Sample records for modelling status progress

  1. STATUS AND PROGRESS IN PARTICULATE MATTER FORECASTING: INITIAL APPLICATION OF THE ETA- CMAQ FORECAST MODEL

    EPA Science Inventory

    This presentation reviews the status and progress in forecasting particulate matter distributions. The shortcomings in representation of particulate matter formation in current atmospheric chemistry/transport models are presented based on analyses and detailed comparisons with me...

  2. Application of Item Response Theory to Modeling of Expanded Disability Status Scale in Multiple Sclerosis.

    PubMed

    Novakovic, A M; Krekels, E H J; Munafo, A; Ueckert, S; Karlsson, M O

    2017-01-01

    In this study, we report the development of the first item response theory (IRT) model within a pharmacometrics framework to characterize the disease progression in multiple sclerosis (MS), as measured by Expanded Disability Status Score (EDSS). Data were collected quarterly from a 96-week phase III clinical study by a blinder rater, involving 104,206 item-level observations from 1319 patients with relapsing-remitting MS (RRMS), treated with placebo or cladribine. Observed scores for each EDSS item were modeled describing the probability of a given score as a function of patients' (unobserved) disability using a logistic model. Longitudinal data from placebo arms were used to describe the disease progression over time, and the model was then extended to cladribine arms to characterize the drug effect. Sensitivity with respect to patient disability was calculated as Fisher information for each EDSS item, which were ranked according to the amount of information they contained. The IRT model was able to describe baseline and longitudinal EDSS data on item and total level. The final model suggested that cladribine treatment significantly slows disease-progression rate, with a 20% decrease in disease-progression rate compared to placebo, irrespective of exposure, and effects an additional exposure-dependent reduction in disability progression. Four out of eight items contained 80% of information for the given range of disabilities. This study has illustrated that IRT modeling is specifically suitable for accurate quantification of disease status and description and prediction of disease progression in phase 3 studies on RRMS, by integrating EDSS item-level data in a meaningful manner.

  3. Status Report on Speech Research: A Report on the Status and Progress of Studies on the Nature of Speech, Instrumentation for Its Investigation, and Practical Applications, October 1-December 31, 1985.

    ERIC Educational Resources Information Center

    O'Brien, Nancy, Ed.

    The articles in this paper explore the status and progress of studies on the nature of speech, instrumentation for its investigation, and practical research applications. Titles of the papers and their authors are as follows: (1) "Task Dynamic Coordination of the Speech Articulators: A Preliminary Model" (Elliot Saltzman); (2) "Some Observations…

  4. Predicting reading outcomes with progress monitoring slopes among middle grade students

    PubMed Central

    Tolar, Tammy D.; Barth, Amy E.; Fletcher, Jack M.; Francis, David J.; Vaughn, Sharon

    2013-01-01

    Effective implementation of response-to-intervention (RTI) frameworks depends on efficient tools for monitoring progress. Evaluations of growth (i.e., slope) may be less efficient than evaluations of status at a single time point, especially if slopes do not add to predictions of outcomes over status. We examined progress monitoring slope validity for predicting reading outcomes among middle school students by evaluating latent growth models for different progress monitoring measure-outcome combinations. We used multi-group modeling to evaluate the effects of reading ability, reading intervention, and progress monitoring administration condition on slope validity. Slope validity was greatest when progress monitoring was aligned with the outcome (i.e., word reading fluency slope was used to predict fluency outcomes in contrast to comprehension outcomes), but effects varied across administration conditions (viz., repeated reading of familiar vs. novel passages). Unless the progress monitoring measure is highly aligned with outcome, slope may be an inefficient method for evaluating progress in an RTI context. PMID:24659899

  5. Human Papillomavirus and Overall Survival After Progression of Oropharyngeal Squamous Cell Carcinoma

    PubMed Central

    Fakhry, Carole; Zhang, Qiang; Nguyen-Tan, Phuc Felix; Rosenthal, David; El-Naggar, Adel; Garden, Adam S.; Soulieres, Denis; Trotti, Andy; Avizonis, Vilija; Ridge, John Andrew; Harris, Jonathan; Le, Quynh-Thu; Gillison, Maura

    2014-01-01

    Purpose Risk of cancer progression is reduced for patients with human papillomavirus (HPV) –positive oropharynx cancer (OPC) relative to HPV-negative OPC, but it is unknown whether risk of death after progression is similarly reduced. Patients and Methods Patients with stage III-IV OPC enrolled onto Radiation Therapy Oncology Group trials 0129 or RTOG 0522 who had known tumor p16 status plus local, regional, and/or distant progression after receiving platinum-based chemoradiotherapy were eligible for a retrospective analysis of the association between tumor p16 status and overall survival (OS) after disease progression. Rates were estimated by Kaplan-Meier method and compared by log-rank; hazard ratios (HRs) were estimated by Cox models. Tests and models were stratified by treatment protocol. Results A total of 181 patients with p16-positive (n = 105) or p16-negative (n = 76) OPC were included in the analysis. Patterns of failure and median time to progression (8.2 v 7.3 months; P = .67) were similar for patients with p16-positive and p16-negative tumors. After a median follow-up period of 4.0 years after disease progression, patients with p16-positive OPC had significantly improved survival rates compared with p16-negative patients (2-year OS, 54.6% v 27.6%; median, 2.6 v 0.8 years; P < .001). p16-positive tumor status (HR, 0.48; 95% CI, 0.31 to 0.74) and receipt of salvage surgery (HR, 0.48; 95% CI; 0.27 to 0.84) reduced risk of death after disease progression whereas distant versus locoregional progression (HR, 1.99; 95% CI, 1.28 to 3.09) increased risk, after adjustment for tumor stage and cigarette pack-years at enrollment. Conclusion Tumor HPV status is a strong and independent predictor of OS after disease progression and should be a stratification factor for clinical trials for patients with recurrent or metastatic OPC. PMID:24958820

  6. Progression of motor and nonmotor features of Parkinson's disease and their response to treatment

    PubMed Central

    Vu, Thuy C.; Nutt, John G.; Holford, Nicholas H. G.

    2012-01-01

    AIMS (i) To describe the progression of the cardinal features of Parkinson's disease (PD); (ii) to investigate whether baseline PD subtypes explain disease progression; and (iii) to quantify the symptomatic and disease-modifying effects of anti-parkinsonian treatments. METHODS Data were available for 795 PD subjects, initially untreated, followed for up to 8 years. Cardinal features [tremor, rigidity, bradykinesia, and postural instability and gait disorder (PIGD)] were derived from the total unified Parkinson's disease rating scale (total UPDRS), cognitive status from the mini-mental status exam score (MMSE) and depression status from the Hamilton depression scale (HAM-D). Analysis was performed using a nonlinear mixed effects approach with an asymptotic model for natural disease progression. Treatment effects (i.e. symptomatic and disease modifying) were evaluated by describing changes in the natural history model parameters. RESULTS Tremor progressed more slowly (half-time of 3.9 years) than all other motor features (half-time 2–3 years). The MMSE progression was negligible, while HAM-D progressed with a half-time of 5 years. Levodopa had marked symptomatic effects on all features, but low potency for effect on PIGD (ED50 of 1237 mg day−1 compared with 7–24 mg day−1 for other motor and nonmotor features). Other anti-parkinsonian treatments had much smaller symptomatic effects. All treatments had disease-modifying effects on the cardinal features of PD. Baseline PD subtypes only explained small differences in disease progression. CONCLUSIONS This analysis indicates that tremor progresses more slowly than other cardinal features and that PIGD is less treatment responsive in early PD patients. There was no evidence of baseline PD subtypes as a clinically useful predictor of disease progression rate. Anti-parkinsonian treatments have symptomatic and disease-modifying effects on all major features of PD. PMID:22283961

  7. Epilepsy and the Wnt Signaling Pathway

    DTIC Science & Technology

    2016-08-01

    instigated by an inciting event (e.g. prolonged seizure called status epilepticus (SE), head injury, infection or stroke). This is followed by a...that define epileptic progression. 15. SUBJECT TERMS Status Epilepticus , Wnt Signaling, Epileptogenesis 16. SECURITY CLASSIFICATION OF: U 17...grant, we will investigate the mechanisms of Status Epilepticus (SE) and the ensuing latent period in animal models of temporal lobe epilepsy (TLE), a

  8. Epilepsy and the Wnt Signaling Pathway

    DTIC Science & Technology

    2016-09-01

    sustains seizures. It is instigated by an inciting event (e.g. prolonged seizure called status epilepticus (SE), head injury, infection or stroke...onset of chronic seizures that define epileptic progression. 15. SUBJECT TERMS Status Epilepticus , Wnt Signaling, Epileptogenesis 16. SECURITY...availability of experimental models to molecularly dissect a disease sub-type. In this grant, we will investigate the mechanisms of Status Epilepticus

  9. Posttraumatic Growth and HIV Disease Progression

    ERIC Educational Resources Information Center

    Milam, Joel

    2006-01-01

    The relationship between posttraumatic growth (PTG; perceiving positive changes since diagnosis) and disease status, determined by changes in viral load and CD4 count over time, was examined among 412 people living with HIV. In controlled multiple regression models, PTG was not associated with disease status over time for the entire sample.…

  10. Finance Project. Status Report and Preliminary Working Papers.

    ERIC Educational Resources Information Center

    California Community Colleges, Sacramento. Office of the Chancellor.

    This status report outlines the progress of the California Community College Finance Project. Working papers, models, and alternative proposals are reviewed in four areas: mission and function, finance, governance, and management. Priorities in mission and function are stated in terms of the characteristics and educational needs of the nearly 1.3…

  11. What progress have we made with tinnitus? The Tonndorf Lecture 2005.

    PubMed

    Baguley, David M

    2006-12-01

    The field of tinnitus research is vibrant and active. Prospects for progress are high, but would be optimized by the growth of inter-disciplinary collaborations. Tinnitus remains a source of urgent scientific investigation, and truly effective treatments continue to be elusive. The Tonndorf Lecture of the International Tinnitus Seminars represents an opportunity to reflect upon progress to date regarding tinnitus, and the actions needed to further that progress in future. Progress regarding tinnitus mechanisms is reviewed, with particular regard to the conceptual distinction between ignition sites for tinnitus, and the physiological mechanisms that then promote the tinnitus through the central auditory pathway. The current status of both the Jastreboff neurophysiological model and the psychological model of tinnitus is reviewed. Some concerns regarding each model are raised, and the need for models that integrate the insights of both perspectives is identified as urgent. There are clear indications of progress in tinnitus, specifically regarding mechanisms, models and treatments. For knowledge to progress further, however, there is a pressing need for an inter-disciplinary approach to tinnitus, more involvement in teaching at a postgraduate level, and the development of experimental models of tinnitus that are both congruent with, and represent the complexity of, human experience of tinnitus.

  12. The relationship between BMI and insulin resistance and progression from single to multiple autoantibody positivity and type 1 diabetes among TrialNet Pathway to Prevention participants.

    PubMed

    Meah, Farah A; DiMeglio, Linda A; Greenbaum, Carla J; Blum, Janice S; Sosenko, Jay M; Pugliese, Alberto; Geyer, Susan; Xu, Ping; Evans-Molina, Carmella

    2016-06-01

    The incidence of type 1 diabetes is increasing at a rate of 3-5% per year. Genetics cannot fully account for this trend, suggesting an influence of environmental factors. The accelerator hypothesis proposes an effect of metabolic factors on type 1 diabetes risk. To test this in the TrialNet Pathway to Prevention (PTP) cohort, we analysed the influence of BMI, weight status and insulin resistance on progression from single to multiple islet autoantibodies (Aab) and progression from normoglycaemia to diabetes. HOMA1-IR was used to estimate insulin resistance in Aab-positive PTP participants. Cox proportional hazards models were used to evaluate the effects of BMI, BMI percentile (BMI%), weight status and HOMA1-IR on the progression of autoimmunity or the development of diabetes. Data from 1,310 single and 1,897 multiple Aab-positive PTP participants were included. We found no significant relationships between BMI, BMI%, weight status or HOMA1-IR and the progression from one to multiple Aabs. Similarly, among all Aab-positive participants, no significant relationships were found between BMI, weight status or HOMA1-IR and progression to diabetes. Diabetes risk was modestly increased with increasing BMI% among the entire cohort, in obese participants 13-20 years of age and with increasing HOMA1-IR in adult Aab-positive participants. Analysis of the accelerator hypothesis in the TrialNet PTP cohort does not suggest a broad influence of metabolic variables on diabetes risk. Efforts to identify other potentially modifiable environmental factors should continue.

  13. An attempt at the computer-aided management of HIV infection

    NASA Astrophysics Data System (ADS)

    Ida, A.; Oharu, Y.; Sankey, O.

    2007-07-01

    The immune system is a complex and diverse system in the human body and HIV virus disrupts and destroys it through extremely complicated but surprisingly logical process. The purpose of this paper is to make an attempt to present a method for the computer-aided management of HIV infection process by means of a mathematical model describing the dynamics of the host pathogen interaction with HIV-1. Treatments for the AIDS disease must be changed to more efficient ones in accordance with the disease progression and the status of the immune system. The level of progression and the status are represented by parameters which are governed by our mathematical model. It is then exhibited that our model is numerically stable and uniquely solvable. With this knowledge, our mathematical model for HIV disease progression is formulated and physiological interpretations are provided. The results of our numerical simulations are visualized, and it is seen that our results agree with medical aspects from the point of view of antiretroviral therapy. It is then expected that our approach will take to address practical clinical issues and will be applied to the computer-aided management of antiretroviral therapies.

  14. County Variation in Children's and Adolescent's Health Status and School District Performance in California

    PubMed Central

    Jung, Sunyoung

    2008-01-01

    Objectives. We examined the association between county-level estimates of children's health status and school district performance in California. Methods. We used 3 data sources: the California Health Interview Survey, district archives from the California Department of Education, and census-based estimates of county demographic characteristics. We used logistic regression to estimate whether a school district's failure to meet adequate yearly progress goals in 2004 to 2005 was a function of child and adolescent's health status. Models included district- and county-level fixed effects and were adjusted for the clustering of districts within counties. Results. County-level changes in children's and adolescent's health status decreased the likelihood that a school district would fail to meet adequate yearly progress goals during the investigation period. Health status did not moderate the relatively poor performance of predominantly minority districts. Conclusions. We found empirical support that area variation in children's and adolescent's health status exerts a contextual effect on school district performance. Future research should explore the specific mechanisms through which area-level child health influences school and district achievement. PMID:18309137

  15. Computer simulation modeling of recreation use: Current status, case studies, and future directions

    Treesearch

    David N. Cole

    2005-01-01

    This report compiles information about recent progress in the application of computer simulation modeling to planning and management of recreation use, particularly in parks and wilderness. Early modeling efforts are described in a chapter that provides an historical perspective. Another chapter provides an overview of modeling options, common data input requirements,...

  16. Integrated metagenomic data analysis demonstrates that a loss of diversity in oral microbiota is associated with periodontitis.

    PubMed

    Ai, Dongmei; Huang, Ruocheng; Wen, Jin; Li, Chao; Zhu, Jiangping; Xia, Li Charlie

    2017-01-25

    Periodontitis is an inflammatory disease affecting the tissues supporting teeth (periodontium). Integrative analysis of metagenomic samples from multiple periodontitis studies is a powerful way to examine microbiota diversity and interactions within host oral cavity. A total of 43 subjects were recruited to participate in two previous studies profiling the microbial community of human subgingival plaque samples using shotgun metagenomic sequencing. We integrated metagenomic sequence data from those two studies, including six healthy controls, 14 sites representative of stable periodontitis, 16 sites representative of progressing periodontitis, and seven periodontal sites of unknown status. We applied phylogenetic diversity, differential abundance, and network analyses, as well as clustering, to the integrated dataset to compare microbiological community profiles among the different disease states. We found alpha-diversity, i.e., mean species diversity in sites or habitats at a local scale, to be the single strongest predictor of subjects' periodontitis status (P < 0.011). More specifically, healthy subjects had the highest alpha-diversity, while subjects with stable sites had the lowest alpha-diversity. From these results, we developed an alpha-diversity logistic model-based naive classifier able to perfectly predict the disease status of the seven subjects with unknown periodontal status (not used in training). Phylogenetic profiling resulted in the discovery of nine marker microbes, and these species are able to differentiate between stable and progressing periodontitis, achieving an accuracy of 94.4%. Finally, we found that the reduction of negatively correlated species is a notable signature of disease progression. Our results consistently show a strong association between the loss of oral microbiota diversity and the progression of periodontitis, suggesting that metagenomics sequencing and phylogenetic profiling are predictive of early periodontitis, leading to potential therapeutic intervention. Our results also support a keystone pathogen-mediated polymicrobial synergy and dysbiosis (PSD) model to explain the etiology of periodontitis. Apart from P. gingivalis, we identified three additional keystone species potentially mediating the progression of periodontitis progression based on pathogenic characteristics similar to those of known keystone pathogens.

  17. The relationship between BMI and insulin resistance and progression from single to multiple autoantibody positivity and type 1 diabetes among TrialNet Pathway to Prevention participants

    PubMed Central

    Meah, Farah A.; DiMeglio, Linda A.; Greenbaum, Carla J.; Blum, Janice S.; Sosenko, Jay M.; Pugliese, Alberto; Geyer, Susan; Xu, Ping; Evans-Molina, Carmella

    2016-01-01

    Aims/hypothesis The incidence of type 1 diabetes is increasing at a rate of 3–5% per year. Genetics cannot fully account for this trend, suggesting an influence of environmental factors. The accelerator hypothesis proposes an effect of metabolic factors on type 1 diabetes risk. To test this in the TrialNet Pathway to Prevention (PTP) cohort, we analysed the influence of BMI, weight status and insulin resistance on progression from single to multiple islet autoantibodies (Aab) and progression from normoglycaemia to diabetes. Methods HOMA1-IR was used to estimate insulin resistance in Aab-positive PTP participants. Cox proportional hazards models were used to evaluate the effects of BMI, BMI percentile (BMI%), weight status and HOMA1-IR on the progression of autoimmunity or the development of diabetes. Results Data from 1,310 single and 1,897 multiple Aab-positive PTP participants were included. We found no significant relationships between BMI, BMI%, weight status or HOMA1-IR and the progression from one to multiple Aabs. Similarly, among all Aab-positive participants, no significant relationships were found between BMI, weight status or HOMA1-IR and progression to diabetes. Diabetes risk was modestly increased with increasing BMI% among the entire cohort, in obese participants 13–20 years of age, and with increasing HOMA1-IR in adult Aab-positive participants. Conclusions/interpretation Analysis of the accelerator hypothesis in the TrialNet PTP cohort does not suggest a broad influence of metabolic variables on diabetes risk. Efforts to identify other potentially modifiable environmental factors should continue. PMID:26995649

  18. [Impact of disease progression on health status, quality of life and costs in rheumatoid arthritis in Hungary].

    PubMed

    Péntek, Márta; Szekanecz, Zoltán; Czirják, László; Poór, Gyula; Rojkovich, Bernadette; Polgár, Anna; Genti, György; Kiss, Csaba György; Sándor, Zsuzsa; Májer, István; Brodszky, Valentin; Gulácsi, László

    2008-04-20

    Rheumatoid arthritis (RA) is a chronic, progressive polyarthritis leading to substantial disability. Standardised data on consequences of disease progression are needed for clinical assessments and also for cost-effectiveness models. To analyse the impact of disease progression on health status, disease specific quality of life and costs in Hungary. A cross-sectional survey was performed between April and August, 2004, involving consecutive RA patients of 6 hospital based rheumatology outpatient centres. Self-completed questionnaires were used to assess functional (HAQ) and health status (EQ-5D), quality of life (RAQoL). Disease activity (DAS) and costs were also surveyed, statistical analysis was performed. 255 patients were involved [mean age 55.5 +/- 12.3 years; disease duration 9.0 +/- 9.3 years; HAQ 1.38 +/- 0.76; EQ-5D 0.46 +/- 0.33; RAQoL 16.2 +/- 8.1; DAS 5.09 +/- 1.42; costs 1,043,163 (+/- 844,750) HUF/patient/year, conversion 1 Euro = 250 HUF]. Correlation was significant between the parameters ( p < 0.01): EQ-5D index = 1.014 - 0.25 x HAQ-0.041 x DAS; HAQ = 0.314 + 0.065 x RAQoL. Analysis by disease severity levels (HAQ groups 0.5 difference) revealed that health status worsens (mean EQ-5D: 0.784; 0.576; 0.504; 0.367; 0.211; 0.022) and costs increase (mean 628,280; 888,187; 953,759; 1,291,218; 1,346,112; 1,371,674 HUF/patient/year) with disease progression. Minimally important worsening of functional ability (0.25 HAQ increase) corresponds to -0.0705 EQ-5D and +1.884 RAQoL change. Lower health status difference (EQ-5D -0.05725) was calculated in patients with lower disease activity (DAS < 5.1). Correlation between disease progression, health status, quality of life and costs does not differ significantly from international results. The amount of costs is much lower in all disease severity levels than in developed European countries. Our study serves baseline data for health economic analysis in RA in Hungary.

  19. Elevated serum progastrin-releasing peptide (31-98) level is a predictor of short response duration after hormonal therapy in metastatic prostate cancer.

    PubMed

    Yashi, Masahiro; Nukui, Akinori; Kurokawa, Shinsuke; Ochi, Masanori; Ishikawa, Shinya; Goto, Kentaro; Kobayashi, Yutaka; Muraishi, Osamu; Tokue, Akihiko

    2003-09-01

    The neuroendocrine (NE) pathway has been attracting attention as a mechanism for the androgen-independent progression because the neuropeptide provokes tumor growth and inhibits apoptosis under androgen-deprived milieu in prostate cancer cells. On the basis that serum progastrin-releasing peptide (ProGRP) is elevated in patients with advanced disease stage, we examined the prognostic value of the neuropeptide. Serum ProGRP status was determined with an enzyme-linked immunosorbent assay (ELISA) in 460 men with benign and malignant prostatic diseases, chronic renal failure, and healthy controls. Seventy patients with metastatic prostate cancer including four patients (5.7%) with NE carcinoma who underwent hormonal therapy were enrolled in the prognostic analyses by Cox proportional hazards model. The serum status steadily shifted toward predominant expression of ProGRP with the progression of prostate cancer into metastatic and androgen-independent stages. Univariate analysis revealed that the deteriorated performance status (PS) and extent of bony disease (EOD), and high serum alkaline phosphatase (ALP), serum ProGRP, and nadir prostate-specific antigen (PSA) levels were associated with a lower progression-free survival (PFS) rate (P < 0.005). Multivariate analysis demonstrated that PS, serum ProGRP, and nadir PSA held an independent predictive value for PFS (P < 0.05), and all correlated with bone-related factors. Serum ProGRP was the most significant predictor among pre-treatment factors in this model (P = 0.0094). The neuropeptide precursor ProGRP is a distinct serum marker that is useful to know the NE milieu and provides prognostic information in patients with advanced prostate cancer. Standard therapy for metastatic prostate cancer may make progress when further studies will clarify the causative link between serum ProGRP level and androgen-independent disease progression. Copyright 2003 Wiley-Liss, Inc.

  20. Racial progress as threat to the status hierarchy: implications for perceptions of anti-White bias.

    PubMed

    Wilkins, Clara L; Kaiser, Cheryl R

    2014-02-01

    In three studies, we examined how racial progress affects Whites' perceptions of anti-White bias. When racial progress was chronically (Study 1) and experimentally (Study 2) salient, Whites who believed the current U.S. status hierarchy was legitimate were more likely to report that Whites were victims of racial discrimination. In contrast, Whites who perceived the current status system as illegitimate were unaffected by the salience of racial progress. The results of Study 3 point to the role of threat in explaining these divergent reactions to racial progress. When self-affirmed, Whites who perceived the status hierarchy as legitimate no longer showed increased perceptions of anti-White bias when confronted with evidence of racial progress. Implications for policies designed to remedy social inequality are discussed.

  1. Vitamin D status is a determinant of atorvastatin effect on carotid intima medial thickening progression rate in children with lupus: an Atherosclerosis Prevention in Pediatric Lupus Erythematosus (APPLE) substudy.

    PubMed

    Robinson, Angela Byun; Tangpricha, Vin; Yow, Eric; Gurion, Reut; Schanberg, Laura E; McComsey, Grace A

    2014-01-01

    Epidemiological associations suggest that vitamin D status may play a role in inflammation and progression of atherosclerosis. Using frozen serum, carotid intima medial thickness (CIMT) measurements and other existing data from the Atherosclerosis Prevention in Pediatric Lupus Erythematosus (APPLE) trial, we assessed interactions between serum 25-hydroxyvitamin D (25(OH)D), atorvastatin randomisation and CIMT progression rate. Participants in the 3-year APPLE trial were randomised to placebo or atorvastatin and CIMT progression rate was measured. Baseline frozen serum was used to measure 25(OH)D concentrations. Mixed effect longitudinal models for CIMT progression at 3 years were used to evaluate interaction between vitamin D deficiency (serum 25(OH)D <20 ng/mL) at baseline and atorvastatin or placebo treatment, adjusting for key systemic lupus erythematosus disease variables and cardiovascular risk factors. 201/221 APPLE participants had available samples and were included in this analysis; 61/201 (30%) had vitamin D deficiency at baseline. In adjusted longitudinal modelling, there was significant interaction between baseline vitamin D deficiency and atorvastatin randomisation in 3-year progression of mean-max CIMT. In four out of six carotid segments, there was a greater decrease in mean-max CIMT progression rate in subjects who were treated with atorvastatin compared with placebo if they had baseline serum 25(OH)D levels ≥20 ng/mL. Subjects with serum 25(OH)D ≥20 ng/mL had less mean-max CIMT progression following 3 years of atorvastatin treatment. Results from secondary analyses must be interpreted cautiously, but findings suggest that underlying vitamin D deficiency may be involved in response to atorvastatin in atherosclerosis prevention. NCT00065806.

  2. Magnetic resonance imaging of osteophytic, chondral, and subchondral structures in a surgically-induced osteoarthritis rabbit model.

    PubMed

    Jia, Lang; Chen, Jinyun; Wang, Yan; Liu, Yingjiang; Zhang, Yu; Chen, Wenzhi

    2014-01-01

    This study aimed to assess changes in osteophytic, chondral, and subchondral structures in a surgically-induced osteoarthritis (OA) rabbit model in order to correlate MRI findings with the macroscopic progress of OA and to define the timepoint for disease status in this OA model. The OA model was constructed by surgery in thirty rabbits with ten normal rabbits serving as controls (baseline). High-resolution three-dimensional MRI using a 1.5-T coil was performed at baseline, two, four, and eight weeks post-surgery. MRIs of cartilage lesions, subchondral bone lesions, and osteophyte formations were independently assessed by two blinded radiologists. Ten rabbits were sacrificed at baseline, two, four, and eight weeks post-surgery, and macroscopic evaluation was independently performed by two blinded orthopedic surgeons. The signal intensities and morphologies of chondral and subchondral structures by MRI accurately reflected the degree of OA. Cartilage defects progressed from a grade of 0.05-0.15 to 1.15-1.30 to 1.90-1.97 to 3.00-3.35 at each successive time point, respectively (p<0.05). Subchondral bone lesions progressed from a grade of 0.00 to 0.78-0.90 to 1.27-1.58 to 1.95-2.23 at each successive time point, respectively (p = 0.000). Osteophytes progressed from a size (mm) of 0.00 to 0.87-1.06 to 1.24-1.87 to 2.21-3.21 at each successive time point, respectively (p = 0.000). Serial observations revealed that MRI can accurately detect the progression of cartilage lesions and subchondral bone edema over an eight-week period but may not be accurate in detecting osteophyte sizes. Week four post-surgery was considered the timepoint between OA-negative and OA-positive status in this OA model. The combination of this OA model with MRI evaluation should provide a promising tool for the pre-clinical evaluation of new disease-modifying osteoarthritis drugs.

  3. Nuclear Power Plant Mechanical Component Flooding Fragility Experiments Status

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

    Pope, C. L.; Savage, B.; Johnson, B.

    This report describes progress on Nuclear Power Plant mechanical component flooding fragility experiments and supporting research. The progress includes execution of full scale fragility experiments using hollow-core doors, design of improvements to the Portal Evaluation Tank, equipment procurement and initial installation of PET improvements, designation of experiments exploiting the improved PET capabilities, fragility mathematical model development, Smoothed Particle Hydrodynamic simulations, wave impact simulation device research, and pipe rupture mechanics research.

  4. Clinical outcomes of patient mobility in a neuroscience intensive care unit.

    PubMed

    Mulkey, Malissa; Bena, James F; Albert, Nancy M

    2014-06-01

    Patients treated in a neuroscience intensive care unit (NICU) are often viewed as too sick to tolerate physical activity. In this study, mobility status in NICU was assessed, and factors and outcomes associated with mobility were examined. Using a prospective design, daily mobility status, medical history, demographics, Acute Physiology and Chronic Health Evaluation (APACHE) III score, and clinical outcomes were collected by medical records and database review. Depression, anxiety, and hostility were assessed before NICU discharge. Analyses included comparative statistics and multivariable modeling. In 228 unique patients, median (minimum, maximum) age was 64.0 (20, 95) years, 66.4% were Caucasian, and 53.6% were men. Of 246 admissions, median NICU stay was 4 (1, 61) days; APACHE III score was 56 (16, 145). Turning, range of motion, and head of bed of >30° were uniformly applied (n = 241), but 94 patients (39%) never progressed; 94 (39%) progressed to head of bed of >45° or dangling legs, 29 (12%) progressed to standing or pivoting to chair, and 24 (10%) progressed to walking. Female gender (p = .019), mechanical ventilation (p < .001), higher APACHE score (p = .004), and 30-day mortality (p = .001) were associated with less mobility. In multivariable modeling, greater mobility was associated with longer unit stay (p < .001) and discharge to home (p < .001). Psychological profile characteristics were not associated with mobility level. Nearly 40% of patients never progressed beyond bed movement, and only 10% walked. Although limited mobility progression was not associated with many patient factors, it was associated with poorer clinical outcomes. Implementation and evaluation of a progressive mobility protocol are needed in NICU patients. For more insights from the authors, see Supplemental Digital Content 1, at http://link.lww.com/JNN/A10.

  5. M3MS-16OR0401086 – Report on NEAMS Workbench Support for MOOSE Applications

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

    Lefebvre, Robert A.; Langley, Brandon R.; Thompson, Adam B.

    This report summarizes the status of the Nuclear Energy Advanced Modeling and Simulation (NEAMS) Workbench from Oak Ridge National Laboratory (ORNL) and the integration of the MOOSE framework. This report marks the completion of NEAMS milestone M3MS-16OR0401086. This report documents the developed infrastructure to support the MOOSE framework applications, the applications’ results, visualization status, the collaboration that facilitated this progress, and future considerations.

  6. Progress on control experiments of flexible structures

    NASA Technical Reports Server (NTRS)

    Juang, Jer-Nan

    1990-01-01

    Progress at the NASA Langley Research Center in the area of control experiments for flexible structures is described. First the author presents the experimental results for a linear model which represents slewing maneuvers of a generic space station solar panel carried out to evaluate experimentally some control technologies. Then the status of the rotational/translational maneuvering experiment of a flexible steel panel carried by a translation cart is presented. Finally, experimental results of the NASA minimast testbed using velocity command stepper motors as reaction mass reactors are shown. All the test configurations are briefly described, including actuator and sensor, test setup, and test software. The status of some research activities oriented primarily to the experimental methods for control of flexible structures is presented.

  7. Predictors of Recurrence, Progression, and Retreatment in Basilar Tip Aneurysms: A Location-Controlled Analysis.

    PubMed

    Abecassis, Isaac Josh; Sen, Rajeev D; Barber, Jason; Shetty, Rakshith; Kelly, Cory M; Ghodke, Basavaraj V; Hallam, Danial K; Levitt, Michael R; Kim, Louis J; Sekhar, Laligam N

    2018-06-14

    Endovascular treatment of intracranial aneurysms is associated with higher rates of recurrence and retreatment, though contemporary rates and risk factors for basilar tip aneurysms (BTAs) are less well-described. To characterize progression, retreatement, and retreated progression of BTAs treated with microsurgical or endovascular interventions. We retrospectively reviewed records for 141 consecutive BTA patients. We included 158 anterior communicating artery (ACoA) and 118 middle cerebral artery (MCA) aneurysms as controls. Univariate and multivariate analyses were used to calculate rates of progression (recurrence of previously obliterated aneurysms and progression of known residual aneurysm dome or neck), retreatment, and retreated progression. Kaplan-Meier analysis was used to characterize 24-mo event rates for primary outcome prediction. Of 141 BTA patients, 62.4% were ruptured and 37.6% were unruptured. Average radiographical follow-up was 33 mo. Among ruptured aneurysms treated with clipping, there were 2 rehemorrhages due to recurrence (6.1%), and none in any other cohorts. Overall rates of progression (28.9%), retreatment (28.9%), and retreated progression (24.7%) were not significantly different between surgical and endovascular subgroups, though ruptured aneurysms had higher event rates. Multivariate modeling confirmed rupture status (P = .003, hazard ratio = 0.14) and aneurysm dome width (P = .005, hazard ratio = 1.23) as independent predictors of progression requiring retreatment. In a separate multivariate analysis with ACoA and MCA aneurysms, basilar tip location was an independent predictor of progression, retreatment, and retreated progression. BTAs have higher rates of progression and retreated progression than other aneurysm locations, independent of treatment modality. Rupture status and dome width are risk factors for progression requiring retreatment.

  8. Experimental primates and non-human primate (NHP) models of human diseases in China: current status and progress.

    PubMed

    Zhang, Xiao-Liang; Pang, Wei; Hu, Xin-Tian; Li, Jia-Li; Yao, Yong-Gang; Zheng, Yong-Tang

    2014-11-18

    Non-human primates (NHPs) are phylogenetically close to humans, with many similarities in terms of physiology, anatomy, immunology, as well as neurology, all of which make them excellent experimental models for biomedical research. Compared with developed countries in America and Europe, China has relatively rich primate resources and has continually aimed to develop NHPs resources. Currently, China is a leading producer and a major supplier of NHPs on the international market. However, there are some deficiencies in feeding and management that have hampered China's growth in NHP research and materials. Nonetheless, China has recently established a number of primate animal models for human diseases and achieved marked scientific progress on infectious diseases, cardiovascular diseases, endocrine diseases, reproductive diseases, neurological diseases, and ophthalmic diseases, etc. Advances in these fields via NHP models will undoubtedly further promote the development of China's life sciences and pharmaceutical industry, and enhance China's position as a leader in NHP research. This review covers the current status of NHPs in China and other areas, highlighting the latest developments in disease models using NHPs, as well as outlining basic problems and proposing effective countermeasures to better utilize NHP resources and further foster NHP research in China.

  9. Integrating gut microbiota immaturity and disease-discriminatory taxa to diagnose the initiation and severity of shrimp disease.

    PubMed

    Xiong, Jinbo; Zhu, Jinyong; Dai, Wenfang; Dong, Chunming; Qiu, Qiongfen; Li, Chenghua

    2017-04-01

    Increasing evidence has emerged a tight link among the gut microbiota, host age and health status. This osculating interplay impedes the definition of gut microbiome features associated with host health from that in developmental stages. Consequently, gut microbiota-based prediction of health status is promising yet not well established. Here we firstly tracked shrimp gut microbiota (N = 118) over an entire cycle of culture; shrimp either stayed healthy or progressively transitioned into severe disease. The results showed that the gut microbiota were significantly distinct over shrimp developmental stages and disease progression. Null model and phylogenetic-based mean nearest taxon distance (MNTD) analyses indicated that deterministic processes that governed gut community became less important as the shrimp aged and disease progressed. The predicted gut microbiota age (using the profiles of age-discriminatory bacterial species as independent variables) fitted well (r = 0.996; P < 0.001) with the age of healthy subjects, while this defined trend was disrupted by disease. Microbiota-for-age Z-scores (MAZ, here defined as immaturity) were relative stable among healthy shrimp, but sharply decreased when disease emerged. By distinguishing between age- and disease- discriminatory taxa, we developed a model, bacterial indicators of shrimp health status, to diagnose disease from healthy subjects with 91.5% accuracy. Notably, the relative abundances of the bacterial indicators were indicative for shrimp disease severity. These findings, in aggregate, add our understanding on the gut community assembly patterns over shrimp developmental stages and disease progression. In addition, shrimp disease initiation and severity can be accurately diagnosed using gut microbiota immaturity and bacterial indicators. © 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.

  10. Androgen receptor (AR) suppresses miRNA-145 to promote renal cell carcinoma (RCC) progression independent of VHL status

    PubMed Central

    Chen, Yuan; Sun, Yin; Rao, Qun; Xu, Hua; Li, Lei; Chang, Chawnshang

    2015-01-01

    Mutational inactivation of the VHL tumor suppressor plays key roles in the development of renal cell carcinoma (RCC), and mutated VHL-mediated VEGF induction has become the main target for the current RCC therapy. Here we identified a signal pathway of VEGF induction by androgen receptor (AR)/miRNA-145 as a new target to suppress RCC progression. Mechanism dissection revealed that AR might function through binding to the androgen receptor element (ARE) located on the promoter region of miRNA-145 to suppress p53's ability to induce expression of miRNA-145 that normally suppresses expression of HIF2α/VEGF/MMP9/CCND1. Suppressing AR with AR-shRNA or introducing exogenous miRNA-145 mimic can attenuate RCC progression independent of VHL status. MiR-145 mimic in preclinical RCC orthotopic xenograft mouse model revealed its efficacy in suppression of RCC progression. These results together identified signals by AR-suppressed miRNA-145 as a key player in the RCC progression via regulating HIF2α/VEGF/MMP9/CCND1 expression levels. Blockade of the newly identified signal by AR inhibition or miRNA-145 mimics has promising therapeutic benefit to suppress RCC progression. PMID:26304926

  11. Intratumoral heterogeneity and TERT promoter mutations in progressive/higher-grade meningiomas

    PubMed Central

    Juratli, Tareq A.; Thiede, Christian; Koerner, Mara V.A.; Tummala, Shilpa S.; Daubner, Dirk; Shankar, Ganesh M.; Williams, Erik A.; Martinez-Lage, Maria; Soucek, Silke; Robel, Katja; Penson, Tristan; Krause, Mechthild; Appold, Steffen; Meinhardt, Matthias; Pinzer, Thomas; Miller, Julie J.; Krex, Dietmar; Ely, Heather A.; Silverman, Ian M.; Christiansen, Jason; Schackert, Gabriele; Wakimoto, Hiroaki; Kirsch, Matthias; Brastianos, Priscilla K.; Cahill, Daniel P.

    2017-01-01

    Background Recent studies have reported mutations in the telomerase reverse transcriptase promoter (TERTp) in meningiomas. We sought to determine the frequency, clonality and clinical significance of telomere gene alterations in a cohort of patients with progressive/higher-grade meningiomas. Methods We characterized 64 temporally- and regionally-distinct specimens from 26 WHO grade III meningioma patients. On initial diagnoses, the meningiomas spanned all WHO grades (3 grade I, 13 grade II and 10 grade III). The tumor samples were screened for TERTp and ATRX/DAXX mutations, and TERT rearrangements. Additionally, TERTp was sequenced in a separate cohort of 19 patients with radiation-associated meningiomas. We examined the impact of mutational status on patients’ progression and overall survival. Results Somatic TERTp mutations were detected in six patients (6/26 = 23%). Regional intratumoral heterogeneity in TERTp mutation status was noted. In 4 patients, TERTp mutations were detected in recurrent specimens but not in the available specimens of the first surgery. Additionally, a TERT gene fusion (LPCAT1-TERT) was found in one sample. In contrary, none of the investigated samples harbored an ATRX or DAXX mutation. In the cohort of radiation-induced meningiomas, TERTp mutation was detected in two patients (10.5%). Importantly, we found that patients with emergence of TERTp mutations had a substantially shorter OS than their TERTp wild-type counterparts (2.7 years, 95% CI 0.9 – 4.5 years versus 10.8 years, 95% CI 7.8 -12.8 years, p=0.003). Conclusions In progressive/higher-grade meningiomas,TERTp mutations are associated with poor survival, supporting a model in which selection of this alteration is a harbinger of aggressive tumor development. In addition, we observe spatial intratumoral heterogeneity of TERTp mutation status, consistent with this model of late emergence in tumor evolution. Thus, early detection of TERTp mutations may define patients with more aggressive meningiomas. Stratification for TERT alterations should be adopted in future clinical trials of progressive/higher-grade meningiomas. PMID:29312603

  12. Status of Complex Langevin

    NASA Astrophysics Data System (ADS)

    Seiler, Erhard

    2018-03-01

    I review the status of the Complex Langevin method, which was invented to make simulations of models with complex action feasible. I discuss the mathematical justification of the procedure, as well as its limitations and open questions. Various pragmatic measures for dealing with the existing problems are described. Finally I report on the progress in the application of the method to QCD, with the goal of determining the phase diagram of QCD as a function of temperature and baryonic chemical potential.

  13. Pretreatment advanced lung cancer inflammation index (ALI) for predicting early progression in nivolumab-treated patients with advanced non-small cell lung cancer.

    PubMed

    Shiroyama, Takayuki; Suzuki, Hidekazu; Tamiya, Motohiro; Tamiya, Akihiro; Tanaka, Ayako; Okamoto, Norio; Nakahama, Kenji; Taniguchi, Yoshihiko; Isa, Shun-Ichi; Inoue, Takako; Imamura, Fumio; Atagi, Shinji; Hirashima, Tomonori

    2018-01-01

    Programmed death-ligand 1 (PD-L1) expression status is inadequate for indicating nivolumab in patients with non-small cell lung cancer (NSCLC). Because the baseline advanced lung cancer inflammation index (ALI) is reportedly associated with patient outcomes, we investigated whether the pretreatment ALI is prognostic in NSCLC patients treated with nivolumab. We retrospectively reviewed the medical records of all patients treated with nivolumab for advanced NSCLC between December 2015 and May 2016 at three Japanese institutes. Multivariate logistic regression and Cox proportional hazards models were used to assess the impact of the pretreatment ALI (and other inflammation-related parameters) on progression-free survival (PFS) and early progression (i.e., within 8 weeks after starting nivolumab). A total of 201 patients were analyzed; their median age was 68 years (range, 27-87 years), 67% were men, and 24% had an Eastern Cooperative Oncology Group (ECOG) performance status of 2 or higher. An ECOG performance status ≥2, serum albumin <3.7 g/dL, neutrophil-to-lymphocyte ratio ≥4, and ALI <18 were significantly associated with poor PFS and early progression on univariate analysis. Multivariate analyses revealed that pretreatment ALI <18 was independently associated with inferior PFS (median, 1.4 vs. 3.7 months, P < 0.001) and a higher likelihood of early progression (odds ratio, 2.76; 95% confidence interval 1.44-5.34; P = 0.002). The pretreatment ALI was found to be a significant independent predictor of early progression in patients with advanced NSCLC receiving nivolumab, and may help identify patients likely to benefit from continued nivolumab treatment in routine clinical practice. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  14. Systemic treatment in advanced biliary cancers: A multicenter Australian analysis and review.

    PubMed

    Brungs, Daniel; Aghmesheh, Morteza; Sjoquist, Katrin; Goldstein, David

    2017-10-01

    While first-line palliative chemotherapy (CT1) improves survival and quality of life in advanced biliary cancer (ABC), there is no randomized evidence to support second-line chemotherapy (CT2) in ABC. We aim to explore to role of CT2 in ABC. We performed a retrospective review of all patients who received one or more lines of chemotherapy for ABC at four Australian cancer centers between 2008 and 2011. A Cox proportional hazard model was developed to determine the impact of clinicopathologic variables on overall survival (OS) from time of progression on CT1. We identified 73 patients who received palliative chemotherapy for ABC. Twenty-five patients (34%) received two or more lines of chemotherapy. Patients with a preserved performance status on progression on first-line chemotherapy (CT1) were more likely to receive second-line chemotherapy (CT2) (P < 0.001). Disease control rate with CT2 was 36%, and mean progression-free survival was 3.2 months (95% confidence interval 1.5-4.9 months). The following variables were significant in the univariate analysis of OS from time of progression on CT1: lines of chemotherapy (P = 0.0001), Eastern Cooperative Oncology Group performance status at progression on CT1 (P < 0.0001) and disease control with CT1 (P = 0.027). Lines of chemotherapy received and performance status remained significant in the multivariate analysis for OS from progression on CT1. Second-line chemotherapy is feasible in a subset of patients with ABC. Even after accounting for confounding variables, CT2 appears to increase OS in ABC, although we are unable to exclude other unmeasured factors such as tumor biology. These findings warrant further evaluation with prospective trials. © 2016 John Wiley & Sons Australia, Ltd.

  15. Current Status and Challenges of Atmospheric Data Assimilation

    NASA Astrophysics Data System (ADS)

    Atlas, R. M.; Gelaro, R.

    2016-12-01

    The issues of modern atmospheric data assimilation are fairly simple to comprehend but difficult to address, involving the combination of literally billions of model variables and tens of millions of observations daily. In addition to traditional meteorological variables such as wind, temperature pressure and humidity, model state vectors are being expanded to include explicit representation of precipitation, clouds, aerosols and atmospheric trace gases. At the same time, model resolutions are approaching single-kilometer scales globally and new observation types have error characteristics that are increasingly non-Gaussian. This talk describes the current status and challenges of atmospheric data assimilation, including an overview of current methodologies, the difficulty of estimating error statistics, and progress toward coupled earth system analyses.

  16. Decision analytic models for Alzheimer's disease: state of the art and future directions.

    PubMed

    Cohen, Joshua T; Neumann, Peter J

    2008-05-01

    Decision analytic policy models for Alzheimer's disease (AD) enable researchers and policy makers to investigate questions about the costs and benefits of a wide range of existing and potential screening, testing, and treatment strategies. Such models permit analysts to compare existing alternatives, explore hypothetical scenarios, and test the strength of underlying assumptions in an explicit, quantitative, and systematic way. Decision analytic models can best be viewed as complementing clinical trials both by filling knowledge gaps not readily addressed by empirical research and by extrapolating beyond the surrogate markers recorded in a trial. We identified and critiqued 13 distinct AD decision analytic policy models published since 1997. Although existing models provide useful insights, they also have a variety of limitations. (1) They generally characterize disease progression in terms of cognitive function and do not account for other distinguishing features, such as behavioral symptoms, functional performance, and the emotional well-being of AD patients and caregivers. (2) Many describe disease progression in terms of a limited number of discrete states, thus constraining the level of detail that can be used to characterize both changes in patient status and the relationships between disease progression and other factors, such as residential status, that influence outcomes of interest. (3) They have focused almost exclusively on evaluating drug treatments, thus neglecting other disease management strategies and combinations of pharmacologic and nonpharmacologic interventions. Future AD models should facilitate more realistic and compelling evaluations of various interventions to address the disease. An improved model will allow decision makers to better characterize the disease, to better assess the costs and benefits of a wide range of potential interventions, and to better evaluate the incremental costs and benefits of specific interventions used in conjunction with other disease management strategies.

  17. Status Report on Speech Research: A Report on the Status and Progress of Studies on the Nature of Speech, Instrumentation for Its Investigation, and Practical Applications, July 1 - December 31, 1977).

    ERIC Educational Resources Information Center

    Haskins Labs., New Haven, CT.

    This report is one of a regular series about the status and progress of studies on the nature of speech, instrumentation for its investigation, and practical applications. The 17 papers discuss the identification of sine-wave analogues of speech sounds; prosodic information for vowel identity; progressive changes in articulatory patterns in verbal…

  18. American Sign Language/English bilingual model: a longitudinal study of academic growth.

    PubMed

    Lange, Cheryl M; Lane-Outlaw, Susan; Lange, William E; Sherwood, Dyan L

    2013-10-01

    This study examines reading and mathematics academic growth of deaf and hard-of-hearing students instructed through an American Sign Language (ASL)/English bilingual model. The study participants were exposed to the model for a minimum of 4 years. The study participants' academic growth rates were measured using the Northwest Evaluation Association's Measure of Academic Progress assessment and compared with a national-normed group of grade-level peers that consisted primarily of hearing students. The study also compared academic growth for participants by various characteristics such as gender, parents' hearing status, and secondary disability status and examined the academic outcomes for students after a minimum of 4 years of instruction in an ASL/English bilingual model. The findings support the efficacy of the ASL/English bilingual model.

  19. Magnetic Resonance Imaging of Osteophytic, Chondral, and Subchondral Structures in a Surgically-Induced Osteoarthritis Rabbit Model

    PubMed Central

    Jia, Lang; Chen, Jinyun; Wang, Yan; Liu, Yingjiang; Zhang, Yu; Chen, Wenzhi

    2014-01-01

    Objective This study aimed to assess changes in osteophytic, chondral, and subchondral structures in a surgically-induced osteoarthritis (OA) rabbit model in order to correlate MRI findings with the macroscopic progress of OA and to define the timepoint for disease status in this OA model. Methods The OA model was constructed by surgery in thirty rabbits with ten normal rabbits serving as controls (baseline). High-resolution three-dimensional MRI using a 1.5-T coil was performed at baseline, two, four, and eight weeks post-surgery. MRIs of cartilage lesions, subchondral bone lesions, and osteophyte formations were independently assessed by two blinded radiologists. Ten rabbits were sacrificed at baseline, two, four, and eight weeks post-surgery, and macroscopic evaluation was independently performed by two blinded orthopedic surgeons. Results The signal intensities and morphologies of chondral and subchondral structures by MRI accurately reflected the degree of OA. Cartilage defects progressed from a grade of 0.05–0.15 to 1.15–1.30 to 1.90–1.97 to 3.00–3.35 at each successive time point, respectively (p<0.05). Subchondral bone lesions progressed from a grade of 0.00 to 0.78–0.90 to 1.27–1.58 to 1.95–2.23 at each successive time point, respectively (p = 0.000). Osteophytes progressed from a size (mm) of 0.00 to 0.87–1.06 to 1.24–1.87 to 2.21–3.21 at each successive time point, respectively (p = 0.000). Conclusions Serial observations revealed that MRI can accurately detect the progression of cartilage lesions and subchondral bone edema over an eight-week period but may not be accurate in detecting osteophyte sizes. Week four post-surgery was considered the timepoint between OA-negative and OA-positive status in this OA model. The combination of this OA model with MRI evaluation should provide a promising tool for the pre-clinical evaluation of new disease-modifying osteoarthritis drugs. PMID:25438155

  20. Disease progression model for Clinical Dementia Rating–Sum of Boxes in mild cognitive impairment and Alzheimer’s subjects from the Alzheimer’s Disease Neuroimaging Initiative

    PubMed Central

    Samtani, Mahesh N; Raghavan, Nandini; Novak, Gerald; Nandy, Partha; Narayan, Vaibhav A

    2014-01-01

    Background The objective of this analysis was to develop a nonlinear disease progression model, using an expanded set of covariates that captures the longitudinal Clinical Dementia Rating Scale–Sum of Boxes (CDR–SB) scores. These were derived from the Alzheimer’s Disease Neuroimaging Initiative ADNI-1 study, of 301 Alzheimer’s disease and mild cognitive impairment patients who were followed for 2–3 years. Methods The model describes progression rate and baseline disease score as a function of covariates. The covariates that were tested fell into five groups: a) hippocampal volume; b) serum and cerebrospinal fluid (CSF) biomarkers; c) demographics and apolipoprotein Epsilon 4 (ApoE4) allele status; d) baseline cognitive tests; and e) disease state and comedications. Results Covariates associated with baseline disease severity were disease state, hippocampal volume, and comedication use. Disease progression rate was influenced by baseline CSF biomarkers, Trail-Making Test part A score, delayed logical memory test score, and current level of impairment as measured by CDR–SB. The rate of disease progression was dependent on disease severity, with intermediate scores around the inflection point score of 10 exhibiting high disease progression rate. The CDR–SB disease progression rate in a typical patient, with late mild cognitive impairment and mild Alzheimer’s disease, was estimated to be approximately 0.5 and 1.4 points/year, respectively. Conclusions In conclusion, this model describes disease progression in terms of CDR–SB changes in patients and its dependency on novel covariates. The CSF biomarkers included in the model discriminate mild cognitive impairment subjects as progressors and nonprogressors. Therefore, the model may be utilized for optimizing study designs, through patient population enrichment and clinical trial simulations. PMID:24926196

  1. Never, non-daily, and daily smoking status and progression to daily cigarette smoking as correlates of major depressive episode in a national sample of youth: Results from the National Survey of Drug Use and Health 2013 to 2015.

    PubMed

    Cohn, Amy M

    2018-09-01

    Cigarette smoking is associated with depression, and new initiates who progress more quickly to daily smoking may be at enhanced risk. In a nationally representative sample of youth, this study examined the association between daily, non-daily, and never smoking with past-year and lifetime major depressive episode (MDE) and, among daily smokers, whether faster progression to daily smoking was associated with increased MDE risk. Data were from n = 44,921 youth aged 12-17 in the 2013-2015 National Survey on Drug Use and Health. Weighted adjusted multivariable logistic regression models were used to examine the association of smoking status (daily, non-daily, never) with lifetime and past-year MDE, and the association between progression from cigarette trial to daily smoking with MDE outcomes among daily smokers. Daily and non-daily smokers had similar rates of lifetime and past-year MDE; rates of MDE were approximately 50% lower among never smokers. Compared to never smokers, adjusted models showed that non-daily smokers had a higher risk of past-year and lifetime MDE, while daily smokers had a higher risk of past-year but not lifetime MDE. Daily smoking youth who progressed more quickly from cigarette trial to daily use had an increased risk of both lifetime and past-year MDE. Prevention programs should target factors associated with the shift from cigarette experimentation to regular use to curb deleterious consequences of use. Copyright © 2018. Published by Elsevier Ltd.

  2. The Changing Status of Women in Cameroon: An Overview.

    ERIC Educational Resources Information Center

    Azevedo, Mario J.; Prater, Gwendolyn Spencer

    1986-01-01

    The improvement in women's status in Cameroon between 1960 and 1985 is examined. Progress and obstacles to progress in the following areas are highlighted: (1) opportunities outside of the home; (2) social status; (3) political role; (4) access to education; (5) marital rights and restrictions; and (6) religious role. (PS)

  3. Impacts of mothers' occupation status and parenting styles on levels of self-control, addiction to computer games, and educational progress of adolescents.

    PubMed

    Abedini, Yasamin; Zamani, Bibi Eshrat; Kheradmand, Ali; Rajabizadeh, Ghodratollah

    2012-01-01

    Addiction to computer (video) games in adolescents and its relationship with educational progress has recently attracted the attention of rearing and education experts as well as organizations and institutes involved in physical and mental health. The current research attempted to propose a structural model of the relationships between parenting styles, mothers' occupation status, and addiction to computer games, self-control, and educational progress of secondary school students. Using multistage cluster random sampling, 500 female and male secondary school students in Kerman (Iran) were selected and studied. The research tools included self-control, parenting styles, and addiction to computer games questionnaires and a self-made questionnaire containing demographic details. The data was analyzed using exploratory factor analysis, Cronbach's alpha coefficient and route analysis (in LISREL). We found self-control to have a linking role in the relationship between four parenting styles and educational progress. Mothers' occupation status was directly and significantly correlated with addiction to computer games. Although four parenting styles directly and significantly affected addiction to computer games, the findings did not support the linking role of addiction to computer games in the relationship between four parenting styles and educational progress. In agreement with previous studies, the current research reflected the impact of four parenting styles on self-control, addiction to computer games, and educational progress of students. Among the parenting styles, authoritative style can affect the severity of addiction to computer games through self-control development. It can thus indirectly influence the educational progress of students. Parents are recommended to use authoritative parenting style to help both self-management and psychological health of their children. The employed mothers are also recommended to have more supervision and control on the degree and type of computer games selected by their children.

  4. Impacts of Mothers’ Occupation Status and Parenting Styles on Levels of Self-Control, Addiction to Computer Games, and Educational Progress of Adolescents

    PubMed Central

    Abedini, Yasamin; Zamani, Bibi Eshrat; Kheradmand, Ali; Rajabizadeh, Ghodratollah

    2012-01-01

    Background Addiction to computer (video) games in adolescents and its relationship with educational progress has recently attracted the attention of rearing and education experts as well as organizations and institutes involved in physical and mental health. The current research attempted to propose a structural model of the relationships between parenting styles, mothers’ occupation status, and addiction to computer games, self-control, and educational progress of secondary school students. Methods Using multistage cluster random sampling, 500 female and male secondary school students in Kerman (Iran) were selected and studied. The research tools included self-control, parenting styles, and addiction to computer games questionnaires and a self-made questionnaire containing demographic details. The data was analyzed using exploratory factor analysis, Cronbach’s alpha coefficient and route analysis (in LISREL). Findings We found self-control to have a linking role in the relationship between four parenting styles and educational progress. Mothers’ occupation status was directly and significantly correlated with addiction to computer games. Although four parenting styles directly and significantly affected addiction to computer games, the findings did not support the linking role of addiction to computer games in the relationship between four parenting styles and educational progress. Conclusion In agreement with previous studies, the current research reflected the impact of four parenting styles on self-control, addiction to computer games, and educational progress of students. Among the parenting styles, authoritative style can affect the severity of addiction to computer games through self-control development. It can thus indirectly influence the educational progress of students. Parents are recommended to use authoritative parenting style to help both self-management and psychological health of their children. The employed mothers are also recommended to have more supervision and control on the degree and type of computer games selected by their children. PMID:24494143

  5. Experimental primates and non-human primate (NHP) models of human diseases in China: current status and progress

    PubMed Central

    ZHANG, Xiao-Liang; PANG, Wei; HU, Xin-Tian; LI, Jia-Li; YAO, Yong-Gang; ZHENG, Yong-Tang

    2014-01-01

    Non-human primates (NHPs) are phylogenetically close to humans, with many similarities in terms of physiology, anatomy, immunology, as well as neurology, all of which make them excellent experimental models for biomedical research. Compared with developed countries in America and Europe, China has relatively rich primate resources and has continually aimed to develop NHPs resources. Currently, China is a leading producer and a major supplier of NHPs on the international market. However, there are some deficiencies in feeding and management that have hampered China’s growth in NHP research and materials. Nonetheless, China has recently established a number of primate animal models for human diseases and achieved marked scientific progress on infectious diseases, cardiovascular diseases, endocrine diseases, reproductive diseases, neurological diseases, and ophthalmic diseases, etc. Advances in these fields via NHP models will undoubtedly further promote the development of China’s life sciences and pharmaceutical industry, and enhance China’s position as a leader in NHP research. This review covers the current status of NHPs in China and other areas, highlighting the latest developments in disease models using NHPs, as well as outlining basic problems and proposing effective countermeasures to better utilize NHP resources and further foster NHP research in China. PMID:25465081

  6. Travel modeling in an era of connected and automated transportation systems: an investigation in the Dallas-Fort Worth area.

    DOT National Transportation Integrated Search

    2017-02-01

    The North Central Texas Council of Governments (NCTCOG) engaged D-STOP to conduct a planned four-year study to analyze the status and progress of connected/autonomous vehicle (CAV) development, determine what the wide-ranging effects of the technolog...

  7. Computational models for the analysis/design of hypersonic scramjet components. I - Combustor and nozzle models

    NASA Technical Reports Server (NTRS)

    Dash, S. M.; Sinha, N.; Wolf, D. E.; York, B. J.

    1986-01-01

    An overview of computational models developed for the complete, design-oriented analysis of a scramjet propulsion system is provided. The modular approach taken involves the use of different PNS models to analyze the individual propulsion system components. The external compression and internal inlet flowfields are analyzed by the SCRAMP and SCRINT components discussed in Part II of this paper. The combustor is analyzed by the SCORCH code which is based upon SPLITP PNS pressure-split methodology formulated by Dash and Sinha. The nozzle is analyzed by the SCHNOZ code which is based upon SCIPVIS PNS shock-capturing methodology formulated by Dash and Wolf. The current status of these models, previous developments leading to this status, and, progress towards future hybrid and 3D versions are discussed in this paper.

  8. Associations of HLA DRB1 alleles with IgG oligoclonal bands and their influence on multiple sclerosis course and disability status.

    PubMed

    Balnytė, Renata; Rastenytė, Daiva; Vaitkus, Antanas; Skrodenienė, Erika; Vitkauskienė, Astra; Ulozienė, Ingrida

    2016-01-01

    Oligoclonal bands (OCB) may be associated with the genes of HLA complex, which allows to consider the possible interaction of genetic and immunological factors and its importance in the development and progression of multiple sclerosis (MS). The aim of this study was to evaluate the associations between HLA DRB1 alleles and oligoclonal bands (OCBs) in the disease course and disability of multiple sclerosis (MS) patients. This was a prospective study of 120 patients with MS. HLA DRB1 alleles were genotyped using the polymerase chain reaction. Matched cerebrospinal fluid (CSF) and plasma samples were analyzed using isoelectric focusing and IgG specific immunofixation to test for the presence of intrathecal specific OCB. HLA DRB1*08 allele was related to a lower degree of disability. Oligoclonal bands were an independent and significant factor that influenced disability status irrespective of HLA DRB1* 04, *07, *08, *13, *15 and *16 alleles. Age at the onset and duration of the disease were independent and significant factors for MS progression in all logistic regression models with each newly added HLA DRB1 allele. HLA DRB1*08 allele was related to 75% lower odds that relapsing remitting (RR) MS will change to a progressive course MS irrespective of the other factors investigated. Detection of OCBs in the CSF was associated with the higher possibility of RR MS progression in all cases, except when the *08 allele was present. OCBs had an influence on disability status, while HLA DRB1*08 allele was significantly associated with lower possibility that RR MS will change to progressive course MS. Copyright © 2016 The Lithuanian University of Health Sciences. Production and hosting by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  9. Personalized dynamic prediction of death according to tumour progression and high-dimensional genetic factors: Meta-analysis with a joint model.

    PubMed

    Emura, Takeshi; Nakatochi, Masahiro; Matsui, Shigeyuki; Michimae, Hirofumi; Rondeau, Virginie

    2017-01-01

    Developing a personalized risk prediction model of death is fundamental for improving patient care and touches on the realm of personalized medicine. The increasing availability of genomic information and large-scale meta-analytic data sets for clinicians has motivated the extension of traditional survival prediction based on the Cox proportional hazards model. The aim of our paper is to develop a personalized risk prediction formula for death according to genetic factors and dynamic tumour progression status based on meta-analytic data. To this end, we extend the existing joint frailty-copula model to a model allowing for high-dimensional genetic factors. In addition, we propose a dynamic prediction formula to predict death given tumour progression events possibly occurring after treatment or surgery. For clinical use, we implement the computation software of the prediction formula in the joint.Cox R package. We also develop a tool to validate the performance of the prediction formula by assessing the prediction error. We illustrate the method with the meta-analysis of individual patient data on ovarian cancer patients.

  10. Status of States' Progress in Implementing Part H of IDEA: Report #3.

    ERIC Educational Resources Information Center

    Harbin, Gloria L.; And Others

    This report focuses on progress in the implementation of Part H of the Individuals with Disabilities Education Act (IDEA) through a comparison of states' status on three yearly administrations of the State Progress Scale. The scale was designed to monitor implementation of the required 14 components in the stages of policy development, policy…

  11. Social cognitive predictors of first- and non-first-generation college students' academic and life satisfaction.

    PubMed

    Garriott, Patton O; Hudyma, Aaron; Keene, Chesleigh; Santiago, Dana

    2015-04-01

    The present study tested Lent's (2004) social-cognitive model of normative well-being in a sample (N = 414) of first- and non-first-generation college students. A model depicting relationships between: positive affect, environmental supports, college self-efficacy, college outcome expectations, academic progress, academic satisfaction, and life satisfaction was examined using structural equation modeling. The moderating roles of perceived importance of attending college and intrinsic goal motivation were also explored. Results suggested the hypothesized model provided an adequate fit to the data while hypothesized relationships in the model were partially supported. Environmental supports predicted college self-efficacy, college outcome expectations, and academic satisfaction. Furthermore, college self-efficacy predicted academic progress while college outcome expectations predicted academic satisfaction. Academic satisfaction, but not academic progress predicted life satisfaction. The structural model explained 44% of the variance in academic progress, 56% of the variance in academic satisfaction, and 28% of the variance in life satisfaction. Mediation analyses indicated several significant indirect effects between variables in the model while moderation analyses revealed a 3-way interaction between academic satisfaction, intrinsic motivation for attending college, and first-generation college student status on life satisfaction. Results are discussed in terms of applying the normative model of well-being to promote first- and non-first-generation college students' academic and life satisfaction. (c) 2015 APA, all rights reserved).

  12. Utilization of Mental Health Services and Mental Health Status Among Children Placed in Out-of-Home Care: A Parallel Process Latent Growth Modeling Approach.

    PubMed

    Yampolskaya, Svetlana; Sharrock, Patty J; Clark, Colleen; Hanson, Ardis

    2017-10-01

    This longitudinal study examined the parallel trajectories of mental health service use and mental health status among children placed in Florida out-of-home care. The results of growth curve modeling suggested that children with greater mental health problems initially received more mental health services. Initial child mental health status, however, had no effect on subsequent service provision when all outpatient mental health services were included. When specific types of mental health services, such as basic outpatient, targeted case management, and intensive mental health services were examined, results suggested that children with compromised functioning during the baseline period received more intensive mental health services over time. However, this increased provision of intensive mental health services did not improve mental health status, rather it was significantly associated with progressively worse mental health functioning. These findings underscore the need for regular comprehensive mental health assessments focusing on specific needs of the child.

  13. Quantitative prediction of shrimp disease incidence via the profiles of gut eukaryotic microbiota.

    PubMed

    Xiong, Jinbo; Yu, Weina; Dai, Wenfang; Zhang, Jinjie; Qiu, Qiongfen; Ou, Changrong

    2018-04-01

    One common notion is emerging that gut eukaryotes are commensal or beneficial, rather than detrimental. To date, however, surprisingly few studies have been taken to discern the factors that govern the assembly of gut eukaryotes, despite growing interest in the dysbiosis of gut microbiota-disease relationship. Herein, we firstly explored how the gut eukaryotic microbiotas were assembled over shrimp postlarval to adult stages and a disease progression. The gut eukaryotic communities changed markedly as healthy shrimp aged, and converged toward an adult-microbiota configuration. However, the adult-like stability was distorted by disease exacerbation. A null model untangled that the deterministic processes that governed the gut eukaryotic assembly tended to be more important over healthy shrimp development, whereas this trend was inverted as the disease progressed. After ruling out the baseline of gut eukaryotes over shrimp ages, we identified disease-discriminatory taxa (species level afforded the highest accuracy of prediction) that characteristic of shrimp health status. The profiles of these taxa contributed an overall 92.4% accuracy in predicting shrimp health status. Notably, this model can accurately diagnose the onset of shrimp disease. Interspecies interaction analysis depicted how the disease-discriminatory taxa interacted with one another in sustaining shrimp health. Taken together, our findings offer novel insights into the underlying ecological processes that govern the assembly of gut eukaryotes over shrimp postlarval to adult stages and a disease progression. Intriguingly, the established model can quantitatively and accurately predict the incidences of shrimp disease.

  14. Progressive failure methodologies for predicting residual strength and life of laminated composites

    NASA Technical Reports Server (NTRS)

    Harris, Charles E.; Allen, David H.; Obrien, T. Kevin

    1991-01-01

    Two progressive failure methodologies currently under development by the Mechanics of Materials Branch at NASA Langley Research Center are discussed. The damage tolerance/fail safety methodology developed by O'Brien is an engineering approach to ensuring adequate durability and damage tolerance by treating only delamination onset and the subsequent delamination accumulation through the laminate thickness. The continuum damage model developed by Allen and Harris employs continuum damage laws to predict laminate strength and life. The philosophy, mechanics framework, and current implementation status of each methodology are presented.

  15. Status Report on Speech Research. A Report on the Status and Progress of Studies on the Nature of Speech, Instrumentation for Its Investigation, and Practical Applications.

    DTIC Science & Technology

    1985-01-01

    vision. In R. Shaw & J. Bransford (Eds.), Perceiving, acting and know- ing: Toward an ecological psychology. Hillsdale, NJ: Erlbaum. 37 6I 37" S! - 7r...may vary across subjects and across languages (Bell-Berti, Raphael, Pisoni, & Sawusch, 1979; Wood , 1982). Second, the tongue has been observed to...Society of America, 75, S23-S24. (Ab- stract) Wood , S. (1982). X-ray and model studies of vowel articulation. Working Pa- pers (Lund Univer3ity

  16. [Status quo and progress of Chinese acupuncture in Algeria].

    PubMed

    Huang, Yisheng

    2015-10-01

    The development of Chinese acupuncture in Algeria and realistic working status in recent years is in- troduced. From five aspects, including general condition of acupuncture in Algeria, clinical application and analysis, of acupuncture, promotion and publicity of acupuncture, existing problem and deficiency, and awards and honor, the status quo and progress of Chinese acupuncture in Algeria are discussed in detail.

  17. Control of diabetes and fibrinogen levels as well as improvement in health care might delay low cognitive performance in societies aging progressively.

    PubMed

    Lopes, Daniele Almeida; Moraes, Suzana Alves de; Freitas, Isabel Cristina Martins de

    2015-01-01

    To know the prevalence and factors associated to low cognitive performance in a representative sample of the adult population in a society aging progressively. Cross-sectional population-based study carried out in a three-stage sampling: 81 census tracts (primary sampling unity) were randomly selected, followed by 1,672 households and 2,471 participants (weighted sample) corresponding to the second and third stages, respectively. The outcome prevalence was calculated according sociodemographic, behavioral and health related variables. Crude and adjusted prevalence ratios were estimated using Poisson regression. The prevalence of low cognitive performance was high, mainly among females, and indicated linear trends into categories of age, schooling, income, plasma fibrinogen and self-reported health status. In multivariate models, gender, diabetes, fibrinogen and self-reported health status presented positive associations, while schooling, employment and sitting time presented negative associations with the outcome. Interventions related to diabetes and fibrinogen levels control as well as improvement in health care might delay low cognitive performance in societies aging progressively as such the study population.

  18. Comparing Private Schools and Public Schools Using Hierarchical Linear Modeling. NCES 2006-461

    ERIC Educational Resources Information Center

    Braun, Henry; Jenkins, Frank; Grigg, Wendy

    2006-01-01

    The goal of the study was to examine differences in mean National Assessment of Educational Progress (NAEP) reading and mathematics scores between public and private schools when selected characteristics of students and/or schools were taken into account. Among the student characteristics considered were gender, race/ethnicity, disability status,…

  19. The "New Doctorate" in Austria: Progress toward a Professional Model or Status Quo?

    ERIC Educational Resources Information Center

    Pechar, Hans; Ates, Gülay; Andres, Lesley

    2012-01-01

    Until recently, both policy direction and public awareness of the Bologna Process has been focused almost unilaterally on the introduction of the Bachelor's degree to European universities. This is understandable, as for most European countries, the Bachelor is a new academic degree. However, commencing with the Berlin Ministerial Conference…

  20. Childhood malnutrition in Egypt using geoadditive Gaussian and latent variable models.

    PubMed

    Khatab, Khaled

    2010-04-01

    Major progress has been made over the last 30 years in reducing the prevalence of malnutrition amongst children less than 5 years of age in developing countries. However, approximately 27% of children under the age of 5 in these countries are still malnourished. This work focuses on the childhood malnutrition in one of the biggest developing countries, Egypt. This study examined the association between bio-demographic and socioeconomic determinants and the malnutrition problem in children less than 5 years of age using the 2003 Demographic and Health survey data for Egypt. In the first step, we use separate geoadditive Gaussian models with the continuous response variables stunting (height-for-age), underweight (weight-for-age), and wasting (weight-for-height) as indicators of nutritional status in our case study. In a second step, based on the results of the first step, we apply the geoadditive Gaussian latent variable model for continuous indicators in which the 3 measurements of the malnutrition status of children are assumed as indicators for the latent variable "nutritional status".

  1. Role of word-of-mouth for programs of voluntary vaccination: A game-theoretic approach.

    PubMed

    Bhattacharyya, Samit; Bauch, Chris T; Breban, Romulus

    2015-11-01

    We propose a model describing the synergetic feedback between word-of-mouth (WoM) and epidemic dynamics controlled by voluntary vaccination. The key feature consists in combining a game-theoretic model for the spread of WoM and a compartmental model describing VSIR disease dynamics in the presence of a program of voluntary vaccination. We evaluate and compare two scenarios for determinants of behavior, depending on what WoM disseminates: (1) vaccine advertising, which may occur whether or not an epidemic is ongoing and (2) epidemic status, notably disease prevalence. Understanding the synergy between the two strategies could be particularly important for designing voluntary vaccination campaigns. We find that, in the initial phase of an epidemic, vaccination uptake is determined more by vaccine advertising than the epidemic status. As the epidemic progresses, epidemic status becomes increasingly important for vaccination uptake, considerably accelerating vaccination uptake toward a stable vaccination coverage. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. A population-based study of tuberculosis epidemiology and innovative service delivery in Canada.

    PubMed

    Jensen, M; Lau, A; Langlois-Klassen, D; Boffa, J; Manfreda, J; Long, R

    2012-01-01

    To compare and interpret tuberculosis (TB) incidence rates in a Canadian population across two decennials (1989-1998 and 1999-2008) as a benchmark for World Health Organization targets and the long-term goal of TB elimination. The population under study was served by two urban clinics in the first decennial and two urban and one provincial clinic in the second. TB rates among Status Indians, Canadian-born 'others' and the foreign-born were estimated using provincial and national databases. Program performance was measured in on-reserve Status Indians in each decennial. In each decennial, the incidence rate in Status Indians and the foreign-born was greater than that in the Canadian-born 'others'; respectively 27.7 and 33.0 times in Status Indians, and 8.0 and 20.9 times in the foreign-born. Between decennials, the rate fell by 56% in Status Indians, 58% in Canadian-born 'others', and 18% in the foreign-born. On-reserve Status Indians had higher rates than off-reserve Status Indians, and the three-clinic model out-performed the two-clinic model among those on-reserve. Rates in the foreign-born varied by World Bank region, and were highest among those from Africa and Asia. Status Indians and the foreign-born are at increased risk of TB in Canada. Significant progress towards TB elimination has been made in Status Indians but not in the foreign-born.

  3. TU-D-207B-01: A Prediction Model for Distinguishing Radiation Necrosis From Tumor Progression After Gamma Knife Radiosurgery Based On Radiomics Features From MR Images

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

    Zhang, Z; MD Anderson Cancer Center, Houston, TX; Ho, A

    Purpose: To develop and validate a prediction model using radiomics features extracted from MR images to distinguish radiation necrosis from tumor progression for brain metastases treated with Gamma knife radiosurgery. Methods: The images used to develop the model were T1 post-contrast MR scans from 71 patients who had had pathologic confirmation of necrosis or progression; 1 lesion was identified per patient (17 necrosis and 54 progression). Radiomics features were extracted from 2 images at 2 time points per patient, both obtained prior to resection. Each lesion was manually contoured on each image, and 282 radiomics features were calculated for eachmore » lesion. The correlation for each radiomics feature between two time points was calculated within each group to identify a subset of features with distinct values between two groups. The delta of this subset of radiomics features, characterizing changes from the earlier time to the later one, was included as a covariate to build a prediction model using support vector machines with a cubic polynomial kernel function. The model was evaluated with a 10-fold cross-validation. Results: Forty radiomics features were selected based on consistent correlation values of approximately 0 for the necrosis group and >0.2 for the progression group. In performing the 10-fold cross-validation, we narrowed this number down to 11 delta radiomics features for the model. This 11-delta-feature model showed an overall prediction accuracy of 83.1%, with a true positive rate of 58.8% in predicting necrosis and 90.7% for predicting tumor progression. The area under the curve for the prediction model was 0.79. Conclusion: These delta radiomics features extracted from MR scans showed potential for distinguishing radiation necrosis from tumor progression. This tool may be a useful, noninvasive means of determining the status of an enlarging lesion after radiosurgery, aiding decision-making regarding surgical resection versus conservative medical management.« less

  4. Relationship between patient-reported outcomes and clinical outcomes in metastatic castration-resistant prostate cancer: post hoc analysis of COU-AA-301 and COU-AA-302.

    PubMed

    Cella, D; Traina, S; Li, T; Johnson, K; Ho, K F; Molina, A; Shore, N D

    2018-02-01

    Patient-reported outcomes (PROs) are used to assess benefit-risk in drug development. The relationship between PROs and clinical outcomes is not well understood. We aim to elucidate the relationships between changes in PRO measures and clinical outcomes in metastatic castration-resistant prostate cancer (mCRPC). We investigated relationships between changes in self-reported fatigue, pain, functional well-being (FWB), physical well-being (PWB) and prostate cancer-specific symptoms with overall survival (OS) and radiographic progression-free survival (rPFS) after 6 and 12 months of treatment in COU-AA-301 (N = 1195) or COU-AA-302 (N = 1088). Eligible COU-AA-301 patients had progressed after docetaxel and had Eastern Cooperative Oncology Group performance status (ECOG PS) ≤ 2. Eligible COU-AA-302 patients had no prior chemotherapy and ECOG PS 0 or 1. Patients were treated with abiraterone acetate (1000 mg/day) plus prednisone (10 mg/day) or prednisone alone daily. Association between self-reported fatigue, pain and functional status, and OS and/or rPFS, using pooled data regardless of treatment, was assessed. Cox proportional hazard regression modeled time to death or radiographic progression. In COU-AA-301 patients, PRO improvements were associated with longer OS and longer time to radiographic progression versus worsening or stable PROs (P < 0.0001). In multivariate models, all except pain intensity remained associated with OS. Pain intensity, PWB and FWB improvements remained associated with rPFS. In COU-AA-302 patients, worsening PROs were associated with higher likelihood of radiographic progression (P ≤ 0.025) compared with improved or stable PROs. In multivariate models, worsening PWB remained associated with worse rPFS. The 12-month analysis confirmed the 6-month results. PROs are significantly associated with clinically relevant time-to-event efficacy outcomes in clinical trials and may complement and help predict traditional clinical practice methods for monitoring patients for disease progression. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  5. A Simple Approach to Inference in Covariance Structure Modeling with Missing Data: Bayesian Analysis. Project 2.4, Quantitative Models To Monitor the Status and Progress of Learning and Performance and Their Antecedents.

    ERIC Educational Resources Information Center

    Muthen, Bengt

    This paper investigates methods that avoid using multiple groups to represent the missing data patterns in covariance structure modeling, attempting instead to do a single-group analysis where the only action the analyst has to take is to indicate that data is missing. A new covariance structure approach developed by B. Muthen and G. Arminger is…

  6. Does hypervascularity of liver metastases as detected on MRI predict disease progression in breast cancer patients?

    PubMed

    Braga, Larissa; Semelka, Richard C; Pietrobon, Ricardo; Martin, Diego; de Barros, Nestor; Guller, Ulrich

    2004-05-01

    The aim of our study was to evaluate the association of the vascularity of liver metastases, as characterized by MRI, and disease progression in breast cancer patients. Sixteen breast cancer patients with liver metastases who underwent MRI before and after systemic therapy were retrospectively identified. On the basis of comparison of each MRI examination with the previous examination, disease status of the patients was classified as complete response, partial response, stable disease, or progressive disease. Liver metastases were characterized as hyper- or hypovascular on the basis of the degree of enhancement in the arterial, portal, and interstitial phases of imaging after administration of a contrast agent. Fisher's exact test and ordinal logistic regression models, including the type of systemic therapy, presence of multiple metastases, and hormone receptor status, were used to estimate the unadjusted and risk-adjusted association between the presence of hypervascular liver metastases and disease progression. All patients in our sample (n = 16) were women and most (12/16, 75%) were white. Their median age was 51.5 years. In unadjusted analyses, the association between the presence of hypervascular liver metastases and disease progression was statistically significant (p < 0.0001). In multiple logistic regression analyses, hypervascular liver metastases were found to be an independent predictor of disease progression. Patients with hypervascular liver lesions were 20.5 times more likely to experience disease progression than patients without hypervascular metastases (odds ratio, 20.5; 95% confidence interval, 5.1-83.5; p < 0.0001). Our analysis provides suggestive evidence that disease progression can be predicted through MRI assessment of the vascularity of liver metastases in patients with breast cancer.

  7. CP violation in the B system.

    PubMed

    Gershon, T; Gligorov, V V

    2017-04-01

    The phenomenon of CP violation is crucial to understand the asymmetry between matter and antimatter that exists in the Universe. Dramatic experimental progress has been made, in particular in measurements of the behaviour of particles containing the b quark, where CP violation effects are predicted by the Kobayashi-Maskawa mechanism that is embedded in the standard model. The status of these measurements and future prospects for an understanding of CP violation beyond the standard model are reviewed.

  8. Secondary analysis of APPLE study suggests atorvastatin may reduce atherosclerosis progression in pubertal lupus patients with higher C reactive protein

    PubMed Central

    Ardoin, Stacy P; Schanberg, Laura Eve; Sandborg, Christy I; Barnhart, Huiman X; Evans, Greg W; Yow, Eric; Mieszkalski, Kelly L; Ilowite, Norman T; Eberhard, Anne; Imundo, Lisa F; Kimura, Yuki; Levy, Deborah; von Scheven, Emily; Silverman, Earl; Bowyer, Suzanne L; Punaro, L; Singer, Nora G; Sherry, David D; McCurdy, Deborah K; Klein-Gitelman, Marissa; Wallace, Carol; Silver, Richard M; Wagner-Weiner, Linda; Higgins, Gloria C; Brunner, Hermine I; Jung, Lawrence; Soep, Jennifer B; Reed, Ann M; Thompson, Susan D

    2014-01-01

    Objective Participants in the Atherosclerosis Prevention in Paediatric Lupus Erythematosus (APPLE) trial were randomised to placebo or atorvastatin for 36 months. The primary endpoint, reduced carotid intima medial thickness (CIMT) progression, was not met but atorvastatin-treated participants showed a trend of slower CIMT progression. Post-hoc analyses were performed to assess subgroup benefit from atorvastatin therapy. Methods Subgroups were prespecified and defined by age (> or ≤15.5 years), systemic lupus erythematosus (SLE) duration (> or ≤24 months), pubertal status (Tanner score ≥4 as post-pubertal or <4 as pre-pubertal), low density lipoprotein cholesterol (LDL) (≥ or <110 mg/dl) and high-sensitivity C reactive protein (hsCRP) (≥ or <1.5 mg/l). A combined subgroup (post-pubertal and hsCRP≥1.5 mg/l) was compared to all others. Longitudinal linear mixed-effects models were developed using 12 CIMT and other secondary APPLE outcomes (lipids, hsCRP, disease activity and damage, and quality of life). Three way interaction effects were assessed for models. Results Significant interaction effects with trends of less CIMT progression in atorvastatin-treated participants were observed in pubertal (3 CIMT segments), high hsCRP (2 CIMT segments), and the combined high hsCRP and pubertal group (5 CIMT segments). No significant treatment effect trends were observed across subgroups defined by age, SLE duration, LDL for CIMT or other outcome measures. Conclusions Pubertal status and higher hsCRP were linked to lower CIMT progression in atorvastatin-treated subjects, with most consistent decreases in CIMT progression in the combined pubertal and high hsCRP group. While secondary analyses must be interpreted cautiously, results suggest further research is needed to determine whether pubertal lupus patients with high CRP benefit from statin therapy. ClinicalTrials.gov identifier NCT00065806. PMID:23436914

  9. [Economic factors related to the Millennium Development Goals: a literature review].

    PubMed

    Palma, Marco; Hernández, Ildefonso; Alvarez-Dardet, Carlos; Gil-González, Diana; Ruiz, María T; Medina, Manuel

    2009-08-01

    To systematize all the information published on the status of and progress made toward the Health-related Millennium Development Goals (HMDGs), as well as to understand associations with certain economic factors and the potential for success. A search was conducted for all scientific articles covering the Millennium Development Goals in general, published from 1 January 2000 to 31 August 2006, in the electronic databases of the EBSCO, CSA Illumina, Thomson Gale, SwetsWise, and BIREME. All original articles in English or Spanish that evaluated HMDG status, progress, and determinants were selected. The analysis evaluated the distribution of determinants of HMDG status or progress, the HMDGs referred to, the study type, the relationship between economic indicators and health, the study location, and the status and potential for attaining the HMDGs. The quality of the articles was also rated. Of the 304 original articles found, 114 (37.5%) covered one or more HMDGs. The most frequently addressed goals were those concerning infant and maternal mortality. Of the 39 articles that evaluated HMDGs and their association with economic variables, 13 dealt with economic factors related to equity, policy, or globalization. Economic and policy factors were most frequently associated with HMDG status or progress. There is a definitive trend toward measuring HMDG status and progress according to economic factors that reflect the population's condition. There is an information gap regarding government spending, international commerce, international aid, and global economic policy. The potential for achieving HMDGs in poor countries is low.

  10. Seizure susceptibility in intact and ovariectomized female rats treated with the convulsant pilocarpine

    PubMed Central

    Scharfman, Helen E.; Goodman, Jeffrey H.; Rigoulot, Marie-Aude; Berger, Russell E.; Walling, Susan G.; Mercurio, Thomas C.; Stormes, Kerry; Maclusky, Neil J.

    2008-01-01

    Despite numerous neuroendocrinological studies of seizures, the influence of estrogen and progesterone on seizures and epilepsy remains unclear. This may be due to the fact that previous studies have not systematically compared distinct endocrine conditions and included all relevant controls. The goal of the present study was to conduct such a study using pilocarpine as chemoconvulsant. Thus, age and weight-matched, intact or ovariectomized rats were tested to determine incidence of status epilepticus and to study events leading to status. Intact female rats were sampled at each cycle stage (proestrus, estrus, metestrus, or diestrus 2). Convulsant was administered at the same time of day, 10:00–10:30 a.m. Statistical analysis showed that there was a significantly lower incidence of status on the morning of estrus, but differences were attenuated in older animals. Ovariectomized rats were distinct in their rapid progression to status. These results show that the incidence of status in female rats following pilocarpine injection, and the progression to pilocarpine-induced status, are influenced by reproductive state as well as age. The hormonal milieu present specifically on the morning of estrus appears to decrease susceptibility to pilocarpine-induced status, particularly at young ages. In contrast, the chronic absence of reproductive steroids that characterizes the ovariectomized rat leads to a more rapid progression to status. This dissociation between incidence vs. progression provides new insight into the influence of estrogen and progesterone on seizures. PMID:16084511

  11. 75 FR 15421 - Proposed Agency Information Collection

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-29

    ... the status of activities, project progress, jobs created and retained, spend rates and performance... information that DOE is developing to collect data on the status of activities, project progress, jobs created and retained, spend rates and performance metrics under the American Recovery and Reinvestment Act of...

  12. Status and future prospects of using numerical methods to study complex flows at High Reynolds numbers

    NASA Technical Reports Server (NTRS)

    Maccormack, R. W.

    1978-01-01

    The calculation of flow fields past aircraft configuration at flight Reynolds numbers is considered. Progress in devising accurate and efficient numerical methods, in understanding and modeling the physics of turbulence, and in developing reliable and powerful computer hardware is discussed. Emphasis is placed on efficient solutions to the Navier-Stokes equations.

  13. Teaching Effective Hand Raising to Children with Autism during Group Instruction

    ERIC Educational Resources Information Center

    Charania, Shaireen M.; LeBlanc, Linda A.; Sabanathan, Narmatha; Ktaech, Inas A.; Carr, James E.; Gunby, Kristin

    2010-01-01

    We taught 3 children with autism to raise a hand or keep both hands down depending on their status (e.g., having heard a target word, possessing a specific item) using modeling, prompting, and reinforcement. All 3 children acquired accurate hand-raising skills in response to progressively more difficult discrimination tasks during group…

  14. ASSESSMENT OF ALLERGIC RESPONSES TO FOOD PROTEINS USING A NOVEL AND SENSITIVE ADJUVANT-FREE INGESTION-BASED MOUSE MODEL

    EPA Science Inventory

    (1)  Work Status: Since our last Progress Report, we have worked to determine the most effective and consistent protocol for evaluating the allergenicity of food proteins in F709 mice, and we have gathered data for peanut, egg white, rice, and chicken meat p...

  15. Cosmic ray astroparticle physics: current status and future perspectives

    NASA Astrophysics Data System (ADS)

    Donato, Fiorenza

    2017-02-01

    The data we are receiving from galactic cosmic rays are reaching an unprecedented precision, over very wide energy ranges. Nevertheless, many problems are still open, while new ones seem to appear when data happen to be redundant. We will discuss some paths to possible progress in the theoretical modeling and experimental exploration of the galactic cosmic radiation.

  16. Status of Computational Aerodynamic Modeling Tools for Aircraft Loss-of-Control

    NASA Technical Reports Server (NTRS)

    Frink, Neal T.; Murphy, Patrick C.; Atkins, Harold L.; Viken, Sally A.; Petrilli, Justin L.; Gopalarathnam, Ashok; Paul, Ryan C.

    2016-01-01

    A concerted effort has been underway over the past several years to evolve computational capabilities for modeling aircraft loss-of-control under the NASA Aviation Safety Program. A principal goal has been to develop reliable computational tools for predicting and analyzing the non-linear stability & control characteristics of aircraft near stall boundaries affecting safe flight, and for utilizing those predictions for creating augmented flight simulation models that improve pilot training. Pursuing such an ambitious task with limited resources required the forging of close collaborative relationships with a diverse body of computational aerodynamicists and flight simulation experts to leverage their respective research efforts into the creation of NASA tools to meet this goal. Considerable progress has been made and work remains to be done. This paper summarizes the status of the NASA effort to establish computational capabilities for modeling aircraft loss-of-control and offers recommendations for future work.

  17. Health utility of patients with advanced gastrointestinal stromal tumors (GIST) after failure of imatinib and sunitinib: findings from GRID, a randomized, double-blind, placebo-controlled phase III study of regorafenib versus placebo.

    PubMed

    Poole, Chris D; Connolly, Mark P; Chang, Jane; Currie, Craig J

    2015-07-01

    In this analysis we report patients with advanced gastrointestinal stromal tumors (GIST) refractory to imatinib and sunitinib therapy as derived from the EuroQol-5D (EQ-5D) for progression-free (PF) and progressive disease health status. Data were analyzed from a phase III trial conducted at 57 hospitals in 17 countries (trial registration number, NCT01271712). Patients with advanced GIST were randomized (2:1) to receive blinded treatment using oral regorafenib 160 mg daily or placebo, plus best supportive care (BSC) in both groups, for the first 3 weeks of each 4-week cycle. EQ-5D-3L was administered on day 1 of each cycle before contact with their physician and before any study-related procedures. The effect of disease progression on the utility of EQ-5D was tested with paired-samples comparison and general linear mixed modeling (GLMM). One hundred and eighty five patients [93 % of the intention-to-treat (ITT) population] completed 803 EQ-5D questionnaires: 77.7 % in progression-free (PF) state, 6.5 % at progression, 13.9 % following first progression, and 1.9 % after second progression. Mean baseline utility was 0.767 (SD 0.221) with no significant between-group differences for active treatment and BSC. The first post-progression health state was 0.647 (SD 0.343), suggesting significantly impaired health-related quality of life after confirmed disease progression showed a decrease of -0.120 (paired samples t test, p = 0.001). GLMM showed no effect of study treatment or cycle number on utility. We demonstrate a significant and clinically meaningful difference in health state utility values between PF and progression. Utility values remained stable over successive regorafenib cycles after controlling for disease status and treatment type.

  18. Chronic Cerebrospinal Vascular Insufficiency Is Not Associated with HLA DRB1*1501 Status in Multiple Sclerosis Patients

    PubMed Central

    Weinstock-Guttman, Bianca; Zivadinov, Robert; Cutter, Gary; Tamaño-Blanco, Miriam; Marr, Karen; Badgett, Darlene; Carl, Ellen; Elfadil, Makki; Kennedy, Cheryl; Benedict, Ralph H. B.; Ramanathan, Murali

    2011-01-01

    Background Chronic cerebrospinal venous insufficiency (CCSVI) was described as a vascular condition characterized by anomalies of veins outside the skull was reported to be associated with multiple sclerosis (MS). The objective was to assess the associations between HLA DRB1*1501 status and the occurrence of CCSVI in MS patients. Methodology/Principal Findings This study included 423 of 499 subjects enrolled in the Combined Transcranial and Extracranial Venous Doppler Evaluation (CTEVD) study. The HLA DRB1*1501 status was obtained in 268 MS patients and 155 controls by genotyping rs3135005, a SNP associated with DRB1*1501 status. All subjects underwent a clinical examination and Doppler scan of the head and neck. The frequency of CCSVI was higher (OR = 4.52, p<0.001) in the MS group 56.0% vs. 21.9% in the controls group and also higher in the progressive MS group 69.8% vs. 49.5% in the non-progressive MS group. The 51.9% frequency of HLA DRB1*1501 positivity (HLA+) in MS was higher compared (OR = 2.33, p<0.001) to 31.6% to controls. The HLA+ frequency in the non-progressive (51.6%) and progressive MS groups (52.3%) was similar. The frequency of HLA+ CCSVI+ was 40.7% in progressive MS, 27.5% in non-progressive MS and 8.4% in controls. The presence of CCSVI was independent of HLA DRB1*1501 status in MS patients. Conclusions/Significance The lack of strong associations of CCSVI with HLA DRB1*1501 suggests that the role of the underlying associations of CCSVI in MS should be interpreted with caution. Further longitudinal studies should determine whether interactions between these factors can contribute to disease progression in MS. PMID:21340025

  19. Psychosocial and Neurohormonal Predictors of HIV Disease Progression (CD4 Cells and Viral Load): A 4 Year Prospective Study.

    PubMed

    Ironson, G; O'Cleirigh, C; Kumar, M; Kaplan, L; Balbin, E; Kelsch, C B; Fletcher, M A; Schneiderman, N

    2015-08-01

    Most studies of psychosocial predictors of disease progression in HIV have not considered norepinephrine (NE), a neurohormone related to emotion and stress, even though NE has been related to accelerated viral replication in vitro and impaired response to antiretroviral therapy (ART). We therefore examined NE, cortisol, depression, hopelessness, coping, and life event stress as predictors of HIV progression in a diverse sample. Participants (n = 177) completed psychological assessment, blood draws [CD4, viral load (VL)], and a 15 h urine sample (NE, cortisol) every 6 months over 4 years. Hierarchical linear modeling (HLM) was used to model slope in CD4 and VL controlling for ART at every time point, gender, age, race, SES, and initial disease status. NE (as well as depression, hopelessness, and avoidant coping) significantly predicted a greater rate of decrease in CD4 and increase in VL. Cortisol was not significantly related to CD4, but predicted VL increase. To our knowledge, this is the first study relating NE, in vivo, to accelerated disease progression over an extended time. It also extends our previous 2 year study by relating depressed mood and coping to accelerated disease progression over 4 years.

  20. A review on PARP1 inhibitors: Pharmacophore modeling, virtual and biological screening studies to identify novel PARP1 inhibitors.

    PubMed

    Singh, Sardar Shamshair; Sarma, Jagarlapudi A R P; Narasu, Lakshmi; Dayam, Raveendra; Xu, Shili; Neamati, Nouri

    2014-01-01

    A tremendous research on Poly (ADP-ribose) polymerase (PARP) pertaining to cancer and ischemia is in very rapid progress. PARP's are a specific class of enzymes that repairs the damaged DNA. Recent findings suggest also that PARP-1 is the most abundantly expressed nuclear enzyme which involves in various therapeutic areas like inflammation, stroke, cardiac ischemia, cancer and diabetes. The current review describes the overview on clinical candidates of PARP1 and its current status in clinical trials. This paper also covers identification of potent PARP1 inhibitors using structure and ligand based pharmacophore models. Finally 36 potential hits were identified from the virtual screening of pharmacophore models and screened for PARP1 activity. 15 actives were identified as potent PARP1 inhibitors and further optimization of these analogues are in progress.

  1. Modelling the Course of an HIV Infection: Insights from Ecology and Evolution

    PubMed Central

    Alizon, Samuel; Magnus, Carsten

    2012-01-01

    The Human Immunodeficiency Virus (HIV) is one of the most threatening viral agents. This virus infects approximately 33 million people, many of whom are unaware of their status because, except for flu-like symptoms right at the beginning of the infection during the acute phase, the disease progresses more or less symptom-free for 5 to 10 years. During this asymptomatic phase, the virus slowly destroys the immune system until the onset of AIDS when opportunistic infections like pneumonia or Kaposi’s sarcoma can overcome immune defenses. Mathematical models have played a decisive role in estimating important parameters (e.g., virion clearance rate or life-span of infected cells). However, most models only account for the acute and asymptomatic latency phase and cannot explain the progression to AIDS. Models that account for the whole course of the infection rely on different hypotheses to explain the progression to AIDS. The aim of this study is to review these models, present their technical approaches and discuss the robustness of their biological hypotheses. Among the few models capturing all three phases of an HIV infection, we can distinguish between those that mainly rely on population dynamics and those that involve virus evolution. Overall, the modeling quest to capture the dynamics of an HIV infection has improved our understanding of the progression to AIDS but, more generally, it has also led to the insight that population dynamics and evolutionary processes can be necessary to explain the course of an infection. PMID:23202449

  2. Satellite freeze forecast system

    NASA Technical Reports Server (NTRS)

    Martsolf, J. D. (Principal Investigator)

    1983-01-01

    Provisions for back-up operations for the satellite freeze forecast system are discussed including software and hardware maintenance and DS/1000-1V linkage; troubleshooting; and digitized radar usage. The documentation developed; dissemination of data products via television and the IFAS computer network; data base management; predictive models; the installation of and progress towards the operational status of key stations; and digital data acquisition are also considered. The d addition of dew point temperature into the P-model is outlined.

  3. Status Report on Speech Research: A Report on the Status and Progress of Studies on the Nature of Speech, Instrumentation for Its Investigation, and Practical Applications, October-December 1986.

    ERIC Educational Resources Information Center

    O'Brien, Nancy, Ed.

    One of a series of semiannual reports, this paper presents articles exploring the status and progress of studies on the nature of speech, instrumentation for its investigation, and practical research applications. Titles of the papers and their authors are as follows: (1) "Lexical Organization and Welsh Consonant Mutations" (S. Boyce, C. P.…

  4. Status Report on Speech Research: A Report on the Status and Progress of Studies on the Nature of Speech, Instrumentation for Its Investigation, and Practical Applications, January 1-March 31, 1977.

    ERIC Educational Resources Information Center

    Haskins Labs., New Haven, CT.

    This report is one of a regular series about the status and progress of studies on the nature of speech, instrumentation for its investigation, and practical applications. The 11 papers discuss the dissociation of spectral and temporal cues to the voicing distinction in initial stopped consonants; perceptual integration and selective attention in…

  5. Status Report on Speech Research: A Report on the Status and Progress of Studies on the Nature of Speech, Instrumentation for Its Investigation, and Practical Applications, April 1-September 30, 1986.

    ERIC Educational Resources Information Center

    O'Brien, Nancy, Ed.

    Focusing on the status, progress, instrumentation, and applications of studies on the nature of speech, this report contains the following research studies: "The Role of Psychophysics in Understanding Speech Perception" (B. H. Repp); "Specialized Perceiving Systems for Speech and Other Biologically Significant Sounds" (I. G. Mattingly; A. M.…

  6. User Interfaces for Patient-Centered Communication of Health Status and Care Progress

    ERIC Educational Resources Information Center

    Wilcox-Patterson, Lauren

    2013-01-01

    The recent trend toward patients participating in their own healthcare has opened up numerous opportunities for computing research. This dissertation focuses on how technology can foster this participation, through user interfaces to effectively communicate personal health status and care progress to hospital patients. I first characterize the…

  7. 76 FR 79754 - Twelfth Meeting: RTCA Special Committee 220, Automatic Flight Guidance and Control

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-22

    ... technologies Administrative items (meeting schedule, location, and next meeting agenda) Any other business... 2 status--progress, issues and plan Review of WG 3 status--progress, issues and plans Review action.... Issued in Washington, DC, on December 15, 2011. Robert L. Bostiga, Manager, Business Operations Branch...

  8. Gender hormones and the progression of experimental polycystic kidney disease.

    PubMed

    Stringer, Kenneth D; Komers, Radko; Osman, Shukri A; Oyama, Terry T; Lindsley, Jessie N; Anderson, Sharon

    2005-10-01

    Male gender is a risk factor for progression of autosomal-dominant polycystic kidney disease (ADPKD), clinically and in the Han:SPRD rat model. Orchiectomy limits progression, but mechanisms of the detrimental effect of androgen, and/or beneficial effects of estrogen, are not known. This protocol tested the hypothesis that male gender (intact androgen status) promotes progression, while female gender (intact estrogen status) is protective; and that these disease-modifying effects are due to changes in expression of known fibrotic mediators. Studies were performed in male and female noncystic control (+/+) and cystic (+/-) rats subjected to orchiectomy, ovariectomy, or sham operation. At 12 weeks of age, renal function was measured. Blood and kidneys were taken for measurement of plasma and renal renin, endothelin (ET-1), endothelial nitric oxide synthase (eNOS), and vascular endothelial growth factor (VEGF), using biochemical, protein expression, and immunohistochemical methods. Cystic male rats exhibited significantly reduced glomerular filtration (GFR) and effective renal plasma flow (ERPF) rates, with suppression of plasma and renal renin, up-regulation of renal ET-1 and eNOS, and down-regulation of renal VEGF expression. Orchiectomy attenuated the fall in GFR and ERPF, while numerically limiting changes in eNOS and VEGF. Female rats exhibited less cystic growth, with normal renin status, lesser elevation of renal ET-1, and proportionately lesser changes in VEGF and eNOS. Ovariectomy led to higher blood pressure and reduced GFR and ERPF, with a trend toward upregulation of ET-1, and significant down-regulation of VEGF and eNOS. Female gender is protective, but ovariectomy attenuates the protective effect of female gender, in association with changes in renal expression of ET-1, VEGF, and eNOS. The accelerated disease in male rats can be attenuated by orchiectomy and consequent changes in expression of disease mediators.

  9. Estimating Time to Event From Longitudinal Categorical Data: An Analysis of Multiple Sclerosis Progression.

    PubMed

    Mandel, Micha; Gauthier, Susan A; Guttmann, Charles R G; Weiner, Howard L; Betensky, Rebecca A

    2007-12-01

    The expanded disability status scale (EDSS) is an ordinal score that measures progression in multiple sclerosis (MS). Progression is defined as reaching EDSS of a certain level (absolute progression) or increasing of one point of EDSS (relative progression). Survival methods for time to progression are not adequate for such data since they do not exploit the EDSS level at the end of follow-up. Instead, we suggest a Markov transitional model applicable for repeated categorical or ordinal data. This approach enables derivation of covariate-specific survival curves, obtained after estimation of the regression coefficients and manipulations of the resulting transition matrix. Large sample theory and resampling methods are employed to derive pointwise confidence intervals, which perform well in simulation. Methods for generating survival curves for time to EDSS of a certain level, time to increase of EDSS of at least one point, and time to two consecutive visits with EDSS greater than three are described explicitly. The regression models described are easily implemented using standard software packages. Survival curves are obtained from the regression results using packages that support simple matrix calculation. We present and demonstrate our method on data collected at the Partners MS center in Boston, MA. We apply our approach to progression defined by time to two consecutive visits with EDSS greater than three, and calculate crude (without covariates) and covariate-specific curves.

  10. Effects of General Medical Health on Alzheimer Progression: the Cache County Dementia Progression Study

    PubMed Central

    Leoutsakos, Jeannie-Marie S.; Han, Dingfen; Mielke, Michelle M.; Forrester, Sarah N.; Tschanz, JoAnn T.; Corcoran, Chris D.; Green, Robert C.; Norton, Maria C.; Welsh-Bohmer, Kathleen A.; Lyketsos, Constantine G.

    2012-01-01

    Background Several observational studies suggested a link between health status and rate of decline among individuals with Alzheimer’s disease (AD). We sought to quantify the relationship in a population-based study of incident AD, and to compare global comorbidity ratings to counts of comorbid conditions and medications as predictors of AD progression. Methods Design Case-only cohort study arising from population-based longitudinal study of memory and aging. Setting Cache County, Utah Participants 335 individuals with incident AD followed for up to 11 years. Measurements Patient descriptors included sex, age, education, dementia duration at baseline, and APOE genotype. Measures of health status made at each visit included the GMHR (General Medical Health Rating), number of comorbid medical conditions, and number of non-psychiatric medications. Dementia outcomes included the Mini-Mental State Exam (MMSE), Clinical Dementia Rating – sum of boxes (CDR-sb), and the Neuropsychiatric Inventory (NPI). Results Health Status tended to fluctuate over time within individuals. None of the baseline medical variables (GMHR, comorbidities, non-psychiatric medications) were associated with differences in rates of decline in longitudinal linear mixed effects models. Over time, low GMHR ratings, but not comorbidities or medications, were associated with poorer outcomes (MMSE: β=−1.07 p=0.01; CDR-sb: β=1.79 p<0.001; NPI: β=4.57 p=0.01) Conclusions Given that time-varying GMHR, but not baseline GMHR, was associated with the outcomes, there is likely a dynamic relationship between medical and cognitive health. GMHR is a more sensitive measure of health than simple counts of comorbidities or medications. Since health status is a potentially modifiable risk factor, further study is warranted. PMID:22687143

  11. Effects of general medical health on Alzheimer's progression: the Cache County Dementia Progression Study.

    PubMed

    Leoutsakos, Jeannie-Marie S; Han, Dingfen; Mielke, Michelle M; Forrester, Sarah N; Tschanz, JoAnn T; Corcoran, Chris D; Green, Robert C; Norton, Maria C; Welsh-Bohmer, Kathleen A; Lyketsos, Constantine G

    2012-10-01

    Several observational studies have suggested a link between health status and rate of decline among individuals with Alzheimer's disease (AD). We sought to quantify the relationship in a population-based study of incident AD, and to compare global comorbidity ratings to counts of comorbid conditions and medications as predictors of AD progression. This was a case-only cohort study arising from a population-based longitudinal study of memory and aging, in Cache County, Utah. Participants comprised 335 individuals with incident AD followed for up to 11 years. Patient descriptors included sex, age, education, dementia duration at baseline, and APOE genotype. Measures of health status made at each visit included the General Medical Health Rating (GMHR), number of comorbid medical conditions, and number of non-psychiatric medications. Dementia outcomes included the Mini-Mental State Examination (MMSE), Clinical Dementia Rating - sum of boxes (CDR-sb), and the Neuropsychiatric Inventory (NPI). Health status tended to fluctuate over time within individuals. None of the baseline medical variables (GMHR, comorbidities, and non-psychiatric medications) was associated with differences in rates of decline in longitudinal linear mixed effects models. Over time, low GMHR ratings, but not comorbidities or medications, were associated with poorer outcomes (MMSE: β = -1.07 p = 0.01; CDR-sb: β = 1.79 p < 0.001; NPI: β = 4.57 p = 0.01). Given that time-varying GMHR, but not baseline GMHR, was associated with the outcomes, it seems likely that there is a dynamic relationship between medical and cognitive health. GMHR is a more sensitive measure of health than simple counts of comorbidities or medications. Since health status is a potentially modifiable risk factor, further study is warranted.

  12. Combined high-field intraoperative magnetic resonance imaging and endoscopy increase extent of resection and progression-free survival for pituitary adenomas

    PubMed Central

    Sylvester, Peter T.; Evans, John A.; Zipfel, Gregory J.; Chole, Richard A.; Uppaluri, Ravindra; Haughey, Bruce H.; Getz, Anne E.; Silverstein, Julie; Rich, Keith M.; Kim, Albert H.; Dacey, Ralph G.

    2014-01-01

    Purpose The clinical benefit of combined intraoperative magnetic resonance imaging (iMRI) and endoscopy for transsphenoidal pituitary adenoma resection has not been completely characterized. This study assessed the impact of microscopy, endoscopy, and/or iMRI on progression-free survival, extent of resection status (gross-, near-, and subtotal resection), and operative complications. Methods Retrospective analyses were performed on 446 transsphenoidal pituitary adenoma surgeries at a single institution between 1998 and 2012. Multivariate analyses were used to control for baseline characteristics, differences during extent of resection status, and progression-free survival analysis. Results Additional surgery was performed after iMRI in 56/156 cases (35.9 %), which led to increased extent of resection status in 15/156 cases (9.6 %). Multivariate ordinal logistic regression revealed no increase in extent of resection status following iMRI or endoscopy alone; however, combining these modalities increased extent of resection status (odds ratio 2.05, 95 % CI 1.21–3.46) compared to conventional transsphenoidal microsurgery. Multivariate Cox regression revealed that reduced extent of resection status shortened progression-free survival for near- versus gross-total resection [hazard ratio (HR) 2.87, 95 % CI 1.24–6.65] and sub- versus near-total resection (HR 2.10; 95 % CI 1.00–4.40). Complication comparisons between microscopy, endoscopy, and iMRI revealed increased perioperative deaths for endoscopy versus microscopy (4/209 and 0/237, respectively), but this difference was non-significant considering multiple post hoc comparisons (Fisher exact, p = 0.24). Conclusions Combined use of endoscopy and iMRI increased pituitary adenoma extent of resection status compared to conventional transsphenoidal microsurgery, and increased extent of resection status was associated with longer progression-free survival. Treatment modality combination did not significantly impact complication rate. PMID:24599833

  13. Modelling of the AGS using Zgoubi - Status

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

    Meot F.; Ahrens, L.; Dutheil, Y.

    2012-05-20

    This paper summarizes the progress achieved so far, and discusses various outcomes, regarding the development of a model of the Alternating Gradient Synchrotron at the RHIC collider. The model, based on stepwise ray-tracing methods, includes beam and polarization dynamics. This is an on-going work, and a follow-on of code developments and particle and spin dynamics simulations that have been subject to earlier publications at IPAC and PAC [1, 2, 3]. A companion paper [4] gives additional informations, regarding the use of the measured magnetic field maps of the AGS main magnets.

  14. Preoperative nutritional status is associated with progression of postoperative cardiac rehabilitation in patients undergoing cardiovascular surgery.

    PubMed

    Arai, Yasuhiro; Kimura, Toru; Takahashi, Yuki; Hashimoto, Takashi; Arakawa, Mamoru; Okamura, Homare

    2018-06-23

    Progression of cardiac rehabilitation after cardiovascular surgery can be affected by frailty. The nutritional status of the patient has been proposed as an indicator of frailty. In this study, we aimed to evaluate the influence of preoperative nutritional status on the progress of postoperative cardiac rehabilitation. This study included 146 patients (82 males, 64 females, average age 71.9 ± 12.0 years) who underwent elective cardiovascular surgery. In-hospital mortality cases were excluded to focus on postoperative cardiac rehabilitation. We classified patients with a Geriatric Nutritional Risk Index of 92 or higher as the good nutrition group and those with a Geriatric Nutritional Risk Index less than 92 as the malnutrition group. Preoperative patient characteristics and postoperative cardiac rehabilitation progress were compared between the good nutrition (n = 93) and malnutrition (n = 53) groups. The patients in the good nutrition group had an earlier progression to walking after postoperative rehabilitation (p = 0.002), a shorter postoperative hospital stay (p = 0.004), and a higher rate of discharge home (p = 0.028) than those in the malnutrition group. Multivariable analysis demonstrated preoperative malnutrition to be an independent predictor for the day to 100 m walking (p = 0.010). Preoperative nutritional status was associated with progression of postoperative cardiac rehabilitation.

  15. Status Report on Speech Research: A Report on the Status and Progress of Studies on the Nature of Speech, Instrumentation for its Investigation, and Practical Applications, April 1-September 30, 1983.

    ERIC Educational Resources Information Center

    Studdert-Kennedy, Michael, Ed.; O'Brien, Nancy, Ed.

    Prepared as part of a regular series on the status and progress of studies on the nature of speech, instrumentation for its evaluation, and practical applications for speech research, this compilation contains 14 reports. Topics covered in the reports include the following: (1) phonetic coding and order memory in relation to reading proficiency,…

  16. Status Report on Speech Research: A Report on the Status and Progress of Studies on the Nature of Speech, Instrumentation for Its Investigation, and Practical Applications, April 1-June 30, 1977.

    ERIC Educational Resources Information Center

    Haskins Labs., New Haven, CT.

    This report is one of a regular series on the status and progress of studies on the nature of speech, instrumentation for its investigation, and practical applications. The ten papers treat the following topics: speech synthesis as a tool for the study of speech production; the study of articulatory organization; phonetic perception; cardiac…

  17. Status Report on Speech Research: A Report on the Status and Progress of Studies on the Nature of Speech, Instrumentation for Its Investigation, and Practical Applications, October 1-December 31, 1983.

    ERIC Educational Resources Information Center

    Studdert-Kennedy, Michael, Ed.; O'Brien, Nancy, Ed.

    One of a regular series on the status and progress of studies on the nature of speech, instrumentation for its investigation, and practical research applications, this report consists of 14 papers. Topics covered in the papers are (1) skilled actions, (2) the control of fundamental frequency declination, (3) selective effects of masking on speech…

  18. Status of the Ford program to evaluate ceramics for stator applications in automotive gas turbine engines

    NASA Technical Reports Server (NTRS)

    Trela, W.

    1980-01-01

    The paper reviews the progress of the major technical tasks of the DOE/NASA/Ford program Evaluation of Ceramics for Stator Applications in Automotive Gas Turbine Engines: reliability prediction, stator fabrication, material characterization, and stator evaluation. A fast fracture reliability model was prepared for a one-piece ceramic stator. Periodic inspection results are presented.

  19. Status of LDEF ionizing radiation measurements and analysis

    NASA Technical Reports Server (NTRS)

    Parnell, T. A.

    1992-01-01

    The LDEF-1 results from the particle astrophysics, radiation environments, and dosimetry measurements on LDEF-1 are summarized, including highlights from presentations at the 2nd symposium. Progress in using LDEF data to improve radiation environment models and calculation methods is reviewed. Radiation effects, or the lack thereof are discussed. Future plans of the LDEF Ionizing Radiation Special Investigation Group are presented.

  20. Widening the Educational Capabilities of Socio-Economically Disadvantaged Students through a Model of Social and Cultural Capital Development

    ERIC Educational Resources Information Center

    Hannon, Cliona; Faas, Daniel; O'Sullivan, Katriona

    2017-01-01

    Widening participation programmes aim to increase the progression of students from low socio-economic status (SES) groups to higher education. This research proposes that the human capabilities approach is a good justice-based framework within which to consider the social and cultural capital processes that impact upon the educational capabilities…

  1. An Update on the VAMOS Extremes Working Group Activities

    NASA Technical Reports Server (NTRS)

    Schubert, Siegfried; Cavalcanti, Iracema

    2011-01-01

    We review here the progress of the Variability of the American MOnsoon Systems (VAMOS) extremes working group since it was formed in February of 2010. The goals of the working group are to 1) develop an atlas of warm-season extremes over the Americas, 2) evaluate existing and planned simulations, and 3) suggest new model runs to address mechanisms and predictability of extremes. Substantial progress has been made in the development of an extremes atlas based on gridded observations and several reanalysis products including Modern Era Retrospective-Analysis for Research and Applications (MERRA) and Climate Forecast System Reanalysis (CFSR). The status of the atlas, remaining issues and plans for its expansion to include model data will be discussed. This includes the possibility of adding a companion atlas based on station observations based on the software developed under the World Climate Research Programme (WCRP) Expert Team on Climate Change. Detection and Indices (ETCCDI) activity. We will also review progress on relevant research and plans for the use and validation of the atlas results.

  2. Community Project for Accelerator Science and Simulation (ComPASS) Final Report

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

    Cary, John R.; Cowan, Benjamin M.; Veitzer, S. A.

    2016-03-04

    Tech-X participated across the full range of ComPASS activities, with efforts in the Energy Frontier primarily through modeling of laser plasma accelerators and dielectric laser acceleration, in the Intensity Frontier primarily through electron cloud modeling, and in Uncertainty Quantification being applied to dielectric laser acceleration. In the following we present the progress and status of our activities for the entire period of the ComPASS project for the different areas of Energy Frontier, Intensity Frontier and Uncertainty Quantification.

  3. Patterns and predictors of skin score change in early diffuse systemic sclerosis from the European Scleroderma Observational Study

    PubMed Central

    Herrick, Ariane L; Peytrignet, Sebastien; Lunt, Mark; Pan, Xiaoyan; Hesselstrand, Roger; Mouthon, Luc; Silman, Alan J; Dinsdale, Graham; Brown, Edith; Czirják, László; Distler, Jörg H W; Distler, Oliver; Fligelstone, Kim; Gregory, William J; Ochiel, Rachel; Vonk, Madelon C; Ancuţa, Codrina; Ong, Voon H; Farge, Dominique; Hudson, Marie; Matucci-Cerinic, Marco; Balbir-Gurman, Alexandra; Midtvedt, Øyvind; Jobanputra, Paresh; Jordan, Alison C; Stevens, Wendy; Moinzadeh, Pia; Hall, Frances C; Agard, Christian; Anderson, Marina E; Diot, Elisabeth; Madhok, Rajan; Akil, Mohammed; Buch, Maya H; Chung, Lorinda; Damjanov, Nemanja S; Gunawardena, Harsha; Lanyon, Peter; Ahmad, Yasmeen; Chakravarty, Kuntal; Jacobsen, Søren; MacGregor, Alexander J; McHugh, Neil; Müller-Ladner, Ulf; Riemekasten, Gabriela; Becker, Michael; Roddy, Janet; Carreira, Patricia E; Fauchais, Anne Laure; Hachulla, Eric; Hamilton, Jennifer; İnanç, Murat; McLaren, John S; van Laar, Jacob M; Pathare, Sanjay; Proudman, Susanna M; Rudin, Anna; Sahhar, Joanne; Coppere, Brigitte; Serratrice, Christine; Sheeran, Tom; Veale, Douglas J; Grange, Claire; Trad, Georges-Selim; Denton, Christopher P

    2018-01-01

    Objectives Our aim was to use the opportunity provided by the European Scleroderma Observational Study to (1) identify and describe those patients with early diffuse cutaneous systemic sclerosis (dcSSc) with progressive skin thickness, and (2) derive prediction models for progression over 12 months, to inform future randomised controlled trials (RCTs). Methods The modified Rodnan skin score (mRSS) was recorded every 3 months in 326 patients. ‘Progressors’ were defined as those experiencing a 5-unit and 25% increase in mRSS score over 12 months (±3 months). Logistic models were fitted to predict progression and, using receiver operating characteristic (ROC) curves, were compared on the basis of the area under curve (AUC), accuracy and positive predictive value (PPV). Results 66 patients (22.5%) progressed, 227 (77.5%) did not (33 could not have their status assessed due to insufficient data). Progressors had shorter disease duration (median 8.1 vs 12.6 months, P=0.001) and lower mRSS (median 19 vs 21 units, P=0.030) than non-progressors. Skin score was highest, and peaked earliest, in the anti-RNA polymerase III (Pol3+) subgroup (n=50). A first predictive model (including mRSS, duration of skin thickening and their interaction) had an accuracy of 60.9%, AUC of 0.666 and PPV of 33.8%. By adding a variable for Pol3 positivity, the model reached an accuracy of 71%, AUC of 0.711 and PPV of 41%. Conclusions Two prediction models for progressive skin thickening were derived, for use both in clinical practice and for cohort enrichment in RCTs. These models will inform recruitment into the many clinical trials of dcSSc projected for the coming years. Trial registration number NCT02339441. PMID:29306872

  4. Status Report on Speech Research: A Report on the Status and Progress of Studies on the Nature of Speech, Instrumentation for its Investigation, and Practical Application, January 1-March 31, 1978. Volumes 1 and 2.

    ERIC Educational Resources Information Center

    Haskins Labs., New Haven, CT.

    This report is part of a continuing series providing information on the status and progress of studies dealing with the nature of speech, instrumentation for its investigation, and practical applications of research. The report covers the period from 1 January 1978 through 31 March 1978, and includes extended reports on the following topics:…

  5. Status Report on Speech Research: A Report on the Status and Progress of Studies on the Nature of Speech, Instrumentation for Its Investigation, and Practical Applications, January 1-June 30, 1974. Report No. SR-37/38(1974).

    ERIC Educational Resources Information Center

    Haskins Labs., New Haven, CT.

    This report, covering the period of January 1 to June 30, 1974, is one of a regular series on the status and progress of studies on the nature of speech, instrumentation for its investigation, and practical applications. Among the 17 manuscripts and extended reports are "The Role of Speech in Language: Introduction to the Conference,""The Human…

  6. Ten-year stability and variability, drinking patterns, and impairment in community youth with diagnostic orphan status of alcohol dependence.

    PubMed

    Grabitz, Maike; Behrendt, Silke; Klotsche, Jens; Buehringer, Gerhard; Lieb, Roselind; Wittchen, Hans-Ullrich

    2012-04-01

    Some adolescents and young adults who do not fulfill criteria for DSM-IV alcohol abuse (AA) report symptoms of DSM-IV alcohol dependence (AD) below the diagnostic threshold (diagnostic orphans, DOs; 1 or 2 symptoms). Contemporarily, little is known on the long-term stability, risk of progression to AD, impairment, and drinking patterns possibly associated with this status in the first decades of life. (1) To identify prevalence rates of the DO status from adolescence to early adulthood. To investigate (2) stability and variability of the DO status over time and (3) associations between DO status, drinking patterns and impairment in comparison to subjects with AA, with AD, or without any symptoms. N=2039 community subjects (aged 14-24 years at baseline) were assessed at baseline and at about four and ten years after baseline. DSM-IV AUD diagnoses were obtained with the DIA-X/M-CIDI. About 11-12% of the sample was classified as DOs at all waves. Over a period of ten years, 18% of DOs were stable in their diagnosis and additional 10% progressed to AD. DOs were comparable to subjects with AA in drinking patterns, impairment and stability of diagnostic status. DOs progressed to AD significantly more often than AA. AD was associated with highest levels in all outcomes of interest. The DO status in adolescence and early adulthood is associated with considerable stability, risk of progression and problematic alcohol intake. In consequence, it can be meaningful for the timely identification of early stages of clinically relevant alcohol problems. For subjects with DO status early specific interventions are required. Copyright © 2011 Elsevier Ltd. All rights reserved.

  7. Changes in Clinical and Microbiological Periodontal Profiles Relate to Progression of Carotid Intima‐Media Thickness: The Oral Infections and Vascular Disease Epidemiology Study

    PubMed Central

    Desvarieux, Moïse; Demmer, Ryan T.; Jacobs, David R.; Papapanou, Panos N.; Sacco, Ralph L.; Rundek, Tatjana

    2013-01-01

    Background No prospective studies exist on the relationship between change in periodontal clinical and microbiological status and progression of carotid atherosclerosis. Methods and Results The Oral Infections and Vascular Disease Epidemiology Study examined 420 participants at baseline (68±8 years old) and follow‐up. Over a 3‐year median follow‐up time, clinical probing depth (PD) measurements were made at 75 766 periodontal sites, and 5008 subgingival samples were collected from dentate participants (average of 7 samples/subject per visit over 2 visits) and quantitatively assessed for 11 known periodontal bacterial species by DNA‐DNA checkerboard hybridization. Common carotid artery intima‐medial thickness (CCA‐IMT) was measured using high‐resolution ultrasound. In 2 separate analyses, change in periodontal status (follow‐up to baseline), defined as (1) longitudinal change in the extent of sites with a ≥3‐mm probing depth (Δ%PD≥3) and (2) longitudinal change in the relative predominance of bacteria causative of periodontal disease over other bacteria in the subgingival plaque (Δetiologic dominance), was regressed on longitudinal CCA‐IMT progression adjusting for age, sex, race/ethnicity, diabetes, smoking status, education, body mass index, systolic blood pressure, and low‐density lipoprotein cholesterol and high‐density lipoprotein cholesterol. Mean (SE) CCA‐IMT increased during follow‐up by 0.139±0.008 mm. Longitudinal IMT progression attenuated with improvement in clinical or microbial periodontal status. Mean CCA‐IMT progression varied inversely across quartiles of longitudinal improvement in clinical periodontal status (Δ%PD≥3) by 0.18 (0.02), 0.16 (0.01), 0.14 (0.01), and 0.07 (0.01) mm (P for trend<0.0001). Likewise, mean CCA‐IMT increased by 0.20 (0.02), 0.18 (0.02), 0.15 (0.02), and 0.12 (0.02) mm (P<0.0001) across quartiles of longitudinal improvement in periodontal microbial status (Δetiologic dominance). Conclusion Longitudinal improvement in clinical and microbial periodontal status is related to a decreased rate of carotid artery IMT progression at 3‐year average follow‐up. PMID:24166489

  8. [A review of pension status quo in China and domestic and overseas pension models].

    PubMed

    Si, J H; Li, L M

    2016-10-10

    With the aging of population and progressive decline of traditional pension model, the problems in the aged supporting have caused serious social concern in China. Since 1980' s, different opinions about pension models have been suggested in many research papers. This paper summarizes the characteristics of different pension model used in both China and abroad in terms of the financial sources of the aged supporting, life style and the combination with medical service, suggesting to establish a pension model with Chinese characteristics to provide multiple and personalized services on the basis of China' s national situation and successful experiences of other countries.

  9. Relationship between periodontal status and intellectual function among community-dwelling elderly persons.

    PubMed

    Moriya, Shingo; Tei, Kanchu; Toyoshita, Yoshifumi; Koshino, Hisashi; Inoue, Nobuo; Miura, Hiroko

    2012-06-01

    The aim of this study was to indicate the relationship between periodontal status and intellectual function in the elderly. Periodontal status has been shown to be related to demographic, socioeconomic, and psychological status. Intellectual function is a significant indicator of health status. Nevertheless, the relationship between periodontal status and intellectual function has not been elucidated in detail among the elderly. A total of 152 community-dwelling elderly persons, aged 70-74 years, were enrolled in the study. Periodontal status was evaluated using the WHO Community Periodontal Index of Treatment Needs (CPITN). Intellectual function was assessed by four neuropsychological tests: Raven's Coloured Progressive Matrices (RCPM) test, the Verbal Paired Associates 1 (VerPA) task and the Visual Paired Associates 1 (VirPA) task, extracted from the Wechsler Memory Scale Revised Edition, and the Block Design subtest, extracted from the Wechsler Adult Intelligence Scales, Third Edition. Correlations between CPITN and each test were examined using Spearman rank correlation coefficients. The ordinal regression model was constructed with CPITN as the dependent variable and neuropsychological test as the principal independent variable to adjust for demographic factors, general health, lifestyle and oral health behaviour. Significant correlations were found between the RCPM test, the VerPA task, the Visual Paired Associates 1 and CPITN. In the ordinal regression model, CPITN was significantly related to measures of RCPM after adjusting for demographic factors, general health status, lifestyle and oral health behaviour. Intellectual function is considered a significant indicator of periodontal status among community-dwelling elderly persons. © 2011 The Gerodontology Society and John Wiley & Sons A/S.

  10. Use of Latent Growth Curve Modeling for Assessing the Effects of Summer and After-School Learning on Adolescent Students' Achievement Gap

    ERIC Educational Resources Information Center

    Lin, Chunn-Ying; Hsieh, Ya-Heng; Chen, Cheng-Hung

    2015-01-01

    Many Western researchers have found that the gaps in the learning progress between students from different socioeconomic statuses primarily occur due to the accumulated effects of long summer vacations, rather than during the school years. However, it remains to be seen whether these findings can be cross-culturally applied to children in Taiwan.…

  11. Expression status and prognostic significance of mammalian target of rapamycin pathway members in urothelial carcinoma of urinary bladder after cystectomy.

    PubMed

    Schultz, Luciana; Albadine, Roula; Hicks, Jessica; Jadallah, Sana; DeMarzo, Angelo M; Chen, Ying-Bei; Nielsen, Matthew E; Neilsen, Matthew E; Gonzalgo, Mark L; Sidransky, David; Schoenberg, Mark; Netto, George J

    2010-12-01

    Bladder urothelial carcinoma has high rates of mortality and morbidity. Identifying novel molecular prognostic factors and targets of therapy is crucial. Mammalian target of rapamycin (mTOR) pathway plays a pivotal role in establishing cell shape, migration, and proliferation. Tissue microarrays were constructed from 132 cystectomies (1994-2002). Immunohistochemistry was performed for Pten, c-myc, p27, phosphorylated (phos)Akt, phosS6, and 4E-BP1. Markers were evaluated for pattern, percentage, and intensity of staining. Mean length of follow-up was 62.6 months (range, 1-182 months). Disease progression, overall survival (OS), and disease-specific survival (DSS) rates were 42%, 60%, and 68%, respectively. Pten showed loss of expression in 35% of bladder urothelial carcinoma. All markers showed lower expression in invasive bladder urothelial carcinoma compared with benign urothelium with the exception of 4E-BP1. Pten, p27, phosAkt, phosS6, and 4E-BP1 expression correlated with pathologic stage (pathological stage; P<.03). Pten, 4E-BP1, and phosAkt expression correlated with divergent aggressive histology and invasion. phosS6 expression inversely predicted OS (P=.01), DSS (P=.001), and progression (P=.05). c-myc expression inversely predicted progression (P=.01). In a multivariate analysis model that included TNM stage grouping, divergent aggressive histology, concomitant carcinoma in situ, phosS6, and c-myc expression, phosS6 was an independent predictor of DSS (P=.03; hazard ratio [HR], -0.19), whereas c-myc was an independent predictor of progression (P=.02; HR, -0.38). In a second model substituting organ-confined disease and lymph node status for TNM stage grouping, phosS6 and c-myc remained independent predictors of DSS (P=.03; HR, -0.21) and progression (P=.03; HR, -0.34), respectively. We found an overall down-regulation of mTOR pathway in bladder urothelial carcinoma. phosS6 independently predicted DSS, and c-myc independently predicted progression. Copyright © 2010 American Cancer Society.

  12. Long-term disability progression in primary progressive multiple sclerosis: a 15-year study.

    PubMed

    Rocca, Maria A; Sormani, Maria Pia; Rovaris, Marco; Caputo, Domenico; Ghezzi, Angelo; Montanari, Enrico; Bertolotto, Antonio; Laroni, Alice; Bergamaschi, Roberto; Martinelli, Vittorio; Comi, Giancarlo; Filippi, Massimo

    2017-11-01

    Prognostic markers of primary progressive multiple sclerosis evolution are needed. We investigated the added value of magnetic resonance imaging measures of brain and cervical cord damage in predicting long-term clinical worsening of primary progressive multiple sclerosis compared to simple clinical assessment. In 54 patients, conventional and diffusion tensor brain scans and cervical cord T1-weighted scans were acquired at baseline and after 15 months. Clinical evaluation was performed after 5 and 15 years in 49 patients. Lesion load, brain and cord atrophy, mean diffusivity and fractional anisotropy values from the brain normal-appearing white matter and grey matter were obtained. Using linear regression models, we screened the clinical and imaging variables as independent predictors of 15-year disability change (measured on the expanded disability status scale). At 15 years, 90% of the patients had disability progression. Integrating clinical and imaging variables at 15 months predicted disability changes at 15 years better than clinical factors at 5 years (R2 = 61% versus R2 = 57%). The model predicted long-term disability change with a precision within one point in 38 of 49 patients (77.6%). Integration of clinical and imaging measures allows identification of primary progressive multiple sclerosis patients at risk of long-term disease progression 4 years earlier than when using clinical assessment alone. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  13. Metastatic pathways in patients with cutaneous melanoma.

    PubMed

    Adler, Nikki R; Haydon, Andrew; McLean, Catriona A; Kelly, John W; Mar, Victoria J

    2017-01-01

    Metastasis represents the end product of an elaborate biological process, which is determined by a complex interplay between metastatic tumour cells, host factors and homoeostatic mechanisms. Cutaneous melanoma can metastasize haematogenously or lymphogenously. The three predominant models that endeavour to explain the patterns of melanoma progression are the stepwise spread model, the simultaneous spread model and the model of differential spread. The time course to the development of metastases differs between the different metastatic routes. There are several clinical and histopathological risk factors for the different metastatic pathways. In particular, patient sex and the anatomical location of the primary tumour influence patterns of disease progression. There is limited existing evidence regarding the relationship between tumour mutation status, other diagnostic and prognostic biomarkers and the metastatic pathways of primary cutaneous melanoma. This knowledge gap needs to be addressed to better identify patients at high risk of disease recurrence and personalize surveillance strategies. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. Atherosclerotic renovascular disease among hypertensive adults

    PubMed Central

    Davis, Ross P.; Pearce, Jeffrey D.; Craven, Timothy E.; Moore, Phillip S.; Edwards, Matthew S.; Godshall, Christopher J.; Hansen, Kimberley J.

    2010-01-01

    Purpose Ths report describes the change in atherosclerotic renovascular disease (AS-RVD) among hypertensive adults referred for renal duplex sonography (RDS) scan. Methods From Oct 1993 through July 2008, 20,994 patients had RDS at our center. A total of 434 hypertensive patients with two or more RDS exams without intervention comprised the study cohort. Patient demographics (blood pressures, medications, serum creatinine levels, and data from RDS) were collected. Analyses of longitudinal changes in Doppler scan parameters, blood pressures, and renal function were performed by fitting linear growth-curve models. After confirming the linearity of change in Doppler scan parameters among patients with variable number of studies, estimates of mean slopes were calculated using maximum likelihood techniques. For changes in renal function, quadratic growth curves were required to describe longitudinal change. Results A total of 434 subjects (212 men [49%] and 222 women [51%]; mean age, 64.6 ± 12.2 years) provided 1351 studies (mean, 3.2 ± 2.4; range, 2 to 18) for 863 kidneys over a mean follow-up of 34.4 ± 25.1 months. At baseline, 20.6% of kidneys demonstrated hemodynamically significant stenosis. On follow-up, 72 kidneys (9.1%) demonstrated anatomic progression of disease. A total of 54 kidneys (6.9%) progressed to significant stenosis and 18 (2.3%) progressed to occlusion. Controlling for progression of disease, baseline renal artery status demonstrated a strong association with baseline kidney length (P = .0006). Significant annualized change in renal length was observed (cm change/year ± standard error of the mean [SEM]: 0.042 ± 0.011; P = .0002) among both kidneys with and without critical disease at baseline, however, decline in length was significantly greater among kidneys exhibiting progression of renovascular disease (−0.152 ± 0.028 cm/year; comparison of slopes between groups P = .0005). In the absence of progression, the presence or absence of critical renal artery stenosis at baseline did not affect the rate of decline in renal length. Fitted models for the natural log transform of serum creatinine demonstrated a significant increase during follow-up (P < .0001). No association was observed between change in serum creatinine and baseline renovascular disease status, or its progression. Conclusion A total of 32% of hypertensive adults referred for RDS demonstrated hemodynamically significant renal artery stenosis. Regardless of the presence or absence of baseline disease, a small percentage of patients demonstrated anatomic progression of AS-RVD. A total of 9.1% demonstrated anatomic progression and 2.3% progressed to occlusion. Although anatomic progression of AS-RVD was associated with an increased rate of decline in renal length, progression did not predict a decline in excretory renal function. Intervention for AS-RVD should be selective and reserved for strict indications. PMID:19700093

  15. A meta-analysis of clinical and radiographic outcomes of posterior horn medial meniscus root repairs.

    PubMed

    Chung, Kyu Sung; Ha, Jeong Ku; Ra, Ho Jong; Kim, Jin Goo

    2016-05-01

    Although interest in medial meniscus posterior root tear (MMPRT) repair has increased, few case series have been reported. This meta-analysis aimed to examine the clinical and radiological effects of MMPRT repair by pooling pre- and post-operative data from case-series reports. A literature search was performed using MEDLINE/PubMed, the Cochrane Central Register of Controlled Trials, and EMBASE databases. Pre- and post-operative data were pooled to investigate the effects of MMPRT repair, including the Lysholm score improvement, meniscal extrusion (mm) reduction, progression of the Kellgren-Lawrence (K-L) grade, and cartilage status according to the Outerbridge classification. Treatment effects included paired standardized mean differences (difference in the pre- and post-operative mean outcomes divided by the standard deviation) for the Lysholm score and meniscal extrusion, as well as the pooled event rates of progression of K-L grade and cartilage status. As treatment effects, the Lysholm score increased by as much as 3.675 (P < 0.001), whereas meniscus extrusion was not reduced (n.s.). The overall pooled event rates of progression of K-L grade and cartilage status were 10.6 and 17.3 % (P < 0.001), respectively. According to the current literature, MMPRT repair resulted in significant improvements in the post-operative clinical subjective scores compared with the preoperative status. However, meniscus extrusion was not reduced. Considering the occurrence of progression of K-L grade and cartilage status, it did not prevent the progression of arthrosis completely. Based on these results, repair results in favourable outcomes for MMPRT. Meta-analysis, Level IV.

  16. Progressive brain damage, synaptic reorganization and NMDA activation in a model of epileptogenic cortical dysplasia.

    PubMed

    Colciaghi, Francesca; Finardi, Adele; Nobili, Paola; Locatelli, Denise; Spigolon, Giada; Battaglia, Giorgio Stefano

    2014-01-01

    Whether severe epilepsy could be a progressive disorder remains as yet unresolved. We previously demonstrated in a rat model of acquired focal cortical dysplasia, the methylazoxymethanol/pilocarpine - MAM/pilocarpine - rats, that the occurrence of status epilepticus (SE) and subsequent seizures fostered a pathologic process capable of modifying the morphology of cortical pyramidal neurons and NMDA receptor expression/localization. We have here extended our analysis by evaluating neocortical and hippocampal changes in MAM/pilocarpine rats at different epilepsy stages, from few days after onset up to six months of chronic epilepsy. Our findings indicate that the process triggered by SE and subsequent seizures in the malformed brain i) is steadily progressive, deeply altering neocortical and hippocampal morphology, with atrophy of neocortex and CA regions and progressive increase of granule cell layer dispersion; ii) changes dramatically the fine morphology of neurons in neocortex and hippocampus, by increasing cell size and decreasing both dendrite arborization and spine density; iii) induces reorganization of glutamatergic and GABAergic networks in both neocortex and hippocampus, favoring excitatory vs inhibitory input; iv) activates NMDA regulatory subunits. Taken together, our data indicate that, at least in experimental models of brain malformations, severe seizure activity, i.e., SE plus recurrent seizures, may lead to a widespread, steadily progressive architectural, neuronal and synaptic reorganization in the brain. They also suggest the mechanistic relevance of glutamate/NMDA hyper-activation in the seizure-related brain pathologic plasticity.

  17. 30 cm Engineering Model thruster design and qualification tests

    NASA Technical Reports Server (NTRS)

    Schnelker, D. E.; Collett, C. R.

    1975-01-01

    Development of a 30-cm mercury electron bombardment Engineering Model ion thruster has successfully brought the thruster from the status of a laboratory experimental device to a point approaching flight readiness. This paper describes the development progress of the Engineering Model (EM) thruster in four areas: (1) design features and fabrication approaches, (2) performance verification and thruster to thruster variations, (3) structural integrity, and (4) interface definition. The design of major subassemblies, including the cathode-isolator-vaporizer (CIV), main isolator-vaporizer (MIV), neutralizer isolator-vaporizer (NIV), ion optical system, and discharge chamber/outer housing is discussed along with experimental results.

  18. The magnetohydrodynamics coal-fired flow facility

    NASA Astrophysics Data System (ADS)

    1995-01-01

    In this quarterly technical progress report, UTSI reports on the status of a multitask contract to develop the technology for the steam bottoming portion of a MHD Steam Combined Cycle Power Plant. The report describes the facility maintenance and environmental work completed, status of completing technical reports and certain key administrative actions occurring during the quarter. With program resources at a minimum to closeout the MHD program, no further testing occurred during the quarter, but the DOE CFFF facility was maintained in a standby status with winterization, preventive maintenance and repairs accomplished as needed. Plans and preparations progressed for environmental actions needed at the site to investigate and characterize the groundwater and for removal/disposal of asbestos in the cooling tower. Work continued to progress on archiving the results of the MHD program.

  19. Benchmarking dairy herd health status using routinely recorded herd summary data.

    PubMed

    Parker Gaddis, K L; Cole, J B; Clay, J S; Maltecca, C

    2016-02-01

    Genetic improvement of dairy cattle health through the use of producer-recorded data has been determined to be feasible. Low estimated heritabilities indicate that genetic progress will be slow. Variation observed in lowly heritable traits can largely be attributed to nongenetic factors, such as the environment. More rapid improvement of dairy cattle health may be attainable if herd health programs incorporate environmental and managerial aspects. More than 1,100 herd characteristics are regularly recorded on farm test-days. We combined these data with producer-recorded health event data, and parametric and nonparametric models were used to benchmark herd and cow health status. Health events were grouped into 3 categories for analyses: mastitis, reproductive, and metabolic. Both herd incidence and individual incidence were used as dependent variables. Models implemented included stepwise logistic regression, support vector machines, and random forests. At both the herd and individual levels, random forest models attained the highest accuracy for predicting health status in all health event categories when evaluated with 10-fold cross-validation. Accuracy (SD) ranged from 0.61 (0.04) to 0.63 (0.04) when using random forest models at the herd level. Accuracy of prediction (SD) at the individual cow level ranged from 0.87 (0.06) to 0.93 (0.001) with random forest models. Highly significant variables and key words from logistic regression and random forest models were also investigated. All models identified several of the same key factors for each health event category, including movement out of the herd, size of the herd, and weather-related variables. We concluded that benchmarking health status using routinely collected herd data is feasible. Nonparametric models were better suited to handle this complex data with numerous variables. These data mining techniques were able to perform prediction of health status and could add evidence to personal experience in herd management. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  20. Molecular Imaging of Tumor Angiogenesis and Therapeutic Effects with Dual Bioluminescence.

    PubMed

    Wang, Ran; Zhang, Kaiyue; Tao, Hongyan; Du, Wei; Wang, Di; Huang, Ziwei; Zhou, Manqian; Xu, Yang; Wang, Yuebing; Liu, Na; Wang, Hui; Li, Zongjin

    2017-01-01

    Angiogenesis is critical for the growth of tumor by supplying nutrients and oxygen that exacerbates the metastasis and progression of cancer. Noninvasive imaging of angiogenesis during the tumor therapeutic processes may provide novel opportunities for image-guided tumor management. Here, we want to develop a mouse animal model for assessing cancer progression and angiogenesis in the same individuals by molecular imaging. Breast cancer model was developed with mouse breast cancer cell line 4T1 carrying a reporter system encoding a triple fusion (TF) reporter gene consisting of renilla luciferase (Rluc), red fluorescent protein (RFP) and herpes simplex virus truncated thymidine kinase (HSV-ttk) in transgenic mice, which expressed firefly luciferase (Fluc) under the promoter of vascular endothelial growth factor receptor 2 (Vegfr2-luc). The mice were subsequently treated with ganciclovir (GCV) and the tumor angiogenesis was tracked by Fluc imaging and the growth status of tumor was monitored by imaging of Rluc simultaneously. Overall, this traceable breast cancer model can simultaneously image the tumor growth and angiogenesis in single individual, which may facilitate a better understanding the mechanisms of angiogenesis in the progression and regression of tumor. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  1. Effective wavefront aberration measurement of spectacle lenses in as-worn status

    NASA Astrophysics Data System (ADS)

    Jia, Zhigang; Xu, Kai; Fang, Fengzhou

    2018-04-01

    An effective wavefront aberration analysis method for measuring spectacle lenses in as-worn status was proposed and verified using an experimental apparatus based on an eye rotation model. Two strategies were employed to improve the accuracy of measurement of the effective wavefront aberrations on the corneal sphere. The influences of three as-worn parameters, the vertex distance, pantoscopic angle, and face form angle, together with the eye rotation and corresponding incident beams, were objectively and quantitatively obtained. The experimental measurements of spherical single vision and freeform progressive addition lenses demonstrate the accuracy and validity of the proposed method and experimental apparatus, which provide a potential means of achieving supernormal vision correction with customization and personalization in optimizing the as-worn status-based design of spectacle lenses and evaluating their manufacturing and imaging qualities.

  2. Modeling cystic fibrosis disease progression in patients with the rare CFTR mutation P67L.

    PubMed

    MacKenzie, Isobel E R; Paquette, Valerie; Gosse, Frances; George, Sheenagh; Chappe, Frederic; Chappe, Valerie

    2017-05-01

    The progression of cystic fibrosis (CF) in patients with the rare mutation P67L was examined to determine if it induced a milder form of CF compared to the common severe ΔF508 mutation. Parameters of lung function, level of bacterial infection, nutritional status and hospitalization were used to represent CF progression. Age at diagnosis and pancreatic status were used to assess CF presentation. Analysis of data from the CF Canada Registry collected over a 15-year period included 266 ΔF508/ΔF508 homozygote patients from CF clinics in Atlantic Canada and 26 compound heterozygote patients with the rare P67L mutation from clinics across Canada. Late age at diagnosis, high incidence of pancreatic sufficiency, maintained Body Mass Index (BMI) with age, delayed life-threatening bacterial infection, and fewer days in hospital were observed for P67L heterozygote patients included in this study. Although the decline of lung function did not differ from ΔF508 homozygotes, the fact that a greater proportion of P67L heterozygotes live to an older age suggests that lung function is not the primary factor determining CF progression for P67L heterozygote patients. The P67L mutation is associated with a mild disease, even when combined with the severe ΔF508 mutation. Copyright © 2017 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  3. Modelling the affordability and distributional implications of future health care financing options in South Africa.

    PubMed

    McIntyre, Di; Ataguba, John E

    2012-03-01

    South Africa is considering introducing a universal health care system. A key concern for policy-makers and the general public is whether or not this reform is affordable. Modelling the resource and revenue generation requirements of alternative reform options is critical to inform decision-making. This paper considers three reform scenarios: universal coverage funded by increased allocations to health from general tax and additional dedicated taxes; an alternative reform option of extending private health insurance coverage to all formal sector workers and their dependents with the remainder using tax-funded services; and maintaining the status quo. Each scenario was modelled over a 15-year period using a spreadsheet model. Statistical analyses were also undertaken to evaluate the impact of options on the distribution of health care financing burden and benefits from using health services across socio-economic groups. Universal coverage would result in total health care spending levels equivalent to 8.6% of gross domestic product (GDP), which is comparable to current spending levels. It is lower than the status quo option (9.5% of GDP) and far lower than the option of expanding private insurance cover (over 13% of GDP). However, public funding of health services would have to increase substantially. Despite this, universal coverage would result in the most progressive financing system if the additional public funding requirements are generated through a surcharge on taxable income (but not if VAT is increased). The extended private insurance scheme option would be the least progressive and would impose a very high payment burden; total health care payments on average would be 10.7% of household consumption expenditure compared with the universal coverage (6.7%) and status quo (7.5%) options. The least pro-rich distribution of service benefits would be achieved under universal coverage. Universal coverage is affordable and would promote health system equity, but needs careful design to ensure its long-term sustainability.

  4. HSR Aerodynamic Performance Status and Challenges

    NASA Technical Reports Server (NTRS)

    Gilbert, William P.; Antani, Tony; Ball, Doug; Calloway, Robert L.; Snyder, Phil

    1999-01-01

    This paper describes HSR (High Speed Research) Aerodynamic Performance Status and Challenges. The topics include: 1) Aero impact on HSR; 2) Goals and Targets; 3) Progress and Status; and 4) Remaining Challenges. This paper is presented in viewgraph form.

  5. Unitary subsector of generalized minimal models

    NASA Astrophysics Data System (ADS)

    Behan, Connor

    2018-05-01

    We revisit the line of nonunitary theories that interpolate between the Virasoro minimal models. Numerical bootstrap applications have brought about interest in the four-point function involving the scalar primary of lowest dimension. Using recent progress in harmonic analysis on the conformal group, we prove the conjecture that global conformal blocks in this correlator appear with positive coefficients. We also compute many such coefficients in the simplest mixed correlator system. Finally, we comment on the status of using global conformal blocks to isolate the truly unitary points on this line.

  6. Department of Defense Landfill Database: A Collection of DoD-Wide Landfill Data for the Assessment of Implementing the Flex Energy Powerstation for Landfill Gas to Energy Projects

    DTIC Science & Technology

    2011-06-01

    Microturbine. Given the approximate nature of the source data and the gas production models , this material can only be used for a preliminary assessment...methane generation rate, k, used in the first order decay model can vary widely from landfill to landfill and are partly dependent on waste composition...State Status (active/closed/ closure in progress) Gross Power Generation Potential (kW) 345 ARMY WHITE SANDS MISSLE RANGE DONA ANA NM ACTIVE

  7. Semiconductor technology program. Progress briefs

    NASA Technical Reports Server (NTRS)

    Bullis, W. M. (Editor)

    1979-01-01

    The current status of NBS work on measurement technology for semiconductor materials, process control, and devices is reported. Results of both in-house and contract research are covered. Highlighted activities include modeling of diffusion processes, analysis of model spreading resistance data, and studies of resonance ionization spectroscopy, resistivity-dopant density relationships in p-type silicon, deep level measurements, photoresist sensitometry, random fault measurements, power MOSFET thermal characteristics, power transistor switching characteristics, and gross leak testing. New and selected on-going projects are described. Compilations of recent publications and publications in press are included.

  8. From Confrontation to Cooperation: 8th International Seminar on Nuclear War

    NASA Astrophysics Data System (ADS)

    Zichichi, A.; Dardo, M.

    1992-09-01

    The Table of Contents for the full book PDF is as follows: * OPENING SESSION * A. Zichichi: Opening Statements * R. Nicolosi: Opening Statements * MESSAGES * CONTRIBUTIONS * "The Contribution of the Erice Seminars in East-West-North-South Scientific Relations" * 1. LASER TECHNOLOGY * "Progress in laser technology" * "Progress in laboratory high gain ICF: prospects for the future" * "Applications of laser in metallurgy" * "Laser tissue interactions in medicine and surgery" * "Laser fusion" * "Compact X-ray lasers in the laboratory" * "Alternative method for inertial confinement" * "Laser technology in China" * 2. NUCLEAR AND CHEMICAL SAFETY * "Reactor safety and reactor design" * "Thereotical analysis and numerical modelling of heat transfer and fuel migration in underlying soils and constructive elements of nuclear plants during an accident release from the core" * "How really to attain reactor safely" * "The problem of chemical weapons" * "Long terms genetic effects of nuclear and chemical accidents" * "Features of the brain which are of importance in understanding the mode of operation of toxic substances and of radiation" * "CO2 and ultra safe reactors" * 3. USE OF MISSILES * "How to convert INF technology for peaceful scientific purposes" * "Beating words into plowshares: a proposal for the peaceful uses of retired nuclear warheads" * "Some thoughts on the peaceful use of retired nuclear warheads" * "Status of the HEFEST project" * 4. OZONE * "Status of the ozone layer problem" * 5. CONVENTIONAL AND NUCLEAR FORCE RESTRUCTURING IN EUROPE * 6. CONFLICT AVOIDANCE MODEL * 7. GENERAL DISCUSSION OF THE WORLD LAB PROJECTS * "East-West-North-South Collaboration in Subnuclear Physics" * "Status of the World Lab in the USSR" * CLOSING SESSION

  9. Speech Research: A Report on the Status and Progress of Studies on the Nature of Speech, Instrumentation for Its Investigation, and Practical Applications, 1 April - 30 June 1973.

    ERIC Educational Resources Information Center

    Haskins Labs., New Haven, CT.

    This document, containing 15 articles and 2 abstracts, is a report on the current status and progress of speech research. The following topics are investigated: phonological fusion, phonetic prerequisites for first-language learning, auditory and phonetic levels of processing, auditory short-term memory in vowel perception, hemispheric…

  10. [How exactly can we predict the prognosis of COPD].

    PubMed

    Atiş, Sibel; Kanik, Arzu; Ozgür, Eylem Sercan; Eker, Suzan; Tümkaya, Münir; Ozge, Cengiz

    2009-01-01

    Predictive models play a pivotal role in the provision of accurate and useful probabilistic assessments of clinical outcomes in chronic diseases. This study was aimed to develop a dedicated prognostic index for quantifying progression risk in chronic obstructive pulmonary disease (COPD). Data were collected prospectively from 75 COPD patients during a three years period. A predictive model of progression risk of COPD was developed using Bayesian logistic regression analysis by Markov chain Monte Carlo method. One-year cycles were used for the disease progression in this model. Primary end points for progression were impairment in basal dyspne index (BDI) score, FEV(1) decline, and exacerbation frequency in last three years. Time-varying covariates age, smoking, body mass index (BMI), severity of disease according to GOLD, PaO2, PaCO(2), IC, RV/TLC, DLCO were used under the study. The mean age was 57.1 + or - 8.1. BDI were strongly correlated with exacerbation frequency (p= 0.001) but not with FEV(1) decline. BMI was found to be a predictor factor for impairment in BDI (p= 0.03). The following independent risk factors were significant to predict exacerbation frequency: GOLD staging (OR for GOLD I vs. II and III = 2.3 and 4.0), hypoxemia (OR for mild vs moderate and severe = 2.1 and 5.1) and hyperinflation (OR= 1.6). PaO2 (p= 0.026), IC (p= 0.02) and RV/TLC (p= 0.03) were found to be predictive factors for FEV(1) decline. The model estimated BDI, lung function and exacerbation frequency at the last time point by testing initial data of three years with 95% reliability (p< 0.001). Accordingly, this model was evaluated as confident of 95% for assessing the future status of COPD patients. Using Bayesian predictive models, it was possible to develop a risk-stratification index that accurately predicted progression of COPD. This model can provide decision-making about future in COPD patients with high reliability looking clinical data of beginning.

  11. Lincoln County nuclear waste project. Quarterly progress report, October 1, 1991--December 31, 1991

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

    NONE

    1996-03-01

    This document included the following three progress reports to the Yucca Mountain Project Office on radioactive waste storage in Lincoln County, Nevada: financial status report; federal cash transactions report; and technical progress report.

  12. Lincoln County nuclear waste project. Quarterly progress report, January 1, 1992--March 31, 1992

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

    NONE

    1996-03-01

    This document included the following three progress reports to the Yucca Mountain Project Office on radioactive waste storage in Lincoln County, Nevada: financial status report; federal cash transactions report; and technical progress report.

  13. Lincoln County nuclear waste project quarterly progress report, April 1, 1992--June 30, 1992

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

    NONE

    1996-03-01

    This document included the following three progress reports to the Yucca Mountain Project Office on radioactive waste storage in Lincoln County, Nevada: financial status report; federal cash transactions report; and technical progress report.

  14. Risk factors associated with disease progression and mortality in chronic kidney disease of uncertain etiology: a cohort study in Medawachchiya, Sri Lanka.

    PubMed

    Senevirathna, Lalantha; Abeysekera, Tilak; Nanayakkara, Shanika; Chandrajith, Rohana; Ratnatunga, Neelakanthi; Harada, Kouji H; Hitomi, Toshiaki; Komiya, Toshiyuki; Muso, Eri; Koizumi, Akio

    2012-05-01

    The alarming rise in the prevalence of chronic kidney disease of uncertain etiology (CKDu) among the low socioeconomic farming community in the North Central Province of Sri Lanka has been recognized as an emerging public health issue in the country. This study sought to determine the possible factors associated with the progression and mortality of CKDu. The study utilized a single-center cohort registered in 2003 and followed up until 2009 in a regional clinic in the endemic region, and used a Cox proportional hazards model. We repeatedly found an association between disease progression and hypertension. Men were at higher risk of CKDu than women. A significant proportion of the patients in this cohort were underweight, which emphasized the need for future studies on the nutritional status of these patients. Compared with findings in western countries and other regions of Asia, we identified hypertension as a major risk factor for progression of CKDu in this cohort.

  15. Predicting progression to dementia in persons with mild cognitive impairment using cerebrospinal fluid markers.

    PubMed

    Handels, Ron L H; Vos, Stephanie J B; Kramberger, Milica G; Jelic, Vesna; Blennow, Kaj; van Buchem, Mark; van der Flier, Wiesje; Freund-Levi, Yvonne; Hampel, Harald; Olde Rikkert, Marcel; Oleksik, Ania; Pirtosek, Zvezdan; Scheltens, Philip; Soininen, Hilkka; Teunissen, Charlotte; Tsolaki, Magda; Wallin, Asa K; Winblad, Bengt; Verhey, Frans R J; Visser, Pieter Jelle

    2017-08-01

    We aimed to determine the added value of cerebrospinal fluid (CSF) to clinical and imaging tests to predict progression from mild cognitive impairment (MCI) to any type of dementia. The risk of progression to dementia was estimated using two logistic regression models based on 250 MCI participants: the first included standard clinical measures (demographic, clinical, and imaging test information) without CSF biomarkers, and the second included standard clinical measures with CSF biomarkers. Adding CSF improved predictive accuracy with 0.11 (scale from 0-1). Of all participants, 136 (54%) had a change in risk score of 0.10 or higher (which was considered clinically relevant), of whom in 101, it was in agreement with their dementia status at follow-up. An individual person's risk of progression from MCI to dementia can be improved by relying on CSF biomarkers in addition to recommended clinical and imaging tests for usual care. Copyright © 2017 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

  16. Health-related quality-of-life parameters as independent prognostic factors in advanced or metastatic bladder cancer.

    PubMed

    Roychowdhury, D F; Hayden, A; Liepa, A M

    2003-02-15

    This retrospective analysis examined prognostic significance of health-related quality-of-life (HRQoL) parameters combined with baseline clinical factors on outcomes (overall survival, time to progressive disease, and time to treatment failure) in bladder cancer. Outcome and HRQoL (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30) data were collected prospectively in a phase III study assessing gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in locally advanced or metastatic bladder cancer. Prespecified baseline clinical factors (performance status, tumor-node-metastasis staging, visceral metastases [VM], alkaline phosphatase [AP] level, number of metastatic sites, prior radiotherapy, disease measurability, sex, time from diagnosis, and sites of disease) and selected HRQoL parameters (global QoL; all functional scales; symptoms: pain, fatigue, insomnia, dyspnea, anorexia) were evaluated using Cox's proportional hazards model. Factors with individual prognostic value (P <.05) on outcomes in univariate models were assessed for joint prognostic value in a multivariate model. A final model was developed using a backward selection strategy. Patients with baseline HRQoL were included (364 of 405, 90%). The final model predicted longer survival with low/normal AP levels, no VM, high physical functioning, low role functioning, and no anorexia. Positive prognostic factors for time to progressive disease were good performance status, low/normal AP levels, no VM, and minimal fatigue; for time to treatment failure, they were low/normal AP levels, minimal fatigue, and no anorexia. Global QoL was a significant predictor of outcome in univariate analyses but was not retained in the multivariate model. HRQoL parameters are independent prognostic factors for outcome in advanced bladder cancer; their prognostic importance needs further evaluation.

  17. Rocket Propulsion 21 Steering Committee Meeting (RP21) NASA In-Space Propulsion Update

    NASA Technical Reports Server (NTRS)

    Klem, Mark

    2015-01-01

    In-house Support of NEXT-C Contract Status Thruster NEXT Long Duration Test post-test destructive evaluation in progress Findings will be used to verify service life models identify potential design improvements Cathode heater fabrication initiated for cyclic life testing Thruster operating algorithm definition verification initiated to provide operating procedures for mission users High voltage propellant isolator life test voluntarily terminated after successfully operating 51,200 h Power processor unit (PPU) Replaced all problematic stacked multilayer ceramic dual inline pin capacitors within PPU Test bed Rebuilt installed discharge power supply primary power board Completed full functional performance characterization Final test report in progress Transferred PPU Testbed to contractor to support prototype design effort.

  18. Design and development status of ETS-7, an RVD and space robot experiment satellite

    NASA Technical Reports Server (NTRS)

    Oda, M.; Inagaki, T.; Nishida, M.; Kibe, K.; Yamagata, F.

    1994-01-01

    ETS-7 (Engineering Test Satellite #7) is an experimental satellite for the in-orbit experiment of the Rendezvous Docking (RVD) and the space robot (RBT) technologies. ETS-7 is a set of two satellites, a chaser satellite and a target satellite. Both satellites will be launched together by NASDA's H-2 rocket into a low earth orbit. Development of ETS-7 started in 1990. Basic design and EM (Engineering Model) development are in progress now in 1994. The satellite will be launched in mid 1997 and the above in-orbit experiments will be conducted for 1.5 years. Design of ETS-7 RBT experiment system and development status are described in this paper.

  19. The natural history of adult pulmonary Langerhans cell histiocytosis: a prospective multicentre study.

    PubMed

    Tazi, Abdellatif; de Margerie, Constance; Naccache, Jean Marc; Fry, Stéphanie; Dominique, Stéphane; Jouneau, Stéphane; Lorillon, Gwenaël; Bugnet, Emmanuelle; Chiron, Raphael; Wallaert, Benoit; Valeyre, Dominique; Chevret, Sylvie

    2015-03-14

    The natural history of pulmonary Langerhans cell histiocytosis (PLCH) has been unclear due to the absence of prospective studies. The rate of patients who experience an early progression of their disease is unknown. Additionally, conflicting effects of smoking cessation on the outcome of PLCH have been reported. In this prospective, multicentre study, 58 consecutive patients with newly diagnosed PLCH were comprehensively evaluated over a two-year period. Our objectives were to estimate the incidence of early progression of the disease and to evaluate the impact of smoking status on lung function outcomes. Lung function deterioration was defined as a decrease of at least 15% in FEV1 and/or FVC and/or DLCO, compared with baseline values. At each visit, smoking status was recorded based on the patients' self-reports and urinary cotinine measurements that were blinded for the patients. The cumulative incidence of lung function outcomes over time was estimated using the non-parametric Kaplan-Meier method. Multivariate Cox models with time-dependent covariates were used to calculate the hazards ratios of the lung function deterioration associated with smoking status with adjustment for potential confounders. The cumulative incidence of lung function deterioration at 24 months was 38% (22% for FEV1 and DLCO, and 9% for FVC). In the multivariate analysis, smoking status and PaO2 at inclusion were the only factors associated with the risk of lung function deterioration. The patients' smoking statuses markedly changed over time. Only 20% of the patients quit using tobacco for the entire study period. Nevertheless, being a non-smoker was associated with a decreased risk of subsequent lung function deterioration, even after adjustment for baseline predictive factors. By serial lung computed tomography, the extent of cystic lesions increased in only 11% of patients. Serial lung function evaluation on a three- to six-month basis is essential for the follow-up of patients with recently diagnosed PLCH to identify those who experience an early progression of their disease. These patients are highly addicted to tobacco, and robust efforts should be undertaken to include them in smoking cessation programs. ClinicalTrials.gov: No: NCT01225601 .

  20. Adaptive changes in renal mitochondrial redox status in diabetic nephropathy

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

    Putt, David A.; Zhong, Qing; Lash, Lawrence H., E-mail: l.h.lash@wayne.edu

    2012-01-15

    Nephropathy is a serious and common complication of diabetes. In the streptozotocin (STZ)-treated rat model of diabetes, nephropathy does not typically develop until 30 to 45 days post-injection, although hyperglycemia occurs within 24 h. We tested the hypothesis that chronic hyperglycemia results in a modest degree of oxidative stress that is accompanied by compensatory changes in certain antioxidants and mitochondrial redox status. We propose that as kidneys progress to a state of diabetic nephropathy, further adaptations occur in mitochondrial redox status. Basic parameters of renal function in vivo and several parameters of mitochondrial function and glutathione (GSH) and redox statusmore » in isolated renal cortical mitochondria from STZ-treated and age-matched control rats were examined at 30 days and 90 days post-injection. While there was no effect of diabetes on blood urea nitrogen, measurement of other, more sensitive parameters, such as urinary albumin and protein, and histopathology showed significant and progressive worsening in diabetic rats. Thus, renal function is compromised even prior to the onset of frank nephropathy. Changes in mitochondrial respiration and enzyme activities indicated existence of a hypermetabolic state. Higher mitochondrial GSH content and rates of GSH transport into mitochondria in kidneys from diabetic rats were only partially due to changes in expression of mitochondrial GSH carriers and were mostly due to higher substrate supply. Although there are few clear indicators of oxidative stress, there are several redox changes that occur early and change further as nephropathy progresses, highlighting the complexity of the disease. Highlights: ►Adaptive changes in renal mitochondrial and redox status in diabetic rats. ►Modest renal dysfunction even prior to onset of nephropathy. ►Elevated concentrations of mitochondrial GSH in diabetic kidneys. ►Change in GSH due partly to increased protein expression of transporter. ►Oxidatively modified proteins in renal mitochondria from diabetic rats.« less

  1. Inflammatory status in human hepatic cirrhosis

    PubMed Central

    Martínez-Esparza, María; Tristán-Manzano, María; Ruiz-Alcaraz, Antonio J; García-Peñarrubia, Pilar

    2015-01-01

    This review focuses on new findings about the inflammatory status involved in the development of human liver cirrhosis induced by the two main causes, hepatitis C virus (HCV) infection and chronic alcohol abuse, avoiding results obtained from animal models. When liver is faced to a persistent and/or intense local damage the maintained inflammatory response gives rise to a progressive replacement of normal hepatic tissue by non-functional fibrotic scar. The imbalance between tissue regeneration and fibrosis will determine the outcome toward health recovery or hepatic cirrhosis. In all cases progression toward liver cirrhosis is caused by a dysregulation of mechanisms that govern the balance between activation/homeostasis of the immune system. Detecting differences between the inflammatory status in HCV-induced vs alcohol-induced cirrhosis could be useful to identify specific targets for preventive and therapeutic intervention in each case. Thus, although survival of patients with alcoholic cirrhosis seems to be similar to that of patients with HCV-related cirrhosis (HCV-C), there are important differences in the altered cellular and molecular mechanisms implicated in the progression toward human liver cirrhosis. The predominant features of HCV-C are more related with those that allow viral evasion of the immune defenses, especially although not exclusively, inhibition of interferons secretion, natural killer cells activation and T cell-mediated cytotoxicity. On the contrary, the inflammatory status of alcohol-induced cirrhosis is determined by the combined effect of direct hepatotoxicity of ethanol metabolites and increases of the intestinal permeability, allowing bacteria and bacterial products translocation, into the portal circulation, mesenteric lymph nodes and peritoneal cavity. This phenomenon generates a stronger pro-inflammatory response compared with HCV-related cirrhosis. Hence, therapeutic intervention in HCV-related cirrhosis must be mainly focused to counteract HCV-immune system evasion, while in the case of alcohol-induced cirrhosis it must try to break the inflammatory loop established at the gut-mesenteric lymph nodes-peritoneal-systemic axis. PMID:26556984

  2. Clinical value of nutritional status in neurodegenerative diseases: What is its impact and how it affects disease progression and management?

    PubMed

    Tsagalioti, Eftyhia; Trifonos, Christina; Morari, Aggeliki; Vadikolias, Konstantinos; Giaginis, Constantinos

    2018-04-01

    Neurodegenerative diseases constitute a major problem of public health that is associated with an increased risk of mortality and poor quality of life. Malnutrition is considered as a major problem that worsens the prognosis of patients suffering from neurodegenerative diseases. In this aspect, the present review is aimed to critically collect and summarize all the available existing clinical data regarding the clinical impact of nutritional assessment in neurodegenerative diseases, highlighting on the crucial role of nutritional status in disease progression and management. According to the currently available clinical data, the nutritional status of patients seems to play a very important role in the development and progression of neurodegenerative diseases. A correct nutritional evaluation of neurodegenerative disease patients and a right nutrition intervention is essential in monitoring their disease.

  3. On Medical Progress and Health Care Demand: A Ces Perspective Using the Grossman Model of Health Status.

    PubMed

    Batinti, Alberto

    2015-12-01

    I propose an application of the pure-consumption version of the Grossman model of health care demand, where utility depends on consumption and health status and health status on medical care and health technology. I derive the conditions under which an improvement in health care technology leads to an increase/decrease in health care consumption. In particular, I show how the direction of the effect depends on the relationship between the constant elasticity of substitution parameters of the utility and health production functions. I find that, under the constancy assumption, the ratio of the two elasticity of substitution parameters determines the direction of a technological change on health care demand. On the other hand, the technology share parameter in the health production function contributes to the size but not to the direction of the technological effect. I finally explore how the ratio of the elasticity of substitution parameters work in measurement and practice and discuss how future research may use the theoretical insight provided here. Copyright © 2014 John Wiley & Sons, Ltd.

  4. Quantitative and empirical demonstration of the Matthew effect in a study of career longevity

    PubMed Central

    Petersen, Alexander M.; Jung, Woo-Sung; Yang, Jae-Suk; Stanley, H. Eugene

    2011-01-01

    The Matthew effect refers to the adage written some two-thousand years ago in the Gospel of St. Matthew: “For to all those who have, more will be given.” Even two millennia later, this idiom is used by sociologists to qualitatively describe the dynamics of individual progress and the interplay between status and reward. Quantitative studies of professional careers are traditionally limited by the difficulty in measuring progress and the lack of data on individual careers. However, in some professions, there are well-defined metrics that quantify career longevity, success, and prowess, which together contribute to the overall success rating for an individual employee. Here we demonstrate testable evidence of the age-old Matthew “rich get richer” effect, wherein the longevity and past success of an individual lead to a cumulative advantage in further developing his or her career. We develop an exactly solvable stochastic career progress model that quantitatively incorporates the Matthew effect and validate our model predictions for several competitive professions. We test our model on the careers of 400,000 scientists using data from six high-impact journals and further confirm our findings by testing the model on the careers of more than 20,000 athletes in four sports leagues. Our model highlights the importance of early career development, showing that many careers are stunted by the relative disadvantage associated with inexperience. PMID:21173276

  5. O6-methylguanine-DNA methyltransferase activity is associated with response to alkylating agent therapy and with MGMT promoter methylation in glioblastoma and anaplastic glioma

    PubMed Central

    Bobola, Michael S.; Alnoor, Mohammad; Chen, John Y.-S.; Kolstoe, Douglas D.; Silbergeld, Daniel L.; Rostomily, Robert C.; Blank, A.; Chamberlain, Marc C.; Silber, John R.

    2014-01-01

    Background CpG methylation in the O6-methylguanine-DNA methyltransferase (MGMT) promoter is associated with better outcome following alkylating agent chemotherapy in glioblastoma (GBM) and anaplastic glioma (AG). To what extent improved response reflects low or absent MGMT activity in glioma tissue has not been unequivocally assessed. This information is central to developing anti-resistance therapies. Methods We examined the relationship of MGMT activity in 91 GBMs and 84 AGs with progression-free survival (PFS) following alkylator therapy and with promoter methylation status determined by methylation-specific PCR (MSP). Results Cox regression analysis revealed that GBMs with high activity had a significantly greater risk for progression in dichotomous (P ≤ 0.001) and continuous (P ≤ 0.003) models, an association observed for different alkylator regimens, including concurrent chemo-radiation with temozolomide. Analysis of MGMT promoter methylation status in 47 of the GBMs revealed that methylated tumors had significantly lower activity (P ≤ 0.005) and longer PFS (P ≤ 0.036) compared to unmethylated tumors, despite overlapping activities. PFS was also significantly greater in methylated vs. unmethylated GBMs with comparable activity (P ≤ 0.005), and among unmethylated tumors with less than median activity (P ≤ 0.026), suggesting that mechanisms in addition to MGMT promote alkylator resistance. Similar associations of MGMT activity with PFS and promoter methylation status were observed for AGs. Conclusions Our results provide strong support for the hypotheses that MGMT activity promotes alkylator resistance and reflects promoter methylation status in malignant gliomas. General significance MGMT activity is an attractive target for anti-resistance therapy regardless of methylation status. PMID:25558448

  6. Curcumin protects neuronal cells against status-epilepticus-induced hippocampal damage through induction of autophagy and inhibition of necroptosis.

    PubMed

    Wang, Jin; Liu, Yuan; Li, Xiao-Hui; Zeng, Xiang-Chang; Li, Jian; Zhou, Jun; Xiao, Bo; Hu, Kai

    2017-05-01

    Status epilepticus, the most severe form of epilepsy, is characterized by progressive functional and structural damage in the hippocampus, ultimately leading to the development and clinical appearance of spontaneous, recurrent seizures. Although the pathogenesis underlying epileptogenesis processes remains unclear, a substantial body of evidence has shown that status epilepticus acts as an important initial factor in triggering epileptogenesis. Notably, besides classical cell death mechanisms such as apoptosis and necrosis, 2 novel regulators of cell fate known as necroptosis and autophagy, are demonstrated to be involved in neuronal damage in various neurodegenerative and neuropsychiatric disorders. However, whether necroptosis and autophagy play a role in post-status-epilepticus rat hippocampus and other epilepsy mechanisms deserves further research effort. In addition, research is needed to determine whether compounds from traditional Chinese herbs possess antiepileptic effects through the modulation of necroptosis and autophagy. In this study, we found that curcumin, a polyphenolic phytochemical extracted from the Curcuma longa plant, protects neuronal cells against status-epilepticus-induced hippocampal neuronal damage in the lithium-pilocarpine-induced status epilepticus rat model through induction of autophagy and inhibition of necroptosis.

  7. Designing HIGH-COST medicine: hospital surveys, health planning, and the paradox of progressive reform.

    PubMed

    Perkins, Barbara Bridgman

    2010-02-01

    Inspired by social medicine, some progressive US health reforms have paradoxically reinforced a business model of high-cost medical delivery that does not match social needs. In analyzing the financial status of their areas' hospitals, for example, city-wide hospital surveys of the 1910s through 1930s sought to direct capital investments and, in so doing, control competition and markets. The 2 national health planning programs that ran from the mid-1960s to the mid-1980s continued similar strategies of economic organization and management, as did the so-called market reforms that followed. Consequently, these reforms promoted large, extremely specialized, capital-intensive institutions and systems at the expense of less complex (and less costly) primary and chronic care. The current capital crisis may expose the lack of sustainability of such a model and open up new ideas and new ways to build health care designed to meet people's health needs.

  8. Accounting for disease modifying therapy in models of clinical progression in multiple sclerosis.

    PubMed

    Healy, Brian C; Engler, David; Gholipour, Taha; Weiner, Howard; Bakshi, Rohit; Chitnis, Tanuja

    2011-04-15

    Identifying predictors of clinical progression in patients with relapsing-remitting multiple sclerosis (RRMS) is complicated in the era of disease modifying therapy (DMT) because patients follow many different DMT regimens. To investigate predictors of progression in a treated RRMS sample, a cohort of RRMS patients was prospectively followed in the Comprehensive Longitudinal Investigation of Multiple Sclerosis at the Brigham and Women's Hospital (CLIMB). Enrollment criteria were exposure to either interferon-β (IFN-β, n=164) or glatiramer acetate (GA, n=114) for at least 6 months prior to study entry. Baseline demographic and clinical features were used as candidate predictors of longitudinal clinical change on the Expanded Disability Status Scale (EDSS). We compared three approaches to account for DMT effects in statistical modeling. In all approaches, we analyzed all patients together and stratified based on baseline DMT. Model 1 used all available longitudinal EDSS scores, even those after on-study DMT changes. Model 2 used only clinical observations prior to changing DMT. Model 3 used causal statistical models to identify predictors of clinical change. When all patients were considered using Model 1, patients with a motor symptom as the first relapse had significantly larger change in EDSS scores during follow-up (p=0.04); none of the other clinical or demographic variables significantly predicted change. In Models 2 and 3, results were generally unchanged. DMT modeling choice had a modest impact on the variables classified as predictors of EDSS score change. Importantly, however, interpretation of these predictors is dependent upon modeling choice. Copyright © 2011 Elsevier B.V. All rights reserved.

  9. Psychosocial Factors Are Associated With Blood Pressure Progression Among African Americans in the Jackson Heart Study

    PubMed Central

    Sims, Mario; Higginbotham, John C.; Crowther, Martha R.; Wyatt, Sharon B.; Musani, Solomon K.; Payne, Thomas J.; Fox, Ervin R.; Parton, Jason M.

    2016-01-01

    BACKGROUND Research that examines the associations of psychosocial factors with incident hypertension among African Americans (AA) is limited. Using Jackson Heart Study (JHS) data, we examined associations of negative affect and stress with incident hypertension and blood pressure (BP) progression among AA. METHODS Our sample consisted of 1,656 normotensive participants at baseline (2000–2004) (mean age 47±12; 61% women). We investigated associations of negative affect (cynical distrust, anger-in, anger-out, and depressive symptoms) and stress (perceived stress, weekly stress inventory (WSI)-event, WSI-impact, and major life events) with BP progression (an increase by one BP stage as defined by JNC VII) and incident hypertension by examination 2 (2005–2008). Poisson regression analysis was utilized to examine the prevalence ratios (PRs; 95% confidence interval (CI)) of BP tracking and incident hypertension with psychosocial factors, adjusting for baseline age, sex, socioeconomic status (SES), and hypertension risk factors. RESULTS Fifty-six percentage of the sample (922 cases) had BP progression from 2005 to 2008. After adjustment for age, sex, and SES, a high anger-out score was associated with a 20% increased risk of BP progression compared to a low anger-out score (PR 1.20; 95% CI 1.05–1.36). High depressive symptoms score was associated with BP progression in the age, sex, and SES-adjusted model (PR 1.14; 95% CI 1.00–1.30). High WSI-event scores were associated with BP progression in the fully adjusted model (PR 1.21; 95% CI 1.04–1.40). We did not observe significant associations with any of the psychosocial measures and incident hypertension. CONCLUSIONS Psychosocial factors were associated with BP progression, with the strongest evidence for number of stressful events that occurred. PMID:26964661

  10. Research subjects for analytical estimation of core degradation at Fukushima-Daiichi nuclear power plant

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

    Nagase, F.; Ishikawa, J.; Kurata, M.

    2013-07-01

    Estimation of the accident progress and status inside the pressure vessels (RPV) and primary containment vessels (PCV) is required for appropriate conductance of decommissioning in the Fukushima-Daiichi NPP. For that, it is necessary to obtain additional experimental data and revised models for the estimation using computer codes with increased accuracies. The Japan Atomic Energy Agency (JAEA) has selected phenomena to be reviewed and developed, considering previously obtained information, conditions specific to the Fukushima-Daiichi NPP accident, and recent progress of experimental and analytical technologies. As a result, research and development items have been picked up in terms of thermal-hydraulic behavior inmore » the RPV and PCV, progression of fuel bundle degradation, failure of the lower head of RPV, and analysis of the accident. This paper introduces the selected phenomena to be reviewed and developed, research plans and recent results from the JAEA's corresponding research programs. (authors)« less

  11. The origin and evolution of dust in interstellar and circumstellar environments

    NASA Technical Reports Server (NTRS)

    Whittet, Douglas C. B.; Leung, Chun M.

    1993-01-01

    This status report covers the period from the commencement of the research program on 1 Jul. 1992 through 30 Apr. 1993. Progress is reported for research in the following areas: (1) grain formation in circumstellar envelopes; (2) photochemistry in circumstellar envelopes; (3) modeling ice features in circumstellar envelopes; (4) episodic dust formation in circumstellar envelopes; (5) grain evolution in the diffuse interstellar medium; and (6) grain evolution in dense molecular clouds.

  12. Patterns and predictors of skin score change in early diffuse systemic sclerosis from the European Scleroderma Observational Study.

    PubMed

    Herrick, Ariane L; Peytrignet, Sebastien; Lunt, Mark; Pan, Xiaoyan; Hesselstrand, Roger; Mouthon, Luc; Silman, Alan J; Dinsdale, Graham; Brown, Edith; Czirják, László; Distler, Jörg H W; Distler, Oliver; Fligelstone, Kim; Gregory, William J; Ochiel, Rachel; Vonk, Madelon C; Ancuţa, Codrina; Ong, Voon H; Farge, Dominique; Hudson, Marie; Matucci-Cerinic, Marco; Balbir-Gurman, Alexandra; Midtvedt, Øyvind; Jobanputra, Paresh; Jordan, Alison C; Stevens, Wendy; Moinzadeh, Pia; Hall, Frances C; Agard, Christian; Anderson, Marina E; Diot, Elisabeth; Madhok, Rajan; Akil, Mohammed; Buch, Maya H; Chung, Lorinda; Damjanov, Nemanja S; Gunawardena, Harsha; Lanyon, Peter; Ahmad, Yasmeen; Chakravarty, Kuntal; Jacobsen, Søren; MacGregor, Alexander J; McHugh, Neil; Müller-Ladner, Ulf; Riemekasten, Gabriela; Becker, Michael; Roddy, Janet; Carreira, Patricia E; Fauchais, Anne Laure; Hachulla, Eric; Hamilton, Jennifer; İnanç, Murat; McLaren, John S; van Laar, Jacob M; Pathare, Sanjay; Proudman, Susanna M; Rudin, Anna; Sahhar, Joanne; Coppere, Brigitte; Serratrice, Christine; Sheeran, Tom; Veale, Douglas J; Grange, Claire; Trad, Georges-Selim; Denton, Christopher P

    2018-04-01

    Our aim was to use the opportunity provided by the European Scleroderma Observational Study to (1) identify and describe those patients with early diffuse cutaneous systemic sclerosis (dcSSc) with progressive skin thickness, and (2) derive prediction models for progression over 12 months, to inform future randomised controlled trials (RCTs). The modified Rodnan skin score (mRSS) was recorded every 3 months in 326 patients. 'Progressors' were defined as those experiencing a 5-unit and 25% increase in mRSS score over 12 months (±3 months). Logistic models were fitted to predict progression and, using receiver operating characteristic (ROC) curves, were compared on the basis of the area under curve (AUC), accuracy and positive predictive value (PPV). 66 patients (22.5%) progressed, 227 (77.5%) did not (33 could not have their status assessed due to insufficient data). Progressors had shorter disease duration (median 8.1 vs 12.6 months, P=0.001) and lower mRSS (median 19 vs 21 units, P=0.030) than non-progressors. Skin score was highest, and peaked earliest, in the anti-RNA polymerase III (Pol3+) subgroup (n=50). A first predictive model (including mRSS, duration of skin thickening and their interaction) had an accuracy of 60.9%, AUC of 0.666 and PPV of 33.8%. By adding a variable for Pol3 positivity, the model reached an accuracy of 71%, AUC of 0.711 and PPV of 41%. Two prediction models for progressive skin thickening were derived, for use both in clinical practice and for cohort enrichment in RCTs. These models will inform recruitment into the many clinical trials of dcSSc projected for the coming years. NCT02339441. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  13. A Status Review of the Commercial Supersonic Technology (CST) Aeroservoelasticity (ASE) Project

    NASA Technical Reports Server (NTRS)

    Silva, Walter A.; Sanetrik, Mark D.; Chwalowski, Pawel; Funk, Christy; Keller, Donald F.; Ringertz, Ulf

    2016-01-01

    An overview of recent progress regarding the computational aeroelastic and aeroservoelastic (ASE) analyses of a low-boom supersonic configuration is presented. The overview includes details of the computational models developed to date with a focus on unstructured CFD grids, computational aeroelastic analyses, sonic boom propagation studies that include static aeroelastic effects, and gust loads analyses. In addition, flutter boundaries using aeroelastic Reduced-Order Models (ROMs) are presented at various Mach numbers of interest. Details regarding a collaboration with the Royal Institute of Technology (KTH, Stockholm, Sweden) to design, fabricate, and test a full-span aeroelastic wind-tunnel model are also presented.

  14. A generative, probabilistic model of local protein structure.

    PubMed

    Boomsma, Wouter; Mardia, Kanti V; Taylor, Charles C; Ferkinghoff-Borg, Jesper; Krogh, Anders; Hamelryck, Thomas

    2008-07-01

    Despite significant progress in recent years, protein structure prediction maintains its status as one of the prime unsolved problems in computational biology. One of the key remaining challenges is an efficient probabilistic exploration of the structural space that correctly reflects the relative conformational stabilities. Here, we present a fully probabilistic, continuous model of local protein structure in atomic detail. The generative model makes efficient conformational sampling possible and provides a framework for the rigorous analysis of local sequence-structure correlations in the native state. Our method represents a significant theoretical and practical improvement over the widely used fragment assembly technique by avoiding the drawbacks associated with a discrete and nonprobabilistic approach.

  15. Changes in food insecurity, nutritional status, and physical health status after antiretroviral therapy initiation in rural Uganda.

    PubMed

    Weiser, Sheri D; Gupta, Reshma; Tsai, Alexander C; Frongillo, Edward A; Grede, Nils; Kumbakumba, Elias; Kawuma, Annet; Hunt, Peter W; Martin, Jeffrey N; Bangsberg, David R

    2012-10-01

    To investigate whether time on antiretroviral therapy (ART) is associated with improvements in food security and nutritional status, and the extent to which associations are mediated by improved physical health status. The Uganda AIDS Rural Treatment Outcomes study, a prospective cohort of HIV-infected adults newly initiating ART in Mbarara, Uganda. Participants initiating ART underwent quarterly structured interview and blood draws. The primary explanatory variable was time on ART, constructed as a set of binary variables for each 3-month period. Outcomes were food insecurity, nutritional status, and PHS. We fit multiple regression models with cluster-correlated robust estimates of variance to account for within-person dependence of observations over time, and analyses were adjusted for clinical and sociodemographic characteristics. Two hundred twenty-eight ART-naive participants were followed for up to 3 years, and 41% were severely food insecure at baseline. The mean food insecurity score progressively declined (test for linear trend P < 0.0001), beginning with the second quarter (b = -1.6; 95% confidence interval: -2.7 to -0.45) and ending with the final quarter (b = -6.4; 95% confidence interval: -10.3 to -2.5). PHS and nutritional status improved in a linear fashion over study follow-up (P < 0.001). Inclusion of PHS in the regression model attenuated the relationship between ART duration and food security. Among HIV-infected individuals in Uganda, food insecurity decreased and nutritional status and PHS improved over time after initiation of ART. Changes in food insecurity were partially explained by improvements in PHS. These data support early initiation of ART in resource-poor settings before decline in functional status to prevent worsening food insecurity and its detrimental effects on HIV treatment outcomes.

  16. Speech Research: A Report on the Status and Progress of Studies on the Nature of Speech, Instrumentation for Its Investigation, and Practical Applications. 1 October - 31 December 1970.

    ERIC Educational Resources Information Center

    Haskins Labs., New Haven, CT.

    This report is one of a regular series on the status and progress of studies on the nature of speech, instrumentation for its investigation, and practical implications. Manuscripts and extended reports cover the following topics: (1) "On Learning a New Contrast," (2) "Letter Confusions and reversals of Sequence in the Beginning Reader:…

  17. “Are You an African?” The Politics of Self-Construction in Status-Based Social Movements

    PubMed Central

    McCorkel, Jill; Rodriquez, Jason

    2011-01-01

    Current debates over identity politics hinge on the question of whether status-based social movements encourage parochialism and self-interest or create possibilities for mutual recognition across lines of difference. Our article explores this question through comparative, ethnographic study of two racially progressive social movements, “pro-black” abolitionism and “conscious” hip hop. We argue that status-based social movements not only enable collective identity, but also the personal identities or selves of their participants. Beliefs about the self create openings and obstacles to mutual recognition and progressive social action. Our analysis centers on the challenges that an influx of progressive, anti-racist whites posed to each movement. We examine first how each movement configured movement participation and racial identity and then how whites crafted strategic narratives of the self to account for their participation in a status-based movement they were not directly implicated in. We conclude with an analysis of the implications of these narratives for a critical politics of recognition. Keywords: identity politics, social movements, race, self, hip hop. PMID:21731113

  18. "Are You an African?" The Politics of Self-Construction in Status-Based Social Movements.

    PubMed

    McCorkel, Jill; Rodriquez, Jason

    2009-05-01

    Current debates over identity politics hinge on the question of whether status-based social movements encourage parochialism and self-interest or create possibilities for mutual recognition across lines of difference. Our article explores this question through comparative, ethnographic study of two racially progressive social movements, "pro-black" abolitionism and "conscious" hip hop. We argue that status-based social movements not only enable collective identity, but also the personal identities or selves of their participants. Beliefs about the self create openings and obstacles to mutual recognition and progressive social action. Our analysis centers on the challenges that an influx of progressive, anti-racist whites posed to each movement. We examine first how each movement configured movement participation and racial identity and then how whites crafted strategic narratives of the self to account for their participation in a status-based movement they were not directly implicated in. We conclude with an analysis of the implications of these narratives for a critical politics of recognition. Keywords: identity politics, social movements, race, self, hip hop.

  19. Health-related quality of life and disease symptoms in postmenopausal women with HR(+), HER2(-) advanced breast cancer treated with everolimus plus exemestane versus exemestane monotherapy.

    PubMed

    Campone, Mario; Beck, J Thaddeus; Gnant, Michael; Neven, Patrick; Pritchard, Kathleen I; Bachelot, Thomas; Provencher, Louise; Rugo, Hope S; Piccart, Martine; Hortobagyi, Gabriel N; Nunzi, Martina; Heng, Daniel Y C; Baselga, José; Komorowski, Anna; Noguchi, Shinzaburo; Horiguchi, Jun; Bennett, Lee; Ziemiecki, Ryan; Zhang, Jie; Cahana, Ayelet; Taran, Tetiana; Sahmoud, Tarek; Burris, Howard A

    2013-11-01

    Everolimus (EVE)+exemestane (EXE; n = 485) more than doubled median progression-free survival versus placebo (PBO) + EXE (n = 239), with a manageable safety profile and no deterioration in health-related quality-of-life (HRQOL) in patients with hormone-receptor-positive (HR(+)) advanced breast cancer (ABC) who recurred or progressed on/after nonsteroidal aromatase inhibitor (NSAI) therapy. To further evaluate EVE + EXE impact on disease burden, we conducted additional post-hoc analyses of patient-reported HRQOL. HRQOL was assessed using EORTC QLQ-C30 and QLQ-BR23 questionnaires at baseline and every 6 weeks thereafter until treatment discontinuation because of disease progression, toxicity, or consent withdrawal. Endpoints included the QLQ-C30 Global Health Status (QL2) scale, the QLQ-BR23 breast symptom (BRBS), and arm symptom (BRAS) scales. Between-group differences in change from baseline were assessed using linear mixed models with selected covariates. Sensitivity analysis using pattern-mixture models determined the effect of study discontinuation on/before week 24. Treatment arms were compared using differences of least squares mean (LSM) changes from baseline and 95% confidence intervals (CIs) at each timepoint and overall. Clinicaltrials.gov: NCT00863655. Progression-free survival, survival, response rate, safety, and HRQOL. Linear mixed models (primary model) demonstrated no statistically significant overall difference between EVE + EXE and PBO + EXE for QL2 (LSM difference = -1.91; 95% CI = -4.61, 0.78), BRBS (LSM difference = -0.18; 95% CI = -1.98, 1.62), or BRAS (LSM difference = -0.42; 95% CI = -2.94, 2.10). Based on pattern-mixture models, patients who dropped out early had worse QL2 decline on both treatments. In the expanded pattern-mixture model, EVE + EXE-treated patients who did not drop out early had stable BRBS and BRAS relative to PBO + EXE. HRQOL data were not collected after disease progression. These analyses confirm that EVE + EXE provides clinical benefit without adversely impacting HRQOL in patients with HR(+) ABC who recurred/progressed on prior NSAIs versus endocrine therapy alone.

  20. Standardized Treatment of Neonatal Status Epilepticus Improves Outcome.

    PubMed

    Harris, Mandy L; Malloy, Katherine M; Lawson, Sheena N; Rose, Rebecca S; Buss, William F; Mietzsch, Ulrike

    2016-12-01

    We aimed to decrease practice variation in treatment of neonatal status epilepticus by implementing a standardized protocol. Our primary goal was to achieve 80% adherence to the algorithm within 12 months. Secondary outcome measures included serum phenobarbital concentrations, number of patients progressing from seizures to status epilepticus, and length of hospital stay. Data collection occurred for 6 months prior and 12 months following protocol implementation. Adherence of 80% within 12 months was partially achieved in patients diagnosed in our hospital; in pretreated patients, adherence was not achieved. Maximum phenobarbital concentrations were decreased (56.8 vs 41.0 µg/mL), fewer patients progressed from seizures to status epilepticus (46% vs 36%), and hospital length of stay decreased by 9.7 days in survivors. In conclusion, standardized, protocol-driven treatment of neonatal status epilepticus improves consistency and short-term outcome. © The Author(s) 2016.

  1. A longitudinal model for disease progression was developed and applied to multiple sclerosis

    PubMed Central

    Lawton, Michael; Tilling, Kate; Robertson, Neil; Tremlett, Helen; Zhu, Feng; Harding, Katharine; Oger, Joel; Ben-Shlomo, Yoav

    2015-01-01

    Objectives To develop a model of disease progression using multiple sclerosis (MS) as an exemplar. Study Design and Settings Two observational cohorts, the University of Wales MS (UoWMS), UK (1976), and British Columbia MS (BCMS) database, Canada (1980), with longitudinal disability data [the Expanded Disability Status Scale (EDSS)] were used; individuals potentially eligible for MS disease-modifying drugs treatments, but who were unexposed, were selected. Multilevel modeling was used to estimate the EDSS trajectory over time in one data set and validated in the other; challenges addressed included the choice and function of time axis, complex observation-level variation, adjustments for MS relapses, and autocorrelation. Results The best-fitting model for the UoWMS cohort (404 individuals, and 2,290 EDSS observations) included a nonlinear function of time since onset. Measurement error decreased over time and ad hoc methods reduced autocorrelation and the effect of relapse. Replication within the BCMS cohort (978 individuals and 7,335 EDSS observations) led to a model with similar time (years) coefficients, time [0.22 (95% confidence interval {CI}: 0.19, 0.26), 0.16 (95% CI: 0.10, 0.22)] and log time [−0.13 (95% CI: −0.39, 0.14), −0.15 (95% CI: −0.70, 0.40)] for BCMS and UoWMS, respectively. Conclusion It is possible to develop robust models of disability progression for chronic disease. However, explicit validation is important given the complex methodological challenges faced. PMID:26071892

  2. Developing and validating a predictive model for stroke progression.

    PubMed

    Craig, L E; Wu, O; Gilmour, H; Barber, M; Langhorne, P

    2011-01-01

    Progression is believed to be a common and important complication in acute stroke, and has been associated with increased mortality and morbidity. Reliable identification of predictors of early neurological deterioration could potentially benefit routine clinical care. The aim of this study was to identify predictors of early stroke progression using two independent patient cohorts. Two patient cohorts were used for this study - the first cohort formed the training data set, which included consecutive patients admitted to an urban teaching hospital between 2000 and 2002, and the second cohort formed the test data set, which included patients admitted to the same hospital between 2003 and 2004. A standard definition of stroke progression was used. The first cohort (n = 863) was used to develop the model. Variables that were statistically significant (p < 0.1) on univariate analysis were included in the multivariate model. Logistic regression was the technique employed using backward stepwise regression to drop the least significant variables (p > 0.1) in turn. The second cohort (n = 216) was used to test the performance of the model. The performance of the predictive model was assessed in terms of both calibration and discrimination. Multiple imputation methods were used for dealing with the missing values. Variables shown to be significant predictors of stroke progression were conscious level, history of coronary heart disease, presence of hyperosmolarity, CT lesion, living alone on admission, Oxfordshire Community Stroke Project classification, presence of pyrexia and smoking status. The model appears to have reasonable discriminative properties [the median receiver-operating characteristic curve value was 0.72 (range 0.72-0.73)] and to fit well with the observed data, which is indicated by the high goodness-of-fit p value [the median p value from the Hosmer-Lemeshow test was 0.90 (range 0.50-0.92)]. The predictive model developed in this study contains variables that can be easily collected in practice therefore increasing its usability in clinical practice. Using this analysis approach, the discrimination and calibration of the predictive model appear sufficiently high to provide accurate predictions. This study also offers some discussion around the validation of predictive models for wider use in clinical practice.

  3. Decadal Vision Progress Report Implementation Plans and Status for the Next Generation ARM Facility

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

    Mather, James

    The reconfiguration of the ARM facility, formally initiated in early 2014, is geared toward implementing the Next Generation of the ARM Facility, which will more tightly link ARM measurements and atmospheric models. The strategy is outlined in the ARM Climate Research Facility Decadal Vision (DOE 2014a). The strategy includes the implementation of a high-resolution model, initially at the Southern Great Plains (SGP) site, and enhancements at the SGP and North Slope of Alaska (NSA) sites to provide additional observations to support modeling and process studies. Enhancements at the SGP site focus on ground-based instruments while enhancements at the NSA makemore » use of Unmanned Aerial Systems (UAS) and Tethered Balloon Systems (TBS). It is also recognized that new data tools and data products will need to be developed to take full advantage of these improvements. This document provides an update on the status of these ARM facility enhancements, beginning with the measurement enhancements at the SGP and NSA, followed by a discussion of the modeling project including associated data-processing activities.« less

  4. Status and progress in large-scale assessment of biological diversity in the United States

    Treesearch

    S. R. Shifley; C. H. Flather; W. B. Smith; K. H. Riitters; C. H. Sieg

    2010-01-01

    Conservation of biological diversity is one of seven criteria used to evaluate forest sustainability in the United States. The status of biological diversity is characterized by nine indicators that report area, protected status, and fragmentation of forest habitats; number and conservation status of forest-associated species; range and abundance of forest species to...

  5. Evaluating the predictive power of multivariate tensor-based morphometry in Alzheimer's disease progression via convex fused sparse group Lasso

    NASA Astrophysics Data System (ADS)

    Tsao, Sinchai; Gajawelli, Niharika; Zhou, Jiayu; Shi, Jie; Ye, Jieping; Wang, Yalin; Lepore, Natasha

    2014-03-01

    Prediction of Alzheimers disease (AD) progression based on baseline measures allows us to understand disease progression and has implications in decisions concerning treatment strategy. To this end we combine a predictive multi-task machine learning method1 with novel MR-based multivariate morphometric surface map of the hippocampus2 to predict future cognitive scores of patients. Previous work by Zhou et al.1 has shown that a multi-task learning framework that performs prediction of all future time points (or tasks) simultaneously can be used to encode both sparsity as well as temporal smoothness. They showed that this can be used in predicting cognitive outcomes of Alzheimers Disease Neuroimaging Initiative (ADNI) subjects based on FreeSurfer-based baseline MRI features, MMSE score demographic information and ApoE status. Whilst volumetric information may hold generalized information on brain status, we hypothesized that hippocampus specific information may be more useful in predictive modeling of AD. To this end, we applied Shi et al.2s recently developed multivariate tensor-based (mTBM) parametric surface analysis method to extract features from the hippocampal surface. We show that by combining the power of the multi-task framework with the sensitivity of mTBM features of the hippocampus surface, we are able to improve significantly improve predictive performance of ADAS cognitive scores 6, 12, 24, 36 and 48 months from baseline.

  6. Multiplexed methylation profiles of tumor suppressor genes and clinical outcome in oligodendroglial tumors.

    PubMed

    Kuo, Lu-Ting; Lu, Hsueh-Yi; Lee, Chien-Chang; Tsai, Jui-Chang; Lai, Hong-Shiee; Tseng, Ham-Min; Kuo, Meng-Fai; Tu, Yong-Kwang

    2016-08-01

    Aberrant methylation has been associated with transcriptional inactivation of tumor-related genes in a wide spectrum of human neoplasms. The influence of DNA methylation in oligodendroglial tumors is not fully understood. Genomic DNA was isolated from 61 oligodendroglial tumors for analysis of methylation using methylation-specific multiplex ligation-dependent probe amplification assay (MS-MLPA). We correlated methylation status with clinicopathological findings and outcome. The genes found to be most frequently methylated in oligodendroglial tumors were RASSF1A (80.3%), CASP8 (70.5%), and CDKN2A (52.5%). Kaplan-Meier survival curve analysis demonstrated longer duration of progression-free survival in patients with 19q loss, aged less than 38 years, and with a proliferative index of less than 5%. Methylation of the ESR1 promoter is significantly associated with shorter duration of overall survival and progression-free survival, and that methylation of IGSF4 and RASSF1A is significantly associated with shorter duration of progression-free survival. However, none of the methylation status of ESR1, IGSF4, and RASSF1A was of prognostic value for survival in a multivariate Cox model. A number of novel and interesting epigenetic alterations were identified in this study. The findings highlight the importance of methylation profiles in oligodendroglial tumors and their possible involvement in tumorigenesis. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  7. Cellular and Molecular effects of Vitamin D on Carcinogenesis

    PubMed Central

    Welsh, JoEllen

    2011-01-01

    Epidemiologic data suggest that the incidence and severity of many types of cancer inversely correlates with indices of vitamin D status. The vitamin D receptor (VDR) is highly expressed in epithelial cells at risk for carcinogenesis including those resident in skin, breast, prostate and colon, providing a direct molecular link by which vitamin D status impacts on carcinogenesis. Consistent with this concept, activation of VDR by its ligand 1,25-dihydroxyvitamin D (1,25D) triggers comprehensive genomic changes in epithelial cells that contribute to maintenance of the differentiated phenotype, resistance to cellular stresses and protection of the genome. Many epithelial cells also express the vitamin D metabolizing enzyme CYP27B1 which enables autocrine generation of 1,25D from the circulating vitamin D metabolite 25-hydroxyvitamin D (25D), critically linking overall vitamin D status with cellular anti-tumor actions. Furthermore, pre-clinical studies in animal models has demonstrated that dietary supplementation with vitamin D or chronic treatment with VDR agonists decreases tumor development in skin, colon, prostate and breast. Conversely, deletion of the VDR gene in mice alters the balance between proliferation and apoptosis, increases oxidative DNA damage, and enhances susceptibility to carcinogenesis in these tissues. Because VDR expression is retained in many human tumors, vitamin D status may be an important modulator of cancer progression in persons living with cancer. Collectively, these observations have reinforced the need to further define the molecular actions of the VDR and the human requirement for vitamin D in relation to cancer development and progression. PMID:22085499

  8. Development and validation of a radiomics nomogram for progression-free survival prediction in stage IV EGFR-mutant non-small cell lung cancer

    NASA Astrophysics Data System (ADS)

    Song, Jiangdian; Zang, Yali; Li, Weimin; Zhong, Wenzhao; Shi, Jingyun; Dong, Di; Fang, Mengjie; Liu, Zaiyi; Tian, Jie

    2017-03-01

    Accurately predict the risk of disease progression and benefit of tyrosine kinase inhibitors (TKIs) therapy for stage IV non-small cell lung cancer (NSCLC) patients with activing epidermal growth factor receptor (EGFR) mutations by current staging methods are challenge. We postulated that integrating a classifier consisted of multiple computed tomography (CT) phenotypic features, and other clinicopathological risk factors into a single model could improve risk stratification and prediction of progression-free survival (PFS) of EGFR TKIs for these patients. Patients confirmed as stage IV EGFR-mutant NSCLC received EGFR TKIs with no resection; pretreatment contrast enhanced CT performed at approximately 2 weeks before the treatment was enrolled. A six-CT-phenotypic-feature-based classifier constructed by the LASSO Cox regression model, and three clinicopathological factors: pathologic N category, performance status (PS) score, and intrapulmonary metastasis status were used to construct a nomogram in a training set of 115 patients. The prognostic and predictive accuracy of this nomogram was then subjected to an external independent validation of 107 patients. PFS between the training and independent validation set is no statistical difference by Mann-Whitney U test (P = 0.2670). PFS of the patients could be predicted with good consistency compared with the actual survival. C-index of the proposed individualized nomogram in the training set (0·707, 95%CI: 0·643, 0·771) and the independent validation set (0·715, 95%CI: 0·650, 0·780) showed the potential of clinical prognosis to predict PFS of stage IV EGFR-mutant NSCLC from EGFR TKIs. The individualized nomogram might facilitate patient counselling and individualise management of patients with this disease.

  9. The NHLBI LAM Registry: Prognostic physiological and radiological biomarkers emerge from a 15-year prospective longitudinal analysis.

    PubMed

    Gupta, Nishant; Lee, Hye-Seung; Ryu, Jay H; Taveira-DaSilva, Angelo M; Beck, Gerald J; Lee, Jar-Chi; McCarthy, Kevin; Finlay, Geraldine A; Brown, Kevin K; Ruoss, Stephen J; Avila, Nilo A; Moss, Joel; McCormack, Francis X

    2018-06-22

    The natural history of lymphangioleiomyomatosis is mainly derived from retrospective cohort analyses and remains incompletely understood. A National Institutes of Health LAM Registry was established to define the natural history and identify prognostic biomarkers that can help guide management and decision-making in patients with LAM. A linear mixed effects model was employed to compute the rate of decline of FEV1, and identify variables impacting FEV1 decline among 217 registry patients who enrolled from 1998-2001. Prognostic variables associated with progression to death/lung transplantation were identified using a Cox proportional hazard model. Mean annual decline of FEV1 was 89±53 ml/year, and remained remarkably constant regardless of baseline lung function. FEV1 decline was more rapid in those with greater cyst profusion on CT scan (p=0.02), and in premenopausal subjects (118ml/year) compared to postmenopausal subjects (74ml/year), (p=0.003). There were 26 deaths and 43 lung transplants during the evaluation period. Estimated 5-, 10-, 15-, and 20-year transplant-free survival rates were 95%, 85%, 75%, and 64%, respectively. Postmenopausal status (hazard ratio 0.30, p=0.0002) and higher baseline FEV1 (hazard ratio 0.97, p=0.008) or DLCO (hazard ratio 0.97, p=0.001) were independently associated with a lower risk of progression to death or lung transplantation. The median transplant-free survival in patients with LAM is greater than 20 years. Menopausal status as well as structural and physiological markers of disease severity significantly affect the rate of decline of FEV1 and progression to death or lung transplantation in LAM. Copyright © 2018. Published by Elsevier Inc.

  10. Cost-effectiveness analysis of bortezomib in combination with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (VR-CAP) in patients with previously untreated mantle cell lymphoma.

    PubMed

    van Keep, Marjolijn; Gairy, Kerry; Seshagiri, Divyagiri; Thilakarathne, Pushpike; Lee, Dawn

    2016-08-04

    Mantle cell lymphoma (MCL) is a rare and aggressive form of non-Hodgkin's lymphoma. Bortezomib is the first product to be approved for the treatment of patients with previously untreated MCL, for whom haematopoietic stem cell transplantation is unsuitable, and is used in combination with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (VR-CAP). The National Institute of Health and Care Excellence recently recommended the use of VR-CAP in the UK following a technology appraisal. We present the cost effectiveness analysis performed as part of that assessment: VR-CAP versus the current standard of care regimen of rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) in a UK setting. A lifetime economic model was developed with health states based upon line of treatment and progression status. Baseline patient characteristics, dosing, safety and efficacy were based on the LYM-3002 trial. As overall survival data were immature, survival was modelled by progression status, and post-progression survival was assumed equal across arms. Utilities were derived from LYM-3002 and literature, and standard UK cost sources were used. Treatment with VR-CAP compared to R-CHOP gave an incremental quality-adjusted life year (QALY) gain of 0.81 at an additional cost of £16,212, resulting in a base case incremental cost-effectiveness ratio of £20,043. Deterministic and probabilistic sensitivity analyses showed that treatment with VR-CAP was cost effective at conventional willingness-to-pay thresholds (£20,000-£30,000 per QALY). VR-CAP is a cost-effective option for previously untreated patients with MCL in the UK.

  11. Predicting and Tracking Short Term Disease Progression in Amnestic Mild Cognitive Impairment Patients with Prodromal Alzheimer's Disease: Structural Brain Biomarkers.

    PubMed

    Marizzoni, Moira; Ferrari, Clarissa; Jovicich, Jorge; Albani, Diego; Babiloni, Claudio; Cavaliere, Libera; Didic, Mira; Forloni, Gianluigi; Galluzzi, Samantha; Hoffmann, Karl-Titus; Molinuevo, José Luis; Nobili, Flavio; Parnetti, Lucilla; Payoux, Pierre; Ribaldi, Federica; Rossini, Paolo Maria; Schönknecht, Peter; Soricelli, Andrea; Hensch, Tilman; Tsolaki, Magda; Visser, Pieter Jelle; Wiltfang, Jens; Richardson, Jill C; Bordet, Régis; Blin, Olivier; Frisoni, Giovanni B

    2018-06-09

    Early Alzheimer's disease (AD) detection using cerebrospinal fluid (CSF) biomarkers has been recommended as enrichment strategy for trials involving mild cognitive impairment (MCI) patients. To model a prodromal AD trial for identifying MRI structural biomarkers to improve subject selection and to be used as surrogate outcomes of disease progression. APOE ɛ4 specific CSF Aβ42/P-tau cut-offs were used to identify MCI with prodromal AD (Aβ42/P-tau positive) in the WP5-PharmaCog (E-ADNI) cohort. Linear mixed models were performed 1) with baseline structural biomarker, time, and biomarker×time interaction as factors to predict longitudinal changes in ADAS-cog13, 2) with Aβ42/P-tau status, time, and Aβ42/P-tau status×time interaction as factors to explain the longitudinal changes in MRI measures, and 3) to compute sample size estimation for a trial implemented with the selected biomarkers. Only baseline lateral ventricle volume was able to identify a subgroup of prodromal AD patients who declined faster (interaction, p = 0.003). Lateral ventricle volume and medial temporal lobe measures were the biomarkers most sensitive to disease progression (interaction, p≤0.042). Enrichment through ventricular volume reduced the sample size that a clinical trial would require from 13 to 76%, depending on structural outcome variable. The biomarker needing the lowest sample size was the hippocampal subfield GC-ML-DG (granule cells of molecular layer of the dentate gyrus) (n = 82 per arm to demonstrate a 20% atrophy reduction). MRI structural biomarkers can enrich prodromal AD with fast progressors and significantly decrease group size in clinical trials of disease modifying drugs.

  12. Association of Age With Survival in Patients With Metastatic Colorectal Cancer: Analysis From the ARCAD Clinical Trials Program

    PubMed Central

    Lieu, Christopher H.; Renfro, Lindsay A.; de Gramont, Aimery; Meyers, Jeffrey P.; Maughan, Timothy S.; Seymour, Matthew T.; Saltz, Leonard; Goldberg, Richard M.; Sargent, Daniel J.; Eckhardt, S. Gail; Eng, Cathy

    2014-01-01

    Purpose This study addressed whether age is prognostic for overall survival (OS) or progression-free survival (PFS) in patients with metastatic colorectal cancer (mCRC). Patients and Methods A total of 20,023 patients from 24 first-line clinical trials in the ARCAD (Aide et Recherche en Cancérologie Digestive) database were analyzed. Primary age effects and interactions with age, sex, performance status (PS), and metastatic site were modeled using Cox proportional hazards stratified by treatment arm within study. Results Of total patients, 3,051 (15%) were age ≤ 50 years. Age was prognostic for both OS (P < .001) and PFS (P < .001), with U-shaped risk (ie, highest risk was evident in youngest and oldest patients). Relative to patients of middle age, the youngest patients experienced 19% (95% CI, 7% to 33%) increased risk of death and 22% (95% CI, 10% to 35%) increased risk of progression. The oldest patients experienced 42% (95% CI, 31% to 54%) increased risk of death and 15% (95% CI, 7% to 24%) increased risk of progression or death. This relationship was more pronounced in the first year of follow-up. Age remained marginally significant for OS (P = .08) when adjusted for PS, sex, and presence of liver, lung, or peritoneal metastases, and age was significant in an adjusted model for PFS (P = .005). The age effect did not differ by site of metastatic disease, year of enrollment, type of therapy received, or biomarker mutational status. Conclusion Younger and older age are associated with poorer OS and PFS among treated patients with mCRC. Younger and older patients may represent higher-risk populations, and additional studies are warranted. PMID:25002720

  13. Salivary pH as a marker of plasma adiponectin concentrations in Women.

    PubMed

    Tremblay, Monique; Loucif, Yacine; Methot, Julie; Brisson, Diane; Gaudet, Daniel

    2012-02-03

    Plasma adiponectin is a significant correlate of the pro-inflammatory cardiometabolic risk profile associated with obesity and type 2 diabetes. Salivary pH is influenced by several cardiometabolic risk components such as inflammation, oxidation and numerous oral and systemic health modulators, including the menopausal status. This study aimed to assess the association between plasma adiponectin concentrations and salivary pH in women according to the menopausal status. Unstimulated saliva collection was performed in 151 Caucasian women of French-Canadian origin (53 premenopausal women (PMW) and 98 menopausal women (MW)). Student's t test, ANOVA and linear regression models were used to assess the association between plasma adiponectin concentrations and salivary pH. Plasma adiponectin levels increased as a function of salivary pH in the whole sample and among MW (r = 0.29 and r = 0.36, p < 0.001). The proportion of the variance of plasma adiponectin levels explained by the salivary pH (R2) was 10.8% (p < 0.001). Plasma adiponectin levels progressively increased across salivary pH quartiles (p = 0.005). These results suggest that salivary pH is a significant correlate of plasma adiponectin levels in women. With the increasing prevalence of type 2 diabetes and obesity, new technologies should be developed to more easily monitor health status, disease onset and progression. Salivary pH, a simple, inexpensive and non-invasive measure, could be a very promising avenue.

  14. 10 CFR 603.1100 - Contracting officer's post-award responsibilities.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... technical progress, financial status, and future program plans. (b) Tracking and processing of reports... progress reports, and patent reports. (c) Handling payment requests and related matters. For a TIA using advance payments, that includes reviews of progress to verify that there is continued justification for...

  15. Detection of ATRX and IDH1-R132H immunohistochemistry in the progression of 211 paired gliomas

    PubMed Central

    Li, Qingbin; Wang, Zhiliang; Li, Guanzhang; Wang, Guangzhi; Yang, Pei; Li, Jianlong; Han, Bo; Jiang, Chuanlu; Sun, Ying; Jiang, Tao

    2016-01-01

    Recurrence and progression to higher grade lesions are key biological events and characteristic behaviors in the evolution process of glioma. A small residual population of cells always escapes surgery and chemoradiation, resulting in a typically fatal tumor recurrence or progression. IDH mutation (isocitrate dehydrogenase) and ATRX (alpha-thalassemia/mental retardation, X-linked) loss/mutation occur in association and may represent early genetic alterations in the development of gliomas. However, their prognostic value in the evolution of gliomas still needs further investigation. Two hundreds and eleven serial sampling of gliomas were included in our study. We used immunohistochemistry (IHC) to detect IDH1-R132H mutation and ATRX status and showed that the IDH1-R132H and (or) ATRX status could be necessary to provide the basic molecular information for the “integrated diagnosis” of gliomas. We illustrated an evaluation formula for the evolution of gliomas by IDH1-R132H combined with ATRX immunohistochemistry and identified the association of IDH1-R132H/ATRX loss accompanied by longer progression time interval of patients with gliomas. Furthermore, we observed that most recurrences had a consistent IDH1 and ATRX status with their matched primary tumors and demonstrated the progressive pattern of grade II astrocytoma/oligodendroglial tumors and anaplastic oligoastrocytoma with or without IDH1-R132H. Identification of IDH1-R132H and ATRX loss status in the primary-recurrent gliomas may aid in treatment strategy selection, therapeutic trial design, and clinical prognosis evaluation. PMID:26918938

  16. Detection of ATRX and IDH1-R132H immunohistochemistry in the progression of 211 paired gliomas.

    PubMed

    Cai, Jinquan; Zhu, Ping; Zhang, Chuanbao; Li, Qingbin; Wang, Zhiliang; Li, Guanzhang; Wang, Guangzhi; Yang, Pei; Li, Jianlong; Han, Bo; Jiang, Chuanlu; Sun, Ying; Jiang, Tao

    2016-03-29

    Recurrence and progression to higher grade lesions are key biological events and characteristic behaviors in the evolution process of glioma. A small residual population of cells always escapes surgery and chemoradiation, resulting in a typically fatal tumor recurrence or progression. IDH mutation (isocitrate dehydrogenase) and ATRX (alpha-thalassemia/mental retardation, X-linked) loss/mutation occur in association and may represent early genetic alterations in the development of gliomas. However, their prognostic value in the evolution of gliomas still needs further investigation.Two hundreds and eleven serial sampling of gliomas were included in our study. We used immunohistochemistry (IHC) to detect IDH1-R132H mutation and ATRX status and showed that the IDH1-R132H and (or) ATRX status could be necessary to provide the basic molecular information for the "integrated diagnosis" of gliomas. We illustrated an evaluation formula for the evolution of gliomas by IDH1-R132H combined with ATRX immunohistochemistry and identified the association of IDH1-R132H/ATRX loss accompanied by longer progression time interval of patients with gliomas. Furthermore, we observed that most recurrences had a consistent IDH1 and ATRX status with their matched primary tumors and demonstrated the progressive pattern of grade II astrocytoma/oligodendroglial tumors and anaplastic oligoastrocytoma with or without IDH1-R132H. Identification of IDH1-R132H and ATRX loss status in the primary-recurrent gliomas may aid in treatment strategy selection, therapeutic trial design, and clinical prognosis evaluation.

  17. Allogeneic transplantation provides durable remission in a subset of DLBCL patients relapsing after autologous transplantation.

    PubMed

    Fenske, Timothy S; Ahn, Kwang W; Graff, Tara M; DiGilio, Alyssa; Bashir, Qaiser; Kamble, Rammurti T; Ayala, Ernesto; Bacher, Ulrike; Brammer, Jonathan E; Cairo, Mitchell; Chen, Andy; Chen, Yi-Bin; Chhabra, Saurabh; D'Souza, Anita; Farooq, Umar; Freytes, Cesar; Ganguly, Siddhartha; Hertzberg, Mark; Inwards, David; Jaglowski, Samantha; Kharfan-Dabaja, Mohamed A; Lazarus, Hillard M; Nathan, Sunita; Pawarode, Attaphol; Perales, Miguel-Angel; Reddy, Nishitha; Seo, Sachiko; Sureda, Anna; Smith, Sonali M; Hamadani, Mehdi

    2016-07-01

    For diffuse large B-cell lymphoma (DLBCL) patients progressing after autologous haematopoietic cell transplantation (autoHCT), allogeneic HCT (alloHCT) is often considered, although limited information is available to guide patient selection. Using the Center for International Blood and Marrow Transplant Research (CIBMTR) database, we identified 503 patients who underwent alloHCT after disease progression/relapse following a prior autoHCT. The 3-year probabilities of non-relapse mortality, progression/relapse, progression-free survival (PFS) and overall survival (OS) were 30, 38, 31 and 37% respectively. Factors associated with inferior PFS on multivariate analysis included Karnofsky performance status (KPS) <80, chemoresistance, autoHCT to alloHCT interval <1-year and myeloablative conditioning. Factors associated with worse OS on multivariate analysis included KPS<80, chemoresistance and myeloablative conditioning. Three adverse prognostic factors were used to construct a prognostic model for PFS, including KPS<80 (4 points), autoHCT to alloHCT interval <1-year (2 points) and chemoresistant disease at alloHCT (5 points). This CIBMTR prognostic model classified patients into four groups: low-risk (0 points), intermediate-risk (2-5 points), high-risk (6-9 points) or very high-risk (11 points), predicting 3-year PFS of 40, 32, 11 and 6%, respectively, with 3-year OS probabilities of 43, 39, 19 and 11% respectively. In conclusion, the CIBMTR prognostic model identifies a subgroup of DLBCL patients experiencing long-term survival with alloHCT after a failed prior autoHCT. © 2016 John Wiley & Sons Ltd.

  18. Stress and tinnitus—from bedside to bench and back

    PubMed Central

    Mazurek, Birgit; Haupt, Heidemarie; Olze, Heidi; Szczepek, Agnieszka J.

    2012-01-01

    The aim of this review is to focus the attention of clinicians and basic researchers on the association between psycho-social stress and tinnitus. Although tinnitus is an auditory symptom, its onset and progression often associates with emotional strain. Recent epidemiological studies have provided evidence for a direct relationship between the emotional status of subjects and tinnitus. In addition, studies of function, morphology, and gene and protein expression in the auditory system of animals exposed to stress support the notion that the emotional status can influence the auditory system. The data provided by clinical and basic research with use of animal stress models offers valuable clues for an improvement in diagnosis and more effective treatment of tinnitus. PMID:22701404

  19. Personalized long-term prediction of cognitive function: Using sequential assessments to improve model performance.

    PubMed

    Chi, Chih-Lin; Zeng, Wenjun; Oh, Wonsuk; Borson, Soo; Lenskaia, Tatiana; Shen, Xinpeng; Tonellato, Peter J

    2017-12-01

    Prediction of onset and progression of cognitive decline and dementia is important both for understanding the underlying disease processes and for planning health care for populations at risk. Predictors identified in research studies are typically accessed at one point in time. In this manuscript, we argue that an accurate model for predicting cognitive status over relatively long periods requires inclusion of time-varying components that are sequentially assessed at multiple time points (e.g., in multiple follow-up visits). We developed a pilot model to test the feasibility of using either estimated or observed risk factors to predict cognitive status. We developed two models, the first using a sequential estimation of risk factors originally obtained from 8 years prior, then improved by optimization. This model can predict how cognition will change over relatively long time periods. The second model uses observed rather than estimated time-varying risk factors and, as expected, results in better prediction. This model can predict when newly observed data are acquired in a follow-up visit. Performances of both models that are evaluated in10-fold cross-validation and various patient subgroups show supporting evidence for these pilot models. Each model consists of multiple base prediction units (BPUs), which were trained using the same set of data. The difference in usage and function between the two models is the source of input data: either estimated or observed data. In the next step of model refinement, we plan to integrate the two types of data together to flexibly predict dementia status and changes over time, when some time-varying predictors are measured only once and others are measured repeatedly. Computationally, both data provide upper and lower bounds for predictive performance. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Status on the Development of a Modeling and Simulation Framework for the Economic Assessment of Nuclear Hybrid Energy

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

    Epiney, Aaron Simon; Chen, Jun; Rabiti, Cristian

    Continued effort to design and build a modeling and simulation framework to assess the economic viability of Nuclear Hybrid Energy Systems (NHES) was undertaken in fiscal year (FY) 2016. The purpose of this report is to document the various tasks associated with the development of such a framework and to provide a status of their progress. Several tasks have been accomplished. First, a synthetic time history generator has been developed in RAVEN, which consists of Fourier series and autoregressive moving average model. The former is used to capture the seasonal trend in historical data, while the latter is to characterizemore » the autocorrelation in residue time series (e.g., measurements with seasonal trends subtracted). As demonstration, both synthetic wind speed and grid demand are generated, showing matching statistics with database. In order to build a design and operations optimizer in RAVEN, a new type of sampler has been developed with highly object-oriented design. In particular, simultaneous perturbation stochastic approximation algorithm is implemented. The optimizer is capable to drive the model to optimize a scalar objective function without constraint in the input space, while the constraints handling is a work in progress and will be implemented to improve the optimization capability. Furthermore, a simplified cash flow model of the performance of an NHES in the electric market has been developed in Python and used as external model in RAVEN to confirm expectations on the analysis capability of RAVEN to provide insight into system economics and to test the capability of RAVEN to identify limit surfaces. Finally, an example calculation is performed that shows the integration and proper data passing in RAVEN of the synthetic time history generator, the cash flow model and the optimizer. It has been shown that the developed Python models external to RAVEN are able to communicate with RAVEN and each other through the newly developed RAVEN capability called “EnsembleModel”.« less

  1. Assessing the Current Status of Atmospheric Radiation Modelling: Progress, Challenges and the Needs for the Next Generation of Models

    NASA Astrophysics Data System (ADS)

    Joyce, C. J.; Tobiska, W. K.; Copeland, K.; Smart, D. F.; Shea, M. A.; Nowicki, S.; Atwell, W.; Benton, E. R.; Wilkins, R.; Hands, A.; Gronoff, G.; Meier, M. M.; Schwadron, N.

    2017-12-01

    Despite its potential for causing a wide range of harmful effects, including health hazards to airline passengers and damage to aircraft and satellite electronics, atmospheric radiation remains a relatively poorly defined risk, lacking sufficient measurements and modelling to fully evaluate the dangers posed. While our reliance on airline travel has increased dramatically over time, there remains an absence of international guidance and standards to protect aircraft passengers from potential health impacts due to radiation exposure. This subject has been gaining traction within the scientific community in recent years, with an expanding number of models with increasing capabilities being made available to evaluate atmospheric radiation hazards. We provide a general description of these modelling efforts, including the physics and methods used by the models, as well as their data inputs and outputs. We also discuss the current capacity for model validation via measurements and discuss the needs for the next generation of models, both in terms of their capabilities and the measurements required to validate them. This review of the status of atmospheric radiation modelling is part of a larger series of studies made as part of the SAFESKY program, with other efforts focusing on the underlying physics and implications, measurements and regulations/standards of atmospheric radiation.

  2. An Evaluation Model for Sustainable Development of China’s Textile Industry: An Empirical Study

    NASA Astrophysics Data System (ADS)

    Zhao, Hong; Lu, Xiaodong; Yu, Ting; Yin, Yanbin

    2018-04-01

    With economy’s continuous rapid growth, textile industry is required to search for new rules and adjust strategies in order to optimize industrial structure and rationalize social spending. The sustainable development of China’s textile industry is a comprehensive research subject. This study analyzed the status of China’s textile industry and constructed the evaluation model based on the economical, ecologic, and social benefits. Analytic Hierarchy Process (AHP) and Data Envelopment Analysis (DEA) were used for an empirical study of textile industry. The result of evaluation model suggested that the status of the textile industry has become the major problems in the sustainable development of China’s textile industry. It’s nearly impossible to integrate into the global economy if no measures are taken. The enterprises concerned with the textile industry status should be reformed in terms of product design, raw material selection, technological reform, technological progress, and management, in accordance with the ideas and requirements of sustainable development. The results of this study are benefit for 1) discover the main elements restricting the industry’s sustainable development; 2) seek for corresponding solutions for policy formulation and implementation of textile industry; 3) provide references for enterprises’ development transformation in strategic deployment, fund allocation, and personnel assignment.

  3. Tumoral vitamin D synthesis by CYP27B1 1-alpha-hydroxylase delays mammary tumor progression in the PyMT-MMTV mouse model and its action involves NF-kappaB modulation

    USDA-ARS?s Scientific Manuscript database

    Biologically-active vitamin D (1,25(OH)2D) is synthetized from inactive prohormone 25(OH)D by the enzyme CYP27B1 1-a-hydroxylase in kidney and several extra-renal tissues including breast. While the development of breast cancer has been linked to inadequate vitamin D status, the importance of bioac...

  4. Changing the Officer Promotion System to Support Unit Focused Stability (UFS)

    DTIC Science & Technology

    2005-05-26

    arms officers will be reduced by one-third.78 This decrement is far from trivial. Since many combat arms officers define career success by these two...their own priorities and definitions of career success , or by inventing informal “work-arounds” to regain the status quo of the old personnel...progression models so that its members are not forced to choose between personal career success and unit cohesion? Perhaps a study of the officer

  5. Annual Research Progress Report Fiscal Year 1987. Volume 1,

    DTIC Science & Technology

    1987-10-01

    Constrictive Pericarditis 86 in Patients. (0) C-20-85 Pressure Waveforms and Reflections in the Human Aorta: Compari- 87 son of a Cadaver Model with In...in Constrictive 125 Pericarditis . (0) C-60-86 The Natural History of HTLV-III Infection and Disease in a 126 United States Military Population. (0...Sheet Date: 18 Mar 87 Proj No: C-16-85 Status: Terminated Title: Significance of Post Radiotherapy Constrictive Pericarditis in Patients. Start Date 21

  6. Nomograms Predicting Progression-Free Survival, Overall Survival, and Pelvic Recurrence in Locally Advanced Cervical Cancer Developed From an Analysis of Identifiable Prognostic Factors in Patients From NRG Oncology/Gynecologic Oncology Group Randomized Trials of Chemoradiotherapy

    PubMed Central

    Rose, Peter G.; Java, James; Whitney, Charles W.; Stehman, Frederick B.; Lanciano, Rachelle; Thomas, Gillian M.; DiSilvestro, Paul A.

    2015-01-01

    Purpose To evaluate the prognostic factors in locally advanced cervical cancer limited to the pelvis and develop nomograms for 2-year progression-free survival (PFS), 5-year overall survival (OS), and pelvic recurrence. Patients and Methods We retrospectively reviewed 2,042 patients with locally advanced cervical carcinoma enrolled onto Gynecologic Oncology Group clinical trials of concurrent cisplatin-based chemotherapy and radiotherapy. Nomograms for 2-year PFS, five-year OS, and pelvic recurrence were created as visualizations of Cox proportional hazards regression models. The models were validated by bootstrap-corrected, relatively unbiased estimates of discrimination and calibration. Results Multivariable analysis identified prognostic factors including histology, race/ethnicity, performance status, tumor size, International Federation of Gynecology and Obstetrics stage, tumor grade, pelvic node status, and treatment with concurrent cisplatin-based chemotherapy. PFS, OS, and pelvic recurrence nomograms had bootstrap-corrected concordance indices of 0.62, 0.64, and 0.73, respectively, and were well calibrated. Conclusion Prognostic factors were used to develop nomograms for 2-year PFS, 5-year OS, and pelvic recurrence for locally advanced cervical cancer clinically limited to the pelvis treated with concurrent cisplatin-based chemotherapy and radiotherapy. These nomograms can be used to better estimate individual and collective outcomes. PMID:25732170

  7. Progressively consolidating historical visual explorations for new discoveries

    NASA Astrophysics Data System (ADS)

    Zhao, Kaiyu; Ward, Matthew O.; Rundensteiner, Elke A.; Higgins, Huong N.

    2013-12-01

    A significant task within data mining is to identify data models of interest. While facilitating the exploration tasks, most visualization systems do not make use of all the data models that are generated during the exploration. In this paper, we introduce a system that allows the user to gain insights from the data space progressively by forming data models and consolidating the generated models on the fly. Each model can be a a computationally extracted or user-defined subset that contains a certain degree of interest and might lead to some discoveries. When the user generates more and more data models, the degree of interest of some portion of some models will either grow (indicating higher occurrence) or will fluctuate or decrease (corresponding to lower occurrence). Our system maintains a collection of such models and accumulates the interestingness of each model into a consolidated model. In order to consolidate the models, the system summarizes the associations between the models in the collection and identifies support (models reinforce each other), complementary (models complement each other), and overlap of the models. The accumulated interestingness keeps track of historical exploration and helps the user summarize their findings which can lead to new discoveries. This mechanism for integrating results from multiple models can be applied to a wide range of decision support systems. We demonstrate our system in a case study involving the financial status of US companies.

  8. Personality and HIV Disease Progression: Role of NEO-PI-R Openness, Extraversion, and Profiles of Engagement

    PubMed Central

    O'Cleirigh, Conall; Schneiderman, Neil; Weiss, Alexander; Costa, Paul T.

    2008-01-01

    Objective To examine the role of the big five personality domains (Neuroticism, Extraversion, Openness, Agreeableness, Conscientiousness) and their respective facets and profiles on change in CD4 and log HIV-RNA copies/ml (VL) over 4 years. The examination of psychosocial predictors of disease progression in human immunodeficiency virus (HIV) has focused primarily on depression, coping, and stress, with little attention paid to stable individual differences. Methods A diverse sample of HIV-seropositive patients (n = 104) completed personality assessment (NEO-PI-R), underwent comprehensive psychological assessment and blood samples every 6 months for 4 years. Linear rates of change for CD4 cells and VL were modeled using Hierarchical Linear Modeling controlling for antiretrovirals (time dependent covariate), initial disease status, age, gender, ethnicity, and education. Results Domains that were significantly associated with slower disease progression over 4 years included Openness (CD4, VL), Extraversion (CD4, VL), and Conscientiousness (VL). Facets of the above domains that were significantly related to slower disease progression were assertiveness, positive emotions, and gregariousness (Extraversion); ideas, esthetics (Openness); achievement striving and order (Conscientiousness). In addition, profile analyses suggested personality styles which seem to underscore the importance of remaining engaged (e.g., Creative Interactors (E+O+), Upbeat Optimists (N−E+), Welcomers (E+A+), Go Getters (C+E+), and Directed (N−C+)) had slower disease progression, whereas the “homebody” profile (Low Extraversion-Low Openness) was significantly associated with faster disease progression. Conclusions These results provide good initial evidence of the relationship between personality and disease progression in HIV and suggest protective aspects of profiles of engagement. These finding may help identify those individuals at risk for poorer disease course and specify targets for psychosocial interventions. PMID:18256349

  9. Assessing Progress in Haiti Act

    THOMAS, 112th Congress

    Rep. Lee, Barbara [D-CA-9

    2011-03-10

    Senate - 04/26/2012 Placed on Senate Legislative Calendar under General Orders. Calendar No. 387. (All Actions) Tracker: This bill has the status Passed HouseHere are the steps for Status of Legislation:

  10. Prevalence of Prostate Cancer Clinical States and Mortality in the United States: Estimates Using a Dynamic Progression Model

    PubMed Central

    Scher, Howard I.; Solo, Kirk; Valant, Jason; Todd, Mary B.; Mehra, Maneesha

    2015-01-01

    Objective To identify patient populations most in need of treatment across the prostate cancer disease continuum, we developed a novel dynamic transition model based on risk of disease progression and mortality. Design and Outcome Measurements We modeled the flow of patient populations through eight prostate cancer clinical states (PCCS) that are characterized by the status of the primary tumor, presence of metastases, prior and current treatment, and testosterone levels. Simulations used published US incidence rates for each year from 1990. Progression and mortality rates were derived from published clinical trials, meta-analyses, and observational studies. Model outputs included the incidence, prevalence, and mortality for each PCCS. The impact of novel treatments was modeled in three distinct scenarios: metastatic castration-resistant prostate cancer (mCRPC), non-metastatic CRPC (nmCRPC), or both. Results and Limitations The model estimated the prevalence of prostate cancer as 2,219,280 in the US in 2009 and 3,072,480 in 2020, and incidence of mCRPC as 36,100 and 42,970, respectively. All-cause mortality in prostate cancer was estimated at 168,290 in 2009 and 219,360 in 2020, with 20.5% and 19.5% of these deaths, respectively, occurring in men with mCRPC. The majority (86%) of incidence flow into mCRPC states was from the nmCRPC clinical state. In the scenario with novel interventions for nmCRPC states, the progression to mCRPC is reduced, thus decreasing mCRPC incidence by 12% in 2020, with a sustained decline in mCRPC mortality. A limitation of the model is that it does not estimate prostate cancer—specific mortality. Conclusion The model informs clinical trial design for prostate cancer by quantifying outcomes in PCCS, and demonstrates the impact of an effective therapy applied in an earlier clinical state of nmCRPC on the incidence of mCRPC morbidity and subsequent mortality. PMID:26460686

  11. Deep dysphasic performance in non-fluent progressive aphasia: a case study.

    PubMed

    Tree, J J; Perfect, T J; Hirsh, K W; Copstick, S

    2001-01-01

    We present a patient (PW) with non-fluent progressive aphasia, characterized by severe word finding difficulties and frequent phonemic paraphasias in spontaneous speech. It has been suggested that such patients have insufficient access to phonological information for output and cannot construct the appropriate sequence of selected phonemes for articulation. Consistent with such a proposal, we found that PW was impaired on a variety of verbal tasks that demand access to phonological representations (reading, repetition, confrontational naming and rhyme judgement); she also demonstrated poor performance on syntactic and grammatical processing tasks. However, examination of PW's repetition performance also revealed that she made semantic paraphasias and that her performance was influenced by imageability and lexical status. Her auditory-verbal short-term memory was also severely compromised. These features are consistent with 'deep dysphasia', a disorder reported in patients suffering from stroke or cerebrovascular accident, and rarely reported in the context of non-fluent progressive aphasia. PW's pattern of performance is evaluated in terms of current models of both non-fluent progressive aphasia and deep dysphasia.

  12. Current status of the Taiwan Photon Source project

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

    Chang, Shih-Lin

    2014-03-05

    The progress of establishment of a high brightness and low emittance mid-energy storage ring is reported. The status of the 3 GeV Taiwan Photon Source (TPS) currently under construction will be presented. The progress on the civil construction, manufacturing of machine components, as well as the opportunity of using low emittace synchrotron source and phase I beamlines at TPS will be mentioned. The future planning of phase II beamlines and related research will be sketched. Future developments will be also briefly outlined.

  13. Subseabed disposal program annual report, January-December 1980. Volume II. Appendices (principal investigator progress reports). Part 1

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

    Hinga, K.R.

    Volume II of the sixth annual report describing the progress and evaluating the status of the Subseabed Disposal Program contains the appendices referred to in Volume I, Summary and Status. Because of the length of Volume II, it has been split into two parts for publication purposes. Part 1 contains Appendices A-Q; Part 2 contains Appendices R-MM. Separate abstracts have been prepared for each appendix for inclusion in the Energy Data Base.

  14. FERMILAB ACCELERATOR R&D PROGRAM TOWARDS INTENSITY FRONTIER ACCELERATORS : STATUS AND PROGRESS

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

    Shiltsev, Vladimir

    2016-11-15

    The 2014 P5 report indicated the accelerator-based neutrino and rare decay physics research as a centrepiece of the US domestic HEP program at Fermilab. Operation, upgrade and development of the accelerators for the near- term and longer-term particle physics program at the Intensity Frontier face formidable challenges. Here we discuss key elements of the accelerator physics and technology R&D program toward future multi-MW proton accelerators and present its status and progress. INTENSITY FRONTIER ACCELERATORS

  15. Reconsidering Clinical Staging Model: A Case of Genetic High Risk for Schizophrenia.

    PubMed

    Lee, Tae Young; Kim, Minah; Kim, Sung Nyun; Kwon, Jun Soo

    2017-01-01

    The clinical staging model is considered a useful and practical method not only in dealing with the early stage of psychosis overcoming the debate about diagnostic boundaries but also in emerging mood disorder. However, its one limitation is that it cannot discriminate the heterogeneity of individuals at clinical high risk for psychosis, but lumps them all together. Even a healthy offspring of schizophrenia can eventually show clinical symptoms and progress to schizophrenia under the influence of genetic vulnerability and environmental stress even after the peak age of onset of schizophrenia. Therefore, individuals with genetic liability of schizophrenia may require a more intensive intervention than recommended by the staging model based on current clinical status.

  16. Use of Flutemetamol F 18-Labeled Positron Emission Tomography and Other Biomarkers to Assess Risk of Clinical Progression in Patients With Amnestic Mild Cognitive Impairment.

    PubMed

    Wolk, David A; Sadowsky, Carl; Safirstein, Beth; Rinne, Juha O; Duara, Ranjan; Perry, Richard; Agronin, Marc; Gamez, Jose; Shi, Jiong; Ivanoiu, Adrian; Minthon, Lennart; Walker, Zuzana; Hasselbalch, Steen; Holmes, Clive; Sabbagh, Marwan; Albert, Marilyn; Fleisher, Adam; Loughlin, Paul; Triau, Eric; Frey, Kirk; Høgh, Peter; Bozoki, Andrea; Bullock, Roger; Salmon, Eric; Farrar, Gillian; Buckley, Christopher J; Zanette, Michelle; Sherwin, Paul F; Cherubini, Andrea; Inglis, Fraser

    2018-05-14

    Patients with amnestic mild cognitive impairment (aMCI) may progress to clinical Alzheimer disease (AD), remain stable, or revert to normal. Earlier progression to AD among patients who were β-amyloid positive vs those who were β-amyloid negative has been previously observed. Current research now accepts that a combination of biomarkers could provide greater refinement in the assessment of risk for clinical progression. To evaluate the ability of flutemetamol F 18 and other biomarkers to assess the risk of progression from aMCI to probable AD. In this multicenter cohort study, from November 11, 2009, to January 16, 2014, patients with aMCI underwent positron emission tomography (PET) at baseline followed by local clinical assessments every 6 months for up to 3 years. Patients with aMCI (365 screened; 232 were eligible) were recruited from 28 clinical centers in Europe and the United States. Physicians remained strictly blinded to the results of PET, and the standard of truth was an independent clinical adjudication committee that confirmed or refuted local assessments. Flutemetamol F 18-labeled PET scans were read centrally as either negative or positive by 5 blinded readers with no knowledge of clinical status. Statistical analysis was conducted from February 19, 2014, to January 26, 2018. Flutemetamol F 18-labeled PET at baseline followed by up to 6 clinical visits every 6 months, as well as magnetic resonance imaging and multiple cognitive measures. Time from PET to probable AD or last follow-up was plotted as a Kaplan-Meier survival curve; PET scan results, age, hippocampal volume, and aMCI stage were entered into Cox proportional hazards logistic regression analyses to identify variables associated with progression to probable AD. Of 232 patients with aMCI (118 women and 114 men; mean [SD] age, 71.1 [8.6] years), 98 (42.2%) had positive results detected on PET scan. By 36 months, the rates of progression to probable AD were 36.2% overall (81 of 224 patients), 53.6% (52 of 97) for patients with positive results detected on PET scan, and 22.8% (29 of 127) for patients with negative results detected on PET scan. Hazard ratios for association with progression were 2.51 (95% CI, 1.57-3.99; P < .001) for a positive β-amyloid scan alone (primary outcome measure), 5.60 (95% CI, 3.14-9.98; P < .001) with additional low hippocampal volume, and 8.45 (95% CI, 4.40-16.24; P < .001) when poorer cognitive status was added to the model. A combination of positive results of flutemetamol F 18-labeled PET, low hippocampal volume, and cognitive status corresponded with a high probability of risk of progression from aMCI to probable AD within 36 months.

  17. GEWEX Cloud System Study (GCSS) Working Group on Cirrus Cloud Systems (WG2)

    NASA Technical Reports Server (NTRS)

    Starr, David

    2002-01-01

    Status, progress and plans will be given for current GCSS (GEWEX Cloud System Study) WG2 (Working Group on Cirrus Cloud Systems) projects, including: (a) the Idealized Cirrus Model Comparison Project, (b) the Cirrus Parcel Model Comparison Project (Phase 2), and (c) the developing Hurricane Nora extended outflow model case study project. Past results will be summarized and plans for the upcoming year described. Issues and strategies will be discussed. Prospects for developing improved cloud parameterizations derived from results of GCSS WG2 projects will be assessed. Plans for NASA's CRYSTAL-FACE (Cirrus Regional Study of Tropical Anvils and Layers - Florida Area Cirrus Experiment) potential opportunities for use of those data for WG2 model simulations (future projects) will be briefly described.

  18. Androgen receptor status is highly conserved during tumor progression of breast cancer.

    PubMed

    Grogg, André; Trippel, Mafalda; Pfaltz, Katrin; Lädrach, Claudia; Droeser, Raoul A; Cihoric, Nikola; Salhia, Bodour; Zweifel, Martin; Tapia, Coya

    2015-11-09

    With the advent of new and more efficient anti-androgen drugs targeting androgen receptor (AR) in breast cancer (BC) is becoming an increasingly important area of investigation. This would potentially be most useful in triple negative BC (TNBC), where better therapies are still needed. The assessment of AR status is generally performed on the primary tumor even if the tumor has already metastasized. Very little is known regarding discrepancies of AR status during tumor progression. To determine the prevalence of AR positivity, with emphasis on TNBCs, and to investigate AR status during tumor progression, we evaluated a large series of primary BCs and matching metastases and recurrences. AR status was performed on 356 primary BCs, 135 matching metastases, and 12 recurrences using a next-generation Tissue Microarray (ngTMA). A commercially available AR antibody was used to determine AR-status by immunohistochemistry. AR positivity was defined as any nuclear staining in tumor cells ≥1 %. AR expression was correlated with pathological tumor features of the primary tumor. Additionally, the concordance rate of AR expression between the different tumor sites was determined. AR status was positive in: 87 % (307/353) of primary tumors, 86.1 % (105/122) of metastases, and in 66.7 % (8/12) of recurrences. TNBC tested positive in 11.4 %, (4/35) of BCs. A discrepant result was seen in 4.3 % (5/117) of primary BC and matching lymph node (LN) metastases. Three AR negative primary BCs were positive in the matching LN metastasis, representing 17.6 % of all negative BCs with lymph node metastases (3/17). Two AR positive primary BCs were negative in the matching LN metastasis, representing 2.0 % of all AR positive BCs with LN metastases (2/100). No discrepancies were seen between primary BC and distant metastases or recurrence (n = 17). Most primary (87 %) and metastasized (86.1 %) BCs are AR positive including a significant fraction of TNBCs (11.4 %). Further, AR status is highly conserved during tumor progression and a change only occurs in a small fraction (4.1 %). Our study supports the notion that targeting AR could be effective for many BC patients and that re-testing of AR status in formerly negative or mixed type BC's is recommended.

  19. Projected status of the Pacific walrus (Odobenus rosmarus divergens) in the twenty-first century

    USGS Publications Warehouse

    Jay, Chadwick V.; Marcot, Bruce G.; Douglas, David C.

    2011-01-01

    Extensive and rapid losses of sea ice in the Arctic have raised conservation concerns for the Pacific walrus (Odobenus rosmarus divergens), a large pinniped inhabiting arctic and subarctic continental shelf waters of the Chukchi and Bering seas. We developed a Bayesian network model to integrate potential effects of changing environmental conditions and anthropogenic stressors on the future status of the Pacific walrus population at four periods through the twenty-first century. The model framework allowed for inclusion of various sources and levels of knowledge, and representation of structural and parameter uncertainties. Walrus outcome probabilities through the century reflected a clear trend of worsening conditions for the subspecies. From the current observation period to the end of century, the greatest change in walrus outcome probabilities was a progressive decrease in the outcome state of robust and a concomitant increase in the outcome state of vulnerable. The probabilities of rare and extirpated states each progressively increased but remained <10% through the end of the century. The summed probabilities of vulnerable, rare, and extirpated (P(v,r,e)) increased from a current level of 10% in 2004 to 22% by 2050 and 40% by 2095. The degree of uncertainty in walrus outcomes increased monotonically over future periods. In the model, sea ice habitat (particularly for summer/fall) and harvest levels had the greatest influence on future population outcomes. Other potential stressors had much smaller influences on walrus outcomes, mostly because of uncertainty in their future states and our current poor understanding of their mechanistic influence on walrus abundance.

  20. National Disability Policy: A Progress Report

    ERIC Educational Resources Information Center

    National Council on Disability, 2009

    2009-01-01

    In recent years, the National Council on Disability (NCD) Progress Report has been a retrospective review and analysis of Federal programs for people with disabilities. For this Progress Report, NCD members have chosen to depart from a retrospective approach, and, instead, will focus on the current status of the quality of life of people with…

  1. Status Update on Translation of Integrated Primary Dental-Medical Care Delivery for Management of Diabetic Patients.

    PubMed

    Glurich, Ingrid; Nycz, Gregory; Acharya, Amit

    2017-06-01

    Escalating prevalence of both diabetes and periodontal disease, two diseases associated with bi-directional exacerbation, has been reported. Periodontal disease represents a modifiable risk factor that may reduce diabetes onset or progression, and integrated models of cross-disciplinary care are needed to establish and manage glycemic control in affected patients. An ad-hoc environmental scan of current literature and media sought to characterize factors impacting status of integrated care models based on review of the existing evidence base in literature and media surrounding: (1) current cross-disciplinary practice patterns, (2) epidemiological updates, (3) status on risk assessment and screening for dysglycemia in the dental setting, (4) status on implementation of quality metrics for oral health, (5) care model pilots, and (6) public health perspectives. The survey revealed: escalating prevalence of diabetes and periodontitis globally; greater emphasis on oral health assessment for diabetic patients in recent medical clinical practice guidelines; high knowledgeability surrounding oral-systemic impacts on diabetes and growing receptivity to medical-dental integration among medical and dental providers; increasing numbers of programs/studies reporting on positive impact of emerging integrated dental-medical care models on diabetic patient healthcare access and health outcomes; a growing evidence base for clinically significant rates of undiagnosed dysglycemia among dental patients reported by point-of-care pilot studies; no current recommendation for population-based screening for dysglycemia in dental settings pending a stronger evidence base; improved definition of true periodontitis prevalence in (pre)/diabetics; emerging recognition of the need for oral health quality indicators and tracking; evidence of persistence in dental access disparity; updated status on barriers to integration. The potential benefit of creating clinically-applicable integrated care models to support holistic management of an escalating diabetic population by targeting modifiable risk factors including periodontitis is being recognized by the health industry. Cross-disciplinary efforts supported by high quality research are needed to mitigate previously- and newly-defined barriers of care integration and expedite development and implementation of integrated care models in various practice settings. Implementation of quality monitoring in the dental setting will support definition of the impact and efficacy of interventional clinical care models on patient outcomes. © 2017 Marshfield Clinic.

  2. Documentation of Assessment Instrumentation--The NORC/CRESST 12th Grade Science Assessment, Item Databases, and Test Booklets. Project 2.6: Analytic Models To Monitor Status & Progress of Learning & Performance & Their Antecedents: The School Science Assessment Project.

    ERIC Educational Resources Information Center

    Bock, H. Darrell

    The hardware and software system used to create the National Opinion Research Center/Center for Research on Evaluation, Standards, and Student Testing (NORC/CRESST) item databases and test booklets for the 12th-grade science assessment are described. A general description of the capabilities of the system is given, with some specific information…

  3. ISS Plasma Environment: Status of CCMC Products for ISS Mission Ops

    NASA Technical Reports Server (NTRS)

    Minow, Joseph

    2010-01-01

    ISS Program currently using FPMU Ne, Te in-situ measurements to support operations and anomaly investigations. Working to acquire alternative data sources if FPMU is not available. Work is progressing on CCMC tools for low Earth orbit ionosphere characterization. Validation against FPMU data required before model output can be used for ISS operational support. MSFC plans to continue comparing CTIP output during FPMU campaigns. Results to date have been useful in identifying ionospheric origins of high latitude charging environments.

  4. Physiologic Mechanisms Underlying the Failure of the Shock Index as a Tool for Accurate Assessment of Patient Status during Progressive Simulated Hemorrhage

    DTIC Science & Technology

    2013-08-01

    in central blood volume similar to hemorrhage in humans. Lower-body negative- pressure (LBNP) is a unique physiologic model that has been adopted to...relatively high tolerance (HT) to reduced blood volume, while 30% to 35% display low toler- ance (LT), with earlier onset of cardiovascular instability (i.e... pressure were recorded by infrared finger photoplethysmography (Finometer Blood Pressure Mon- itor, TNO-TPD Biomedical Instrumentation, Amsterdam

  5. The transition from managed care to consumerism: a community-level status report.

    PubMed

    Christianson, Jon B; Ginsburg, Paul B; Draper, Debra A

    2008-01-01

    This paper assesses the evolving "facilitated consumerism" model of health care at the community level using data from the Community Tracking Study (CTS). We find that in a relatively short time, large employers and health plans have made notable progress in putting the building blocks in place to support their vision of consumerism. However, developments in the CTS communities suggest that the consumerism strategy evolving in local markets is more nuanced than implied by some descriptions of health care consumerism.

  6. Recent Trends in Quantum Chemical Modeling of Enzymatic Reactions.

    PubMed

    Himo, Fahmi

    2017-05-24

    The quantum chemical cluster approach is a powerful method for investigating enzymatic reactions. Over the past two decades, a large number of highly diverse systems have been studied and a great wealth of mechanistic insight has been developed using this technique. This Perspective reviews the current status of the methodology. The latest technical developments are highlighted, and challenges are discussed. Some recent applications are presented to illustrate the capabilities and progress of this approach, and likely future directions are outlined.

  7. Resistance exercise improves muscle strength, health status and pain intensity in fibromyalgia--a randomized controlled trial.

    PubMed

    Larsson, Anette; Palstam, Annie; Löfgren, Monika; Ernberg, Malin; Bjersing, Jan; Bileviciute-Ljungar, Indre; Gerdle, Björn; Kosek, Eva; Mannerkorpi, Kaisa

    2015-06-18

    Fibromyalgia (FM) is characterized by persistent widespread pain, increased pain sensitivity and tenderness. Muscle strength in women with FM is reduced compared to healthy women. The aim of this study was to examine the effects of a progressive resistance exercise program on muscle strength, health status, and current pain intensity in women with FM. A total of 130 women with FM (age 22-64 years, symptom duration 0-35 years) were included in this assessor-blinded randomized controlled multi-center trial examining the effects of progressive resistance group exercise compared with an active control group. A person-centred model of exercise was used to support the participants' self-confidence for management of exercise because of known risks of activity-induced pain in FM. The intervention was performed twice a week for 15 weeks and was supervised by experienced physiotherapists. Primary outcome measure was isometric knee-extension force (Steve Strong®), secondary outcome measures were health status (FIQ total score), current pain intensity (VAS), 6MWT, isometric elbow-flexion force, hand-grip force, health related quality of life, pain disability, pain acceptance, fear avoidance beliefs, and patient global impression of change (PGIC). Outcomes were assessed at baseline and immediately after the intervention. Long-term follow up comprised the self-reported questionnaires only and was conducted after 13-18 months. Between-group and within-group differences were calculated using non-parametric statistics. Significant improvements were found for isometric knee-extension force (p = 0.010), health status (p = 0.038), current pain intensity (p = 0.033), 6MWT (p = 0.003), isometric elbow flexion force (p = 0.02), pain disability (p = 0.005), and pain acceptance (p = 0.043) in the resistance exercise group (n = 56) when compared to the control group (n = 49). PGIC differed significantly (p = 0.001) in favor of the resistance exercise group at post-treatment examinations. No significant differences between the resistance exercise group and the active control group were found regarding change in self-reported questionnaires from baseline to 13-18 months. Person-centered progressive resistance exercise was found to be a feasible mode of exercise for women with FM, improving muscle strength, health status, and current pain intensity when assessed immediately after the intervention. ClinicalTrials.gov identification number: NCT01226784, Oct 21, 2010.

  8. Advancing automation and robotics technology for the Space Station Freedom and for the U.S. economy. Submitted to the Congress of the U.S. May 1991

    NASA Technical Reports Server (NTRS)

    Lum, Henry, Jr.

    1991-01-01

    In April 1985, as required by Public Law 98-371, the NASA Advanced Technology Advisory Committee (ATAC) reported to Congress the results of its studies on advanced automation and robotics technology for use on Space Station Freedom. This material was documented in the initial report (NASA Technical Memorandum 87566). A further requirement of the law was that ATAC follow NASA's progress in this area and report to Congress semiannually. The report describes the progress made by Levels 1, 2 and 3 of the Office Space Station in developing and applying advanced automation and robotics technology. Emphasis has been placed upon the Space Station Freedom Program responses to specific recommendations made in ATAC Progress Report 11, the status of the Flight Telerobotic Servicer, and the status of the Advanced Development Program. In addition, an assessment is provided of the automation and robotics status of the Canadian Space Station Program.

  9. Ubiquitous Health in Korea: Progress, Barriers, and Prospects

    PubMed Central

    Lee, Yountae

    2012-01-01

    Objectives Korea has one of the most advanced information technology (IT) infrastructures in the world, and the application of IT in health systems is rapidly progressing from computerization to information systems, ubiquitous systems, and smart systems. This study aims to analyze Korean environments in regards to the development of their u-Health industry and propose directions for u-Healthcare services based on this analysis. Methods This paper reviews the background, progress history, and current status of u-Health in Korea, and suggests strategies for the u-Health industry based on an analysis of its barriers and obstacles. Results When u-Health was introduced to Koreans, their policies and approaches focused mainly on environmental factors, yet these efforts have not progressed further to impact the u-Healthcare service industry itself. To develop the u-Healthcare industry, four points need to be considered: the development and support of the practical service model, institutional support, support of core technology and industry, and the institutionalization of health management service. Conclusions Korea is at a strategic point to start building u-Healthcare service delivery models. u-Healthcare is a healthcare service that provides added value through u-Health environments. By identifying critical success factors in u-Healthcare, we can strengthen the u-Health industry and implement policies to coordinate our efforts in the process of value chains to which we belong. PMID:23346474

  10. Progress and challenges in the prevention and control of nonalcoholic fatty liver disease.

    PubMed

    Cai, Jingjing; Zhang, Xiao-Jing; Li, Hongliang

    2018-05-30

    Nonalcoholic fatty liver disease (NAFLD) is rapidly becoming the most common liver disease worldwide. Individuals with NAFLD have a high frequency of developing progressive liver disease and metabolism-related comorbidities, which result from of a lack of awareness and poor surveillance of the disease and a paucity of approved and effective therapies. Managing the complications of NAFLD has already begun to place a tremendous burden on health-care systems. Although efforts to identify effective therapies are underway, the lack of validated preclinical NAFLD models that represent the biology and outcomes of human disease remains a major barrier. This review summarizes the characteristics and prevalence of the disease and the status of our understanding of its mechanisms and potential therapeutic targets. © 2018 Wiley Periodicals, Inc.

  11. Poor preoperative nutritional status is an important predictor of the retardation of rehabilitation after cardiac surgery in elderly cardiac patients.

    PubMed

    Ogawa, Masato; Izawa, Kazuhiro P; Satomi-Kobayashi, Seimi; Kitamura, Aki; Ono, Rei; Sakai, Yoshitada; Okita, Yutaka

    2017-04-01

    Preoperative nutritional status and physical function are important predictors of mortality and morbidity after cardiac surgery. However, the influence of nutritional status before cardiac surgery on physical function and the progress of postoperative rehabilitation requires clarification. To determine the effect of preoperative nutritional status on preoperative physical function and progress of rehabilitation after elective cardiac surgery. We enrolled 131 elderly patients with mean age of 73.7 ± 5.8 years undergoing cardiac surgery. We divided them into two groups by nutritional status as measured by the Geriatric Nutritional Risk Index (GNRI): high GNRI group (GNRI ≥ 92, n = 106) and low GNRI group (GNRI < 92, n = 25). Physical function was estimated by handgrip strength, knee extensor muscle strength (KEMS), the Short Physical Performance Battery (SPPB), and 6-minute walk test (6MWT). Progress of postoperative rehabilitation was evaluated by the number of days to independent walking after surgery, length of stay in the ICU, and length of hospital stay. After adjusting for potential confounding factors, preoperative handgrip strength (P = 0.034), KEMS (P = 0.009), SPPB (P < 0.0001), and 6MWT (P = 0.012) were all significantly better in the high GNRI group. Multiple regression analysis revealed that a low GNRI was an independent predictor of the retardation of postoperative rehabilitation. Preoperative nutritional status as assessed by the GNRI could reflect perioperative physical function. Preoperative poor nutritional status may be an independent predictor of the retardation of postoperative rehabilitation in patients undergoing elective cardiac surgery.

  12. Designing HIGH-COST Medicine Hospital Surveys, Health Planning, and the Paradox of Progressive Reform

    PubMed Central

    2010-01-01

    Inspired by social medicine, some progressive US health reforms have paradoxically reinforced a business model of high-cost medical delivery that does not match social needs. In analyzing the financial status of their areas’ hospitals, for example, city-wide hospital surveys of the 1910s through 1930s sought to direct capital investments and, in so doing, control competition and markets. The 2 national health planning programs that ran from the mid-1960s to the mid-1980s continued similar strategies of economic organization and management, as did the so-called market reforms that followed. Consequently, these reforms promoted large, extremely specialized, capital-intensive institutions and systems at the expense of less complex (and less costly) primary and chronic care. The current capital crisis may expose the lack of sustainability of such a model and open up new ideas and new ways to build health care designed to meet people's health needs. PMID:20019312

  13. Examining Predictive Validity of Oral Reading Fluency Slope in Upper Elementary Grades Using Quantile Regression.

    PubMed

    Cho, Eunsoo; Capin, Philip; Roberts, Greg; Vaughn, Sharon

    2017-07-01

    Within multitiered instructional delivery models, progress monitoring is a key mechanism for determining whether a child demonstrates an adequate response to instruction. One measure commonly used to monitor the reading progress of students is oral reading fluency (ORF). This study examined the extent to which ORF slope predicts reading comprehension outcomes for fifth-grade struggling readers ( n = 102) participating in an intensive reading intervention. Quantile regression models showed that ORF slope significantly predicted performance on a sentence-level fluency and comprehension assessment, regardless of the students' reading skills, controlling for initial ORF performance. However, ORF slope was differentially predictive of a passage-level comprehension assessment based on students' reading skills when controlling for initial ORF status. Results showed that ORF explained unique variance for struggling readers whose posttest performance was at the upper quantiles at the end of the reading intervention, but slope was not a significant predictor of passage-level comprehension for students whose reading problems were the most difficult to remediate.

  14. Assessing Progress in Haiti Act of 2013

    THOMAS, 113th Congress

    Rep. Lee, Barbara [D-CA-13

    2013-11-15

    Senate - 12/13/2013 Received in the Senate and Read twice and referred to the Committee on Foreign Relations. (All Actions) Tracker: This bill has the status Passed HouseHere are the steps for Status of Legislation:

  15. Progress and New Problems Mark Your Battle Against School Asbestos.

    ERIC Educational Resources Information Center

    McCormick, Kathleen

    1985-01-01

    Reviews a survey of asbestos in the schools and the status of asbestos regulations enforcement policy. Reviews the status of asbestos litigation and recovery of abatement costs. Provides suggestions for choosing asbestos abatement contractors. (MD)

  16. Workshop on Computational Turbulence Modeling

    NASA Technical Reports Server (NTRS)

    Shabbir, A. (Compiler); Shih, T.-H. (Compiler); Povinelli, L. A. (Compiler)

    1994-01-01

    The purpose of this meeting was to discuss the current status and future development of turbulence modeling in computational fluid dynamics for aerospace propulsion systems. Various turbulence models have been developed and applied to different turbulent flows over the past several decades and it is becoming more and more urgent to assess their performance in various complex situations. In order to help users in selecting and implementing appropriate models in their engineering calculations, it is important to identify the capabilities as well as the deficiencies of these models. This also benefits turbulence modelers by permitting them to further improve upon the existing models. This workshop was designed for exchanging ideas and enhancing collaboration between different groups in the Lewis community who are using turbulence models in propulsion related CFD. In this respect this workshop will help the Lewis goal of excelling in propulsion related research. This meeting had seven sessions for presentations and one panel discussion over a period of two days. Each presentation session was assigned to one or two branches (or groups) to present their turbulence related research work. Each group was asked to address at least the following points: current status of turbulence model applications and developments in the research; progress and existing problems; and requests about turbulence modeling. The panel discussion session was designed for organizing committee members to answer management and technical questions from the audience and to make concluding remarks.

  17. The Ignition Physics Campaign on NIF: Status and Progress

    NASA Astrophysics Data System (ADS)

    Edwards, M. J.; Ignition Team

    2016-03-01

    We have made significant progress in ICF implosion performance on NIF since the 2011 IFSA. Employing a 3-shock, high adiabat CH (“High-Foot”) design, total neutron yields have increased 10-fold to 6.3 x1015 (a yield of ∼ 17 kJ, which is greater than the energy invested in the DT fuel ∼ 12kJ). At that level, the yield from alpha self-heating is essentially equivalent to the compression yield, indicating that we are close to the alpha self-heating regime. Low adiabat, 4-shock High Density Carbon (HDC) capsules have been imploded in conventional gas-filled hohlraums, and employing a 6 ns, 2-shock pulse, HDC capsules were imploded in near-vacuum hohlraums with overall coupling ∼ 98%. Both the 4- and 2-shock HDC capsules had very low mix and high yield over simulated performance. Rugby holraums have demonstrated uniform x-ray drive with minimal Cross Beam Energy Transfer (CBET), and we have made good progress in measuring and modelling growth of ablation front hydro instabilities.

  18. 3-D inelastic analysis methods for hot section components. Volume 2: Advanced special functions models

    NASA Technical Reports Server (NTRS)

    Wilson, R. B.; Banerjee, P. K.

    1987-01-01

    This Annual Status Report presents the results of work performed during the third year of the 3-D Inelastic Analysis Methods for Hot Sections Components program (NASA Contract NAS3-23697). The objective of the program is to produce a series of computer codes that permit more accurate and efficient three-dimensional analyses of selected hot section components, i.e., combustor liners, turbine blades, and turbine vanes. The computer codes embody a progression of mathematical models and are streamlined to take advantage of geometrical features, loading conditions, and forms of material response that distinguish each group of selected components.

  19. X-ray satellite

    NASA Technical Reports Server (NTRS)

    1985-01-01

    The 3rd Quarter Status Report on DFVLR's ROSAT project confirms that with regard to technical performance and costs the project is on schedule. The valid schedule for engineering model and flight model completion on May 7, 1985 leads to a launch date on October 30, 1987. Progress in each department is compared to and explained with regard to the milestone plan. Continued problems with the gold damping of the FM-mirror system and contamination of the sterile rooms where the mirrors are stored have led to postponement of milestone 7. It is not yet completely clear to what extent all successive milestones will be affected by this factor.

  20. Fine-Scale Mapping by Spatial Risk Distribution Modeling for Regional Malaria Endemicity and Its Implications under the Low-to-Moderate Transmission Setting in Western Cambodia

    PubMed Central

    Okami, Suguru; Kohtake, Naohiko

    2016-01-01

    The disease burden of malaria has decreased as malaria elimination efforts progress. The mapping approach that uses spatial risk distribution modeling needs some adjustment and reinvestigation in accordance with situational changes. Here we applied a mathematical modeling approach for standardized morbidity ratio (SMR) calculated by annual parasite incidence using routinely aggregated surveillance reports, environmental data such as remote sensing data, and non-environmental anthropogenic data to create fine-scale spatial risk distribution maps of western Cambodia. Furthermore, we incorporated a combination of containment status indicators into the model to demonstrate spatial heterogeneities of the relationship between containment status and risks. The explanatory model was fitted to estimate the SMR of each area (adjusted Pearson correlation coefficient R2 = 0.774; Akaike information criterion AIC = 149.423). A Bayesian modeling framework was applied to estimate the uncertainty of the model and cross-scale predictions. Fine-scale maps were created by the spatial interpolation of estimated SMRs at each village. Compared with geocoded case data, corresponding predicted values showed conformity [Spearman’s rank correlation r = 0.662 in the inverse distance weighed interpolation and 0.645 in ordinal kriging (95% confidence intervals of 0.414–0.827 and 0.368–0.813, respectively), Welch’s t-test; Not significant]. The proposed approach successfully explained regional malaria risks and fine-scale risk maps were created under low-to-moderate malaria transmission settings where reinvestigations of existing risk modeling approaches were needed. Moreover, different representations of simulated outcomes of containment status indicators for respective areas provided useful insights for tailored interventional planning, considering regional malaria endemicity. PMID:27415623

  1. Experiments in concept modeling for radiographic image reports.

    PubMed Central

    Bell, D S; Pattison-Gordon, E; Greenes, R A

    1994-01-01

    OBJECTIVE: Development of methods for building concept models to support structured data entry and image retrieval in chest radiography. DESIGN: An organizing model for chest-radiographic reporting was built by analyzing manually a set of natural-language chest-radiograph reports. During model building, clinician-informaticians judged alternative conceptual structures according to four criteria: content of clinically relevant detail, provision for semantic constraints, provision for canonical forms, and simplicity. The organizing model was applied in representing three sample reports in their entirety. To explore the potential for automatic model discovery, the representation of one sample report was compared with the noun phrases derived from the same report by the CLARIT natural-language processing system. RESULTS: The organizing model for chest-radiographic reporting consists of 62 concept types and 17 relations, arranged in an inheritance network. The broadest types in the model include finding, anatomic locus, procedure, attribute, and status. Diagnoses are modeled as a subtype of finding. Representing three sample reports in their entirety added 79 narrower concept types. Some CLARIT noun phrases suggested valid associations among subtypes of finding, status, and anatomic locus. CONCLUSIONS: A manual modeling process utilizing explicitly stated criteria for making modeling decisions produced an organizing model that showed consistency in early testing. A combination of top-down and bottom-up modeling was required. Natural-language processing may inform model building, but algorithms that would replace manual modeling were not discovered. Further progress in modeling will require methods for objective model evaluation and tools for formalizing the model-building process. PMID:7719807

  2. Role of levetiracetam in refractory seizures due to a rare progressive myoclonic epilepsy: Lafora body disease

    PubMed Central

    Hashmi, Mubashira; Saleem, Feroza; Mustafa, Muhammad Shahid; Sheerani, Mughis; Ehtesham, Zeeshan; Siddiqui, Khurram

    2010-01-01

    Lafora disease is one of the rare, most fatal progressive myoclonic epilepsies reported. We present a case of a teenager with intractable seizures and progressive mental decline, diagnosed as Lafora body disease on axillary skin biopsy. He was admitted with status epilepticus with refractory myoclonic and generalised tonic clonic seizures. Despite on maximum doses of multiple antiepileptic drugs and infusions of propofol and midazolam, his seizures were refractory to all forms of medical therapy tried. Levetiracetam (LEV), a pyrrolidine derivative, was introduced; he showed a prompt response and was weaned off successfully from infusions of anticonvulsants and mechanical ventilation within 48 h of introduction of LEV, followed by an almost seizure-free status. PMID:22791845

  3. Tobacco Smoking and Increased Risk of Death and Progression for Patients With p16-Positive and p16-Negative Oropharyngeal Cancer

    PubMed Central

    Gillison, Maura L.; Zhang, Qiang; Jordan, Richard; Xiao, Weihong; Westra, William H.; Trotti, Andy; Spencer, Sharon; Harris, Jonathan; Chung, Christine H.; Ang, K. Kian

    2012-01-01

    Purpose Tobacco smoking is associated with oropharynx cancer survival, but to what extent cancer progression or death increases with increasing tobacco exposure is unknown. Patients and Methods Patients with oropharynx cancer enrolled onto a phase III trial of radiotherapy from 1991 to 1997 (Radiation Therapy Oncology Group [RTOG] 9003) or of chemoradiotherapy from 2002 to 2005 (RTOG 0129) were evaluated for tumor human papillomavirus status by a surrogate, p16 immunohistochemistry, and for tobacco exposure by a standardized questionnaire. Associations between tobacco exposure and overall survival (OS) and progression-free survival (PFS) were estimated by Cox proportional hazards models. Results Prevalence of p16-positive cancer was 39.5% among patients in RTOG 9003 and 68.0% in RTOG 0129. Median pack-years of tobacco smoking were lower among p16-positive than p16-negative patients in both trials (RTOG 9003: 29 v 45.9 pack-years; P = .02; RTOG 0129: 10 v 40 pack-years; P < .001). After adjustment for p16 and other factors, risk of progression (PFS) or death (OS) increased by 1% per pack-year (for both, hazard ratio [HR], 1.01; 95% CI, 1.00 to 1.01; P = .002) or 2% per year of smoking (for both, HR, 1.02; 95% CI, 1.01 to 1.03; P < .001) in both trials. In RTOG 9003, risk of death doubled (HR, 2.19; 95% CI, 1.46 to 3.28) among those who smoked during radiotherapy after accounting for pack-years and other factors, and risk of second primary tumors increased by 1.5% per pack-year (HR, 1.015; 95% CI, 1.005 to 1.026). Conclusion Risk of oropharyngeal cancer progression and death increases directly as a function of tobacco exposure at diagnosis and during therapy and is independent of tumor p16 status and treatment. PMID:22565003

  4. Psychosocial Factors Are Associated With Blood Pressure Progression Among African Americans in the Jackson Heart Study.

    PubMed

    Ford, Cassandra D; Sims, Mario; Higginbotham, John C; Crowther, Martha R; Wyatt, Sharon B; Musani, Solomon K; Payne, Thomas J; Fox, Ervin R; Parton, Jason M

    2016-08-01

    Research that examines the associations of psychosocial factors with incident hypertension among African Americans (AA) is limited. Using Jackson Heart Study (JHS) data, we examined associations of negative affect and stress with incident hypertension and blood pressure (BP) progression among AA. Our sample consisted of 1,656 normotensive participants at baseline (2000-2004) (mean age 47±12; 61% women). We investigated associations of negative affect (cynical distrust, anger-in, anger-out, and depressive symptoms) and stress (perceived stress, weekly stress inventory (WSI)-event, WSI-impact, and major life events) with BP progression (an increase by one BP stage as defined by JNC VII) and incident hypertension by examination 2 (2005-2008). Poisson regression analysis was utilized to examine the prevalence ratios (PRs; 95% confidence interval (CI)) of BP tracking and incident hypertension with psychosocial factors, adjusting for baseline age, sex, socioeconomic status (SES), and hypertension risk factors. Fifty-six percentage of the sample (922 cases) had BP progression from 2005 to 2008. After adjustment for age, sex, and SES, a high anger-out score was associated with a 20% increased risk of BP progression compared to a low anger-out score (PR 1.20; 95% CI 1.05-1.36). High depressive symptoms score was associated with BP progression in the age, sex, and SES-adjusted model (PR 1.14; 95% CI 1.00-1.30). High WSI-event scores were associated with BP progression in the fully adjusted model (PR 1.21; 95% CI 1.04-1.40). We did not observe significant associations with any of the psychosocial measures and incident hypertension. Psychosocial factors were associated with BP progression, with the strongest evidence for number of stressful events that occurred. © American Journal of Hypertension, Ltd 2016. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  5. Absence of IDH1-R132H mutation predicts rapid progression of nonenhancing diffuse glioma in older adults.

    PubMed

    Olar, Adriana; Raghunathan, Aditya; Albarracin, Constance T; Aldape, Kenneth D; Cahill, Daniel P; Powell, Suzanne Z; Goodman, J Clay; Fuller, Gregory N

    2012-06-01

    Advanced age and contrast enhancement portend a poor prognosis in diffuse glioma (DG). Diffuse glioma may present as nonenhancing tumors that rapidly progress in weeks to months to a pattern of ring enhancement, characteristic of glioblastoma (GBM). Mutations involving isocitrate dehydrogenase 1 (IDH1) have recently emerged as important diagnostic and prognostic markers in DG. R132H is the most common mutation, expressed in more than 80% of DG and secondary GBM but in less than 10% of primary GBM. Adults older than 50 years with nonenhancing, rapidly progressing DG were identified. A comparison group comprised randomly selected, age-matched patients with nonenhancing, nonprogressing DG. Isocitrate dehydrogenase 1 status was evaluated using anti-IDH1-R132H antibodies (Dianova, Hamburg, Germany). The results were correlated with the clinical outcomes. We identified 4 patients who presented with nonenhancing DG that rapidly progressed to ring-enhancing lesions that were subsequently diagnosed on surgical resection as GBM. This group showed absent IDH1-R132H expression, which is characteristic of primary GBM. The comparison group of 5 patients presented with nonenhancing, nonprogressing DG, and all 5 tumors showed IDH1-R132H expression. In conclusion, negative IDH1-R132H mutation status in nonenhancing DG of older adults is a poor prognostic factor associated with rapid progression to ring-enhancing GBM. The shorter interval of progression and negative IDH1-R132H mutation status suggest a similar molecular pathway as seen in primary GBM. Copyright © 2012 Elsevier Inc. All rights reserved.

  6. Age dependent mortality in the pilocarpine model of status epilepticus

    PubMed Central

    Blair, Robert E.; Deshpande, Laxmikant S.; Holbert, William H.; Churn, Severn B.; DeLorenzo, Robert J.

    2010-01-01

    Status epilepticus (SE) is an acute neurological emergency associated with significant morbidity and mortality. Age has been shown to be a critical factor in determining outcome after SE. Understanding the causes of this increased mortality with aging by developing an animal model to study this condition would play a major role in studying mechanisms to limit the mortality due to SE. Here we employed pilocarpine to induce SE in rats aged between 5 to 28 weeks. Similar to clinical studies in man, we observed that age was a significant predictor of mortality following SE. While no deaths were observed in 5-week old animals, mortality due to SE increased progressively with age and reached 90% in 28-week old animals. There was no correlation between the age of animals and severity of SE. With increasing age mortality occurred earlier after the onset of SE. These results indicate that pilocarpine-induced SE in the rat provides a useful model to study age-dependent SE-induced mortality and indicates the importance of using animal models to elucidate the mechanisms contributing to SE-induced mortality and the development of novel therapeutic interventions to prevent SE-induced death. PMID:19429042

  7. Age-dependent mortality in the pilocarpine model of status epilepticus.

    PubMed

    Blair, Robert E; Deshpande, Laxmikant S; Holbert, William H; Churn, Severn B; DeLorenzo, Robert J

    2009-04-10

    Status epilepticus (SE) is an acute neurological emergency associated with significant morbidity and mortality. Age has been shown to be a critical factor in determining outcome after SE. Understanding the causes of this increased mortality with aging by developing an animal model to study this condition would play a major role in studying mechanisms to limit the mortality due to SE. Here we employed pilocarpine to induce SE in rats aged between 5 and 28 weeks. Similar to clinical studies in man, we observed that age was a significant predictor of mortality following SE. While no deaths were observed in 5-week-old animals, mortality due to SE increased progressively with age and reached 90% in 28-week-old animals. There was no correlation between the age of animals and severity of SE. With increasing age mortality occurred earlier after the onset of SE. These results indicate that pilocarpine-induced SE in the rat provides a useful model to study age-dependent SE-induced mortality and indicates the importance of using animal models to elucidate the mechanisms contributing to SE-induced mortality and the development of novel therapeutic interventions to prevent SE-induced death.

  8. A Work of Justice and Progress. The Story of the UNESCO/ILO 1966 Recommendation Concerning the Status of Teachers.

    ERIC Educational Resources Information Center

    Towsley, Lona

    The paper presents a history of the 1966 United Nations Educational, Scientific, and Cultural Organisation (UNESCO)/International Labour Organisation (ILO) recommendation concerning the status of teachers. It spans the years 1945-1966, explaining how the recommendation evolved into the present text designed to improve teacher status and working…

  9. Assessment of Food Chain Pathway Parameters in Biosphere Models: Annual Progress Report for Fiscal Year 2004

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

    Napier, Bruce A.; Krupka, Kenneth M.; Fellows, Robert J.

    2004-12-02

    This Annual Progress Report describes the work performed and summarizes some of the key observations to date on the U.S. Nuclear Regulatory Commission’s project Assessment of Food Chain Pathway Parameters in Biosphere Models, which was established to assess and evaluate a number of key parameters used in the food-chain models used in performance assessments of radioactive waste disposal facilities. Section 2 of this report describes activities undertaken to collect samples of soils from three regions of the United States, the Southeast, Northwest, and Southwest, and perform analyses to characterize their physical and chemical properties. Section 3 summarizes information gathered regardingmore » agricultural practices and common and unusual crops grown in each of these three areas. Section 4 describes progress in studying radionuclide uptake in several representative crops from the three soil types in controlled laboratory conditions. Section 5 describes a range of international coordination activities undertaken by Project staff in order to support the underlying data needs of the Project. Section 6 provides a very brief summary of the status of the GENII Version 2 computer program, which is a “client” of the types of data being generated by the Project, and for which the Project will be providing training to the US NRC staff in the coming Fiscal Year. Several appendices provide additional supporting information.« less

  10. Developing and Validating a Predictive Model for Stroke Progression

    PubMed Central

    Craig, L.E.; Wu, O.; Gilmour, H.; Barber, M.; Langhorne, P.

    2011-01-01

    Background Progression is believed to be a common and important complication in acute stroke, and has been associated with increased mortality and morbidity. Reliable identification of predictors of early neurological deterioration could potentially benefit routine clinical care. The aim of this study was to identify predictors of early stroke progression using two independent patient cohorts. Methods Two patient cohorts were used for this study – the first cohort formed the training data set, which included consecutive patients admitted to an urban teaching hospital between 2000 and 2002, and the second cohort formed the test data set, which included patients admitted to the same hospital between 2003 and 2004. A standard definition of stroke progression was used. The first cohort (n = 863) was used to develop the model. Variables that were statistically significant (p < 0.1) on univariate analysis were included in the multivariate model. Logistic regression was the technique employed using backward stepwise regression to drop the least significant variables (p > 0.1) in turn. The second cohort (n = 216) was used to test the performance of the model. The performance of the predictive model was assessed in terms of both calibration and discrimination. Multiple imputation methods were used for dealing with the missing values. Results Variables shown to be significant predictors of stroke progression were conscious level, history of coronary heart disease, presence of hyperosmolarity, CT lesion, living alone on admission, Oxfordshire Community Stroke Project classification, presence of pyrexia and smoking status. The model appears to have reasonable discriminative properties [the median receiver-operating characteristic curve value was 0.72 (range 0.72–0.73)] and to fit well with the observed data, which is indicated by the high goodness-of-fit p value [the median p value from the Hosmer-Lemeshow test was 0.90 (range 0.50–0.92)]. Conclusion The predictive model developed in this study contains variables that can be easily collected in practice therefore increasing its usability in clinical practice. Using this analysis approach, the discrimination and calibration of the predictive model appear sufficiently high to provide accurate predictions. This study also offers some discussion around the validation of predictive models for wider use in clinical practice. PMID:22566988

  11. The impact of menopause on functional status in women with rheumatoid arthritis.

    PubMed

    Mollard, Elizabeth; Pedro, Sofia; Chakravarty, Eliza; Clowse, Megan; Schumacher, Rebecca; Michaud, Kaleb

    2018-05-01

    The aim of this study was to investigate the association of menopause with functional status outcomes in women with RA. Participants were women in a US-wide observational cohort who developed RA before menopause. The HAQ measured functional status. We controlled for confounding variables and used univariate and multivariable generalized estimating equation methods with the sandwich estimator of variance. Best models were selected using the quasi-likelihood under the independence model criterion. A sensitivity analysis was performed using linear mixed effects regression models. A total of 8189 women were eligible. Of these, 2005 (24.5%) were pre-menopausal, 611 (7.5%) transitioned through menopause during the study, and 5573 (68.1%) were post-menopausal. Within each respective group, the mean (s.d.) ages were 39.7 (7.8), 50.7 (3.4) and 62.3 (9.3) years. Our results showed that women who were pre-menopausal had less functional decline as measured by the HAQ compared with women who were post-menopausal; these results were robust and strong even after adjustment for other significant factors. The ever-use of hormonal replacement therapy, ever having a pregnancy, and longer length of reproductive life were associated with less functional decline. After menopause, the trajectory of functional decline worsened and accelerated in women with RA. The results suggest that menopausal status is associated with functional decline in women with RA. Furthermore, menopause is associated with a worsening progression of functional decline. These data indicate that menopause has a significant impact on the level and rate of functional decline in women with RA.

  12. Implementing the Institute of Medicine definition of disparities: an application to mental health care.

    PubMed

    McGuire, Thomas G; Alegria, Margarita; Cook, Benjamin L; Wells, Kenneth B; Zaslavsky, Alan M

    2006-10-01

    In a recent report, the Institute of Medicine (IOM) defines a health service disparity between population groups to be the difference in treatment or access not justified by the differences in health status or preferences of the groups. This paper proposes an implementation of this definition, and applies it to disparities in outpatient mental health care. Health Care for Communities (HCC) reinterviewed 9,585 respondents from the Community Tracking Study in 1997-1998, oversampling individuals with psychological distress, alcohol abuse, drug abuse, or mental health treatment. The HCC is designed to make national estimates of service use. Expenditures are modeled using generalized linear models with a log link for quantity and a probit model for any utilization. We adjust for group differences in health status by transforming the entire distribution of health status for minority populations to approximate the white distribution. We compare disparities according to the IOM definition to other methods commonly used to assess health services disparities. Our method finds significant service disparities between whites and both blacks and Latinos. Estimated disparities from this method exceed those for competing approaches, because of the inclusion of effects of mediating factors (such as income) in the IOM approach. A rigorous definition of disparities is needed to monitor progress against disparities and to compare their magnitude across studies. With such a definition, disparities can be estimated by adjusting for group differences in models for expenditures and access to mental health services.

  13. Cognition, academic achievement, and epilepsy in school-age children: a case-control study in a developing country.

    PubMed

    Melbourne Chambers, R; Morrison-Levy, N; Chang, S; Tapper, J; Walker, S; Tulloch-Reid, M

    2014-04-01

    We conducted a case-control study of 33 Jamaican children 7 to 12years old with uncomplicated epilepsy and 33 of their classroom peers matched for age and gender to determine whether epilepsy resulted in differences in cognitive ability and school achievement and if socioeconomic status or the environment had a moderating effect on any differences. Intelligence, language, memory, attention, executive function, and mathematics ability were assessed using selected tests from NEPSY, WISCR, TeaCh, WRAT3 - expanded, and Raven's Coloured Progressive Matrices. The child's environment at home was measured using the Middle Childhood HOME inventory. Socioeconomic status was determined from a combination of household, crowding, possessions, and sanitation. We compared the characteristics of the cases and controls and used random effects regression models (using the matched pair as the cluster) to examine the relationship between cognition and epilepsy. We found that there was no significant difference in IQ, but children with epilepsy had lower scores on tests of memory (p<0.05), language (p<0.05), and attention (p<0.01) compared with their controls. In random effects models, epilepsy status had a significant effect on memory (coefficient=-0.14, CI: -0.23, -0.05), language (coefficient=-0.13, CI: -0.23, -0.04), and mathematics ability (coefficient=-0.01, CI: -0.02, -0.00). Adjustment for the home environment and socioeconomic status and inclusion of interaction terms for these variables did not alter these effects. In conclusion, we found that epilepsy status in Jamaican children has a significant effect on performance on tests of memory, language, and mathematics and that this effect is not modified or explained by socioeconomic status or the child's home environment. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Early Cerebral Blood Volume Changes Predict Progression After Convection-Enhanced Delivery of Topotecan for Recurrent Malignant Glioma.

    PubMed

    Surapaneni, Krishna; Kennedy, Benjamin C; Yanagihara, Ted K; DeLaPaz, Robert; Bruce, Jeffrey N

    2015-07-01

    To assess whether early changes in enhancing tumor volume (eTV) and relative cerebral blood volume (rCBV) 1 month after convection-enhanced delivery of topotecan in patients with recurrent malignant glioma correlated with 6-month disease progression status. Sixteen patients were enrolled in a Phase Ib trial of convection-enhanced delivery of topotecan for recurrent malignant glioma. Each patient was evaluated with serial follow-up magnetic resonance imaging at baseline and at 4- to 8-week intervals. Changes at 1 month compared with baseline in eTV and rCBV were evaluated as potential predictors of 6-month progression status, classified as either progressive disease or nonprogressive disease. Relationships between percent changes in eTV and rCBV at 1 month with the probability of progressive disease at 6 months were estimated by the use of logistic regression analysis. Receiver operating characteristic curves for varying percent change thresholds in eTV and rCBV were evaluated by the use of 6-month progressive disease as the reference. There was a significant difference in the percent change in rCBV at 1 month in patients with progressive disease compared with those with nonprogressive disease at 6 months (+12% vs. -29%, P = 0.02). Logistic regression analysis demonstrated on average that a 10% increase in rCBV at 1 month after convection-enhanced delivery of topotecan was associated with 1.7 times the odds of developing progressive disease at 6 months (95% confidence interval [CI] 1.0-2.9 P = 0.05). Receiver operating characteristic analysis for determining progressive disease at 6 months showed a greater area under the curve with rCBV (0.867; 95% CI 0.66-1.00) than with change in enhancing tumor volume (0.767; 95% CI 0.51-1.00). In this selected population of patients with recurrent malignant glioma treated with convection-enhanced delivery of topotecan, early changes in rCBV at 4 weeks after therapy may help predict progression status at 6 months. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. From cancer genomes to cancer models: bridging the gaps

    PubMed Central

    Baudot, Anaïs; Real, Francisco X.; Izarzugaza, José M. G.; Valencia, Alfonso

    2009-01-01

    Cancer genome projects are now being expanded in an attempt to provide complete landscapes of the mutations that exist in tumours. Although the importance of cataloguing genome variations is well recognized, there are obvious difficulties in bridging the gaps between high-throughput resequencing information and the molecular mechanisms of cancer evolution. Here, we describe the current status of the high-throughput genomic technologies, and the current limitations of the associated computational analysis and experimental validation of cancer genetic variants. We emphasize how the current cancer-evolution models will be influenced by the high-throughput approaches, in particular through efforts devoted to monitoring tumour progression, and how, in turn, the integration of data and models will be translated into mechanistic knowledge and clinical applications. PMID:19305388

  16. On 3-D inelastic analysis methods for hot section components. Volume 1: Special finite element models

    NASA Technical Reports Server (NTRS)

    Nakazawa, S.

    1988-01-01

    This annual status report presents the results of work performed during the fourth year of the 3-D Inelastic Analysis Methods for Hot Section Components program (NASA Contract NAS3-23697). The objective of the program is to produce a series of new computer codes permitting more accurate and efficient 3-D analysis of selected hot section components, i.e., combustor liners, turbine blades and turbine vanes. The computer codes embody a progression of math models and are streamlined to take advantage of geometrical features, loading conditions, and forms of material response that distinguish each group of selected components. Volume 1 of this report discusses the special finite element models developed during the fourth year of the contract.

  17. Nutritional Status is Associated with Faster Cognitive Decline and Worse Functional Impairment in the Progression of Dementia: The Cache County Dementia Progression Study1

    PubMed Central

    Sanders, Chelsea; Behrens, Stephanie; Schwartz, Sarah; Wengreen, Heidi; Corcoran, Chris D.; Lyketsos, Constantine G.; Tschanz, JoAnn T.

    2017-01-01

    Nutritional status may be a modifiable factor in the progression of dementia. We examined the association of nutritional status and rate of cognitive and functional decline in a U.S. population-based sample. Study design was an observational longitudinal study with annual follow-ups up to 6 years of 292 persons with dementia (72% Alzheimer’s disease, 56% female) in Cache County, UT using the Mini-Mental State Exam (MMSE), Clinical Dementia Rating Sum of Boxes (CDR-sb), and modified Mini Nutritional Assessment (mMNA). mMNA scores declined by approximately 0.50 points/year, suggesting increasing risk for malnutrition. Lower mMNA score predicted faster rate of decline on the MMSE at earlier follow-up times, but slower decline at later follow-up times, whereas higher mMNA scores had the opposite pattern (mMNA by time β = 0.22, p = 0.017; mMNA by time2 β = −0.04, p = 0.04). Lower mMNA score was associated with greater impairment on the CDR-sb over the course of dementia (β = 0.35, p < 0.001). Assessment of malnutrition may be useful in predicting rates of progression in dementia and may provide a target for clinical intervention. PMID:26967207

  18. Nutritional Status is Associated with Faster Cognitive Decline and Worse Functional Impairment in the Progression of Dementia: The Cache County Dementia Progression Study1.

    PubMed

    Sanders, Chelsea; Behrens, Stephanie; Schwartz, Sarah; Wengreen, Heidi; Corcoran, Chris D; Lyketsos, Constantine G; Tschanz, JoAnn T

    2016-02-27

    Nutritional status may be a modifiable factor in the progression of dementia. We examined the association of nutritional status and rate of cognitive and functional decline in a U.S. population-based sample. Study design was an observational longitudinal study with annual follow-ups up to 6 years of 292 persons with dementia (72% Alzheimer's disease, 56% female) in Cache County, UT using the Mini-Mental State Exam (MMSE), Clinical Dementia Rating Sum of Boxes (CDR-sb), and modified Mini Nutritional Assessment (mMNA). mMNA scores declined by approximately 0.50 points/year, suggesting increasing risk for malnutrition. Lower mMNA score predicted faster rate of decline on the MMSE at earlier follow-up times, but slower decline at later follow-up times, whereas higher mMNA scores had the opposite pattern (mMNA by time β= 0.22, p = 0.017; mMNA by time2 β= -0.04, p = 0.04). Lower mMNA score was associated with greater impairment on the CDR-sb over the course of dementia (β= 0.35, p <  0.001). Assessment of malnutrition may be useful in predicting rates of progression in dementia and may provide a target for clinical intervention.

  19. HPV status and favourable outcome in vulvar squamous cancer.

    PubMed

    Wakeham, Katie; Kavanagh, Kim; Cuschieri, Kate; Millan, David; Pollock, Kevin G; Bell, Sarah; Burton, Kevin; Reed, Nicholas S; Graham, Sheila V

    2017-03-01

    It is universally accepted that high-risk human papillomavirus (HR-HPV) is the cause of cervical dysplasia and cancer. More recently, it has been shown that HPV is also a marker of clinical outcome in oropharyngeal cancer. However, contemporary information is lacking on both the prevalence of HPV infection in vulvar cancer (VSCC), its precursor lesion, vulvar intraepithelial neoplasia (VIN) and the influence of HPV-status on the prognosis of this malignancy. We have conducted a detailed population-based study to examine rates of progression of VIN to VSCC, type-specific HPV prevalence in vulvar disease and the influence of HPV status on clinical outcome in VSCC. We observed that the age at which women are diagnosed with VSCC is falling and there is a significant time gap between first diagnosis of VIN and progression to invasive disease. HR-HPV infection was detected in 87% (97/112) cases of VIN and 52% cases (32/62) of VSCC. The presence of HR-HPV in squamous intraepithelial lesion was associated with lower rates of progression to invasive cancer (hazard ratio, 0.22, p = 0.001). In the adjusted analysis, HR-HPV was associated with improved progression-free survival of VSCC compared to those with HPV negative tumours (hazard ratio, 0.32, p = 0.02). © 2016 UICC.

  20. SF Bay Delta TMDL Progress Assessment

    EPA Pesticide Factsheets

    EPA assessed the progress 14 TMDLs in the SF Bay Delta Estuary (SF Bay Delta) to determine if the actions called for in the TMDL were being accomplished and water quality was improving. Status and water quality reports can be found here.

  1. 78 FR 24750 - Scientific Information Request Therapies for Clinically Localized Prostate Cancer

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-26

    ... and benefits of the following therapies for clinically localized prostate cancer? a. Radical... prostate cancer: radical prostatectomy (including retropubic, perineal, laparoscopic, robotic-assisted..., biochemical (PSA) progression, metastatic and/or clinical progression-free survival, health status, and...

  2. Contemporary rates and predictors of fast progression of chronic kidney disease in adults with and without diabetes mellitus.

    PubMed

    Go, Alan S; Yang, Jingrong; Tan, Thida C; Cabrera, Claudia S; Stefansson, Bergur V; Greasley, Peter J; Ordonez, Juan D

    2018-06-22

    Chronic kidney disease (CKD) is highly prevalent but identification of patients at high risk for fast CKD progression before reaching end-stage renal disease in the short-term has been challenging. Whether factors associated with fast progression vary by diabetes status is also not well understood. We examined a large community-based cohort of adults with CKD to identify predictors of fast progression during the first 2 years of follow-up in the presence or absence of diabetes mellitus. Within a large integrated healthcare delivery system in northern California, we identified adults with estimated glomerular filtration rate (eGFR) 30-59 ml/min/1.73 m 2 by CKD-EPI equation between 2008 and 2010 who had no previous dialysis or renal transplant, who had outpatient serum creatinine values spaced 10-14 months apart and who did not initiate renal replacement therapy, die or disenroll during the first 2 years of follow-up. Through 2012, we calculated the annual rate of change in eGFR and classified patients as fast progressors if they lost > 4 ml/min/1.73 m 2 per year. We used multivariable logistic regression to identify patient characteristics that were independently associated with fast CKD progression stratified by diabetes status. We identified 36,195 eligible adults with eGFR 30-59 ml/min/1.73 m 2 and mean age 73 years, 55% women, 11% black, 12% Asian/Pacific Islander and 36% with diabetes mellitus. During 24-month follow-up, fast progression of CKD occurred in 23.0% of patients with diabetes vs. 15.3% of patients without diabetes. Multivariable predictors of fast CKD progression that were similar by diabetes status included proteinuria, age ≥ 80 years, heart failure, anemia and higher systolic blood pressure. Age 70-79 years, prior ischemic stroke, current or former smoking and lower HDL cholesterol level were also predictive in patients without diabetes, while age 18-49 years was additionally predictive in those with diabetes. In a large, contemporary population of adults with eGFR 30-59 ml/min/1.73 m 2 , accelerated progression of kidney dysfunction within 2 years affected ~ 1 in 4 patients with diabetes and ~ 1 in 7 without diabetes. Regardless of diabetes status, the strongest independent predictors of fast CKD progression included proteinuria, elevated systolic blood pressure, heart failure and anemia.

  3. The influence of gender and hormone status on the severity and progression of keratoconus.

    PubMed

    Fink, Barbara A; Sinnott, Loraine T; Wagner, Heidi; Friedman, Chad; Zadnik, Karla

    2010-01-01

    To assess the effects of gender and hormone status on the severity and progression of keratoconus in patients enrolled in the Collaborative Longitudinal Evaluation of Keratoconus Study. The severity and progression of keratoconus in both men (M) and women were evaluated over a 4-year period that encompassed menopausal transition for hormone-active women (HA) and hormone-inactive women (HI). Four outcome measures were selected as indicators of the severity of keratoconus: high-contrast best-corrected visual acuity, low-contrast best-corrected visual acuity, the steep keratometric measurement, and corneal scarring (yes/no). There were no statistically significant differences among the 3 groups (M, HA, and HI) in race, history of atopic disease, family history of keratoconus, or rigid contact lens wear in the right and left eyes. At baseline, there were no significant differences among the 3 groups in high-contrast best-corrected visual acuity, low-contrast best-corrected visual acuity, or steep keratometric reading. Progression of keratoconus, as assessed by changes in these 3 continuous variables, was equal for the 3 groups. M had more corneal scarring than did HA or HI; however, there was no progression of scarring for any of the groups. Keratoconus progressed in both men and women, aged 48-59 years; however, there were no differences among the groups in progression.

  4. Continuous DC-CIK infusions restore CD8+ cellular immunity, physical activity and improve clinical efficacy in advanced cancer patients unresponsive to conventional treatments.

    PubMed

    Zhao, Yan-Jie; Jiang, Ni; Song, Qing-Kun; Wu, Jiang-Ping; Song, Yu-Guang; Zhang, Hong-Mei; Chen, Feng; Zhou, Lei; Wang, Xiao-Li; Zhou, Xin-Na; Yang, Hua-Bing; Ren, Jun; Lyerly, Herbert Kim

    2015-01-01

    There are few choices for treatment of advanced cancer patients who do not respond to or tolerate conventional anti-cancer treatments. Therefore this study aimed to deploy the benefits and clinical efficacy of continuous dendritic cell-cytokine induced killer cell infusions in such patients. A total of 381 infusions (from 67 advanced cases recruited) were included in this study. All patients underwent peripheral blood mononuclear cell apheresis for the following cellular therapy and dendritic cells-cytokine induced killer cells were expanded in vitro. Peripheral blood T lymphocyte subsets were quantified through flow cytometry to address the cellular immunity status. Clinical efficacy and physical activities were evaluated by RECIST criteria and Eastern Cooperative Oncology Group scores respectively. Logistic regression model was used to estimate the association between cellular infusions and clinical benefits. An average of 5.7±2.94x10(9) induced cells were infused each time and patients were exposed to 6 infusions. Cellular immunity was improved in that cytotoxic CD8+CD28+T lymphocytes were increased by 74% and suppressive CD8+CD28-T lymphocytes were elevated by 16% (p<0.05). Continuous infusion of dendritic cells-cytokine induced killer cells was associated with improvement of both patient status and cellular immunity. A median of six infusions were capable of reducing risk of progression by 70% (95%CI 0.10-0.91). Every elevation of one ECOG score corresponded to a 3.90-fold higher progression risk (p<0.05) and 1% increase of CD8+CD28- T cell proportion reflecting a 5% higher risk of progression (p<0.05). In advanced cancer patients, continuous dendritic cell-cytokine induced killer cell infusions are capable of recovering cellular immunity, improving patient status and quality of life in those who are unresponsive to conventional cancer treatment.

  5. Predicting Handwriting Difficulties Through Spelling Processes.

    PubMed

    Rodríguez, Cristina; Villarroel, Rebeca

    This study examined whether spelling tasks contribute to the prediction of the handwriting status of children with poor and good handwriting skills in a cross-sectional study with 276 Spanish children from Grades 1 and 3. The main hypothesis was that the spelling tasks would predict the handwriting status of the children, although this influence would decrease with age due to a gradual automatization of handwriting skills. The results confirmed this hypothesis. Another interesting result was that the pattern of pseudoword and irregular word spellings as predictors of handwriting status changed from Grade 1 to Grade 3. In Grade 1, the pseudoword spelling task made a significant contribution, whereas the irregular word spelling task did not. The opposite pattern was found in Grade 3. These results may be a consequence of progressive acquisition of orthographic representations. The orthographic role of the task of writing the alphabet in order from memory in the prediction model was also analyzed. The writing of the alphabet in order from memory task made a significant contribution to the prediction of handwriting status of the children beyond the orthographic influence of spelling tasks. The additional effect of this task on the prediction of handwriting status is presumably due to the fact that this measure is based on fluency.

  6. Ageing, health status and coverage rate effects on community prescription costs in Ireland.

    PubMed

    Kenneally, Martin; Lynch, Brenda

    2018-06-01

    This paper aims to explore how GMS drug costs depend on age, gender, income, health status, community drug scheme coverage rates and whether they display significant differences across regions of Ireland. We also aim to find out whether the GMS drug costs of high and low income cohorts respond similarly to changes in their health status. The paper projects GMS drug costs in 2026 and examines the separate cost of population ageing and population growth over the period. We also aim to simulate the estimated model to show how much giving free prescription drugs to all persons aged 'under 5' would add to 2026 GMS drug costs, and also how much giving universal GMS coverage to all persons in 2026 would add to 2026 GMS drug costs. We construct a multivariate logistic regression model of GMS community drug costs in Ireland. We progress the methodology used in earlier studies by explicitly modelling how regional incomes and regional health status interact in determining GMS drug costs in Ireland. An age cohort and region breakdown of the simulated GMS drug costs, of both projected demographic trends and public policy measures that have been adopted or are under consideration, are also investigated. We find that GMS drug costs depend on age-but not gender-on income, health status, community drug scheme coverage rates, and they are significantly lower for all age cohorts in Donegal and the North West region. The GMS drug costs of high income cohorts tend to increase as their health status improves, whereas they tend to decrease as the health status of low income cohorts improves. A uniform 1% gain in health status has little impact on total GMS prescribing costs. Similarly, if the health status of all Irish regions improved to match that of the East region in 2010 it would only have reduced public prescription costs by around 32 € million of the 1.8 € billion GMS drugs bill. We find that giving free prescription drugs to all persons aged 'under 5' in 2010 would have only a minor impact on 2010 GMS drug costs, whereas giving universal GMS coverage to all persons would have doubled public prescription costs from 1.8 € billion to circa 3.6 € billion.

  7. Astronomical Data Center Bulletin, volume 1, no. 1

    NASA Technical Reports Server (NTRS)

    Warren, W. H., Jr. (Editor); Nagy, T. A. (Editor); Mead, J. M. (Editor)

    1980-01-01

    Information about work in progress on astronomical catalogs is presented. In addition to progress reports, an upadated status list for astronomical catalogs available at the Astronomical Data Center is included. Papers from observatories and individuals involved with astronomical data are also presented.

  8. Assessing Progress in Haiti Act

    THOMAS, 113th Congress

    Rep. Lee, Barbara [D-CA-13

    2013-04-25

    House - 06/07/2013 Referred to the Subcommittee on the Western Hemisphere. (All Actions) Notes: For further action, see S.1104, which became Public Law 113-162 on 8/8/2014. Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

  9. Report: EPA’s Management of Interim Status Permitting Needs Improvement to Ensure Continued Progress

    EPA Pesticide Factsheets

    Report #2007-P-00005, December 4, 2006. Interim status is a temporary designation, but some units have existed for as many as 25 years without formal issuance or denial of a permit, or other regulatory controls.

  10. Labour participation of people living with HIV/AIDS in Spain.

    PubMed

    Oliva, Juan

    2010-04-01

    This study explores the relationship between the employment status of human immunodeficiency virus (HIV)-positive individuals and socioeconomic and health characteristics in Spain. Data were obtained from four waves of the HIV/AIDS Hospital Survey from the period 2001 to 2004. The sample was composed of 3376 individuals between 16 and 64 years. Assessment of employment participation was performed using a probit model on a wide range of socioeconomic and lifestyle-related variables. The main variables explaining the probability of participation in the labour market were age, gender, education level, CD4 cell count, health status, time since HIV diagnosis, psychological impact of contracting the disease or its progression, the most likely means of transmission and intravenous drug use (IDU). The significance of each of these variables differs for men and women as well as for injecting drug users (IDUs) and non-IDUs. The employment status of HIV-positive individuals is directly related to their health status and other personal characteristics. Policies to improve the well-being of HIV-positive individuals should not be limited to any one sector as their needs require strategies with a multidisciplinary approach. Copyright (c) 2009 John Wiley & Sons, Ltd.

  11. Increasing maternal healthcare use in Rwanda: implications for child nutrition and survival.

    PubMed

    Pierce, Hayley; Heaton, Tim B; Hoffmann, John

    2014-04-01

    Rwanda has made great progress in improving maternal utilization of health care through coordination of external aid and more efficient health policy. Using data from the 2005 and 2010 Rwandan Demographic and Health Surveys, we examine three related questions regarding the impact of expansion of health care in Rwanda. First, did the increased use of health center deliveries apply to women across varying levels of education, economic status, and area of residency? Second, did the benefits associated with being delivered at a health center diminish as utilization became more widespread? Finally, did inequality in child outcomes decline as a result of increased health care utilization? Propensity score matching was used to address the selectivity that arises when choosing to deliver at a hospital. In addition, the regression models include a linear model to predict child nutritional status and Cox regression to predict child survival. The analysis shows that the largest increases in delivery at a health center occur among less educated, less wealthy, and rural Rwandan women. In addition, delivery at a health center is associated with better nutritional status and survival and the benefit is not diminished following the dramatic increase in use of health centers. Finally, educational, economic and residential inequality in child survival and nutrition did not decline. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Clinical risk factors associated with incidence and progression of periodontal conditions in pregnant women.

    PubMed

    Moss, Kevin L; Beck, James D; Offenbacher, Steven

    2005-05-01

    Few large studies have investigated the progression of periodontal conditions during pregnancy in a comprehensive manner. This study aimed to identify clinical factors that were predictive of incidence/progression of periodontal measures in pregnant women adjusting for relevant predictors. Periodontal examinations were conducted on 891 pregnant women prior to 26 weeks gestational age and within 48 h after delivery. Gingivitis/periodontitis incidence/progression (GPIP) was defined as four plus sites with 2+ mm increase in probing depth (PD) that resulted in PD of at least 4 mm at delivery. Multivariable models including relevant clinical variables and significant covariates were developed. While several clinical measures were significantly associated with the outcome, having >/=10% of sites with bleeding on probing (BOP) and four plus sites with PD >/=4 mm (PD4) were the best two predictors of GPIP (odds ratio (OR)=2.8, 95% confidence interval (CI)=1.8-4.2; OR=2.0, 95% CI=1.4-2.9, respectively), adjusting for maternal race, age, enrollment weight, smoking during pregnancy, marital status, food stamp eligibility, and private health insurance. Multivariable models assessed the impact of BOP on the PD4-GPIP relationship. PD4 was significant in the presence of BOP (low BOP OR=1.3, 95% CI=0.5-3.3; high BOP OR=3.0, 95% CI=2.2-4.3). Enrollment BOP and PD4 were significant predictors of PD in pregnant women, however; PD4 is only a predictor with BOP.

  13. Epidermal growth factor receptor (EGFr) status associated with failure of primary endocrine therapy in elderly postmenopausal patients with breast cancer.

    PubMed Central

    Nicholson, S.; Halcrow, P.; Sainsbury, J. R.; Angus, B.; Chambers, P.; Farndon, J. R.; Harris, A. L.

    1988-01-01

    We have used primary endocrine therapy for 61 elderly women with operable breast cancer (median age 77 years). Eleven patients (18%) had complete and 24 (39%) partial tumour regression, 12 (20%) had stable disease for a minimum of six months and 14 (23%) no response. Salvage surgery was undertaken in the 14 with no response and 8/9 with progressive disease following initial response, thus samples were available from relapse patients only. Assays for EGFr (two point radioreceptor assay) and oestrogen receptors (ER) (dextran coated charcoal method and an immunohistochemical method) were performed on 20/22 patients. Ten of these 20 tumours were EGFr+ (greater than 10 fmol mg-1 binding) and 9/13 patients progressing within six months had EGFr+ tumours. 15/22 were available for ER evaluation and there was no such association with ER status. EGFr status was also associated with early recurrence after surgery and death in the endocrine failure group (P less than 0.005 and P less than 0.05 respectively). Of a control population of 33 patients (median age 72 years) treated by primary surgery, only 6 were EGFr+. In this group early relapse was predicted by EGFr status, but not by ER status (median disease free survival for EGFr+ patients 15 months, and for EGFr- patients 40 months, P less than 0.01, logrank test). There was a significantly higher proportion of EGFr+ tumours in the endocrine failure group compared with the control population (P less than 0.001). EGFr status is a marker for rapid early progression on primary endocrine therapy and the development of non-excisional methods of EGFr analysis would allow better directed therapeutic decisions. PMID:3224082

  14. [The application progress of 3D printing technology in ophthalmology].

    PubMed

    Ji, Z K; Zhao, Y; Yu, S S; Zhao, H

    2018-01-11

    3D printing is a kind of technology that makes 3D models from computer-aided designs through additive manufacturing, in which successive layers of the material are deposited onto underlying layers to construct 3D objects. In recent years, 3D printing is gradually applied in the field of ophthalmology, such as the cornea, retina, orbital operation, ocular tumor radiotherapy, ocular implants and ophthalmology teaching. This article reviews the application status of 3D printing technology in the basic research and clinical treatment in ophthalmology. (Chin J Ophthalmol, 2018, 54: 72-76) .

  15. A general software reliability process simulation technique

    NASA Technical Reports Server (NTRS)

    Tausworthe, Robert C.

    1991-01-01

    The structure and rationale of the generalized software reliability process, together with the design and implementation of a computer program that simulates this process are described. Given assumed parameters of a particular project, the users of this program are able to generate simulated status timelines of work products, numbers of injected anomalies, and the progress of testing, fault isolation, repair, validation, and retest. Such timelines are useful in comparison with actual timeline data, for validating the project input parameters, and for providing data for researchers in reliability prediction modeling.

  16. Investigating the role of the land surface in explaining the interannual variation of the net radiation balance over the Western Sahara and sub-Sahara

    NASA Technical Reports Server (NTRS)

    Smith, Eric A.; Nicholson, Sharon

    1987-01-01

    The status of the data sets is discussed. Progress was made in both data analysis and modeling areas. The atmospheric and land surface contributions to the net radiation budget over the Sahara-Sahel region is being decoupled. The interannual variability of these two processes was investigated and this variability related to seasonal rainfall fluctuations. A modified Barnes objective analysis scheme was developed which uses an eliptic scan pattern and a 3-pass iteration of the difference fields.

  17. Generalizability of New Standards Project, 1993 Pilot Study Tasks in Mathematics. Technical Issues in Procedures To Link State Results to a Common National Standard. Project 2.4 Quantitative Models To Monitor the Status and Progress of Learning and Performance and Their Antecedents.

    ERIC Educational Resources Information Center

    Linn, Robert L.

    The New Standards Project conducted a pilot test of a series of performance-based assessment tasks in mathematics and English language arts at Grades 4 and 8 in the spring of 1993. This paper reports the results of a series of generalizability analyses conducted for a subset of the 1993 pilot study data in mathematics. Generalizability analyses…

  18. A simulation model to estimate cost-offsets for a disease-management program for chronic kidney disease.

    PubMed

    Gandjour, Afschin; Tschulena, Ulrich; Steppan, Sonja; Gatti, Emanuele

    2015-04-01

    The aim of this paper is to develop a simulation model that analyzes cost-offsets of a hypothetical disease management program (DMP) for patients with chronic kidney disease (CKD) in Germany compared to no such program. A lifetime Markov model with simulated 65-year-old patients with CKD was developed using published data on costs and health status and simulating the progression to end-stage renal disease (ESRD), cardiovascular disease and death. A statutory health insurance perspective was adopted. This modeling study shows considerable potential for cost-offsets from a DMP for patients with CKD. The potential for cost-offsets increases with relative risk reduction by the DMP and baseline glomerular filtration rate. Results are most sensitive to the cost of dialysis treatment. This paper presents a general 'prototype' simulation model for the prevention of ESRD. The model allows for further modification and adaptation in future applications.

  19. Development of a MELCOR Sodium Chemistry (NAC) Package - FY17 Progress.

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

    Louie, David; Humphries, Larry L.

    This report describes the status of the development of MELCOR Sodium Chemistry (NAC) package. This development is based on the CONTAIN-LMR sodium physics and chemistry models to be implemented in MELCOR. In the past three years, the sodium equation of state as a working fluid from the nuclear fusion safety research and from the SIMMER code has been implemented into MELCOR. The chemistry models from the CONTAIN-LMR code, such as the spray and pool fire mode ls, have also been implemented into MELCOR. This report describes the implemented models and the issues encountered. Model descriptions and input descriptions are provided.more » Development testing of the spray and pool fire models is described, including the code-to-code comparison with CONTAIN-LMR. The report ends with an expected timeline for the remaining models to be implemented, such as the atmosphere chemistry, sodium-concrete interactions, and experimental validation tests .« less

  20. Technical Status and Progress of Lead Recycling of Battery

    NASA Astrophysics Data System (ADS)

    Li, Wei-feng; Jiang, Li-hua; Zhan, Jing; Zhang, Chuan-fu

    The characteristics of various components in waste lead acid battery are analyzed in this paper. The present status and the study progress situation in industry production and research field of recycling of waste lead acid battery and lead paste used broken-separation technology are introduced. The comparison of advantages and disadvantages in different industry processes is carried. The advantages of redox bath smelting of lead concentrate and lead paste are analyzed. The method of redox bath smelting will be a low-carbon, environmentally friendly and efficient processes of secondary lead production and can be intensive to desulfurize for high temperature pool.

  1. 45 CFR 1307.2 - Definitions.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... progress of the children it serves that have been combined to provide summary information about groups of... other groups of children such as dual language learners, or to provide summary information by specific... children's status and progress across domains of language and literacy development, cognition and general...

  2. 45 CFR 1307.2 - Definitions.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... progress of the children it serves that have been combined to provide summary information about groups of... other groups of children such as dual language learners, or to provide summary information by specific... children's status and progress across domains of language and literacy development, cognition and general...

  3. 45 CFR 1307.2 - Definitions.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... progress of the children it serves that have been combined to provide summary information about groups of... other groups of children such as dual language learners, or to provide summary information by specific... children's status and progress across domains of language and literacy development, cognition and general...

  4. Proposing an amendment to the Constitution of the United States relative to taxing the people of the United States progressively.

    THOMAS, 111th Congress

    Rep. Jackson, Jesse L., Jr. [D-IL-2

    2009-03-03

    House - 03/16/2009 Referred to the Subcommittee on the Constitution, Civil Rights, and Civil Liberties. (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

  5. Schedule and status of irradiation experiments

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

    Rowcliffe, A.F.; Grossbeck, M.L.; Robertson, J.P.

    1998-09-01

    The current status of reactor irradiation experiments is presented in tables summarizing the experimental objectives, conditions, and schedule. Currently, the program has one irradiation experiment in reactor and five experiments in the design or construction stages. Postirradiation examination and testing is in progress on ten experiments.

  6. Fuel Cell Buses in U.S. Transit Fleets: Current Status 2011

    DOT National Transportation Integrated Search

    2011-11-11

    his report is the fifth in a series of annual status reports that summarize the progress resulting from fuel cell transit bus demonstrations in the United States and provide a discussion of the achievements and challenges of fuel cell propulsion in t...

  7. Interdependence of plant water status with photosynthetic performance and root defense responses in Vigna radiata (L.) Wilczek under progressive drought stress and recovery.

    PubMed

    Sengupta, Debashree; Guha, Anirban; Reddy, Attipalli Ramachandra

    2013-10-05

    The present study investigates the interdependence of plant water status with foliar and root responses in Vigna radiata L.Wilczek under progressive drought. Vegetatively-mature V. radiata plants were subjected to water withdrawal for 3 and 6days (D3 and D6, respectively) and then re-watered subsequently for 6days (6R) for stress-recovery. Changes in plant water status were expressed in terms of leaf and root moisture contents (LMC and RMC, respectively) and leaf relative water content (LRWC). Progressive drought caused apparent decrease in LRWC, LMC and RMC depicting significant level of dehydration of leaf and root tissues. Stomatal limitation alone could not account for the observed decrease in net CO2 assimilation rates (Pn) due to comparatively less decrease in sub-stomatal CO2 (Ci) concentrations with respect to other gas exchange parameters indicating possible involvement of non-stomatal limitations. Analysis of polyphasic chl a fluorescence kinetics during progressive drought showed decreased energy connectivity among PSII units as defined by a positive L-band with highest amplitude during D6. Efficiency of electron flux from OEC towards PSII acceptor side was not significantly affected during drought conditions as evidenced by the absence of a positive K-band. Increasing root-level water-limitation enforced a gradual oxidative stress through H2O2 accumulation and membrane lipid peroxidation in V. radiata roots exhibiting drastic enhancement of proline content and a significant but gradual increase in ascorbic acid content as well as guaiacol peroxidase activity under progressive drought. Expression analysis of Δ(1) pyrroline-5-carboxylate synthetase (P5CS) through real time PCR and enzyme activity studies showed a strong positive correlation between VrP5CS gene expression, enzyme activity and proline accumulation in the roots of V. radiata under progressive drought and recovery. Drought-induced changes in root moisture content (RMC) showed positive linear correlations with leaf water content, stomatal conductance as well as transpirational water loss dynamics and a significant negative correlation with the corresponding drought-induced expression patterns of ascorbate, guaiacol peroxidase and proline in roots of V. radiata. The study provides new insights into the plant water status-dependent interrelationship between photosynthetic performance and major root defense responses of V. radiata under progressive drought conditions. Copyright © 2013 Elsevier B.V. All rights reserved.

  8. Mirror Technology Development for The International X-Ray Observatory Mission

    NASA Technical Reports Server (NTRS)

    Zhang, Will

    2010-01-01

    Presentation slides include: International X-ray Observatory (IXO), Lightweight and High Resolution X-ray Optics is Needed; Modular Design of Mirror Assembly, IXO Mirror Technology Development Objectives, Focus of Technology Development, Slumping - Status, Mirror Fabrication Progress, Temporary Bonding - Status, Alignment - Status, Permanent Bonding - Status, Mirror Housing Simulator (MHS) - TRL-4, Mini-Module (TRL-5), Flight-Like Module (TRL-6), Mirror Technology Development Team, Outlook, and Small Technology Firms that Have Made Direct Contributions to IXO Mirror Technology Development.

  9. Low hydrogen sulphide and chronic kidney disease: a dangerous liaison.

    PubMed

    Perna, Alessandra F; Ingrosso, Diego

    2012-02-01

    Hydrogen sulphide, H(2)S, is a gaseous compound involved in a number of biological responses, e.g. blood pressure, vascular function and energy metabolism. In particular, H(2)S is able to lower blood pressure, protect from injury in models of ischaemia-reperfusion and induce a hypometabolic state. In chronic kidney disease (CKD), low plasma hydrogen sulphide levels have been established in humans and in animal models. The enzymes involved in its production are cystathionine β-synthase, cystathionine γ-lyase and 3-mercaptopyruvate sulphurtransferase. The mechanisms for H(2)S decrease in CKD are related to the reduced gene expression (demonstrated in uraemic patient blood cells) and decreased protein levels (in tissues such as liver, kidney, brain in a CKD rat model). In the present Nephrol Dial Transplant issue, in fact, Aminzadeh and Vaziri document that the alterations in this pathway complicate the uraemic state and are linked to CKD progression. They furnish a time frame in CKD and record enzyme tissue distribution. It remains to be established if low H(2)S is causally linked to CKD progression and if interventions aimed to restore the status quo ante are able to modify this picture.

  10. Role of the intrarenal renin-angiotensin system in the progression of renal disease.

    PubMed

    Urushihara, Maki; Kagami, Shoji

    2017-09-01

    The intrarenal renin-angiotensin system (RAS) has many well-documented pathophysiologic functions in both blood pressure regulation and renal disease development. Angiotensin II (Ang II) is the major bioactive product of the RAS. It induces inflammation, renal cell growth, mitogenesis, apoptosis, migration, and differentiation. In addition, Ang II regulates the gene expression of bioactive substances and activates multiple intracellular signaling pathways that are involved in renal damage. Activation of the Ang II type 1 (AT1) receptor pathway results in the production of proinflammatory mediators, intracellular formation of reactive oxygen species, cell proliferation, and extracellular matrix synthesis, which in turn facilities renal injury. Involvement of angiotensinogen (AGT) in intrarenal RAS activation and development of renal disease has previously been reported. Moreover, studies have demonstrated that the urinary excretion rates of AGT provide a specific index of the intrarenal RAS status. Enhanced intrarenal AGT levels have been observed in experimental models of renal disease, supporting the concept that AGT plays an important role in the development and progression of renal disease. In this review, we focus on the role of intrarenal RAS activation in the pathophysiology of renal disease. Additionally, we explored the potential of urinary AGT as a novel biomarker of intrarenal RAS status in renal disease.

  11. Muscle-Derived Proteins as Serum Biomarkers for Monitoring Disease Progression in Three Forms of Muscular Dystrophy

    PubMed Central

    Burch, Peter M.; Pogoryelova, Oksana; Goldstein, Richard; Bennett, Donald; Guglieri, Michela; Straub, Volker; Bushby, Kate; Lochmüller, Hanns; Morris, Carl

    2015-01-01

    Abstract Background: Identifying translatable, non-invasive biomarkers of muscular dystrophy that better reflect the disease pathology than those currently available would aid the development of new therapies, the monitoring of disease progression and the response to therapy. Objective: The goal of this study was to evaluate a panel of serum protein biomarkers with the potential to specifically detect skeletal muscle injury. Method: Serum concentrations of skeletal troponin I (sTnI), myosin light chain 3 (Myl3), fatty acid binding protein 3 (FABP3) and muscle-type creatine kinase (CKM) proteins were measured in 74 Duchenne muscular dystrophy (DMD), 38 Becker muscular dystrophy (BMD) and 49 Limb-girdle muscular dystrophy type 2B (LGMD2B) patients and 32 healthy controls. Results: All four proteins were significantly elevated in the serum of these three muscular dystrophy patient populations when compared to healthy controls, but, interestingly, displayed different profiles depending on the type of muscular dystrophy. Additionally, the effects of patient age, ambulatory status, cardiac function and treatment status on the serum concentrations of the proteins were investigated. Statistical analysis revealed correlations between the serum concentrations and certain clinical endpoints including forced vital capacity in DMD patients and the time to walk ten meters in LGMD2B patients. Serum concentrations of these proteins were also elevated in two preclinical models of muscular dystrophy, the mdx mouse and the golden-retriever muscular dystrophy dog. Conclusions: These proteins, therefore, are potential muscular dystrophy biomarkers for monitoring disease progression and therapeutic response in both preclinical and clinical studies. PMID:26870665

  12. Patterns of relapse and prognosis after bevacizumab failure in recurrent glioblastoma

    PubMed Central

    Iwamoto, F M.; Abrey, L E.; Beal, K; Gutin, P H.; Rosenblum, M K.; Reuter, V E.; DeAngelis, L M.; Lassman, A B.

    2009-01-01

    Background: Bevacizumab has recently been approved by the US Food and Drug Administration for recurrent glioblastoma (GBM). However, patterns of relapse, prognosis, and outcome of further therapy after bevacizumab failure have not been studied systematically. Methods: We identified patients at Memorial Sloan-Kettering Cancer Center with recurrent GBM who discontinued bevacizumab because of progressive disease. Results: There were 37 patients (26 men with a median age of 54 years). The most common therapies administered concurrently with bevacizumab were irinotecan (43%) and hypofractionated reirradiation (38%). The median overall survival (OS) after progressive disease on bevacizumab was 4.5 months; 34 patients died. At the time bevacizumab was discontinued for tumor progression, 17 patients (46%) had an increase in the size of enhancement at the initial site of disease (local recurrence), 6 (16%) had a new enhancing lesion outside of the initial site of disease (multifocal), and 13 (35%) had progression of predominantly nonenhancing tumor. Factors associated with shorter OS after discontinuing bevacizumab were lower performance status and nonenhancing pattern of recurrence. Additional salvage chemotherapy after bevacizumab failure was given to 19 patients. The median progression-free survival (PFS) among these 19 patients was 2 months, the median OS was 5.2 months, and the 6-month PFS rate was 0%. Conclusions: Contrast enhanced MRI does not adequately assess disease status during bevacizumab therapy for recurrent glioblastoma (GBM). A nonenhancing tumor pattern of progression is common after treatment with bevacizumab for GBM and is correlated with worse survival. Treatments after bevacizumab failure provide only transient tumor control. GLOSSARY CA9 = carbonic anhydrase 9; CI = confidence interval; FDG = [18F]fluorodeoxyglucose; FLAIR = fluid-attenuation inversion recovery; GBM = glioblastoma; HIF-1 α = hypoxia-inducible factor 1α; KPS = Karnofsky performance status; MR = magnetic resonance; OS = overall survival; PFS = progression-free survival; TMZ = temozolomide; VEGF = vascular endothelial growth factor; VEGFR = vascular endothelial growth factor receptor. PMID:19822869

  13. 2015 NWEA Measures of Academic Progress Normative Data

    ERIC Educational Resources Information Center

    Northwest Evaluation Association, 2015

    2015-01-01

    By using carefully constructed measurement scales that span grades, Measures of Academic Progress (MAP) interim assessments from Northwest Evaluation Association™ (NWEA™) offer educators efficient and very accurate estimates of student achievement status within a subject. Before achievement test scores can be useful to educators, however, they…

  14. 75 FR 14588 - Proposed Agency Information Collection

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-26

    ... progress, jobs created and retained, spend rates and performance metrics under the American Recovery and... information that DOE is developing to collect data on the status of activities, project progress, jobs created and retained, spend rates and performance metrics under the American Recovery and Reinvestment Act of...

  15. Southeastern Community College Annual Progress Report, December 1995.

    ERIC Educational Resources Information Center

    Gardner, R. Gene

    Presenting information on the status of Southeastern Community College (SCC), in Iowa, this annual progress report highlights basic institutional data, financial information, and improvements and planned changes of the college as of 1995. Part 1 presents basic data on SCC, including facility locations, assessed property valuation, district…

  16. On 3-D inelastic analysis methods for hot section components. Volume 1: Special finite element models

    NASA Technical Reports Server (NTRS)

    Nakazawa, S.

    1987-01-01

    This Annual Status Report presents the results of work performed during the third year of the 3-D Inelastic Analysis Methods for Hot Section Components program (NASA Contract NAS3-23697). The objective of the program is to produce a series of new computer codes that permit more accurate and efficient three-dimensional analysis of selected hot section components, i.e., combustor liners, turbine blades, and turbine vanes. The computer codes embody a progression of mathematical models and are streamlined to take advantage of geometrical features, loading conditions, and forms of material response that distinguish each group of selected components. This report is presented in two volumes. Volume 1 describes effort performed under Task 4B, Special Finite Element Special Function Models, while Volume 2 concentrates on Task 4C, Advanced Special Functions Models.

  17. Pharmacometric Analysis of the Relationship Between Absolute Lymphocyte Count and Expanded Disability Status Scale and Relapse Rate, Efficacy End Points, in Multiple Sclerosis Trials.

    PubMed

    Novakovic, A M; Thorsted, A; Schindler, E; Jönsson, S; Munafo, A; Karlsson, M O

    2018-05-10

    The aim of this work was to assess the relationship between the absolute lymphocyte count (ALC), and disability (as measured by the Expanded Disability Status Scale [EDSS]) and occurrence of relapses, 2 efficacy endpoints, respectively, in patients with remitting-relasping multiple sclerosis. Data for ALC, EDSS, and relapse rate were available from 1319 patients receiving placebo and/or cladribine tablets. Pharmacodynamic models were developed to characterize the time course of the endpoints. ALC-related measures were then evaluated as predictors of the efficacy endpoints. EDSS data were best fitted by a model where the logit-linear disease progression is affected by the dynamics of ALC change from baseline. Relapse rate data were best described by the Weibull hazard function, and the ALC change from baseline was also found to be a significant predictor of time to relapse. Presented models have shown that once cladribine exposure driven ALC-derived measures are included in the model, the need for drug effect components is of less importance (EDSS) or disappears (relapse rate). This simplifies the models and theoretically makes them mechanism specific rather than drug specific. Having a reliable mechanism-specific model would allow leveraging historical data across compounds, to support decision making in drug development and possibly shorten the time to market. © 2018, The American College of Clinical Pharmacology.

  18. Data-driven models of dominantly-inherited Alzheimer's disease progression.

    PubMed

    Oxtoby, Neil P; Young, Alexandra L; Cash, David M; Benzinger, Tammie L S; Fagan, Anne M; Morris, John C; Bateman, Randall J; Fox, Nick C; Schott, Jonathan M; Alexander, Daniel C

    2018-05-01

    See Li and Donohue (doi:10.1093/brain/awy089) for a scientific commentary on this article.Dominantly-inherited Alzheimer's disease is widely hoped to hold the key to developing interventions for sporadic late onset Alzheimer's disease. We use emerging techniques in generative data-driven disease progression modelling to characterize dominantly-inherited Alzheimer's disease progression with unprecedented resolution, and without relying upon familial estimates of years until symptom onset. We retrospectively analysed biomarker data from the sixth data freeze of the Dominantly Inherited Alzheimer Network observational study, including measures of amyloid proteins and neurofibrillary tangles in the brain, regional brain volumes and cortical thicknesses, brain glucose hypometabolism, and cognitive performance from the Mini-Mental State Examination (all adjusted for age, years of education, sex, and head size, as appropriate). Data included 338 participants with known mutation status (211 mutation carriers in three subtypes: 163 PSEN1, 17 PSEN2, and 31 APP) and a baseline visit (age 19-66; up to four visits each, 1.1 ± 1.9 years in duration; spanning 30 years before, to 21 years after, parental age of symptom onset). We used an event-based model to estimate sequences of biomarker changes from baseline data across disease subtypes (mutation groups), and a differential equation model to estimate biomarker trajectories from longitudinal data (up to 66 mutation carriers, all subtypes combined). The two models concur that biomarker abnormality proceeds as follows: amyloid deposition in cortical then subcortical regions (∼24 ± 11 years before onset); phosphorylated tau (17 ± 8 years), tau and amyloid-β changes in cerebrospinal fluid; neurodegeneration first in the putamen and nucleus accumbens (up to 6 ± 2 years); then cognitive decline (7 ± 6 years), cerebral hypometabolism (4 ± 4 years), and further regional neurodegeneration. Our models predicted symptom onset more accurately than predictions that used familial estimates: root mean squared error of 1.35 years versus 5.54 years. The models reveal hidden detail on dominantly-inherited Alzheimer's disease progression, as well as providing data-driven systems for fine-grained patient staging and prediction of symptom onset with great potential utility in clinical trials.

  19. Speech Research Status Report, January-June 1992.

    ERIC Educational Resources Information Center

    Studdert-Kennedy, Michael, Ed.

    One of a series of semi-annual reports, this publication contains 23 articles which report the status and progress of studies on the nature of speech, instruments for its investigation, and practical applications. Articles are as follows: "Phonological and Articulatory Characteristics of Spoken Language" (Carol A. Fowler);…

  20. Treatments for compulsive buying: A systematic review of the quality, effectiveness and progression of the outcome evidence.

    PubMed

    Hague, Ben; Hall, Jo; Kellett, Stephen

    2016-09-01

    Background and aims This review appraises the progression and status of the evidence base for the treatment of compulsive buying disorder (CBD), in order to highlight what currently works and to prompt useful future research. Methods Online databases ISI Web of Knowledge, PsycINFO, and PubMed via Ovid were searched at two time points. Two quality checklists and an established model of therapy evaluation (hourglass model) evaluated the quality and progression of both psychotherapy and pharmacotherapy treatments for CBD. Uncontrolled effect sizes were calculated and meta-regression analyses were performed regarding treatment duration. Results A total of 29 articles met the inclusion criteria, which were divided into psychotherapy (n = 17) and pharmacotherapy treatments (n = 12). Of the 29 studies, only 5 studies have been tested under conditions of high methodological quality. Both forms of treatment had been evaluated in a haphazard manner across the stages of the hourglass model. Although large effects were demonstrated for group psychotherapy and pharmacotherapy, such evidence of effectiveness was undermined by poor study quality and risk of publication bias. Long-term CBD treatment was associated with improved outcome with pharmacotherapy, but not when delivering psychotherapy. Discussion Group psychotherapy currently appears the most promising treatment option for CBD. Poor methodological control and sporadic evaluation of specific treatments have slowed the generation of a convincing evidence base for CBD treatment. Defining the active ingredients of effective CBD treatment is a key research goal.

  1. Treatments for compulsive buying: A systematic review of the quality, effectiveness and progression of the outcome evidence

    PubMed Central

    Hague, Ben; Hall, Jo; Kellett, Stephen

    2016-01-01

    Background and aims This review appraises the progression and status of the evidence base for the treatment of compulsive buying disorder (CBD), in order to highlight what currently works and to prompt useful future research. Methods Online databases ISI Web of Knowledge, PsycINFO, and PubMed via Ovid were searched at two time points. Two quality checklists and an established model of therapy evaluation (hourglass model) evaluated the quality and progression of both psychotherapy and pharmacotherapy treatments for CBD. Uncontrolled effect sizes were calculated and meta-regression analyses were performed regarding treatment duration. Results A total of 29 articles met the inclusion criteria, which were divided into psychotherapy (n = 17) and pharmacotherapy treatments (n = 12). Of the 29 studies, only 5 studies have been tested under conditions of high methodological quality. Both forms of treatment had been evaluated in a haphazard manner across the stages of the hourglass model. Although large effects were demonstrated for group psychotherapy and pharmacotherapy, such evidence of effectiveness was undermined by poor study quality and risk of publication bias. Long-term CBD treatment was associated with improved outcome with pharmacotherapy, but not when delivering psychotherapy. Discussion Group psychotherapy currently appears the most promising treatment option for CBD. Poor methodological control and sporadic evaluation of specific treatments have slowed the generation of a convincing evidence base for CBD treatment. Defining the active ingredients of effective CBD treatment is a key research goal. PMID:27640529

  2. Implementing the Institute of Medicine Definition of Disparities: An Application to Mental Health Care

    PubMed Central

    McGuire, Thomas G; Alegria, Margarita; Cook, Benjamin L; Wells, Kenneth B; Zaslavsky, Alan M

    2006-01-01

    Objective In a recent report, the Institute of Medicine (IOM) defines a health service disparity between population groups to be the difference in treatment or access not justified by the differences in health status or preferences of the groups. This paper proposes an implementation of this definition, and applies it to disparities in outpatient mental health care. Data Sources Health Care for Communities (HCC) reinterviewed 9,585 respondents from the Community Tracking Study in 1997–1998, oversampling individuals with psychological distress, alcohol abuse, drug abuse, or mental health treatment. The HCC is designed to make national estimates of service use. Study Design Expenditures are modeled using generalized linear models with a log link for quantity and a probit model for any utilization. We adjust for group differences in health status by transforming the entire distribution of health status for minority populations to approximate the white distribution. We compare disparities according to the IOM definition to other methods commonly used to assess health services disparities. Principal Findings Our method finds significant service disparities between whites and both blacks and Latinos. Estimated disparities from this method exceed those for competing approaches, because of the inclusion of effects of mediating factors (such as income) in the IOM approach. Conclusions A rigorous definition of disparities is needed to monitor progress against disparities and to compare their magnitude across studies. With such a definition, disparities can be estimated by adjusting for group differences in models for expenditures and access to mental health services. PMID:16987312

  3. Automated Assessment of Disease Progression in Acute Myeloid Leukemia by Probabilistic Analysis of Flow Cytometry Data

    PubMed Central

    Rajwa, Bartek; Wallace, Paul K.; Griffiths, Elizabeth A.; Dundar, Murat

    2017-01-01

    Objective Flow cytometry (FC) is a widely acknowledged technology in diagnosis of acute myeloid leukemia (AML) and has been indispensable in determining progression of the disease. Although FC plays a key role as a post-therapy prognosticator and evaluator of therapeutic efficacy, the manual analysis of cytometry data is a barrier to optimization of reproducibility and objectivity. This study investigates the utility of our recently introduced non-parametric Bayesian framework in accurately predicting the direction of change in disease progression in AML patients using FC data. Methods The highly flexible non-parametric Bayesian model based on the infinite mixture of infinite Gaussian mixtures is used for jointly modeling data from multiple FC samples to automatically identify functionally distinct cell populations and their local realizations. Phenotype vectors are obtained by characterizing each sample by the proportions of recovered cell populations, which are in turn used to predict the direction of change in disease progression for each patient. Results We used 200 diseased and non-diseased immunophenotypic panels for training and tested the system with 36 additional AML cases collected at multiple time points. The proposed framework identified the change in direction of disease progression with accuracies of 90% (9 out of 10) for relapsing cases and 100% (26 out of 26) for the remaining cases. Conclusions We believe that these promising results are an important first step towards the development of automated predictive systems for disease monitoring and continuous response evaluation. Significance Automated measurement and monitoring of therapeutic response is critical not only for objective evaluation of disease status prognosis but also for timely assessment of treatment strategies. PMID:27416585

  4. Basic fibroblast growth factor in an animal model of spontaneous mammary tumor progression.

    PubMed

    Kao, Steven; Mo, Jeffrey; Baird, Andrew; Eliceiri, Brian P

    2012-06-01

    Although basic fibroblast growth factor (FGF2) was the first pro-angiogenic molecule discovered, it has numerous activities on the growth and differentiation of non-vascular cell types. FGF2 is both stimulatory and inhibitory, depending on the cell type evaluated, the experimental design used and the context in which it is tested. Here, we investigated the effects of manipulating endogenous FGF2 on the development of mammary cancer to determine whether its endogenous contribution in vivo is pro- or anti-tumorigenic. Specifically, we examined the effects of FGF2 gene dosing in a cross between a spontaneous breast tumor model (PyVT+ mice) and FGF2-/- (FGF KO) mice. Using these mice, the onset and progression of mammary tumors was determined. As predicted, female FGF2 WT mice developed mammary tumors starting around 60 days after birth and by 80 days, 100% of FGF2 WT female mice had mammary tumors. In contrast, 80% of FGF2 KO female mice had no palpable tumors until nearly three weeks later (85 days) at times when 100% of the WT cohort was tumor positive. All FGF KO mice were tumor-bearing by 115 days. When we compared the onset of mammary tumor development and the tumor progression curves between FGF het and FGF KO mice, we observed a difference, which suggested a gene dosing effect. Analysis of the tumors demonstrated that there were significant differences in tumor size depending on FGF2 status. The delay in tumor onset supports a functional role for FGF2 in mammary tumor progression, but argues against an essential role for FGF2 in overall mammary tumor progression.

  5. Progression of regional grey matter atrophy in multiple sclerosis

    PubMed Central

    Marinescu, Razvan V; Young, Alexandra L; Firth, Nicholas C; Jorge Cardoso, M; Tur, Carmen; De Angelis, Floriana; Cawley, Niamh; Brownlee, Wallace J; De Stefano, Nicola; Laura Stromillo, M; Battaglini, Marco; Ruggieri, Serena; Gasperini, Claudio; Filippi, Massimo; Rocca, Maria A; Rovira, Alex; Sastre-Garriga, Jaume; Geurts, Jeroen J G; Vrenken, Hugo; Wottschel, Viktor; Leurs, Cyra E; Uitdehaag, Bernard; Pirpamer, Lukas; Enzinger, Christian; Ourselin, Sebastien; Gandini Wheeler-Kingshott, Claudia A; Chard, Declan; Thompson, Alan J; Barkhof, Frederik; Alexander, Daniel C; Ciccarelli, Olga

    2018-01-01

    Abstract See Stankoff and Louapre (doi:10.1093/brain/awy114) for a scientific commentary on this article. Grey matter atrophy is present from the earliest stages of multiple sclerosis, but its temporal ordering is poorly understood. We aimed to determine the sequence in which grey matter regions become atrophic in multiple sclerosis and its association with disability accumulation. In this longitudinal study, we included 1417 subjects: 253 with clinically isolated syndrome, 708 with relapsing-remitting multiple sclerosis, 128 with secondary-progressive multiple sclerosis, 125 with primary-progressive multiple sclerosis, and 203 healthy control subjects from seven European centres. Subjects underwent repeated MRI (total number of scans 3604); the mean follow-up for patients was 2.41 years (standard deviation = 1.97). Disability was scored using the Expanded Disability Status Scale. We calculated the volume of brain grey matter regions and brainstem using an unbiased within-subject template and used an established data-driven event-based model to determine the sequence of occurrence of atrophy and its uncertainty. We assigned each subject to a specific event-based model stage, based on the number of their atrophic regions. Linear mixed-effects models were used to explore associations between the rate of increase in event-based model stages, and T2 lesion load, disease-modifying treatments, comorbidity, disease duration and disability accumulation. The first regions to become atrophic in patients with clinically isolated syndrome and relapse-onset multiple sclerosis were the posterior cingulate cortex and precuneus, followed by the middle cingulate cortex, brainstem and thalamus. A similar sequence of atrophy was detected in primary-progressive multiple sclerosis with the involvement of the thalamus, cuneus, precuneus, and pallidum, followed by the brainstem and posterior cingulate cortex. The cerebellum, caudate and putamen showed early atrophy in relapse-onset multiple sclerosis and late atrophy in primary-progressive multiple sclerosis. Patients with secondary-progressive multiple sclerosis showed the highest event-based model stage (the highest number of atrophic regions, P < 0.001) at the study entry. All multiple sclerosis phenotypes, but clinically isolated syndrome, showed a faster rate of increase in the event-based model stage than healthy controls. T2 lesion load and disease duration in all patients were associated with increased event-based model stage, but no effects of disease-modifying treatments and comorbidity on event-based model stage were observed. The annualized rate of event-based model stage was associated with the disability accumulation in relapsing-remitting multiple sclerosis, independent of disease duration (P < 0.0001). The data-driven staging of atrophy progression in a large multiple sclerosis sample demonstrates that grey matter atrophy spreads to involve more regions over time. The sequence in which regions become atrophic is reasonably consistent across multiple sclerosis phenotypes. The spread of atrophy was associated with disease duration and with disability accumulation over time in relapsing-remitting multiple sclerosis. PMID:29741648

  6. Progression of regional grey matter atrophy in multiple sclerosis.

    PubMed

    Eshaghi, Arman; Marinescu, Razvan V; Young, Alexandra L; Firth, Nicholas C; Prados, Ferran; Jorge Cardoso, M; Tur, Carmen; De Angelis, Floriana; Cawley, Niamh; Brownlee, Wallace J; De Stefano, Nicola; Laura Stromillo, M; Battaglini, Marco; Ruggieri, Serena; Gasperini, Claudio; Filippi, Massimo; Rocca, Maria A; Rovira, Alex; Sastre-Garriga, Jaume; Geurts, Jeroen J G; Vrenken, Hugo; Wottschel, Viktor; Leurs, Cyra E; Uitdehaag, Bernard; Pirpamer, Lukas; Enzinger, Christian; Ourselin, Sebastien; Gandini Wheeler-Kingshott, Claudia A; Chard, Declan; Thompson, Alan J; Barkhof, Frederik; Alexander, Daniel C; Ciccarelli, Olga

    2018-06-01

    See Stankoff and Louapre (doi:10.1093/brain/awy114) for a scientific commentary on this article.Grey matter atrophy is present from the earliest stages of multiple sclerosis, but its temporal ordering is poorly understood. We aimed to determine the sequence in which grey matter regions become atrophic in multiple sclerosis and its association with disability accumulation. In this longitudinal study, we included 1417 subjects: 253 with clinically isolated syndrome, 708 with relapsing-remitting multiple sclerosis, 128 with secondary-progressive multiple sclerosis, 125 with primary-progressive multiple sclerosis, and 203 healthy control subjects from seven European centres. Subjects underwent repeated MRI (total number of scans 3604); the mean follow-up for patients was 2.41 years (standard deviation = 1.97). Disability was scored using the Expanded Disability Status Scale. We calculated the volume of brain grey matter regions and brainstem using an unbiased within-subject template and used an established data-driven event-based model to determine the sequence of occurrence of atrophy and its uncertainty. We assigned each subject to a specific event-based model stage, based on the number of their atrophic regions. Linear mixed-effects models were used to explore associations between the rate of increase in event-based model stages, and T2 lesion load, disease-modifying treatments, comorbidity, disease duration and disability accumulation. The first regions to become atrophic in patients with clinically isolated syndrome and relapse-onset multiple sclerosis were the posterior cingulate cortex and precuneus, followed by the middle cingulate cortex, brainstem and thalamus. A similar sequence of atrophy was detected in primary-progressive multiple sclerosis with the involvement of the thalamus, cuneus, precuneus, and pallidum, followed by the brainstem and posterior cingulate cortex. The cerebellum, caudate and putamen showed early atrophy in relapse-onset multiple sclerosis and late atrophy in primary-progressive multiple sclerosis. Patients with secondary-progressive multiple sclerosis showed the highest event-based model stage (the highest number of atrophic regions, P < 0.001) at the study entry. All multiple sclerosis phenotypes, but clinically isolated syndrome, showed a faster rate of increase in the event-based model stage than healthy controls. T2 lesion load and disease duration in all patients were associated with increased event-based model stage, but no effects of disease-modifying treatments and comorbidity on event-based model stage were observed. The annualized rate of event-based model stage was associated with the disability accumulation in relapsing-remitting multiple sclerosis, independent of disease duration (P < 0.0001). The data-driven staging of atrophy progression in a large multiple sclerosis sample demonstrates that grey matter atrophy spreads to involve more regions over time. The sequence in which regions become atrophic is reasonably consistent across multiple sclerosis phenotypes. The spread of atrophy was associated with disease duration and with disability accumulation over time in relapsing-remitting multiple sclerosis.

  7. Welfare Reform: Progress in Meeting Work-Focused TANF Goals. Testimony before the Subcommittee on Human Resources, Committee on Ways and Means, House of Representatives.

    ERIC Educational Resources Information Center

    Fagnoni, Cynthia M.

    The General Accounting Office (GAO) examined progress in meeting work-focused goals of the Temporary Assistance for Needy Families (TANF) program. The following issues were considered: (1) states' progress in implementing TANF; (2) the status of families who have left welfare; (3) the characteristics of adults currently receiving TANF; (4) states'…

  8. Status Report on Speech Research: A Report on the Status and Progress of Studies on the Nature of Speech, Instrumentation for Its Investigation, and Practical Applications, January-June 1987.

    ERIC Educational Resources Information Center

    O'Brien, Nancy, Ed.

    One of a series of reports on the status of speech investigation, this collection of articles deals with topics including intonation and morphological knowledge. The titles of the articles and their authors are as follows: (1) "Integration and Segregation in Speech Perception" (Bruno H. Repp); (2) "Speech Perception Takes Precedence…

  9. Progress report on PIXIE3D, a fully implicit 3D extended MHD solver

    NASA Astrophysics Data System (ADS)

    Chacon, Luis

    2008-11-01

    Recently, invited talk at DPP07 an optimal, massively parallel implicit algorithm for 3D resistive magnetohydrodynamics (PIXIE3D) was demonstrated. Excellent algorithmic and parallel results were obtained with up to 4096 processors and 138 million unknowns. While this is a remarkable result, further developments are still needed for PIXIE3D to become a 3D extended MHD production code in general geometries. In this poster, we present an update on the status of PIXIE3D on several fronts. On the physics side, we will describe our progress towards the full Braginskii model, including: electron Hall terms, anisotropic heat conduction, and gyroviscous corrections. Algorithmically, we will discuss progress towards a robust, optimal, nonlinear solver for arbitrary geometries, including preconditioning for the new physical effects described, the implementation of a coarse processor-grid solver (to maintain optimal algorithmic performance for an arbitrarily large number of processors in massively parallel computations), and of a multiblock capability to deal with complicated geometries. L. Chac'on, Phys. Plasmas 15, 056103 (2008);

  10. Non-Native Language Use and Risk of Incident Dementia in the Elderly

    PubMed Central

    Sanders, Amy E.; Hall, Charles B.; Katz, Mindy J.; Lipton, Richard B.

    2012-01-01

    Cognitive reserve is invoked to explain the protective effects of education and cognitively-stimulating activities against all-cause dementia and Alzheimer’s disease (AD). For non-native English speakers (n-NES), speaking English may be a cognitive activity associated with lower dementia risk. We hypothesized that n-NES have lower risk of incident dementia/AD and that educational level might modify this relationship. Participants took part in the Einstein Aging Study (Bronx, NY), a longitudinal study of aging and dementia. All (n = 1779) spoke fluent English and self-reported birthplace and whether English was their first language. n-NES additionally reported mother tongue, age of English acquisition, and current percentile-use of a non-English language. Nested Cox proportional hazards models progressively adjusted for gender, race, education, and immigrant and marital status estimated hazard ratios (HR) for incident dementia/AD as a function of n-NES status. 390 (22%) participants were n-NES. 126 incident dementia cases occurred during 4174 person-years of follow-up (median 1.44; range 0–16); 101 individuals met criteria for probable/possible AD. There was no statistically-significant association between n-NES status and incident dementia in the fully-adjusted model (HR 1.26; 95% CI 0.76–2.09; p = 0.36). Results were similar for AD. Stratification of education into three groups revealed increased risk of dementia for n-NES with ≥16 years of education (HR 3.97; 95% CI 1.62–9.75; p = 0.003). We conclude that n-NES status does not appear to have an independent protective effect against incident dementia/AD, and that n-NES status may contribute to risk of dementia in an education-dependent manner. PMID:22232011

  11. Non-native language use and risk of incident dementia in the elderly.

    PubMed

    Sanders, Amy E; Hall, Charles B; Katz, Mindy J; Lipton, Richard B

    2012-01-01

    Cognitive reserve is invoked to explain the protective effects of education and cognitively-stimulating activities against all-cause dementia and Alzheimer's disease (AD). For non-native English speakers (n-NES), speaking English may be a cognitive activity associated with lower dementia risk. We hypothesized that n-NES have lower risk of incident dementia/AD and that educational level might modify this relationship. Participants took part in the Einstein Aging Study (Bronx, NY), a longitudinal study of aging and dementia. All (n = 1779) spoke fluent English and self-reported birthplace and whether English was their first language. n-NES additionally reported mother tongue, age of English acquisition, and current percentile-use of a non-English language. Nested Cox proportional hazards models progressively adjusted for gender, race, education, and immigrant and marital status estimated hazard ratios (HR) for incident dementia/AD as a function of n-NES status. 390 (22%) participants were n-NES. 126 incident dementia cases occurred during 4174 person-years of follow-up (median 1.44; range 0-16); 101 individuals met criteria for probable/possible AD. There was no statistically-significant association between n-NES status and incident dementia in the fully-adjusted model (HR 1.26; 95% CI 0.76-2.09; p = 0.36). Results were similar for AD. Stratification of education into three groups revealed increased risk of dementia for n-NES with ≥ 16 years of education (HR 3.97; 95% CI 1.62-9.75; p = 0.003). We conclude that n-NES status does not appear to have an independent protective effect against incident dementia/AD, and that n-NES status may contribute to risk of dementia in an education-dependent manner.

  12. Dopamine Transporter Neuroimaging as an Enrichment Biomarker in Early Parkinson's Disease Clinical Trials: A Disease Progression Modeling Analysis

    PubMed Central

    Nicholas, Timothy; Tsai, Kuenhi; Macha, Sreeraj; Sinha, Vikram; Stone, Julie; Corrigan, Brian; Bani, Massimo; Muglia, Pierandrea; Watson, Ian A.; Kern, Volker D.; Sheveleva, Elena; Marek, Kenneth; Stephenson, Diane T.; Romero, Klaus

    2017-01-01

    Abstract Given the recognition that disease‐modifying therapies should focus on earlier Parkinson's disease stages, trial enrollment based purely on clinical criteria poses significant challenges. The goal herein was to determine the utility of dopamine transporter neuroimaging as an enrichment biomarker in early motor Parkinson's disease clinical trials. Patient‐level longitudinal data of 672 subjects with early‐stage Parkinson's disease in the Parkinson's Progression Markers Initiative (PPMI) observational study and the Parkinson Research Examination of CEP‐1347 Trial (PRECEPT) clinical trial were utilized in a linear mixed‐effects model analysis. The rate of worsening in the motor scores between subjects with or without a scan without evidence of dopamine transporter deficit was different both statistically and clinically. The average difference in the change from baseline of motor scores at 24 months between biomarker statuses was –3.16 (90% confidence interval [CI] = –0.96 to –5.42) points. Dopamine transporter imaging could identify subjects with a steeper worsening of the motor scores, allowing trial enrichment and 24% reduction of sample size. PMID:28749580

  13. Markers of Oxidative Status in a Clinical Model of Oxidative Assault: a Pilot Study in Human Blood Following Doxorubicin Administration

    PubMed Central

    Il'yasova, Dora; Mixon, Gabriel; Wang, Frances; Marcom, P Kelly; Marks, Jeffrey; Spasojevich, Ivan; Craft, Neal; Arredondo, Francisco; DiGiulio, Richard

    2009-01-01

    We used doxorubicin-based chemotherapy as a clinical model for oxidative assault. Study recruited 23 breast cancer patients and collected blood samples before (T0), at 1 (T1) and 24 hours (T24) after treatment administration. Measurements included protein carbonyl content (PPCC), malondialdehyde (MDA), and α- and γ-tocopherols in plasma and total glutathione content in erythrocytes (erGSHt). In all subjects, PPCC and MDA levels did not change. erGSHt levels increased at T24 by 8% (p=0.03). Levels of α, γ, and total tocopherols progressively decreased by 7%−15% (P<0.05). In subjects with low erGSHt levels (below median), PPCC mean levels progressively increased from 0.35 (T0) to 0.56 (T1) and 0.72 nmol carbonyl/mg protein (T24) (p=0.2). These results indicate that (1) plasma MDA is not a sensitive biomarker in humans; (2) PPCC potentially may be used, if antioxidant reserves are taken into account; (3) antioxidant reserves play an important role in the reaction to oxidative stress. PMID:19476408

  14. Capturing transitions and trajectories: the role of socioeconomic status in later life disability.

    PubMed

    Taylor, Miles G

    2010-11-01

    Disability is conceptualized as a life course process and measured using either transitions or trajectories. Previous research does not simultaneously explore both aspects of disablement, accounting for timing and trajectory. The role of education is noted in disability research, but its independent effects over time have not been fully examined. I investigate the effects of education and income on disability onset and progression over a decade. I use a latent curve modeling approach with four waves of the Duke Established Populations for Epidemiologic Studies of the Elderly data to independently test the preventive and mediating effects education and income provide for disability. Education has a preventive effect for disability onset but no significant effect on progression once income is held constant. Income has both a preventive and mediating effect on disability, although preventive effects are stronger for education. Later life disability is measured here using both onset and trajectory. Findings are consistent with health research suggesting that education and income work through shared and independent mechanisms to affect disability over time. These findings also highlight the importance of modeling timing when studying health trajectories.

  15. 77 FR 33454 - Adequacy Status: South Carolina: Reasonable Further Progress Plan Motor Vehicle Emissions Budget...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-06

    .... Conformity to a SIP means that transportation activities will not produce new air quality violations, worsen... Carolina: Reasonable Further Progress Plan Motor Vehicle Emissions Budget for Transportation Conformity for... adequate for transportation conformity purposes. The South Carolina portion of the Charlotte bi-state Area...

  16. Quality of life attenuates age-related decline in functional status of older adults.

    PubMed

    Palgi, Yuval; Shrira, Amit; Zaslavsky, Oleg

    2015-08-01

    In the present study, we aimed to examine the total and moderating effects of needs-satisfaction-driven quality-of-life (QoL) measure on age-related change in functional status. Participants in the Survey of Health and Retirement in Europe (N = 18,781 at Wave 1) completed a measure of QoL (CASP-12) at baseline and reported their functional status across subsequent three waves using activities of daily living (ADL), instrumental activities of daily living (IADL), and functional limitation indices. Growth-curve model estimates revealed that aged individuals with lower QoL scores at baseline had a steeper increase in disability deficits accumulation and functional limitation progression than their counterparts with a higher sense of QoL. The effects were more pronounced in ADL and IADL disability scales in which QoL moderated both linear and quadratic age-related changes. Higher QoL attenuates processes of functional decline in late adulthood. Practitioners may seek strategies for improving and enhancing patients' QoL, as its salutary effects diffuse beyond psychological experience and include long-term effects on physical functioning.

  17. A model for patient participation in quality of life measurement to improve rehabilitation outcomes.

    PubMed

    Callahan, M B; LeSage, L; Johnstone, S

    1999-01-01

    Health-related quality of life (HRQOL) measurement is being used to assess end-stage renal disease (ESRD) patients' functional status and well-being from the patient's perspective. Research shows that HRQOL can screen for patients at high risk for death, hospitalization, treatment adherence, and depression. This study investigated whether patient goal setting and interdisciplinary collaboration and support could increase HRQOL scores in ESRD patients on chronic maintenance hemodialysis. Differences were found to be statistically significant in two of the MOS Short Form 36 (SF-36) categories (role physical and role emotional) following the intervention at the 95% confidence interval using a t-test statistic. This indicates that the intervention had a positive impact on patient perceptions of their health status. Eighty-seven percent indicated that there had been at least some progress made in reaching the goal. The results of this study support the utilization of HRQOL data at the facility level to improve patient's perceptions of their health status. A further study is needed to examine the long-term impact on HRQOL and other patient outcome measures through consistent use of this intervention.

  18. Status Report on Speech Research, January-June 1991.

    ERIC Educational Resources Information Center

    Studdert-Kennedy, Michael, Ed.

    One of a series of semiannual reports, this publication contains 18 articles which report the status and progress of studies on the nature of speech, instrumentation for its investigation, and practical applications. Articles and their authors are as follows: "Phonology and Beginning Reading Revisited (Isabelle Y. Liberman); "The Role of…

  19. Speech Research, Status Report July-December 1991.

    ERIC Educational Resources Information Center

    Studdert-Kennedy, Michael, Ed.

    One of a series of semi-annual reports, this publication contains 18 articles which report the status and progress of studies on the nature of speech, instruments for its investigation, and practical applications. Articles are as follows: "The Emergence of Native-Language Phonological Influences in Infants: A Perceptual Assimilation…

  20. Status and Future of Lunar Geoscience.

    ERIC Educational Resources Information Center

    1986

    A review of the status, progress, and future direction of lunar research is presented in this report from the lunar geoscience working group of the National Aeronautics and Space Administration. Information is synthesized and presented in four major sections. These include: (1) an introduction (stating the reasons for lunar study and identifying…

  1. Status Report on Speech Research, January-June 1989.

    ERIC Educational Resources Information Center

    Studdert-Kennedy, Michael, Ed.

    One of a series of semiannual reports, this publication contains 14 articles which report the status and progress of studies on the nature of speech, instrumentation for its investigation, and practical applications. The titles of the articles and their authors are as follows: "Gestural Structure and Phonological Patterns" (Catherine P.…

  2. Status Report on Speech Research, July-December 1993. SR-115/116.

    ERIC Educational Resources Information Center

    Fowler, Carol A., Ed.

    This publication (one of a series) contains 12 articles which report the status and progress of studies on the nature of speech, instruments for its investigation, and practical applications. Articles in the publication are: "Dynamics and Coordinate Systems on Skilled Sensorimotor Activity" (Elliot L. Saltzman); "Speech Motor…

  3. Status Report on Speech Research, July-December 1989.

    ERIC Educational Resources Information Center

    Studdert-Kennedy, Michael, Ed.

    One of a series of semiannual reports, this publication contains 12 articles which report the status and progress of studies on the nature of speech, instrumentation for its investigation, and practical applications. The titles of the articles and their authors are as follows: "Coarticulatory Organization for Lip-rounding in Turkish and…

  4. 14 CFR 91.417 - Maintenance records.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... alteration and records of the 100-hour, annual, progressive, and other required or approved inspections, as... propeller, and each rotor. (ii) The current status of life-limited parts of each airframe, engine, propeller... are required to be overhauled on a specified time basis. (iv) The current inspection status of the...

  5. 14 CFR 91.417 - Maintenance records.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... alteration and records of the 100-hour, annual, progressive, and other required or approved inspections, as... propeller, and each rotor. (ii) The current status of life-limited parts of each airframe, engine, propeller... are required to be overhauled on a specified time basis. (iv) The current inspection status of the...

  6. Current status and challenges in developing Ni phytomining: An agronomic perspective

    USDA-ARS?s Scientific Manuscript database

    This review examines the current status, progress and challenges in Ni phytomining agronomy undertaken since the first field trial two decades ago. To date, over 400 Ni hyperaccumulators have been documented (of which >30% are in Cuba) including approximately 50 species with potential for use in Ni ...

  7. Speech Research Status Report, January-March 1993.

    ERIC Educational Resources Information Center

    Fowler, Carol A., Ed.

    One of a series of quarterly reports, this publication contains 14 articles which report the status and progress of studies on the nature of speech, instruments for its investigation, and practical applications. Articles in the publication are: "Some Assumptions about Speech and How They Changed" (Alvin M. Liberman); "On the…

  8. Speech Research Status Report, July-December 1992.

    ERIC Educational Resources Information Center

    Fowler, Carol A., Ed.

    One of a series of semi-annual reports, this publication contains 25 articles which report the status and progress of studies on the nature of speech, instruments for its investigation, and practical applications. Articles are as follows: "Acoustic Shards, Perceptual Glue" (Robert E. Remez and Philip E. Rubin); "F0 Gives Voicing…

  9. Status Report on Speech Research, July 1994-December 1995.

    ERIC Educational Resources Information Center

    Fowler, Carol A., Ed.

    This publication (one of a series) contains 19 articles which report the status and progress of studies on the nature of speech, instruments for its investigation, and practical applications. Articles are: "Speech Perception Deficits in Poor Readers: Auditory Processing or Phonological Coding?" (Maria Mody and others); "Auditory…

  10. Union Carbide Corp. polysilicon status and plans

    NASA Technical Reports Server (NTRS)

    Leipold, M. H.

    1982-01-01

    The status of polysilicon activities is summarized highlighted by moving the silane portion of the experimental process system development unit (EPSDU) to Washougal, Washington. The completion and operation of the silane EPSDU, is discussed along with research on the silane-to-silicon deposition process. Progress on the dichlorosilane process is also reported.

  11. Early Childhood Inclusion in the United States: Goals, Current Status, and Future Directions

    ERIC Educational Resources Information Center

    Guralnick, Michael J.; Bruder, Mary Beth

    2016-01-01

    The current status and future directions of early childhood inclusion in the United States are discussed from the perspective of 4 key goals: access, accommodations and feasibility, developmental progress, and social integration. Recommendations are put forward to promote inclusion goals emphasizing administrative structures, personnel…

  12. A bill to amend the National Flood Insurance Act of 1968 to clarify the effective date of policies covering properties affected by floods in progress.

    THOMAS, 112th Congress

    Sen. Johanns, Mike [R-NE

    2011-07-12

    Senate - 07/12/2011 Read twice and referred to the Committee on Banking, Housing, and Urban Affairs. (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

  13. Status Report on Speech Research, July-December 1990.

    ERIC Educational Resources Information Center

    Studdert-Kennedy, Michael, Ed.

    One of a series of semiannual reports, this publication contains 13 articles which report the status and progress of studies on the nature of speech, instrumentation for its investigation, and practical applications. Articles and their authors are as follows: "The Role of Contrast in Limiting Vowel-to-Vowel Coarticulation in Different…

  14. Levels of uninvolved immunoglobulins predict clinical status and progression-free survival for multiple myeloma patients.

    PubMed

    Harutyunyan, Nika M; Vardanyan, Suzie; Ghermezi, Michael; Gottlieb, Jillian; Berenson, Ariana; Andreu-Vieyra, Claudia; Berenson, James R

    2016-07-01

    Multiple myeloma (MM) is characterized by the enhanced production of the same monoclonal immunoglobulin (M-Ig or M protein). Techniques such as serum protein electrophoresis and nephelometry are routinely used to quantify levels of this protein in the serum of MM patients. However, these methods are not without their shortcomings and problems accurately quantifying M proteins remain. Precise quantification of the types and levels of M-Ig present is critical to monitoring patient response to therapy. In this study, we investigated the ability of the HevyLite (HLC) immunoassay to correlate with clinical status based on levels of involved and uninvolved antibodies. In our cohort of MM patients, we observed that significantly higher ratios and greater differences of involved HLC levels compared to uninvolved HLC levels correlated with a worse clinical status. Similarly, higher absolute levels of involved HLC antibodies and lower levels of uninvolved HLC antibodies also correlated with a worse clinical status and a shorter progression-free survival. These findings suggest that the HLC assay is a useful and a promising tool for determining the clinical status and survival time for patients with multiple myeloma. © 2016 John Wiley & Sons Ltd.

  15. Experimental realization of dynamo action: present status and prospects

    NASA Astrophysics Data System (ADS)

    Giesecke, André; Stefani, Frank; Gundrum, Thomas; Gerbeth, Gunter; Nore, Caroline; Léorat, Jacques

    2013-07-01

    In the last decades, the experimental study of dynamo action has made great progress. However, after the dynamo experiments in Karlsruhe and Riga, the von-Kármán-Sodium (VKS) dynamo is only the third facility that has been able to demonstrate fluid flow driven self-generation of magnetic fields in a laboratory experiment. Further progress in the experimental examination of dynamo action is expected from the planned precession driven dynamo experiment that will be designed in the framework of the liquid sodium facility DRESDYN (DREsden Sodium facility for DYNamo and thermohydraulic studies). In this paper, we briefly present numerical models of the VKS dynamo that demonstrate the close relation between the axisymmetric field observed in that experiment and the soft iron material used for the flow driving impellers. We further show recent results of preparatory water experiments and design studies related to the precession dynamo and delineate the scientific prospects for the final set-up.

  16. Traditional and emerging molecular markers in neuroblastoma prognosis: the good, the bad and the ugly.

    PubMed

    Poremba, C; Hero, B; Goertz, H G; Scheel, C; Wai, D; Schaefer, K L; Christiansen, H; Berthold, F; Juergens, H; Boecker, W; Dockhorn-Dworniczak, B

    2001-01-01

    Neuroblastomas (NB) are a heterogeneous group of childhood tumours with a wide range of likelihood for tumour progression. As traditional parameters do not ensure completely accurate prognostic grouping, new molecular markers are needed for assessing the individual patient's prognosis more precisely. 133 NB of all stages were analysed in blind-trial fashion for telomerase activity (TA), expression of surviving, and MYCN status. These data were correlated with other traditional prognostic indicators and disease outcome. TA is a powerful independent prognostic marker for all stages and is capable of differentiating between good and poor outcome in putative "favourable" clinical or biological subgroups of NB patients. High surviving expression is associated with an adverse outcome, but is more difficult to interprete than TA because survivin expression needs to be accurately quantified to be of predictive value. We propose an extended progression model for NB including emerging prognostic markers, with emphasis on telomerase activity.

  17. Activation of Müller cells occurs during retinal degeneration in RCS rats.

    PubMed

    Zhao, Tong Tao; Tian, Chun Yu; Yin, Zheng Qin

    2010-01-01

    Müller cells can be activated and included in different functions under many kinds of pathological conditions, however, the status of Müller cells in retinitis pigmentosa are still unknown. Using immunohistochemisty, Western blots and co-culture, we found that Müller cells RCS rats, a classic model of RP, could be activated during the progression of retinal degeneration. After being activated at early stage, Müller cells began to proliferate and hypertrophy, while at later stages, they formed a local 'glial seal' in the subretinal space. As markers of Müller cells activation, the expression of GFAP and ERK increased significantly with progression of retinal degeneration. Co-cultures of normal rat Müller cells and mixed RCS rat retinal cells show that Müller cells significantly increase GFAP and ERK in response to diffusable factors from the degenerting retina, which implies that Müller cells activation is a secondary response to retinal degeneration.

  18. An audit of the predictors of outcome in status epilepticus from a resource-poor country: a comparison with developed countries.

    PubMed

    Hassan, Haseeb; Rajiv, Keni Ravish; Menon, Ramshekhar; Menon, Deepak; Nair, Muralidharan; Radhakrishnan, Ashalatha

    2016-06-01

    Status epilepticus is a neurological emergency with significant morbidity and mortality. This study describes the clinical profile, treatment, and predictors of outcome of status epilepticus in a tertiary referral centre in a developing country and aims to highlight the similarities and differences from data available from the western world. A retrospective analysis of data of patients treated for status epilepticus was conducted from prospectively maintained records, between January 2000 and September 2010. The demographic data, clinical profile and investigations (including neuroimaging and EEG), aetiology, treatment, and outcomes were studied and compared with data available from the western world. The analysis included 108 events in 84 patients. A single episode of status epilepticus was treated in 72 patients (86%) and multiple status epilepticus events, ranging from two to six per patient, were managed in 12 patients (14%). Mean age was 24.1±20.3 years and 63% were males. The types of status epilepticus included convulsive status in 98 (90.7%), non-convulsive status in seven (6.5%), and myoclonic status in three (2.8%). The majority of events (60%) were remote symptomatic, 16% were acute symptomatic, 16% were of unexplained aetiology, and 8% were progressive symptomatic. In 85 events (79%), status epilepticus could be aborted with first and second-line drugs. The remaining 23 events (21%) progressed to refractory status epilepticus, among which, 13 (56%) were controlled with continuous intravenous midazolam infusion. Case fatality rate was 11%, neurological sequelae were reported in 22%, and 67% returned to baseline. Acute symptomatic status, older age, altered sensorium at the time of admission, and delayed hospitalisation were predictors of poor outcome. Aetiology was the most important determinant of outcome of status epilepticus, as in reports from the western world, with remote symptomatic aetiology secondary to gliosis being the most common. Treatment delay was frequent and adversely affected the outcome.

  19. Prognostic value of tumor necrosis at CT in diffuse large B-cell lymphoma.

    PubMed

    Adams, Hugo J A; de Klerk, John M H; Fijnheer, Rob; Dubois, Stefan V; Nievelstein, Rutger A J; Kwee, Thomas C

    2015-03-01

    To determine the prognostic value of tumor necrosis at computed tomography (CT) in newly diagnosed diffuse large B-cell lymphoma (DLBCL). This retrospective study included 51 patients with newly diagnosed DLBCL who had undergone both unenhanced and intravenous contrast-enhanced CT before R-CHOP (rituximab, cyclophosphamide, hydroxydaunorubicin, oncovin and prednisolone) chemo-immunotherapy. Presence of tumor necrosis was visually and quantitatively assessed at CT. Associations between tumor necrosis status at CT and the National Comprehensive Cancer Network (NCCN) International Prognostic Index (IPI) factors were assessed. Cox regression analysis was used to determine the prognostic impact of NCCN-IPI scores and tumor necrosis status at CT. There were no correlations between tumor necrosis status at CT and the NCCN-IPI factors categorized age (ρ=-0.042, P=0.765), categorized lactate dehydrogenase (LDH) ratio (ρ=0.201, P=0.156), extranodal disease in major organs (φ=-0.245, P=0.083), Ann Arbor stage III/IV disease (φ=-0.208, P=0.141), and Eastern Cooperative Oncology Group (ECOG) performance status (φ=0.015, P=0.914). In the multivariate Cox proportional hazards model, only tumor necrosis status at CT was an independent predictive factor of progression-free survival (P=0.003) and overall survival (P=0.004). The findings of this study indicate the prognostic potential of tumor necrosis at CT in newly diagnosed DLBCL. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  20. Preclinical Magnetic Resonance Imaging and Systems Biology in Cancer Research

    PubMed Central

    Albanese, Chris; Rodriguez, Olga C.; VanMeter, John; Fricke, Stanley T.; Rood, Brian R.; Lee, YiChien; Wang, Sean S.; Madhavan, Subha; Gusev, Yuriy; Petricoin, Emanuel F.; Wang, Yue

    2014-01-01

    Biologically accurate mouse models of human cancer have become important tools for the study of human disease. The anatomical location of various target organs, such as brain, pancreas, and prostate, makes determination of disease status difficult. Imaging modalities, such as magnetic resonance imaging, can greatly enhance diagnosis, and longitudinal imaging of tumor progression is an important source of experimental data. Even in models where the tumors arise in areas that permit visual determination of tumorigenesis, longitudinal anatomical and functional imaging can enhance the scope of studies by facilitating the assessment of biological alterations, (such as changes in angiogenesis, metabolism, cellular invasion) as well as tissue perfusion and diffusion. One of the challenges in preclinical imaging is the development of infrastructural platforms required for integrating in vivo imaging and therapeutic response data with ex vivo pathological and molecular data using a more systems-based multiscale modeling approach. Further challenges exist in integrating these data for computational modeling to better understand the pathobiology of cancer and to better affect its cure. We review the current applications of preclinical imaging and discuss the implications of applying functional imaging to visualize cancer progression and treatment. Finally, we provide new data from an ongoing preclinical drug study demonstrating how multiscale modeling can lead to a more comprehensive understanding of cancer biology and therapy. PMID:23219428

  1. Survey of current situation in radiation belt modeling

    NASA Technical Reports Server (NTRS)

    Fung, Shing F.

    2004-01-01

    The study of Earth's radiation belts is one of the oldest subjects in space physics. Despite the tremendous progress made in the last four decades, we still lack a complete understanding of the radiation belts in terms of their configurations, dynamics, and detailed physical accounts of their sources and sinks. The static nature of early empirical trapped radiation models, for examples, the NASA AP-8 and AE-8 models, renders those models inappropriate for predicting short-term radiation belt behaviors associated with geomagnetic storms and substorms. Due to incomplete data coverage, these models are also inaccurate at low altitudes (e.g., <1000 km) where many robotic and human space flights occur. The availability of radiation data from modern space missions and advancement in physical modeling and data management techniques have now allowed the development of new empirical and physical radiation belt models. In this paper, we will review the status of modern radiation belt modeling. Published by Elsevier Ltd on behalf of COSPAR.

  2. Speech Research: A Report on the Status and Progress of Studies on the Nature of Speech, Instrumentation for Its Investigation, and Practical Applications, Status Report, July 1-December 31, 1982.

    ERIC Educational Resources Information Center

    Haskins Labs., New Haven, CT.

    Research reports on the nature of speech, instrumentation for the investigation of speech, and practical applications of speech research are presented in this status report. The 18 reports deal with a variety of topics, including the following: (1) cyclic production of vowels in sequences of monosyllabic stress feet; (2) differences between…

  3. Speech Research: A Report on the Status and Progress of Studies on the Nature of Speech, Instrumentation for Its Investigation, and Practical Applications, April 1-June 30, 1981. Status Report 66.

    ERIC Educational Resources Information Center

    Haskins Labs., New Haven, CT.

    Research reports on the nature of speech, instrumentation for the investigation of speech, and practical applications of speech research are included in this status report for the April 1-June 30, 1981, period. The 14 reports deal with the following topics: (1) electromyography as a technique for laryngeal investigation, (2) the phonatory…

  4. Speech Research: A Report on the Status and Progress of Studies on the Nature of Speech, Instrumentation for Its Investigation, and Practical Applications, Status Report, April 1-June 30, 1982.

    ERIC Educational Resources Information Center

    Haskins Labs., New Haven, CT.

    Research reports on the nature of speech, instrumentation for its investigation, and practical applications of research are provided in this status report covering the period of April 1 through June 30, 1982. The 13 reports deal with the following topics: (1) the functional significance of physiological tremor, (2) differences between experienced…

  5. Estimation of genetic parameters and response to selection for a continuous trait subject to culling before testing.

    PubMed

    Arnason, T; Albertsdóttir, E; Fikse, W F; Eriksson, S; Sigurdsson, A

    2012-02-01

    The consequences of assuming a zero environmental covariance between a binary trait 'test-status' and a continuous trait on the estimates of genetic parameters by restricted maximum likelihood and Gibbs sampling and on response from genetic selection when the true environmental covariance deviates from zero were studied. Data were simulated for two traits (one that culling was based on and a continuous trait) using the following true parameters, on the underlying scale: h² = 0.4; r(A) = 0.5; r(E) = 0.5, 0.0 or -0.5. The selection on the continuous trait was applied to five subsequent generations where 25 sires and 500 dams produced 1500 offspring per generation. Mass selection was applied in the analysis of the effect on estimation of genetic parameters. Estimated breeding values were used in the study of the effect of genetic selection on response and accuracy. The culling frequency was either 0.5 or 0.8 within each generation. Each of 10 replicates included 7500 records on 'test-status' and 9600 animals in the pedigree file. Results from bivariate analysis showed unbiased estimates of variance components and genetic parameters when true r(E) = 0.0. For r(E) = 0.5, variance components (13-19% bias) and especially (50-80%) were underestimated for the continuous trait, while heritability estimates were unbiased. For r(E) = -0.5, heritability estimates of test-status were unbiased, while genetic variance and heritability of the continuous trait together with were overestimated (25-50%). The bias was larger for the higher culling frequency. Culling always reduced genetic progress from selection, but the genetic progress was found to be robust to the use of wrong parameter values of the true environmental correlation between test-status and the continuous trait. Use of a bivariate linear-linear model reduced bias in genetic evaluations, when data were subject to culling. © 2011 Blackwell Verlag GmbH.

  6. Multi-state modelling of repeated hospitalisation and death in patients with heart failure: The use of large administrative databases in clinical epidemiology.

    PubMed

    Ieva, Francesca; Jackson, Christopher H; Sharples, Linda D

    2017-06-01

    In chronic diseases like heart failure (HF), the disease course and associated clinical event histories for the patient population vary widely. To improve understanding of the prognosis of patients and enable health care providers to assess and manage resources, we wish to jointly model disease progression, mortality and their relation with patient characteristics. We show how episodes of hospitalisation for disease-related events, obtained from administrative data, can be used as a surrogate for disease status. We propose flexible multi-state models for serial hospital admissions and death in HF patients, that are able to accommodate important features of disease progression, such as multiple ordered events and competing risks. Fully parametric and semi-parametric semi-Markov models are implemented using freely available software in R. The models were applied to a dataset from the administrative data bank of the Lombardia region in Northern Italy, which included 15,298 patients who had a first hospitalisation ending in 2006 and 4 years of follow-up thereafter. This provided estimates of the associations of age and gender with rates of hospital admission and length of stay in hospital, and estimates of the expected total time spent in hospital over five years. For example, older patients and men were readmitted more frequently, though the total time in hospital was roughly constant with age. We also discuss the relative merits of parametric and semi-parametric multi-state models, and model assessment and comparison.

  7. Oxidative Stress during the Progression of β-Amyloid Pathology in the Neocortex of the Tg2576 Mouse Model of Alzheimer's Disease.

    PubMed

    Porcellotti, Sara; Fanelli, Francesca; Fracassi, Anna; Sepe, Sara; Cecconi, Francesco; Bernardi, Cinzia; Cimini, AnnaMaria; Cerù, Maria Paola; Moreno, Sandra

    2015-01-01

    Alzheimer's disease (AD) is the most common form of dementia, characterized by progressive neurodegeneration. Pathogenetic mechanisms, triggered by β-amyloid (Aβ) accumulation, include oxidative stress, derived from energy homeostasis deregulation and involving mitochondria and peroxisomes. We here addressed the oxidative stress status and the elicited cellular response at the onset and during the progression of Aβ pathology, studying the neocortex of Tg2576 model of AD. Age-dependent changes of oxidative damage markers, antioxidant enzymes, and related transcription factors were analysed in relation to the distribution of Aβ peptide and oligomers, by a combined molecular/morphological approach. Nucleic acid oxidative damage, accompanied by defective antioxidant defences, and decreased PGC1α expression are already detected in 3-month-old Tg2576 neurons. Conversely, PPARα is increased in these cells, with its cytoplasmic localization suggesting nongenomic, anti-inflammatory actions. At 6 months, when intracellular Aβ accumulates, PMP70 is downregulated, indicating impairment of fatty acids peroxisomal translocation and their consequent harmful accumulation. In 9-month-old Tg2576 neocortex, Aβ oligomers and acrolein deposition correlate with GFAP, GPX1, and PMP70 increases, supporting a compensatory response, involving astroglial peroxisomes. At severe pathological stages, when senile plaques disrupt cortical cytoarchitecture, antioxidant capacity is gradually lost. Overall, our data suggest early therapeutic intervention in AD, also targeting peroxisomes.

  8. 75 FR 9232 - Measuring Progress on Food Safety: Current Status and Future Directions; Public Workshop

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-01

    ... for assessing progress in food safety and associated methodological issues and to discuss potential.... The FoodNet also conducts special studies to determine risk factors for acquiring those illnesses... production, studies on the prevalence of specific pathogens in specific classes of food, and studies of...

  9. Curriculum in Conflict: Social Visions, Educational Agendas, and Progressive School Reform.

    ERIC Educational Resources Information Center

    Beyer, Landon E.; Liston, Daniel P.

    The construction and reconstruction of public school and college curricula cannot be understood without an understanding of how they are intimately tied to larger social currents and cross-currents. This book attempts to provide a coherent yet inconclusive synthesis of the progressive tradition that challenges both the curricular status quo and…

  10. Association between circulating vitamin K1 and coronary calcium progression in community-dwelling adults: the Multi-Ethnic Study of Atherosclerosis

    USDA-ARS?s Scientific Manuscript database

    While animal studies found vitamin K treatment reduced vascular calcification, human data are limited. Using a case-cohort design, we determined the association between vitamin K status and coronary artery calcium (CAC) progression in the Multi-ethnic Study of Atherosclerosis. Serum phylloquinone (v...

  11. On Campus with Women, 1999-2000.

    ERIC Educational Resources Information Center

    Reiss, Susan, Ed.

    2000-01-01

    The four issues in this newsletter volume present information on the status and education of women. The focus of issue 1 is women and scientific literacy. Issue 2 contains the lead article, "Progress in Fits and Starts," which concentrates on the progress of women in higher education and trends in enrollment and degree completion. Issue 3 focuses…

  12. Voices for America's Children: The Progress and the Promise.

    ERIC Educational Resources Information Center

    Foster, Catherine Crystal

    On the occasion of the fifteenth anniversary of the National Association of Child Advocates (NACA), this report discusses the current status of children, demonstrates the progress in the well-being of children due to the organization's efforts, identifies current challenges for child advocates, and describes the history of the organization.…

  13. Category and Letter Fluency in Semantic Dementia, Primary Progressive Aphasia, and Alzheimer's Disease

    ERIC Educational Resources Information Center

    Marczinski, Cecile A.; Kertesz, Andrew

    2006-01-01

    This study examined the impact of various degenerative dementias on access to semantic knowledge and the status of semantic representations. Patients with semantic dementia, primary progressive aphasia, and Alzheimer's disease were compared with elderly controls on tasks of category and letter fluency, with number of words generated, mean lexical…

  14. Development and Implementation of Joint Programs in Laser Ranging and Other Space Geodetic Techniques

    NASA Technical Reports Server (NTRS)

    Pearlman, Michael R.; Carter, David (Technical Monitor)

    2004-01-01

    This progress report discusses the status and progress made in joint international programs including: 1) WEGENER; 2) Arabian Peninsula program; 3) Asia-Pacific Space Geodynamics (APSG) program; 4) the Fourteenth International Workshop on Laser Ranging; 5) the International Laser Ranging Service; and 6) current support for the NASA network.

  15. The Relationship between Adequate Yearly Progress and the Quality of Professional Development

    ERIC Educational Resources Information Center

    Wolff, Lori A.; McClelland, Susan S.; Stewart, Stephanie E.

    2010-01-01

    Based on publicly available data, the study examined the relationship between adequate yearly progress status and teachers' perceptions of the quality of their professional development. The sample included responses of 5,558 teachers who completed the questionnaire in the 2005-2006 school year. Results of the statistical analysis show a…

  16. 32 CFR 34.41 - Monitoring and reporting program and financial performance.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... performance. 34.41 Section 34.41 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE DoD... and business status, as follows: (1) The program portions of the reports must address progress toward... program progress reported in the periodic report, in relation to reported expenditures, is sufficient to...

  17. 32 CFR 34.41 - Monitoring and reporting program and financial performance.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... performance. 34.41 Section 34.41 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE DoD... and business status, as follows: (1) The program portions of the reports must address progress toward... program progress reported in the periodic report, in relation to reported expenditures, is sufficient to...

  18. 32 CFR 34.41 - Monitoring and reporting program and financial performance.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... performance. 34.41 Section 34.41 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE DoD... and business status, as follows: (1) The program portions of the reports must address progress toward... program progress reported in the periodic report, in relation to reported expenditures, is sufficient to...

  19. 32 CFR 34.41 - Monitoring and reporting program and financial performance.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... performance. 34.41 Section 34.41 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE DoD... and business status, as follows: (1) The program portions of the reports must address progress toward... program progress reported in the periodic report, in relation to reported expenditures, is sufficient to...

  20. Progress Report on Rural Development for Fiscal Year 1970.

    ERIC Educational Resources Information Center

    Department of Agriculture, Washington, DC.

    Rural development progress relative to State-U.S. Department of Agriculture (USDA) committees is presented via exemplary citation in this 1970 report. Summaries are given for: (1) Status of State-USDA Organization for Rural Development, (2) Functional Relationships of USDA Committees on Rural Development, (3) Activities and Projects Underway, (4)…

  1. THE U.S. ENVIRONMENTAL PROTECTION AGENCY PARTICULATE MATTER HEALTH EFFECTS RESEARCH CENTERS PROGRAM: A MIDCOURSE REPORT OF STATUS, PROGRESS, AND PLANS. (R827351)

    EPA Science Inventory

    The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

  2. Creating a Government That Works Better & Costs Less. Status Report. Report of the National Performance Review.

    ERIC Educational Resources Information Center

    Gore, Al

    This publication reports on progress 1 year into the Clinton Administration's "Reinventing Government" initiative, a long-term effort at significantly revamping the federal government's operations. A preliminary chapter notes the culture change involved in the reinvention process. Individual chapters then report progress for each of the…

  3. Chemical vapor deposition modeling: An assessment of current status

    NASA Technical Reports Server (NTRS)

    Gokoglu, Suleyman A.

    1991-01-01

    The shortcomings of earlier approaches that assumed thermochemical equilibrium and used chemical vapor deposition (CVD) phase diagrams are pointed out. Significant advancements in predictive capabilities due to recent computational developments, especially those for deposition rates controlled by gas phase mass transport, are demonstrated. The importance of using the proper boundary conditions is stressed, and the availability and reliability of gas phase and surface chemical kinetic information are emphasized as the most limiting factors. Future directions for CVD are proposed on the basis of current needs for efficient and effective progress in CVD process design and optimization.

  4. CALIPSO at Four: Results and Progress

    NASA Technical Reports Server (NTRS)

    Winker, Dave; Hu, Yong; Pitts, Mike; Tackett, Jason; Kittaka, Chieko; Liu, Zhaoyan; Vaughan, Mark

    2010-01-01

    Aerosols and clouds play important roles in Earth?s climate system, but limitations in our ability to observe them globally limit our understanding of the climate system and our ability to model it. The CALIPSO satellite was developed to provide new capabilities to observe aerosol and cloud from space. CALIPSO carries the first polarization-sensitive lidar to fly in space, which has now provided a four-year record of global aerosol and cloud profiles. This paper briefly summarizes the status of the CALIPSO mission, describes some of the results from CALIPSO, and presents highlights of recent improvements in data products.

  5. Ultralightweight Ballute Technology Advances

    NASA Technical Reports Server (NTRS)

    Masciarelli, Jim; Miller, Kevin

    2005-01-01

    Ultralightweight ballutes offer the potential to provide the deceleration for entry and aerocapture missions at a fraction of the mass of traditional methods. A team consisting of Ball Aerospace, ILC Dover, NASA Langley, NASA Johnson, and the Jet Propulsion Laboratory has been addressing the technical issues associated with ultralightweight ballutes for aerocapture at Titan. Significant progress has been made in the areas of ballute materials, aerothermal analysis, trajectory control, and aeroelastic modeling. The status and results of efforts in these areas are presented. The results indicate that an ultralightweight ballute system mass of 8 to 10 percent of the total entry mass is possible.

  6. Current Status of Programs and Research within the NASA Orbital Debris Program Office

    NASA Technical Reports Server (NTRS)

    Bacon, Jack

    2016-01-01

    The NASA Orbital Debris Program Office (ODPO) is the world's longest-standing orbital debris research organization. It supports all aspects of international and US national policy-making related to the orbital environment and to spacecraft life cycle requirements. Representing more than just NASA projects, it is the United States' center of expertise in the field. The office continues to advance research in all aspects of orbital debris, including its measurement, modeling, and risk assessment for both orbital and ground safety concerns. This presentation will highlight current activities and recent progress in all aspects of the ODPO's mission.

  7. JWST and Exoplanets

    NASA Technical Reports Server (NTRS)

    Mather, John C.

    2009-01-01

    The James Webb Space Telescope is on track for a launch in 2013. The author reviews the status and progress on the key hardware. The first primary mirror segments are already at MSFC for cryogenic tests, the mid IR instrument (MIRI) has already had successful tests of the engineering model, and the detectors are showing excellent performance. The author also describes the scientific objectives of the mission, with emphasis on the predicted capabilities for observing planets by the transit technique and through direct imaging. Recent direct observations of planets by HST and by adaptive optics from the ground have shown that, under favorable circumstances, much can be learned.

  8. Status Report on Speech Research, No. 29/30, January-June 1972.

    ERIC Educational Resources Information Center

    Haskins Labs., New Haven, CT.

    This report is one of a regular series on the status and progress of studies on the nature of speech, instrumentation for its investigation, and practical applications. Manuscripts and extended reports cover the following topics: iconic storage, voice-timing perception, oral anesthesia, laryngeal function, electromyography of speech production,…

  9. 94-1 Research and development project lead laboratory support. Status report, January 1--March 31, 1996

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

    Dinehart, M.

    1996-09-01

    This document reports status and technical progress for Los Alamos National Laboratories 94-1 Research and Development projects. An introduction to the project structure and an executive summary are included. Projects described include Electrolytic Decontamination, Combustibles, Detox, Sand, Slag, and Crucible, Surveillance, and Core Technology.

  10. Nurse Education in Higher Education: Understanding Cultural Barriers to Progress.

    ERIC Educational Resources Information Center

    Miers, Margaret

    2002-01-01

    Review of nursing education research revealed cultural factors that contribute to nursing's lack of equal status in higher education: antiintellectualism in nursing and academic denigration of practice. These factors are linked to the history of women's education, separation between intellectual and practical, and the low status of caring in the…

  11. Child Abuse and Neglect: A Report on the Status of the Research.

    ERIC Educational Resources Information Center

    Hurt, Maure, Jr.

    This state-of-the-art report provides preliminary information on the status of child abuse and neglect research projects currently in progress or recently completed. Each chapter discusses a particular research problem area and outlines the relevant demonstration projects. Chapter I describes the background of our present perception of child abuse…

  12. The effects of progressing and nonprogressing Mycobacterium avium ssp. paratuberculosis infection on milk production in dairy cows

    USDA-ARS?s Scientific Manuscript database

    Longitudinal data from three commercial dairy herds in the northeast United States, collected from 2004 to 2011, were analyzed to determine the effect of Johne’s disease status and path on milk production. Disease status, as indicated by Mycobacterium avium subsp. paratuberculosis test results, was ...

  13. Speech Research Status Report, January-June 1994.

    ERIC Educational Resources Information Center

    Fowler, Carol A., Ed.

    This publication (one of a series) contains 14 articles which report the status and progress of studies on the nature of speech, instruments for its investigation, and practical applications. Articles include: "The Universality of Intrinsic FO of Vowels: (D. H. Whalen and Andrea G. Levitt); "Intrinsic F0 of Vowels in the Babbling of 6-,…

  14. Stages of Change in Relationship Status Questionnaire: Development and Validation

    ERIC Educational Resources Information Center

    Ritter, Kathrin; Handsel, Vanessa; Moore, Todd

    2016-01-01

    This study involved the development of the Stages of Change in Relationship Status (SOCRS) measure in 2 samples of college students. This scale is designed to measure how individuals progress through stages of change when terminating violent and nonviolent intimate relationships. Results indicated that the SOCRS is a reliable and valid tool to…

  15. How Numbers, Nature, and Immune Status of Foxp3+ Regulatory T-Cells Shape the Early Immunological Events in Tumor Development

    PubMed Central

    Darrasse-Jèze, Guillaume; Podsypanina, Katrina

    2013-01-01

    The influence of CD4+CD25+Foxp3+ regulatory T-cells (Tregs) on cancer progression has been demonstrated in a large number of preclinical models and confirmed in several types of malignancies. Neoplastic processes trigger an increase of Treg numbers in draining lymph nodes, spleen, blood, and tumors, leading to the suppression of anti-tumor responses. Treg-depletion before or early in tumor development may lead to complete tumor eradication and extends survival of mice and humans. However this strategy is ineffective in established tumors, highlighting the critical role of the early Treg-tumor encounters. In this review, after discussing old and new concepts of immunological tumor tolerance, we focus on the nature (thymus-derived vs. peripherally derived) and status (naïve or activated/memory) of the regulatory T-cells at tumor emergence. The recent discoveries in this field suggest that the activation status of Tregs and effector T-cells (Teffs) at the first encounter with the tumor are essential to shape the fate and speed of the immune response across a variety of tumor models. The relative timing of activation/recruitment of anti-tumor cells vs. tolerogenic cells at tumor emergence appears to be crucial in the identification of tumor cells as friend or foe, which has broad implications for the design of cancer immunotherapies. PMID:24133490

  16. Current status and patent prospective of animal models in diabetic research

    PubMed Central

    Dhuria, Radhey S.; Singh, Gurpreet; Kaur, Anudeep; Kaur, Ramandeep; Kaur, Tanurajvir

    2015-01-01

    Diabetes mellitus is a heterogeneous complex metabolic disorder with multiple etiology which characterized by chronic hyperglycemia resulting from defects in insulin secretion, insulin action or both. The widespread occurrence of diabetes throughout the world has increased dramatically over the past few years. For better understanding, appropriate animal models that closely mimic the changes in humans needed, as vital tool for understanding the etiology and pathogenesis of the disease at the cellular/molecular level and for preclinical testing of drugs. This review aims to describe the animal models of type-1 diabetes (T1Ds) and T2Ds to mimic the causes and progression of the disease in humans. And also we highlight patent applications published in the last few years related to animal models in diabetes as an important milestone for future therapies that are aim to treating diabetes with specific symptoms and complications. PMID:26261819

  17. Current status and patent prospective of animal models in diabetic research.

    PubMed

    Dhuria, Radhey S; Singh, Gurpreet; Kaur, Anudeep; Kaur, Ramandeep; Kaur, Tanurajvir

    2015-01-01

    Diabetes mellitus is a heterogeneous complex metabolic disorder with multiple etiology which characterized by chronic hyperglycemia resulting from defects in insulin secretion, insulin action or both. The widespread occurrence of diabetes throughout the world has increased dramatically over the past few years. For better understanding, appropriate animal models that closely mimic the changes in humans needed, as vital tool for understanding the etiology and pathogenesis of the disease at the cellular/molecular level and for preclinical testing of drugs. This review aims to describe the animal models of type-1 diabetes (T1Ds) and T2Ds to mimic the causes and progression of the disease in humans. And also we highlight patent applications published in the last few years related to animal models in diabetes as an important milestone for future therapies that are aim to treating diabetes with specific symptoms and complications.

  18. Reducing social inequalities in health: work-related strategies.

    PubMed

    Siegrist, Johannes

    2002-01-01

    Despite reduced health risks in terms of physical and chemical hazards current trends in occupational life continue to contribute to ill health and disease among economically active people. Stress at work plays a crucial role in this respect, as evidenced by recent scientific progress. This paper discusses two leading theoretical models of work-related stress, the demand-control model and the model of effort-reward imbalance, and it summarizes available evidence on adverse health effects. As work stress in terms of these models is more prevalent among lower socioeconomic status groups, these conditions contribute to the explanation of socially graded risks of morbidity and mortality in midlife. Implications of this new knowledge for the design and implementation of worksite health-promotion measures are elaborated. In conclusion, it is argued that workplace strategies deserve high priority on any agenda that aims at reducing social inequalities in health.

  19. A Longitudinal Item Response Theory Model to Characterize Cognition Over Time in Elderly Subjects

    PubMed Central

    Bornkamp, Björn; Krahnke, Tillmann; Mielke, Johanna; Monsch, Andreas; Quarg, Peter

    2017-01-01

    For drug development in neurodegenerative diseases such as Alzheimer's disease, it is important to understand which cognitive domains carry the most information on the earliest signs of cognitive decline, and which subject characteristics are associated with a faster decline. A longitudinal Item Response Theory (IRT) model was developed for the Basel Study on the Elderly, in which the Consortium to Establish a Registry for Alzheimer's Disease – Neuropsychological Assessment Battery (with additions) and the California Verbal Learning Test were measured on 1,750 elderly subjects for up to 13.9 years. The model jointly captured the multifaceted nature of cognition and its longitudinal trajectory. The word list learning and delayed recall tasks carried the most information. Greater age at baseline, fewer years of education, and positive APOEɛ4 carrier status were associated with a faster cognitive decline. Longitudinal IRT modeling is a powerful approach for progressive diseases with multifaceted endpoints. PMID:28643388

  20. Is Fluid Overload More Important than Diabetes in Renal Progression in Late Chronic Kidney Disease?

    PubMed Central

    Tsai, Yi-Chun; Tsai, Jer-Chia; Chiu, Yi-Wen; Kuo, Hung-Tien; Chen, Szu-Chia; Hwang, Shang-Jyh; Chen, Tzu-Hui; Kuo, Mei-Chuan; Chen, Hung-Chun

    2013-01-01

    Fluid overload is one of the major presentations in patients with late stage chronic kidney disease (CKD). Diabetes is the leading cause of renal failure, and progression of diabetic nephropathy has been associated with changes in extracellular fluid volume. The aim of the study was to assess the association of fluid overload and diabetes in commencing dialysis and rapid renal function decline (the slope of estimated glomerular filtration rate (eGFR) less than -3 ml/min per 1.73 m2/y) in 472 patients with stages 4-5 CKD. Fluid status was determined by bioimpedance spectroscopy method, Body Composition Monitor. The study population was further classified into four groups according to the median of relative hydration status (△HS =fluid overload/extracellular water) and the presence or absence of diabetes. The median level of relative hydration status was 7%. Among all patients, 207(43.9 %) were diabetic. 71 (15.0%) subjects had commencing dialysis, and 187 (39.6%) subjects presented rapid renal function decline during a median 17.3-month follow-up. Patients with fluid overload had a significantly increased risk for commencing dialysis and renal function decline independent of the presence or absence of diabetes. No significantly increased risk for renal progression was found between diabetes and non-diabetes in late CKD without fluid overload. In conclusion, fluid overload has a higher predictive value of an elevated risk for renal progression than diabetes in late CKD. PMID:24349311

  1. Regenerative life support system research and concepts

    NASA Technical Reports Server (NTRS)

    1988-01-01

    Life support systems that involve recycling of atmospheres, water, food and waste are so complex that models incorporating all the interactions and relationships are vital to design, development, simulations, and ultimately to control of space qualified systems. During early modeling studies, FORTRAN and BASIC programs were used to obtain numerical comparisons of the performance of different regenerative concepts. Recently, models were made by combining existing capabilities with expert systems to establish an Intelligent Design Support Environment for simpliflying user interfaces and to address the need for the engineering aspects. Progress was also made toward modeling and evaluating the operational aspects of closed loop life support systems using Time-step and Dynamic simulations over a period of time. Example models are presented which show the status and potential of developed modeling techniques. For instance, closed loop systems involving algae systeMs for atmospheric purification and food supply augmentation, plus models employing high plants and solid waste electrolysis are described and results of initial evaluations are presented.

  2. A unified model of the hierarchical and stochastic theories of gastric cancer

    PubMed Central

    Song, Yanjing; Wang, Yao; Tong, Chuan; Xi, Hongqing; Zhao, Xudong; Wang, Yi; Chen, Lin

    2017-01-01

    Gastric cancer (GC) is a life-threatening disease worldwide. Despite remarkable advances in treatments for GC, it is still fatal to many patients due to cancer progression, recurrence and metastasis. Regarding the development of novel therapeutic techniques, many studies have focused on the biological mechanisms that initiate tumours and cause treatment resistance. Tumours have traditionally been considered to result from somatic mutations, either via clonal evolution or through a stochastic model. However, emerging evidence has characterised tumours using a hierarchical organisational structure, with cancer stem cells (CSCs) at the apex. Both stochastic and hierarchical models are reasonable systems that have been hypothesised to describe tumour heterogeneity. Although each model alone inadequately explains tumour diversity, the two models can be integrated to provide a more comprehensive explanation. In this review, we discuss existing evidence supporting a unified model of gastric CSCs, including the regulatory mechanisms of this unified model in addition to the current status of stemness-related targeted therapy in GC patients. PMID:28301871

  3. OpenMDAO Framework Status

    NASA Technical Reports Server (NTRS)

    Naiman, Cynthia Gutierrez

    2010-01-01

    Advancing and exploring the science of Multidisciplinary Analysis & Optimization (MDAO) capabilities are high-level goals in the Fundamental Aeronautics Program s Subsonic Fixed Wing (SFW) project. The OpenMDAO team has made significant progress toward completing the Alpha OpenMDAO deliverable due in September 2010. Included in the presentation are: details of progress on developing the OpenMDAO framework, example usage of OpenMDAO, technology transfer plans, near term plans, progress toward establishing partnerships with external parties, and discussion of additional potential collaborations.

  4. Delineating the regulation of energy homeostasis using hypothalamic cell models.

    PubMed

    Wellhauser, Leigh; Gojska, Nicole M; Belsham, Denise D

    2015-01-01

    Attesting to its intimate peripheral connections, hypothalamic neurons integrate nutritional and hormonal cues to effectively manage energy homeostasis according to the overall status of the system. Extensive progress in the identification of essential transcriptional and post-translational mechanisms regulating the controlled expression and actions of hypothalamic neuropeptides has been identified through the use of animal and cell models. This review will introduce the basic techniques of hypothalamic investigation both in vivo and in vitro and will briefly highlight the key advantages and challenges of their use. Further emphasis will be place on the use of immortalized models of hypothalamic neurons for in vitro study of feeding regulation, with a particular focus on cell lines proving themselves most fruitful in deciphering fundamental basics of NPY/AgRP, Proglucagon, and POMC neuropeptide function. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Status Report on Speech Research: A Report on the Status and Progress of Studies on the Nature of Speech, Instrumentation for Its Investigation, and Practical Applications, April 1-June 30, 1980.

    ERIC Educational Resources Information Center

    Haskins Labs., New Haven, CT.

    Research reports on the nature of speech, instrumentation for the investigation of speech, and practical applications of research are included in this status report for the April 1-June 30, 1980, period. The reports deal with the following topics: (1) the perceptual equivalent of two acoustic cues for a speech contrast is specific to phonetic…

  6. Status Report on Speech Research: A Report on the Status and Progress of Studies on the Nature of Speech, Instrumentation for Its Investigation, and Practical Applications, January 1-March 31, 1983.

    ERIC Educational Resources Information Center

    Studdert-Kennedy, Michael, Ed.; O'Brian, Nancy, Ed.

    Research reports on the nature of speech, instrumentation for its investigation, and practical applications of research are provided in this status report covering the period of January 1 through March 31, 1983. The 16 reports deal with the following topics: (1) the influence of subcategorical mismatches on lexical access, (2) the Serbo-Croatian…

  7. The Anticholinergic and Antiglutamatergic Drug Caramiphen Reduces Seizure Duration in Soman-Exposed Rats: Synergism with the Benzodiazepine Diazepam

    DTIC Science & Technology

    2012-01-01

    progress to self-sustained seizures ( status epilepticus , SE) and result in extensive neuropathology as seen in rats (de Araujo Furtado et al., 2009, 2010...physostigmineOP organophosphorus BuChE butyrylcholinesterase ChE cholinesterase SE status epilepticus ATR atropine sulfate 2-PAM 2-pralidoxime NMDA N...L.C., Lichtenstein, S., Yourick, D.L., 2010. Spontaneous recurrent seizures after status epilepticus induced by soman in Sprague-Dawley rats

  8. Nutritional status in patients with hepatitis C.

    PubMed

    Ismail, Faisal Wasim; Khan, Rustam A; Kamani, Lubna; Wadalawala, Ashfaq A; Shah, Hasnain Ali; Hamid, Saeed S; Jafri, Wasim

    2012-03-01

    To assess the nutritional status via the SGA (subjective global assessment) screening tool of patients at all stages of hepatitis C virus (HCV) liver disease. Descriptive study. Out-patient Clinics of the Aga Khan University Hospital, Karachi, conducted from October 2009 to January 2011. Patients with hepatitis C virus infection and their HCV-negative attendants were enrolled from the outpatient clinics, and categorized into 4 groups of 100 patients each: healthy controls (HC), those with chronic hepatitis C infection (CHC), compensated cirrhotics (CC) and decompensated cirrhotics (DC). The validated subjective global assessment (SGA) tool was used to assess nutritional status. A total of 400 patients were enrolled. Most of the patients in the HC group were class 'A' (best nutritional status). In contrast, the majority (64%) in the DC group were in the class 'C' (worst status). The compensated cirrhosis (CC) group showed that 90% of patients were malnourished, while 98% of all patients were malnourished in the DC group, predominantly class 'C'. Most importantly, 14% of patients with chronic hepatitis C (CHC) also scored a 'B' on the SGA; which when compared to HC was statistically significant (p=0.005). As the groups progressed in their disease from CHC to DC, the transition in nutritional status from 'A' to 'C' between groups was statistically significant. Malnutrition occurs early in the course of HCV, and progresses relentlessly throughout the spectrum of HCVdisease.

  9. Hypothermia for Neuroprotection in Convulsive Status Epilepticus.

    PubMed

    Legriel, Stephane; Lemiale, Virginie; Schenck, Maleka; Chelly, Jonathan; Laurent, Virginie; Daviaud, Fabrice; Srairi, Mohamed; Hamdi, Aicha; Geri, Guillaume; Rossignol, Thomas; Hilly-Ginoux, Julia; Boisramé-Helms, Julie; Louart, Benjamin; Malissin, Isabelle; Mongardon, Nicolas; Planquette, Benjamin; Thirion, Marina; Merceron, Sybille; Canet, Emmanuel; Pico, Fernando; Tran-Dinh, Yves-Roger; Bedos, Jean-Pierre; Azoulay, Elie; Resche-Rigon, Matthieu; Cariou, Alain

    2016-12-22

    Convulsive status epilepticus often results in permanent neurologic impairment. We evaluated the effect of induced hypothermia on neurologic outcomes in patients with convulsive status epilepticus. In a multicenter trial, we randomly assigned 270 critically ill patients with convulsive status epilepticus who were receiving mechanical ventilation to hypothermia (32 to 34°C for 24 hours) in addition to standard care or to standard care alone; 268 patients were included in the analysis. The primary outcome was a good functional outcome at 90 days, defined as a Glasgow Outcome Scale (GOS) score of 5 (range, 1 to 5, with 1 representing death and 5 representing no or minimal neurologic deficit). The main secondary outcomes were mortality at 90 days, progression to electroencephalographically (EEG) confirmed status epilepticus, refractory status epilepticus on day 1, "super-refractory" status epilepticus (resistant to general anesthesia), and functional sequelae on day 90. A GOS score of 5 occurred in 67 of 138 patients (49%) in the hypothermia group and in 56 of 130 (43%) in the control group (adjusted common odds ratio, 1.22; 95% confidence interval [CI], 0.75 to 1.99; P=0.43). The rate of progression to EEG-confirmed status epilepticus on the first day was lower in the hypothermia group than in the control group (11% vs. 22%; odds ratio, 0.40; 95% CI, 0.20 to 0.79; P=0.009), but there were no significant differences between groups in the other secondary outcomes. Adverse events were more frequent in the hypothermia group than in the control group. In this trial, induced hypothermia added to standard care was not associated with significantly better 90-day outcomes than standard care alone in patients with convulsive status epilepticus. (Funded by the French Ministry of Health; HYBERNATUS ClinicalTrials.gov number, NCT01359332 .).

  10. Occurrence of spontaneous periodontal disease in the SAMP1/YitFc murine model of Crohn disease.

    PubMed

    Pietropaoli, Davide; Del Pinto, Rita; Corridoni, Daniele; Rodriguez-Palacios, Alexander; Di Stefano, Gabriella; Monaco, Annalisa; Weinberg, Aaron; Cominelli, Fabio

    2014-12-01

    Oral involvement is often associated with inflammatory bowel disease (IBD). Recent evidence suggests a high incidence of periodontal disease in patients with Crohn disease (CD). To the best of the authors' knowledge, no animal model of IBD that displays associated periodontal disease was reported previously. The aim of this study is to investigate the occurrence and progression of periodontal disease in SAMP1/YitFc (SAMP) mice that spontaneously develop a CD-like ileitis. In addition, the temporal correlation between the onset and progression of periodontal disease and the onset of ileitis in SAMP mice was studied. At different time points, SAMP and parental AKR/J (AKR) control mice were sacrificed, and mandibles were prepared for stereomicroscopy and histology. Terminal ilea were collected for histologic assessment of inflammation score. Periodontal status, i.e., alveolar bone loss (ABL) and alveolar bone crest, was examined by stereomicroscopy and histomorphometry, respectively. ABL increased in both strains with age. SAMP mice showed greater ABL compared with AKR mice by 12 weeks of age, with maximal differences observed at 27 weeks of age. AKR control mice did not show the same severity of periodontal disease. Interestingly, a strong positive correlation was found between ileitis severity and ABL in SAMP mice, independent of age. The present results demonstrate the occurrence of periodontal disease in a mouse model of progressive CD-like ileitis. In addition, the severity of periodontitis strongly correlated with the severity of ileitis, independent of age, suggesting that common pathogenic mechanisms, such as abnormal immune response and dysbiosis, may be shared between these two phenotypes.

  11. Non-invasive imaging of prostate cancer progression in nude mice using iRFP gene reporter

    NASA Astrophysics Data System (ADS)

    Zhu, Banghe; Wu, Grace; Robinson, Holly; Wilganowski, Nathaniel; Sevick-Muraca, Eva M.

    2013-03-01

    Prostate cancer (PCa) is the second most common cancer in US men. Metastasis is the final step of tumor progression and remains the primary cause of PCa death. Hence preclinical, orthotopic models of PCa metastasis are necessary to develop new therapeutics against metastatic disease. Yet unlike irrelevant subcutaneous tumor models, the deployment of orthotopic models of cancer metastasis in drug research and development is limited by the inability to longitudinally monitor cancer progression/regression in response to administration of experimental pharmaceuticals. Recently, a nearinfrared fluorescent protein (iRFP) was created for deeper imaging [1]. Imaging prostate tumor growth and lymph node metastasis in nude mice therefore becomes possible using this new fluorescent gene reporter. In this study, we first developed an intensified CCD (ICCD)-based iRFP fluorescence imaging device. Then human PCa PC3 cell lines expressing iRFP gene reporter were orthotopically implanted in male Nu/Nu mice at 8-10 weeks old. After 6-10 weeks, in vivo, in situ and ex vivo fluorescence imaging was performed. In vivo iRFP fluorescence imaging showed that the detected fluorescence concentrated at the prostate and became stronger over time, indicating the growth of implanted PCa. Fluorescence was non-invasively detected at locations of prostate-draining lymph nodes as early as 5 weeks post implantation, indicating the metastasis to lymph nodes. In situ and ex vivo fluorescence imaging demonstrated that the detected signals from PCa and lymph nodes were correlated with cancer positive status of tissues as assessed through standard pathology.

  12. Discussion on the progress and future of satellite communication (Japan)

    NASA Technical Reports Server (NTRS)

    Ogata, M.; Mizusawa, H.; Irie, K.

    1985-01-01

    The current status of communications satellite development in Japan is presented. It is shown that beginning with research on satellite communucations in the late 1950's, progress was made in the areas of communications, remote sensing, and technology experimentation. The current status of communication satellites is presented, stressing development in the areas of CFRP construction elements, the use of LSI and MIC circuits, advanced multibeam antenna systems, Ku and Ka band transmission systems, and the shift to small-scale earth stations. Methods for reducing costs and increasing transmission efficiency are shown. The technical specifications of all satellite projects currently under development are given. Users of Japanese communications satellite are presented.

  13. Long-Term Outcome of Inflammatory Breast Cancer Compared to Non-Inflammatory Breast Cancer in the Setting of High-Dose Chemotherapy with Autologous Hematopoietic Cell Transplantation

    PubMed Central

    Cheng, Yee Chung; Shi, Yushu; Zhang, Mei-Jie; Brazauskas, Ruta; Hemmer, Michael T.; Bishop, Michael R.; Nieto, Yago; Stadtmauer, Edward; Ayash, Lois; Gale, Robert Peter; Lazarus, Hillard; Holmberg, Leona; Lill, Michael; Olsson, Richard F.; Wirk, Baldeep Mona; Arora, Mukta; Hari, Parameswaran; Ueno, Naoto

    2017-01-01

    Introduction: Inflammatory breast cancer (IBC) is a rare aggressive form of breast cancer. It is well known that the long-term survival and progression-free survival of IBC are worse than that of non-IBC. We report the long term outcomes of patients with IBC and non-IBC who had undergone high-dose chemotherapy (HDC) with autologous hematopoietic cell transplantation (AHCT). Methods: All 3387 patients with IBC or non-IBC who underwent HDC with AHCT between1990-2002 and registered with CIBMTR were included in this analysis. Transplant-related mortality (TRM), disease relapse/progression, progression-free survival (PFS) and overall survival (OS) were compared between the two cohorts. Multivariate Cox regression model was used to determine the independent impact of stage on outcomes. Results: 527 patients with IBC and 2,860 patients with non-IBC were included; the median age at transplantation (47 vs 46 years old) and median follow-up period in the 2 groups (167 vs 168 months) were similar. The most common conditioning regimen was cyclophosphamide and carboplatin based in both groups (54% in IBC and 50% in non-IBC). AHCT was well tolerated in both groups. TRM was similar in both groups (one year TRM was 2% for IBC and 3% for non-IBC, p=0.16). The most common cause of death was disease progression or relapse (81% in IBC and 75% in non-IBC). The median survival for both IBC and non-IBC was the same at 40 months. The PFS at 10 years was 27% (95% CI: 23-31%) for IBC and 24% (95% CI: 22-26%) for non-IBC (p=0.21), and the OS at 10 years was 31% (95% CI: 27-35%) for IBC and 28% (95% CI: 26-30%) for non-IBC (p=0.16). In univariate analysis, patients with stage III IBC and no active diseases at transplantation had lower PFS and OS than that in non-IBC. In multivariate analysis, controlling for age, disease status at AHCT, hormonal receptor status, time from diagnosis to AHCT, and performance status at AHCT, patients with stage III IBC had higher mortality (HR 1.16, 95% CI: 1-1.34, p= 0.0459), worse PFS (HR: 1.17, 95% CI: 1.01-1.36, p= 0.0339) and higher risk of disease relapse/progression (HR: 1.24, 95% CI: 1.06-1.45, p= 0.0082) as compared to stage III non-IBC. Amongst all patients a higher stage disease was associated with worse PFS, OS and disease relapse/progression. Conclusions: Long-term outcomes of stage III IBC patients who underwent AHCT were poorer than that in non-IBC patients confirming that the poor prognosis of IBC even in the setting of HDC with AHCT. PMID:28529613

  14. Noninvasive models for assessment of liver fibrosis in patients with chronic hepatitis B virus infection

    PubMed Central

    Zeng, Da-Wu; Dong, Jing; Liu, Yu-Rui; Jiang, Jia-Ji; Zhu, Yue-Yong

    2016-01-01

    There are approximately 240 million patients with chronic hepatitis B virus (HBV) infection worldwide. Up to 40% of HBV-infected patients can progress to liver cirrhosis, hepatocellular carcinoma or chronic end-stage liver disease during their lifetime. This, in turn, is responsible for around 650000 deaths annually worldwide. Repeated hepatitis flares may increase the progression of liver fibrosis, making the accurate diagnosis of the stage of liver fibrosis critical in order to make antiviral therapeutic decisions for HBV-infected patients. Liver biopsy remains the “gold standard” for diagnosing liver fibrosis. However, this technique has recently been challenged by the development of several novel noninvasive tests to evaluate liver fibrosis, including serum markers, combined models and imaging techniques. In addition, the cost and accessibility of imaging techniques have been suggested as additional limitations for invasive assessment of liver fibrosis in developing countries. Therefore, a noninvasive assessment model has been suggested to evaluate liver fibrosis, specifically in HBV-infected patients, owing to its high applicability, inter-laboratory reproducibility, wide availability for repeated assays and reasonable cost. The current review aims to present the status of knowledge in this new and exciting field, and to highlight the key points in HBV-infected patients for clinicians. PMID:27547009

  15. Health Assessment Questionnaire disability progression in early rheumatoid arthritis: Systematic review and analysis of two inception cohorts

    PubMed Central

    Norton, Sam; Fu, Bo; Scott, David L.; Deighton, Chris; Symmons, Deborah P.M.; Wailoo, Allan J.; Tosh, Jonathan; Lunt, Mark; Davies, Rebecca; Young, Adam; Verstappen, Suzanne M.M

    2014-01-01

    Objective The Health Assessment Questionnaire is widely used for patients with inflammatory polyarthritis (IP) and its subset, rheumatoid arthritis (RA). In this study, we evaluated the progression of HAQ scores in RA (i) by systematically reviewing the published literature on the methods used to assess changes in functional disability over time and (ii) to study in detail HAQ progression in two large prospective observational studies from the UK. Methods Data from two large inception cohorts, ERAS and NOAR, were studied to determine trajectories of HAQ progression over time by applying latent class growth models (LCGMs) to each dataset separately. Age, sex, baseline DAS28, symptom duration, rheumatoid factor, fulfilment of the 1987 ACR criteria and socio-economic status (SES) were included as potential predictors of HAQ trajectory subgroup membership. Results The literature search identified 49 studies showing that HAQ progression has mainly been based on average changes in the total study population. In the HAQ progression study, a LCGM with four HAQ trajectory subgroups was selected as providing the best fit in both cohorts. In both the cohorts, older age, female sex, longer symptom duration, fulfilment of the 1987 ACR criteria, higher DAS28 and lower SES were associated with increased likelihood of membership of subgroups with worse HAQ progression. Conclusion Four distinct HAQ trajectory subgroups were derived from the ERAS and NOAR cohorts. The fact that the subgroups identified were nearly identical supports their validity. Identifying distinct groups of patients who are at risk of poor functional outcome may help to target therapy to those who are most likely to benefit. PMID:24925692

  16. Juvenile myopia progression, risk factors and interventions.

    PubMed

    Myrowitz, Elliott H

    2012-07-01

    The development and progression of early onset myopia is actively being investigated. While myopia is often considered a benign condition it should be considered a public health problem for its visual, quality of life, and economic consequences. Nearly half of the visually impaired population in the world has uncorrected refractive errors, with myopia a high percent of that group. Uncorrected visual acuity should be screened for and treated in order to improve academic performance, career opportunities and socio-economic status. Genetic and environmental factors contribute to the onset and progression of myopia. Twin studies have supported genetic factors and research continues to identify myopia genetic loci. While multiple myopia genetic loci have been identified establishing myopia as a common complex disorder, there is not yet a genetic model explaining myopia progression in populations. Environmental factors include near work, education levels, urban compared to rural location, and time spent outdoors. In this field of study where there continues to be etiology controversies, there is recent agreement that children who spend more time outdoors are less likely to become myopic. Worldwide population studies, some completed and some in progress, with a common protocol are gathering both genetic and environmental cohort data of great value. There have been rapid population changes in prevalence rates supporting an environmental influence. Interventions to prevent juvenile myopia progression include pharmacologic agents, glasses and contact lenses. Pharmacological interventions over 1-2 year trials have shown benefits. Peripheral vision defocus has been found to affect the emmetropization process and may be affected by wearing glasses or contacts. Accommodation accuracy also has been implicated in myopia progression. Further research will aim to assess both the role and interaction of environmental influences and genetic factors.

  17. Feasibility and safety of extended adjuvant temozolomide beyond six cycles for patients with glioblastoma.

    PubMed

    Hsieh, S Yp; Chan, D Tm; Kam, M Km; Loong, H Hf; Tsang, W K; Poon, D Mc; Ng, S Cp; Poon, W S

    2017-12-01

    Temozolomide is the first chemotherapeutic agent proven effective for patients with newly diagnosed glioblastoma. The drug is well tolerated for its low toxicity. The current standard practice is concomitant chemoradiotherapy for 6 weeks followed by 6 cycles of adjuvant temozolomide. Some Caucasian studies have suggested that patients might benefit from extended adjuvant cycles of temozolomide (>6 cycles) to lengthen both progression-free survival and overall survival. In the present study, we compared differences in survival and toxicity profile between patients who received conventional 6-cycle temozolomide and those who received more than 6 cycles of temozolomide. Patients with newly diagnosed glioblastoma without progressive disease and completed concomitant chemoradiotherapy during a 4-year period were studied. Progression-free survival was compared using Kaplan-Meier survival curves. t Test, U test, and correlation were chosen accordingly to examine the impact of age, extent of resection, MGMT promoter methylation status and adjuvant cycles on progression-free survival. For factors with a P value of <0.05 in univariate analyses, Cox regression hazard model was adopted to determine the strongest factors related to progression-free survival. The median progression-free survival was 17.0 months for patients who received 6 cycles of temozolomide (n=7) and 43.4 months for those who received more than 6 cycles (n=7) [P=0.007, log-rank test]. Two patients in the former group and one in the latter group encountered grade 1 toxicity and recovered following dose adjustment. Cycles of adjuvant temozolomide were correlated with progression-free survival (P=0.016, hazard ratio=0.68). Extended cycles of temozolomide are safe and feasible for Chinese patients with disease responsive to temozolomide.

  18. Unfinished Agendas: New and Continuing Gender Challenges in Higher Education

    ERIC Educational Resources Information Center

    Glazer-Raymo, Judith, Ed.

    2008-01-01

    This revealing volume examines the current role and status of women in higher education--and suggests a direction for the future. Judith Glazer-Raymo and other distinguished scholars and administrators assess the progress of women in academe using three lenses: the feminist agenda as a work in progress, growing internal and external challenges to…

  19. Reliability of the Raven Coloured Progressive Matrices for Anglo and for Mexican-American Children.

    ERIC Educational Resources Information Center

    Valencia, Richard R.

    1984-01-01

    Investigated the internal consistency reliability estimates of the Raven Coloured Progressive Matrices (CPM) for 96 Anglo and Mexican American third-grade boys from low socioeconomic status background. The results showed that the reliability estimates of the CPM for the two ethnic groups were acceptably high and extremely similar in magnitude.…

  20. Solar Thermal Power Systems parabolic dish project

    NASA Technical Reports Server (NTRS)

    Truscello, V. C.

    1981-01-01

    The status of the Solar Thermal Power Systems Project for FY 1980 is summarized. Included is: a discussion of the project's goals, program structure, and progress in parabolic dish technology. Analyses and test results of concentrators, receivers, and power converters are discussed. Progress toward the objectives of technology feasibility, technology readiness, system feasibility, and system readiness are covered.

  1. Postsecondary Progression of 1993-94 Florida Public High School Graduates: 2002 Update.

    ERIC Educational Resources Information Center

    Florida State Council for Education Policy, Research and Improvement, Tallahassee.

    This status report documents the postsecondary progress of the 1993-1994 Florida public high school graduating class through the spring term of 2001, or 7 years after high school graduation. The two major outcomes addressed were baccalaureate degree completion and the time/credit hours to baccalaureate degree completion. The study focused on…

  2. First-Grade Cognitive Abilities as Long-Term Predictors of Reading Comprehension and Disability Status

    PubMed Central

    Fuchs, Douglas; Compton, Donald L.; Fuchs, Lynn S.; Bryant, V. Joan; Hamlett, Carol L.; Lambert, Warren

    2012-01-01

    In a sample of 195 first graders selected for poor reading performance, the authors explored four cognitive predictors of later reading comprehension and reading disability (RD) status. In fall of first grade, the authors measured the children’s phonological processing, rapid automatized naming (RAN), oral language comprehension, and nonverbal reasoning. Throughout first grade, they also modeled the students’ reading progress by means of weekly Word Identification Fluency (WIF) tests to derive December and May intercepts. The authors assessed their reading comprehension in the spring of Grades 1–5. With the four cognitive variables and the WIF December intercept as predictors, 50.3% of the variance in fifth-grade reading comprehension was explained: 52.1% of this 50.3% was unique to the cognitive variables, 13.1% to the WIF December intercept, and 34.8% was shared. All five predictors were statistically significant. The same four cognitive variables with the May (rather than December) WIF intercept produced a model that explained 62.1% of the variance. Of this amount, the cognitive variables and May WIF intercept accounted for 34.5% and 27.7%, respectively; they shared 37.8%. All predictors in this model were statistically significant except RAN. Logistic regression analyses indicated that the accuracy with which the cognitive variables predicted end-of-fifth-grade RD status was 73.9%. The May WIF intercept contributed reliably to this prediction; the December WIF intercept did not. Results are discussed in terms of a role for cognitive abilities in identifying, classifying, and instructing students with severe reading problems. PMID:22539057

  3. First-grade cognitive abilities as long-term predictors of reading comprehension and disability status.

    PubMed

    Fuchs, Douglas; Compton, Donald L; Fuchs, Lynn S; Bryant, V Joan; Hamlett, Carol L; Lambert, Warren

    2012-01-01

    In a sample of 195 first graders selected for poor reading performance, the authors explored four cognitive predictors of later reading comprehension and reading disability (RD) status. In fall of first grade, the authors measured the children's phonological processing, rapid automatized naming (RAN), oral language comprehension, and nonverbal reasoning. Throughout first grade, they also modeled the students' reading progress by means of weekly Word Identification Fluency (WIF) tests to derive December and May intercepts. The authors assessed their reading comprehension in the spring of Grades 1-5. With the four cognitive variables and the WIF December intercept as predictors, 50.3% of the variance in fifth-grade reading comprehension was explained: 52.1% of this 50.3% was unique to the cognitive variables, 13.1% to the WIF December intercept, and 34.8% was shared. All five predictors were statistically significant. The same four cognitive variables with the May (rather than December) WIF intercept produced a model that explained 62.1% of the variance. Of this amount, the cognitive variables and May WIF intercept accounted for 34.5% and 27.7%, respectively; they shared 37.8%. All predictors in this model were statistically significant except RAN. Logistic regression analyses indicated that the accuracy with which the cognitive variables predicted end-of-fifth-grade RD status was 73.9%. The May WIF intercept contributed reliably to this prediction; the December WIF intercept did not. Results are discussed in terms of a role for cognitive abilities in identifying, classifying, and instructing students with severe reading problems.

  4. Prolonged Febrile Seizures in the Immature Rat Model Enhance Hippocampal Excitability Long Term

    PubMed Central

    Dube, Celine; Chen, Kang; Eghbal-Ahmadi, Mariam; Brunson, Kristen; Soltesz, Ivan; Baram, Tallie Z.

    2011-01-01

    Febrile seizures (FSs) constitute the most prevalent seizure type during childhood. Whether prolonged FSs alter limbic excitability, leading to spontaneous seizures (temporal lobe epilepsy) during adulthood, has been controversial. Recent data indicate that, in the immature rat model, prolonged FSs induce transient structural changes of some hippocampal pyramidal neurons and long-term functional changes of hippocampal circuitry. However, whether these neuroanatomical and electrophysiological changes promote hippocampal excitability and lead to epilepsy has remained unknown. By using in vivo and in vitro approaches, we determined that prolonged hyperthermia-induced seizures in immature rats caused long-term enhanced susceptibility to limbic convulsants that lasted to adulthood. Thus, extensive hippocampal electroencephalographic and behavioral monitoring failed to demonstrate spontaneous seizures in adult rats that had experienced hyperthermic seizures during infancy. However, 100% of animals developed hippocampal seizures after systemic administration of a low dose of kainate, and most progressed to status epilepticus. Conversely, a minority of normothermic and hyperthermic controls had (brief) seizures, none developing status epilepticus. In vitro, spontaneous epileptiform discharges were not observed in hippocampal-entorhinal cortex slices derived from either control or experimental groups. However, Schaeffer collateral stimulation induced prolonged, self-sustaining, status epilepticus-like discharges exclusively in slices from experimental rats. These data indicate that hyperthermic seizures in the immature rat model of FSs do not cause spontaneous limbic seizures during adulthood. However, they reduce thresholds to chemical convulsants in vivo and electrical stimulation in vitro, indicating persistent enhancement of limbic excitability that may facilitate the development of epilepsy. PMID:10716253

  5. The Association of Statin Use with Age-Related Macular Degeneration Progression: The Age-Related Eye Disease Study 2 Report Number 9.

    PubMed

    Al-Holou, Shaza N; Tucker, William R; Agrón, Elvira; Clemons, Traci E; Cukras, Catherine; Ferris, Frederick L; Chew, Emily Y

    2015-12-01

    To evaluate the association of statin use with progression of age-related macular degeneration (AMD). Preplanned, prospective cohort study within a controlled clinical trial of oral supplementation for age-related eye diseases. Age-Related Eye Disease Study 2 (AREDS2) participants, aged 50 to 85 years. Factors, including age, gender, smoking status, aspirin use, and history of diabetes, hypertension, heart disease, angina, and stroke-all known to be associated with statin use-were included in a logistic regression model to estimate propensity scores for each participant. Age-adjusted proportional hazards regression models, with and without propensity score matching, were performed to evaluate the association of statin use with progression to late AMD. Analyses adjusting for the competing risk of death were also performed. Baseline and annual stereoscopic fundus photographs were assessed centrally by masked graders for the development of late AMD, either neovascular AMD or geographic atrophy (GA). Of the 3791 participants (2462 with bilateral large drusen and 1329 with unilateral late AMD at baseline), 1659 (43.8%) were statin users. The overall analysis, with no matching of propensity scores and no adjustment for death as a competing risk, showed that statin use was not associated with progression to late AMD (hazard ratio [HR], 1.08; 95% confidence interval [CI], 0.83-1.41; P = 0.56). When matched for propensity scores and adjusted for death as a competing risk, the result was not statistically significant (HR, 0.81; 95% CI, 0.55-1.20; P = 0.29). Furthermore, subgroup analyses of persons with or without late AMD at baseline and the various components of late AMD (neovascular AMD, central GA, or any GA) also showed no statistically significant association of statin use with progression to AMD. Statin use was not statistically significantly associated with progression to late AMD in the AREDS2 participants, and these findings are consistent with findings in the majority of previous studies. Statins have been demonstrated to reduce the risk of cardiovascular disease, but our data do not provide evidence of a beneficial effect on slowing AMD progression. Published by Elsevier Inc.

  6. Status and Problems of Humanities Education with Respect to Pharmacy Education.

    PubMed

    Ishikawa, Satoko

    2017-01-01

    In 2006, a model core curriculum in pharmaceutical studies was developed prior to the outset of the 6-year pharmacy degree. In the 10 years that followed, medical care and life science technology has progressed, pharmaceutical laws have been revised, and the responsibilities of pharmacists have increased. In response to such social changes and needs, the Model Core Curriculum for Pharmacy Education was revised in December 2013. In order to play an active role as a pharmacist in any medical workplace, it is important for pharmacy students to develop their communication skills and attitudes in order to foster the trust of their patients and other medical professionals. In the new Model Core Curriculum, education in the humanities is clearly described as a foundation to pharmaceutical education, which pertains to the clinical role of a pharmacist; hence, each pharmacy school has outlined strategies for students to learn bioethics and medical ethics, and to develop communication skills. Today, although the importance of humanities education is rapidly increasing, it is difficult to immediately evaluate the outcome of learning humanities subjects and communication. Such an evaluation requires a longer-term perspective. This paper describes the status and problems of humanities education as a component of pharmacy education, and considers future directions of research in humanities education with respect to pharmacy education.

  7. Nurse shift report: who says you can't talk in front of the patient?

    PubMed

    Anderson, Cherri D; Mangino, Ruthie R

    2006-01-01

    Bedside nurse shift report is a process where nurses provide shift-to-shift report at the patient's bedside so the patient can be more involved in his or her care. There are many benefits of bedside report, including relationship building between staff members and increased patient satisfaction, to both the patient and to the healthcare team. Concerns about the traditional methods of communication between the various shifts helped drive a nursing unit's decision to move to a more patient-involved model of shift-to-shift report. The change from the traditional taped report between healthcare providers to bedside reporting focused on patients wanting more involvement in their care, activities, and current status. Patients also wanted updates about their health status, their medical plan as well as information about their progress toward their goals. This, coupled with Banner Desert Medical Center's Care Model, embraces patient-centered care, King's Theory of Goal Attainment, and keeps the patient informed. The current nursing shift report did not meet the medical center's model of care on any of these aspects. This article will include information on the benefits of bedside nurse shift-to-shift report, how one unit implemented bedside reporting, and some of the outcomes achieved after implementing this change at a 600-bed urban medical center.

  8. A resolution recognizing the important progress made by the people of Ukraine in the establishment of democratic institutions following the presidential run-off election on February 7, 2010.

    THOMAS, 111th Congress

    Sen. Lugar, Richard G. [R-IN

    2010-02-25

    Senate - 03/04/2010 Resolution agreed to in Senate without amendment and with a preamble by Unanimous Consent. (All Actions) Tracker: This bill has the status Agreed to in SenateHere are the steps for Status of Legislation:

  9. 78 FR 7429 - Adequacy Status of the Dallas-Fort Worth, TX Reasonable Further Progress 8-Hour Ozone Motor...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-01

    ... ENVIRONMENTAL PROTECTION AGENCY [FRL-9774-9] Adequacy Status of the Dallas-Fort Worth, TX... notifying the public that it has found that the motor vehicle emissions budgets (MVEBs) in the Dallas-Fort... Planning Section (6PD-L), U.S. Environmental Protection Agency, Region 6, 1445 Ross Avenue, Dallas, Texas...

  10. A resolution commemorating the 80th anniversary of the Daughters of Penelope, a preeminent international women's association and affiliate organization of the American Hellenic Educational Progressive Association (AHEPA).

    THOMAS, 111th Congress

    Sen. Snowe, Olympia J. [R-ME

    2009-04-29

    Senate - 03/26/2010 Resolution agreed to in Senate without amendment and with a preamble by Unanimous Consent. (All Actions) Tracker: This bill has the status Agreed to in SenateHere are the steps for Status of Legislation:

  11. PROGRESS REPORT ON THE STATUS OF WOMEN, OCTOBER 11, 1963 THROUGH OCTOBER 10, 1964.

    ERIC Educational Resources Information Center

    Citizens Advisory Council on the Status of Women, Washington, DC.

    THE FEDERAL GOVERNMENT HAS ATTEMPTED TO ADVANCE THE STATUS OF WOMEN BY PROVIDING INCREASED EMPLOYMENT FOR WOMEN IN IMPORTANT GOVERNMENT POSTS, EQUAL HEALTH INSURANCE RATES FOR FEMALE CIVIL SERVICE EMPLOYEES, AND OVERSEAS TRAVEL ALLOWANCES FOR HUSBANDS OF WOMEN IN THE STATE AND DEFENSE DEPARTMENTS. FOR PRIVATE EMPLOYMENT, LEGISLATION SUCH AS THE…

  12. Status and Trends in the Education of Racial and Ethnic Groups 2016. NCES 2016-007

    ERIC Educational Resources Information Center

    Musu-Gillette, Lauren; Robinson, Jennifer; McFarland, Joel; KewalRamani, Angelina; Zhang, Anlan; Wilkinson-Flicker, Sidney

    2016-01-01

    "Status and Trends in the Education of Racial and Ethnic Groups" examines the educational progress and challenges students face in the United States by race/ethnicity. This report shows that, over time, students in the racial/ethnic groups of White, Black, Hispanic, Asian, Native Hawaiian or Other Pacific Islander, American Indian/Alaska…

  13. The Current Status of Unsteady CFD Approaches for Aerodynamic Flow Control

    NASA Technical Reports Server (NTRS)

    Carpenter, Mark H.; Singer, Bart A.; Yamaleev, Nail; Vatsa, Veer N.; Viken, Sally A.; Atkins, Harold L.

    2002-01-01

    An overview of the current status of time dependent algorithms is presented. Special attention is given to algorithms used to predict fluid actuator flows, as well as other active and passive flow control devices. Capabilities for the next decade are predicted, and principal impediments to the progress of time-dependent algorithms are identified.

  14. Annual Report of the Secretary of Defense on Reserve Forces for Fiscal Year 1975

    DTIC Science & Technology

    1976-06-08

    acquisition and distribution of equipment continued to be achieved. Progress was made in both filling uxisting shortfalls and in modernization and... progress of the KOTC flight instruction programs. vArmy Air Force Units Participating 200 56 161 Students Enrolled 412 436 2,036 Students Completed 321 361...Resurve Forces IV Current Status and Progress Made in 4 Strengthening the Reserve Components * A. General 4 1. 24 Division rorce 4 4ii 2. Total Force

  15. Long-term disability trajectories in primary progressive MS patients: A latent class growth analysis.

    PubMed

    Signori, Alessio; Izquierdo, Guillermo; Lugaresi, Alessandra; Hupperts, Raymond; Grand'Maison, Francois; Sola, Patrizia; Horakova, Dana; Havrdova, Eva; Prat, Alexandre; Girard, Marc; Duquette, Pierre; Boz, Cavit; Grammond, Pierre; Terzi, Murat; Singhal, Bhim; Alroughani, Raed; Petersen, Thor; Ramo, Cristina; Oreja-Guevara, Celia; Spitaleri, Daniele; Shaygannejad, Vahid; Butzkueven, Helmut; Kalincik, Tomas; Jokubaitis, Vilija; Slee, Mark; Fernandez Bolaños, Ricardo; Sanchez-Menoyo, Jose Luis; Pucci, Eugenio; Granella, Franco; Lechner-Scott, Jeannette; Iuliano, Gerardo; Hughes, Stella; Bergamaschi, Roberto; Taylor, Bruce; Verheul, Freek; Edite Rio, Maria; Amato, Maria Pia; Sajedi, Seyed Aidin; Majdinasab, Nastaran; Van Pesch, Vincent; Sormani, Maria Pia; Trojano, Maria

    2018-04-01

    Several natural history studies on primary progressive multiple sclerosis (PPMS) patients detected a consistent heterogeneity in the rate of disability accumulation. To identify subgroups of PPMS patients with similar longitudinal trajectories of Expanded Disability Status Scale (EDSS) over time. All PPMS patients collected within the MSBase registry, who had their first EDSS assessment within 5 years from onset, were included in the analysis. Longitudinal EDSS scores were modeled by a latent class mixed model (LCMM), using a nonlinear function of time from onset. LCMM is an advanced statistical approach that models heterogeneity between patients by classifying them into unobserved groups showing similar characteristics. A total of 853 PPMS (51.7% females) from 24 countries with a mean age at onset of 42.4 years (standard deviation (SD): 10.8 years), a median baseline EDSS of 4 (interquartile range (IQR): 2.5-5.5), and 2.4 years of disease duration (SD: 1.5 years) were included. LCMM detected three different subgroups of patients with a mild ( n = 143; 16.8%), moderate ( n = 378; 44.3%), or severe ( n = 332; 38.9%) disability trajectory. The probability of reaching EDSS 6 at 10 years was 0%, 46.4%, and 81.9% respectively. Applying an LCMM modeling approach to long-term EDSS data, it is possible to identify groups of PPMS patients with different prognosis.

  16. The Agricultural Model Intercomparison and Improvement Project (AgMIP): Progress and Preliminary Results

    NASA Astrophysics Data System (ADS)

    Rosenzweig, C.

    2011-12-01

    The Agricultural Model Intercomparison and Improvement Project (AgMIP) is a distributed climate-scenario simulation exercise for historical model intercomparison and future climate change conditions with participation of multiple crop and agricultural trade modeling groups around the world. The goals of AgMIP are to improve substantially the characterization of risk of hunger and world food security due to climate change and to enhance adaptation capacity in both developing and developed countries. Recent progress and the current status of AgMIP will be presented, highlighting three areas of activity: preliminary results from crop pilot studies, outcomes from regional workshops, and emerging scientific challenges. AgMIP crop modeling efforts are being led by pilot studies, which have been established for wheat, maize, rice, and sugarcane. These crop-specific initiatives have proven instrumental in testing and contributing to AgMIP protocols, as well as creating preliminary results for aggregation and input to agricultural trade models. Regional workshops are being held to encourage collaborations and set research activities in motion for key agricultural areas. The first of these workshops was hosted by Embrapa and UNICAMP and held in Campinas, Brazil. Outcomes from this meeting have informed crop modeling research activities within South America, AgMIP protocols, and future regional workshops. Several scientific challenges have emerged and are currently being addressed by AgMIP researchers. Areas of particular interest include geospatial weather generation, ensemble methods for climate scenarios and crop models, spatial aggregation of field-scale yields to regional and global production, and characterization of future changes in climate variability.

  17. It is the economy, stupid! Projecting the fate of fish populations using ecological-economic modeling.

    PubMed

    Quaas, Martin F; Reusch, Thorsten B H; Schmidt, Jörn O; Tahvonen, Olli; Voss, Rudi

    2016-01-01

    Four marine fish species are among the most important on the world market: cod, salmon, tuna, and sea bass. While the supply of North American and European markets for two of these species - Atlantic salmon and European sea bass - mainly comes from fish farming, Atlantic cod and tunas are mainly caught from wild stocks. We address the question what will be the status of these wild stocks in the midterm future, in the year 2048, to be specific. Whereas the effects of climate change and ecological driving forces on fish stocks have already gained much attention, our prime interest is in studying the effects of changing economic drivers, as well as the impact of variable management effectiveness. Using a process-based ecological-economic multispecies optimization model, we assess the future stock status under different scenarios of change. We simulate (i) technological progress in fishing, (ii) increasing demand for fish, and (iii) increasing supply of farmed fish, as well as the interplay of these driving forces under different scenarios of (limited) fishery management effectiveness. We find that economic change has a substantial effect on fish populations. Increasing aquaculture production can dampen the fishing pressure on wild stocks, but this effect is likely to be overwhelmed by increasing demand and technological progress, both increasing fishing pressure. The only solution to avoid collapse of the majority of stocks is institutional change to improve management effectiveness significantly above the current state. We conclude that full recognition of economic drivers of change will be needed to successfully develop an integrated ecosystem management and to sustain the wild fish stocks until 2048 and beyond. © 2015 John Wiley & Sons Ltd.

  18. p53 predictive value for pT1-2 N0 disease at radical cystectomy.

    PubMed

    Shariat, Shahrokh F; Lotan, Yair; Karakiewicz, Pierre I; Ashfaq, Raheela; Isbarn, Hendrik; Fradet, Yves; Bastian, Patrick J; Nielsen, Matthew E; Capitanio, Umberto; Jeldres, Claudio; Montorsi, Francesco; Müller, Stefan C; Karam, Jose A; Heukamp, Lukas C; Netto, George; Lerner, Seth P; Sagalowsky, Arthur I; Cote, Richard J

    2009-09-01

    Approximately 15% to 30% of patients with pT1-2N0M0 urothelial carcinoma of the bladder experience disease progression despite radical cystectomy with curative intent. We determined whether p53 expression would improve the prediction of disease progression after radical cystectomy for pT1-2N0M0 UCB. In a multi-institutional retrospective cohort we identified 324 patients with pT1-2N0M0 urothelial carcinoma of the bladder who underwent radical cystectomy. Analysis focused on a testing cohort of 272 patients and an external validation of 52. Competing risks regression models were used to test the association of variables with cancer specific mortality after accounting for nonbladder cancer caused mortality. In the testing cohort 91 patients (33.5%) had altered p53 expression (p53alt). On multivariate competing risks regression analysis altered p53 achieved independent status for predicting disease recurrence and cancer specific mortality (each p <0.001). Adding p53 increased the accuracy of multivariate competing risks regression models predicting recurrence and cancer specific mortality by 5.7% (62.0% vs 67.7%) and 5.4% (61.6% vs 67.0%), respectively. Alterations in p53 represent a highly promising marker of disease recurrence and cancer specific mortality after radical cystectomy for urothelial carcinoma of the bladder. Analysis confirmed previous findings and showed that considering p53 can result in substantial accuracy gains relative to the use of standard predictors. The value and the level of the current evidence clearly exceed previous proof of the independent predictor status of p53 for predicting recurrence and cancer specific mortality.

  19. Defining local-regional control and its importance in locally advanced non-small cell lung carcinoma.

    PubMed

    Machtay, Mitchell; Paulus, Rebecca; Moughan, Jennifer; Komaki, Ritsuko; Bradley, J Effrey; Choy, Hak; Albain, Kathy; Movsas, Benjamin; Sause, William T; Curran, Walter J

    2012-04-01

    Local-regional control (LRC) rates for non-small cell lung cancer after chemoradiotherapy were studied (using two different definitions of LRC) for the association between LRC and survival. Seven legacy Radiation Therapy Ooncology Group trials of chemoradiotherapy for locally advanced non-small cell lung cancer were analyzed. Two different definitions of LRC were studied: (1) freedom from local progression (FFLP-LRC), the traditional Radiation Therapy Oncology Group methodology, in which a failure is intrathoracic tumor progression by World Health Oorganization criteria; and (2) response-mandatory (strict-LRC), in which any patient not achieving at least partial response was considered to have failure at day 0. Testing for associations between LRC and survival was performed using a Cox multivariate model that included other potential predictive factors. A total of 1390 patients were analyzed. The LRC rate at 3 years was 38% based on the FFLP-LRC definition and 14% based on the strict-LRC definition. Performance status, concurrent chemotherapy, and radiotherapy dose intensity (biologically equivalent dose) were associated with better LRC (using either definition). With the strict-LRC definition (but not FFLP-LRC), age was also important. There was a powerful association between LRC and overall survival (p, 0.0001) on univariate and multivariate analyses. Age, performance status, chemotherapy sequencing, and biologically equivalent dose were also significantly associated with survival. Histology and gender were also significant if the strict-LRC model was used. LRC is associated with survival. The definition of LRC affects the results of these analyses. A consensus definition of LRC, incorporating functional imaging and/or central review, is needed, with the possibility of using LRC as a surrogate end point in future trials.

  20. Family Violence Pathways and Externalizing Behavior in Youth.

    PubMed

    Bozzay, Melanie L; Joy, Lendi N; Verona, Edelyn

    2017-08-01

    While studies suggest that youth who experience violence in the home are more likely to engage in externalizing behaviors (e.g., aggression, substance use, rule breaking), research is needed to understand factors that may explain how family violence is linked to externalizing, and whether there may be gender-specific trajectories to this outcome. The present study used a cross-sectional design and multigroup, path analytic modeling to test the degree to which personality traits (negative emotionality, constraint) in boys and girls (Model 1), as well as status offending primarily in girls (Model 2), may help explain relationships between exposure to familial adversity (witnessing family violence and child abuse) and adolescent externalizing behaviors in a mixed-gender, community sample with both caregiver and youth reports ( N = 237, 57% female, 10-17 years old). Results indicated that personality traits fully explained the relationship between witnessing family violence and externalizing and partially explained the relationship between child abuse and externalizing among youth. Despite theory suggesting a female-specific trajectory involving status offenses, both models were similarly relevant for boys and girls. These findings have implications for understanding processes by which adverse family circumstances may relate to externalizing behavior in youth. Preliminary suggestions are provided for future longitudinal research, policy changes, and clinical techniques that may be essential in preventing the progression to long-term adverse outcomes among youth.

  1. Usefulness of optic nerve ultrasound to predict clinical progression in multiple sclerosis.

    PubMed

    Pérez Sánchez, S; Eichau Madueño, S; Rus Hidalgo, M; Domínguez Mayoral, A M; Vilches-Arenas, A; Navarro Mascarell, G; Izquierdo, G

    2018-03-21

    Progressive neuronal and axonal loss are considered the main causes of disability in patients with multiple sclerosis (MS). The disease frequently involves the visual system; the accessibility of the system for several functional and structural tests has made it a model for the in vivo study of MS pathogenesis. Orbital ultrasound is a non-invasive technique that enables various structures of the orbit, including the optic nerve, to be evaluated in real time. We conducted an observational, ambispective study of MS patients. Disease progression data were collected. Orbital ultrasound was performed on all patients, with power set according to the 'as low as reasonably achievable' (ALARA) principle. Optical coherence tomography (OCT) data were also collected for those patients who underwent the procedure. Statistical analysis was conducted using SPSS version 22.0. Disease progression was significantly correlated with ultrasound findings (P=.041 for the right eye and P=.037 for the left eye) and with Expanded Disability Status Scale (EDSS) score at the end of the follow-up period (P=.07 for the right eye and P=.043 for the left eye). No statistically significant differences were found with relation to relapses or other clinical variables. Ultrasound measurement of optic nerve diameter constitutes a useful, predictive factor for the evaluation of patients with MS. Smaller diameters are associated with poor clinical progression and greater disability (measured by EDSS). Copyright © 2018 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  2. Overview of Botanical Status in EU, USA, and Thailand

    PubMed Central

    Mahady, Gail B.

    2013-01-01

    The botanical status in EU, USA, and Thailand is different owing to the regulatory status, the progress of science, and the influence of culture and society. In the EU, botanicals are positioned as herbal medicinal products and food supplements, in the US they are regulated as dietary supplements but often used as traditional medicines, and in Thailand, they are regulated and used as traditional medicines. Information for some of the most popular botanicals from each country is included in this review. PMID:24228061

  3. Use of bio-informatics assessment schema (BIAS) to improve diagnosis and prognosis of myocardial perfusion data: results from the NHLBI-sponsored women's ischemia syndrome evaluation (WISE).

    PubMed

    Doyle, Mark; Pohost, Gerald M; Bairey Merz, C Noel; Shaw, Leslee J; Sopko, George; Rogers, William J; Sharaf, Barry L; Pepine, Carl J; Thompson, Diane V; Rayarao, Geetha; Tauxe, Lindsey; Kelsey, Sheryl F; Biederman, Robert W W

    2016-10-01

    We introduce an algorithmic approach to optimize diagnostic and prognostic value of gated cardiac single photon emission computed tomography (SPECT) and magnetic resonance (MR) myocardial perfusion imaging (MPI) modalities in women with suspected myocardial ischemia. The novel approach: bio-informatics assessment schema (BIAS) forms a mathematical model utilizing MPI data and cardiac metrics generated by one modality to predict the MPI status of another modality. The model identifies cardiac features that either enhance or mask the image-based evidence of ischemia. For each patient, the BIAS model value is used to set an appropriate threshold for the detection of ischemia. Women (n=130), with symptoms and signs of suspected myocardial ischemia, underwent MPI assessment for regional perfusion defects using two different modalities: gated SPECT and MR. To determine perfusion status, MR data were evaluated qualitatively (MRI QL ) and semi-quantitatively (MRI SQ ) while SPECT data were evaluated using conventional clinical criteria. Evaluators were masked to results of the alternate modality. These MPI status readings were designated "original". Two regression models designated "BIAS" models were generated to model MPI status obtained with one modality (e.g., MRI) compared with a second modality (e.g., SPECT), but importantly, the BIAS models did not include the primary Original MPI reading of the predicting modality. Instead, the BIAS models included auxiliary measurements like left ventricular chamber volumes and myocardial wall thickness. For each modality, the BIAS model was used to set a progressive threshold for interpretation of MPI status. Women were then followed for 38±14 months for the development of a first major adverse cardiovascular event [MACE: CV death, nonfatal myocardial infarction (MI) or hospitalization for heart failure]. Original and BIAS-augmented perfusion status were compared in their ability to detect coronary artery disease (CAD) and for prediction of MACE. Adverse events occurred in 14 (11%) women and CAD was present in 13 (10%). There was a positive correlation of maximum coronary artery stenosis and BIAS score for MRI and SPECT (P<0.001). Receiver operator characteristic (ROC) analysis was conducted and showed an increase in the area under the curve of the BIAS-augmented MPI interpretation of MACE vs . the original for MRI SQ (0.78 vs . 0.54), MRI QL (0.78 vs . 0.64), SPECT (0.82 vs . 0.63) and the average of the three readings (0.80±0.02 vs . 0.60±0.05, P<0.05). Increasing values of the BIAS score generated by both MRI and SPECT corresponded to the increasing prevalence of CAD and MACE. The BIAS-augmented detection of ischemia better predicted MACE compared with the Original reading for the MPI data for both MRI and SPECT.

  4. Use of bio-informatics assessment schema (BIAS) to improve diagnosis and prognosis of myocardial perfusion data: results from the NHLBI-sponsored women’s ischemia syndrome evaluation (WISE)

    PubMed Central

    Pohost, Gerald M.; Bairey Merz, C. Noel; Shaw, Leslee J.; Sopko, George; Rogers, William J.; Sharaf, Barry L.; Pepine, Carl J.; Thompson, Diane V.; Rayarao, Geetha; Tauxe, Lindsey; Kelsey, Sheryl F.; Biederman, Robert W. W.

    2016-01-01

    Background We introduce an algorithmic approach to optimize diagnostic and prognostic value of gated cardiac single photon emission computed tomography (SPECT) and magnetic resonance (MR) myocardial perfusion imaging (MPI) modalities in women with suspected myocardial ischemia. The novel approach: bio-informatics assessment schema (BIAS) forms a mathematical model utilizing MPI data and cardiac metrics generated by one modality to predict the MPI status of another modality. The model identifies cardiac features that either enhance or mask the image-based evidence of ischemia. For each patient, the BIAS model value is used to set an appropriate threshold for the detection of ischemia. Methods Women (n=130), with symptoms and signs of suspected myocardial ischemia, underwent MPI assessment for regional perfusion defects using two different modalities: gated SPECT and MR. To determine perfusion status, MR data were evaluated qualitatively (MRIQL) and semi-quantitatively (MRISQ) while SPECT data were evaluated using conventional clinical criteria. Evaluators were masked to results of the alternate modality. These MPI status readings were designated “original”. Two regression models designated “BIAS” models were generated to model MPI status obtained with one modality (e.g., MRI) compared with a second modality (e.g., SPECT), but importantly, the BIAS models did not include the primary Original MPI reading of the predicting modality. Instead, the BIAS models included auxiliary measurements like left ventricular chamber volumes and myocardial wall thickness. For each modality, the BIAS model was used to set a progressive threshold for interpretation of MPI status. Women were then followed for 38±14 months for the development of a first major adverse cardiovascular event [MACE: CV death, nonfatal myocardial infarction (MI) or hospitalization for heart failure]. Original and BIAS-augmented perfusion status were compared in their ability to detect coronary artery disease (CAD) and for prediction of MACE. Results Adverse events occurred in 14 (11%) women and CAD was present in 13 (10%). There was a positive correlation of maximum coronary artery stenosis and BIAS score for MRI and SPECT (P<0.001). Receiver operator characteristic (ROC) analysis was conducted and showed an increase in the area under the curve of the BIAS-augmented MPI interpretation of MACE vs. the original for MRISQ (0.78 vs. 0.54), MRIQL (0.78 vs. 0.64), SPECT (0.82 vs. 0.63) and the average of the three readings (0.80±0.02 vs. 0.60±0.05, P<0.05). Conclusions Increasing values of the BIAS score generated by both MRI and SPECT corresponded to the increasing prevalence of CAD and MACE. The BIAS-augmented detection of ischemia better predicted MACE compared with the Original reading for the MPI data for both MRI and SPECT. PMID:27747165

  5. Kinetics, prognostic and predictive values of ESR1 circulating mutations in metastatic breast cancer patients progressing on aromatase inhibitor

    PubMed Central

    Clatot, Florian; Perdrix, Anne; Augusto, Laetitia; Beaussire, Ludivine; Delacour, Julien; Calbrix, Céline; Sefrioui, David; Viailly, Pierre-Julien; Bubenheim, Michael; Moldovan, Cristian; Alexandru, Cristina; Tennevet, Isabelle; Rigal, Olivier; Guillemet, Cécile; Leheurteur, Marianne; Gouérant, Sophie; Petrau, Camille; Théry, Jean-Christophe; Picquenot, Jean-Michel; Veyret, Corinne; Frébourg, Thierry; Jardin, Fabrice

    2016-01-01

    Purpose To assess the prognostic and predictive value of circulating ESR1 mutation and its kinetics before and after progression on aromatase inhibitor (AI) treatment. Patients and methods ESR1 circulating D538G and Y537S/N/C mutations were retrospectively analyzed by digital droplet PCR after first-line AI failure in patients treated consecutively from 2010 to 2012 for hormone receptor-positive metastatic breast cancer. Progression-free survival (PFS) and overall survival (OS) were analyzed according to circulating mutational status and subsequent lines of treatment. The kinetics of ESR1 mutation before (3 and 6 months) and after (3 months) AI progression were determined in the available archive plasmas. Results Circulating ESR1 mutations were found at AI progression in 44/144 patients included (30.6%). Median follow-up from AI initiation was 40 months (range 4-94). The median OS was decreased in patients with circulating ESR1 mutation than in patients without mutation (15.5 versus 23.8 months, P=0.0006). The median PFS was also significantly decreased in patients with ESR1 mutation than in patients without mutation (5.9 vs 7 months, P=0.002). After AI failure, there was no difference in outcome for patients receiving chemotherapy (n = 58) versus non-AI endocrine therapy (n=51) in patients with and without ESR1 mutation. ESR1 circulating mutations were detectable in 75% of all cases before AI progression, whereas the kinetics 3 months after progression did not correlate with outcome. Conclusion ESR1 circulating mutations are independent risk factors for poor outcome after AI failure, and are frequently detectable before clinical progression. Interventional studies based on ESR1 circulating status are warranted. PMID:27801670

  6. Kinetics, prognostic and predictive values of ESR1 circulating mutations in metastatic breast cancer patients progressing on aromatase inhibitor.

    PubMed

    Clatot, Florian; Perdrix, Anne; Augusto, Laetitia; Beaussire, Ludivine; Delacour, Julien; Calbrix, Céline; Sefrioui, David; Viailly, Pierre-Julien; Bubenheim, Michael; Moldovan, Cristian; Alexandru, Cristina; Tennevet, Isabelle; Rigal, Olivier; Guillemet, Cécile; Leheurteur, Marianne; Gouérant, Sophie; Petrau, Camille; Théry, Jean-Christophe; Picquenot, Jean-Michel; Veyret, Corinne; Frébourg, Thierry; Jardin, Fabrice; Sarafan-Vasseur, Nasrin; Di Fiore, Frédéric

    2016-11-15

    To assess the prognostic and predictive value of circulating ESR1 mutation and its kinetics before and after progression on aromatase inhibitor (AI) treatment. ESR1 circulating D538G and Y537S/N/C mutations were retrospectively analyzed by digital droplet PCR after first-line AI failure in patients treated consecutively from 2010 to 2012 for hormone receptor-positive metastatic breast cancer. Progression-free survival (PFS) and overall survival (OS) were analyzed according to circulating mutational status and subsequent lines of treatment. The kinetics of ESR1 mutation before (3 and 6 months) and after (3 months) AI progression were determined in the available archive plasmas. Circulating ESR1 mutations were found at AI progression in 44/144 patients included (30.6%). Median follow-up from AI initiation was 40 months (range 4-94). The median OS was decreased in patients with circulating ESR1 mutation than in patients without mutation (15.5 versus 23.8 months, P=0.0006). The median PFS was also significantly decreased in patients with ESR1 mutation than in patients without mutation (5.9 vs 7 months, P=0.002). After AI failure, there was no difference in outcome for patients receiving chemotherapy (n = 58) versus non-AI endocrine therapy (n=51) in patients with and without ESR1 mutation. ESR1 circulating mutations were detectable in 75% of all cases before AI progression, whereas the kinetics 3 months after progression did not correlate with outcome. ESR1 circulating mutations are independent risk factors for poor outcome after AI failure, and are frequently detectable before clinical progression. Interventional studies based on ESR1 circulating status are warranted.

  7. Population biology of the Florida manatee: An overview

    USGS Publications Warehouse

    O'Shea, Thomas J.; Ackerman, B.B.; O'Shea, Thomas J.; Ackerman, B.B.; Percival, H. Franklin

    1995-01-01

    In the following overview we discuss progress toward meeting the three objectives of the 1992 workshop: to provide a synthesis of existing information about manatee population biology; to evaluate the strengths and weaknesses of current data sets and approaches to research on manatee population biology; and to provide recommendations for research. We discuss progress in six topics that were assigned to working groups at the workshop: aerial survey and estimation of population size, reproduction, age structure, mortality, photoidentification and estimation of survival, and integration and modeling of population data. The overview includes recommendations by working group participants (*2 0'Shea et al. 1992). This workshop on manatee population biology was the most recent conference on the topic since 1978 (*BrowneIl and Rails 1981). Partly as a result of recommendations made at the 1978 workshop, several long-term population-related research projects were established. Therefore, we also measure progress in relation to knowledge available at the time of the earlier workshop. Finally, we provide a brief synopsis of pertinent new information on manatee population biology that became available between the 1992 workshop and publication of the proceedings and our conclusions about the status of the Florida manatee.

  8. Characteristics and longitudinal progression of chronic obstructive pulmonary disease in GOLD B patients.

    PubMed

    Lawrence, Philip J; Kolsum, Umme; Gupta, Vandana; Donaldson, Gavin; Singh, Richa; Barker, Bethan; George, Leena; Webb, Adam; Brookes, Anthony J; Brightling, Christopher; Wedzicha, Jadwiga; Singh, Dave

    2017-02-20

    The characteristics and natural history of GOLD B COPD patients are not well described. The clinical characteristics and natural history of GOLD B patients over 1 year in a multicentre cohort of COPD patients in the COPDMAP study were assessed. We aimed to identify the subgroup of patients who progressed to GOLD D (unstable GOLD B patients) and identify characteristics associated with progression. Three hundred seventy COPD patients were assessed at baseline and 12 months thereafter. Demographics, lung function, health status, 6 min walk tests and levels of systemic inflammation were assessed. Students t tests and Mann Whitney-U tests were used. One hundred seven (28.9%) of patients were categorised as GOLD B at baseline. These GOLD B patients had similar FEV1 to GOLD A patients (66% predicted). More GOLD B patients were current smokers (p = 0.031), had chronic bronchitis (p = 0.0003) and cardiovascular comorbidities (p = 0.019) compared to GOLD A. At 12 months, 25.3% of GOLD B patients progressed to GOLD D. These patients who progressed (unstable patients) had worse health status and symptoms (SGRQ-C Total, 50.0 v 41.1, p = 0.019 and CAT, 21.0 v 14.0, p = 0.006) and lower FEV 1 (60% v 69% p = 0.014) at baseline compared to stable patients who remained in GOLD B. Unstable GOLD B patients who progressed to GOLD D had a higher level of symptoms at baseline. A high symptom burden may predict an increased likelihood of disease progression in GOLD B patients.

  9. Age-dependent increment of hydroxymethylation in the brain cortex in the triple-transgenic mouse model of Alzheimer's disease.

    PubMed

    Cadena-del-Castillo, Carla; Valdes-Quezada, Christian; Carmona-Aldana, Francisco; Arias, Clorinda; Bermúdez-Rattoni, Federico; Recillas-Targa, Félix

    2014-01-01

    Alzheimer's disease (AD) is a complex disorder whose etiology is associated with environmental and genetic factors. Recently there have been several attempts to analyze the role of epigenetic alterations in the origin and progression of this neurodegenerative condition. To evaluate the potential participation of the methylation status of the genome that may contribute to AD progression, we have studied the levels and distribution of the 5-methylcytosine and 5-hydroxymethylcytosine in different brain regions at different ages. We analyzed and quantified the immunosignal of these two epigenetic marks in young versus old wild-type mice and in the triple-transgenic mouse model of AD (3xTg-AD). The results show a decline in global 5-methylcytosine mark over time in all studied brain regions concomitant with a significant and widespread increase in 5-hydroxymethylcytosine mark in the aged transgenic mice in contrast to the age-matched controls. These differences in the methylation pattern of brain DNA in the 3xTg-AD that accumulates along age indicates abnormal formation of permissive chromatin structure associated with the increase in AD-related markers.

  10. Technology Readiness of the NEXT Ion Propulsion System

    NASA Technical Reports Server (NTRS)

    Benson, Scott W.; Patterson, Michael J.

    2008-01-01

    The NASA's Evolutionary Xenon Thruster (NEXT) ion propulsion system has been in advanced technology development under the NASA In-Space Propulsion Technology project. The highest fidelity hardware planned has now been completed by the government/industry team, including: a flight prototype model (PM) thruster, an engineering model (EM) power processing unit, EM propellant management assemblies, a breadboard gimbal, and control unit simulators. Subsystem and system level technology validation testing is in progress. To achieve the objective Technology Readiness Level 6, environmental testing is being conducted to qualification levels in ground facilities simulating the space environment. Additional tests have been conducted to characterize the performance range and life capability of the NEXT thruster. This paper presents the status and results of technology validation testing accomplished to date, the validated subsystem and system capabilities, and the plans for completion of this phase of NEXT development. The next round of competed planetary science mission announcements of opportunity, and directed mission decisions, are anticipated to occur in 2008 and 2009. Progress to date, and the success of on-going technology validation, indicate that the NEXT ion propulsion system will be a primary candidate for mission consideration in these upcoming opportunities.

  11. Prolonged seizure activity leads to increased Protein Kinase A activation in the rat pilocarpine model of status epilepticus.

    PubMed

    Bracey, James M; Kurz, Jonathan E; Low, Brian; Churn, Severn B

    2009-08-04

    Status epilepticus is a life-threatening form of seizure activity that represents a major medical emergency associated with significant morbidity and mortality. Protein Kinase A is an important regulator of synaptic strength that may play an important role in the development of status epilepticus-induced neuronal pathology. This study demonstrated an increase in PKA activity against exogenous and endogenous substrates during later stages of SE. As SE progressed, a significant increase in PKA-mediated phosphorylation of an exogenous peptide substrate was demonstrated in cortical structures. The increased activity was not due to altered expression of either regulatory or catalytic subunits of the enzyme. Through the use of phospho-specific antibodies, this study also investigated the effects of SE on the phosphorylation of the GluR1 subunit of the AMPA subtype of glutamate receptor. After the onset of continuous seizure activity, an increase in phosphorylation of the PKA site on the GluR1 subunit of the AMPA receptor was observed. These data suggest a potential mechanism by which SE may increase neuronal excitability in the cortex, potentially leading to maintenance of seizure activity or long-term neuronal pathology.

  12. A socioeconomic and behavioral survey of patients with difficult-to-control type 2 diabetes mellitus reveals an association between diabetic retinopathy and educational attainment.

    PubMed

    Emoto, Naoya; Okajima, Fumitaka; Sugihara, Hitoshi; Goto, Rei

    2016-01-01

    We have recently reported that the attitude of patients toward risk could be a factor in the progression of diabetic complications. In general, risk preference is closely related to socioeconomic status (SES), which includes factors such as age, sex, income, and educational attainment. We aimed to determine the effect of SES and behavioral propensity on the progress of diabetic complications in patients with type 2 diabetes mellitus (T2DM). We conducted a survey of 238 patients with difficult-to-control T2DM treated at a hospital in Japan using a modified behavioral economics questionnaire that included questions related to SES. The patients had been referred by general practitioners or other departments in the hospital because of poor metabolic control or unstable complications. Educational attainment was significantly associated with progression of retinopathy in patients <65 years of age. Educational attainment of a high school diploma (12 years of education) or lower was a significant risk factor, but there were no differences among levels of attainment beyond high school (13-16 years or more of education). Behavioral propensities were also weakly associated with complications, but not as much as educational attainment. Personal income level and economic status did not show an association with the retinopathy levels. Lower educational attainment is a strong risk factor for diabetic retinopathy, and it is independent of the economic status. The result suggests that cognitive function may play an important role in the progression of diabetic retinopathy in patients with T2DM.

  13. Patient-reported outcomes, body composition, and nutrition status in patients with head and neck cancer: Results from an exploratory randomized controlled exercise trial.

    PubMed

    Capozzi, Lauren C; McNeely, Margaret L; Lau, Harold Y; Reimer, Raylene A; Giese-Davis, Janine; Fung, Tak S; Culos-Reed, S Nicole

    2016-04-15

    Patients with head and neck cancer experience loss of weight and muscle mass, decreased functioning, malnutrition, depression, and declines in quality of life during and after treatment. The purpose of this exploratory randomized study was to determine the optimal timing for the initiation of a lifestyle and progressive resistance exercise training intervention (during or after radiation therapy), as determined by intervention adherence and by comparing between-group outcomes across 24 weeks. Sixty patients with head and neck cancer were randomized to engage in a 12-week lifestyle intervention and progressive resistance-training program either during radiation treatment or immediately after completion. The primary outcome of body composition--specifically, lean body mass, body mass index, and body fat--as well as secondary outcomes of fitness, quality of life, depression, and nutrition status were evaluated. The progressive resistance-training intervention carried out during treatment did not significantly influence the primary outcome of body composition, despite a significant increase in weekly physical activity reported by the intervention group. A small-to-medium intervention effect was noted for some secondary outcomes, including fitness, quality of life, and nutrition status. Regardless of whether patients received the immediate or delayed progressive resistance-training intervention, the analysis revealed a main effect of time on body composition, fitness, quality of life, depression, and nutritional scores. Although the intervention during treatment did not reduce the loss of lean body mass, delaying the exercise program until after treatment completion was associated with improved intervention adherence, a finding with important clinical implications. © 2016 American Cancer Society.

  14. Preclinical magnetic resonance imaging and systems biology in cancer research: current applications and challenges.

    PubMed

    Albanese, Chris; Rodriguez, Olga C; VanMeter, John; Fricke, Stanley T; Rood, Brian R; Lee, YiChien; Wang, Sean S; Madhavan, Subha; Gusev, Yuriy; Petricoin, Emanuel F; Wang, Yue

    2013-02-01

    Biologically accurate mouse models of human cancer have become important tools for the study of human disease. The anatomical location of various target organs, such as brain, pancreas, and prostate, makes determination of disease status difficult. Imaging modalities, such as magnetic resonance imaging, can greatly enhance diagnosis, and longitudinal imaging of tumor progression is an important source of experimental data. Even in models where the tumors arise in areas that permit visual determination of tumorigenesis, longitudinal anatomical and functional imaging can enhance the scope of studies by facilitating the assessment of biological alterations, (such as changes in angiogenesis, metabolism, cellular invasion) as well as tissue perfusion and diffusion. One of the challenges in preclinical imaging is the development of infrastructural platforms required for integrating in vivo imaging and therapeutic response data with ex vivo pathological and molecular data using a more systems-based multiscale modeling approach. Further challenges exist in integrating these data for computational modeling to better understand the pathobiology of cancer and to better affect its cure. We review the current applications of preclinical imaging and discuss the implications of applying functional imaging to visualize cancer progression and treatment. Finally, we provide new data from an ongoing preclinical drug study demonstrating how multiscale modeling can lead to a more comprehensive understanding of cancer biology and therapy. Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  15. Progress toward a new beam measurement of the neutron lifetime

    NASA Astrophysics Data System (ADS)

    Hoogerheide, Shannon Fogwell; BL2 Collaboration

    2017-01-01

    Neutron beta decay is the simplest example of nuclear beta decay. A precise value of the neutron lifetime is important for consistency tests of the Standard Model and Big Bang Nucleosynthesis models. The beam neutron lifetime method requires the absolute counting of the decay protons in a neutron beam of precisely known flux. Recent work has resulted in improvements in both the neutron and proton detection systems that should permit a significant reduction in systematic uncertainties. A new measurement of the neutron lifetime using the beam method is underway at the National Institute of Standards and Technology Center for Neutron Research. The projected uncertainty of this new measurement is 1 s. An overview of the measurement, its current status, and the technical improvements will be discussed.

  16. Fulvestrant plus palbociclib versus fulvestrant plus placebo for treatment of hormone-receptor-positive, HER2-negative metastatic breast cancer that progressed on previous endocrine therapy (PALOMA-3): final analysis of the multicentre, double-blind, phase 3 randomised controlled trial.

    PubMed

    Cristofanilli, Massimo; Turner, Nicholas C; Bondarenko, Igor; Ro, Jungsil; Im, Seock-Ah; Masuda, Norikazu; Colleoni, Marco; DeMichele, Angela; Loi, Sherene; Verma, Sunil; Iwata, Hiroji; Harbeck, Nadia; Zhang, Ke; Theall, Kathy Puyana; Jiang, Yuqiu; Bartlett, Cynthia Huang; Koehler, Maria; Slamon, Dennis

    2016-04-01

    In the PALOMA-3 study, the combination of the CDK4 and CDK6 inhibitor palbociclib and fulvestrant was associated with significant improvements in progression-free survival compared with fulvestrant plus placebo in patients with metastatic breast cancer. Identification of patients most suitable for the addition of palbociclib to endocrine therapy after tumour recurrence is crucial for treatment optimisation in metastatic breast cancer. We aimed to confirm our earlier findings with this extended follow-up and show our results for subgroup and biomarker analyses. In this multicentre, double-blind, randomised phase 3 study, women aged 18 years or older with hormone-receptor-positive, HER2-negative metastatic breast cancer that had progressed on previous endocrine therapy were stratified by sensitivity to previous hormonal therapy, menopausal status, and presence of visceral metastasis at 144 centres in 17 countries. Eligible patients-ie, any menopausal status, Eastern Cooperative Oncology Group performance status 0-1, measurable disease or bone disease only, and disease relapse or progression after previous endocrine therapy for advanced disease during treatment or within 12 months of completion of adjuvant therapy-were randomly assigned (2:1) via a centralised interactive web-based and voice-based randomisation system to receive oral palbociclib (125 mg daily for 3 weeks followed by a week off over 28-day cycles) plus 500 mg fulvestrant (intramuscular injection on days 1 and 15 of cycle 1; then on day 1 of subsequent 28-day cycles) or placebo plus fulvestrant. The primary endpoint was investigator-assessed progression-free survival. Analysis was by intention to treat. We also assessed endocrine therapy resistance by clinical parameters, quantitative hormone-receptor expression, and tumour PIK3CA mutational status in circulating DNA at baseline. This study is registered with ClinicalTrials.gov, NCT01942135. Between Oct 7, 2013, and Aug 26, 2014, 521 patients were randomly assigned, 347 to fulvestrant plus palbociclib and 174 to fulvestrant plus placebo. Study enrolment is closed and overall survival follow-up is in progress. By March 16, 2015, 259 progression-free-survival events had occurred (145 in the fulvestrant plus palbociclib group and 114 in the fulvestrant plus placebo group); median follow-up was 8·9 months (IQR 8·7-9·2). Median progression-free survival was 9·5 months (95% CI 9·2-11·0) in the fulvestrant plus palbociclib group and 4·6 months (3·5-5·6) in the fulvestrant plus placebo group (hazard ratio 0·46, 95% CI 0·36-0·59, p<0·0001). Grade 3 or 4 adverse events occurred in 251 (73%) of 345 patients in the fulvestrant plus palbociclib group and 38 (22%) of 172 patients in the fulvestrant plus placebo group. The most common grade 3 or 4 adverse events were neutropenia (223 [65%] in the fulvestrant plus palbociclib group and one [1%] in the fulvestrant plus placebo group), anaemia (ten [3%] and three [2%]), and leucopenia (95 [28%] and two [1%]). Serious adverse events (all causalities) occurred in 44 patients (13%) of 345 in the fulvestrant plus palbociclib group and 30 (17%) of 172 patients in the fulvestrant plus placebo group. PIK3CA mutation was detected in the plasma DNA of 129 (33%) of 395 patients for whom these data were available. Neither PIK3CA status nor hormone-receptor expression level significantly affected treatment response. Fulvestrant plus palbociclib was associated with significant and consistent improvement in progression-free survival compared with fulvestrant plus placebo, irrespective of the degree of endocrine resistance, hormone-receptor expression level, and PIK3CA mutational status. The combination could be considered as a therapeutic option for patients with recurrent hormone-receptor-positive, HER2-negative metastatic breast cancer that has progressed on previous endocrine therapy. Pfizer. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Changes in Hippocampal Volume are Correlated with Cell Loss but Not with Seizure Frequency in Two Chronic Models of Temporal Lobe Epilepsy

    PubMed Central

    Polli, Roberson S.; Malheiros, Jackeline M.; dos Santos, Renan; Hamani, Clement; Longo, Beatriz M.; Tannús, Alberto; Mello, Luiz E.; Covolan, Luciene

    2014-01-01

    Kainic acid (KA) or pilocarpine (PILO) have been used in rats to model human temporal lobe epilepsy (TLE) but the distribution and severity of structural lesions between these two models may differ. Magnetic resonance imaging (MRI) studies have used quantitative measurements of hippocampal T2 (T2HP) relaxation time and volume, but simultaneous comparative results have not been reported yet. The aim of this study was to compare the MRI T2HP and volume with histological data and frequency of seizures in both models. KA- and PILO-treated rats were imaged with a 2 T MRI scanner. T2HP and volume values were correlated with the number of cells, mossy fiber sprouting, and spontaneous recurrent seizures (SRS) frequency over the 9 months following status epilepticus (SE). Compared to controls, KA-treated rats had unaltered T2HP, pronounced reduction in hippocampal volume and concomitant cell reduction in granule cell layer, CA1 and CA3 at 3 months post SE. In contrast, hippocampal volume was unchanged in PILO-treated animals despite detectable increased T2HP and cell loss in granule cell layer, CA1 and CA3. In the following 6 months, MRI hippocampal volume remained stable with increase of T2HP signal in the KA-treated group. The number of CA1 and CA3 cells was smaller than age-matched CTL group. In contrast, PILO group had MRI volumetric reduction accompanied by reduction in the number of CA1 and CA3 cells. In this group, T2HP signal was unaltered at 6 or 9 months after status. Reductions in the number of cells were not progressive in both models. Notably, the SRS frequency was higher in PILO than in the KA model. The volumetry data correlated well with tissue damage in the epileptic brain, suggesting that MRI may be useful for tracking longitudinal hippocampal changes, allowing the assessment of individual variability and disease progression. Our results indicate that the temporal changes in hippocampal morphology are distinct for both models of TLE and that these are not significantly correlated to the frequency of SRS. PMID:25071699

  18. Increasing methylation of the calcitonin gene during disease progression in sequential samples from CML patients.

    PubMed

    Mills, K I; Guinn, B A; Walsh, V A; Burnett, A K

    1996-09-01

    In chronic myeloid leukaemia (CML), disease progression from the initial chronic phase to the acute phase or blast crisis has previously been shown to be correlated with progressive increases in hyper-methylation of the calcitonin gene, located at chromosome 11p15. However, sequential studies of individual patients were not performed in these investigations. We have analysed 44 samples from nine patients with typical Philadelphia chromosome positive CML throughout their disease progression to determine the methylation state of the calcitonin gene at these time points. Densitometry was used to quantitate the ratio of the normal 2.0 kb Hpa II fragments, indicating normal methylation status of the gene, compared to the intensity of the abnormal, hyper-methylated, 2.6-3.1 kb Hpa II fragments. We found a gradual increase in the ratio of methylated:unmethylated calcitonin gene during chronic phase with a dramatic rise at blast crisis. Further, the ratio of the abnormal hypermethylated 3.1 kb fragments to the methylated 2.6 kb fragment resulted in the identification of a clonal expansion of abnormally methylated cells. This expansion of cells with hypermethylation of the calcitonin gene during chronic phase was shown to coincide with the presence of a mutation in the p53 gene. The data presented in this study would suggest that an increased methylation status of the calcitonin gene during disease progression may indicate the expansion of abnormal blast cell populations and subsequent progression to blast crisis.

  19. Thiols of flagellar proteins are essential for progressive motility in human spermatozoa.

    PubMed

    Cabrillana, María Eugenia; Monclus, María de Los Ángeles; Lancellotti, Tania Estefania Sáez; Boarelli, Paola Vanina; Vincenti, Amanda Edith; Fornés, Miguel Matias; Sanabria, Eduardo Alfredo; Fornés, Miguel Walter

    2017-07-01

    Male infertility is a disorder of the reproductive system defined by the failure to achieve a clinical pregnancy after 12 months or more of regular unprotected sexual intercourse. The presence of low-motile or immotile spermatozoa is one of many causes of infertility; however, this observation provides little or no information regarding the pathogenesis of the malfunction. Good sperm motility depends on correct assembly of the sperm tail in the testis and efficient maturation during epididymal transit. Thiols of flagellar proteins, such as outer dense fibre protein 1 (ODF1), are oxidised to form disulfides during epididymal transit and the spermatozoa become motile. This study was designed to determine how oxidative changes in protein thiol status affect progressive motility in human spermatozoa. Monobromobimane (mBBr) was used as a specific thiol marker and disruptor of sperm progressive motility. When mBBr was blocked by dithiothreitol it did not promote motility changes. The analysis of mBBr-treated spermatozoa revealed a reduction of progressive motility and an increased number of spermatozoa with non-progressive motility without affecting ATP production. Laser confocal microscopy and western blot analysis showed that one of the mBBr-positive proteins reacted with an antibody to ODF1. Monobromobimane fluorescence intensity of the sperm tail was lower in normozoospermic than asthenozoospermic men, suggesting that thiol oxidation in spermatozoa of asthenozoospermic men is incomplete. Our findings indicate that mBBr affects the thiol status of ODF1 in human spermatozoa and interferes with progressive motility.

  20. The effect of preexisting respiratory co-morbidities on burn outcomes☆

    PubMed Central

    Knowlin, Laquanda T.; Stanford, Lindsay B.; Cairns, Bruce A.; Charles, Anthony G.

    2018-01-01

    Introduction Burns cause physiologic changes in multiple organ systems in the body. Burn mortality is usually attributable to pulmonary complications, which can occur in up to 41% of patients admitted to the hospital after burn. Patients with preexisting comorbidities such as chronic lung diseases may be more susceptible. We therefore sought to examine the impact of preexisting respiratory disease on burn outcomes. Methods A retrospective analysis of patients admitted to a regional burn center from 2002–2012. Independent variables analyzed included basic demographics, burn mechanism, presence of inhalation injury, TBSA, pre-existing comorbidities, smoker status, length of hospital stay, and days of mechanical ventilation. Bivariate analysis was performed and Cox regression modeling using significant variables was utilized to estimate hazard of progression to mechanical ventilation and mortality. Results There were a total of 7640 patients over the study period. Overall survival rate was 96%. 8% (n=672) had a preexisting respiratory disease. Chronic lung disease patients had a higher mortality rate (7%) compared to those without lung disease (4%, p<0.01). The adjusted Cox regression model to estimate the hazard of progression to mechanical ventilation in patients with respiratory disease was 21% higher compared to those without respiratory disease (HR=1.21, 95% CI=1.01–1.44). The hazard of progression to mortality is 56% higher (HR=1.56, 95% CI=1.10–2.19) for patients with pre-existing respiratory disease compared to those without respiratory disease after controlling for patient demographics and injury characteristics. Conclusion Preexisting chronic respiratory disease significantly increases the hazard of progression to mechanical ventilation and mortality in patients following burn. Given the increasing number of Americans with chronic respiratory diseases, there will likely be a greater number of individuals at risk for worse outcomes following burn. PMID:28341260

  1. The effect of preexisting respiratory co-morbidities on burn outcomes.

    PubMed

    Knowlin, Laquanda T; Stanford, Lindsay B; Cairns, Bruce A; Charles, Anthony G

    2017-03-01

    Burns cause physiologic changes in multiple organ systems in the body. Burn mortality is usually attributable to pulmonary complications, which can occur in up to 41% of patients admitted to the hospital after burn. Patients with preexisting comorbidities such as chronic lung diseases may be more susceptible. We therefore sought to examine the impact of preexisting respiratory disease on burn outcomes. A retrospective analysis of patients admitted to a regional burn center from 2002-2012. Independent variables analyzed included basic demographics, burn mechanism, presence of inhalation injury, TBSA, pre-existing comorbidities, smoker status, length of hospital stay, and days of mechanical ventilation. Bivariate analysis was performed and Cox regression modeling using significant variables was utilized to estimate hazard of progression to mechanical ventilation and mortality. There were a total of 7640 patients over the study period. Overall survival rate was 96%. 8% (n=672) had a preexisting respiratory disease. Chronic lung disease patients had a higher mortality rate (7%) compared to those without lung disease (4%, p<0.01). The adjusted Cox regression model to estimate the hazard of progression to mechanical ventilation in patients with respiratory disease was 21% higher compared to those without respiratory disease (HR=1.21, 95% CI=1.01-1.44). The hazard of progression to mortality is 56% higher (HR=1.56, 95% CI=1.10-2.19) for patients with pre-existing respiratory disease compared to those without respiratory disease after controlling for patient demographics and injury characteristics. Preexisting chronic respiratory disease significantly increases the hazard of progression to mechanical ventilation and mortality in patients following burn. Given the increasing number of Americans with chronic respiratory diseases, there will likely be a greater number of individuals at risk for worse outcomes following burn. Copyright © 2016 Elsevier Ltd and ISBI. All rights reserved.

  2. Florida's Progress toward Excellence in Education in the State Community College System. A Report to the State Board of Education.

    ERIC Educational Resources Information Center

    Florida State Board of Education, Tallahassee.

    Covering the 1983-84 academic year, this report describes the status of the Florida state community college system according to 19 different indicators of progress toward excellence. The 19 indicators are: (1) academic scholarships and fellowships awarded to graduates; (2) College Level Academic Skills Test scores; (3) findings of follow-up…

  3. Temperament, Select Home Environment Characteristics and Reading Readiness as Predictors of Reading Progress.

    ERIC Educational Resources Information Center

    Brown, T.J.

    Progress in a primary-grade reading program was determined for 106 first-born, second-grade students at the end of the school year. Previous data available for this sample included Thomas-Chase-Birch temperament ratings, family intactness and socioeconomic status at age four, and Metropolitan Readiness Test scores at age six. The value of these…

  4. Predictive Utility and Classification Accuracy of Oral Reading Fluency and the Measures of Academic Progress for the Wisconsin Knowledge and Concepts Exam

    ERIC Educational Resources Information Center

    Ball, Carrie R.; O'Connor, Edward

    2016-01-01

    This study examined the predictive validity and classification accuracy of two commonly used universal screening measures relative to a statewide achievement test. Results indicated that second-grade performance on oral reading fluency and the Measures of Academic Progress (MAP), together with special education status, explained 68% of the…

  5. Damaging effects of visible light. Comprehensive progress report

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

    None

    1981-01-01

    Research progress is reported on studies of retinal light damage. A myriad of variables effect the production of light damage. These include age, prior light history, body temperature, vitamin A status, intensity, wavelength and duration of light. The intensity-duration function and the age function have been studied in detail in rats. Studies have been begun on the wavelength variable. (ACR)

  6. Focal status epilepticus and progressive dyskinesia: A novel phenotype for glycine receptor antibody-mediated neurological disease in children.

    PubMed

    Chan, D W S; Thomas, T; Lim, M; Ling, S; Woodhall, M; Vincent, A

    2017-03-01

    Antibody-associated disorders of the central nervous system are increasingly recognised in adults and children. Some are known to be paraneoplastic, whereas in others an infective trigger is postulated. They include disorders associated with antibodies to N-methyl-d-aspartate receptor (NMDAR), voltage-gated potassium channel-complexes (VGKC-complex), GABA B receptor or glycine receptor (GlyR). With antibodies to NMDAR or VGKC-complexes, distinct clinical patterns are well characterised, but as more antibodies are discovered, the spectra of associated disorders are evolving. GlyR antibodies have been detected in patients with progressive encephalopathy with rigidity and myoclonus (PERM), or stiff man syndrome, both rare but disabling conditions. We report a case of a young child with focal seizures and progressive dyskinesia in whom GlyR antibodies were detected. Anticonvulsants and immunotherapy were effective in treating both the seizures and movement disorder with good neurological outcome and with a decline in the patient's serum GlyR-Ab titres. Glycine receptor antibodies are associated with focal status epilepticus and seizures, encephalopathy and progressive dyskinesia and should be evaluated in autoimmune encephalitis. Copyright © 2016 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  7. Assessment of Individuals with Primary Progressive Aphasia.

    PubMed

    Henry, Maya L; Grasso, Stephanie M

    2018-07-01

    Speech-language pathologists play a crucial role in the assessment and treatment of individuals with primary progressive aphasia (PPA). The speech-language evaluation is a critical aspect of the diagnostic and rehabilitative process, informing differential diagnosis as well as intervention planning and monitoring of cognitive-linguistic status over time. The evaluation should include a thorough case history and interview and a detailed assessment of speech-language and cognitive functions, with tasks designed to detect core and associated deficits outlined in current diagnostic criteria. In this paper, we review assessments that can be utilized to examine communication and cognition in PPA, including general aphasia batteries designed for stroke and/or progressive aphasia as well as tests of specific cognitive-linguistic functions, including naming, object/person knowledge, single-word and sentence comprehension, repetition, spontaneous speech/language production, motor speech, written language, and nonlinguistic cognitive domains. The comprehensive evaluation can inform diagnostic decision making and facilitate planning of interventions that are tailored to the patient's current status and likely progression of deficits. As such, the speech-language evaluation allows the medical team to provide individuals with PPA and their families with appropriate recommendations for the present and the future. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  8. Progressive decline of decision-making performances during multiple sclerosis.

    PubMed

    Simioni, Samanta; Ruffieux, Christiane; Kleeberg, Joerg; Bruggimann, Laure; du Pasquier, Renaud A; Annoni, Jean-Marie; Schluep, Myriam

    2009-03-01

    The purpose of this study was to evaluate longitudinally, using the Iowa Gambling Task (IGT), the dynamics of decision-making capacity at a two-year interval (median: 2.1 years) in a group of patients with multiple sclerosis (MS) (n = 70) and minor neurological disability [Expanded Disability Status Scale (EDSS) < or = 2.5 at baseline]. Cognition (memory, executive functions, attention), behavior, handicap, and perceived health status were also investigated. Standardized change scores [(score at retest-score at baseline)/standard deviation of baseline score] were computed. Results showed that IGT performances decreased from baseline to retest (from 0.3, SD = 0.4 to 0.1, SD = 0.3, p = .005). MS patients who worsened in the IGT were more likely to show a decreased perceived health status and emotional well-being (SEP-59; p = .05 for both). Relapsing rate, disability progression, cognitive, and behavioral changes were not associated with decreased IGT performances. In conclusion, decline in decision making can appear as an isolated deficit in MS.

  9. A Closer Look at Gender in NAEP Mathematics Achievement and Affect Data: Intersections with Achievement, Race/Ethnicity, and Socioeconomic Status

    ERIC Educational Resources Information Center

    McGraw, Rebecca; Lubienski, Sarah Theule; Strutchens, Marilyn E.

    2006-01-01

    In this article we describe gender gaps in mathematics achievement and attitude as measured by the U.S. National Assessment of Educational Progress (NAEP) from 1990 to 2003. Analyzing relationships among achievement and mathematical content, student proficiency and percentile levels, race, and socioeconomic status (SES), we found that gender gaps…

  10. The Impact of Students' Working Status on Academic Progress: Assessing the Implications of Policy Change in Greece

    ERIC Educational Resources Information Center

    Katsikas, Elias

    2013-01-01

    The study examines whether the reduction in the timeframe for the completion of university studies in Greece will affect students of different socio-economic background disproportionally. To this intent, it assesses the influence of the status of students, defined as working and non-working, on the duration of studies but the relevance of other…

  11. "Culture-Fair" Mental Ability Testing with Schoolchildren: A Review of the Silent Raven; Adequate If Used with Caution.

    ERIC Educational Resources Information Center

    Sigmon, Scott B.

    This paper examines Raven's Colored Progressive Matrices Scale (CPM) IQ test which is considered by many to be "culture fair." The emphasis is on socioeconomic status but factors of sex and ethnicity are also considered. Two major studies from which socioeconomic status data can be extracted are examined. These and other studies found…

  12. Helicopter Rotor Noise Prediction: Background, Current Status, and Future Direction

    NASA Technical Reports Server (NTRS)

    Brentner, Kenneth S.

    1997-01-01

    Helicopter noise prediction is increasingly important. The purpose of this viewgraph presentation is to: 1) Put into perspective the recent progress; 2) Outline current prediction capabilities; 3) Forecast direction of future prediction research; 4) Identify rotorcraft noise prediction needs. The presentation includes an historical perspective, a description of governing equations, and the current status of source noise prediction.

  13. Status and trends monitoring of riparian and aquatic habitat in the Olympic Experimental State Forest: Monitoring protocols

    Treesearch

    Teodora Minkova; Alex D. Foster

    2017-01-01

    Presented here are the monitoring protocols for the Status and Trends Monitoring of Riparian and Aquatic Habitats project in the Olympic Experimental State Forest (OESF). The procedures yield the empirical data needed to address key uncertainties regarding the integration of timber production and habitat conservation across landscapes and assess progress toward...

  14. Winning Public Support of a Desegregated School System. Title III ESEA Progress Report, School District 151 (South Holland, Illinois).

    ERIC Educational Resources Information Center

    South Holland School District 151, IL.

    Thirteen objectives of the program and analyses of each in terms of procedure, evaluation, the status of procedure, and status of the evaluation are listed in this report. The objectives are: the establishment of a community relations program to promote two-way communication between school board, administration, teachers, students, and parents;…

  15. Current Status of Cable Television in the Top-100 Broadcast Markets.

    ERIC Educational Resources Information Center

    Kaplan, Stuart J.

    1978-01-01

    A study of the status of cable television in the major broadcast markets suggests that the cable industry has made very little progress in penetrating the top-100 markets, that the rate of development of new cable systems in the top-100 markets has slowed in recent years, and that the primary function of cable television is to retransmit…

  16. Epidemiological Characteristics, EGFR Status and Management Patterns of Advanced Non-small Cell Lung Cancer Patients: The Greek REASON Observational Registry Study.

    PubMed

    Syrigos, Konstantinos N; Georgoulias, Vasilis; Zarogoulidis, Konstantinos; Makrantonakis, Paris; Charpidou, Andriani; Christodoulou, Christos

    2018-06-01

    Real-world evidence regarding the prevalence of epidermal growth factor receptor (EGFR) mutation-positive status (M+) and the clinicopathological characteristics associated with the presence of EGFR mutations in advanced non-small cell lung cancer (NSCLC) is scarce, especially among Caucasian populations. The present study aimed to bridge this gap, as well as to record treatment patterns and outcomes in routine-care settings. REASON (NCT01153399) was a prospective study of patients with stage IIIB/IV NSCLC and known EGFR mutation status. Clinicopathological, treatment characteristics and clinical outcomes were recorded and correlated with EGFR mutation testing results. Of 575 enrolled patients, EGFR mutations were detected in 15.7% of them. Male gender (p=0.008) and smoking (p<0.001), but not adenocarcinoma, were associated with EGFR M+ status. In the EGFR M+ subpopulation (n=88), absence of bone and/or brain metastasis and presence of exon 19 EGFR M+ status at diagnosis were independently associated with longer progression-free survival (PFS) (p=0.011 and p=0.040, respectively). In our population, males and smokers had decreased odds of harboring an EGFR mutation, while adenocarcinoma histology was not a significant predictor of EGFR M+ status. EGFR M+ patients with bone and/or brain metastases at diagnosis or mutations other than exon 19 deletions were at increased risk for earlier disease progression. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  17. Corpus callosum atrophy as a marker of clinically meaningful cognitive decline in secondary progressive multiple sclerosis. Impact on employment status.

    PubMed

    Papathanasiou, Athanasios; Messinis, Lambros; Zampakis, Petros; Papathanasopoulos, Panagiotis

    2017-09-01

    Cognitive impairment in Multiple Sclerosis (MS) is more frequent and pronounced in secondary progressive MS (SPMS). Cognitive decline is an important predictor of employment status in patients with MS. Magnetic Resonance Imaging (MRI) markers have been used to associate tissue damage with cognitive dysfunction. The aim of the study was to designate the MRI marker that predicts cognitive decline in SPMS and explore its effect on employment status. 30 SPMS patients and 30 healthy participants underwent neuropsychological assessment using the Trail Making Test (TMT) parts A and B, semantic and phonological verbal fluency task and a computerized cognitive screening battery (Central Nervous System Vital Signs). Employment status was obtained as a quality of life measure. Brain MRI was performed in all participants. We measured total lesion volume, third ventricle width, thalamic and corpus callosum atrophy. The frequency of cognitive decline for our SPMS patients was 80%. SPMS patients differed significantly from controls in all neuropsychological measures. Corpus callosum area was correlated with cognitive flexibility, processing speed, composite memory, executive functions, psychomotor speed, reaction time and phonological verbal fluency task. Processing speed and composite memory were the most sensitive markers for predicting employment status. Corpus callosum area was the most sensitive MRI marker for memory and processing speed. Corpus callosum atrophy predicts a clinically meaningful cognitive decline, affecting employment status in our SPMS patients. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Vitamin B-12 status and neurologic function in older people: a cross-sectional analysis of baseline trial data from the Older People and Enhanced Neurological Function (OPEN) study.

    PubMed

    Miles, Lisa M; Allen, Elizabeth; Mills, Kerry; Clarke, Robert; Uauy, Ricardo; Dangour, Alan D

    2016-09-01

    Aging is associated with a progressive decline in vitamin B-12 status. Overt vitamin B-12 deficiency causes neurologic disturbances in peripheral and central motor and sensory systems, but the public health impact for neurologic disease of moderately low vitamin B-12 status in older people is unclear. Evidence from observational studies is limited by heterogeneity in the definition of vitamin B-12 status and imprecise measures of nerve function. We aimed to determine whether vitamin B-12 status is associated with electrophysiologic indexes of peripheral or central neurologic function in asymptomatic older people with moderately low vitamin B-12 status. We used a cross-sectional analysis of baseline data from the Older People and Enhanced Neurological Function study conducted in Southeast England. This trial investigated the effectiveness of vitamin B-12 supplementation on electrophysiologic indexes of neurologic function in asymptomatic older people (mean age: 80 y) with moderately low vitamin B-12 status (serum vitamin B-12 concentrations ≥107 and <210 pmol/L without anemia, n = 201). Vitamin B-12 status was assessed with the use of total vitamin B-12, holotranscobalamin, and a composite indicator of vitamin B-12 status (cB-12). Electrophysiologic measures of sensory and motor components of peripheral and central nerve function were assessed in all participants by a single observer. In multivariate models, there was no evidence of an association of vitamin B-12, holotranscobalamin, or cB-12 with any nerve conduction outcome. There was also no evidence of an association of vitamin B-12 status with clinical markers of neurologic function. This secondary analysis of high-quality trial data did not show any association of any measure of vitamin B-12 status with either peripheral or central neurologic function or any clinical markers of neurologic function in older people with moderately low vitamin B-12 status. The results of this study are unlikely to be generalizable to a less healthy older population with more severe vitamin B-12 deficiency. This trial was registered at www.controlled-trials.com as ISRCTN54195799. © 2016 American Society for Nutrition.

  19. The Relationship Between Human Papillomavirus Status and Other Molecular Prognostic Markers in Head and Neck Squamous Cell Carcinomas

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

    Kong, Christina S.; Narasimhan, Balasubramanian; Cao Hongbin

    2009-06-01

    Purpose: To evaluate the relationship between human papillomavirus (HPV) status and known prognostic makers for head and neck cancers including tumor hypoxia, epidermal growth factor receptor (EGFR) expression and intratumoral T-cell levels and to determine the prognostic impact of these markers by HPV status. Methods and Materials: HPV status in 82 evaluable head and neck squamous cell carcinomas patients was determined by pyrosequencing and related to p16{sup INK4a} staining and treatment outcomes. It was correlated with tumor hypoxia (tumor pO{sub 2} and carbonic anhydrase [CAIX] staining), EGFR status, and intratumoral lymphocyte expression (CD3 staining). Results: Forty-four percent of evaluable tumorsmore » had strong HPV signal by pyrosequencing. There was a significant relationship between strong HPV signal and p16{sup INK4a} staining as well as oropharynx location. The strong HPV signal group fared significantly better than others, both in time to progression (TTP, p = 0.008) and overall survival (OS, p = 0.004) for all patients and for the oropharyngeal subset. Positive p16{sup INK4a} staining was associated with better TTP (p = 0.014) and OS (p = 0.00002). There was no relationship between HPV status and tumor pO{sub 2} or CAIX staining. However, HPV status correlated inversely with EGFR reactivity (p = 0.0006) and directly with CD3(+) T-lymphocyte level (p = 0.03). Whereas CAIX and EGFR overexpression were negative prognostic factors regardless of HPV status, CD3(+) T-cell levels was prognostic only in HPV(-) tumors. Conclusion: HPV status was a prognostic factor for progression and survival. It correlated inversely with EGFR expression and directly with T-cell infiltration. The prognostic effect of CAIX and EGFR expression was not influenced by HPV status, whereas intratumoral T-cell levels was significant only for HPV(-) tumors.« less

  20. Cost-effectiveness of a New Opportunistic Screening Strategy for Walk-in Fingertip HbA1c Testing at Community Pharmacies in Japan.

    PubMed

    Shono, Aiko; Kondo, Masahide; Hoshi, Shu-Ling; Okubo, Reiko; Yahagi, Naoya

    2018-06-01

    A new opportunistic community-based strategy was launched in Japan in April 2014 to detect lifestyle-related diseases, including diabetes, by creating Specimen Measurement Offices (SMOs). SMOs offer walk-in fingertip HbA 1c testing. This article aimed to assess the value-for-money of HbA 1c testing services at SMOs by conducting a cost-effectiveness analysis. We compared two scenarios: 1 ) status quo, defined as HbA 1c testing that is available only through conventional screening, and 2 ) HbA 1c testing available at SMOs as a complement to the status quo scenario. The model consisted of a screening module with a decision tree and a disease progression module with a Markov model. We calculated incremental cost-effectiveness ratios (i.e., cost per quality-adjusted life-years [QALYs]) over the lifetime analytic horizon as the primary end point of the cost-effectiveness analysis. In this model, we assumed the participant cohort to be people 40-74 years of age who sought walk-in fingertip HbA 1c testing at SMOs on the premises of community pharmacies. Costs and outcomes were discounted at a rate of 3%. The cost-effectiveness was analyzed from a societal perspective. The incremental cost per individual for those 40-74 years of age was estimated to be -527 U.S. dollars (USD) (-52,722 Japanese yen [JPY]) for HbA 1c testing at SMOs compared with the status quo. Incremental effectiveness was estimated to be 0.0203 QALYs for HbA 1c testing at SMOs compared with the status quo. Therefore, this cost-effectiveness analysis showed that compared with the status quo, HbA 1c testing at SMOs was more effective and had lower cost for the population studied. We consider our results to be robust because most simulations were under the threshold of USD 50,000 (JPY 5,000,000) per QALYs gained, by sensitivity analysis. These results will be useful to managers of pharmacies or other health institutions and/or policy makers in local government. © 2018 by the American Diabetes Association.

  1. BFLCRM: A BAYESIAN FUNCTIONAL LINEAR COX REGRESSION MODEL FOR PREDICTING TIME TO CONVERSION TO ALZHEIMER’S DISEASE*

    PubMed Central

    Lee, Eunjee; Zhu, Hongtu; Kong, Dehan; Wang, Yalin; Giovanello, Kelly Sullivan; Ibrahim, Joseph G

    2015-01-01

    The aim of this paper is to develop a Bayesian functional linear Cox regression model (BFLCRM) with both functional and scalar covariates. This new development is motivated by establishing the likelihood of conversion to Alzheimer’s disease (AD) in 346 patients with mild cognitive impairment (MCI) enrolled in the Alzheimer’s Disease Neuroimaging Initiative 1 (ADNI-1) and the early markers of conversion. These 346 MCI patients were followed over 48 months, with 161 MCI participants progressing to AD at 48 months. The functional linear Cox regression model was used to establish that functional covariates including hippocampus surface morphology and scalar covariates including brain MRI volumes, cognitive performance (ADAS-Cog), and APOE status can accurately predict time to onset of AD. Posterior computation proceeds via an efficient Markov chain Monte Carlo algorithm. A simulation study is performed to evaluate the finite sample performance of BFLCRM. PMID:26900412

  2. Computerized symbolic manipulation in structural mechanics Progress and potential

    NASA Technical Reports Server (NTRS)

    Noor, A. K.; Andersen, C. M.

    1978-01-01

    Status and recent applications of computerized symbolic manipulation to structural mechanics problems are summarized. The applications discussed include; (1) generation of characteristic arrays of finite elements; (2) evaluation of effective stiffness and mass coefficients of continuum models for repetitive lattice structures; and (3) application of Rayleigh-Ritz technique to free vibration analysis of laminated composite elliptic plates. The major advantages of using computerized symbolic manipulation in each of these applications are outlined. A number of problem areas which limit the realization of the full potential of computerized symbolic manipulation in structural mechanics are examined and some of the means of alleviating them are discussed.

  3. Manufacturing Marginality among Women and Latinos in Neoliberal America.

    PubMed

    Massey, Douglas S

    2014-01-01

    Intersectionality is the study of how categorical distinctions made on the basis of race, class, and gender interact to generate inequality, and this concept has become a primary lens by which scholars have come to model social stratification in the United States. In addition to the historically powerful interaction between race and class, gender interactions have become increasingly powerful in exacerbating class inequalities while the growing exclusion of foreigners on the basis of legal status has progressively marginalized Latinos in U.S. society. As a result, poor whites and immigrant-origin Latinos have increasingly joined African Americans at the bottom of American society to form a new, expanded underclass.

  4. Memory performance on the story recall test and prediction of cognitive dysfunction progression in mild cognitive impairment and Alzheimer's dementia.

    PubMed

    Park, Jong-Hwan; Park, Hyuntae; Sohn, Sang Wuk; Kim, Sungjae; Park, Kyung Won

    2017-10-01

    To determine the factors that influence diagnosis and differentiation of patients with mild cognitive impairment (MCI) and Alzheimer's dementia (AD) by comparing memory test results at baseline with those at 1-2-year follow up. We consecutively recruited 23 healthy participants, 44 MCI patients and 27 patients with very mild AD according to the National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorder Association criteria for probable Alzheimer's disease and Petersen's clinical diagnostic criteria. We carried out detailed neuropsychological tests, including the Story Recall Test (SRT) and the Seoul Verbal Learning Test, for all participants. We defined study participants as the "progression group" as follows: (i) participants who showed conversion to dementia from the MCI state; and (ii) those with dementia who showed more than a three-point decrement in their Mini-Mental State Examination scores with accompanying functional decline from baseline status, which were ascertained by physician's clinical judgment. The SRT delayed recall scores were significantly lower in the patients with mild AD than in those with MCI and after progression. Lower (relative risk 1.1, 95% confidence interval 0.1-1.6) and higher SRT delayed recall scores (relative risk 2.1, confidence interval 1.0-2.8), and two-test combined immediate and delayed recall scores (relative risk 2.0, confidence interval 0.9-2.3; and relative risk 2.8, confidence interval 1.1-4.2, respectively) were independent predictors of progression in a stepwise multiple adjusted Cox proportional hazards model, with age, sex, depression and educational level forced into the model. The present study suggests that the SRT delayed recall score independently predicts progression to dementia in patients with MCI. Geriatr Gerontol Int 2017; 17: 1603-1609. © 2016 Japan Geriatrics Society.

  5. Measurement and computer simulation of antennas on ships and aircraft for results of operational reliability

    NASA Astrophysics Data System (ADS)

    Kubina, Stanley J.

    1989-09-01

    The review of the status of computational electromagnetics by Miller and the exposition by Burke of the developments in one of the more important computer codes in the application of the electric field integral equation method, the Numerical Electromagnetic Code (NEC), coupled with Molinet's summary of progress in techniques based on the Geometrical Theory of Diffraction (GTD), provide a clear perspective on the maturity of the modern discipline of computational electromagnetics and its potential. Audone's exposition of the application to the computation of Radar Scattering Cross-section (RCS) is an indication of the breadth of practical applications and his exploitation of modern near-field measurement techniques reminds one of progress in the measurement discipline which is essential to the validation or calibration of computational modeling methodology when applied to complex structures such as aircraft and ships. The latter monograph also presents some comparison results with computational models. Some of the results presented for scale model and flight measurements show some serious disagreements in the lobe structure which would require some detailed examination. This also applies to the radiation patterns obtained by flight measurement compared with those obtained using wire-grid models and integral equation modeling methods. In the examples which follow, an attempt is made to match measurements results completely over the entire 2 to 30 MHz HF range for antennas on a large patrol aircraft. The problem of validating computer models of HF antennas on a helicopter and using computer models to generate radiation pattern information which cannot be obtained by measurements are discussed. The use of NEC computer models to analyze top-side ship configurations where measurement results are not available and only self-validation measures are available or at best comparisons with an alternate GTD computer modeling technique is also discussed.

  6. Status of costing hospital nursing work within Australian casemix activity-based funding policy.

    PubMed

    Heslop, Liza

    2012-02-01

    Australia has a long history of patient level costing initiated when casemix funding was implemented in several states in the early 1990s. Australia includes, to some extent, hospital payment based on nursing intensity adopted within casemix funding policy and the Diagnostic Related Group system. Costing of hospital nursing services in Australia has not changed significantly in the last few decades despite widespread introduction of casemix funding policy at the state level. Recent Commonwealth of Australia National Health Reform presents change to the management of the delivery of health care including health-care costing. There is agreement for all Australian jurisdictions to progress to casemix-based activity funding. Within this context, nurse costing infrastructure presents contemporary issues and challenges. An assessment is made of the progress of costing nursing services within casemix funding models in Australian hospitals. Valid and reliable Australian-refined nursing service weights might overcome present cost deficiencies and limitations. © 2012 Blackwell Publishing Asia Pty Ltd.

  7. Equitable science education in urban middle schools: Do reform efforts make a difference?

    NASA Astrophysics Data System (ADS)

    Hewson, Peter W.; Butler Kahle, Jane; Scantlebury, Kathryn; Davies, Darleen

    2001-12-01

    A central commitment of current reforms in science education is that all students, regardless of culture, gender, race, and/ or socioeconomic status, are capable of understanding and doing science. The study Bridging the Gap: Equity in Systemic Reform assessed equity in systemic reform using a nested research design that drew on both qualitative and quantitative methodologies. As part of the study, case studies were conducted in two urban middle schools in large Ohio cities. The purpose of the case studies was to identify factors affecting equity in urban science education reform. Data were analyzed using Kahle's (1998) equity metric. That model allowed us to assess progress toward equity using a range of research-based indicators grouped into three categories critical for equitable education: access to, retention in, and achievement in quality science education. In addition, a fourth category was defined for systemic indicators of equity. Analyses indicated that the culture and climate of the case study schools differentially affected their progress toward equitable reform in science education.

  8. Self-reported levels of education and disability progression in multiple sclerosis.

    PubMed

    D'hooghe, M B; Haentjens, P; Van Remoortel, A; De Keyser, J; Nagels, G

    2016-12-01

    The purpose of our study is to investigate whether socioeconomic indicators such as education, financial concerns, employment, and living status are associated with disease progression in relapsing-onset and progressive-onset Multiple Sclerosis (MS). We performed a cross-sectional survey among individuals with MS, registered by the Flemish MS society and included socioeconomic indicators. A Cox proportional hazard regression was performed with the time from MS onset and from birth to reach an ambulatory disability milestone corresponding to Expanded Disability Status Scale (EDSS) 6 (requiring a cane) as outcome measure, adjusted for gender, age at MS onset, and immunomodulatory treatment. Among the participants with relapsing-onset MS, subjects reporting education for more than 12 years had a reduced risk of reaching EDSS 6 compared to subjects reporting education for less than 12 years [HR from onset 0.68 (95% CI 0.49-0.95); HR from birth 0.71 (95% CI 0.51-0.99)]. In progressive-onset MS, longer education was associated with an increased hazard to reach EDSS 6 [HR from onset 1.25 (95% CI 0.91-1.70); HR from birth 1.39 (95% CI 1.02-1.90)]. Our study shows an association of self-reported levels of education with disability progression in MS, with the highest level being protective in relapsing-onset MS. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. Attempts to probe the ozone layer and the ultraviolet-B levels of the past.

    PubMed

    Björn, Lars Olof; McKenzie, Richard L

    2007-07-01

    To get a proper perspective on the current status of atmospheric ozone, which protects the biosphere from ultraviolet-B (UV-B; 280-315 nm) radiation, it would be of value to know how ozone and UV-B radiation have varied in the past. The record of worldwide ozone monitoring goes back only a few decades, and the record of reliable UV-B measurements is even shorter. Here we review indirect methods to assess their status further back in time. These include variations in the Sun's emission and how these affect the atmosphere, changes in the Earth's orbit, geologic imprints of atmospheric ozone, effects of catastrophic events such as volcanic eruptions, biological proxies of UV-B radiation, the spectral signature of terrestrial ozone in old recordings of star spectra, and the modeling of UV-B irradiance from ozone data and meteorological recordings. Although reliable reconstructions do not yet extend far into the past, there is some hope for future progress.

  10. Defining the therapeutic time window for suppressing the inflammatory prostaglandin E2 signaling after status epilepticus

    PubMed Central

    Du, Yifeng; Kemper, Timothy; Qiu, Jiange; Jiang, Jianxiong

    2016-01-01

    Neuroinflammation is a common feature in nearly all neurological and some psychiatric disorders. Resembling its extraneural counterpart, neuroinflammation can be both beneficial and detrimental depending on the responding molecules. The overall effect of inflammation on disease progression is highly dependent on the extent of inflammatory mediator production and the duration of inflammatory induction. The time-dependent aspect of inflammatory responses suggests that the therapeutic time window for quelling neuroinflammation might vary with molecular targets and injury types. Therefore, it is important to define the therapeutic time window for anti-inflammatory therapeutics, as contradicting or negative results might arise when different treatment regimens are utilized even in similar animal models. Herein, we discuss a few critical factors that can help define the therapeutic time window and optimize treatment paradigm for suppressing the cyclooxygenase-2/prostaglandin-mediated inflammation after status epilepticus. These determinants should also be relevant to other anti-inflammatory therapeutic strategies for the CNS diseases. PMID:26689339

  11. New Archiving Distributed InfrastructuRe (NADIR): Status and Evolution

    NASA Astrophysics Data System (ADS)

    De Marco, M.; Knapic, C.; Smareglia, R.

    2015-09-01

    The New Archiving Distributed InfrastructuRe (NADIR) has been developed at INAF-OATs IA2 (Italian National Institute for Astrophysics - Astronomical Observatory of Trieste, Italian center of Astronomical Archives), as an evolution of the previous archiving and distribution system, used on several telescopes (LBT, TNG, Asiago, etc.) to improve performance, efficiency and reliability. At the present, NADIR system is running on LBT telescope and Vespa (Italian telescopes network for outreach) Ramella et al. (2014), and will be used on TNG, Asiago and IRA (Istituto Radio Astronomia) archives of Medicina, Noto and SRT radio telescopes Zanichelli et al. (2014) as the data models for radio data will be ready. This paper will discuss the progress status, the architectural choices and the solutions adopted, during the development and the commissioning phase of the project. A special attention will be given to the LBT case, due to some critical aspect of data flow and policies and standards compliance, adopted by the LBT organization.

  12. Theranostics of Neuroendocrine Tumors.

    PubMed

    Lee, Sze Ting; Kulkarni, Harshad R; Singh, Aviral; Baum, Richard P

    2017-10-01

    Somatostatin receptor positron emission tomography/computed tomography using 68 Ga-labeled somatostatin analogs is the mainstay for the evaluation of receptor status in neuroendocrine tumors (NETs). This translates towards better therapy options, with increasing evidence of peptide receptor radionuclide therapy (PRRT) as the treatment of choice for advanced or progressive NETs. There are benefits in progression-free and overall survival as well as a significant improvement in clinical condition. In patients with progressive NETs, fractionated, personalized PRRT results in good therapeutic responses with no significant severe hematological and/or renal toxicity, thus improving quality of life.

  13. Space Shuttle External Tank Project status

    NASA Technical Reports Server (NTRS)

    Davis, R. M.

    1980-01-01

    The External Tank Project is reviewed with emphasis on the DDT&E and production phases and the lightweight tank development. It is noted that the DDT&E phase is progressing well with the structural and ground vibration test article programs complete, the propulsion test article program progressing well, and the component qualification and verification testing 92% complete. New tools and facilities are being brought on line to support the increased build rate for the production phase. The lightweight tank, which will provide additional payload in orbit, is progressing to schedule with first delivery in early 1982.

  14. Comparison of progress of patients with professional and paraprofessional counselors in a methadone maintenance program.

    PubMed

    Connett, G E

    1980-05-01

    The progress of two groups of patients on methadone maintenance were compared by examining urine results for use or nonuse of illicit drugs, attaiment of a drug-free status, employment, continuous time in treatment, and take-out-clinic (TOC) medication (an assessment of a patient's overall progress as determined by the treatment team). Four paraprofessional counselors with an average education level of 12.7 years followed Group A patients (CGA) while five master's degree trained counselors followed Group B patients (CGB) (Table 1).

  15. PI3K pathway mutations are associated with longer time to local progression after radioembolization of colorectal liver metastases.

    PubMed

    Ziv, Etay; Bergen, Michael; Yarmohammadi, Hooman; Boas, F Ed; Petre, E Nadia; Sofocleous, Constantinos T; Yaeger, Rona; Solit, David B; Solomon, Stephen B; Erinjeri, Joseph P

    2017-04-04

    To establish the relationship between common mutations in the MAPK and PI3K signaling pathways and local progression after radioembolization. Retrospective review of a HIPAA-compliant institutional review-board approved database identified 40 patients with chemo-refractory colorectal liver metastases treated with radioembolization who underwent tumor genotyping for hotspot mutations in 6 key genes in the MAPK/PI3K pathways (KRAS, NRAS, BRAF, MEK1, PIK3CA, and AKT1). Mutation status as well as clinical, tumor, and treatment variables were recorded. These factors were evaluated in relation to time to local progression (TTLP), which was calculated from time of radioembolization to first radiographic evidence of local progression. Predictors of outcome were identified using a proportional hazards model for both univariate and multivariate analysis with death as a competing risk. Sixteen patients (40%) had no mutations in either pathway, eighteen patients (45%) had mutations in the MAPK pathway, ten patients (25%) had mutations in the PI3K pathway and four patients (10%) had mutations in both pathways. The cumulative incidence of progression at 6 and 12 months was 33% and 55% for the PI3K mutated group compared with 76% and 92% in the PI3K wild type group. Mutation in the PI3K pathway was a significant predictor of longer TTLP in both univariate (p=0.031, sHR 0.31, 95% CI: 0.11-0.90) and multivariate (p=0.015, sHR=0.27, 95% CI: 0.096-0.77) analysis. MAPK pathway alterations were not associated with TTLP. PI3K pathway mutation predicts longer time to local progression after radioembolization of colorectal liver metastases.

  16. Spontaneous and induced aneuploidy, considerations which may influence chromosome malsegregation.

    PubMed

    Parry, James M; Al-Obaidly, A; Al-Walhaib, M; Kayani, M; Nabeel, T; Strefford, J; Parry, E M

    2002-07-25

    Aneuploidy plays a major role in the production of human birth defects and is becoming increasingly recognised as a critical event in the etiology of a wide range of human cancers. Thus, the detection of aneuploidy and the characterisation of the mechanisms which lead to chromosome malsegregation is an important area of genotoxicological research. As an aid to aneuploidy research, methods have been developed to analyse the mechanisms of chromosome malsegregation and to investigate the role of aneuploidy in tumour progression. The presence of aneuploid cells is a common characteristic of many of tumour cell types as illustrated by the wide range of chromosome number changes detected in post-menopausal breast tumours. To investigate the time of occurrence of aneuploidy during tumour progression, we have studied the chromosome number status of Syrian hamster dermal (SHD) cells cultures progressing to morphological transformation. The production of both polyploid and aneuploid cells is a common feature of progressing cells in this model. The elevation of both progression to morphological transformation and aneuploid frequencies can be produced by exposure to a diverse range of carcinogens and tumour promoters. Analysis of the genotoxic activity of the hormone 17-beta oestradiol demonstrated its ability to induce both chromosome loss and non-disjunction in human lymphoblastoid cells implicating aneugenic activity in hormone related cancers. Mutations in the p53 tumour suppressor gene introduced into human fibroblasts produced modifications in chromosome separation at mitosis which may lead to the production of both aneuploidy and polyploid cells. Our studies indicate that the production of aneuploid cells can be influenced by both endogenous and exogenous factors and occur throughout the progression of normal cells to a malignant phenotype.

  17. Health-related quality of life impact in a randomised phase III study of the combination of dabrafenib and trametinib versus dabrafenib monotherapy in patients with BRAF V600 metastatic melanoma.

    PubMed

    Schadendorf, Dirk; Amonkar, Mayur M; Stroyakovskiy, Daniil; Levchenko, Evgeny; Gogas, Helen; de Braud, Filippo; Grob, Jean-Jacques; Bondarenko, Igor; Garbe, Claus; Lebbe, Celeste; Larkin, James; Chiarion-Sileni, Vanna; Millward, Michael; Arance, Ana; Mandalà, Mario; Flaherty, Keith T; Nathan, Paul; Ribas, Antoni; Robert, Caroline; Casey, Michelle; DeMarini, Douglas J; Irani, Jhangir G; Aktan, Gursel; Long, Georgina V

    2015-05-01

    To present the impact of treatments on health-related quality of life (HRQoL) from the double-blind, randomised phase III COMBI-d study that investigated the combination of dabrafenib and trametinib versus dabrafenib monotherapy in patients with BRAF V600E/K-mutant metastatic melanoma. COMBI-d showed significantly prolonged progression-free survival for the combination. HRQoL was evaluated using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30, a generic cancer questionnaire (completed at baseline, during study treatment, at progression and post progression) assessing various dimensions (global health/QoL, functional status, and symptom impact). A mixed-model, repeated-measures analyses of covariance evaluated differences between arms. Questionnaire completion rates were >95% at baseline, >85% to week 40 and >70% at disease progression. Baseline scores across both arms were comparable for all dimensions. Global health dimension scores were significantly better at weeks 8, 16 and 24 for patients receiving the combination during treatment and at progression. The majority of functional dimension scores (physical, social, role, emotional and cognitive functioning) trended in favour of the combination. Pain scores were significantly improved and clinically meaningful (6-13 point difference) for patients receiving the combination for all follow-up assessments versus those receiving dabrafenib monotherapy. For other symptom dimensions (nausea and vomiting, diarrhoea, dyspnoea, and constipation), scores trended in favour of dabrafenib monotherapy. This analysis demonstrates that the combination of dabrafenib and trametinib provides better preservation of HRQoL and pain improvements versus dabrafenib monotherapy while also delaying progression. (Clinicaltrials.gov registration number: NCT01584648). Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. The Status of Women in Physics in the U.S.: Progress and New Actions

    NASA Astrophysics Data System (ADS)

    Xie, Aihua

    2005-10-01

    The 2005 Chair of the American Physical Society Committee on the Status of Women in Physics describes the committee's recent activities to recognize distinguished women physicists, improve the climate for women in physics, and provide leadership training for women in physics. The committee's response to the Harvard University president's suggestion of innate gender differences as regards women's representation in math and science is also discussed, as well as some encouraging developments in the status of women in physics in the U.S.

  19. Neonatal Iron Supplementation Induces Striatal Atrophy in Female YAC128 Huntington's Disease Mice.

    PubMed

    Berggren, Kiersten L; Lu, Zhen; Fox, Julia A; Dudenhoeffer, Megan; Agrawal, Sonal; Fox, Jonathan H

    2016-01-01

    Dysregulation of iron homeostasis is implicated in the pathogenesis of Huntington's disease. We have previously shown that increased iron intake in R6/2 HD neonatal mice, but not adult R6/2 HD mice potentiates disease outcomes at 12-weeks of age corresponding to advanced HD [Redox Biol. 2015;4 : 363-74]. However, whether these findings extend to other HD models is unknown. In particular, it is unclear if increased neonatal iron intake can promote neurodegeneration in mouse HD models where disease onset is delayed to mid-adult life. To determine if increased dietary iron intake in neonatal and adult life-stages potentiates HD in the slowly progressive YAC128 HD mouse model. Female neonatal mice were supplemented daily from days 10-17 with 120μg/g body weight of carbonyl iron. Adult mice were provided diets containing low (50 ppm), medium (150 ppm) and high (500 ppm) iron concentrations from 2-months of age. HD progression was determined using behavioral, brain morphometric and biochemical approaches. Neonatal-iron supplemented YAC128 HD mice had significantly lower striatal volumes and striatal neuronal cell body volumes as compared to control HD mice at 1-year of age. Neonatal-iron supplementation of HD mice had no effect on rota-rod motor endurance and brain iron or glutathione status. Adult iron intake level had no effect on HD progression. YAC128 HD mice had altered peripheral responses to iron intake compared to iron-matched wild-type controls. Female YAC128 HD mice supplemented with nutritionally-relevant levels of iron as neonates demonstrate increased striatal degeneration 1-year later.

  20. Neonatal Iron Supplementation Induces Striatal Atrophy in Female YAC128 Huntington’s Disease Mice

    PubMed Central

    Berggren, Kiersten L.; Lu, Zhen; Fox, Julia A.; Dudenhoeffer, Megan; Agrawal, Sonal; Fox, Jonathan H.

    2016-01-01

    Background: Dysregulation of iron homeostasis is implicated in the pathogenesis of Huntington’s disease. We have previously shown that increased iron intake in R6/2 HD neonatal mice, but not adult R6/2 HD mice potentiates disease outcomes at 12-weeks of age corresponding to advanced HD [Redox Biol. 2015;4 : 363–74]. However, whether these findings extend to other HD models is unknown. In particular, it is unclear if increased neonatal iron intake can promote neurodegeneration in mouse HD models where disease onset is delayed to mid-adult life. Objective: To determine if increased dietary iron intake in neonatal and adult life-stages potentiates HD in the slowly progressive YAC128 HD mouse model. Methods: Female neonatal mice were supplemented daily from days 10–17 with 120μg/g body weight of carbonyl iron. Adult mice were provided diets containing low (50 ppm), medium (150 ppm) and high (500 ppm) iron concentrations from 2-months of age. HD progression was determined using behavioral, brain morphometric and biochemical approaches. Results: Neonatal-iron supplemented YAC128 HD mice had significantly lower striatal volumes and striatal neuronal cell body volumes as compared to control HD mice at 1-year of age. Neonatal-iron supplementation of HD mice had no effect on rota-rod motor endurance and brain iron or glutathione status. Adult iron intake level had no effect on HD progression. YAC128 HD mice had altered peripheral responses to iron intake compared to iron-matched wild-type controls. Conclusions: Female YAC128 HD mice supplemented with nutritionally-relevant levels of iron as neonates demonstrate increased striatal degeneration 1-year later. PMID:27079948

  1. The status, recent progress and promise of superconducting materials for practical applications

    NASA Astrophysics Data System (ADS)

    Rowell, J. M.

    1989-03-01

    The author summarizes the progress in materials science and engineering that created today's superconducting technology. He reviews the state of the technology with conventional materials by looking at two particular applications: large-scale applications involving conductors, for example, magnets; and electronics and instrumentation applications. The state-of-the art is contrasted with the present understanding of the high-Tc oxide materials.

  2. Gas-heat-pump development

    NASA Astrophysics Data System (ADS)

    Creswick, F. A.

    Incentives for the development of gas heat pumps are discussed. Technical progress made on several promising technologies was reviewed. The status of development of gas-engine-driven heat pumps, the absorption cycle for the near- and long-term gas heat pump systems, the Stirling engine, the small Rankine-cycle engines, and gas-turbine-driven heat pump systems were briefly reviewed. Progress in the US, Japan, and Europe is noted.

  3. Examining the Relationships among Mathematics Coaches and Specialists, Student Achievement, and Disability Status: A Multilevel Analysis Using National Assessment of Educational Progress Data

    ERIC Educational Resources Information Center

    Harbour, Kristin E.; Adelson, Jill L.; Pittard, Caroline M.; Karp, Karen S.

    2018-01-01

    Using restricted-use data from the 2011 National Assessment of Educational Progress mathematics assessment, the current study examined the relationship between the presence of elementary mathematics coaches and specialists (MCSs) and the mathematics achievement of more than 190,000 fourth-grade students in more than 7,400 schools nationwide. In…

  4. Association between use of interferon beta and progression of disability in patients with relapsing-remitting multiple sclerosis.

    PubMed

    Shirani, Afsaneh; Zhao, Yinshan; Karim, Mohammad Ehsanul; Evans, Charity; Kingwell, Elaine; van der Kop, Mia L; Oger, Joel; Gustafson, Paul; Petkau, John; Tremlett, Helen

    2012-07-18

    Interferon beta is widely prescribed to treat multiple sclerosis (MS); however, its relationship with disability progression has yet to be established. To investigate the association between interferon beta exposure and disability progression in patients with relapsing-remitting MS. Retrospective cohort study based on prospectively collected data (1985-2008) from British Columbia, Canada. Patients with relapsing-remitting MS treated with interferon beta (n = 868) were compared with untreated contemporary (n = 829) and historical (n = 959) cohorts. The main outcome measure was time from interferon beta treatment eligibility (baseline) to a confirmed and sustained score of 6 (requiring a cane to walk 100 m; confirmed at >150 days with no measurable improvement) on the Expanded Disability Status Scale (EDSS) (range, 0-10, with higher scores indicating higher disability). A multivariable Cox regression model with interferon beta treatment included as a time-varying covariate was used to assess the hazard of disease progression associated with interferon beta treatment. Analyses also included propensity score adjustment to address confounding by indication. The median active follow-up times (first to last EDSS measurement) were as follows: for the interferon beta-treated cohort, 5.1 years (interquartile range [IQR], 3.0-7.0 years); for the contemporary control cohort, 4.0 years (IQR, 2.1-6.4 years); and for the historical control cohort, 10.8 years (IQR, 6.3-14.7 years). The observed outcome rates for reaching a sustained EDSS score of 6 were 10.8%, 5.3%, and 23.1% in the 3 cohorts, respectively. After adjustment for potential baseline confounders (sex, age, disease duration, and EDSS score), exposure to interferon beta was not associated with a statistically significant difference in the hazard of reaching an EDSS score of 6 when either the contemporary control cohort (hazard ratio, 1.30; 95% CI, 0.92-1.83; P = .14) or the historical control cohort (hazard ratio, 0.77; 95% CI, 0.58-1.02; P = .07) were considered. Further adjustment for comorbidities and socioeconomic status, where possible, did not change interpretations, and propensity score adjustment did not substantially change the results. Among patients with relapsing-remitting MS, administration of interferon beta was not associated with a reduction in progression of disability.

  5. Natural history of age-related lobular involution and impact on breast cancer risk.

    PubMed

    Radisky, Derek C; Visscher, Daniel W; Frank, Ryan D; Vierkant, Robert A; Winham, Stacey; Stallings-Mann, Melody; Hoskin, Tanya L; Nassar, Aziza; Vachon, Celine M; Denison, Lori A; Hartmann, Lynn C; Frost, Marlene H; Degnim, Amy C

    2016-02-01

    Age-related lobular involution (LI) is a physiological process in which the terminal duct lobular units of the breast regress as a woman ages. Analyses of breast biopsies from women with benign breast disease (BBD) have found that extent of LI is negatively associated with subsequent breast cancer development. Here we assess the natural course of LI within individual women, and the impact of progressive LI on breast cancer risk. The Mayo Clinic BBD cohort consists of 13,455 women with BBD from 1967 to 2001. The BBD cohort includes 1115 women who had multiple benign biopsies, 106 of whom had developed breast cancer. Within this multiple biopsy cohort, the progression of the LI process was examined by age at initial biopsy and time between biopsies. The relationship between LI progression and breast cancer risk was assessed using standardized incidence ratios and by Cox proportional hazards analysis. Women who had multiple biopsies were younger age and had a slightly higher family history of breast cancer as compared with the overall BBD cohort. Extent of LI at subsequent biopsy was greater with increasing time between biopsies and for women age 55 + at initial biopsy. Among women with multiple biopsies, there was a significant association of higher breast cancer risk among those with involution stasis (lack of progression, HR 1.63) as compared with those with involution progression, p = 0.036. The multiple biopsy BBD cohort allows for a longitudinal study of the natural progression of LI. The majority of women in the multiple biopsy cohort showed progression of LI status between benign biopsies, and extent of progression was highest for women who were in the perimenopausal age range at initial biopsy. Progression of LI status between initial and subsequent biopsy was associated with decreased breast cancer risk.

  6. Detection of minimal residual disease following induction immunochemotherapy predicts progression free survival in mantle cell lymphoma: final results of CALGB 59909

    PubMed Central

    Liu, Hongtao; Johnson, Jeffrey L.; Koval, Greg; Malnassy, Greg; Sher, Dorie; Damon, Lloyd E.; Hsi, Eric D.; Bucci, Donna Marie; Linker, Charles A.; Cheson, Bruce D.; Stock, Wendy

    2012-01-01

    Background In the present study, the prognostic impact of minimal residual disease during treatment on time to progression and overall survival was analyzed prospectively in patients with mantle cell lymphoma treated on the Cancer and Leukemia Group B 59909 clinical trial. Design and Methods Peripheral blood and bone marrow samples were collected during different phases of the Cancer and Leukemia Group B 59909 study for minimal residual disease analysis. Minimal residual disease status was determined by quantitative polymerase chain reaction of IgH and/or BCL-1/JH gene rearrangement. Correlation of minimal residual disease status with time to progression and overall survival was determined. In multivariable analysis, minimal residual disease, and other risk factors were correlated with time to progression. Results Thirty-nine patients had evaluable, sequential peripheral blood and bone marrow samples for minimal residual disease analysis. Using peripheral blood monitoring, 18 of 39 (46%) achieved molecular remission following induction therapy. The molecular remission rate increased from 46 to 74% after one course of intensification therapy. Twelve of 21 minimal residual disease positive patients (57%) progressed within three years of follow up compared to 4 of 18 (22%) molecular remission patients (P=0.049). Detection of minimal residual disease following induction therapy predicted disease progression with a hazard ratio of 3.7 (P=0.016). The 3-year probability of time to progression among those who were in molecular remission after induction chemotherapy was 82% compared to 48% in patients with detectable minimal residual disease. The prediction of time to progression by post-induction minimal residual disease was independent of other prognostic factors in multivariable analysis. Conclusions Detection of minimal residual disease following induction immunochemotherapy was an independent predictor of time to progression following immunochemotherapy and autologous stem cell transplantation for mantle cell lymphoma. The clinical trial was registered at ClinicalTrials.gov: NCT00020943. PMID:22102709

  7. Progressive multiple sclerosis: prospects for disease therapy, repair, and restoration of function.

    PubMed

    Ontaneda, Daniel; Thompson, Alan J; Fox, Robert J; Cohen, Jeffrey A

    2017-04-01

    Multiple sclerosis is a major cause of neurological disability, which accrues predominantly during progressive forms of the disease. Although development of multifocal inflammatory lesions is the underlying pathological process in relapsing-remitting multiple sclerosis, the gradual accumulation of disability that characterises progressive multiple sclerosis seems to result more from diffuse immune mechanisms and neurodegeneration. As a result, the 14 anti-inflammatory drugs that have regulatory approval for treatment of relapsing-remitting multiple sclerosis have little or no efficacy in progressive multiple sclerosis without inflammatory lesion activity. Effective therapies for progressive multiple sclerosis that prevent worsening, reverse damage, and restore function are a major unmet need. In this Series paper we summarise the current status of therapy for progressive multiple sclerosis and outline prospects for the future. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Solar-B Mission Extreme Ultraviolet (EUV) Imaging Spectrometer (EIS) Instrument Components

    NASA Technical Reports Server (NTRS)

    Doschek, George A.

    2002-01-01

    This Monthly Progress Report covers the reporting period August 2002 of the Detailed Design and Development through Launch plus Thirty Days, Phase C/D, for selected components and subsystems of the Extreme ultraviolet Imaging Spectrometer (EIS) instrument, hereafter referred to as EIS Instrument Components. This document contains the program status through the reporting period and forecasts the status for the upcoming reporting period.

  9. SOLAR-B Mission Extreme Ultraviolet (EUV) Imaging Spectrometer (EIS) Instrument Components

    NASA Technical Reports Server (NTRS)

    Doschek, George A.

    2001-01-01

    This Monthly Progress Report covers the reporting period through June 2001, Phase C/D, Detailed Design and Development Through Launch Plus Thirty Days, for selected components and subsystems of the Extreme ultraviolet Imaging Spectrometer (EIS) instrument, hereafter referred to as EIS Instrument Components. This document contains the program status through the reporting period and forecasts the status for the upcoming reporting period.

  10. SOLAR-B Mission Extreme Ultraviolet (EUV) Imaging Spectrometer (EIS) Instrument Components

    NASA Technical Reports Server (NTRS)

    Doschek, George A.

    2001-01-01

    This Monthly Progress Report covers the reporting period July 2001 of the Detailed Design and Development through Launch plus Thirty Days, Phase C/D, for selected components and subsystems of the Extreme Ultraviolet Imaging Spectrometer (EIS) instrument, hereafter referred to as EIS Instrument Components. This document contains the program status through the reporting period and forecasts the status for the upcoming reporting period.

  11. Status of silicon solar cell technology

    NASA Technical Reports Server (NTRS)

    Brandhorst, H. W., Jr.

    1976-01-01

    Major progress in solar cell technology leading to increased efficiency has occurred since 1970. Technical approaches leading to this increased output include surface texturing, improved antireflection coatings, reduced grid pattern area coverage, shallow junctions and back surface fields. The status of these developments and their incorporation into cell production is discussed. Future research and technology trends leading to further efficiency increases and substantial cost reductions are described.

  12. A bill to authorize the President to posthumously award a gold medal on behalf of Congress to Robert M. LaFollette, Sr., in recognition of his important contributions to the Progressive movement, the State of Wisconsin, and the United States.

    THOMAS, 111th Congress

    Sen. Feingold, Russell D. [D-WI

    2009-05-04

    Senate - 05/04/2009 Read twice and referred to the Committee on Banking, Housing, and Urban Affairs. (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

  13. ACRF Instrumentation Status: New, Current, and Future - October – November 2007

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

    JW Voyles

    2007-11-30

    The purpose of this report is to provide a concise but comprehensive overview of Atmospheric Radiation Measurement (ARM) Climate Research Facility (ACRF) instrumentation status. The report is divided into the following four sections: (1) new instrumentation in the process of being acquired and deployed, (2) existing instrumentation and progress on improvements or upgrades, (3) proposed future instrumentation, and (4) SBIR instrument development.

  14. Evaluating the HATCH score for predicting progression to sustained atrial fibrillation in ED patients with new atrial fibrillation.

    PubMed

    Barrett, Tyler W; Self, Wesley H; Wasserman, Brian S; McNaughton, Candace D; Darbar, Dawood

    2013-05-01

    Atrial fibrillation (AF) is often first detected in the emergency department (ED). Not all AF patients progress to sustained AF (ie, episodes lasting >7 days), which is associated with increased morbidity. The HATCH score stratifies patients with paroxysmal AF according to their risk for progression to sustained AF within 1 year. The HATCH score has previously never been tested in ED patients. We evaluated the accuracy of the HATCH score to predict progression to sustained AF within 1 year of initial AF diagnosis in the ED. We conducted a retrospective cohort study of 253 ED patients with new onset AF and known rhythm status for 1 year following the initial AF detection. The exposure variable was the HATCH score at initial ED evaluation. The primary outcome was rhythm status at 1 year following initial AF diagnosis. We constructed a receiver operating characteristic curve and calculated the area under the curve to estimate the HATCH score's accuracy of predicting progression to sustained AF. Overall, 61 (24%) of 253 of patients progressed to sustained AF within 1 year of initial detection, and the HATCH score receiver operating characteristic area under the curve was 0.62 (95% confidence interval, 0.54-0.70). Among ED patients with new onset AF, the HATCH score was a modest predictor of progression to sustained AF. Because only 2 patients had a HATCH greater than 5, this previously recommended cut-point was not useful in identifying high-risk patients in this cohort. Refinement of this decision aid is needed to improve its prognostic accuracy in the ED population. Copyright © 2013 Elsevier Inc. All rights reserved.

  15. CLL Cells Respond to B-Cell Receptor Stimulation with a MicroRNA/mRNA Signature Associated with MYC Activation and Cell Cycle Progression

    PubMed Central

    Pede, Valerie; Rombout, Ans; Vermeire, Jolien; Naessens, Evelien; Mestdagh, Pieter; Robberecht, Nore; Vanderstraeten, Hanne; Van Roy, Nadine; Vandesompele, Jo; Speleman, Frank; Philippé, Jan; Verhasselt, Bruno

    2013-01-01

    Chronic lymphocytic leukemia (CLL) is a disease with variable clinical outcome. Several prognostic factors such as the immunoglobulin heavy chain variable genes (IGHV) mutation status are linked to the B-cell receptor (BCR) complex, supporting a role for triggering the BCR in vivo in the pathogenesis. The miRNA profile upon stimulation and correlation with IGHV mutation status is however unknown. To evaluate the transcriptional response of peripheral blood CLL cells upon BCR stimulation in vitro, miRNA and mRNA expression was measured using hybridization arrays and qPCR. We found both IGHV mutated and unmutated CLL cells to respond with increased expression of MYC and other genes associated with BCR activation, and a phenotype of cell cycle progression. Genome-wide expression studies showed hsa-miR-132-3p/hsa-miR-212 miRNA cluster induction associated with a set of downregulated genes, enriched for genes modulated by BCR activation and amplified by Myc. We conclude that BCR triggering of CLL cells induces a transcriptional response of genes associated with BCR activation, enhanced cell cycle entry and progression and suggest that part of the transcriptional profiles linked to IGHV mutation status observed in isolated peripheral blood are not cell intrinsic but rather secondary to in vivo BCR stimulation. PMID:23560086

  16. Calcitriol accelerates vascular calcification irrespective of vitamin K status in a rat model of CKD with hyperphosphatemia and secondary hyperparathyroidism.

    PubMed

    McCabe, Kristin M; Zelt, Jason G; Kaufmann, Martin; Laverty, Kimberly; Ward, Emilie; Barron, Henry; Jones, Glenville; Adams, Michael A; Holden, Rachel M

    2018-06-14

    Patients with chronic kidney disease have a markedly increased risk for developing cardiovascular disease. Non-traditional risk factors, such as increased phosphate retention, and deficiencies in vitamins D and K metabolism, likely play key roles in the development of vascular calcification during CKD progression. Calcitriol (1,25-(OH)2-D3) is a key transcriptional regulator of Matrix Gla protein (MGP), a vitamin K dependent protein that inhibits vascular calcification. The objective of this study was to determine if calcitriol treatment could inhibit the development of vascular calcification and if this inhibition was dependent on vitamin K status in a rat model of CKD. Rats were treated with dietary adenine (0.25%) to induce CKD, with either 0, 20 or 80 ng/kg of calcitriol with low or high dietary vitamin K1 (0.2 or 100 mg/kg) for 7 weeks. Calcitriol at both low (20 ng/kg) and moderate (80 ng/kg) doses increased the severity of vascular calcification and, contrary to our hypothesis, this was unaffected by high dietary vitamin K1. Calcitriol had a dose-dependent effect on: (i) lowering serum PTH, (ii) increasing serum calcium and (iii) increasing serum FGF-23. Calcitriol treatment significantly increased aortic expression of the calcification genes Runx2 and Pit-1. This data also implicates impaired vitamin D catabolism in CKD, which may contribute to the development of calcitriol toxicity and increased vascular calcification. The present findings demonstrate that in an adenine-induced rat model of CKD, calcitriol treatment at doses as low as 20 ng/kg can increase the severity of vascular calcification regardless of vitamin K status. The American Society for Pharmacology and Experimental Therapeutics.

  17. A review of radiation countermeasures focusing on injury-specific medicinals and regulatory approval status: part II. Countermeasures for limited indications, internalized radionuclides, emesis, late effects, and agents demonstrating efficacy in large animals with or without FDA IND status.

    PubMed

    Singh, Vijay K; Garcia, Melissa; Seed, Thomas M

    2017-09-01

    The threat of a radiological/nuclear event is a critical concern for all government agencies involved in national security and public health preparedness. Countermeasures that are safe, easily administered, and effective at diminishing or eliminating adverse health effects to individuals and the overall public health impact of radiation exposure are urgently needed. Radiation countermeasures included in this three-part series have been classified under various subheadings based specifically on their developmental stages for United States Food and Drug Administration (FDA) approval. We have included FDA-approved agents for acute radiation syndrome (ARS) in part I. This is part II in which we have reviewed FDA-approved agents for limited indications, internalized radionuclides, emesis, late effects, radiomitigators available in the strategic national stockpile (SNS), agents with FDA investigational new drug (IND) status, and those with NHP efficacy data without FDA IND. Agents discussed in part III are those agents that have been peer reviewed, published, and have demonstrated significant survival benefits in animal models of ARS. Agents investigated in in vitro models only or studied in animal models without peer-reviewed publications have not been included. The dearth of FDA-approved radiation countermeasures has prompted intensified research for a new generation of radiation countermeasures. A number of promising radiation countermeasures are currently moving forward with continued support and effort by both governmental agencies and by publicly and privately held pharmaceutical companies. There is a limited number of countermeasures which are progressing well following the Animal Rule and may get approved in the near future, thus serving to close the gap of this critically important, unmet radiobiomedical need.

  18. Disparities in access to care and satisfaction among U.S. children: the roles of race/ethnicity and poverty status.

    PubMed

    Shi, Leiyu; Stevens, Gregory D

    2005-01-01

    The study assessed the progress made toward reducing racial and ethnic disparities in access to health care among U.S. children between 1996 and 2000. Data are from the Household Component of the 1996 and 2000 Medical Expenditure Panel Survey. Bivariate associations of combinations of race/ethnicity and poverty status groups were examined with four measures of access to health care and a single measure of satisfaction. Logistic regression was used to examine the association of race/ethnicity with access, controlling for sociodemographic factors associated with access to care. To highlight the role of income, we present models with and without controlling for poverty status. Racial and ethnic minority children experience significant deficits in accessing medical care compared with whites. Asians, Hispanics, and blacks were less likely than whites to have a usual source of care, health professional or doctor visit, and dental visit in the past year. Asians were more likely than whites to be dissatisfied with the quality of medical care in 2000 (but not 1996), while blacks and Hispanics were more likely than whites to be dissatisfied with the quality of medical care in 1996 (but not in 2000). Both before and after controlling for health insurance coverage, poverty status, health status, and several other factors associated with access to care, these disparities in access to care persisted between 1996 and 2000. Continued monitoring of racial and ethnic differences is necessary in light of the persistence of racial/ethnic and socioeconomic disparities in access to care. Given national goals to achieve equity in health care and eliminate racial/ ethnic disparities in health, greater attention needs to be paid to the interplay of race/ethnicity factors and poverty status in influencing access.

  19. Model-based economic evaluation in Alzheimer's disease: a review of the methods available to model Alzheimer's disease progression.

    PubMed

    Green, Colin; Shearer, James; Ritchie, Craig W; Zajicek, John P

    2011-01-01

    To consider the methods available to model Alzheimer's disease (AD) progression over time to inform on the structure and development of model-based evaluations, and the future direction of modelling methods in AD. A systematic search of the health care literature was undertaken to identify methods to model disease progression in AD. Modelling methods are presented in a descriptive review. The literature search identified 42 studies presenting methods or applications of methods to model AD progression over time. The review identified 10 general modelling frameworks available to empirically model the progression of AD as part of a model-based evaluation. Seven of these general models are statistical models predicting progression of AD using a measure of cognitive function. The main concerns with models are on model structure, around the limited characterization of disease progression, and on the use of a limited number of health states to capture events related to disease progression over time. None of the available models have been able to present a comprehensive model of the natural history of AD. Although helpful, there are serious limitations in the methods available to model progression of AD over time. Advances are needed to better model the progression of AD and the effects of the disease on peoples' lives. Recent evidence supports the need for a multivariable approach to the modelling of AD progression, and indicates that a latent variable analytic approach to characterising AD progression is a promising avenue for advances in the statistical development of modelling methods. Copyright © 2011 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

  20. Diffusion tensor MRI shows progressive changes in the hippocampus and dentate gyrus after status epilepticus in rat - histological validation with Fourier-based analysis.

    PubMed

    Salo, Raimo A; Miettinen, Tuukka; Laitinen, Teemu; Gröhn, Olli; Sierra, Alejandra

    2017-05-15

    Imaging markers for monitoring disease progression, recovery, and treatment efficacy are a major unmet need for many neurological diseases, including epilepsy. Recent evidence suggests that diffusion tensor imaging (DTI) provides high microstructural contrast even outside major white matter tracts. We hypothesized that in vivo DTI could detect progressive microstructural changes in the dentate gyrus and the hippocampal CA3bc in the rat brain after status epilepticus (SE). To test this hypothesis, we induced SE with systemic kainic acid or pilocarpine in adult male Wistar rats and subsequently scanned them using in vivo DTI at five time-points: prior to SE, and 10, 20, 34, and 79 days post SE. In order to tie the DTI findings to changes in the tissue microstructure, myelin- and glial fibrillary acidic protein (GFAP)-stained sections from the same animals underwent Fourier analysis. We compared the Fourier analysis parameters, anisotropy index and angle of myelinated axons or astrocyte processes, to corresponding DTI parameters, fractional anisotropy (FA) and the orientation angle of the principal eigenvector. We found progressive detectable changes in DTI parameters in both the dentate gyrus (FA, axial diffusivity [D || ], linear anisotropy [CL] and spherical anisotropy [CS], p<0.001, linear mixed-effects model [LMEM]) and the CA3bc (FA, D || , CS, and angle, p<0.001, LMEM; CL and planar anisotropy [CP], p<0.01, LMEM) post SE. The Fourier analysis revealed that both myelinated axons and astrocyte processes played a role in the water diffusion anisotropy changes detected by DTI in individual portions of the dentate gyrus (suprapyramidal blade, mid-portion, and infrapyramidal blade). In the whole dentate gyrus, myelinated axons markedly contributed to the water diffusion changes. In CA3bc as well as in CA3b and CA3c, both myelinated axons and astrocyte processes contributed to water diffusion anisotropy and orientation. Our study revealed that DTI is a promising method for noninvasive detection of microstructural alterations in the hippocampus proper. These alterations may be potential imaging markers for epileptogenesis. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. [Chronically ill and unemployed? A review on vocational status in multiple sclerosis].

    PubMed

    Kern, S; Kühn, M; Ziemssen, T

    2013-02-01

    Multiple sclerosis (MS) is one of the most common neurological disorders in young adults. It is characterised by a chronic progressive course with far reaching implications on the patient's private and professional life. Based on the current literature, employment status is analysed in relation to disease-specific, therapeutic, psychosocial, and socioeconomic factors. A special emphasis is placed on the vocational status of MS patients in Germany. According national and international studies, around 40 % of all MS patients are currently unemployed. Main reasons for early retirement are disease-specific factors such as impaired mobility, disability in the upper extremities, fatigue, and cognitive impairment. According to the German Multiple Sclerosis Registry (GMSR), these symptoms are still insufficiently treated. In patients with minor motoric impairment (EDSS ≤ 3.0), depressive symptoms seem to have a major impact on employment status. Disease progression, older age at diagnosis, and hard physical work are negative predictors in terms of employment situation. The lack of flexible working hours, the inability to have flexible resting times at work, a lack of understanding from colleagues and employers as well as the personal attitude were main non-disease-specific reasons for early retirement. The current knowledge on the vocational status in MS is mainly based on international studies (e. g., Scandinavia, England, USA, Australia, MSIF Survey). For Germany, only the GMSR supports significant information on the employment status of MS patients. According to the GMSR, ataxia, fatigue and cognitive dysfunction are still insufficiently treated - a situation that is at least partly due to insufficient treatment options. Comprehensive studies that focus on a broad range of possible influencing factors on vocational status of German MS patients are currently lacking. © Georg Thieme Verlag KG Stuttgart · New York.

  2. Outcome and prognostic factors in metastatic urothelial carcinoma patients receiving second-line chemotherapy: an analysis of real-world clinical practice data in Japan.

    PubMed

    Matsumoto, Ryuji; Abe, Takashige; Ishizaki, Junji; Kikuchi, Hiroshi; Harabayashi, Toru; Minami, Keita; Sazawa, Ataru; Mochizuki, Tango; Akino, Tomoshige; Murakumo, Masashi; Osawa, Takahiro; Maruyama, Satoru; Murai, Sachiyo; Shinohara, Nobuo

    2018-06-25

    The objective of the present study was to investigate the survival outcome and prognostic factors of metastatic urothelial carcinoma patients treated with second-line systemic chemotherapy in real-world clinical practice. Overall, 114 patients with metastatic urothelial carcinoma undergoing second-line systemic chemotherapy were included in this retrospective analysis. The dominant second-line chemotherapy was a paclitaxel-based combination regimen (60%, 68/114). We assessed the progression-free survival and overall survival times using the Kaplan-Meier method. The Cox proportional hazards model was applied to identify the factors affecting overall survival. The median progression-free survival and overall survival times were 4 and 9 months, respectively. In the multivariate analysis, an Eastern Cooperative Oncology Group performance status score greater than 0 at presentation, C-reactive protein level ≧1 mg/dl and poor response to prior chemotherapy were adverse prognostic indicators. Patients with 0, 1, 2 and 3 of those risk factors had a median overall survival of 17, 12, 7 and 3 months, respectively. The Eastern Cooperative Oncology Group performance status at presentation, C-reactive protein level and response to prior chemotherapy were prognostic factors for metastatic urothelial carcinoma patients undergoing second-line chemotherapy. In the future, this information might help guide the choice of salvage treatment, such as second-line chemotherapy or immune checkpoint inhibitors, after the failure of first-line chemotherapy.

  3. IGFBP2 is a candidate biomarker for Ink4a-Arf status and a therapeutic target for high-grade gliomas.

    PubMed

    Moore, Lynette M; Holmes, Kristen M; Smith, Sarah M; Wu, Ying; Tchougounova, Elena; Uhrbom, Lene; Sawaya, Raymond; Bruner, Janet M; Fuller, Gregory N; Zhang, Wei

    2009-09-29

    The levels of insulin-like growth factor-binding protein 2 (IGFBP2) are elevated during progression of many human cancers. By using a glial-specific transgenic mouse system (RCAS/Ntv-a), we reported previously that IGFBP2 is an oncogenic factor for glioma progression in combination with platelet-derived growth factor-beta (PDGFB). Because the INK4a-ARF locus is often deleted in high-grade gliomas (anaplastic oligodendroglioma and glioblastoma), we investigated the effect of the Ink4a-Arf-null background on IGFBP2-mediated progression of PDGFB-initiated oligodendroglioma. We demonstrate here that homozygous deletion of Ink4a-Arf bypasses the requirement of exogenously introduced IGFBP2 for glioma progression. Instead, absence of Ink4a-Arf resulted in elevated endogenous tumor cell IGFBP2. An inverse relationship between p16(INK4a) and IGFBP2 expression was also observed in human glioma tissue samples and in 90 different cancer cell lines by using Western blotting and reverse-phase protein lysate arrays. When endogenous IGFBP2 expression was attenuated by an RCAS vector expressing antisense IGFBP2 in our mouse model, a decreased incidence of anaplastic oligodendroglioma as well as prolonged survival was observed. Thus, p16(INK4a) is a negative regulator of the IGFBP2 oncogene. Loss of Ink4a-Arf results in increased IGFBP2, which contributes to glioma progression, thereby implicating IGFBP2 as a marker and potential therapeutic target for Ink4a-Arf-deleted gliomas.

  4. IGFBP2 is a candidate biomarker for Ink4a-Arf status and a therapeutic target for high-grade gliomas

    PubMed Central

    Moore, Lynette M.; Holmes, Kristen M.; Smith, Sarah M.; Wu, Ying; Tchougounova, Elena; Uhrbom, Lene; Sawaya, Raymond; Bruner, Janet M.; Fuller, Gregory N.; Zhang, Wei

    2009-01-01

    The levels of insulin-like growth factor-binding protein 2 (IGFBP2) are elevated during progression of many human cancers. By using a glial-specific transgenic mouse system (RCAS/Ntv-a), we reported previously that IGFBP2 is an oncogenic factor for glioma progression in combination with platelet-derived growth factor-β (PDGFB). Because the INK4a-ARF locus is often deleted in high-grade gliomas (anaplastic oligodendroglioma and glioblastoma), we investigated the effect of the Ink4a-Arf-null background on IGFBP2-mediated progression of PDGFB-initiated oligodendroglioma. We demonstrate here that homozygous deletion of Ink4a-Arf bypasses the requirement of exogenously introduced IGFBP2 for glioma progression. Instead, absence of Ink4a-Arf resulted in elevated endogenous tumor cell IGFBP2. An inverse relationship between p16INK4a and IGFBP2 expression was also observed in human glioma tissue samples and in 90 different cancer cell lines by using Western blotting and reverse-phase protein lysate arrays. When endogenous IGFBP2 expression was attenuated by an RCAS vector expressing antisense IGFBP2 in our mouse model, a decreased incidence of anaplastic oligodendroglioma as well as prolonged survival was observed. Thus, p16INK4a is a negative regulator of the IGFBP2 oncogene. Loss of Ink4a-Arf results in increased IGFBP2, which contributes to glioma progression, thereby implicating IGFBP2 as a marker and potential therapeutic target for Ink4a-Arf-deleted gliomas. PMID:19805356

  5. Disease modeling and phenotypic drug screening for diabetic cardiomyopathy using human induced pluripotent stem cells.

    PubMed

    Drawnel, Faye M; Boccardo, Stefano; Prummer, Michael; Delobel, Frédéric; Graff, Alexandra; Weber, Michael; Gérard, Régine; Badi, Laura; Kam-Thong, Tony; Bu, Lei; Jiang, Xin; Hoflack, Jean-Christophe; Kiialainen, Anna; Jeworutzki, Elena; Aoyama, Natsuyo; Carlson, Coby; Burcin, Mark; Gromo, Gianni; Boehringer, Markus; Stahlberg, Henning; Hall, Benjamin J; Magnone, Maria Chiara; Kolaja, Kyle; Chien, Kenneth R; Bailly, Jacques; Iacone, Roberto

    2014-11-06

    Diabetic cardiomyopathy is a complication of type 2 diabetes, with known contributions of lifestyle and genetics. We develop environmentally and genetically driven in vitro models of the condition using human-induced-pluripotent-stem-cell-derived cardiomyocytes. First, we mimic diabetic clinical chemistry to induce a phenotypic surrogate of diabetic cardiomyopathy, observing structural and functional disarray. Next, we consider genetic effects by deriving cardiomyocytes from two diabetic patients with variable disease progression. The cardiomyopathic phenotype is recapitulated in the patient-specific cells basally, with a severity dependent on their original clinical status. These models are incorporated into successive levels of a screening platform, identifying drugs that preserve cardiomyocyte phenotype in vitro during diabetic stress. In this work, we present a patient-specific induced pluripotent stem cell (iPSC) model of a complex metabolic condition, showing the power of this technique for discovery and testing of therapeutic strategies for a disease with ever-increasing clinical significance. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  6. In Vivo Models of Human Immunodeficiency Virus Persistence and Cure Strategies

    PubMed Central

    Mavigner, Maud; Silvestri, Guido; Garcia, J. Victor

    2017-01-01

    Abstract Current HIV therapy is not curative regardless of how soon after infection it is initiated or how long it is administered, and therapy interruption almost invariably results in robust viral rebound. Human immunodeficiency virus persistence is therefore the major obstacle to a cure for AIDS. The testing and implementation of novel yet unproven approaches to HIV eradication that could compromise the health status of HIV-infected individuals might not be ethically warranted. Therefore, adequate in vitro and in vivo evidence of efficacy is needed to facilitate the clinical implementation of promising strategies for an HIV cure. Animal models of HIV infection have a strong and well-documented history of bridging the gap between laboratory discoveries and eventual clinical implementation. More recently, animal models have been developed and implemented for the in vivo evaluation of novel HIV cure strategies. In this article, we review the recent progress in this rapidly moving area of research, focusing on the two most promising model systems: humanized mice and nonhuman primates. PMID:28520967

  7. Growth Models of Dyadic Synchrony and Mother-Child Vagal Tone in the Context of Parenting At-Risk

    PubMed Central

    Giuliano, Ryan J.; Skowron, Elizabeth A.; Berkman, Elliot T.

    2015-01-01

    We used multilevel modeling to examine dynamic changes in respiratory sinus arrhythmia (RSA) and observer-coded interactive synchrony for mother-child dyads engaged in a laboratory interaction, to characterize parenting-at-risk. Seventy-nine preschooler-mother dyads including a subset with documented child maltreatment (CM; n=43) were observed completing a joint puzzle task while physiological measures were recorded. Dyads led by CM mothers showed decreases in positive synchrony over time, whereas no variation was observed in non-CM dyads. Growth models of maternal RSA indicated that mothers who maintained high levels of positive interactive synchrony with their child evidenced greater RSA reactivity, characterized by an initial withdrawal followed by augmentation as the task progressed, after accounting for CM group status. These results help to clarify patterns of RSA responding in the context of caregiver-child interactions, and demonstrate the importance of modeling dynamic changes in physiology over time in order to better understanding biological correlates of parenting-at-risk. PMID:25542759

  8. Helicobacter pylori-induced gastric pathology: insights from in vivo and ex vivo models

    PubMed Central

    Williams, Jonathan M.

    2017-01-01

    ABSTRACT Gastric colonization with Helicobacter pylori induces diverse human pathological conditions, including superficial gastritis, peptic ulcer disease, mucosa-associated lymphoid tissue (MALT) lymphoma, and gastric adenocarcinoma and its precursors. The treatment of these conditions often relies on the eradication of H. pylori, an intervention that is increasingly difficult to achieve and that does not prevent disease progression in some contexts. There is, therefore, a pressing need to develop new experimental models of H. pylori-associated gastric pathology to support novel drug development in this field. Here, we review the current status of in vivo and ex vivo models of gastric H. pylori colonization, and of Helicobacter-induced gastric pathology, focusing on models of gastric pathology induced by H. pylori, Helicobacter felis and Helicobacter suis in rodents and large animals. We also discuss the more recent development of gastric organoid cultures from murine and human gastric tissue, as well as from human pluripotent stem cells, and the outcomes of H. pylori infection in these systems. PMID:28151409

  9. A comparative analysis of EGFR mutation status in association with the efficacy of TKI in combination with WBRT/SRS/surgery plus chemotherapy in brain metastasis from non-small cell lung cancer.

    PubMed

    Cai, Ling; Zhu, Jian-fei; Zhang, Xue-wen; Lin, Su-xia; Su, Xiao-dong; Lin, Peng; Chen, Kai; Zhang, Lan-jun

    2014-11-01

    We proposed to identify the efficacy of an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) using whole brain radiotherapy (WBRT)/stereotactic radiosurgery (SRS)/surgery in brain metastases from patients with non-small cell lung cancer (NSCLC) and clarify the association between treatment outcome and EGFR gene mutation status. A total of 282 patients with NSCLC brain metastases who underwent WBRT/SRS/surgery alone or in combination with TKI were enrolled in our study from 2003-2013. Amplification mutation refractory system technology was used to determine the EGFR mutation status in 109 tissue samples. EGFR mutation detection was performed in 109 patients with tumor tissues. The EGFR positive rate was 50 % (55/109), including 26 exon 19 deletions and 24 L858R mutations. The median follow-up time was 28 months. The median overall survival, median progression-free survival of intracranial disease, and median progression-free survival of extracranial disease was significantly longer for patients with TKI treatment (31.9 vs 17.0 months, P < 0.0001; 19.8 vs 12.0 months, P < 0.0001; and 19.6 vs 12.3 months, P < 0.0001; respectively). In subgroup analysis within the TKI group, patients harboring EGFR mutations had better extracranial disease control (20.4 vs 14.1 months, P = 0.032). Administration of TKI agents with conventional therapy compared with conventional therapy alone might be beneficial for overall survival, progression-free survival of intracranial disease and progression-free survival of extracranial disease in patients with brain metastases from NSCLC independent of EGFR mutations.

  10. Serum TK levels in CLL identify Binet stage A patients within biologically defined prognostic subgroups most likely to undergo disease progression.

    PubMed

    Matthews, Christine; Catherwood, Mark A; Morris, T C M; Kettle, Paul J; Drake, Mary B; Gilmore, William S; Alexander, H Denis

    2006-10-01

    Serum thymidine kinase (TK) levels have been shown to be correlated with survival in many malignancies, including chronic lymphocytic leukaemia (CLL). This study was designed to investigate associations between TK levels and other prognostic markers, in newly and previously diagnosed Binet stage A patients. Furthermore, the use of serum TK measurement to identify subcategories of disease within those defined by IgV(H) mutational status, gene usage and chromosomal aberrations was investigated. Ninety-one CLL patients were enrolled. Serum TK levels were measured using a radioenzyme assay. IgV(H) mutational status and V(H) gene usage were determined using BIOMED-2 primers and protocol. Recurring chromosomal abnormalities were detected by interphase fluorescent in situ hybridisation (FISH). Flow cytometry and reverse transcriptase polymerase chain reaction (RT-PCR) determined CD38 and Zap-70 expression, respectively. Significantly higher serum TK levels were found in IgV(H) unmutated, compared with IgV(H) mutated, patients (P < 0.001). Elevated TK levels were also found in patients with CD38 and Zap-70 positivity (P = 0.004, P < 0.001, respectively), short lymphocyte doubling time (LDT) (P = 0.044) and poor or intermediate prognosis chromosomal aberrations (P < 0.001). A TK level of >8.5 U/L best identified patients with progressive disease. Elevated TK levels could identify patients categorised, at diagnosis, into good prognosis subgroups by the various biological markers (mutated IgV(H), good prognosis chromosomal aberrations, Zap-70(-) and CD38(-)) who subsequently showed disease progression. Additionally, patients with V(H)3-21 gene usage showed high TK levels, irrespective of mutational status, and serum TK measurement retained predictive power as disease progressed in all subcategories studied.

  11. Progression and effect of cognitive-behavioral changes in patients with amyotrophic lateral sclerosis.

    PubMed

    Bock, Meredith; Duong, Y-Nhy; Kim, Anthony; Allen, Isabel; Murphy, Jennifer; Lomen-Hoerth, Catherine

    2017-12-01

    To prospectively evaluate the progression of cognitive-behavioral function in amyotrophic lateral sclerosis (ALS) and examine the association of cognitive-behavioral deficits with disease progression, patient quality of life (QOL), and caregiver burden. We evaluated cognitive-behavioral function using the Amyotrophic Lateral Sclerosis Cognitive Behavioral Screen at enrollment and after 7 months in a cohort of patients with ALS. Paired t tests were used to evaluate the change in the 2 assessments. Linear regression and Kruskal-Wallis tests were applied to investigate how initial cognitive or behavioral status related to outcomes. The mean test-retest interval was 6.8 months (SD 1.6). Cognitive status of the study population (n = 49) overall did not change over the study period ( p = 0.06) despite progression of motor weakness ( p < 0.001), though small subsets of the sample demonstrate cognitive change. Patients initially classified as behaviorally normal showed increased behavioral problems over time ( t = -2.8, p = 0.009). Decline in cognitive (β = -1.3, p = 0.03) and behavioral (β = -0.76, p = 0.002) status predicted increasing caregiver burden. Behavioral abnormalities predicted decline in forced vital capacity and ALS Functional Rating Scale-Revised score ( p = 0.008, 0.012) in the study population and patient QOL in the most severely affected group ( t = 4.3, p = 0.003). Cognitive-behavioral change is a key aspect of disease heterogeneity in ALS. Executive function in ALS overall remains stable over 7 months as detected by an administered screening tool. However, patients may develop caregiver-reported behavioral symptoms in that time period. Screening for caregiver-reported symptoms has a particular utility in predicting future clinical decline, increased caregiver burden, and worsening patient QOL.

  12. [Evaluation of the nutritional status, insulin resistance and cardiovascular risk in a population of adolescents in the cities of Granada and Almeria (Spain)].

    PubMed

    Montero Alonso, Miguel A; González-Jiménez, Emilio

    2013-01-01

    The first objective of this study was to evaluate the nutritional status and insulin resistance index in a population of adolescents as calculated by Homeostatic Model Assessment (HOMA). The second objective was to establish correlations between the nutritional status of the subjects, the possible existence of insulin resistance, and the risk of high blood pressure. POPULATION SAMPLE AND METHODOLOGY: The sample was composed of 1001 adolescents, 9-17 years of age, from 18 schools in the provinces of Granada and Almeria. Their nutritional status was determined by means of anthropometric evaluation. For the metabolic study, a blood sample was collected from each subject by venipuncture. An analysis was performed of the basal glucose and insulin levels as well as the Homeostatic Model Assessment- Insulin Resistance (HOMAIR) index. Also evaluated were the levels of glycosylated haemoglobin (HbA1c), serum lipoprotein (a), and non-esterified fatty acids (NEFAs). Insulin resistance was calculated with the formula, proposed by Matthews et al. (1985) : HOMA-IR = (insulin[mmol/L] x glucose[mU/L])/22.5. The evaluation of the nutritional status of the subjects reflected a progressive increase in the values of anthropometric variables as the nutritional status of the subjects worsened. The results of this study showed, regardless of age and gender, 85.01% of the subjects were of normal weight, whereas 9.99% were overweight, and 4.99% were obese. The metabolic study reflected that in comparison to normal-weight and overweight students, obese students had significantly higher serum levels (p < 0,0001) of HbA1c, basal insulin, basal glycemia, basal NEFA, lipoprotein (a), and HOMA-IR. Obesity was found to be a serious health problem in the population of adolescents studied, especially given the high cardiovascular risk that is characteristic of this condition. As reflected in the results of this study, obesity led to the premature development of metabolic disorders, which generally do not appear until adulthood. Copyright © AULA MEDICA EDICIONES 2013. Published by AULA MEDICA. All rights reserved.

  13. Can Human Pluripotent Stem Cell-Derived Cardiomyocytes Advance Understanding of Muscular Dystrophies?

    PubMed

    Kalra, Spandan; Montanaro, Federica; Denning, Chris

    2016-08-30

    Muscular dystrophies (MDs) are clinically and molecularly a highly heterogeneous group of single-gene disorders that primarily affect striated muscles. Cardiac disease is present in several MDs where it is an important contributor to morbidity and mortality. Careful monitoring of cardiac issues is necessary but current management of cardiac involvement does not effectively protect from disease progression and cardiac failure. There is a critical need to gain new knowledge on the diverse molecular underpinnings of cardiac disease in MDs in order to guide cardiac treatment development and assist in reaching a clearer consensus on cardiac disease management in the clinic. Animal models are available for the majority of MDs and have been invaluable tools in probing disease mechanisms and in pre-clinical screens. However, there are recognized genetic, physiological, and structural differences between human and animal hearts that impact disease progression, manifestation, and response to pharmacological interventions. Therefore, there is a need to develop parallel human systems to model cardiac disease in MDs. This review discusses the current status of cardiomyocytes (CMs) derived from human induced pluripotent stem cells (hiPSC) to model cardiac disease, with a focus on Duchenne muscular dystrophy (DMD) and myotonic dystrophy (DM1). We seek to provide a balanced view of opportunities and limitations offered by this system in elucidating disease mechanisms pertinent to human cardiac physiology and as a platform for treatment development or refinement.

  14. Toll-like receptor 3 deficiency decreases epileptogenesis in a pilocarpine model of SE-induced epilepsy in mice.

    PubMed

    Gross, Adi; Benninger, Felix; Madar, Ravit; Illouz, Tomer; Griffioen, Kathleen; Steiner, Israel; Offen, Daniel; Okun, Eitan

    2017-04-01

    Epilepsy affects 60 million people worldwide. Despite the development of antiepileptic drugs, up to 35% of patients are drug refractory with uncontrollable seizures. Toll-like receptors (TLRs) are central components of the nonspecific innate inflammatory response. Because TLR3 was recently implicated in neuronal plasticity, we hypothesized that it may contribute to the development of epilepsy after status epilepticus (SE). To test the involvement of TLR3 in epileptogenesis, we used the pilocarpine model for SE in TLR3-deficient mice and their respective wild-type controls. In this model, a single SE event leads to spontaneous recurrent seizures (SRS). Two weeks after SE, mice were implanted with wireless electroencephalography (EEG) transmitters for up to 1 month. The impact of TLR3 deficiency on SE was assessed using separate cohorts of mice regarding EEG activity, seizure progression, hippocampal microglial distribution, and expression of the proinflammatory cytokines tumor necrosis factor (TNF)α and interferon (IFN)β. Our data indicate that TLR3 deficiency reduced SRS, microglial activation, and the levels of the proinflammatory cytokines TNFα and IFNβ, and increased survival following SE. This study reveals novel insights into the pathophysiology of epilepsy and the contribution of TLR3 to disease progression. Our results identify the TLR3 pathway as a potential future therapeutic target in SE. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

  15. AIM1 and LINE-1 Epigenetic Aberrations In Tumor and Serum Relate to Melanoma Progression and Disease Outcome

    PubMed Central

    Hoshimoto, Sojun; Kuo, Christine; Chong, Kelly; Takeshima, Ling; Takei, Yoshiki; Li, Michelle; Huang, Sharon; Sim, Myung-Shin; Morton, Donald L.; Hoon, Dave S.B.

    2012-01-01

    Aberrations in the methylation status of non-coding genomic repeat DNA sequences and specific gene promoter region are important epigenetic events in melanoma progression. Promoter methylation status in LINE-1 and Absent in melanoma-1(AIM1;6q21) associated with melanoma progression and disease outcome was assessed. LINE-1 and AIM1 methylation status was assessed in paraffin-embedded archival tissues(PEAT)(n=133) and melanoma patients’ serum(n=56). LINE-1 U-Index(hypomethylation) and AIM1 were analyzed in microdissected melanoma PEAT sections. The LINE-1 U-Index of melanoma(n=100) was significantly higher than that of normal skin(n=14) and nevi(n=12)(P=0.0004). LINE-1 U-Index level was elevated with increasing AJCC stage(P<0.0001). AIM1 promoter hypermethylation was found in higher frequency(P=0.005) in metastatic melanoma(65%) than in primary melanomas(38%). When analyzed, high LINE-1 U-Index and/or AIM1 methylation in melanomas were associated with disease-free survival(DFS) and overall survival(OS) in Stage I/II patients (P=0.017, 0.027; respectively). In multivariate analysis, melanoma AIM1 methylation status was a significant prognostic factor of OS(P=0.032). Furthermore, serum unmethylated LINE-1 was at higher levels in both stage III(n=20) and stage IV(n=36) patients compared to healthy donors(n=14)(P=0.022). Circulating methylated AIM1 was detected in patients’ serum and was predictive of OS in Stage IV patients (P=0.009). LINE-1 hypomethylation and AIM1 hypermethylation have prognostic utility in both melanoma patients’ tumors and serum. PMID:22402438

  16. Inequity in India: the case of maternal and reproductive health

    PubMed Central

    Sanneving, Linda; Trygg, Nadja; Saxena, Deepak; Mavalankar, Dileep; Thomsen, Sarah

    2013-01-01

    Background Millennium Development Goal (MDG) 5 is focused on reducing maternal mortality and achieving universal access to reproductive health care. India has made extensive efforts to achieve MDG 5 and in some regions much progress has been achieved. Progress has been uneven and inequitable however, and many women still lack access to maternal and reproductive health care. Objective In this review, a framework developed by the Commission on Social Determinants of Health (CSDH) is used to categorize and explain determinants of inequity in maternal and reproductive health in India. Design A review of peer-reviewed, published literature was conducted using the electronic databases PubMed and Popline. The search was performed using a carefully developed list of search terms designed to capture published papers from India on: 1) maternal and reproductive health, and 2) equity, including disadvantaged populations. A matrix was developed to sort the relevant information, which was extracted and categorized based on the CSDH framework. In this way, the main sources of inequity in maternal and reproductive health in India and their inter-relationships were determined. Results Five main structural determinants emerged from the analysis as important in understanding equity in India: economic status, gender, education, social status (registered caste or tribe), and age (adolescents). These five determinants were found to be closely interrelated, a feature which was reflected in the literature. Conclusion In India, economic status, gender, and social status are all closely interrelated when influencing use of and access to maternal and reproductive health care. Appropriate attention should be given to how these social determinants interplay in generating and sustaining inequity when designing policies and programs to reach equitable progress toward improved maternal and reproductive health. PMID:23561028

  17. Non-invasive estimation of hydration status changes through tear fluid osmolarity during exercise and post-exercise rehydration.

    PubMed

    Ungaro, Corey T; Reimel, Adam J; Nuccio, Ryan P; Barnes, Kelly A; Pahnke, Matthew D; Baker, Lindsay B

    2015-05-01

    To determine if tear fluid osmolarity (Tosm) can track changes in hydration status during exercise and post-exercise rehydration. Nineteen male athletes (18-37 years, 74.6 ± 7.9 kg) completed two randomized, counterbalanced trials; cycling (~95 min) with water intake to replace fluid losses or water restriction to progressively dehydrate to 3 % body mass loss (BML). After exercise, subjects drank water to maintain body mass (water intake trials) or progressively rehydrate to pre-exercise body mass (water restriction trials) over a 90-min recovery period. Plasma osmolality (Posm) and Tosm measurements (mean of right and left eyes) were taken pre-exercise, during rest periods between exercise bouts corresponding to 1, 2, and 3 % BML, and rehydration at 2, 1, and 0 % BML. During exercise mean (± SD) Tosm was significantly higher in water restriction vs. water intake trials at 1 % BML (299 ± 9 vs. 293 ± 9 mmol/L), 2 % BML (301 ± 9 vs. 294 ± 9 mmol/L), and 3 % BML (302 ± 9 vs. 292 ± 8 mmol/L). Mean Tosm progressively decreased during post-exercise rehydration and was not different between trials at 1 % BML (291 ± 8 vs. 290 ± 7 mmol/L) and 0 % BML (288 ± 7 vs. 289 ± 8 mmol/L). Mean Tosm tracked changes in hydration status similar to that of mean Posm; however, the individual responses in Tosm to water restriction and water intake was considerably more variable than that of Posm. Tosm is a valid indicator of changes in hydration status when looking at the group mean; however, large differences among subjects in the Tosm response to hydration changes limit its validity for individual recommendations.

  18. Long-term consequences of a prolonged febrile seizure in a dual pathology model.

    PubMed

    Gibbs, Steve; Chattopadhyaya, Bidisha; Desgent, Sébastien; Awad, Patricia N; Clerk-Lamalice, Olivier; Levesque, Maxime; Vianna, Rose-Mari; Rébillard, Rose-Marie; Delsemme, Andrée-Anne; Hébert, David; Tremblay, Luc; Lepage, Martin; Descarries, Laurent; Di Cristo, Graziella; Carmant, Lionel

    2011-08-01

    Clinical evidence suggests that febrile status epilepticus (SE) in children can lead to acute hippocampal injury and subsequent temporal lobe epilepsy. The contribution of febrile SE to the mechanisms underlying temporal lobe epilepsy are however poorly understood. A rat model of temporal lobe epilepsy following hyperthermic SE was previously established in our laboratory, wherein a focal cortical lesion induced at postnatal day 1 (P1), followed by a hyperthermic SE (more than 30 min) at P10, leads to hippocampal atrophy at P22 (dual pathology model) and spontaneous recurrent seizures (SRS) with mild visuospatial memory deficits in adult rats. The goal of this study was to identify the long term electrophysiological, anatomical and molecular changes in this model. Following hyperthermic SE, all cortically lesioned pups developed progressive SRS as adults, characterized by the onset of highly rhythmic activity in the hippocampus. A reduction of hippocampal volume on the side of the lesion preceded the SRS and was associated with a loss of hippocampal neurons, a marked decrease in pyramidal cell spine density, an increase in the hippocampal levels of NMDA receptor NR2A subunit, but no significant change in GABA receptors. These findings suggest that febrile SE in the abnormal brain leads to hippocampal injury that is followed by progressive network reorganization and molecular changes that contribute to the epileptogenesis as well as the observed memory deficits. Copyright © 2011 Elsevier Inc. All rights reserved.

  19. 20 CFR 437.50 - Closeout.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...) Final request for payment (SF-270) (if applicable). (iv) Invention disclosure (if applicable). (v... are not limited to: (i) Final performance or progress report. (ii) Financial Status Report (SF 269) or...

  20. User interface development

    NASA Technical Reports Server (NTRS)

    Aggrawal, Bharat

    1994-01-01

    This viewgraph presentation describes the development of user interfaces for OS/2 versions of computer codes for the analysis of seals. Current status, new features, work in progress, and future plans are discussed.

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