treatment in those subjects with a lower likelihood of success. © The Author(s) 2016.

Huntington's disease (HD): the neuropathology of a multisystem neurodegenerative disorder of the human brain.

PubMed

Rüb, U; Seidel, K; Heinsen, H; Vonsattel, J P; den Dunnen, W F; Korf, H W

2016-11-01

Huntington's disease (HD) is an autosomal dominantly inherited, and currently untreatable, neuropsychiatric disorder. This progressive and ultimately fatal disease is named after the American physician George Huntington and according to the underlying molecular biological mechanisms is assigned to the human polyglutamine or CAG-repeat diseases. In the present article we give an overview of the currently known neurodegenerative hallmarks of the brains of HD patients. Subsequent to recent pathoanatomical studies the prevailing reductionistic concept of HD as a human neurodegenerative disease, which is primarily and more or less exclusively confined to the striatum (ie, caudate nucleus and putamen) has been abandoned. Many recent studies have improved our neuropathological knowledge of HD; many of the early groundbreaking findings of neuropathological HD research have been rediscovered and confirmed. The results of this investigation have led to the stepwise revision of the simplified pathoanatomical and pathophysiological HD concept and culminated in the implementation of the current concept of HD as a multisystem degenerative disease of the human brain. The multisystem character of the neuropathology of HD is emphasized by a brain distribution pattern of neurodegeneration (i) which apart from the striatum includes the cerebral neo-and allocortex, thalamus, pallidum, brainstem and cerebellum, and which (ii) therefore, shares more similarities with polyglutamine spinocerebellar ataxias than previously thought. © 2016 International Society of Neuropathology.

Middle Atmosphere Program. Handbook for MAP. Volume 14: URSI/SCOSTEP Workshop on Technical Aspects of MST Radar

NASA Technical Reports Server (NTRS)

Bowhill, S. A. (Editor); Edwards, B. (Editor)

1984-01-01

Various topics relative to middle atmosphere research were discussed. meteorological and aeronomical requirements for mesosphere-stratosphere-troposphere (MST) radar networks, general circulation of the middle atmosphere, the interpretation of radar returns from clear air, spaced antenna and Doppler techniques for velocity measurement, and techniques for the study of gravity waves and turbulence are among the topics discussed.

Nursing Integration and Innovation Across a Multisystem Enterprise: Priorities for Nurse Leaders.

PubMed

Pappas, Sharon; McCauley, Linda

There is no escaping the fact that the ability to skillfully influence change is a requirement for nurse leaders. This need is intensified as the national health care system reforms and as the morphology of health care systems continues to change, especially in academic health care systems. The purpose of this article was 2-fold. The first objective was to relay the experience of the integration of nursing practice, education, and research within an academic health care system. The second was to, through this story of integration, expose the uniqueness and importance of nurse leader roles influencing innovation across a multisystem enterprise to fulfill the organization's mission.

Plasma Rotation During Neutral Beam Injection In MST

NASA Astrophysics Data System (ADS)

Hudson, Ben; Ding, W.; Fiksel, G.; Prager, S.; Yates, T.

2006-10-01

The effect of fast ions from neutral beam injection (20 keV, 30 A, 1.5 ms) on plasma rotation and magnetic tearing modes is studied. We observe that during co-injected NBI (with the injection in the same direction as the plasma and mode rotation) the rotation of the core-resonant n = 5 magnetic mode decreases and in many instances lock to the vessel wall. There is an associated drop in the poloidal component of n = 5 magnetic mode amplitude. The drop in the mode velocity suggests a counter-directed torque, perhaps due to modification of the radial electric field. The rotation slows during the injection phase, then restores itself on the timescale of the fast ion slowing down time (5 ms @ Te = 100 eV). The fluctuation-induced j x b Maxwell stress is measured using MST's FIR diagnostic and presented for comparison. Equilibrium reconstruction suggests a small increase in on-axis J||, consistent with the presence of a localized fast ion population moving in the direction of the plasma current. Mode rotation during NBI counter-injection is also presented.

An upgraded x-ray spectroscopy diagnostic on MST.

PubMed

Clayton, D J; Almagri, A F; Burke, D R; Forest, C B; Goetz, J A; Kaufman, M C; O'Connell, R

2010-10-01

An upgraded x-ray spectroscopy diagnostic is used to measure the distribution of fast electrons in MST and to determine Z(eff) and the particle diffusion coefficient D(r). A radial array of 12 CdZnTe hard-x-ray detectors measures 10-150 keV Bremsstrahlung from fast electrons, a signature of reduced stochasticity and improved confinement in the plasma. A new Si soft-x-ray detector measures 2-10 keV Bremsstrahlung from thermal and fast electrons. The shaped output pulses from both detector types are digitized and the resulting waveforms are fit with Gaussians to resolve pileup and provide good time and energy resolution. Lead apertures prevent detector saturation and provide a well-known etendue, while lead shielding prevents pickup from stray x-rays. New Be vacuum windows transmit >2 keV x-rays, and additional Al and Be filters are sometimes used to reduce low energy flux for better resolution at higher energies. Measured spectra are compared to those predicted by the Fokker-Planck code CQL3D to deduce Z(eff) and D(r).

Panhypopituitarism after multisystem trauma.

PubMed

Wiechecka, Joanna; Krzewska, Aleksandra; Droń, Izabela; Beń-Skowronek, Iwona

2013-01-01

The pituitary gland plays a key role in hormonal regulation in the organism, contributing to maintenance of balance of basic vital functions. To emphasise the need for assessment of pituitary function after head injury, as correct diagnosis and hormone replacement therapy prove to be a life-saving therapy accelerating the recovery process. A healthy, normally developing 9-year-old girl, a child of young and healthy parents, was struck by a falling tree. The results of severe head trauma included adrenal crisis, hypothyroidism, and diabetes insipidus as manifestations of damage to the anterior and posterior pituitary gland. Administration of hormone replacement therapy, i.e. hydrocortisone, L-thyroxine, and desmopressin greatly improved the patient´s condition and facilitated effective rehabilitation. Determination of pituitary hormones in children after severe head injury should be an important part of diagnosis allowing identification of an early stage of acute hypopituitarism and acceleration of recovery through hormone replacement therapy.

Sample results from the integrated salt disposition program macrobatch 6 tank 21H qualifications MST solids sample

DOE Office of Scientific and Technical Information (OSTI.GOV)

Peters, T. B.

2013-02-26

Savannah River National Laboratory (SRNL) performed experiments on qualification material for use in the Integrated Salt Disposition Program (ISDP) Batch 6 processing. As part of this qualification work, SRNL performed an Actinide Removal Process (ARP) test. From this test, the residual monosodium titanate (MST) was analyzed for radionuclide uptake. The results of these analyses are reported and are within historical precedent.

The MST radar technique: Requirements for operational weather forecasting

NASA Technical Reports Server (NTRS)

Larsen, M. F.

1983-01-01

There is a feeling that the accuracy of mesoscale forecasts for spatial scales of less than 1000 km and time scales of less than 12 hours can be improved significantly if resources are applied to the problem in an intensive effort over the next decade. Since the most dangerous and damaging types of weather occur at these scales, there are major advantages to be gained if such a program is successful. The interest in improving short term forecasting is evident. The technology at the present time is sufficiently developed, both in terms of new observing systems and the computing power to handle the observations, to warrant an intensive effort to improve stormscale forecasting. An assessment of the extent to which the so-called MST radar technique fulfills the requirements for an operational mesoscale observing network is reviewed and the extent to which improvements in various types of forecasting could be expected if such a network is put into operation are delineated.

Artificial Gravity as a Multi-System Countermeasure to Bed Rest Deconditioning: Pilot Study Overview

NASA Technical Reports Server (NTRS)

Paloski, William H.; Young, L. R.

2007-01-01

Efficient, effective, multi-system countermeasures will likely be required to protect the health, safety, and performance of crews aboard planned exploration-class space flight missions to Mars and beyond. To that end, NASA, DLR, and IMBP initiated a multi-center international project to begin systematically exploring the utility of artificial gravity (AG) as a multi-system countermeasure in ground based venues using test subjects deconditioned by bed rest. The goal of this project is to explore the efficacy of short-radius, intermittent AG as a countermeasure to bone, muscle, cardiovascular, and sensory-motor adaptations to hypogravity. This session reports the results from a pilot study commissioned to validate a standardized protocol to be used by all centers involved in the project. Subject selection criteria, medical monitoring requirements, medical care procedures, experiment control procedures, and standardized dependent measures were established jointly. Testing was performed on 15 rigorously screened male volunteers subjected to 21 days of 6deg HDT bed rest. (All provided written consent to volunteer after the nature of the study and its hazards were clearly explained to them.) Eight were treated with daily 1hr AG exposures (2.5g at the feet decreasing to 1.0g at the heart) aboard a short radius (3m) centrifuge, while the other seven served as controls. Multiple tests of multiple dependent measures were made in each of the primary physiological systems of interest during a 10 day acclimatization period prior to HDT bed rest and again during an 8 day recovery period after the bed rest period was complete. Analyses of these data (presented in other papers in this session) suggest the AG prescription had salutary effects on aspects of the bone, muscle, and cardiovascular systems, with no untoward effects on the vestibular system, the immune system, or cognitive function. Furthermore, treatment subjects were able to tolerate 153/160 centrifuge sessions over

TEMPORAL AND SPATIAL VARIABILITY OF FECAL INDICATOR BACTERIA: IMPLICATIONS FOR THE APPLICATION OF MST METHODOLOGIES TO DIFFERENTIATE SOURCES OF FECAL CONTAMINATION

EPA Science Inventory

Temporal variability in the gastrointestinal flora of animals impacting water resources with fecal material can be one of the factors producing low source identification rates when applying microbial source tracking (MST) methods. Understanding how bacterial species and genotype...

Improvements to the MST Thomson Scattering Diagnostic

NASA Astrophysics Data System (ADS)

Adams, D. T.; Borchardt, M. T.; den Hartog, D. J.; Holly, D. J.; Kile, T.; Kubala, S. Z.; Jacobson, C. M.; Thomas, M. A.; Wallace, J. P.; Young, W. C.; MST Thomson Scattering Team

2017-10-01

Multiple upgrades to the MST Thomson Scattering diagnostic have been implemented to expand capabilities of the system. In the past, stray laser light prevented electron density measurements everywhere and temperature measurements for -z/a >0.75. To mitigate stray light, a new laser beamline is being commissioned that includes a longer entrance flight tube, close-fitting apertures, and baffles. A polarizer has been added to the collection optics to further reduce stray light. An absolute density calibration using Rayleigh scattering in argon will be performed. An insertable integrating sphere will provide a full-system spectral calibration as well as maps optical fibers to machine coordinates. Reduced transmission of the collection optics due to coatings from plasma-surface interactions is regularly monitored to inform timely replacements of the first lens. Long-wavelength filters have been installed to better characterize non-Maxwellian electron distribution features. Previous work has identified residual photons not described by a Maxwellian distribution during m =0 magnetic bursts. Further effort to characterize the distribution function will be described. This material is based upon work supported by the U.S. Department of Energy, Office of Science, Office of Fusion Energy Sciences program under Award No. DE-FC02-05ER54814.

Absolute brightness modeling for improved measurement of electron temperature from soft x-rays on MST

NASA Astrophysics Data System (ADS)

Reusch, L. M.; Franz, P.; Goetz, J. A.; den Hartog, D. J.; Nornberg, M. D.; van Meter, P.

2017-10-01

The two-color soft x-ray tomography (SXT) diagnostic on MST is now capable of Te measurement down to 500 eV. The previous lower limit was 1 keV, due to the presence of SXR emission lines from Al sputtered from the MST wall. The two-color technique uses two filters of different thickness to form a coarse spectrometer to estimate the slope of the continuum x-ray spectrum, which depends on Te. The 1.6 - 2.0 keV Al emission lines were previously filtered out by using thick Be filters (400 µm and 800 µm), thus restricting the range of the SXT diagnostic to Te >= 1 keV. Absolute brightness modeling explicitly includes several sources of radiation in the analysis model, enabling the use of thinner filters and measurement of much lower Te. Models based on the atomic database and analysis structure (ADAS) agree very well with our experimental SXR measurements. We used ADAS to assess the effect of bremsstrahlung, recombination, dielectronic recombination, and line emission on the inferred Te. This assessment informed the choice of the optimum filter pair to extend the Te range of the SXT diagnostic. This material is based upon work supported by the U.S. Department of Energy Office of Science, Office of Fusion Energy Sciences program under Award Numbers DE-FC02-05ER54814 and DE-SC0015474.

A case of vascular Ehlers-Danlos Syndrome with a cardiomyopathy and multi-system involvement.

PubMed

Lan, Nick Si Rui; Fietz, Michael; Pachter, Nicholas; Paul, Vincent; Playford, David

Ehlers-Danlos Syndrome comprises a heterogeneous group of heritable connective tissue disorders resulting from various gene mutations. We present an unusual case of vascular Ehlers-Danlos Syndrome with distinctive physical characteristics and a cardiomyopathy with features suggesting isolated left ventricular non-compaction. The cardiac features represent the first report of a cardiomyopathy associated with a mutation in the COL3A1 gene. This case also illustrates the multi-system nature of Ehlers-Danlos Syndrome and the complexity of managing patients with the vascular subtype. Copyright © 2018 Elsevier Inc. All rights reserved.

Ion heat transport in improved confinement MST plasmas

NASA Astrophysics Data System (ADS)

Xing, Zichuan; Nornberg, Mark; den Hartog, Daniel J.; Kumar, Santhosh; Anderson, Jay K.

2016-10-01

Ion power balance in improved confinement (PPCD) plasmas in MST is dominated by electron collisional heating balanced by charge exchange transport. Neoclassical effects on ions in the RFP are inherently small and PPCD plasmas have reduced turbulence and stochasticity. Thus PPCD plasmas provide a good starting point for a transport model developed to account for collisional equilibration between species, classical conductive energy transport, and energy loss due to charge exchange collisions. This model also allows a possible noncollisional anomalous term to be isolated for study, and correlations between residual magnetic fluctuations during PPCD plasmas and anomalous heating and transport will be investigated. Recent modeling with DEGAS2 Monte Carlo neutral simulation suggests higher core neutral temperature than previously estimated with more simplistic assumptions. However, the working model does not fully account for the electron density increase in the core during PPCD, which is higher than expected from classical particle transport, and neutral and impurity ionization. Other possible mechanisms are considered and analyzed, including more complex impurity charge-state balance and pinch effects. Work supported by the US DOE. DEGAS2 is provided by PPPL.

Genetic ataxia telangiectasia porcine model phenocopies the multisystemic features of the human disease.

PubMed

Beraldi, Rosanna; Meyerholz, David K; Savinov, Alexei; Kovács, Attila D; Weimer, Jill M; Dykstra, Jordan A; Geraets, Ryan D; Pearce, David A

2017-11-01

Ataxia telangiectasia (AT) is a progressive multisystem autosomal recessive disorder caused by mutations in the AT-mutated (ATM) gene. Early onset AT in children is characterized by cerebellar degeneration, leading to motor impairment. Lung disease and cancer are the two most common causes of death in AT patients. Accelerated thymic involution may contribute to the cancer, and recurrent and/or chronic respiratory infections may be a contributing factor to lung disease in AT. AT patients have fertility issues, are highly sensitive to ionizing radiation and they present oculocutaneous telangiectasia. Current treatments only slightly ameliorate disease symptoms; therapy that alters or reverses the course of the disease has not yet been discovered. Previously, we have shown that ATM -/- pigs, a novel model of AT, present with a loss of Purkinje cells, altered cerebellar cytoarchitecture and motor coordination deficits. ATM -/- porcine model not only recapitulates the neurological phenotype, but also other multifaceted clinical features of the human disease. Our current study shows that ATM -/- female pigs are infertile, with anatomical and functional signs of an immature reproductive system. Both male and female ATM -/- pigs show abnormal thymus structure with decreased cell cycle and apoptosis markers in the gland. Moreover, ATM -/- pigs have an altered immune system with decreased CD8 + and increased natural killer and CD4 + CD8 + double-positive cells. Nevertheless, ATM -/- pigs manifest a deficient IgG response after a viral infection. Based on the neurological and peripheral phenotypes, the ATM -/- pig is a novel genetic model that may be used for therapeutic assessments and to identify pathomechanisms of this disease. Copyright © 2017 Elsevier B.V. All rights reserved.

Multisystemic diseases and ethnicity: a focus on lupus erythematosus, systemic sclerosis, sarcoidosis and Behçet disease.

PubMed

Petit, A; Dadzie, O E

2013-10-01

We present an overview of the association between ethnicity and the clinical and epidemiological aspects of four multisystemic diseases: lupus erythematosus, systemic sclerosis, sarcoidosis and Behçet disease. In particular, we highlight observed ethnic differences in cutaneous manifestations of these diseases. This article should help guide clinical management, as well as serve to highlight future areas for research. © 2013 The Authors BJD © 2013 British Association of Dermatologists.

Phenotype variability of infantile-onset multisystem neurologic, endocrine, and pancreatic disease IMNEPD.

PubMed

Picker-Minh, Sylvie; Mignot, Cyril; Doummar, Diane; Hashem, Mais; Faqeih, Eissa; Josset, Patrice; Dubern, Béatrice; Alkuraya, Fowzan S; Kraemer, Nadine; Kaindl, Angela M

2016-04-29

Infantile-onset multisystem neurologic, endocrine, and pancreatic disease (IMNEPD) has been recently linked to biallelic mutation of the peptidyl-tRNA hydrolase 2 gene PTRH2. Two index patients with IMNEPD in the original report had multiple neurological symptoms such as postnatal microcephaly, intellectual disability, developmental delay, sensorineural deafness, cerebellar atrophy, ataxia, and peripheral neuropathy. In addition, distal muscle weakness and abnormalities of thyroid, pancreas, and liver were found. Here, we report five further IMNEPD patients with a different homozygous PTRH2 mutation, broaden the phenotypic spectrum of the disease and differentiate common symptoms and interindividual variability in IMNEPD associated with a unique mutation. We thereby hope to better define IMNEPD and promote recognition and diagnosis of this novel disease entity.

Emergent multisystemic Enterococcus infection threatens endangered Christmas Island reptile populations

PubMed Central

Hall, Jane; Thompson, Paul; Eden, John-Sebastian; Srivastava, Mukesh; Tiernan, Brendan; Jenkins, Cheryl; Phalen, David

2017-01-01

Multisystemic infections with a morphologically unusual bacterium were first observed in captive critically endangered Lister’s geckos (Lepidodactylus listeri) on Christmas Island in October 2014. Since then the infection was identified in another captive critically endangered lizard species, the blue-tailed skink (Cryptoblepharus egeriae) and two species of invasive geckos; the four clawed gecko (Gehyra mutilata) and Asian house gecko (Hemidactylus frenatus), in a wide geographic range across the east side of the island. The Gram and periodic acid-Schiff positive cocci to diplococci have a propensity to form chains surrounded by a matrix, which ultrastructurally appears to be formed by fibrillar capsular projections. The bacterium was associated with severe and extensive replacement of tissues, but minimal host inflammatory response. Attempts to grow the organism in culture and in embryonated eggs were unsuccessful. Molecular characterisation of the organism placed it as a novel member of the genus Enterococcus. Disease Risk Analyses including this organism should now be factored into conservation management actions and island biosecurity. PMID:28727845

Overview of MST Results and Plans

NASA Astrophysics Data System (ADS)

Sarff, J. S.

2008-11-01

Improved confinement with high beta has been established in MST over its full range of plasma current capability using transient inductive current profile control. Both thermal electron and ion confinement are increased, and energetic electrons are observed to 100 keV. The global energy confinement time is 12 ms at high current and high temperature (Te=2 keV, Ti =1 keV), with βtot=10% (only Ohmic heating). Maximum βtot=26% is attained at lower current and temperature with D2 pellet injection, without evidence of hard-beta-limit phenomena. Momentum transport associated with MHD tearing shows the fascinating behavior that the Maxwell and Reynolds turbulent stresses are both large but oppositely directed in sawtooth magnetic relaxation events. Momentum is transported rapidly in these events, presumably through the imbalance in the stresses. Electron temperature fluctuations associated with MHD tearing are measured using a multi-point, multi-pulse Thomson scattering diagnostic. A 5-250 kHz pulse-burst laser is under construction to extend the Thomson capability to high frequency. Lower hybrid and electron Bernstein wave injection are under development to provide more sustained current profile control and heating. X-ray emission from the plasma is observed for both waves at 175 kW injected power. Substantial new experimental capability will be provided by a recently installed programmable power supply for the toroidal field, a new 1 MW, 20 ms neutral beam injection system, and upgraded OFCD system. Supported by U.S. DoE and NSF.

First Absolutely Calibrated Localized Measurements of Ion Velocity in the MST in Locked and Rotating Plasmas

NASA Astrophysics Data System (ADS)

Baltzer, M.; Craig, D.; den Hartog, D. J.; Nornberg, M. D.; Munaretto, S.

2015-11-01

An Ion Doppler Spectrometer (IDS) is used on MST for high time-resolution passive and active measurements of impurity ion emission. Absolutely calibrated measurements of flow are difficult because the spectrometer records data within 0.3 nm of the C+5 line of interest, and commercial calibration lamps do not produce lines in this narrow range . A novel optical system was designed to absolutely calibrate the IDS. The device uses an UV LED to produce a broad emission curve in the desired region. A Fabry-Perot etalon filters this light, cutting transmittance peaks into the pattern of the LED emission. An optical train of fused silica lenses focuses the light into the IDS with f/4. A holographic diffuser blurs the light cone to increase homogeneity. Using this light source, the absolute Doppler shift of ion emissions can be measured in MST plasmas. In combination with charge exchange recombination spectroscopy, localized ion velocities can now be measured. Previously, a time-averaged measurement along the chord bisecting the poloidal plane was used to calibrate the IDS; the quality of these central chord calibrations can be characterized with our absolute calibration. Calibration errors may also be quantified and minimized by optimizing the curve-fitting process. Preliminary measurements of toroidal velocity in locked and rotating plasmas will be shown. This work has been supported by the US DOE.

Signal and noise level estimation for narrow spectral width returns observed by the Indian MST radar

NASA Astrophysics Data System (ADS)

Hooper, D. A.

1999-07-01

Use is made of five sets of multibeam observations of the lower atmosphere made by the Indian mesosphere-stratosphere-troposphere (MST) radar. Two aspects of signal processing which can lead to serious underestimates of the signal-to-noise ratio are considered. First, a comparison is made of the effects of different data weighting windows applied to the inphase and quadrature components of the radar return samples prior to Fourier transformation. The relatively high degree of spectral leakage associated with the rectangular and Hamming windows can give rise to overestimates of the noise levels by up to 28 dB for the strongest signals. Use of the Hanning window is found to be the most appropriate for these particular data. Second, a technique for removing systematic dc biases from the data in the time domain is compared with the more well-known practice of correction in the frequency domain. The latter technique, which is often used to remove the effects of ground clutter, is shown to be particularly inappropriate for the characteristically narrow spectral width signals observed by the Indian MST radar. For cases of near-zero Doppler shift it can remove up to 30 dB of signal information. The consequences of noise and signal level discrepancies for studies of refractivity structures are discussed. It is shown that neither problem has a significant effect on Doppler shift or spectral width estimates.

Reducing and measuring fluctuations in the MST RFP: Enhancement of energy confinement and measurement of the MHD dynamo

DOE Office of Scientific and Technical Information (OSTI.GOV)

Den Hartog, D.J.; Almagri, A.F.; Cekic, M.

1996-09-01

A three- to five-fold enhancement of the energy confinement time in a reversed-field pinch (RFP) has been achieved in the Madison Symmetric Torus (MST) by reducing the amplitude of tearing mode fluctuations responsible for anomalous transport in the core of the RFP. By applying a transient poloidal inductive electric field to flatten the current density profile, the fluctuation amplitude {tilde b}/B decreases from 1.5% to 0.8%, the electron temperature T{sub e0} increases from 250 eV to 370 eV, the ohmic input power decreases from 4.5 MW to approximately 1.5 MW, the poloidal beta {beta}{sub 0} increases from 6% to 9%,more » and the energy confinement time {tau}{sub E} increases from 1 ms to {approximately}5 ms in I{sub {phi}} = 340 kA plasmas with density {tilde n} = 1 {times} 10{sup 19} m{sup -3}. Current profile control methods are being developed for the RFP in a program to eliminate transport associated with these current-gradient-driven fluctuations. In addition to controlling the amplitude of the tearing modes, we are vigorously pursuing an understanding of the physics of these fluctuations. In particular, plasma flow, both equilibrium and fluctuating, plays a critical role in a diversity of physical phenomena in MST. The key results: 1) Edge probe measurements show that the MHD dynamo is active in low collisionality plasmas, while at high collisionality a new mechanism, the `electron diamagnetic dynamo,` is observed. 2) Core spectroscopic measurements show that the toroidal velocity fluctuations of the plasma are coherent with the large-scale magnetic tearing modes; the scalar product of these two fluctuating quantities is similar to that expected for the MHD dynamo electromotive force. 3) Toroidal plasma flow in MST exhibits large radial shear and can be actively controlled, including unlocking locked discharges, by modifying E{sub r} with a robust biased probe. 24 refs.« less

Symposium Review: Metal and Polymer Matrix Composites at MS&T 2013

NASA Astrophysics Data System (ADS)

Gupta, Nikhil; Paramsothy, Muralidharan

2014-06-01

This article reflects on the presentations made during the Metal and Polymer Matrix Composites symposium at Materials Science and Technology 2013 (MS&T'13) held in Montreal (Quebec, Canada) from October 27 to 31. The symposium had three sessions on metal matrix composites and one session on polymer matrix composites containing a total of 23 presentations. While the abstracts and full-text papers are available through databases, the discussion that took place during the symposium is often not captured in writing and gets immediately lost. We have tried to recap some of the discussion in this article and hope that it will supplement the information present in the proceedings. The strong themes in the symposium were porous composites, aluminum matrix composites, and nanocomposites. The development of processing methods was also of interest to the speakers and attendees.

Results from CoMStOC - The Coronal Magnetic Structures Observing Campaign

NASA Technical Reports Server (NTRS)

Schmelz, J. T.; Holman, G. D.

1991-01-01

The Coronal Magnetic Structures Observing Campaign (CoMStOC) was designed to measure the magnetic field strength and determine its structure in the solar corona. Simultaneous soft X-ray and microwave observations were taken by the Solar Maximum Mission's X-ray Polychromator (XRP) and the Very Large Array (VLA) on four days in the campaign period (Nov 25 to Dec 21, 1987). XRP maps in soft X-ray resonance lines formed at different coronal temperatures provide accurate temperature and emission measure diagnostics. VLA maps at several frequencies in the 20 cm and 6 cm bands yield information on microwave structure, spectrum and polarization. The combined data set separates contributions from the two dominant microwave emission mechanisms, thermal bremsstrahlung and gyroresonance. Where gyroresonance dominates, the coronal magnetic field strength has been determined with the aid of theoretical modeling.

Results from CoMStOC - The Coronal Magnetic Structures Observing Campaign

NASA Astrophysics Data System (ADS)

Schmelz, J. T.; Holman, G. D.

The Coronal Magnetic Structures Observing Campaign (CoMStOC) was designed to measure the magnetic field strength and determine its structure in the solar corona. Simultaneous soft X-ray and microwave observations were taken by the Solar Maximum Mission's X-ray Polychromator (XRP) and the Very Large Array (VLA) on four days in the campaign period (Nov 25 to Dec 21, 1987). XRP maps in soft X-ray resonance lines formed at different coronal temperatures provide accurate temperature and emission measure diagnostics. VLA maps at several frequencies in the 20 cm and 6 cm bands yield information on microwave structure, spectrum and polarization. The combined data set separates contributions from the two dominant microwave emission mechanisms, thermal bremsstrahlung and gyroresonance. Where gyroresonance dominates, the coronal magnetic field strength has been determined with the aid of theoretical modeling.

Therapist perception of treatment outcome: Evaluating treatment outcomes among youth with antisocial behavior problems.

PubMed

Crandal, Brent R; Foster, Sharon L; Chapman, Jason E; Cunningham, Phillippe B; Brennan, Patricia A; Whitmore, Elizabeth A

2015-06-01

Effective evaluation of treatment requires the use of measurement tools producing reliable scores that can be used to make valid decisions about the outcomes of interest. Therapist-rated treatment outcome scores that are obtained within the context of empirically supported treatments (ESTs) could provide clinicians and researchers with data that are easily accessible and complimentary to existing instrumentation. We examined the psychometric properties of scores from the Therapist Perception of Treatment Outcome: Youth Antisocial Behavior (TPTO:YAB), an instrument developed to assess therapist judgments of treatment success among families participating in an EST, Multisystemic Therapy (MST), for youth with antisocial behavior problems. Data were drawn from a longitudinal study of MST. The initial 20-item TPTO:YAB was completed by therapists of 111 families at midtreatment and 163 families at treatment termination. Rasch model dimensionality analyses provided evidence for 2 dimensions reflecting youth- and caregiver-related aspects of treatment outcome, although a bifactor analyses suggested that these dimensions reflected a single more general construct. Rasch analyses were also used to assess item and rating scale characteristics and refine the number of items. These analyses suggested items performed similarly across time and that scores reflect treatment outcome in similar ways at mid and posttreatment. Multilevel and zero-order analyses provided evidence for the validity of TPTO:YAB scores. TPTO:YAB scores were moderately correlated with scores of youth and caregiver behaviors targeted in treatment, adding support to its use as a treatment outcome measurement instrument. (c) 2015 APA, all rights reserved).

An overview of data acquisition, signal coding and data analysis techniques for MST radars

NASA Technical Reports Server (NTRS)

Rastogi, P. K.

1986-01-01

An overview is given of the data acquisition, signal processing, and data analysis techniques that are currently in use with high power MST/ST (mesosphere stratosphere troposphere/stratosphere troposphere) radars. This review supplements the works of Rastogi (1983) and Farley (1984) presented at previous MAP workshops. A general description is given of data acquisition and signal processing operations and they are characterized on the basis of their disparate time scales. Then signal coding, a brief description of frequently used codes, and their limitations are discussed, and finally, several aspects of statistical data processing such as signal statistics, power spectrum and autocovariance analysis, outlier removal techniques are discussed.

Adenosine decreases oxidative stress and protects H2O2-treated neural stem cells against apoptosis through decreasing Mst1 expression.

PubMed

Gholinejad, Masoumeh; Jafari Anarkooli, Iraj; Taromchi, Amirhossein; Abdanipour, Alireza

2018-05-01

Overproduction of free radicals during oxidative stress induces damage to key biomolecules and activates programed cell death pathways. Neuronal cell death in the nervous system leads to a number of neurodegenerative diseases. The aim of the present study was to evaluate the neuroprotective effect of adenosine on inhibition of apoptosis induced by hydrogen peroxide (H 2 O 2 ) in bone marrow-derived neural stem cells (B-dNSCs), with focus on its regulatory effect on the expression of mammalian sterile 20-like kinase 1 ( Mst1 ), as a novel proapoptotic kinase. B-dNSCs were exposed to adenosine at different doses (2, 4, 6, 8 and 10 µM) for 48 h followed by 125 µM H 2 O 2 for 30 min. Using MTT, terminal deoxynucleotidyl transferase dUTP nick-end labeling and real-time reverse transcription polymerase chain reaction assays, the effects of adenosine on cell survival, apoptosis and Mst1 , nuclear factor (erythroid-derived 2)-like 2 and B-cell lymphoma 2 and adenosine A1 receptor expression were evaluated in pretreated B-dNSCs compared with controls (cells treated with H 2 O 2 only). Firstly, results of the MTT assay indicated 6 µM adenosine to be the most protective dose in terms of promotion of cell viability. Subsequent assays using this dosage indicated that apoptosis rate and Mst1 expression in B-dNSCs pretreated with 6 µM adenosine were significantly decreased compared with the control group. These findings suggest that adenosine protects B-dNSCs against oxidative stress-induced cell death, and therefore, that it may be used to promote the survival rate of B-dNSCs and as a candidate for the treatment of oxidative stress-mediated neurological diseases.

Practicality of electronic beam steering for MST/ST radars, part 6.2A

NASA Technical Reports Server (NTRS)

Clark, W. L.; Green, J. L.

1984-01-01

Electronic beam steering is described as complex and expensive. The Sunset implementation of electronic steering is described, and it is demonstrated that such systems are cost effective, versatile, and no more complex than fixed beam alternatives, provided three or more beams are needed. The problem of determining accurate meteorological wind components in the presence of spatial variation is considered. A cost comparison of steerable and fixed systems allowing solution of this problem is given. The concepts and relations involved in phase steering are given, followed by the description of the Sunset ST radar steering system. The implications are discussed, references to the competing SAD method are provided, and a recommendation concerning the design of the future Doppler ST/MST systems is made.

EDITORIAL: MST Best Paper Award for 2004

NASA Astrophysics Data System (ADS)

Gill, Patrick

2005-12-01

For the last 13 years, Measurement Science and Technology has awarded a Best Paper prize. The Editorial Board of the journal believes that such a prize is an opportunity to thank authors for submitting their work, and serves as an integral part of the on-going quality review of the journal. An Editorial Board working party, comprising Patrick Gill (Chairman), David Birch and Ralph Tatam undertook the task of selecting as Best Paper 2004 a single contributed paper describing new and significant work, well aligned with the measurement scope of the journal, and presented in clear and rigorous form. They received a number of recommendations from the Editorial and International Advisory Board Members, and they would like to record their thanks to the Members for these recommendations, as they form an all-important first stage in the assessment process. There were responses from some five Board Members. In total, there were 16 papers nominated, plus another six from the working party. All these papers had quality ratings of 2 or higher from the referees, and note was also taken of the total electronic accesses for those papers subsequently short-listed. Review Articles, and papers that included a Board Member as an author, were automatically excluded. From the submitted nominations and working party deliberations, a short list of two papers was drawn up. The winning paper was then selected on the totality of criteria. Thus the paper recommended by the working party for the MST Best Paper Award for 2004 is: 'Adsorptive pressure-sensitive coatings on porous anodised aluminium' by Masaharu Kameda, Norikazu Tezuka, Tomohiro Hangai, Keisuke Asai, Kazuyuki Nakakita and Yutaka Amao, 15 489-500 (2004) This paper describes a novel pressure sensor based on a luminescent coating applied to a porous anodized aluminium layer, with application to the measurement of fluctuating pressures on short timescales with high spatial resolution. The research has particular application to

Multi-System Effects of Daily Artificial Gravity Exposures in Humans Deconditioned by Bed Rest

NASA Technical Reports Server (NTRS)

Paloski, William H.

2007-01-01

We have begun to explore the utility of intermittent artificial gravity (AG) as a multi-system countermeasure to the untoward health and performance effects of adaptation to decreased gravity during prolonged space flight. The first study in this exploration was jointly designed by an international, multi-disciplinary team of scientists interested in standardizing an approach so that comparable data could be obtained from follow-on studies performed in multiple international locations. Fifteen rigorously screened male volunteers participated in the study after providing written informed consent. All were subjected to 21 days of 6deg head-down-tilt (HDT) bed rest. Eight were treated with daily 1hr AG exposures (2.5g at the feet decreasing to 1.0g at the heart) aboard a short radius (3m) centrifuge, while the other seven served as controls. Multiple observations were made of dependent measures in the bone, muscle, cardiovascular, sensory-motor, immune, and behavioral systems during a 10 day acclimatization period prior to HDT bed rest and again during an 8 day recovery period after the bed rest period. Comparisons between the treatment and control subjects demonstrated salutary effects of the AG exposure on aspects of the muscle and cardiovascular systems, with no untoward effects on the vestibular system, the immune system, or cognitive function. Bone deconditioning was similar between the treatment and control groups, suggesting that the loading provided by this specific AG paradigm was insufficient to protect that system from deconditioning. Future work will be devoted to varying the loading duty cycle and/or coupling the AG loading with exercise to provide maximum physiological protection across all systems. Testing will also be extended to female subjects. The results of this study suggest that intermittent AG could be an effective multi-system countermeasure.

Altitude profiles of temperature from 4 to 80 km over the tropics from MST radar and lidar

NASA Astrophysics Data System (ADS)

Parameswaran, K.; Sasi, M. N.; Ramkumar, G.; Nair, P. R.; Deepa, V.; Murthy, B. V. K.; Nayar, S. R. P.; Revathy, K.; Mrudula, G.; Satheesan, K.; Bhavanikumar, Y.; Sivakumar, V.; Raghunath, K.; Rajendraprasad, T.; Krishnaiah, M.

2000-10-01

Using ground-based techniques of MST radar and Lidar, temperature profiles in the entire height range of 4 to 75km are obtained for the first time at a tropical location. The temporal resolution of the profiles is ~1h in the lower altitudes and 12.5min in the higher altitudes and altitude resolution is ~300m. The errors involved in the derived values are presented. Preliminary analysis of temperature variations in a night revealed fluctuations with characteristics resembling those of large-scale gravity waves.

The instrumental principles of MST radars and incoherent scatter radars and the configuration of radar system hardware

NASA Technical Reports Server (NTRS)

Roettger, Juergen

1989-01-01

The principle of pulse modulation used in the case of coherent scatter radars (MST radars) is discussed. Coherent detection and the corresponding system configuration is delineated. Antenna requirements and design are outlined and the phase-coherent transmitter/receiver system is described. Transmit/receive duplexers, transmitters, receivers, and quadrature detectors are explained. The radar controller, integrator, decoder and correlator design as well as the data transfer and the control and monitoring by the host computer are delineated. Typical operation parameters of some well-known radars are summarized.

Key Elements of a Successful Multi-System Collaboration for School-Based Mental Health: In-Depth Interviews with District and Agency Administrators

ERIC Educational Resources Information Center

Powers, Joelle D.; Edwards, Jeffrey D.; Blackman, Kate F.; Wegmann, Kate M.

2013-01-01

The alarming number of youth with unmet mental health needs in the US is a significant social problem. The pilot school-based mental health project described here established an innovative multi-system partnership between an urban school district, a public mental health agency, and a local university to better meet the mental health needs of youth…

The Resilience of Kepler Multi-systems to Stellar Obliquity

NASA Astrophysics Data System (ADS)

Spalding, Christopher; Marx, Noah W.; Batygin, Konstantin

2018-04-01

The Kepler mission and its successor K2 have brought forth a cascade of transiting planets. Many of these planetary systems exhibit multiple transiting members. However, a large fraction possesses only a single transiting planet. This high abundance of singles, dubbed the "Kepler Dichotomy," has been hypothesized to arise from significant mutual inclinations between orbits in multi-planet systems. Alternatively, the single-transiting population truly possesses no other planets in the system, but the true origin of the overabundance of single systems remains unresolved. In this work, we propose that planetary systems typically form with a coplanar, multiple-planetary architecture, but that quadrupolar gravitational perturbations from their rapidly-rotating host star subsequently disrupt this primordial coplanarity. We demonstrate that, given sufficient stellar obliquity, even systems beginning with 2 planetary constituents are susceptible to dynamical instability soon after planet formation, as a result of the stellar quadrupole moment. This mechanism stands as a widespread, yet poorly explored pathway toward planetary system instability. Moreover, by requiring that observed multi-systems remain coplanar on Gyr timescales, we are able to place upper limits on the stellar obliquity in systems such as K2-38 (obliquity < 20 degrees), where other methods of measuring spin-orbit misalignment are not currently available.

Prognostic utility of gene therapy with herpes simplex virus thymidine kinase for patients with high-grade malignant gliomas: a systematic review and meta analysis.

PubMed

Zhao, Fei; Tian, Jinhui; An, Lifeng; Yang, Kehu

2014-06-01

The aim of this study was to assess the effectiveness of adding viral vector-mediated gene therapy with herpes simplex virus thymidine kinase (HSV-tk) to standard treatment, in comparison with standard treatment alone to treat patients with high-grade gliomas (HGGs). A literature search of the databases PubMed, Embase, the Cochrane Library, Web of Science, and Chinese biomedicine was performed to identify eligible studies. Three randomized controlled trials (involving a total of 532 patients) were included in this systematic review. A meta-analysis of included studies demonstrated a significant increase in median survival time (MST) in patients who were treated with HSV-tk gene therapy (mean deviation 0.59, 95% CI: 0.41-0.76, p < 0.0001). The results of pooled analysis for different patient groups show that overall survival (OS) for all HGG patients was improved by adding gene therapy [hazard ratio (HR) = 0.91, 95% CI: 0.74-1.13, p = 0.42], while a different result was seen for glioblastoma multiforme (GBM) patients (HR = 1.06, 95% CI: 0.80-1.41, p = 0.70). Furthermore, the combined results for tumor progression implied that standard therapy was superior to gene therapy [odds ratio (OR) = 1.31, p = 0.09]; yet differences in HR and OR between experimental groups and control groups had no statistical significance (p > 0.05). Based on the best available evidence, it appears that adding gene therapy with HSV-tk has some effect in treating HGG patients, especially with respect to MST. However, neither the pooled analysis of OS, nor the combined analysis of tumor progress indicates any significant advantage to adding gene therapy compared with standard treatment alone. More prospective studies are needed to draw solid conclusions about whether gene therapy has significant prognostic advantage.

Modeling multisystem biological risk in young adults: The Coronary Artery Risk Development in Young Adults Study.

PubMed

Seeman, Teresa; Gruenewald, Tara; Karlamangla, Arun; Sidney, Steve; Liu, Kiang; McEwen, Bruce; Schwartz, Joseph

2010-01-01

Although much prior research has focused on identifying the roles of major regulatory systems in health risks, the concept of allostatic load (AL) focuses on the importance of a more multisystems view of health risks. How best to operationalize allostatic load, however, remains the subject of some debate. We sought to test a hypothesized metafactor model of allostatic load composed of a number of biological system factors, and to investigate model invariance across sex and ethnicity. Biological data from 782 men and women, aged 32-47, from the Oakland, CA and Chicago, IL sites of the Coronary Artery Risk Development in Young Adults Study (CARDIA) were collected as part of the Year 15exam in 2000. These include measures of blood pressure, metabolic parameters (glucose, insulin, lipid profiles, and waist circumference), markers of inflammation (interleukin-6, C-reactive protein, and fibrinogen), heart rate variability, sympathetic nervous system activity (12-hr urinary norepinephrine and epinephrine) and hypothalamic-pituitary-adrenal axis activity (diurnal salivary free cortisol). A "metafactor" model of AL as an aggregate measure of six underlying latent biological subfactors was found to fit the data, with the metafactor structure capturing 84% of variance of all pairwise associations among biological subsystems. There was little evidence of model variance across sex and/or ethnicity. These analyses extend work operationalizing AL as a multisystems index of biological dysregulation, providing initial support for a model of AL as a metaconstruct of inter-relationships among multiple biological regulatory systems, that varies little across sex or ethnicity.

Low-dose maintenance steroid treatment could reduce the relapse rate in patients with type 1 autoimmune pancreatitis: a long-term Japanese multicenter analysis of 510 patients.

PubMed

Kubota, Kensuke; Kamisawa, Terumi; Okazaki, Kazuichi; Kawa, Shigeyuki; Hirano, Kenji; Hirooka, Yoshiki; Uchida, Kazushige; Shiomi, Hideyuki; Ohara, Hirotaka; Shimizu, Kyoko; Arakura, Norikazu; Kanno, Atsushi; Sakagami, Junichi; Itoi, Takao; Ito, Tetsuhide; Ueki, Toshiharu; Nishino, Takayoshi; Inui, Kazuo; Mizuno, Nobumasa; Yoshida, Hitoshi; Sugiyama, Masanori; Iwasaki, Eisuke; Irisawa, Atshishi; Shimosegawa, Toru; Takeyama, Yoshifumi; Chiba, Tsutomu

2017-08-01

The effect of maintenance steroid treatment (MST) in reducing the risk of relapse in patients with autoimmune pancreatitis (AIP) remains under debate. The aim of this study was to validate the effect of MST on AIP administered in accordance with the 2010 Japanese consensus guidelines. The clinical data of patients with (n = 510) from 22 high-volume centers in Japan were studied. The primary endpoints were the relapse rates (RRs) in patients administered MST versus those not administered MST. The secondary endpoints were the optimal dose and duration of MST in terms of steroid toxicity and the predictors of relapse. The RRs were 10.0% within 1 year, 25.8% within 3 years and 35.1% within 5 years. The RR in the steroid therapy group reached a plateau at 42.7% at 7 years. In terms of the optimal dosage, the overall RR in the MST 5 mg/day group was 26.1%, which was significantly lower than that in the group which had discontinued steroid therapy (45.2%; p = 0.023) or was receiving MST at 2.5 mg/day (43.4%, p = 0.001). The RRs in the group receiving MST at ≥5 mg/day versus the patient group receiving MST at <5 mg/day were 10.6 vs. 10.3% within 1 year, 23.5 vs. 32.9% within 3 years and 32.2 vs. 41.3% within 5 years, respectively (log-rank, p = 0.028). The best cutoff value of the total steroid dose for serious steroid toxicity was 6405 mg, with a moderate accuracy of 0.717 determined using the area under the curve. Presence of diffuse pancreatic swelling [odds ratio OR) 1.745; p = 0.008) and MST at >5 mg/day were identified as predictors of relapse (OR 0.483; p = 0.001). The RR could continue to increase for 7 years even under MST. Based on our analysis of the side effects of steroid therapy, MST at 5 mg/day for 2 (total 4625 mg) to 3 (total 6425 mg) years might be a rational and safe therapeutic strategy in terms of keeping the RR to <30% while avoiding potential steroid toxicity.

Ehlers–Danlos Syndrome—Hypermobility Type: A Much Neglected Multisystemic Disorder

PubMed Central

Gazit, Yael; Jacob, Giris; Grahame, Rodney

2016-01-01

Ehlers–Danlos syndrome (EDS)—hypermobility type (HT) is considered to be the most common subtype of EDS and the least severe one; EDS-HT is considered to be identical to the joint hypermobility syndrome and manifests with musculoskeletal complaints, joint instability, and soft tissue overuse injury. Musculoskeletal complaints manifest with joint pain of non-inflammatory origin and/or spinal pain. Joint instability leads to dislocation or subluxation and involves peripheral joints as well as central joints, including the temporomandibular joints, sacroiliac joints, and hip joints. Soft tissue overuse injury may lead to tendonitis and bursitis without joint inflammation in most cases. Ehlers–Danlos syndrome-HT carries a high potential for disability due to recurrent dislocations and subluxations and chronic pain. Throughout the years, extra-articular manifestations have been described, including cardiovascular, autonomic nervous system, gastrointestinal, hematologic, ocular, gynecologic, neurologic, and psychiatric manifestations, emphasizing the multisystemic nature of EDS-HT. Unfortunately, EDS-HT is under-recognized and inadequately managed, leading to neglect of these patients, which may lead to severe disability that almost certainly could have been avoided. In this review article we will describe the known manifestations of the extra-articular systems. PMID:27824552

[Xanthoma disseminatum with asymptomatic multisystem involvement].

PubMed

Zinoun, M; Hali, F; Marnissi, F; Lazaar, S; Benchikhi, H

2015-04-01

Xanthogranulomas belong to non-Langerhans histiocytosis of the second group in the Histiocyte Society classification. They comprise a heterogeneous group of rare entities frequently involving cutaneous tropism. Xanthoma disseminatum belongs to this group of non-Langerhans histiocytosis. We report a case of xanthoma disseminatum (XD) in which localized skin and mucous impairment revealed multisystem involvement. A 28-year-old man presented with a two-year history of progressive yellow-orange and infiltrated xanthomatous papulonodular lesions of the face. Lesions of the oral mucosa and genital region were seen, with no functional repercussions. No ophthalmic or other complications were found. Histopathology showed a dense histiocytic infiltrate within the dermis with Touton giant cells, foamy multinucleated giant cells and inflammatory cells, without necrobiosis. Histiocytes were positive for CD68 but negative for CD1a. Gastric and lung involvement was seen and was confirmed at histology. Bone scintigraphy showed suspicious left ulnar hyperfixation suggesting bone involvement. No monoclonal gammopathy or diabetes insipidus was seen. Our patient was treated with corticosteroids 1mg/kg/day and thalidomide 100 mg/day. The outcome was marked by regression and exfiltration of the cutaneous lesions from the second week of treatment, with subsidence continuing at 3 months. This case involves a very rare form of xanthoma disseminatum. The localized facial skin lesions revealed multifocal non-Langerhans histiocytosis that was in fact asymptomatic. The diagnosis of XD was based on clinical, histological and immunohistochemical criteria. Xanthoma disseminatum is a non-Langerhans histiocytic proliferation first described by Montgomery in 1938. This rare entity is characterized by skin and mucous membrane xanthomatosis in which the facial involvement is common, together with diabetes insipidus and normal lipid metabolism. The prognosis is determined by the presence of mucosal

Developmental origins of infant stress reactivity profiles: A multi-system approach.

PubMed

Rash, Joshua A; Thomas, Jenna C; Campbell, Tavis S; Letourneau, Nicole; Granger, Douglas A; Giesbrecht, Gerald F

2016-07-01

This study tested the hypothesis that maternal physiological and psychological variables during pregnancy discriminate between theoretically informed infant stress reactivity profiles. The sample comprised 254 women and their infants. Maternal mood, salivary cortisol, respiratory sinus arrhythmia (RSA), and salivary α-amylase (sAA) were assessed at 15 and 32 weeks gestational age. Infant salivary cortisol, RSA, and sAA reactivity were assessed in response to a structured laboratory frustration task at 6 months of age. Infant responses were used to classify them into stress reactivity profiles using three different classification schemes: hypothalamic-pituitary-adrenal (HPA)-axis, autonomic, and multi-system. Discriminant function analyses evaluated the prenatal variables that best discriminated infant reactivity profiles within each classification scheme. Maternal stress biomarkers, along with self-reported psychological distress during pregnancy, discriminated between infant stress reactivity profiles. These results suggest that maternal psychological and physiological states during pregnancy have broad effects on the development of the infant stress response systems. © 2016 Wiley Periodicals, Inc. Dev Psychobiol 58: 578-599, 2016. © 2016 Wiley Periodicals, Inc.

Beyond cervical lipomas: myoclonus, gait disorder and multisystem involvement leading to mitochondrial disease.

PubMed

López-Blanco, Roberto; Rojo-Sebastián, Ana; Torregrosa-Martínez, Maria Henedina; Blazquez, Alberto

2017-06-19

Madelung's disease (benign symmetric lipomatosis) is a rare syndrome in which there are multiple lipomas around the neck, upper limbs and trunk in the context of chronic alcoholism. We report on a female patient with lipomas and slightly progressive myoclonus, neuropathy, myopathy, ataxia and respiratory systemic involvement (labelled in the past as Madelung's disease). Multisystem involvement and family history of lipomas led to the development of mitochondrial genetic tests, which can assess two concurrent mitochondrial mutations: the m.8344A>G mutation in MT-TK gene, related MERRF (myoclonic epilepsy with ragged-red fibre) phenotype and m.14484T>C mutation in the MT-ND6 gene responsible for Leber hereditary optic neuropathy phenotype. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Congenital portosystemic shunt: characterization of a multisystem disease.

PubMed

Sokollik, Christiane; Bandsma, Robert H J; Gana, Juan C; van den Heuvel, Meta; Ling, Simon C

2013-06-01

Congenital portosystemic shunts (CPSSs) are rare but increasingly recognized as a cause of important multisystem morbidity. We present new cases and a systematic literature review and propose an algorithm for the identification and care of affected patients. We reviewed the charts of consecutive patients seen in our pediatric liver clinic between 2003 and 2010 and systematically reviewed the literature of cases with CPSS. We identified 316 published cases and 12 patients in our own clinic. Of the published cases (177 male), 185 had an extrahepatic and 131 an intrahepatic portosystemic shunt. Diagnosis was made at any age, from prenatal to late adulthood. Cardiac anomalies were found in 22% of patients. The main complications were hyperammonemia/neurological abnormalities (35%), liver tumors (26%), and pulmonary hypertension or hepatopulmonary syndrome (18%). The spectrum of neurological involvement ranged from changes in brain imaging, subtle abnormalities on neuropsychological testing, through learning disabilities to overt encephalopathy. Spontaneous shunt closure occurred mainly in infants with intrahepatic shunts. Therapeutic interventions included shunt closure by surgery or interventional radiology techniques (35%) and liver transplantation (10%) leading to an improvement of symptoms in the majority. These findings mirror the observations in our own patients. In this largest review of the reported clinical experience, we identify that children with CPSS may present with otherwise unexplained developmental delay, encephalopathy, pulmonary hypertension, hypoxemia, or liver tumors. When CPSS is diagnosed, children should be screened for all of these complications. Spontaneous closure of intrahepatic shunts may occur in infancy. Closure of the shunt is indicated in symptomatic patients and is associated with a favorable outcome.

Resolution of Hydronephrosis in a Patient With Mucopolysaccharidosis Type II With Enzyme Replacement Therapy.

PubMed

Nishiyama, Kei; Imai, Takashi; Ohkubo, Kazuhiro; Sanefuji, Masafumi; Takada, Hidetoshi

2017-03-01

Mucopolysaccharidosis type II (MPS II) is caused by deficiency of lysosomal enzyme iduronate-2-sulfatase. Insufficient activity of the enzyme results in accumulation of glycosaminoglycans leading to progressive multisystem pathologies. MPS II is less likely to be complicated by kidney and urinary tract problems. We report a boy with MPS II, who developed left hydronephrosis. His hydronephrosis improved after starting enzyme replacement therapy. It was suggested that MPS II was closely associated with the pathogenesis of hydronephrosis. Copyright © 2016 Elsevier Inc. All rights reserved.

Emerging therapies in systemic lupus erythematous: from clinical trial to the real life.

PubMed

Zhang, Huza; Chambers, William; Sciascia, Savino; Cuadrado, Maria J

2016-01-01

Systemic lupus erythematous (SLE) is a chronic autoimmune disease characterised by multisystem involvement and a relapsing remitting course. SLE is a highly heterogeneous condition, with wide variations in both the presentation and severity of disease and the biological markers identified. The use of biologics in SLE has lagged behind that of other rheumatological conditions such as rheumatoid arthritis, in part due to the diverse clinical manifestations of SLE, making it difficult to design appropriate trials for novel treatments. As such, broad immunosuppressive treatment regimens are still widely used in SLE. Nevertheless, in recent years, elucidation of some aspects of SLE pathogenesis have allowed the development of therapies targeted at molecular mediators of SLE. This review provides an update of biological available therapies and those currently under development.

AAV9-based gene therapy partially ameliorates the clinical phenotype of a mouse model of Leigh syndrome

PubMed Central

Di Meo, I; Marchet, S; Lamperti, C; Zeviani, M; Viscomi, C

2017-01-01

Leigh syndrome (LS) is the most common infantile mitochondrial encephalopathy. No treatment is currently available for this condition. Mice lacking Ndufs4, encoding NADH: ubiquinone oxidoreductase iron-sulfur protein 4 (NDUFS4) recapitulates the main findings of complex I (cI)-related LS, including severe multisystemic cI deficiency and progressive neurodegeneration. In order to develop a gene therapy approach for LS, we used here an AAV2/9 vector carrying the human NDUFS4 coding sequence (hNDUFS4). We administered AAV2/9-hNDUFS4 by intravenous (IV) and/or intracerebroventricular (ICV) routes to either newborn or young Ndufs4−/− mice. We found that IV administration alone was only able to correct the cI deficiency in peripheral organs, whereas ICV administration partially corrected the deficiency in the brain. However, both treatments failed to improve the clinical phenotype or to prolong the lifespan of Ndufs4−/− mice. In contrast, combined IV and ICV treatments resulted, along with increased cI activity, in the amelioration of the rotarod performance and in a significant prolongation of the lifespan. Our results indicate that extraneurological organs have an important role in LS pathogenesis and provide an insight into current limitations of adeno-associated virus (AAV)-mediated gene therapy in multisystem disorders. These findings warrant future investigations to develop new vectors able to efficiently target multiple organs. PMID:28753212

AAV9-based gene therapy partially ameliorates the clinical phenotype of a mouse model of Leigh syndrome.

PubMed

Di Meo, I; Marchet, S; Lamperti, C; Zeviani, M; Viscomi, C

2017-10-01

Leigh syndrome (LS) is the most common infantile mitochondrial encephalopathy. No treatment is currently available for this condition. Mice lacking Ndufs4, encoding NADH: ubiquinone oxidoreductase iron-sulfur protein 4 (NDUFS4) recapitulates the main findings of complex I (cI)-related LS, including severe multisystemic cI deficiency and progressive neurodegeneration. In order to develop a gene therapy approach for LS, we used here an AAV2/9 vector carrying the human NDUFS4 coding sequence (hNDUFS4). We administered AAV2/9-hNDUFS4 by intravenous (IV) and/or intracerebroventricular (ICV) routes to either newborn or young Ndufs4 -/- mice. We found that IV administration alone was only able to correct the cI deficiency in peripheral organs, whereas ICV administration partially corrected the deficiency in the brain. However, both treatments failed to improve the clinical phenotype or to prolong the lifespan of Ndufs4 -/- mice. In contrast, combined IV and ICV treatments resulted, along with increased cI activity, in the amelioration of the rotarod performance and in a significant prolongation of the lifespan. Our results indicate that extraneurological organs have an important role in LS pathogenesis and provide an insight into current limitations of adeno-associated virus (AAV)-mediated gene therapy in multisystem disorders. These findings warrant future investigations to develop new vectors able to efficiently target multiple organs.

Adsorption of biometals to monosodium titanate in biological environments

DOE Office of Scientific and Technical Information (OSTI.GOV)

HOBBS, D.T.; MESSER, R. L. W.; LEWIS, J. B.

2005-06-06

Monosodium titanate (MST) is an inorganic sorbent/ion exchanger developed for the removal of radionuclides from nuclear wastes. We investigated the ability of MST to bind Cd(II), Hg(II), or Au(III) to establish the utility of MST for applications in environmental decontamination or medical therapy (drug delivery). Adsorption isotherms for MST were determined at pH 7-7.5 in water or phosphate-buffered saline. The extent of metal binding was determined spectroscopically by measuring the concentrations of the metals in solution before and after contact with the MST. Cytotoxic responses to MST were assessed using THP1 monocytes and succinate dehydrogenase activity. Monocytic activation by MSTmore » was assessed by TNF{alpha} secretion (ELISA) with or without lipopolysaccharide (LPS) activation. MST sorbed Cd(II), Hg(II), and Au(III) under conditions similar to that in physiological systems. MST exhibited the highest affinity for Cd(II) followed by Hg(II) and Au (III). MST (up to 100 mg/L) exhibited only minor (< 25% suppression of succinate dehydrogenase) cytotoxicity and did not trigger TNF{alpha} secretion nor modulate LPS-induced TNF{alpha} secretion from monocytes. MST exhibits high affinity for biometals with no significant biological liabilities in these introductory studies. MST deserves further scrutiny as a substance with the capacity to decontaminate biological environments or deliver metals in a controlled fashion.« less

Lipotoxicity Causes Multisystem Organ Failure and Exacerbates Acute Pancreatitis in Obesity

PubMed Central

Navina, Sarah; Acharya, Chathur; DeLany, James P.; Orlichenko, Lidiya S.; Baty, Catherine J.; Shiva, Sruti S.; Durgampudi, Chandra; Karlsson, Jenny M.; Lee, Kenneth; Bae, Kyongtae T.; Furlan, Alessandro; Behari, Jaideep; Liu, Shiguang; McHale, Teresa; Nichols, Larry; Papachristou, Georgios Ioannis; Yadav, Dhiraj; Singh, Vijay P.

2012-01-01

Obesity increases the risk of adverse outcomes during acute critical illnesses such as burns, severe trauma, and acute pancreatitis. Although individuals with more body fat and higher serum cytokines and lipase are more likely to experience problems, the roles that these characteristics play are not clear. We used severe acute pancreatitis as a representative disease to investigate the effects of obesity on local organ function and systemic processes. In obese humans, we found that an increase in the volume of intrapancreatic adipocytes was associated with more extensive pancreatic necrosis during acute pancreatitis and that acute pancreatitis was associated with multisystem organ failure in obese individuals. In vitro studies of pancreatic acinar cells showed that unsaturated fatty acids were proinflammatory, releasing intracellular calcium, inhibiting mitochondrial complexes I and V, and causing necrosis. Saturated fatty acids had no such effects. Inhibition of lipolysis in obese (ob/ob) mice with induced pancreatitis prevented a rise in serum unsaturated fatty acids and prevented renal injury, lung injury, systemic inflammation, hypocalcemia, reduced pancreatic necrosis, and mortality. Thus, therapeutic approaches that target unsaturated fatty acid–mediated lipotoxicity may reduce adverse outcomes in obese patients with critical illnesses such as severe acute pancreatitis. PMID:22049070

Hippo-YAP signaling pathway: A new paradigm for cancer therapy.

PubMed

Ma, Yanlei; Yang, Yongzhi; Wang, Feng; Wei, Qing; Qin, Huanlong

2015-11-15

In the past decades, the Hippo signaling pathway has been delineated and shown to play multiple roles in the control of organ size in both Drosophila and mammals. In mammals, the Hippo pathway is a kinase cascade leading from Mst1/2 to YAP and its paralog TAZ. Several studies have demonstrated that YAP/TAZ is a candidate oncogene and that other members of the Hippo pathway are tumor suppressive genes. The dysregulation of the Hippo pathway has been observed in a variety of cancers. This review chronicles the recent progress in elucidating the function of Hippo signaling in tumorigenesis and provide a rich source of potential targets for cancer therapy. © 2014 UICC.

Soft X-ray studies on MST: Measuring the effects of toroidicity on tearing mode phase and installation of a multi-energy camera

NASA Astrophysics Data System (ADS)

Vanmeter, Patrick; Reusch, Lisa; Franz, Paolo; Sarff, John; Goetz, John; Delgado-Aparicio, Louis; den Hartog, Daniel

2017-10-01

The soft X-ray tomography (SXT) system on MST uses four cameras in a double-filter configuration to measure the emitted brightness along forty distinct lines of sight. These measurements can then be inverted to determine the emissivity, which depends on physical properties such as temperature, density, and impurity content. The SXR emissivity should correspond to the structure of the magnetic field; however, there is a discrepancy between the phase of the emissivity inversions and magnetic field reconstructions when using the typical cylindrical approximation to interpret the signal from the toroidal magnetics array. This discrepancy was measured for two distinct plasma conditions using all four SXT cameras, with results supporting the interpretation that it emerges from physical effects of the toroidal geometry. In addition, a new soft x-ray measurement system based on the PILATUS3 photon counting detector will be installed on MST. Emitted photons are counted by an array of pixels with individually adjustable energy cutoffs giving the device more spectral information than the double-filter system. This material is based upon work supported by the U.S. Department of Energy, Office of Science, Office of Fusion Energy Sciences program under Award Numbers DE-FC02-05ER54814 and DE-SC0015474.

Characterization and safety evaluation of HPPD W336, a modified 4-hydroxyphenylpyruvate dioxygenase protein, and the impact of its expression on plant metabolism in herbicide-tolerant MST-FGØ72-2 soybean.

PubMed

Dreesen, Rozemarijn; Capt, Annabelle; Oberdoerfer, Regina; Coats, Isabelle; Pallett, Kenneth Edward

2018-06-09

By transgenic expression technology, a modified 4-hydroxyphenylpyruvate dioxygenase enzyme (HPPD W336) originating from Pseudomonas fluorescens is expressed in MST-FGØ72-2 soybean to confer tolerance to 4-benzoyl isoxazole and triketone type of herbicides1F. Characterization and safety assessment of HPPD W336 were performed. No relevant sequence homologies were found with known allergens or toxins. Although sequence identity to known toxins showed identity to HPPD proteins annotated as hemolysins, the absence of hemolytic activity of HPPD W336 was demonstrated in vitro. HPPD W336 degrades rapidly in simulated gastric fluid. The absence of toxicity and hemolytic potential of HPPD W336 was confirmed by in vivo studies. The substrate spectrum of HPPD W336 was compared with wild type HPPD proteins, demonstrating that its expression is unlikely to induce any metabolic shifts in soybean. The potential effect of expression of HPPD W336 on metabolic pathways related to tyrosine was investigated by comparing seed composition of MST-FGØ72-2 soybean with non-genetically modified varieties, demonstrating that expression of HPPD W336 does not change aromatic amino acid, homogentisate and tocochromanol levels. In conclusion, HPPD W336 was demonstrated to be as safe as other food proteins. No adverse metabolic effects were identified related to HPPD W336 expression in MST-FGØ72-2 soybean. Copyright © 2018. Published by Elsevier Inc.

Data processing techniques used with MST radars: A review

NASA Technical Reports Server (NTRS)

Rastogi, P. K.

1983-01-01

The data processing methods used in high power radar probing of the middle atmosphere are examined. The radar acts as a spatial filter on the small scale refractivity fluctuations in the medium. The characteristics of the received signals are related to the statistical properties of these fluctuations. A functional outline of the components of a radar system is given. Most computation intensive tasks are carried out by the processor. The processor computes a statistical function of the received signals, simultaneously for a large number of ranges. The slow fading of atmospheric signals is used to reduce the data input rate to the processor by coherent integration. The inherent range resolution of the radar experiments can be improved significant with the use of pseudonoise phase codes to modulate the transmitted pulses and a corresponding decoding operation on the received signals. Commutability of the decoding and coherent integration operations is used to obtain a significant reduction in computations. The limitations of the processors are outlined. At the next level of data reduction, the measured function is parameterized by a few spectral moments that can be related to physical processes in the medium. The problems encountered in estimating the spectral moments in the presence of strong ground clutter, external interference, and noise are discussed. The graphical and statistical analysis of the inferred parameters are outlined. The requirements for special purpose processors for MST radars are discussed.

Descriptive summary of an outbreak of porcine post-weaning multisystemic wasting syndrome (PMWS ) in New Zealand.

PubMed

Neumann, E J; Dobbinson, S S A; Welch, E B M; Morris, R S

2007-12-01

Investigations were conducted to determine the cause of an acute, multi-farm outbreak of porcine respiratory disease that included diarrhoea and subsequent loss of body condition in affected pigs. A definition for post-weaning multisystemic wasting syndrome (PMWS) including both clinical and pathological features, previously developed for the pig industry in New Zealand, was applied to the current outbreak. In addition to self-reporting by owners of affected farms, local veterinarians, disease and epidemiology consultants, and animal health officials from the Ministry of Agriculture and Forestry (MAF) were involved in conducting farm visits and submission of diagnostic specimens. Pathogens known to be endemic in the pig industry in New Zealand as well as likely exotic diseases were excluded as causative agents of the outbreak. Clinical signs including dyspnoea, diarrhoea, and rapid loss of body condition were consistent with the New Zealand case definition for PMWS. Interstitial pneumonia, pulmonary oedema, generalised lymph-node enlargement, and presence of porcine circovirus type 2 (PCV2) inclusion bodies were consistently identified in affected pigs. Classical swine fever virus (CSFv), Porcine reproductive and respiratory syndrome virus (PRRSv), and Influenza virus were ruled out, using molecular and traditional virological techniques. Spread of the disease between farms was hypothesised to be facilitated by locally migrating flocks of black-backed seagulls. The original source of the disease incursion was not identified. Based on the consistent presence of circovirus-associated lesions in lymphoid tissues in combination with generalised enlargement of lymph nodes, histiocytic interstitial pneumonia, clinical wasting, and poor response to antibiotic therapy, a diagnosis of PMWS was made. PMWS should be considered in the differential diagnoses of sudden onset of respiratory dyspnoea, diarrhoea, and rapid loss of body condition in young pigs in New Zealand pig

Mutations in PTRH2 cause novel infantile-onset multisystem disease with intellectual disability, microcephaly, progressive ataxia, and muscle weakness.

PubMed

Hu, Hao; Matter, Michelle L; Issa-Jahns, Lina; Jijiwa, Mayumi; Kraemer, Nadine; Musante, Luciana; de la Vega, Michelle; Ninnemann, Olaf; Schindler, Detlev; Damatova, Natalia; Eirich, Katharina; Sifringer, Marco; Schrötter, Sandra; Eickholt, Britta J; van den Heuvel, Lambert; Casamina, Chanel; Stoltenburg-Didinger, Gisela; Ropers, Hans-Hilger; Wienker, Thomas F; Hübner, Christoph; Kaindl, Angela M

2014-12-01

To identify the cause of a so-far unreported phenotype of infantile-onset multisystem neurologic, endocrine, and pancreatic disease (IMNEPD). We characterized a consanguineous family of Yazidian-Turkish descent with IMNEPD. The two affected children suffer from intellectual disability, postnatal microcephaly, growth retardation, progressive ataxia, distal muscle weakness, peripheral demyelinating sensorimotor neuropathy, sensorineural deafness, exocrine pancreas insufficiency, hypothyroidism, and show signs of liver fibrosis. We performed whole-exome sequencing followed by bioinformatic analysis and Sanger sequencing on affected and unaffected family members. The effect of mutations in the candidate gene was studied in wild-type and mutant mice and in patient and control fibroblasts. In a consanguineous family with two individuals with IMNEPD, we identified a homozygous frameshift mutation in the previously not disease-associated peptidyl-tRNA hydrolase 2 (PTRH2) gene. PTRH2 encodes a primarily mitochondrial protein involved in integrin-mediated cell survival and apoptosis signaling. We show that PTRH2 is highly expressed in the developing brain and is a key determinant in maintaining cell survival during human tissue development. Moreover, we link PTRH2 to the mTOR pathway and thus the control of cell size. The pathology suggested by the human phenotype and neuroimaging studies is supported by analysis of mutant mice and patient fibroblasts. We report a novel disease phenotype, show that the genetic cause is a homozygous mutation in the PTRH2 gene, and demonstrate functional effects in mouse and human tissues. Mutations in PTRH2 should be considered in patients with undiagnosed multisystem neurologic, endocrine, and pancreatic disease.

Developing a multi-systemic fall prevention model, incorporating the physical environment, the care process and technology: a systematic review.

PubMed

Choi, Young-Seon; Lawler, Erin; Boenecke, Clayton A; Ponatoski, Edward R; Zimring, Craig M

2011-12-01

This paper reports a review that assessed the effectiveness and characteristics of fall prevention interventions implemented in hospitals. A multi-systemic fall prevention model that establishes a practical framework was developed from the evidence. Falls occur through complex interactions between patient-related and environmental risk factors, suggesting a need for multifaceted fall prevention approaches that address both factors. We searched Medline, CINAHL, PsycInfo and the Web of Science databases for references published between January 1990 and June 2009 and scrutinized secondary references from acquired papers. Due to the heterogeneity of interventions and populations, we conducted a quantitative systematic review without a meta-analysis and used a narrative summary to report findings. From the review, three distinct characteristics of fall prevention interventions emerged: (1) the physical environment, (2) the care process and culture and (3) technology. While clinically significant evidence shows the efficacy of environment-related interventions in reducing falls and fall-related injuries, the literature identified few hospitals that had introduced environment-related interventions in their multifaceted fall intervention strategies. Using the multi-systemic fall prevention model, hospitals should promote a practical strategy that benefits from the collective effects of the physical environment, the care process and culture and technology to prevent falls and fall-related injuries. By doing so, they can more effectively address the various risk factors for falling and therefore, prevent falls. Studies that test the proposed model need to be conducted to establish the efficacy of the model in practice. © 2011 The Authors. Journal of Advanced Nursing © 2011 Blackwell Publishing Ltd.

Mutations in PTRH2 cause novel infantile-onset multisystem disease with intellectual disability, microcephaly, progressive ataxia, and muscle weakness

PubMed Central

Hu, Hao; Matter, Michelle L; Issa-Jahns, Lina; Jijiwa, Mayumi; Kraemer, Nadine; Musante, Luciana; de la Vega, Michelle; Ninnemann, Olaf; Schindler, Detlev; Damatova, Natalia; Eirich, Katharina; Sifringer, Marco; Schrötter, Sandra; Eickholt, Britta J; van den Heuvel, Lambert; Casamina, Chanel; Stoltenburg-Didinger, Gisela; Ropers, Hans-Hilger; Wienker, Thomas F; Hübner, Christoph; Kaindl, Angela M

2014-01-01

Objective To identify the cause of a so-far unreported phenotype of infantile-onset multisystem neurologic, endocrine, and pancreatic disease (IMNEPD). Methods We characterized a consanguineous family of Yazidian-Turkish descent with IMNEPD. The two affected children suffer from intellectual disability, postnatal microcephaly, growth retardation, progressive ataxia, distal muscle weakness, peripheral demyelinating sensorimotor neuropathy, sensorineural deafness, exocrine pancreas insufficiency, hypothyroidism, and show signs of liver fibrosis. We performed whole-exome sequencing followed by bioinformatic analysis and Sanger sequencing on affected and unaffected family members. The effect of mutations in the candidate gene was studied in wild-type and mutant mice and in patient and control fibroblasts. Results In a consanguineous family with two individuals with IMNEPD, we identified a homozygous frameshift mutation in the previously not disease-associated peptidyl-tRNA hydrolase 2 (PTRH2) gene. PTRH2 encodes a primarily mitochondrial protein involved in integrin-mediated cell survival and apoptosis signaling. We show that PTRH2 is highly expressed in the developing brain and is a key determinant in maintaining cell survival during human tissue development. Moreover, we link PTRH2 to the mTOR pathway and thus the control of cell size. The pathology suggested by the human phenotype and neuroimaging studies is supported by analysis of mutant mice and patient fibroblasts. Interpretation We report a novel disease phenotype, show that the genetic cause is a homozygous mutation in the PTRH2 gene, and demonstrate functional effects in mouse and human tissues. Mutations in PTRH2 should be considered in patients with undiagnosed multisystem neurologic, endocrine, and pancreatic disease. PMID:25574476

A multisystemic Acanthamoeba infection in a dog in Tenerife, Canary Islands, Spain.

PubMed

Valladares, María; Reyes-Batlle, María; Mora-Peces, Inmaculada; Martín-Navarro, Carmen M; López-Arencibia, Atteneri; Dorta-Gorrín, Alexis; Comyn-Afonso, Estefanía; Martínez-Carretero, Enrique; Maciver, Sutherland K; Piñero, José E; Valladares, Basilio; Lorenzo-Morales, Jacob

2014-10-15

A 22-month-old male Spanish water dog was hospitalized after its physical examination revealed fever and movement difficulty. After 24h, the dog was found to have a high fever (39.5 °C) and was treated empirically with doxycycline/ciprofloxacin. At 48 h, after submission the fever rose to 41 °C and the animal presented with a stiff neck and dehydration. Peripheral blood and cerebrospinal fluid (CSF) were sampled and trophozoites with an Acanthamoeba-like morphology were observed in the CSF. PCR specific for Acanthamoeba, Naegleria fowleri and Balamuthia mandrillaris were performed and the CSF sample found positive for Acanthamoeba. Lungs, kidney, liver and spleen samples were collected post mortem. All collected organ samples were positive for Acanthamoeba by PCR, thus confirming a multisystemic infection. Water samples taken at a suspected site of infection yielded an almost identical PCR fragment to those of the clinical samples, indicating that this was probably where the infection originated. This is the first report of a fatal case of Acanthamoeba disseminated infection in a dog in Spain. Copyright © 2014 Elsevier B.V. All rights reserved.

Outcome in dogs with advanced (stage 3b) anal sac gland carcinoma treated with surgery or hypofractionated radiation therapy.

PubMed

Meier, V; Polton, G; Cancedda, S; Roos, M; Laganga, P; Emmerson, T; Rohrer Bley, C

2017-09-01

Stage 3b anal sac gland carcinoma (ASGC) can be life-threatening. A surgical approach is not always possible or may be declined. Dogs with stage 3b ASGC treated with surgery or conformal radiation therapy (RT) with 8 × 3.8 Gy (total dose 30.4 Gy, over 2.5 weeks) were retrospectively evaluated. Patient characteristics, median progression-free interval (PFI) and median survival time (MST) were compared. Twenty-eight dogs were included; 15 underwent surgery, 13 underwent RT. At the time of presentation, 21% showed life-threatening obstipation and 25% showed hypercalcaemia. PFI and MST for surgery cases were 159 days (95% CI: 135-184 days) and 182 days (95% CI: 146-218 days), both significantly lower than for RT cases with 347 days (95% CI: 240-454 days) and 447 days (95% CI: 222-672 days), (P = 0.01, P = 0.019). Surgery as well as RT led to a fast relief of symptoms. PFI and survival of surgical patients were significantly inferior to that of a comparable patient group treated with conformal hypofractionated RT. © 2016 John Wiley & Sons Ltd.

Impact of Multisystem Health Care on Readmission and Follow-up Among Veterans Hospitalized for Chronic Obstructive Pulmonary Disease.

PubMed

Rinne, Seppo T; Elwy, Anashua R; Bastian, Lori A; Wong, Edwin S; Wiener, Renda S; Liu, Chuan-Fen

2017-07-01

Chronic obstructive pulmonary disease (COPD) is one of the most common causes of readmission at Veterans Affairs (VA) hospitals. Previous studies demonstrate worse outcomes for veterans with multisystem health care, though the impact of non-VA care on COPD readmissions is unknown. To examine the association of use of non-VA outpatient care with 30-day readmission and 30-day follow-up among veterans admitted to the VA for COPD. This is a retrospective cohort study using VA administrative data and Medicare claims. In total, 20,472 Medicare-eligible veterans who were admitted to VA hospitals for COPD during October 1, 2008 and September 30, 2011. We identified the source of outpatient care during the year before the index hospitalization as VA-only, dual-care (VA and Medicare), and Medicare-only. Outcomes of interest included any-cause 30-day readmission, COPD-specific 30-day readmission and follow-up visit within 30 days of discharge. We used mixed-effects logistic regression, controlling for baseline severity of illness, to examine the association between non-VA care and postdischarge outcomes. There was no association between non-VA care and any-cause readmission. We did identify an increased COPD-specific readmission risk with both dual-care [odds ratio (OR)=1.20; 95% confidence interval (CI), 1.02-1.40] and Medicare-only (OR=1.41; 95% CI, 1.15-1.75). Medicare-only outpatient care was also associated with significantly lower rates of follow-up (OR=0.81; 95% CI, 0.72-0.91). Differences in disease-specific readmission risk may reflect differences in disease management between VA and non-VA providers. Further research is needed to understand how multisystem care affects coordination and other measures of quality for veterans with COPD.

Dynamics of particulate organic matter composition in coastal systems: Forcing of spatio-temporal variability at multi-systems scale

NASA Astrophysics Data System (ADS)

Liénart, Camilla; Savoye, Nicolas; David, Valérie; Ramond, Pierre; Rodriguez Tress, Paco; Hanquiez, Vincent; Marieu, Vincent; Aubert, Fabien; Aubin, Sébastien; Bichon, Sabrina; Boinet, Christophe; Bourasseau, Line; Bozec, Yann; Bréret, Martine; Breton, Elsa; Caparros, Jocelyne; Cariou, Thierry; Claquin, Pascal; Conan, Pascal; Corre, Anne-Marie; Costes, Laurence; Crouvoisier, Muriel; Del Amo, Yolanda; Derriennic, Hervé; Dindinaud, François; Duran, Robert; Durozier, Maïa; Devesa, Jérémy; Ferreira, Sophie; Feunteun, Eric; Garcia, Nicole; Geslin, Sandrine; Grossteffan, Emilie; Gueux, Aurore; Guillaudeau, Julien; Guillou, Gaël; Jolly, Orianne; Lachaussée, Nicolas; Lafont, Michel; Lagadec, Véronique; Lamoureux, Jézabel; Lauga, Béatrice; Lebreton, Benoît; Lecuyer, Eric; Lehodey, Jean-Paul; Leroux, Cédric; L'Helguen, Stéphane; Macé, Eric; Maria, Eric; Mousseau, Laure; Nowaczyk, Antoine; Pineau, Philippe; Petit, Franck; Pujo-Pay, Mireille; Raimbault, Patrick; Rimmelin-Maury, Peggy; Rouaud, Vanessa; Sauriau, Pierre-Guy; Sultan, Emmanuelle; Susperregui, Nicolas

2018-03-01

In costal systems, particulate organic matter (POM) results from a multiplicity of sources having their respective dynamics in terms of production, decomposition, transport and burial. The POM pool experiences thus considerable spatial and temporal variability. In order to better understand this variability, the present study employs statistical multivariate analyses to investigate links between POM composition and environmental forcings for a panel of twelve coastal systems distributed along the three maritime regions of France and monitored weekly to monthly for 1 to 8 years. At multi-system scale, two main gradients of POC composition have been identified: a 'Continent-Ocean' gradient associated with hydrodynamics, sedimentary dynamics and depth of the water column, and a gradient of trophic status related to nutrient availability. At local scale, seasonality of POC composition appears to be station-specific but still related to part of the above-mentioned forcings. A typology of systems was established by coupling spatial and temporal variability of POC composition. Four groups were highlighted: (1) the estuarine stations where POC composition is dominated by terrestrial POM and driven by hydrodynamics and sedimentary processes, (2) the oligotrophic systems, characterized by the contribution of diazotrophs due to low nutrient availability, and the marine meso/eutroph systems whose POC composition is (3) either deeply dominated by phytoplankton or (4) dominated by phytoplankton but where the contribution of continental and benthic POC is not negligible and is driven by hydrodynamics, sedimentary processes and the height of the water column. Finally, the present study provides several insights into the different forcings to POM composition and dynamics in temperate coastal systems at local and multi-system scales. This work also presents a methodological approach that establishes statistical links between forcings and POM composition, helping to gain more

The Spectrum of Monogenic Autoinflammatory Syndromes: Understanding Disease Mechanisms and Use of Targeted Therapies

PubMed Central

Glaser, Rachel L.; Goldbach-Mansky, Raphaela

2009-01-01

Monogenic autoinflammatory diseases encompass a distinct and growing clinical entity of multisystem inflammatory diseases with known genetic defects in the innate immune system. The diseases present clinically with episodes of seemingly unprovoked inflammation (fever, rashes, and elevation of acute phase reactants). Understanding the genetics has led to discovery of new molecules involved in recognizing exogenous and endogenous danger signals, and the inflammatory response to these stimuli. These advances have furthered understanding of innate inflammatory pathways and spurred collaborative research in rheumatology and infectious diseases. The pivotal roles of interleukin (IL)-1β in cryopyrin-associated periodic syndromes, tumor necrosis factor (TNF) in TNF receptor-associated periodic syndrome, and links to inflammatory cytokine dysregulation in other monogenic autoinflammatory diseases have resulted in effective therapies targeting proinflammatory cytokines IL-1β and TNF and uncovered other new potential targets for anti-inflammatory therapies. PMID:18606080

Intrinsic Flow and Momentum Transport during Improved Confinement in MST

NASA Astrophysics Data System (ADS)

Craig, D.; Tan, E.; Schott, B.; Anderson, J. K.; Boguski, J.; Nornberg, M. D.; Xing, Z. A.

2017-10-01

Progress in absolute wavelength calibration of the Charge Exchange Recombination Spectroscopy (CHERS) system on MST has enabled new observations and analysis of intrinsic flow and momentum transport. Localized toroidal and poloidal flow measurements with systematic accuracy of +/- 3 km/s have been obtained during improved confinement Pulsed Parallel Current Drive (PPCD) plasmas at high plasma current (400-500 kA). The magnetic activity prior to and during the transition to improved confinement tends to increase the flow and sets the initial condition for the momentum profile evolution during improved confinement where intrinsic flow drive appears to weaken. Inboard flows change in time during PPCD, consistent with changes in the core-resonant m =1, n =6 tearing mode phase velocity. Outboard flows near the magnetic axis are time-independent, resulting in the development of a strongly sheared toroidal flow in the core and asymmetry in the poloidal flow profile. The deceleration of the n =6 mode during the period of improved confinement correlates well with the n =6 mode amplitude and is roughly consistent with the expected torque from eddy currents in the conducting shell. The level of Dα emission and secondary mode amplitudes (n =7-10) do not correlate with the mode deceleration suggesting that the momentum loss from charge exchange with neutrals and diffusion due to residual magnetic stochasticity are not significant in PPCD. This work has been supported by the U.S.D.O.E.

Intravenous immunoglobulin therapy and systemic lupus erythematosus.

PubMed

Zandman-Goddard, Gisele; Levy, Yair; Shoenfeld, Yehuda

2005-12-01

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease with diverse manifestations. We suggest that intravenous immunoglobulin (IVIg) therapy may be beneficial and safe for various manifestations in SLE. A structured literature search of articles published on the efficacy of IVIg in the treatment of SLE between 1983 and 2005 was conducted. We searched the terms "IVIg," "intravenous immunoglobulin," "lupus," "SLE," and "systemic lupus erythematosus." The various clinical manifestations of SLE that were reported to be successfully treated by IVIg in case reports include autoimmune hemolytic anemia, acquired factor VIII inhibitors, acquired von Willebrand disease, pure red cell aplasia, thrombocytopenia, pancytopenia, myelofibrosis, pneumonitis, pleural effusion, pericarditis, myocarditis, cardiogenic shock, nephritis, end-stage renal disease, encephalitis, neuropsychiatric lupus, psychosis, peripheral neuropathy, polyradiculoneuropathy, and vasculitis. The most extensive experience is with lupus nephritis. There are only a few case series of IVIg use in patients with SLE with various manifestations, in which the response rate to IVIg therapy ranged from 33 to 100%. We suggest that IVIg devoid of sucrose, at a dose of 2 g/kg over a 5-d period given uniformly and at a slow infusion rate in patients without an increased risk for thromboembolic events or renal failure, is a safe and beneficial adjunct therapy for cases of SLE that are resistant to or refuse conventional treatment. The duration of therapy is yet to be established. Controlled trials are warranted.

Multisystemic Listeriosis in a Common Brushtail Possum (Trichosurus vulpecula) and Two Common Ringtail Possums (Pseudocheirus peregrinus).

PubMed

Sangster, C R

2016-05-01

A single free-ranging common brushtail possum (Trichosurus vulpecula) and 2 captive sibling common ringtail possums (Pseudocheirus peregrinus)from a zoological facility in Sydney, Australia, were diagnosed with multisystemic listeriosis. The brushtail was found dead in an animal enclosure while the ringtails presented with signs of cardiovascular collapse and died shortly thereafter. All 3 animals were culture positive forListeria monocytogenesand demonstrated focal suppurative lesions within the brainstem in addition to fulminant disease in other areas of the thorax and/or abdomen. Listeriosis in phalangeriformes species has rarely been reported, and brainstem lesions have not previously been described. It is speculated that access to the brainstem by the organism may have occurred hematogenously or via retrograde migration along cranial nerves. Sources of infection and the possibility of transmission between animals are also discussed. © The Author(s) 2015.

Kcne2 Deletion Creates a Multisystem Syndrome Predisposing to Sudden Cardiac Death

PubMed Central

Hu, Zhaoyang; Kant, Ritu; Anand, Marie; King, Elizabeth C.; Krogh-Madsen, Trine; Christini, David J.; Abbott, Geoffrey W.

2014-01-01

Background Sudden cardiac death (SCD) is the leading global cause of mortality, exhibiting increased incidence in diabetics. Ion channel gene perturbations provide a well-established ventricular arrhythmogenic substrate for SCD. However, most arrhythmia susceptibility genes - including the KCNE2 K+ channel β subunit - are expressed in multiple tissues, suggesting potential multiplex SCD substrates. Methods and Results Using “whole transcript” transcriptomics, we uncovered cardiac angiotensinogen upregulation and remodeling of cardiac angiotensinogen interaction networks in P21 Kcne2−/− mouse pups, and adrenal remodeling consistent with metabolic syndrome in adult Kcne2−/− mice. This led to the discovery that Kcne2 disruption causes multiple acknowledged SCD substrates of extracardiac origin: diabetes, hypercholesterolemia, hyperkalemia, anemia and elevated angiotensin II. Kcne2 deletion was also prerequisite for aging-dependent QT prolongation, ventricular fibrillation and SCD immediately following transient ischemia, and fasting-dependent hypoglycemia, myocardial ischemia and atrioventricular block. Conclusions Disruption of a single, widely expressed arrhythmia susceptibility gene can generate a multisystem syndrome comprising manifold electrical and systemic substrates and triggers of SCD. This paradigm is expected to apply to other arrhythmia susceptibility genes, the majority of which encode ubiquitously expressed ion channel subunits or regulatory proteins. PMID:24403551

Neuroimaging to Investigate Multisystem Involvement and Provide Biomarkers in Amyotrophic Lateral Sclerosis

PubMed Central

Pradat, Pierre-François; El Mendili, Mohamed-Mounir

2014-01-01

Neuroimaging allows investigating the extent of neurological systems degeneration in amyotrophic lateral sclerosis (ALS). Advanced MRI methods can detect changes related to the degeneration of upper motor neurons but have also demonstrated the participation of other systems such as the sensory system or basal ganglia, demonstrating in vivo that ALS is a multisystem disorder. Structural and functional imaging also allows studying dysfunction of brain areas associated with cognitive signs. From a biomarker perspective, numerous studies using diffusion tensor imaging showed a decrease of fractional anisotropy in the intracranial portion of the corticospinal tract but its diagnostic value at the individual level remains limited. A multiparametric approach will be required to use MRI in the diagnostic workup of ALS. A promising avenue is the new methodological developments of spinal cord imaging that has the advantage to investigate the two motor system components that are involved in ALS, that is, the lower and upper motor neuron. For all neuroimaging modalities, due to the intrinsic heterogeneity of ALS, larger pooled banks of images with standardized image acquisition and analysis procedures are needed. In this paper, we will review the main findings obtained with MRI, PET, SPECT, and nuclear magnetic resonance spectroscopy in ALS. PMID:24949452

Fast ion beta limit measurements by collimated neutron detection in MST plasmas

NASA Astrophysics Data System (ADS)

Capecchi, William; Anderson, Jay; Bonofiglo, Phillip; Kim, Jungha; Sears, Stephanie

2015-11-01

Fast ion orbits in the reversed field pinch (RFP) are well ordered and classically confined despite magnetic field stochasticity generated by multiple tearing modes. Classical TRANSP modeling of a 1MW tangentially injected hydrogen neutral beam in MST deuterium plasmas predicts a core-localized fast ion density that can be up to 25% of the electron density and a fast ion beta of many times the local thermal beta. However, neutral particle analysis of an NBI-driven mode (presumably driven by a fast ion pressure gradient) shows mode-induced transport of core-localized fast ions and a saturated fast ion density. The TRANSP modeling is presumed valid until the onset of the beam-driven mode and gives an initial estimate of the volume-averaged fast ion beta of 1-2% (local core value up to 10%). A collimated neutron detector for fusion product profile measurements will be used to determine the spatial distribution of fast ions, allowing for a first measurement of the critical fast-ion pressure gradient required for mode destabilization. Testing/calibration data and initial fast-ion profiles will be presented. Characterization of both the local and global fast ion beta will be done for deuterium beam injection into deuterium plasmas for comparison to TRANSP predictions. Work supported by US DOE.

Design of an RF System for Electron Bernstein Wave Studies in MST

NASA Astrophysics Data System (ADS)

Kauffold, J. X.; Seltzman, A. H.; Anderson, J. K.; Nonn, P. D.; Forest, C. B.

2010-11-01

Motivated by the possibility of current profile control a 5.5GHz RF system for EBW is being developed. The central component is a standard radar Klystron with 1.2MW peak power and 4μs typical pulse length. Meaningful experiments require RF pulse lengths similar to the characteristic electron confinement times in MST necessitating the creation of a power supply providing 80kV at 40A for 10ms. A low inductance IGBT network switches power at 20kHz from an electrolytic capacitor bank into the primary of a three-phase resonant transformer system that is then rectified and filtered. The system uses three magnetically separate transformers with microcrystalline iron cores to provide suitable volt-seconds and low hysteresis losses. Each phase has a secondary with a large leakage inductance and a parallel capacitor providing a boost ratio greater than 60:1 with a physical turns ratio of 13.5:1. A microprocessor feedback control system varies the drive frequency around resonance to regulate the boost ratio and provide a stable output as the storage bank discharges. The completed system will deliver RF to the plasma boundary where coupling to the Bernstein mode and subsequent heating and current drive can occur.

Do You Really Expect Me to Get MST Care in a VA Where Everyone Is Male Innovative Delivery of Evidence Based Psychotherapy to Women with Military Sexual Trauma

DTIC Science & Technology

2017-08-01

INTRODUCTION: Veterans who experience military sexual trauma (MST) are at heightened risk of developing psychiatric difficulties such as post ...have the potential to experience significant symptom reduction related to their military sexual trauma post -intervention (i.e., within 12 weeks...PTSD treatment outcome study focused exclusively on female Veterans and no extant studies testing home-based telehealth for sexual assault victims

Inhibition of in vitro and in vivo brown fat differentiation program by myostatin.

PubMed

Braga, Melissa; Pervin, Shehla; Norris, Keith; Bhasin, Shalender; Singh, Rajan

2013-06-01

Obesity arises mainly due to the imbalance between energy storage and its expenditure. Metabolically active brown adipose tissue (BAT) has recently been detected in humans and has been proposed as a new target for anti-obesity therapy because of its unique capacity to regulate energy expenditure. Myostatin (Mst), a negative regulator of muscle mass, has been identified as a potential target to regulate overall body composition. Although the beneficial effects of Mst inhibition on muscle mass are well known, its role in the regulation of lipid metabolism, and energy expenditure is not very clear. We tested the effects of Mst inhibition on the gene regulatory networks that control BAT differentiation using both in vivo and in vitro model systems. PRDM16 and UCP1, two key regulators of brown fat differentiation were significantly up regulated in levator-ani (LA) and gastrocnemius (Gastroc) muscles as well as in epididymal (Epi) and subcutaneous (SC) fat pads isolated from Mst knock out (Mst KO) male mice compared with wild type (WT) mice. Using mouse embryonic fibroblast (MEFs) primary cultures obtained from Mst KO group compared to the WT group undergoing adipogenic differentiation, we also demonstrate a significant increase in select genes and proteins that improve lipid metabolism and energy expenditure. Treatment of Mst KO MEFs with recombinant Mst protein significantly inhibited the gene expression levels of UCP1, PRDM16, PGC1-α/β as well as BMP7. Future studies to extend these findings and explore the therapeutic potential of Mst inhibition on metabolic disorders are warranted. Copyright © 2012 The Obesity Society.

The multi-systemic nature of diabetes mellitus: Genotype or phenotype?

PubMed Central

Ewing, Graham Wilfred; Parvez, Syed Hasan

2010-01-01

Background: This article discusses factors which materially influence the diagnosis, prevention and treatment of diabetes mellitus but which may be overlooked by the prevailing biomedical paradigm. That cognition can be mathematically linked to the function of the autonomic nervous system and physiological systems casts new light upon the mechanisms responsible for homeostasis and origins of disease. In particular, it highlights the limitations of the reductionist biomedical approach which considers mainly the biochemistry of single pathologies rather than considering the neural mechanisms which regulate the function of physiological systems, and inherent visceral organs; and which are subsequently manifest as biochemistries of varying degrees of complexity and severity. As a consequence, histopathological tests are fraught with inherent limitations and many categories of drugs are significantly ineffective. Aims: Such limitations may be explained if disease (in particular diabetes mellitus) has multiple origins, is multi-systemic in nature and, depending upon the characteristics of each pathology, is influenced by genotype and/or phenotype. Results: This article highlights the influence of factors which are not yet considered re. the aetiology of diabetes mellitus e.g. the influence of light and sensory input upon the stability of the autonomic nervous system; the influence of raised plasma viscosity upon rates of reaction; the influence of viruses and/or of modified live viruses given in vaccinations; systemic instability, in particular the adverse influence of drinks and lack of exercise upon the body's prevailing pH and its subsequent influence upon levels of magnesium and other essential trace elements. Conclusions: This application of the top-down systems biology approach may provide a plausible and inclusive explanation for the nature and occurrence of diabetes mellitus. PMID:22558546

The gut microbiota and inflammatory noncommunicable diseases: associations and potentials for gut microbiota therapies.

PubMed

West, Christina E; Renz, Harald; Jenmalm, Maria C; Kozyrskyj, Anita L; Allen, Katrina J; Vuillermin, Peter; Prescott, Susan L

2015-01-01

Rapid environmental transition and modern lifestyles are likely driving changes in the biodiversity of the human gut microbiota. With clear effects on physiologic, immunologic, and metabolic processes in human health, aberrations in the gut microbiome and intestinal homeostasis have the capacity for multisystem effects. Changes in microbial composition are implicated in the increasing propensity for a broad range of inflammatory diseases, such as allergic disease, asthma, inflammatory bowel disease (IBD), obesity, and associated noncommunicable diseases (NCDs). There are also suggestive implications for neurodevelopment and mental health. These diverse multisystem influences have sparked interest in strategies that might favorably modulate the gut microbiota to reduce the risk of many NCDs. For example, specific prebiotics promote favorable intestinal colonization, and their fermented products have anti-inflammatory properties. Specific probiotics also have immunomodulatory and metabolic effects. However, when evaluated in clinical trials, the effects are variable, preliminary, or limited in magnitude. Fecal microbiota transplantation is another emerging therapy that regulates inflammation in experimental models. In human subjects it has been successfully used in cases of Clostridium difficile infection and IBD, although controlled trials are lacking for IBD. Here we discuss relationships between gut colonization and inflammatory NCDs and gut microbiota modulation strategies for their treatment and prevention. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

A new paradigm: Diagnosis and management of HSCT-associated thrombotic microangiopathy as multi-system endothelial injury

PubMed Central

Jodele, Sonata; Laskin, Benjamin L; Dandoy, Christopher E.; Myers, Kasiani C.; El-Bietar, Javier; Davies, Stella M.; Goebel, Jens; Dixon, Bradley P.

2015-01-01

Hematopoietic stem cell transplantation (HSCT)-associated thrombotic microangiopathy (TA-TMA) is now a well-recognized and potentially severe complication of HSCT that carries a high risk of death. In those who survive, TA-TMA may be associated with long-term morbidity and chronic organ injury. Recently, there have been new insights into the incidence, pathophysiology, and management of TA-TMA. Specifically, TA-TMA can manifest as a multi-system disease occurring after various triggers of small vessel endothelial injury, leading to subsequent tissue damage in different organs. While the kidney is most commonly affected, TA-TMA involving organs such as the lung, bowel, heart, and brain is now known to have specific clinical presentations. We now review the most up-to-date research on TA-TMA, focusing on the pathogenesis of endothelial injury, the diagnosis of TA-TMA affecting the kidney and other organs, and new clinical approaches to the management of this complication after HSCT. PMID:25483393

BRAF Mutation Correlates With High-Risk Langerhans Cell Histiocytosis and Increased Resistance to First-Line Therapy.

PubMed

Héritier, Sébastien; Emile, Jean-François; Barkaoui, Mohamed-Aziz; Thomas, Caroline; Fraitag, Sylvie; Boudjemaa, Sabah; Renaud, Florence; Moreau, Anne; Peuchmaur, Michel; Chassagne-Clément, Catherine; Dijoud, Frédérique; Rigau, Valérie; Moshous, Despina; Lambilliotte, Anne; Mazingue, Françoise; Kebaili, Kamila; Miron, Jean; Jeziorski, Eric; Plat, Geneviève; Aladjidi, Nathalie; Ferster, Alina; Pacquement, Hélène; Galambrun, Claire; Brugières, Laurence; Leverger, Guy; Mansuy, Ludovic; Paillard, Catherine; Deville, Anne; Armari-Alla, Corinne; Lutun, Anne; Gillibert-Yvert, Marion; Stephan, Jean-Louis; Cohen-Aubart, Fleur; Haroche, Julien; Pellier, Isabelle; Millot, Frédéric; Lescoeur, Brigitte; Gandemer, Virginie; Bodemer, Christine; Lacave, Roger; Hélias-Rodzewicz, Zofia; Taly, Valérie; Geissmann, Frédéric; Donadieu, Jean

2016-09-01

Langerhans cell histiocytosis (LCH) is an inflammatory myeloid neoplasia with a broad spectrum of clinical manifestations and outcomes in children. The somatic BRAF(V600E) mutation occurs frequently, but clinical significance remains to be determined. BRAF(V600E) mutation was investigated in a French LCH cohort. We analyzed associations between mutation status and clinical presentation, extent of disease, reactivation rate, response to therapy, and long-term permanent sequelae. Among 315 patients with successfully determined BRAF status, 173 (54.6%) carried a BRAF(V600E) mutation. Patients with BRAF(V600E) manifested more severe disease than did those with wild-type BRAF. Patients with BRAF(V600E) comprised 87.8% of patients (43 of 49) with multisystem LCH with risk organ involvement (liver, spleen, hematology), 68.6% of patients (35 of 51) with multisystem LCH without risk organ involvement, 43.9% of patients (86 of 196) with single-system LCH, and 42.1% of patients (8 of 19) with lung-involved LCH (P < .001). BRAF(V600E) mutation was also associated with organ involvement that could lead to permanent, irreversible damage, such as neurologic (75%) and pituitary (72.9%) injuries. Compared with patients with wild-type BRAF, patients with BRAF(V600E) more commonly displayed resistance to combined vinblastine and corticosteroid therapy (21.9% v 3.3%; P = .001), showed a higher reactivation rate (5-year reactivation rate, 42.8% v 28.1%; P = .006), and had more permanent, long-term consequences from disease or treatment (27.9% v 12.6%; P = .001). In children with LCH, BRAF(V600E) mutation was associated with high-risk features, permanent injury, and poor short-term response to chemotherapy. Further population-based studies should be undertaken to confirm our observations and to assess the impact of BRAF inhibitors for this subgroup of patients who may benefit from targeted therapy. © 2016 by American Society of Clinical Oncology.

Reproduction of post-weaning multi-systemic wasting syndrome in an animal disease model as a tool for vaccine testing under controlled conditions.

PubMed

McKillen, John; McNair, Irene; Lagan, Paula; McKay, Karen; McClintock, Julie; Casement, Veronica; Charreyre, Catherine; Allan, Gordon

2016-04-01

Snatch farrowed, colostrum deprived piglets were inoculated with different combinations of porcine circovirus 2, porcine parvovirus and Erysipelothrix rhusiopathiae candidate vaccines. 10 piglets were mock-vaccinated. Following virus challenge with a combined porcine circovirus 2/porcine parvovirus inoculum, all animals were monitored and samples taken for serology, immunohistochemistry and qPCR. At 24 dpc all non-vaccinated animals remaining were exhibiting signs of post-weaning multi-systemic wasting syndrome which was confirmed by laboratory analysis. Details of the study, analysis of samples and performance of the candidate vaccines are described. Copyright © 2016 Elsevier Ltd. All rights reserved.

ST2 blockade reduces sST2-producing T cells while maintaining protective mST2-expressing T cells during graft-versus-host disease

PubMed Central

Zhang, Jilu; Ramadan, Abdulraouf M.; Griesenauer, Brad; Li, Wei; Turner, Matthew J.; Liu, Chen; Kapur, Reuben; Hanenberg, Helmut; Blazar, Bruce R.; Tawara, Isao; Paczesny, Sophie

2015-01-01

Graft-versus-host disease (GVHD) remains a devastating complication after allogeneic hematopoietic cell transplantation (HCT). We previously identified high plasma soluble suppression of tumorigenicity 2 (sST2) as a biomarker of the development of GVHD and death. sST2 sequesters interleukin (IL)-33, limiting its availability to T cells expressing membrane-bound ST2 (mST2) [Th2 cells and ST2+FoxP3+regulatory T cells]. Here, we report that blockade of sST2 in the peri-transplant period with a neutralizing monoclonal antibody (anti-ST2 mAb) reduced GVHD severity and mortality. We identified intestinal stromal cells and T cells as major sources of sST2 during GVHD. ST2 blockade decreased systemic interferon-γ, IL-17, and IL-23 but increased IL-10 and IL-33 plasma levels. ST2 blockade also reduced sST2 production by IL-17–producing T cells while maintaining protective mST2-expressing T cells, increasing the frequency of intestinal myeloid-derived suppressor cells, and decreasing frequency of intestinal CD103 dendritic cells. Finally, ST2 blockade preserved graft-versus-leukemia activity in a model of GFP+MLL-AF9 acute myeloid leukemia. Our findings suggest that ST2 is a therapeutic target for severe GVHD, and that the ST2/IL-33 pathway could be investigated in other T-cell mediated immune disorders with loss of tolerance. PMID:26446957

Upgrades to improve the usability, reliability, and spectral range of the MST Thomson scattering diagnostic

NASA Astrophysics Data System (ADS)

Kubala, S. Z.; Borchardt, M. T.; Den Hartog, D. J.; Holly, D. J.; Jacobson, C. M.; Morton, L. A.; Young, W. C.

2016-11-01

The Thomson scattering diagnostic on MST records both equilibrium and fluctuating electron temperature with a range capability of 10 eV-5 keV. Standard operation with two modified commercial Nd:YAG lasers allows measurements at rates of 1 kHz-25 kHz. Several subsystems of the diagnostic are being improved. The power supplies for the avalanche photodiode detectors (APDs) that record the scattered light are being replaced to improve usability, reliability, and maintainability. Each of the 144 APDs will have an individual rack mounted switching supply, with bias voltage adjustable to match the APD. Long-wavelength filters (1140 nm center, 80 nm bandwidth) have been added to the polychromators to improve capability to resolve non-Maxwellian distributions and to enable directed electron flow measurements. A supercontinuum (SC) pulsed white light source has replaced the tungsten halogen lamp previously used for spectral calibration of the polychromators. The SC source combines substantial brightness produced in nanosecond pulses with a spectrum that covers the entire range of the polychromators.

Upgrades to improve the usability, reliability, and spectral range of the MST Thomson scattering diagnostic.

PubMed

Kubala, S Z; Borchardt, M T; Den Hartog, D J; Holly, D J; Jacobson, C M; Morton, L A; Young, W C

2016-11-01

The Thomson scattering diagnostic on MST records both equilibrium and fluctuating electron temperature with a range capability of 10 eV-5 keV. Standard operation with two modified commercial Nd:YAG lasers allows measurements at rates of 1 kHz-25 kHz. Several subsystems of the diagnostic are being improved. The power supplies for the avalanche photodiode detectors (APDs) that record the scattered light are being replaced to improve usability, reliability, and maintainability. Each of the 144 APDs will have an individual rack mounted switching supply, with bias voltage adjustable to match the APD. Long-wavelength filters (1140 nm center, 80 nm bandwidth) have been added to the polychromators to improve capability to resolve non-Maxwellian distributions and to enable directed electron flow measurements. A supercontinuum (SC) pulsed white light source has replaced the tungsten halogen lamp previously used for spectral calibration of the polychromators. The SC source combines substantial brightness produced in nanosecond pulses with a spectrum that covers the entire range of the polychromators.

Gravity-wave spectra in the atmosphere observed by MST radar, part 4.2B

NASA Technical Reports Server (NTRS)

Scheffler, A. O.; Liu, C. H.

1984-01-01

A universal spectrum of atmospheric buoyancy waves is proposed based on data from radiosonde, Doppler navigation, not-wire anemometer and Jimsphere balloon. The possible existence of such a universal spectrum clearly will have significant impact on several areas in the study of the middle atmosphere dynamics such as the parameterization of sub-grid scale gravity waves in global circulation models; the transport of trace constituents and heat in the middle atmosphere, etc. Therefore, it is important to examine more global wind data with temporal and spatial resolutions suitable for the investigation of the wave spectra. Mesosphere-stratosphere-troposphere (MST) radar observations offer an excellent opportunity for such studies. It is important to realize that radar measures the line-of-sight velocity which, in general, contains the combination of the vertical and horizontal components of the wave-associated particle velocity. Starting from a general oblique radar observation configuration, applying the dispersion relation for the gravity waves, the spectrum for the observed fluctuations in the line-of-sight gravity-wave spectrum is investigated through a filter function. The consequence of the filter function on data analysis is discussed.

Judging sound rotation when listeners and sounds rotate: Sound source localization is a multisystem process.

PubMed

Yost, William A; Zhong, Xuan; Najam, Anbar

2015-11-01

In four experiments listeners were rotated or were stationary. Sounds came from a stationary loudspeaker or rotated from loudspeaker to loudspeaker around an azimuth array. When either sounds or listeners rotate the auditory cues used for sound source localization change, but in the everyday world listeners perceive sound rotation only when sounds rotate not when listeners rotate. In the everyday world sound source locations are referenced to positions in the environment (a world-centric reference system). The auditory cues for sound source location indicate locations relative to the head (a head-centric reference system), not locations relative to the world. This paper deals with a general hypothesis that the world-centric location of sound sources requires the auditory system to have information about auditory cues used for sound source location and cues about head position. The use of visual and vestibular information in determining rotating head position in sound rotation perception was investigated. The experiments show that sound rotation perception when sources and listeners rotate was based on acoustic, visual, and, perhaps, vestibular information. The findings are consistent with the general hypotheses and suggest that sound source localization is not based just on acoustics. It is a multisystem process.

High-frequency fluctuation measurements by far-infrared laser Faraday-effect polarimetry-interferometry and forward scattering system on MST.

PubMed

Ding, W X; Lin, L; Duff, J R; Brower, D L

2014-11-01

Magnetic fluctuation-induced transport driven by global tearing modes has been measured by Faraday-effect polarimetry and interferometry (phase measurements) in the MST reversed field pinch. However, the role of small-scale broadband magnetic and density turbulence in transport remains unknown. In order to investigate broadband magnetic turbulence, we plan to upgrade the existing detector system by using planar-diode fundamental waveguide mixers optimized for high sensitivity. Initial tests indicate these mixers have ×10 sensitivity improvement compared to currently employed corner-cube Schottky-diode mixers and ×5 lower noise. Compact mixer design will allow us to resolve the wavenumbers up to k ∼ 1-2 cm(-1) for beam width w = 1.5 cm and 15 cm(-1) for beam width w = 2 mm. The system can also be used to measure the scattered signal (amplitude measurement) induced by both plasma density and magnetic fluctuations.

Integrated multisystem analysis in a mental health and criminal justice ecosystem.

PubMed

Falconer, Erin; El-Hay, Tal; Alevras, Dimitris; Docherty, John; Yanover, Chen; Kalton, Alan; Goldschmidt, Yaara; Rosen-Zvi, Michal

2014-01-01

Patients with a serious mental illness often receive care that is fragmented due to reduced availability of or access to resources, and inadequate, discontinuous, and uncoordinated care across health, social services, and criminal justice organizations. These gaps in care may lead to increased mental health disease burden and relapse, as well as repeated incarcerations. Further, the complex health, social service, and criminal justice ecosystem within which the patient may be embedded makes it difficult to examine the role of modifiable risk factors and delivered services on patient outcomes, particularly given that agencies often maintain isolated sets of relevant data. Here we describe an approach to creating a multisystem analysis that derives insights from an integrated data set including patient access to case management services, medical services, and interactions with the criminal justice system. We combined data from electronic systems within a US mental health ecosystem that included mental health and substance abuse services, as well as data from the criminal justice system. We applied Cox models to test the associations between delivery of services and re-incarceration. Using this approach, we found an association between arrests and crisis stabilization services in this population. We also found that delivery of case management or medical services provided after release from jail was associated with a reduced risk for re-arrest. Additionally, we used machine learning to train and validate a predictive model linking non-modifiable and modifiable risk factors and outcomes. A predictive model, constructed using elastic net regularized logistic regression, and considering age, past arrests, mental health diagnosis, as well as use of a jail diversion program, outpatient, medical and case management services predicted the probability of re-arrests with fair accuracy (AUC=.67). By modeling the complex interactions between risk factors, service delivery and

The multisystem degeneration amyotrophic lateral sclerosis - neuropathological staging and clinical translation.

PubMed

Verde, Federico; Del Tredici, Kelly; Braak, Heiko; Ludolph, Albert

2017-12-01

Amyotrophic lateral sclerosis (ALS) is traditionally considered a disease affecting exclusively motor neurons. However, much evidence points towards additional involvement of brain systems other than the motor. As much as half of ALS patients display cognitive-behavioral disturbances. ALS shares with a considerable proportion of FTD cases the same neuropathological substrate, namely, inclusions of abnormally phosphorylated protein TDP-43 (pTDP-43). In analogy with pathological staging systems elaborated in the past decades for Alzheimer's disease (AD) and Parkinson's disease (PD), a model of staging of pTDP-43 pathology in sporadic ALS (sALS) has been recently proposed. According to it, 4 stages can be recognized, where pTDP-43 inclusions are found in the agranular motor cortex and α-motor neurons of the brain stem and spinal cord (stage 1), in prefrontal neocortex (middle frontal gyrus), reticular formation, and precerebellar nuclei (stage 2), in further areas of the prefrontal neocortex (gyrus rectus and orbitofrontal gyri), postcentrally located sensory cortex, and basal ganglia (stage 3), and in the anteromedial temporal lobe including the hippocampus (stage 4). Based on this staging effort, a corticofugal axonal model for spreading of pathology can be hypothesized, whereby pathology starts in the primary motor cortex and spreads from there via axonal projections to lower motor neurons and to subcortical structures. Recent neuroradiological evidence seems to support the proposed staging system. From the clinical standpoint, a proportion of ALS patients display extramotor deficits (namely cognitive-behavioural disturbances, impaired ocular movements, and extrapyramidal alterations), which seem to correspond to the pathological involvement of the relevant cerebral structures. This review describes neuropathological sALS staging and addresses clinical evidence corresponding to this staging, pointing towards the concept of ALS as a multisystem brain degeneration

OUTCOME OF DOGS WITH INTRANASAL LYMPHOMA TREATED WITH VARIOUS RADIATION AND CHEMOTHERAPY PROTOCOLS: 24 CASES.

PubMed

George, Rebecca; Smith, Annette; Schleis, Stephanie; Brawner, William; Almond, Gregory; Kent, Michael; Wypij, Jackie; Borrego, Juan; Moore, Antony; Keyerleber, Michele; Kraiza, Sarah

2016-05-01

Tumors of the nasal cavity comprise approximately 1% of all neoplasms in dogs. Canine intranasal lymphoma is rare and reports evaluating the outcome of treatment are lacking. The goal of this observational, descriptive, multi-institutional study was to evaluate the overall median survival times (MSTs) in a group of dogs with intranasal lymphoma that were treated with irradiation and/or chemotherapy. Dogs meeting these inclusion criteria were retrospectively recruited from medical archives at multiple institutions. Eighteen cases of intermediate to high grade intranasal lymphoma and six cases of low-grade intranasal lymphoma were identified. The date of diagnosis, method of diagnosis, treatment received (radiation and/or chemotherapy protocols), and date of death were recorded. Kaplan-Meier survival analysis was performed on the intermediate to high grade group to calculate overall MST. Log-rank tests were performed to compare effects of treatment with radiation therapy ± chemotherapy and chemotherapy alone. Kaplan-Meier survival analysis was performed separately on the low-grade group. The overall MST was 375 days for the intermediate to high grade group. Cases treated with radiation ± chemotherapy had an MST of 455 days (n = 12) and those treated with chemotherapy alone (n = 6) had an MST of 157 days in the intermediate to high grade group. The MST was 823 days for the low-grade group. Results support the use of radiation therapy for treatment of canine intranasal lymphoma, however a randomized, controlled, clinical trial would be needed for more definitive recommendations. The role of adjunctive chemotherapy also may require further investigation. © 2016 American College of Veterinary Radiology.

Variations in optical coherence tomography resolution and uniformity: a multi-system performance comparison

PubMed Central

Fouad, Anthony; Pfefer, T. Joshua; Chen, Chao-Wei; Gong, Wei; Agrawal, Anant; Tomlins, Peter H.; Woolliams, Peter D.; Drezek, Rebekah A.; Chen, Yu

2014-01-01

Point spread function (PSF) phantoms based on unstructured distributions of sub-resolution particles in a transparent matrix have been demonstrated as a useful tool for evaluating resolution and its spatial variation across image volumes in optical coherence tomography (OCT) systems. Measurements based on PSF phantoms have the potential to become a standard test method for consistent, objective and quantitative inter-comparison of OCT system performance. Towards this end, we have evaluated three PSF phantoms and investigated their ability to compare the performance of four OCT systems. The phantoms are based on 260-nm-diameter gold nanoshells, 400-nm-diameter iron oxide particles and 1.5-micron-diameter silica particles. The OCT systems included spectral-domain and swept source systems in free-beam geometries as well as a time-domain system in both free-beam and fiberoptic probe geometries. Results indicated that iron oxide particles and gold nanoshells were most effective for measuring spatial variations in the magnitude and shape of PSFs across the image volume. The intensity of individual particles was also used to evaluate spatial variations in signal intensity uniformity. Significant system-to-system differences in resolution and signal intensity and their spatial variation were readily quantified. The phantoms proved useful for identification and characterization of irregularities such as astigmatism. Our multi-system results provide evidence of the practical utility of PSF-phantom-based test methods for quantitative inter-comparison of OCT system resolution and signal uniformity. PMID:25071949

Pachymeningeal involvement in POEMS syndrome: dramatic cerebral MRI improvement after lenalidomide therapy.

PubMed

Briani, Chiara; Manara, Renzo; Lessi, Federica; Citton, Valentina; Zambello, Renato; Adami, Fausto

2012-05-01

POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) syndrome is a rare multisystemic disease associated with plasma cell dyscrasia and increased serum or plasma vascular endothelial growth factor (VEGF) levels, the latter likely responsible for several POEMS syndrome manifestations. Whereas peripheral neuropathy is the main neurological feature and a mandatory diagnostic criterium, central nervous system involvement is less common except for papilledema and stroke. We recently reported the frequent occurrence at brain MRI of cranial pachymeningeal involvement ina series of POEMS syndrome patients. Meningeal histopathology revealed hyperplasia of meningothelial cells, neovascularization, and obstructive vessel remodeling without inflammatory signs pointing to a role of VEGF in the meningeal manifestations. Here, we report the dramatic pachymeningeal improvement in patients undergoing lenalidomide therapy. These findings support the therapeutic role of lenalidomide and might shed further light on the pathophysiology of the disease

Quantitative, competitive PCR analysis of porcine circovirus DNA in serum from pigs with postweaning multisystemic wasting syndrome.

PubMed

Liu, Q; Wang, L; Willson, P; Babiuk, L A

2000-09-01

A competitive PCR (cPCR) assay was developed for monitoring porcine circovirus (PCV) DNA in serum samples from piglets. The cPCR was based on competitive coamplification of a 502- or 506-bp region of the PCV type 1 (PCV1) or PCV2 ORF2, respectively, with a known concentration of competitor DNA, which produced a 761- or 765-bp fragment, respectively. The cPCR was validated by quantification of a known amount of PCV wild-type plasmids. We also used this technique to determine PCV genome copy numbers in infected cells. Furthermore, we measured PCV DNA loads in clinical samples. More than 50% of clinically healthy piglets could harbor both types of PCV. While PCV1 was detected in only 3 of 16 pigs with postweaning multisystemic wasting syndrome (PMWS), all the sick piglets contained PCV2. A comparison of the PCV2 DNA loads of healthy and sick animals revealed a significant difference, indicating that the development of PMWS may require a certain amount of PCV2.

Characterization of beam-driven instabilities and current redistribution in MST plasmas

NASA Astrophysics Data System (ADS)

Parke, E.

2015-11-01

A unique, high-rep-rate (>10 kHz) Thomson scattering diagnostic and a high-bandwidth FIR interferometer-polarimeter on MST have enabled characterization of beam-driven instabilities and magnetic equilibrium changes observed during high power (1 MW) neutral beam injection (NBI). While NBI leads to negligible net current drive, an increase in on-axis current density observed through Faraday rotation is offset by a reduction in mid-radius current. Identification of the phase flip in temperature fluctuations associated with tearing modes provides a sensitive measure of rational surface locations. This technique strongly constrains the safety factor for equilibrium reconstruction and provides a powerful new tool for measuring the equilibrium magnetic field. For example, the n = 6 temperature structure is observed to shift inward 1.1 +/- 0.6 cm, with an estimated reduction of q0 by 5%. This is consistent with a mid-radius reduction in current, and together the Faraday rotation and Thomson scattering measurements corroborate an inductive redistribution of current that compares well with TRANSP/MSTFit predictions. Interpreting tearing mode temperature structures in the RFP remains challenging; the effects of multiple, closely-spaced tearing modes on the mode phase measurement require further verification. In addition to equilibrium changes, previous work has shown that the large fast ion population drives instabilities at higher frequencies near the Alfvén continuum. Recent observations reveal a new instability at much lower frequency (~7 kHz) with strongly chirping behavior. It participates in extensive avalanches of the higher frequency energetic particle and Alfvénic modes to drive enhanced fast ion transport. Internal structures measured from Te and ne fluctuations, their dependence on the safety factor, as well as frequency scaling motivate speculation about mode identity. Work supported by U.S. DOE.

Quasi-monochromatic inertia-gravity waves in the lower stratosphere from MST radar observations

NASA Astrophysics Data System (ADS)

Nastrom, G. D.; Eaton, F. D.

2006-10-01

The frequency of occurrence of quasi-monochromatic oscillations with periods near the inertial period is examined using hourly mean wind observations from the MST radars at White Sands Missile Range, New Mexico, and Vandenberg Air Force Base, California, spanning 6 years and 4 years, respectively. Power spectral analyses show that the energy levels near the inertial frequency during summer are nearly constant with altitude from about 12 km up to the highest altitude available, about 20 km, while energy levels at lower frequencies decrease with altitude. This decrease leads to a relative enhancement of energy near the inertial frequency. During winter the relative enhancement near the inertial frequency is much smaller. Results from least squares curve fitting used to find the percent of wind variance explained (PEV) by a single wave over data blocks 72 hours long and 2 km deep indicate that a quasi-monochromatic oscillation is present when PEV ≥ 25%. During summer in the stratosphere over 50% of the cases have PEV ≥ 25%. The best fit waveform has mean period near 21 hours and vertical wavelength near 3 km. The wind vectors exhibit anticyclonic rotation in time and with height, consistent with upward propagating gravity waves. The mean ratio of the intrinsic to the inertial frequency is about 1.3 in this data set, and the associated mean horizontal wavelength of these waves is slightly over 1000 km.

MST development for medical applications: results of the German Research Programme on MST over ten years.

PubMed

Weiss, Christine

2007-01-01

Today microsystems are important for the prevention, diagnosis and therapy of diseases. Physicians use small endoscopes for minimally invasive surgery. Patients regain their mobility by high-tech prostheses equipped with several sensors and actuators. Intelligent implants such as pacemakers support existential functions. Cochlea-implants enable deaf persons to hear. Safe convalescence at home is possible by tele-monitoring devices. Point-of-care such as biochips supply quick diagnostic results. A number of these remarkable developments have been successfully supported by the German Federal Ministry of Education and Research (BMBF) since 1990.

Rapamycin and Chloroquine: The In Vitro and In Vivo Effects of Autophagy-Modifying Drugs Show Promising Results in Valosin Containing Protein Multisystem Proteinopathy

PubMed Central

Nalbandian, Angèle; Llewellyn, Katrina J.; Nguyen, Christopher; Yazdi, Puya G.; Kimonis, Virginia E.

2015-01-01

Mutations in the valosin containing protein (VCP) gene cause hereditary Inclusion body myopathy (hIBM) associated with Paget disease of bone (PDB), frontotemporal dementia (FTD), more recently termed multisystem proteinopathy (MSP). Affected individuals exhibit scapular winging and die from progressive muscle weakness, and cardiac and respiratory failure, typically in their 40s to 50s. Histologically, patients show the presence of rimmed vacuoles and TAR DNA-binding protein 43 (TDP-43)-positive large ubiquitinated inclusion bodies in the muscles. We have generated a VCPR155H/+ mouse model which recapitulates the disease phenotype and impaired autophagy typically observed in patients with VCP disease. Autophagy-modifying agents, such as rapamycin and chloroquine, at pharmacological doses have previously shown to alter the autophagic flux. Herein, we report results of administration of rapamycin, a specific inhibitor of the mechanistic target of rapamycin (mTOR) signaling pathway, and chloroquine, a lysosomal inhibitor which reverses autophagy by accumulating in lysosomes, responsible for blocking autophagy in 20-month old VCPR155H/+ mice. Rapamycin-treated mice demonstrated significant improvement in muscle performance, quadriceps histological analysis, and rescue of ubiquitin, and TDP-43 pathology and defective autophagy as indicated by decreased protein expression levels of LC3-I/II, p62/SQSTM1, optineurin and inhibiting the mTORC1 substrates. Conversely, chloroquine-treated VCPR155H/+ mice revealed progressive muscle weakness, cytoplasmic accumulation of TDP-43, ubiquitin-positive inclusion bodies and increased LC3-I/II, p62/SQSTM1, and optineurin expression levels. Our in vitro patient myoblasts studies treated with rapamycin demonstrated an overall improvement in the autophagy markers. Targeting the mTOR pathway ameliorates an increasing list of disorders, and these findings suggest that VCP disease and related neurodegenerative multisystem proteinopathies can

Development of a Multisystemic Parent Management Training Intervention for Incarcerated Parents, Their Children and Families

PubMed Central

Eddy, J. Mark; Martinez, Charles R.; Schiffmann, Tracy; Newton, Rex; Olin, Laura; Leve, Leslie; Foney, Dana M.; Shortt, Joann Wu

2008-01-01

The majority of men and women prison inmates are parents. Many lived with children prior to incarceration, and most have at least some contact with their children and families while serving their sentences. As prison populations have increased in the United States, there has been a renewed interest in finding ways not only to reduce recidivism, but also to prevent incarceration in the first place, particularly amongst the children of incarcerated parents. Positive family interaction is related to both issues. The ongoing development of a multisystemic intervention designed to increase positive family interaction for parents and families involved in the criminal justice system is described. The intervention package currently includes a prison-based parent management training program called Parenting Inside Out (PIO); a prison-based therapeutic visitation program; and complimentary versions of PIO designed for jail and probation and parole settings. Work on other components designed for justice-involved parents, children and for caregivers during reunification from prison is ongoing. Program development has occurred within the context of strong support from the state department of corrections and other key governmental and non-profit sector groups, and support systems have been established to help maintain the interventions as well as to develop complimentary interventions, policies and procedures. PMID:19885365

Pazopanib therapy for cerebellar hemangioblastomas in von Hippel–Lindau disease

PubMed Central

Kim, Betty Y. S.; Jonasch, Eric

2016-01-01

von Hippel–Lindau (VHL) disease is a genetically acquired multisystem tumor syndrome of the viscera and central nervous system (CNS). The most common tumors associated with this disease are histologically benign, slow-growing CNS hemangioblastomas affecting the retina, cerebellum, brainstem, spinal cord or nerve roots. With mean age at diagnosis of 30 years, CNS hemangioblastomas are usually the first manifestation of the disease. Ongoing clinical and radiological surveillance is required, with symptomatic lesions necessitating treatment. As tumor growth is inevitable during the lifetime of most VHL patients, and the multiplicity of tumors may preclude surgical cure, the search for effective therapies is ongoing. Here we provide the first report demonstrating clinical and radiological anti-tumor response using pazopanib, a small molecule multi-receptor tyrosine kinase inhibitor, in a patient with treatment-refractory VHL-associated CNS hemangioblastoma. Treatment initiation with daily oral pazopanib (800 mg/day) resulted in significant neurologic improvement and radiologic tumor volume reduction. PMID:22374327

A Molecular MST Approach to Investigate Fecal Indicator Bacteria in Bioaerosols, Bathing Water, Seaweed Wrack, and Sand at Recreational Beaches

NASA Astrophysics Data System (ADS)

Thoren, K. M.; Sinigalliano, C. D.

2016-02-01

Despite numerous cases of beach bacteria affecting millions of people worldwide, the persistence of the bacteria populations in coastal areas is still not well understood. The purpose of this study was to test the levels of persistence of Fecal Indicating Bacteria (FIB) of enterococci, Escherichia coli, and Human-source Bacteroidales, within the intertidal "swash zone" and the deeper waist zone in which people commonly bathe and play. In addition, the study sought to determine if these bacterial contaminants may also be found in aerosols at the beach. Measuring solar insolation in relation to bacterial persistence in seaweed wrack was used to determine if sunlight plays a role in modifying concentrations of FIB at the beach. Light intensity measured by a solar photometer and air quality measured by aerosol plate counts and qPCR Microbial Source Tracking (MST) was compared to varying locations where the beach samples were collected. Results from water samples demonstrate that bacteria measured using plate counts and qPCR were indeed higher within the swash zone than in the waist zone. This is in contrast with the way that the EPA currently measures and determines the public safety of beach waters. They commonly measure the waist zone, but disregard the swash zone. Results from beach bio-aerosol samples showed a wide variety of fungi and bacteria in the beach air, and qPCR MST analysis of these bio-aerosols showed the presence of FIBs such as enterococci on several of the aerosol collection plates. This emphasizes the need to collect samples from the entire beach instead of just measuring at an isolated area, and that exposure to microbial contaminants may include bathing water, beach sand, seaweed wrack, and bio-aerosols. Thus, the data reveals a potential way to identify harmful levels of bacteria and dangerous levels of poor air quality at recreational beaches. These results expound the need for broader assessment of potential beach contamination, not only the

Empirically Supported Family-Based Treatments for Conduct Disorder and Delinquency in Adolescents

ERIC Educational Resources Information Center

Henggeler, Scott W.; Sheidow, Ashli J.

2012-01-01

Several family-based treatments of conduct disorder and delinquency in adolescents have emerged as evidence-based and, in recent years, have been transported to more than 800 community practice settings. These models include multisystemic therapy, functional family therapy, multidimensional treatment foster care, and, to a lesser extent, brief…

Current and future prospects in the management of granulomatosis with polyangiitis (Wegener’s granulomatosis)

PubMed Central

Tarzi, Ruth M; Pusey, Charles D

2014-01-01

Granulomatosis with polyangiitis (GPA, formerly Wegener’s granulomatosis) is a multisystem autoimmune condition associated with anti-neutrophil cytoplasm antibodies. Management of GPA can be complex, owing to the sometimes fulminant and multisystem nature of the presentation, the age demographics of the affected population, and a significant incidence of disease relapse. In this paper, we discuss how some of the challenges in the management of GPA have been and continue to be addressed including: reducing the toxicity of induction therapy; developing biomarkers to determine who can safely stop maintenance immunosuppression; improving the efficacy of maintenance therapy for relapsing patients; managing localized disease; and management of disease and treatment-associated comorbidity. Consideration is also given to emerging therapeutics in the treatment of GPA. PMID:24790453

Absolute Wavelength Calibration of the IDSII Spectrometer for Impurity Ion Velocity Measurements in the MST

NASA Astrophysics Data System (ADS)

Baltzer, M.; Craig, D.; den Hartog, D. J.; Nornberg, M. D.; MST Team

2014-10-01

The MST operates two Ion Doppler Spectrometers (IDS) for high time-resolution passive and active measurements of impurity ion emission. Absolutely calibrated measurements of flow are difficult because the spectrometers record data within 0.3 nm of the line of interest, and commercial calibration lamps do not produce lines in this narrow range . Four calibration methods were investigated. First, emission along the chord bisecting the poloidal plane was measured as it should have no time-averaged Doppler shift. Second, a calibrated CCD spectrometer and the IDSII were used to observe the same plasma from opposing sides so as to measure opposite Doppler shifts. The unshifted line is located halfway between the two opposing measurements. Third, the two fibers of the IDSI were positioned to take absolute flow measurements using opposing views. Substituting the IDSII for one of the IDSI fibers, absolute measurements of flow from the IDSI were used to calibrate the IDSII. Finally, an optical system was designed to filter an ultraviolet LED, providing a known wavelength source within the spectral range covered by the IDSII. The optical train is composed of an air-gapped etalon and fused silica lenses. The quality of calibration for each of these methods is analyzed and their results compared. Preliminary impurity ion velocity measurements are shown. This work has been supported by the US DOE and the NSF.

Non-axisymmetric Flows and Transport in the Edge of MST

NASA Astrophysics Data System (ADS)

Miller, Matthew Charles

Magnetic reconnection occurs in plasmas all throughout the universe and is responsible for spectacular and perplexing phenomena. In the Madison Symmetric Torus (MST) reversed field pinch (RFP), reconnection occurs as quasi-periodic bursts of tearing instabilities (saw-teeth), which give rise to a number of processes that affect the RFP's global behavior and confinement. This work examines the structure of turbulent plasma flow in the edge region and its role in affecting momentum and particle transport through the use of several insertable probes and novel ensemble techniques. Very few measurements exist of tearing mode flow structures. The flow structure has now been measured for m = 0 modes and is in good agreement with theoretical expectations for nonlinear resistive MHD calculated for the RFP using DEBS and NIMROD. The flows are predicted and measured to be different than the classical Sweet-Parker picture with symmetric inward flows. The flow fluctuations have a profound effect on momentum transport, which is trans- ported rapidly at the crash. This work advances the understanding of this process by measuring the Reynolds stress associated with turbulent flow. Combined with measurements of the Maxwell stress, a new picture for magnetic self-organization in the RFP via two-fluid physics has emerged. The Reynolds and Maxwell stresses are measured to be an order of magnitude larger than the rate of change in inertia but oppositely directed such that they almost cancel. Two-fluid effects are significant because of the relationship be- tween the Maxwell stress and the Hall dynamo, a term only existing in two-fluid theories. This relationship inextricably couples the momentum dynamics with the current dynamics. Indeed, the parallel momentum profile exhibits a relaxation at the crash akin to the relaxation seen in the parallel current density profile. Tearing modes also drive particle transport. Fluctuation-induced particle flux is resolved through a crash by

Antarctic meteor observations using the Davis MST and meteor radars

NASA Astrophysics Data System (ADS)

Holdsworth, David A.; Murphy, Damian J.; Reid, Iain M.; Morris, Ray J.

2008-07-01

This paper presents the meteor observations obtained using two radars installed at Davis (68.6°S, 78.0°E), Antarctica. The Davis MST radar was installed primarily for observation of polar mesosphere summer echoes, with additional transmit and receive antennas installed to allow all-sky interferometric meteor radar observations. The Davis meteor radar performs dedicated all-sky interferometric meteor radar observations. The annual count rate variation for both radars peaks in mid-summer and minimizes in early Spring. The height distribution shows significant annual variation, with minimum (maximum) peak heights and maximum (minimum) height widths in early Spring (mid-summer). Although the meteor radar count rate and height distribution variations are consistent with a similar frequency meteor radar operating at Andenes (69.3°N), the peak heights show a much larger variation than at Andenes, while the count rate maximum-to-minimum ratios show a much smaller variation. Investigation of the effects of the temporal sampling parameters suggests that these differences are consistent with the different temporal sampling strategies used by the Davis and Andenes meteor radars. The new radiant mapping procedure of [Jones, J., Jones, W., Meteor radiant activity mapping using single-station radar observations, Mon. Not. R. Astron. Soc., 367(3), 1050-1056, doi: 10.1111/j.1365-2966.2006.10025.x, 2006] is investigated. The technique is used to detect the Southern delta-Aquarid meteor shower, and a previously unknown weak shower. Meteoroid speeds obtained using the Fresnel transform are presented. The diurnal, annual, and height variation of meteoroid speeds are presented, with the results found to be consistent with those obtained using specular meteor radars. Meteoroid speed estimates for echoes identified as Southern delta-Aquarid and Sextantid meteor candidates show good agreement with the theoretical pre-atmospheric speeds of these showers (41 km s -1 and 32 km s -1

[Corticosteroid therapy in Henoch-Schönlein gastritis].

PubMed

Pavlović, Momcilo; Radlović, Nedeljko; Leković, Zoran; Berenji, Karolina; Novak, Arpad

2007-01-01

Henoch-Schönlein purpura (HSP) is the most common vascular disease of childhood. It is a multisystem disease most commonly affecting the skin,joints, gastrointestinal tract, and kidneys, but other organs may be affected, too. Gastrointestinal involvement occurs in approximately 65-90% of patients, ranging from mild symptoms such as abdominal pain, nausea, and vomiting, to more severe manifestations such as gastrointestinal bleeding and intussusception. In most cases, HSP spontaneously resolves without treatment. The use of corticosteroids is controversial and usually reserved for severe systemic manifestations. Some authors suggest that the abdominal pain and gastrointestinal hemorrhage of HSP may respond to steroids, with some suggesting that there is a benefit in their use and describing a regimen. This is a case report of HSP in a fourteen-year-old boy with abdominal pain and hematemesis. Upper endoscopy showed an edematous and erythematous change in the body of the stomach and purpuric lesions in the duodenum, while multiple erosions were found in the antral area. Parenteral corticosteroid therapy with gastric acid secretion inhibitor administration led to regression of gastrointestinal symptoms on the seventh day, with relapses on the fourth and sixth day. Peroral administration of corticosteroids and gradual decrease of daily doses started on the eighth day of abdominal symptoms. New purpuric skin rashes appeared during six weeks. Corticosteroid therapy with gastric acid secretion inhibitors showed a positive effect in our patient with a severe form of HSP accompanied by abdominal pain and gastrointestinal hemorrhage.

hnRNPA2B1 and hnRNPA1 mutations are rare in patients with "multisystem proteinopathy" and frontotemporal lobar degeneration phenotypes.

PubMed

Le Ber, Isabelle; Van Bortel, Inge; Nicolas, Gael; Bouya-Ahmed, Kawtar; Camuzat, Agnès; Wallon, David; De Septenville, Anne; Latouche, Morwena; Lattante, Serena; Kabashi, Edor; Jornea, Ludmila; Hannequin, Didier; Brice, Alexis

2014-04-01

hnRNPA2B1 and hnRNPA1 mutations have been recently identified by exome sequencing in three families presenting with multisystem proteinopathy (MSP), a rare complex phenotype associating frontotemporal lobar degeneration (FTLD), Paget disease of bone (PDB), inclusion body myopathy (IBM), and amyotrophic lateral sclerosis (ALS). No study has evaluated the exact frequency of these genes in cohorts of MSP or FTD patients so far. We sequenced both genes in 17 patients with MSP phenotypes, and in 60 patients with FTLD and FTLD-ALS to test whether mutations could be implicated in the pathogenesis of these disorders. No disease-causing mutation was identified. We conclude that hnRNPA2B1 and hnRNPA1 mutations are rare in MSP and FTLD spectrum of diseases, although further investigations in larger populations are needed. Copyright © 2014 Elsevier Inc. All rights reserved.

Extensive intramuscular manifestation of sarcoidosis with initially missed diagnosis and delayed therapy: a case report.

PubMed

Meyer, Niklaus; Sutter, Reto; Schirp, Udo; Gutzeit, Andreas

2017-08-24

Sarcoidosis is a multisystemic granulomatous disorder, which in nearly all cases involves the lungs and other organs. Isolated forms of sarcoidosis within the muscles, but without lung involvement, are extremely rare and can lead to delayed or even false diagnosis. A 52-year-old white, Swiss man presented with painful arm cramps and a history of symptoms over the previous 3 years. In the initial clinical investigation, our patient also showed edema in both legs without any other complaints. After performing an magnetic resonance imaging scan of his extremities and a positron emission tomography/computed tomography scan, diffuse myositis was described. The subsequent muscle biopsy provided the surprising diagnosis of muscle sarcoidosis, without involvement of the lungs or any other organ. After starting therapy with glucocorticoids, his symptoms improved immediately. Sarcoidosis is a common disorder, which in most cases affects the lungs. In this case report an isolated sarcoidosis is described without lung involvement, but with involvement of the muscles of the extremities and the trunk. Reported cases of sarcoidosis only involving skeletal muscle and without lung involvement are extremely rare. Radiologists should consider this presentation of sarcoidosis to avoid delayed diagnosis and therapy.

Mitochondrial Replacement: Ethics and Identity

PubMed Central

Wilkinson, Stephen; Appleby, John B.

2015-01-01

Abstract Mitochondrial replacement techniques (MRTs) have the potential to allow prospective parents who are at risk of passing on debilitating or even life‐threatening mitochondrial disorders to have healthy children to whom they are genetically related. Ethical concerns have however been raised about these techniques. This article focuses on one aspect of the ethical debate, the question of whether there is any moral difference between the two types of MRT proposed: Pronuclear Transfer (PNT) and Maternal Spindle Transfer (MST). It examines how questions of identity impact on the ethical evaluation of each technique and argues that there is an important difference between the two. PNT, it is argued, is a form of therapy based on embryo modification while MST is, instead, an instance of selective reproduction. The article's main ethical conclusion is that, in some circumstances, there is a stronger obligation to use PNT than MST. PMID:26481204

Thyroid storm masked by hemodialysis and glucocorticoid therapy in a patient with rheumatoid arthritis.

PubMed

Sasaki, Yohei; Shimizu, Yoshio; Nakata, Junichiro; Kameda, Toshiaki; Muto, Masahiro; Ohsawa, Isao; Io, Hiroaki; Hamada, Chieko; Horikoshi, Satoshi; Tomino, Yasuhiko

2012-01-01

Thyroid function test values are generally at low levels in patients with end-stage kidney disease. Life-threatening thyrotoxicosis or thyroid storm is rare, especially in hemodialysis (HD) patients, and is characterized by multisystem involvement and a high mortality rate if not immediately recognized and treated. Here, we report a female patient with severe symptomatic thyroid storm, receiving long-term HD and glucocorticoid therapy. Methimazole at a dose of 15 mg per day, β-adrenergic blockade and HD succeeded in controlling the patient's condition by gradually adjusting the target dry weight for hyperthyroidism-induced weight loss. When she was discharged from the hospital, her dry weight was reduced from 47.2 to 39.2 kg. The management of patients with severe symptomatic thyroid storm on HD represents a rare scenario. It is essential to initiate the available treatments as early as possible to reduce its mortality.

Current therapy and drug pipeline for the treatment of patients with acromegaly.

PubMed

Kumar, Sampath Satish; Ayuk, John; Murray, Robert D

2009-04-01

Acromegaly is a multisystem disease resulting from chronic exposure to supraphysiological levels of growth hormone (GH), and is associated with significant morbidity and excess mortality. The etiology is almost exclusively an underlying pituitary adenoma. Current therapeutic interventions include surgery, radiotherapy, and medical therapy. Despite surgery, around 50% of patients fail to achieve the biochemical targets shown to correlate with normalization of mortality rates. Radiotherapy is efficacious in controlling tumor growth and GH secretion; still, achievement of biochemical targets may take up to a decade and a number of safety issues have been raised with this treatment modality. Medical therapy, therefore, has an important role as adjuvant therapy in patients who fail to achieve control with surgery, or while awaiting the effects of radiotherapy to be realized. Furthermore, medical therapy is increasingly being used as primary therapy. Current medical therapies include dopaminergic agonists, somatostatin analogs, and GH receptor (GHR) antagonists. Dopaminergic agonists achieve biochemical targets in up to 30% of patients, and somatostatin analogs in around 60%. The currently available GHR antagonist pegvisomant effectively controls insulin-like growth factor-I levels in over 90% of patients; however, it has no effect on the tumor itself and has considerable financial implications. Research into optimizing the somatostatin and dopaminergic systems has led to promising advances in agonist development. Moieties with selectivity for various combinations of somatostatin receptor subtype receptors have been examined, along with molecules that additionally show high affinity for the dopaminergic D2 receptor. Of the molecules studied in vitro, only pasireotide (SOM230) and BIM-23A760 are currently undergoing further development. Other innovations to improve convenience of currently available drugs are also being investigated. Significant advances in under standing

Recursive partitioning analysis of 1999 Radiation Therapy Oncology Group (RTOG) patients with locally-advanced non-small-cell lung cancer (LA-NSCLC): identification of five groups with different survival.

PubMed

Werner-Wasik, M; Scott, C; Cox, J D; Sause, W T; Byhardt, R W; Asbell, S; Russell, A; Komaki, R; Lee, J S

2000-12-01

Survival of patients with locally-advanced non-small-cell lung cancer (LA-NSCLC) is predicted by the stage of the disease and other characteristics. This analysis was undertaken to identify these characteristics in a large cooperative group patient population, as well as to define subgroups of the population with differing outcomes. Analysis included 1,999 patients treated in 9 RTOG trials between 1983 and 1994 with thoracic irradiation (RT) with (n = 355) or without chemotherapy (CT). In univariate analysis, the following characteristics were significantly associated with an improved survival: use of CT, CT delivered without major deviation, abnormal pulmonary function tests, normal hemoglobin, protein, LDH and BUN, presence of dyspnea, hemoptysis, cough or hoarseness, uninvolved lymph nodes, T1 or T2 stage, no malignant pleural effusion (PE), weight loss of < 8%, Karnofsky performance status (KPS) of at least 90, adenocarcinoma histology, female gender, and age less than 70 years. Recursive partitioning analysis (RPA) was subsequently applied to identify 5 patient subgroups with significantly different median survival times (MST): Group I, KPS of > or = 90, who received chemotherapy (MST 16.2 months); Group II, KPS of > or = 90, who received no CT, but had no PE (MST 11.9 months); Group III, KPS < 90, younger than 70 years, with non-large cell histology (MST 9.6 months); Group IV, KPS > or = 90, but with PE, or KPS < 90, younger than 70 years, and with large cell histology, or older than 70 years, but without PE (MST 5.6-6.4 months); Group V, older than 70, with PE (MST 2.9 months). Cisplatinum-based CT improves survival, for excellent prognosis of LA-NSCLC patients, over RT alone. The presence of a malignant pleural effusion is a major negative prognostic factor for survival. The identification of RPA prognostic groups among patients with LA-NSCLC provides prognostic information and may serve as a basis of stratification in future trials.

Artificial Gravity as a Multi-System Countermeasure to Bed Rest Deconditioning: Preliminary Results

NASA Technical Reports Server (NTRS)

Warren, L. E.; Paloski, William H.; Young, L. R.

2006-01-01

Artificial gravity paradigms may offer effective, efficient, multi-system protection from the untoward effects of adaptation to the microgravity of space or the hypogravity of planetary surfaces. Intermittent artificial gravity (AG) produced by a horizontal short-radius centrifuge (SRC) has recently been utilized on human test subjects deconditioned by bed rest. This presentation will review preliminary results of a 41 day study conducted at the University of Texas Medical Branch, Galveston, TX bed rest facility. During the first eleven days of the protocol, subjects were ambulatory, but confined to the facility. They began a carefully controlled diet, and participated in multiple baseline tests of bone, muscle, cardiovascular, sensory-motor, immunological, and psychological function. On the twelfth day, subjects entered the bed rest phase of the study, during which they were confined to strict 6deg head down tilt bed rest for 21 days. Beginning 24 hrs into this period, treatment subjects received one hour daily exposures to artificial gravity which was produced by spinning the subjects on a 3.0 m radius SRC. They were oriented radially in the supine position so that the centrifugal force was aligned with their long body axis, and while spinning, they "stood" on a force plate, supporting the centrifugal loading (2.5 g at the feet, 1.0 g at the heart). The subject station allowed free translation over approximately 10 cm to ensure full loading of the lower extremities and to allow for anti-orthostatic muscle contractions. Control subjects were positioned on the centrifuge but did not spin. Following the bed rest phase, subjects were allowed to ambulate again, but remained within the facility for an additional 9 days and participated in multiple follow-up tests of physiological function.

Damping Rates of Energetic Particle Modes and Stability With Changing Equilibrium Conditions in the MST Reversed-Field Pinch

NASA Astrophysics Data System (ADS)

Sears, S. H.; Almagri, A. F.; Anderson, J. K.; Bonofiglo, P. J.; Capecchi, W.; Kim, J.

2016-10-01

The damping of Alfvenic waves is an important process, with implications varying from anomalous ion heating in laboratory and astrophysical plasmas to the stability of fusion alpha-driven modes in a burning plasma. With a 1 MW NBI on the MST, a controllable set of energetic particle modes (EPMs) and Alfvenic eigenmodes can be excited. We investigate the damping of these modes as a function of both magnetic and flow shear. Typical EPM damping rates are -104 s-1 in standard RFP discharges. Magnetic shear in the region of large energetic ion density is -2 cm-1 and can be increased up to -2.5 cm-1 by varying the boundary field. Continuum mode damping rates can be reduced up to 50%. New experiments use a bias probe to control the rotation profile. Accelerating the edge plasma relative to the rapidly rotating NBI-driven core decreases the flow shear, while decelerating the edge plasma increases the flow shear in the region of strong energetic ion population. Mode damping rates measured as a function of the local flow shear are compared to ideal MHD predictions. Work supported by US DOE.

Stable MOB1 interaction with Hippo/MST is not essential for development and tissue growth control.

PubMed

Kulaberoglu, Yavuz; Lin, Kui; Holder, Maxine; Gai, Zhongchao; Gomez, Marta; Assefa Shifa, Belul; Mavis, Merdiye; Hoa, Lily; Sharif, Ahmad A D; Lujan, Celia; Smith, Ewan St John; Bjedov, Ivana; Tapon, Nicolas; Wu, Geng; Hergovich, Alexander

2017-09-25

The Hippo tumor suppressor pathway is essential for development and tissue growth control, encompassing a core cassette consisting of the Hippo (MST1/2), Warts (LATS1/2), and Tricornered (NDR1/2) kinases together with MOB1 as an important signaling adaptor. However, it remains unclear which regulatory interactions between MOB1 and the different Hippo core kinases coordinate development, tissue growth, and tumor suppression. Here, we report the crystal structure of the MOB1/NDR2 complex and define key MOB1 residues mediating MOB1's differential binding to Hippo core kinases, thereby establishing MOB1 variants with selective loss-of-interaction. By studying these variants in human cancer cells and Drosophila, we uncovered that MOB1/Warts binding is essential for tumor suppression, tissue growth control, and development, while stable MOB1/Hippo binding is dispensable and MOB1/Trc binding alone is insufficient. Collectively, we decrypt molecularly, cell biologically, and genetically the importance of the diverse interactions of Hippo core kinases with the pivotal MOB1 signal transducer.The Hippo tumor suppressor pathway is essential for development and tissue growth control. Here the authors employ a multi-disciplinary approach to characterize the interactions of the three Hippo kinases with the signaling adaptor MOB1 and show how they differently affect development, tissue growth and tumor suppression.

Assessment and quantification of post-weaning multi-systemic wasting syndrome severity at farm level.

PubMed

Alarcon, Pablo; Velasova, Martina; Werling, Dirk; Stärk, Katharina D C; Chang, Yu-Mei; Nevel, Amanda; Pfeiffer, Dirk U; Wieland, Barbara

2011-01-01

Post-weaning multi-systemic wasting syndrome (PMWS) causes major economic losses for the English pig industry and severity of clinical signs and economic impact vary considerably between affected farms. We present here a novel approach to quantify severity of PMWS based on morbidity and mortality data and presence of porcine circovirus type 2 (PCV2). In 2008-2009, 147 pig farms across England, non-vaccinating for PCV2, were enrolled in a cross-sectional study. Factor analysis was used to generate variables representing biologically meaningful aspects of variation among qualitative and quantitative morbidity variables. Together with other known variables linked to PMWS, the resulting factors were included in a principal component analysis (PCA) to derive an algorithm for PMWS severity. Factor analysis resulted in two factors: Morbidity Factor 1 (MF1) representing mainly weaner and grower morbidity, and Morbidity Factor 2 (MF2) which mainly reflects variation in finisher morbidity. This indicates that farms either had high morbidity mainly in weaners/growers or mainly in finishers. Subsequent PCA resulted in the extraction of one component representing variation in MF1, post-weaning mortality and percentage of PCV2 PCR positive animals. Component scores were normalised to a value range from 0 to 10 and farms classified into: non or slightly affected farms with a score <4, moderately affected farms with scores 4-6.5 and highly affected farms with a score >6.5. The identified farm level PMWS severities will be used to identify risk factors related to these, to assess the efficacy of PCV2 vaccination and investigating the economic impact of potential control measures. Copyright © 2010 Elsevier B.V. All rights reserved.

Management of patients with metastatic teratoma with malignant somatic transformation.

PubMed

Speir, Ryan; Cary, Clint; Foster, Richard S; Masterson, Timothy A

2018-06-22

The purpose of this review is to examine the historical context alongside contemporary studies in order to provide the most current recommendations for the management of patients with metastatic teratoma with malignant somatic transformation (MST). The main themes in the recent literature covered herein include prognostic features, the management of early-stage disease, recommended chemotherapeutic and surgical strategies as well as recognized patterns of late relapse. Recent literature, combined with a significant contribution from historical studies, suggests that while MST is uncommon, its aggressive nature coupled with its resistance with traditional germ cell tumor chemotherapies makes it very difficult to manage. The key message is that surgery is recommended in all resectable MST from primary retroperitoneal lymph node dissection for clinical stage I, to radical removal of disease after chemotherapy and when chemotherapy fails. In advanced cases with documented spread of the transformed histologic subtype, systemic therapies targeted to the identified tumor type should be considered.

A study of gravity-wave spectra in the troposphere and stratosphere at 5-min to 5-day periods with the Poker Flat MST radar

NASA Technical Reports Server (NTRS)

Bemra, R. S.; Rastogi, P. K.; Balsley, B. B.

1986-01-01

An analysis of frequency spectra at periods of about 5 days to 5 min from two 20-day sets of velocity measurements in the stratosphere and troposphere region obtained with the Poker Flat mesosphere-stratosphere-troposphere (MST) radar during January and June, 1984 is presented. A technique based on median filtering and averaged order statistics for automatic editing, smoothing and spectral analysis of velocity time series contaminated with spurious data points or outliers is outlined. The validity of this technique and its effects on the inferred spectral index was tested through simulation. Spectra obtained with this technique are discussed. The measured spectral indices show variability with season and height, especially across the tropopause. The discussion briefly outlines the need for obtaining better climatologies of velocity spectra and for the refinements of the existing theories to explain their behavior.

Adjuvant therapy with carboplatin and pamidronate for canine appendicular osteosarcoma.

PubMed

Kozicki, A R; Robat, C; Chun, R; Kurzman, I D

2015-09-01

Amputation and chemotherapy are the mainstay of treatment for canine appendicular osteosarcoma (OSA). In vitro studies have demonstrated anti-tumour activity of pamidronate against canine OSA. The purpose of this study was to assess the safety of adding pamidronate to standard post-operative carboplatin chemotherapy in 17 dogs with appendicular OSA treated with limb amputation. Median disease-free interval (DFI) and median survival time (MST) were evaluated as secondary endpoints. Incidence of side effects and treatment outcomes were compared to 14 contemporary control patients treated with carboplatin alone. There were no identified side effects to the pamidronate treatment. The median DFI for the study group was 185 days compared to 172 days for the control group (P = 0.90). The MST of the study group was 311 days compared to 294 days for the control group (P = 0.89). Addition of pamidronate to carboplatin chemotherapy for the treatment of canine appendicular OSA is safe and does not impair efficacy of standard carboplatin treatment. © 2013 Blackwell Publishing Ltd.

An energy-confinement study of the MST reversed-field pinch using a Thomson-scattering diagnostic

DOE Office of Scientific and Technical Information (OSTI.GOV)

Den Hartog, D.J.

1989-01-01

Thomson scattering measurements of the central electron temperature and density during the plasma current peak have been performed on the MST Reversed Field Pinch (RFP). This Thomson scattering diagnostic was calibrated for absolute electron density measurements. These measurements of T{sub e} and n{sub e}, when combined with profile assumptions, were used to calculate estimates of energy confinement time ({tau}{sub E}) and poloidal beta ({beta}{sub {theta}}). A standard discharge with I{sub p} {approx} 400 kA, F {approx} {minus}0.1, and {theta} {approx} 1.6 typically exhibited T{sub e} {approx} 275 eV, n{sub e} {approx} 2.0 {times} 10{sup 13} cm{sup {minus}3}, {tau}{sub E}

Biological and targeted therapies of systemic lupus erythematosus: evidence and the state of the art.

PubMed

Mok, Chi Chiu

2017-07-01

Systemic lupus erythematosus (SLE) is a multi-systemic disease characterized by an unpredictable disease course and periods of remission and flare, leading to organ damage and mortality. Novel biological agents are being developed (targeting the lymphocytes, accessory molecules and cytokines) that aim to enhance the therapeutic efficacy when combined with standard therapies. Areas covered: This article updates recent data on the use of biological and targeted therapies in SLE. Expert commentary: B cells remain the main target of development of novel therapeutics in SLE. Similar to the intravenous preparation, subcutaneous belimumab has been shown to be superior to placebo when added to the standard of care in SLE. However, two phase III trials of epratuzumab and blisibimod did not meet their primary endpoints. Recent data on the inhibition of type I interferons (anifrolumab) appear promising. Newer calcineurin inhibitors and combination strategies using conventional immunosuppressive agents are being tested in lupus nephritis. Finally, international groups are developing consensus definitions on disease remission and low disease activity state to explore the benefits of the treat-to-target strategy in SLE. Hopefully, the armamentarium for the treatment of SLE can be expanded in the near future, so that the longevity and quality of life of patients can be further improved.

Nonpharmacological, somatic treatments of depression: electroconvulsive therapy and novel brain stimulation modalities

PubMed Central

Eitan, Renana; Lerer, Bernard

2006-01-01

Until recently, a review of nonpharmacological, somatic treatments of psychiatric disorders would have included only electroconvulsive therapy (ECT). This situation is now changing very substantially Although ECT remains the only modality in widespread clinical use, several new techniques are under investigation. Their principal indication in the psychiatric context is the treatment of major depression, but other applications are also being studied. All the novel treatments involve brain stimulation, which is achieved by different technological methods. The treatment closest to the threshold of clinical acceptability is transcranial magnetic stimulation (TMS). Although TMS is safe and relatively easy to administer, its efficacy has still to be definitively established. Other modalities, at various stages of research development, include magnetic seizure therapy (MST), deep brain stimulation (DBS), and vagus nerve stimulation (VNS). We briefly review the development and technical aspects of these treatments, their potential role in the treatment of major depression, adverse effects, and putative mechanism of action. As the only one of these treatment modalities that is in widespread clinical use, more extended consideration is given to ECT. Although more than half a century has elapsed since ECT was first introduced, it remains the most effective treatment for major depression, with efficacy in patients refractory to antidepressant drugs and an acceptable safety profile. Although they hold considerable promise, the novel brain stimulation techniques reviewed here will be need to be further developed before they achieve clinical acceptability. PMID:16889109

Acute diffuse alveolar haemorrhage accompanied by gastrointestinal bleeding in a patient with serious systemic lupus erythematosus: A case report.

PubMed

Du, Jing; Wang, Ying; Li, Yan-Chun; Wang, Tong-Tong; Zhou, Yong-Lie; Ying, Zhen-Hua

2018-05-01

Systemic lupus erythematosus (SLE) is an autoimmune disease that affects many organs, but multisystem dysfunction is rare. Here, we report a case of a 29-year-old woman who was initially diagnosed with SLE complications including lupus nephritis, lupus encephalopathy, renal hypertension, thrombocytopenia, anaemia and hyperkalaemia. She recovered following treatment with high dose methylprednisolone, intravenous immunoglobulin (IVIG) and continuous renal replacement therapy (CRRT). However, a few days after hospital discharge, she developed gastrointestinal bleeding. Although intensive treatment was administered, the patient deteriorated rapidly and had a progressive decline in oxygen saturation followed by diffuse alveolar haemorrhage and acute left heart failure. Inotropic therapy, mechanical ventilation, blood transfusion, CRRT, antibiotics, intravenous glucocorticoids and other support therapies were initiated and gradually the patient's vital signs stabilized and haemoptysis subsided. This case report emphasises that complications of SLE can occur at any stage of the disease, especially in patients with active SLE. Therefore, it is important for clinicians to be aware of the rare presentations of SLE and its complex management. For multisystem dysfunction, early intensive treatment with high dose corticosteroids and cyclophosphamide is advocated.

Juvenile delinquency treatment and prevention: a literature review.

PubMed

May, Jessica; Osmond, Kristina; Billick, Stephen

2014-09-01

In the last three decades there has been ample research to demonstrate that instituting Multisystemic Therapy for serious juvenile offenders, keeping them in the community with intensive intervention, can significantly reduce recidivism. When there is recidivism, it is less severe than in released incarcerated juveniles. Multisystemic Therapy provides 24 h available parental guidance, family therapy, individual therapy, group therapy, educational support and quite importantly a change of peer group. In New York City, there is the new mandate through the Juvenile Justice Initiative to implement interventions to keep juvenile offenders in the community rather than sending them to be incarcerated. However, this paper aims to examine how teaching prosocial values in early childhood can reduce the incidence of first-time juvenile delinquency. Programs such as the Perry School Project will be discussed to demonstrate that although somewhat expensive, these innovative programs nonetheless are quite cost-effective as the cost to society of adjudication, incarceration and victim damages are significantly greater. Along with teaching prosocial 0020 values, there has been renewed interest in early identification of youth at risk for developing Antisocial Personality Disorder. An update is given on the status of both promising approaches in early intervention to prevent serious juvenile delinquency and hence adult criminality.

Electromagnetic Field Modeling of Transcranial Electric and Magnetic Stimulation: Targeting, Individualization, and Safety of Convulsive and Subconvulsive Applications

NASA Astrophysics Data System (ADS)

Deng, Zhi-De

The proliferation of noninvasive transcranial electric and magnetic brain stimulation techniques and applications in recent years has led to important insights into brain function and pathophysiology of brain-based disorders. Transcranial electric and magnetic stimulation encompasses a wide spectrum of methods that have developed into therapeutic interventions for a variety of neurological and psychiatric disorders. Although these methods are at different stages of development, the physical principle underlying these techniques is the similar. Namely, an electromagnetic field is induced in the brain either via current injection through scalp electrodes or via electromagnetic induction. The induced electric field modulates the neuronal transmembrane potentials and, thereby, neuronal excitability or activity. Therefore, knowledge of the induced electric field distribution is key in the design and interpretation of basic research and clinical studies. This work aims to delineate the fundamental physical limitations, tradeoffs, and technological feasibility constraints associated with transcranial electric and magnetic stimulation, in order to inform the development of technologies that deliver safer, and more spatially, temporally, and patient specific stimulation. Part I of this dissertation expounds on the issue of spatial targeting of the electric field. Contrasting electroconvulsive therapy (ECT) and magnetic seizure therapy (MST) configurations that differ markedly in efficacy, side effects, and seizure induction efficiency could advance our understanding of the principles linking treatment parameters and therapeutic outcome and could provide a means of testing hypotheses of the mechanisms of therapeutic action. Using the finite element method, we systematically compare the electric field characteristics of existing forms of ECT and MST. We introduce a method of incorporating a modality-specific neural activation threshold in the electric field models that can

Treatment of feline intermediate- to high-grade lymphoma with a modified university of Wisconsin-Madison protocol: 119 cases (2004-2012).

PubMed

Collette, S A; Allstadt, S D; Chon, E M; Vernau, W; Smith, A N; Garrett, L D; Choy, K; Rebhun, R B; Rodriguez, C O; Skorupski, K A

2016-08-01

CHOP-based (cyclophosphamide, doxorubicin, vinca alkaloid, prednisolone) chemotherapy protocols are often recommended for treatment of feline lymphoma. While maintenance-free CHOP-based protocols have been published and readily used in dogs, there is limited literature regarding similar maintenance-free protocols in cats. The purpose of this study was to describe the outcome of cats with intermediate- to high-grade lymphoma that were prescribed a modified 25-week University of Wisconsin-Madison (UW-25) chemotherapy protocol. A secondary objective was examination of potential prognostic factors. One hundred and nineteen cats from five institutions treated with a UW-25-based protocol were included. The Kaplan-Meier median progression-free interval (PFI) and survival time (MST) were 56 and 97 (range 2-2019) days, respectively. Cats assessed as having a complete response (CR) to therapy had significantly longer PFI and MST than those with partial or no response (PFI 205 versus 54 versus 21 days, respectively, P < 0.0001 and MST 318 versus 85 versus 27 days, respectively, P < 0.0001). © 2015 John Wiley & Sons Ltd.

[Enzyme replacement therapy in patients with Fabry disease: state of the art and review of the literature].

PubMed

Riccio, Eleonora; Capuano, Ivana; Visciano, Bianca; Marchetiello, Cristina; Petrillo, Fortunato; Pisani, Antonio

2013-01-01

Anderson-Fabry disease is a hereditary X-linked lysosomal storage disorder caused by a deficiency of the lysosomal enzyme alpha galactosidase A. It results in the accumulation of the glycosphingolypid globotrioasoyl ceramide (Gb3 in different cells and organs, resulting in a multi-system pathology including end organ failure. Patients with Fabry disease present clinically with cardiac, renal and neurological involvement; both life expectancy and quality of life are severely compromised. The current causal treatment for Fabry disease is enzyme replacement therapy (ERT), available since 2001. The two recombinant preparations available for ERT are agalsidase alfa (Replagal) and agalsidase beta (Fabrazyme). They have both been showed to have positive effect on kidney and heart, on the symptoms of pain and quality of life. Few data to date are available on comparison of the two preparations of ERT. This article reviews evidence of the literature and shows our personal experience about the safety and efficacy of ERT.

Guidelines of care for the management of psoriasis and psoriatic arthritis Section 3. Guidelines of care for the management and treatment of psoriasis with topical therapies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Menter, A.; Korman, N.J.; Elmets, C.A.

2009-04-15

Psoriasis is a common, chronic, inflammatory, multi-system disease with predominantly skin and joint manifestations affecting approximately 2% of the Population. In this third of 6 sections of the guidelines of care for psoriasis, we discuss the use of topical medications for the treatment of psoriasis. The majority of patients with psoriasis have limited disease (<5% body surface area involvement) and can be treated with topical agents, which generally provide a high efficacy-to-safety ratio. Topical agents may also be used adjunctively for patients with more extensive psoriasis undergoing therapy with either ultraviolet light, systemic or biologic medications. However, the use ofmore » topical agents as monotherapy in the setting of extensive disease or in the setting of limited, but recalcitrant, disease is not routinely recommended. Treatment should be tailored to meet individual patients' needs. We will discuss the efficacy and safety of as well as offer recommendations for the use of topical corticosteroids, vitamin D analogues, tazarotene, tacrolimus, pimecrolimus, emollients, salicylic acid, anthralin, coal tar, as well as combination therapy.« less

Enzyme replacement therapy for Fabry disease: some answers but more questions.

PubMed

Alfadhel, Majid; Sirrs, Sandra

2011-01-01

Fabry disease (FD) is a multisystem, X-linked disorder of glycosphingolipid metabolism caused by enzyme deficiency of α-galactosidase A. Affected patients have symptoms including acroparesthesias, angiokeratomas, and hypohidrosis. More serious manifestations include debilitating pain and gastrointestinal symptoms, proteinuria and gradual deterioration of renal function leading to end-stage renal disease, hypertrophic cardiomyopathy, and stroke. Heterozygous females may have symptoms as severe as males with the classic phenotype. Before 2001, treatment of patients with FD was supportive. The successful development of enzyme replacement therapy (ERT) has been a great advancement in the treatment of patients with FD and can stabilize renal function and cardiac size, as well as improve pain and quality of life of patients with FD. In this review, we have provided a critical appraisal of the literature on the effects of ERT for FD. This analysis shows that data available on the treatment of FD are often derived from studies which are not controlled, rely on surrogate markers, and are of insufficient power to detect differences on hard clinical endpoints. Further studies of higher quality are needed to answer the questions that remain concerning the efficacy of ERT for FD.

A Morbidity Screening Tool for identifying fatigue, pain, upper limb dysfunction and lymphedema after breast cancer treatment: a validity study.

PubMed

Bulley, Catherine; Coutts, Fiona; Blyth, Christine; Jack, Wilma; Chetty, Udi; Barber, Matthew; Tan, Chee Wee

2014-04-01

This study aimed to investigate validity of a newly developed Morbidity Screening Tool (MST) to screen for fatigue, pain, swelling (lymphedema) and arm function after breast cancer treatment. A cross-sectional study included women attending reviews after completing treatment (surgery, chemotherapy and radiotherapy), without recurrence, who could read English. They completed the MST and comparator questionnaires: Disability of the Arm, Shoulder and Hand questionnaire (DASH), Chronic Pain Grade Questionnaire (CPGQ), Lymphedema and Breast Cancer Questionnaire (LBCQ) and Functional Assessment of Cancer Therapy questionnaire with subscales for fatigue (FACT F) and breast cancer (FACT B + 4). Bilateral combined shoulder ranges of motion were compared (upward reach; hand behind back) and percentage upper limb volume difference (%LVD =/>10% diagnosed as lymphedema) measured with the vertical perometer (400T). 613 of 617 participants completed questionnaires (mean age 62.3 years, SD 10.0; mean time since treatment 63.0 months, SD 46.6) and 417 completed objective testing. Morbidity prevalence was estimated as 35.8%, 21.9%, 19.8% and 34.4% for fatigue, impaired upper limb function, lymphedema and pain respectively. Comparing those self-reporting the presence or absence of each type of morbidity, statistically significant differences in comparator variables supported validity of the MST. Statistically significant correlations resulted between MST scores focussing on impact of morbidity, and comparator variables that reflect function and quality of life. Analysis supports the validity of all four short-forms of the MST as providing indications of both presence of morbidity and impacts on participants' lives. This may facilitate early and appropriate referral for intervention. Copyright © 2013 Elsevier Ltd. All rights reserved.

Refining the multisystem view of the stress response: coordination among cortisol, alpha-amylase, and subjective stress in response to relationship conflict.

PubMed

Laurent, Heidemarie K; Powers, Sally I; Granger, Douglas A

2013-07-02

This study investigated associations among young adults' hypothalamic-pituitary-adrenal axis activity, autonomic nervous system activity, and subjective stress in response to interpersonal conflict to better characterize coordination across stress systems. Seven saliva samples were collected from 199 young adult opposite-sex couples before, during, and after they discussed an unresolved relationship conflict. Samples were later assayed for cortisol and alpha-amylase (sAA). Couples rated anticipatory stress prior to the conflict and perceived stress immediately following the task. Growth curve modeling was used to examine two possible levels of within-person coordination across physiological systems: alignment between cortisol and sAA responses throughout the sampling period ("matched phase coordination"), and association between overall levels of cortisol and sAA in response to conflict ("average level coordination"). Whereas both partners showed the former type of coordination, only women showed the latter type. Positive anticipation of the stressor predicted stronger cortisol-sAA matched phase coordination for women. Pre-task ratings related to women's sAA, and post-task ratings related to both partners' cortisol responses. Implications for a multisystem interpretation of normal and pathological responses to daily stress are discussed. Copyright © 2013 Elsevier Inc. All rights reserved.

Refining the multisystem view of the stress response: Coordination among cortisol, alpha-amylase, and subjective stress in response to relationship conflict

PubMed Central

Powers, Sally I.; Granger, Douglas A.

2013-01-01

This study investigated associations among young adults' hypothalamic-pituitary-adrenal axis activity, autonomic nervous system activity, and subjective stress in response to interpersonal conflict to better characterize coordination across stress systems. Seven saliva samples were collected from 199 young adult opposite-sex couples before, during, and after they discussed an unresolved relationship conflict. Samples were later assayed for cortisol and alpha-amylase (sAA). Couples rated anticipatory stress prior to the conflict and perceived stress immediately following the task. Growth curve modeling was used to examine two possible levels of within-person coordination across physiological systems: alignment between cortisol and sAA responses throughout the sampling period (“matched phase coordination”), and association between overall levels of cortisol and sAA in response to conflict (“average level coordination”). Whereas both partners showed the former type of coordination, only women showed the latter type. Positive anticipation of the stressor predicted stronger cortisol-sAA matched phase coordination for women. Pre-task ratings related to women's sAA, and post-task ratings related to both partners' cortisol responses. Implications for a multisystem interpretation of normal and pathological responses to daily stress are discussed. PMID:23684904

[Postoperative adjuvante Therapie mit einem Mistelextrakt (Viscum album ssp. album) bei Hündinnen mit Mammatumoren].

PubMed

Biegel, Ulrike; Stratmann, Nina; Knauf, Yvonne; Ruess, Katja; Reif, Marcus; Wehrend, Axel

2017-01-01

Hintergrund: Canine Mammatumoren (CMT) sind wegen ihrer Häufigkeit und hohen Malignitätsrate eine Herausforderung für die Veterinärmedizin. Bisher ist noch keine postoperative adjuvante Therapie als wirksamer Standard etabliert und in den nächsten Jahren wohl auch nicht zu erwarten. Zusätzlich ist die Frage nach der Verträglichkeit einer adjuvanten Therapie mit Erhaltung oder Verbesserung der Lebensqualität (LQ) wichtig. Die Therapie mit Mistelextrakten (Viscum album L.; VAE) ist in der Humanonkologie nach adjuvanter Tumorbasistherapie (Chemotherapie und Bestrahlung) eine sehr häufig verwendete, zusätzliche adjuvante Behandlungsmethode. Auch bei verschiedenen Tierarten werden inzwischen Mistelpräparate in der Onkologie erfolgreich angewendet. Methoden: Überprüfung von Wirkung und Nutzen einer postoperativen, adjuvanten Misteltherapie beim CMT sowie Erfassung der LQ unter der VAE-Behandlung. Ausgewertet wurden 56 Hündinnen mit Mammaadenokarzinom, 33 ausschließlich operierte Kontrolltiere und 23 operierte Tiere, die adjuvant VAE erhielten. Ergebnisse: Die mediane Überlebenszeit (MST) aller Tiere (n = 56) betrug 32 Monate (Interquartilbereich 13-51 Monate). Im deskriptiven Vergleich der Überlebenszeiten (ST) nach Kaplan-Meier waren nach 12, 24, 36 bzw. 48 Monaten noch 24, 20, 15 bzw. 5 Hündinnen (entsprechend 72,7%, 60,6%, 45,1%, 12,4%) der Kontrollgruppe sowie 19, 14, 11 und 1 Hündin (82,6%, 60,9%, 47,8%, 4,3%) der VAE-Gruppe am Leben. Die VAE-Therapie führte zu einem geringeren Gesamtversterberisiko, das statistisch nicht signifikant war (Hazard Ratio (HR) 0,530, 95%-Konfidenzintervall (KI) 0,222-1,262; p = 0,15). Tendenziell (p = 0,07) zeigte sich eine Verringerung des tumorbedingten Sterberisikos auf 25% (HR 0,251, 95%-KI 0,056-1,122). Schlussfolgerungen: Es kann eine Tendenz zur Senkung des tumorbedingten Sterberisikos der VAE-Gruppe bei guter Verträglichkeit der Therapie angenommen werden. Die LQ der Tiere blieb über die gesamte

Promoting the Implementation of an Evidence-Based Intervention for Adolescent Marijuana Abuse in Community Settings: Testing the Use of Intensive Quality Assurance

ERIC Educational Resources Information Center

Henggeler, Scott W.; Sheidow, Ashli J.; Cunningham, Phillippe B.; Donohue, Bradley C.; Ford, Julian D.

2008-01-01

The development and evaluation of effective strategies for transporting evidence-based practices to community-based clinicians has become a research and policy priority. Using multisystemic therapy programs as a platform, an experimental design examined the capacity of an Intensive Quality Assurance (IQA) system to promote therapist implementation…

Multi-system Component Phenotypes of Bipolar Disorder for Genetic Investigations of Extended Pedigrees

PubMed Central

Fears, Scott C.; Service, Susan K.; Kremeyer, Barbara; Araya, Carmen; Araya, Xinia; Bejarano, Julio; Ramirez, Margarita; Castrillón, Gabriel; Gomez-Franco, Juliana; Lopez, Maria C.; Montoya, Gabriel; Montoya, Patricia; Aldana, Ileana; Teshiba, Terri M.; Abaryan, Zvart; Al-Sharif, Noor B.; Ericson, Marissa; Jalbrzikowski, Maria; Luykx, Jurjen J.; Navarro, Linda; Tishler, Todd A.; Altshuler, Lori; Bartzokis, George; Escobar, Javier; Glahn, David C.; Ospina-Duque, Jorge; Risch, Neil; Ruiz-Linares, Andrés; Thompson, Paul M.; Cantor, Rita M.; Lopez-Jaramillo, Carlos; Macaya, Gabriel; Molina, Julio; Reus, Victor I.; Sabatti, Chiara; Freimer, Nelson B.; Bearden, Carrie E.

2014-01-01

IMPORTANCE Genetic factors contribute to risk for bipolar disorder (BP), yet its pathogenesis remains poorly understood. A focus on measuring multi-system quantitative traits that may be components of BP psychopathology may enable genetic dissection of this complex disorder, and investigation of extended pedigrees from genetically isolated populations may facilitate the detection of specific genetic variants that impact on BP as well as its component phenotypes. OBJECTIVE To identify quantitative neurocognitive, temperament-related, and neuroanatomic phenotypes that appear heritable and associated with severe bipolar disorder (BP-I), and therefore suitable for genetic linkage and association studies aimed at identifying variants contributing to BP-I risk. DESIGN Multi-generational pedigree study in two closely related, genetically isolated populations: the Central Valley of Costa Rica (CVCR) and Antioquia, Colombia (ANT). PARTICIPANTS 738 individuals, all from CVCR and ANT pedigrees, of whom 181 are affected with BP-I. MAIN OUTCOME MEASURE Familial aggregation (heritability) and association with BP-I of 169 quantitative neurocognitive, temperament, magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) phenotypes. RESULTS Seventy-five percent (126) of the phenotypes investigated were significantly heritable, and 31% (53) were associated with BP-I. About 1/4 of the phenotypes, including measures from each phenotype domain, were both heritable and associated with BP-I. Neuroimaging phenotypes, particularly cortical thickness in prefrontal and temporal regions, and volume and microstructural integrity of the corpus callosum, represented the most promising candidate traits for genetic mapping related to BP based on strong heritability and association with disease. Analyses of phenotypic and genetic covariation identified substantial correlations among the traits, at least some of which share a common underlying genetic architecture. CONCLUSIONS AND

Confirming, Validating, and Norming the Factor Structure of Systemic Therapy Inventory of Change Initial and Intersession.

PubMed

Pinsof, William M; Zinbarg, Richard E; Shimokawa, Kenichi; Latta, Tara A; Goldsmith, Jacob Z; Knobloch-Fedders, Lynne M; Chambers, Anthony L; Lebow, Jay L

2015-09-01

Progress or feedback research tracks and feeds back client progress data throughout the course of psychotherapy. In the effort to empirically ground psychotherapeutic practice, feedback research is both a complement and alternative to empirically supported manualized treatments. Evidence suggests that tracking and feeding back progress data with individual or nonsystemic feedback systems improves outcomes in individual and couple therapy. The research reported in this article pertains to the STIC(®) (Systemic Therapy Inventory of Change)-the first client-report feedback system designed to empirically assess and track change within client systems from multisystemic and multidimensional perspectives in individual, couple, and family therapy. Clients complete the STIC Initial before the first session and the shorter STIC Intersession before every subsequent session. This study tested and its results supported the hypothesized factor structure of the six scales that comprise both STIC forms in a clinical outpatient sample and in a normal, random representative sample of the U.S. This study also tested the STIC's concurrent validity and found that its 6 scales and 40 of its 41 subscales differentiated the clinical and normal samples. Lastly, the study derived clinical cut-offs for each scale and subscale to determine whether and how much a client's score falls in the normal or clinical range. Beyond supporting the factorial and concurrent validity of both STIC forms, this research supported the reliabilities of the six scales (Omegahierarchical ) as well as the reliabilities of most subscales (alpha and rate-rerate). This article delineates clinical implications and directions for future research. © 2015 Family Process Institute.

CONVECTION ENHANCED DELIVERY OF CARBORANYLPORPHYRINS FOR NEUTRON CAPTURE THERAPY OF BRAIN TUMORS

PubMed Central

Kawabata, Shinji; Yang, Weilian; Wu, Gong; Huo, Tianyao; Binns, Peter J.; Riley, Kent J.; Ongayi, Owendi; Gottumukkala, Vijay; Vicente, M. Graça H.

2010-01-01

Boron neutron capture therapy (BNCT) is based on the nuclear capture and fission reactions that occur when non-radioactive 10B is irradiated with low energy thermal neutrons to produce α-particles (10B[n,α]7Li). Carboranylporphyrins are a class of substituted porphyrins containing multiple carborane clusters. Three of these have been evaluated in the present study: 5,10,15,20-tetra-(4-nido-carboranyphenyl)tetrabenzoporphyrin (H2TBP), 5,10,15,20-tetra-(4-nido-carboranylphenyl)porphyrin (H2TCP) and 5,15-di-[3,5-(nido-carboranylmethyl)phenyl]-porphyrin (H2DCP). The goals of this study were two-fold. First, to determine the biodistribution of H2TBP, H2TCP and H2DCP following intracerebral (i.c.) administration by means of short term (30 min) convection enhanced delivery (CED) or sustained delivery over 24 h by osmotic pumps to F98 glioma bearing rats. Second, to determine the efficacy of H2TCP and H2TBP as boron delivery agents for BNCT in F98 glioma bearing rats. Tumor boron concentrations immediately after i.c. osmotic pump delivery were high (36–88 µg/g) and they remained so at 24 h (62–103 µg/g) The corresponding normal brain concentrations were low (0.8–5.2 µg/g) and the blood and liver concentrations were all undetectable. Based on these data, therapy studies were initiated at the Massachusetts Institute of Technology (MIT) Research Reactor (MITRR) with H2TCP and H2TBP 24 h after CED or osmotic pump delivery. Mean survival times (MST) of untreated and irradiated control rats were 23±3 and 27±3 d, respectively, while animals that received H2TCP or H2TBP, followed by BNCT, had a MST of 35±4 d and 44±10 d, respectively, which were better than those obtained following i.v. administration of boronophenylalanine (37±3 d). However, since the tumor boron concentrations of the carboranylporphyrins were 3–5X > i.v. BPA (~25 µg/g), we had expected that the MSTs would have been greater. Histopathologic examination of brains of BNCT treated rats revealed

Phase 2 Study of Temozolomide-Based Chemoradiation Therapy for High-Risk Low-Grade Gliomas: Preliminary Results of Radiation Therapy Oncology Group 0424

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fisher, Barbara J., E-mail: barbara.fisher@lhsc.on.ca; Hu, Chen; Macdonald, David R.

2015-03-01

Purpose: Radiation Therapy Oncology Group (RTOG) 0424 was a phase 2 study of a high-risk low-grade glioma (LGG) population who were treated with temozolomide (TMZ) and radiation therapy (RT), and outcomes were compared to those of historical controls. This study was designed to detect a 43% increase in median survival time (MST) from 40.5 to 57.9 months and a 20% improvement in 3-year overall survival (OS) rate from 54% to 65% at a 10% significance level (1-sided) and 96% power. Methods and Materials: Patients with LGGs with 3 or more risk factors for recurrence (age ≥40 years, astrocytoma histology, bihemispherical tumor, preoperativemore » tumor diameter of ≥6 cm, or a preoperative neurological function status of >1) were treated with RT (54 Gy in 30 fractions) and concurrent and adjuvant TMZ. Results: From 2005 to 2009, 129 evaluable patients (75 males and 54 females) were accrued. Median age was 49 years; 91% had a Zubrod score of 0 or 1; and 69%, 25%, and 6% of patients had 3, 4, and 5 risk factors, respectively. Patients had median and minimum follow-up examinations of 4.1 years and 3 years, respectively. The 3-year OS rate was 73.1% (95% confidence interval: 65.3%-80.8%), which was significantly improved compared to that of prespecified historical control values (P<.001). Median survival time has not yet been reached. Three-year progression-free survival was 59.2%. Grades 3 and 4 adverse events occurred in 43% and 10% of patients, respectively. One patient died of herpes encephalitis. Conclusions: The 3-year OS rate of 73.1% for RTOG 0424 high-risk LGG patients is higher than that reported for historical controls (P<.001) and the study-hypothesized rate of 65%.« less

Effects of Topiramate in Adults with Prader-Willi Syndrome

ERIC Educational Resources Information Center

Shapira, Nathan A.; Lessig, Mary C.; Lewis, Mark H.; Goodman, Wayne K.; Driscoll, Daniel J.

2004-01-01

Prader-Willi syndrome is a multisystem neurogenetic obesity disorder with behavioral manifestations, including hyperphagia, compulsive behavior, self-injury, and mild to moderate mental retardation. In an 8-week open-label study, we evaluated adjunctive therapy with the anticonvulsant topiramate in 8 adults with Prader-Willi syndrome. Appetite was…

Cell surface marker profiling of human tracheal basal cells reveals distinct subpopulations, identifies MST1/MSP as a mitogenic signal, and identifies new biomarkers for lung squamous cell carcinomas.

PubMed

Van de Laar, Emily; Clifford, Monica; Hasenoeder, Stefan; Kim, Bo Ram; Wang, Dennis; Lee, Sharon; Paterson, Josh; Vu, Nancy M; Waddell, Thomas K; Keshavjee, Shaf; Tsao, Ming-Sound; Ailles, Laurie; Moghal, Nadeem

2014-12-31

The large airways of the lungs (trachea and bronchi) are lined with a pseudostratified mucociliary epithelium, which is maintained by stem cells/progenitors within the basal cell compartment. Alterations in basal cell behavior can contribute to large airway diseases including squamous cell carcinomas (SQCCs). Basal cells have traditionally been thought of as a uniform population defined by basolateral position, cuboidal cell shape, and expression of pan-basal cell lineage markers like KRT5 and TP63. While some evidence suggests that basal cells are not all functionally equivalent, few heterogeneously expressed markers have been identified to purify and study subpopulations. In addition, few signaling pathways have been identified that regulate their cell behavior. The goals of this work were to investigate tracheal basal cell diversity and to identify new signaling pathways that regulate basal cell behavior. We used flow cytometry (FACS) to profile cell surface marker expression at a single cell level in primary human tracheal basal cell cultures that maintain stem cell/progenitor activity. FACS results were validated with tissue staining, in silico comparisons with normal basal cell and lung cancer datasets, and an in vitro proliferation assay. We identified 105 surface markers, with 47 markers identifying potential subpopulations. These subpopulations generally fell into more (~ > 13%) or less abundant (~ < 6%) groups. Microarray gene expression profiling supported the heterogeneous expression of these markers in the total population, and immunostaining of large airway tissue suggested that some of these markers are relevant in vivo. 24 markers were enriched in lung SQCCs relative to adenocarcinomas, with four markers having prognostic significance in SQCCs. We also identified 33 signaling receptors, including the MST1R/RON growth factor receptor, whose ligand MST1/MSP was mitogenic for basal cells. This work provides the largest description to date of

The Hippo pathway in disease and therapy: cancer and beyond

PubMed Central

2014-01-01

The Hippo tumour suppressor pathway co-ordinates cell proliferation, cell death and cell differentiation to regulate tissue growth control. In mammals, a conserved core Hippo signalling module receives signal inputs on different levels to ensure the proper regulation of YAP/TAZ activities as transcriptional co-activators. While the core module members MST1/2, Salvador, LATS1/2 and MOB1 have been attributed tumour suppressive functions, YAP/TAZ have been mainly described to have oncogenic roles, although some reports provided evidence supporting growth suppressive roles of YAP/TAZ in certain cancer settings. Intriguingly, mammalian Hippo signalling is also implicated in non-cancer diseases and plays a role in tissue regeneration following injury. Cumulatively, these findings indicate that the pharmacological inhibition or activation of the Hippo pathway could be desirable depending on the disease context. In this review, we first summarise the functions of the mammalian Hippo pathway in tumour formation, and then discuss non-cancer diseases involving Hippo signalling core components with a specific focus on our current understanding of the non-cancer roles of MST1/2 and YAP/TAZ. In addition, the pros and cons of possible pharmacological interventions with Hippo signalling will be reviewed, with particular emphasis on anti-cancer drug development and regenerative medicine. PMID:25097725

Cytotoxicity of Titanate-Calcium Complexes to MC3T3 Osteoblast-Like Cells

DOE PAGES

Chen, Yen-Wei; Drury, Jeanie L.; Moussi, Joelle; ...

2016-11-30

Monosodium titanates (MST) are a relatively novel form of particulate titanium dioxide that have been proposed for biological use as metal sorbents or delivery agents, most recently calcium (II). In these roles, the toxicity of the titanate or its metal complex is crucial to its biological utility. The aim of this study was to determine the cytotoxicity of MST and MST-calcium complexes with MC3T3 osteoblast-like cells; MST-Ca(II) complexes could be useful to promote bone formation in various hard tissue applications. MC3T3 cells were exposed to native MST or MST-Ca(II) complexes for 24–72 h. A CellTiter-Blue ® assay was employed tomore » assess the metabolic activity of the cells. The results showed that MST and MST-Ca(II) suppressed MC3T3 metabolic activity significantly in a dose-, time-, and cell-density-dependent fashion. MST-Ca(II) suppressed MC3T3 metabolism in a statistically identical manner as native MST at all concentrations. We concluded that MST and MST-Ca(II) are significantly cytotoxic to MC3T3 cells through a mechanism yet unknown; this is a potential problem to the biological utility of these complexes.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Yen-Wei; Drury, Jeanie L.; Moussi, Joelle

Monosodium titanates (MST) are a relatively novel form of particulate titanium dioxide that have been proposed for biological use as metal sorbents or delivery agents, most recently calcium (II). In these roles, the toxicity of the titanate or its metal complex is crucial to its biological utility. The aim of this study was to determine the cytotoxicity of MST and MST-calcium complexes with MC3T3 osteoblast-like cells; MST-Ca(II) complexes could be useful to promote bone formation in various hard tissue applications. MC3T3 cells were exposed to native MST or MST-Ca(II) complexes for 24–72 h. A CellTiter-Blue ® assay was employed tomore » assess the metabolic activity of the cells. The results showed that MST and MST-Ca(II) suppressed MC3T3 metabolic activity significantly in a dose-, time-, and cell-density-dependent fashion. MST-Ca(II) suppressed MC3T3 metabolism in a statistically identical manner as native MST at all concentrations. We concluded that MST and MST-Ca(II) are significantly cytotoxic to MC3T3 cells through a mechanism yet unknown; this is a potential problem to the biological utility of these complexes.« less

Cytotoxicity of Titanate-Calcium Complexes to MC3T3 Osteoblast-Like Cells

PubMed Central

Drury, Jeanie L.; Moussi, Joelle; Taylor-Pashow, Kathryn M. L.

2016-01-01

Monosodium titanates (MST) are a relatively novel form of particulate titanium dioxide that have been proposed for biological use as metal sorbents or delivery agents, most recently calcium (II). In these roles, the toxicity of the titanate or its metal complex is crucial to its biological utility. The aim of this study was to determine the cytotoxicity of MST and MST-calcium complexes with MC3T3 osteoblast-like cells; MST-Ca(II) complexes could be useful to promote bone formation in various hard tissue applications. MC3T3 cells were exposed to native MST or MST-Ca(II) complexes for 24–72 h. A CellTiter-Blue® assay was employed to assess the metabolic activity of the cells. The results showed that MST and MST-Ca(II) suppressed MC3T3 metabolic activity significantly in a dose-, time-, and cell-density-dependent fashion. MST-Ca(II) suppressed MC3T3 metabolism in a statistically identical manner as native MST at all concentrations. We concluded that MST and MST-Ca(II) are significantly cytotoxic to MC3T3 cells through a mechanism yet unknown; this is a potential problem to the biological utility of these complexes. PMID:28044136

BRAVEMIND: Advancing the Virtual Iraq/Afghanistan PTSD Exposure Therapy for MST

DTIC Science & Technology

2017-08-01

The 122nd Annual Convention of the American Psychological Association. Washington D.C. August 7, 2011.  Website(s) or other Internet site(s) o The...be subject to any penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number. PLEASE...can produce additional risk for the development of PTSD in a population that is already at high risk due to the existing occupational hazards present

BRAVEMIND: Advancing the Virtual Iraq/Afghanistan PTSD Exposure Therapy for MST

DTIC Science & Technology

2016-06-01

assaults have been on the rise over the last ten years , and have garnered significant popular media attention. The current project proposes to develop...chological research and behavioral health applications in the 21st century. More specifically, the spike over the last 10 years in the number of US service...Cycloserine (DCS). DCS, an N-methyl-d-aspartate partial agonist, has been shown to facilitate extinction learning in laboratory animals when infused

Secondary Analysis of RTOG 9508, a Phase 3 Randomized Trial of Whole-Brain Radiation Therapy Versus WBRT Plus Stereotactic Radiosurgery in Patients With 1-3 Brain Metastases; Poststratified by the Graded Prognostic Assessment (GPA)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sperduto, Paul W., E-mail: psperduto@mropa.com; Shanley, Ryan; Luo, Xianghua

2014-11-01

Purpose: Radiation Therapy Oncology Group (RTOG) 9508 showed a survival advantage for patients with 1 but not 2 or 3 brain metastasis (BM) treated with whole-brain radiation therapy (WBRT) and stereotactic radiosurgery (SRS) versus WBRT alone. An improved prognostic index, the graded prognostic assessment (GPA) has been developed. Our hypothesis was that if the data from RTOG 9508 were poststratified by the GPA, the conclusions may vary. Methods and Materials: In this analysis, 252 of the 331 patients were evaluable by GPA. Of those, 211 had lung cancer. Breast cancer patients were excluded because the components of the breast GPAmore » are not in the RTOG database. Multiple Cox regression was used to compare survival between treatment groups, adjusting for GPA. Treatment comparisons within subgroups were performed with the log-rank test. A free online tool ( (brainmetgpa.com)) simplified GPA use. Results: The fundamental conclusions of the primary analysis were confirmed in that there was no survival benefit overall for patients with 1 to 3 metastases; however, there was a benefit for the subset of patients with GPA 3.5 to 4.0 (median survival time [MST] for WBRT + SRS vs WBRT alone was 21.0 versus 10.3 months, P=.05) regardless of the number of metastases. Among patients with GPA 3.5 to 4.0 treated with WBRT and SRS, the MST for patients with 1 versus 2 to 3 metastases was 21 and 14.1 months, respectively. Conclusions: This secondary analysis of predominantly lung cancer patients, consistent with the original analysis, shows no survival advantage for the group overall when treated with WBRT and SRS; however, in patients with high GPA (3.5-4), there is a survival advantage regardless of whether they have 1, 2, or 3 BM. This benefit did not extend to patients with lower GPA. Prospective validation of this survival benefit for patients with multiple BM and high GPA when treated with WBRT and SRS is warranted.« less

Secondary Analysis of RTOG 9508, a Phase 3 Randomized Trial of Whole-Brain Radiation Therapy Versus WBRT Plus Stereotactic Radiosurgery in Patients With 1-3 Brain Metastases; Poststratified by the Graded Prognostic Assessment (GPA)

PubMed Central

Sperduto, Paul W.; Shanley, Ryan; Luo, Xianghua; Andrews, David; Werner-Wasik, Maria; Valicenti, Richard; Bahary, Jean-Paul; Souhami, Luis; Won, Minhee; Mehta, Minesh

2015-01-01

Purpose Radiation Therapy Oncology Group (RTOG) 9508 showed a survival advantage for patients with 1 but not 2 or 3 brain metastasis (BM) treated with whole-brain radiation therapy (WBRT) and stereotactic radiosurgery (SRS) versus WBRT alone. An improved prognostic index, the graded prognostic assessment (GPA) has been developed. Our hypothesis was that if the data from RTOG 9508 were poststratified by the GPA, the conclusions may vary. Methods and Materials In this analysis, 252 of the 331 patients were evaluable by GPA. Of those, 211 had lung cancer. Breast cancer patients were excluded because the components of the breast GPA are not in the RTOG database. Multiple Cox regression was used to compare survival between treatment groups, adjusting for GPA. Treatment comparisons within subgroups were performed with the log-rank test. A free online tool (brainmetgpa.com) simplified GPA use. Results The fundamental conclusions of the primary analysis were confirmed in that there was no survival benefit overall for patients with 1 to 3 metastases; however, there was a benefit for the subset of patients with GPA 3.5 to 4.0 (median survival time [MST] for WBRT + SRS vs WBRT alone was 21.0 versus 10.3 months, P = .05) regardless of the number of metastases. Among patients with GPA 3.5 to 4.0 treated with WBRT and SRS, the MST for patients with 1 versus 2 to 3 metastases was 21 and 14.1 months, respectively. Conclusions This secondary analysis of predominantly lung cancer patients, consistent with the original analysis, shows no survival advantage for the group overall when treated with WBRT and SRS; however, in patients with high GPA (3.5-4), there is a survival advantage regardless of whether they have 1, 2, or 3 BM. This benefit did not extend to patients with lower GPA. Prospective validation of this survival benefit for patients with multiple BM and high GPA when treated with WBRT and SRS is warranted. PMID:25304947

Secondary analysis of RTOG 9508, a phase 3 randomized trial of whole-brain radiation therapy versus WBRT plus stereotactic radiosurgery in patients with 1-3 brain metastases; poststratified by the graded prognostic assessment (GPA).

PubMed

Sperduto, Paul W; Shanley, Ryan; Luo, Xianghua; Andrews, David; Werner-Wasik, Maria; Valicenti, Richard; Bahary, Jean-Paul; Souhami, Luis; Won, Minhee; Mehta, Minesh

2014-11-01

Radiation Therapy Oncology Group (RTOG) 9508 showed a survival advantage for patients with 1 but not 2 or 3 brain metastasis (BM) treated with whole-brain radiation therapy (WBRT) and stereotactic radiosurgery (SRS) versus WBRT alone. An improved prognostic index, the graded prognostic assessment (GPA) has been developed. Our hypothesis was that if the data from RTOG 9508 were poststratified by the GPA, the conclusions may vary. In this analysis, 252 of the 331 patients were evaluable by GPA. Of those, 211 had lung cancer. Breast cancer patients were excluded because the components of the breast GPA are not in the RTOG database. Multiple Cox regression was used to compare survival between treatment groups, adjusting for GPA. Treatment comparisons within subgroups were performed with the log-rank test. A free online tool (brainmetgpa.com) simplified GPA use. The fundamental conclusions of the primary analysis were confirmed in that there was no survival benefit overall for patients with 1 to 3 metastases; however, there was a benefit for the subset of patients with GPA 3.5 to 4.0 (median survival time [MST] for WBRT + SRS vs WBRT alone was 21.0 versus 10.3 months, P=.05) regardless of the number of metastases. Among patients with GPA 3.5 to 4.0 treated with WBRT and SRS, the MST for patients with 1 versus 2 to 3 metastases was 21 and 14.1 months, respectively. This secondary analysis of predominantly lung cancer patients, consistent with the original analysis, shows no survival advantage for the group overall when treated with WBRT and SRS; however, in patients with high GPA (3.5-4), there is a survival advantage regardless of whether they have 1, 2, or 3 BM. This benefit did not extend to patients with lower GPA. Prospective validation of this survival benefit for patients with multiple BM and high GPA when treated with WBRT and SRS is warranted. Copyright © 2014 Elsevier Inc. All rights reserved.

A Phase III Clinical Trial of the Epidermal Growth Factor Vaccine CIMAvax-EGF as Switch Maintenance Therapy in Advanced Non-Small Cell Lung Cancer Patients.

PubMed

Rodriguez, Pedro C; Popa, Xitllaly; Martínez, Odeth; Mendoza, Silvia; Santiesteban, Eduardo; Crespo, Tatiana; Amador, Rosa M; Fleytas, Ricardo; Acosta, Soraida C; Otero, Yanine; Romero, Gala N; de la Torre, Ana; Cala, Mireysi; Arzuaga, Lina; Vello, Loisel; Reyes, Delmairis; Futiel, Niurka; Sabates, Teresa; Catala, Mauricio; Flores, Yoanna I; Garcia, Beatriz; Viada, Carmen; Lorenzo-Luaces, Patricia; Marrero, Maria A; Alonso, Liuba; Parra, Jenelin; Aguilera, Nadia; Pomares, Yaisel; Sierra, Patricia; Rodríguez, Gryssell; Mazorra, Zaima; Lage, Agustin; Crombet, Tania; Neninger, Elia

2016-08-01

EGFR is a well-validated target for patients with non-small cell lung cancer (NSCLC). CIMAvax-EGF is a therapeutic cancer vaccine composed of human recombinant EGF conjugated to a carrier protein and Montanide ISA51 as adjuvant. The vaccine is intended to induce antibodies against self EGFs that block EGF-EGFR interaction. To evaluate overall survival, safety, immunogenicity, and EGF concentration in serum after CIMAvax-EGF, a randomized phase III trial was done in patients with advanced NSCLC. Four to 6 weeks after first-line chemotherapy, 405 patients with stage IIIB/IV NSCLC were randomly assigned to a vaccine group, which received CIMAvax-EGF or a control group, treated with best supportive care. Long-term vaccination was very safe. Most frequent adverse reactions were grade 1 or 2 injection-site pain, fever, vomiting, and headache. Vaccination induced anti-EGF antibodies and decreased serum EGF concentration. In the safety population, median survival time (MST) was 10.83 months in the vaccine arm versus 8.86 months in the control arm. These differences were not significant according the standard log rank (HR, 0.82; P = 0.100), but according a weighted log rank (P = 0.04) that was applied once the nonproportionality of the HR was verified. Survival benefit was significant (HR, 0.77; P = 0.036) in the per-protocol setting (patients receiving at least four vaccine doses): MST was 12.43 months for the vaccine arm versus 9.43 months for the control arm. MST was higher (14.66 months) for vaccinated patients with high EGF concentration at baseline. Switch maintenance with CIMAvax-EGF was well tolerated and significantly increased MST of patients that completed induction vaccination. Baseline EGF concentration predicted survival benefit. Clin Cancer Res; 22(15); 3782-90. ©2016 AACR. ©2016 American Association for Cancer Research.

From Diagnosis, to Life Saving Therapy, to Hollywood: The Journey of John Crowley

ERIC Educational Resources Information Center

Apel, Laura

2010-01-01

In February of 2000, "Exceptional Parent" introduced readers to the Crowley family. The author profiled John, Aileen, and their three children: Megan, Patrick, and John Jr. They told "Exceptional Parent" that in 1998 both Megan and Patrick were diagnosed with Pompe disease, a progressive, multisystemic, debilitating, and often fatal muscular…

Military sexual trauma among homeless veterans.

PubMed

Pavao, Joanne; Turchik, Jessica A; Hyun, Jenny K; Karpenko, Julie; Saweikis, Meghan; McCutcheon, Susan; Kane, Vincent; Kimerling, Rachel

2013-07-01

Military sexual trauma (MST) is the Veteran Health Administration's (VHA) term for sexual assault and/or sexual harassment that occurs during military service. The experience of MST is associated with a variety of mental health conditions. Preliminary research suggests that MST may be associated with homelessness among female Veterans, although to date MST has not been examined in a national study of both female and male homeless Veterans. To estimate the prevalence of MST, examine the association between MST and mental health conditions, and describe mental health utilization among homeless women and men. National, cross-sectional study of 126,598 homeless Veterans who used VHA outpatient care in fiscal year 2010. All variables were obtained from VHA administrative databases, including MST screening status, ICD-9-CM codes to determine mental health diagnoses, and VHA utilization. Of homeless Veterans in VHA, 39.7 % of females and 3.3 % of males experienced MST. Homeless Veterans who experienced MST demonstrated a significantly higher likelihood of almost all mental health conditions examined as compared to other homeless women and men, including depression, posttraumatic stress disorder, other anxiety disorders, substance use disorders, bipolar disorders, personality disorders, suicide, and, among men only, schizophrenia and psychotic disorders. Nearly all homeless Veterans had at least one mental health visit and Veterans who experienced MST utilized significantly more mental health visits compared to Veterans who did not experience MST. A substantial proportion of homeless Veterans using VHA services have experienced MST, and those who experienced MST had increased odds of mental health diagnoses. Homeless Veterans who had experienced MST had higher intensity of mental health care utilization and high rates of MST-related mental health care. This study highlights the importance of trauma-informed care among homeless Veterans and the success of VHA homeless

Identification of Novel Rosavirus Species That Infects Diverse Rodent Species and Causes Multisystemic Dissemination in Mouse Model

PubMed Central

Fan, Rachel Y. Y.; Zhang, Anna J. X.; Chan, Brandon C. C.; Lam, Carol S. F.; Yip, Cyril C. Y.; Chan, Kwok-Hung; Chen, Zhi-Wei; Yuen, Kwok-Yung

2016-01-01

While novel picornaviruses are being discovered in rodents, their host range and pathogenicity are largely unknown. We identified two novel picornaviruses, rosavirus B from the street rat, Norway rat, and rosavirus C from five different wild rat species (chestnut spiny rat, greater bandicoot rat, Indochinese forest rat, roof rat and Coxing's white-bellied rat) in China. Analysis of 13 complete genome sequences showed that “Rosavirus B” and “Rosavirus C” represent two potentially novel picornavirus species infecting different rodents. Though being most closely related to rosavirus A, rosavirus B and C possessed distinct protease cleavage sites and variations in Yn-Xm-AUG sequence in 5’UTR and myristylation site in VP4. Anti-rosavirus B VP1 antibodies were detected in Norway rats, whereas anti-rosavirus C VP1 and neutralizing antibodies were detected in Indochinese forest rats and Coxing's white-bellied rats. While the highest prevalence was observed in Coxing's white-bellied rats by RT-PCR, the detection of rosavirus C from different rat species suggests potential interspecies transmission. Rosavirus C isolated from 3T3 cells causes multisystemic diseases in a mouse model, with high viral loads and positive viral antigen expression in organs of infected mice after oral or intracerebral inoculation. Histological examination revealed alveolar fluid exudation, interstitial infiltration, alveolar fluid exudate and wall thickening in lungs, and hepatocyte degeneration and lymphocytic/monocytic inflammatory infiltrates with giant cell formation in liver sections of sacrificed mice. Since rosavirus A2 has been detected in fecal samples of children, further studies should elucidate the pathogenicity and emergence potential of different rosaviruses. PMID:27737017

Gender, Race, and Survival: A Study in Non-Small-Cell Lung Cancer Brain Metastases Patients Utilizing the Radiation Therapy Oncology Group Recursive Partitioning Analysis Classification

DOE Office of Scientific and Technical Information (OSTI.GOV)

Videtic, Gregory M.M., E-mail: videtig@ccf.or; Reddy, Chandana A.; Chao, Samuel T.

Purpose: To explore whether gender and race influence survival in non-small-cell lung cancer (NSCLC) in patients with brain metastases, using our large single-institution brain tumor database and the Radiation Therapy Oncology Group recursive partitioning analysis (RPA) brain metastases classification. Methods and materials: A retrospective review of a single-institution brain metastasis database for the interval January 1982 to September 2004 yielded 835 NSCLC patients with brain metastases for analysis. Patient subsets based on combinations of gender, race, and RPA class were then analyzed for survival differences. Results: Median follow-up was 5.4 months (range, 0-122.9 months). There were 485 male patients (M)more » (58.4%) and 346 female patients (F) (41.6%). Of the 828 evaluable patients (99%), 143 (17%) were black/African American (B) and 685 (83%) were white/Caucasian (W). Median survival time (MST) from time of brain metastasis diagnosis for all patients was 5.8 months. Median survival time by gender (F vs. M) and race (W vs. B) was 6.3 months vs. 5.5 months (p = 0.013) and 6.0 months vs. 5.2 months (p = 0.08), respectively. For patients stratified by RPA class, gender, and race, MST significantly favored BFs over BMs in Class II: 11.2 months vs. 4.6 months (p = 0.021). On multivariable analysis, significant variables were gender (p = 0.041, relative risk [RR] 0.83) and RPA class (p < 0.0001, RR 0.28 for I vs. III; p < 0.0001, RR 0.51 for II vs. III) but not race. Conclusions: Gender significantly influences NSCLC brain metastasis survival. Race trended to significance in overall survival but was not significant on multivariable analysis. Multivariable analysis identified gender and RPA classification as significant variables with respect to survival.« less

Enzyme replacement therapy in patients with Fabry disease: state of the art and review of the literature.

PubMed

Pisani, Antonio; Visciano, Bianca; Roux, Graciana Diez; Sabbatini, Massimo; Porto, Caterina; Parenti, Giancarlo; Imbriaco, Massimo

2012-11-01

Anderson-Fabry disease is an X-linked lysosomal storage disorder resulting from the deficiency of the hydrolytic enzyme alpha galactosidase A, with consequent accumulation of globotrioasoyl ceramide in cells and tissues of the body, resulting in a multi-system pathology including end organ failure. In the classical phenotype, cardiac failure, renal failure and stroke result in a reduced median life expectancy. The current causal treatment for Fabry disease is the enzyme replacement therapy (ERT): two different products, Replagal (agalsidase alfa) and Fabrazyme (agalsidase beta), have been commercially available in Europe for almost 10 years and they are both indicated for long-term treatment. In fact, clinical trials, observational studies and registry data have provided many evidences for safety and efficacy of ERT in improving symptoms of pain, gastrointestinal disturbances, hypohidrosis, left ventricular mass index, glomerular filtration rate and quality of life. Few data are available on comparison of the two treatments and on the clinical course of the disease. This article reviews the published evidence for clinical efficacy of the two available enzyme preparations. Copyright © 2012 Elsevier Inc. All rights reserved.

An energy confinement study of the MST (Madison Symmetric Torus) reversed field pinch using a Thomson scattering diagnostic

DOE Office of Scientific and Technical Information (OSTI.GOV)

Den Hartog, D.J.

1989-11-01

Thomson scattering measurements of the central electron temperature and density during the plasma current peak have been performed on the MST Reversed Field Pinch (RFP). This Thomson scattering diagnostic was calibrated for absolute electron density measurements. These measurements of T{sub e} and n{sub e}, when combined with profile assumptions, were used to calculate estimates of energy confinement time ({tau}{sub E}) and poloidal beta ({beta}{sub {theta}}). A standard discharge with I{sub p} {approx} 400 kA, F {approx} {minus}0.1, and {theta} {approx} 1.6 typically exhibited T{sub e} {approx} 275 eV, n{sub e} {approx} 2.0 {times} 10{sup 13} cm{sup {minus}3}, {tau}{sub E} {le}more » 1 ms, and {beta}{sub {theta}} {le} 8%. The results of a limited plasma current scaling study did not indicate a strong scaling of T{sub e} or {tau}{sub E} with I{sub p}. The Thomson scattering diagnostic was used in conjunction with a bolometer, VUV radiation monitor, and edge magnetic coils to study the loss of energy from the plasma. Results indicate that thermal transport from stochastic magnetic fields, particle loss, and radiation are important energy loss processes. The experiments done for this study included an F-scan, a paddle limiter insertion series, and an argon doping series. The plasma maintained a constant {beta}{tau} during these perturbation experiments, suggesting that increases in one energy loss channel are compensated by drops in other channels and increases in input power to the plasma.« less

1. GENERAL VIEW OF SLC3W SHOWING SOUTH FACE AND EAST ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

1. GENERAL VIEW OF SLC-3W SHOWING SOUTH FACE AND EAST SIDE OF A-FRAME MOBILE SERVICE TOWER (MST). MST IN SERVICE POSITION OVER LAUNCHER AND FLAME BUCKET. CABLE TRAYS BETWEEN LAUNCH OPERATIONS BUILDING (BLDG. 763) AND SLC-3W IN FOREGROUND. LIQUID OXYGEN APRON VISIBLE IMMEDIATELY EAST (RIGHT) OF MST; FUEL APRON VISIBLE IMMEDIATELY WEST (LEFT) OF MST. A PORTION OF THE FLAME BUCKET VISIBLE BELOW THE SOUTH FACE OF THE MST. CAMERA TOWERS VISIBLE EAST OF MST BETWEEN ROAD AND CABLE TRAY, AND SOUTH OF MST NEAR LEFT MARGIN OF PHOTOGRAPH. - Vandenberg Air Force Base, Space Launch Complex 3, Launch Pad 3 West, Napa & Alden Roads, Lompoc, Santa Barbara County, CA

Patient-Centered Perioperative Care for a Victim of Military Sexual Trauma.

PubMed

Hickey, Thomas R; Kirwin, Paul D; Gardner, Elizabeth C; Feinleib, Jessica

2017-05-01

The patient population seen in our nation's Veterans Affairs Healthcare system is increasingly female and an alarming percentage of our veterans, male and female alike, report a history of military sexual trauma (MST), which is associated with an increased burden of morbidities including post-traumatic stress disorder (PTSD) and substance abuse. The experience of surgery can produce symptoms of PTSD in a clinically significant percentage of patients. This article describes the challenges of achieving a patient-centered perioperative care plan in the case of a female veteran who suffers from PTSD as a result of MST. We provide a brief background on the changing demographics of our nation's veterans, a review of MST and patient-centered care, and a description of the interdisciplinary care plan created and implemented for our patient. We note how this care model employs key elements of the Perioperative Surgical Home Model as developed by the American Society of Anesthesiologists. Finally, we propose an agenda for improving perioperative care for this group of veterans. No institutional review board was required for this case report-based discussion. The patient-centered care plan developed and implemented by an interdisciplinary team was well received by the patient and enabled her to comply with her postsurgical physical therapy. This recent interdisciplinary experience was in stark contrast to her experience of former surgical procedures, and produced much higher patient satisfaction. Improvements are needed in patient-centered perioperative care for victims of MST, both within the Veterans Affairs system and in the larger health care system. We suggest an agenda to improve care for these patients including: (1) increasing provider awareness and education about MST and about the potential psychological trauma of surgery per se, (2) employing elements of the Perioperative Surgical Home to encourage patient-centered care involving collaboration within an

[Detection and prognostic significance of micrometastasis in peripheral blood of patients with non-small cell lung cancer treated by chemo-radiation therapy].

PubMed

Chen, Ting-feng; Jiang, Guo-liang; Zhang, Yi-qin; Wang, Li-juan; Fu, Xiao-long; Qian, Hao; Wu, Kai-liang; Zhao, Sen

2007-05-01

To investigate the prognostic significance of micrometastasis (MM) in peripheral blood of patients with non-small cell lung cancer (NSCLC) treated by chemo-radiation therapy. Peripheral blood was taken from 67 NSCLC patients before and after definitive chemo-radiation therapy. CK19 mRNA of the peripheral blood was measured by nested RT-PCR and both their relationship with clinicopathological features and prognostic significance were further investigated. The micrometastasis-positive rates were 65.7% (44/67) and 32.8% (22/67), respectively, before and after the treatment. The micrometastasis-positive rate before treatment was closely in correlation with N-stage (P = 0.014). In contrast, it turned out to be more closely related with histological types (P = 0.019), weight loss (P = 0.01), KPS status (P = 0.027) as well as N-stage (P = 0.032) after chemo-radiation therapy. 4-yr distant metastasis rates (DMR) for micrometastasis-positive and -negative patients were 78.3% and 70.4%, respectively, before the treatment (P = 0.544) while they were 100% and 62.9%, respectively, after the chemoradiation (P < 0.001). The median survival time (MST) and 4-yr overall survival rate (OSR) for pretreatment micrometastasis-positive and -negative patients were 13.8 months and 17.6 months, and 18.2% and 17.4%, respectively (P = 0.619), while for post-treatment micrometastasis-positive and -negative patients they were 7.8 months and 27.6 months and 0 and 26.4%, respectively (P < 0.001). Multivariate analysis showed that the post-treatment positive micrometastasis was an independent unfavorable prognostic factor (P = 0.000). Detection of micrometastasis in peripheral blood may possess a prognostic significance after definitive chemo-radiation therapy. Micrometastasis-negative patients have better prognosis compared to those with positive micrometastasis.

Negative posttraumatic cognitions among military sexual trauma survivors.

PubMed

Carroll, Kathryn K; Lofgreen, Ashton M; Weaver, Darian C; Held, Philip; Klassen, Brian J; Smith, Dale L; Karnik, Niranjan S; Pollack, Mark H; Zalta, Alyson K

2018-05-19

Unique aspects of military sexual trauma (MST) may result in specific maladaptive cognitions among survivors. Understanding which posttraumatic cognitions are particularly strong among MST survivors could help clinicians target and improve treatment for these individuals. This study explored the impact of experiencing MST on posttraumatic cognitions among veterans with posttraumatic stress disorder (PTSD). Veterans enrolled in an Intensive Outpatient Program for PTSD (N = 226) were assessed for MST, PTSD severity, depression severity, and posttraumatic cognitions as part of a standard clinical intake. Multivariate analyses examined differences in posttraumatic cognitions between veterans who did and did not experience MST. MST survivors (n = 88) endorsed significantly stronger posttraumatic cognitions related to self-blame compared to non-MST counterparts (n = 138), even when accounting for current symptom severity. Specifically, MST predicted the following cognitions: "The event happened to me because of the sort of person I am," "Somebody else would have stopped the event from happening," "Somebody else would not have gotten into this situation," and "There is something about me that made the event happen," after controlling for severity of PTSD and depression. Study population was a treatment-seeking sample of veterans diagnosed with PTSD from a non-VA clinic. Veterans in MST group endorsed either sexual harassment, sexual assault, or both. Sample size of males who endorsed MST (n = 21) may be too small to generalize to all males. Beliefs related to self-blame may be important treatment targets for MST survivors. Copyright © 2018. Published by Elsevier B.V.

Within-unit relationship quality mediates the association between military sexual trauma and posttraumatic stress symptoms in veterans separating from military service.

PubMed

Laws, Holly; Mazure, Carolyn M; McKee, Sherry A; Park, Crystal L; Hoff, Rani

2016-09-01

Few studies have examined the impact of military sexual trauma (MST) on social functioning during deployment. Yet consideration of unit relationships during deployment may be important, given that military unit cohesion and support can provide protective effects against the stress of combat, and reduce the likelihood of developing posttraumatic stress disorder. Although prior research has posited that depleted social resources are one pathway through which MST is associated with posttraumatic stress symptoms (PTSS), no studies have statistically tested this theory. This study examined the association of MST and PTSS and evaluated the potential mediating role of decreased unit relationship quality. Mediational analyses were conducted on a sample of veterans following discharge from military service (N = 818; 328 women, 490 men). Women were significantly more likely to experience MST than men. As hypothesized, experiences of MST during deployment were associated with higher PTSS. MST experiences were associated with less trust in and support from one's military unit, which partially mediated the association between MST and PTSS. The indirect effect of MST on PTSS through lower unit relationship quality accounted for 20.4% of the total effect of MST on PTSS. While the retrospective study design precludes tests of causality, mediational findings provided statistical evidence that lower unit relationship quality partially explains the association between MST and PTSS. This finding is consistent with interpersonal theories of trauma response suggesting that the deleterious effects of MST may be in part due to its erosion of social resources during deployment. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Military Sexual Trauma Among Recent Veterans: Correlates of Sexual Assault and Sexual Harassment.

PubMed

Barth, Shannon K; Kimerling, Rachel E; Pavao, Joanne; McCutcheon, Susan J; Batten, Sonja V; Dursa, Erin; Peterson, Michael R; Schneiderman, Aaron I

2016-01-01

Military sexual trauma (MST) includes sexual harassment or sexual assault that occurs during military service and is of increasing public health concern. The population prevalence of MST among female and male veterans who served during Operations Enduring Freedom and Iraqi Freedom (OEF/OIF) has not been estimated to our knowledge. The purpose of this study is to assess the population prevalence and identify military correlates of MST, sexual harassment, and sexual assault among OEF/OIF veterans. MST was assessed in the 2009-2011 National Health Study for a New Generation of U.S. Veterans, a survey of 60,000 veterans who served during the OEF/OIF eras (response rate, 34%, n=20,563). Weighted prevalence estimates and AORs of MST, sexual harassment, and sexual assault among women and men were calculated. Gender-stratified logistic regression models controlled for military and demographic characteristics. Data analyses were conducted in 2013-2014. Approximately 41% of women and 4% of men reported experiencing MST. Deployed men had lower risk for MST compared with non-deployed men, though no difference was found among women. However, veterans reporting combat exposure during deployment had increased risk for MST compared with those without, while controlling for OEF/OIF deployment. Among women, Marines and Navy veterans had increased risk for MST compared with Air Force veterans. MST was significantly higher among veterans who reported using Veterans Affairs healthcare services. These prevalence estimates underscore the importance of public awareness and continued investigation of the public health impact of MST. Published by Elsevier Inc.

Observation of Polar Mesosphere Summer Echoes using the northernmost MST radar at Eureka (80°N)

NASA Astrophysics Data System (ADS)

Swarnalingam, N.; Hocking, W.; Janches, D.; Drummond, J.

2017-09-01

We investigate long-term Polar Mesosphere Summer Echoes (PMSEs) observations conducted by the northernmost geographically located MST radar at Eureka (80°N, 86°W). While PMSEs are a well recognized summer phenomenon in the polar regions, previous calibrated studies at Resolute Bay and Eureka using 51.5 MHz and 33 MHz radars respectively, showed that PMSE backscatter signal strengths are relatively weak in the polar cap sites, compared to the auroral zone sites (Swarnalingam et al., 2009b; Singer et al., 2010). Complications arise with PMSEs in which the echo strength is controlled by the electrons, which are, in turn, influenced by heavily charged ice particles as well as the variability in the D-region plasma. In recent years, PMSE experiments were conducted inside the polar cap utilizing a 51 MHz radar located at Eureka. In this paper, we investigate calibrated observations, conducted during 2009-2015. Seasonal and diurnal variations of the backscatter signal strengths are discussed and compared to previously published results from the ALOMAR radar, which is a radar of similar design located in the auroral zone at Andenes, Norway (69°N, 16°E). At Eureka, while PMSEs are present with a daily occurrence rate which is comparable to the rate observed at the auroral zone site for at least two seasons, they show a great level of inter-annual variability. The occurrence rate for the strong echoes tends to be low. Furthermore, comparison of the absolute backscatter signal strengths at these two sites clearly indicates that the PMSE backscatter signal strength at Eureka is weak. Although this difference could be caused by several factors, we investigate the intensity of the neutral air turbulence at Eureka from the measurements of the Doppler spectrum of the PMSE backscatter signals. We found that the level of the turbulence intensity at Eureka is weak relative to previously reported results from three high latitude sites.

Observation of Polar Mesosphere Summer Echoes using the Northernmost MST Radar at Eureka (80 deg N)

NASA Technical Reports Server (NTRS)

Swarnalingam, N.; Hocking, W.; Janches, D.; Drummond, J.

2017-01-01

We investigate long-term Polar Mesosphere Summer Echoes (PMSEs) observations conducted by the northern most geographically located MST radar at Eureka (80 deg N, 86 deg W). While PMSEs are a well recognized summer phenomenon in the polar regions, previous calibrated studies at Resolute Bay and Eureka using 51.5 MHz and33 MHz radars respectively, showed that PMSE backscatter signal strengths are relatively weak in the polar cap sites, compared to the auroral zone sites (Swarnalingam et al., 2009b; Singer et al., 2010). Complications arise with PMSEs in which the echo strength is controlled by the electrons, which are, in turn, influenced by heavily charged ice particles as well as the variability in the D-region plasma. In recent years, PMSE experiments were conducted inside the polar cap utilizing a 51 MHz radar located at Eureka. In this paper, we investigate calibrated observations, conducted during 2009-2015. Seasonal and diurnal variations of the backscatter signal strengths are discussed and compared to previously published results from the ALOMAR radar, which is a radar of similar design located in the auroral zone at Andenes, Norway (69 deg N, 16 deg E). At Eureka, while PMSEs are present with a daily occurrence rate which is comparable to the rate observed at the auroral zone site for at least two seasons, they show a great level of inter-annual variability. The occurrence rate for the strong echoes tends to be low. Furthermore, comparison of the absolute backscatter signal strengths at these two sites clearly indicates that the PMSE backscatter signal strength at Eureka is weak. Although this difference could be caused by several factors, we investigate the intensity of the neutral air turbulence at Eureka from the measurements of the Doppler spectrum of the PMSE backscatter signals. We found that the level of the turbulence intensity at Eureka is weak relative to previously reported results from three high latitude sites.

SAV1 promotes Hippo kinase activation through antagonizing the PP2A phosphatase STRIPAK

PubMed Central

Osinski, Adam; Tomchick, Diana R; Brautigam, Chad A

2017-01-01

The Hippo pathway controls tissue growth and homeostasis through a central MST-LATS kinase cascade. The scaffold protein SAV1 promotes the activation of this kinase cascade, but the molecular mechanisms remain unknown. Here, we discover SAV1-mediated inhibition of the PP2A complex STRIPAKSLMAP as a key mechanism of MST1/2 activation. SLMAP binding to autophosphorylated MST2 linker recruits STRIPAK and promotes PP2A-mediated dephosphorylation of MST2 at the activation loop. Our structural and biochemical studies reveal that SAV1 and MST2 heterodimerize through their SARAH domains. Two SAV1–MST2 heterodimers further dimerize through SAV1 WW domains to form a heterotetramer, in which MST2 undergoes trans-autophosphorylation. SAV1 directly binds to STRIPAK and inhibits its phosphatase activity, protecting MST2 activation-loop phosphorylation. Genetic ablation of SLMAP in human cells leads to spontaneous activation of the Hippo pathway and alleviates the need for SAV1 in Hippo signaling. Thus, SAV1 promotes Hippo activation through counteracting the STRIPAKSLMAP PP2A phosphatase complex. PMID:29063833

Biological treatments in Behçet's disease: beyond anti-TNF therapy.

PubMed

Caso, Francesco; Costa, Luisa; Rigante, Donato; Lucherini, Orso Maria; Caso, Paolo; Bascherini, Vittoria; Frediani, Bruno; Cimaz, Rolando; Marrani, Edoardo; Nieves-Martín, Laura; Atteno, Mariangela; Raffaele, Carmela G L; Tarantino, Giusyda; Galeazzi, Mauro; Punzi, Leonardo; Cantarini, Luca

2014-01-01

Behçet's disease (BD) is universally recognized as a multisystemic inflammatory disease of unknown etiology with chronic course and unpredictable exacerbations: its clinical spectrum varies from pure vasculitic manifestations with thrombotic complications to protean inflammatory involvement of multiple organs and tissues. Treatment has been revolutionized by the progressed knowledge in the pathogenetic mechanisms of BD, involving dysfunction and oversecretion of multiple proinflammatory molecules, chiefly tumor necrosis factor- (TNF-) α, interleukin- (IL-) 1β, and IL-6. However, although biological treatment with anti-TNF-α agents has been largely demonstrated to be effective in BD, not all patients are definite responders, and this beneficial response might drop off over time. Therefore, additional therapies for a subset of refractory patients with BD are inevitably needed. Different agents targeting various cytokines and their receptors or cell surface molecules have been studied: the IL-1 receptor has been targeted by anakinra, the IL-1 by canakinumab and gevokizumab, the IL-6 receptor by tocilizumab, the IL12/23 receptor by ustekinumab, and the B-lymphocyte antigen CD-20 by rituximab. The aim of this review is to summarize all current experiences and the most recent evidence regarding these novel approaches with biological drugs other than TNF-α blockers in BD, providing a valuable addition to the actually available therapeutic armamentarium.

Longitudinal Multistage Testing

ERIC Educational Resources Information Center

Pohl, Steffi

2013-01-01

This article introduces longitudinal multistage testing (lMST), a special form of multistage testing (MST), as a method for adaptive testing in longitudinal large-scale studies. In lMST designs, test forms of different difficulty levels are used, whereas the values on a pretest determine the routing to these test forms. Since lMST allows for…

Synthesis and Reaction Chemistry of Nanosize Monosodium Titanate

PubMed Central

Elvington, Mark C.; Taylor-Pashow, Kathryn M. L.; Tosten, Michael H.; Hobbs, David T.

2016-01-01

This paper describes the synthesis and peroxide-modification of nanosize monosodium titanate (nMST), along with an ion-exchange reaction to load the material with Au(III) ions. The synthesis method was derived from a sol-gel process used to produce micron-sized monosodium titanate (MST), with several key modifications, including altering reagent concentrations, omitting a particle seed step, and introducing a non-ionic surfactant to facilitate control of particle formation and growth. The resultant nMST material exhibits spherical-shaped particle morphology with a monodisperse distribution of particle diameters in the range from 100 to 150 nm. The nMST material was found to have a Brunauer-Emmett-Teller (BET) surface area of 285 m2g-1, which is more than an order of magnitude higher than the micron-sized MST. The isoelectric point of the nMST measured 3.34 pH units, which is a pH unit lower than that measured for the micron-size MST. The nMST material was found to serve as an effective ion exchanger under weakly acidic conditions for the preparation of an Au(III)-exchange nanotitanate. In addition, the formation of the corresponding peroxotitanate was demonstrated by reaction of the nMST with hydrogen peroxide. PMID:26967828

Military sexual trauma research: a proposed agenda.

PubMed

Allard, Carolyn B; Nunnink, Sarah; Gregory, Amber M; Klest, Bridget; Platt, Melissa

2011-01-01

Military sexual trauma (MST) is a widespread problem associated with negative psychological and physical health problems. This article presents the current state of MST research and highlights specific areas in need of more focused study. Areas that have produced the greatest body of knowledge include MST prevalence and psychological and physical health correlates. We propose a research agenda based on gaps noted in our research review and empirical and theoretical evidence of issues relevant to but not studied directly in MST populations. We present evidence that MST is qualitatively distinct from other forms of sexual maltreatment in terms of its relational and vocational context as well as the severity of associated psychological distress, examine underexplored gender and sexual issues in MST, and discuss the lack of treatment and prevention studies specific to MST. Specific recommendations are made throughout in an attempt to guide and advance the field.

Analysis of a novel protocol of combined induction chemotherapy and concurrent chemoradiation in unresected non-small-cell lung cancer: a ten-year experience with vinblastine, Cisplatin, and radiation therapy.

PubMed

Waters, Eugenie; Dingle, Brian; Rodrigues, George; Vincent, Mark; Ash, Robert; Dar, Rashid; Inculet, Richard; Kocha, Walter; Malthaner, Richard; Sanatani, Michael; Stitt, Larry; Yaremko, Brian; Younus, Jawaid; Yu, Edward

2010-07-01

The London Regional Cancer Program (LRCP) uses a unique schedule of induction plus concurrent chemoradiation, termed VCRT (vinblastine, cisplatin, and radiation therapy), for the treatment of a subset of unresectable stage IIIA and IIIB non-small-cell lung cancer (NSCLC). This analysis was conducted to better understand the outcomes in VCRT-treated patients. We report a retrospective analysis of a large cohort of patients who underwent VCRT at the LRCP over a 10-year period, from 1996 to 2006. The analysis focused on OS, toxicities, and the outcomes from completion surgery in a small subset of patients. A total of 294 patients were included and 5-year OS, determined using Kaplan-Meier methodology, was 19.8% with a MST of 18.2 months. Reported grade 3-4 toxicities included neutropenia (39%), anemia (10%), pneumonitis (1%), and esophagitis (3%). Significant differences in survival between groups of patients were demonstrated with log-rank tests for completion surgery, use of radiation therapy, and cisplatin dose. Similarly, Univariate Cox regression showed that completion surgery, use of radiation therapy, cisplatin dose, and vinblastine dose were associated with increased survival. This retrospective analysis of a large cohort of patients reveals an OS for VCRT comparable to that reported in the literature for other current combined chemoradiation protocols. The success of this protocol seems to be dose dependent and the outcomes in those who underwent completion surgery suggests that pathologic complete remission is possible for IIIA and IIIB NSCLC.

Convection enhanced delivery of boronated EGF as a molecular targeting agent for neutron capture therapy of brain tumors

PubMed Central

Yang, Weilian; Wu, Gong; Huo, Tianyao; Tjarks, Werner; Ciesielski, Michael; Fenstermaker, Robert A.; Ross, Brain D.; Wikstrand, Carol J.; Riley, Kent J.; Binns, Peter J.

2010-01-01

In the present study, we have evaluated a boronated dendrimer-epidermal growth factor (BD-EGF) bioconjugate as a molecular targeting agent for boron neutron capture therapy (BNCT) of the human EGFR gene-transfected F98 rat glioma, designated F98EGFR. EGF was chemically linked to a heavily boronated polyamidoamine dendrimer (BD) by means of the heterobifunctional reagent, mMBS. Biodistribution studies were carried out at 6 h and 24 h following intratumoral (i.t.) injection or intracerebral (i.c.) convection enhanced delivery (CED) of 125I-labeled or unlabeled BD-EGF (40 μg 10B/10 μg EGF) to F98 glioma bearing rats. At 24 h. there was 43% more radioactivity in EGFR(+) tumors following CED compared to i.t. injection, and a doubling of the tumor boron concentration (22.3 μg/g vs. 11.7 μg/g). CED of BD-EGF resulted in a 7.2× increase in the volume of distribution within the infused cerebral hemisphere and a 1.9× increase in tumor uptake of BD-EGF compared with i.t. injection. Based on these favorable bio-distribution data, BNCT was carried out at the Massachusetts Institute of Technology nuclear reactor 14 days following i.c. tumor implantation and 24 h. after CED of BD-EGF. These animals had a MST of 54.1 ± 4.7 days compared to 43.0 ± 2.8 days following i.t. injection. Rats that received BD-EGF by CED in combination with i.v. boronophenylalanine (BPA), which has been used in both experimental and clinical studies, had a MST of 86.0 ± 28.1 days compared to 39.8 ± 1.6 days for i.v. BPA alone (P < 0.01), 30.9 ± 1.4 days for irradiated controls and 25.1 ± 1.0 days for untreated controls (overall P < 0.0001). These data have demonstrated that the efficacy of BNCT was significantly increased (P < 0.006), following i.c CED of BD-EGF compared to i.t injection, and that the survival data were equivalent to those previously reported by us using the boronated anti-human-EGF mAb, C225 (cetuximab). PMID:19588228

Military Sexual Trauma Among US Servicewomen During Deployment: A Qualitative Study

PubMed Central

Grindlay, Kate; Holt, Kelsey; Manski, Ruth; Grossman, Daniel

2014-01-01

Objectives. We explored qualitatively US servicewomen’s experiences with and perceptions of military sexual trauma (MST), reporting, and related services. Methods. From May 2011 to January 2012, we conducted 22 telephone interviews with US servicewomen deployed overseas between 2002 and 2011. We analyzed data thematically with modified grounded theory methods. Results. Factors identified as contributing to MST included deployment dynamics, military culture, and lack of consequences for perpetrators. Participants attributed low MST reporting to negative reactions and blame from peers and supervisors, concerns about confidentiality, and stigma. Unit cohesion was cited as both a facilitator and a barrier to reporting. Availability and awareness of MST services during deployment varied. Barriers to care seeking were similar to reporting barriers and included confidentiality concerns and stigma. We identified several avenues to address MST, including strengthening consequences for perpetrators. Conclusions. We identified barriers to MST reporting and services. Better understanding of these issues will allow policymakers to improve MST prevention and services. PMID:24328617

SAV1 promotes Hippo kinase activation through antagonizing the PP2A phosphatase STRIPAK

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bae, Sung Jun; Ni, Lisheng; Osinski, Adam

The Hippo pathway controls tissue growth and homeostasis through a central MST-LATS kinase cascade. The scaffold protein SAV1 promotes the activation of this kinase cascade, but the molecular mechanisms remain unknown. Here, we discover SAV1-mediated inhibition of the PP2A complex STRIPAKSLMAP as a key mechanism of MST1/2 activation. SLMAP binding to autophosphorylated MST2 linker recruits STRIPAK and promotes PP2A-mediated dephosphorylation of MST2 at the activation loop. Our structural and biochemical studies reveal that SAV1 and MST2 heterodimerize through their SARAH domains. Two SAV1–MST2 heterodimers further dimerize through SAV1 WW domains to form a heterotetramer, in which MST2 undergoes trans-autophosphorylation. SAV1more » directly binds to STRIPAK and inhibits its phosphatase activity, protecting MST2 activation-loop phosphorylation. Genetic ablation of SLMAP in human cells leads to spontaneous activation of the Hippo pathway and alleviates the need for SAV1 in Hippo signaling. Thus, SAV1 promotes Hippo activation through counteracting the STRIPAKSLMAP PP2A phosphatase complex.« less

Characterization of in vivo metabolites in rat urine following an oral dose of masitinib by liquid chromatography tandem mass spectrometry.

PubMed

Kadi, Adnan A; Amer, Sawsan M; Darwish, Hany W; Attwa, Mohamed W

2018-05-15

Masitinib (MST) is an orally administered drug that targets mast cells and macrophages, important cells for immunity, by inhibiting a limited number of tyrosine kinases. It is currently registered in Europe and USA for the treatment of mast cell tumors in dogs. AB Science announced that the European Medicines Agency has accepted a conditional marketing authorization application for MST to treat amyotrophic lateral sclerosis. In our work, we focused on studying in vivo metabolism of MST in Sprague-Dawley rats. Single oral dose of MST (33 mg kg -1 ) was given to Sprague-Dawley rats (kept in metabolic cages) using oral gavage. Urine was collected and filtered at 0, 6, 12, 18, 24, 48, 72 and 96 h from MST dosing. An equal amount of ACN was added to urine samples. Both organic and aqueous layers were injected into liquid chromatography-tandem mass spectrometry (LC-MS/MS) to detect in vivo phase I and phase II MST metabolites. The current work reports the identification and characterization of twenty in vivo phase I and four in vivo phase II metabolites of MST by LC-MS/MS. Phase I metabolic pathways were reduction, demethylation, hydroxylation, oxidative deamination, oxidation and N-oxide formation. Phase II metabolic pathways were the direct conjugation of MST, N-demethyl metabolites and oxidative metabolites with glucuronic acid. Part of MST dose was excreted unchanged in urine. The literature review showed no previous articles have been made on in vivo metabolism of MST or detailed structural identification of the formed in vivo phase I and phase II metabolites.

The Protective Effect of Poloxamer-188 on Platelet Functions.

PubMed

Guler, Nil; Abro, Schuharazad; Emanuele, Marty; Iqbal, Omer; Hoppensteadt, Debra; Fareed, Jawed

2017-11-01

Poloxamer-188 (MST-188) is effective in the repair/recovery of damaged cell membranes. MST-188 is a promising agent for protecting blood cell viability. The aim of the study is to test the hypothesis that MST-188 can extend the duration of platelet function. Blood samples were collected from 20 healthy volunteers. MST-188 (10 or 2 mg/mL) containing platelet-rich plasma (PRP) was prepared with 2 procedures. First, PRP prepared from MST-188 added whole blood (WB); second, MST-188 was added to PRP. These were referred to MST-188-WB preparation (WBP) and MST-188-PRP preparation (PRPP), respectively. For control, saline was used in the same manner. Agonist-induced aggregation (AIA) studies were performed at 30, 180, and 300 minutes using Platelet Aggregation Profiler (PAP-8) aggregometer (Bio/Data Corporation, Horsham, Pennsylvania) and Adenosine diphosphate (ADP), arachidonic acid, collagen, and epinephrine as agonists at final concentration of 20 µM, 500 µg/mL, 0.19 mg/mL, and 100 µM, respectively. There was a protective effect of MST-188 on ADP and collagen AIA. At 300 minutes, ADP AIA was found to be 50.2% higher than saline control in 2-mg WBP, 43% at 10-mg PRPP, and 10.4% at 2-mg PRPP. Protective effect of on collagen AIA was 65.9% in 2-mg WBP, 42.74% at 10-mg PRPP, and 11.42% at 2-mg PRPP. In comparison between 30 and 300 minutes, MST-188 showed significant protection in terms of ADP and collagen receptors and for both types of preparations (WBP and PRPP). The protective effects of MST-188 on ADP- and collagen-induced platelet aggregation may contribute to the preservation of platelet functionality upon storage in blood banks.

Acute tubulointerstitial nephritis with severe renal impairment associated with multisystem IgG4-related disease.

PubMed

Beltrame, Rafael Coimbra Ferreira; Friderichs, Maurício; Fior, Bárbara Rayanne; Schaefer, Pedro Guilherme; Thomé, Gustavo Gomes; Silva, Dirceu Reis da; Barros, Elvino José Guardão; Seligman, Renato; Veronese, Francisco Veríssimo

2016-01-01

The IgG4-related disease has a wide clinical spectrum where multiple organs can be affected, and the diagnosis depends on typical histopathological findings and an elevated IgG4 expression in plasma cells in the affected tissue. We describe the clinical presentation and evolution of a patient with acute tubulointerstitial nephritis, severe kidney failure and systemic manifestations such as lymphadenomegaly and chronic pancreatitis. The diagnosis was confirmed by the clinical picture and kidney and lymph node histopathology, in which immunohistochemistry of the lymphoid tissue showed policlonality and increased expression of IgG4, with a IgG4/total IgG ratio > 80%. The patient was treated with prednisone at a dose of 60 mg/day, followed by mycophenolate mofetil, and showed clinical and renal function improvement at 6 months of follow-up. The high index of suspicion of IgG4-related disease with multisystem involvement and the early treatment of this condition are essential to improve the prognosis of affected patients. Resumo A doença relacionada à IgG4 tem um espectro clínico amplo em que múltiplos órgãos podem ser afetados, e o diagnóstico depende de achados histopatológicos típicos e elevada expressão de IgG4 em plasmócitos no tecido afetado. Descrevemos o quadro clínico e a evolução de um paciente com nefrite túbulo-intersticial aguda, insuficiência renal grave e manifestações sistêmicas como linfoadenomegalias e pancreatite crônica. O diagnóstico foi confirmado pelas características clínicas e pela histopatologia renal e de linfonodo, na qual a imunohistoquímica mostrou tecido linfoide com policlonalidade e expressão aumentada de IgG4, com uma relação IgG4/IgG total > 80%. O paciente foi tratado com prednisona na dose de 60 mg/dia, seguido de micofenolato mofetil, e apresentou melhora clínica e da função renal depois de 6 meses de tratamento. O alto índice de suspeição da doença relacionada ao IgG4 com comprometimento multissist

Pathogenesis and treatment of psoriasis: exploiting pathophysiological pathways for precision medicine.

PubMed

Alwan, Wisam; Nestle, Frank O

2015-01-01

Psoriasis is a common, chronic inflammatory skin disease associated with multi-system manifestations including arthritis and obesity. Our knowledge of the aetiology of the condition, including the key genomic, immune and environmental factors, has led to the development of targeted, precision therapies that alleviate patient morbidity. This article reviews the key pathophysiological pathways and therapeutic targets and highlights future areas of interest in psoriasis research.

Military sexual trauma as a determinant in the development of mental and physical illness in male and female veterans.

PubMed

O'Brien, Betsy S; Sher, Leo

2013-01-01

Military Sexual Trauma (MST) is defined as sexual harassment and or sexual assault experienced by a military service member. It is much more widespread and common than reported. It is associated with pre-combat traumatic experiences and pathologic sequelae including mental and medical illness. An electronic search of the major behavioral science databases was conducted to retrieve studies detailing the social, epidemiological and clinical characteristics of MST and its relationship to psychiatric and medical illness. Studies indicate that military sexual trauma is related to an increase in psychiatric pathology, including posttraumatic stress disorder (PTSD), substance abuse and dependence, depression, anxiety, eating disorders and suicidal behavior. MST is also related to an increase in medical illness, primarily pain-related symptoms involving multiple organ systems, including gastrointestinal, neurological, genitourinary and musculoskeletal. MST is associated with an increased prevalence of mental and physical illness. Although there are some gender differences in the reported rates of MST and there may be some variables, such as prior traumatic experiences, that may make an individual more vulnerable to the psychiatric and medical sequela of MST, it is clear that MST is a major healthcare issue that affects both sexes and warrants further attention and an increase in clinical resources devoted to it. Some preventive measures for decreasing the prevalence of MST may include increasing education and legal prosecution of perpetrators in the military, and increasing access to mental health services for individuals who have suffered from MST.

Mindfulness-based stress reduction for veterans exposed to military sexual trauma: rationale and implementation considerations.

PubMed

Gallegos, Autumn M; Cross, Wendi; Pigeon, Wilfred R

2015-06-01

Military sexual trauma (MST) represents a significant public health concern among military personnel and Veterans and is associated with considerable morbidity and suicide risk. It is estimated that 22% of Veteran women and 1% of Veteran men experienced sexual assault or repeated, threatening sexual harassment during their military service. Exposure to traumatic stress has detrimental effects on emotion regulation, which refers to a set of strategies used to modulate different components of emotion at different points on the trajectory of an emotional response. Mindfulness-based interventions offer approaches to health that focus on mind and body practices that can help regulate the experience and expression of difficult emotions. Mindfulness-based stress reduction (MBSR) is an evidence-based therapy shown to be effective for depression, anxiety, and post-traumatic stress disorder. This article discusses the rationale for providing MBSR to Veterans who have been exposed to MST. The article also discusses ways to facilitate implementation of this practice in the U.S. Department of Veterans Affairs health care system. We address potential barriers to care and ways to facilitate implementation at the patient, provider, organization/local, and policy levels. MBSR is likely to be an important component of a comprehensive approach to care for Veterans exposed to MST. Reprint & Copyright © 2015 Association of Military Surgeons of the U.S.

Combined mnemonic strategy training and high-definition transcranial direct current stimulation for memory deficits in mild cognitive impairment.

PubMed

Hampstead, Benjamin M; Sathian, Krishnankutty; Bikson, Marom; Stringer, Anthony Y

2017-09-01

Memory deficits characterize Alzheimer's dementia and the clinical precursor stage known as mild cognitive impairment. Nonpharmacologic interventions hold promise for enhancing functioning in these patients, potentially delaying functional impairment that denotes transition to dementia. Previous findings revealed that mnemonic strategy training (MST) enhances long-term retention of trained stimuli and is accompanied by increased blood oxygen level-dependent signal in the lateral frontal and parietal cortices as well as in the hippocampus. The present study was designed to enhance MST generalization, and the range of patients who benefit, via concurrent delivery of transcranial direct current stimulation (tDCS). This protocol describes a prospective, randomized controlled, four-arm, double-blind study targeting memory deficits in those with mild cognitive impairment. Once randomized, participants complete five consecutive daily sessions in which they receive either active or sham high definition tDCS over the left lateral prefrontal cortex, a region known to be important for successful memory encoding and that has been engaged by MST. High definition tDCS (active or sham) will be combined with either MST or autobiographical memory recall (comparable to reminiscence therapy). Participants undergo memory testing using ecologically relevant measures and functional magnetic resonance imaging before and after these treatment sessions as well as at a 3-month follow-up. Primary outcome measures include face-name and object-location association tasks. Secondary outcome measures include self-report of memory abilities as well as a spatial navigation task (near transfer) and prose memory (medication instructions; far transfer). Changes in functional magnetic resonance imaging will be evaluated during both task performance and the resting-state using activation and connectivity analyses. The results will provide important information about the efficacy of cognitive and

Tree Morphologic Plasticity Explains Deviation from Metabolic Scaling Theory in Semi-Arid Conifer Forests, Southwestern USA

PubMed Central

O’Connor, Christopher D.; Lynch, Ann M.

2016-01-01

A significant concern about Metabolic Scaling Theory (MST) in real forests relates to consistent differences between the values of power law scaling exponents of tree primary size measures used to estimate mass and those predicted by MST. Here we consider why observed scaling exponents for diameter and height relationships deviate from MST predictions across three semi-arid conifer forests in relation to: (1) tree condition and physical form, (2) the level of inter-tree competition (e.g. open vs closed stand structure), (3) increasing tree age, and (4) differences in site productivity. Scaling exponent values derived from non-linear least-squares regression for trees in excellent condition (n = 381) were above the MST prediction at the 95% confidence level, while the exponent for trees in good condition were no different than MST (n = 926). Trees that were in fair or poor condition, characterized as diseased, leaning, or sparsely crowned had exponent values below MST predictions (n = 2,058), as did recently dead standing trees (n = 375). Exponent value of the mean-tree model that disregarded tree condition (n = 3,740) was consistent with other studies that reject MST scaling. Ostensibly, as stand density and competition increase trees exhibited greater morphological plasticity whereby the majority had characteristically fair or poor growth forms. Fitting by least-squares regression biases the mean-tree model scaling exponent toward values that are below MST idealized predictions. For 368 trees from Arizona with known establishment dates, increasing age had no significant impact on expected scaling. We further suggest height to diameter ratios below MST relate to vertical truncation caused by limitation in plant water availability. Even with environmentally imposed height limitation, proportionality between height and diameter scaling exponents were consistent with the predictions of MST. PMID:27391084

Responsiveness and Minimally Important Difference of the 6-Minute Stepper Test in Patients with Chronic Obstructive Pulmonary Disease.

PubMed

Pichon, Romain; Couturaud, Francis; Mialon, Philippe; Le Ber-Moy, Catherine; Péran, Loïc; Lochon, Chantal; Nowak, Emmanuel; Beaumont, Marc

2016-01-01

The validity and reproducibility of the 6-minute stepper test (6MST) have already been demonstrated in patients with chronic obstructive pulmonary disease (COPD). The aim of this study was to evaluate the responsiveness of the 6MST to pulmonary rehabilitation (PR) in patients with COPD, to determine a minimal important difference (MID) for the 6MST, and to compare the 6MST and the 6-minute walk test (6MWT). Sixty-two patients with COPD were included in a prospective experimental study. Participants underwent a 3-week inpatient PR program. The primary outcome was the change in the number of steps during the 6MST measured before and after PR. The secondary outcome included the change in the 6-minute walking distance (6MWD) pulse oximetry, heart rate, dyspnea, and leg discomfort during the tests measured before and after PR. MID was determined by anchor-based and distribution approaches. After PR, we observed a significant increase in the number of steps during the 6MST (22.5 steps; 95% CI 13.8-31.3; p < 0.0001) and in the 6MWD (26.6 m; 95% CI 17.6-35.5; p < 0.0001). The 6MST and 6MWT were improved by 10.1 and 6.5%, respectively. The number of steps during the 6MST was significantly correlated with the 6MWD before (r = 0.72; p < 0.0001) and after PR (r = 0.66; p < 0.0001). MID was estimated to be around 20 steps. The 6MST appears to be as responsive as the 6MWT in assessing functional improvement during PR in patients with COPD. The 6MST is a low-cost assessment and requires limited space. © 2016 S. Karger AG, Basel.

Tree Morphologic Plasticity Explains Deviation from Metabolic Scaling Theory in Semi-Arid Conifer Forests, Southwestern USA.

PubMed

Swetnam, Tyson L; O'Connor, Christopher D; Lynch, Ann M

2016-01-01

A significant concern about Metabolic Scaling Theory (MST) in real forests relates to consistent differences between the values of power law scaling exponents of tree primary size measures used to estimate mass and those predicted by MST. Here we consider why observed scaling exponents for diameter and height relationships deviate from MST predictions across three semi-arid conifer forests in relation to: (1) tree condition and physical form, (2) the level of inter-tree competition (e.g. open vs closed stand structure), (3) increasing tree age, and (4) differences in site productivity. Scaling exponent values derived from non-linear least-squares regression for trees in excellent condition (n = 381) were above the MST prediction at the 95% confidence level, while the exponent for trees in good condition were no different than MST (n = 926). Trees that were in fair or poor condition, characterized as diseased, leaning, or sparsely crowned had exponent values below MST predictions (n = 2,058), as did recently dead standing trees (n = 375). Exponent value of the mean-tree model that disregarded tree condition (n = 3,740) was consistent with other studies that reject MST scaling. Ostensibly, as stand density and competition increase trees exhibited greater morphological plasticity whereby the majority had characteristically fair or poor growth forms. Fitting by least-squares regression biases the mean-tree model scaling exponent toward values that are below MST idealized predictions. For 368 trees from Arizona with known establishment dates, increasing age had no significant impact on expected scaling. We further suggest height to diameter ratios below MST relate to vertical truncation caused by limitation in plant water availability. Even with environmentally imposed height limitation, proportionality between height and diameter scaling exponents were consistent with the predictions of MST.

Minimum spanning tree analysis of the human connectome.

PubMed

van Dellen, Edwin; Sommer, Iris E; Bohlken, Marc M; Tewarie, Prejaas; Draaisma, Laurijn; Zalesky, Andrew; Di Biase, Maria; Brown, Jesse A; Douw, Linda; Otte, Willem M; Mandl, René C W; Stam, Cornelis J

2018-06-01

One of the challenges of brain network analysis is to directly compare network organization between subjects, irrespective of the number or strength of connections. In this study, we used minimum spanning tree (MST; a unique, acyclic subnetwork with a fixed number of connections) analysis to characterize the human brain network to create an empirical reference network. Such a reference network could be used as a null model of connections that form the backbone structure of the human brain. We analyzed the MST in three diffusion-weighted imaging datasets of healthy adults. The MST of the group mean connectivity matrix was used as the empirical null-model. The MST of individual subjects matched this reference MST for a mean 58%-88% of connections, depending on the analysis pipeline. Hub nodes in the MST matched with previously reported locations of hub regions, including the so-called rich club nodes (a subset of high-degree, highly interconnected nodes). Although most brain network studies have focused primarily on cortical connections, cortical-subcortical connections were consistently present in the MST across subjects. Brain network efficiency was higher when these connections were included in the analysis, suggesting that these tracts may be utilized as the major neural communication routes. Finally, we confirmed that MST characteristics index the effects of brain aging. We conclude that the MST provides an elegant and straightforward approach to analyze structural brain networks, and to test network topological features of individual subjects in comparison to empirical null models. © 2018 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

Minimum spanning tree analysis of the human connectome

PubMed Central

Sommer, Iris E.; Bohlken, Marc M.; Tewarie, Prejaas; Draaisma, Laurijn; Zalesky, Andrew; Di Biase, Maria; Brown, Jesse A.; Douw, Linda; Otte, Willem M.; Mandl, René C.W.; Stam, Cornelis J.

2018-01-01

Abstract One of the challenges of brain network analysis is to directly compare network organization between subjects, irrespective of the number or strength of connections. In this study, we used minimum spanning tree (MST; a unique, acyclic subnetwork with a fixed number of connections) analysis to characterize the human brain network to create an empirical reference network. Such a reference network could be used as a null model of connections that form the backbone structure of the human brain. We analyzed the MST in three diffusion‐weighted imaging datasets of healthy adults. The MST of the group mean connectivity matrix was used as the empirical null‐model. The MST of individual subjects matched this reference MST for a mean 58%–88% of connections, depending on the analysis pipeline. Hub nodes in the MST matched with previously reported locations of hub regions, including the so‐called rich club nodes (a subset of high‐degree, highly interconnected nodes). Although most brain network studies have focused primarily on cortical connections, cortical–subcortical connections were consistently present in the MST across subjects. Brain network efficiency was higher when these connections were included in the analysis, suggesting that these tracts may be utilized as the major neural communication routes. Finally, we confirmed that MST characteristics index the effects of brain aging. We conclude that the MST provides an elegant and straightforward approach to analyze structural brain networks, and to test network topological features of individual subjects in comparison to empirical null models. PMID:29468769

Increased Health Care Utilization and Costs Among Veterans With a Positive Screen for Military Sexual Trauma.

PubMed

Brignone, Emily; Gundlapalli, Adi V; Blais, Rebecca K; Kimerling, Rachel; Barrett, Tyson S; Nelson, Richard E; Carter, Marjorie E; Samore, Matthew H; Fargo, Jamison D

2017-09-01

The effects of sexual trauma on long-term health care utilization and costs are not well understood due to infrequent documentation of sexual trauma history in health care systems. The Veteran's Health Administration provides a unique opportunity to address this constraint as sexual trauma is actively screened for as part of routine care. We used a retrospective cohort design to analyze Veteran's Health Administration mental health and medical service utilization and costs as a function of a positive screen for exposure to military sexual trauma (MST) among Veterans of recent conflicts in Iraq and Afghanistan. We computed adjusted 5-year estimates of overall utilization and costs, and utilization and costs determined not to be related to MST. The cohort included 426,223 men and 59,611 women. A positive MST screen was associated with 50% higher health care utilization and costs relative to a negative screen. Overall, a positive relative to negative MST screen was associated with a 5-year incremental difference of 34.6 encounters and $10,734 among women, and 33.5 encounters and $11,484 among men. After accounting for MST-related treatment, positive MST screen was associated with 11.9 encounters and $4803 among women, and 19.5 encounters and $8001 among men. Results demonstrate significant and consistent differences in health care utilization and costs between Veterans with a positive relative to negative MST screen. Even after accounting for MST-related care, a positive screen was associated with significantly higher utilization and costs. MST-related needs may be more readily recognized in women relative to men.

Anti-IgE therapy for allergic bronchopulmonary aspergillosis in people with cystic fibrosis.

PubMed

Jat, Kana R; Walia, Dinesh K; Khairwa, Anju

2018-03-18

Cystic fibrosis is an autosomal recessive multisystem disorder with an approximate prevalence of 1 in 3500 live births. Allergic bronchopulmonary aspergillosis is a lung disease caused by aspergillus-induced hypersensitivity with a prevalence of 2% to 15% in people with cystic fibrosis. The mainstay of treatment includes corticosteroids and itraconazole. The treatment with corticosteroids for prolonged periods of time, or repeatedly for exacerbations of allergic bronchopulmonary aspergillosis, may lead to many adverse effects. The monoclonal anti-IgE antibody, omalizumab, has improved asthma control in severely allergic asthmatics. The drug is given as a subcutaneous injection every two to four weeks. Since allergic bronchopulmonary aspergillosis is also a condition resulting from hypersensitivity to specific allergens, as in asthma, it may be a candidate for therapy using anti-IgE antibodies. Therefore, anti-IgE therapy, using agents like omalizumab, may be a potential therapy for allergic bronchopulmonary aspergillosis in people with cystic fibrosis. This is an updated version of the review. To evaluate the efficacy and adverse effects of anti-IgE therapy for allergic bronchopulmonary aspergillosis in people with cystic fibrosis. We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles and reviews. Last search: 29 September 2017.We searched two ongoing trial registries (Clinicaltrials.gov and the WHO trials platform). Date of latest search: 24 January 2018. Randomized and quasi-randomized controlled trials comparing anti-IgE therapy to placebo or other therapies for allergic bronchopulmonary aspergillosis in people with cystic fibrosis. Two review authors independently extracted data and assessed the risk of bias in the included study. They planned to perform data analysis using Review Manager. Only one

Assailant Identity and Self-Reported Nondisclosure of Military Sexual Trauma in Partnered Women Veterans.

PubMed

Blais, Rebecca K; Brignone, Emily; Fargo, Jamison D; Galbreath, Nathan W; Gundlapalli, Adi V

2017-10-09

Department of Veterans Affairs estimates of military sexual trauma (MST) suggest 27% of female veterans have experienced MST. However, Department of Defense data (Department of Defense, 2014) show that a subgroup of active-duty women do not report sexual assaults to a military authority, suggesting barriers to disclosure exist among military samples. No study of female veterans has examined rates of nondisclosure among those with previous screens for MST; these data could inform screening efforts and establishment of safe havens for candid disclosures. Using an explanatory sequential mixed-methods survey, a history of MST, and postservice MST disclosures during screening and their associations with demographic, assault, and screening-setting characteristics were evaluated in 359 female veterans. Open-ended responses regarding barriers to disclosure were analyzed using editing analysis style. Eighty-one percent (n = 289) reported MST. Of these, 50% (n = 143) reported a prior screening and 25% (n = 35) reported they did not disclose their true MST status. Veterans who experienced MST by a unit-member assailant were significantly less likely to disclose (adjusted odds ratio = 4.75, 95% confidence interval = 1.20-18.30). Disclosure barriers included stigma, experiential avoidance, and discomfort with the screening setting. Creative interventions to reduce nondisclosure among female veterans, with specific attention to those assaulted by a unit member, are urgently needed. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Structure and Kinetic Analysis of H2S Production by Human Mercaptopyruvate Sulfurtransferase*

PubMed Central

Yadav, Pramod Kumar; Yamada, Kazuhiro; Chiku, Taurai; Koutmos, Markos; Banerjee, Ruma

2013-01-01

Mercaptopyruvate sulfurtransferase (MST) is a source of endogenous H2S, a gaseous signaling molecule implicated in a wide range of physiological processes. The contribution of MST versus the other two H2S generators, cystathionine β-synthase and γ-cystathionase, has been difficult to evaluate because many studies on MST have been conducted at high pH and have used varied reaction conditions. In this study, we have expressed, purified, and crystallized human MST in the presence of the substrate 3-mercaptopyruvate (3-MP). The kinetics of H2S production by MST from 3-MP was studied at pH 7.4 in the presence of various physiological persulfide acceptors: cysteine, dihydrolipoic acid, glutathione, homocysteine, and thioredoxin, and in the presence of cyanide. The crystal structure of MST reveals a mixture of the product complex containing pyruvate and an active site cysteine persulfide (Cys248-SSH) and a nonproductive intermediate in which 3-MP is covalently linked via a disulfide bond to an active site cysteine. The crystal structure analysis allows us to propose a detailed mechanism for MST in which an Asp-His-Ser catalytic triad is positioned to activate the nucleophilic cysteine residue and participate in general acid-base chemistry, whereas our kinetic analysis indicates that thioredoxin is likely to be the major physiological persulfide acceptor for MST. PMID:23698001

Selection and application of microbial source tracking tools for water-quality investigations

USGS Publications Warehouse

Stoeckel, Donald M.

2005-01-01

Microbial source tracking (MST) is a complex process that includes many decision-making steps. Once a contamination problem has been defined, the potential user of MST tools must thoroughly consider study objectives before deciding upon a source identifier, a detection method, and an analytical approach to apply to the problem. Regardless of which MST protocol is chosen, underlying assumptions can affect the results and interpretation. It is crucial to incorporate tests of those assumptions in the study quality-control plan to help validate results and facilitate interpretation. Detailed descriptions of MST objectives, protocols, and assumptions are provided in this report to assist in selection and application of MST tools for water-quality investigations. Several case studies illustrate real-world applications of MST protocols over a range of settings, spatial scales, and types of contamination. Technical details of many available source identifiers and detection methods are included as appendixes. By use of this information, researchers should be able to formulate realistic expectations for the information that MST tools can provide and, where possible, successfully execute investigations to characterize sources of fecal contamination to resource waters.

Lupus erythematosus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tuffanelli, D.L.

1981-02-01

Lupus erythematosus (LE) is a multisystem disease. Genetic predisposition, altered immunity, hormones, drugs, viruses, and ultraviolet light all may play a role in etiology. A wide range of cutaneous lesions occur, and variants such as subacute cutaneous LE, complement-deficient LE, and neonatal LE have recently been emphasized. Management of the LE patient, including appropriate diagnostic studies and therapy relevant to the dermatologist, is discussed in the review.

Utilization and intensity of outpatient care related to military sexual trauma for veterans from Afghanistan and Iraq.

PubMed

Turchik, Jessica A; Pavao, Joanne; Hyun, Jenny; Mark, Hanna; Kimerling, Rachel

2012-07-01

Little research has examined factors associated with the utilization of outpatient health care services related to sexual assault experiences. The Veterans Health Administration provides free outpatient treatment services to veterans who report military sexual trauma (MST); this system provides a unique opportunity to examine factors related to the utilization of mental health and non-mental health outpatient services by patients with sexual trauma. The current study examined sociodemographic, military service factors, and primary diagnoses related to utilization and utilization intensity of MST-related care among 4,458 Operation Enduring Freedom/Operation Iraqi Freedom Veterans in a 1-year period after reporting an experience of MST. Of the veterans who reported MST, 75.9% received MST-related care. The most notable factor that influenced receipt and intensity of MST-related care was gender, where male veterans used less care than female veterans. These results have important treatment implications for both veteran and civilian sexual trauma survivors.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Grabaskas, David; Bucknor, Matthew; Jerden, James

A mechanistic source term (MST) calculation attempts to realistically assess the transport and release of radionuclides from a reactor system to the environment during a specific accident sequence. The U.S. Nuclear Regulatory Commission (NRC) has repeatedly stated its expectation that advanced reactor vendors will utilize an MST during the U.S. reactor licensing process. As part of a project to examine possible impediments to sodium fast reactor (SFR) licensing in the U.S., an analysis was conducted regarding the current capabilities to perform an MST for a metal fuel SFR. The purpose of the project was to identify and prioritize any gapsmore » in current computational tools, and the associated database, for the accurate assessment of an MST. The results of the study demonstrate that an SFR MST is possible with current tools and data, but several gaps exist that may lead to possibly unacceptable levels of uncertainty, depending on the goals of the MST analysis.« less

Not seeing the forest for the trees: size of the minimum spanning trees (MSTs) forest and branch significance in MST-based phylogenetic analysis.

PubMed

Teixeira, Andreia Sofia; Monteiro, Pedro T; Carriço, João A; Ramirez, Mário; Francisco, Alexandre P

2015-01-01

Trees, including minimum spanning trees (MSTs), are commonly used in phylogenetic studies. But, for the research community, it may be unclear that the presented tree is just a hypothesis, chosen from among many possible alternatives. In this scenario, it is important to quantify our confidence in both the trees and the branches/edges included in such trees. In this paper, we address this problem for MSTs by introducing a new edge betweenness metric for undirected and weighted graphs. This spanning edge betweenness metric is defined as the fraction of equivalent MSTs where a given edge is present. The metric provides a per edge statistic that is similar to that of the bootstrap approach frequently used in phylogenetics to support the grouping of taxa. We provide methods for the exact computation of this metric based on the well known Kirchhoff's matrix tree theorem. Moreover, we implement and make available a module for the PHYLOViZ software and evaluate the proposed metric concerning both effectiveness and computational performance. Analysis of trees generated using multilocus sequence typing data (MLST) and the goeBURST algorithm revealed that the space of possible MSTs in real data sets is extremely large. Selection of the edge to be represented using bootstrap could lead to unreliable results since alternative edges are present in the same fraction of equivalent MSTs. The choice of the MST to be presented, results from criteria implemented in the algorithm that must be based in biologically plausible models.

Hydrogen peroxide modified sodium titanates with improved sorption capabilities

DOEpatents

Nyman, May D [Albuquerque, NM; Hobbs, David T [North Augusta, SC

2009-02-24

The sorption capabilities (e.g., kinetics, selectivity, capacity) of the baseline monosodium titanate (MST) sorbent material currently being used to sequester Sr-90 and alpha-emitting radioisotopes at the Savannah River Site are significantly improved when treated with hydrogen peroxide; either during the original synthesis of MST, or, as a post-treatment step after the MST has been synthesized. It is expected that these peroxide-modified MST sorbent materials will have significantly improved sorption capabilities for non-radioactive cations found in industrial processes and waste streams.

Materials science tetrahedron--a useful tool for pharmaceutical research and development.

PubMed

Sun, Changquan Calvin

2009-05-01

The concept of materials science tetrahedron (MST) concisely depicts the inter-dependent relationship among the structure, properties, performance, and processing of a drug. Similar to its role in traditional materials science, MST encompasses the development in the emerging field of pharmaceutical materials science and forms a scientific foundation to the design and development of new drug products. Examples are given to demonstrate the applicability of MST to both pharmaceutical research and product development. It is proposed that a systematic implementation of MST can expedite the transformation of pharmaceutical product development from an art to a science. By following the principle of MST, integration of research among different laboratories can be attained. The pharmaceutical science community as a whole can conduct more efficient, collaborative, and coherent research.

Misato Controls Mitotic Microtubule Generation by Stabilizing the TCP-1 Tubulin Chaperone Complex [corrected].

PubMed

Palumbo, Valeria; Pellacani, Claudia; Heesom, Kate J; Rogala, Kacper B; Deane, Charlotte M; Mottier-Pavie, Violaine; Gatti, Maurizio; Bonaccorsi, Silvia; Wakefield, James G

2015-06-29

Mitotic spindles are primarily composed of microtubules (MTs), generated by polymerization of α- and β-Tubulin hetero-dimers. Tubulins undergo a series of protein folding and post-translational modifications in order to fulfill their functions. Defects in Tubulin polymerization dramatically affect spindle formation and disrupt chromosome segregation. We recently described a role for the product of the conserved misato (mst) gene in regulating mitotic MT generation in flies, but the molecular function of Mst remains unknown. Here, we use affinity purification mass spectrometry (AP-MS) to identify interacting partners of Mst in the Drosophila embryo. We demonstrate that Mst associates stoichiometrically with the hetero-octameric Tubulin Chaperone Protein-1 (TCP-1) complex, with the hetero-hexameric Tubulin Prefoldin complex, and with proteins having conserved roles in generating MT-competent Tubulin. We show that RNAi-mediated in vivo depletion of any TCP-1 subunit phenocopies the effects of mutations in mst or the Prefoldin-encoding gene merry-go-round (mgr), leading to monopolar and disorganized mitotic spindles containing few MTs. Crucially, we demonstrate that Mst, but not Mgr, is required for TCP-1 complex stability and that both the efficiency of Tubulin polymerization and Tubulin stability are drastically compromised in mst mutants. Moreover, our structural bioinformatic analyses indicate that Mst resembles the three-dimensional structure of Tubulin monomers and might therefore occupy the TCP-1 complex central cavity. Collectively, our results suggest that Mst acts as a co-factor of the TCP-1 complex, playing an essential role in the Tubulin-folding processes required for proper assembly of spindle MTs. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

The effect from maximal bench press strength training on work economy during wheelchair propulsion in men with spinal cord injury.

PubMed

Tørhaug, T; Brurok, B; Hoff, J; Helgerud, J; Leivseth, G

2016-10-01

To assess the effect from maximal bench press strength training (MST) on wheelchair propulsion work economy (WE). Pretest-posttest case-control group design. St Olavs Hospital, Trondheim, Norway. Seventeen male individuals with spinal cord injury (SCI) paraplegia were allocated to either MST bench press (n=11) or the control group (CG) (n=7). The MST group trained bench press three times per week, for 6 weeks, starting at 85-95% of their pretest bench press one-repetition maximum (1RM). For calculation of WE during wheelchair propulsion, oxygen uptake (VO 2 ) measurements were collected during wheelchair ergometry (WCE) at submaximal workload of 50 W. Similarly, peak oxygen uptake (VO 2peak ) and peak power output (W) were measured during WCE. Individuals in the MST regimen significantly improved WE compared with the CG by 17.3 % (mean between-group differences: 95% confidence interval) of 2.63 ml kg -1  min -1 : (-4.34, -0.91) (P=0.007). Between pretest and posttest, the increase in bench press 1RM was by 17% higher in the MST group compared with the CG. At peak testing, the MST group generated significantly higher peak power compared with the CG. All other physiological variables were comparable within and between groups. A 6-week MST bench press regimen significantly improved WE during wheelchair propulsion at 50 W workload. These preliminary data support a possible beneficial role for MST to reduce the energy cost of wheelchair propulsion for SCI individuals.

Multiple subpial transection for intractable partial epilepsy: an international meta-analysis.

PubMed

Spencer, Susan S; Schramm, Johannes; Wyler, Allen; O'Connor, Michael; Orbach, Darren; Krauss, Gregory; Sperling, Michael; Devinsky, Orrin; Elger, Christian; Lesser, Ronald; Mulligan, Lisa; Westerveld, Michael

2002-02-01

Because the number and variety of patients at any single facility is not sufficient for clinical or statistical analysis, data from six major epilepsy centers that performed multiple subpial transections (MSTs) for medically intractable epilepsy were collected. A meta-analysis was performed to elucidate the indications and outcome, and to assess the results of the procedure. Overall, 211 patients were represented with data regarding preoperative evaluation, procedures, seizure types and frequencies before and after surgery, postoperative deficits, and demographic information. Fifty-three patients underwent MST without resection. In patients with MST plus resection, excellent outcome (>95% reduction in seizure frequency) was obtained in 87% of patients for generalized seizures, 68% for complex partial seizures, and 68% for simple partial seizures. For the patients who underwent MST without resection, the rate of excellent outcome was only slightly lower, at 71% for generalized, 62% for complex partial, and 63% for simple partial seizures. EEG localization, age at epilepsy onset, duration of epilepsy, and location of MST were not significant predictors of outcome for any kinds of seizures after MST, with or without resection. New neurologic deficits were found in 47 patients overall, comparable in MST with resection (23%) or without (19%). These preliminary results suggest that MST has efficacy by itself, with minimal neurologic compromise, in cases in which resective surgery cannot be used to treat uncontrolled epilepsy. MST should be investigated as a stand-alone procedure to allow further development of criteria and predictive factors for outcome.

Effects of enzyme-replacement therapy in patients with Anderson-Fabry disease: a prospective long-term cardiac magnetic resonance imaging study.

PubMed

Imbriaco, M; Pisani, A; Spinelli, L; Cuocolo, A; Messalli, G; Capuano, E; Marmo, M; Liuzzi, R; Visciano, B; Cianciaruso, B; Salvatore, M

2009-07-01

Anderson-Fabry disease is a multisystem X linked disorder of lipid metabolism frequently associated with cardiac symptoms, including left ventricular (LV) hypertrophy gradually impairing cardiac function. Evidence showing that enzyme-replacement therapy (ERT) can be effective in reducing LV hypertrophy and improving myocardial function in the long term is limited. This study aimed to assess the long-term effects of ERT with recombinant alpha-galactosidase A (agalsidase beta, Fabrazyme) on LV function and myocardial signal intensity in 11 patients with Anderson-Fabry disease. Eleven patients (eight males, three females) with varying stages of genetically confirmed Anderson-Fabry disease were examined by means of physical examination and magnetic resonance imaging before ERT with agalsidase beta at 1 mg/kg every other week (study 1) and after a mean treatment duration of 45 months (study 2). At 45 months of treatment, LV mass and LV wall thickness had significantly reduced: 188 (SD 60) g versus 153 (47) g, and 16 (4) mm versus 14 (4) mm, respectively. Furthermore, a significant reduction in myocardial T2 relaxation times was noted in all myocardial regions, that is, interventricular septum 80 (5) ms versus 66 (8) ms, apex 79 (10) ms versus 64 (10) ms, and lateral wall 80 (8) ms versus 65 (16) ms. Changes in LV ejection fraction were not significant. Amelioration of clinical symptoms was observed in all patients. Long-term therapy with agalsidase beta at 1 mg/kg every 2 weeks was effective in significantly reducing LV hypertrophy, improving overall cardiac performance and ameliorating clinical symptoms in patients with Anderson-Fabry disease.

Middle Atmosphere Program. Handbook for MAP, volume 28

NASA Technical Reports Server (NTRS)

Liu, C. H. (Editor); Edwards, Belva (Editor)

1989-01-01

Extended abstracts from the fourth workshop on the technical and scientific aspects of MST (mesosphere stratosphere troposphere) radar are presented. Individual sessions addressed the following topics: meteorological applications of MST and ST radars, networks, and campaigns; dynamics of the equatorial middle atmosphere; interpretation of radar returns from clear air; techniques for studying gravity waves and turbulence; intercomparison and calibration of wind and wave measurements at various frequencies; progress in existing and planned MST and ST radars; hardware design for MST and ST radars and boundary layer/lower troposphere profilers; signal processing; and data management.

Handbook for MAP, volume 32. Part 1: MAP summary. Part 2: MAPSC minutes, reading, August 1989. MAP summaries from nations. Part 3: MAP data catalogue

NASA Technical Reports Server (NTRS)

Vincent, R. A. (Editor); Edwards, B. (Editor); Hirota, I. (Editor)

1991-01-01

Extended abstracts from the fourth workshop on the technical and scientific aspects of mesosphere stratosphere troposphere (MST) radar are presented. Individual sessions addressed the following topics: meteorological applications of MST and ST radars, networks, and campaigns; the dynamics of the equatorial middle atmosphere; interpretation of radar returns from clear air; techniques for studying gravity waves and turbulence, intercomparison and calibration of wind and wave measurements at various frequencies; progress in existing and planned MST and ST radars; hardware design for MST and ST radars and boundary layer/lower troposphere profilers; signal processing; and data management.

Plant interactions alter the predictions of metabolic scaling theory.

PubMed

Lin, Yue; Berger, Uta; Grimm, Volker; Huth, Franka; Weiner, Jacob

2013-01-01

Metabolic scaling theory (MST) is an attempt to link physiological processes of individual organisms with macroecology. It predicts a power law relationship with an exponent of -4/3 between mean individual biomass and density during density-dependent mortality (self-thinning). Empirical tests have produced variable results, and the validity of MST is intensely debated. MST focuses on organisms' internal physiological mechanisms but we hypothesize that ecological interactions can be more important in determining plant mass-density relationships induced by density. We employ an individual-based model of plant stand development that includes three elements: a model of individual plant growth based on MST, different modes of local competition (size-symmetric vs. -asymmetric), and different resource levels. Our model is consistent with the observed variation in the slopes of self-thinning trajectories. Slopes were significantly shallower than -4/3 if competition was size-symmetric. We conclude that when the size of survivors is influenced by strong ecological interactions, these can override predictions of MST, whereas when surviving plants are less affected by interactions, individual-level metabolic processes can scale up to the population level. MST, like thermodynamics or biomechanics, sets limits within which organisms can live and function, but there may be stronger limits determined by ecological interactions. In such cases MST will not be predictive.

Mammalian Ste20-like protein kinase 3 mediates trophoblast apoptosis in spontaneous delivery.

PubMed

Wu, Hung-Yi; Lin, Chia-Ying; Lin, Tze-Yi; Chen, Tai-Chang; Yuan, Chiun-Jye

2008-02-01

The placenta is essential in transferring gases and nutrients from the mother to the developing fetus. Trophoblast apoptosis may cause labor or other pregnancy-related disorders. This study demonstrated the essential role of Mst3, a human Ste20-like protein kinase, in the oxidative stress-induced apoptosis of trophoblasts of term placenta in normal spontaneous delivery. Oxidative stress, but not hormones released during labor such as prostaglandin E1, oxytocin or angiotensin II, induces the expression of Mst3 and apoptosis of human term placenta after elective Cesarean section without labor pain. The role of Mst3 in oxidative stress-induced apoptosis was further demonstrated in the 3A-sub-E, a human trophoblast cell line. The H2O2-induced apoptosis of 3A-sub-E cells was largely suppressed by overexpressed Mst3KR, the kinase-dead mutant or by selective knockdown of endogenous Mst3. Further studies showed that Jun N-terminal kinase (JNK) may participate in the signaling pathway of H2O2-induced apoptosis by mediating the level of Mst3. Subsequently, caspase 3 and other downstream apoptotic components may be activated by Mst3 and trigger the apoptotic process in human trophoblasts.

Preliminary data suggest rates of male military sexual trauma may be higher than previously reported.

PubMed

Sheppard, Sean C; Hickling, Edward J; Earleywine, Mitch; Hoyt, Tim; Russo, Amanda R; Donati, Matthew R; Kip, Kevin E

2015-11-01

Stigma associated with disclosing military sexual trauma (MST) makes estimating an accurate base rate difficult. Anonymous assessment may help alleviate stigma. Although anonymous research has found higher rates of male MST, no study has evaluated whether providing anonymity sufficiently mitigates the impact of stigma on accurate reporting. This study used the unmatched count technique (UCT), a form of randomized response techniques, to gain information about the accuracy of base rate estimates of male MST derived via anonymous assessment of Operation Enduring Freedom (OEF)/Operation Iraqi Freedom (OIF) combat veterans. A cross-sectional convenience sample of 180 OEF/OIF male combat veterans, recruited via online websites for military populations, provided data about history of MST via traditional anonymous self-report and the UCT. The UCT revealed a rate of male MST more than 15 times higher than the rate derived via traditional anonymous assessment (1.1% vs. 17.2%). These data suggest that anonymity does not adequately mitigate the impact of stigma on disclosure of male MST. Results, though preliminary, suggest that published rates of male MST may substantially underestimate the true rate of this problem. The UCT has significant potential to improve base rate estimation of sensitive behaviors in the military. (c) 2015 APA, all rights reserved).

An Investigation on Computer-Adaptive Multistage Testing Panels for Multidimensional Assessment

ERIC Educational Resources Information Center

Wang, Xinrui

2013-01-01

The computer-adaptive multistage testing (ca-MST) has been developed as an alternative to computerized adaptive testing (CAT), and been increasingly adopted in large-scale assessments. Current research and practice only focus on ca-MST panels for credentialing purposes. The ca-MST test mode, therefore, is designed to gauge a single scale. The…

Propaganda, Collective Participation and the "War of Position" in the Brazilian Landless Workers' Movement

ERIC Educational Resources Information Center

Meek, David

2011-01-01

The Landless Workers' Movement (MST) is recognized as Brazil's most successful social movement. Although its goal is agrarian reform, the MST has been the subject of significant educational scholarship due to the emphasis it places on education reform, and formal and informal education. The MST's pedagogy has been extensively analysed. However,…

“Do You Expect Me to Receive PTSD Care in a Setting Where Most of the Other Patients Remind Me of the Perpetrator?”: Home-Based Telemedicine to Address Barriers to Care Unique to Military Sexual Trauma and Veterans Affairs Hospitals

PubMed Central

Gilmore, Amanda K.; Davis, Margaret T.; Grubaugh, Anouk; Resnick, Heidi; Birks, Anna; Denier, Carol; Muzzy, Wendy; Tuerk, Peter; Acierno, Ron

2016-01-01

Home-based telemedicine (HBT) is a validated method of evidence-based treatment delivery for posttraumatic stress disorder (PTSD), and justification for its use has centered on closing gaps related to provider availability and distance to treatment centers. However, another potential use of HBT may be to overcome barriers to care that are inherent to the treatment environment, such as with female veterans who have experienced military sexual trauma (MST) and who must present to VA Medical Centers where the majority of patients share features with perpetrator (e.g. gender, clothing) and may function as reminders of the trauma. Delivering evidence-based therapies to female veterans with MST-related PTSD via HBT can provide needed treatment to this population. This manuscript describes an ongoing federally funded randomized controlled trial comparing Prolonged Exposure (PE) delivered in-person to PE delivered via HBT. Outcomes include session attendance, satisfaction with services, and clinical and quality of life indices. It is hypothesized that based on intent-to-treat analyses, HBT delivery of PE will be more effective than SD at improving both clinical and quality of life outcomes at post, 3-, and 6-month follow-up. This is because ‘dose received’, that is fewer sessions missed, and lower attrition, will be observed in the HBT group. Although the current manuscript focuses on female veterans with MST-related PTSD, implications for other populations facing systemic barriers are discussed. PMID:26992740

"Do you expect me to receive PTSD care in a setting where most of the other patients remind me of the perpetrator?": Home-based telemedicine to address barriers to care unique to military sexual trauma and veterans affairs hospitals.

PubMed

Gilmore, Amanda K; Davis, Margaret T; Grubaugh, Anouk; Resnick, Heidi; Birks, Anna; Denier, Carol; Muzzy, Wendy; Tuerk, Peter; Acierno, Ron

2016-05-01

Home-based telemedicine (HBT) is a validated method of evidence-based treatment delivery for posttraumatic stress disorder (PTSD), and justification for its use has centered on closing gaps related to provider availability and distance to treatment centers. However, another potential use of HBT may be to overcome barriers to care that are inherent to the treatment environment, such as with female veterans who have experienced military sexual trauma (MST) and who must present to VA Medical Centers where the majority of patients share features with perpetrator (e.g. gender, clothing) and may function as reminders of the trauma. Delivering evidence-based therapies to female veterans with MST-related PTSD via HBT can provide needed treatment to this population. This manuscript describes an ongoing federally funded randomized controlled trial comparing Prolonged Exposure (PE) delivered in-person to PE delivered via HBT. Outcomes include session attendance, satisfaction with services, and clinical and quality of life indices. It is hypothesized that based on intent-to-treat analyses, HBT delivery of PE will be more effective than SD at improving both clinical and quality of life outcomes at post, 3-, and 6-month follow-up. This is because 'dose received', that is fewer sessions missed, and lower attrition, will be observed in the HBT group. Although the current manuscript focuses on female veterans with MST-related PTSD, implications for other populations facing systemic barriers are discussed. Copyright © 2016 Elsevier Inc. All rights reserved.

A Phase 3 Trial of Whole Brain Radiation Therapy and Stereotactic Radiosurgery Alone Versus WBRT and SRS With Temozolomide or Erlotinib for Non-Small Cell Lung Cancer and 1 to 3 Brain Metastases: Radiation Therapy Oncology Group 0320

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sperduto, Paul W., E-mail: psperduto@mropa.com; Wang, Meihua; Robins, H. Ian

2013-04-01

Background: A phase 3 Radiation Therapy Oncology Group (RTOG) study subset analysis demonstrated improved overall survival (OS) with the addition of stereotactic radiosurgery (SRS) to whole brain radiation therapy (WBRT) in non-small cell lung cancer (NSCLC) patients with 1 to 3 brain metastases. Because temozolomide (TMZ) and erlotinib (ETN) cross the blood-brain barrier and have documented activity in NSCLC, a phase 3 study was designed to test whether these drugs would improve the OS associated with WBRT + SRS. Methods and Materials: NSCLC patients with 1 to 3 brain metastases were randomized to receive WBRT (2.5 Gy × 15 tomore » 37.5 Gy) and SRS alone, versus WBRT + SRS + TMZ (75 mg/m{sup 2}/day × 21 days) or ETN (150 mg/day). ETN (150 mg/day) or TMZ (150-200 mg/m{sup 2}/day × 5 days/month) could be continued for as long as 6 months after WBRT + SRS. The primary endpoint was OS. Results: After 126 patients were enrolled, the study closed because of accrual limitations. The median survival times (MST) for WBRT + SRS, WBRT + SRS + TMZ, and WBRT + SRS + ETN were qualitatively different (13.4, 6.3, and 6.1 months, respectively), although the differences were not statistically significant. Time to central nervous system progression and performance status at 6 months were better in the WBRT + SRS arm. Grade 3 to 5 toxicity was 11%, 41%, and 49% in arms 1, 2, and 3, respectively (P<.001). Conclusion: The addition of TMZ or ETN to WBRT + SRS in NSCLC patients with 1 to 3 brain metastases did not improve survival and possibly had a deleterious effect. Because the analysis is underpowered, these data suggest but do not prove that increased toxicity was the cause of inferior survival in the drug arms.« less

A Phase 3 Trial of Whole Brain Radiation Therapy and Stereotactic Radiosurgery Alone Versus WBRT and SRS With Temozolomide or Erlotinib for Non-Small Cell Lung Cancer and 1 to 3 Brain Metastases: Radiation Therapy Oncology Group 0320.

PubMed Central

Sperduto, Paul W.; Wang, Meihua; Robins, H. Ian; Schell, Michael C.; Werner-Wasik, Maria; Komaki, Ritsuko; Souhami, Luis; Buyyounouski, Mark K.; Khuntia, Deepak; Demas, William; Shah, Sunjay A.; Nedzi, Lucien A.; Perry, Gad; Suh, John H.; Mehta, Minesh P.

2013-01-01

Background A phase 3 Radiation Therapy Oncology Group (RTOG) study subset analysis demonstrated improved overall survival (OS) with the addition of stereotactic radiosurgery (SRS) to whole brain radiation therapy (WBRT) in non-small cell lung cancer (NSCLC) patients with 1 to 3 brain metastases. Because temozolomide (TMZ) and erlotinib (ETN) cross the bloodbrain barrier and have documented activity in NSCLC, a phase 3 study was designed to test whether these drugs would improve the OS associated with WBRT + SRS. Methods and Materials NSCLC patients with 1 to 3 brain metastases were randomized to receive WBRT (2.5 Gy×15 to 37.5 Gy) and SRS alone, versus WBRT + SRS + TMZ (75 mg/m2/day× 21 days) or ETN (150 mg/day). ETN (150 mg/day) or TMZ (150–200 mg/m2/day ×5 days/month) could be continued for as long as 6 months after WBRT þ SRS. The primary endpoint was OS. Results After 126 patients were enrolled, the study closed because of accrual limitations. The median survival times (MST) for WBRT + SRS, WBRT + SRS + TMZ, and WBRT + SRS + ETN were qualitatively different (13.4, 6.3, and 6.1 months, respectively), although the differences were not statistically significant. Time to central nervous system progression and performance status at 6 months were better in the WBRT þ SRS arm. Grade 3 to 5 toxicity was 11%, 41%, and 49% in arms 1, 2, and 3, respectively (P<.001). Conclusion The addition of TMZ or ETN to WBRT + SRS in NSCLC patients with 1 to 3 brain metastases did not improve survival and possibly had a deleterious effect. Because the analysis is underpowered, these data suggest but do not prove that increased toxicity was the cause of inferior survival in the drug arms. PMID:23391814

A phase 3 trial of whole brain radiation therapy and stereotactic radiosurgery alone versus WBRT and SRS with temozolomide or erlotinib for non-small cell lung cancer and 1 to 3 brain metastases: Radiation Therapy Oncology Group 0320.

PubMed

Sperduto, Paul W; Wang, Meihua; Robins, H Ian; Schell, Michael C; Werner-Wasik, Maria; Komaki, Ritsuko; Souhami, Luis; Buyyounouski, Mark K; Khuntia, Deepak; Demas, William; Shah, Sunjay A; Nedzi, Lucien A; Perry, Gad; Suh, John H; Mehta, Minesh P

2013-04-01

A phase 3 Radiation Therapy Oncology Group (RTOG) study subset analysis demonstrated improved overall survival (OS) with the addition of stereotactic radiosurgery (SRS) to whole brain radiation therapy (WBRT) in non-small cell lung cancer (NSCLC) patients with 1 to 3 brain metastases. Because temozolomide (TMZ) and erlotinib (ETN) cross the blood-brain barrier and have documented activity in NSCLC, a phase 3 study was designed to test whether these drugs would improve the OS associated with WBRT + SRS. NSCLC patients with 1 to 3 brain metastases were randomized to receive WBRT (2.5 Gy × 15 to 37.5 Gy) and SRS alone, versus WBRT + SRS + TMZ (75 mg/m(2)/day × 21 days) or ETN (150 mg/day). ETN (150 mg/day) or TMZ (150-200 mg/m(2)/day × 5 days/month) could be continued for as long as 6 months after WBRT + SRS. The primary endpoint was OS. After 126 patients were enrolled, the study closed because of accrual limitations. The median survival times (MST) for WBRT + SRS, WBRT + SRS + TMZ, and WBRT + SRS + ETN were qualitatively different (13.4, 6.3, and 6.1 months, respectively), although the differences were not statistically significant. Time to central nervous system progression and performance status at 6 months were better in the WBRT + SRS arm. Grade 3 to 5 toxicity was 11%, 41%, and 49% in arms 1, 2, and 3, respectively (P<.001). The addition of TMZ or ETN to WBRT + SRS in NSCLC patients with 1 to 3 brain metastases did not improve survival and possibly had a deleterious effect. Because the analysis is underpowered, these data suggest but do not prove that increased toxicity was the cause of inferior survival in the drug arms. Copyright © 2013 Elsevier Inc. All rights reserved.

Long-lasting response to oral therapy in a young male with monogenic diabetes as part of HNF1B-related disease.

PubMed

Carrillo, Elena; Lomas, Amparo; Pinés, Pedro J; Lamas, Cristina

2017-01-01

Mutations in hepatocyte nuclear factor 1β gene ( HNF1B ) are responsible for a multisystemic syndrome where monogenic diabetes (classically known as MODY 5) and renal anomalies, mostly cysts, are the most characteristic findings. Urogenital malformations, altered liver function tests, hypomagnesemia or hyperuricemia and gout are also part of the syndrome. Diabetes in these patients usually requires early insulinization. We present the case of a young non-obese male patient with a personal history of renal multicystic dysplasia and a debut of diabetes during adolescence with simple hyperglycemia, negative pancreatic autoimmunity and detectable C-peptide levels. He also presented epididymal and seminal vesicle cysts, hypertransaminasemia, hyperuricemia and low magnesium levels. In the light of these facts we considered the possibility of a HNF1B mutation. The sequencing study of this gene confirmed a heterozygous mutation leading to a truncated and less functional protein. Genetic studies of his relatives were negative; consequently, it was classified as a de novo mutation. In particular, our patient maintained good control of his diabetes on oral antidiabetic agents for a long period of time. He eventually needed insulinization although oral therapy was continued alongside, allowing reduction of prandial insulin requirements. The real prevalence of mutations in HNF1B is probably underestimated owing to a wide phenotypical variability. As endocrinologists, we should consider this possibility in young non-obese diabetic patients with a history of chronic non-diabetic nephropathy, especially in the presence of some of the other characteristic manifestations. HNF1B mutations are a rare cause of monogenic diabetes, often being a part of a multisystemic syndrome.The combination of young-onset diabetes and genitourinary anomalies with slowly progressive nephropathy of non-diabetic origin in non-obese subjects should rise the suspicion of such occurrence. A family history

Six-minute stepper test: a valid clinical exercise tolerance test for COPD patients

PubMed Central

Grosbois, JM; Riquier, C; Chehere, B; Coquart, J; Béhal, H; Bart, F; Wallaert, B; Chenivesse, C

2016-01-01

Introduction Exercise tolerance testing is an integral part of the pulmonary rehabilitation (PR) management of patients with chronic obstructive pulmonary disease (COPD). The 6-minute stepper test (6MST) is a new, well-tolerated, reproducible exercise test, which can be performed without any spatial constraints. Objective The aim of this study was to compare the results of the 6MST to those obtained during a 6-minute walk test (6MWT) and cardiopulmonary exercise testing (CPET) in a cohort of COPD patients. Methods Ninety-one COPD patients managed by outpatient PR and assessed by 6MST, 6MWT, and CPET were retrospectively included in this study. Correlations between the number of steps on the 6MST, the distance covered on the 6MWT, oxygen consumption, and power at the ventilatory threshold and at maximum effort during CPET were analyzed before starting PR, and the improvement on the 6MST and 6MWT was compared after PR. Results The number of steps on the 6MST was significantly correlated with the distance covered on the 6MWT (r=0.56; P<0.0001), the power at maximum effort (r=0.46; P<0.0001), and oxygen consumption at maximum effort (r=0.39; P<0.005). Performances on the 6MST and 6MWT were significantly improved after PR (570 vs 488 steps, P=0.001 and 448 vs 406 m, respectively; P<0.0001). Improvements of the 6MST and 6MWT after PR were significantly correlated (r=0.34; P=0.03). Conclusion The results of this study show that the 6MST is a valid test to evaluate exercise tolerance in COPD patients. The use of this test in clinical practice appears to be particularly relevant for the assessment of patients managed by home PR. PMID:27099483

Maximal strength training improves work economy, rate of force development and maximal strength more than conventional strength training.

PubMed

Heggelund, Jørn; Fimland, Marius S; Helgerud, Jan; Hoff, Jan

2013-06-01

This study compared maximal strength training (MST) with equal training volume (kg × sets × repetitions) of conventional strength training (CON) primarily with regard to work economy, and second one repetition maximum (1RM) and rate of force development (RFD) of single leg knee extension. In an intra-individual design, one leg was randomized to knee-extension MST (4 or 5RM) and the other leg to CON (3 × 10RM) three times per week for 8 weeks. MST was performed with maximal concentric mobilization of force while CON was performed with moderate velocity. Eight untrained or moderately trained men (26 ± 1 years) completed the study. The improvement in gross work economy was -0.10 ± 0.08 L min(-1) larger after MST (P = 0.011, between groups). From pre- to post-test the MST and CON improved net work economy with 31 % (P < 0.001) and 18 % (P = 0.01), respectively. Compared with CON, the improvement in 1RM and dynamic RFD was 13.7 ± 8.4 kg (P = 0.002) and 587 ± 679 N s(-1) (P = 0.044) larger after MST, whereas isometric RFD was of borderline significance 3,028 ± 3,674 N s(-1) (P = 0.053). From pre- to post-test, MST improved 1RM and isometric RFD with 50 % (P < 0.001) and 155 % (P < 0.001), respectively whereas CON improved 1RM and isometric RFD with 35 % (P < 0.001) and 83 % (P = 0.028), respectively. Anthropometric measures of quadriceps femoris muscle mass and peak oxygen uptake did not change. In conclusion, 8 weeks of MST was more effective than CON for improving work economy, 1RM and RFD in untrained and moderately trained men. The advantageous effect of MST to improve work economy could be due to larger improvements in 1RM and RFD.

Tree morphologic plasticity explains deviation from metabolic scaling theory in semi-arid conifer forests, southwestern USA

Treesearch

Tyson L. Swetnam; Christopher D. O' Connor; Ann M. Lynch

2016-01-01

A significant concern about Metabolic Scaling Theory (MST) in real forests relates to consistent differences between the values of power law scaling exponents of tree primary size measures used to estimate mass and those predicted by MST. Here we consider why observed scaling exponents for diameter and height relationships deviate from MST predictions across...

Functional grouping of similar genes using eigenanalysis on minimum spanning tree based neighborhood graph.

PubMed

Jothi, R; Mohanty, Sraban Kumar; Ojha, Aparajita

2016-04-01

Gene expression data clustering is an important biological process in DNA microarray analysis. Although there have been many clustering algorithms for gene expression analysis, finding a suitable and effective clustering algorithm is always a challenging problem due to the heterogeneous nature of gene profiles. Minimum Spanning Tree (MST) based clustering algorithms have been successfully employed to detect clusters of varying shapes and sizes. This paper proposes a novel clustering algorithm using Eigenanalysis on Minimum Spanning Tree based neighborhood graph (E-MST). As MST of a set of points reflects the similarity of the points with their neighborhood, the proposed algorithm employs a similarity graph obtained from k(') rounds of MST (k(')-MST neighborhood graph). By studying the spectral properties of the similarity matrix obtained from k(')-MST graph, the proposed algorithm achieves improved clustering results. We demonstrate the efficacy of the proposed algorithm on 12 gene expression datasets. Experimental results show that the proposed algorithm performs better than the standard clustering algorithms. Copyright © 2016 Elsevier Ltd. All rights reserved.

The maize stripe virus major noncapsid protein messenger RNA transcripts contain heterogeneous leader sequences at their 5' termini.

PubMed

Huiet, L; Feldstein, P A; Tsai, J H; Falk, B W

1993-12-01

Primer extension analyses and a PCR-based cloning strategy were used to identify and characterize 5' nucleotide sequences on the maize stripe virus (MStV) RNA4 mRNA transcripts encoding the major noncapsid protein (NCP). Direct RNA sequence analysis by primer extension showed that the NCP mRNA transcripts had 10-15 nucleotides beyond the 5' terminus of the MStV RNA4 nucleotide sequence. MStV genomic RNAs isolated from ribonucleoprotein particles (RNPs) lacked the additional 5' nucleotides. cDNA clones representing the 5' region of the mRNA transcripts were constructed, and the nucleotide sequences of the 5' regions were determined for 16 clones. Each was found to have a distinct 10-15 nucleotide sequence immediately 5' of the MStV RNA4 sequence. Eleven of 16 clones had the correct MStV RNA4 5' nucleotide sequence, while five showed minor variations at or near the 5' most MStV RNA4 nucleotide. These characteristics show strong similarities to other viral mRNA transcripts which are synthesized by cap snatching.

A new mouse model to explore therapies for preeclampsia.

PubMed

Ahmed, Abdulwahab; Singh, Jameel; Khan, Ysodra; Seshan, Surya V; Girardi, Guillermina

2010-10-27

Pre-eclampsia, a pregnancy-specific multisystemic disorder is a leading cause of maternal and perinatal mortality and morbidity. This syndrome has been known to medical science since ancient times. However, despite considerable research, the cause/s of preeclampsia remain unclear, and there is no effective treatment. Development of an animal model that recapitulates this complex pregnancy-related disorder may help to expand our understanding and may hold great potential for the design and implementation of effective treatment. Here we show that the CBA/J x DBA/2 mouse model of recurrent miscarriage is also a model of immunologically-mediated preeclampsia (PE). DBA/J mated CBA/J females spontaneously develop many features of human PE (primigravidity, albuminuria, endotheliosis, increased sensitivity to angiotensin II and increased plasma leptin levels) that correlates with bad pregnancy outcomes. We previously reported that antagonism of vascular endothelial growth factor (VEGF) signaling by soluble VEGF receptor 1 (sFlt-1) is involved in placental and fetal injury in CBA/J x DBA/2 mice. Using this animal model that recapitulates many of the features of preeclampsia in women, we found that pravastatin restores angiogenic balance, ameliorates glomerular injury, diminishes hypersensitivity to angiotensin II and protects pregnancies. We described a new mouse model of PE, were the relevant key features of human preeclampsia develop spontaneously. The CBA/J x DBA/2 model, that recapitulates this complex disorder, helped us identify pravastatin as a candidate therapy to prevent preeclampsia and its related complications. We recognize that these studies were conducted in mice and that clinical trials are needed to confirm its application to humans.

Lyme Disease: What the Wilderness Provider Needs to Know.

PubMed

Forrester, Joseph D; Vakkalanka, J Priyanka; Holstege, Christopher P; Mead, Paul S

2015-12-01

Lyme disease is a multisystem tickborne illness caused by the spirochete Borrelia burgdorferi and is the most common vectorborne disease in the United States. Prognosis after initiation of appropriate antibiotic therapy is typically good if treated early. Wilderness providers caring for patients who live in or travel to high-incidence Lyme disease areas should be aware of the basic biology, epidemiology, clinical manifestations, and treatment of Lyme disease. Published by Elsevier Inc.

A Comparison of IRT Proficiency Estimation Methods under Adaptive Multistage Testing

ERIC Educational Resources Information Center

Kim, Sooyeon; Moses, Tim; Yoo, Hanwook

2015-01-01

This inquiry is an investigation of item response theory (IRT) proficiency estimators' accuracy under multistage testing (MST). We chose a two-stage MST design that includes four modules (one at Stage 1, three at Stage 2) and three difficulty paths (low, middle, high). We assembled various two-stage MST panels (i.e., forms) by manipulating two…

Prevalence and Mental Health Correlates of Insomnia in First-Encounter Veterans with and without Military Sexual Trauma.

PubMed

Jenkins, Melissa M; Colvonen, Peter J; Norman, Sonya B; Afari, Niloofar; Allard, Carolyn B; Drummond, Sean P A

2015-10-01

There is limited information about prevalence of insomnia in general populations of veterans of recent wars in Iraq and Afghanistan. No studies have examined insomnia in veterans with military sexual trauma (MST). We assess prevalence of insomnia, identify types of services sought by veterans with insomnia, and examine correlates of insomnia in veterans with and without MST. A cross-sectional study of first-encounter veterans registering to establish care. Veteran Affairs San Diego Healthcare System. Nine hundred seventeen veterans completed questionnaires assessing insomnia, MST, service needs, traumatic brain injury, resilience, and symptoms of depression, posttraumatic stress disorder (PTSD), pain, alcohol misuse, and hypomania. N/A. 53.1% of veterans without MST and 60.8% of veterans with MST had clinically significant insomnia symptoms, with the MST subsample reporting more severe symptoms, P < 0.05. Insomnia was more prevalent than depression, hypomania, PTSD, and substance misuse. Veterans with insomnia were more likely to seek care for physical health problems and primary care versus mental health concerns, P < 0.001. For the veteran sample without MST, age, combat service, traumatic brain injury, pain, and depression were associated with worse insomnia, P < 0.001. For the MST subsample, employment status, pain, and depression were associated with worse insomnia, P < 0.001. Study findings indicate a higher rate of insomnia in veterans compared to what has been found in the general population. Insomnia is more prevalent, and more severe, in veterans with military sexual trauma. Routine insomnia assessments and referrals to providers who can provide evidence-based treatment are crucial. © 2015 Associated Professional Sleep Societies, LLC.

Manual suction versus femtosecond laser trephination for penetrating keratoplasty: intraocular pressure, endothelial cell damage, incision geometry, and wound healing responses.

PubMed

Angunawela, Romesh I; Riau, Andri; Chaurasia, Shyam S; Tan, Donald T; Mehta, Jodhbir S

2012-05-04

To measure real-time intraocular pressure (IOP) during trephination with a manual suction trephine (MST) and the femtosecond laser (FSL), and to assess endothelial cell damage, incision geometry, and wound healing response with these procedures. IOP was monitored with an intracameral sensor. Eight rabbits underwent manual suction trephination. Eight rabbits had FSL trephination (FSL-T). Slit lamp photography, confocal microscopy, and anterior segment optical coherence tomography (AS-OCT) were performed at baseline and postoperatively. Animals were sacrificed at 4 hours and 3 days. Tissue was examined with scanning electron microscopy (SEM) and immunohistochemistry for an array of wound-healing markers. Separately, 6 human corneas had MST (3) and FSL-T (3). Incision geometry was imaged with high resolution Optovue AS-OCT. The average IOP during MST and FSL-T was similar (37 mm Hg). There was wider IOP fluctuation during the MST cutting phase (60 mm Hg maximum). There were 1-2 rows of endothelial loss on either side of the incision for FSL-T and 2-5 rows deep for MST. Immune cell responses at 4 hours (CD11b) were comparable, greater apoptosis with FSL-T (TUNEL) occurred at 4 hours, and there was increased keratocyte proliferation at 3 days (Ki67) with FSL-T. There was significantly greater undercutting of the cornea with MST (46.86 degrees versus 16.72 degrees). There is more IOP variation during MST. Average IOP is 37 mm Hg for both techniques. More endothelial damage and undercutting of the cornea occurs with MST. The wound healing response to FSL-T appears greater at 3 days.

Hybrid micro/nanostructural surface offering improved stress distribution and enhanced osseointegration properties of the biomedical titanium implant.

PubMed

Hou, Ping-Jen; Ou, Keng-Liang; Wang, Chin-Chieh; Huang, Chiung-Fang; Ruslin, Muhammad; Sugiatno, Erwan; Yang, Tzu-Sen; Chou, Hsin-Hua

2018-03-01

The aim of the present study was to investigate the surface characteristic, biomechanical behavior, hemocompatibility, bone tissue response and osseointegration of the optimal micro-arc oxidation surface-treated titanium (MST-Ti) dental implant. The surface characteristic, biomechanical behavior and hemocompatibility of the MST-Ti dental implant were performed using scanning electron microscope, finite element method, blood dripping and immersion tests. The mini-pig model was utilized to evaluate the bone tissue response and osseointegration of the MST-Ti dental implant in vivo. Data were analyzed by analysis of variance using the Student's t-test (P ≤ 0.05). The hybrid volcano-like micro/nanoporous structure was formed on the surface of the MST-Ti dental implant. The hybrid volcano-like micro/nanoporous surface played an important role to improve the stress transfer between fixture, cortical bone and cancellous bone for the MST-Ti dental implant. Moreover, the MST-Ti implant was considered to have the outstanding hemocompatibility. In vivo testing results showed that the bone-to-implant contact (BIC) ratio significantly altered as the implant with micro/nanoporous surface. After 12 weeks of implantation, the MST-Ti dental implant group exhibited significantly higher BIC ratio than the untreated dental implant group. In addition, the MST-Ti dental implant group also presented an enhancing osseointegration, particularly in the early stages of bone healing. It can be concluded that the micro-arc oxidation approach induced the formation of micro/nanoporous surface is a promising and reliable alternative surface modification for Ti dental implant applications. Copyright © 2017 Elsevier Ltd. All rights reserved.

A 3.7 Mb Deletion Encompassing ZEB2 Causes a Novel Polled and Multisystemic Syndrome in the Progeny of a Somatic Mosaic Bull

PubMed Central

Capitan, Aurélien; Allais-Bonnet, Aurélie; Pinton, Alain; Marquant-Le Guienne, Brigitte; Le Bourhis, Daniel; Grohs, Cécile; Bouet, Stéphan; Clément, Laëtitia; Salas-Cortes, Laura; Venot, Eric; Chaffaux, Stéphane; Weiss, Bernard; Delpeuch, Arnaud; Noé, Guy; Rossignol, Marie-Noëlle; Barbey, Sarah; Dozias, Dominique; Cobo, Emilie; Barasc, Harmonie; Auguste, Aurélie; Pannetier, Maëlle; Deloche, Marie-Christine; Lhuilier, Emeline; Bouchez, Olivier; Esquerré, Diane; Salin, Gérald; Klopp, Christophe; Donnadieu, Cécile; Chantry-Darmon, Céline; Hayes, Hélène; Gallard, Yves; Ponsart, Claire; Boichard, Didier; Pailhoux, Eric

2012-01-01

Polled and Multisystemic Syndrome (PMS) is a novel developmental disorder occurring in the progeny of a single bull. Its clinical spectrum includes polledness (complete agenesis of horns), facial dysmorphism, growth delay, chronic diarrhea, premature ovarian failure, and variable neurological and cardiac anomalies. PMS is also characterized by a deviation of the sex-ratio, suggesting male lethality during pregnancy. Using Mendelian error mapping and whole-genome sequencing, we identified a 3.7 Mb deletion on the paternal bovine chromosome 2 encompassing ARHGAP15, GTDC1 and ZEB2 genes. We then produced control and affected 90-day old fetuses to characterize this syndrome by histological and expression analyses. Compared to wild type individuals, affected animals showed a decreased expression of the three deleted genes. Based on a comparison with human Mowat-Wilson syndrome, we suggest that deletion of ZEB2, is responsible for most of the effects of the mutation. Finally sperm-FISH, embryo genotyping and analysis of reproduction records confirmed somatic mosaicism in the founder bull and male-specific lethality during the first third of gestation. In conclusion, we identified a novel locus involved in bovid horn ontogenesis and suggest that epithelial-to-mesenchymal transition plays a critical role in horn bud differentiation. We also provide new insights into the pathogenicity of ZEB2 loss of heterozygosity in bovine and humans and describe the first case of male-specific lethality associated with an autosomal locus in a non-murine mammalian species. This result sets PMS as a unique model to study sex-specific gene expression/regulation. PMID:23152852

Update on role of agalsidase alfa in management of Fabry disease

PubMed Central

Ramaswami, Uma

2011-01-01

Fabry disease (FD) is an X-linked lysosomal storage disorder that affects both men and women. The manifestations of this heterogeneous disease are multisystemic and progressive. Prior to the development of enzyme replacement therapy, the management and treatment for Fabry disease was largely nonspecific and supportive. Because enzyme replacement therapy became commercially available in 2001, a variety of clinical benefits in Fabry patients have been consistently reported, including improved renal pathology and cardiac function, and reduced severity of neuropathic pain and improved pain-related quality of life. This update focuses on published data on the efficacy and tolerability of enzyme replacement therapy with agalsidase alfa, and gives a brief overview on some of the outstanding management issues in the treatment of this complex disease. PMID:21552486

Hippo/Yap signaling controls epithelial progenitor cell proliferation and differentiation in the embryonic and adult lung

PubMed Central

Lange, Alexander W.; Sridharan, Anusha; Xu, Yan; Stripp, Barry R.; Perl, Anne-Karina; Whitsett, Jeffrey A.

2015-01-01

The Hippo/Yap pathway is a well-conserved signaling cascade that regulates cell proliferation and differentiation to control organ size and stem/progenitor cell behavior. Following airway injury, Yap was dynamically regulated in regenerating airway epithelial cells. To determine the role of Hippo signaling in the lung, the mammalian Hippo kinases, Mst1 and Mst2, were deleted in epithelial cells of the embryonic and mature mouse lung. Mst1/2 deletion in the fetal lung enhanced proliferation and inhibited sacculation and epithelial cell differentiation. The transcriptional inhibition of cell proliferation and activation of differentiation during normal perinatal lung maturation were inversely regulated following embryonic Mst1/2 deletion. Ablation of Mst1/2 from bronchiolar epithelial cells in the adult lung caused airway hyperplasia and altered differentiation. Inhibitory Yap phosphorylation was decreased and Yap nuclear localization and transcriptional targets were increased after Mst1/2 deletion, consistent with canonical Hippo/Yap signaling. YAP potentiated cell proliferation and inhibited differentiation of human bronchial epithelial cells in vitro. Loss of Mst1/2 and expression of YAP regulated transcriptional targets controlling cell proliferation and differentiation, including Ajuba LIM protein. Ajuba was required for the effects of YAP on cell proliferation in vitro. Hippo/Yap signaling regulates Ajuba and controls proliferation and differentiation of lung epithelial progenitor cells. PMID:25480985

Newly Isolated Paenibacillus tyrfis sp. nov., from Malaysian Tropical Peat Swamp Soil with Broad Spectrum Antimicrobial Activity

PubMed Central

Aw, Yoong-Kit; Ong, Kuan-Shion; Lee, Learn-Han; Cheow, Yuen-Lin; Yule, Catherine M.; Lee, Sui-Mae

2016-01-01

Emergence of antimicrobial resistance coupled with the slowdown in discovery of new antimicrobial compounds points to serious consequences for human health. Therefore, scientists are looking for new antimicrobial compounds from unique and understudied ecosystems such as tropical peat swamp forests. Over the course of isolating antimicrobial producing bacteria from North Selangor tropical peat swamp forest, Malaysia, a Gram variable, rod shaped, endospore forming, facultative anaerobic novel strain MSt1T that exerts potent and broad spectrum antimicrobial activity was isolated. Phylogenetic analysis using 16S rRNA gene sequences showed that strain MSt1T belonged to the genus Paenibacillus with the highest similarity to Paenibacillus elgii SD17T (99.5%). Whole genome comparison between strain MSt1T with its closely related species using average nucleotide identity (ANI) revealed that similarity between strain MSt1T with P. elgii B69 (93.45%) and Paenibacillus ehimensis A2 (90.42%) was below the recommended threshold of 95%. Further analysis using in silico pairwise DDH also showed that similarity between strain MSt1T with P. elgii B69 (55.4%) and P. ehimensis A2 (43.7%) was below the recommended threshold of 70%. Strain MSt1T contained meso-diaminopilemic acid in the cell wall and MK-7 as the major menaquinone. The major fatty acids of strain MSt1T were anteiso-C15:0 (48.2%) and C16:0 (29.0%) whereas the polar lipid profile consisted of phosphatidylglycerol, phosphatidylethanolamine, diphosphatidylglycerol, one unknown lipid, two unknown glycolipids, and one unknown phospholipid. Total DNA G+C content of strain MSt1T was 51.5 mol%. The extract from strain MSt1T exerted strong antimicrobial activity against Escherichia coli ATCC 25922 (MIC = 1.5 μg/mL), MRSA ATCC 700699 (MIC = 25 μg/mL) and Candida albicans IMR (MIC = 12.5 μg/mL). Partially purified active fraction exerted a strong effect against E. coli ATCC 25922 resulting in cell rupture when viewed with SEM

Treatment with agalsidase beta during pregnancy in Fabry disease.

PubMed

Politei, Juan M

2010-04-01

Fabry disease is an X-linked lysosomal storage disease caused by a deficiency of alpha-galactosidase A, which leads to excessive accumulation of glycosphingolipids in most tissues in the body, with life-threatening clinical consequences in the kidney, heart, and cerebrovascular system. Enzyme replacement therapy using exogenously produced alpha-galactosidase has been available for treatment of this multisystem progressive disease since 2001. Two different preparations of enzyme replacement therapy for Fabry disease are available outside of the USA: agalsidase alfa and agalsidase beta. Despite being X-linked, Fabry disease affects many female patients, and this report presents a successful pregnancy of a female patient receiving agalsidase beta.

Is nectar reabsorption restricted by the stalk cells of floral and extrafloral nectary trichomes?

PubMed

Cardoso-Gustavson, P; Davis, A R

2015-01-01

Reabsorption is a phase of nectar dynamics that occurs concurrently with secretion; it has been described in floral nectaries that exude nectar through stomata or unicellular trichomes, but has not yet been recorded in extrafloral glands. Apparently, nectar reabsorption does not occur in multicellular secretory trichomes (MST) due to the presence of lipophilic impregnations - which resemble Casparian strips - in the anticlinal walls of the stalk cells. It has been assumed that these impregnations restrict solute movement within MST to occur unidirectionally and exclusively by the symplast, thereby preventing nectar reflux toward the underlying nectary tissues. We hypothesised that reabsorption is absent in nectaries possessing MST. The fluorochrome lucifer yellow (LYCH) was applied to standing nectar of two floral and extrafloral glands of distantly related species, and then emission spectra from nectary sections were systematically analysed using confocal microscopy. Passive uptake of LYCH via the stalk cells to the nectary tissues occurred in all MST examined. Moreover, we present evidence of nectar reabsorption in extrafloral nectaries, demonstrating that LYCH passed the stalk cells of MST, although it did not reach the deepest nectary tissues. Identical (control) experiments performed with neutral red (NR) demonstrated no uptake of this stain by actively secreting MST, whereas diffusion of NR did occur in plasmolysed MST of floral nectaries at the post-secretory phase, indicating that nectar reabsorption by MST is governed by stalk cell physiology. Interestingly, non-secretory trichomes failed to reabsorb nectar. The role of various nectary components is discussed in relation to the control of nectar reabsorption by secretory trichomes. © 2014 German Botanical Society and The Royal Botanical Society of the Netherlands.

The influence of military sexual trauma on returning OEF/OIF male veterans.

PubMed

Mondragon, Sasha A; Wang, David; Pritchett, Lonique; Graham, David P; Plasencia, M Leili; Teng, Ellen J

2015-11-01

Military sexual trauma (MST) encompasses experiences of sexual harassment and/or assault that occur during active duty military service. MST is associated with postdeployment mental health, interpersonal, and physical difficulties and appears to be more influential in the development of posttraumatic stress disorder (PTSD) than other active duty experiences, including combat, among women veterans. Although some literature suggests that men who experience MST also evidence significant postdeployment difficulties, research in this area is lacking. The current study evaluated a large sample of returning male veterans (N = 961) who served in Iraq and/or Afghanistan. Veterans were referred for treatment in a trauma and anxiety specialty clinic at a large VA hospital. Of this sample, 18% (n = 173) reported MST perpetrated by a member of their unit. Results indicated veterans who reported MST were younger (p = .001), less likely to be currently married (p < .001), more likely to be diagnosed with a mood disorder (p = .040), and more likely to have experienced non-MST sexual abuse either as children or adults (p < .001). Analyses revealed that MST was negatively associated with postdeployment social support (p < .001 and positively associated with postdeployment perceived emotional mistreatment (p = .004), but was not associated with postdeployment loss of romantic relationship (p = .264), job loss (p = .351), or unemployment (p = .741) after statistically controlling for other trauma exposures and current social support. Results reflect the detrimental associations of MST on male veterans and the need for more research in this area. These findings also highlight the need for treatment interventions that address social and interpersonal functioning in addition to symptoms of depressive disorders. (c) 2015 APA, all rights reserved).

Perceived barriers to care and provider gender preferences among veteran men who have experienced military sexual trauma: a qualitative analysis.

PubMed

Turchik, Jessica A; McLean, Caitlin; Rafie, Samantha; Hoyt, Tim; Rosen, Craig S; Kimerling, Rachel

2013-05-01

Research suggests that there may be unique barriers to accessing care among men who have experienced sexual trauma. The primary goal of the current research was to elucidate potential barriers to accessing military sexual trauma (MST)-related care for male veterans. A secondary goal was to explore whether veterans have preferences regarding the gender of clinicians providing MST-related care. Qualitative analyses were used to examine data collected from semistructured interviews conducted with 20 male veterans enrolled in Veterans Health Administration care who reported MST but who had not received any MST-related mental health care. Veterans identified a number of potential barriers, with the majority of reported barriers relating to issues of stigma and gender. Regarding provider gender preferences, veterans were mixed, with 50% preferring a female provider, 25% a male provider, and 25% reporting no gender preference. These preliminary data suggest that stigma, gender, and knowledge-related barriers may exist for men regarding seeking MST-related care. Interventions to address potential barriers, such as outreach interventions and providing gender-specific psychoeducation, may increase access to care for male veterans who report MST. PsycINFO Database Record (c) 2013 APA, all rights reserved.

Meta-cognitive skills training enhances computerized cognitive remediation outcomes among individuals with first-episode psychosis.

PubMed

Breitborde, Nicholas J K; Woolverton, Cindy; Dawson, Spencer C; Bismark, Andrew; Bell, Emily K; Bathgate, Christina J; Norman, Kaila

2017-06-01

Meta-cognitive skills training (MST) is a frequent component of cognitive remediation programmes for individuals with psychosis. However, no study has investigated whether incorporating such activities produces increased clinical benefits compared with computerized cognitive remediation alone. Individuals with first-episode psychosis who completed computerized cognitive remediation with concurrent meta-cognitive skills training (CCR + MST) were compared with a historical control group who received computerized cognitive remediation alone (CCR) and did not differ from the CCR + MST group with regard to pre-intervention cognition, diagnosis, age, duration of psychotic illness or sex. Participants completed assessments of cognition and real-world functioning before and after 6 months of treatment. Individual receiving CCR + MST experience greater gains in cognition and real-world functioning than individuals who received CCR. MST may be an important component within cognitive remediation programmes for first-episode psychosis. © 2015 Wiley Publishing Asia Pty Ltd.

Military sexual trauma among U.S. female veterans.

PubMed

Williams, Irene; Bernstein, Kunsook

2011-04-01

Sexual abuse among female veterans reportedly occurs in significant numbers in the U.S. military and has been recognized to cause posttraumatic stress disorder (PTSD). PTSD, which stems from sexual abuse, has been called military sexual trauma (MST), which has only recently been recognized by the Department of Defense. Consequently, there has been scant research on the prevalence, impact, and treatment of MST. This article explores the phenomenon of sexual aggression against female veterans in the U.S. military, risk factors for MST, PTSD as a result of MST, a conceptual framework for treating PTSD stress, and treatment strategies for PTSD. Published by Elsevier Inc.

Local applications of myostatin-siRNA with atelocollagen increase skeletal muscle mass and recovery of muscle function.

PubMed

Kawakami, Emi; Kawai, Nobuhiko; Kinouchi, Nao; Mori, Hiroyo; Ohsawa, Yutaka; Ishimaru, Naozumi; Sunada, Yoshihide; Noji, Sumihare; Tanaka, Eiji

2013-01-01

Growing evidence suggests that small-interfering RNA (siRNA) can promote gene silencing in mammalian cells without induction of interferon synthesis or nonspecific gene suppression. Recently, a number of highly specific siRNAs targeted against disease-causing or disease-promoting genes have been developed. In this study, we evaluate the effectiveness of atelocollagen (ATCOL)-mediated application of siRNA targeting myostatin (Mst), a negative regulator of skeletal muscle growth, into skeletal muscles of muscular dystrophy model mice. We injected a nanoparticle complex containing myostatin-siRNA and ATCOL (Mst-siRNA/ATCOL) into the masseter muscles of mutant caveolin-3 transgenic (mCAV-3Tg) mice, an animal model for muscular dystrophy. Scrambled (scr) -siRNA/ATCOL complex was injected into the contralateral muscles as a control. Two weeks after injection, the masseter muscles were dissected for histometric analyses. To investigate changes in masseter muscle activity by local administration of Mst-siRNA/ATCOL complex, mouse masseter electromyography (EMG) was measured throughout the experimental period via telemetry. After local application of the Mst-siRNA/ATCOL complex, masseter muscles were enlarged, while no significant change was observed on the contralateral side. Histological analysis showed that myofibrils of masseter muscles treated with the Mst-siRNA/ATCOL complex were significantly larger than those of the control side. Real-time PCR analysis revealed a significant downregulation of Mst expression in the treated masseters of mCAV-3Tg mice. In addition, expression of myogenic transcription factors was upregulated in the Mst-siRNA-treated masseter muscle, while expression of adipogenic transcription factors was significantly downregulated. EMG results indicate that masseter muscle activity in mCAV-3Tg mice was increased by local administration of the Mst-siRNA/ATCOL complex. These data suggest local administration of Mst-siRNA/ATCOL complex could lead to

Inotuzumab Ozogamicin Murine Analog–Mediated B-Cell Depletion Reduces Anti-islet Allo- and Autoimmune Responses

PubMed Central

Carvello, Michele; Petrelli, Alessandra; Vergani, Andrea; Lee, Kang Mi; Tezza, Sara; Chin, Melissa; Orsenigo, Elena; Staudacher, Carlo; Secchi, Antonio; Dunussi-Joannopoulos, Kyri; Sayegh, Mohamed H.; Markmann, James F.; Fiorina, Paolo

2012-01-01

B cells participate in the priming of the allo- and autoimmune responses, and their depletion can thus be advantageous for islet transplantation. Herein, we provide an extensive study of the effect of B-cell depletion in murine models of islet transplantation. Islet transplantation was performed in hyperglycemic B-cell–deficient(μMT) mice, in a purely alloimmune setting (BALB/c into hyperglycemic C57BL/6), in a purely autoimmune setting (NOD.SCID into hyperglycemic NOD), and in a mixed allo-/autoimmune setting (BALB/c into hyperglycemic NOD). Inotuzumab ozogamicin murine analog (anti-CD22 monoclonal antibody conjugated with calicheamicin [anti-CD22/cal]) efficiently depleted B cells in all three models of islet transplantation examined. Islet graft survival was significantly prolonged in B-cell–depleted mice compared with control groups in transplants of islets from BALB/c into C57BL/6 (mean survival time [MST]: 16.5 vs. 12.0 days; P = 0.004), from NOD.SCID into NOD (MST: 23.5 vs. 14.0 days; P = 0.03), and from BALB/c into NOD (MST: 12.0 vs. 5.5 days; P = 0.003). In the BALB/c into B-cell–deficient mice model, islet survival was prolonged as well (MST: μMT = 32.5 vs. WT = 14 days; P = 0.002). Pathology revealed reduced CD3+ cell islet infiltration and confirmed the absence of B cells in treated mice. Mechanistically, effector T cells were reduced in number, concomitant with a peripheral Th2 profile skewing and ex vivo recipient hyporesponsiveness toward donor-derived antigen as well as islet autoantigens. Finally, an anti-CD22/cal and CTLA4-Ig–based combination therapy displayed remarkable prolongation of graft survival in the stringent model of islet transplantation (BALB/c into NOD). Anti-CD22/cal–mediated B-cell depletion promotes the reduction of the anti-islet immune response in various models of islet transplantation. PMID:22076927

Hippo/Yap signaling controls epithelial progenitor cell proliferation and differentiation in the embryonic and adult lung.

PubMed

Lange, Alexander W; Sridharan, Anusha; Xu, Yan; Stripp, Barry R; Perl, Anne-Karina; Whitsett, Jeffrey A

2015-02-01

The Hippo/Yap pathway is a well-conserved signaling cascade that regulates cell proliferation and differentiation to control organ size and stem/progenitor cell behavior. Following airway injury, Yap was dynamically regulated in regenerating airway epithelial cells. To determine the role of Hippo signaling in the lung, the mammalian Hippo kinases, Mst1 and Mst2, were deleted in epithelial cells of the embryonic and mature mouse lung. Mst1/2 deletion in the fetal lung enhanced proliferation and inhibited sacculation and epithelial cell differentiation. The transcriptional inhibition of cell proliferation and activation of differentiation during normal perinatal lung maturation were inversely regulated following embryonic Mst1/2 deletion. Ablation of Mst1/2 from bronchiolar epithelial cells in the adult lung caused airway hyperplasia and altered differentiation. Inhibitory Yap phosphorylation was decreased and Yap nuclear localization and transcriptional targets were increased after Mst1/2 deletion, consistent with canonical Hippo/Yap signaling. YAP potentiated cell proliferation and inhibited differentiation of human bronchial epithelial cells in vitro. Loss of Mst1/2 and expression of YAP regulated transcriptional targets controlling cell proliferation and differentiation, including Ajuba LIM protein. Ajuba was required for the effects of YAP on cell proliferation in vitro. Hippo/Yap signaling regulates Ajuba and controls proliferation and differentiation of lung epithelial progenitor cells. © The Author (2014). Published by Oxford University Press on behalf of Journal of Molecular Cell Biology, IBCB, SIBS, CAS. All rights reserved.

Rényi indices of financial minimum spanning trees

NASA Astrophysics Data System (ADS)

Nie, Chun-Xiao; Song, Fu-Tie; Li, Sai-Ping

2016-02-01

The Rényi index is used here to describe topological structures of minimum spanning trees (MSTs) of financial markets. We categorize the topological structures of MSTs as dragon, star and super-star types. The MST based on Geometric Brownian motion is of dragon type, the MST constructed by One-Factor Model is super-star type, and most MSTs based on real market data belong to the star type. The Rényi index of the MST corresponding to S&P500 is evaluated, and the result shows that the Rényi index varies significantly in different time periods. In particular, it rose during crises and dropped when the S&P500 index rose significantly. A comparison study between the CSI300 index of the Chinese market and the S&P500 index shows that the MST structure of the CSI300 index varies more dramatically than the MST structure of the S&P500.

Evaluating Mobile Survey Tools (MSTs) for Field-Level Monitoring and Data Collection: Development of a Novel Evaluation Framework, and Application to MSTs for Rural Water and Sanitation Monitoring

PubMed Central

Fisher, Michael B.; Mann, Benjamin H.; Cronk, Ryan D.; Shields, Katherine F.; Klug, Tori L.; Ramaswamy, Rohit

2016-01-01

Information and communications technologies (ICTs) such as mobile survey tools (MSTs) can facilitate field-level data collection to drive improvements in national and international development programs. MSTs allow users to gather and transmit field data in real time, standardize data storage and management, automate routine analyses, and visualize data. Dozens of diverse MST options are available, and users may struggle to select suitable options. We developed a systematic MST Evaluation Framework (EF), based on International Organization for Standardization/International Electrotechnical Commission (ISO/IEC) software quality modeling standards, to objectively assess MSTs and assist program implementers in identifying suitable MST options. The EF is applicable to MSTs for a broad variety of applications. We also conducted an MST user survey to elucidate needs and priorities of current MST users. Finally, the EF was used to assess seven MSTs currently used for water and sanitation monitoring, as a validation exercise. The results suggest that the EF is a promising method for evaluating MSTs. PMID:27563916

Evaluating Mobile Survey Tools (MSTs) for Field-Level Monitoring and Data Collection: Development of a Novel Evaluation Framework, and Application to MSTs for Rural Water and Sanitation Monitoring.

PubMed

Fisher, Michael B; Mann, Benjamin H; Cronk, Ryan D; Shields, Katherine F; Klug, Tori L; Ramaswamy, Rohit

2016-08-23

Information and communications technologies (ICTs) such as mobile survey tools (MSTs) can facilitate field-level data collection to drive improvements in national and international development programs. MSTs allow users to gather and transmit field data in real time, standardize data storage and management, automate routine analyses, and visualize data. Dozens of diverse MST options are available, and users may struggle to select suitable options. We developed a systematic MST Evaluation Framework (EF), based on International Organization for Standardization/International Electrotechnical Commission (ISO/IEC) software quality modeling standards, to objectively assess MSTs and assist program implementers in identifying suitable MST options. The EF is applicable to MSTs for a broad variety of applications. We also conducted an MST user survey to elucidate needs and priorities of current MST users. Finally, the EF was used to assess seven MSTs currently used for water and sanitation monitoring, as a validation exercise. The results suggest that the EF is a promising method for evaluating MSTs.

CE: Military Sexual Trauma in Male Service Members.

PubMed

Eckerlin, Denise M; Kovalesky, Andrea; Jakupcak, Matthew

2016-09-01

: The experience of military sexual trauma (MST), which can result from assault, battery, or harassment of a sexual nature, may jeopardize the mental health of service members as well as that of their family members, colleagues, and community members. Although a greater proportion of female than male service members are subjected to MST, the Department of Defense estimates that the absolute numbers of affected men and women, across all ranks and branches of military service, are nearly equal because roughly 85% of military members are men. Little research has explored the effects of MST on men. This article discusses the unique ways in which men may experience MST, and examines how social stereotypes of masculinity, myths surrounding sexual assault, and military culture and structure often influence a man's interpretation of an attack and his likelihood of reporting the incident or seeking treatment. It describes current treatments for MST-related mental health conditions and addresses implications for nurses and other health care professionals.

Post-translational regulation of mercaptopyruvate sulfurtransferase via a low redox potential cysteine-sulfenate in the maintenance of redox homeostasis.

PubMed

Nagahara, Noriyuki; Katayama, Akira

2005-10-14

3-Mercaptopyruvate sulfurtransferase (MST) (EC 2.8.1.2), a multifunctional enzyme, catalyzes a transsulfuration from mercaptopyruvate to pyruvate in the degradation process of cysteine. A stoichiometric concentration of hydrogen peroxide and of tetrathionate (S(4)O(6)(2-)) inhibited rat MST (k(i) = 3.3 min(-1), K(i) = 120.5 microM and k(i) = 2.5 min(-1), K(i) = 178.6 microM, respectively). The activity was completely restored by dithiothreitol or thioredoxin with a reducing system containing thioredoxin reductase and NADPH, but glutathione did not restore the activity. On the other hand, an excess molar ratio dose of hydrogen peroxide inactivated MST. Oxidation with a stoichiometric concentration of hydrogen peroxide protected the enzyme against reaction by iodoacetate, which modifies a catalytic Cys(247), suggesting that Cys(247) is a target of the oxidants. A matrix-assisted laser desorption/ionization-time-of-flight mass spectrometric analysis revealed that hydrogen peroxide- and tetrathionate-inhibited MSTs were increased in molecular mass consistent with the addition of atomic oxygen and with a thiosulfate (S(2)O(3)(-)), respectively. Treatment with dithiothreitol restored modified MST to the original mass. These findings suggested that there was no nearby cysteine with which to form a disulfide, and mild oxidation of MST resulted in formation of a sulfenate (SO(-)) at Cys(247), which exhibited exceptional stability and a lower redox potential than that of glutathione. Oxidative stress decreases MST activity so as to increase the amount of cysteine, a precursor of thioredoxin or glutathione, and furthermore, these cellular reductants restore the activity. Thus the redox state regulates MST activity at the enzymatic level, and on the other hand, MST controls redox to maintain cellular redox homeostasis.

Role of cardiac MRI in evaluating patients with Anderson-Fabry disease: assessing cardiac effects of long-term enzyme replacement therapy.

PubMed

Messalli, G; Imbriaco, M; Avitabile, G; Russo, R; Iodice, D; Spinelli, L; Dellegrottaglie, S; Cademartiri, F; Salvatore, M; Pisani, A

2012-02-01

Anderson-Fabry disease is a multisystemic disorder of lipid metabolism secondary to X-chromosome alterations and is frequently associated with cardiac manifestations such as left ventricular (LV) hypertrophy, gradually leading to an alteration in cardiac performance. The purpose of this study was to monitor, using magnetic resonance imaging (MRI), any changes produced by enzyme replacement therapy with agalsidase beta at the cardiac level in patients with Anderson-Fabry disease. Sixteen (ten men, six women) patients with genetically confirmed Anderson-Fabry disease underwent cardiac MRI before starting enzyme replacement therapy (baseline study) and after 48 months of treatment with agalsidase beta at the dose of 1 mg/kg (follow-up study). After 48 months of treatment, a significant reduction in LV mass and wall thickness was observed: 187±59 g vs. 149±44 g, and 16±3 mm vs. 13±3 mm, respectively. A significant reduction in T2 relaxation time was noted at the level of the interventricular septum (81±3 ms vs. 67±7 ms), at the apical level (80±8 ms vs. 63±6 ms) and at the level of the lateral wall (82±8 ms vs. 63±10 ms) (p<0.05). No significant variation was observed in ejection fraction between the two studies (65±3% vs. 64±2%; p>0.05) (mean bias 1.0); however, an improvement was noted in the New York Heart Association (NYHA) class of the majority of patients (12/16) (p<0.05). In patients with Anderson-Fabry disease undergoing enzyme replacement therapy with agalsidase beta, MRI documented a significant reduction in myocardial T2 relaxation time, a significant decrease in maximal myocardial thickness and in total LV mass. MRI did not reveal significant improvements in LV global systolic function; however, improvement in NYHA functional class was noted, consistent with improved diastolic function.

Immunoglobulin G4-related acquired hemophilia: A case report

PubMed Central

Li, Xiaoyan; Duan, Wei; Zhu, Xiang; Xu, Jianying

2016-01-01

Acquired hemophilia A (AHA) is a relatively rare and life-threatening bleeding disorder whose pathogenesis is not completely understood. The present study reports a rare case of immunogubulin (IgG)4-related AHA with multisystemic involvement. A 55-year old male patient presented with symptoms of bronchial asthma and multiple subdermal hematomas. Chest computed tomography showed multiple diffuse nodular lesions with thickening of bronchovascular bundles, and scattered high-density spots in both lung lobes. Laboratory investigations showed increased activated partial prothrombin time (120.0 sec), a markedly decreased factor VIII (FVIII) activity (0.5%), a high-titer of FVIII inhibitor (27.2 Bethesda units/ml) and a marked increase in serum IgG4 (>4.03 g/l) level. Left inguinal lymph node biopsy revealed capsular thickening with marked lymphoplasmacytic infiltration, occlusive phlebitis and irregular fibrosis. Immunostaining revealed numerous IgG4-positive plasma cells (>100 cells/human plasma fibronectin) in the nodular lesions, with an IgG4/IgG ratio of >40%. The symptoms were markedly alleviated following corticosteroid therapy. The current study presents the first reported case of a rare IgG4-related AHA that presented with unusual clinical features and multisystemic involvement. The patient responded well to corticosteroid therapy. Documentation of such rare cases will help in characterizing the pathogenesis, and prompt recognition and timely treatment of this rare disorder. PMID:28105131

Scale free effects in world currency exchange network

NASA Astrophysics Data System (ADS)

Górski, A. Z.; Drożdż, S.; Kwapień, J.

2008-11-01

A large collection of daily time series for 60 world currencies' exchange rates is considered. The correlation matrices are calculated and the corresponding Minimal Spanning Tree (MST) graphs are constructed for each of those currencies used as reference for the remaining ones. It is shown that multiplicity of the MST graphs' nodes to a good approximation develops a power like, scale free distribution with the scaling exponent similar as for several other complex systems studied so far. Furthermore, quantitative arguments in favor of the hierarchical organization of the world currency exchange network are provided by relating the structure of the above MST graphs and their scaling exponents to those that are derived from an exactly solvable hierarchical network model. A special status of the USD during the period considered can be attributed to some departures of the MST features, when this currency (or some other tied to it) is used as reference, from characteristics typical to such a hierarchical clustering of nodes towards those that correspond to the random graphs. Even though in general the basic structure of the MST is robust with respect to changing the reference currency some trace of a systematic transition from somewhat dispersed - like the USD case - towards more compact MST topology can be observed when correlations increase.

Application of electrically invisible antennas to the Modulated Scatterer Technique

DOE PAGES

Crocker, Dylan A.; Donnell, Kristen M.

2015-09-16

The modulated scatterer technique (MST) has shown promise for applications in microwave imaging, electric field mapping, and materials characterization. Traditionally, MST scatterers are dipoles centrally loaded with an element capable of modulation (e.g., a p-i-n diode). By modulating the load element, signals scattered from the MST scatterer are also modulated. However, due to the small size of such scatterers, it can be difficult to reliably detect the modulated signal. Increasing the modulation depth (MD; a parameter related to how well the scatterer modulates the scattered signal) may improve the detectability of the scattered signal. In an effort to improve themore » MD, the concept of electrically invisible antennas is applied to the design of MST scatterers. Our paper presents simulations and measurements of MST scatterers that have been designed to be electrically invisible during the reverse bias state of the modulated element (a p-i-n diode in this case), while producing detectable scattering during the forward bias state (i.e., operate in an electrically visible state). Furthermore, the results using the new design show significant improvement to the MD of the scattered signal as compared with a traditional MST scatterer (i.e., dipole centrally loaded with a p-i-n diode).« less

Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical Guidelines for the Management of Adults with Major Depressive Disorder

PubMed Central

Giacobbe, Peter; Kennedy, Sidney H.; Blumberger, Daniel M.; Daskalakis, Zafiris J.; Downar, Jonathan; Modirrousta, Mandana; Patry, Simon; Vila-Rodriguez, Fidel; Lam, Raymond W.; MacQueen, Glenda M.; Parikh, Sagar V.; Ravindran, Arun V.

2016-01-01

Background: The Canadian Network for Mood and Anxiety Treatments (CANMAT) conducted a revision of the 2009 guidelines by updating the evidence and recommendations. The scope of the 2016 guidelines remains the management of major depressive disorder (MDD) in adults, with a target audience of psychiatrists and other mental health professionals. Methods: Using the question-answer format, we conducted a systematic literature search focusing on systematic reviews and meta-analyses. Evidence was graded using CANMAT-defined criteria for level of evidence. Recommendations for lines of treatment were based on the quality of evidence and clinical expert consensus. “Neurostimulation Treatments” is the fourth of six sections of the 2016 guidelines. Results: Evidence-informed responses were developed for 31 questions for 6 neurostimulation modalities: 1) transcranial direct current stimulation (tDCS), 2) repetitive transcranial magnetic stimulation (rTMS), 3) electroconvulsive therapy (ECT), 4) magnetic seizure therapy (MST), 5) vagus nerve stimulation (VNS), and 6) deep brain stimulation (DBS). Most of the neurostimulation treatments have been investigated in patients with varying degrees of treatment resistance. Conclusions: There is increasing evidence for efficacy, tolerability, and safety of neurostimulation treatments. rTMS is now a first-line recommendation for patients with MDD who have failed at least 1 antidepressant. ECT remains a second-line treatment for patients with treatment-resistant depression, although in some situations, it may be considered first line. Third-line recommendations include tDCS and VNS. MST and DBS are still considered investigational treatments. PMID:27486154

Systemic lupus erythematosus: an update.

PubMed

Golder, Vera; Hoi, Alberta

2017-03-20

Systemic lupus erythematosus (SLE) is a chronic multisystem autoimmune disease predominantly affecting women of childbearing age. New classification criteria for SLE have greater sensitivity and therefore improve the diagnostic certainty for some patients, especially those who may previously have been labelled as having undifferentiated symptoms. Uncontrolled disease activity leads to irreversible end-organ damage, which in turn increases the risk of premature death; early and sustained control of disease activity can usually be achieved by conventional immunosuppressant therapy. The development of biological therapy lags behind that for other rheumatic diseases, with belimumab being the only targeted therapy approved by the Therapeutic Goods Administration. "Treat-to-target" concepts are changing trial design and clinical practice, with evidence-based definition of response criteria in the form of remission and low disease activity now on the horizon. While new therapies are awaited, research should also focus on optimising the use of current therapy and improving the quality of care of patients with SLE.

Effect of Maxing Shigan Tang on H1N1 Influenza A Virus-Associated Acute Lung Injury in Mice.

PubMed

Zhong, Yanchun; Zhou, Jie; Liang, Ning; Liu, Bihao; Lu, Ruirui; He, Yu; Liang, Chunlin; Wu, Junbiao; Zhou, Yuan; Hu, Miaomiao; Zhou, Jiuyao

2016-01-01

This study is aimed at examining the effects of Maxing Shigan Tang (MST) treatment on H1N1-associated acute lung injury (ALI) and exploring the possible mechanism. Mice were randomly divided into a control group, model group, peroxisomal proliferator activator receptor γ (PPARγ) inhibition group (PPARγ-), PPARγ activation group (PPARγ+), and MST group. Influenza A (H1N1) virus of the Fort Monmouth 1 (FM1) strain was used to induce an ALI mice model. Hematoxylin and eosin staining was performed to investigate the effect of MST treatment on H1N1-associated ALI. Cell apoptosis of lung tissues of each group were conducted through transferase-mediated dUTP nick end-labeling methods. Moreover, the expression level of caspase 3, activity of caspase 3, and serum level of tumor necrosis factor (TNF)-α of each group were also analyzed. Finally, quantitative real-time polymerase chain reaction and Western blotting analysis were carried out to detect angiopoietin-like 4 (ANGPTL4) expression level. We found that mice infected with the FM1 strain of H1N1 influenza A virus developed severe ALI, and MST could improve H1N1-induced ALI. Moreover, MST decreased lung cell apoptosis and reduced the serum content of TNF-α. In addition, MST significantly induced the ANGPTL4 expression in H1N1-induced ALI. MST improves H1N1-associated ALI maybe through targeting ANGPTL4 in mice. © 2017 S. Karger AG, Basel.

Is military sexual trauma associated with trading sex among women veterans seeking outpatient mental health care?

PubMed

Strauss, Jennifer L; Marx, Christine E; Weitlauf, Julie C; Stechuchak, Karen M; Straits-Troster, Kristy; Worjoloh, Ayaba W; Sherrod, Christina B; Olsen, Maren K; Butterfield, Marian I; Calhoun, Patrick S

2011-01-01

A robust association between sexual trauma and trading sex has been documented in civilian samples but has not been examined in veterans. Women veterans experience high rates of sexual victimization across the lifespan, including during military service (military sexual trauma [MST]). Associations between MST and trading sex were examined in 200 women enrolled in a crosssectional study of HIV risks and seroprevalence among women receiving outpatient mental health care at a Veterans Affairs (VA) medical center. Each woman completed an assessment interview composed of validated measures that queried childhood sexual trauma; substance use; and risk behaviors, including trading sex for money, drugs, shelter, food, or other things. History of MST was derived from mandated VA screening results and chart notes. Overall, 19.7% reported a history of trading sex. Those who reported trading sex had a higher rate of MST than those who did not report trading sex (87.2% vs. 62.9%, respectively). A multivariable logistic regression model examined the relationship between trading sex and MST, controlling a priori for substance abuse and childhood sexual trauma (both associated with trading sex in civilian samples) and education, which was associated with trading sex in our sample. In this adjusted model, MST was associated with trading sex: odds ratio = 3.26, p = .025, 95% confidence interval = [1.16, 9.18]. To our knowledge, this is the 1st report of an association between MST and trading sex. Results extend previously observed associations between sexual trauma and trading sex in civilian cohorts and underscore the pernicious influence of sexual victimization across the lifespan.

Associations of military sexual trauma, combat exposure, and number of deployments with physical and mental health indicators in Iraq and Afghanistan veterans.

PubMed

Godfrey, Kathryn M; Mostoufi, Sheeva; Rodgers, Carie; Backhaus, Autumn; Floto, Elizabeth; Pittman, James; Afari, Niloofar

2015-11-01

Trauma exposure (TE) and numerous deployments have been associated with negative health outcomes in veterans, many of whom have military sexual trauma (MST) and combat exposure (CE). The aims of this study were to examine the relationships between physical and mental health symptoms with MST and CE and number of deployments. Iraq and Afghanistan veterans at the Veterans Affairs San Diego Healthcare System completed self-report measures for MST, CE, number of deployments, posttraumatic stress disorder (PTSD) symptoms, depression symptoms, alcohol use, somatic symptoms, health functioning, and body mass index (BMI). Regression analyses examined main and interaction effects of CE and MST and the linear and quadratic trends of number of deployments. The sample (N = 1,294) had a mean age of 31 and was 85% male. The MST by CE interaction on BMI was significant (p = .005), such that MST was associated with lower BMI in veterans with CE and with higher BMI in veterans without CE. MST and CE were associated with higher somatic, PTSD, and depression symptoms and with lower mental health functioning (ps < .001 to .002). CE was associated with lower physical health functioning and higher alcohol use (ps < .001 to .025). Number of deployments was linearly related to higher BMI (p = .004) and had a quadratic association with alcohol use (p = .008). Findings highlight the relationship between TE and poor health outcomes and the need to further study the mechanisms of TE on physical and mental health. (c) 2015 APA, all rights reserved).

Multi-system verification of registrations for image-guided radiotherapy in clinical trials.

PubMed

Cui, Yunfeng; Galvin, James M; Straube, William L; Bosch, Walter R; Purdy, James A; Li, X Allen; Xiao, Ying

2011-09-01

To provide quantitative information on the image registration differences from multiple systems for image-guided radiotherapy (IGRT) credentialing and margin reduction in clinical trials. Images and IGRT shift results from three different treatment systems (Tomotherapy Hi-Art, Elekta Synergy, Varian Trilogy) have been sent from various institutions to the Image-Guided Therapy QA Center (ITC) for evaluation for the Radiation Therapy Oncology Group (RTOG) trials. Nine patient datasets (five head-and-neck and four prostate) were included in the comparison, with each patient having 1-4 daily individual IGRT studies. In all cases, daily shifts were re-calculated by re-registration of the planning CT with the daily IGRT data using three independent software systems (MIMvista, FocalSim, VelocityAI). Automatic fusion was used in all calculations. The results were compared with those submitted from institutions. Similar regions of interest (ROIs) and same initial positions were used in registrations for inter-system comparison. Different slice spacings for CBCT sampling and different ROIs for registration were used in some cases to observe the variation of registration due to these factors. For the 54 comparisons with head-and-neck datasets, the absolute values of differences of the registration results between different systems were 2.6±2.1 mm (mean±SD; range 0.1-8.6 mm, left-right [LR]), 1.7±1.3 mm (0.0-4.9 mm, superior-inferior [SI]), and 1.8±1.1 mm (0.1-4.0 mm, anterior-posterior [AP]). For the 66 comparisons in prostate cases, the differences were 1.1±1.0 mm (0.0-4.6 mm, LR), 2.1±1.7 mm (0.0-6.6 mm, SI), and 2.0±1.8 mm (0.1-6.9 mm, AP). The differences caused by the slice spacing variation were relatively small, and the different ROI selections in FocalSim and MIMvista also had limited impact. The extent of differences was reported when different systems were used for image registration. Careful examination and quality assurance of the image registration process

Differential Risk for Homelessness Among US Male and Female Veterans With a Positive Screen for Military Sexual Trauma.

PubMed

Brignone, Emily; Gundlapalli, Adi V; Blais, Rebecca K; Carter, Marjorie E; Suo, Ying; Samore, Matthew H; Kimerling, Rachel; Fargo, Jamison D

2016-06-01

Military sexual trauma (MST) is associated with adverse physical and mental health outcomes following military separation. Recent research suggests that MST may be a determinant in several factors associated with postdeployment homelessness. To evaluate MST as an independent risk factor for homelessness and to determine whether risk varies by sex. A retrospective cohort study of US veterans who used Veterans Health Administration (VHA) services between fiscal years 2004 and 2013 was conducted using administrative data from the Department of Defense and VHA. Included in the study were 601 892 US veterans deployed in Iraq or Afghanistan who separated from the military between fiscal years 2001 and 2011 and subsequently used VHA services. Positive response to screen for MST administered in VHA facilities. Administrative evidence of homelessness within 30 days, 1 year, and 5 years following the first VHA encounter after last deployment. The mean (SD) age of the 601 892 participants was 38.9 (9.4) years, 527 874 (87.7%) were male, 310 854 (51.6%) were white, and 382 361 (63.5%) were enlisted in the Army. Among veterans with a positive screen for MST, rates of homelessness were 1.6% within 30 days, 4.4% within 1 year, and 9.6% within 5 years, more than double the rates of veterans with a negative MST screen (0.7%, 1.8%, and 4.3%, respectively). A positive screen for MST was significantly and independently associated with postdeployment homelessness. In regression models adjusted for demographic and military service characteristics, odds of experiencing homelessness were higher among those who screened positive for MST compared with those who screened negative (30-day: adjusted odds ratio [AOR], 1.89; 95% CI, 1.58-2.24; 1-year: AOR, 2.27; 95% CI, 2.04-2.53; and 5-year: AOR, 2.63; 95% CI, 2.36-2.93). Military sexual trauma screen status remained independently associated with homelessness after adjusting for co-occurring mental health and substance abuse diagnoses

Advances in the diagnosis and treatment of cystic fibrosis.

PubMed

Martiniano, Stacey L; Hoppe, Jordana E; Sagel, Scott D; Zemanick, Edith T

2014-08-01

CF is a genetic, life-shortening, multisystem disease that is most commonly diagnosed through newborn screen performed in all 50 states in the United States. In the past, therapies for CF lung disease have primarily targeted the downstream effects of a dysfunctional CFTR protein. Newer CFTR modulator therapies, targeting the basic defect in CF, are available for a limited group of people with CF, and offer the hope of improved treatment options for many more people with CF in the near future. Best practice is directed by consensus clinical care guidelines from the CFF and is provided with a multidisciplinary approach by the team at the CF care center and the primary care office.

Therapeutic effects of maximal strength training on walking efficiency in patients with schizophrenia - a pilot study.

PubMed

Heggelund, Jørn; Morken, Gunnar; Helgerud, Jan; Nilsberg, Geir E; Hoff, Jan

2012-07-03

Patients with schizophrenia frequently have disabling gait deficits. The net mechanical efficiency of walking (ϵnet) is an accurate measure often used to evaluate walking performance. Patients with gait deficits have a reduced ϵnet with excessive energy expenditure during sub-maximal walking. Maximal strength training (MST) improves ϵnet in healthy individuals and is associated with reduced risk of mortality. The aim of this study was to investigate whether MST improves ϵnet in patients with schizophrenia. Patients (ICD-10 schizophrenia, schizotypal or delusional disorders (F20-F29)) were included in a non-randomized trial. Patients were assigned to one of two groups: 1) MST consisting of 4x4 repetitions at 85-90% one repetition maximum (1RM) performed in a leg press apparatus or 2) playing computer games (CG). Both groups carried out their activity three days per week for eight weeks. 1RM, ϵnet at 60 watt walking, peak oxygen uptake (VO2peak), the Positive and Negative Syndrome Scale (PANSS) and the 36-items short form (SF-36) were measured pre and post intervention. The baseline ϵnet was 17.3 ± 1.2% and 19.4 ± 3.0% in the MST (n = 6) and CG groups (n = 7), respectively, which is categorized as mechanical inefficiency. The MST group improved 1RM by 79 kg (p = 0.006) and ϵnet by 3.4% (p = 0.046) more than the CG group. The MST group improved 1RM and ϵnet, by a mean of 83 kg (p = 0.028) and 3.4% (p = 0.028), respectively. VO2peak at baseline was 34.2 ± 10.2 and 38.3 ± 9.8 ml·kg-1·min-1 in the MST and CG groups, respectively, and did not change (p > 0.05). No change was observed in PANSS or SF-36 (p > 0.05). MST improves 1RM and ϵnet in patients with schizophrenia. MST could be used as a therapeutic intervention for patients with schizophrenia to normalize their reduced ϵnet.

Neuromodulation for mood and memory: from the engineering bench to the patient bedside

PubMed Central

Deng, Zhi-De; McClintock, Shawn M.; Oey, Nicodemus E.; Luber, Bruce; Lisanby, Sarah H.

2014-01-01

Brain stimulation, in the form of electroconvulsive therapy (ECT), has long been a gold standard treatment for depression, but today, the field of neuromodulation is rapidly changing with the advent of newer and more precise tools to alter neuroplasticity and to treat brain-based disorders. Now there are new means to induce focal seizures, as with magnetic seizure therapy (MST), or modifications to ECT. There are also surgical approaches to target brain circuits via implanted stimulators placed in the brain or on cranial nerves. Finally, there are noninvasive subconvulsive approaches for the transcranial application of either electric or magnetic fields. Collectively, these tools have transformed the face of neurotherapeutics and informed our understanding of the brain basis of complex neurobehavioral conditions. PMID:25222617

Disentangling neural processes of egocentric and allocentric mental spatial transformations using whole-body photos of self and other.

PubMed

Ganesh, Shanti; van Schie, Hein T; Cross, Emily S; de Lange, Floris P; Wigboldus, Daniël H J

2015-08-01

Mental imagery of one's body moving through space is important for imagining changing visuospatial perspectives, as well as for determining how we might appear to other people. Previous neuroimaging research has implicated the temporoparietal junction (TPJ) in this process. It is unclear, however, how neural activity in the TPJ relates to the rotation perspectives from which mental spatial transformation (MST) of one's own body can take place, i.e. from an egocentric or an allocentric perspective. It is also unclear whether TPJ involvement in MST is self-specific or whether the TPJ may also be involved in MST of other human bodies. The aim of the current study was to disentangle neural processes involved in egocentric versus allocentric MSTs of human bodies representing self and other. We measured functional brain activity of healthy participants while they performed egocentric and allocentric MSTs in relation to whole-body photographs of themselves and a same-sex stranger. Findings indicated higher blood oxygen level-dependent (BOLD) response in bilateral TPJ during egocentric versus allocentric MST. Moreover, BOLD response in the TPJ during egocentric MST correlated positively with self-report scores indicating how awkward participants felt while viewing whole-body photos of themselves. These findings considerably advance our understanding of TPJ involvement in MST and its interplay with self-awareness. Copyright © 2015 Elsevier Inc. All rights reserved.

Corticotherapy vs. Corticotherapy Plus Immunosuppressive Therapy in Acute Vogt-Koyanagi-Harada Disease.

PubMed

Concha-Del Río, L E; Gómez, L; Arellanes-García, L

2018-05-01

Vogt-Koyanagi-Harada disease is a multisystem disorder characterized by a bilateral granulomatous panuveitis. Multiple therapeutic regimens have been used to control inflammation in acute uveitic stage to prevent irreversible visual loss. The purpose of this paper is to compare the effect, on functional and anatomic outcomes, of early treatment with standard corticotherapy vs. corticotherapy plus immunosuppressive (IMT) therapy in acute Vogt-Koyanagi-Harada disease (Group A vs Group B). A retrospective chart review of patients with Vogt-Koyanagi-Harada disease, with an evolution time of 2 weeks or less, who attended the Inflammatory Eye Disease Clinic, from 2001 to 2015. Data collected included demographic information, presenting features, treatment and improvement in visual acuity (VA). Sixteen charts were reviewed; 15 females (93.75%). Mean age: 30.81±10.53 years, follow-up time (months): 54.94±43.43. Ten patients (66.6%) had IMT, azathioprine, methotrexate and cyclophosphamide. In group A, initial VA<20/200 in 66.7%; final VA was ≥20/40 in 9 eyes (75%). In group B, initial VA<20/200 in 65%; final VA≥20/40 in 15 eyes (75%). In group A, VA improved faster at one and 3 months (ANOVA P<.057). Clinical characteristics in convalescent stage and complications were similar. Anterior chamber recurrences occurred in both groups and posterior pole recurrences were observed in group A. Time to first recurrence was similar (P<.279). Frequency of recurrence was 2.33±1.80 vs 1.5±0.79 (P<.01). At recurrence 15 patients were still having oral steroids, nine in group A, 6 in Group B. In group A, prednisone was given during more time: mean 15.17±12.08 months, and time to reach to 10mg dose was longer: 8.60±11.7 (P<.008 and P<.046). Adding IMT as first line therapy to corticosteroids, do not matter significantly in terms of final VA or development of visually significant complications. In the IMT plus corticosteroids group number of recurrences was significantly lower

Therapeutic options for lymphangioleiomyomatosis (LAM): where we are and where we are going

PubMed Central

Steagall, Wendy K; Moss, Joel

2009-01-01

Lymphangioleiomyomatosis (LAM), a multisystem disease affecting predominantly premenopausal and middle-aged women, causes progressive respiratory failure due to cystic lung destruction and is associated with lymphatic and kidney tumors. In the past, the treatment of LAM comprised exclusively anti-estrogen and related hormonal therapies. These treatments, however, have not been proven effective. In this article, we discuss new findings regarding the molecular mechanisms involved in the regulation of LAM cell growth, which may offer opportunities to develop effective and targeted therapeutic agents. PMID:20948684

Mobile Multi-System Overview

NASA Technical Reports Server (NTRS)

Witoff, Robert J.; Doody, David F.

2012-01-01

At the time of this reporting, there are 2,589 rich mobile devices used at JPL, including 1,550 iPhones and 968 Blackberrys. Considering a total JPL population of 5,961 employees, mobile applications have a total addressable market of 43 percent of the employees at JPL, and that number is rising. While it was found that no existing desktop tools can realistically be replaced by a mobile application, there is certainly a need to improve access to these desktop tools. When an alarm occurs and an engineer is away from his desk, a convenient means of accessing relevant data can save an engineer a great deal of time and improve his job efficiency. To identify which data is relevant, an engineer benefits from a succinct overview of the data housed in 13+ tools. This need can be well met by a single, rich, mobile application that provides access to desired data across tools in the ops infrastructure.

Neuromagnetic beta and gamma oscillations in the somatosensory cortex after music training in healthy older adults and a chronic stroke patient.

PubMed

Jamali, Shahab; Fujioka, Takako; Ross, Bernhard

2014-06-01

Extensive rehabilitation training can lead to functional improvement even years after a stroke. Although neuronal plasticity is considered as a main origin of such ameliorations, specific subtending mechanisms need further investigation. Our aim was to obtain objective neuromagnetic measures sensitive to brain reorganizations induced by a music-supported training. We applied 20-Hz vibrotactile stimuli to the index finger and the ring finger, recorded somatosensory steady-state responses with magnetoencephalography, and analyzed the cortical sources displaying oscillations synchronized with the external stimuli in two groups of healthy older adults before and after musical training or without training. In addition, we applied the same analysis for an anecdotic report of a single chronic stroke patient with hemiparetic arm and hand problems, who received music-supported therapy (MST). Healthy older adults showed significant finger separation within the primary somatotopic map. Beta dipole sources were more anterior located compared to gamma sources. An anterior shift of sources and increases in synchrony between the stimuli and beta and gamma oscillations were observed selectively after music training. In the stroke patient a normalization of somatotopic organization was observed after MST, with digit separation recovered after training and stimulus induced gamma synchrony increased. The proposed stimulation paradigm captures the integrity of primary somatosensory hand representation. Source position and synchronization between the stimuli and gamma activity are indices, sensitive to music-supported training. Responsiveness was also observed in a chronic stroke patient, encouraging for the music-supported therapy. Notably, changes in somatosensory responses were observed, even though the therapy did not involve specific sensory discrimination training. The proposed protocol can be used for monitoring changes in neuronal organization during training and will improve

Artificial Gravity: Will it Preserve Bone Health on Long-Duration Missions?

NASA Technical Reports Server (NTRS)

Davis-Street, Janis; Paloski, William H.

2005-01-01

Prolonged microgravity exposure disrupts bone, muscle, and cardiovascular homeostasis, sensory-motor coordination, immune function, and behavioral performance. Bone loss, in particular, remains a serious impediment to the success of exploration-class missions by increasing the risks of bone fracture and renal stone formation for crew members. Current countermeasures, consisting primarily of resistive and aerobic exercise, have not yet proven fully successful for preventing bone loss during long-duration spaceflight. While other bone-specific countermeasures, such as pharmacological therapy and dietary modifications, are under consideration, countermeasure approaches that simultaneously address multiple physiologic systems may be more desirable for exploration-class missions, particularly if they can provide effective protection at reduced mission resource requirements (up-mass, power, crew time, etc). The most robust of the multi-system approaches under consideration, artificial gravity (AG), could prevent all of the microgravity-related physiological changes from occurring. The potential methods for realizing an artificial gravity countermeasure are reviewed, as well as selected animal and human studies evaluating the effects of artificial gravity on bone function. Future plans for the study of the multi-system effects of artificial gravity include a joint, cooperative international effort that will systematically seek an optimal prescription for intermittent AG to preserve bone, muscle, and cardiovascular function in human subjects deconditioned by 6 degree head-down-tilt-bed rest. It is concluded that AG has great promise as a multi-system countermeasure, but that further research is required to determine the appropriate parameters for implementation of such a countermeasure for exploration-class missions.

Fresh frozen plasma resuscitation attenuates platelet dysfunction compared with normal saline in a large animal model of multisystem trauma.

PubMed

Sillesen, Martin; Johansson, Pär I; Rasmussen, Lars S; Jin, Guang; Jepsen, Cecilie H; Imam, Ayesha; Hwabejire, John O; Deperalta, Danielle; Duggan, Michael; DeMoya, Marc; Velmahos, George C; Alam, Hasan B

2014-04-01

Platelet dysfunction following trauma has been identified as an independent predictor of mortality. We hypothesized that fresh frozen plasma (FFP) resuscitation would attenuate platelet dysfunction compared with 0.9% normal saline (NS). Twelve swine were subjected to multisystem trauma (traumatic brain injury, liver injury, rib fracture, and soft tissue injury) with hemorrhagic shock (40% of estimated blood volume). Animals were left in shock (mean arterial pressure, 30-35 mm Hg) for 2 hours followed by resuscitation with three times shed volume NS (n = 6) or one times volume FFP (n = 6) and monitored for 6 hours. Platelet function was assessed by adenosine diphosphate (ADP)-induced platelet aggregation at baseline, after 2 hours of shock following resuscitation, and 6 hours after resuscitation. Fibrinogen levels and markers of platelet activation (transforming growth factor β [TGF-β], sP-Selectin, and CD40L) as well as endothelial injury (intercellular adhesion molecule 1 [ICAM-1], vascular cell adhesion molecule 1 [VCAM-1]) were also assayed. Thromboelastography was used to measure clotting activity. ADP-induced platelet aggregation was significantly higher in the FFP group (46.3 U vs. 25.5 U, p < 0.01) following resuscitation. This was associated with higher fibrinogen levels (202 mg/dL vs. 80 mg/dL, p < 0.01) but lower endothelial activation (VCAM-1, 1.25 ng/mL vs. 3.87 ng/mL, p = 0.05). Other markers did not differ.After 6 hours of observation, ADP-induced platelet aggregation remained higher in the FFP group (53.8 U vs. 37.0 U, p = 0.03) as was fibrinogen levels (229 mg/dL vs. 153 mg/dL, p < 0.01). Endothelial activation was lower (ICAM-1, 21.0 ng/mL vs. 24.4 ng/mL, p = 0.05), whereas TGF-β levels were higher (2,138 pg/mL vs. 1,802 pg/mL, p = 0.03) in the FFP group. Other markers did not differ. Thromboelastography revealed increased clot strength in the FFP group at both postresuscitation time points. Resuscitation with FFP resulted in an immediate and

The efficacy of prospective memory rehabilitation plus metacognitive skills training for adults with traumatic brain injury: study protocol for a randomized controlled trial.

PubMed

Fleming, Jennifer; Ownsworth, Tamara; Doig, Emmah; Hutton, Lauren; Griffin, Janelle; Kendall, Melissa; Shum, David H K

2017-01-05

Impairment of prospective memory (PM) is common following traumatic brain injury (TBI) and negatively impacts on independent living. Compensatory approaches to PM rehabilitation have been found to minimize the impact of PM impairment in adults with TBI; however, poor self-awareness after TBI poses a major barrier to the generalization of compensatory strategies in daily life. Metacognitive skills training (MST) is a cognitive rehabilitation approach that aims to facilitate the development of self-awareness in adults with TBI. This paper describes the protocol of a study that aims to evaluate the efficacy of a MST approach to compensatory PM rehabilitation for improving everyday PM performance and psychosocial outcomes after TBI. This randomized controlled trial has three treatment groups: compensatory training plus metacognitive skills training (COMP-MST), compensatory training only (COMP), and waitlist control. Participants in the COMP-MST and COMP groups will complete a 6-week intervention consisting of six 2-h weekly training sessions. Each 1.5-h session will involve compensatory strategy training and 0.5 h will incorporate either MST (COMP-MST group) or filler activity as an active control (COMP group). Participants in the waitlist group receive care as usual for 6 weeks, followed by the COMP-MST intervention. Based on the sample size estimate, 90 participants with moderate to severe TBI will be randomized into the three groups using a stratified sampling approach. The primary outcomes include measures of PM performance in everyday life and level of psychosocial reintegration. Secondary outcomes include measures of PM function on psychometric testing, strategy use, self-awareness, and level of support needs following TBI. Blinded assessments will be conducted pre and post intervention, and at 3-month and 6-month follow-ups. This study seeks to determine the efficacy of COMP-MST for improving and maintaining everyday PM performance and level of psychosocial

A Methodology for the Integration of a Mechanistic Source Term Analysis in a Probabilistic Framework for Advanced Reactors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Grabaskas, Dave; Brunett, Acacia J.; Bucknor, Matthew

GE Hitachi Nuclear Energy (GEH) and Argonne National Laboratory are currently engaged in a joint effort to modernize and develop probabilistic risk assessment (PRA) techniques for advanced non-light water reactors. At a high level, the primary outcome of this project will be the development of next-generation PRA methodologies that will enable risk-informed prioritization of safety- and reliability-focused research and development, while also identifying gaps that may be resolved through additional research. A subset of this effort is the development of PRA methodologies to conduct a mechanistic source term (MST) analysis for event sequences that could result in the release ofmore » radionuclides. The MST analysis seeks to realistically model and assess the transport, retention, and release of radionuclides from the reactor to the environment. The MST methods developed during this project seek to satisfy the requirements of the Mechanistic Source Term element of the ASME/ANS Non-LWR PRA standard. The MST methodology consists of separate analysis approaches for risk-significant and non-risk significant event sequences that may result in the release of radionuclides from the reactor. For risk-significant event sequences, the methodology focuses on a detailed assessment, using mechanistic models, of radionuclide release from the fuel, transport through and release from the primary system, transport in the containment, and finally release to the environment. The analysis approach for non-risk significant event sequences examines the possibility of large radionuclide releases due to events such as re-criticality or the complete loss of radionuclide barriers. This paper provides details on the MST methodology, including the interface between the MST analysis and other elements of the PRA, and provides a simplified example MST calculation for a sodium fast reactor.« less

Six-minute Stepper Test to Set Pulmonary Rehabilitation Intensity in Patients with COPD - A Retrospective Study.

PubMed

Bonnevie, Tristan; Gravier, Francis-Edouard; Leboullenger, Marie; Médrinal, Clément; Viacroze, Catherine; Cuvelier, Antoine; Muir, Jean-François; Tardif, Catherine; Debeaumont, David

2017-06-01

Pulmonary rehabilitation (PR) improves outcomes in patients with chronic obstructive pulmonary disease (COPD). Optimal assessment includes cardiopulmonary exercise testing (CPET), but consultations are limited. Field tests could be used to individualize PR instead of CPET. The six-minute stepper test (6MST) is easy to set up and its sensitivity and reproducibility have previously been reported in patients with COPD. The aim of this study was to develop a prediction equation to set intensity in patients attending PR, based on the 6MST. The following relationships were analyzed: mean heart rate (HR) during the first (HR 1-3 ) and last (HR 4-6 ) 3 minutes of the 6MST and HR at the ventilatory threshold (HRvt) from CPET; step count at the end of the 6MST and workload at the Ventilatory threshold (VT) (Wvt); and forced expiratory volume in 1 second and step count during the 6MST. This retrospective study included patients with COPD referred for PR who underwent CPET, pulmonary function evaluations and the 6MST. Twenty-four patients were included. Prediction equations were HRvt = 0.7887 × HR 1-3 + 20.83 and HRvt = 0.6180 × HR 4-6 + 30.77. There was a strong correlation between HR 1-3 and HR 4-6 and HRvt (r = 0.69, p < 0.001 and r = 0.57, p < 0.01 respectively). A significant correlation was also found between step count and LogWvt (r = 0.63, p < 0.01). The prediction equation was LogWvt = 0.001722 × step count + 1.248. The 6MST could be used to individualize aerobic training in patients with COPD. Further prospective studies are needed to confirm these results.

Application of electrically invisible antennas to the modulated scatterer technique

NASA Astrophysics Data System (ADS)

Crocker, Dylan Andrew

The Modulated Scatterer Technique (MST) has shown promise for applications in microwave imaging, electric field mapping, and materials characterization. Traditionally, MST scatterers consist of dipole antennas centrally loaded with a lumped element capable of modulation (commonly a PIN diode). By modulating the load element, the signal scattered from the MST scatterer is also modulated. However, due to the small size of such scatterers, it can be difficult to reliably detect the modulated signal. Increasing the modulation depth (a parameter related to how well the scatterer modulates the scattered signal) may improve the detectability of the scattered signal. In an effort to improve the modulation depth of scatterers commonly used in MST, the concept of electrically invisible antennas is applied to the design of these scatterers and is the focus of this work. Electrical invisibility of linear antennas, such as loaded dipoles, can be achieved by loading a scatterer in such a way that, when illuminated by an electromagnetic wave, the integral of the current induced along the length of the scatterer (and hence the scattered field as well) approaches zero. By designing a scatterer to be capable of modulation between visible (scattering) and invisible (minimum scattering) states, the modulation depth may be improved. This thesis presents simulations and measurements of new MST scatterers that have been designed to be electrically invisible during the reverse bias state of the modulated element (i.e., a PIN diode). Further, the scattering during the forward bias state remains the same as that of a traditional MST scatterer, resulting in an increase in modulation depth. This new MST scatterer design technique may also have application in improving the performance of similar sensors such as radio frequency identification (RFID) tags.

Military sexual trauma is associated with post-deployment eating disorders among Afghanistan and Iraq veterans.

PubMed

Blais, Rebecca K; Brignone, Emily; Maguen, Shira; Carter, Marjorie E; Fargo, Jamison D; Gundlapalli, Adi V

2017-07-01

Evaluate the association of military sexual trauma (MST) screen status with eating disorder diagnoses among veterans within 1- and 5-years after initiating Veterans Health Administration (VHA) care, and whether the association varied by sex. Retrospective cohort study of US Afghanistan/Iraq veterans who used VHA services between FY 2004 and 2014 (N = 595,525). This study used VHA administrative data to assess the presence of eating disorder diagnoses in medical records within 1- and 5-years of initiating VHA care, and whether a positive screen for MST was associated with eating disorders. Three percent (n = 18,488) screened positive for MST. At 1- and 5-year follow up, 0.1% (n= 513, 74% female), and 0.2% (n = 504, 71% female) were diagnosed with an eating disorder, respectively. In regression models adjusted for demographic variables, military service, and psychiatric comorbidities, the presence of an eating disorder diagnosis was nearly two times higher among those with a positive screen for MST in the 1-year (adjusted odds ratio [AOR] = 1.94, 95% confidence interval [CI] = 1.57-2.40) and 5-year (AOR = 1.86, 95%CI = 1.49-2.32) cohorts. The increased likelihood conferred by MST for an eating disorder diagnosis was differentially stronger among male veterans than female veterans in the 1-year cohort only (AOR = 2.13, 95%CI = 1.01-4.50). Veterans with a positive screen for MST, especially male veterans, had a nearly two-fold increased likelihood of having an eating disorder diagnosis. Screening for eating disorders may be important in both male and female veterans who report MST. © 2017 Wiley Periodicals, Inc.

Nuclear criticality safety bounding analysis for the in-tank-precipitation (ITP) process, impacted by fissile isotopic weight fractions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bess, C.E.

The In-Tank Precipitation process (ITP) receives High Level Waste (HLW) supernatant liquid containing radionuclides in waste processing tank 48H. Sodium tetraphenylborate, NaTPB, and monosodium titanate (MST), NaTi{sub 2}O{sub 5}H, are added for removal of radioactive Cs and Sr, respectively. In addition to removal of radio-strontium, MST will also remove plutonium and uranium. The majority of the feed solutions to ITP will come from the dissolution of supernate that had been concentrated by evaporation to a crystallized salt form, commonly referred to as saltcake. The concern for criticality safety arises from the adsorption of U and Pt onto MST. If sufficientmore » mass and optimum conditions are achieved then criticality is credible. The concentration of u and Pt from solution into the smaller volume of precipitate represents a concern for criticality. This report supplements WSRC-TR-93-171, Nuclear Criticality Safety Bounding Analysis For The In-Tank-Precipitation (ITP) Process. Criticality safety in ITP can be analyzed by two bounding conditions: (1) the minimum safe ratio of MST to fissionable material and (2) the maximum fissionable material adsorption capacity of the MST. Calculations have provided the first bounding condition and experimental analysis has established the second. This report combines these conditions with canyon facility data to evaluate the potential for criticality in the ITP process due to the adsorption of the fissionable material from solution. In addition, this report analyzes the potential impact of increased U loading onto MST. Results of this analysis demonstrate a greater safety margin for ITP operations than the previous analysis. This report further demonstrates that the potential for criticality in the ITP process due to adsorption of fissionable material by MST is not credible.« less

Contraceptive Provision in the VA Healthcare System to Women Who Report Military Sexual Trauma

PubMed Central

Mattocks, Kristin; Schwarz, Eleanor Bimla; Borrero, Sonya; Skanderson, Melissa; Zephyrin, Laurie; Brandt, Cynthia; Haskell, Sally

2014-01-01

Abstract Background: Women Veterans who suffered military sexual trauma (MST) may be at high risk for unintended pregnancy and benefit from contraceptive services. The objective of this study is to compare documented provision of contraceptives to women Veterans using the Department of Veterans Affairs (VA) health system who report or deny MST. Methods: This retrospective cohort study included women Veterans aged 18–45 years who served in Operation Enduring or Iraqi Freedom and had at least one visit to a VA medical center between 2002 and 2010. Data were obtained from VA administrative and clinical databases. Chi-squared tests and logistic regression were conducted to evaluate the association between MST, ascertained by routine clinical screening, and first documented receipt of hormonal or long-acting contraception. Results: Of 68,466 women Veterans, 13% reported, 59% denied and 28% had missing data for the MST screen. Among the entire study cohort, 30% of women had documented receipt of a contraceptive method. Women reporting MST were significantly more likely than those denying MST to receive a method of contraception (adjusted odds ratio [aOR] 1.12, 95% confidence interval [CI] 1.07–1.18) including an intrauterine device (odds ratio [OR] 1.29, 95% CI 1.17–1.41) or contraceptive injection (OR 1.17, 95% CI 1.05–1.29). Women who were younger, unmarried, seen at a women's health clinic, or who had more than one visit were more likely to receive contraception. Conclusions: A minority of women Veterans of reproductive age receive contraceptive services from the VA. Women Veterans who report MST, and particularly those who seek care at VA women's health clinics, are more likely to receive contraception. PMID:24787680

Prediction of Cardiorespiratory Fitness by the Six-Minute Step Test and Its Association with Muscle Strength and Power in Sedentary Obese and Lean Young Women: A Cross-Sectional Study

PubMed Central

Bonjorno Junior, José Carlos; de Oliveira, Cláudio Ricardo; Luporini, Rafael Luís; Mendes, Renata Gonçalves; Zangrando, Katiany Thais Lopes; Trimer, Renata; Arena, Ross

2015-01-01

Impaired cardiorespiratory fitness (CRF) is a hallmark characteristic in obese and lean sedentary young women. Peak oxygen consumption (VO2peak) prediction from the six-minute step test (6MST) has not been established for sedentary females. It is recognized that lower-limb muscle strength and power play a key role during functional activities. The aim of this study was to investigate cardiorespiratory responses during the 6MST and CPX and to develop a predictive equation to estimate VO2peak in both lean and obese subjects. Additionally we aim to investigate how muscle function impacts functional performance. Lean (LN = 13) and obese (OB = 18) women, aged 20–45, underwent a CPX, two 6MSTs, and isokinetic and isometric knee extensor strength and power evaluations. Regression analysis assessed the ability to predict VO2peak from the 6MST, age and body mass index (BMI). CPX and 6MST main outcomes were compared between LN and OB and correlated with strength and power variables. CRF, functional capacity, and muscle strength and power were lower in the OB compared to LN (<0.05). During the 6MST, LN and OB reached ~90% of predicted maximal heart rate and ~80% of the VO2peak obtained during CPX. BMI, age and number of step cycles (NSC) explained 83% of the total variance in VO2peak. Moderate to strong correlations between VO2peak at CPX and VO2peak at 6MST (r = 0.86), VO2peak at CPX and NSC (r = 0.80), as well as between VO2peak, NSC and muscle strength and power variables were found (p<0.05). These findings indicate the 6MST, BMI and age accurately predict VO2peak in both lean and obese young sedentary women. Muscle strength and power were related to measures of aerobic and functional performance. PMID:26717568

Improvement of 10-km time-trial cycling with motivational self-talk compared with neutral self-talk.

PubMed

Barwood, Martin J; Corbett, Jo; Wagstaff, Christopher R D; McVeigh, Dan; Thelwell, Richard C

2015-03-01

Unpleasant physical sensations during maximal exercise may manifest themselves as negative cognitions that impair performance, alter pacing, and are linked to increased rating of perceived exertion (RPE). This study examined whether motivational self-talk (M-ST) could reduce RPE and change pacing strategy, thereby enhancing 10-km time-trial (TT) cycling performance in contrast to neutral self-talk (N-ST). Fourteen men undertook 4 TTs, TT1-TT4. After TT2, participants were matched into groups based on TT2 completion time and underwent M-ST (n=7) or N-ST (n=7) after TT3. Performance, power output, RPE, and oxygen uptake (VO2) were compared across 1-km segments using ANOVA. Confidence intervals (95%CI) were calculated for performance data. After TT3 (ie, before intervention), completion times were not different between groups (M-ST, 1120±113 s; N-ST, 1150±110 s). After M-ST, TT4 completion time was faster (1078±96 s); the N-ST remained similar (1165±111 s). The M-ST group achieved this through a higher power output and VO2 in TT4 (6th-10th km). RPE was unchanged. CI data indicated the likely true performance effect lay between 13- and 71-s improvement (TT4 vs TT3). M-ST improved endurance performance and enabled a higher power output, whereas N-ST induced no change. The VO2 response matched the increase in power output, yet RPE was unchanged, thereby inferring a perceptual benefit through M-ST. The valence and content of self-talk are important determinants of the efficacy of this intervention. These findings are primarily discussed in the context of the psychobiological model of pacing.

The use of real-time, hardware-in-the-loop simulation in the design and development of the new Hughes HS601 spacecraft attitude control system

NASA Technical Reports Server (NTRS)

Slafer, Loren I.

1989-01-01

Realtime simulation and hardware-in-the-loop testing is being used extensively in all phases of the design, development, and testing of the attitude control system (ACS) for the new Hughes HS601 satellite bus. Realtime, hardware-in-the-loop simulation, integrated with traditional analysis and pure simulation activities is shown to provide a highly efficient and productive overall development program. Implementation of high fidelity simulations of the satellite dynamics and control system algorithms, capable of real-time execution (using applied Dynamics International's System 100), provides a tool which is capable of being integrated with the critical flight microprocessor to create a mixed simulation test (MST). The MST creates a highly accurate, detailed simulated on-orbit test environment, capable of open and closed loop ACS testing, in which the ACS design can be validated. The MST is shown to provide a valuable extension of traditional test methods. A description of the MST configuration is presented, including the spacecraft dynamics simulation model, sensor and actuator emulators, and the test support system. Overall system performance parameters are presented. MST applications are discussed; supporting ACS design, developing on-orbit system performance predictions, flight software development and qualification testing (augmenting the traditional software-based testing), mission planning, and a cost-effective subsystem-level acceptance test. The MST is shown to provide an ideal tool in which the ACS designer can fly the spacecraft on the ground.

Mission Simulation Toolkit

NASA Technical Reports Server (NTRS)

Pisaich, Gregory; Flueckiger, Lorenzo; Neukom, Christian; Wagner, Mike; Buchanan, Eric; Plice, Laura

2007-01-01

The Mission Simulation Toolkit (MST) is a flexible software system for autonomy research. It was developed as part of the Mission Simulation Facility (MSF) project that was started in 2001 to facilitate the development of autonomous planetary robotic missions. Autonomy is a key enabling factor for robotic exploration. There has been a large gap between autonomy software (at the research level), and software that is ready for insertion into near-term space missions. The MST bridges this gap by providing a simulation framework and a suite of tools for supporting research and maturation of autonomy. MST uses a distributed framework based on the High Level Architecture (HLA) standard. A key feature of the MST framework is the ability to plug in new models to replace existing ones with the same services. This enables significant simulation flexibility, particularly the mixing and control of fidelity level. In addition, the MST provides automatic code generation from robot interfaces defined with the Unified Modeling Language (UML), methods for maintaining synchronization across distributed simulation systems, XML-based robot description, and an environment server. Finally, the MSF supports a number of third-party products including dynamic models and terrain databases. Although the communication objects and some of the simulation components that are provided with this toolkit are specifically designed for terrestrial surface rovers, the MST can be applied to any other domain, such as aerial, aquatic, or space.