Improving Procedure Start Times and Decreasing Delays in Interventional Radiology: A Department's Quality Improvement Initiative.

PubMed

Villarreal, Monica C; Rostad, Bradley S; Wright, Richard; Applegate, Kimberly E

2015-12-01

To identify and reduce reasons for delays in procedure start times, particularly the first cases of the day, within the interventional radiology (IR) divisions of the Department of Radiology using principles of continuous quality improvement. An interdisciplinary team representative of the IR and preprocedure/postprocedure care area (PPCA) health care personnel, managers, and data analysts was formed. A standardized form was used to document both inpatient and outpatient progress through the PPCA and IR workflow in six rooms and to document reasons for delays. Data generated were used to identify key problems areas, implement improvement interventions, and monitor their effects. Project duration was 6 months. The average number of on-time starts for the first case of the day increased from 23% to 56% (P value < .01). The average number of on-time, scheduled outpatients increased from 30% to 45% (P value < .01). Patient wait time to arrive at treatment room once they were ready for their procedure was reduced on average by 10 minutes (P value < .01). Patient care delay duration per 100 patients was reduced from 30.3 to 21.6 hours (29% reduction). Number of patient care delays per 100 patients was reduced from 46.6 to 40.1 (17% reduction). Top reasons for delay included waiting for consent (26% of delays duration) and laboratory tests (12%). Many complex factors contribute to procedure start time delays within an IR practice. A data-driven and patient-centered, interdisciplinary team approach was effective in reducing delays in IR. Copyright © 2015 AUR. Published by Elsevier Inc. All rights reserved.

A phase 3 randomized controlled trial of the efficacy and safety of atrasentan in men with metastatic hormone-refractory prostate cancer.

PubMed

Carducci, Michael A; Saad, Fred; Abrahamsson, Per-Anders; Dearnaley, David P; Schulman, Claude C; North, Scott A; Sleep, Darryl J; Isaacson, Jeffrey D; Nelson, Joel B

2007-11-01

The objective of this study was to evaluate the efficacy and safety of atrasentan (Xinlay), a selective endothelin-A receptor antagonist, in patients with metastatic hormone-refractory prostate cancer (HRPC). This multinational, double-blind, placebo-controlled trial enrolled 809 men with metastatic HRPC. Patients were randomized 1:1 to receive either atrasentan 10 mg per day or placebo. The primary endpoint was time to disease progression (TTP), which was determined according to radiographic and clinical measures. Analyses of overall survival and changes in biomarkers also were performed. Atrasentan did not reduce the risk of disease progression relative to placebo (hazards ratio, 0.89; 95% confidence interval, 0.76-1.04; P = .136). Most patients progressed radiographically at the first 12-week bone scan without concomitant clinical progression. In exploratory analyses, increases from baseline to final bone alkaline phosphatase (BAP) and prostate-specific antigen (PSA) levels were significantly lower with atrasentan treatment (P < .05 for each). The median time to BAP progression (>/=50% increase from nadir) was twice as long with atrasentan treatment (505 days vs 254 days; P < .01). The delay in time to PSA progression did not reach statistical significance. Atrasentan generally was tolerated well, and the most common adverse events associated with treatment were headache, rhinitis, and peripheral edema, reflecting the vasodilatory and fluid-retention properties of endothelin-A receptor antagonism. Atrasentan did not delay disease progression in men with metastatic HRPC despite evidence of biologic effects on PSA and BAP as markers of disease burden.

The effect of oral preexposure prophylaxis on the progression of HIV-1 seroconversion

PubMed Central

Donnell, Deborah; Ramos, Eric; Celum, Connie; Baeten, Jared; Dragavon, Joan; Tappero, Jordan; Lingappa, Jairam R.; Ronald, Allan; Fife, Kenneth; Coombs, Robert W.

2017-01-01

Objective: To investigate whether oral preexposure prophylaxis (PrEP) alters timing and patterns of seroconversion when PrEP use continues after HIV-1 infection. Design: Retrospective testing of the timing of Fiebig stage HIV-1 seroconversion in the Partners PrEP Study, a randomized placebo-controlled clinical trial of PrEP conducted in Kenya and Uganda. Methods: Specimens from 138 seroconverters were collected every 3 months and when HIV-1 infection was suspected based on monthly rapid HIV-1 tests. Progression of seroconversion was compared between randomized groups (PrEP versus placebo) and per-protocol groups (placebo versus PrEP participants with detectable tenofovir during the seroconversion period) using laboratory assessment of Fiebig stage. Delay in site-detection of seroconversion and association with PrEP drug-regimen resistant virus were assessed using logistic regression. Analysis of time to each Fiebig stage used maximum likelihood estimation with a parametric model to accommodate the varying lengths of HIV-infection intervals. Results: There was a significant increase in delayed site detection of infection associated with PrEP (odds ratio = 3.49, P = 0.044). Delay in detection was not associated with increased risk of resistance in the PrEP arm (odds ratio = 0.93, P = 0.95). Estimated time to each Fiebig stage was elongated in seroconverters with evidence of ongoing PrEP use, significantly for only Stage 5 (28 versus 17 days, P = 0.05). Adjusted for Fiebig stage, viral RNA was ∼2/3 log lower in those assigned to PrEP compared with placebo; no differences were found in Architect signal to cut-off at any stage. Conclusion: Ongoing PrEP use in seroconverters may delay detection of infection and elongate seroconversion, although the delay does not increase risk of resistance. PMID:28692542

Depletion of CD4 T Lymphocytes at the time of infection with M. avium subsp. paratuberculosis does not accelerate disease progression

USDA-ARS?s Scientific Manuscript database

A calf model was used to determine if the depletion of CD4 T cells prior to inoculation of Mycobacterium avium subsp. paratuberculosis (Map) would delay development of an immune response to Map and accelerate disease progression. Ileal cannulas were surgically implanted in 5 bull calves at two month...

Longitudinal Theory of Mind (ToM) Development From Preschool to Adolescence With and Without ToM Delay.

PubMed

Peterson, Candida C; Wellman, Henry M

2018-04-16

Longitudinal tracking of 107 three- to-thirteen-year-olds in a cross-sequential design showed a 6-step theory of mind (ToM) sequence identified by a few past cross-sectional studies validly depicted longitudinal ToM development from early to middle childhood for typically developing (TD) children and those with ToM delays owing to deafness or autism. Substantively, all groups showed ToM progress throughout middle childhood. Atypical development was more extended and began and ended at lower levels than for TD children. Yet most children in all groups progressed over the study's mean 1.5 years. Findings help resolve theoretical debates about ToM development for children with and without delay and gain strength and weight via their applicability to three disparate groups varying in ToM timing and sequencing. © 2018 Society for Research in Child Development.

Active doublet method for measuring small changes in physical properties

DOEpatents

Roberts, Peter M.; Fehler, Michael C.; Johnson, Paul A.; Phillips, W. Scott

1994-01-01

Small changes in material properties of a work piece are detected by measuring small changes in elastic wave velocity and attenuation within a work piece. Active, repeatable source generate coda wave responses from a work piece, where the coda wave responses are temporally displaced. By analyzing progressive relative phase and amplitude changes between the coda wave responses as a function of elapsed time, accurate determinations of velocity and attenuation changes are made. Thus, a small change in velocity occurring within a sample region during the time periods between excitation origin times (herein called "doublets") will produce a relative delay that changes with elapsed time over some portion of the scattered waves. This trend of changing delay is easier to detect than an isolated delay based on a single arrival and provides a direct measure of elastic wave velocity changes arising from changed material properties of the work piece.

Delayed-Type Hypersensitivity and Hepatitis B Vaccine Responses, in vivo Markers of Cellular and Humoral Immune Function, and the Risk of AIDS or Death

PubMed Central

Patterson, Shane B.; Landrum, Michael L; Okulicz, Jason F.

2014-01-01

Background Delayed-type hypersensitivity (DTH) test responsiveness is associated with HIV disease progression; however it is unknown whether other immune markers, such as hepatitis B virus (HBV) vaccine seroresponse, also predict HIV outcomes. Methods Eligible participants received HBV vaccine after HIV diagnosis, had non-anergic DTH testing at the time of last HBV vaccination, and available post-vaccine HBV antibody responses. The risk of progression to AIDS or death from the time of last HBV vaccination was evaluated. Results Of 369 eligible participants with non-anergic DTH responses, 148 (40%) were HBV vaccine responders. In a multivariate model adjusted for age, CD4 count, viral load, and number of vaccinations, HBV vaccine non-responders had an increased risk of progression to AIDS or death (HR 1.81; 95% CI, 1.03–3.19). Conclusions HBV vaccine seroresponses were independent of DTH responses which suggest that non-response to HBV vaccine is not solely due to cell-mediated immune dysfunction in HIV-infected persons. PMID:24793945

Ongoing Progress in Spacecraft Controls

NASA Technical Reports Server (NTRS)

Ghosh, Dave (Editor)

1992-01-01

This publication is a collection of papers presented at the Mars Mission Research Center workshop on Ongoing Progress in Spacecraft Controls. The technical program addressed additional Mars mission control problems that currently exist in robotic missions in addition to human missions. Topics include control systems design in the presence of large time delays, fuel-optimal propulsive control, and adaptive control to handle a variety of unknown conditions.

SSATP progress report 2004

DOT National Transportation Integrated Search

2005-07-01

there were a number of problems and delays, by the time the year drew to a close implementation : was well underway, donor promises had been transformed into hard cash. Most importantly, new : recruits were joining the Program Management Team (PMT) g...

Short- and long-term clinical outcomes of use of beta-interferon or glatiramer acetate for people with clinically isolated syndrome: a systematic review of randomised controlled trials and network meta-analysis.

PubMed

Armoiry, X; Kan, A; Melendez-Torres, G J; Court, R; Sutcliffe, P; Auguste, P; Madan, J; Counsell, C; Clarke, A

2018-05-01

Beta-interferon (IFN-β) and glatiramer acetate (GA) have been evaluated in people with clinically isolated syndrome (CIS) with the aim to delay a second clinical attack and a diagnosis of clinically definite multiple sclerosis (CDMS). We systematically reviewed trials evaluating the short- and long-term clinical effectiveness of these drugs in CIS. We searched multiple electronic databases. We selected randomised controlled studies (RCTs) conducted in CIS patients and where the interventions were IFN-β and GA. Main outcomes were time to CDMS, and discontinuation due to adverse events (AE). We compared interventions using random-effect network meta-analyses (NMA). We also reported outcomes from long-term open-label extension (OLE) studies. We identified five primary studies. Four had open-label extensions following double-blind periods comparing outcomes between early vs delayed DMT. Short-term clinical results (double-blind period) showed that all drugs delayed CDMS compared to placebo. Indirect comparisons did not suggest superiority of any one active drug over another. We could not undertake a NMA for discontinuation due to AE. Long-term clinical results (OLE studies) showed that the risk of developing CDMS was consistently reduced across studies after early DMT treatment compared to delayed DMT (HR = 0.64, 95% CI 0.55, 0.74). No data supported the benefit of DMTs in reducing the time to, and magnitude of, disability progression. Meta-analyses confirmed that IFN-β and GA delay time to CDMS compared to placebo. In the absence of evidence that early DMTs can reduce disability progression, future research is needed to better identify patients most likely to benefit from long-term DMTs.

The dynamics of sensory buffers: geometric, spatial, and experience-dependent shaping of iconic memory.

PubMed

Graziano, Martin; Sigman, Mariano

2008-05-23

When a stimulus is presented, its sensory trace decays rapidly, lasting for approximately 1000 ms. This brief and labile memory, referred as iconic memory, serves as a buffer before information is transferred to working memory and executive control. Here we explored the effect of different factors--geometric, spatial, and experience--with respect to the access and the maintenance of information in iconic memory and the progressive distortion of this memory. We studied performance in a partial report paradigm, a design wherein recall of only part of a stimulus array is required. Subjects had to report the identity of a letter in a location that was cued in a variable delay after the stimulus onset. Performance decayed exponentially with time, and we studied the different parameters (time constant, zero-delay value, and decay amplitude) as a function of the different factors. We observed that experience (determined by letter frequency) affected the access to iconic memory but not the temporal decay constant. On the contrary, spatial position affected the temporal course of delay. The entropy of the error distribution increased with time reflecting a progressive morphological distortion of the iconic buffer. We discuss our results on the context of a model of information access to executive control and how it is affected by learning and attention.

Impact of rivastigmine on costs and on time spent in caregiving for families of patients with Alzheimer's disease.

PubMed

Marin, Deborah; Amaya, Karine; Casciano, Roman; Puder, Katherine L; Casciano, Julian; Chang, Sobin; Snyder, Edward H; Cheng, Isaac; Cuccia, Anthony J

2003-12-01

Alzheimer's disease (AD) places a significant burden on health care systems worldwide. As new treatments are developed, their cost-effectiveness is often assessed to help health care professionals make informed decisions. In addition to the more common practice of assessing direct medical costs, indirect costs, including time spent in caregiving, should be evaluated. This study examined the potential effects of the dual cholinesterase inhibitor rivastigmine (Exelon) on caregivers of patients with AD. Results from two 26-week, placebo-controlled trials have demonstrated the clinically relevant and statistically significant efficacy of rivastigmine (6-12 mg/day) compared to placebo, on cognition, activities of daily living, and global functioning. By delaying progression of AD, significant savings in caregiver burden are anticipated, as measured by time spent caregiving and its related costs. Data collected in a prospective, observational study of AD patients and their caregivers were used to establish the relationship between disease severity (based on Mini-Mental State Examination [MMSE] score) and time spent caregiving (according to the 5-item Caregivers Activity Survey score). A significant correlation was observed between the two scores (N = 43, r = -.56, p < .0001), demonstrating that more time for supervision from caregivers is required as the disease progresses. This finding was used to estimate the reduced caregiver burden resulting from the delay in disease progression that was demonstrated with use of rivastigmine. Over a 2-year period, the reduction in time spent in caregiving reached 691 hours for caregivers of patients with mild AD (MMSE score 21-30), resulting in a total savings of approximately 11,253 dollars. Treatment of patients with moderately severe AD was also evaluated. The trend was similar but the impact was less, suggesting an economic benefit to early therapy. Early diagnosis and a pharmacologic intervention that allows the patients to remain at home longer by delaying disease progression would have a beneficial impact on patients, caregivers, and payers, and should therefore be encouraged through initiatives designed to identify and treat patients early in the course of disease.

Early versus delayed initiation of antiretroviral therapy for Indian HIV-Infected individuals with tuberculosis on antituberculosis treatment.

PubMed

Sinha, Sanjeev; Shekhar, Rahul C; Singh, Gurjeet; Shah, Nipam; Ahmad, Hafiz; Kumar, Narendra; Sharma, Surendra K; Samantaray, J C; Ranjan, Sanjai; Ekka, Meera; Sreenivas, Vishnu; Mitsuyasu, Ronald T

2012-07-31

For antiretroviral therapy (ART) naive human immunodeficiency virus (HIV) infected adults suffering from tuberculosis (TB), there is uncertainty about the optimal time to initiate highly active antiretroviral therapy (HAART) after starting antituberculosis treatment (ATT), in order to minimize mortality, HIV disease progression, and adverse events. In a randomized, open label trial at All India Institute of Medical Sciences, New Delhi, India, eligible HIV positive individuals with a diagnosis of TB were randomly assigned to receive HAART after 2-4 or 8-12 weeks of starting ATT, and were followed for 12 months after HAART initiation. Participants received directly observed therapy short course (DOTS) for TB, and an antiretroviral regimen comprising stavudine or zidovudine, lamivudine, and efavirenz. Primary end points were death from any cause, and progression of HIV disease marked by failure of ART. A total of 150 patients with HIV and TB were initiated on HAART: 88 received it after 2-4 weeks (early ART) and 62 after 8-12 weeks (delayed ART) of starting ATT. There was no significant difference in mortality between the groups after the introduction of HAART. However, incidence of ART failure was 31% in delayed versus 16% in early ART arm (p = 0.045). Kaplan Meier disease progression free survival at 12 months was 79% for early versus 64% for the delayed ART arm (p = 0.05). Rates of adverse events were similar. Early initiation of HAART for patients with HIV and TB significantly decreases incidence of HIV disease progression and has good tolerability. CTRI/2011/12/002260.

Distinguishing time-delayed causal interactions using convergent cross mapping

PubMed Central

Ye, Hao; Deyle, Ethan R.; Gilarranz, Luis J.; Sugihara, George

2015-01-01

An important problem across many scientific fields is the identification of causal effects from observational data alone. Recent methods (convergent cross mapping, CCM) have made substantial progress on this problem by applying the idea of nonlinear attractor reconstruction to time series data. Here, we expand upon the technique of CCM by explicitly considering time lags. Applying this extended method to representative examples (model simulations, a laboratory predator-prey experiment, temperature and greenhouse gas reconstructions from the Vostok ice core, and long-term ecological time series collected in the Southern California Bight), we demonstrate the ability to identify different time-delayed interactions, distinguish between synchrony induced by strong unidirectional-forcing and true bidirectional causality, and resolve transitive causal chains. PMID:26435402

Comparison of Progressive Prompt Delay with and without Instructive Feedback

ERIC Educational Resources Information Center

Reichow, Brian; Wolery, Mark

2011-01-01

We examined the effectiveness and efficiency of 2 instructional arrangements using progressive prompt delay (PPD) with 3 young children with autism and 1 child with developmental delays. Specifically, we compared PPD with instructive feedback (IF) to PPD without IF in an adapted alternating treatment design. The results suggested that (a) children…

Successful tocolysis: does cervical change affect time to delivery?

PubMed

Lewis, D F; Gallaspy, J W; Fontenot, M T; Burlison, R D; Imseis, J M; Edwards, M S

1997-11-01

Generally, it is preferable to tocolyze patients with idiopathic preterm labor (PTL). Little information is available about ultimate outcomes after successful tocolysis. Our objective is to evaluate the relationship between cervical change after the initiation of tocolysis and the delay in time to delivery in patients with preterm labor. A historical analysis of all patients with successful tocolysis after PTL between January 1992 and December 1993 was undertaken. The patients were then placed in one of three categories (regression, unchanged, or progression) based on cervical change after the initiation of tocolysis. Various demographic pregnancy characteristics and pregnancy outcome data were analyzed. One hundred and twenty-six patients had successful tocolysis and met the admission criteria. Patients who had cervical progression had shorter delay to delivery, delivered at an earlier gestational age (31.7 weeks compared to 34.0 and 34.1 weeks, respectively, p < 0.05), and were more likely to deliver before 35 weeks (88% compared to 50.0 and 55.0%, respectively, p < 0.05). Also, neonates remained in the hospital longer and were more likely to have respiratory distress syndrome when compared to the other two groups. Patients who had cervical progression after the initiation of tocolysis are more likely to deliver prematurely, had a shorter delay to delivery, and delivered lower birth weight infants than did patients whose cervix regressed or remained unchanged. In our population, patients who had successful tocolysis had a preterm delivery rate of 59.5% before the 35th week of gestation.

[Delayed neurological syndrome after CO intoxication of elderly female].

PubMed

Vander Weyden, Liesbeth; Voigt, Roxana-Maria; Boonen, Steven; Fagard, Katleen; Dejaeger, Eddy

2015-10-01

This article discusses the case history of an 87-year old woman with loss of consciousness following accidental CO intoxication. A few weeks later, the patient's cognitive abilities progressively deteriorated. This is hence a case of Delayed Neurological Symptoms after CO intoxication. This condition occurs in 40% of patients with CO intoxication and manifests itself 3-240 days after apparent recovery. Symptoms can linger for a long time and are in some cases even permanent. Treatment of CO intoxication usually consists of administering normobaric oxygen and in certain cases hyperbaric oxygen. The role of treatment with hyberbaric oxygen in delayed neurological symptoms after CO intoxication remains controversial, however.

Tolerable hearing-aid delays: IV. effects on subjective disturbance during speech production by hearing-impaired subjects.

PubMed

Stone, Michael A; Moore, Brian C J

2005-04-01

We assessed the effects of time delay in a hearing aid on subjective disturbance and reading rates while the user of the aid was speaking, using hearing-impaired subjects and real-time processing. The time delay was constant across frequency. A digital signal processor was programmed as a four-channel, fast-acting, wide-dynamic-range compression hearing aid. One of four delays could be selected on the aid to produce a total delay of 13, 21, 30, or 40 msec between microphone and receiver. Twenty-five subjects, mostly with near-symmetric hearing impairment of cochlear origin, were fitted bilaterally with behind-the-ear aids connected to the processor. The aids were programmed with insertion gains prescribed by the CAMEQ loudness equalization procedure for each subject and ear. Subjects were asked to read aloud from scripts: speech production rates were measured and subjective ratings of the disturbance of the delay were obtained. Subjects required some training to recognize the effects of the delay to rate it consistently. Subjective disturbance increased progressively with increasing delay and was a nonmonotonic function of low-frequency hearing loss. Subjects with mild or severe low-frequency hearing loss were generally less disturbed by the delay than those with moderate loss. Disturbance ratings tended to decrease over successive tests. Word production rates were not significantly affected by delay over the range of delays tested. The results follow a pattern similar to those presented in , obtained using a simulation of hearing loss and normally hearing subjects, except for the nonmonotonic variation of disturbance with low-frequency hearing loss. We hypothesize that disturbance is maximal when the levels in the ear canal of the low-frequency components are similar for the unaided and aided sounds. A rating of 3, which is probably just acceptable, was obtained for delays ranging from 14 to 30 msec, depending on the hearing loss. Some acclimatization to the subjective disturbance occurred over a time scale of about 1 hour.

Assessment of progressively delayed prompts on guided skill learning in rats.

PubMed

Reid, Alliston K; Futch, Sara E; Ball, Katherine M; Knight, Aubrey G; Tucker, Martha

2017-03-01

We examined the controlling factors that allow a prompted skill to become autonomous in a discrete-trials implementation of Touchette's (1971) progressively delayed prompting procedure, but our subjects were rats rather than children with disabilities. Our prompted skill was a left-right lever-press sequence guided by two panel lights. We manipulated (a) the effectiveness of the guiding lights prompt and (b) the presence or absence of a progressively delayed prompt in four groups of rats. The less effective prompt yielded greater autonomy than the more effective prompt. The ability of the progressively delayed prompt procedure to produce behavioral autonomy depended upon characteristics of the obtained delay (trial duration) rather than on the pending prompt. Sequence accuracy was reliably higher in unprompted trials than in prompted trials, and this difference was maintained in the 2 groups that received no prompts but yielded equivalent trial durations. Overall sequence accuracy decreased systematically as trial duration increased. Shorter trials and their greater accuracy were correlated with higher overall reinforcement rates for faster responding. Waiting for delayed prompts (even if no actual prompt was provided) was associated with lower overall reinforcement rate by decreasing accuracy and by lengthening trials. These findings extend results from previous studies regarding the controlling factors in delayed prompting procedures applied to children with disabilities.

The 11-year long-term follow-up study from the randomized BENEFIT CIS trial

PubMed Central

Edan, Gilles; Freedman, Mark S.; Montalbán, Xavier; Hartung, Hans-Peter; Hemmer, Bernhard; Fox, Edward J.; Barkhof, Frederik; Schippling, Sven; Schulze, Andrea; Pleimes, Dirk; Pohl, Christoph; Sandbrink, Rupert; Suarez, Gustavo; Wicklein, Eva-Maria

2016-01-01

Objective: To assess outcomes for patients treated with interferon beta-1b immediately after clinically isolated syndrome (CIS) or after a short delay. Methods: Participants in BENEFIT (Betaferon/Betaseron in Newly Emerging MS for Initial Treatment) were randomly assigned to receive interferon beta-1b (early treatment) or placebo (delayed treatment). After conversion to clinically definite multiple sclerosis (CDMS) or 2 years, patients on placebo could switch to interferon beta-1b or another treatment. Eleven years after randomization, patients were reassessed. Results: Two hundred seventy-eight (59.4%) of the original 468 patients (71.3% of those eligible at participating sites) were enrolled (early: 167 [57.2%]; delayed: 111 [63.1%]). After 11 years, risk of CDMS remained lower in the early-treatment arm compared with the delayed-treatment arm (p = 0.0012), with longer time to first relapse (median [Q1, Q3] days: 1,888 [540, not reached] vs 931 [253, 3,296]; p = 0.0005) and lower overall annualized relapse rate (0.21 vs 0.26; p = 0.0018). Only 25 patients (5.9%, overall; early, 4.5%; delayed, 8.3%) converted to secondary progressive multiple sclerosis. Expanded Disability Status Scale scores remained low and stable, with no difference between treatment arms (median [Q1, Q3]: 2.0 [1.0, 3.0]). The early-treatment group had better Paced Auditory Serial Addition Task–3 total scores (p = 0.0070). Employment rates remained high, and health resource utilization tended to be low in both groups. MRI metrics did not differ between groups. Conclusions: Although the delay in treatment was relatively short, several clinical outcomes favored earlier treatment. Along with low rates of disability and disease progression in both groups, this supports the value of treatment at CIS. ClinicalTrials.gov identifier: NCT01795872. Classification of evidence: This study provides Class IV evidence that early compared to delayed treatment prolongs time to CDMS in CIS after 11 years. PMID:27511182

Using Constant Time Delay to Teach Braille and the Nemeth Code for Mathematics and Science Notation to Students Making the Transition from Print to Braille

ERIC Educational Resources Information Center

Ivy, Sarah E.; Hooper, Jonathan D.

2015-01-01

Introduction: Many students with adventitious vision loss or progressive vision loss need to transition from print to braille as a primary literacy medium. It is important that this transition is handled efficiently so that the student can have continued access to a literacy medium and make progress in the core curriculum. For this study, we used…

The Changes They are A-Timed: Metabolism, Endogenous Clocks, and the Timing of Puberty

PubMed Central

Tolson, Kristen P.; Chappell, Patrick E.

2012-01-01

Childhood obesity has increased dramatically over the last several decades, particularly in industrialized countries, often accompanied by acceleration of pubertal progression and associated reproductive abnormalities (Biro et al., 2006; Rosenfield et al., 2009). The timing of pubertal initiation and progression in mammals is likely influenced by nutritional and metabolic state, leading to the hypothesis that deviations from normal metabolic rate, such as those seen in obesity, may contribute to observed alterations in the rate of pubertal progression. While several recent reviews have addressed the effects of metabolic disorders on reproductive function in general, this review will explore previous and current models of pubertal timing, outlining a potential role of endogenous timing mechanisms such as cellular circadian clocks in the initiation of puberty, and how these clocks might be altered by metabolic factors. Additionally, we will examine recently elucidated neuroendocrine regulators of pubertal progression such as kisspeptin, explore models detailing how the mammalian reproductive axis is silenced during the juvenile period and reactivated at appropriate developmental times, and emphasize how metabolic dysfunction such as childhood obesity may alter timing cues that advance or delay pubertal progression, resulting in diminished reproductive capacity. PMID:22645521

Cone responses in Usher syndrome types 1 and 2 by microvolt electroretinography.

PubMed

Zein, Wadih M; Falsini, Benedetto; Tsilou, Ekaterina T; Turriff, Amy E; Schultz, Julie M; Friedman, Thomas B; Brewer, Carmen C; Zalewski, Christopher K; King, Kelly A; Muskett, Julie A; Rehman, Atteeq U; Morell, Robert J; Griffith, Andrew J; Sieving, Paul A

2014-11-25

Progressive decline of psychophysical cone-mediated measures has been reported in type 1 (USH1) and type 2 (USH2) Usher syndrome. Conventional cone electroretinogram (ERG) responses in USH demonstrate poor signal-to-noise ratio. We evaluated cone signals in USH1 and USH2 by recording microvolt level cycle-by-cycle (CxC) ERG. Responses of molecularly genotyped USH1 (n = 18) and USH2 (n = 24) subjects (age range, 15-69 years) were compared with those of controls (n = 12). A subset of USH1 (n = 9) and USH2 (n = 9) subjects was examined two to four times over 2 to 8 years. Photopic CxC ERG and conventional 30-Hz flicker ERG were recorded on the same visits. Usher syndrome subjects showed considerable cone flicker ERG amplitude losses and timing phase delays (P < 0.01) compared with controls. USH1 and USH2 had similar rates of progressive logarithmic ERG amplitude decline with disease duration (-0.012 log μV/y). Of interest, ERG phase delays did not progress over time. Two USH1C subjects retained normal response timing despite reduced amplitudes. The CxC ERG method provided reliable responses in all subjects, whereas conventional ERG was undetectable in 7 of 42 subjects. Cycle-by-cycle ERG showed progressive loss of amplitude in both USH1 and USH2 subjects, comparable to that reported with psychophysical measures. Usher subjects showed abnormal ERG response latency, but this changed less than amplitude with time. In USH syndrome, CxC ERG is more sensitive than conventional ERG and warrants consideration as an outcome measure in USH treatment trials. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

Clinical Epidemiology of Buruli Ulcer from Benin (2005-2013): Effect of Time-Delay to Diagnosis on Clinical Forms and Severe Phenotypes.

PubMed

Capela, Carlos; Sopoh, Ghislain E; Houezo, Jean G; Fiodessihoué, René; Dossou, Ange D; Costa, Patrício; Fraga, Alexandra G; Menino, João F; Silva-Gomes, Rita; Ouendo, Edgard M; Rodrigues, Fernando; Pedrosa, Jorge

2015-01-01

Buruli Ulcer (BU) is a neglected infectious disease caused by Mycobacterium ulcerans that is responsible for severe necrotizing cutaneous lesions that may be associated with bone involvement. Clinical presentations of BU lesions are classically classified as papules, nodules, plaques and edematous infiltration, ulcer or osteomyelitis. Within these different clinical forms, lesions can be further classified as severe forms based on focality (multiple lesions), lesions' size (>15 cm diameter) or WHO Category (WHO Category 3 lesions). There are studies reporting an association between delay in seeking medical care and the development of ulcerative forms of BU or osteomyelitis, but the effect of time-delay on the emergence of lesions classified as severe has not been addressed. To address both issues, and in a cohort of laboratory-confirmed BU cases, 476 patients from a medical center in Allada, Benin, were studied. In this laboratory-confirmed cohort, we validated previous observations, demonstrating that time-delay is statistically related to the clinical form of BU. Indeed, for non-ulcerated forms (nodule, edema, and plaque) the median time-delay was 32.5 days (IQR 30.0-67.5), while for ulcerated forms it was 60 days (IQR 20.0-120.0) (p = 0.009), and for bone lesions, 365 days (IQR 228.0-548.0). On the other hand, we show here that time-delay is not associated with the more severe phenotypes of BU, such as multi-focal lesions (median 90 days; IQR 56-217.5; p = 0.09), larger lesions (diameter >15 cm) (median 60 days; IQR 30-120; p = 0.92) or category 3 WHO classification (median 60 days; IQR 30-150; p = 0.20), when compared with unifocal (median 60 days; IQR 30-90), small lesions (diameter ≤15 cm) (median 60 days; IQR 30-90), or WHO category 1+2 lesions (median 60 days; IQR 30-90), respectively. Our results demonstrate that after an initial period of progression towards ulceration or bone involvement, BU lesions become stable regarding size and focal/multi-focal progression. Therefore, in future studies on BU epidemiology, severe clinical forms should be systematically considered as distinct phenotypes of the same disease and thus subjected to specific risk factor investigation.

Resolution of tracheal aspiration after the acute phase of stroke-related oropharyngeal Dysphagia.

PubMed

Terré, Rosa; Mearin, Fermín

2009-04-01

We set out to ascertain the evolution and the clinical and videofluoroscopic (VFS) prognostic factors of aspiration recovery and return to oral intake in patients with stroke and VFS diagnosis of tracheal aspiration. Twenty patients with stroke and VFS diagnosis of tracheal aspiration were prospectively evaluated. Clinical evaluation of oropharyngeal dysphagia and VFS examination were performed at admission and repeated at 1, 3, 6 and 12 months of follow-up. At admission, videofluoroscopy showed 40% of patients to have an increase in oral transit time and 65% impaired tongue control; in the pharyngeal phase, mean pharyngeal transit time was increased in 70% of patients and the time required to trigger the swallowing reflex was delayed in 70%. During follow-up, an improvement was observed, and the number of patients with aspiration decreased progressively (the most significant change occurred at 6 months). Evolution was related to the vascular territory affected: at 1 year, aspiration persisted in 12% of anterior territory lesions vs. 58% of posterior territory lesions. Also, the number of silent aspirators decreased from 35% at baseline to no patients after 3 months. Persistent aspiration at 1 year of follow-up significantly correlated with the following baseline variables: vascular territory, gag reflex abolition, palatoglossal seal alteration and pharyngeal delay time. Swallowing physiology in stroke greatly improved during follow-up, mainly between 3 and 6 months, and the number of aspirations decreased progressively. Prognostic factors for persisting aspiration are posterior vascular territory lesions, oropharyngeal reflex abolition, palatoglossal seal alteration and pharyngeal delay time at baseline.

PROGRESS ON THE STUDY OF BETA TREATMENT OF URANIUM, APRIL 1, 1961 TO JULY 31, 1961

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

Russell, R.B.; Wolff, A.K.

Progress on the work on the effect of variables affecting the beta treatment of uranium is described. Included are results on the effect of beta time and temperature on the as-quenched grain size, the influence of air delay before quenching, and the growth index of metal isothermally transformed at different temperatures. The relative effects of both size and cooling medium on the radial growth index are summarized. (auth)

Delayed Presentation of Ureteropelvic Junction Obstruction and Loss of Renal Function After Initially Mild (SFU Grade 1-2) Hydronephrosis.

PubMed

Bowen, Diana K; Yerkes, Elizabeth B; Lindgren, Bruce W; Gong, Edward M; Faasse, Mark A

2015-07-01

We report 4 pediatric cases of ureteropelvic junction obstruction involving delayed progression of initially mild postnatal hydronephrosis. All 4 children became symptomatic; however, 3 already had a substantial decrement of ipsilateral kidney function by the time of diagnosis. Two of these 3 patients had previous renal scintigraphy demonstrating normal differential function. We caution that counseling regarding hydronephrosis should emphasize the importance of prompt re-evaluation for any symptoms potentially referable to delayed presentation of ureteropelvic junction obstruction, irrespective of initial hydronephrosis grade. Future studies are needed to determine the optimal follow-up regimen for conservative management of hydronephrosis. Copyright © 2015 Elsevier Inc. All rights reserved.

Sequencing of Local Therapy Affects the Pattern of Treatment Failure and Survival in Children With Atypical Teratoid Rhabdoid Tumors of the Central Nervous System

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

Pai Panandiker, Atmaram S., E-mail: atmaram.pai-panandiker@stjude.org; Merchant, Thomas E.; Beltran, Chris

Purpose: To assess the pattern of treatment failure associated with current therapeutic paradigms for childhood atypical teratoid rhabdoid tumors (AT/RT). Methods and Materials: Pediatric patients with AT/RT of the central nervous system treated at our institution between 1987 and 2007 were retrospectively evaluated. Overall survival (OS), progression-free survival, and cumulative incidence of local failure were correlated with age, sex, tumor location, extent of disease, and extent of surgical resection. Radiotherapy (RT) sequencing, chemotherapy, dose, timing, and volume administered after resection were also evaluated. Results: Thirty-one patients at a median age of 2.3 years at diagnosis (range, 0.45-16.87 years) were enrolledmore » into protocols that included risk- and age-stratified RT. Craniospinal irradiation with focal tumor bed boost (median dose, 54 Gy) was administered to 18 patients. Gross total resection was achieved in 16. Ten patients presented with metastases at diagnosis. RT was delayed more than 3 months in 20 patients and between 1 and 3 months in 4; 7 patients received immediate postoperative irradiation preceding high-dose alkylator-based chemotherapy. At a median follow-up of 48 months, the cumulative incidence of local treatment failure was 37.5% {+-} 9%; progression-free survival was 33.2% {+-} 10%; and OS was 53.5% {+-} 10%. Children receiving delayed RT ({>=}1 month postoperatively) were more likely to experience local failure (hazard ratio [HR] 1.23, p = 0.007); the development of distant metastases before RT increased the risk of progression (HR 3.49, p = 0.006); and any evidence of disease progressionbefore RT decreased OS (HR 20.78, p = 0.004). Disease progression occurred in 52% (11/21) of children with initially localized tumors who underwent gross total resection, and the progression rate increased proportionally with increasing delay from surgery to RT. Conclusions: Delayed RT is associated with a higher rate of local and metastatic disease progression in children with AT/RT. Current treatment regimens for pediatric patients with AT/RT are distinctly age stratified; novel protocols investigating RT volumes and sequencing are needed.« less

Effects of free-air CO2 and temperature enrichment on soybean growth and development

NASA Astrophysics Data System (ADS)

Ruiz Vera, U. M.; Bernacchi, C. J.

2012-12-01

According to the growing degree days approach, the progression of plant developmental stages requires certain accumulation of heat; therefore greenhouse gas-induced warming of the atmosphere could contribute to more rapid plant development. However, the influence of rising carbon dioxide concentration ([CO2]) on development of crops is uncertain, accelerating and other times delaying certain developmental stages. In soybean, the increase of [CO2] is shown to delay reproductive development, which is attributed to a higher investment of resources into extra nodes. The combined effects of elevated temperature and [CO2] can have significant changes in the progression through development that can influence on total grain production, carbon uptake, and susceptibility to early end-of-season frosts. We designed the Temperature by Free Air CO2 Enrichment (T-FACE) experiment to test over two growing seasons (2009 and 2011) and under field conditions the impact of increased temperature and/or [CO2] on soybean. The heated T-FACE subplots were situated in the larger FACE plots at 385 or 585 ppm of [CO2] and subjected to either ambient or heated (+~3.5°C) temperatures. The experiment is full factorial with ambient temperature and [CO2] (control), elevated temperature (eT), elevated [CO2] (eC) and combined (eT+eC) treatments. We hypothesized that soybean grown (1) under elevated [CO2] will produce more nodes than control, (2) under high temperature will produce nodes faster than control and (3) under both elevated temperature and [CO2] will produce more nodes in less time than control. For reproductive development, we hypothesized that (1) reproductive development will initiate simultaneously regardless of increased [CO2] or temperature because soybean reproduction is triggered by day length, (2) elevated temperature will accelerate the progression through key reproductive stages and (3) the delay in soybean reproductive development by elevated [CO2] will be ameliorated by the raise in temperature. Soybean developmental stages were recorded on six plants per subplot three times per week from emergence to senescence. In 2009, no temperature effect was detected on the vegetative development, but in 2011 temperature accelerates node formation. Elevated [CO2] was not significant on vegetative development, however plants under this effect produced more nodes than control. Reproductive development was delayed by elevated [CO2]. High temperature accelerated reproductive stages only in 2009, ameliorating the effect of elevated [CO2] in eT+eC. In 2011 elevated temperature delayed reproductive stages, a response that could be related with stress imposed by the weather conditions of that season. In the Midwest, the soybean cultivars generally mature before the first frost of the year avoiding seed damage. The delayed in soybean maturation by the increasing of [CO2] could potentially reduce yield; however the increase of temperature could diminish this risk by mitigating this delay. Alternatively, the more rapid progression through the reproductive stages could decrease the translocation of resources to pods, thereby negatively impacting yields. Using soybean as a model for leguminous C3 species suggested implications could arise for yield in crop plants and reproductive fitness in native vegetation.

Influence of age on delayed surgical treatment of proximal femoral fractures

PubMed Central

Gomes, Lisiane Pinto; do Nascimento, Leandra Delfim; Campos, Tulio Vinicius de Oliveira; Paiva, Edson Barreto; de Andrade, Marco Antonio Percope; Guimarães, Henrique Cerqueira

2015-01-01

ABSTRACT OBJECTIVE : To investigate the influence of patients' age on the delay between diagnosis and surgical treatment of proximal femoral fractures METHODS : This is a retrospective study, con-ducted at a tertiary university hospital, including all patients admitted with proximal femoral fractures between March 2013 and March 2014. The participants were categorized into four groups according to age levels. The groups were compared according to demographics, comorbidities, fracture type, trau-ma circumstances, and time between diagnosis and surgical procedure RESULTS : One hundred and sixty one patients were included, 37 adults and 124 elderly. Among adults, the mean delay between diagnosis and surgical procedure was 6.4±5.3 days; among elderly the delay was 9.5±7.6 days. There was a progressive increase in the delay from the young-adults group through the elderly individuals (Kruskal-Wallis: 13.7; p=0.003) CONCLUSION : In spite of being the patients most susceptible to complications due to surgical delay, the elderly individuals pre-sented the longest delays from admission to surgical treatment. Level of Evidence III, Retrospective Study. PMID:27057145

Comparative effects of 60Co gamma-rays and neon and helium ions on cycle duration and division probability of EMT 6 cells. A time-lapse cinematography study.

PubMed

Collyn-d'Hooghe, M; Hemon, D; Gilet, R; Curtis, S B; Valleron, A J; Malaise, E P

1981-03-01

Exponentially growing cultures of EMT 6 cells were irradiated in vitro with neon ions, helium ions or 60Co gamma-rays. Time-lapse cinematography allowed the determination, for individual cells, of cycle duration, success of the mitotic division and the age of the cell at the moment of irradiation. Irradiation induced a significant mitotic delay increasing proportionally with the delivered dose. Using mitotic delay as an endpoint, the r.b.e. for neon ions with respect to 60Co gamma-rays was 3.3 +/- 0.2 while for helium ions it was 1.2 +/- 0.1. Mitotic delay was greatest in those cells that had progressed furthest in their cycle at the time of irradiation. No significant mitotic delay was observed in the post-irradiation generation. Division probability was significantly reduced by irradiation both in the irradiated and in the post-irradiated generation. The reduction in division probability obtained with 3 Gy of neon ions was similar to that obtained after irradiation with 6 Gy of helium ions or 60Co gamma-rays.

A clinical tool for predicting survival in ALS.

PubMed

Knibb, Jonathan A; Keren, Noa; Kulka, Anna; Leigh, P Nigel; Martin, Sarah; Shaw, Christopher E; Tsuda, Miho; Al-Chalabi, Ammar

2016-12-01

Amyotrophic lateral sclerosis (ALS) is a progressive and usually fatal neurodegenerative disease. Survival from diagnosis varies considerably. Several prognostic factors are known, including site of onset (bulbar or limb), age at symptom onset, delay from onset to diagnosis and the use of riluzole and non-invasive ventilation (NIV). Clinicians and patients would benefit from a practical way of using these factors to provide an individualised prognosis. 575 consecutive patients with incident ALS from a population-based registry in South-East England register for ALS (SEALS) were studied. Their survival was modelled as a two-step process: the time from diagnosis to respiratory muscle involvement, followed by the time from respiratory involvement to death. The effects of predictor variables were assessed separately for each time interval. Younger age at symptom onset, longer delay from onset to diagnosis and riluzole use were associated with slower progression to respiratory involvement, and NIV use was associated with lower mortality after respiratory involvement, each with a clinically significant effect size. Riluzole may have a greater effect in younger patients and those with longer delay to diagnosis. A patient's survival time has a roughly 50% chance of falling between half and twice the predicted median. A simple and clinically applicable graphical method of predicting an individual patient's survival from diagnosis is presented. The model should be validated in an independent cohort, and extended to include other important prognostic factors. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

First Drink to First Drunk: Age of Onset and Delay to Intoxication are Associated with Adolescent Alcohol Use and Binge Drinking

PubMed Central

Morean, Meghan E.; Kong, Grace; Camenga, Deepa R.; Cavallo, Dana A.; Connell, Christian; Krishnan-Sarin, Suchitra

2014-01-01

Background Quickly progressing from initiating alcohol use to drinking to intoxication recently was identified as a novel risk factor for hazardous drinking in college students (Morean, Corbin, & Fromme, 2012). The current study evaluated the risk associated with age of onset (AO) and delay to first intoxication (Delay) in a high school sample. Methods Adolescent drinkers (N=295, age 16.29[1.14], 55.3% female, 80.3% Caucasian, AO = 13.51[2.29] years, Delay = 0.80[1.43] years) completed an anonymous survey about their substance use in February of 2010. Self-report questions assessed AO and age of first intoxication (i.e., “How old were you the first time you tried alcohol/got drunk?”) and past-month alcohol use/binge drinking (i.e., How often did you drink alcohol/drink ≥ 5 drinks?). Results Bivariate correlations indicated that AO was positively correlated with AI and inversely correlated with Delay, the frequency of any drinking, and the frequency of binge drinking. When considered alone, Delay was not significantly correlated with either alcohol use outcome. In contrast, hierarchical regression analyses indicated that, when considered in concert, an earlier AO and a shorter Delay were each associated with heavier drinking (any drinking adjusted R2 = .08; binge drinking R2 = .06, p-values < .001) beyond demographic characteristics. Two-way interactions among study variables were non-significant, suggesting that AO and Delay conferred risk similarly by racial/ethnic status, gender, and grade in high school. Conclusions When considered simultaneously, both an early AO and a quick progression to drinking to intoxication appear to be important determinants of high school student drinking. In addition to continuing efforts to postpone AO, efforts designed to delay intoxication may modulate alcohol-related risk associated with early drinking. PMID:25257574

First drink to first drunk: age of onset and delay to intoxication are associated with adolescent alcohol use and binge drinking.

PubMed

Morean, Meghan E; Kong, Grace; Camenga, Deepa R; Cavallo, Dana A; Connell, Christian; Krishnan-Sarin, Suchitra

2014-10-01

Quickly progressing from initiating alcohol use to drinking to intoxication recently was identified as a novel risk factor for hazardous drinking in college students (ME Morean et al. [2012] Alcohol Clin Exp Res, 36, 1991-1999). The current study evaluated the risk associated with age of onset (AO) and delay to first intoxication (Delay) in a high school sample. Adolescent drinkers (N = 295, age 16.29 [1.14], 55.3% female, 80.3% Caucasian, AO = 13.51 [2.29] years, Delay = 0.80 [1.43] years) completed an anonymous survey about their substance use in February of 2010. Self-report questions assessed AO and age of first intoxication (AI) (i.e., "How old were you the first time you tried alcohol/got drunk?") and past-month alcohol use/binge drinking (i.e., How often did you drink alcohol/drink ≥5 drinks?). Bivariate correlations indicated that AO was positively correlated with AI and inversely correlated with Delay, the frequency of any drinking, and the frequency of binge drinking. When considered alone, Delay was not significantly correlated with either alcohol use outcome. In contrast, hierarchical regression analyses indicated that when considered in concert, an earlier AO and a shorter Delay were each associated with heavier drinking (any drinking adjusted R(2)  = 0.08; binge drinking R(2)  = 0.06, p-values <0.001) beyond demographic characteristics. Two-way interactions among study variables were nonsignificant, suggesting that AO and Delay conferred risk similarly by racial/ethnic status, gender, and grade in high school. When considered simultaneously, both an early AO and a quick progression to drinking to intoxication appear to be important determinants of high school student drinking. In addition to continuing efforts to postpone AO, efforts designed to delay intoxication may modulate alcohol-related risk associated with early drinking. Copyright © 2014 by the Research Society on Alcoholism.

Transition from Target to Gaze Coding in Primate Frontal Eye Field during Memory Delay and Memory-Motor Transformation.

PubMed

Sajad, Amirsaman; Sadeh, Morteza; Yan, Xiaogang; Wang, Hongying; Crawford, John Douglas

2016-01-01

The frontal eye fields (FEFs) participate in both working memory and sensorimotor transformations for saccades, but their role in integrating these functions through time remains unclear. Here, we tracked FEF spatial codes through time using a novel analytic method applied to the classic memory-delay saccade task. Three-dimensional recordings of head-unrestrained gaze shifts were made in two monkeys trained to make gaze shifts toward briefly flashed targets after a variable delay (450-1500 ms). A preliminary analysis of visual and motor response fields in 74 FEF neurons eliminated most potential models for spatial coding at the neuron population level, as in our previous study (Sajad et al., 2015). We then focused on the spatiotemporal transition from an eye-centered target code (T; preferred in the visual response) to an eye-centered intended gaze position code (G; preferred in the movement response) during the memory delay interval. We treated neural population codes as a continuous spatiotemporal variable by dividing the space spanning T and G into intermediate T-G models and dividing the task into discrete steps through time. We found that FEF delay activity, especially in visuomovement cells, progressively transitions from T through intermediate T-G codes that approach, but do not reach, G. This was followed by a final discrete transition from these intermediate T-G delay codes to a "pure" G code in movement cells without delay activity. These results demonstrate that FEF activity undergoes a series of sensory-memory-motor transformations, including a dynamically evolving spatial memory signal and an imperfect memory-to-motor transformation.

Teaching Self-Control to Small Groups of Dually Diagnosed Adults.

ERIC Educational Resources Information Center

Dixon, Mark R.; Holcomb, Sharon

2000-01-01

A study used a progressive delay procedure to teach self-control to six adults with mental retardation. At baseline, participants chose an immediate smaller reinforcer rather than a larger delayed reinforcer. Progressive increases in work requirements for gaining access to a larger reinforcer resulted in participants selecting larger delayed…

Relationship between time management in construction industry and project management performance

NASA Astrophysics Data System (ADS)

Nasir, Najuwa; Nawi, Mohd Nasrun Mohd; Radzuan, Kamaruddin

2016-08-01

Nowadays, construction industry particularly in Malaysia struggle in achieving status of eminent time management for construction project. Project managers have a great responsibility to keep the project success under time of project completion. However, studies shows that delays especially in Malaysian construction industry still unresolved due to weakness in managing the project. In addition, quality of time management on construction projects is generally poor. Due to the progressively extended delays issue, time performance becomes an important subject to be explored to investigate delay factors. The method of this study is review of literature towards issues in construction industry which affecting time performance of project in general by focusing towards process involved for project management. Based on study, it was found that knowledge, commitment, cooperation are the main criteria as an overall to manage the project into a smooth process during project execution until completion. It can be concluded that, the strength between project manager and team members in these main criteria while conducting the project towards good time performance is highly needed. However, there is lack of establishment towards factors of poor time performance which strongly related with project management. Hence, this study has been conducted to establish factors of poor time performance and its relations with project management.

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.

Systematic Analysis of Cell Cycle Effects of Common Drugs Leads to the Discovery of a Suppressive Interaction between Gemfibrozil and Fluoxetine

PubMed Central

Hoose, Scott A.; Duran, Camille; Malik, Indranil; Eslamfam, Shabnam; Shasserre, Samantha C.; Downing, S. Sabina; Hoover, Evelyn M.; Dowd, Katherine E.; Smith, Roger; Polymenis, Michael

2012-01-01

Screening chemical libraries to identify compounds that affect overall cell proliferation is common. However, in most cases, it is not known whether the compounds tested alter the timing of particular cell cycle transitions. Here, we evaluated an FDA-approved drug library to identify pharmaceuticals that alter cell cycle progression in yeast, using DNA content measurements by flow cytometry. This approach revealed strong cell cycle effects of several commonly used pharmaceuticals. We show that the antilipemic gemfibrozil delays initiation of DNA replication, while cells treated with the antidepressant fluoxetine severely delay progression through mitosis. Based on their effects on cell cycle progression, we also examined cell proliferation in the presence of both compounds. We discovered a strong suppressive interaction between gemfibrozil and fluoxetine. Combinations of interest among diverse pharmaceuticals are difficult to identify, due to the daunting number of possible combinations that must be evaluated. The novel interaction between gemfibrozil and fluoxetine suggests that identifying and combining drugs that show cell cycle effects might streamline identification of drug combinations with a pronounced impact on cell proliferation. PMID:22567160

Systematic analysis of cell cycle effects of common drugs leads to the discovery of a suppressive interaction between gemfibrozil and fluoxetine.

PubMed

Hoose, Scott A; Duran, Camille; Malik, Indranil; Eslamfam, Shabnam; Shasserre, Samantha C; Downing, S Sabina; Hoover, Evelyn M; Dowd, Katherine E; Smith, Roger; Polymenis, Michael

2012-01-01

Screening chemical libraries to identify compounds that affect overall cell proliferation is common. However, in most cases, it is not known whether the compounds tested alter the timing of particular cell cycle transitions. Here, we evaluated an FDA-approved drug library to identify pharmaceuticals that alter cell cycle progression in yeast, using DNA content measurements by flow cytometry. This approach revealed strong cell cycle effects of several commonly used pharmaceuticals. We show that the antilipemic gemfibrozil delays initiation of DNA replication, while cells treated with the antidepressant fluoxetine severely delay progression through mitosis. Based on their effects on cell cycle progression, we also examined cell proliferation in the presence of both compounds. We discovered a strong suppressive interaction between gemfibrozil and fluoxetine. Combinations of interest among diverse pharmaceuticals are difficult to identify, due to the daunting number of possible combinations that must be evaluated. The novel interaction between gemfibrozil and fluoxetine suggests that identifying and combining drugs that show cell cycle effects might streamline identification of drug combinations with a pronounced impact on cell proliferation.

Delayed central nervous system manifestation of Chikungunya virus with magnetic resonance T2 weighted imaging high signal changes—a case report

PubMed Central

Hamilton, Preci L; Cruickshank, Garth

2018-01-01

Abstract CHIKV is a relatively new virus and we are still learning about the illness. Very little is known about CNS its involvement and even less about its delayed or long-term manifestations if any. It therefore behoves us to consider delayed CNS involvement when assessing patients with CHIKV infections that may not have had an acute neurological manifestation at the time of diagnosis coupled with new onset neurological manifestations and MRI abnormalities. It seems likely that patients with CHIKV may experience delayed CNS manifestation of the viral infection. This report highlights the importance of a travel history when assessing patients with a neurological complaint. The pathway to best manage such cases is with repeated imaging to assess if the signal changes either progress, resolve or more importantly if there is any MRI correlation should changes in neurology develop during the surveillance period. PMID:29942482

Massed Trials versus Trials Embedded into Game Play: Child Outcomes and Preference

ERIC Educational Resources Information Center

Ledford, Jennifer R.; Chazin, Kate T.; Harbin, Emilee R.; Ward, Sarah E.

2017-01-01

Limited data are available regarding how response prompting procedures should be used in early childhood settings. The purpose of this study was to compare the efficiency of progressive time delay instruction presented via two trial arrangements: massed and embedded. During massed trial sessions, a short instructional session was conducted,…

Real-Time Estimation of Amplitude and Group Delay Distortion in a PSK Line-of-Sight Communications Channel.

DTIC Science & Technology

1984-06-01

appears to have a progressively more difinitive concave minimum as the amount of distortion in the channel increases. These measurements illustrate...apparent nonlinear behavior in this relationship, it S 149 might not be possible to obtain a useful quantitative characterization. The next logical step in

PROGRESS ON THE STUDY OF BETA TREATMENT OF URANIUM, DECEMBER 1, 1960-MARCH 30, 1961

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

Russell, R.B.

The variables affecting the beta treatment of uranium are described. Results are included on the effects of time at beta temperature, the influence of air delay before quenching, and the effects of 800 l C annealing. A description of x-ray automation equipment is presented. (N.W.R.)

Quantitative measurement of feline colonic transit

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

Krevsky, B.; Somers, M.B.; Maurer, A.H.

1988-10-01

Colonic transit scintigraphy, a method for quantitatively evaluating the movement of the fecal stream in vivo, was employed to evaluate colonic transit in the cat. Scintigraphy was performed in duplicate in five cats and repeated four times in one cat. After instillation of an 111In marker into the cecum through a surgically implanted silicone cecostomy tube, colonic movement of the instillate was quantitated for 24 h using gamma scintigraphy. Antegrade and retrograde motion of radionuclide was observed. The cecum and ascending colon emptied rapidly, with a half-emptying time of 1.68 +/- 0.56 h (mean +/- SE). After 24 h, 25.1more » +/- 5.2% of the activity remained in the transverse colon. The progression of the geometric center was initially rapid, followed later by a delayed phase. Geometric center reproducibility was found to be high when analyzed using simple linear regression (slope = 0.92; r = 0.73; P less than 0.01). Atropine (0.1 mg/kg im) was found to delay cecum and ascending colon emptying and delay progression of the geometric center. These results demonstrate both 1) the ability of colonic transit scintigraphy to detect changes in transit induced by pharmacological manipulation and 2) the fact that muscarinic blockade inhibits antegrade transit of the fecal stream. We conclude that feline colonic transit may be studied in a quantitative and reproducible manner with colonic transit scintigraphy.« less

Chronic lymphadenopathic toxoplasmosis. A case with marked hyperglobulinemia and impaired delayed hypersensitivity responses during active infection.

PubMed

Sheagren, J N; Lunde, M N; Simon, H B

1976-02-01

A patient with lymphadenopathic toxoplasmosis characterized by prolonged symptoms and repeated relapses with isolation of toxoplasma from lymph nodes is described. As the disease persisted and progressed, striking immunologic changes occurred that ultimately resulted in a state of extreme hyperglobulinemia associated with impaired delayed hypersensitivity responses. The case in question illustrates that progressive infection may occur in the face of high antibody levels of all immunoglobulin types whereas the only demonstrable immunologic impairment was of delayed hypersensitivity.

Teaching self-control to small groups of dually diagnosed adults.

PubMed

Dixon, M R; Holcomb, S

2000-01-01

The present study examined the use of a progressive delay procedure to teach self-control to two groups of dually diagnosed adults. When given a choice between an immediate smaller reinforcer and a larger delayed reinforcer, both groups chose the smaller reinforcer during baseline. During treatment, progressive increases in work requirements for gaining access to a larger reinforcer resulted in both groups selecting larger delayed reinforcers. The results are discussed with respect to increasing cooperative work behavior and self-control.

Biodemography of human ageing

PubMed Central

Vaupel, James W.

2014-01-01

Human senescence has been delayed by a decade. This finding, documented in 1994 and bolstered since, is a fundamental discovery about the biology of human ageing, and one with profound implications for individuals, society and the economy. Remarkably, the rate of deterioration with age seems to be constant across individuals and over time: it seems that death is being delayed because people are reaching old age in better health. Research by demographers, epidemiologists and other biomedical researchers suggests that further progress is likely to be made in advancing the frontier of survival — and healthy survival — to even greater ages. PMID:20336136

Effect of antibodies on pathogen dynamics with delays and two routes of infection

NASA Astrophysics Data System (ADS)

Elaiw, A. M.; Almatrafi, A. A.; Hobiny, A. D.

2018-06-01

We study the global stability of pathogen dynamics models with saturated pathogen-susceptible and infected-susceptible incidence. The models incorporate antibody immune response and three types of discrete or distributed time delays. We first show that the solutions of the model are nonnegative and ultimately bounded. We determine two threshold parameters, the basic reproduction number and antibody response activation number. We establish the existence and stability of the steady states. We study the global stability analysis of models using Lyapunov method. The numerical simulations have shown that antibodies can reduce the pathogen progression.

Oxytocin versus no treatment or delayed treatment for slow progress in the first stage of spontaneous labour.

PubMed

Bugg, George J; Siddiqui, Farah; Thornton, Jim G

2013-06-23

Slow progress in the first stage of spontaneous labour is associated with an increased caesarean section rate and fetal and maternal morbidity. Oxytocin has long been advocated as a treatment for slow progress in labour but it is unclear to what extent it improves the outcomes for that labour and whether it actually reduces the caesarean section rate or maternal and fetal morbidity. This review will address the use of oxytocin and whether it improves the outcomes for women who are progressing slowly in labour compared to situations where it is not used or where its administration is delayed. To determine if the use of oxytocin for the treatment of slow progress in the first stage of spontaneous labour is associated with a reduction in the incidence of caesarean sections, or maternal and fetal morbidity compared to situations where it is not used or where its administration is delayed. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (23 February 2013) and bibliographies of relevant papers. Randomised controlled trials which compared oxytocin with either placebo, no treatment or delayed oxytocin in the active stage of spontaneous labour in low-risk women at term. Two authors independently assessed studies for inclusion, assessed risk of bias and extracted data. We sought additional information from trial authors. We included eight studies in the review involving a total of 1338 low-risk women in the first stage of spontaneous labour at term. Two comparisons were made; 1) the use of oxytocin versus placebo or no treatment (three trials); 2) the early use of oxytocin versus its delayed use (five trials). There were no significant differences in the rates of caesarean section or instrumental vaginal delivery in either comparison. Early use of oxytocin resulted in an increase in uterine hyperstimulation associated with fetal heart changes. However, the early use of oxytocin versus its delayed use resulted in no significant differences in a range of neonatal and maternal outcomes. Use of early oxytocin resulted in a statistically significant reduction in the mean duration in labour of approximately two hours but did not increase the normal delivery rate. There was significant heterogeneity for this analysis and we carried out a random-effects meta-analysis; however, all of the trials are strongly in the same direction so it is reasonable to conclude that this is the true effect. We also performed a random-effects meta-analysis for the four other analyses which showed substantial heterogeneity in the review. For women making slow progress in spontaneous labour, treatment with oxytocin as compared with no treatment or delayed oxytocin treatment did not result in any discernable difference in the number of caesarean sections performed. In addition there were no detectable adverse effects for mother or baby. The use of oxytocin was associated with a reduction in the time to delivery of approximately two hours which might be important to some women. However, if the primary goal of this treatment is to reduce caesarean section rates, then doctors and midwives may have to look for alternative options.

A Progress Report on the Reforms in D.C. Public Schools. Hearing before the Subcommittee on Oversight of Government Management, Restructuring, and the District of Columbia of the Committee on Governmental Affairs. United States Senate, One Hundred Fifth Congress, First Session (September 8, 1997).

ERIC Educational Resources Information Center

Congress of the U.S., Washington, DC. Senate Committee on Governmental Affairs.

A hearing before the oversight committee for the District of Columbia (D.C.) public schools provided the opportunity for several senators and educators to comment on the progress of educational reform in the District's public schools. The hearing was held at a time when the opening of the city's public schools was delayed because of their many…

Transition from Target to Gaze Coding in Primate Frontal Eye Field during Memory Delay and Memory–Motor Transformation123

PubMed Central

Sajad, Amirsaman; Sadeh, Morteza; Yan, Xiaogang; Wang, Hongying

2016-01-01

Abstract The frontal eye fields (FEFs) participate in both working memory and sensorimotor transformations for saccades, but their role in integrating these functions through time remains unclear. Here, we tracked FEF spatial codes through time using a novel analytic method applied to the classic memory-delay saccade task. Three-dimensional recordings of head-unrestrained gaze shifts were made in two monkeys trained to make gaze shifts toward briefly flashed targets after a variable delay (450-1500 ms). A preliminary analysis of visual and motor response fields in 74 FEF neurons eliminated most potential models for spatial coding at the neuron population level, as in our previous study (Sajad et al., 2015). We then focused on the spatiotemporal transition from an eye-centered target code (T; preferred in the visual response) to an eye-centered intended gaze position code (G; preferred in the movement response) during the memory delay interval. We treated neural population codes as a continuous spatiotemporal variable by dividing the space spanning T and G into intermediate T–G models and dividing the task into discrete steps through time. We found that FEF delay activity, especially in visuomovement cells, progressively transitions from T through intermediate T–G codes that approach, but do not reach, G. This was followed by a final discrete transition from these intermediate T–G delay codes to a “pure” G code in movement cells without delay activity. These results demonstrate that FEF activity undergoes a series of sensory–memory–motor transformations, including a dynamically evolving spatial memory signal and an imperfect memory-to-motor transformation. PMID:27092335

Physiological denoising of BOLD fMRI data using Regressor Interpolation at Progressive Time Delays (RIPTiDe) processing of concurrent fMRI and near-infrared spectroscopy (NIRS).

PubMed

Frederick, Blaise deB; Nickerson, Lisa D; Tong, Yunjie

2012-04-15

Confounding noise in BOLD fMRI data arises primarily from fluctuations in blood flow and oxygenation due to cardiac and respiratory effects, spontaneous low frequency oscillations (LFO) in arterial pressure, and non-task related neural activity. Cardiac noise is particularly problematic, as the low sampling frequency of BOLD fMRI ensures that these effects are aliased in recorded data. Various methods have been proposed to estimate the noise signal through measurement and transformation of the cardiac and respiratory waveforms (e.g. RETROICOR and respiration volume per time (RVT)) and model-free estimation of noise variance through examination of spatial and temporal patterns. We have previously demonstrated that by applying a voxel-specific time delay to concurrently acquired near infrared spectroscopy (NIRS) data, we can generate regressors that reflect systemic blood flow and oxygenation fluctuations effects. Here, we apply this method to the task of removing physiological noise from BOLD data. We compare the efficacy of noise removal using various sets of noise regressors generated from NIRS data, and also compare the noise removal to RETROICOR+RVT. We compare the results of resting state analyses using the original and noise filtered data, and we evaluate the bias for the different noise filtration methods by computing null distributions from the resting data and comparing them with the expected theoretical distributions. Using the best set of processing choices, six NIRS-generated regressors with voxel-specific time delays explain a median of 10.5% of the variance throughout the brain, with the highest reductions being seen in gray matter. By comparison, the nine RETROICOR+RVT regressors together explain a median of 6.8% of the variance in the BOLD data. Detection of resting state networks was enhanced with NIRS denoising, and there were no appreciable differences in the bias of the different techniques. Physiological noise regressors generated using Regressor Interpolation at Progressive Time Delays (RIPTiDe) offer an effective method for efficiently removing hemodynamic noise from BOLD data. Copyright © 2012 Elsevier Inc. All rights reserved.

Optimal Timing for Laparoscopic Cholecystectomy After Endoscopic Retrograde Cholangiopancreatography: A Systematic Review.

PubMed

Friis, C; Rothman, J P; Burcharth, J; Rosenberg, J

2018-06-01

Endoscopic retrograde cholangiopancreatography followed by laparoscopic cholecystectomy is often used as definitive treatment for common bile duct stones. The aim of this study was to investigate the optimal time interval between endoscopic retrograde cholangiopancreatography and laparoscopic cholecystectomy. PubMed and Embase were searched for studies comparing different time delays between endoscopic retrograde cholangiopancreatography and laparoscopic cholecystectomy. Observational studies and randomized controlled trials were included. Primary outcome was conversion rate from laparoscopic to open cholecystectomy and secondary outcomes were complications, mortality, operating time, and length of stay. A total of 14 studies with a total of 1930 patients were included. The pooled estimate revealed an increase from a 4.2% conversion rate when laparoscopic cholecystectomy was performed within 24 h of endoscopic retrograde cholangiopancreatography to 7.6% for 24-72 h delay to 12.3% when performed within 2 weeks, to 12.3% for 2-6 weeks, and to a 14% conversion rate when operation was delayed more than 6 weeks. According to this systematic review, it is preferable to perform cholecystectomy within 24 h of endoscopic retrograde cholangiopancreatography to reduce conversion rate. Early laparoscopic cholecystectomy does not increase mortality, perioperative complications, or length of stay and on the contrary it reduces the risk of reoccurrence and progression of disease in the delay between endoscopic retrograde cholangiopancreatography and laparoscopic cholecystectomy.

Initiation and Generalization of Self-Instructional Skills in Adolescents with Autism and Intellectual Disability

ERIC Educational Resources Information Center

Smith, Katherine A.; Ayres, Kevin A.; Alexander, Jennifer; Ledford, Jennifer R.; Shepley, Collin; Shepley, Sally B.

2016-01-01

Self-instruction using videos or other supports on a mobile device is a pivotal skill and can increase independence for individuals with disabilities by decreasing a need for adult supports. This study evaluated the effects of progressive time delay (PTD) to teach four adolescents with autism and intellectual disability how to initiate…

Ionizing radiation and cell cycle progression in ataxia telangiectasia

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

Beamish, H.; Khanna, K.K.; Lavin, M.F.

1994-04-01

Exposure of mammalian cells to ionizing radiation causes delay in normal progress through the cell cycle at a number of different checkpoints. Abnormalities in these checkpoints have been described for ataxia telangiectasia cells after irradiation. In this report we show that these abnormalities occur at different phases in the cell cycle in several ataxia telangiectasia lymphoblastoid cells. Ataxia telangiectasia cells, synchronized in late G{sub 1} phase with either mimosine or aphidicolin and exposed to radiation, showed a reduced delay in entering S phase compared to irradiated control cells. Failure to exhibit G{sub 1}-phase delay in ataxia telangiectasia cells is accompaniedmore » by a reduced ability of radiation to activate the product of the tumor suppressor gene p53, a protein involved in G{sub 1}/S-phase delay. When the progress of irradiated G{sub 1}-phase cells was followed into the subsequent G{sub 2} and G{sub 1} phases ataxia telangiectasia cells showed a more pronounced accumulation in G{sub 2} phase than control cells. When cells were irradiated in S phase and extent of delay was more evident in G{sub 2} phase and ataxia telangiectasia cells were delayed to a greater extent. These results suggest that the lack of initial delay in both G{sub 1} and S phases to the radiosensitivity observed in this syndrome. 26 refs., 3 figs., 2 tabs.« less

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.

A Link between Meiotic Prophase Progression and CrossoverControl

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

Carlton, Peter M.; Farruggio, Alfonso P.; Dernburg, Abby F.

2005-07-06

During meiosis, most organisms ensure that homologous chromosomes undergo at least one exchange of DNA, or crossover, to link chromosomes together and accomplish proper segregation. How each chromosome receives a minimum of one crossover is unknown. During early meiosis in Caenorhabditis elegans and many other species, chromosomes adopt a polarized organization within the nucleus, which normally disappears upon completion of homolog synapsis. Mutations that impair synapsis even between a single pair of chromosomes in C. elegans delay this nuclear reorganization. We quantified this delay by developing a classification scheme for discrete stages of meiosis. Immunofluorescence localization of RAD-51 protein revealedmore » that delayed meiotic cells also contained persistent recombination intermediates. Through genetic analysis, we found that this cytological delay in meiotic progression requires double-strand breaks and the function of the crossover-promoting heteroduplex HIM-14 (Msh4) and MSH-5. Failure of X chromosome synapsis also resulted in impaired crossover control on autosomes, which may result from greater numbers and persistence of recombination intermediates in the delayed nuclei. We conclude that maturation of recombination events on chromosomes promotes meiotic progression, and is coupled to the regulation of crossover number and placement. Our results have broad implications for the interpretation of meiotic mutants, as we have shown that asynapsis of a single chromosome pair can exert global effects on meiotic progression and recombination frequency.« less

Type 1 and type 2 cytokines in HIV infection -- a possible role in apoptosis and disease progression.

PubMed

Clerici, M; Fusi, M L; Ruzzante, S; Piconi, S; Biasin, M; Arienti, D; Trabattoni, D; Villa, M L

1997-06-01

The progression of HIV-infected subjects to AIDS was recently postulated to be controlled by the balance between type 1 cytokines (mainly enhancing cell-mediated immunity) and type 2 cytokines (mainly augmenting antibody production). Thus, progression of HIV infection was suggested to be accompanied by a decline of in vitro production of interleukin-2 (IL-2), IL-12 and interferon gamma (IFN-gamma) (type 1 cytokines) and an increase in the production of IL-4, IL-5, IL-6 and IL-10 (type 2 cytokines) by peripheral blood mononuclear cells of HIV-seropositive patients. According to this hypothesis, clinical markers of progression would be considered the loss of the ability to elicit a delayed-type hypersensitivity reaction to ubiquitous antigens (secondary to defective IL-2 production), hyper-IgE (secondary to increased IL-4 production) and hypereosynophilia (secondary to increased IL-5 production). The type 1 to type 2 shift was suggested to be predictive for the following events: (i) reduction in CD4 counts; (ii) time to AIDS diagnosis; (iii) time to death. Support for this hypothesis stems from the recent observation that a strong type 1/weak type 2 cytokine production profile was observed in HIV-seropositive patients with delayed or absent disease progression, whereas progression of HIV infection was characterized by a weak type 1/strong type 2 cytokine production profile. PBMC of HIV-seropositive individuals are susceptible to antigen-induced cell death (AICD) after antigen recognition via T-cell receptor (TcR). While TcR-induced AICD is seen in CD4+ and CD8+ cells programmed cell death induced by recall antigens is preferentially observed in CD4+ cells, a situation more closely resembling the CD4 depletion of HIV infection. Because type 1 cytokines reduce, whereas type 2 cytokines augment T-lymphocyte AICD, an increase in the concentration of type 2 cytokines could result in the decline in CD4+ cells seen in HIV infection.

Clinical progression, acute urinary retention, prostate-related surgeries, and costs in patients with benign prostatic hyperplasia taking early versus delayed combination 5α-reductase inhibitor therapy and α-blocker therapy: a retrospective analysis.

PubMed

Morlock, Robert; Goodwin, Bridgett; Gomez Rey, Gabriel; Eaddy, Michael

2013-05-01

Two previous retrospective database analyses compared early combination therapy with an α-blocker (AB) and 5-α reductase inhibitor (5-ARI) to delayed combination therapy and found that patients receiving the delayed combination therapy were more likely to have clinical progression, acute urinary retention (AUR), and surgery. Although these studies indicate the clinical benefits of early treatment, both studies failed to take into account important baseline clinical measures, such as prostate-specific antigen (PSA) values. This study was designed to compare clinical and cost differences in men with benign prostatic hyperplasia (BPH) who initiated early versus delayed combination therapy with a 5-ARI + an AB, factoring in baseline PSA values. This retrospective claims data analysis assessed data from >14 million US men with linked medical data, pharmacy data, laboratory results, and enrollment information from January 1, 2000, to December 31, 2009. Men aged 50 or older and treated for BPH with a 5-ARI + an AB were identified. Patients were required to be eligible for services at least 6 months before and 12 months after the index medication date. Patients were assigned to 1 of 2 treatment groups based on therapy (early or delayed) and 3 cohorts based on availability of PSA laboratory values (patients with a PSA value, patients with a PSA value >1.5 and <10, and all patients). Using a logistic model, the likelihood of clinical progression (defined as the occurrence of AUR or prostate surgery) during the 12 months after the date of first prescription fill was compared between BPH patients receiving early versus delayed combination therapy. BPH-related medical costs (excluding pharmacy costs) were assessed using generalized linear models. Among the 13,551 patients identified for study inclusion, the highest risks for clinical progression, AUR, and prostate-related surgery were consistently demonstrated in patients with a PSA >1.5 and <10. Across all 3 cohorts, the delayed combination-treatment group was more likely to have clinical progression, AUR, and prostate-related surgeries versus the early combination-treatment group. The incremental difference in BPH-related costs between the delayed and early combination-treatment groups was $190 per patient overall; the greatest incremental difference ($397) was observed in patients with PSA >1.5 and <10. The results suggest that early initiation of combination therapy with 5-ARI + an AB, compared with delayed initiation, can reduce the risks for clinical progression, AUR, and prostate-related surgeries, as well as BPH-related medical costs, in patients with BPH. Copyright © 2013 Elsevier HS Journals, Inc. All rights reserved.

Choice in situations of time-based diminishing returns: immediate versus delayed consequences of action.

PubMed Central

Hackenberg, T D; Hineline, P N

1992-01-01

Pigeons chose between two schedules of food presentation, a fixed-interval schedule and a progressive-interval schedule that began at 0 s and increased by 20 s with each food delivery provided by that schedule. Choosing one schedule disabled the alternate schedule and stimuli until the requirements of the chosen schedule were satisfied, at which point both schedules were again made available. Fixed-interval duration remained constant within individual sessions but varied across conditions. Under reset conditions, completing the fixed-interval schedule not only produced food but also reset the progressive interval to its minimum. Blocks of sessions under the reset procedure were interspersed with sessions under a no-reset procedure, in which the progressive schedule value increased independent of fixed-interval choices. Median points of switching from the progressive to the fixed schedule varied systematically with fixed-interval value, and were consistently lower during reset than during no-reset conditions. Under the latter, each subject's choices of the progressive-interval schedule persisted beyond the point at which its requirements equaled those of the fixed-interval schedule at all but the highest fixed-interval value. Under the reset procedure, switching occurred at or prior to that equality point. These results qualitatively confirm molar analyses of schedule preference and some versions of optimality theory, but they are more adequately characterized by a model of schedule preference based on the cumulated values of multiple reinforcers, weighted in inverse proportion to the delay between the choice and each successive reinforcer. PMID:1548449

The evaluation of clinical and cost outcomes associated with earlier initiation of insulin in patients with type 2 diabetes mellitus.

PubMed

Smolen, Harry J; Murphy, Daniel R; Gahn, James C; Yu, Xueting; Curtis, Bradley H

2014-09-01

The treatment for patients with type 2 diabetes mellitus (T2DM) follows a stepwise progression. As a treatment loses its effectiveness, it is typically replaced with a more complex and frequently more costly treatment. Eventually this progression leads to the use of basal insulin typically with concomitant treatments (e.g., metformin, a GLP-1 RA [glucagon-like peptide-1 receptor agonist], a TZD [thiazolidinedione] or a DPP-4i [dipeptidyl peptidase 4 inhibitor]) and, ultimately, to basal-bolus insulin in some forms. As the cost of oral antidiabetics (OADs) and noninsulin injectables have approached, and in some cases exceeded, the cost of insulin, we reexamined the placement of insulin in T2DM treatment progression. Our hypothesis was that earlier use of insulin produces clinical and cost benefits due to its superior efficacy and treatment scalability at an acceptable cost when considered over a 5-year period. To (a) estimate clinical and payer cost outcomes of initiating insulin treatment for patients with T2DM earlier in their treatment progression and (b) estimate clinical and payer cost outcomes resulting from delays in escalating treatment for T2DM when indicated by patient hemoglobin A1c levels. We developed a Monte Carlo microsimulation model to estimate patients reaching target A1c, diabetes-related complications, mortality, and associated costs under various treatment strategies for newly diagnosed patients with T2DM. Treatment efficacies were modeled from results of randomized clinical trials, including the time and rate of A1c drift. A typical treatment progression was selected based on the American Diabetes Association and the European Association for the Study of Diabetes guidelines as the standard of care (SOC). Two treatment approaches were evaluated: two-stage insulin (basal plus antidiabetics followed by biphasic plus metformin) and single-stage insulin (biphasic plus metformin). For each approach, we analyzed multiple strategies. For each analysis, treatment steps were sequentially and cumulatively removed from the SOC until only the insulin steps remained. Delays in escalating treatment were evaluated by increasing the minimum time on a treatment within each strategy. The analysis time frame was 5 years. Relative to SOC, the two-stage insulin approach resulted in 0.10% to 1.79% more patients achieving target A1c (<7.0%), at incremental costs of $95 to $3,267. (The ranges are due to the different strategies within the approach.) With the single-stage approach, 0.50% to 2.63% more patients achieved the target A1c compared with SOC at an incremental cost of -$1,642 to $1,177. Major diabetes-related complications were reduced by 0.38% to 17.46% using the two-stage approach and 0.72% to 25.92% using the single-stage approach. Severe hypoglycemia increased by 17.97% to 60.43% using the two-stage approach and 6.44% to 68.87% using the single-stage approach. In the base case scenario, the minimum time on a specific treatment was 3 months. When the minimum time on each treatment was increased to 12 months (i.e., delayed), patients reaching A1c targets were reduced by 57%, complications increased by 13% to 76%, and mortality increased by 8% over 5 years when compared with the base case for the SOC. However, severe hypoglycemic events were reduced by 83%. As insulin was advanced earlier in therapy in the two-stage and single-stage approaches, patients reaching their A1c targets increased, severe hypoglycemic events increased, and diabetes-related complications and mortality decreased. Cost savings were estimated for 3 (of 4) strategies in the single-stage approach. Delays in treatment escalation substantially reduced patients reaching target A1c levels and increased the occurrence of major nonhypoglycemic diabetic complications. With the exception of substantial increases in severe hypoglycemic events, earlier use of insulin mitigates the clinical consequences of these delays.

Mild cognitive impairment: an opportunity to identify patients at high risk for progression to Alzheimer's disease.

PubMed

Levey, Allan; Lah, James; Goldstein, Felicia; Steenland, Kyle; Bliwise, Donald

2006-07-01

There is increasing evidence that subtle losses in cognitive function may be symptomatic of a transition to early Alzheimer's disease (AD). Ongoing research is focusing on the identification of those individuals with mild cognitive impairment (MCI) who are most likely to convert to AD. Of the MCI subtypes, patients with amnestic MCI (a-MCI) are at greatest risk. The objectives of this article were to review the relationship between MCI, normal aging, and AD, and to summarize recent research on the diagnosis and potential treatment of MCI. Relevant articles were identified through searches of MEDLINE and EMBASE using the terms mild cognitive impairment; cognitive impairment, no dementia; and dementia prodrome, with no restrictions as to year. Additional papers of interest were identified from the reference lists of the identified articles. The search was current as of February 2006. Guidelines and recommendations are being developed to assist physicians in diagnosing MCI, identifying its subtype and etiology, understanding the risks for conversion to AD, and managing disease progression. Given the existence of a subset of individuals with a-MCI, who are at greatest risk for progression to AD but still have high levels of cognition and function, the ability to improve symptoms and delay progression to AD would be particularly beneficial. In a 3-year, randomized, double-blind, placebo-controlled study in 769 patients with a-MCI, treatment with the cholinesterase inhibitor donepezil was associated with a significantly lower rate of progression to AD compared with placebo during the first 12 months of treatment (hazard ratio=0.42; 95% CI, 0.24-0.76; P=0.004) but not at later time points. Of other types of agents that have been investigated (antioxidants, estrogen replacement therapy, cyclooxygenase-2-selective inhibitors), none have shown significant beneficial effects in delaying cognitive decline or progression to AD. New drugs such as secretase inhibitors, small molecules that disrupt amyloid aggregation, and immunotherapies are in preclinical development. MCI involves more substantial cognitive and memory decline than normal aging and represents a significant risk factor for the development of dementia. Further research is needed into treatments to delay the conversion from MCI to AD.

Mental and physical activities delay cognitive decline in older persons with dementia.

PubMed

Cheng, Sheung-Tak; Chow, Pizza K; Song, You-Qiang; Yu, Edwin C S; Chan, Alfred C M; Lee, Tatia M C; Lam, John H M

2014-01-01

To examine the effects of cognitive stimulation (mahjong) and physical exercise (tai chi [TC]) on cognitive performance in persons with dementia. Cluster-randomized open-label controlled design. Nursing homes. One hundred ten residents, most of whom were cholinesterase-inhibitor naive. Inclusion criteria were Mini-Mental State Examination (MMSE) = 10-24 and suffering from at least very mild dementia (Clinical Dementia Rating ≥ 0.5). Exclusion criteria were being bedbound, audio/visual impairment, regular activity participation before study, or contraindications for physical or group activities. Homes were randomized into three conditions (mahjong, TC, and simple handicrafts [control]). Activities were conducted three times weekly for 12 weeks. Primary outcome was MMSE. Secondary outcomes were immediate/delayed recall, categorical fluency, and digit span. Various biological risk factors, including apolipoprotein E ε4 allele, were included as covariates. Measures were collected at 0 (baseline), 3 (posttreatment), 6, and 9 months. Intent-to-treat analyses were performed using mixed-effects regression. Mahjong's effect varied by time for MMSE, delayed recall, and forward digit span. TC had similar effects but not for delayed recall. The typical pattern was that control participants deteriorated while mahjong and TC participants maintained their abilities over time, leading to enlarged treatment effects as time progressed. By 9 months, mahjong and TC differed from control by 4.5 points (95% confidence interval: 2.0-6.9; d = 0.48) and 3.7 points (95% confidence interval: 1.4-6.0; d = 0.40), respectively, on MMSE. No treatment effects were observed for immediate recall and backward digit span. Mahjong and TC can preserve functioning or delay decline in certain cognitive domains, even in those with significant cognitive impairment. Copyright © 2014 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

Economic impact of disease progression in follicular non-Hodgkin lymphoma

PubMed Central

Beveridge, Roy; Satram-Hoang, Sacha; Sail, Kavita; Darragh, Joseph; Chen, Clara; Forsyth, Michael; Reyes, Carolina

2011-01-01

Using a retrospective claims database, we estimated the economic costs of progression among patients with follicular non-Hodgkin lymphoma (f-NHL) treated in an outpatient community-based setting. Patients with f-NHL who received care between 1 July 2006 and 31 December 2009 were categorized into two cohorts based on whether they experienced progressive disease (PD) or not. Costs per patient per month (PPPM) were compared between patients with PD versus non-PD. Follow-up time was censored at the last entry for disease status or 6 months after the date of remission/stable disease or progression. Of the 1002 patients with f-NHL identified, 268 progressed and 734 did not. The mean overall costs PPPM over the 6-month follow-up period were significantly higher for patients with PD versus non-PD ($3527 vs. $860; difference = $2667; p < 0.001). This cost difference persisted within all resource categories evaluated. Results of this study indicate that therapies which delay progression for patients with f-NHL may result in potential cost savings. PMID:21745172

Value of delayed duplex ultrasound assessment after endothermal ablation of the great saphenous vein.

PubMed

Ryer, Evan J; Elmore, James R; Garvin, Robert P; Cindric, Matthew C; Dove, James T; Kekulawela, Stephanie; Franklin, David P

2016-08-01

Endothermal ablation (ETA) of the great saphenous vein (GSV) is associated with a small but definite risk of endothermal heat-induced thrombosis (EHIT) extending into the common femoral vein. Follow-up duplex ultrasound imaging to detect EHIT after ETA is considered standard of care, although the exact timing of duplex ultrasound imaging to detect EHIT after ETA remains unclear. We hypothesized that an additional duplex ultrasound assessment 1 week after ETA would not identify a significant number of patients with EHIT and would significantly increase health care costs. This was a retrospective review of consecutive ETA GSV procedures from 2007 to 2014. All patients were evaluated with duplex ultrasound imaging on postprocedure day 1, and 79% of patients underwent a second ultrasound assessment 1 week postprocedure. EHIT was considered present when proximal GSV closure progressed to level ≥4, based on a six-tier classification system. From January 1, 2007, until December 31, 2014, 842 patients underwent GSV ETA. Patients with EHIT were more likely to have had a prior deep venous thrombosis (DVT; P = .002) and a larger GSV (P = .006). Forty-three procedures (5.1%) were classified as having EHIT requiring anticoagulation, based on a level ≥4 proximal closure level. Of the 43 patients with EHIT, 20 (47%) were found on the initial ultrasound assessment performed 24 hours postprocedure, but 19 patients (44%) with EHIT would not have been identified with a single postoperative ultrasound scan performed 24 hours after intervention. These 19 patients had a level ≤3 closure level at the duplex ultrasound scan performed 24 hours postprocedure and progressed to EHIT on the delayed duplex ultrasound scan. Lastly, thrombotic complications in four patients (9%), representing three late DVT and one DVT/pulmonary embolism presenting to another hospital, would not have been identified regardless of the postoperative surveillance strategy. Maximum GSV diameter was the only significant predictor of progression to EHIT on multivariate analysis (P = .007). Based on 2014 United States dollars, the two-ultrasound surveillance paradigm is associated with health care charges of $31,109 per identified delayed venous thromboembolism event. Delayed duplex ultrasound assessment after ETA of the GSV comes with associated health care costs but does yield a significant number of patients with progression to EHIT. Better understanding of the timing, risk factors, and significance of EHIT is needed to cost-effectively care for patients after ETA for varicose veins. Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Chronic kidney disease among children in Guatemala.

PubMed

Cerón, Alejandro; Fort, Meredith P; Morine, Chris M; Lou-Meda, Randall

2014-12-01

To describe the distribution of pediatric chronic kidney disease (CKD) in Guatemala, estimate incidence and prevalence of pediatric end-stage renal disease (ESRD), and estimate time to progress to ESRD. This study analyzed the registry of the only pediatric nephrology center in Guatemala, from 2004-2013. Incidence and prevalence were calculated for annual periods. Moran's index for spatial autocorrelation was used to determine significance of geographic distribution of incidence. Time to progress to ESRD and associated risk factors were calculated with multivariate Cox regression. Of 1 545 patients from birth to less than 20 years of age, 432 had chronic renal failure (CRF). Prevalence and incidence of ESRD were 4.9 and 4.6 per million age-related population, respectively. Incidence was higher for the Pacific coast and Guatemala City. The cause of CRF was undetermined in 43% of patients. Average time to progress to ESRD was 21.9 months; factors associated with progression were: older age, diagnosis of glomerulopathies, and advanced-stage CKD at consultation. Prevalence and incidence of ESRD in Guatemala are lower than in other countries. This may reflect poor access to diagnosis. Areas with higher incidence and large proportion of CKD of undetermined cause are compatible with other studies from the geographic subregion. Findings on progression to ESRD may reflect delayed referral.

Androgen deprivation results in time-dependent hypoxia in LNCaP prostate tumours: informed scheduling of the bioreductive drug AQ4N improves treatment response.

PubMed

Ming, Louise; Byrne, Niall M; Camac, Sarah Nicole; Mitchell, Christopher A; Ward, Claire; Waugh, David J; McKeown, Stephanie R; Worthington, Jenny

2013-03-15

Androgen withdrawal induces hypoxia in androgen-sensitive tissue; this is important as in the tumour microenvironment, hypoxia is known to drive malignant progression. Our study examined the time-dependent effect of androgen deprivation therapy (ADT) on tumour oxygenation and investigated the role of ADT-induced hypoxia on malignant progression in prostate tumours. LNCaP xenografted tumours were treated with anti-androgens and tumour oxygenation measured. Dorsal skin fold (DSF) chambers were used to image tumour vasculature in vivo. Quantitative PCR (QPCR) identified differential gene expression following treatment with bicalutamide. Bicalutamide-treated and vehicle-only-treated tumours were re-established in vitro, and invasion and sensitivity to docetaxel were measured. Tumour growth delay was calculated following treatment with bicalutamide combined with the bioreductive drug AQ4N. Tumour oxygenation measurements showed a precipitate decrease following initiation of ADT. A clinically relevant dose of bicalutamide (2 mg/kg/day) decreased tumour oxygenation by 45% within 24 hr, reaching a nadir of 0.09% oxygen (0.67 ± 0.06 mmHg) by Day 7; this persisted until Day 14 when it increased up to Day 28. Using DSF chambers, LNCaP tumours treated with bicalutamide showed loss of small vessels at Days 7 and 14 with revascularisation occurring by Day 21. QPCR showed changes in gene expression consistent with the vascular changes and malignant progression. Cells from bicalutamide-treated tumours were more malignant than vehicle-treated controls. Combining bicalutamide with AQ4N (50 mg/kg, single dose) caused greater tumour growth delay than bicalutamide alone. Our study shows that bicalutamide-induced hypoxia selects for cells that show malignant progression; targeting hypoxic cells may provide greater clinical benefit. Copyright © 2012 UICC.

Transfer Students: Postsecondary Institutions Could Promote More Consistent Consideration of Coursework by Not Basing Determinations on Accreditation. Report to Congressional Requesters. GAO-06-22

ERIC Educational Resources Information Center

Ashby, Cornelia M.

2005-01-01

Each year thousands of students transfer from one postsecondary institution to another. The credit transfer process, to the extent that it delays students' progress, can affect the affordability of postsecondary education and the time it takes students to graduate. Seeking information on the processes and requirements that postsecondary…

Delayed Anterior Cruciate Ligament Reconstruction in Young Patients With Previous Anterior Tibial Spine Fractures.

PubMed

Mitchell, Justin J; Mayo, Meredith H; Axibal, Derek P; Kasch, Anthony R; Fader, Ryan R; Chadayammuri, Vivek; Terhune, E Bailey; Georgopoulos, Gaia; Rhodes, Jason T; Vidal, Armando F

2016-08-01

Avulsion fractures of the anterior tibial spine in young athletes are injuries similar to anterior cruciate ligament (ACL) injuries in adults. Sparse data exist on the association between anterior tibial spine fractures (ATSFs) and later ligamentous laxity or injuries leading to ACL reconstruction. To better delineate the incidence of delayed instability or ACL ruptures requiring delayed ACL reconstruction in young patients with prior fractures of the tibial eminence. Case series; Level of evidence, 4. We identified 101 patients between January 1993 and January 2012 who sustained an ATSF and who met inclusion criteria for this study. All patients had been followed for at least 2 years after the initial injury and were included for analysis after completion of a questionnaire via direct contact, mail, and/or telephone. If patients underwent further surgical intervention and/or underwent later ACL reconstruction, clinical records and operative reports pertaining to these secondary interventions were obtained and reviewed. Differences between categorical variables were assessed using the Fisher exact test. The association between time to revision ACL surgery and fracture type was assessed by Kaplan-Meier plots. The association between need for revision ACL surgery and age, sex, and mechanism of surgery was assessed using logistic regression. Nineteen percent of all patients evaluated underwent delayed ACL reconstruction after a previous tibial spine fracture on the ipsilateral side. While there were a higher proportion of ACL reconstructions in type II fractures, there was not a statistically significant difference in the number of patients within each fracture group who went on to undergo later surgery (P = .29). Further, there was not a significant association between fracture type, sex, or mechanism of injury as it related to the progression to later ACL reconstruction. However, there was a significant association between age at the time of injury and progression to later ACL reconstruction (P = .02). For every year increase in age at the time of injury, the odds of going on to undergo delayed ACL reconstruction were greater by a factor of 1.3 (95% CI, 1.1-1.6). Although an ATSF is a relatively rare injury, our cohort of patients suggests that a subset of young patients with all types of tibial spine fractures will require later ACL reconstruction. There is a need to counsel patients that a delayed ACL rupture is a potential risk after an ATSF, especially as children approach skeletal maturity. Further patient follow-up and prospective studies are required. © 2016 The Author(s).

Roles for the Histone Modifying and Exchange Complex NuA4 in Cell Cycle Progression in Drosophila melanogaster.

PubMed

Flegel, Kerry; Grushko, Olga; Bolin, Kelsey; Griggs, Ellen; Buttitta, Laura

2016-07-01

Robust and synchronous repression of E2F-dependent gene expression is critical to the proper timing of cell cycle exit when cells transition to a postmitotic state. Previously NuA4 was suggested to act as a barrier to proliferation in Drosophila by repressing E2F-dependent gene expression. Here we show that NuA4 activity is required for proper cell cycle exit and the repression of cell cycle genes during the transition to a postmitotic state in vivo However, the delay of cell cycle exit caused by compromising NuA4 is not due to additional proliferation or effects on E2F activity. Instead NuA4 inhibition results in slowed cell cycle progression through late S and G2 phases due to aberrant activation of an intrinsic p53-independent DNA damage response. A reduction in NuA4 function ultimately produces a paradoxical cell cycle gene expression program, where certain cell cycle genes become derepressed in cells that are delayed during the G2 phase of the final cell cycle. Bypassing the G2 delay when NuA4 is inhibited leads to abnormal mitoses and results in severe tissue defects. NuA4 physically and genetically interacts with components of the E2F complex termed D: rosophila, R: bf, E: 2F A: nd M: yb/ M: ulti-vulva class B: (DREAM/MMB), and modulates a DREAM/MMB-dependent ectopic neuron phenotype in the posterior wing margin. However, this effect is also likely due to the cell cycle delay, as simply reducing Cdk1 is sufficient to generate a similar phenotype. Our work reveals that the major requirement for NuA4 in the cell cycle in vivo is to suppress an endogenous DNA damage response, which is required to coordinate proper S and G2 cell cycle progression with differentiation and cell cycle gene expression. Copyright © 2016 by the Genetics Society of America.

Roles for the Histone Modifying and Exchange Complex NuA4 in Cell Cycle Progression in Drosophila melanogaster

PubMed Central

Flegel, Kerry; Grushko, Olga; Bolin, Kelsey; Griggs, Ellen; Buttitta, Laura

2016-01-01

Robust and synchronous repression of E2F-dependent gene expression is critical to the proper timing of cell cycle exit when cells transition to a postmitotic state. Previously NuA4 was suggested to act as a barrier to proliferation in Drosophila by repressing E2F-dependent gene expression. Here we show that NuA4 activity is required for proper cell cycle exit and the repression of cell cycle genes during the transition to a postmitotic state in vivo. However, the delay of cell cycle exit caused by compromising NuA4 is not due to additional proliferation or effects on E2F activity. Instead NuA4 inhibition results in slowed cell cycle progression through late S and G2 phases due to aberrant activation of an intrinsic p53-independent DNA damage response. A reduction in NuA4 function ultimately produces a paradoxical cell cycle gene expression program, where certain cell cycle genes become derepressed in cells that are delayed during the G2 phase of the final cell cycle. Bypassing the G2 delay when NuA4 is inhibited leads to abnormal mitoses and results in severe tissue defects. NuA4 physically and genetically interacts with components of the E2F complex termed Drosophila, Rbf, E2F and Myb/Multi-vulva class B (DREAM/MMB), and modulates a DREAM/MMB-dependent ectopic neuron phenotype in the posterior wing margin. However, this effect is also likely due to the cell cycle delay, as simply reducing Cdk1 is sufficient to generate a similar phenotype. Our work reveals that the major requirement for NuA4 in the cell cycle in vivo is to suppress an endogenous DNA damage response, which is required to coordinate proper S and G2 cell cycle progression with differentiation and cell cycle gene expression. PMID:27184390

Regional P-wave Tomography in the Caribbean Region for Plate Reconstruction

NASA Astrophysics Data System (ADS)

Li, X.; Bedle, H.; Suppe, J.

2017-12-01

The complex plate-tectonic interactions around the Caribbean Sea have been studied and interpreted by many researchers, but questions still remain regarding the formation and subduction history of the region. Here we report current progress towards creating a new regional tomographic model, with better lateral and spatial coverage and higher resolution than has been presented previously. This new model will provide improved constraints on the plate-tectonic evolution around the Caribbean Plate. Our three-dimensional velocity model is created using taut spline parameterization. The inversion is computed by the code of VanDecar (1991), which is based on the ray theory method. The seismic data used in this inversion are absolute P wave arrival times from over 700 global earthquakes that were recorded by over 400 near Caribbean stations. There are over 25000 arrival times that were picked and quality checked within frequency band of 0.01 - 0.6 Hz by using a MATLAB GUI-based software named Crazyseismic. The picked seismic delay time data are analyzed and compared with other studies ahead of doing the inversion model, in order to examine the quality of our dataset. From our initial observations of the delay time data, the more equalized the ray azimuth coverage, the smaller the deviation of the observed travel times from the theoretical travel time. Networks around the NE and SE side of the Caribbean Sea generally have better ray coverage, and smaller delay times. Specifically, seismic rays reaching SE Caribbean networks, such as XT network, generally pass through slabs under South American, Central American, Lesser Antilles, Southwest Caribbean, and the North Caribbean transform boundary, which leads to slightly positive average delay times. In contrast, the Puerto Rico network records seismic rays passing through regions that may lack slabs in the upper mantle and show slightly negative or near zero average delay times. These results agree with previous tomographic models. Based on our delay time observations, slabs and velocity structures near the East side of the Caribbean plate might be better imaged due to its denser ray coverage. More caution in selecting the seismic data for inversion on the west margin of Caribbean will be required to avoid possible smearing effects and artifacts from unequal ray path distributions.

Everyday episodic memory in amnestic mild cognitive impairment: a preliminary investigation.

PubMed

Irish, Muireann; Lawlor, Brian A; Coen, Robert F; O'Mara, Shane M

2011-08-04

Decline in episodic memory is one of the hallmark features of Alzheimer's disease (AD) and is also a defining feature of amnestic Mild Cognitive Impairment (MCI), which is posited as a potential prodrome of AD. While deficits in episodic memory are well documented in MCI, the nature of this impairment remains relatively under-researched, particularly for those domains with direct relevance and meaning for the patient's daily life. In order to fully explore the impact of disruption to the episodic memory system on everyday memory in MCI, we examined participants' episodic memory capacity using a battery of experimental tasks with real-world relevance. We investigated episodic acquisition and delayed recall (story-memory), associative memory (face-name pairings), spatial memory (route learning and recall), and memory for everyday mundane events in 16 amnestic MCI and 18 control participants. Furthermore, we followed MCI participants longitudinally to gain preliminary evidence regarding the possible predictive efficacy of these real-world episodic memory tasks for subsequent conversion to AD. The most discriminating tests at baseline were measures of acquisition, delayed recall, and associative memory, followed by everyday memory, and spatial memory tasks, with MCI patients scoring significantly lower than controls. At follow-up (mean time elapsed: 22.4 months), 6 MCI cases had progressed to clinically probable AD. Exploratory logistic regression analyses revealed that delayed associative memory performance at baseline was a potential predictor of subsequent conversion to AD. As a preliminary study, our findings suggest that simple associative memory paradigms with real-world relevance represent an important line of enquiry in future longitudinal studies charting MCI progression over time.

Zidovudine (AZT) versus AZT plus didanosine (ddI) versus AZT plus zalcitabine (ddC) in HIV infected adults.

PubMed

Darbyshire, J; Foulkes, M; Peto, R; Duncan, W; Babiker, A; Collins, R; Hughes, M; Peto, T; Walker, A

2000-01-01

Zidovudine (AZT) monotherapy was the first antiretroviral drug to be tested widely. The next two drugs to be developed were didanosine (ddI) and zalcitabine (ddC). To assess the effects of zidovudine (AZT), zidovudine plus didanosine (ddI) and zidovudine plus zalcitabine (ddC) on HIV disease progression and survival. Investigators and pharmaceutical companies were contacted, and MEDLINE searches were supplemented by searching conference abstracts. Randomised controlled trials comparing any two of AZT plus ddI, AZT plus ddC or AZT alone in participants with or without AIDS which collected information on deaths and new AIDS events. Individual patient data with, wherever possible, follow-up obtained beyond that previously published were obtained and checked for internal consistency and consistency with any published reports; any apparent discrepancies were resolved with the trialists. Time to death and to disease progression (defined as a new AIDS-defining event or prior death) were analysed on an intention to treat basis, stratified to avoid direct comparisons between participants in different trials. Six trials were included in the meta-analysis. During a median follow-up of 29 months, 2904 individuals progressed, of whom 1850 died. The addition of ddI to AZT delayed both progression (RR 0.74; 95% CI 0.67 to 0.82, P<0.0001) and death (RR 0.72; 95% CI 0.64 to 0.82, P<0.0001). Likewise, the addition of ddC to AZT also delayed progression (RR 0. 86; 95% CI 0.78 to 0.94, P=0.001) and death (RR 0.87; 95% CI 0.77 to 0.98, P=0.02). After 3 years the estimated percentages alive and without a new AIDS event were 53% for AZT+ddI, 49% for AZT+ddC and 44% for AZT alone; the percentages alive were 68%, 63% and 59% respectively. Five of the six trials involved randomised comparisons of AZT+ddI versus AZT+ddC: in these, the AZT+ddI regimen had greater effects on disease progression (P=0.004) and death (P=0.009). The use of ddI and, to a lesser extent, ddC delayed both HIV disease progression and death, at least when added to AZT.

Mitigating delay and non-payment in the Malaysian construction industry

NASA Astrophysics Data System (ADS)

Mohamad, N.; Suman, A. S.; Harun, H.; Hashim, H.

2018-02-01

Construction industry is one of the industries that have contributed towards the rapid growth of development and economics in Malaysia. However, the industry is inundated with delay and non-payment issues between the two parties in contract that is the clients and contractors Even though there are contractual and administrative provisions in the standard forms of contract in Malaysia regarding payments, delay and non-payment issues still occur between them. The aim of the study is to develop measures to mitigate delay and non-payment issues between contractors and clients in the Malaysian construction industry. Questionnaire survey was conducted with clients and contractors in Klang Valley. Results from data analysis identified significant measures to mitigate delay and non-payment issues between contractors and clients which include contractors should submit their progress work invoicing with adequate documents; contractors should follow up constantly with client regarding payment; proper understanding of requirements with regards to payment; mutual discussion of problems with client to address problems in a timely manner and proper use of payment provisions in the standard form of contract. This study is significant to contractors and clients and to other construction players in order to reduce and minimise delay and non-payment issues for the growth of economy in the Malaysian construction industry.

Delayed introduction of progressive enteral feeds to prevent necrotising enterocolitis in very low birth weight infants.

PubMed

Morgan, Jessie; Young, Lauren; McGuire, William

2014-01-01

The introduction of enteral feeds for very preterm (less than 32 weeks' gestation) or very low birth weight (VLBW; less than 1500 g) infants is often delayed for several days or longer after birth due to concern that early introduction may not be tolerated and may increase the risk of necrotising enterocolitis (NEC). However, delaying enteral feeding could diminish the functional adaptation of the gastrointestinal tract and prolong the need for parenteral nutrition with its attendant infectious and metabolic risks. To determine the effect of delayed introduction of progressive enteral feeds on the incidence of NEC, mortality and other morbidities in very preterm or VLBW infants. We searched the Cochrane Central Register of Controlled Trials (CENTRAL, 2014, Issue 8), MEDLINE (1966 to September 2014), EMBASE (1980 to September 2014), CINAHL (1982 to September 2014), conference proceedings and previous reviews. We included randomised or quasi-randomised controlled trials that assessed the effect of delayed (more than four days after birth) versus earlier introduction of progressive enteral feeds on the incidence of NEC, mortality and other morbidities in very preterm or VLBW infants. Two review authors independently assessed trial eligibility and risk of bias and undertook data extraction. We analysed the treatment effects in the individual trials and reported the risk ratio (RR) and risk difference for dichotomous data and mean difference for continuous data, with respective 95% confidence intervals (CI). We used a fixed-effect model in meta-analyses and explored the potential causes of heterogeneity in sensitivity analyses. We identified nine randomised controlled trials in which 1106 infants participated. Few participants were extremely preterm (less 28 weeks' gestation) or extremely low birth weight (less than 1000 g). The trials defined delayed introduction of progressive enteral feeds as later than four to seven days after birth and early introduction as four days or less after birth. Meta-analyses did not detect statistically significant effects on the risk of NEC (typical RR 0.93, 95% CI 0.64 to 1.34; 8 trials; 1092 infants) or all-cause mortality (typical RR 1.18, 95% CI 0.75 to 1.88; 7 trials; 967 infants). Four of the trials restricted participation to growth-restricted infants with Doppler ultrasound evidence of abnormal fetal circulatory distribution or flow. Planned subgroup analyses of these trials found no statistically significant effects on the risk of NEC or all-cause mortality. Infants who had delayed introduction of enteral feeds took longer to establish full enteral feeding (reported median differences two to four days). The evidence available from randomised controlled trials suggested that delaying the introduction of progressive enteral feeds beyond four days after birth did not reduce the risk of developing NEC in very preterm or VLBW infants, including growth-restricted infants. Delaying the introduction of progressive enteral feeds resulted in a few days' delay in establishing full enteral feeds but the clinical importance of this effect was unclear. The applicability of these findings to extremely preterm or extremely low birth weight was uncertain. Further randomised controlled trials in this population may be warranted.

Intracystic interferon-alpha in pediatric craniopharyngioma patients: an international multicenter assessment on behalf of SIOPE and ISPN.

PubMed

Kilday, John-Paul; Caldarelli, Massimo; Massimi, Luca; Chen, Robert Hsin-Hung; Lee, Yi Yen; Liang, Muh-Lii; Parkes, Jeanette; Naiker, Thuran; van Veelen, Marie-Lise; Michiels, Erna; Mallucci, Conor; Pettorini, Benedetta; Meijer, Lisethe; Dorfer, Christian; Czech, Thomas; Diezi, Manuel; Schouten-van Meeteren, Antoinette Y N; Holm, Stefan; Gustavsson, Bengt; Benesch, Martin; Müller, Hermann L; Hoffmann, Anika; Rutkowski, Stefan; Flitsch, Joerg; Escherich, Gabriele; Grotzer, Michael; Spoudeas, Helen A; Azquikina, Kristian; Capra, Michael; Jiménez-Guerra, Rolando; MacDonald, Patrick; Johnston, Donna L; Dvir, Rina; Constantini, Shlomi; Kuo, Meng-Fai; Yang, Shih-Hung; Bartels, Ute

2017-10-01

Craniopharyngiomas are frequent hypothalamo-pituitary tumors in children, presenting predominantly as cystic lesions. Morbidity from conventional treatment has focused attention on intracystic drug delivery, hypothesized to cause fewer clinical consequences. However, the efficacy of intracystic therapy remains unclear. We report the retrospective experiences of several global centers using intracystic interferon-alpha. European Société Internationale d'Oncologie Pédiatrique and International Society for Pediatric Neurosurgery centers were contacted to submit a datasheet capturing pediatric patients with cystic craniopharyngiomas who had received intracystic interferon-alpha. Patient demographics, administration schedules, adverse events, and outcomes were obtained. Progression was clinical or radiological (cyst reaccumulation, novel cysts, or solid growth). Fifty-six children (median age, 6.3 y) from 21 international centers were identified. Median follow-up from diagnosis was 5.1 years (0.3-17.7 y). Lesions were cystic (n = 22; 39%) or cystic/solid (n = 34; 61%). Previous progression was treated in 43 (77%) patients before interferon use. In such cases, further progression was delayed by intracystic interferon compared with the preceding therapy for cystic lesions (P = 0.0005). Few significant attributable side effects were reported. Progression post interferon occurred in 42 patients (median 14 mo; 0-8 y), while the estimated median time to definitive therapy post interferon was 5.8 (1.8-9.7) years. Intracystic interferon-alpha can delay disease progression and potentially offer a protracted time to definitive surgery or radiotherapy in pediatric cystic craniopharyngioma, yet demonstrates a favorable toxicity profile compared with other therapeutic modalities-important factors for this developing age group. A prospective, randomized international clinical trial assessment is warranted. © The Author(s) 2017. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Design and End Points of Clinical Trials for Patients With Progressive Prostate Cancer and Castrate Levels of Testosterone: Recommendations of the Prostate Cancer Clinical Trials Working Group

PubMed Central

Scher, Howard I.; Halabi, Susan; Tannock, Ian; Morris, Michael; Sternberg, Cora N.; Carducci, Michael A.; Eisenberger, Mario A.; Higano, Celestia; Bubley, Glenn J.; Dreicer, Robert; Petrylak, Daniel; Kantoff, Philip; Basch, Ethan; Kelly, William Kevin; Figg, William D.; Small, Eric J.; Beer, Tomasz M.; Wilding, George; Martin, Alison; Hussain, Maha

2014-01-01

Purpose To update eligibility and outcome measures in trials that evaluate systemic treatment for patients with progressive prostate cancer and castrate levels of testosterone. Methods A committee of investigators experienced in conducting trials for prostate cancer defined new consensus criteria by reviewing previous criteria, Response Evaluation Criteria in Solid Tumors (RECIST), and emerging trial data. Results The Prostate Cancer Clinical Trials Working Group (PCWG2) recommends a two-objective paradigm: (1) controlling, relieving, or eliminating disease manifestations that are present when treatment is initiated and (2) preventing or delaying disease manifestations expected to occur. Prostate cancers progressing despite castrate levels of testosterone are considered castration resistant and not hormone refractory. Eligibility is defined using standard disease assessments to authenticate disease progression, prior treatment, distinct clinical subtypes, and predictive models. Outcomes are reported independently for prostate-specific antigen (PSA), imaging, and clinical measures, avoiding grouped categorizations such as complete or partial response. In most trials, early changes in PSA and/or pain are not acted on without other evidence of disease progression, and treatment should be continued for at least 12 weeks to ensure adequate drug exposure. Bone scans are reported as “new lesions” or “no new lesions,” changes in soft-tissue disease assessed by RECIST, and pain using validated scales. Defining eligibility for prevent/delay end points requires attention to estimated event frequency and/or random assignment to a control group. Conclusion PCWG2 recommends increasing emphasis on time-to-event end points (ie, failure to progress) as decision aids in proceeding from phase II to phase III trials. Recommendations will evolve as data are generated on the utility of intermediate end points to predict clinical benefit. PMID:18309951

Rho/ROCK signaling in regulation of corneal epithelial cell cycle progression.

PubMed

Chen, Jian; Guerriero, Emily; Lathrop, Kira; SundarRaj, Nirmala

2008-01-01

The authors' previous study showed that the expression of a Rho-associated serine/threonine kinase (ROCK) is regulated during cell cycle progression in corneal epithelial cells. The present study was conducted to determine whether and how Rho/ROCK signaling regulates cell cycle progression. Rabbit corneal epithelial cells (RCECs) in culture were arrested in the G(0) phase of the cell cycle by serum deprivation and then allowed to re-enter the cell cycle in the presence or absence of the ROCK inhibitor (Y27632) in serum-supplemented medium. The number of cells in the S phase, the relative levels of specific cyclins and CDKs and their intracellular distribution, and the relative levels of mRNAs were determined by BrdU labeling, Western blot and immunocytochemical analyses, and real-time RT-PCR, respectively. ROCK inhibition delayed the progression of G(1) to S phase and led to a decrease in the number of RCECs entering the S phase between 12 and 24 hours from 31.5% +/- 4.5% to 8.1% +/- 2.6%. During the cell cycle progression, protein and mRNA levels of cyclin-D1 and -D3 and cyclin-dependent kinases CDK4 and CDK6 were significantly lower, whereas the protein levels of the CDK inhibitor p27(Kip1) were higher in ROCK-inhibited cells. Intracellular mRNA or protein levels of cyclin-E and protein levels of CDK2 were not significantly affected, but their nuclear translocation was delayed by ROCK inhibition. ROCK signaling is involved in cell cycle progression in RCECs, possibly by upregulation of cyclin-D1 and -D3 and CDK4, -6, and -2; nuclear translocation of CDK2 and cyclin-E; and downregulation of p27(Kip1).

Early versus late Gamma Knife radiosurgery following transsphenoidal surgery for nonfunctioning pituitary macroadenomas: a multicenter matched-cohort study.

PubMed

Pomeraniec, I Jonathan; Kano, Hideyuki; Xu, Zhiyuan; Nguyen, Brandon; Siddiqui, Zaid A; Silva, Danilo; Sharma, Mayur; Radwan, Hesham; Cohen, Jonathan A; Dallapiazza, Robert F; Iorio-Morin, Christian; Wolf, Amparo; Jane, John A; Grills, Inga S; Mathieu, David; Kondziolka, Douglas; Lee, Cheng-Chia; Wu, Chih-Chun; Cifarelli, Christopher P; Chytka, Tomas; Barnett, Gene H; Lunsford, L Dade; Sheehan, Jason P

2017-10-27

OBJECTIVE Gamma Knife radiosurgery (GKRS) is frequently used to treat residual or recurrent nonfunctioning pituitary macroadenomas. There is no consensus as to whether GKRS should be used early after surgery or if radiosurgery should be withheld until there is evidence of imaging-defined progression of tumor. Given the high incidence of adenoma progression after subtotal resection over time, the present study intended to evaluate the effect of timing of radiosurgery on outcome. METHODS This is a multicenter retrospective review of patients with nonfunctioning pituitary macroadenomas who underwent transsphenoidal surgery followed by GKRS from 1987 to 2015 at 9 institutions affiliated with the International Gamma Knife Research Foundation. Patients were matched by adenoma and radiosurgical parameters and stratified based on the interval between last resection and radiosurgery. Operative results, imaging data, and clinical outcomes were compared across groups following early (≤ 6 months after resection) or late (> 6 months after resection) radiosurgery. RESULTS After matching, 222 patients met the authors' study criteria (from an initial collection of 496 patients) and were grouped based on early (n = 111) or late (n = 111) GKRS following transsphenoidal surgery. There was a greater risk of tumor progression after GKRS (p = 0.013) and residual tumor (p = 0.038) in the late radiosurgical group over a median imaging follow-up period of 68.5 months. No significant difference in the occurrence of post-GKRS endocrinopathy was observed (p = 0.68). Thirty percent of patients without endocrinopathy in the early cohort developed new endocrinopathies during the follow-up period versus 27% in the late cohort (p = 0.84). Fourteen percent of the patients in the early group and 25% of the patients in the late group experienced the resolution of endocrine dysfunction after original presentation (p = 0.32). CONCLUSIONS In this study, early GKRS was associated with a lower risk of radiological progression of subtotally resected nonfunctioning pituitary macroadenomas compared with expectant management followed by late radiosurgery. Delaying radiosurgery may increase patient risk for long-term adenoma progression. The timing of radiosurgery does not appear to significantly affect the rate of delayed endocrinopathy.

Number needed to treat and associated incremental costs of treatment with enzalutamide versus abiraterone acetate plus prednisone in chemotherapy-naïve patients with metastatic castration-resistant prostate cancer.

PubMed

Massoudi, Marjan; Balk, Mark; Yang, Hongbo; Bui, Cat N; Pandya, Bhavik J; Guo, Jenny; Song, Yan; Wu, Eric Q; Brown, Bruce; Barlev, Arie; Flanders, Scott

2017-02-01

Enzalutamide (ENZA) and abiraterone acetate plus prednisone (AA) are approved second-generation hormone therapies for chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC). This study compared ENZA with AA in chemotherapy-naïve mCRPC by calculating the number needed to treat (NNT) and associated incremental costs to achieve one additional chemotherapy-naïve patient with mCRPC free of radiographic progression, chemotherapy, or death over a 1-year time horizon. Clinical outcomes were obtained from the PREVAIL and COU-AA-302 trials. Three outcomes were evaluated: radiographic progression-free survival, time to cytotoxic chemotherapy initiation, and overall survival at 1 year. NNT was calculated as the reciprocal of the outcome event rate difference for ENZA compared with AA. The incremental costs to achieve one additional outcome at 1 year were calculated as the difference in cost per treated patient multiplied by the NNT. Per-treated-patient costs were considered from a US payer perspective and included medications, monitoring, adverse events, post-progression treatments, and end-of-life care. Within a 1-year time horizon, the total cost per treated patient for ENZA was $2,666 less than AA. Compared with AA, treating 14 patients with ENZA resulted in one additional patient free of progression or death over 1 year; treating 26 patients with ENZA resulted in one additional patient with chemotherapy delayed over 1 year; and treating 91 patients with ENZA resulted in one additional patient free of death over 1 year. Therefore, ENZA is cost-effective compared with AA for all three outcomes evaluated, and the modeled results suggest ENZA is associated with potentially improved clinical outcomes in delaying chemotherapy initiation and disease progression for chemotherapy-naïve patients. The results are robust in sensitivity analyses, where the effect of changes in key model inputs and assumptions were tested. The results modeled in the present study suggest ENZA is cost-effective compared with AA for treating chemotherapy-naïve patients with mCRPC.

Delayed diagnosis of Alport syndrome without hematuria.

PubMed

Yin-Yin, Chen; You-Ming, Peng; Yu-Mei, Liang

2014-05-01

Alport syndrome is a progressive hereditary disease caused by mutations in the genes encoding type IV collagen. Persistent microscopic hematuria is the hallmark of Alport syndrome, occurring in almost all boys according to previous reports. We report the case of a 20-year-old man presented with proteinuria but no hematuria that was initially misdiagnosed with refractory nephrotic syndrome and was eventually diagnosed with Alport syndrome following kidney and skin biopsy. During the follow-up period, he experienced a rapid progression to end-stage renal disease. Timely diagnosis of Alport syndrome is important, because patients may benefit from early intervention and avoid suffering from unnecessary nephrotoxic drug use.

Role of p53 in cdk Inhibitor VMY-1-103-induced Apoptosis in Prostate Cancer

DTIC Science & Technology

2013-11-01

DAOY medulloblastoma cells, which have a p53 mutation (6). In order to examine if this holds true in prostate cancer cell lines, I stably transfected...disrupts chromosome organization and delays metaphase progression in medulloblastoma cells. Cancer Biol Ther. 2011 Nov 1;12(9):818-26  Other...1-103 is a novel CDK inhibitor that disrupts chromosome organization and delays metaphase progression in medulloblastoma cells. Cancer Biol Ther

Fire behavior, fuel treatments, and fire suppression on the Hayman Fire - Part 4: Relation of roads to burn severity

Treesearch

Charles W. McHugh; Mark A. Finney

2003-01-01

Effects of roads on fire behavior intensity and severity can be studied directly or indirectly. A direct study of road effects would include uses by fire suppression, burnout operations, and delay of fire progress at the roadside. Interpretations after the fire burns are easily confounded by the unknown nature of suppression activities and fire arrival time, and fire...

FDA advisory committees meet January 26 on Salk HIV-1 immunogen.

PubMed

1995-01-06

Two advisory committees of the Food and Drug Administration (FDA) will meet to consider future trials of the HIV-1 immunogen developed by Dr. Jonas Salk. The Immune Response Corporation has already conducted several studies of the immunogen, and has found improvement in various immunological and other blood tests, and no adverse effects. However, the studies have not been large enough to show conclusively that the treatment has clinical benefit in delaying disease progression. The new, larger trials are intended to demonstrate a delay in disease progression and validate the use of blood-test markers of disease progression for studying an immune-based treatment.

Improving time-delay cosmography with spatially resolved kinematics

NASA Astrophysics Data System (ADS)

Shajib, Anowar J.; Treu, Tommaso; Agnello, Adriano

2018-01-01

Strongly gravitational lensed quasars can be used to measure the so-called time-delay distance DΔt, and thus the Hubble constant H0 and other cosmological parameters. Stellar kinematics of the deflector galaxy play an essential role in this measurement by: (i) helping break the mass-sheet degeneracy; (ii) determining in principle the angular diameter distance Dd to the deflector and thus further improving the cosmological constraints. In this paper we simulate observations of lensed quasars with integral field spectrographs and show that spatially resolved kinematics of the deflector enables further progress by helping break the mass-anisotropy degeneracy. Furthermore, we use our simulations to obtain realistic error estimates with current/upcoming instruments like OSIRIS on Keck and NIRSPEC on the James Webb Space Telescope for both distances (typically ∼6 per cent on DΔt and ∼10 per cent on Dd). We use the error estimates to compute cosmological forecasts for the sample of nine lenses that currently have well-measured time delays and deep Hubble Space Telescope images and for a sample of 40 lenses that is projected to be available in a few years through follow-up of candidates found in ongoing wide field surveys. We find that H0 can be measured with 2 per cent (1 per cent) precision from nine (40) lenses in a flat Λcold dark matter cosmology. We study several other cosmological models beyond the flat Λcold dark matter model and find that time-delay lenses with spatially resolved kinematics can greatly improve the precision of the cosmological parameters measured by cosmic microwave background data.

Delayed P100-Like Latencies in Multiple Sclerosis: A Preliminary Investigation Using Visual Evoked Spread Spectrum Analysis

PubMed Central

Kiiski, Hanni S. M.; Ní Riada, Sinéad; Lalor, Edmund C.; Gonçalves, Nuno R.; Nolan, Hugh; Whelan, Robert; Lonergan, Róisín; Kelly, Siobhán; O'Brien, Marie Claire; Kinsella, Katie; Bramham, Jessica; Burke, Teresa; Ó Donnchadha, Seán; Hutchinson, Michael; Tubridy, Niall; Reilly, Richard B.

2016-01-01

Conduction along the optic nerve is often slowed in multiple sclerosis (MS). This is typically assessed by measuring the latency of the P100 component of the Visual Evoked Potential (VEP) using electroencephalography. The Visual Evoked Spread Spectrum Analysis (VESPA) method, which involves modulating the contrast of a continuous visual stimulus over time, can produce a visually evoked response analogous to the P100 but with a higher signal-to-noise ratio and potentially higher sensitivity to individual differences in comparison to the VEP. The main objective of the study was to conduct a preliminary investigation into the utility of the VESPA method for probing and monitoring visual dysfunction in multiple sclerosis. The latencies and amplitudes of the P100-like VESPA component were compared between healthy controls and multiple sclerosis patients, and multiple sclerosis subgroups. The P100-like VESPA component activations were examined at baseline and over a 3-year period. The study included 43 multiple sclerosis patients (23 relapsing-remitting MS, 20 secondary-progressive MS) and 42 healthy controls who completed the VESPA at baseline. The follow-up sessions were conducted 12 months after baseline with 24 MS patients (15 relapsing-remitting MS, 9 secondary-progressive MS) and 23 controls, and again at 24 months post-baseline with 19 MS patients (13 relapsing-remitting MS, 6 secondary-progressive MS) and 14 controls. The results showed P100-like VESPA latencies to be delayed in multiple sclerosis compared to healthy controls over the 24-month period. Secondary-progressive MS patients had most pronounced delay in P100-like VESPA latency relative to relapsing-remitting MS and controls. There were no longitudinal P100-like VESPA response differences. These findings suggest that the VESPA method is a reproducible electrophysiological method that may have potential utility in the assessment of visual dysfunction in multiple sclerosis. PMID:26726800

Tafamidis delays disease progression in patients with early stage transthyretin familial amyloid polyneuropathy: additional supportive analyses from the pivotal trial.

PubMed

Keohane, Denis; Schwartz, Jeffrey; Gundapaneni, Balarama; Stewart, Michelle; Amass, Leslie

2017-03-01

Tafamidis, a non-NSAID highly specific transthyretin stabilizer, delayed neurologic disease progression as measured by Neuropathy Impairment Score-Lower Limbs (NIS-LL) in an 18-month, double-blind, placebo-controlled randomized trial in 128 patients with early-stage transthyretin V30M familial amyloid polyneuropathy (ATTRV30M-FAP). The current post hoc analyses aimed to further evaluate the effects of tafamidis in delaying ATTRV30M-FAP progression in this trial. Pre-specified, repeated-measures analysis of change from baseline in NIS-LL in this trial (ClinicalTrials.gov NCT00409175) was repeated with addition of baseline as covariate and multiple imputation analysis for missing data by treatment group. Change in NIS-LL plus three small-fiber nerve tests (NIS-LL + Σ3) and NIS-LL plus seven nerve tests (NIS-LL + Σ7) were assessed without baseline as covariate. Treatment outcomes over the NIS-LL, Σ3, Σ7, modified body mass index and Norfolk Quality of Life-Diabetic Neuropathy Total Quality of Life Score were also examined using multivariate analysis techniques. Neuropathy progression based on NIS-LL change from baseline to Month 18 remained significantly reduced for tafamidis versus placebo in the baseline-adjusted and multiple imputation analyses. NIS-LL + Σ3 and NIS-LL + Σ7 captured significant treatment group differences. Multivariate analyses provided strong statistical evidence for a superior tafamidis treatment effect. These supportive analyses confirm that tafamidis delays neurologic progression in early-stage ATTRV30M-FAP. NCT00409175.

Conventional medical management of inflammatory bowel disease.

PubMed

Burger, Daniel; Travis, Simon

2011-05-01

Conventional therapies for ulcerative colitis and Crohn's disease (CD) include aminosalicylates, corticosteroids, thiopurines, methotrexate, and anti-tumor necrosis factor agents. A time-structured approach is required for appropriate management. Traditional step-up therapy has been partly replaced during the last decade by potent drugs and top-down therapies, with an accelerated step-up approach being the most appropriate in the majority of patients. When patients are diagnosed with CD or ulcerative colitis, physicians should consider the probable pattern of disease progression so that effective therapy is not delayed. This can be achieved by setting arbitrary time limits for administration of biological therapies, changing therapy from mesalamine in patients with active ulcerative colitis, or using rescue therapy for acute severe colitis. In this review, we provide algorithms with a time-structured approach for guidance of therapy. Common mistakes in conventional therapy include overprescription of mesalamine for CD; inappropriate use of steroids (for perianal CD, when there is sepsis, or for maintenance); delayed introduction or underdosing with azathioprine, 6-mercaptopurine, or methotrexate; and failure to consider timely surgery. The paradox of anti-tumor necrosis factor therapy is that although it too is used inappropriately (when patients have sepsis or fibrostenotic strictures) or too frequently (for diseases that would respond to less-potent therapy), it is also often introduced too late in disease progression. Conventional drugs are the mainstay of current therapy for inflammatory bowel diseases, but drug type, timing, and context must be optimized to manage individual patients effectively. Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.

Global Effects of DDX3 Inhibition on Cell Cycle Regulation Identified by a Combined Phosphoproteomics and Single Cell Tracking Approach.

PubMed

Heerma van Voss, Marise R; Kammers, Kai; Vesuna, Farhad; Brilliant, Justin; Bergman, Yehudit; Tantravedi, Saritha; Wu, Xinyan; Cole, Robert N; Holland, Andrew; van Diest, Paul J; Raman, Venu

2018-06-01

DDX3 is an RNA helicase with oncogenic properties. The small molecule inhibitor RK-33 is designed to fit into the ATP binding cleft of DDX3 and hereby block its activity. RK-33 has shown potent activity in preclinical cancer models. However, the mechanism behind the antineoplastic activity of RK-33 remains largely unknown. In this study we used a dual phosphoproteomic and single cell tracking approach to evaluate the effect of RK-33 on cancer cells. MDA-MB-435 cells were treated for 24 hours with RK-33 or vehicle control. Changes in phosphopeptide abundance were analyzed with quantitative mass spectrometry using isobaric mass tags (Tandem Mass Tags). At the proteome level we mainly observed changes in mitochondrial translation, cell division pathways and proteins related to cell cycle progression. Analysis of the phosphoproteome indicated decreased CDK1 activity after RK-33 treatment. To further evaluate the effect of DDX3 inhibition on cell cycle progression over time, we performed timelapse microscopy of Fluorescent Ubiquitin Cell Cycle Indicators labeled cells after RK-33 or siDDX3 exposure. Single cell tracking indicated that DDX3 inhibition resulted in a global delay in cell cycle progression in interphase and mitosis. In addition, we observed an increase in endoreduplication. Overall, we conclude that DDX3 inhibition affects cells in all phases and causes a global cell cycle progression delay. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Comparing cognition by integrating concept learning, proactive interference, and list memory.

PubMed

Wright, Anthony A; Kelly, Debbie M; Katz, Jeffrey S

2018-06-01

This article describes an approach for training a variety of species to learn the abstract concept of same/different, which in turn forms the basis for testing proactive interference and list memory. The stimulus set for concept-learning training was progressively doubled from 8, 16, 32, 64, 128 . . . to 1,024 different pictures with novel-stimulus transfer following learning. All species fully learned the same/different abstract concept: capuchin and rhesus monkeys learned more readily than pigeons; nutcrackers and magpies were at least equivalent to monkeys and transferred somewhat better following initial training sets. A similar task using the 1,024-picture set plus delays was used to test proactive interference on occasional trials. Pigeons revealed greater interference with 10-s than with 1-s delays, whereas delay time had no effect on rhesus monkeys, suggesting that the monkeys' interference was event based. This same single-item same/different task was expanded to a 4-item list memory task to test animal list memory. Humans were tested similarly with lists of kaleidoscope pictures. Delays between the list and test were manipulated, resulting in strong initial recency effects (i.e., strong 4th-item memory) at short delays and changing to a strong primacy effect (i.e., strong 1st-item memory) at long delays (pigeons 0-s to 10-s delays; monkeys 0-s to 30-s delays; humans 0-s to 100-s delays). Results and findings are discussed in terms of these species' cognition and memory comparisons, evolutionary implications, and future directions for testing other species in these synergistically related tasks.

UV-C irradiation delays mitotic progression by recruiting Mps1 to kinetochores.

PubMed

Zhang, Xiaojuan; Ling, Youguo; Wang, Wenjun; Zhang, Yanhong; Ma, Qingjun; Tan, Pingping; Song, Ting; Wei, Congwen; Li, Ping; Liu, Xuedong; Ma, Runlin Z; Zhong, Hui; Cao, Cheng; Xu, Quanbin

2013-04-15

The effect of UV irradiation on replicating cells during interphase has been studied extensively. However, how the mitotic cell responds to UV irradiation is less well defined. Herein, we found that UV-C irradiation (254 nm) increases recruitment of the spindle checkpoint proteins Mps1 and Mad2 to the kinetochore during metaphase, suggesting that the spindle assembly checkpoint (SAC) is reactivated. In accordance with this, cells exposed to UV-C showed delayed mitotic progression, characterized by a prolonged chromosomal alignment during metaphase. UV-C irradiation also induced the DNA damage response and caused a significant accumulation of γ-H2AX on mitotic chromosomes. Unexpectedly, the mitotic delay upon UV-C irradiation is not due to the DNA damage response but to the relocation of Mps1 to the kinetochore. Further, we found that UV-C irradiation activates Aurora B kinase. Importantly, the kinase activity of Aurora B is indispensable for full recruitment of Mps1 to the kinetochore during both prometaphase and metaphase. Taking these findings together, we propose that UV irradiation delays mitotic progression by evoking the Aurora B-Mps1 signaling cascade, which exerts its role through promoting the association of Mps1 with the kinetochore in metaphase.

Department of Defense Weapon System Acquisition Policy: A System Dynamics Model and Analysis.

DTIC Science & Technology

1982-09-01

dimensionless) PRPRD = Perceived Pressure for R&D (dimensionless) PU - Programs in Progress (programs) RPRD - Raw Pressure for R&D (dimensionless) TDPP - Time...ECAP) TH9 Pressure Ra Pressure_.- for Acquisition ( TDPP ) TH25 4for Acquisition (DPFAO) TH22D (DPPFAO) TH21 US Intelligence \\ - 7 Delay Time / efense...DIBP, DPPFAQ. K) TH22 A CPPFAG.K=DLINF3(RPFAG.KTCPP) TH23 A CPFAQ.K=MAX (DIBPCPPFAQ.K) TH24 C TDPP =12 TH25 C TCPP-24 TH26 CPFAQ Congressional Pressure

PULSE SYNTHESIZING GENERATOR

DOEpatents

Kerns, Q.A.

1963-08-01

>An electronlc circuit for synthesizing electrical current pulses having very fast rise times includes several sinewave generators tuned to progressively higher harmonic frequencies with signal amplitudes and phases selectable according to the Fourier series of the waveform that is to be synthesized. Phase control is provided by periodically triggering the generators at precisely controlled times. The outputs of the generators are combined in a coaxial transmission line. Any frequency-dependent delays that occur in the transmission line can be readily compensated for so that the desired signal wave shape is obtained at the output of the line. (AEC)

Does the Zone of Injury in Combat-Related Type III Open Tibia Fractures Preclude the Use of Local Soft Tissue Coverage?

DTIC Science & Technology

2010-11-01

delayed union , non- union , and deep infection.39 The large zone of injury surrounding the open fracture site led to the rationale that free flap coverage...also lower for the rotational flap cohort (7% versus 27%, P 0.08). The average time to fracture union for the free flap group was 9.5 months (range, 5...success of coverage, complication rates, visual pain scores, time to radiographic fracture union , and progression to amputation for local rotational

A Study on the Decision Factors in the Delay of the ROK-U.S. Wartime OPCON Transfer: Focusing on the Domestic Determinants

DTIC Science & Technology

2015-12-01

the role of state: the conservatives emphasize development ( laissez - faire ), and the progressives stress a distribution (intervention). 84 Therefore...opinion; (3) perception of threat; (4) and leadership of the ROK president.39 He focuses on the tendency of the ROK government to follow...presidential leadership .40 Similarly to Jang, his work neglects a huge discourse between the ROK conservatives and progressives and U.S. factors on the delay

Prognostic value of a CCR5 defective allele in pediatric HIV-1 infection.

PubMed Central

Romiti, M. L.; Colognesi, C.; Cancrini, C.; Mas, A.; Berrino, M.; Salvatori, F.; Orlandi, P.; Jansson, M.; Palomba, E.; Plebani, A.; Bertran, J. M.; Hernandez, M.; de Martino, M.; Amoroso, A.; Tovo, P. A.; Rossi, P.; Espanol, T.; Scarlatti, G.

2000-01-01

BACKGROUND: A deletion of 32 base pairs in the CCR5 gene (delta32 CCR5) has been linked to resistance to HIV-1 infection in exposed adults and to the delay of disease progression in infected adults. MATERIALS AND METHODS: To determine the role of delta32 CCR5 in disease progression of HIV-1 infected children born to seropositive mothers, we studied a polymerase chain reaction in 301 HIV-1 infected, 262 HIV-1 exposed-uninfected and 47 HIV-1 unexposed-uninfected children of Spanish and Italian origin. Infected children were further divided into two groups according to their rate of HIV-1 disease progression: rapid progressors who developed severe clinical and/or immunological conditions within the second year of life, and delayed progressors with any other evolution of disease. Among the latter were the long-term, non-progressors (LTNP) who presented with mild or no symptoms of HIV-1 infection above 8 years of age. Viral phenotype was studied for 45 delayed progressors. RESULTS: No correlation was found between delta32 CCR5 and mother-to-child transmission of HIV-1. However, the frequency of the deletion was substantially higher in LTNP, compared with delayed (p = 0.019) and rapid progressors (p = 0.0003). In children carrying the delta32 CCRS mutation, the presence of MT-2 tropic virus isolate was associated with a severe immune suppression (p = 0.028); whereas, the presence of MT-2 negative viruses correlated with LTNP (p = 0.010). CONCLUSIONS: Given the rapidity and simplicity of the assay, the delta32 CCR5 mutation may be a useful predictive marker to identify children with delayed disease progression who, consequently, may not require immediate antiretroviral treatment. PMID:10803406

Prognostic value of a CCR5 defective allele in pediatric HIV-1 infection.

PubMed

Romiti, M L; Colognesi, C; Cancrini, C; Mas, A; Berrino, M; Salvatori, F; Orlandi, P; Jansson, M; Palomba, E; Plebani, A; Bertran, J M; Hernandez, M; de Martino, M; Amoroso, A; Tovo, P A; Rossi, P; Espanol, T; Scarlatti, G

2000-01-01

A deletion of 32 base pairs in the CCR5 gene (delta32 CCR5) has been linked to resistance to HIV-1 infection in exposed adults and to the delay of disease progression in infected adults. To determine the role of delta32 CCR5 in disease progression of HIV-1 infected children born to seropositive mothers, we studied a polymerase chain reaction in 301 HIV-1 infected, 262 HIV-1 exposed-uninfected and 47 HIV-1 unexposed-uninfected children of Spanish and Italian origin. Infected children were further divided into two groups according to their rate of HIV-1 disease progression: rapid progressors who developed severe clinical and/or immunological conditions within the second year of life, and delayed progressors with any other evolution of disease. Among the latter were the long-term, non-progressors (LTNP) who presented with mild or no symptoms of HIV-1 infection above 8 years of age. Viral phenotype was studied for 45 delayed progressors. No correlation was found between delta32 CCR5 and mother-to-child transmission of HIV-1. However, the frequency of the deletion was substantially higher in LTNP, compared with delayed (p = 0.019) and rapid progressors (p = 0.0003). In children carrying the delta32 CCRS mutation, the presence of MT-2 tropic virus isolate was associated with a severe immune suppression (p = 0.028); whereas, the presence of MT-2 negative viruses correlated with LTNP (p = 0.010). Given the rapidity and simplicity of the assay, the delta32 CCR5 mutation may be a useful predictive marker to identify children with delayed disease progression who, consequently, may not require immediate antiretroviral treatment.

Time course of changes in sperm morphometry and semen variables during testosterone-induced suppression of human spermatogenesis.

PubMed

Garrett, C; Liu, D Y; McLachlan, R I; Baker, H W G

2005-11-01

Quantification of changes in semen may give insight into the testosterone (T)-induced disruption of spermatogenesis in man. A model analogous to flushing of sperm from the genital tract after vasectomy was used to quantify the time course of semen changes in subjects participating in male contraceptive trials using 800 mg T-implant (n = 25) or 200 mg weekly intramuscular injection (IM-T; n = 33). A modified exponential decay model allowed for delayed onset and incomplete disruption to spermatogenesis. Semen variables measured weekly during a 91-day period after initial treatment were fitted to the model. Sperm concentration, total count, motility and morphometry exhibited similar average decay rates (5 day half-life). The mean delay to onset of decline in concentration was 15 (IM-T) and 18 (T-implant) days. The significantly longer (P < 0.005) delays deduced for the commencement of fall in normal morphology (41 days), normal morphometry (40 days) and sperm viability (43 and 55 days), and the change of morphometry to smaller more compact sperm heads are consistent with sperm being progressively cleared from the genital tract rather than continued shedding of immature or abnormal sperm by the seminiferous epithelium. A significant negative relationship was found between lag time and baseline sperm concentration, consistent with longer sperm-epididymal transit times associated with lower daily production rates.

Cyclophosphamide's addition in relapsed/refractory multiple myeloma patients with biochemical progression during lenalidomide-dexamethasone treatment.

PubMed

Cesini, Laura; Siniscalchi, Agostina; Grammatico, Sara; Andriani, Alessandro; Fiorini, Alessia; De Rosa, Luca; Za, Tommaso; Rago, Angela; Caravita, Tommaso; Petrucci, Maria Teresa

2018-05-02

The aim of this study was to evaluate the addition of cyclophosphamide in relapsed-refractory multiple myeloma patients (RRMM) who experienced biochemical relapse or progression without CRAB, during treatment with lenalidomide and dexamethasone (Rd), to slow down the progression in active relapse. This analysis included 31 patients with RRMM treated with Rd who received cyclophosphamide (CRd) at biochemical relapse. The CRd regimen was continued until disease progression. The median number of CRd cycles administered was 8 (range: 1-35). A response was observed in 9 (29%) patients. After a median observation time of 11 months, the median overall survival (OS) from the beginning of CRd was 17.7 months. The median progression-free survival (PFS) from the beginning of CRd was 13.1 months. The addition of cyclophosphamide delays the progression in patients who present a biochemical relapse during Rd treatment. The response rate and the duration of PFS obtained with minimal toxicities and low costs induced us to setting up a randomized clinical trial. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Endpoint Naming for Space Delay/Disruption Tolerant Networking

NASA Technical Reports Server (NTRS)

Clare, Loren; Burleigh, Scott; Scott, Keith

2010-01-01

Delay/Disruption Tolerant Networking (DTN) provides solutions to space communication challenges such as disconnections when orbiters lose line-of-sight with landers, long propagation delays over interplanetary links, and other operational constraints. DTN is critical to enabling the future space internetworking envisioned by NASA. Interoperability with international partners is essential and standardization is progressing through both the CCSDS and the IETF.

Factors Associated With Development of Nonunion or Delayed Healing After an Open Long Bone Fracture: A Prospective Cohort Study of 736 Subjects.

PubMed

Westgeest, Joseph; Weber, Donald; Dulai, Sukhdeep K; Bergman, Joseph W; Buckley, Richard; Beaupre, Lauren A

2016-03-01

To determine factors associated with developing nonunion or delayed healing after open fracture. Prospective cohort between 2001 and 2009. Three level 1 Canadian trauma centers. Seven hundred thirty-six (791 fractures) subjects were enrolled. Six hundred eighty-nine (94%) subjects (739 fractures) provided adequate outcome data. Subjects were followed until fracture(s) healed; phone interviews and chart reviews were conducted 1 year after fracture. Patient, fracture, and injury information, and time to surgery and antibiotics were recorded during hospitalization. Nonunion defined as unplanned surgical intervention after definitive wound closure or incomplete radiographic healing at 1 year and delayed healing defined as 2 consecutive clinical assessments showing no radiographic progression or incomplete radiographic healing between 6 months and 1 year. There were 413 (52%) tibia/fibular, 285 (36%) upper extremity, and 93 (13%) femoral fractures. Nonunion developed in 124 (17%) and delayed healing in 63 (8%) fractures. The median time to surgery was not different for fractures that developed nonunion compared with those who did not (P = 0.36). Deep infection [Odd ratio (OR) 12.75; 95% confidence interval (CI) 6.07-26.8], grade 3A fractures (OR 2.49; 95% CI, 1.30-4.78), and smoking (OR 1.73; 95% CI, 1.09-2.76) were significantly associated with developing a nonunion. Delayed healing was also significantly associated with deep infection (OR 4.34; 95% CI, 1.22-15.48) and grade 3B/C fractures (OR 3.69; 95% CI, 1.44-9.44). Multivariate regression found no association between nonunion and time to surgery (P = 0.15) or antibiotics (P = 0.70). Deep infection and higher Gustilo grade fractures were associated with nonunion and delayed healing. Prognostic Level I. See Instructions for Authors for a complete description of levels of evidence.

Everyday episodic memory in amnestic mild cognitive impairment: a preliminary investigation

PubMed Central

2011-01-01

Background Decline in episodic memory is one of the hallmark features of Alzheimer's disease (AD) and is also a defining feature of amnestic Mild Cognitive Impairment (MCI), which is posited as a potential prodrome of AD. While deficits in episodic memory are well documented in MCI, the nature of this impairment remains relatively under-researched, particularly for those domains with direct relevance and meaning for the patient's daily life. In order to fully explore the impact of disruption to the episodic memory system on everyday memory in MCI, we examined participants' episodic memory capacity using a battery of experimental tasks with real-world relevance. We investigated episodic acquisition and delayed recall (story-memory), associative memory (face-name pairings), spatial memory (route learning and recall), and memory for everyday mundane events in 16 amnestic MCI and 18 control participants. Furthermore, we followed MCI participants longitudinally to gain preliminary evidence regarding the possible predictive efficacy of these real-world episodic memory tasks for subsequent conversion to AD. Results The most discriminating tests at baseline were measures of acquisition, delayed recall, and associative memory, followed by everyday memory, and spatial memory tasks, with MCI patients scoring significantly lower than controls. At follow-up (mean time elapsed: 22.4 months), 6 MCI cases had progressed to clinically probable AD. Exploratory logistic regression analyses revealed that delayed associative memory performance at baseline was a potential predictor of subsequent conversion to AD. Conclusions As a preliminary study, our findings suggest that simple associative memory paradigms with real-world relevance represent an important line of enquiry in future longitudinal studies charting MCI progression over time. PMID:21816065

Disent to Pairing Mechanism

NASA Astrophysics Data System (ADS)

Cheng, Kaijia; Cheng, Shuyu

Up to now, the pairing mechanism is regarded as the rule of thumb criterion of an acceptable theory of superconductivity. It is generally held as a taboo for any theory which is not founded on this basis. However this is not true and it misleads the direction for the theoretical research for both the high and low temperature regions and eventually delays the progress in practice. It is now the time to clear up the situation.

The Relationship among Health Education Systems, Inc. Progression and Exit Examination Scores, Day or Evening Enrollment, Final Grade Point Average and NCLEX-RN® Success in Associate Degree Nursing Students

ERIC Educational Resources Information Center

Barnwell-Sanders, Pamela

2015-01-01

Graduates of associate degree (AD) nursing programs form the largest segment of first-time National Council Licensure Examination for Registered Nurses (NCLEX-RN®) test takers, yet also experience the highest rate of NCLEX-RN® failures. NCLEX-RN® failure delays entry into the profession, adding an emotional and financial toll to the unsuccessful…

Delayed splenic rupture: dating the sub-capsular hemorrhage as a useful task to evaluate causal relationships with trauma.

PubMed

Riezzo, Irene; Di Battista, Benedetta; De Salvia, Alessandra; Cantatore, Santina; Neri, Margherita; Pomara, Cristoforo; Turillazzi, Emanuela; Fineschi, Vittorio

2014-01-01

The aim of the paper was to perform a chronological assessment of the phenomenon of delayed rupture of the spleen, to assess the phenomenological order about the sub-capsular hematoma transformation to determine the causal relationship with trauma as hypothetical cause of death. 80 cases of blunt trauma with splenic capsular hematoma and subsequent rupture of the spleen were evaluated: 38 had an acute rupture of the spleen, 42 presented a break in days or weeks after the traumatic injury. Time between the traumatic event and delayed rupture of the spleen is within a range of time from one day to more than one month. Data recorded included age, sex, type of trauma, injury severity score, grade of splenic injury, associated intra-abdominal injuries, pathologic specimen evaluation. Immunohistochemical investigation of perisplenic hematoma or laceration was performed utilizing polyclonal antibodies anti-fibrinogen, CD61 and CD68, and showed structural chronological differences of sub-capsular hematoma. Expression of modification and organization of erythrocytes, fibrinogen, platelets and macrophages provides an informative picture of the progression of reparative phenomena associated with sub-capsular hematoma and subsequent delayed splenic rupture. Sub-capsular splenic hematoma dating, which we divided into 4 phases, is representing a task in both clinical practice and forensic pathology. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Tobacco demand, delay discounting, and smoking topography among smokers with and without psychopathology.

PubMed

Farris, Samantha G; Aston, Elizabeth R; Abrantes, Ana M; Zvolensky, Michael J

2017-10-01

Tobacco demand (i.e., relative value attributed to a given reinforcer) and delay discounting (i.e., relative preference for smaller immediate rewards over larger delayed rewards) are two behavioral economic processes that are linked to the progression of problematic substance use. These processes have not been studied among those with psychopathology, a vulnerable group of smokers. The current study examined differences in tobacco demand and delay discounting, and their association with smoking topography among smokers with (n=43) and without (n=64) past-year psychopathology. Adult daily smokers (n=107,M age =43.5; SD=9.7) participated in a study on "smoking behavior." Past-year psychological disorders were assessed via a clinician-administered diagnostic assessment. All subjects participated in an ad libitum smoking trial and then completed an assessment of delay discounting (Monetary Choice Questionnaire) and tobacco demand (Cigarette Purchase Task) approximately 45-60min post-smoking. Smokers with psychopathology, compared to those without, had significantly higher demand intensity and maximum expenditure on tobacco (O max ), but did not differ on other demand indices or delay discounting. Smokers with psychopathology had shorter average inter-puff intervals and shorter time to cigarette completion than smokers without psychopathology. Tobacco demand and delay discounting measures were significantly intercorrelated among smokers with psychopathology, but not those without. Both behavioral economic measures were associated with specific aspects of smoking topography in smokers with psychopathology. The association between tobacco demand and delay discounting is evident among smokers with psychopathology and both measures were most consistently related to smoking behavior. Copyright © 2017 Elsevier B.V. All rights reserved.

Efficacy of benazepril hydrochloride to delay the progression of occult dilated cardiomyopathy in Doberman Pinschers.

PubMed

O'Grady, M R; O'Sullivan, M L; Minors, S L; Horne, R

2009-01-01

Angiotensin converting enzyme inhibitors (ACEIs) are recommended in people to treat asymptomatic (occult) dilated cardiomyopathy (DCM). Efficacy of therapy in occult DCM in dogs is unknown. ACEIs, specifically benazepril hydrochloride (BH), will delay the onset of overt DCM in Doberman Pinschers. Ninety-one Doberman Pinschers were studied, 57 dogs received BH, and 34 dogs no ACEI. Retrospective study of the medical records of all Doberman Pinschers with occult DCM that received BH or no ACEI between April 1989 and February 2003. Two criteria of left ventricular enlargement were used for enrollment: one independent of body weight (BW) (C1) and the other indexed to BW (C2). Cox proportional hazards analyses were used to identify variables associated with the onset of overt DCM. On univariate analysis the median time to onset of overt DCM was significantly longer for the benazepril group (for C1: 425 days for BH, 95% confidence interval [CI] 264-625 days; 339 days for no ACEI, CI 172-453 days, P= .02; for C2: 454 days for BH, CI 264-628 days; 356 days for no ACEI, CI 181-547 days, P= .02). The hazard ratio (HR) (benazepril/no ACEI) was 0.57, CI 0.35-0.94, P= .03 for C1; HR = 0.56, CI 0.34-0.93, P= .02 for C2. On multivariate analysis, BH significantly delayed onset of overt DCM (HR [benazepril/no ACEI] = 0.45, CI 0.26-0.78, P < .01, for C1; HR = 0.36, CI 0.21-0.63, P < .01, for C2). BH in particular and ACEIs in general might delay the progression of occult DCM. Prospective studies are warranted to test this theory.

Measuring and modeling the interaction among reward size, delay to reward, and satiation level on motivation in monkeys.

PubMed

Minamimoto, Takafumi; La Camera, Giancarlo; Richmond, Barry J

2009-01-01

Motivation is usually inferred from the likelihood or the intensity with which behavior is carried out. It is sensitive to external factors (e.g., the identity, amount, and timing of a rewarding outcome) and internal factors (e.g., hunger or thirst). We trained macaque monkeys to perform a nonchoice instrumental task (a sequential red-green color discrimination) while manipulating two external factors: reward size and delay-to-reward. We also inferred the state of one internal factor, level of satiation, by monitoring the accumulated reward. A visual cue indicated the forthcoming reward size and delay-to-reward in each trial. The fraction of trials completed correctly by the monkeys increased linearly with reward size and was hyperbolically discounted by delay-to-reward duration, relations that are similar to those found in free operant and choice tasks. The fraction of correct trials also decreased progressively as a function of the satiation level. Similar (albeit noiser) relations were obtained for reaction times. The combined effect of reward size, delay-to-reward, and satiation level on the proportion of correct trials is well described as a multiplication of the effects of the single factors when each factor is examined alone. These results provide a quantitative account of the interaction of external and internal factors on instrumental behavior, and allow us to extend the concept of subjective value of a rewarding outcome, usually confined to external factors, to account also for slow changes in the internal drive of the subject.

Measuring and Modeling the Interaction Among Reward Size, Delay to Reward, and Satiation Level on Motivation in Monkeys

PubMed Central

Minamimoto, Takafumi; La Camera, Giancarlo; Richmond, Barry J.

2009-01-01

Motivation is usually inferred from the likelihood or the intensity with which behavior is carried out. It is sensitive to external factors (e.g., the identity, amount, and timing of a rewarding outcome) and internal factors (e.g., hunger or thirst). We trained macaque monkeys to perform a nonchoice instrumental task (a sequential red-green color discrimination) while manipulating two external factors: reward size and delay-to-reward. We also inferred the state of one internal factor, level of satiation, by monitoring the accumulated reward. A visual cue indicated the forthcoming reward size and delay-to-reward in each trial. The fraction of trials completed correctly by the monkeys increased linearly with reward size and was hyperbolically discounted by delay-to-reward duration, relations that are similar to those found in free operant and choice tasks. The fraction of correct trials also decreased progressively as a function of the satiation level. Similar (albeit noiser) relations were obtained for reaction times. The combined effect of reward size, delay-to-reward, and satiation level on the proportion of correct trials is well described as a multiplication of the effects of the single factors when each factor is examined alone. These results provide a quantitative account of the interaction of external and internal factors on instrumental behavior, and allow us to extend the concept of subjective value of a rewarding outcome, usually confined to external factors, to account also for slow changes in the internal drive of the subject. PMID:18987119

Pain management trend of vaso-occulsive crisis (VOC) at a community hospital emergency department (ED) for patients with sickle cell disease.

PubMed

Inoue, Susumu; Khan, Isra'a; Mushtaq, Rao; Sanikommu, Srinivasa Reddy; Mbeumo, Carline; LaChance, Jenny; Roebuck, Michael

2016-01-01

Pain management at the emergency department (ED) for vaso-occulsive crisis (VOC) for patients with sickle cell disease has not been optimum, with a long delay in giving the initial analgesic. We conducted a retrospective survey over a 7-year period to determine our ED's timing in giving pain medication to patients with VOC as a quality improvement project. We compared different periods, children vs adults, and the influence of gender in the analgesic administration timing. This is a retrospective chart review of three different periods: (1) years 2007-2008, (2) years 2011-2012, and (3) year 2013. We extracted relevant information from ED records. Data were analyzed using Student t test, chi-square analysis, and the Kruskal-Wallis test. There was a progressive improvement in the time interval to the 1st analgesic over these three periods. Children received analgesics more quickly than adults in all periods. Male adult patients received pain medication faster than female adult patients, although initial pain scores were higher in female than in male patients. Progressively fewer pediatric patients utilized ED over these three periods, but no difference for adult patients was observed. The proportion of pediatric patients admitted to the hospital increased with each period. The progressive decrease in both the number of patients and the number of visits to the ED by children suggested that the collective number of VOC in children has decreased, possibly secondary to the dissemination of hydroxyurea use. We failed to observe the same trend in adult patients. The need for IV access, and ordering laboratory tests or imaging studies tends to delay analgesic administration. Delay in administration of the first analgesic was more pronounced for female adult patients than male adult patients in spite of their higher pain score. Health care providers working in ED should make conscious efforts to respect pain in women as well as pain in men. Though not proven from this study, we believe that a significantly wider use of hydroxyurea by adult patients most likely would reduce their utilization of ED for the purpose of relief of pain, and further pediatric hematologists may be better positioned to increase hydroxyurea adherence by young adult patients, since they have had established rapport with them before transitioning to adult care.

Factors affecting the diagnostic delay in amyotrophic lateral sclerosis.

PubMed

Cellura, Eleonora; Spataro, Rossella; Taiello, Alfonsa Claudia; La Bella, Vincenzo

2012-07-01

Although amyotrophic lateral sclerosis (ALS) is a relentlessly progressive disorder, early diagnosis allows a prompt start with the specific drug riluzole and an accurate palliative care planning. ALS at onset may however mimic several disorders, some of them treatable (e.g., multifocal motor neuropathy) or epidemiologically more frequent (e.g., cervical myelopathy). To study the delay from onset to diagnosis in a cohort of ALS patients and to the variables that may affect it. We performed a retrospective analysis of the diagnostic delays in a cohort of 260 patients affected by ALS (M/F = 1.32) followed at our tertiary referral ALS Center between 2000 and 2007. The median time from onset to diagnosis was 11 months (range: 6-21) for the whole ALS cohort, 10 months (range: 6-15) in bulbar-onset (n = 65) and 12 months (range: 7-23) in spinal-onset (n = 195) patients (p = 0.3). 31.1% of patients received other diagnoses before ALS and this led to a significant delay of the correct diagnosis in this group (other diagnoses before ALS, n = 81: median delay, 15 months [9.75-24.25] vs ALS, n = 179, median delay, 9 months [6-15.25], p < 0.001). The diagnostic delay in ALS is about one year, besides the growing number of tertiary centres and the spread of information about the disease through media and internet. Cognitive errors based on an incorrect use of heuristics might represent an important contributing factor. Furthermore, the length of the differential diagnosis from other disorders and delays in referral to the neurologist seems to be positively associated with the delay in diagnosis. Copyright © 2011 Elsevier B.V. All rights reserved.

UV-C irradiation delays mitotic progression by recruiting Mps1 to kinetochores

PubMed Central

Zhang, Xiaojuan; Ling, Youguo; Wang, Wenjun; Zhang, Yanhong; Ma, Qingjun; Tan, Pingping; Song, Ting; Wei, Congwen; Li, Ping; Liu, Xuedong; Ma, Runlin Z.; Zhong, Hui; Cao, Cheng; Xu, Quanbin

2013-01-01

The effect of UV irradiation on replicating cells during interphase has been studied extensively. However, how the mitotic cell responds to UV irradiation is less well defined. Herein, we found that UV-C irradiation (254 nm) increases recruitment of the spindle checkpoint proteins Mps1 and Mad2 to the kinetochore during metaphase, suggesting that the spindle assembly checkpoint (SAC) is reactivated. In accordance with this, cells exposed to UV-C showed delayed mitotic progression, characterized by a prolonged chromosomal alignment during metaphase. UV-C irradiation also induced the DNA damage response and caused a significant accumulation of γ-H2AX on mitotic chromosomes. Unexpectedly, the mitotic delay upon UV-C irradiation is not due to the DNA damage response but to the relocation of Mps1 to the kinetochore. Further, we found that UV-C irradiation activates Aurora B kinase. Importantly, the kinase activity of Aurora B is indispensable for full recruitment of Mps1 to the kinetochore during both prometaphase and metaphase. Taking these findings together, we propose that UV irradiation delays mitotic progression by evoking the Aurora B-Mps1 signaling cascade, which exerts its role through promoting the association of Mps1 with the kinetochore in metaphase. PMID:23531678

Autophagy and TGF-Beta Antagonist Signaling in Breast Cancer at Premetastatic Sites

DTIC Science & Technology

2015-06-01

dormant legions. These inhibitors will be the drug leads for further medicinal chemistry and preclinical/clinical studies. 4 Body Overview Over the...autophagy, largely due to unexpected half-year delay of the official approval of our ACURO animal protocol . Below we report our progress, starting with...sections taken at various times after tail vein injection will enable us to verify that the anti-Coco MAb does not affect extravasation or homing but

Distribution of a Generic Mission Planning and Scheduling Toolkit for Astronomical Spacecraft

NASA Technical Reports Server (NTRS)

Kleiner, Steven C.

1998-01-01

This 2-year report describes the progress made to date on the project to package and distribute the planning and scheduling toolkit for the SWAS astronomical spacecraft. SWAS was scheduled to be launched on a Pegasus XL vehicle in fall 1995. Three separate failures in the launch vehicle have delayed the SWAS launch. The researchers have used this time to continue developing scheduling algorithms and GUI design. SWAS is expected to be launched this year.

Delayed diagnosis of Addison's disease: an approach to management.

PubMed

Mascarenhas, Janice V; Jude, Edward B

2014-07-18

Addison's disease accounts for the majority of cases of adrenal failure that are detected during hospital admissions. Unfortunately, prompt diagnosis of this condition is often delayed due to varied atypical manifestations and inadequate assessment at the time of presentation. We report a case of a 52-year-old woman who was detected to have hypotension during routine colonoscopy for evaluation of anaemia and progressive weight loss. During admission for evaluation of hypotension, she was also detected to have hyponatremia. Hyponatremia and hypotension failed to improve despite fluid resuscitation. Our endocrinological opinion was sought for and on further evaluation she was diagnosed with primary adrenal insufficiency. Glucocorticoid and mineralocorticoid replacement therapy were eventually instituted, which was followed by restoration of blood pressure and normalisation of serum sodium levels. 2014 BMJ Publishing Group Ltd.

Activation of BRCA1/BRCA2-Associated Helicase BACH1 Is Required for Timely Progression through S Phase▿

PubMed Central

Kumaraswamy, Easwari; Shiekhattar, Ramin

2007-01-01

BACH1 (also known as FANCJ and BRIP1) is a DNA helicase that directly interacts with the C-terminal BRCT repeat of the breast cancer susceptibility protein BRCA1. Previous biochemical and functional analyses have suggested a role for the BACH1 homolog in Caenorhabditis elegans during DNA replication. Here, we report the association of BACH1 with a distinct BRCA1/BRCA2-containing complex during the S phase of the cell cycle. Depletion of BACH1 or BRCA1 using small interfering RNAs results in delayed entry into the S phase of the cell cycle. Such timely progression through S phase requires the helicase activity of BACH1. Importantly, cells expressing a dominant negative mutation in BACH1 that results in a defective helicase displayed increased activation of DNA damage checkpoints and genomic instability. BACH1 helicase is silenced during the G1 phase of the cell cycle and is activated through a dephosphorylation event as cells enter S phase. These results point to a critical role for BACH1 helicase activity not only in the timely progression through the S phase but also in maintaining genomic stability. PMID:17664283

Non-standard radiotherapy fractionations delay the time to malignant transformation of low-grade gliomas.

PubMed

Henares-Molina, Araceli; Benzekry, Sebastien; Lara, Pedro C; García-Rojo, Marcial; Pérez-García, Víctor M; Martínez-González, Alicia

2017-01-01

Grade II gliomas are slowly growing primary brain tumors that affect mostly young patients. Cytotoxic therapies (radiotherapy and/or chemotherapy) are used initially only for patients having a bad prognosis. These therapies are planned following the "maximum dose in minimum time" principle, i. e. the same schedule used for high-grade brain tumors in spite of their very different behavior. These tumors transform after a variable time into high-grade gliomas, which significantly decreases the patient's life expectancy. In this paper we study mathematical models describing the growth of grade II gliomas in response to radiotherapy. We find that protracted metronomic fractionations, i.e. therapeutical schedules enlarging the time interval between low-dose radiotherapy fractions, may lead to a better tumor control without an increase in toxicity. Other non-standard fractionations such as protracted or hypoprotracted schemes may also be beneficial. The potential survival improvement depends on the tumor's proliferation rate and can be even of the order of years. A conservative metronomic scheme, still being a suboptimal treatment, delays the time to malignant progression by at least one year when compared to the standard scheme.

Open reduction of nasal bone fractures through an intercartilaginous incision.

PubMed

Kim, Ji Heui; Lee, Jun Ho; Hong, Seok Min; Park, Chan Hum

2013-01-01

Open reduction through an intercartilaginous incision was useful for treating delayed-diagnosed nasal bone fractures because it resulted in a successful outcome with minimal complications. Nasal bone fractures are generally managed with closed reduction, which is usually inadequate and results in airway obstruction with a delayed diagnosis of nasal bone fracture when bone healing and fibrotic adhesions around the bone fragment have progressed. This study investigated the surgical outcome of open reduction through an intercartilaginous incision for delayed-diagnosis nasal bone fractures. The study enrolled 18 patients who underwent open reduction through an intercartilaginous incision to correct delayed-diagnosis nasal bone fractures. Three independent otorhinolaryngologists evaluated the outcomes 4-35 months (average 12.7 months) postoperatively as excellent, fair or poor. The time from injury to surgery was 11-39 days (20-39 days in adults and 11-30 days in children). The 18 cases included 16 primary repairs and two revisions. A Kirschner wire was inserted in six (33.3%) patients who had unstable reduced nasal bones. Postoperatively, l5 (83%) patients had excellent results, two (11%) had fair, and one (6%) had a poor outcome. No patient experienced any complication.

The impact of delays on maternal and neonatal outcomes in Ugandan public health facilities: the role of absenteeism.

PubMed

Ackers, Louise; Ioannou, Elena; Ackers-Johnson, James

2016-11-01

Maternal mortality in low- and middle-income countries continues to remain high. The Ugandan Ministry of Health's Strategic Plan suggests that little, if any, progress has been made in Uganda in terms of improvements in Maternal Health [Millennium Development Goal (MDG) 5] and, more specifically, in reducing maternal mortality. Furthermore, the UNDP report on the MDGs describes Uganda's progress as 'stagnant'. The importance of understanding the impact of delays on maternal and neonatal outcomes in low resource settings has been established for some time. Indeed, the '3-delays' model has exposed the need for holistic multi-disciplinary approaches focused on systems change as much as clinical input. The model exposes the contribution of social factors shaping individual agency and care-seeking behaviour. It also identifies complex access issues which, when combined with the lack of timely and adequate care at referral facilities, contributes to extensive and damaging delays. It would be hard to find a piece of research on this topic that does not reference human resource factors or 'staff shortages' as a key component of this 'puzzle'. Having said that, it is rare indeed to see these human resource factors explored in any detail. In the absence of detailed critique (implicit) 'common sense' presumptions prevail: namely that the economic conditions at national level lead to inadequacies in the supply of suitably qualified health professionals exacerbated by losses to international emigration. Eight years' experience of action-research interventions in Uganda combining a range of methods has lead us to a rather stark conclusion: the single most important factor contributing to delays and associated adverse outcomes for mothers and babies in Uganda is the failure of doctors to be present at work during contracted hours. Failure to acknowledge and respond to this sensitive problem will ultimately undermine all other interventions including professional voluntarism which relies on local 'co-presence' to be effective. Important steps forward could be achieved within the current resource framework, if the political will existed. International NGOs have exacerbated this problem encouraging forms of internal 'brain drain' particularly among doctors. Arguably the system as it is rewards doctors for non-compliance resulting in massive resource inefficiencies. © The Author 2016. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine.

Effective recombination coefficient and solar zenith angle effects on low-latitude D-region ionosphere evaluated from VLF signal amplitude and its time delay during X-ray solar flares

NASA Astrophysics Data System (ADS)

Basak, Tamal; Chakrabarti, Sandip Kumar

Excess solar X-ray radiation during solar flares causes an enhancement of ionization in the ionospheric D-region and hence affects sub-ionospherically propagating VLF signal amplitude and phase. VLF signal amplitude perturbation (DeltaA) and amplitude time delay (Deltat) (vis- ´a-vis corresponding X-ray light curve as measured by GOES-15) of NWC/19.8 kHz signal have been computed for solar flares which is detected by us during Jan-Sep 2011. The signal is recorded by SoftPAL facility of IERC/ICSP, Sitapur (22(°) 27'N, 87(°) 45'E), West Bengal, India. In first part of the work, using the well known LWPC technique, we simulated the flare induced excess lower ionospheric electron density by amplitude perturbation method. Unperturbed D-region electron density is also obtained from simulation and compared with IRI-model results. Using these simulation results and time delay as key parameters, we calculate the effective electron recombination coefficient (alpha_{eff}) at solar flare peak region. Our results match with the same obtained by other established models. In the second part, we dealt with the solar zenith angle effect on D-region during flares. We relate this VLF data with the solar X-ray data. We find that the peak of the VLF amplitude occurs later than the time of the X-ray peak for each flare. We investigate this so-called time delay (Deltat). For the C-class flares we find that there is a direct correspondence between Deltat of a solar flare and the average solar zenith angle Z over the signal propagation path at flare occurrence time. Now for deeper analysis, we compute the Deltat for different local diurnal time slots DT. We find that while the time delay is anti-correlated with the flare peak energy flux phi_{max} independent of these time slots, the goodness of fit, as measured by reduced-chi(2) , actually worsens as the day progresses. The variation of the Z dependence of reduced-chi(2) seems to follow the variation of standard deviation of Z along the T_x-R_x propagation path. In other words, for the flares having almost constant Z over the path a tighter anti-correlation between Deltat and phi_{max} was observed.

Effective recombination coefficient and solar zenith angle effects on low-latitude D-region ionosphere evaluated from VLF signal amplitude and its time delay during X-ray solar flares

NASA Astrophysics Data System (ADS)

Basak, Tamal; Chakrabarti, Sandip K.

2013-12-01

Excess solar X-ray radiation during solar flares causes an enhancement of ionization in the ionospheric D-region and hence affects sub-ionospherically propagating VLF signal amplitude and phase. VLF signal amplitude perturbation (Δ A) and amplitude time delay (Δ t) (vis-á-vis corresponding X-ray light curve as measured by GOES-15) of NWC/19.8 kHz signal have been computed for solar flares which is detected by us during Jan-Sep 2011. The signal is recorded by SoftPAL facility of IERC/ICSP, Sitapur (22∘ 27'N, 87∘ 45'E), West Bengal, India. In first part of the work, using the well known LWPC technique, we simulated the flare induced excess lower ionospheric electron density by amplitude perturbation method. Unperturbed D-region electron density is also obtained from simulation and compared with IRI-model results. Using these simulation results and time delay as key parameters, we calculate the effective electron recombination coefficient ( α eff ) at solar flare peak region. Our results match with the same obtained by other established models. In the second part, we dealt with the solar zenith angle effect on D-region during flares. We relate this VLF data with the solar X-ray data. We find that the peak of the VLF amplitude occurs later than the time of the X-ray peak for each flare. We investigate this so-called time delay (Δ t). For the C-class flares we find that there is a direct correspondence between Δ t of a solar flare and the average solar zenith angle Z over the signal propagation path at flare occurrence time. Now for deeper analysis, we compute the Δ t for different local diurnal time slots DT. We find that while the time delay is anti-correlated with the flare peak energy flux ϕ max independent of these time slots, the goodness of fit, as measured by reduced- χ 2, actually worsens as the day progresses. The variation of the Z dependence of reduced- χ 2 seems to follow the variation of standard deviation of Z along the T x - R x propagation path. In other words, for the flares having almost constant Z over the path a tighter anti-correlation between Δ t and ϕ max was observed.

Chronic Disease and Perceived Developmental Progression in Adolescence.

ERIC Educational Resources Information Center

Seiffge-Krenke, Inge

1998-01-01

Examined whether chronic illness causes delays in adolescents' perceived developmental status, using annually-completed questionnaires from insulin-dependent and healthy adolescents. Found that, in first year of study, diabetic adolescents reported delays in physical maturity and an independent lifestyle compared with healthy peers. Overall…

Randomized prospective trial of ganciclovir maintenance therapy for cytomegalovirus retinitis.

PubMed

Jacobson, M A; O'Donnell, J J; Brodie, H R; Wofsy, C; Mills, J

1988-07-01

We report the first randomized prospective comparative study of long-term maintenance ganciclovir (9-[2-hydroxy-1-(hydroxymethyl)ethoxymethyl]guanine, BW759U, DHPG) therapy for cytomegalovirus retinitis in patients with the acquired immunodeficiency syndrome (AIDS). Eleven retinitis patients who received a 10-day course of ganciclovir induction therapy and then were randomized to receive either immediate daily ganciclovir maintenance therapy or deferred maintenance (eight deferred maintenance, three immediate maintenance) were evaluated for drug efficacy. Median time to retinitis progression was 42 days for the immediate maintenance group compared with 16 days for the deferred maintenance group, (P = 0.07). After crossing over to maintenance therapy, patients in the deferred group had a median time to retinitis progression of 58 days compared to 16 days while not on maintenance therapy (P = 0.13). Only 9% of cultures obtained while patients received maintenance therapy were positive for cytomegalovirus, vs 40% of those obtained off maintenance (P less than 0.001). We can state then that maintenance therapy with ganciclovir delays, but does not halt, progression of cytomegalovirus retinitis and suppresses, but does not eradicate, cytomegalovirus shedding in patients with AIDS.

Potential control of multiple sclerosis by cannabis and the endocannabinoid system.

PubMed

Pryce, Gareth; Baker, David

2012-08-01

For many years, multiple sclerosis (MS) patients have been self-medicating with illegal street cannabis to alleviate symptoms associated with MS. Data from animal models of MS and clinical studies have supported the anecdotal data that cannabis can improve symptoms such as limb spasticity, which are commonly associated with progressive MS, by the modulation of excessive neuronal signalling. This has lead to cannabis-based medicines being approved for the treatment of pain and spasticity in MS for the first time. Experimental studies into the biology of the endocannabinoid system have revealed that cannabinoids have activity, not only in symptom relief but also potentially in neuroprotective strategies which may slow disease progression and thus delay the onset of symptoms such as spasticity. This review appraises the current knowledge of cannabinoid biology particularly as it pertains to MS and outlines potential future therapeutic strategies for the treatment of disease progression in MS.

Necrotizing fasciitis in a patient with type 2 diabetes mellitus.

PubMed

Kanuck, David M; Zgonis, Thomas; Jolly, Gary Peter

2006-01-01

Necrotizing fasciitis is a soft-tissue infection characterized by extensive necrosis of subcutaneous fat, neurovascular structures, and fascia. In general, fascial necrosis precedes muscle and skin involvement, hence its namesake. Initially, this uncommon and rapidly progressive disease process can present as a form of cellulitis or superficial abscess. However, the high morbidity and mortality rates associated with necrotizing fasciitis suggest a more serious, ominous condition. A delay in diagnosis can result in progressive advancement highlighted by widespread infection, multiple-organ involvement, and, ultimately, death. We present a case of limb salvage in a 52-year-old patient with type 2 diabetes mellitus and progressive fascial necrosis. A detailed review of the literature is presented, and current treatment modalities are described. Aggressive surgical debridement, comprehensive medical management of the sepsis and comorbidities, and timely closure of the resultant wound or wounds are essential for a successful outcome.

Clearance of Hepatitis C Virus Prior to Lung Transplantation: A Case Report.

PubMed

Shafii, A E; Harris, D D; Baz, M

2017-09-01

Hepatitis C virus (HCV) continues to be considered a relative contraindication to lung transplantation due to concerns of progression of liver disease with the introduction of immunosuppression. Since the recent introduction of effective antiviral therapy for HCV, new approaches in the management of the HCV-positive recipient are being utilized in liver transplantation to clear HCV pre- and post-transplant. Herein, we report use of ledipasvir/sofosbuvir for HCV clearance prior to lung transplantation in a patient with usual interstitial pneumonia. Listing for transplant was delayed until completion of HCV treatment, and he subsequently required extracorporeal membrane oxygenation as a bridge to transplantation due to progressive hypoxia. With antiviral cure rates exceeding 90%, HCV should no longer be considered a relative contraindication to lung transplant, and timing of antiviral treatment should consider the progressive nature of the recipient's lung disease. Copyright © 2017 Elsevier Inc. All rights reserved.

Autonomous Mission Operations Roadmap

NASA Technical Reports Server (NTRS)

Frank, Jeremy David

2014-01-01

As light time delays increase, the number of such situations in which crew autonomy is the best way to conduct the mission is expected to increase. However, there are significant open questions regarding which functions to allocate to ground and crew as the time delays increase. In situations where the ideal solution is to allocate responsibility to the crew and the vehicle, a second question arises: should the activity be the responsibility of the crew or an automated vehicle function? More specifically, we must answer the following questions: What aspects of mission operation responsibilities (Plan, Train, Fly) should be allocated to ground based or vehicle based planning, monitoring, and control in the presence of significant light-time delay between the vehicle and the Earth?How should the allocated ground based planning, monitoring, and control be distributed across the flight control team and ground system automation? How should the allocated vehicle based planning, monitoring, and control be distributed between the flight crew and onboard system automation?When during the mission should responsibility shift from flight control team to crew or from crew to vehicle, and what should the process of shifting responsibility be as the mission progresses? NASA is developing a roadmap of capabilities for Autonomous Mission Operations for human spaceflight. This presentation will describe the current state of development of this roadmap, with specific attention to in-space inspection tasks that crews might perform with minimum assistance from the ground.

Outcome and toxicity associated with a dose-intensified, maintenance-free CHOP-based chemotherapy protocol in canine lymphoma: 130 cases.

PubMed

Sorenmo, Karin; Overley, B; Krick, E; Ferrara, T; LaBlanc, A; Shofer, F

2010-09-01

A dose-intensified/dose-dense chemotherapy protocol for canine lymphoma was designed and implemented at the Veterinary Hospital of the University of Pennsylvania. In this study, we describe the clinical characteristics, prognostic factors, efficacy and toxicity in 130 dogs treated with this protocol. The majority of the dogs had advanced stage disease (63.1% stage V) and sub-stage b (58.5%). The median time to progression (TTP) and lymphoma-specific survival were 219 and 323 days, respectively. These results are similar to previous less dose-intense protocols. Sub-stage was a significant negative prognostic factor for survival. The incidence of toxicity was high; 53.9 and 45% of the dogs needed dose reductions and treatment delays, respectively. Dogs that required dose reductions and treatment delays had significantly longer TTP and lymphoma-specific survival times. These results suggest that dose density is important, but likely relative, and needs to be adjusted according to the individual patient's toxicity for optimal outcome.

Forming Human-Robot Teams Across Time and Space

NASA Technical Reports Server (NTRS)

Hambuchen, Kimberly; Burridge, Robert R.; Ambrose, Robert O.; Bluethmann, William J.; Diftler, Myron A.; Radford, Nicolaus A.

2012-01-01

NASA pushes telerobotics to distances that span the Solar System. At this scale, time of flight for communication is limited by the speed of light, inducing long time delays, narrow bandwidth and the real risk of data disruption. NASA also supports missions where humans are in direct contact with robots during extravehicular activity (EVA), giving a range of zero to hundreds of millions of miles for NASA s definition of "tele". . Another temporal variable is mission phasing. NASA missions are now being considered that combine early robotic phases with later human arrival, then transition back to robot only operations. Robots can preposition, scout, sample or construct in advance of human teammates, transition to assistant roles when the crew are present, and then become care-takers when the crew returns to Earth. This paper will describe advances in robot safety and command interaction approaches developed to form effective human-robot teams, overcoming challenges of time delay and adapting as the team transitions from robot only to robots and crew. The work is predicated on the idea that when robots are alone in space, they are still part of a human-robot team acting as surrogates for people back on Earth or in other distant locations. Software, interaction modes and control methods will be described that can operate robots in all these conditions. A novel control mode for operating robots across time delay was developed using a graphical simulation on the human side of the communication, allowing a remote supervisor to drive and command a robot in simulation with no time delay, then monitor progress of the actual robot as data returns from the round trip to and from the robot. Since the robot must be responsible for safety out to at least the round trip time period, the authors developed a multi layer safety system able to detect and protect the robot and people in its workspace. This safety system is also running when humans are in direct contact with the robot, so it involves both internal fault detection as well as force sensing for unintended external contacts. The designs for the supervisory command mode and the redundant safety system will be described. Specific implementations were developed and test results will be reported. Experiments were conducted using terrestrial analogs for deep space missions, where time delays were artificially added to emulate the longer distances found in space.

Cost-effectiveness analysis of interferon beta-1b for the treatment of patients with a first clinical event suggestive of multiple sclerosis.

PubMed

Caloyeras, John P; Zhang, Bin; Wang, Cheng; Eriksson, Marianne; Fredrikson, Sten; Beckmann, Karola; Knappertz, Volker; Pohl, Christoph; Hartung, Hans-Peter; Shah, Dhvani; Miller, Jeffrey D; Sandbrink, Rupert; Lanius, Vivian; Gondek, Kathleen; Russell, Mason W

2012-05-01

To assess, from a Swedish societal perspective, the cost effectiveness of interferon β-1b (IFNB-1b) after an initial clinical event suggestive of multiple sclerosis (MS) (ie, early treatment) compared with treatment after onset of clinically definite MS (CDMS) (ie, delayed treatment). A Markov model was developed, using patient level data from the BENEFIT trial and published literature, to estimate health outcomes and costs associated with IFNB-1b for hypothetical cohorts of patients after an initial clinical event suggestive of MS. Health states were defined by Kurtzke Expanded Disability Status Scale (EDSS) scores. Model outcomes included quality-adjusted life years (QALYs), total costs (including both direct and indirect costs), and incremental cost-effectiveness ratios. Sensitivity analyses were performed on key model parameters to assess the robustness of model results. In the base case scenario, early IFNB-1b treatment was economically dominant (ie, less costly and more effective) versus delayed IFNB-1b treatment when QALYs were used as the effectiveness metric. Sensitivity analyses showed that the cost-effectiveness results were sensitive to model time horizon. Compared with the delayed treatment strategy, early treatment of MS was also associated with delayed EDSS progressions, prolonged time to CDMS diagnosis, and a reduction in frequency of relapse. Early treatment with IFNB-1b for a first clinical event suggestive of MS was found to improve patient outcomes while controlling costs. Copyright © 2012 Elsevier HS Journals, Inc. All rights reserved.

Role of Diet Modulation and AMPK in Ovarian Cancer Progression and Outcome

DTIC Science & Technology

2014-10-01

preventive agent in not only preventing or delaying ovarian cancer growth but also cancers. It can be the ‘ aspirin ’ for cancers...preventive agent in not only preventing or delaying ovarian cancer growth but also cancers. It can be the ‘ aspirin ’ for cancers

Time-Restricted Feeding Improves Circadian Dysfunction as well as Motor Symptoms in the Q175 Mouse Model of Huntington's Disease.

PubMed

Wang, Huei-Bin; Loh, Dawn H; Whittaker, Daniel S; Cutler, Tamara; Howland, David; Colwell, Christopher S

2018-01-01

Huntington's disease (HD) patients suffer from a progressive neurodegeneration that results in cognitive, psychiatric, cardiovascular, and motor dysfunction. Disturbances in sleep/wake cycles are common among HD patients with reports of delayed sleep onset, frequent bedtime awakenings, and fatigue during the day. The heterozygous Q175 mouse model of HD has been shown to phenocopy many HD core symptoms including circadian dysfunctions. Because circadian dysfunction manifests early in the disease in both patients and mouse models, we sought to determine if early intervention that improve circadian rhythmicity can benefit HD and delay disease progression. We determined the effects of time-restricted feeding (TRF) on the Q175 mouse model. At six months of age, the animals were divided into two groups: ad libitum (ad lib) and TRF. The TRF-treated Q175 mice were exposed to a 6-h feeding/18-h fasting regimen that was designed to be aligned with the middle of the time when mice are normally active. After three months of treatment (when mice reached the early disease stage), the TRF-treated Q175 mice showed improvements in their locomotor activity rhythm and sleep awakening time. Furthermore, we found improved heart rate variability (HRV), suggesting that their autonomic nervous system dysfunction was improved. Importantly, treated Q175 mice exhibited improved motor performance compared to untreated Q175 controls, and the motor improvements were correlated with improved circadian output. Finally, we found that the expression of several HD-relevant markers was restored to WT levels in the striatum of the treated mice using NanoString gene expression assays.

The corpus callosum in primates: processing speed of axons and the evolution of hemispheric asymmetry

PubMed Central

Phillips, Kimberley A.; Stimpson, Cheryl D.; Smaers, Jeroen B.; Raghanti, Mary Ann; Jacobs, Bob; Popratiloff, Anastas; Hof, Patrick R.; Sherwood, Chet C.

2015-01-01

Interhemispheric communication may be constrained as brain size increases because of transmission delays in action potentials over the length of axons. Although one might expect larger brains to have progressively thicker axons to compensate, spatial packing is a limiting factor. Axon size distributions within the primate corpus callosum (CC) may provide insights into how these demands affect conduction velocity. We used electron microscopy to explore phylogenetic variation in myelinated axon density and diameter of the CC from 14 different anthropoid primate species, including humans. The majority of axons were less than 1 µm in diameter across all species, indicating that conduction velocity for most interhemispheric communication is relatively constant regardless of brain size. The largest axons within the upper 95th percentile scaled with a progressively higher exponent than the median axons towards the posterior region of the CC. While brain mass among the primates in our analysis varied by 97-fold, estimates of the fastest cross-brain conduction times, as conveyed by axons at the 95th percentile, varied within a relatively narrow range between 3 and 9 ms across species, whereas cross-brain conduction times for the median axon diameters differed more substantially between 11 and 38 ms. Nonetheless, for both size classes of axons, an increase in diameter does not entirely compensate for the delay in interhemispheric transmission time that accompanies larger brain size. Such biophysical constraints on the processing speed of axons conveyed by the CC may play an important role in the evolution of hemispheric asymmetry. PMID:26511047

Key changes in denervated muscles and their impact on regeneration and reinnervation

PubMed Central

Wu, Peng; Chawla, Aditya; Spinner, Robert J.; Yu, Cong; Yaszemski, Michael J.; Windebank, Anthony J.; Wang, Huan

2014-01-01

The neuromuscular junction becomes progressively less receptive to regenerating axons if nerve repair is delayed for a long period of time. It is difficult to ascertain the denervated muscle's residual receptivity by time alone. Other sensitive markers that closely correlate with the extent of denervation should be found. After a denervated muscle develops a fibrillation potential, muscle fiber conduction velocity, muscle fiber diameter, muscle wet weight, and maximal isometric force all decrease; remodeling increases neuromuscular junction fragmentation and plantar area, and expression of myogenesis-related genes is initially up-regulated and then down-regulated. All these changes correlate with both the time course and degree of denervation. The nature and time course of these denervation changes in muscle are reviewed from the literature to explore their roles in assessing both the degree of detrimental changes and the potential success of a nerve repair. Fibrillation potential amplitude, muscle fiber conduction velocity, muscle fiber diameter, mRNA expression levels of myogenic regulatory factors and nicotinic acetylcholine receptor could all reflect the severity and length of denervation and the receptiveness of denervated muscle to regenerating axons, which could possibly offer an important clue for surgical choices and predict the outcomes of delayed nerve repair. PMID:25422641

Socio-economic status influences access to second-line disease modifying treatment in Relapsing Remitting Multiple Sclerosis patients

PubMed Central

Dejardin, Olivier; Droulon, Karine; Launoy, Guy; Defer, Gilles

2018-01-01

Objective In MS, Socio-Economic status (SES) may influence healthcare and access to disease-modifying treatments (DMTs). Optimising delays to switch patients to a second-line DMT may hamper disease progression most effectively and achieve long term disease control. The objective of this study is to identify the influence of SES on the delay between first and second line DMT in RRMS patients, in Western-Normandy, France. Methods The association between SES and the delay to access a second-line DMT were studied using data from the MS registry of Western-Normandy including 733 patients with a diagnosis of RRMS during the period in question [1982–2011]. We used the European Deprivation Index (EDI), a score with a rank level inversely related to SES. We performed multivariate adjusted Cox models for studying EDI effect on the delay between first and second line DMT. Results No significant influence of SES was observed on delay to access a second-line DMT if first-line DMT exposure time was less than 5 years. After 5 years from initiation of first-line treatment the risk of accessing a second-line DMT is 3 times higher for patients with lower deprivation indices (1st quintile of EDI) ([HR] 3.14 95%CI [1.72–5.72], p-value<0.001) compared to patients with higher values (EDI quintiles 2 to 5). Interpretation In RRMS, a high SES may facilitate access to a second-line DMT a few years after first-line DMT exposure. Greater consideration should also be given to the SES of MS patients as a risk factor in therapeutic healthcare issues throughout medical follow-up. PMID:29390025

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.

Nucleus accumbens core lesions induce sub-optimal choice and reduce sensitivity to magnitude and delay in impulsive choice tasks

PubMed Central

Steele, Catherine C.; Peterson, Jennifer R.; Marshall, Andrew T.; Stuebing, Sarah L.; Kirkpatrick, Kimberly

2017-01-01

The nucleus accumbens core (NAc) has long been recognized as an important contributor to the computation of reward value that is critical for impulsive choice behavior. Impulsive choice refers to choosing a smaller-sooner (SS) over a larger-later (LL) reward when the LL is more optimal in terms of the rate of reward delivery. Two experiments examined the role of the NAc in impulsive choice and its component processes of delay and magnitude processing. Experiment 1 delivered an impulsive choice task with manipulations of LL reward magnitude, followed by a reward magnitude discrimination task. Experiment 2 tested impulsive choice under manipulations of LL delay, followed by temporal bisection and progressive interval tasks. NAc lesions, in comparison to sham control lesions, produced suboptimal preferences that resulted in lower reward earning rates, and led to reduced sensitivity to magnitude and delay within the impulsive choice task. The secondary tasks revealed intact reward magnitude and delay discrimination abilities, but the lesion rats persisted in responding more as the progressive interval increased during the session. The results suggest that the NAc is most critical for demonstrating good sensitivity to magnitude and delay, and adjusting behavior accordingly. Ultimately, the NAc lesions induced suboptimal choice behavior rather than simply promoting impulsive choice, suggesting that an intact NAc is necessary for optimal decision making. PMID:29146281

Dynamical Consequences of Bandpass Feedback Loops in a Bacterial Phosphorelay

PubMed Central

Sen, Shaunak; Garcia-Ojalvo, Jordi; Elowitz, Michael B.

2011-01-01

Under conditions of nutrient limitation, Bacillus subtilis cells terminally differentiate into a dormant spore state. Progression to sporulation is controlled by a genetic circuit consisting of a phosphorelay embedded in multiple transcriptional feedback loops, which is used to activate the master regulator Spo0A by phosphorylation. These transcriptional regulatory interactions are “bandpass”-like, in the sense that activation occurs within a limited band of Spo0A∼P concentrations. Additionally, recent results show that the phosphorelay activation occurs in pulses, in a cell-cycle dependent fashion. However, the impact of these pulsed bandpass interactions on the circuit dynamics preceding sporulation remains unclear. In order to address this question, we measured key features of the bandpass interactions at the single-cell level and analyzed them in the context of a simple mathematical model. The model predicted the emergence of a delayed phase shift between the pulsing activity of the different sporulation genes, as well as the existence of a stable state, with elevated Spo0A activity but no sporulation, embedded within the dynamical structure of the system. To test the model, we used time-lapse fluorescence microscopy to measure dynamics of single cells initiating sporulation. We observed the delayed phase shift emerging during the progression to sporulation, while a re-engineering of the sporulation circuit revealed behavior resembling the predicted additional state. These results show that periodically-driven bandpass feedback loops can give rise to complex dynamics in the progression towards sporulation. PMID:21980382

Buying time: a rationale for examining the use of circadian rhythm and sleep interventions to delay progression of mild cognitive impairment to Alzheimer's disease.

PubMed

Landry, Glenn J; Liu-Ambrose, Teresa

2014-01-01

As of 2010, the worldwide economic impact of dementia was estimated at $604 billion USD; and without discovery of a cure or effective interventions to delay disease progression, dementia's annual global economic impact is expected to surpass $1 trillion USD as early as 2030. Alzheimer's disease (AD) is the leading cause of dementia accounting for over 75% of all cases. Toxic accumulation of amyloid beta (Aβ), either by overproduction or some clearance failure, is thought to be an underlying mechanism of the neuronal cell death characteristic of AD-though this amyloid hypothesis has been increasingly challenged in recent years. A compelling alternative hypothesis points to chronic neuroinflammation as a common root in late-life degenerative diseases including AD. Apolipoprotein-E (APOE) genotype is the strongest genetic risk factor for AD: APOE-ε4 is proinflammatory and individuals with this genotype accumulate more Aβ, are at high risk of developing AD, and almost half of all AD patients have at least one ε4 allele. Recent studies suggest a bidirectional relationship exists between sleep and AD pathology. Sleep may play an important role in Aβ clearance, and getting good quality sleep vs. poor quality sleep might reduce the AD risk associated with neuroinflammation and the ε4 allele. Taken together, these findings are particularly important given the sleep disruptions commonly associated with AD and the increased burden disrupted sleep poses for AD caregivers. The current review aims to: (1) identify individuals at high risk for dementia who may benefit most from sleep interventions; (2) explore the role poor sleep quality plays in exacerbating AD type dementia; (3) examine the science of sleep interventions to date; and (4) provide a road map in pursuit of comprehensive sleep interventions, specifically targeted to promote cognitive function and delay progression of dementia.

Buying time: a rationale for examining the use of circadian rhythm and sleep interventions to delay progression of mild cognitive impairment to Alzheimer’s disease

PubMed Central

Landry, Glenn J.; Liu-Ambrose, Teresa

2014-01-01

As of 2010, the worldwide economic impact of dementia was estimated at $604 billion USD; and without discovery of a cure or effective interventions to delay disease progression, dementia’s annual global economic impact is expected to surpass $1 trillion USD as early as 2030. Alzheimer’s disease (AD) is the leading cause of dementia accounting for over 75% of all cases. Toxic accumulation of amyloid beta (Aβ), either by overproduction or some clearance failure, is thought to be an underlying mechanism of the neuronal cell death characteristic of AD—though this amyloid hypothesis has been increasingly challenged in recent years. A compelling alternative hypothesis points to chronic neuroinflammation as a common root in late-life degenerative diseases including AD. Apolipoprotein-E (APOE) genotype is the strongest genetic risk factor for AD: APOE-ε4 is proinflammatory and individuals with this genotype accumulate more Aβ, are at high risk of developing AD, and almost half of all AD patients have at least one ε4 allele. Recent studies suggest a bidirectional relationship exists between sleep and AD pathology. Sleep may play an important role in Aβ clearance, and getting good quality sleep vs. poor quality sleep might reduce the AD risk associated with neuroinflammation and the ε4 allele. Taken together, these findings are particularly important given the sleep disruptions commonly associated with AD and the increased burden disrupted sleep poses for AD caregivers. The current review aims to: (1) identify individuals at high risk for dementia who may benefit most from sleep interventions; (2) explore the role poor sleep quality plays in exacerbating AD type dementia; (3) examine the science of sleep interventions to date; and (4) provide a road map in pursuit of comprehensive sleep interventions, specifically targeted to promote cognitive function and delay progression of dementia. PMID:25538616

The effects of AST-120 on chronic kidney disease progression in the United States of America: a post hoc subgroup analysis of randomized controlled trials.

PubMed

Schulman, Gerald; Berl, Tomas; Beck, Gerald J; Remuzzi, Giuseppe; Ritz, Eberhard; Shimizu, Miho; Shobu, Yuko; Kikuchi, Mami

2016-09-30

The orally administered spherical carbon adsorbent AST-120 is used on-label in Asian countries to slow renal disease progression in patients with progressive chronic kidney disease (CKD). Recently, two multinational, randomized, double-blind, placebo-controlled, phase 3 trials (Evaluating Prevention of Progression in Chronic Kidney Disease [EPPIC] trials) examined AST-120's efficacy in slowing CKD progression. This study assessed the efficacy of AST-120 in the subgroup of patients from the United States of America (USA) in the EPPIC trials. In the EPPIC trials, 2035 patients with moderate to severe CKD were studied, of which 583 were from the USA. The patients were randomly assigned to two groups of equal size that were treated with AST-120 or placebo (9 g/day). The primary end point was a composite of dialysis initiation, kidney transplantation, or serum creatinine doubling. The Kaplan-Meier curve for the time to achieve the primary end point in the placebo-treated patients from the USA was similar to that projected before the study. The per protocol subgroup analysis of the population from the USA which included patients with compliance rates of ≥67 % revealed a significant difference between the treatment groups in the time to achieve the primary end point (Hazard Ratio, 0.74; 95 % Confidence Interval, 0.56-0.97). This post hoc subgroup analysis of EPPIC study data suggests that treatment with AST-120 might delay the time to primary end point in CKD patients from the USA. A further randomized controlled trial in progressive CKD patients in the USA is necessary to confirm the beneficial effect of adding AST-120 to standard therapy regimens. ClinicalTrials.gov NCT00500682 ; NCT00501046 .

Development of in Vivo Biomarkers for Progressive Tau Pathology after Traumatic Brain Injury

DTIC Science & Technology

2016-02-01

14. ABSTRACT Athletes in contact sports who have sustained multiple concussive traumatic brain injuries are at high risk for delayed, progressive...pugilistica 3, 11 or ‘punch drunk’ syndrome 9, 12. US military personnel 13, 14 and others who have sustained multiple concussive traumatic brain...Progress to date: To date, none of the attempts to model progressive tau pathology after repetitive concussive TBI in mice has been optimal. Ongoing

Diagnostic and Treatment Challenges of Sighted Non-24-Hour Sleep-Wake Disorder.

PubMed

Malkani, Roneil G; Abbott, Sabra M; Reid, Kathryn J; Zee, Phyllis C

2018-04-15

To report the diagnostic and treatment challenges of sighted non-24-hour sleep-wake disorder (N24SWD). We report a series of seven sighted patients with N24SWD clinically evaluated by history and sleep diaries, and when available wrist actigraphy and salivary melatonin levels, and treated with timed melatonin and bright light therapy. Most patients had a history of a delayed sleep-wake pattern prior to developing N24SWD. The typical sleep-wake pattern of N24SWD was seen in the sleep diaries (and in actigraphy when available) in all patients with a daily delay in midpoint of sleep ranging 0.8 to 1.8 hours. Salivary dim light melatonin onset (DLMO) was evaluated in four patients but was missed in one. The estimated phase angle from DLMO to sleep onset ranged from 5.25 to 9 hours. All six patients who attempted timed melatonin and bright light therapy were able to entrain their sleep-wake schedules. Entrainment occurred at a late circadian phase, possibly related to the late timing of melatonin administration, though the patients often preferred late sleep times. Most did not continue treatment and continued to have a non-24-hour sleep-wake pattern. N24SWD is a chronic debilitating disorder that is often overlooked in sighted people and can be challenging to diagnose and treat. Tools to assess circadian pattern and timing can be effectively applied to aid the diagnosis. The progressive delay of the circadian rhythm poses a challenge for determining the most effective timing for melatonin and bright light therapies. Furthermore, once the circadian sleep-wake rhythm is entrained, long-term effectiveness is limited because of the behavioral and environmental structure that is required to maintain stable entrainment. © 2018 American Academy of Sleep Medicine.

First-aid with warm water delays burn progression and increases skin survival.

PubMed

Tobalem, M; Harder, Y; Tschanz, E; Speidel, V; Pittet-Cuénod, B; Wettstein, R

2013-02-01

First aid treatment for thermal injuries with cold water removes heat and decreases inflammation. However, perfusion in the ischemic zone surrounding the coagulated core can be compromised by cold-induced vasoconstriction and favor burn progression. The aim of this study is to evaluate the effect of local warming on burn progression in the rat comb burn model. 24 male Wistar rats were randomly assigned to either no treatment (control) or application of cold (17 °C) or warm (37 °C) water applied for 20 min. Evolution of burn depth, interspace necrosis, and microcirculatory perfusion were assessed with histology, planimetry, respectively with Laser Doppler flowmetry after 1 h, as well as 1, 4, and 7 days. Consistent conversion from a superficial to a deep dermal burn within 24 h was obtained in control animals. Warm and cold water significantly delayed burn depth progression, however after 4 days the burn depth was similar in all groups. Interspace necrosis was significantly reduced by warm water treatment (62±4% vs. 69±5% (cold water) and 82±3% (control); p<0.05). This was attributed to the significantly improved perfusion after warming, which was present 1 h after burn induction and was maintained thereafter (103±4% of baseline vs. 91±3% for cold water and 80±2% for control, p<0.05). In order to limit damage after burn injury, burn progression has to be prevented. Besides delaying burn progression, the application of warm water provided an additional benefit by improving the microcirculatory perfusion, which translated into increased tissue survival. Copyright © 2012 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Local Stability of AIDS Epidemic Model Through Treatment and Vertical Transmission with Time Delay

NASA Astrophysics Data System (ADS)

Novi W, Cascarilla; Lestari, Dwi

2016-02-01

This study aims to explain stability of the spread of AIDS through treatment and vertical transmission model. Human with HIV need a time to positively suffer AIDS. The existence of a time, human with HIV until positively suffer AIDS can be delayed for a time so that the model acquired is the model with time delay. The model form is a nonlinear differential equation with time delay, SIPTA (susceptible-infected-pre AIDS-treatment-AIDS). Based on SIPTA model analysis results the disease free equilibrium point and the endemic equilibrium point. The disease free equilibrium point with and without time delay are local asymptotically stable if the basic reproduction number is less than one. The endemic equilibrium point will be local asymptotically stable if the time delay is less than the critical value of delay, unstable if the time delay is more than the critical value of delay, and bifurcation occurs if the time delay is equal to the critical value of delay.

Development and Validation of the Delaying Gratification Inventory

ERIC Educational Resources Information Center

Hoerger, Michael; Quirk, Stuart W.; Weed, Nathan C.

2011-01-01

Deficits in gratification delay are associated with a broad range of public health problems, such as obesity, risky sexual behavior, and substance abuse. However, 6 decades of research on the construct has progressed less quickly than might be hoped, largely because of measurement issues. Although past research has implicated 5 domains of delay…

The effects of the framing of time on delay discounting.

PubMed

DeHart, William Brady; Odum, Amy L

2015-01-01

We examined the effects of the framing of time on delay discounting. Delay discounting is the process by which delayed outcomes are devalued as a function of time. Time in a titrating delay discounting task is often framed in calendar units (e.g., as 1 week, 1 month, etc.). When time is framed as a specific date, delayed outcomes are discounted less compared to the calendar format. Other forms of framing time; however, have not been explored. All participants completed a titrating calendar unit delay-discounting task for money. Participants were also assigned to one of two delay discounting tasks: time as dates (e.g., June 1st, 2015) or time in units of days (e.g., 5000 days), using the same delay distribution as the calendar delay-discounting task. Time framed as dates resulted in less discounting compared to the calendar method, whereas time framed as days resulted in greater discounting compared to the calendar method. The hyperboloid model fit best compared to the hyperbola and exponential models. How time is framed may alter how participants attend to the delays as well as how the delayed outcome is valued. Altering how time is framed may serve to improve adherence to goals with delayed outcomes. © Society for the Experimental Analysis of Behavior.

Puberty is delayed in male mice with dextran sodium sulfate colitis out of proportion to changes in food intake, body weight, and serum levels of leptin.

PubMed

Deboer, Mark D; Li, Yongli

2011-01-01

In boys, inflammatory bowel disease often results in delayed puberty associated with decreased bone mineral density and decreased linear growth. Our goal was to investigate whether pubertal timing and levels of leptin differed between prepubertal male mice with colitis and food-restricted (FR) mice maintained at a similar weight. We induced colitis in 32-d-old male mice using dextran sodium sulfate (DSS), resulting in 10 d of worsening colitis. We followed up these mice for separation of the prepuce from the glans penis as a marker of pubertal progression. Compared with free-feeding control mice, DSS and FR mice had significantly lower weight on d 7-10 of treatment. DSS mice had later puberty than control and FR mice. DSS mice also had smaller testes, lower FSH levels, increased systemic cytokines, and increased colonic inflammation by histology. Leptin levels were similar between DSS and FR mice, whereas both had decreases in leptin compared with controls. We conclude that DSS colitis causes delayed puberty in sexually immature male mice beyond what is seen among FR mice of similar weight, food intake, and leptin levels. These experiments provide support for the hypothesis that pubertal delay in colitis is influenced by factors beyond poor weight gain alone.

Delayed emergency department presentation in critically ill patients.

PubMed

Rodriguez, R M; Passanante, M; Phelps, M A; Dresden, G; Kriza, K; Carrasco, M; Franklin, J

2001-12-01

To determine the frequency and causes of delayed emergency department presentation in critically ill patients who did not have acute myocardial infarction and to evaluate whether factors such as age, gender, prior medical advice, lack of insurance, or low educational level are associated with delayed presentation. Prospective, descriptive analysis. Emergency department and medical intensive care unit of an urban county hospital. All adult patients admitted from the emergency department to the medical intensive care unit for reasons other than unstable angina, acute myocardial infarction, or stroke over two 9-wk blocks. Within 72 hrs of intensive care unit admission, patients or their families were interviewed to determine time elapsed between the onset of symptoms and patient emergency department presentation and to elicit reasons for delays in seeking medical treatment. We interviewed 155 of 173 (90%) of eligible patients and found that 58% waited >24 hrs before presenting to the emergency department. The most commonly cited primary reason for delays were beliefs that symptoms were not serious enough for emergency care (31%) and that symptoms would resolve spontaneously (29%). Most (55%) sought medical treatment only at the urging of family members or other advocates. Although variables such as lack of insurance and low educational level were not associated with delayed presentation, male gender and having sought medical advice before presenting to the emergency department were significantly associated with delay (p =.036 for each). Because of poor understanding of the gravity and natural progression of their symptoms, most critically ill patients waited >24 hrs to present to our emergency department. Education on warning symptom recognition for serious illnesses may be warranted not only for patients themselves but also for family members and caregivers.

The use of picture prompts and prompt delay to teach receptive labeling.

PubMed

Vedora, Joseph; Barry, Tiffany

2016-12-01

The current study extended research on picture prompts by using them with a progressive prompt delay to teach receptive labeling of pictures to 2 teenagers with autism. The procedure differed from prior research because the auditory stimulus was not presented or was presented only once during the picture-prompt condition. The results indicated that the combination of picture prompts and prompt delay was effective, although 1 participant required a procedural modification. © 2016 Society for the Experimental Analysis of Behavior.

Surfactant protein D delays Fas- and TRAIL-mediated extrinsic pathway of apoptosis in T cells.

PubMed

Djiadeu, Pascal; Kotra, Lakshmi P; Sweezey, Neil; Palaniyar, Nades

2017-05-01

Only a few extracellular soluble proteins are known to modulate apoptosis. We considered that surfactant-associated protein D (SP-D), an innate immune collectin present on many mucosal surfaces, could regulate apoptosis. Although SP-D is known to be important for immune cell homeostasis, whether SP-D affects apoptosis is unknown. In this study we aimed to determine the effects of SP-D on Jurkat T cells and human T cells dying by apoptosis. Here we show that SP-D binds to Jurkat T cells and delays the progression of Fas (CD95)-Fas ligand and TRAIL-TRAIL receptor induced, but not TNF-TNF receptor-mediated apoptosis. SP-D exerts its effects by reducing the activation of initiator caspase-8 and executioner caspase-3. SP-D also delays the surface exposure of phosphatidylserine. The effect of SP-D was ablated by the presence of caspase-8 inhibitor, but not by intrinsic pathway inhibitors. The binding ability of SP-D to dying cells decreases during the early stages of apoptosis, suggesting the release of apoptotic cell surface targets during apoptosis. SP-D also delays FasL-induced death of primary human T cells. SP-D delaying the progression of the extrinsic pathway of apoptosis could have important implications in regulating immune cell homeostasis at mucosal surfaces.

Cidofovir.

PubMed

Lea, A P; Bryson, H M

1996-08-01

Cidofovir is a nucleotide analogue which inhibits viral DNA polymerase and is effective against human cytomegalovirus (CMV) infection. It is phosphorylated to its active form by cellular enzymes. With the long intracellular half-life of its metabolites, cidofovir can be administered weekly during induction and every other week during maintenance therapy. Viral resistance has not been documented in patients treated with cidofovir to date, but has developed in vitro. Immediate cidofovir therapy delayed progression of CMV retinitis compared with deferred treatment in patients with AIDS. Cidofovir also delayed the progression of CMV retinitis relapsing after previous treatment. To avoid nephrotoxicity, probenecid and intravenous saline hydration must be administered with each dose of cidofovir.

Adult age differences in information foraging in an interactive reading environment.

PubMed

Liu, Xiaomei; Chin, Jessie; Payne, Brennan R; Fu, Wai-Tat; Morrow, Daniel G; Stine-Morrow, Elizabeth A L

2016-05-01

When learning about a single topic in natural reading environments, readers are confronted with multiple sources varying in the type and amount of information. In this situation, readers are free to adaptively respond to the constraints of the environment (e.g., through selection of resources and time allocation for study), but there may be costs of exploring and switching between sources (e.g., disruption of attention, opportunity costs for study). From an ecological perspective, such properties of the environment are expected to influence learning strategies. In the current study, we used a novel reading paradigm to investigate age differences in the effects of information richness (i.e., sentence elaboration) and costs of switching between texts (i.e., time delay) on selection of sources and study time allocation. Consistent with the ecological view, participants progressed from less informative to more informative texts. Furthermore, increased switch cost led to a tendency to allocate more effort to easier materials and to greater persistence in reading, which in turn, led to better memory in both immediate and delayed recall. Older adults showed larger effects of switch cost, such that the age difference in delayed recall was eliminated in the high switch cost condition. Based on an ecological paradigm of reading that affords choice and self-regulation, our study provided evidence for preservation with age in the ability to adapt to changing learning environments so as to improve performance. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Nutraceuticals and their preventive or potential therapeutic value in Parkinson's disease.

PubMed

Chao, Jianfei; Leung, Yen; Wang, Mingfu; Chang, Raymond Chuen-Chung

2012-07-01

Parkinson's disease (PD) is the second most common aging-related disorder in the world, after Alzheimer's disease. It is characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta and other parts of the brain, leading to motor impairment, cognitive impairment, and dementia. Current treatment methods, such as L-dopa therapy, are focused only on relieving symptoms and delaying progression of the disease. To date, there is no known cure for PD, making prevention of PD as important as ever. More than a decade of research has revealed a number of major risk factors, including oxidative stress and mitochondrial dysfunction. Moreover, numerous nutraceuticals have been found to target and attenuate these risk factors, thereby preventing or delaying the progression of PD. These nutraceuticals include vitamins C, D, E, coenzyme Q10, creatine, unsaturated fatty acids, sulfur-containing compounds, polyphenols, stilbenes, and phytoestrogens. This review examines the role of nutraceuticals in the prevention or delay of PD as well as the mechanisms of action of nutraceuticals and their potential applications as therapeutic agents, either alone or in combination with current treatment methods. © 2012 International Life Sciences Institute.

A novel live cell imaging system reveals a reversible hydrostatic pressure impact on cell cycle progression.

PubMed

Brooker, Holly R; Gyamfi, Irene A; Wieckowska, Agnieszka; Brooks, Nicholas J; Mulvihill, Daniel P; Geeves, Michael A

2018-06-21

Life is dependent upon the ability of a cell to rapidly respond to changes in environment. Small perturbations in local environments change the ability of molecules to interact and hence communicate. Hydrostatic pressure provides a rapid non-invasive, fully-reversible method for modulating affinities between molecules both in vivo and in vitro We have developed a simple fluorescence imaging chamber that allows intracellular protein dynamics and molecular events to be followed at pressures up to 200 bar in living cells. Using yeast we investigate the impact of hydrostatic pressure upon cell growth and cell cycle progression. While 100 bar has no affect upon viability, it induces a delay in chromosome segregation, resulting in the accumulation of long-undivided-bent cells, consistent with disruption of the cytoskeletons. This delay is independent of stress signalling and induces synchronisation of cell-cycle progression. Equivalent affects were observed in Candida albicans , with pressure inducing a reversible cell-cycle delay and hyphal growth. We present a simple novel non-invasive fluorescence microscopy based approach to transiently impact molecular dynamics to visualise, dissect and study signalling pathways and cellular processes in living cells. © 2018. Published by The Company of Biologists Ltd.

Dynamics of scroll waves with time-delay propagation in excitable media

NASA Astrophysics Data System (ADS)

Chen, Jiang-Xing; Xiao, Jie; Qiao, Li-Yan; Xu, Jiang-Rong

2018-06-01

Information transmission delay can be widely observed in various systems. Here, we study the dynamics of scroll waves with time-delay propagation among slices in excitable media. Weak time delay induces scroll waves to meander. Through increasing the time delay, we find a series of dynamical transitions. Firstly, the straight filament of a scroll wave becomes twisted. Then, the scroll wave breaks and forms interesting patterns. With long time delay, loosed scroll waves are maintained while their period are greatly decreased. Also, cylinder waves appears. The influences of diffusively coupling strength on the time-delay-induced scroll waves are studied. It is found that the critical time delay characterizing those transitions decreases as the coupling strength is increased. A phase diagram in the diffusive coupling-time delay plane is presented.

SIRT6 knockout cells resist apoptosis initiation but not progression: a computational method to evaluate the progression of apoptosis.

PubMed

Domanskyi, Sergii; Nicholatos, Justin W; Schilling, Joshua E; Privman, Vladimir; Libert, Sergiy

2017-11-01

Apoptosis is essential for numerous processes, such as development, resistance to infections, and suppression of tumorigenesis. Here, we investigate the influence of the nutrient sensing and longevity-assuring enzyme SIRT6 on the dynamics of apoptosis triggered by serum starvation. Specifically, we characterize the progression of apoptosis in wild type and SIRT6 deficient mouse embryonic fibroblasts using time-lapse flow cytometry and computational modelling based on rate-equations and cell distribution analysis. We find that SIRT6 deficient cells resist apoptosis by delaying its initiation. Interestingly, once apoptosis is initiated, the rate of its progression is higher in SIRT6 null cells compared to identically cultured wild type cells. However, SIRT6 null cells succumb to apoptosis more slowly, not only in response to nutrient deprivation but also in response to other stresses. Our data suggest that SIRT6 plays a role in several distinct steps of apoptosis. Overall, we demonstrate the utility of our computational model to describe stages of apoptosis progression and the integrity of the cellular membrane. Such measurements will be useful in a broad range of biological applications.

On the importance of accounting for competing risks in pediatric cancer trials designed to delay or avoid radiotherapy: I. Basic concepts and first analyses.

PubMed

Tai, Bee-Choo; Grundy, Richard G; Machin, David

2010-04-01

In trials designed to delay or avoid irradiation among children with malignant brain tumor, although irradiation after disease progression is an important event, patients who have disease progression may decline radiotherapy (RT), or those without disease progression may opt for elective RT. To accurately describe the cumulative need for RT in such instances, it is crucial to account for these distinct events and to evaluate how each contributes to the delay or advancement of irradiation via a competing risks analysis. We describe the summary of competing events in such trials using competing risks methods based on cumulative incidence functions and Gray's test. The results obtained are contrasted with standard survival methods based on Kaplan-Meier curves, cause-specific hazard functions and log-rank test. The Kaplan-Meier method overestimates all event-specific rates. The cause-specific hazard analysis showed reduction in hazards for all events (A: RT after progression; B: no RT after progression; C: elective RT) among children with ependymoma. For event A, a higher cumulative incidence was reported for ependymoma. Although Gray's test failed to detect any difference (p = 0.331) between histologic subtypes, the log-rank test suggested marginal evidence (p = 0.057). Similarly, for event C, the log-rank test found stronger evidence of reduction in hazard among those with ependymoma (p = 0.005) as compared with Gray's test (p = 0.086). To evaluate treatment differences, failing to account for competing risks using appropriate methodology may lead to incorrect interpretations.

Increased impulsive action in rats: effects of morphine in a short and long fixed-delay response inhibition task.

PubMed

Mahoney, Megan K; Silveira, Mason M; Olmstead, Mary C

2013-12-01

Impulsive action is mediated through several neurochemical systems, although it is not clear which role each of these plays in the inability to withhold inappropriate responses. Manipulations of the opioid system alter impulsive action in rodents, although the effects are not consistent across tasks. Previously, we speculated that these discrepancies reflect differences in the cognitive mechanisms that control responding in each task. We investigated whether the effect of morphine, a mu opioid receptor (MOR) agonist, on impulsive action depends on the ability of the subjects to time the interval during which they must inhibit a response. Male Long-Evans rats were trained in a response inhibition (RI) task to withhold responding for sucrose during a 4- or 60-s delay; impulsive action was assessed as increased responding during the delay. The rats were tested following an injection of morphine (0, 1, 3, 6 mg/kg). In a subsequent experiment, the effects of morphine (6 mg/kg) plus the MOR antagonist naloxone (0, 0.3, 1, 3 mg/kg) were investigated. Morphine increased impulsive action, but had different effects in the two conditions: the drug increased the proportion of premature responses as the 4-s interval progressed and produced a general increase in responding across the 60-s interval. Naloxone blocked all morphine-induced effects. The finding that morphine increases impulsive action in a fixed-delay RI task contrasts with our previous evidence which shows no effect in the same task with a variable delay. Thus, MORs disrupt impulsive action only when rats can predict the delay to respond.

Climate change and decadal shifts in the phenology of larval fishes in the California Current ecosystem

PubMed Central

Asch, Rebecca G.

2015-01-01

Climate change has prompted an earlier arrival of spring in numerous ecosystems. It is uncertain whether such changes are occurring in Eastern Boundary Current Upwelling ecosystems, because these regions are subject to natural decadal climate variability, and regional climate models predict seasonal delays in upwelling. To answer this question, the phenology of 43 species of larval fishes was investigated between 1951 and 2008 off southern California. Ordination of the fish community showed earlier phenological progression in more recent years. Thirty-nine percent of seasonal peaks in larval abundance occurred earlier in the year, whereas 18% were delayed. The species whose phenology became earlier were characterized by an offshore, pelagic distribution, whereas species with delayed phenology were more likely to reside in coastal, demersal habitats. Phenological changes were more closely associated with a trend toward earlier warming of surface waters rather than decadal climate cycles, such as the Pacific Decadal Oscillation and North Pacific Gyre Oscillation. Species with long-term advances and delays in phenology reacted similarly to warming at the interannual time scale as demonstrated by responses to the El Niño Southern Oscillation. The trend toward earlier spawning was correlated with changes in sea surface temperature (SST) and mesozooplankton displacement volume, but not coastal upwelling. SST and upwelling were correlated with delays in fish phenology. For species with 20th century advances in phenology, future projections indicate that current trends will continue unabated. The fate of species with delayed phenology is less clear due to differences between Intergovernmental Panel on Climate Change models in projected upwelling trends. PMID:26159416

49 CFR 236.563 - Delay time.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false Delay time. 236.563 Section 236.563 Transportation... Cab Signal Systems Rules and Instructions; Locomotives § 236.563 Delay time. Delay time of automatic... requirements of § 236.24 shall take into consideration the delay time. ...

49 CFR 236.563 - Delay time.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 4 2014-10-01 2014-10-01 false Delay time. 236.563 Section 236.563 Transportation... Cab Signal Systems Rules and Instructions; Locomotives § 236.563 Delay time. Delay time of automatic... requirements of § 236.24 shall take into consideration the delay time. ...

Social and emotional predictors of the tempo of puberty in female rhesus monkeys

PubMed Central

Wilson, Mark E; Bounar, Shannon; Godfrey, Jodi; Michopoulos, Vasiliki; Higgins, Melinda; Sanchez, Mar

2012-01-01

A cascade of neuroendocrine events regulates the initiation and progression of female puberty. However, the factors that determine the timing of these events across individuals are still uncertain. While the consequences of puberty on subsequent emotional development and adult behavior have received significant attention, what is less understood are the social and environmental factors that actually alter the initiation and progression of puberty. In order to more fully understand what factors influence pubertal timing in females, the present study quantified social and emotional behavior; stress physiology; and growth and activity measures in juvenile female rhesus monkeys to determine what best predicts eventual puberty. Based on previous reports, we hypothesized that increased agonistic behavior resulting from subordinate status in their natal group, in combination with slowed growth, reduced prosocial behavior, and increased emotional reactivity would predict delayed puberty. The analyses were restricted to behavioral and physiological measures obtained prior to the onset of puberty, defined as menarche. Together, our findings indicate that higher rates of aggression but lower rates of submission received from group mates; slower weight gain; and greater emotional reactivity, evidenced by higher anxiety, distress and appeasing behaviors, and lower cortisol responsivity in response to a potentially threatening situation, predicts delayed puberty. Together the combination of these variables accounted for 58% of the variance in the age of menarche, 71% in age at first ovulation, and 45% in the duration of adolescent sterility. While early puberty may be more advantageous for the individual from a fertility standpoint, it presents significant health risks, including increased risk for a number of estrogen dependent cancers and as well as the emergence of mood disorders during adulthood. On the other hand, it is possible that increased emotional reactivity associated with delayed puberty could persist, increasing the risk for emotional dysregulation to socially challenging situations. The data argue for prospective studies that will determine how emotional reactivity shown to be important for pubertal timing is affected by early social experience and temperament, and how these stress-related variables contribute to body weight accumulation, affecting the neuroendocrine regulation of puberty. PMID:22658962

Immediate Postsession Feeding Reduces Operant Responding in Rats

ERIC Educational Resources Information Center

Smethells, John R.; Fox, Andrew T.; Andrews, Jennifer J.; Reilly, Mark P.

2012-01-01

Three experiments investigated the effects of immediate and delayed postsession feeding on progressive-ratio and variable-interval schedule performance in rats. During Experiments 1 and 2, immediate postsession feeding decreased the breakpoint, or largest completed ratio, under progressive-ratio schedules. Experiment 3 was conducted to extend the…

Using a Self-Control Training Procedure To Increase Appropriate Behavior.

ERIC Educational Resources Information Center

Dixon, Mark R.; Hayes, Linda J.; Binder, Lisa M.; Manthey, Sharon; Sigman, Connie; Zdanowski, Darlene M.

1998-01-01

A study evaluated teaching a technique for self-control to three adults with developmental disabilities. Concurrent fixed-duration/progressive-duration reinforcement schedules were introduced in which both smaller and larger reinforcers were available immediately. When progressively increasing delays were introduced for the larger reinforcer,…

Waiting can be an optimal conservation strategy, even in a crisis discipline

PubMed Central

Possingham, Hugh P.; Bode, Michael

2017-01-01

Biodiversity conservation projects confront immediate and escalating threats with limited funding. Conservation theory suggests that the best response to the species extinction crisis is to spend money as soon as it becomes available, and this is often an explicit constraint placed on funding. We use a general dynamic model of a conservation landscape to show that this decision to “front-load” project spending can be suboptimal if a delay allows managers to use resources more strategically. Our model demonstrates the existence of temporal efficiencies in conservation management, which parallel the spatial efficiencies identified by systematic conservation planning. The optimal timing of decisions balances the rate of biodiversity decline (e.g., the relaxation of extinction debts, or the progress of climate change) against the rate at which spending appreciates in value (e.g., through interest, learning, or capacity building). We contrast the benefits of acting and waiting in two ecosystems where restoration can mitigate forest bird extinction debts: South Australia’s Mount Lofty Ranges and Paraguay’s Atlantic Forest. In both cases, conservation outcomes cannot be maximized by front-loading spending, and the optimal solution recommends substantial delays before managers undertake conservation actions. Surprisingly, these delays allow superior conservation benefits to be achieved, in less time than front-loading. Our analyses provide an intuitive and mechanistic rationale for strategic delay, which contrasts with the orthodoxy of front-loaded spending for conservation actions. Our results illustrate the conservation efficiencies that could be achieved if decision makers choose when to spend their limited resources, as opposed to just where to spend them. PMID:28894004

Waiting can be an optimal conservation strategy, even in a crisis discipline.

PubMed

Iacona, Gwenllian D; Possingham, Hugh P; Bode, Michael

2017-09-26

Biodiversity conservation projects confront immediate and escalating threats with limited funding. Conservation theory suggests that the best response to the species extinction crisis is to spend money as soon as it becomes available, and this is often an explicit constraint placed on funding. We use a general dynamic model of a conservation landscape to show that this decision to "front-load" project spending can be suboptimal if a delay allows managers to use resources more strategically. Our model demonstrates the existence of temporal efficiencies in conservation management, which parallel the spatial efficiencies identified by systematic conservation planning. The optimal timing of decisions balances the rate of biodiversity decline (e.g., the relaxation of extinction debts, or the progress of climate change) against the rate at which spending appreciates in value (e.g., through interest, learning, or capacity building). We contrast the benefits of acting and waiting in two ecosystems where restoration can mitigate forest bird extinction debts: South Australia's Mount Lofty Ranges and Paraguay's Atlantic Forest. In both cases, conservation outcomes cannot be maximized by front-loading spending, and the optimal solution recommends substantial delays before managers undertake conservation actions. Surprisingly, these delays allow superior conservation benefits to be achieved, in less time than front-loading. Our analyses provide an intuitive and mechanistic rationale for strategic delay, which contrasts with the orthodoxy of front-loaded spending for conservation actions. Our results illustrate the conservation efficiencies that could be achieved if decision makers choose when to spend their limited resources, as opposed to just where to spend them.

Tandem mass spectrometry, but not T-cell receptor excision circle analysis, identifies newborns with late-onset adenosine deaminase deficiency.

PubMed

la Marca, Giancarlo; Canessa, Clementina; Giocaliere, Elisa; Romano, Francesca; Duse, Marzia; Malvagia, Sabrina; Lippi, Francesca; Funghini, Silvia; Bianchi, Leila; Della Bona, Maria Luisa; Valleriani, Claudia; Ombrone, Daniela; Moriondo, Maria; Villanelli, Fabio; Speckmann, Carsten; Adams, Stuart; Gaspar, Bobby H; Hershfield, Michael; Santisteban, Ines; Fairbanks, Lynette; Ragusa, Giovanni; Resti, Massimo; de Martino, Maurizio; Guerrini, Renzo; Azzari, Chiara

2013-06-01

Adenosine deaminase (ADA)-severe combined immunodeficiency (SCID) is caused by genetic variants that disrupt the function of ADA. In its early-onset form, it is rapidly fatal to infants. Delayed or late-onset ADA-SCID is characterized by insidious progressive immunodeficiency that leads to permanent organ damage or death. Quantification of T-cell receptor excision circles (TRECs) or tandem mass spectrometry (tandem-MS) analysis of dried blood spots (DBSs) collected at birth can identify newborns with early-onset ADA-SCID and are used in screening programs. However, it is not clear whether these analyses can identify newborns who will have delayed or late-onset ADA-SCID before symptoms appear. We performed a retrospective study to evaluate whether tandem-MS and quantitative TREC analyses of DBSs could identify newborns who had delayed-onset ADA-SCID later in life. We tested stored DBSs collected at birth from 3 patients with delayed-onset ADA-SCID using tandem-MS (PCT EP2010/070517) to evaluate levels of adenosine and 2'-deoxyadenosine and real-time PCR to quantify TREC levels. We also analyzed DBSs from 3 newborns with early-onset ADA-SCID and 2 healthy newborn carriers of ADA deficiency. The DBSs taken at birth from the 3 patients with delayed-onset ADA-SCID had adenosine levels of 10, 25, and 19 μmol/L (normal value, <1.5 μmol/L) and 2'-deoxyadenosine levels of 0.7, 2.7, and 2.4 μmol/L (normal value, <0.07 μmol/L); the mean levels of adenosine and 2'-deoxyadenosine were respectively 12.0- and 27.6-fold higher than normal values. DBSs taken at birth from all 3 patients with delayed-onset ADA deficiency had normal TREC levels, but TRECs were undetectable in blood samples taken from the same patients at the time of diagnosis. Tandem-MS but not TREC quantification identifies newborns with delayed- or late-onset ADA deficiency. Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

A new role of the Rac-GAP β2-chimaerin in cell adhesion reveals opposite functions in breast cancer initiation and tumor progression

PubMed Central

Casado-Medrano, Victoria; Barrio-Real, Laura; García-Rostán, Ginesa; Baumann, Matti; Rocks, Oliver; Caloca, María J.

2016-01-01

β2-chimaerin is a Rac1-specific negative regulator and a candidate tumor suppressor in breast cancer but its precise function in mammary tumorigenesis in vivo is unknown. Here, we study for the first time the role of β2-chimaerin in breast cancer using a mouse model and describe an unforeseen role for this protein in epithelial cell-cell adhesion. We demonstrate that expression of β2-chimaerin in breast cancer epithelial cells reduces E-cadherin protein levels, thus loosening cell-cell contacts. In vivo, genetic ablation of β2-chimaerin in the MMTV-Neu/ErbB2 mice accelerates tumor onset, but delays tumor progression. Finally, analysis of clinical databases revealed an inverse correlation between β2-chimaerin and E-cadherin gene expressions in Her2+ breast tumors. Furthermore, breast cancer patients with low β2-chimaerin expression have reduced relapse free survival but develop metastasis at similar times. Overall, our data redefine the role of β2-chimaerin as tumor suppressor and provide the first in vivo evidence of a dual function in breast cancer, suppressing tumor initiation but favoring tumor progression. PMID:27058424

The Use of Picture Prompts and Prompt Delay to Teach Receptive Labeling

ERIC Educational Resources Information Center

Vedora, Joseph; Barry, Tiffany

2016-01-01

The current study extended research on picture prompts by using them with a progressive prompt delay to teach receptive labeling of pictures to 2 teenagers with autism. The procedure differed from prior research because the auditory stimulus was not presented or was presented only once during the picture-prompt condition. The results indicated…

32 CFR 884.12 - Delays in returning members to the United States.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 32 National Defense 6 2010-07-01 2010-07-01 false Delays in returning members to the United States. 884.12 Section 884.12 National Defense Department of Defense (Continued) DEPARTMENT OF THE AIR FORCE... one or more of the following are present: (1) Efforts are in progress to resolve the controversy to...

32 CFR 884.12 - Delays in returning members to the United States.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 32 National Defense 6 2013-07-01 2013-07-01 false Delays in returning members to the United States. 884.12 Section 884.12 National Defense Department of Defense (Continued) DEPARTMENT OF THE AIR FORCE... one or more of the following are present: (1) Efforts are in progress to resolve the controversy to...

32 CFR 884.12 - Delays in returning members to the United States.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 32 National Defense 6 2014-07-01 2014-07-01 false Delays in returning members to the United States. 884.12 Section 884.12 National Defense Department of Defense (Continued) DEPARTMENT OF THE AIR FORCE... one or more of the following are present: (1) Efforts are in progress to resolve the controversy to...

32 CFR 884.12 - Delays in returning members to the United States.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 32 National Defense 6 2011-07-01 2011-07-01 false Delays in returning members to the United States. 884.12 Section 884.12 National Defense Department of Defense (Continued) DEPARTMENT OF THE AIR FORCE... one or more of the following are present: (1) Efforts are in progress to resolve the controversy to...

32 CFR 884.12 - Delays in returning members to the United States.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 32 National Defense 6 2012-07-01 2012-07-01 false Delays in returning members to the United States. 884.12 Section 884.12 National Defense Department of Defense (Continued) DEPARTMENT OF THE AIR FORCE... one or more of the following are present: (1) Efforts are in progress to resolve the controversy to...

Wigner time delay in photodetachment of Tm-and in photoionization of Yb: A comparative study

NASA Astrophysics Data System (ADS)

Saha, Soumyajit; Jose, Jobin; Deshmukh, Pranawa; Dolmatov, Valeriy; Kheifets, Anatoli; Manson, Steven

2017-04-01

Preliminary studies of Wigner time delay in photodetachment spectra of negative ions have been reported. Photodetachment time delay for some dipole channels of Tm- and of Cl- were calculated using relativistic random phase approximation (RRPA). Comparisons between photodetachment time delay of Cl- and photoionization time delay of Ar were made. We investigate the photodetachment time delay for all three relativistically split nd -> ɛ f channels of Tm- and for nd -> ɛ f channels of Yb (isoelectronic to Tm-) using RRPA. We study the effect of the shape resonance, brought about by the centrifugal barrier potential, on photodetachment time delay. A negative ion is a good laboratory for studying the effects of shape resonances on time delay since the phase is unaffected by the Coulomb component. Wigner time delay in photodetachment of Tm- and in photoionization of Yb: A comparative study.

Health-Related Quality of Life in a Randomized Phase III Study of Bevacizumab, Temozolomide, and Radiotherapy in Newly Diagnosed Glioblastoma.

PubMed

Taphoorn, Martin J B; Henriksson, Roger; Bottomley, Andrew; Cloughesy, Timothy; Wick, Wolfgang; Mason, Warren P; Saran, Frank; Nishikawa, Ryo; Hilton, Magalie; Theodore-Oklota, Christina; Ravelo, Arliene; Chinot, Olivier L

2015-07-01

As glioblastoma progresses, patients experience a decline in health-related quality of life (HRQoL). Delaying this decline is an important treatment goal. In newly diagnosed glioblastoma, progression-free survival was prolonged when bevacizumab was added to radiotherapy plus temozolomide (RT/TMZ) versus placebo plus RT/TMZ (phase III AVAglio study; hazard ratio, 0.64; 95% CI, 0.55 to 0.74; P < .001). To ensure that addition of bevacizumab to standard-of-care therapy was not associated with HRQoL detriment, HRQoL assessment was a secondary objective. Patients completed European Organisation for Research and Treatment of Cancer Quality of Life Questionnaires C30 and BN20 at each tumor assessment (Appendix Table A1, online only). Raw scores were converted to a 100-point scale and mean changes from baseline scores were evaluated (stable: < 10-point change; clinically relevant deterioration/improvement: ≥ 10-point change). Deterioration-free survival was the time to deterioration/progression/death; time to deterioration was the time to deterioration/death. Most evaluable patients who had not progressed (> 74%) completed all HRQoL assessments for at least 1 year of treatment, and almost all completed at least one HRQoL assessment at baseline (98.3% and 97.6%, bevacizumab and placebo arms, respectively). Mean changes from baseline did not reach a clinically relevant difference between arms for most items. HRQoL declined at progression in both arms. The addition of bevacizumab to RT/TMZ resulted in statistically longer (P < .001) deterioration-free survival across all items. Time to deterioration was not statistically longer in the placebo plus RT/TMZ arm (v bevacizumab) for any HRQoL item. The addition of bevacizumab to standard-of-care treatment for newly diagnosed glioblastoma had no impact on HRQoL during the progression-free period. © 2015 by American Society of Clinical Oncology.

Effects of partial time delays on phase synchronization in Watts-Strogatz small-world neuronal networks.

PubMed

Sun, Xiaojuan; Perc, Matjaž; Kurths, Jürgen

2017-05-01

In this paper, we study effects of partial time delays on phase synchronization in Watts-Strogatz small-world neuronal networks. Our focus is on the impact of two parameters, namely the time delay τ and the probability of partial time delay p delay , whereby the latter determines the probability with which a connection between two neurons is delayed. Our research reveals that partial time delays significantly affect phase synchronization in this system. In particular, partial time delays can either enhance or decrease phase synchronization and induce synchronization transitions with changes in the mean firing rate of neurons, as well as induce switching between synchronized neurons with period-1 firing to synchronized neurons with period-2 firing. Moreover, in comparison to a neuronal network where all connections are delayed, we show that small partial time delay probabilities have especially different influences on phase synchronization of neuronal networks.

Plasma concentrations of osteocalcin are associated with the timing of pubertal progress in boys.

PubMed

Schündeln, Michael M; Bäder, Lena; Kiewert, Cordula; Herrmann, Ralf; Führer, Dagmar; Hauffa, Berthold P; Grasemann, Corinna

2017-02-01

Animal models have shown that the skeletal hormone osteocalcin stimulates testicular testosterone synthesis. To assess whether osteocalcin might be a useful marker to detect pubertal development disorders, we examined osteocalcin plasma concentrations in children and adolescents with and without disorders of pubertal development. Osteocalcin concentrations were investigated in a total of 244 patients with endocrine disorders (122 males, mean age: 11.87+3.77 years), including patients with precocious puberty and constitutional delay of puberty. Osteocalcin concentrations were highest among adolescents with precocious puberty and advanced pubertal development (120.60±45.22 ng/mL), while the concentrations were lowest among patients with constitutional delay of puberty (102.20±37.13 ng/mL). Overall, osteocalcin concentrations were strongly correlated with markers of bone metabolism. Although plasma osteocalcin concentrations are associated with pubertal development in boys, it does not appear to be a useful diagnostic marker for altered pubertal development.

Effect of acarbose to delay progression of carotid intima-media thickness in early diabetes.

PubMed

Patel, Y R; Kirkman, M S; Considine, R V; Hannon, T S; Mather, K J

2013-10-01

The anti-diabetic agent acarbose reduces postprandial glucose excursions. We have evaluated the effect of randomized treatment with acarbose on the progression of carotid intima-media thickness (IMT) in early diabetes. The Early Diabetes Intervention Program was a randomized trial of acarbose versus placebo in 219 participants with early diabetes characterized by glucose values over 11.1 mmol/L 2 h after a 75 g oral glucose load and a mean HbA1c of 6.3%. IMT was measured at baseline and yearly. Follow-up was discontinued if participants progressed to the study glucose endpoints; IMT readings were available for a median of 2 years, with 72 subjects followed for 5 years. Progressive increases in IMT were seen in both treatment groups, but progression was reduced in participants randomized to acarbose (p = 0.047). In age, sex and smoking-adjusted analyses, IMT progression was associated with greater fasting and oral glucose tolerance test-excursion glucose, fasting insulin, cholesterol and glycated low-density lipoprotein concentrations. IMT progression was reduced with study-related changes in weight, insulin and non-esterified fatty acids; these features were more strongly associated with reduced IMT progression than acarbose treatment. Despite strong associations of baseline glycemia with IMT progression, study-related changes in glucose were not important determinants of IMT progression. Acarbose can delay progression of carotid intima-media thickness in early diabetes defined by an oral glucose tolerance test. Glucose, weight, insulin and lipids contributed to risk of progression but reductions in glycemia were not major determinants of reduced rate of IMT progression. Vascular benefits of acarbose may be independent of its glycemic effects. Copyright © 2013 John Wiley & Sons, Ltd.

Delay-range-dependent chaos synchronization approach under varying time-lags and delayed nonlinear coupling.

PubMed

Zaheer, Muhammad Hamad; Rehan, Muhammad; Mustafa, Ghulam; Ashraf, Muhammad

2014-11-01

This paper proposes a novel state feedback delay-range-dependent control approach for chaos synchronization in coupled nonlinear time-delay systems. The coupling between two systems is esteemed to be nonlinear subject to time-lags. Time-varying nature of both the intrinsic and the coupling delays is incorporated to broad scope of the present study for a better-quality synchronization controller synthesis. Lyapunov-Krasovskii (LK) functional is employed to derive delay-range-dependent conditions that can be solved by means of the conventional linear matrix inequality (LMI)-tools. The resultant control approach for chaos synchronization of the master-slave time-delay systems considers non-zero lower bound of the intrinsic as well as the coupling time-delays. Further, the delay-dependent synchronization condition has been established as a special case of the proposed LK functional treatment. Furthermore, a delay-range-dependent condition, independent of the delay-rate, has been provided to address the situation when upper bound of the delay-derivative is unknown. A robust state feedback control methodology is formulated for synchronization of the time-delay chaotic networks against the L2 norm bounded perturbations by minimizing the L2 gain from the disturbance to the synchronization error. Numerical simulation results are provided for the time-delay chaotic networks to show effectiveness of the proposed delay-range-dependent chaos synchronization methodologies. Copyright © 2014 ISA. Published by Elsevier Ltd. All rights reserved.

[Ventilatory dysfunction in motor neuron disease: when and how to act?].

PubMed

Rocha, J Afonso; Miranda, M J

2007-01-01

Amyotrophic lateral sclerosis is a devastating progressive neurodegenerative disorder, involving motor neurons in the cerebral cortex, brainstem and spinal cord. Mean duration of survival from the time of diagnosis is around 15 months, being pulmonary complications and respiratory failure responsible for more than 85% of deaths. Albeit the inevitability of respiratory failure and short-term death, standardized intervention protocols have been shown to significantly delay the need for invasive ventilatory support, thus prolonging survival and enhancing quality of life. The authors present an intervention protocol based on clinical progression and respiratory parameters. Decisions regarding initiation of non-invasive positive pressure ventilation (NIPPV) and mechanically assisted coughing, depend on development of symptoms of hypoventilation and on objective deterioration of respiratory parameters especially in what concerns bulbar muscle function. These include maximum inspiratory capacity (MIC), difference between MIC and vital capacity (MIC-VC), and assisted peak cough flow (PCF). These standardized protocols along with patient and caregivers education, allow for improved quality of life, prolonged survival and delay or eventually prevent the need for tracheotomy and invasive ventilatory support. Supplemental oxygen should be avoided in these patients, since it precludes use of oxymetry as feedback for titrating NIPPV and MAC, and is associated with decreased ventilatory drive and aggravated hypercapnia.

The effectiveness of parent participation in occupational therapy for children with developmental delay

PubMed Central

Lin, Chien-Lin; Lin, Chin-Kai; Yu, Jia-Jhen

2018-01-01

Introduction This study aims to explore the impact of Parent Participation Program on the development of developmental delay children. Methods Pretest-posttest equivalent-group experimental design study was used in this paper. A total of 30 pairs of developmental delay children aged 0–72 months and their parents participated into this study. They were divided into two groups, namely control group and experimental group, according to parents’ wishes. The objects of study in control group received 16 courses of direct rehabilitation therapy; those in experimental group received 8 courses of direct rehabilitation therapy and 8 courses of instruction and tracking of Parent Participation Program. The duration of the intervention was 8 weeks. All cases should be evaluated before and after the intervention, to analyze the difference before and after intervention and among groups. The statistical methods in this paper included descriptive analysis, Chi-square test, independent sample t-test, pair-sample t-test. Results and conclusion The intervention of Parent Participation Occupational Program has positive impact on the development of developmental delay children in various fields. Among all the intervention results, the progress of the experimental group is 1.895 times more than that of the control group. With parent involvement, Parent Participation Occupational Therapy can promote the cognitive ability, language ability, action ability (gross and fine movement), social competence and self-care ability of children with developmental delay. Finally, the researcher presents suggestions and directions for future research in accordance with the results. PMID:29503546

Downhole delay assembly for blasting with series delay

DOEpatents

Ricketts, Thomas E.

1982-01-01

A downhole delay assembly is provided which can be placed into a blasthole for initiation of explosive in the blasthole. The downhole delay assembly includes at least two detonating time delay devices in series in order to effect a time delay of longer than about 200 milliseconds in a round of explosions. The downhole delay assembly provides a protective housing to prevent detonation of explosive in the blasthole in response to the detonation of the first detonating time delay device. There is further provided a connection between the first and second time delay devices. The connection is responsive to the detonation of the first detonating time delay device and initiates the second detonating time delay device. A plurality of such downhole delay assemblies are placed downhole in unfragmented formation and are initiated simultaneously for providing a round of explosive expansions. The explosive expansions can be used to form an in situ oil shale retort containing a fragmented permeable mass of formation particles.

Parenting Predictors of Delay Inhibition in Socioeconomically Disadvantaged Preschoolers

PubMed Central

Merz, Emily C.; Landry, Susan H.; Zucker, Tricia A.; Barnes, Marcia A.; Assel, Michael; Taylor, Heather B.; Lonigan, Christopher J.; Phillips, Beth M.; Clancy-Menchetti, Jeanine; Eisenberg, Nancy; Spinrad, Tracy L.; Valiente, Carlos; de Villiers, Jill; Consortium, the School Readiness Research

2016-01-01

This study examined longitudinal associations between specific parenting factors and delay inhibition in socioeconomically disadvantaged preschoolers. At Time 1, parents and 2- to 4-year-old children (mean age = 3.21 years; N = 247) participated in a videotaped parent-child free play session, and children completed delay inhibition tasks (gift delay-wrap, gift delay-bow, and snack delay tasks). Three months later, at Time 2, children completed the same set of tasks. Parental responsiveness was coded from the parent-child free play sessions, and parental directive language was coded from transcripts of a subset of 127 of these sessions. Structural equation modeling was used, and covariates included age, gender, language skills, parental education, and Time 1 delay inhibition. Results indicated that in separate models, Time 1 parental directive language was significantly negatively associated with Time 2 delay inhibition, and Time 1 parental responsiveness was significantly positively associated with Time 2 delay inhibition. When these parenting factors were entered simultaneously, Time 1 parental directive language significantly predicted Time 2 delay inhibition whereas Time 1 parental responsiveness was no longer significant. Findings suggest that parental language that modulates the amount of autonomy allotted the child may be an important predictor of early delay inhibition skills. PMID:27833461

Photonics for microwave systems and ultra-wideband signal processing

NASA Astrophysics Data System (ADS)

Ng, W.

2016-08-01

The advantages of using the broadband and low-loss distribution attributes of photonics to enhance the signal processing and sensing capabilities of microwave systems are well known. In this paper, we review the progress made in the topical areas of true-time-delay beamsteering, photonic-assisted analog-to-digital conversion, RF-photonic filtering and link performances. We also provide an outlook on the emerging field of integrated microwave photonics (MWP) that promise to reduce the cost of MWP subsystems and components, while providing significantly improved form-factors for system insertion.

Progress in obstetrics or the road to the Promised Land

PubMed Central

2008-01-01

The exceptional progress in obstetrics, especially in the second half of the 20th century, creates a series of dilemmas, without having yet the answer to old, basic questions, such as premature delivery and prevention of preeclampsia. Sexual liberty and the delay of the first pregnancy are responsible for the drop in natality rate and the increasing demand for assisted reproductive technologies. Their success is marked, though, by a drastic increase in the multiple birth rate and its complications. The advancing maternal age brings along a number of cardiovascular pathologies that endanger not only the present pregnancy, but also the long distance health prognosis. Plus, there is a marked risk for foetal chromosomal anomalies, which explains the need and the importance of prenatal diagnosis. Probably the newest branch in materno–foetal medicine, it offers many answers and solutions, but there are still a lot of question marks. In conclusion, the progress is necessary, is expected, but it should always be filtered by time and experience. PMID:20108480

[Localized scleroderma (morphea) in childhood].

PubMed

Weibel, L

2012-02-01

Localized scleroderma or morphea is a sclerosing connective tissue disease of the skin, which may affect underlying tissues such as subcutis, muscle and bone. Many patients show extracutaneous symptoms and antinuclear antibodies, however, secondary transformation into systemic sclerosis does not occur. Localized scleroderma usually begins in childhood with a wide variation in its clinical spectrum. The linear variant is the most common subtype in children, associated with a progressive course and increased risk of complications. The disease may progress over years and result in severe functional and cosmetic disability. The etiology of localized scleroderma remains unknown. A genetic background is suspected, while triggers such as trauma, vaccinations and infections may lead to secondary immunologic phenomena. Localized scleroderma often remains unrecognized for a long time, resulting in substantial delay in treatment. The combination of systemic corticosteroids and methotrexate has been established as first-line therapy for progressive (usually linear) disease, whereas phototherapy (UVA-1 or UVB-narrow band) is suitable for adolescents with superficial circumscribed subtypes.

[Effect of inhibitors serine/threonine protein kinases and protein phosphatases on mitosis progression of synchronized tobacco by-2 cells].

PubMed

Sheremet, Ia A; Emets, A I; Azmi, A; Vissenberg, K; Verbelen, J-P; Blium, Ia B

2012-01-01

In order to investigate the role of various serine/ threonine protein kinases and protein phosphatases in the regulation of mitosis progression in plant cells the influence of cyclin-dependent (olomoucine) and Ca2+ -calmodulin-dependent (W7) protein kinases inhibitors, as well as protein kinase C inhibitors (H7 and staurosporine) and protein phosphatases inhibitor (okadaic acid) on mitosis progression in synchronized tobacco BY-2 cells has been studied. It was found that BY-2 culture treatment with inhibitors of cyclin dependent protein kinases and protein kinase C causes prophase delay, reduces the mitotic index and displaces of mitotic peak as compare with control cells. Inhibition of Ca2+ -calmodulin dependent protein kinases enhances the cell entry into prophase and delays their exit from mitosis. Meanwhile inhibition of serine/threonine protein phosphatases insignificantly enhances of synchronized BY-2 cells entering into all phases of mitosis.

Time-delayed feedback control of diffusion in random walkers.

PubMed

Ando, Hiroyasu; Takehara, Kohta; Kobayashi, Miki U

2017-07-01

Time delay in general leads to instability in some systems, while specific feedback with delay can control fluctuated motion in nonlinear deterministic systems to a stable state. In this paper, we consider a stochastic process, i.e., a random walk, and observe its diffusion phenomenon with time-delayed feedback. As a result, the diffusion coefficient decreases with increasing delay time. We analytically illustrate this suppression of diffusion by using stochastic delay differential equations and justify the feasibility of this suppression by applying time-delayed feedback to a molecular dynamics model.

A computational method for computing an Alzheimer’s Disease Progression Score; experiments and validation with the ADNI dataset

PubMed Central

Jedynak, Bruno M.; Liu, Bo; Lang, Andrew; Gel, Yulia; Prince, Jerry L.

2014-01-01

Understanding the time-dependent changes of biomarkers related to Alzheimer’s disease (AD) is a key to assessing disease progression and to measuring the outcomes of disease-modifying therapies. In this paper, we validate an Alzheimer’s disease progression score model which uses multiple biomarkers to quantify the AD progression of subjects following three assumptions: (1) there is a unique disease progression for all subjects, (2) each subject has a different age of onset and rate of progression, and (3) each biomarker is sigmoidal as a function of disease progression. Fitting the parameters of this model is a challenging problem which we approach using an alternating least squares optimization algorithm. In order to validate this optimization scheme under realistic conditions, we use the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort. With the help of Monte Carlo simulations, we show that most of the global parameters of the model are tightly estimated, thus enabling an ordering of the biomarkers that fit the model well, ordered as: the Rey auditory verbal learning test with 30 minutes delay, the sum of the two lateral hippocampal volumes divided by the intra-cranial volume, followed by (the clinical dementia rating sum of boxes score and the mini mental state examination score) in no particular order and lastly the Alzheimer’s disease assessment scale-cognitive subscale. PMID:25444605

Effects of Acarbose to Delay Progression of Carotid Intima-Media Thickness in Early Diabetes

PubMed Central

Patel, YR; Kirkman, MS; Considine, RV; Hannon, TS; Mather, KJ

2014-01-01

Background The antidiabetic agent acarbose reduces postprandial glucose excursions. We have evaluated the effect of randomized treatment with acarbose on the progression of carotid intima-media thickness (IMT) in early diabetes. Methods The Early Diabetes Intervention Program (EDIP) was a randomized trial of acarbose versus placebo, in 219 participants with early diabetes characterized by glucose values over 11.1 mmol/L 2 hours after a 75g oral glucose load, and mean HbA1c 6.3%. IMT was measured at baseline and yearly. Follow-up was discontinued if participants progressed to the study glucose endpoints; IMT readings were available for a median of 2 years, with 72 subjects followed for 5 years. Results Progressive increases in IMT were seen in both treatment groups, but this was reduced in participants randomized to acarbose (p=0.047). In age, sex and smoking-adjusted analyses IMT progression was associated with greater fasting and OGTT-excursion glucose, fasting insulin, cholesterol, and glycated LDL concentrations. IMT progression was reduced with study-related changes in weight, insulin, and nonesterified fatty acids; these features were more strongly associated with reduced IMT progression than acarbose treatment. Despite strong associations of baseline glycemia with IMT progression, study-related changes in glucose were not important determinants of IMT progression. Conclusions Acarbose can delay progression of carotid intima-media thickness in early diabetes defined by an oral glucose tolerance test. Glucose, weight, insulin and lipids contributed to risk of progression but reductions in glycemia were not major determinants of reduced rate of IMT progression. Vascular benefits of acarbose may be independent of its glycemic effects. PMID:23908125

Caffeine stabilizes Cdc25 independently of Rad3 in S chizosaccharomyces pombe contributing to checkpoint override

PubMed Central

Alao, John P; Sjölander, Johanna J; Baar, Juliane; Özbaki-Yagan, Nejla; Kakoschky, Bianca; Sunnerhagen, Per

2014-01-01

Cdc25 is required for Cdc2 dephosphorylation and is thus essential for cell cycle progression. Checkpoint activation requires dual inhibition of Cdc25 and Cdc2 in a Rad3-dependent manner. Caffeine is believed to override activation of the replication and DNA damage checkpoints by inhibiting Rad3-related proteins in both S chizosaccharomyces pombe and mammalian cells. In this study, we have investigated the impact of caffeine on Cdc25 stability, cell cycle progression and checkpoint override. Caffeine induced Cdc25 accumulation in S . pombe independently of Rad3. Caffeine delayed cell cycle progression under normal conditions but advanced mitosis in cells treated with replication inhibitors and DNA-damaging agents. In the absence of Cdc25, caffeine inhibited cell cycle progression even in the presence of hydroxyurea or phleomycin. Caffeine induces Cdc25 accumulation in S . pombe by suppressing its degradation independently of Rad3. The induction of Cdc25 accumulation was not associated with accelerated progression through mitosis, but rather with delayed progression through cytokinesis. Caffeine-induced Cdc25 accumulation appears to underlie its ability to override cell cycle checkpoints. The impact of Cdc25 accumulation on cell cycle progression is attenuated by Srk1 and Mad2. Together our findings suggest that caffeine overrides checkpoint enforcement by inducing the inappropriate nuclear localization of Cdc25. PMID:24666325

Effects of partial time delays on phase synchronization in Watts-Strogatz small-world neuronal networks

NASA Astrophysics Data System (ADS)

Sun, Xiaojuan; Perc, Matjaž; Kurths, Jürgen

2017-05-01

In this paper, we study effects of partial time delays on phase synchronization in Watts-Strogatz small-world neuronal networks. Our focus is on the impact of two parameters, namely the time delay τ and the probability of partial time delay pdelay, whereby the latter determines the probability with which a connection between two neurons is delayed. Our research reveals that partial time delays significantly affect phase synchronization in this system. In particular, partial time delays can either enhance or decrease phase synchronization and induce synchronization transitions with changes in the mean firing rate of neurons, as well as induce switching between synchronized neurons with period-1 firing to synchronized neurons with period-2 firing. Moreover, in comparison to a neuronal network where all connections are delayed, we show that small partial time delay probabilities have especially different influences on phase synchronization of neuronal networks.

Multiple intracerebroventricular injections of human umbilical cord mesenchymal stem cells delay motor neurons loss but not disease progression of SOD1G93A mice.

PubMed

Sironi, Francesca; Vallarola, Antonio; Violatto, Martina Bruna; Talamini, Laura; Freschi, Mattia; De Gioia, Roberta; Capelli, Chiara; Agostini, Azzurra; Moscatelli, Davide; Tortarolo, Massimo; Bigini, Paolo; Introna, Martino; Bendotti, Caterina

2017-12-01

Stem cell therapy is considered a promising approach in the treatment of amyotrophic lateral sclerosis (ALS) and mesenchymal stem cells (MSCs) seem to be the most effective in ALS animal models. The umbilical cord (UC) is a source of highly proliferating fetal MSCs, more easily collectable than other MSCs. Recently we demonstrated that human (h) UC-MSCs, double labeled with fluorescent nanoparticles and Hoechst-33258 and transplanted intracerebroventricularly (ICV) into SOD1G93A transgenic mice, partially migrated into the spinal cord after a single injection. This prompted us to assess the effect of repeated ICV injections of hUC-MSCs on disease progression in SOD1G93A mice. Although no transplanted cells migrated to the spinal cord, a partial but significant protection of motor neurons (MNs) was found in the lumbar spinal cord of hUC-MSCs-treated SOD1G93A mice, accompanied by a shift from a pro-inflammatory (IL-6, IL-1β) to anti-inflammatory (IL-4, IL-10) and neuroprotective (IGF-1) environment in the lumbar spinal cord, probably linked to the activation of p-Akt survival pathway in both motor neurons and reactive astrocytes. However, this treatment neither prevented the muscle denervation nor delayed the disease progression of mice, emphasizing the growing evidence that protecting the motor neuron perikarya is not sufficient to delay the ALS progression. Copyright © 2017. Published by Elsevier B.V.

Effect of time delay on surgical performance during telesurgical manipulation.

PubMed

Fabrizio, M D; Lee, B R; Chan, D Y; Stoianovici, D; Jarrett, T W; Yang, C; Kavoussi, L R

2000-03-01

Telementoring allows a less experienced surgeon to benefit from an expert surgical consultation, reducing cost, travel, and the learning curve associated with new procedures. However, there are several technical limitations that affect practical applications. One potentially serious problem is the time delay that occurs any time data are transferred across long distances. To date, the effect of time delay on surgical performance has not been studied. A two-phase trial was designed to examine the effect of time delay on surgical performance. In the first phase, a series of tasks was performed, and the numbers of robotic movements required for completion was counted. Programmed incremental time delays were made in audiovisual acquisition and robotic controls. The number of errors made while performing each task at various time delay intervals was noted. In the second phase, a remote surgeon in Baltimore performed the tasks 9000 miles away in Singapore. The number of errors made was recorded. As the time delay increased, the number of operator errors increased. The accuracy needed to perform remote robotic procedures was diminished as the time delay increased. A learning curve did exist for each task, but as the time delay interval increased, it took longer to complete the task. Time delay does affect surgical performance. There is an acceptable delay of <700 msec in which surgeons can compensate for this phenomenon. Clinical studies will be needed to evaluate the true impact of time delay.

Finite time synchronization of memristor-based Cohen-Grossberg neural networks with mixed delays.

PubMed

Chen, Chuan; Li, Lixiang; Peng, Haipeng; Yang, Yixian

2017-01-01

Finite time synchronization, which means synchronization can be achieved in a settling time, is desirable in some practical applications. However, most of the published results on finite time synchronization don't include delays or only include discrete delays. In view of the fact that distributed delays inevitably exist in neural networks, this paper aims to investigate the finite time synchronization of memristor-based Cohen-Grossberg neural networks (MCGNNs) with both discrete delay and distributed delay (mixed delays). By means of a simple feedback controller and novel finite time synchronization analysis methods, several new criteria are derived to ensure the finite time synchronization of MCGNNs with mixed delays. The obtained criteria are very concise and easy to verify. Numerical simulations are presented to demonstrate the effectiveness of our theoretical results.

ELECTRICAL PULSE COUNTER APPARATUS

DOEpatents

Kaufman, W.M.; Jeeves, T.A.

1962-09-01

A progressive electrical pulse counter circuit rs designed for the counting of a chain of input pulses. The circuit employs a series of direct connected bistable counting stages simultaneously pulsed by each input pulse and a delay means connected between each of the stages. Each bistable stage has two d-c operative states, which stage, when in its initial state, prevents the next succeeding stage from changing its condition when the latter stage is pulsed. Since the delay circuits between the stages prevents the immediate decay of the d-c state of each stage when the stages are pulsed, only one stage will change its state for each input pulse, thereby providing progressive stage-by-stage counting. (AEC)

Charge carrier recombination dynamics in perovskite and polymer solar cells

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

Paulke, Andreas; Kniepert, Juliane; Kurpiers, Jona

2016-03-14

Time-delayed collection field experiments are applied to planar organometal halide perovskite (CH{sub 3}NH{sub 3}PbI{sub 3}) based solar cells to investigate charge carrier recombination in a fully working solar cell at the nanosecond to microsecond time scale. Recombination of mobile (extractable) charges is shown to follow second-order recombination dynamics for all fluences and time scales tested. Most importantly, the bimolecular recombination coefficient is found to be time-dependent, with an initial value of ca. 10{sup −9} cm{sup 3}/s and a progressive reduction within the first tens of nanoseconds. Comparison to the prototypical organic bulk heterojunction device PTB7:PC{sub 71}BM yields important differences with regardmore » to the mechanism and time scale of free carrier recombination.« less

Plumage development and molt in Long-tailed Manakins (Chiroxiphia linearis): Variation according to sex and age

USGS Publications Warehouse

Doucet, S.M.; McDonald, D.B.; Foster, M.S.; Clay, R.P.

2007-01-01

Lek-mating Long-tailed Manakins (Chiroxiphia linearis) exhibit an unusual pattern of delayed plumage maturation. Each year, males progress through a series of predefinitive plumages before attaining definitive plumage in their fifth calendar year. Females also exhibit variation in plumage coloration, with some females displaying male-like plumage characteristics. Using data from mist-net captures in northwest Costa Rica (n = 1,315) and museum specimens from throughout the range of Long-tailed Manakins (n = 585), we documented the plumage sequence progression of males, explored variation in female plumage, and described the timing of molt in this species. Males progressed through a series of age-specific predefinitive plumages, which enabled the accurate aging of predefinitive-plumaged males in the field; this predefinitive plumage sequence is the basis for age-related status-signaling in these males. Females tended to acquire red coloration in the crown as they aged. However, colorful plumage in females may be a byproduct of selection on bright male plumage. Females exhibited an early peak of molt activity from February to April, little molt from May through July, and a second, more pronounced peak of molt activity in October. By contrast, males in older predefinitive-plumage stages and males in definitive plumage exhibited comparable unimodal distributions in molt activity beginning in June and peaking between July and October. Our data are consistent with selective pressure to avoid the costs of molt-breeding overlap in females and older males. Our findings have important implications for social organization and signaling in Long- tailed Manakins, and for the evolution of delayed plumage maturation in birds.

Preliminary experience with a new device for delayed sternal closure strategy in cardiac surgery.

PubMed

Santini, Francesco; Onorati, Francesco; Telesca, Mariassunta; Faggian, Giuseppe; Mazzucco, Alessandro

2012-06-01

Open chest management with delayed sternal closure (DSC) is a valuable strategy in the management of patients with postcardiotomy hemodynamic instability or severe coagulopathy. The conventional extemporized material available for off-label sternal stenting however may limit its efficacy. We evaluated outcomes of patients with refractory severe postcardiotomy cardiogenic shock (SPCCS) treated with DSC using a novel temporary sternal spreader (NTSS) which allows myocardial recovery by progressive controlled approximation of the sternal edges. Seven patients (4 male, mean age 66.5 ± 5 years) with refractory SPCCS showing acute hemodynamic instability at sternal closure, were implanted with the NTSS, consisting of stainless-steel branches linked to 2 diverging plates of polyether-ether ketone, whose progressive opening/closing mechanism can be controlled from outside the chest with a rotating steel wire. The sternal wound was closed by an elastic membrane to achieve a sterile field. Swan-Ganz monitoring was employed, and clinical outcomes evaluated. The device was successfully implanted in all patients without device-related complications or failures. Progressive approximation of sternal edges, titrated on cardiac index values, was successfully completed allowing subsequent uneventful sternal closure in all. Mean time from SPCCS to sternal closure was 70 ± 21 hours. No patient developed infective complications or late hemodynamic instability after device removal and sternal closure. One patient (14%) died of multiorgan failure on postoperative day 9. Despite the limited number of patients enrolled, the NTSS proved safe and effective in allowing complete myocardial recovery after SPCCS, avoiding hemodynamic instability related to abrupt sternal closure, with no occurrence of infective complications.

Time-delayed chameleon: Analysis, synchronization and FPGA implementation

NASA Astrophysics Data System (ADS)

Rajagopal, Karthikeyan; Jafari, Sajad; Laarem, Guessas

2017-12-01

In this paper we report a time-delayed chameleon-like chaotic system which can belong to different families of chaotic attractors depending on the choices of parameters. Such a characteristic of self-excited and hidden chaotic flows in a simple 3D system with time delay has not been reported earlier. Dynamic analysis of the proposed time-delayed systems are analysed in time-delay space and parameter space. A novel adaptive modified functional projective lag synchronization algorithm is derived for synchronizing identical time-delayed chameleon systems with uncertain parameters. The proposed time-delayed systems and the synchronization algorithm with controllers and parameter estimates are then implemented in FPGA using hardware-software co-simulation and the results are presented.

The impact of delays on maternal and neonatal outcomes in Ugandan public health facilities: the role of absenteeism

PubMed Central

Ackers, Louise; Ioannou, Elena; Ackers-Johnson, James

2016-01-01

Maternal mortality in low- and middle-income countries continues to remain high. The Ugandan Ministry of Health’s Strategic Plan suggests that little, if any, progress has been made in Uganda in terms of improvements in Maternal Health [Millennium Development Goal (MDG) 5] and, more specifically, in reducing maternal mortality. Furthermore, the UNDP report on the MDGs describes Uganda’s progress as ‘stagnant’. The importance of understanding the impact of delays on maternal and neonatal outcomes in low resource settings has been established for some time. Indeed, the ‘3-delays’ model has exposed the need for holistic multi-disciplinary approaches focused on systems change as much as clinical input. The model exposes the contribution of social factors shaping individual agency and care-seeking behaviour. It also identifies complex access issues which, when combined with the lack of timely and adequate care at referral facilities, contributes to extensive and damaging delays. It would be hard to find a piece of research on this topic that does not reference human resource factors or ‘staff shortages’ as a key component of this ‘puzzle’. Having said that, it is rare indeed to see these human resource factors explored in any detail. In the absence of detailed critique (implicit) ‘common sense’ presumptions prevail: namely that the economic conditions at national level lead to inadequacies in the supply of suitably qualified health professionals exacerbated by losses to international emigration. Eight years’ experience of action-research interventions in Uganda combining a range of methods has lead us to a rather stark conclusion: the single most important factor contributing to delays and associated adverse outcomes for mothers and babies in Uganda is the failure of doctors to be present at work during contracted hours. Failure to acknowledge and respond to this sensitive problem will ultimately undermine all other interventions including professional voluntarism which relies on local ‘co-presence’ to be effective. Important steps forward could be achieved within the current resource framework, if the political will existed. International NGOs have exacerbated this problem encouraging forms of internal ‘brain drain’ particularly among doctors. Arguably the system as it is rewards doctors for non-compliance resulting in massive resource inefficiencies. PMID:27142803

Ultraviolet-Visible and Fluorescence Spectroscopy Techniques Are Important Diagnostic Tools during the Progression of Atherosclerosis: Diet Zinc Supplementation Retarded or Delayed Atherosclerosis

PubMed Central

Abdelhalim, Mohamed Anwar K.; Moussa, Sherif A. Abdelmottaleb; AL-Mohy, Yanallah Hussain

2013-01-01

Background. In this study, we examined whether UV-visible and fluorescence spectroscopy techniques detect the progression of atherosclerosis in serum of rabbits fed on high-cholesterol diet (HCD) and HCD supplemented with zinc (HCD + Zn) compared with the control. Methods. The control rabbits group was fed on 100 g/day of normal diet. The HCD group was fed on Purina Certified Rabbit Chow supplemented with 1.0% cholesterol plus 1.0% olive oil (100 g/day) for the same period. The HCD + Zn group was fed on normal Purina Certified Rabbit Chow plus 1.0% cholesterol and 1.0% olive oil supplemented with 470 ppm Zn for the same feeding period. UV-visible and fluorescence spectroscopy and biochemistry in Rabbit's blood serum and blood hematology were measured in Rabbit's blood. Results. We found that the fluorescent peak of HCD shifted toward UV-visible wavelength compared with the control using fluorescent excitation of serum at 192 nm. In addition, they showed that supplementation of zinc (350 ppm) restored the fluorescent peak closely to the control. By using UV-visible spectroscopy approach, we found that the peak absorbance of HCD (about 280 nm) was higher than that of control and that zinc supplementation seemed to decrease the absorbance. Conclusions. This study demonstrates that ultraviolet-visible and fluorescence spectroscopy techniques can be applied as noninvasive techniques on a sample blood serum for diagnosing or detecting the progression of atherosclerosis. The Zn supplementation to rabbits fed on HCD delays or retards the progression of atherosclerosis. Inducing anemia in rabbits fed on HCD delays the progression of atherosclerosis. PMID:24350281

Adding Recognition Discriminability Index to the Delayed Recall Is Useful to Predict Conversion from Mild Cognitive Impairment to Alzheimer's Disease in the Alzheimer's Disease Neuroimaging Initiative.

PubMed

Russo, María J; Campos, Jorge; Vázquez, Silvia; Sevlever, Gustavo; Allegri, Ricardo F

2017-01-01

Background: Ongoing research is focusing on the identification of those individuals with mild cognitive impairment (MCI) who are most likely to convert to Alzheimer's disease (AD). We investigated whether recognition memory tasks in combination with delayed recall measure of episodic memory and CSF biomarkers can predict MCI to AD conversion at 24-month follow-up. Methods: A total of 397 amnestic-MCI subjects from Alzheimer's disease Neuroimaging Initiative were included. Logistic regression modeling was done to assess the predictive value of all RAVLT measures, risk factors such as age, sex, education, APOE genotype, and CSF biomarkers for progression to AD. Estimating adjusted odds ratios was used to determine which variables would produce an optimal predictive model, and whether adding tests of interaction between the RAVLT Delayed Recall and recognition measures (traditional score and d-prime) would improve prediction of the conversion from a-MCI to AD. Results: 112 (28.2%) subjects developed dementia and 285 (71.8%) subjects did not. Of the all included variables, CSF Aβ1-42 levels, RAVLT Delayed Recall, and the combination of RAVLT Delayed Recall and d-prime were predictive of progression to AD (χ 2 = 38.23, df = 14, p < 0.001). Conclusions: The combination of RAVLT Delayed Recall and d-prime measures may be predictor of conversion from MCI to AD in the ADNI cohort, especially in combination with amyloid biomarkers. A predictive model to help identify individuals at-risk for dementia should include not only traditional episodic memory measures (delayed recall or recognition), but also additional variables (d-prime) that allow the homogenization of the assessment procedures in the diagnosis of MCI.

Adding Recognition Discriminability Index to the Delayed Recall Is Useful to Predict Conversion from Mild Cognitive Impairment to Alzheimer's Disease in the Alzheimer's Disease Neuroimaging Initiative

PubMed Central

Russo, María J.; Campos, Jorge; Vázquez, Silvia; Sevlever, Gustavo; Allegri, Ricardo F.; Weiner, Michael W.

2017-01-01

Background: Ongoing research is focusing on the identification of those individuals with mild cognitive impairment (MCI) who are most likely to convert to Alzheimer's disease (AD). We investigated whether recognition memory tasks in combination with delayed recall measure of episodic memory and CSF biomarkers can predict MCI to AD conversion at 24-month follow-up. Methods: A total of 397 amnestic-MCI subjects from Alzheimer's disease Neuroimaging Initiative were included. Logistic regression modeling was done to assess the predictive value of all RAVLT measures, risk factors such as age, sex, education, APOE genotype, and CSF biomarkers for progression to AD. Estimating adjusted odds ratios was used to determine which variables would produce an optimal predictive model, and whether adding tests of interaction between the RAVLT Delayed Recall and recognition measures (traditional score and d-prime) would improve prediction of the conversion from a-MCI to AD. Results: 112 (28.2%) subjects developed dementia and 285 (71.8%) subjects did not. Of the all included variables, CSF Aβ1-42 levels, RAVLT Delayed Recall, and the combination of RAVLT Delayed Recall and d-prime were predictive of progression to AD (χ2 = 38.23, df = 14, p < 0.001). Conclusions: The combination of RAVLT Delayed Recall and d-prime measures may be predictor of conversion from MCI to AD in the ADNI cohort, especially in combination with amyloid biomarkers. A predictive model to help identify individuals at-risk for dementia should include not only traditional episodic memory measures (delayed recall or recognition), but also additional variables (d-prime) that allow the homogenization of the assessment procedures in the diagnosis of MCI. PMID:28344552

The time delay in strong gravitational lensing with Gauss-Bonnet correction

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

Man, Jingyun; Cheng, Hongbo, E-mail: jingyunman@mail.ecust.edu.cn, E-mail: hbcheng@ecust.edu.cn

2014-11-01

The time delay between two relativistic images in the strong gravitational lensing governed by Gauss-Bonnet gravity is studied. We make a complete analytical derivation of the expression of time delay in presence of Gauss-Bonnet coupling. With respect to Schwarzschild, the time delay decreases as a consequence of the shrinking of the photon sphere. As the coupling increases, the second term in the time delay expansion becomes more relevant. Thus time delay in strong limit encodes some new information about geometry in five-dimensional spacetime with Gauss-Bonnet correction.

Mimics and chameleons in motor neurone disease

PubMed Central

Turner, Martin R; Talbot, Kevin

2013-01-01

The progression of motor neurone disease (MND) is currently irreversible, and the grave implications of diagnosis naturally fuels concern among neurologists over missing a potential mimic disorder. There is no diagnostic test for MND but in reality there are few plausible mimics in routine clinical practice. In the presence of a progressive pure motor disorder, signs such as florid fasciculations, bilateral tongue wasting, the ‘split hand’, head drop, emotionality, and cognitive or behavioural impairment carry high positive predictive value. MND is clinically heterogeneous, however, with some important chameleon-like presentations and considerable variation in clinical course. Lack of confidence about the scope of such variation, or an approach to diagnosis emphasising investigations over clinical common sense, has the potential to exacerbate diagnostic delay in MND and impede timely planning of the care which is essential to maximising quality of life. PMID:23616620

Straight A's: Public Education Policy and Progress. Volume 11, Number 1

ERIC Educational Resources Information Center

Alliance for Excellent Education, 2011

2011-01-01

"Straight A's: Public Education Policy and Progress" is a biweekly newsletter that focuses on education news and events both in Washington, DC and around the country. The following articles are included in this issue: (1) Congress Delays Education Funding Decisions: Short-Term Measure Funds Government Into March, Ensures Greater Role for…

Straight A's: Public Education Policy and Progress. Volume 9, Number 18

ERIC Educational Resources Information Center

Alliance for Excellent Education, 2009

2009-01-01

"Straight A's: Public Education Policy and Progress" is a biweekly newsletter that focuses on education news and events both in Washington, DC and around the country. The following articles are included in this issue: (1)"Quality Education Too Long Delayed Is Education Denied": In Campaign-Like Speech, Secretary Duncan Turns Up…

Outcomes for Children Served through IDEA's Early Childhood Programs: 2014-15

ERIC Educational Resources Information Center

Early Childhood Technical Assistance Center, 2016

2016-01-01

In 2014-2015, children with delays or disabilities who received services under the Individuals with Disabilities Act (IDEA) showed greater than expected developmental progress. Many children exited the program functioning within age expectations, and most made progress. States' Part C and Part B Preschool programs report data annually on three…

Large-scale Chromosomal Movements During Interphase Progression in Drosophila

PubMed Central

Csink, Amy K.; Henikoff, Steven

1998-01-01

We examined the effect of cell cycle progression on various levels of chromosome organization in Drosophila. Using bromodeoxyuridine incorporation and DNA quantitation in combination with fluorescence in situ hybridization, we detected gross chromosomal movements in diploid interphase nuclei of larvae. At the onset of S-phase, an increased separation was seen between proximal and distal positions of a long chromsome arm. Progression through S-phase disrupted heterochromatic associations that have been correlated with gene silencing. Additionally, we have found that large-scale G1 nuclear architecture is continually dynamic. Nuclei display a Rabl configuration for only ∼2 h after mitosis, and with further progression of G1-phase can establish heterochromatic interactions between distal and proximal parts of the chromosome arm. We also find evidence that somatic pairing of homologous chromosomes is disrupted during S-phase more rapidly for a euchromatic than for a heterochromatic region. Such interphase chromosome movements suggest a possible mechanism that links gene regulation via nuclear positioning to the cell cycle: delayed maturation of heterochromatin during G1-phase delays establishment of a silent chromatin state. PMID:9763417

Delays reducing waterborne and water-related infectious diseases in China under climate change

PubMed Central

Hodges, Maggie; Belle, Jessica H.; Carlton, Elizabeth J.; Liang, Song; Li, Huazhong; Luo, Wei; Freeman, Matthew C.; Liu, Yang; Gao, Yang; Hess, Jeremy J.; Remais, Justin V.

2014-01-01

Despite China’s rapid progress improving water, sanitation and hygiene (WSH) access, in 2011, 471 million people lacked access to improved sanitation and 401 million to household piped water. Because certain infectious diseases are sensitive to changes in both climate and WSH conditions, we projected impacts of climate change on WSH-attributable diseases in China in 2020 and 2030 by coupling estimates of the temperature sensitivity of diarrheal diseases and three vector-borne diseases, temperature projections from global climate models, WSH-infrastructure development scenarios, and projected demographic changes. By 2030, climate change is projected to delay China’s rapid progress toward reducing WSH-attributable infectious disease burden by 8–85 months. This development delay summarizes the adverse impact of climate change on WSH-attributable infectious diseases in China, and can be used in other settings where a significant health burden may accompany future changes in climate even as the total burden of disease falls due to non-climate reasons. PMID:25530812

Effects of episodic future thinking on discounting: Personalized age-progressed pictures improve risky long-term health decisions.

PubMed

Kaplan, Brent A; Reed, Derek D; Jarmolowicz, David P

2016-03-01

Many everyday choices are associated with both delayed and probabilistic outcomes. The temporal attention hypothesis suggests that individuals' decision making can be improved by focusing attention on temporally distal events and implies that environmental manipulations that bring temporally distal outcomes into focus may alter an individual's degree of discounting. One such manipulation, episodic future thinking, has shown to lower discount rates; however, several questions remain about the applicability of episodic future thinking to domains other than delay discounting. The present experiments examine the effects of a modified episodic-future-thinking procedure in which participants viewed age-progressed computer-generated images of themselves and answered questions related to their future, on probability discounting in the context of both a delayed health gain and loss. Results indicate that modified episodic future thinking effectively altered individuals' degree of discounting in the predicted directions and demonstrate the applicability of episodic future thinking to decision making of socially significant outcomes. © 2015 Society for the Experimental Analysis of Behavior.

MC1R and cAMP signaling inhibit cdc25B activity and delay cell cycle progression in melanoma cells

PubMed Central

Lyons, Jesse; Bastian, Boris C.; McCormick, Frank

2013-01-01

The melanocortin 1 receptor (MC1R) mediates the tanning response through induction of cAMP and downstream pigmentary enzymes. Diminished function alleles of MC1R are associated with decreased tanning and increased melanoma risk, which has been attributed to increased rates of mutation. We have found that MC1R or cAMP signaling also directly decreases proliferation in melanoma cell lines. MC1R overexpression, treatment with the MC1R ligand, or treatment with small-molecule activators of cAMP signaling causes delayed progression from G2 into mitosis. This delay is caused by phosphorylation and inhibition of cdc25B, a cyclin dependent kinase 1-activating phosphatase, and is rescued by expression of a cdc25B mutant that cannot be phosphorylated at the serine 323 residue. These results show that MC1R and cAMP signaling can directly inhibit melanoma growth through regulation of the G2/M checkpoint. PMID:23908401

Delays in reducing waterborne and water-related infectious diseases in China under climate change

NASA Astrophysics Data System (ADS)

Hodges, Maggie; Belle, Jessica H.; Carlton, Elizabeth J.; Liang, Song; Li, Huazhong; Luo, Wei; Freeman, Matthew C.; Liu, Yang; Gao, Yang; Hess, Jeremy J.; Remais, Justin V.

2014-12-01

Despite China's rapid progress in improving water, sanitation and hygiene (WSH) access, in 2011, 471 million people lacked access to improved sanitation and 401 million to household piped water. As certain infectious diseases are sensitive to changes in both climate and WSH conditions, we projected impacts of climate change on WSH-attributable diseases in China in 2020 and 2030 by coupling estimates of the temperature sensitivity of diarrhoeal diseases and three vector-borne diseases, temperature projections from global climate models, WSH-infrastructure development scenarios, and projected demographic changes. By 2030, climate change is projected to delay China's rapid progress towards reducing WSH-attributable infectious disease burden by 8-85 months. This development delay summarizes the adverse impact of climate change on WSH-attributable infectious diseases in China, and can be used in other settings where a significant health burden may accompany future changes in climate even as the total burden of disease falls owing to non-climate reasons.

Delays reducing waterborne and water-related infectious diseases in China under climate change.

PubMed

Hodges, Maggie; Belle, Jessica H; Carlton, Elizabeth J; Liang, Song; Li, Huazhong; Luo, Wei; Freeman, Matthew C; Liu, Yang; Gao, Yang; Hess, Jeremy J; Remais, Justin V

2014-12-01

Despite China's rapid progress improving water, sanitation and hygiene (WSH) access, in 2011, 471 million people lacked access to improved sanitation and 401 million to household piped water. Because certain infectious diseases are sensitive to changes in both climate and WSH conditions, we projected impacts of climate change on WSH-attributable diseases in China in 2020 and 2030 by coupling estimates of the temperature sensitivity of diarrheal diseases and three vector-borne diseases, temperature projections from global climate models, WSH-infrastructure development scenarios, and projected demographic changes. By 2030, climate change is projected to delay China's rapid progress toward reducing WSH-attributable infectious disease burden by 8-85 months. This development delay summarizes the adverse impact of climate change on WSH-attributable infectious diseases in China, and can be used in other settings where a significant health burden may accompany future changes in climate even as the total burden of disease falls due to non-climate reasons.

Neuropsychological study of amyotrophic lateral sclerosis and parkinsonism-dementia complex in Kii peninsula, Japan

PubMed Central

2014-01-01

Background The Kii peninsula of Japan is one of the foci of amyotrophic lateral sclerosis and parkinsonism-dementia complex (ALS/PDC) in the world. The purpose of this study is to clarify the neuropsychological features of the patients with ALS/PDC of the Kii peninsula (Kii ALS/PDC). Methods The medical interview was done on 13 patients with Kii ALS/PDC, 12 patients with Alzheimer’s disease, 10 patients with progressive supranuclear palsy, 10 patients with frontotemporal lobar degeneration and 10 patients with dementia with Lewy bodies. These patients and their carer/spouse were asked to report any history of abulia-apathy, hallucination, personality change and other variety of symptoms. Patients also underwent brain magnetic resonance imaging (MRI), single photon emission computed tomography (SPECT), and neuropsychological tests comprising the Mini Mental State Examination, Raven’s Colored Progressive Matrices, verbal fluency, and Paired-Associate Word Learning Test and some of them were assessed with the Frontal Assessment Battery (FAB). Results All patients with Kii ALS/PDC had cognitive dysfunction including abulia-apathy, bradyphrenia, hallucination, decrease of extraversion, disorientation, and delayed reaction time. Brain MRI showed atrophy of the frontal and/or temporal lobes, and SPECT revealed a decrease in cerebral blood flow of the frontal and/or temporal lobes in all patients with Kii ALS/PDC. Disorientation, difficulty in word recall, delayed reaction time, and low FAB score were recognized in Kii ALS/PDC patients with cognitive dysfunction. Conclusions The core neuropsychological features of the patients with Kii ALS/PDC were characterized by marked abulia-apathy, bradyphrenia, and hallucination. PMID:25041813

Enhanced Efficacy of Cidofovir Combined with Vaccinia Immune Globulin in Treating Progressive Cutaneous Vaccinia Virus Infections in Immunosuppressed Hairless Mice

PubMed Central

Dagley, Ashley; Downs, Brittney; Hagloch, Joseph; Tarbet, E. Bart

2014-01-01

The treatment of progressive vaccinia in individuals has involved antiviral drugs, such as cidofovir (CDV), brincidofovir, and/or tecovirimat, combined with vaccinia immune globulin (VIG). VIG is costly, and its supply is limited, so sparing the use of VIG during treatment is an important objective. VIG sparing was modeled in immunosuppressed mice by maximizing the treatment benefits of CDV combined with VIG to determine the effective treatments that delayed the time to death, reduced cutaneous lesion severity, and/or decreased tissue viral titers. SKH-1 hairless mice immunosuppressed with cyclophosphamide and hairless SCID mice (SHO strain) were infected cutaneously with vaccinia virus. Monotherapy, dual combinations (CDV plus VIG), or triple therapy (topical CDV, parenteral CDV, and VIG) were initiated 2 days postinfection and were given every 3 to 4 days through day 11. The efficacy assessment included survival rate, cutaneous lesion severity, and viral titers. Delays in the time to death and the reduction in lesion severity occurred in the following order of efficacy: triple therapy had greater efficacy than double combinations (CDV plus VIG or topical plus parenteral CDV), which had greater efficacy than VIG alone. Parenteral administration of CDV or VIG was necessary to suppress virus titers in internal organs (liver, lung, and spleen). The skin viral titers were significantly reduced by triple therapy only. The greatest efficacy was achieved by triple therapy. In humans, this regimen should translate to a faster cure rate, thus sparing the amount of VIG used for treatment. PMID:25385098

"Conclusions about exposure to ETS and health that will be unhelpful to us"*: How the tobacco industry attempted to delay and discredit the 1997 Australian National Health and Medical Research Council report on passive smoking

PubMed Central

Trotter, L; Chapman, S

2003-01-01

Background: Major reviews of the health effects of passive smoking have been subjected to tobacco industry campaigns to refute the scientific evidence. Following the 1992 US Environmental Protection Agency review, the Australian National Health and Medical Research Council (NHMRC) initiated a review of the health effects of passive smoking. At the time of this review, evidence that environmental tobacco smoke causes disease was being increasingly accepted in courts of law and voluntary adoption of smoking restrictions was rapidly growing. Objective: To demonstrate how the tobacco industry attempted to delay and discredit the publication of a report on passive smoking that the tobacco industry anticipated to contain recommendations that would be unfavourable to their business. Methods: A search of tobacco industry documents on the Master Settlement Agreement websites was conducted using the terms and acronyms representative of the NHMRC review. Results: The tobacco industry sought to impede the progress of the NHMRC Working Party by launching an intensive campaign to delay and discredit the report. The main strategies used were attempts to criticise the science, extensive use of Freedom of Information provisions to monitor all activity of the group, legal challenges, ad hominem attacks on the credibility of the Working Party members, rallying support from industry allies, and influencing public opinion through the media. Conclusions: The Australian tobacco industry deliberately impeded the NHMRC Working Party's progress and successfully prevented the publication of the report's recommendations. The tobacco industry's motivation and capacity to disrupt the advancement of scientific knowledge and policy in tobacco control should be recognised and anticipated. PMID:14645955

Development of in Vivo Biomarkers for Progressive Tau Pathology after Traumatic Brain Injury

DTIC Science & Technology

2015-02-01

Athletes in contact sports who have sustained multiple concussive traumatic brain injuries are at high risk for delayed, progressive neurological and...11 or ‘punch drunk’ syndrome 9, 12. US military personnel 13, 14 and others who have sustained multiple concussive traumatic brain injuries 15-17...To date, none of the attempts to model progressive tau pathology after repetitive concussive TBI in mice has been optimal. Ongoing efforts include

Departmental of Clinical Investigation: Annual Research Progress Report for Fiscal Year 1992. Volume 1

DTIC Science & Technology

1993-01-01

effect of cisapride on the symptoms of unexplained upper abdominal pain, nausea, vomiting, anorexia, early satiety, bloating/ distension in patients with...for 30 minutes following eccentric exercise will less the 3 indices of delayed-onset muscle soreness (DOMS): perceived muscular soreness, reduced...post-exercise and the Talag Pain Rating Scale will be used to assess muscular soreness. Progress: No progress report was furnished by the principal

Changes in breathing pattern in the normal horse at rest up to age one year.

PubMed

Koterba, A M; Wozniak, J A; Kosch, P C

1995-07-01

Changes in pattern of airflow, sequence of respiratory muscle activation and generated pressures were measured serially in a group of foals during the first year post partum, in order to describe the maturation of the equine breathing pattern. In neonatal foals, inspiration and expiration were both primarily active and airflow pattern was essentially monophasic. By age 1 year, foals displayed essentially the same breathing pattern previously described in adult horses, utilising a combination of active and passive inspiration and expiration to breathe around, rather than from, the relaxation volume of the respiratory system (Vrx). A strong temporal relationship during growth was found between the timing of changes observed in airflow pattern and in the neuromuscular strategy of breathing. The transition to the adult breathing pattern appeared to involve a time delay in activation of both inspiratory and expiratory muscle groups, establishing a passive and active component to both inspiration and expiration. Throughout the study period, concurrent with the increase in delay of abdominal muscle activation, the expiratory flow pattern became progressively more biphasic in appearance. The time of appearance of a consistent biphasic inspiratory flow pattern was considerably later, at approximately age 1 year and coincided with the appearance of a delay in inspiratory muscle activation. From our results, we conclude that the transition from the neonatal to the adult breathing strategy in the horse appears not to be induced by the time course of chest wall stiffening during maturation. While changes in relative body proportions and size of abdominal contents during growth may influence the transition in breathing, our results also indicate that respiratory control mechanisms play an essential role in the expression of the polyphasic breathing pattern.

Block of HERG human K(+) channel and IKr of guinea pig cardiomyocytes by chlorpromazine.

PubMed

Lee, So-Young; Choi, Se-Young; Youm, Jae Boum; Ho, Won-Kyung; Earm, Yung E; Lee, Chin O; Jo, Su-Hyun

2004-05-01

Chlorpromazine, a commonly used antipsychotic drug, has been known to induce QT prolongation and torsades de pointes, which can cause sudden death. We studied the effects of chlorpromazine on the human ether-a-go-go-related gene (HERG) channel expressed in Xenopus oocytes and on delayed rectifier K current of guinea pig ventricular myocytes. Application of chlorpromazine showed a dose-dependent decrease in the amplitudes of steady-state currents and tail currents of HERG. The decrease became more pronounced at increasingly positive potential, suggesting that the blockade of HERG by chlorpromazine is voltage dependent. IC50 for chlorpromazine block of HERG current was progressively decreased according to depolarization: IC50 values at -30, 0, and +30 mV were 10.5, 8.8, and 4.9 microM, respectively. The block of HERG current during the voltage step increased with time starting from a level 89% of the control current. In guinea pig ventricular myocytes, bath application of 2 and 5 microM chlorpromazine at 36 degree C blocked rapidly activating delayed rectifier K current (IKr) by 31 and 83%, respectively. How-ever, the same concentrations of chlorpromazine failed to significantly block slowly activating delayed rectifier K current (IKs). Our findings suggest that the arrhythmogenic side effect of chlorpromazine is caused by blockade of HERG and rapid component of delayed rectifier K current rather than by blockade of the slow component.

[Cormorbidity in multiple sclerosis and its therapeutic approach].

PubMed

Estruch, Bonaventura Casanova

2014-12-01

Multiple sclerosis (MS) is a long-term chronic disease, in which intercurrent processes develop three times more frequently in affected individuals than in persons without MS. Knowledge of the comorbidity of MS, its definition and measurement (Charlson index) improves patient management. Acting on comorbid conditions delays the progression of disability, which is intimately linked to the number of concurrent processes and with health states and habits. Moreover, the presence of comorbidities delays the diagnosis of MS, which in turn delays the start of treatment. The main comorbidity found in MS includes other autoimmune diseases (thyroiditis, systemic lupus erythematosus, or pemphigus) but can also include general diseases, such as asthma or osteomuscular alterations, and, in particular, psychiatric disturbances. All these alterations should be evaluated with multidimensional scales (Disability Expectancy Table, DET), which allow more accurate determination of the patient's real clinical course and quality of life. These scales also allow identification of how MS, concurrent and intercurrent processes occurring during the clinical course, and the treatment provided affect patients with MS. An overall approach to patients' health status helps to improve quality of life. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

The developmental switch in GABA polarity is delayed in fragile X mice.

PubMed

He, Qionger; Nomura, Toshihiro; Xu, Jian; Contractor, Anis

2014-01-08

Delays in synaptic and neuronal development in the cortex are key hallmarks of fragile X syndrome, a prevalent neurodevelopmental disorder that causes intellectual disability and sensory deficits and is the most common known cause of autism. Previous studies have demonstrated that the normal progression of plasticity and synaptic refinement during the critical period is altered in the cortex of fragile X mice. Although the disruptions in excitatory synapses are well documented in fragile X, there is less known about inhibitory neurotransmission during the critical period. GABAergic transmission plays a crucial trophic role in cortical development through its early depolarizing action. At the end of cortical critical period, response properties of GABA transform into their mature hyperpolarizing type due to developmental changes in intracellular chloride homeostasis. We found that the timing of the switch from depolarizing to hyperpolarizing GABA is delayed in the cortex of fragile X mice and there is a concurrent alteration in the expression of the neuronal chloride cotransporter NKCC1 that promotes the accumulation of intracellular chloride. Disruption of the trophic effects of GABA during cortical development could contribute to the altered trajectory of synaptic maturation in fragile X syndrome.

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

Chen, Ying; Li, Cuiying; Weng, Dong

Silica exposure can cause lung inflammation and fibrosis, known as silicosis. Interleukin-17A (IL-17A) and Th17 cells play a pivotal role in controlling inflammatory diseases. However, the roles of IL-17A and Th17 cells in the progress of silica-induced inflammation and fibrosis are poorly understood. This study explored the effects of IL-17A on silica-induced inflammation and fibrosis. We used an anti-mouse IL-17A antibody to establish an IL-17A-neutralized mice model, and mice were exposed to silica to establish an experimental silicosis model. We showed that IL-17A neutralization delayed neutrophil accumulation and progression of silica-induced lung inflammation and fibrosis. IL-17A neutralization reduced the percentagemore » of Th17 in CD4 + T cells, decreased IL-6 and IL-1β expression, and increased Tregs at an early phase of silica-induced inflammation. Neutralization of IL-17A delayed silica-induced Th1/Th2 immune and autoimmune responses. These results suggest that IL-17A neutralization alleviates early stage silica-induced lung inflammation and delays progression of silica-induced lung inflammation and fibrosis. Neutralization of IL-17A suppressed Th17 cell development by decreasing IL-6 and/or IL-1β and increased Tregs at an early phase of silica-induced inflammation. Neutralization of IL-17A also delayed the Th1/Th2 immune response during silica-induced lung inflammation and fibrosis. IL-17A may play a pivotal role in the early phase of silica-induced inflammation and may mediate the Th immune response to influence silica-induced lung inflammation and fibrosis in mice. - Highlights: • Neutralization of IL-17A alleviated silica-induced lung inflammation of early stage. • Neutralization of IL-17A decreased Th17 cells and increased Tregs. • IL-17A mediated the reciprocal relationship of Th17/Tregs by IL-6 and/or IL-1β. • Neutralization of IL-17A delayed silica-induced Th1/Th2 immune response. • Neutralization of IL-17A delayed silica-induced lung inflammation and fibrosis.« less

Gravitational force modulates G2/M phase exit in mechanically unloaded myoblasts

PubMed Central

Benavides Damm, Tatiana; Franco-Obregón, Alfredo; Egli, Marcel

2013-01-01

Prolonged spaceflight gives rise to muscle loss and reduced strength, a condition commonly referred to as space atrophy. During exposure to microgravity, skeletal muscle myoblasts are mechanically unloaded and respond with attenuated cell proliferation, slowed cell cycle progression, and modified protein expression. To elucidate the underlying mechanisms by which muscle mass declines in response to prolonged microgravity exposure, we grew C2C12 mouse muscle cells under conditions of simulated microgravity (SM) and analyzed their proliferative capacity, cell cycle progression, and cyclin B and D expression. We demonstrated that the retarded cell growth observed in SM was correlated with an approximate 16 h delay in G2/M phase progression, where cells accumulated specifically between the G2 checkpoint and the onset of anaphase, concomitantly with a positive expression for cyclin B. The effect was specific for gravitational mechanical unloading as cells grown under conditions of hypergravity (HG, 4 g) for similar durations of time exhibited normal proliferation and normal cell cycle progression. Our results show that SM and HG exert phenomenological distinct responses over cell cycle progression. The deficits of SM can be restored by terrestrial gravitational force, whereas the effects of HG are indistinguishable from the 1 g control. This suggests that the mechanotransduction apparatus of cells responds differently to mechanical unloading and loading. PMID:23974110

Effect of Time Delay on Recognition Memory for Pictures: The Modulatory Role of Emotion

PubMed Central

Wang, Bo

2014-01-01

This study investigated the modulatory role of emotion in the effect of time delay on recognition memory for pictures. Participants viewed neutral, positive and negative pictures, and took a recognition memory test 5 minutes, 24 hours, or 1 week after learning. The findings are: 1) For neutral, positive and negative pictures, overall recognition accuracy in the 5-min delay did not significantly differ from that in the 24-h delay. For neutral and positive pictures, overall recognition accuracy in the 1-week delay was lower than in the 24-h delay; for negative pictures, overall recognition in the 24-h and 1-week delay did not significantly differ. Therefore negative emotion modulates the effect of time delay on recognition memory, maintaining retention of overall recognition accuracy only within a certain frame of time. 2) For the three types of pictures, recollection and familiarity in the 5-min delay did not significantly differ from that in the 24-h and the 1-week delay. Thus emotion does not appear to modulate the effect of time delay on recollection and familiarity. However, recollection in the 24-h delay was higher than in the 1-week delay, whereas familiarity in the 24-h delay was lower than in the 1-week delay. PMID:24971457

Propagation of damage in the rat brain following sarin exposure: Differential progression of early processes

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

Lazar, Shlomi; Egoz, Inbal; Brandeis, Rachel

Sarin is an irreversible organophosphate cholinesterase inhibitor and a highly toxic warfare agent. Following the overt, dose-dependent signs (e.g. tremor, hyper secretion, seizures, respiratory depression and eventually death), brain damage is often reported. The goal of the present study was to characterize the early histopathological and biochemical events leading to this damage. Rats were exposed to 1LD50 of sarin (80 μg/kg, i.m.). Brains were removed at 1, 2, 6, 24 and 48 h and processed for analysis. Results showed that TSPO (translocator protein) mRNA increased at 6 h post exposure while TSPO receptor density increased only at 24 h. Inmore » all brain regions tested, bax mRNA decreased 1 h post exposure followed by an increase 24 h later, with only minor increase in bcl2 mRNA. At this time point a decrease was seen in both anti-apoptotic protein Bcl2 and pro-apoptotic Bax, followed by a time and region specific increase in Bax. An immediate elevation in ERK1/2 activity with no change in JNK may indicate an endogenous “first response” mechanism used to attenuate the forthcoming apoptosis. The time dependent increase in the severity of brain damage included an early bi-phasic activation of astrocytes, a sharp decrease in intact neuronal cells, a time dependent reduction in MAP2 and up to 15% of apoptosis. Thus, neuronal death is mostly due to necrosis and severe astrocytosis. The data suggests that timing of possible treatments should be determined by early events following exposure. For example, the biphasic changes in astrocytes activity indicate a possible beneficial effects of delayed anti-inflammatory intervention. - Highlights: • The severity of brain damage post 1LD50 sarin exposure is time dependent. • Sarin induce differential progression of early processes in the rat brain. • Potential treatments should be timed according to early events following exposure. • The biphasic astrocytes activity suggests a delay in anti-inflammatory intervention.« less

Using filtered forecasting techniques to determine personalized monitoring schedules for patients with open-angle glaucoma.

PubMed

Schell, Greggory J; Lavieri, Mariel S; Helm, Jonathan E; Liu, Xiang; Musch, David C; Van Oyen, Mark P; Stein, Joshua D

2014-08-01

To determine whether dynamic and personalized schedules of visual field (VF) testing and intraocular pressure (IOP) measurements result in an improvement in disease progression detection compared with fixed interval schedules for performing these tests when evaluating patients with open-angle glaucoma (OAG). Secondary analyses using longitudinal data from 2 randomized controlled trials. A total of 571 participants from the Advanced Glaucoma Intervention Study (AGIS) and the Collaborative Initial Glaucoma Treatment Study (CIGTS). Perimetric and tonometric data were obtained for AGIS and CIGTS trial participants and used to parameterize and validate a Kalman filter model. The Kalman filter updates knowledge about each participant's disease dynamics as additional VF tests and IOP measurements are obtained. After incorporating the most recent VF and IOP measurements, the model forecasts each participant's disease dynamics into the future and characterizes the forecasting error. To determine personalized schedules for future VF tests and IOP measurements, we developed an algorithm by combining the Kalman filter for state estimation with the predictive power of logistic regression to identify OAG progression. The algorithm was compared with 1-, 1.5-, and 2-year fixed interval schedules of obtaining VF and IOP measurements. Length of diagnostic delay in detecting OAG progression, efficiency of detecting progression, and number of VF and IOP measurements needed to assess for progression. Participants were followed in the AGIS and CIGTS trials for a mean (standard deviation) of 6.5 (2.8) years. Our forecasting model achieved a 29% increased efficiency in identifying OAG progression (P<0.0001) and detected OAG progression 57% sooner (reduced diagnostic delay) (P = 0.02) than following a fixed yearly monitoring schedule, without increasing the number of VF tests and IOP measurements required. The model performed well for patients with mild and advanced disease. The model performed significantly more testing of patients who exhibited OAG progression than nonprogressing patients (1.3 vs. 1.0 tests per year; P<0.0001). Use of dynamic and personalized testing schedules can enhance the efficiency of OAG progression detection and reduce diagnostic delay compared with yearly fixed monitoring intervals. If further validation studies confirm these findings, such algorithms may be able to greatly enhance OAG management. Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Pivotal roles of Kupffer cells in the progression and regression of DDC-induced chronic cholangiopathy.

PubMed

Jemail, Leila; Miyao, Masashi; Kotani, Hirokazu; Kawai, Chihiro; Minami, Hirozo; Abiru, Hitoshi; Tamaki, Keiji

2018-04-23

Kupffer cells (KCs) are key players in maintaining tissue homeostasis and are involved in various liver diseases. However, the roles of KCs in the pathogenesis of cholangiopathy are largely unknown. We aimed to investigate the precise roles of KCs in both the progression and regression phases of the 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-induced cholangiopathy model. In the early phase of DDC-induced cholangiopathy, the number of KCs significantly increased over time. Moreover, KCs were associated with abnormal phenotypic changes in other liver cells, such as hepatocytes, biliary epithelial cells, liver sinusoidal endothelial cells, and hepatic stellate cells. In contrast, KC depletion by clodronate administration suppressed the progression of the disease, and maintained the phenotypes of other cells. In the regression phase, the numbers of KCs significantly decreased, and the cells redifferentiated to their quiescent state. In contrast, KC depletion delayed the recovery of cells by maintaining other liver cells in an active state. These findings suggest that KCs play detrimental roles in the progression phase; however, they are beneficial in the regression phase by mediating interactions between other liver cells. Our data provide new insights into the roles of KCs in the pathogenesis of cholangiopathy.

Angular dependence of EWS time delay for photoionization of @Xe

NASA Astrophysics Data System (ADS)

Mandal, Ankur; Deshmukh, Pranawa; Kheifets, Anatoli; Dolmatov, Valeriy; Manson, Steven

2017-04-01

Interference between photoionization channels leads to angular dependence in photoionization time delay. Angular dependence is found to be a common effect for two-photon absorption experiments very recently. The effect of confinement on the time delay where each partial wave contributions to the ionization are studied. In this work we report angular dependence and confinement effects on Eisenbud-Wigner-Smith (EWS) time delay in atomic photoionization. Using and we computed the EWS time delay for free and confined Xe atom for photoionization from inner 4d3/2 and 4d5/2 and outer 5p1/2 and 5p3/2 subshells at various angles. The calculated EWS time delay is few tens to few hundreds of attoseconds (10-18 second). The photoionization time delay for @Xe follows that in the free Xe atom on which the confinement oscillations are built. The present work reveals the effect of confinement on the photoionization time delay at different angles between photoelectron ejection and the photon polarization.

Crash testing difference-smoothing algorithm on a large sample of simulated light curves from TDC1

NASA Astrophysics Data System (ADS)

Rathna Kumar, S.

2017-09-01

In this work, we propose refinements to the difference-smoothing algorithm for the measurement of time delay from the light curves of the images of a gravitationally lensed quasar. The refinements mainly consist of a more pragmatic approach to choose the smoothing time-scale free parameter, generation of more realistic synthetic light curves for the estimation of time delay uncertainty and using a plot of normalized χ2 computed over a wide range of trial time delay values to assess the reliability of a measured time delay and also for identifying instances of catastrophic failure. We rigorously tested the difference-smoothing algorithm on a large sample of more than thousand pairs of simulated light curves having known true time delays between them from the two most difficult 'rungs' - rung3 and rung4 - of the first edition of Strong Lens Time Delay Challenge (TDC1) and found an inherent tendency of the algorithm to measure the magnitude of time delay to be higher than the true value of time delay. However, we find that this systematic bias is eliminated by applying a correction to each measured time delay according to the magnitude and sign of the systematic error inferred by applying the time delay estimator on synthetic light curves simulating the measured time delay. Following these refinements, the TDC performance metrics for the difference-smoothing algorithm are found to be competitive with those of the best performing submissions of TDC1 for both the tested 'rungs'. The MATLAB codes used in this work and the detailed results are made publicly available.

Endogenous T cell responses to antigens expressed in lung adenocarcinomas delay malignant tumor progression

PubMed Central

DuPage, Michel; Cheung, Ann; Mazumdar, Claire; Winslow, Monte M.; Bronson, Roderick; Schmidt, Leah M.; Crowley, Denise; Chen, Jianzhu; Jacks, Tyler

2010-01-01

SUMMARY Neoantigens derived from somatic mutations in tumors may provide a critical link between the adaptive immune system and cancer. Here we describe a system to introduce exogenous antigens into genetically engineered mouse lung cancers to mimic tumor neoantigens. We show that endogenous T cells respond to and infiltrate tumors, significantly delaying malignant progression. Despite continued antigen expression, T cell infiltration does not persist and tumors ultimately escape immune attack. Transplantation of cell lines derived from these lung tumors or prophylactic vaccination against the autochthonous tumors, however, results in rapid tumor eradication or selection of tumors that lose antigen expression. These results provide insight into the dynamic nature of the immune response to naturally arising tumors. PMID:21251614

Delayed Disease Progression in Cynomolgus Macaques Infected with Ebola Virus Makona Strain.

PubMed

Marzi, Andrea; Feldmann, Friederike; Hanley, Patrick W; Scott, Dana P; Günther, Stephan; Feldmann, Heinz

2015-10-01

In late 2013, the largest documented outbreak of Ebola hemorrhagic fever started in Guinea and has since spread to neighboring countries, resulting in almost 27,000 cases and >11,000 deaths in humans. In March 2014, Ebola virus (EBOV) was identified as the causative agent. This study compares the pathogenesis of a new EBOV strain, Makona, which was isolated in Guinea in 2014 with the prototype strain from the 1976 EBOV outbreak in the former Zaire. Both strains cause lethal disease in cynomolgus macaques with similar pathologic changes and hallmark features of Ebola hemorrhagic fever. However, disease progression was delayed in EBOV-Makona-infected animals, suggesting decreased rather than increased virulence of this most recent EBOV strain.

Applying a behavioral economic framework to understanding adolescent smoking.

PubMed

Audrain-McGovern, Janet; Rodriguez, Daniel; Tercyak, Kenneth P; Epstein, Leonard H; Goldman, Paula; Wileyto, E Paul

2004-03-01

Adolescents' choice to smoke may depend on substitute reinforcers for smoking, complementary activities to smoking, and individual differences in reinforcer value. The influence of these variables on smoking was determined among 983 adolescents. Substitutes were school involvement, academic performance, physical activity, and sports team participation: complements were peer smoking and substance use; delay discounting assessed individual differences in reinforcer value. Latent growth modeling indicated that substitute reinforcers reduced the odds of smoking progression almost two-fold, complementary reinforcers increased the odds by 1.14. and delay discounting indirectly influenced the odds of smoking progression through complementary reinforcers. Adolescents who smoke may have fewer reinforcers that protect against smoking and more reinforcers that promote smoking. Discounting of future rewards affects smoking through reinforcer type.

Straight A's: Public Education Policy and Progress. Volume 6, Number 23

ERIC Educational Resources Information Center

Amos, Jason, Ed.

2006-01-01

"Straight A's: Public Education Policy and Progress" is a biweekly newsletter that focuses on education news and events both in Washington, DC and around the country. The following articles are included in this issue: (1) See You Next Year: Congress Wraps Up for 2006, Delays Education Funding Decisions to 2007; (2) "Healthier and Wealthier":…

Technical Adequacy of Early Numeracy Curriculum-Based Progress Monitoring Measures for Kindergarten and First-Grade Students

ERIC Educational Resources Information Center

Hampton, David D.; Lembke, Erica S.; Lee, Young-Sun; Pappas, Sandra; Chiong, Cynthia; Ginsburg, Herbert P.

2012-01-01

The purpose of this study was to examine six early numeracy measures used to monitor the mathematics progress of kindergarten and first-grade students. Seventy-one kindergarten students and 75 first-grade students were administered the measures each week. Delayed-alternate form reliability was adequate for instructional decision making on some…

True-time-delay photonic beamformer for an L-band phased array radar

NASA Astrophysics Data System (ADS)

Zmuda, Henry; Toughlian, Edward N.; Payson, Paul M.; Malowicki, John E.

1995-10-01

The problem of obtaining a true-time-delay photonic beamformer has recently been a topic of great interest. Many interesting and novel approaches to this problem have been studied. This paper examines the design, construction, and testing of a dynamic optical processor for the control of a 20-element phased array antenna operating at L-band (1.2-1.4 GHz). The approach taken here has several distinct advantages. The actual optical control is accomplished with a class of spatial light modulator known as a segmented mirror device (SMD). This allows for the possibility of controlling an extremely large number (tens of thousands) of antenna elements using integrated circuit technology. The SMD technology is driven by the HDTV and laser printer markets so ultimate cost reduction as well as technological improvements are expected. Optical splitting is efficiently accomplished using a diffractive optical element. This again has the potential for use in antenna array systems with a large number of radiating elements. The actual time delay is achieved using a single acousto-optic device for all the array elements. Acousto-optic device technologies offer sufficient delay as needed for a time steered array. The topological configuration is an optical heterodyne system, hence high, potentially millimeter wave center frequencies are possible by mixing two lasers of slightly differing frequencies. Finally, the entire system is spatially integrated into a 3D glass substrate. The integrated system provides the ruggedness needed in most applications and essentially eliminates the drift problems associated with free space optical systems. Though the system is presently being configured as a beamformer, it has the ability to operate as a general photonic signal processing element in an adaptive (reconfigurable) transversal frequency filter configuration. Such systems are widely applicable in jammer/noise canceling systems, broadband ISDN, and for spread spectrum secure communications. This paper also serves as an update of work-in-progress at the Rome Laboratory Photonics Center Optical Beamforming Lab. The multi-faceted aspects of the design and construction of this state-of-the-art beamforming project will be discussed. Experimental results which demonstrate the performance of the system to-date with regard to both maximum delay and resolution over a broad bandwidth are presented.

Comparison of delay enhancement mechanisms for SBS-based slow light systems.

PubMed

Schneider, Thomas; Henker, Ronny; Lauterbach, Kai-Uwe; Junker, Markus

2007-07-23

We compare two simple mechanisms for the enhancement of the time delay in slow light systems. Both are based on the superposition of the Brillouin gain with additional loss. As we will show in theory and experiment if two losses are placed at the wings of a SBS gain, contrary to other methods, the loss power increases the time delay. This leads to higher delay times at lower optical powers and to an increase of the zero gain delay of more than 50%. With this method we achieved a time delay of more than 120ns for pulses with a temporal width of 30ns. To the best of our knowledge, this is the highest time delay in just one fiber spool. Beside the enhancement of the time delay the method could have the potential to decrease the pulse distortions for high bit rate signals.

Impact of Partial Time Delay on Temporal Dynamics of Watts-Strogatz Small-World Neuronal Networks

NASA Astrophysics Data System (ADS)

Yan, Hao; Sun, Xiaojuan

2017-06-01

In this paper, we mainly discuss effects of partial time delay on temporal dynamics of Watts-Strogatz (WS) small-world neuronal networks by controlling two parameters. One is the time delay τ and the other is the probability of partial time delay pdelay. Temporal dynamics of WS small-world neuronal networks are discussed with the aid of temporal coherence and mean firing rate. With the obtained simulation results, it is revealed that for small time delay τ, the probability pdelay could weaken temporal coherence and increase mean firing rate of neuronal networks, which indicates that it could improve neuronal firings of the neuronal networks while destroying firing regularity. For large time delay τ, temporal coherence and mean firing rate do not have great changes with respect to pdelay. Time delay τ always has great influence on both temporal coherence and mean firing rate no matter what is the value of pdelay. Moreover, with the analysis of spike trains and histograms of interspike intervals of neurons inside neuronal networks, it is found that the effects of partial time delays on temporal coherence and mean firing rate could be the result of locking between the period of neuronal firing activities and the value of time delay τ. In brief, partial time delay could have great influence on temporal dynamics of the neuronal networks.

Piloted simulator study of allowable time delay in pitch flight control system of a transport airplane with negative static stability

NASA Technical Reports Server (NTRS)

Grantham, William D.; Smith, Paul M.; Person, Lee H., Jr.; Meyer, Robert T.; Tingas, Stephen A.

1987-01-01

A piloted simulation study was conducted to determine the permissible time delay in the flight control system of a 10-percent statically unstable transport airplane during cruise flight conditions. The math model used for the simulation was a derivative Lockheed L-1011 wide-body jet transport. Data were collected and analyzed from a total of 137 cruising flights in both calm- and turbulent-air conditions. Results of this piloted simulation study verify previous findings that show present military specifications for allowable control-system time delay may be too stringent when applied to transport-size airplanes. Also, the degree of handling-qualities degradation due to time delay is shown to be strongly dependent on the source of the time delay in an advanced flight control system. Maximum allowable time delay for each source of time delay in the control system, in addition to a less stringent overall maximum level of time delay, should be considered for large aircraft. Preliminary results also suggest that adverse effects of control-system time delay may be at least partially offset by variations in control gearing. It is recommended that the data base include different airplane baselines, control systems, and piloting tasks with many pilots participating, so that a reasonable set of limits for control-system time delay can be established to replace the military specification limits currently being used.

Cost Effectiveness of Alectinib vs. Crizotinib in First-Line Anaplastic Lymphoma Kinase-Positive Advanced Non-Small-Cell Lung Cancer.

PubMed

Carlson, Josh J; Suh, Kangho; Orfanos, Panos; Wong, William

2018-04-01

The recently completed ALEX trial demonstrated that alectinib improved progression-free survival, and delayed time to central nervous system progression compared with crizotinib in patients with anaplastic lymphoma kinase-positive non-small-cell lung cancer. However, the long-term clinical and economic impact of using alectinib vs. crizotinib has not been evaluated. The objective of this study was to determine the potential cost utility of alectinib vs. crizotinib from a US payer perspective. A cost-utility model was developed using partition survival methods and three health states: progression-free, post-progression, and death. ALEX trial data informed the progression-free and overall survival estimates. Costs included drug treatments and supportive care (central nervous system and non-central nervous system). Utility values were obtained from trial data and literature. Sensitivity analyses included one-way and probabilistic sensitivity analyses. Treatment with alectinib vs. crizotinib resulted in a gain of 0.91 life-years, 0.87 quality-adjusted life-years, and incremental costs of US$34,151, resulting in an incremental cost-effectiveness ratio of US$39,312/quality-adjusted life-year. Drug costs and utilities in the progression-free health state were the main drivers of the model in the one-way sensitivity analysis. From the probabilistic sensitivity analysis, alectinib had a 64% probability of being cost effective at a willingness-to-pay threshold of US$100,000/quality adjusted life-year. Alectinib increased time in the progression-free state and quality-adjusted life-years vs. crizotinib. The marginal cost increase was reflective of longer treatment durations in the progression-free state. Central nervous system-related costs were considerably lower with alectinib. Our results suggest that compared with crizotinib, alectinib may be a cost-effective therapy for treatment-naïve patients with anaplastic lymphoma kinase-positive non-small-cell lung cancer.

Model predictions of higher-order normal alkane ignition from dilute shock-tube experiments

NASA Astrophysics Data System (ADS)

Rotavera, B.; Petersen, E. L.

2013-07-01

Shock-induced oxidation of two higher-order linear alkanes was measured using a heated shock tube facility. Experimental overlap in stoichiometric ignition delay times obtained under dilute (99 % Ar) conditions near atmospheric pressure was observed in the temperature-dependent ignition trends of n-nonane ( n-C9H20) and n-undecane ( n-C11H24). Despite the overlap, model predictions of ignition using two different detailed chemical kinetics mechanisms show discrepancies relative to both the measured data as well as to one another. The present study therefore focuses on the differences observed in the modeled, high-temperature ignition delay times of higher-order n-alkanes, which are generally regarded to have identical ignition behavior for carbon numbers above C7. Comparisons are drawn using experimental data from the present study and from recent work by the authors relative to two existing chemical kinetics mechanisms. Time histories from the shock-tube OH* measurements are also compared to the model predictions; a double-peaked structure observed in the data shows that the time response of the detector electronics is crucial for properly capturing the first, incipient peak near time zero. Calculations using the two mechanisms were carried out at the dilution level employed in the shock-tube experiments for lean {({φ} = 0.5)}, stoichiometric, and rich {({φ} = 2.0)} equivalence ratios, 1230-1620 K, and for both 1.5 and 10 atm. In general, the models show differing trends relative to both measured data and to one another, indicating that agreement among chemical kinetics models for higher-order n-alkanes is not consistent. For example, under certain conditions, one mechanism predicts the ignition delay times to be virtually identical between the n-nonane and n-undecane fuels (in fact, also for all alkanes between at least C8 and C12), which is in agreement with the experiment, while the other mechanism predicts the larger fuels to ignite progressively more slowly.

76 FR 68734 - Taking and Importing Marine Mammals: Taking Marine Mammals Incidental to Navy Training Exercises...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-07

... marine mammal is likely to travel during the time associated with the TDFD's time delay, and that... Navy provided the approximate distance that an animal would typically travel within a given time-delay... Speed and Length of Time-Delay Potential distance Species group Swim speed Time-delay traveled Delphinid...

Probability of Loss of Assured Safety in Systems with Multiple Time-Dependent Failure Modes: Incorporation of Delayed Link Failure in the Presence of Aleatory Uncertainty.

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

Helton, Jon C.; Brooks, Dusty Marie; Sallaberry, Cedric Jean-Marie.

Probability of loss of assured safety (PLOAS) is modeled for weak link (WL)/strong link (SL) systems in which one or more WLs or SLs could potentially degrade into a precursor condition to link failure that will be followed by an actual failure after some amount of elapsed time. The following topics are considered: (i) Definition of precursor occurrence time cumulative distribution functions (CDFs) for individual WLs and SLs, (ii) Formal representation of PLOAS with constant delay times, (iii) Approximation and illustration of PLOAS with constant delay times, (iv) Formal representation of PLOAS with aleatory uncertainty in delay times, (v) Approximationmore » and illustration of PLOAS with aleatory uncertainty in delay times, (vi) Formal representation of PLOAS with delay times defined by functions of link properties at occurrence times for failure precursors, (vii) Approximation and illustration of PLOAS with delay times defined by functions of link properties at occurrence times for failure precursors, and (viii) Procedures for the verification of PLOAS calculations for the three indicated definitions of delayed link failure.« less

Local Immune Responsiveness of Mice Bearing Premalignant Oral Lesions to PD-1 Antibody Treatment.

PubMed

Levingston, Corinne A; Young, M Rita I

2017-06-02

A carcinogen-induced premalignant oral lesion model that progresses to oral cancer was used to examine the immunological impact of a 5-week treatment regimen to block programmed cell death protein 1 (PD-1). PD-1 antibody treatment resulted in concurrent, but transient, increases in interleukin (IL)-2, IFN-γ and IL-17, and delayed increases in IL-6 and IL-10 within the lesion-bearing tongue epithelium. In contrast, cytokine secretion by lymph node cells of PD-1 antibody-treated mice was lower than for mice treated with control antibodies, with the exception of interferon (IFN)-γ, whose secretion increased late in the treatment period. This delayed secretion of IFN-γ coincided with an increase in CD4⁺ lymph node cells expressing IFN-γ. Lymph node cells of PD-1 antibody-treated mice reacted to a challenge with lysates of lesions or cancer by early production of IFN-γ, but this rapidly subsided. There also was increased production IL-17 and tumor necrosis factor (TNF)-α in response to the challenge, but the response was greatest by cells of control lesion-bearing mice. Clinical assessment showed an early but transient, stabilization of disease in mice treated with PD-1 antibody. These results show an early beneficial, but time-limited, response to PD-1 antibody treatment, which then fails with continued lesion progression.

Novel insights into a retinoic-acid-induced cleft palate based on Rac1 regulation of the fibronectin arrangement.

PubMed

Tang, Qinghuang; Li, Liwen; Lee, Min-Jung; Ge, Qing; Lee, Jong-Min; Jung, Han-Sung

2016-03-01

Retinoic acid (RA)-induced cleft palate results from both extrinsic obstructions by the tongue and internal factors within the palatal shelves. Our previous study showed that the spatiotemporal expression of Rac1 regulates the fibronectin (FN) arrangement through cell density alterations that play an important role in palate development. In this study, we investigate the involvement of the Rac1 regulation of the FN arrangement in RA-induced cleft palate. Our results demonstrate that RA-induced intrinsic alterations in palatal shelves, including a delayed progress of cell condensation, delay palate development, even after the removal of the tongue. Further analysis shows that RA treatment diminishes the region-distinctive expression of Rac1 within the palatal shelves, which reversely alters the fibrillar arrangement of FN. Furthermore, RA treatment disrupts the formation of lamellipodia, which are indicative structures of cell migration that are regulated by Rac1. These results suggest that the Rac1 regulation of the FN arrangement is involved in RA-induced cleft palate through the regulation of cell migration, which delays the progress of cell condensation and subsequently influences the FN arrangement, inducing a delay in palate development. Our study provides new insights into the RA-induced impairment of palatal shelf elevation based on cell migration dynamics.

Concordance of CCR5 genotypes that influence cell-mediated immunity and HIV-1 disease progression rates.

PubMed

Catano, Gabriel; Chykarenko, Zoya A; Mangano, Andrea; Anaya, J-M; He, Weijing; Smith, Alison; Bologna, Rosa; Sen, Luisa; Clark, Robert A; Lloyd, Andrew; Shostakovich-Koretskaya, Ludmila; Ahuja, Sunil K

2011-01-15

We used cutaneous delayed-type hypersensitivity responses, a powerful in vivo measure of cell-mediated immunity, to evaluate the relationships among cell-mediated immunity, AIDS, and polymorphisms in CCR5, the HIV-1 coreceptor. There was high concordance between CCR5 polymorphisms and haplotype pairs that influenced delayed-type hypersensitivity responses in healthy persons and HIV disease progression. In the cohorts examined, CCR5 genotypes containing -2459G/G (HHA/HHA, HHA/HHC, HHC/HHC) or -2459A/A (HHE/HHE) associated with salutary or detrimental delayed-type hypersensitivity and AIDS phenotypes, respectively. Accordingly, the CCR5-Δ32 allele, when paired with non-Δ32-bearing haplotypes that correlate with low (HHA, HHC) versus high (HHE) CCR5 transcriptional activity, associates with disease retardation or acceleration, respectively. Thus, the associations of CCR5-Δ32 heterozygosity partly reflect the effect of the non-▵32 haplotype in a background of CCR5 haploinsufficiency. The correlations of increased delayed-type hypersensitivity with -2459G/G-containing CCR5 genotypes, reduced CCR5 expression, decreased viral replication, and disease retardation suggest that CCR5 may influence HIV infection and AIDS, at least in part, through effects on cell-mediated immunity.

Time delay can facilitate coherence in self-driven interacting-particle systems

NASA Astrophysics Data System (ADS)

Sun, Yongzheng; Lin, Wei; Erban, Radek

2014-12-01

Directional switching in a self-propelled particle model with delayed interactions is investigated. It is shown that the average switching time is an increasing function of time delay. The presented results are applied to studying collective animal behavior. It is argued that self-propelled particle models with time delays can explain the state-dependent diffusion coefficient measured in experiments with locust groups. The theory is further generalized to heterogeneous groups where each individual can respond to its environment with a different time delay.

High-sucrose diets in male rats disrupt aspects of decision making tasks, motivation and spatial memory, but not impulsivity measured by operant delay-discounting.

PubMed

Wong, Alanna; Dogra, Vimi R; Reichelt, Amy C

2017-06-01

Excessive consumption of sugar sweetened drinks is proposed to produce functional changes in the hippocampus and prefrontal cortex, leading to perturbations in behavioural control. Impairments in behavioural control have been observed in obese people on tasks that involve making choices, including delay-discounting, indicative of increased impulsivity. In this study we examined the impact of 2h daily access to 10% sucrose (or no sucrose in controls) in young male rats on behavioural tasks reliant on hippocampal function including delay-discounting, T-maze forced choice alternation and place recognition memory, as well as progressive ratio to measure motivation. We observed deficits in place recognition memory and T-maze forced choice alternation, indicative of hippocampal deficits in rats with a history of sucrose consumption. Moreover, rats with a history of sucrose consumption were less motivated to lever press for rewards on a progressive ratio schedule. However, rats with a history of sucrose consumption performed equally to control animals during the delay-discounting task, suggesting that they discounted for reward size over a delay in a manner comparable to control animals. These findings indicate that high-sucrose diets impact on spatial and working memory processes, but do not induce impulsive-like choice behaviours in rats, suggesting that unhealthy diet choices may not influence this aspect of decision-making behaviour. Copyright © 2017 Elsevier B.V. All rights reserved.

Patients’ Heart Monitoring System Based on Wireless Sensor Network

NASA Astrophysics Data System (ADS)

Sollu, T. S.; Alamsyah; Bachtiar, M.; Sooai, A. G.

2018-04-01

Wireless sensor network (WSN) has been utilized to support the health field such as monitoring the patient’s heartbeat. Heart health monitoring is essential in maintaining health, especially in the elderly. Such an arrangement is needed to understand the patient’s heart characteristics. The increasing number of patients certainly will enhance the burdens of doctors or nurses in dealing with the condition of the patients. Therefore, required a solution that could help doctors or nurses in monitoring the progress of patients’ health at a real time. This research proposes a design and application of a patient heart monitoring system based on WSN. This system with using electrocardiograph (ECG) mounted on the patients’ body and sent to the server through the ZigBee. The results indicated that the retrieval of data for 15 seconds in male patients, with the age of 25 years was 17 times rate or equal to 68 bpm. For 884 data packets sent for 15 minutes using ZigBee produce a data as much as 4488 bytes, throughput of 2.39 Kbps, and 0.24486 seconds of average delay. The measurement of the communication coverage based on the open space conditions within 15 seconds through ZigBee resulting throughput value of 4.19 Kbps, packet loss of 0 %, and 6.667 seconds of average delay. While, the measurement of communication range based on closed space condition through ZigBee resulting throughput of 4.27 Kbps, packet loss of 0 %, and 6.55 seconds of average delay.

Dietary aspartyl-phenylalanine-1-methyl ester delays osteoarthritis and prevents associated bone loss in STR/ORT mice

PubMed Central

Manion, Carl V.; Hochgeschwender, Ute; Edmundson, Allen B.; Hugli, Tony E.

2011-01-01

Objective. STR/ORT mice provide a well-known model for murine idiopathic OA, with histological joint lesions resembling those of human OA. This model was used to investigate protective effects of the dipeptide aspartyl-phenylalanine-1-methyl ester (Asp-Phe-OMe or aspartame) via the oral route vs a regular diet. Methods. STR/ORT mice were housed individually and fed diets with or without Asp-Phe-OMe (4 mg/kg), after weaning at the age of 3 weeks, until 15 months of age (average of 20 animals per group). The study groups were kept blinded to the investigators, who measured food consumption and body weight and performed gait mobility tests. Radiographic scans were also performed at regular time intervals to evaluate differential radiographic anomalies associated with progress of OA in response to oral Asp-Phe-OMe therapy. Results. The Asp-Phe-OMe-fed animals presented a pattern of significantly delayed disease onset. In addition, their muscle and bone mass were highly preserved, even at later time points after OA was established. Moreover, control animals presented a higher variability in gait motility in comparison with the Asp-Phe-OMe-fed animals, suggesting a protective effect from movement limitations associated with advanced OA. Conclusion. Asp-Phe-OMe, given orally, delays OA in the spontaneous STR/ORT model, improves bone cortical density and muscle mass, and may contribute to a better quality of life for these diseased animals. PMID:21372000

Impact of SSRI Therapy on Risk of Conversion From Mild Cognitive Impairment to Alzheimer's Dementia in Individuals With Previous Depression.

PubMed

Bartels, Claudia; Wagner, Michael; Wolfsgruber, Steffen; Ehrenreich, Hannelore; Schneider, Anja

2018-03-01

Depression is associated with an increased risk of Alzheimer's disease. Research has shown that the selective serotonin reuptake inhibitor (SSRI) citalopram decreases amyloid-β generation and plaque load. The authors evaluated the impact of SSRI treatment on CSF biomarkers and progression from mild cognitive impairment (MCI) to Alzheimer's dementia. Data sets from 755 currently nondepressed participants from the longitudinal Alzheimer's Disease Neuroimaging Initiative were evaluated by Kaplan-Meier analysis and analyses of variance and covariance with ApoE4 status and age as covariates. In MCI patients with a history of depression, long-term SSRI treatment (>4 years) was significantly associated with a delayed progression to Alzheimer's dementia by approximately 3 years, compared with short-term SSRI treatment, treatment with other antidepressants, or no treatment and compared with MCI patients without a history of depression. No differences in CSF biomarker levels were observed between treatment groups. Long-term SSRI treatment may delay progression from MCI to Alzheimer's dementia.

Delay banking for air traffic management

NASA Technical Reports Server (NTRS)

Green, Steven M. (Inventor)

2007-01-01

A method and associated system for time delay banking for aircraft arrival time, aircraft departure time and/or en route flight position. The delay credit value for a given flight may decrease with passage of time and may be transferred to or traded with other flights having the same or a different user (airline owner or operator). The delay credit value for a given aircraft flight depends upon an initial delay credit value, which is determined by a central system and depends upon one or more other flight characteristics. Optionally, the delay credit value decreases with passage of time. Optionally, a transaction cost is assessed against a delay credit value that is used on behalf of another flight with the same user or is traded with a different user.

General relation between the group delay and dwell time in multicomponent electron systems

NASA Astrophysics Data System (ADS)

Zhai, Feng; Lu, Junqiang

2016-10-01

For multicomponent electron scattering states, we derive a general relation between the Wigner group delay and the Bohmian dwell time. It is found that the definition of group delay should account for the phase of the spinor wave functions of propagating modes. The difference between the group delay and dwell time comes from both the interference delay and the decaying modes. For barrier tunneling of helical electrons on a surface of topological insulators, our calculations including the trigonal-warping term show that the decaying modes can contribute greatly to the group delay. The derived relation between the group delay and the dwell time is helpful to unify the two definitions of tunneling time in a quite general situation.

CAN LARGE TIME DELAYS OBSERVED IN LIGHT CURVES OF CORONAL LOOPS BE EXPLAINED IN IMPULSIVE HEATING?

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

Lionello, Roberto; Linker, Jon A.; Mikić, Zoran

The light curves of solar coronal loops often peak first in channels associated with higher temperatures and then in those associated with lower temperatures. The delay times between the different narrowband EUV channels have been measured for many individual loops and recently for every pixel of an active region observation. The time delays between channels for an active region exhibit a wide range of values. The maximum time delay in each channel pair can be quite large, i.e., >5000 s. These large time delays make-up 3%–26% (depending on the channel pair) of the pixels where a trustworthy, positive time delaymore » is measured. It has been suggested that these time delays can be explained by simple impulsive heating, i.e., a short burst of energy that heats the plasma to a high temperature, after which the plasma is allowed to cool through radiation and conduction back to its original state. In this paper, we investigate whether the largest observed time delays can be explained by this hypothesis by simulating a series of coronal loops with different heating rates, loop lengths, abundances, and geometries to determine the range of expected time delays between a set of four EUV channels. We find that impulsive heating cannot address the largest time delays observed in two of the channel pairs and that the majority of the large time delays can only be explained by long, expanding loops with photospheric abundances. Additional observations may rule out these simulations as an explanation for the long time delays. We suggest that either the time delays found in this manner may not be representative of real loop evolution, or that the impulsive heating and cooling scenario may be too simple to explain the observations, and other potential heating scenarios must be explored.« less

Cognitive person variables in the delay of gratification of older children at risk.

PubMed

Rodriguez, M L; Mischel, W; Shoda, Y

1989-08-01

The components of self-regulation were analyzed, extending the self-imposed delay of gratification paradigm to older children with social adjustment problems. Delay behavior was related to a network of conceptually relevant cognitive person variables, consisting of attention deployment strategies during delay, knowledge of delay rules, and intelligence. A positive relationship was demonstrated between concurrent indexes of intelligence, attention deployment, and actual delay time. Moreover, attention deployment, measured as an individual differences variable during the delay process, had a direct, positive effect on delay behavior. Specifically, as the duration of delay and the frustration of the situation increased, children who spent a higher proportion of the time distracting themselves from the tempting elements of the delay situation were able to delay longer. The effect of attention deployment on delay behavior was significant even when age, intelligence, and delay rule knowledge were controlled. Likewise, delay rule knowledge significantly predicted delay time, even when age, attention deployment, and intelligence were controlled.

Model-Based Phenotypic Signatures Governing the Dynamics of the Stem and Semi-differentiated Cell Populations in Dysplastic Colonic Crypts.

PubMed

Nikolov, Svetoslav; Santos, Guido; Wolkenhauer, Olaf; Vera, Julio

2018-02-01

Mathematical modeling of cell differentiated in colonic crypts can contribute to a better understanding of basic mechanisms underlying colonic tissue organization, but also its deregulation during carcinogenesis and tumor progression. Here, we combined bifurcation analysis to assess the effect that time delay has in the complex interplay of stem cells and semi-differentiated cells at the niche of colonic crypts, and systematic model perturbation and simulation to find model-based phenotypes linked to cancer progression. The models suggest that stem cell and semi-differentiated cell population dynamics in colonic crypts can display chaotic behavior. In addition, we found that clinical profiling of colorectal cancer correlates with the in silico phenotypes proposed by the mathematical model. Further, potential therapeutic targets for chemotherapy resistant phenotypes are proposed, which in any case will require experimental validation.

The potential of epigenetic therapies in neurodegenerative diseases

PubMed Central

Coppedè, Fabio

2014-01-01

Available treatments for neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease, do not arrest disease progression but mainly help keeping patients from getting worse for a limited period of time. Increasing evidence suggests that epigenetic mechanisms such as DNA methylation and histone tail modifications are dynamically regulated in neurons and play a fundamental role in learning and memory processes. In addition, both global and gene-specific epigenetic changes and deregulated expression of the writer and eraser proteins of epigenetic marks are believed to contribute to the onset and progression of neurodegeneration. Studies in animal models of neurodegenerative diseases have highlighted the potential role of epigenetic drugs, including inhibitors of histone deacetylases and methyl donor compounds, in ameliorating the cognitive symptoms and preventing or delaying the motor symptoms of the disease, thereby opening the way for a potential application in human pathology. PMID:25071843

EPG5-related Vici syndrome: a paradigm of neurodevelopmental disorders with defective autophagy.

PubMed

Byrne, Susan; Jansen, Lara; U-King-Im, Jean-Marie; Siddiqui, Ata; Lidov, Hart G W; Bodi, Istvan; Smith, Luke; Mein, Rachael; Cullup, Thomas; Dionisi-Vici, Carlo; Al-Gazali, Lihadh; Al-Owain, Mohammed; Bruwer, Zandre; Al Thihli, Khalid; El-Garhy, Rana; Flanigan, Kevin M; Manickam, Kandamurugu; Zmuda, Erik; Banks, Wesley; Gershoni-Baruch, Ruth; Mandel, Hanna; Dagan, Efrat; Raas-Rothschild, Annick; Barash, Hila; Filloux, Francis; Creel, Donnell; Harris, Michael; Hamosh, Ada; Kölker, Stefan; Ebrahimi-Fakhari, Darius; Hoffmann, Georg F; Manchester, David; Boyer, Philip J; Manzur, Adnan Y; Lourenco, Charles Marques; Pilz, Daniela T; Kamath, Arveen; Prabhakar, Prab; Rao, Vamshi K; Rogers, R Curtis; Ryan, Monique M; Brown, Natasha J; McLean, Catriona A; Said, Edith; Schara, Ulrike; Stein, Anja; Sewry, Caroline; Travan, Laura; Wijburg, Frits A; Zenker, Martin; Mohammed, Shehla; Fanto, Manolis; Gautel, Mathias; Jungbluth, Heinz

2016-03-01

Vici syndrome is a progressive neurodevelopmental multisystem disorder due to recessive mutations in the key autophagy gene EPG5. We report genetic, clinical, neuroradiological, and neuropathological features of 50 children from 30 families, as well as the neuronal phenotype of EPG5 knock-down in Drosophila melanogaster. We identified 39 different EPG5 mutations, most of them truncating and predicted to result in reduced EPG5 protein. Most mutations were private, but three recurrent mutations (p.Met2242Cysfs*5, p.Arg417*, and p.Gln336Arg) indicated possible founder effects. Presentation was mainly neonatal, with marked hypotonia and feeding difficulties. In addition to the five principal features (callosal agenesis, cataracts, hypopigmentation, cardiomyopathy, and immune dysfunction), we identified three equally consistent features (profound developmental delay, progressive microcephaly, and failure to thrive). The manifestation of all eight of these features has a specificity of 97%, and a sensitivity of 89% for the presence of an EPG5 mutation and will allow informed decisions about genetic testing. Clinical progression was relentless and many children died in infancy. Survival analysis demonstrated a median survival time of 24 months (95% confidence interval 0-49 months), with only a 10th of patients surviving to 5 years of age. Survival outcomes were significantly better in patients with compound heterozygous mutations (P = 0.046), as well as in patients with the recurrent p.Gln336Arg mutation. Acquired microcephaly and regression of skills in long-term survivors suggests a neurodegenerative component superimposed on the principal neurodevelopmental defect. Two-thirds of patients had a severe seizure disorder, placing EPG5 within the rapidly expanding group of genes associated with early-onset epileptic encephalopathies. Consistent neuroradiological features comprised structural abnormalities, in particular callosal agenesis and pontine hypoplasia, delayed myelination and, less frequently, thalamic signal intensity changes evolving over time. Typical muscle biopsy features included fibre size variability, central/internal nuclei, abnormal glycogen storage, presence of autophagic vacuoles and secondary mitochondrial abnormalities. Nerve biopsy performed in one case revealed subtotal absence of myelinated axons. Post-mortem examinations in three patients confirmed neurodevelopmental and neurodegenerative features and multisystem involvement. Finally, downregulation of epg5 (CG14299) in Drosophila resulted in autophagic abnormalities and progressive neurodegeneration. We conclude that EPG5-related Vici syndrome defines a novel group of neurodevelopmental disorders that should be considered in patients with suggestive features in whom mitochondrial, glycogen, or lysosomal storage disorders have been excluded. Neurological progression over time indicates an intriguing link between neurodevelopment and neurodegeneration, also supported by neurodegenerative features in epg5-deficient Drosophila, and recent implication of other autophagy regulators in late-onset neurodegenerative disease. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain.

EPG5-related Vici syndrome: a paradigm of neurodevelopmental disorders with defective autophagy

PubMed Central

Byrne, Susan; Jansen, Lara; U-King-Im, Jean-Marie; Siddiqui, Ata; Lidov, Hart G. W.; Bodi, Istvan; Smith, Luke; Mein, Rachael; Cullup, Thomas; Dionisi-Vici, Carlo; Al-Gazali, Lihadh; Al-Owain, Mohammed; Bruwer, Zandre; Al Thihli, Khalid; El-Garhy, Rana; Flanigan, Kevin M.; Manickam, Kandamurugu; Zmuda, Erik; Banks, Wesley; Gershoni-Baruch, Ruth; Mandel, Hanna; Dagan, Efrat; Raas-Rothschild, Annick; Barash, Hila; Filloux, Francis; Creel, Donnell; Harris, Michael; Hamosh, Ada; Kölker, Stefan; Ebrahimi-Fakhari, Darius; Hoffmann, Georg F.; Manchester, David; Boyer, Philip J.; Manzur, Adnan Y.; Lourenco, Charles Marques; Pilz, Daniela T.; Kamath, Arveen; Prabhakar, Prab; Rao, Vamshi K.; Rogers, R. Curtis; Ryan, Monique M.; Brown, Natasha J.; McLean, Catriona A.; Said, Edith; Schara, Ulrike; Stein, Anja; Sewry, Caroline; Travan, Laura; Wijburg, Frits A.; Zenker, Martin; Mohammed, Shehla; Fanto, Manolis; Gautel, Mathias

2016-01-01

Vici syndrome is a progressive neurodevelopmental multisystem disorder due to recessive mutations in the key autophagy gene EPG5. We report genetic, clinical, neuroradiological, and neuropathological features of 50 children from 30 families, as well as the neuronal phenotype of EPG5 knock-down in Drosophila melanogaster. We identified 39 different EPG5 mutations, most of them truncating and predicted to result in reduced EPG5 protein. Most mutations were private, but three recurrent mutations (p.Met2242Cysfs*5, p.Arg417*, and p.Gln336Arg) indicated possible founder effects. Presentation was mainly neonatal, with marked hypotonia and feeding difficulties. In addition to the five principal features (callosal agenesis, cataracts, hypopigmentation, cardiomyopathy, and immune dysfunction), we identified three equally consistent features (profound developmental delay, progressive microcephaly, and failure to thrive). The manifestation of all eight of these features has a specificity of 97%, and a sensitivity of 89% for the presence of an EPG5 mutation and will allow informed decisions about genetic testing. Clinical progression was relentless and many children died in infancy. Survival analysis demonstrated a median survival time of 24 months (95% confidence interval 0–49 months), with only a 10th of patients surviving to 5 years of age. Survival outcomes were significantly better in patients with compound heterozygous mutations (P = 0.046), as well as in patients with the recurrent p.Gln336Arg mutation. Acquired microcephaly and regression of skills in long-term survivors suggests a neurodegenerative component superimposed on the principal neurodevelopmental defect. Two-thirds of patients had a severe seizure disorder, placing EPG5 within the rapidly expanding group of genes associated with early-onset epileptic encephalopathies. Consistent neuroradiological features comprised structural abnormalities, in particular callosal agenesis and pontine hypoplasia, delayed myelination and, less frequently, thalamic signal intensity changes evolving over time. Typical muscle biopsy features included fibre size variability, central/internal nuclei, abnormal glycogen storage, presence of autophagic vacuoles and secondary mitochondrial abnormalities. Nerve biopsy performed in one case revealed subtotal absence of myelinated axons. Post-mortem examinations in three patients confirmed neurodevelopmental and neurodegenerative features and multisystem involvement. Finally, downregulation of epg5 (CG14299) in Drosophila resulted in autophagic abnormalities and progressive neurodegeneration. We conclude that EPG5-related Vici syndrome defines a novel group of neurodevelopmental disorders that should be considered in patients with suggestive features in whom mitochondrial, glycogen, or lysosomal storage disorders have been excluded. Neurological progression over time indicates an intriguing link between neurodevelopment and neurodegeneration, also supported by neurodegenerative features in epg5-deficient Drosophila, and recent implication of other autophagy regulators in late-onset neurodegenerative disease. PMID:26917586

Firing patterns transition and desynchronization induced by time delay in neural networks

NASA Astrophysics Data System (ADS)

Huang, Shoufang; Zhang, Jiqian; Wang, Maosheng; Hu, Chin-Kun

2018-06-01

We used the Hindmarsh-Rose (HR) model (Hindmarsh and Rose, 1984) to study the effect of time delay on the transition of firing behaviors and desynchronization in neural networks. As time delay is increased, neural networks exhibit diversity of firing behaviors, including regular spiking or bursting and firing patterns transitions (FPTs). Meanwhile, the desynchronization of firing and unstable bursting with decreasing amplitude in neural system, are also increasingly enhanced with the increase of time delay. Furthermore, we also studied the effect of coupling strength and network randomness on these phenomena. Our results imply that time delays can induce transition and desynchronization of firing behaviors in neural networks. These findings provide new insight into the role of time delay in the firing activities of neural networks, and can help to better understand the firing phenomena in complex systems of neural networks. A possible mechanism in brain that can cause the increase of time delay is discussed.

Increased expression of cyclin B1 mRNA coincides with diminished G{sub 2}-phase arrest in irradiated HeLa cells treated with staurosporine or caffeine

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

Bernhard, E.J.; Maity, A.; McKenna, W.G.

1994-12-01

The irradiation of cells results in delayed progression through the G{sub 2} phase of the cell cycle. Treatment of irradiated HeLa cells with caffeine greatly reduces the G{sub 2}-phase delay, while caffeine does not alter progression of cells through the cell cycle in unirradiated cells. In this report we demonstrate that treatment of HeLa cells with the kinase inhibitor staurosporine, but not with the inhibitor H7, also results in a reduction of the G{sub 2}-phase arrest after irradiation. Cell cycle progression in unirradiated cells is unaffected by 4.4 nM (2ng/ml) staurosporine, which releases the radiation-induced G{sub 2}-phase arrest. In HeLamore » cells, the G{sub 2}-phase delay after irradiation in S phase is accompanied by decreased expression of cyclin B1 mRNA. Coincident with the reduction in G{sub 2}-phase delay, we observed an increase in cyclin B1 mRNA accumulation in irradiated, staurosporine-treated cells compared to cells treated with irradiation alone. Caffeine treatment of irradiated HeLa cells also resulted in an elevation in the levels of cyclin B1 message. These results support the hypothesis that diminished cyclin B1 mRNA levels influence G{sub 2}-phase arrest to some degree. The findings that both staurosporine and caffeine treatments reverse the depression in cyclin B1 expression suggest that these two compounds may act on a common pathway of cell cycle control in response to radiation injury. 33 refs., 6 figs.« less

Delay time in a single barrier for a movable quantum shutter

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

Hernandez, Alberto

2010-05-15

The transient solution and delay time for a {delta} potential scatterer with a movable quantum shutter is calculated by solving analytically the time-dependent Schroedinger equation. The delay time is analyzed as a function of the distance between the shutter and the potential barrier and also as a function of the distance between the potential barrier and the detector. In both cases, it is found that the delay time exhibits a dynamical behavior and that it tends to a saturation value {Delta}t{sub sat} in the limit of very short distances, which represents the maximum delay produced by the potential barrier nearmore » the interaction region. The phase time {tau}{sub {theta},} on the other hand, is not an appropriate time scale for measuring the time delay near the interaction region, except if the shutter is moved far away from the potential. The role played by the antibound state of the system on the behavior of the delay time is also discussed.« less

Vertebrate behavior and ecology. Progress report, July 1, 1977-May 31, 1980

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

Tester, J R; Siniff, D B

Engineering design and development concentrated on five aspects during the past year: (1) development of high power output transmitters for monitoring animals from greater distances; (2) improvement and updating of a sonic transmitting and receiving system for monitoring fish and marine mammals; (3) design and testing of corrosive links which permit a transmitter to release from an animal at a specified time; (4) development of high frequency transmitters; and (5) development and testing of time delay transmitters. Field efforts resulted in further information on activity patterns and movements of sea otters in California and Alaska and of walleye pike inmore » experimental channels. Three manuscripts and two theses presented as part of this report describe these aspects in detail.« less

LiDAR-IMU Time Delay Calibration Based on Iterative Closest Point and Iterated Sigma Point Kalman Filter.

PubMed

Liu, Wanli

2017-03-08

The time delay calibration between Light Detection and Ranging (LiDAR) and Inertial Measurement Units (IMUs) is an essential prerequisite for its applications. However, the correspondences between LiDAR and IMU measurements are usually unknown, and thus cannot be computed directly for the time delay calibration. In order to solve the problem of LiDAR-IMU time delay calibration, this paper presents a fusion method based on iterative closest point (ICP) and iterated sigma point Kalman filter (ISPKF), which combines the advantages of ICP and ISPKF. The ICP algorithm can precisely determine the unknown transformation between LiDAR-IMU; and the ISPKF algorithm can optimally estimate the time delay calibration parameters. First of all, the coordinate transformation from the LiDAR frame to the IMU frame is realized. Second, the measurement model and time delay error model of LiDAR and IMU are established. Third, the methodology of the ICP and ISPKF procedure is presented for LiDAR-IMU time delay calibration. Experimental results are presented that validate the proposed method and demonstrate the time delay error can be accurately calibrated.

Vitamin E Supplementation Reduces Cellular Loss in the Brain of a Premature Aging Mouse Model.

PubMed

La Fata, G; van Vliet, N; Barnhoorn, S; Brandt, R M C; Etheve, S; Chenal, E; Grunenwald, C; Seifert, N; Weber, P; Hoeijmakers, J H J; Mohajeri, M H; Vermeij, W P

2017-01-01

Aging is a highly complex biological process driven by multiple factors. Its progression can partially be influenced by nutritional interventions. Vitamin E is a lipid-soluble anti-oxidant that is investigated as nutritional supplement for its ability to prevent or delay the onset of specific aging pathologies, including neurodegenerative disorders. We aimed here to investigate the effect of vitamin E during aging progression in a well characterized mouse model for premature aging. Xpg-/- animals received diets with low (~2.5 mg/kg feed), medium (75 mg/kg feed) or high (375 mg/kg feed) vitamin E concentration and their phenotype was monitored during aging progression. Vitamin E content was analyzed in the feed, for stability reasons, and in mouse plasma, brain, and liver, for effectiveness of the treatment. Subsequent age-related changes were monitored for improvement by increased vitamin E or worsening by depletion in both liver and nervous system, organs sensitive to oxidative stress. Mice supplemented with high levels of vitamin E showed a delayed onset of age-related body weight decline and appearance of tremors when compared to mice with a low dietary vitamin E intake. DNA damage resulting in liver abnormalities such as changes in polyploidy, was considerably prevented by elevated amounts of vitamin E. Additionally, immunohistochemical analyses revealed that high intake of vitamin E, when compared with low and medium levels of vitamin E in the diet, reduces the number of p53-positive cells throughout the brain, indicative of a lower number of cells dying due to DNA damage accumulated over time. Our data underline a neuroprotective role of vitamin E in the premature aging animal model used in this study, likely via a reduction of oxidative stress, and implies the importance of improved nutrition to sustain health.

Cellular and molecular characterization of gametogenic progression in ex vivo cultured prepuberal mouse testes.

PubMed

Isoler-Alcaraz, J; Fernández-Pérez, D; Larriba, E; Del Mazo, J

2017-10-18

Recently, an effective testis culture method using a gas-liquid interphase, capable of differentiate male germ cells from neonatal spermatogonia to spermatozoa has been developed. Nevertheless, this methodology needs deep analyses that allow future experimental approaches in basic, pathologic and/or reprotoxicologic studies. Because of this, we characterized at cellular and molecular levels the entire in vitro spermatogenic progression, in order to understand and evaluate the characteristics that define the spermatogenic process in ex vivo cultured testes compared to the in vivo development. Testicular explants of CD1 mice aged 6 and 10 days post-partum were respectively cultured during 55 and 89 days. Cytological and molecular approaches were performed, analyzing germ cell proportion at different time culture points, meiotic markers immunodetecting synaptonemal complex protein SYCP3 by immunocytochemistry and the relative expression of different marker genes along the differentiation process by Reverse Transcription - quantitative Polymerase Chain Reaction. In addition, microRNA and piwi-interactingRNA profiles were also evaluated by Next Generation Sequencing and bioinformatic approaches. The method promoted and maintained the spermatogenic process during 89 days. At a cytological level we detected spermatogenic development delays of cultured explants compared to the natural in vivo process. The expression of different spermatogenic stages gene markers correlated with the proportion of different cell types detected in the cytological preparations. In vitro progression analysis of the different spermatogenic cell types, from both 6.5 dpp and 10.5 dpp testes explants, has revealed a relative delay in relation to in vivo process. The expression of the genes studied as biomarkers correlates with the cytologically and functional detected progression and differential expression identified in vivo. After a first analysis of deep sequencing data it has been observed that as long as cultures progress, the proportion of microRNAs declined respect to piwi-interactingRNAs levels that increased, showing a similar propensity than which happens in in vivo spermatogenesis. Our study allows to improve and potentially to control the ex vivo spermatogenesis development, opening new perspectives in the reproductive biology fields including male fertility.

The Hippocampus Remains Activated over the Long Term for the Retrieval of Truly Episodic Memories

PubMed Central

Harand, Caroline; Bertran, Françoise; La Joie, Renaud; Landeau, Brigitte; Mézenge, Florence; Desgranges, Béatrice; Peigneux, Philippe; Eustache, Francis; Rauchs, Géraldine

2012-01-01

The role of the hippocampus in declarative memory consolidation is a matter of intense debate. We investigated the neural substrates of memory retrieval for recent and remote information using functional magnetic resonance imaging (fMRI). 18 young, healthy participants learned a series of pictures. Then, during two fMRI recognition sessions, 3 days and 3 months later, they had to determine whether they recognized or not each picture using the “Remember/Know” procedure. Presentation of the same learned images at both delays allowed us to track the evolution of memories and distinguish consistently episodic memories from those that were initially episodic and then became familiar or semantic over time and were retrieved without any contextual detail. Hippocampal activation decreased over time for initially episodic, later semantic memories, but remained stable for consistently episodic ones, at least in its posterior part. For both types of memories, neocortical activations were observed at both delays, notably in the ventromedial prefrontal and anterior cingulate cortices. These activations may reflect a gradual reorganization of memory traces within neural networks. Our data indicate maintenance and strengthening of hippocampal and cortico-cortical connections in the consolidation and retrieval of episodic memories over time, in line with the Multiple Trace theory (Nadel and Moscovitch, 1997). At variance, memories becoming semantic over time consolidate through strengthening of cortico-cortical connections and progressive disengagement of the hippocampus. PMID:22937055

On Time Delay Margin Estimation for Adaptive Control and Optimal Control Modification

NASA Technical Reports Server (NTRS)

Nguyen, Nhan T.

2011-01-01

This paper presents methods for estimating time delay margin for adaptive control of input delay systems with almost linear structured uncertainty. The bounded linear stability analysis method seeks to represent an adaptive law by a locally bounded linear approximation within a small time window. The time delay margin of this input delay system represents a local stability measure and is computed analytically by three methods: Pade approximation, Lyapunov-Krasovskii method, and the matrix measure method. These methods are applied to the standard model-reference adaptive control, s-modification adaptive law, and optimal control modification adaptive law. The windowing analysis results in non-unique estimates of the time delay margin since it is dependent on the length of a time window and parameters which vary from one time window to the next. The optimal control modification adaptive law overcomes this limitation in that, as the adaptive gain tends to infinity and if the matched uncertainty is linear, then the closed-loop input delay system tends to a LTI system. A lower bound of the time delay margin of this system can then be estimated uniquely without the need for the windowing analysis. Simulation results demonstrates the feasibility of the bounded linear stability method for time delay margin estimation.

Monitoring road safety development at regional level: A case study in the ASEAN region.

PubMed

Chen, Faan; Wang, Jianjun; Wu, Jiaorong; Chen, Xiaohong; Zegras, P Christopher

2017-09-01

Persistent monitoring of progress, evaluating the results of interventions and recalibrating to achieve continuous improvement over time is widely recognized as being crucial towards the successful development of road safety. In the ASEAN (Association of Southeast Asian Nations) region there is a lack of well-resourced teams that contain multidisciplinary safety professionals, and specialists in individual countries, who are able to carry out this work effectively. In this context, not only must the monitoring framework be effective, it must also be easy to use and adapt. This paper provides a case study that can be easily reproduced; based on an updated and refined Road Safety Development Index (RSDI), by means of the RSR (Rank-sum ratio)-based model, for monitoring/reporting road safety development at regional level. The case study was focused on the road safety achievements in eleven Southeast Asian countries; identifying the areas of poor performance, potential problems and delays. These countries are finally grouped into several classes based on an overview of their progress and achievements regarding to road safety. The results allow the policymakers to better understand their own road safety progress toward their desired impact; more importantly, these results enable necessary interventions to be made in a quick and timely manner. Keeping action plans on schedule if things are not progressing as desired. This would avoid 'reinventing the wheel' and trial and error approaches to road safety, making the implementation of action plans more effective. Copyright © 2017 Elsevier Ltd. All rights reserved.

Helicobacter pylori Eradication Prevents Progression of Gastric Cancer in Hypergastrinemic INS-GAS Mice

PubMed Central

Lee, Chung-Wei; Rickman, Barry; Rogers, Arlin B.; Ge, Zhongming; Wang, Timothy C.; Fox, James G.

2009-01-01

Helicobacter pylori infection results in chronic gastritis, which may progress to gastric cancer. In this study, we investigated the efficacy of H. pylori eradication in preventing the progression of gastritis to gastric cancer in H. pylori–infected transgenic INS-GAS mice. H. pylori infection induced severe dysplasia and gastric cancer classified as high-grade and low-grade gastrointestinal intraepithelial neoplasia (GIN) in INS-GAS mice at 28 weeks postinfection (WPI). H. pylori eradication therapy using omeprazole, metronidazole, and clarithromycin was administered p.o. at 8, 12, or 22 WPI. Compared with untreated infected mice, H. pylori eradication at 8, 12, and 22 WPI significantly reduced the severity of dysplasia (P < 0.01). Moreover, H. pylori eradication at 8 WPI completely prevented the development of GIN (P < 0.001). Although not as effective as early antimicrobial treatment, prevention of progression to high-grade GIN was achieved by H. pylori eradication at 12 and 22 WPI (P < 0.05). Consistent with reduced gastric pathology, H. pylori eradication at all time points significantly down-regulated gastric Interferon-γ, tumor necrosis factor-α, inducible nitric oxide synthase, and Reg 1 mRNA levels (P < 0.05) and reduced epithelial proliferation in the corpus (P < 0.01) compared with untreated infected mice. We concluded that H. pylori eradication prevented gastric cancer to the greatest extent when antibiotics are given at an early point of infection, but that eradication therapy given at a later time point delayed the development of severe dysplastic lesions. PMID:18441088

Leveraging delay discounting for health: Can time delays influence food choice?

PubMed

Appelhans, Bradley M; French, Simone A; Olinger, Tamara; Bogucki, Michael; Janssen, Imke; Avery-Mamer, Elizabeth F; Powell, Lisa M

2018-07-01

Delay discounting, the tendency to choose smaller immediate rewards over larger delayed rewards, is theorized to promote consumption of immediately rewarding but unhealthy foods at the expense of long-term weight maintenance and nutritional health. An untested implication of delay discounting models of decision-making is that selectively delaying access to less healthy foods may promote selection of healthier (immediately available) alternatives, even if they may be less desirable. The current study tested this hypothesis by measuring healthy versus regular vending machine snack purchasing before and during the implementation of a 25-s time delay on the delivery of regular snacks. Purchasing was also examined under a $0.25 discount on healthy snacks, a $0.25 tax on regular snacks, and the combination of both pricing interventions with the 25-s time delay. Across 32,019 vending sales from three separate vending locations, the 25-s time delay increased healthy snack purchasing from 40.1% to 42.5%, which was comparable to the impact of a $0.25 discount (43.0%). Combining the delay and the discount had a roughly additive effect (46.0%). However, the strongest effects were seen under the $0.25 tax on regular snacks (53.7%) and the combination of the delay and the tax (50.2%). Intervention effects varied substantially between vending locations. Importantly, time delays did not harm overall vending sales or revenue, which is relevant to the real-world feasibility of this intervention. More investigation is needed to better understand how the impact of time delays on food choice varies across populations, evaluate the effects of time delays on beverage vending choices, and extend this approach to food choices in contexts other than vending machines. ClinicalTrials.gov, NCT02359916. Copyright © 2018 Elsevier Ltd. All rights reserved.

Secondary and tertiary preventions of thyroid disease.

PubMed

Azizi, Fereidoun; Mehran, Ladan; Hosseinpanah, Farhad; Delshad, Hossein; Amouzegar, Atieh

2018-05-01

Secondary and tertiary preventions are concerned with the recognition of the disease process in a very early stage and delay in progression to complete disease and minimization of complications and the impact of illness. All articles related to secondary and tertiary prevention of thyroid diseases were reviewed. Using related key words, articles published between 2001 and 2015 were evaluated, categorized, and analyzed. In secondary prevention, congenital hypothyroidism and subclinical hypo and hyperthyroidism are equally important. Routine screening of patients with multinodular goiter by either ultrasonography or calcitonin is a controversial issue, while calcitonin assessments in medullary cancer and RET in family members are recommended. Screening of thyroid disease in pregnancy is limited to those with risk factors. Views regarding the importance of thyroid autoimmunity in secondary prevention are also presented. In tertiary prevention, prescribing excessive doses of levothyroxine, in the elderly in particular and appropriate care of all patients to avoid progression and complications are the key issues. Optimization of management of thyroid diseases requires timely screening, prevention of progression to more sever disease, optimal medical care, and avoidance of iatrogenic conditions.

Cascading disasters in the huge coastal aquifer of Salento (Apulia region, Southern Italy) ensuing droughts

NASA Astrophysics Data System (ADS)

Parisi, Alessandro; Fidelibus, Maria Dolores

2017-04-01

Physical extremes can be distinguished in "sudden physical extremes" (e.g. earthquakes, tsunami) and "progressive physical extremes" (e.g. drought, desertification, landslides). They differ for frequency, intensity, spatial extent, duration and timing of occurrence. If a physical extreme, by interacting with human systems, induces negative consequences, its outcome can be a "disaster". The disasters are, in both above cases, characterized by a few phases: physical extreme occurrence, emergency, response, and recovery. However, in the case of a progressive physical extreme, the disaster develops with an overlap in the time of the above-mentioned phases. When the events are repetitive, the emergency planning (which follows a cycle) succeeds with preparedness and mitigation with the intent of reducing the risk. Both the sudden and progressive physical extremes produce cascading effects of consequences on social, environmental and economic systems. Disasters consequent to sudden and progressive extremes show, however, some differences, mainly attributable to the "visibility" of the effects and to their time scale of evolution. As matter of fact, a disaster consequent to a progressive physical extreme produces "emerging signals" that are often invisible. Moreover, the emergency phase can arise with a time delay compared to the occurrence of the physical extreme, depending on the spatial scale of impacted system. The above differences allow defining "creeping disasters" the potential disasters related to progressive physical extremes. This study deals with some peculiar "cascading disasters" consequent to drought, which is the main "creeping disaster", namely the groundwater drought and the consequent salinization of coastal aquifers. In regional flow systems, their effects are invisible in the immediate to common people (and often even to managers) because of the concealed nature of groundwater; moreover, they are difficult to assess because of the shift over time of their evolution compared to the promptness of surface effects. The study area is the Salento coastal karstic aquifer (Apulia region, Southern Italy), where the groundwater flows according to a regional flow system. It has been subject to successive meteorological droughts between 1960 and 2010. The groundwater monitoring performed during this period, even with some gaps, allows identifying time lags between superficial effects and underground system response, potential tipping points, and emerging signals of the cascading disasters.

Effect of time delay on flying qualities: An update

NASA Technical Reports Server (NTRS)

Smith, R. E.; Sarrafian, S. K.

1986-01-01

Flying qualities problems of modern, full-authority electronic flight control systems are most often related to the introduction of additional time delay in aircraft response to a pilot input. These delays can have a significant effect on the flying qualities of the aircraft. Time delay effects are reexamined in light of recent flight test experience with aircraft incorporating new technology. Data from the X-29A forward-swept-wing demonstrator, a related preliminary in-flight experiment, and other flight observations are presented. These data suggest that the present MIL-F-8785C allowable-control system time delay specifications are inadequate or, at least, incomplete. Allowable time delay appears to be a function of the shape of the aircraft response following the initial delay. The cockpit feel system is discussed as a dynamic element in the flight control system. Data presented indicate that the time delay associated with a significant low-frequency feel system does not result in the predicted degradation in aircraft flying qualities. The impact of the feel system is discussed from two viewpoints: as a filter in the control system which can alter the initial response shape and, therefore, the allowable time delay, and as a unique dynamic element whose delay contribution can potentially be discounted by special pilot loop closures.

Molecular diagnosis of Papaya meleira virus (PMeV) from leaf samples of Carica papaya L. using conventional and real-time RT-PCR.

PubMed

Abreu, Paolla M V; Piccin, João G; Rodrigues, Silas P; Buss, David S; Ventura, José A; Fernandes, Patricia M B

2012-03-01

Papaya meleira virus (PMeV) is the causal agent of papaya sticky disease. This study describes two methods for molecular diagnosis of PMeV using conventional and real-time PCR. These methods were shown to be more efficient than current methods of viral detection using extraction of PMeV dsRNA and observation of symptoms in the field. The methods described here were used to evaluate the effect of inoculation of papaya plants with purified PMeV dsRNA on the progress of PMeV infection. A single inoculation with PMeV dsRNA was observed to delay the progress of the virus infection by several weeks. The possibility of vertical transmission of PMeV was also investigated. No evidence was found for PMeV transmission through seeds collected from diseased fruit. The implications of these results for the epidemiology of PMeV and the management of papaya sticky disease are discussed. Copyright © 2011 Elsevier B.V. All rights reserved.

Internationally adopted children from non-European countries: general development during the first two years in the adoptive family.

PubMed

Dalen, Monica; Theie, Steinar

2012-01-01

Internationally adopted children are often delayed in their development and demonstrate more behaviour problems than nonadopted children due to adverse preadoption circumstances. This is especially true for children adopted from Eastern European countries. Few studies have focused on children adopted from non-European countries. This paper presents results from an ongoing longitudinal study of 119 internationally adopted children from non-European countries during their first two years in Norway. Several scales measuring different aspects of the children's development are included in the study: communication and gross motor development, temperamental characteristics, and behaviour problems. The results show that internationally adopted children are delayed in their general development when they first arrive in their adoptive families. After two years the children have made significant progress in development. However, they still lag behind in communication and motor skills compared to non-adopted children. The temperamental characteristics seem very stable from time of adoption until two years after adoption. The children demonstrate a low frequency of behaviour problems. However, the behaviour problems have changed during the two years. At time of adoption they show more nonphysically challenging behaviour while after two years their physically challenging behaviour has increased.

Describing-function analysis of a ripple regulator with slew-rate limits and time delays

NASA Technical Reports Server (NTRS)

Wester, Gene W.

1990-01-01

The effects of time delays and slew-rate limits on the steady-state operating points and performance of a free-running ripple regulator are evaluated using describing-function analysis. The describing function of an ideal comparator (no time delays or slew rate limits) has no phase shift and is independent of frequency. It is found that turn-on delay and turn-off delay have different effects on gain and phase and cannot be combined. Comparator hysteresis affects both gain and phase; likewise, time delays generally affect both gain and phase. It is found that the effective time delay around the feedback loop is one half the sum of turn-on and turn-off delays, regardless of whether the delays are caused by storage time or slew rate limits. Expressions are formulated for the switching frequency, switch duty ratio, dc output, and output ripple. For the case of no hysteresis, a simple, graphical solution for the switching frequency is possible, and the resulting switching frequency is independent of first-order variations of input or load.

Perception of Construction Participants in Construction delays: A case study in Tamilnadu, India.

NASA Astrophysics Data System (ADS)

Rathinakumar, V.; Vignesh, T.; Dhivagar, K.

2017-07-01

Delays in the construction industry are universal fact, which affects the construction participants. The research work spotlights on determining the prevailing delays in the cities of Tamil Nadu, as perceived by the participants. After a few field level interactions, a questionnaire was framed and administered to the participants i.e., Consultants (50 Nos.), contractors (50 Nos.) and clients (150 Nos.) to understand their perception on the causes of delays. The factors for delay was categorized into 4 groups say Improper project planning, Design related issues, Finance related issues and Resource related issues. The responses were analysed using the SPSS software by applying ANOVA and Regression analysis. From the analysis, it was found that the personal financial problems of the client dominantly affect the entire construction progress and the subsequent design changes by the clients, Inadequate early project planning, labour related issues. Also, the delay groups were found to be the improper project planning and the Resource related issues.

Nfix Regulates Temporal Progression of Muscle Regeneration through Modulation of Myostatin Expression.

PubMed

Rossi, Giuliana; Antonini, Stefania; Bonfanti, Chiara; Monteverde, Stefania; Vezzali, Chiara; Tajbakhsh, Shahragim; Cossu, Giulio; Messina, Graziella

2016-03-08

Nfix belongs to a family of four highly conserved proteins that act as transcriptional activators and/or repressors of cellular and viral genes. We previously showed a pivotal role for Nfix in regulating the transcriptional switch from embryonic to fetal myogenesis. Here, we show that Nfix directly represses the Myostatin promoter, thus controlling the proper timing of satellite cell differentiation and muscle regeneration. Nfix-null mice display delayed regeneration after injury, and this deficit is reversed upon in vivo Myostatin silencing. Conditional deletion of Nfix in satellite cells results in a similar delay in regeneration, confirming the functional requirement for Nfix in satellite cells. Moreover, mice lacking Nfix show reduced myofiber cross sectional area and a predominant slow twitching phenotype. These data define a role for Nfix in postnatal skeletal muscle and unveil a mechanism for Myostatin regulation, thus providing insights into the modulation of its complex signaling pathway. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Microinjection of recombinant O-GlcNAc transferase potentiates Xenopus oocytes M-phase entry

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

Dehennaut, Vanessa; EA 4020, Laboratoire de Regulation des Signaux de Division, USTL, IFR147, Villeneuve d'Ascq; Hanoulle, Xavier

2008-05-02

In order to understand the importance of the cytosolic and nuclear-specific O-linked N-acetylglucosaminylation (O-GlcNAc) on cell cycle regulation, we recently reported that inhibition of O-GlcNAc transferase (OGT) delayed or blocked Xenopus laevis oocyte germinal vesicle breakdown (GVBD). Here, we show that increased levels of the long OGT isoform (ncOGT) accelerate X. laevis oocyte GVBD. A N-terminally truncated isoform (sOGT) with a similar in vitro catalytic activity towards a synthetic CKII-derived peptide had no effect, illustrating the important role played by the N-terminal tetratrico-peptide repeats. ncOGT microinjection in the oocytes increases both the speed and extent of O-GlcNAc addition, leads tomore » a quicker activation of the MPF and MAPK pathways and finally results in a faster GVBD. Microinjection of anti-OGT antibodies leads to a delay of the GVBD kinetics. Our results hence demonstrate that OGT is a key molecule for the timely progression of the cell cycle.« less

Impact of age at onset for children with renal failure on education and employment transitions.

PubMed

Lewis, Helen; Arber, Sara

2015-01-01

Previous medical research has shown that children with end-stage renal failure experience delay or underachievement of key markers of transition to adulthood. This article analyses 35 qualitative interviews with end-stage renal failure patients, aged 20-30 years, first diagnosed at 0-19 years of age, to explore how far delayed or underachievement in education and employment is related to their age at onset of end-stage renal failure. This study shows how unpredictable failures of renal replacement therapies, comorbidities and/or side effects of treatment in the early life course often coincided with critical moments for education and employment. Entering school, college, work-related training or employment, and disclosing health status or educational underachievement to an employer, were particularly critical, and those who were ill before puberty became progressively more disadvantaged in terms of successful transition into full-time employment, compared with those first diagnosed after puberty. © The Author(s) 2014.

Market-based control strategy for long-span structures considering the multi-time delay issue

NASA Astrophysics Data System (ADS)

Li, Hongnan; Song, Jianzhu; Li, Gang

2017-01-01

To solve the different time delays that exist in the control device installed on spatial structures, in this study, discrete analysis using a 2 N precise algorithm was selected to solve the multi-time-delay issue for long-span structures based on the market-based control (MBC) method. The concept of interval mixed energy was introduced from computational structural mechanics and optimal control research areas, and it translates the design of the MBC multi-time-delay controller into a solution for the segment matrix. This approach transforms the serial algorithm in time to parallel computing in space, greatly improving the solving efficiency and numerical stability. The designed controller is able to consider the issue of time delay with a linear controlling force combination and is especially effective for large time-delay conditions. A numerical example of a long-span structure was selected to demonstrate the effectiveness of the presented controller, and the time delay was found to have a significant impact on the results.

Delay time and Hartman effect in strain engineered graphene

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

Chen, Xi, E-mail: xchen@shu.edu.cn; Deng, Zhi-Yong; Ban, Yue, E-mail: yban@shu.edu.cn

2014-05-07

Tunneling times, including group delay and dwell time, are studied for massless Dirac electrons transmitting through a one-dimensional barrier in strain-engineered graphene. The Hartman effect, the independence of group delay on barrier length, is induced by the strain effect, and associated with the transmission gap and the evanescent mode. The influence of barrier height/length and strain modulus/direction on the group delay is also discussed, which provides the flexibility to control the group delay with applications in graphene-based devices. The relationship between group delay and dwell time is finally derived to clarify the nature of the Hartman effect.

Reconstructions of parameters of radiophysical chaotic generator with delayed feedback from short time series

NASA Astrophysics Data System (ADS)

Ishbulatov, Yu. M.; Karavaev, A. S.; Kiselev, A. R.; Semyachkina-Glushkovskaya, O. V.; Postnov, D. E.; Bezruchko, B. P.

2018-04-01

A method for the reconstruction of time-delayed feedback system is investigated, which is based on the detection of synchronous response of a slave time-delay system with respect to the driving from the master system under study. The structure of the driven system is similar to the structure of the studied time-delay system, but the feedback circuit is broken in the driven system. The method efficiency is tested using short and noisy data gained from an electronic chaotic oscillator with time-delayed feedback.

Reconstruction of ensembles of coupled time-delay systems from time series.

PubMed

Sysoev, I V; Prokhorov, M D; Ponomarenko, V I; Bezruchko, B P

2014-06-01

We propose a method to recover from time series the parameters of coupled time-delay systems and the architecture of couplings between them. The method is based on a reconstruction of model delay-differential equations and estimation of statistical significance of couplings. It can be applied to networks composed of nonidentical nodes with an arbitrary number of unidirectional and bidirectional couplings. We test our method on chaotic and periodic time series produced by model equations of ensembles of diffusively coupled time-delay systems in the presence of noise, and apply it to experimental time series obtained from electronic oscillators with delayed feedback coupled by resistors.

Stability of Nonlinear Systems with Unknown Time-varying Feedback Delay

NASA Astrophysics Data System (ADS)

Chunodkar, Apurva A.; Akella, Maruthi R.

2013-12-01

This paper considers the problem of stabilizing a class of nonlinear systems with unknown bounded delayed feedback wherein the time-varying delay is 1) piecewise constant 2) continuous with a bounded rate. We also consider application of these results to the stabilization of rigid-body attitude dynamics. In the first case, the time-delay in feedback is modeled specifically as a switch among an arbitrarily large set of unknown constant values with a known strict upper bound. The feedback is a linear function of the delayed states. In the case of linear systems with switched delay feedback, a new sufficiency condition for average dwell time result is presented using a complete type Lyapunov-Krasovskii (L-K) functional approach. Further, the corresponding switched system with nonlinear perturbations is proven to be exponentially stable inside a well characterized region of attraction for an appropriately chosen average dwell time. In the second case, the concept of the complete type L-K functional is extended to a class of nonlinear time-delay systems with unknown time-varying time-delay. This extension ensures stability robustness to time-delay in the control design for all values of time-delay less than the known upper bound. Model-transformation is used in order to partition the nonlinear system into a nominal linear part that is exponentially stable with a bounded perturbation. We obtain sufficient conditions which ensure exponential stability inside a region of attraction estimate. A constructive method to evaluate the sufficient conditions is presented together with comparison with the corresponding constant and piecewise constant delay. Numerical simulations are performed to illustrate the theoretical results of this paper.

Effect of metrology time delay on overlay APC

NASA Astrophysics Data System (ADS)

Carlson, Alan; DiBiase, Debra

2002-07-01

The run-to-run control strategy of lithography APC is primarily composed of a feedback loop as shown in the diagram below. It is known that the insertion of a time delay in a feedback loop can cause degradation in control performance and could even cause a stable system to become unstable, if the time delay becomes sufficiently large. Many proponents of integrated metrology methods have cited the damage caused by metrology time delays as the primary justification for moving from a stand-alone to integrated metrology. While there is little dispute over the qualitative form of this argument, there has been very light published about the quantitative effects under real fab conditions - precisely how much control is lost due to these time delays. Another issue regarding time delays is that the length of these delays is not typically fixed - they vary from lot to lot and in some cases this variance can be large - from one hour on the short side to over 32 hours on the long side. Concern has been expressed that the variability in metrology time delays can cause undesirable dynamics in feedback loops that make it difficult to optimize feedback filters and gains and at worst could drive a system unstable. By using data from numerous fabs, spanning many sizes and styles of operation, we have conducted a quantitative study of the time delay effect on overlay run- to-run control. Our analysis resulted in the following conclusions: (1) There is a significant and material relationship between metrology time delay and overlay control under a variety of real world production conditions. (2) The run-to-run controller can be configured to minimize sensitivity to time delay variations. (3) The value of moving to integrated metrology can be quantified.

Economic mitigation challenges: how further delay closes the door for achieving climate targets

NASA Astrophysics Data System (ADS)

Luderer, Gunnar; Pietzcker, Robert C.; Bertram, Christoph; Kriegler, Elmar; Meinshausen, Malte; Edenhofer, Ottmar

2013-09-01

While the international community aims to limit global warming to below 2 ° C to prevent dangerous climate change, little progress has been made towards a global climate agreement to implement the emissions reductions required to reach this target. We use an integrated energy-economy-climate modeling system to examine how a further delay of cooperative action and technology availability affect climate mitigation challenges. With comprehensive emissions reductions starting after 2015 and full technology availability we estimate that maximum 21st century warming may still be limited below 2 ° C with a likely probability and at moderate economic impacts. Achievable temperature targets rise by up to ˜0.4 ° C if the implementation of comprehensive climate policies is delayed by another 15 years, chiefly because of transitional economic impacts. If carbon capture and storage (CCS) is unavailable, the lower limit of achievable targets rises by up to ˜0.3 ° C. Our results show that progress in international climate negotiations within this decade is imperative to keep the 2 ° C target within reach.

Controversies and Evolving New Mechanisms in Subarachnoid Hemorrhage

PubMed Central

Chen, Sheng; Feng, Hua; Sherchan, Prativa; Klebe, Damon; Zhao, Gang; Sun, Xiaochuan; Zhang, Jianmin; Tang, Jiping; Zhang, John H.

2013-01-01

Despite decades of study, subarachnoid hemorrhage (SAH) continues to be a serious and significant health problem in the United States and worldwide. The mechanisms contributing to brain injury after SAH remain unclear. Traditionally, most in vivo research has heavily emphasized the basic mechanisms of SAH over the pathophysiological or morphological changes of delayed cerebral vasospasm after SAH. Unfortunately, the results of clinical trials based on this premise have mostly been disappointing, implicating some other pathophysiological factors, independent of vasospasm, as contributors to poor clinical outcomes. Delayed cerebral vasospasm is no longer the only culprit. In this review, we summarize recent data from both experimental and clinical studies of SAH and discuss the vast array of physiological dysfunctions following SAH that ultimately lead to cell death. Based on the progress in neurobiological understanding of SAH, the terms “early brain injury” and “delayed brain injury” are used according to the temporal progression of SAH-induced brain injury. Additionally, a new concept of the vasculo-neuronal-glia triad model for SAH study is highlighted and presents the challenges and opportunities of this model for future SAH applications. PMID:24076160

Wide variation of prostate-specific antigen doubling time of untreated, clinically localized, low-to-intermediate grade, prostate carcinoma.

PubMed

Choo, Richard; Klotz, Laurence; Deboer, Gerrit; Danjoux, Cyril; Morton, Gerard C

2004-08-01

To assess the prostate specific antigen (PSA) doubling time of untreated, clinically localized, low-to-intermediate grade prostate carcinoma. A prospective single-arm cohort study has been in progress since November 1995 to assess the feasibility of a watchful-observation protocol with selective delayed intervention for clinically localized, low-to-intermediate grade prostate adenocarcinoma. The PSA doubling time was estimated from a linear regression of ln(PSA) against time, assuming a simple exponential growth model. As of March 2003, 231 patients had at least 6 months of follow-up (median 45) and at least three PSA measurements (median 8, range 3-21). The distribution of the doubling time was: < 2 years, 26 patients; 2-5 years, 65; 5-10 years, 42; 10-20 years, 26; 20-50 years, 16; >50 years, 56. The median doubling time was 7.0 years; 42% of men had a doubling time of >10 years. The doubling time of untreated clinically localized, low-to-intermediate grade prostate cancer varies widely.

Digital time delay

DOEpatents

Martin, A.D.

1986-05-09

Method and apparatus are provided for generating an output pulse following a trigger pulse at a time delay interval preset with a resolution which is high relative to a low resolution available from supplied clock pulses. A first lumped constant delay provides a first output signal at predetermined interpolation intervals corresponding to the desired high resolution time interval. Latching circuits latch the high resolution data to form a first synchronizing data set. A selected time interval has been preset to internal counters and corrected for circuit propagation delay times having the same order of magnitude as the desired high resolution. Internal system clock pulses count down the counters to generate an internal pulse delayed by an internal which is functionally related to the preset time interval. A second LCD corrects the internal signal with the high resolution time delay. A second internal pulse is then applied to a third LCD to generate a second set of synchronizing data which is complementary with the first set of synchronizing data for presentation to logic circuits. The logic circuits further delay the internal output signal with the internal pulses. The final delayed output signal thereafter enables the output pulse generator to produce the desired output pulse at the preset time delay interval following input of the trigger pulse.

Traversal of electromagnetic pulses through dispersive media with negative refractive index

NASA Astrophysics Data System (ADS)

Nanda, L.; Ramakrishna, S. A.

2017-05-01

We investigate the traversal of electromagnetic pulses through dispersive media with negative refractive index in such a way that no resonant effects come into play. It has been verified that for evanescent waves, the definitions of the group delay and the reshaping delay times get interchanged in comparison to the propagating waves. We show that for a negative refractive index medium (NRM) with ɛ(ω)=μ(ω), the reshaping delay time identically vanishes for propagating waves. The total delay time in NRM is otherwise contributed by both the group and the reshaping delay times, whereas for the case of broadband pulses in NRM the total delay time is always subluminal.

Simulation analysis of the effect of initial delay on flight delay diffusion

NASA Astrophysics Data System (ADS)

Que, Zufu; Yao, Hongguang; Yue, Wei

2018-01-01

The initial delay of the flight is an important factor affecting the spread of flight delays, so clarifying their relationship conduces to control flight delays in the aeronautical network. Through establishing a model of the chain aviation network and making simulation analysis of the effects of initial delay on the delay longitudinal diffusion, it’s found that the number of delayed airports in the air network, the total delay time and the average delay time of the delayed airport are generally positively correlated with the initial delay. This indicates that the occurrence of the initial delay should be avoided or reduced as much as possible to improve the punctuality of the flight.

Early amniotomy and early oxytocin for prevention of, or therapy for, delay in first stage spontaneous labour compared with routine care

PubMed Central

Wei, Shuqin; Wo, Bi Lan; Qi, Hui-Ping; Xu, Hairong; Luo, Zhong-Cheng; Roy, Chantal; Fraser, William D

2014-01-01

Background Caesarean section rates are over 20% in many developed countries. The main diagnosis contributing to the high rate in nulliparae is dystocia or prolonged labour. The present review assesses the effects of a policy of early amniotomy with early oxytocin administration for the prevention of, or the therapy for, delay in labour progress. Objectives To estimate the effects of early augmentation with amniotomy and oxytocin for prevention of, or therapy for, delay in labour progress on the caesarean birth rate and on indicators of maternal and neonatal morbidity. Search methods We searched the Cochrane Pregnancy and Childbirth Group’s Trials Register (15 February 2012), MEDLINE (1966 to 15 February 2012), EMBASE (1980 to 15 February 2012), CINAHL (1982 to 15 February 2012), MIDIRS (1985 to February 2012) and contacted authors for data from unpublished trials. Selection criteria Randomized and quasi-randomized controlled trials that compared oxytocin and amniotomy with expectant management. Data collection and analysis Three review authors extracted data independently. We stratified the analyses into ’Prevention Trials’ and ’Therapy Trials’ according to the status of the woman at the time of randomization. Participants in the ’Prevention Trials’ were unselected women, without slow progress in labour, who were randomized to a policy of early augmentation or to routine care. In ’Treatment Trials’ women were eligible if they had an established delay in labour progress. Main results For this update, we have included a further two new clinical trials. This updated review includes 14 trials, randomizing a total of 8033 women. The unstratified analysis found early intervention with amniotomy and oxytocin to be associated with a modest reduction in the risk of caesarean section; however, the confidence interval (CI) included the null effect (risk ratio (RR) 0.89; 95% CI 0.79 to 1.01; 14 trials; 8033 women). In prevention trials, early augmentation was associated with a modest reduction in the number of caesarean births (RR 0.87; 95% CI 0.77 to 0.99; 11 trials; 7753). A policy of early amniotomy and early oxytocin was associated with a shortened duration of labour (average mean difference (MD) −1.28 hours; 95% CI −1.97 to −0.59; eight trials; 4816 women). Sensitivity analyses excluding four trials with a full package of active management did not substantially affect the point estimate for risk of caesarean section (RR 0.87; 95% CI 0.73 to 1.05; 10 trials; 5165 women). We found no other significant effects for the other indicators of maternal or neonatal morbidity. Authors’ conclusions In prevention trials, early intervention with amniotomy and oxytocin appears to be associated with a modest reduction in the rate of caesarean section over standard care. PMID:22972098

Estimation of coupling between time-delay systems from time series

NASA Astrophysics Data System (ADS)

Prokhorov, M. D.; Ponomarenko, V. I.

2005-07-01

We propose a method for estimation of coupling between the systems governed by scalar time-delay differential equations of the Mackey-Glass type from the observed time series data. The method allows one to detect the presence of certain types of linear coupling between two time-delay systems, to define the type, strength, and direction of coupling, and to recover the model equations of coupled time-delay systems from chaotic time series corrupted by noise. We verify our method using both numerical and experimental data.

LiDAR-IMU Time Delay Calibration Based on Iterative Closest Point and Iterated Sigma Point Kalman Filter

PubMed Central

Liu, Wanli

2017-01-01

The time delay calibration between Light Detection and Ranging (LiDAR) and Inertial Measurement Units (IMUs) is an essential prerequisite for its applications. However, the correspondences between LiDAR and IMU measurements are usually unknown, and thus cannot be computed directly for the time delay calibration. In order to solve the problem of LiDAR-IMU time delay calibration, this paper presents a fusion method based on iterative closest point (ICP) and iterated sigma point Kalman filter (ISPKF), which combines the advantages of ICP and ISPKF. The ICP algorithm can precisely determine the unknown transformation between LiDAR-IMU; and the ISPKF algorithm can optimally estimate the time delay calibration parameters. First of all, the coordinate transformation from the LiDAR frame to the IMU frame is realized. Second, the measurement model and time delay error model of LiDAR and IMU are established. Third, the methodology of the ICP and ISPKF procedure is presented for LiDAR-IMU time delay calibration. Experimental results are presented that validate the proposed method and demonstrate the time delay error can be accurately calibrated. PMID:28282897

Effect of caffeine on radiation-induced mitotic delay: delayed expression of G/sub 2/ arrest

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

Rowley, R.; Zorch, M.; Leeper, D.B.

1984-01-01

In the presence of 5 mM caffeine, irradiated (1.5 Gy) S and G/sub 2/ cells progressed to mitosis in register and without arrest in G/sub 2/. Caffeine (5 mM) markedly reduced mitotic delay even after radiation doses up to 20 Gy. When caffeine was removed from irradiated (1.5 Gy) and caffeine-treated cells, a period of G/sub 2/ arrest followed, similar in length to that produced by radiation alone. The arrest expressed was independent of the duration of the caffeine treatment for exposures up to 3 hr. The similarity of the response to the cited effects of caffeine on S-phase delaymore » suggests a common basis for delay induction in S and G/sub 2/ phases.« less

[Time perception in depressed and manic patients].

PubMed

Zhao, Qi-yuan; Ji, Yi-fu; Wang, Kai; Zhang, Lei; Liu, Ping; Jiang, Yu-bao

2010-02-02

To investigate the time perception in affective disorders by using neuropsychological tests and to try to elucidate its neurobiochemical mechanism. Using a time reproduction task, a comparative study was conducted for 28 depressive patients, 22 manic patients, and 26 age and education level matched healthy persons as healthy controls. Both depressive patients and manic patients are abnormal (P < 0.001), depressive patients over-reproduced the time interval than healthy controls (600 ms/delay 1 s: 1.6 +/- 0.6, P < 0.001; 600 ms/delay 5 s: 1.7 +/- 0.6, P < 0.001; 3 s/delay 1 s: 3.9 +/- 0.9, P < 0.001; 3 s/delay 5 s: 3.9 +/- 0.7, P < 0.001; 5 s/delay 1 s: 5.9 +/- 1.3, P < 0.001; 5 s/delay 5 s: 6.1 +/- 1.3, P < 0.001), yet manic patients under-reproduced the time interval (600 ms/delay 1 s: 0.7 +/- 0.2, P < 0.01; 600 ms/delay 5 s: 0.6 +/- 0.3, P < 0.001; 3 s/delay 1 s: 1.7 +/- 0.5, P < 0.001; 3 s/delay 5 s: 1.8 +/- 0.6, P < 0.001; 5 s/delay 1 s: 2.9 +/- 0.7, P < 0.001; 5 s/delay 5 s: 3.0 +/- 0.8, P < 0.001). The results of time reproduction task in patients were not related to age, education, duration of illness, number of admission (P > 0.05), but had some relation to severity of illness.And the results were positively correlated with the score of HAMD in depressive patients (six times: r = 0.44, 0.46, 0.73, 0.61, 0.55, 0.50, P < 0.05), but negatively with the score of BRMS in manic patients (six times: r = -0.57, -0.54, -0.71, -0.69, -0.80, -0.71, P < 0.05). Emotion will affect one's time perception. And the neurotransmitter in brain may participate in the processes of time perception.

Matefin/SUN-1 Phosphorylation Is Part of a Surveillance Mechanism to Coordinate Chromosome Synapsis and Recombination with Meiotic Progression and Chromosome Movement

PubMed Central

Woglar, Alexander; Daryabeigi, Anahita; Adamo, Adele; Habacher, Cornelia; Machacek, Thomas; La Volpe, Adriana; Jantsch, Verena

2013-01-01

Faithful chromosome segregation during meiosis I depends on the establishment of a crossover between homologous chromosomes. This requires induction of DNA double-strand breaks (DSBs), alignment of homologs, homolog association by synapsis, and repair of DSBs via homologous recombination. The success of these events requires coordination between chromosomal events and meiotic progression. The conserved SUN/KASH nuclear envelope bridge establishes transient linkages between chromosome ends and cytoskeletal forces during meiosis. In Caenorhabditis elegans, this bridge is essential for bringing homologs together and preventing nonhomologous synapsis. Chromosome movement takes place during synapsis and recombination. Concomitant with the onset of chromosome movement, SUN-1 clusters at chromosome ends associated with the nuclear envelope, and it is phosphorylated in a chk-2- and plk-2-dependent manner. Identification of all SUN-1 phosphomodifications at its nuclear N terminus allowed us to address their role in prophase I. Failures in recombination and synapsis led to persistent phosphorylations, which are required to elicit a delay in progression. Unfinished meiotic tasks elicited sustained recruitment of PLK-2 to chromosome ends in a SUN-1 phosphorylation–dependent manner that is required for continued chromosome movement and characteristic of a zygotene arrest. Furthermore, SUN-1 phosphorylation supported efficient synapsis. We propose that signals emanating from a failure to successfully finish meiotic tasks are integrated at the nuclear periphery to regulate chromosome end–led movement and meiotic progression. The single unsynapsed X chromosome in male meiosis is precluded from inducing a progression delay, and we found it was devoid of a population of phosphorylated SUN-1. This suggests that SUN-1 phosphorylation is critical to delaying meiosis in response to perturbed synapsis. SUN-1 may be an integral part of a checkpoint system to monitor establishment of the obligate crossover, inducible only in leptotene/zygotene. Unrepaired DSBs and unsynapsed chromosomes maintain this checkpoint, but a crossover intermediate is necessary to shut it down. PMID:23505384

Epoetin beta pegol alleviates oxidative stress and exacerbation of renal damage from iron deposition, thereby delaying CKD progression in progressive glomerulonephritis rats.

PubMed

Hirata, Michinori; Tashiro, Yoshihito; Aizawa, Ken; Kawasaki, Ryohei; Shimonaka, Yasushi; Endo, Koichi

2015-12-01

The increased deposition of iron in the kidneys that occurs with glomerulopathy hinders the functional and structural recovery of the tubules and promotes progression of chronic kidney disease (CKD). Here, we evaluated whether epoetin beta pegol (continuous erythropoietin receptor activator: CERA), which has a long half-life in blood and strongly suppresses hepcidin-25, exerts renoprotection in a rat model of chronic progressive glomerulonephritis (cGN). cGN rats showed elevated urinary total protein excretion (uTP) and plasma urea nitrogen (UN) from day 14 after the induction of kidney disease (day 0) and finally declined into end-stage kidney disease (ESKD), showing reduced creatinine clearance with glomerulosclerosis, tubular dilation, and tubulointerstitial fibrosis. A single dose of CERA given on day 1, but not on day 16, alleviated increasing uTP and UN, thereby delaying ESKD. In the initial disease phase, CERA significantly suppressed urinary 8-OHdG and liver-type fatty acid-binding protein (L-FABP), a tubular damage marker. CERA also inhibited elevated plasma hepcidin-25 levels and alleviated subsequent iron accumulation in kidneys in association with elevated urinary iron excretion and resulted in alleviation of growth of Ki67-positive tubular and glomerular cells. In addition, at day 28 when the exacerbation of uTP occurs, a significant correlation was observed between iron deposition in the kidney and urinary L-FABP. In our study, CERA mitigated increasing kidney damage, thereby delaying CKD progression in this glomerulonephritis rat model. Alleviation by CERA of the exacerbation of kidney damage could be attributable to mitigation of tubular damage that might occur with lowered iron deposition in tubules. © 2015 Chugai Pharmaceutical Co., Ltd. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Bounded Linear Stability Analysis - A Time Delay Margin Estimation Approach for Adaptive Control

NASA Technical Reports Server (NTRS)

Nguyen, Nhan T.; Ishihara, Abraham K.; Krishnakumar, Kalmanje Srinlvas; Bakhtiari-Nejad, Maryam

2009-01-01

This paper presents a method for estimating time delay margin for model-reference adaptive control of systems with almost linear structured uncertainty. The bounded linear stability analysis method seeks to represent the conventional model-reference adaptive law by a locally bounded linear approximation within a small time window using the comparison lemma. The locally bounded linear approximation of the combined adaptive system is cast in a form of an input-time-delay differential equation over a small time window. The time delay margin of this system represents a local stability measure and is computed analytically by a matrix measure method, which provides a simple analytical technique for estimating an upper bound of time delay margin. Based on simulation results for a scalar model-reference adaptive control system, both the bounded linear stability method and the matrix measure method are seen to provide a reasonably accurate and yet not too conservative time delay margin estimation.

Broadband true time delay for microwave signal processing, using slow light based on stimulated Brillouin scattering in optical fibers.

PubMed

Chin, Sanghoon; Thévenaz, Luc; Sancho, Juan; Sales, Salvador; Capmany, José; Berger, Perrine; Bourderionnet, Jérôme; Dolfi, Daniel

2010-10-11

We experimentally demonstrate a novel technique to process broadband microwave signals, using all-optically tunable true time delay in optical fibers. The configuration to achieve true time delay basically consists of two main stages: photonic RF phase shifter and slow light, based on stimulated Brillouin scattering in fibers. Dispersion properties of fibers are controlled, separately at optical carrier frequency and in the vicinity of microwave signal bandwidth. This way time delay induced within the signal bandwidth can be manipulated to correctly act as true time delay with a proper phase compensation introduced to the optical carrier. We completely analyzed the generated true time delay as a promising solution to feed phased array antenna for radar systems and to develop dynamically reconfigurable microwave photonic filters.

Delayed mTOR inhibition with low dose of everolimus reduces TGFβ expression, attenuates proteinuria and renal damage in the renal mass reduction model.

PubMed

Kurdián, Melania; Herrero-Fresneda, Inmaculada; Lloberas, Nuria; Gimenez-Bonafe, Pepita; Coria, Virginia; Grande, María T; Boggia, José; Malacrida, Leonel; Torras, Joan; Arévalo, Miguel A; González-Martínez, Francisco; López-Novoa, José M; Grinyó, Josep; Noboa, Oscar

2012-01-01

The immunosuppressive mammalian target of rapamycin (mTOR) inhibitors are widely used in solid organ transplantation, but their effect on kidney disease progression is controversial. mTOR has emerged as one of the main pathways regulating cell growth, proliferation, differentiation, migration, and survival. The aim of this study was to analyze the effects of delayed inhibition of mTOR pathway with low dose of everolimus on progression of renal disease and TGFβ expression in the 5/6 nephrectomy model in Wistar rats. This study evaluated the effects of everolimus (0.3 mg/k/day) introduced 15 days after surgical procedure on renal function, proteinuria, renal histology and mechanisms of fibrosis and proliferation. Everolimus treated group (EveG) showed significantly less proteinuria and albuminuria, less glomerular and tubulointerstitial damage and fibrosis, fibroblast activation cell proliferation, when compared with control group (CG), even though the EveG remained with high blood pressure. Treatment with everolimus also diminished glomerular hypertrophy. Everolimus effectively inhibited the increase of mTOR developed in 5/6 nephrectomy animals, without changes in AKT mRNA or protein abundance, but with an increase in the pAKT/AKT ratio. Associated with this inhibition, everolimus blunted the increased expression of TGFβ observed in the remnant kidney model. Delayed mTOR inhibition with low dose of everolimus significantly prevented progressive renal damage and protected the remnant kidney. mTOR and TGFβ mRNA reduction can partially explain this anti fibrotic effect. mTOR can be a new target to attenuate the progression of chronic kidney disease even in those nephropathies of non-immunologic origin.

Delayed mTOR Inhibition with Low Dose of Everolimus Reduces TGFβ Expression, Attenuates Proteinuria and Renal Damage in the Renal Mass Reduction Model

PubMed Central

Kurdián, Melania; Herrero-Fresneda, Inmaculada; Lloberas, Nuria; Gimenez-Bonafe, Pepita; Coria, Virginia; Grande, María T.; Boggia, José; Malacrida, Leonel; Torras, Joan; Arévalo, Miguel A.; González-Martínez, Francisco; López-Novoa, José M.; Grinyó, Josep; Noboa, Oscar

2012-01-01

Background The immunosuppressive mammalian target of rapamycin (mTOR) inhibitors are widely used in solid organ transplantation, but their effect on kidney disease progression is controversial. mTOR has emerged as one of the main pathways regulating cell growth, proliferation, differentiation, migration, and survival. The aim of this study was to analyze the effects of delayed inhibition of mTOR pathway with low dose of everolimus on progression of renal disease and TGFβ expression in the 5/6 nephrectomy model in Wistar rats. Methods This study evaluated the effects of everolimus (0.3 mg/k/day) introduced 15 days after surgical procedure on renal function, proteinuria, renal histology and mechanisms of fibrosis and proliferation. Results Everolimus treated group (EveG) showed significantly less proteinuria and albuminuria, less glomerular and tubulointerstitial damage and fibrosis, fibroblast activation cell proliferation, when compared with control group (CG), even though the EveG remained with high blood pressure. Treatment with everolimus also diminished glomerular hypertrophy. Everolimus effectively inhibited the increase of mTOR developed in 5/6 nephrectomy animals, without changes in AKT mRNA or protein abundance, but with an increase in the pAKT/AKT ratio. Associated with this inhibition, everolimus blunted the increased expression of TGFβ observed in the remnant kidney model. Conclusion Delayed mTOR inhibition with low dose of everolimus significantly prevented progressive renal damage and protected the remnant kidney. mTOR and TGFβ mRNA reduction can partially explain this anti fibrotic effect. mTOR can be a new target to attenuate the progression of chronic kidney disease even in those nephropathies of non-immunologic origin. PMID:22427849

The presence of anti-Tat antibodies in HIV-infected individuals is associated with containment of CD4+ T-cell decay and viral load, and with delay of disease progression: results of a 3-year cohort study

PubMed Central

2014-01-01

Background Tat is a key HIV-1 virulence factor, which plays pivotal roles in virus gene expression, replication, transmission and disease progression. After release, extracellular Tat accumulates in tissues and exerts effects on both the virus and the immune system, promoting immune activation and virus spreading while disabling the host immune defense. In particular, Tat binds Env spikes on virus particles forming a virus entry complex, which favors infection of dendritic cells and efficient transmission to T cells via RGD-binding integrins. Tat also shields the CCR5-binding sites of Env rendering ineffective virus neutralization by anti-Env antibodies (Abs). This is reversed by the anti-Tat Abs present in natural infection or induced by vaccination. Findings Here we present the results of a cohort study, showing that the presence of anti-Tat Abs in asymptomatic and treatment-naïve HIV-infected subjects is associated with containment of CD4+ T-cell loss and viral load and with a delay of disease progression. In fact, no subjects with high anti-Tat Ab titers initiated antiretroviral therapy during the three years of follow-up. In contrast, no significant effects were seen for anti-Env and anti-Gag Abs. The increase of anti-Env Ab titers was associated with a reduced risk of starting therapy only in the presence of anti-Tat Abs, suggesting an effect of combined anti-Tat and anti-Env Abs on the Tat/Env virus entry complex and on virus neutralization. Conclusions Anti-Tat immunity may help delay HIV disease progression, thus, targeting Tat may offer a novel therapeutic intervention to postpone antiretroviral treatment or to increase its efficacy. PMID:24961156

Finite-Time Stabilization and Adaptive Control of Memristor-Based Delayed Neural Networks.

PubMed

Wang, Leimin; Shen, Yi; Zhang, Guodong

Finite-time stability problem has been a hot topic in control and system engineering. This paper deals with the finite-time stabilization issue of memristor-based delayed neural networks (MDNNs) via two control approaches. First, in order to realize the stabilization of MDNNs in finite time, a delayed state feedback controller is proposed. Then, a novel adaptive strategy is applied to the delayed controller, and finite-time stabilization of MDNNs can also be achieved by using the adaptive control law. Some easily verified algebraic criteria are derived to ensure the stabilization of MDNNs in finite time, and the estimation of the settling time functional is given. Moreover, several finite-time stability results as our special cases for both memristor-based neural networks (MNNs) without delays and neural networks are given. Finally, three examples are provided for the illustration of the theoretical results.Finite-time stability problem has been a hot topic in control and system engineering. This paper deals with the finite-time stabilization issue of memristor-based delayed neural networks (MDNNs) via two control approaches. First, in order to realize the stabilization of MDNNs in finite time, a delayed state feedback controller is proposed. Then, a novel adaptive strategy is applied to the delayed controller, and finite-time stabilization of MDNNs can also be achieved by using the adaptive control law. Some easily verified algebraic criteria are derived to ensure the stabilization of MDNNs in finite time, and the estimation of the settling time functional is given. Moreover, several finite-time stability results as our special cases for both memristor-based neural networks (MNNs) without delays and neural networks are given. Finally, three examples are provided for the illustration of the theoretical results.

The effect of visual-motion time delays on pilot performance in a pursuit tracking task

NASA Technical Reports Server (NTRS)

Miller, G. K., Jr.; Riley, D. R.

1976-01-01

A study has been made to determine the effect of visual-motion time delays on pilot performance of a simulated pursuit tracking task. Three interrelated major effects have been identified: task difficulty, motion cues, and time delays. As task difficulty, as determined by airplane handling qualities or target frequency, increases, the amount of acceptable time delay decreases. However, when relatively complete motion cues are included in the simulation, the pilot can maintain his performance for considerably longer time delays. In addition, the number of degrees of freedom of motion employed is a significant factor.

Robust stability bounds for multi-delay networked control systems

NASA Astrophysics Data System (ADS)

Seitz, Timothy; Yedavalli, Rama K.; Behbahani, Alireza

2018-04-01

In this paper, the robust stability of a perturbed linear continuous-time system is examined when controlled using a sampled-data networked control system (NCS) framework. Three new robust stability bounds on the time-invariant perturbations to the original continuous-time plant matrix are presented guaranteeing stability for the corresponding discrete closed-loop augmented delay-free system (ADFS) with multiple time-varying sensor and actuator delays. The bounds are differentiated from previous work by accounting for the sampled-data nature of the NCS and for separate communication delays for each sensor and actuator, not a single delay. Therefore, this paper expands the knowledge base in multiple inputs multiple outputs (MIMO) sampled-data time delay systems. Bounds are presented for unstructured, semi-structured, and structured perturbations.

Discrete-time BAM neural networks with variable delays

NASA Astrophysics Data System (ADS)

Liu, Xin-Ge; Tang, Mei-Lan; Martin, Ralph; Liu, Xin-Bi

2007-07-01

This Letter deals with the global exponential stability of discrete-time bidirectional associative memory (BAM) neural networks with variable delays. Using a Lyapunov functional, and linear matrix inequality techniques (LMI), we derive a new delay-dependent exponential stability criterion for BAM neural networks with variable delays. As this criterion has no extra constraints on the variable delay functions, it can be applied to quite general BAM neural networks with a broad range of time delay functions. It is also easy to use in practice. An example is provided to illustrate the theoretical development.

Local Bifurcations and Optimal Theory in a Delayed Predator-Prey Model with Threshold Prey Harvesting

NASA Astrophysics Data System (ADS)

Tankam, Israel; Tchinda Mouofo, Plaire; Mendy, Abdoulaye; Lam, Mountaga; Tewa, Jean Jules; Bowong, Samuel

2015-06-01

We investigate the effects of time delay and piecewise-linear threshold policy harvesting for a delayed predator-prey model. It is the first time that Holling response function of type III and the present threshold policy harvesting are associated with time delay. The trajectories of our delayed system are bounded; the stability of each equilibrium is analyzed with and without delay; there are local bifurcations as saddle-node bifurcation and Hopf bifurcation; optimal harvesting is also investigated. Numerical simulations are provided in order to illustrate each result.

Autophagy is required for efficient meiosis progression and proper meiotic chromosome segregation in fission yeast.

PubMed

Matsuhara, Hirotada; Yamamoto, Ayumu

2016-01-01

Autophagy is a conserved intracellular degradation system, which contributes to development and differentiation of various organisms. Yeast cells undergo meiosis under nitrogen-starved conditions and require autophagy for meiosis initiation. However, the precise roles of autophagy in meiosis remain unclear. Here, we show that autophagy is required for efficient meiosis progression and proper meiotic chromosome segregation in fission yeast. Autophagy-defective strains bearing a mutation in the autophagy core factor gene atg1, atg7, or atg14 exhibit deformed nuclear structures during meiosis. These mutant cells require an extracellular nitrogen supply for meiosis progression following their entry into meiosis and show delayed meiosis progression even with a nitrogen supply. In addition, they show frequent chromosome dissociation from the spindle together with spindle overextension, forming extra nuclei. Furthermore, Aurora kinase, which regulates chromosome segregation and spindle elongation, is significantly increased at the centromere and spindle in the mutant cells. Aurora kinase down-regulation eliminated delayed initiation of meiosis I and II, chromosome dissociation, and spindle overextension, indicating that increased Aurora kinase activity may cause these aberrances in the mutant cells. Our findings show a hitherto unrecognized relationship of autophagy with the nuclear structure, regulation of cell cycle progression, and chromosome segregation in meiosis. © 2015 The Molecular Biology Society of Japan and Wiley Publishing Asia Pty Ltd.

Effect of time to initiation of postoperative radiation therapy on survival in surgically managed head and neck cancer.

PubMed

Graboyes, Evan M; Garrett-Mayer, Elizabeth; Ellis, Mark A; Sharma, Anand K; Wahlquist, Amy E; Lentsch, Eric J; Nussenbaum, Brian; Day, Terry A

2017-12-15

The objective of this study was to determine the effects of National Comprehensive Cancer Network (NCCN) guideline-adherent initiation of postoperative radiation therapy (PORT) and different time-to-PORT intervals on the overall survival (OS) of patients with head and neck squamous cell carcinoma (HNSCC). The National Cancer Data Base was reviewed for the period of 2006-2014, and patients with HNSCC undergoing surgery and PORT were identified. Kaplan-Meier survival estimates, Cox regression analysis, and propensity score matching were used to determine the effects of initiating PORT within 6 weeks of surgery and different time-to-PORT intervals on survival. This study included 41,291 patients. After adjustments for covariates, starting PORT >6 weeks postoperatively was associated with decreased OS (adjusted hazard ratio [aHR], 1.13; 99% confidence interval [CI], 1.08-1.19). This finding remained in the propensity score-matched subset (hazard ratio, 1.21; 99% CI, 1.15-1.28). In comparison with starting PORT 5 to 6 weeks postoperatively, initiating PORT earlier was not associated with improved survival (aHR for ≤ 4 weeks, 0.93; 99% CI, 0.85-1.02; aHR for 4-5 weeks, 0.92; 99% CI, 0.84-1.01). Increasing durations of delay beyond 7 weeks were associated with small, progressive survival decrements (aHR, 1.09, 1.10, and 1.12 for 7-8, 8-10, and >10 weeks, respectively). Nonadherence to NCCN guidelines for initiating PORT within 6 weeks of surgery was associated with decreased survival. There was no survival benefit to initiating PORT earlier within the recommended 6-week timeframe. Increasing durations of delay beyond 7 weeks were associated with small, progressive survival decrements. Cancer 2017;123:4841-50. © 2017 American Cancer Society. © 2017 American Cancer Society.

Incidence and progression of Parvovirus B19 infection and molecular changes in circulating B19V strains in children with haematological malignancy: A follow up study.

PubMed

Jain, Amita; Jain, Parul; Kumar, Archana; Prakash, Shantanu; Khan, Danish Nasar; Kant, Ravi

2018-01-01

The present study was planned to estimate the incidence of human Parvovirus B19 infection and understand its progression in children suffering with hematological malignancy. The circulating B19V genotypes and viral mutations occurring in strains of B19V over one-year period were also studied. Children with malignancies were enrolled consecutively and were followed up for one-year period. Serum sample was collected at the time of enrolment and each follow up visit and was tested for anti B19V IgG and IgM as well as for B19V DNA. At least one B19V DNA positive sample from each patient was processed for sequencing. For patients positive for B19V DNA >1 time and at least 6 months apart, last positive sample from the same patient was also sequenced to study the nucleotide change over time. We have found very high incidence of B19V infection (100%) in the study population. All the patients tested positive for at least one B19V infection parameter (either antibodies or DNA) at least once, over one year of follow up. Cumulative percent positivity of anti B19V IgG, anti B19V IgM and B19V DNA was 85.3%, 45.2% and 72.1% respectively. Genotype 3b was reported, with occasional nucleotide change over one year period. DNA clearance was delayed in spite of appearance of IgG antibodies. Appearance of IgM class of antibodies was either delayed or absent. To conclude, children with haematological malignancies have high incidence of B19V infection with late and short lived serological response and persistence of DNA for long duration. Copyright © 2017 Elsevier B.V. All rights reserved.

A Strain-Sonde Technique for the Measurement of Mechanical Time-Delay Fuze Function Times and Performance

DTIC Science & Technology

1983-09-01

AD IV) MEMORANDUM REPORT ARBRL-MR-03309 N(Supersedes IMR No. 760) A STRAIN -SONDE TECHNIQUE FOR THE MEASUREMENT OF MECHANICAL TIME- DELAY FUZE...and BkuWel) S. TYPE OF REPORT & PERIOD COVERED A STRAIN -SONDE TECHNIQUE FOR THE MEASUREMENT OF Final MECHANICAL TIME-DELAY FUZE FUNCTION TIMES AND S...nmber) M577 Mechanical Time-Delay Fuze F"/FM Telemeter Interlock Pin Release Semiconductor Strain Gage Rotor Signal Condition Amplifier Firing Pin In

Robust optimization for nonlinear time-delay dynamical system of dha regulon with cost sensitivity constraint in batch culture

NASA Astrophysics Data System (ADS)

Yuan, Jinlong; Zhang, Xu; Liu, Chongyang; Chang, Liang; Xie, Jun; Feng, Enmin; Yin, Hongchao; Xiu, Zhilong

2016-09-01

Time-delay dynamical systems, which depend on both the current state of the system and the state at delayed times, have been an active area of research in many real-world applications. In this paper, we consider a nonlinear time-delay dynamical system of dha-regulonwith unknown time-delays in batch culture of glycerol bioconversion to 1,3-propanediol induced by Klebsiella pneumonia. Some important properties and strong positive invariance are discussed. Because of the difficulty in accurately measuring the concentrations of intracellular substances and the absence of equilibrium points for the time-delay system, a quantitative biological robustness for the concentrations of intracellular substances is defined by penalizing a weighted sum of the expectation and variance of the relative deviation between system outputs before and after the time-delays are perturbed. Our goal is to determine optimal values of the time-delays. To this end, we formulate an optimization problem in which the time delays are decision variables and the cost function is to minimize the biological robustness. This optimization problem is subject to the time-delay system, parameter constraints, continuous state inequality constraints for ensuring that the concentrations of extracellular and intracellular substances lie within specified limits, a quality constraint to reflect operational requirements and a cost sensitivity constraint for ensuring that an acceptable level of the system performance is achieved. It is approximated as a sequence of nonlinear programming sub-problems through the application of constraint transcription and local smoothing approximation techniques. Due to the highly complex nature of this optimization problem, the computational cost is high. Thus, a parallel algorithm is proposed to solve these nonlinear programming sub-problems based on the filled function method. Finally, it is observed that the obtained optimal estimates for the time-delays are highly satisfactory via numerical simulations.

PSA doubling time of prostate carcinoma managed with watchful observation alone.

PubMed

Choo, R; DeBoer, G; Klotz, L; Danjoux, C; Morton, G C; Rakovitch, E; Fleshner, N; Bunting, P; Kapusta, L; Hruby, G

2001-07-01

To study prostate-specific antigen (PSA) doubling time of untreated, favorable grade, prostate carcinoma. A prospective single-arm cohort study has been in progress to assess the feasibility of a watchful observation protocol with selective delayed intervention using clinical, histologic, or PSA progression as treatment indication in untreated, localized, favorable grade prostate adenocarcinoma (T1b-T2bN0 M0, Gleason Score < or = 7, and PSA < or = 15 ng/mL). Patients are conservatively managed with watchful observation alone, as long as they do not meet the arbitrarily defined disease progression criteria. Patients are followed regularly and undergo blood tests including PSA at each visit. PSA doubling time (Td) is estimated from a linear regression of ln(PSA) on time, assuming a simple exponential growth model. As of March 2000, 134 patients have been on the study for a minimum of 12 months (median, 24; range, 12-52) and have a median frequency of PSA measurement of 7 times (range, 3-15). Median age is 70 years. Median PSA at enrollment is 6.3 (range, 0.5-14.6). The distribution of Td is as follows: <2 years, 19 patients; 2-5 years, 46; 5-10 years, 25; 10-20 years, 11; 20-50 years, 6; > 50 years, 27. The median Td is 5.1 years. In 44 patients (33%), Td is greater than 10 years. There was no correlation between Td and patient age, clinical T stage, Gleason score, or initial PSA level. Td of untreated prostate cancer varies widely. In our cohort, 33% have Td > 10 years. Td may be a useful tool to guide treatment intervention for patients managed conservatively with watchful observation alone.

Time delay and noise explaining the behaviour of the cell growth in fermentation process

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

Ayuobi, Tawfiqullah; Rosli, Norhayati; Bahar, Arifah

2015-02-03

This paper proposes to investigate the interplay between time delay and external noise in explaining the behaviour of the microbial growth in batch fermentation process. Time delay and noise are modelled jointly via stochastic delay differential equations (SDDEs). The typical behaviour of cell concentration in batch fermentation process under this model is investigated. Milstein scheme is applied for solving this model numerically. Simulation results illustrate the effects of time delay and external noise in explaining the lag and stationary phases, respectively for the cell growth of fermentation process.

Time delay and noise explaining the behaviour of the cell growth in fermentation process

NASA Astrophysics Data System (ADS)

Ayuobi, Tawfiqullah; Rosli, Norhayati; Bahar, Arifah; Salleh, Madihah Md

2015-02-01

This paper proposes to investigate the interplay between time delay and external noise in explaining the behaviour of the microbial growth in batch fermentation process. Time delay and noise are modelled jointly via stochastic delay differential equations (SDDEs). The typical behaviour of cell concentration in batch fermentation process under this model is investigated. Milstein scheme is applied for solving this model numerically. Simulation results illustrate the effects of time delay and external noise in explaining the lag and stationary phases, respectively for the cell growth of fermentation process.

The Effects of Financial Education on Impulsive Decision Making

PubMed Central

DeHart, William B.; Friedel, Jonathan E.; Lown, Jean M.; Odum, Amy L.

2016-01-01

Delay discounting, as a behavioral measure of impulsive choice, is strongly related to substance abuse and other risky behaviors. Therefore, effective techniques that alter delay discounting are of great interest. We explored the ability of a semester long financial education course to change delay discounting. Participants were recruited from a financial education course (n = 237) and an abnormal psychology course (n = 80). Both groups completed a delay-discounting task for $100 during the first two weeks (Time 1) of the semester as well as during the last two weeks (Time 2) of the semester. Participants also completed a personality inventory and financial risk tolerance scale both times and a delay-discounting task for $1,000 during Time 2. Delay discounting decreased in the financial education group at the end of the semester whereas there was no change in delay discounting in the abnormal psychology group. Financial education may be an effective method for reducing delay discounting. PMID:27442237

The Effects of Financial Education on Impulsive Decision Making.

PubMed

DeHart, William B; Friedel, Jonathan E; Lown, Jean M; Odum, Amy L

2016-01-01

Delay discounting, as a behavioral measure of impulsive choice, is strongly related to substance abuse and other risky behaviors. Therefore, effective techniques that alter delay discounting are of great interest. We explored the ability of a semester long financial education course to change delay discounting. Participants were recruited from a financial education course (n = 237) and an abnormal psychology course (n = 80). Both groups completed a delay-discounting task for $100 during the first two weeks (Time 1) of the semester as well as during the last two weeks (Time 2) of the semester. Participants also completed a personality inventory and financial risk tolerance scale both times and a delay-discounting task for $1,000 during Time 2. Delay discounting decreased in the financial education group at the end of the semester whereas there was no change in delay discounting in the abnormal psychology group. Financial education may be an effective method for reducing delay discounting.

Delay-induced stochastic bifurcations in a bistable system under white noise

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

Sun, Zhongkui, E-mail: sunzk@nwpu.edu.cn; Fu, Jin; Xu, Wei

2015-08-15

In this paper, the effects of noise and time delay on stochastic bifurcations are investigated theoretically and numerically in a time-delayed Duffing-Van der Pol oscillator subjected to white noise. Due to the time delay, the random response is not Markovian. Thereby, approximate methods have been adopted to obtain the Fokker-Planck-Kolmogorov equation and the stationary probability density function for amplitude of the response. Based on the knowledge that stochastic bifurcation is characterized by the qualitative properties of the steady-state probability distribution, it is found that time delay and feedback intensity as well as noise intensity will induce the appearance of stochasticmore » P-bifurcation. Besides, results demonstrated that the effects of the strength of the delayed displacement feedback on stochastic bifurcation are accompanied by the sensitive dependence on time delay. Furthermore, the results from numerical simulations best confirm the effectiveness of the theoretical analyses.« less

The rates and time-delay distribution of multiply imaged supernovae behind lensing clusters

NASA Astrophysics Data System (ADS)

Li, Xue; Hjorth, Jens; Richard, Johan

2012-11-01

Time delays of gravitationally lensed sources can be used to constrain the mass model of a deflector and determine cosmological parameters. We here present an analysis of the time-delay distribution of multiply imaged sources behind 17 strong lensing galaxy clusters with well-calibrated mass models. We find that for time delays less than 1000 days, at z = 3.0, their logarithmic probability distribution functions are well represented by P(log Δt) = 5.3 × 10-4Δttilde beta/M2502tilde beta, with tilde beta = 0.77, where M250 is the projected cluster mass inside 250 kpc (in 1014M⊙), and tilde beta is the power-law slope of the distribution. The resultant probability distribution function enables us to estimate the time-delay distribution in a lensing cluster of known mass. For a cluster with M250 = 2 × 1014M⊙, the fraction of time delays less than 1000 days is approximately 3%. Taking Abell 1689 as an example, its dark halo and brightest galaxies, with central velocity dispersions σ>=500kms-1, mainly produce large time delays, while galaxy-scale mass clumps are responsible for generating smaller time delays. We estimate the probability of observing multiple images of a supernova in the known images of Abell 1689. A two-component model of estimating the supernova rate is applied in this work. For a magnitude threshold of mAB = 26.5, the yearly rate of Type Ia (core-collapse) supernovae with time delays less than 1000 days is 0.004±0.002 (0.029±0.001). If the magnitude threshold is lowered to mAB ~ 27.0, the rate of core-collapse supernovae suitable for time delay observation is 0.044±0.015 per year.

Elapsed Time Between the First Symptoms of Breast Cancer and Medical Help-Seeking Behavior and the Affecting Factors.

PubMed

Gözüm, Sebahat; Tuzcu, Ayla

Many studies have determined that the time between women's realization of first symptoms and seeking help from a healthcare professional is more than 1 month. The situation is defined as delay in medical help-seeking behavior (MHSB). The purpose of this study was to determine the time elapsed between the first symptoms of breast cancer and MHSB, as well as the factors contributing to the delay. In this descriptive study, the data were collected from 132 patients who received a diagnosis of breast cancer and are receiving treatment in the Oncology Clinic of Akdeniz University Hospital. The questionnaire used in the study was structured in 3 parts: sociodemographic characteristics, breast cancer history/screening behaviors, and psychological factors affecting MHSB. The elapsed time between patients' first symptoms and MHSB was classified into "normal" when it was less than 1 month, "delay" when it was between 1 and 3 months, "long-term delay" when it was more than 3 months, and "very serious delay" when it was more than 6 months. A total of 59.8% were classified as normal, 16.7% as delayed, 5.3% as a long-term delay, and 18.2% as a very serious delay after first symptoms. The delay in MHSB time was affected 18.55 times by "not caring/minding," 10.73 times by "fear," 7.13 times by "having more important problems," and 4.23 times by "realization of first symptoms" by themselves. Psychological factors were the most important determinants in delay. The MHSB time was less if those first realizing the symptoms were healthcare professionals. Healthcare professionals should direct women to screenings and train them to interpret symptoms correctly.

Effects of computing time delay on real-time control systems

NASA Technical Reports Server (NTRS)

Shin, Kang G.; Cui, Xianzhong

1988-01-01

The reliability of a real-time digital control system depends not only on the reliability of the hardware and software used, but also on the speed in executing control algorithms. The latter is due to the negative effects of computing time delay on control system performance. For a given sampling interval, the effects of computing time delay are classified into the delay problem and the loss problem. Analysis of these two problems is presented as a means of evaluating real-time control systems. As an example, both the self-tuning predicted (STP) control and Proportional-Integral-Derivative (PID) control are applied to the problem of tracking robot trajectories, and their respective effects of computing time delay on control performance are comparatively evaluated. For this example, the STP (PID) controller is shown to outperform the PID (STP) controller in coping with the delay (loss) problem.

The influences of delay time on the stability of a market model with stochastic volatility

NASA Astrophysics Data System (ADS)

Li, Jiang-Cheng; Mei, Dong-Cheng

2013-02-01

The effects of the delay time on the stability of a market model are investigated, by using a modified Heston model with a cubic nonlinearity and cross-correlated noise sources. These results indicate that: (i) There is an optimal delay time τo which maximally enhances the stability of the stock price under strong demand elasticity of stock price, and maximally reduces the stability of the stock price under weak demand elasticity of stock price; (ii) The cross correlation coefficient of noises and the delay time play an opposite role on the stability for the case of the delay time <τo and the same role for the case of the delay time >τo. Moreover, the probability density function of the escape time of stock price returns, the probability density function of the returns and the correlation function of the returns are compared with other literatures.

The Altimetric Wet Tropospheric Correction: Progress Since The ERS-1 Mission

NASA Astrophysics Data System (ADS)

Eymard, L.; Obligis, E.

2006-07-01

To correct for the path delay due to humidity in the troposphere, dedicated microwave radiometers have been added to altimeters on ESA and NASA/CNES missions. This paper presents the major issues with calibration and retrieval of the wet tropospheric path d elay s ince E RS1, a s w ell a s n ew developments for in-flight monitoring, retrieval of the path delay over the open ocean and in coastal regions.

Interrelationships between Marijuana Demand and Discounting of Delayed Rewards: Convergence in Behavioral Economic Methods

PubMed Central

Aston, Elizabeth R.; Metrik, Jane; Amlung, Michael; Kahler, Christopher W.; MacKillop, James

2016-01-01

Background Distinct behavioral economic domains, including high perceived drug value (demand) and delay discounting (DD), have been implicated in the initiation of drug use and the progression to dependence. However, it is unclear whether frequent marijuana users conform to a “reinforcer pathology” addiction model wherein marijuana demand and DD jointly increase risk for problematic marijuana use and cannabis dependence (CD). Methods Participants (n=88, 34% female, 14% cannabis dependent) completed a marijuana purchase task at baseline. A delay discounting task was completed following placebo marijuana cigarette (0% THC) administration during a separate experimental session. Results Marijuana demand and DD were quantified using area under the curve (AUC). In multiple regression models, demand uniquely predicted frequency of marijuana use while DD did not. In contrast, DD uniquely predicted CD symptom count while demand did not. There were no significant interactions between demand and DD in either model. Conclusions These findings suggest that frequent marijuana users exhibit key constituents of the reinforcer pathology model: high marijuana demand and steep discounting of delayed rewards. However, demand and DD appear to be independent rather than synergistic risk factors for elevated marijuana use and risk for progression to CD. Findings also provide support for using AUC as a singular marijuana demand metric, particularly when also examining other behavioral economic constructs that apply similar statistical approaches, such as DD, to support analytic methodological convergence. PMID:27810657

Differential S-phase progression after irradiation of p53 functional versus non-functional tumour cells

PubMed Central

Zölzer, Friedo; Mußfeldt, Tamare; Streffer, Christian

2014-01-01

Background Many pathways seem to be involved in the regulation of the intra-S-phase checkpoint after exposure to ionizing radiation, but the role of p53 has proven to be rather elusive. Here we have a closer look at the progression of irradiated cells through S-phase in dependence of their p53 status. Materials and methods. Three pairs of tumour cell lines were used, each consisting of one p53 functional and one p53 non-functional line. Cells were labelled with bromodeoxyuridine(BrdU) immediately after irradiation, they were then incubated in label-free medium, and at different times afterwards their position within the S-phase was determined by means of flow cytometry. Results While in the p53 deficient cells progression through S-phase was slowed significantly over at least a few hours, it was halted for just about an hour in the p53 proficient cells and then proceeded without further delay or even at a slightly accelerated pace. Conclusions It is clear from the experiments presented here that p53 does play a role for the progress of cells through the S-phase after X-ray exposure, but the exact mechanisms by which replicon initiation and elongation is controlled in irradiated cells remain to be elucidated. PMID:25435848

Building Construction Progress Monitoring Using Unmanned Aerial System (uas), Low-Cost Photogrammetry, and Geographic Information System (gis)

NASA Astrophysics Data System (ADS)

Bognot, J. R.; Candido, C. G.; Blanco, A. C.; Montelibano, J. R. Y.

2018-05-01

Monitoring the progress of building's construction is critical in construction management. However, measuring the building construction's progress are still manual, time consuming, error prone, and impose tedious process of analysis leading to delays, additional costings and effort. The main goal of this research is to develop a methodology for building construction progress monitoring based on 3D as-built model of the building from unmanned aerial system (UAS) images, 4D as-planned model (with construction schedule integrated) and, GIS analysis. Monitoring was done by capturing videos of the building with a camera-equipped UAS. Still images were extracted, filtered, bundle-adjusted, and 3D as-built model was generated using open source photogrammetric software. The as-planned model was generated from digitized CAD drawings using GIS. The 3D as-built model was aligned with the 4D as-planned model of building formed from extrusion of building elements, and integration of the construction's planned schedule. The construction progress is visualized via color-coding the building elements in the 3D model. The developed methodology was conducted and applied from the data obtained from an actual construction site. Accuracy in detecting `built' or `not built' building elements ranges from 82-84 % and precision of 50-72 %. Quantified progress in terms of the number of building elements are 21.31% (November 2016), 26.84 % (January 2017) and 44.19 % (March 2017). The results can be used as an input for progress monitoring performance of construction projects and improving related decision-making process.

Time delay and long-range connection induced synchronization transitions in Newman-Watts small-world neuronal networks.

PubMed

Qian, Yu

2014-01-01

The synchronization transitions in Newman-Watts small-world neuronal networks (SWNNs) induced by time delay τ and long-range connection (LRC) probability P have been investigated by synchronization parameter and space-time plots. Four distinct parameter regions, that is, asynchronous region, transition region, synchronous region, and oscillatory region have been discovered at certain LRC probability P = 1.0 as time delay is increased. Interestingly, desynchronization is observed in oscillatory region. More importantly, we consider the spatiotemporal patterns obtained in delayed Newman-Watts SWNNs are the competition results between long-range drivings (LRDs) and neighboring interactions. In addition, for moderate time delay, the synchronization of neuronal network can be enhanced remarkably by increasing LRC probability. Furthermore, lag synchronization has been found between weak synchronization and complete synchronization as LRC probability P is a little less than 1.0. Finally, the two necessary conditions, moderate time delay and large numbers of LRCs, are exposed explicitly for synchronization in delayed Newman-Watts SWNNs.

Time Delay and Long-Range Connection Induced Synchronization Transitions in Newman-Watts Small-World Neuronal Networks

PubMed Central

Qian, Yu

2014-01-01

The synchronization transitions in Newman-Watts small-world neuronal networks (SWNNs) induced by time delay and long-range connection (LRC) probability have been investigated by synchronization parameter and space-time plots. Four distinct parameter regions, that is, asynchronous region, transition region, synchronous region, and oscillatory region have been discovered at certain LRC probability as time delay is increased. Interestingly, desynchronization is observed in oscillatory region. More importantly, we consider the spatiotemporal patterns obtained in delayed Newman-Watts SWNNs are the competition results between long-range drivings (LRDs) and neighboring interactions. In addition, for moderate time delay, the synchronization of neuronal network can be enhanced remarkably by increasing LRC probability. Furthermore, lag synchronization has been found between weak synchronization and complete synchronization as LRC probability is a little less than 1.0. Finally, the two necessary conditions, moderate time delay and large numbers of LRCs, are exposed explicitly for synchronization in delayed Newman-Watts SWNNs. PMID:24810595

[Analysis of characteristics and influence factors of diagnostic delay of endometriosis].

PubMed

Han, X T; Guo, H Y; Kong, D L; Han, J S; Zhang, L F

2018-02-25

Objective: To access the influence factors of diagnostic delay of endometriosis. Methods: We designed a questionnaire of diagnostic delay of endometriosis. From February 2014 to February 2016, 400 patients who had dysmenorrhea and diagnosed with endometriosis by surgery in Peking University Third Hospital were surveyed retrospectively. Time and risk factors of diagnostic delay were analyzed. Results: The diagnostic delay of 400 patients was 13.0 years (0.2-43.0 years), 78.5%(314/400) patients thought pain was a normal phenomenon and didn't see the doctor. Patients who suffered dysmenorrhea at menarche experienced longer diagnostic delay than those who had dysmenorrhea after menarche (18.0 vs 4.5 years; Z= 191.800, P< 0.01) . Patients who suffered aggravating dysmenorrhea experienced shorter delay time than those who suffered stable or relieving dysmenorrhea (11.0 vs 12.5 vs 18.0 years; Z= 8.270, P< 0.05) , with the difference statistically significant, single factor analysis shows. Severe dysmenorrhea, deep infiltration endometriosis (DIE) , family history of dysmenorrhea or endometriosis, previous surgical history of endometriosis, high stage, with infertility, adenomyoma or other symptoms, could help to shorten diagnostic delay with no significant difference ( P> 0.05) . By multiple logistic regression analysis, the results shown that whether have dysmenorrhea at menarche and clinical diagnosis time were the independent factors affecting delayed diagnosis ( P< 0.01) . Conclusions: Diagnostic delay of endometriosis is common and the mean delay time is 13.0 years mainly due to the unawareness of dysmenorrhea. Dysmenorrhea at menarche, clinical diagnosis time and dysmenorrhea intensity are the factors affecting time of diagnostic delay.

LMI designmethod for networked-based PID control

NASA Astrophysics Data System (ADS)

Souza, Fernando de Oliveira; Mozelli, Leonardo Amaral; de Oliveira, Maurício Carvalho; Palhares, Reinaldo Martinez

2016-10-01

In this paper, we propose a methodology for the design of networked PID controllers for second-order delayed processes using linear matrix inequalities. The proposed procedure takes into account time-varying delay on the plant, time-varying delays induced by the network and packed dropouts. The design is carried on entirely using a continuous-time model of the closed-loop system where time-varying delays are used to represent sampling and holding occurring in a discrete-time digital PID controller.

High throughput detection of antibody self-interaction by bio-layer interferometry.

PubMed

Sun, Tingwan; Reid, Felicia; Liu, Yuqi; Cao, Yuan; Estep, Patricia; Nauman, Claire; Xu, Yingda

2013-01-01

Self-interaction of an antibody may lead to aggregation, low solubility or high viscosity. Rapid identification of highly developable leads remains challenging, even though progress has been made with the introduction of techniques such as self-interaction chromatography (SIC) and cross-interaction chromatography (CIC). Here, we report a high throughput method to detect antibody clone self-interaction (CSI) using bio-layer interferometry (BLI) technology. Antibodies with strong self-interaction responses in the CSI-BLI assay also show delayed retention times in SIC and CIC. This method allows hundreds of candidates to be screened in a matter of hours with minimal material consumption.

Accurate time delay technology in simulated test for high precision laser range finder

NASA Astrophysics Data System (ADS)

Chen, Zhibin; Xiao, Wenjian; Wang, Weiming; Xue, Mingxi

2015-10-01

With the continuous development of technology, the ranging accuracy of pulsed laser range finder (LRF) is higher and higher, so the maintenance demand of LRF is also rising. According to the dominant ideology of "time analog spatial distance" in simulated test for pulsed range finder, the key of distance simulation precision lies in the adjustable time delay. By analyzing and comparing the advantages and disadvantages of fiber and circuit delay, a method was proposed to improve the accuracy of the circuit delay without increasing the count frequency of the circuit. A high precision controllable delay circuit was designed by combining the internal delay circuit and external delay circuit which could compensate the delay error in real time. And then the circuit delay accuracy could be increased. The accuracy of the novel circuit delay methods proposed in this paper was actually measured by a high sampling rate oscilloscope actual measurement. The measurement result shows that the accuracy of the distance simulated by the circuit delay is increased from +/- 0.75m up to +/- 0.15m. The accuracy of the simulated distance is greatly improved in simulated test for high precision pulsed range finder.

Kalman filters for fractional discrete-time stochastic systems along with time-delay in the observation signal

NASA Astrophysics Data System (ADS)

Torabi, H.; Pariz, N.; Karimpour, A.

2016-02-01

This paper investigates fractional Kalman filters when time-delay is entered in the observation signal in the discrete-time stochastic fractional order state-space representation. After investigating the common fractional Kalman filter, we try to derive a fractional Kalman filter for time-delay fractional systems. A detailed derivation is given. Fractional Kalman filters will be used to estimate recursively the states of fractional order state-space systems based on minimizing the cost function when there is a constant time delay (d) in the observation signal. The problem will be solved by converting the filtering problem to a usual d-step prediction problem for delay-free fractional systems.

Time Delay of CGM Sensors

PubMed Central

Schmelzeisen-Redeker, Günther; Schoemaker, Michael; Kirchsteiger, Harald; Freckmann, Guido; Heinemann, Lutz; del Re, Luigi

2015-01-01

Background: Continuous glucose monitoring (CGM) is a powerful tool to support the optimization of glucose control of patients with diabetes. However, CGM systems measure glucose in interstitial fluid but not in blood. Rapid changes in one compartment are not accompanied by similar changes in the other, but follow with some delay. Such time delays hamper detection of, for example, hypoglycemic events. Our aim is to discuss the causes and extent of time delays and approaches to compensate for these. Methods: CGM data were obtained in a clinical study with 37 patients with a prototype glucose sensor. The study was divided into 5 phases over 2 years. In all, 8 patients participated in 2 phases separated by 8 months. A total number of 108 CGM data sets including raw signals were used for data analysis and were processed by statistical methods to obtain estimates of the time delay. Results: Overall mean (SD) time delay of the raw signals with respect to blood glucose was 9.5 (3.7) min, median was 9 min (interquartile range 4 min). Analysis of time delays observed in the same patients separated by 8 months suggests a patient dependent delay. No significant correlation was observed between delay and anamnestic or anthropometric data. The use of a prediction algorithm reduced the delay by 4 minutes on average. Conclusions: Prediction algorithms should be used to provide real-time CGM readings more consistent with simultaneous measurements by SMBG. Patient specificity may play an important role in improving prediction quality. PMID:26243773

A comparison of control modes for time-delayed remote manipulation

NASA Technical Reports Server (NTRS)

Starr, G. P.

1982-01-01

Transmission time delay in the communication channel of a manual control system is investigated. A time delay can exist in remote manipulation systems, caused by long communication distances or bandwidth limitations. Ferrell 1 conducted the first research in time-delayed manipulation using a two degree-of-freedom manipulator. His subjects, working at time delays of 1.0, 2.1, and 3.2 s, could accomplish tasks even requiring great accuracy. The subjects spontaneously adopted a pattern of moving cautiously, then waiting to see the results of their actions. In experiments with a six degree-of-freedom master-slave manipulator system and time delays of 1.0 to 6 s, Black 2 saw that subjects tried to use the move-and-wait strategy; but there were often difficulties. The subjects seemed to have a problem in holding the master arm stationary while waiting for feedback. Any undesired drifting of the master arm introduced a discrepancy between the positions of the master and slave. This discrepancy was not perceived because of the time delay. The subject would then begin his next move with an inherent error. The difficulty of effectively using the move-and-wait strategy with a master-slave manipulator suggested that rate control might be a more effective control mode with time delay.

TIMEDELN: A programme for the detection and parametrization of overlapping resonances using the time-delay method

NASA Astrophysics Data System (ADS)

Little, Duncan A.; Tennyson, Jonathan; Plummer, Martin; Noble, Clifford J.; Sunderland, Andrew G.

2017-06-01

TIMEDELN implements the time-delay method of determining resonance parameters from the characteristic Lorentzian form displayed by the largest eigenvalues of the time-delay matrix. TIMEDELN constructs the time-delay matrix from input K-matrices and analyses its eigenvalues. This new version implements multi-resonance fitting and may be run serially or as a high performance parallel code with three levels of parallelism. TIMEDELN takes K-matrices from a scattering calculation, either read from a file or calculated on a dynamically adjusted grid, and calculates the time-delay matrix. This is then diagonalized, with the largest eigenvalue representing the longest time-delay experienced by the scattering particle. A resonance shows up as a characteristic Lorentzian form in the time-delay: the programme searches the time-delay eigenvalues for maxima and traces resonances when they pass through different eigenvalues, separating overlapping resonances. It also performs the fitting of the calculated data to the Lorentzian form and outputs resonance positions and widths. Any remaining overlapping resonances can be fitted jointly. The branching ratios of decay into the open channels can also be found. The programme may be run serially or in parallel with three levels of parallelism. The parallel code modules are abstracted from the main physics code and can be used independently.

14 CFR 417.221 - Time delay analysis.

Code of Federal Regulations, 2010 CFR

2010-01-01

... OF TRANSPORTATION LICENSING LAUNCH SAFETY Flight Safety Analysis § 417.221 Time delay analysis. (a) General. A flight safety analysis must include a time delay analysis that establishes the mean elapsed time between the violation of a flight termination rule and the time when the flight safety system is...

14 CFR 417.221 - Time delay analysis.

Code of Federal Regulations, 2011 CFR

2011-01-01

... OF TRANSPORTATION LICENSING LAUNCH SAFETY Flight Safety Analysis § 417.221 Time delay analysis. (a) General. A flight safety analysis must include a time delay analysis that establishes the mean elapsed time between the violation of a flight termination rule and the time when the flight safety system is...

Does tight control of systemic factors help in the management of diabetic retinopathy?

PubMed Central

Rajalakshmi, Ramachandran; Prathiba, Vijayaraghavan; Mohan, Viswanathan

2016-01-01

Diabetic retinopathy (DR), one of the leading causes of preventable blindness, is associated with many systemic factors that contribute to the development and progression of this microvascular complication of diabetes. While the duration of diabetes is the major risk factor for the development of DR, the main modifiable systemic risk factors for development and progression of DR are hyperglycemia, hypertension, and dyslipidemia. This review article looks at the evidence that control of these systemic factors has significant benefits in delaying the onset and progression of DR. PMID:26953026

Micronutrients, N-Acetyl Cysteine, Probiotics and Prebiotics, a Review of Effectiveness in Reducing HIV Progression

PubMed Central

Hummelen, Ruben; Hemsworth, Jaimie; Reid, Gregor

2010-01-01

Low serum concentrations of micronutrients, intestinal abnormalities, and an inflammatory state have been associated with HIV progression. These may be ameliorated by micronutrients, N-acetyl cysteine, probiotics, and prebiotics. This review aims to integrate the evidence from clinical trials of these interventions on the progression of HIV. Vitamin B, C, E, and folic acid have been shown to delay the progression of HIV. Supplementation with selenium, N-acetyl cysteine, probiotics, and prebiotics has considerable potential, but the evidence needs to be further substantiated. Vitamin A, iron, and zinc have been associated with adverse effects and caution is warranted for their use. PMID:22254046

49 CFR 236.831 - Time, delay.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false Time, delay. 236.831 Section 236.831 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION... Time, delay. As applied to an automatic train stop or train control system, the time which elapses...

Lesions Responsible for Delayed Oral Transit Time in Post-stroke Dysphagia.

PubMed

Moon, Hyun Im; Yoon, Seo Yeon; Yi, Tae Im; Jeong, Yoon Jeong; Cho, Tae Hwan

2018-06-01

Some stroke patients show oral phase dysphagia, characterized by a markedly prolonged oral transit time that hinders oral feeding. The aim of this study was to clarify the clinical characteristics and lesions responsible for delayed swallowing. We reviewed 90 patients with stroke. The oral processing time plus the postfaucial aggregation time required to swallow semisolid food was assessed. The patients were divided into two groups according to oral transit time, and we analyzed the differences in characteristics such as demographic factors, lesion factors, and cognitive function. Logistic regression analyses were performed to examine the predictors of delayed oral transit time. Lesion location and volume were measured on brain magnetic resonance images. We generated statistic maps of lesions related to delayed oral phase in swallowing using voxel-based lesion symptom mapping (VLSM). The group of patients who showed delayed oral transit time had significantly low cognitive function. Also, in a regression model, delayed oral phase was predicted with low K-MMSE (Korean version of the Mini Mental Status Exam). Using VLSM, we found the lesion location to be associated with delayed oral phase after adjusting for K-MMSE score. Although these results did not reach statistical significance, they showed the lesion pattern with predominant distribution in the left frontal lobe. Delayed oral phase in post-stroke patients was not negligible clinically. Patients' cognitive impairments affect the oral transit time. When adjusting it, we found a trend that the lesion responsible for delayed oral phase was located in the left frontal lobe, though the association did not reach significance. The delay might be related to praxis function.

The effect of visual-motion time-delays on pilot performance in a simulated pursuit tracking task

NASA Technical Reports Server (NTRS)

Miller, G. K., Jr.; Riley, D. R.

1977-01-01

An experimental study was made to determine the effect on pilot performance of time delays in the visual and motion feedback loops of a simulated pursuit tracking task. Three major interrelated factors were identified: task difficulty either in the form of airplane handling qualities or target frequency, the amount and type of motion cues, and time delay itself. In general, the greater the task difficulty, the smaller the time delay that could exist without degrading pilot performance. Conversely, the greater the motion fidelity, the greater the time delay that could be tolerated. The effect of motion was, however, pilot dependent.

Optimal estimation of parameters and states in stochastic time-varying systems with time delay

NASA Astrophysics Data System (ADS)

Torkamani, Shahab; Butcher, Eric A.

2013-08-01

In this study estimation of parameters and states in stochastic linear and nonlinear delay differential systems with time-varying coefficients and constant delay is explored. The approach consists of first employing a continuous time approximation to approximate the stochastic delay differential equation with a set of stochastic ordinary differential equations. Then the problem of parameter estimation in the resulting stochastic differential system is represented as an optimal filtering problem using a state augmentation technique. By adapting the extended Kalman-Bucy filter to the resulting system, the unknown parameters of the time-delayed system are estimated from noise-corrupted, possibly incomplete measurements of the states.

Opto-VLSI-based photonic true-time delay architecture for broadband adaptive nulling in phased array antennas.

PubMed

Juswardy, Budi; Xiao, Feng; Alameh, Kamal

2009-03-16

This paper proposes a novel Opto-VLSI-based tunable true-time delay generation unit for adaptively steering the nulls of microwave phased array antennas. Arbitrary single or multiple true-time delays can simultaneously be synthesized for each antenna element by slicing an RF-modulated broadband optical source and routing specific sliced wavebands through an Opto-VLSI processor to a high-dispersion fiber. Experimental results are presented, which demonstrate the principle of the true-time delay unit through the generation of 5 arbitrary true-time delays of up to 2.5 ns each. (c) 2009 Optical Society of America

Cognitive impairment at diagnosis predicts 10-year multiple sclerosis progression.

PubMed

Moccia, Marcello; Lanzillo, Roberta; Palladino, Raffaele; Chang, Kiara Chu-Mei; Costabile, Teresa; Russo, Cinzia; De Rosa, Anna; Carotenuto, Antonio; Saccà, Francesco; Maniscalco, Giorgia Teresa; Brescia Morra, Vincenzo

2016-04-01

Cognitive impairment occurs from the early phases of multiple sclerosis (MS), and more frequently affects secondary progressive (SP) subjects than relapsing-remitting (RR). To investigate relationships between cognitive dysfunctions in newly diagnosed RRMS, and long-term MS-related outcomes. The present 10-year retrospective longitudinal study included 155 RRMS subjects, tested with the Rao Brief Repeatable Battery at MS diagnosis. The reaching of Expanded Disability Status Scale (EDSS) 4.0, and the SP conversion were recorded. 67 subjects (43.2%) reached EDSS 4.0, and 34 subjects (21.9%) converted to SP during a follow-up period of 10.0±1.8 years. Subjects with cognitive impairment at diagnosis had a rate of reaching EDSS 4.0 more than three times greater (p<0.001; HR=3.183), and a rate of SP conversion more than two times greater, as compared to cognitively preserved subjects (p=0.008; HR=2.535). In particular, better scores in the Selective Reminding Test-Delayed Recall and in the Symbol Digit Modalities Test at baseline were associated with lower SP conversion rates during the follow-up period (p=0.018; HR=0.835; and p=0.001; HR=0.941, respectively). Cognitive impairment, with particular involvement of processing speed and memory, predicts disability progression and SP conversion in newly diagnosed RRMS, highlighting the importance of cognitive assessment from the beginning of MS. © The Author(s), 2015.

Solar oscillation time delay measurement assisted celestial navigation method

NASA Astrophysics Data System (ADS)

Ning, Xiaolin; Gui, Mingzhen; Zhang, Jie; Fang, Jiancheng; Liu, Gang

2017-05-01

Solar oscillation, which causes the sunlight intensity and spectrum frequency change, has been studied in great detail, both observationally and theoretically. In this paper, owing to the existence of solar oscillation, the time delay between the sunlight coming from the Sun directly and the sunlight reflected by the other celestial body such as the satellite of planet or asteroid can be obtained with two optical power meters. Because the solar oscillation time delay is determined by the relative positions of the spacecraft, reflective celestial body and the Sun, it can be adopted as the navigation measurement to estimate the spacecraft's position. The navigation accuracy of single solar oscillation time delay navigation system depends on the time delay measurement accuracy, and is influenced by the distance between spacecraft and reflective celestial body. In this paper, we combine it with the star angle measurement and propose a solar oscillation time delay measurement assisted celestial navigation method for deep space exploration. Since the measurement model of time delay is an implicit function, the Implicit Unscented Kalman Filter (IUKF) is applied. Simulations demonstrate the effectiveness and superiority of this method.

System for sensing droplet formation time delay in a flow cytometer

DOEpatents

Van den Engh, Ger; Esposito, Richard J.

1997-01-01

A droplet flow cytometer system which includes a system to optimize the droplet formation time delay based on conditions actually experienced includes an automatic droplet sampler which rapidly moves a plurality of containers stepwise through the droplet stream while simultaneously adjusting the droplet time delay. Through the system sampling of an actual substance to be processed can be used to minimize the effect of the substances variations or the determination of which time delay is optimal. Analysis such as cell counting and the like may be conducted manually or automatically and input to a time delay adjustment which may then act with analysis equipment to revise the time delay estimate actually applied during processing. The automatic sampler can be controlled through a microprocessor and appropriate programming to bracket an initial droplet formation time delay estimate. When maximization counts through volume, weight, or other types of analysis exists in the containers, the increment may then be reduced for a more accurate ultimate setting. This may be accomplished while actually processing the sample without interruption.

Tunable delay time and Hartman effect in graphene magnetic barriers

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

Ban, Yue; Wang, Lin-Jun; Chen, Xi, E-mail: xchen@shu.edu.cn

2015-04-28

Tunable group delay and Hartman effect have been investigated for massless Dirac electrons in graphene magnetic barriers. In the presence of magnetic field, dwell time is found to be equal to net group delay plus the group delay contributing from the lateral shifts. The group delay times are discussed in both cases of normal and oblique incidence, to clarify the nature of Hartman effect. In addition, the group delay in transmission can be modulated from subluminality to superluminality by adjusting the magnetic field, which may also lead to potential applications in graphene-based microelectronics.

Causes of delay in door-to-balloon time in south-east Asian patients undergoing primary percutaneous coronary intervention.

PubMed

Sim, Wen Jun; Ang, An Shing; Tan, Mae Chyi; Xiang, Wen Wei; Foo, David; Loh, Kwok Kong; Jafary, Fahim Haider; Watson, Timothy James; Ong, Paul Jau Lueng; Ho, Hee Hwa

2017-01-01

To evaluate causes and impact of delay in the door-to-balloon (D2B) time for patients undergoing primary percutaneous coronary intervention (PPCI). From January 2009 to December 2012, 1268 patients (86% male, mean age of 58 ± 12 years) presented to our hospital for ST-elevation myocardial infarction (STEMI) and underwent PPCI. They were divided into two groups: Non-delay defined as D2B time ≤ 90 mins and delay group defined as D2B time > 90 mins. Data were collected retrospectively on baseline clinical characteristics, mode of presentation, angiographic findings, therapeutic modality and inhospital outcome. 202 patients had delay in D2B time. There were more female patients in the delay group. They were older and tend to self-present to hospital. They were less likely to be smokers and have a higher prevalence of prior MI. The incidence of posterior MI was higher in the delay group. They also had a higher incidence of triple vessel disease. The 3 most common reasons for D2B delay was delay in the emergency department (39%), atypical clinical presentation (37.6%) and unstable medical condition requiring stabilisation/computed tomographic imaging (26.7%). The inhospital mortality was numerically higher in the delay group (7.4% versus 4.8%, p = 0.12). Delay in D2B occurred in 16% of our patients undergoing PPCI. Several key factors for delay were identified and warrant further intervention.

A new framework for modeling decisions about changing information: The Piecewise Linear Ballistic Accumulator model

PubMed Central

Heathcote, Andrew

2016-01-01

In the real world, decision making processes must be able to integrate non-stationary information that changes systematically while the decision is in progress. Although theories of decision making have traditionally been applied to paradigms with stationary information, non-stationary stimuli are now of increasing theoretical interest. We use a random-dot motion paradigm along with cognitive modeling to investigate how the decision process is updated when a stimulus changes. Participants viewed a cloud of moving dots, where the motion switched directions midway through some trials, and were asked to determine the direction of motion. Behavioral results revealed a strong delay effect: after presentation of the initial motion direction there is a substantial time delay before the changed motion information is integrated into the decision process. To further investigate the underlying changes in the decision process, we developed a Piecewise Linear Ballistic Accumulator model (PLBA). The PLBA is efficient to simulate, enabling it to be fit to participant choice and response-time distribution data in a hierarchal modeling framework using a non-parametric approximate Bayesian algorithm. Consistent with behavioral results, PLBA fits confirmed the presence of a long delay between presentation and integration of new stimulus information, but did not support increased response caution in reaction to the change. We also found the decision process was not veridical, as symmetric stimulus change had an asymmetric effect on the rate of evidence accumulation. Thus, the perceptual decision process was slow to react to, and underestimated, new contrary motion information. PMID:26760448

Developmental Changes in Sensory-Evoked Optical Intrinsic Signals in the Rat Barrel Cortex.

PubMed

Sintsov, Mikhail; Suchkov, Dmitrii; Khazipov, Rustem; Minlebaev, Marat

2017-01-01

Optical Intrinsic Signal imaging (OISi) is a powerful technique for optical brain studies. OIS mainly reflects the hemodynamic response (HR) and metabolism, but it may also involve changes in tissue light scattering (LS) caused by transient cellular swelling in the active tissue. Here, we explored the developmental features of sensory-evoked OIS in the rat barrel cortex during the first 3 months after birth. Multispectral OISi revealed that two temporally distinct components contribute to the neonatal OIS: an early phase of LS followed by a late phase of HR. The contribution of LS to the early response was also evidenced by an increase in light transmission through the active barrel. The early OIS phase correlated in time and amplitude with the sensory-evoked electrophysiological response. Application of the Modified Beer-Lambert Law (MBLL) to the OIS data revealed that HR during the early phase involved only a slight decrease in blood oxygenation without any change in blood volume. In contrast, HR during the late phase manifested an adult-like increase in blood volume and oxygenation. During development, the peak time of the delayed HR progressively shortened with age, nearly reaching the stimulus onset and overlapping with the early LS phase by the fourth postnatal week. Thus, LS contributes to the sensory-evoked OIS in the barrel cortex of rats at all ages, and it dominates the early OIS phase in neonatal rats due to delayed HR. Our results are also consistent with the delayed blood oxygen level dependent (BOLD) signal in human preterm infants.

Developmental Changes in Sensory-Evoked Optical Intrinsic Signals in the Rat Barrel Cortex

PubMed Central

Sintsov, Mikhail; Suchkov, Dmitrii; Khazipov, Rustem; Minlebaev, Marat

2017-01-01

Optical Intrinsic Signal imaging (OISi) is a powerful technique for optical brain studies. OIS mainly reflects the hemodynamic response (HR) and metabolism, but it may also involve changes in tissue light scattering (LS) caused by transient cellular swelling in the active tissue. Here, we explored the developmental features of sensory-evoked OIS in the rat barrel cortex during the first 3 months after birth. Multispectral OISi revealed that two temporally distinct components contribute to the neonatal OIS: an early phase of LS followed by a late phase of HR. The contribution of LS to the early response was also evidenced by an increase in light transmission through the active barrel. The early OIS phase correlated in time and amplitude with the sensory-evoked electrophysiological response. Application of the Modified Beer-Lambert Law (MBLL) to the OIS data revealed that HR during the early phase involved only a slight decrease in blood oxygenation without any change in blood volume. In contrast, HR during the late phase manifested an adult-like increase in blood volume and oxygenation. During development, the peak time of the delayed HR progressively shortened with age, nearly reaching the stimulus onset and overlapping with the early LS phase by the fourth postnatal week. Thus, LS contributes to the sensory-evoked OIS in the barrel cortex of rats at all ages, and it dominates the early OIS phase in neonatal rats due to delayed HR. Our results are also consistent with the delayed blood oxygen level dependent (BOLD) signal in human preterm infants. PMID:29311827

'Nobody really gets it': a qualitative exploration of youth mental health in deprived urban areas.

PubMed

Schaffalitzky, Elisabeth; Leahy, Dorothy; Armstrong, Claire; Gavin, Blanaid; Latham, Linda; McNicholas, Fiona; Meagher, David; O'Connor, Ray; O'Toole, Thomas; Smyth, Bobby P; Cullen, Walter

2015-10-01

To examine the experience of developing and living with mental health and substance use disorders among young people living in urban-deprived areas in Ireland to inform primary care interventions. Semi-structured qualitative interviews with 20 young adults attending health and social care agencies in two deprived urban areas, and analysed using thematic analysis. Five themes were identified: experiencing symptoms, symptom progression, delay accessing help, loss of control/crisis point, and consequences of mental health and substance use disorders. As young people delayed help, symptoms disrupted normal life progression and they found themselves unable to engage in everyday activities, and living with reduced potential. Living in deprived areas influenced the development of problems: many had added stressors, less familial support and early exposure to violence, addiction and bereavement. Young people in urban-deprived areas are especially vulnerable to mental health and substance use disorders. Early identification in primary care appears necessary in halting symptom and illness progression, improving young people's chances of achieving their potential. © 2014 Wiley Publishing Asia Pty Ltd.

Survival analysis and prognostic factors of timing of first childbirth among women in Nigeria.

PubMed

Fagbamigbe, Adeniyi Francis; Idemudia, Erhabor Sunday

2016-05-13

First childbirth in a woman's life is one of the most important events in her life. It marks a turnaround when she might have to drop roles of career building and education, for motherhood and parenthood. The timing of the commencement of these roles affects the child bearing behavior of women as they progress in their reproductive ages. Prevalent early first childbirth in Nigeria has been reported as the main cause of high population growth and high  fertility, mortality and morbidity among women, but little has been documented on the progression into first birth as well as factors affecting it in Nigeria. This paper modelled timing of first birth among women in Nigeria and determined socio-demographic and other factors affecting its timing. We hypothesized that background characteristics of a woman will influence her progression into having first birth. We developed and fitted a survival analysis model to understand the timing of first birth among women in Nigeria using a national representative 2013 NDHS data. Women with no children were right censored as of the date of the survey. The Kaplan Meier survival function was used to estimate the probabilities of first birth not occurring until certain ages of women while Cox proportional hazard regression was used to model the timing of first births at 5 % significance level. About 75.7 % of the respondents had given birth in the Northern region of Nigerian compared with 63.8 % in the South. Half (50.1 %) of the first childbirth occurred within the 15-19 years age bracket and 38.1 % within 20-29 years. The overall median survival time to first birth was 20 years (North 19, South 22), 27 years among women with higher education and 18 years for those with no formal education. The adjusted hazard of first birth was higher in the Northern region of Nigeria than in the South (aHR = 1.24, 95 % CI: 1.20-1.27), and higher in rural areas than in urban areas (aHR = 1.15, 95 % CI: 1.12-1.19). Also, hazard of earlier first birth tripled among women with no education (aHR = 3.36, 95 % CI: 3.17-3.55) compared to women with higher education. The significant factors affecting age at first birth are education, place and zone of residence, age at first marriage, religion, ethnicity and use of contraceptives. This study showed that progression into early first birth is most affected by the education standing of women as well as age at first marriage. Delay of first childbirths as a strategy for fertility reduction and maternal health improvement can be achieved if women are empowered early in life with quality education. Stakeholders should therefore, give adequate attention to educating the girl child. Adverse socio-cultural norms of betrothing and marrying young girls should be abrogated, while health education and promotion of need to delay child bearing must be intensified especially among rural dwellers and also in Northern Nigeria.

Delay-correlation landscape reveals characteristic time delays of brain rhythms and heart interactions

PubMed Central

Lin, Aijing; Liu, Kang K. L.; Bartsch, Ronny P.; Ivanov, Plamen Ch.

2016-01-01

Within the framework of ‘Network Physiology’, we ask a fundamental question of how modulations in cardiac dynamics emerge from networked brain–heart interactions. We propose a generalized time-delay approach to identify and quantify dynamical interactions between physiologically relevant brain rhythms and the heart rate. We perform empirical analysis of synchronized continuous EEG and ECG recordings from 34 healthy subjects during night-time sleep. For each pair of brain rhythm and heart interaction, we construct a delay-correlation landscape (DCL) that characterizes how individual brain rhythms are coupled to the heart rate, and how modulations in brain and cardiac dynamics are coordinated in time. We uncover characteristic time delays and an ensemble of specific profiles for the probability distribution of time delays that underly brain–heart interactions. These profiles are consistently observed in all subjects, indicating a universal pattern. Tracking the evolution of DCL across different sleep stages, we find that the ensemble of time-delay profiles changes from one physiologic state to another, indicating a strong association with physiologic state and function. The reported observations provide new insights on neurophysiological regulation of cardiac dynamics, with potential for broad clinical applications. The presented approach allows one to simultaneously capture key elements of dynamic interactions, including characteristic time delays and their time evolution, and can be applied to a range of coupled dynamical systems. PMID:27044991

Delay-correlation landscape reveals characteristic time delays of brain rhythms and heart interactions

NASA Astrophysics Data System (ADS)

Lin, Aijing; Liu, Kang K. L.; Bartsch, Ronny P.; Ivanov, Plamen Ch.

2016-05-01

Within the framework of `Network Physiology', we ask a fundamental question of how modulations in cardiac dynamics emerge from networked brain-heart interactions. We propose a generalized time-delay approach to identify and quantify dynamical interactions between physiologically relevant brain rhythms and the heart rate. We perform empirical analysis of synchronized continuous EEG and ECG recordings from 34 healthy subjects during night-time sleep. For each pair of brain rhythm and heart interaction, we construct a delay-correlation landscape (DCL) that characterizes how individual brain rhythms are coupled to the heart rate, and how modulations in brain and cardiac dynamics are coordinated in time. We uncover characteristic time delays and an ensemble of specific profiles for the probability distribution of time delays that underly brain-heart interactions. These profiles are consistently observed in all subjects, indicating a universal pattern. Tracking the evolution of DCL across different sleep stages, we find that the ensemble of time-delay profiles changes from one physiologic state to another, indicating a strong association with physiologic state and function. The reported observations provide new insights on neurophysiological regulation of cardiac dynamics, with potential for broad clinical applications. The presented approach allows one to simultaneously capture key elements of dynamic interactions, including characteristic time delays and their time evolution, and can be applied to a range of coupled dynamical systems.

Determinants of delay in malaria care-seeking behaviour for children 15 years and under in Bata district, Equatorial Guinea.

PubMed

Romay-Barja, Maria; Cano, Jorge; Ncogo, Policarpo; Nseng, Gloria; Santana-Morales, Maria A; Valladares, Basilio; Riloha, Matilde; Benito, Agustin

2016-03-31

Malaria remains a major cause of morbidity and mortality in children under 5 years of age in Equatorial Guinea. Early appropriate treatment can reduce progression of the illness to severe stages, thus reducing of mortality, morbidity and onward transmission. The factors that contribute to malaria treatment delay have not been studied previously in Equatorial Guinea. The objective of this study was to assess the determinants of delay in seeking malaria treatment for children in the Bata district, in mainland Equatorial Guinea. A cross-sectional study was conducted in Bata district, in 2013, which involved 428 houses in 18 rural villages and 26 urban neighbourhoods. Household caregivers were identified in each house and asked about their knowledge of malaria and about the management of the last reported malaria episode in a child 15 years and younger under their care. Bivariate and multivariate statistical analyses were conducted to determine the relevance of socio-economic, geographical and behavioural factors on delays in care-seeking behaviour. Nearly half of the children sought treatment at least 24 h after the onset of the symptoms. The median delay in seeking care was 2.8 days. Children from households with the highest socio-economic status were less likely to be delayed in seeking care than those from households with the lowest socio-economic status (OR 0.37, 95% CI 0.19-0.72). Children that first received treatment at home, mainly paracetamol, were more than twice more likely to be delayed for seeking care, than children who did not first receive treatment at home (OR 2.36, 95% CI 1.45-3.83). Children living in a distance >3 km from the nearest health facility were almost two times more likely to be delayed in seeking care than those living closer to a facility but with non significant association once adjusted for other variables (OR 1.75, 95% CI 0.88-3.47). To decrease malaria morbidity and mortality in Bata district, efforts should be addressed to reduce household delays in seeking care. It is necessary to provide free access to effective malaria diagnosis and treatment, to reinforce malaria management at community level through community health workers and drug sellers and to increase awareness on the severity of malaria, the importance of early diagnosis and appropriate treatment.

Control of amplitude chimeras by time delay in oscillator networks

NASA Astrophysics Data System (ADS)

Gjurchinovski, Aleksandar; Schöll, Eckehard; Zakharova, Anna

2017-04-01

We investigate the influence of time-delayed coupling in a ring network of nonlocally coupled Stuart-Landau oscillators upon chimera states, i.e., space-time patterns with coexisting partially coherent and partially incoherent domains. We focus on amplitude chimeras, which exhibit incoherent behavior with respect to the amplitude rather than the phase and are transient patterns, and we show that their lifetime can be significantly enhanced by coupling delay. To characterize their transition to phase-lag synchronization (coherent traveling waves) and other coherent structures, we generalize the Kuramoto order parameter. Contrasting the results for instantaneous coupling with those for constant coupling delay, for time-varying delay, and for distributed-delay coupling, we demonstrate that the lifetime of amplitude chimera states and related partially incoherent states can be controlled, i.e., deliberately reduced or increased, depending upon the type of coupling delay.

Time domain passivity controller for 4-channel time-delay bilateral teleoperation.

PubMed

Rebelo, Joao; Schiele, Andre

2015-01-01

This paper presents an extension of the time-domain passivity control approach to a four-channel bilateral controller under the effects of time delays. Time-domain passivity control has been used successfully to stabilize teleoperation systems with position-force and position-position controllers; however, the performance with such control architectures is sub-optimal both with and without time delays. This work extends the network representation of the time-domain passivity controller to the four-channel architecture, which provides perfect transparency to the user without time delay. The proposed architecture is based on modelling the controllers as dependent voltage sources and using only series passivity controllers. The obtained results are shown on a one degree-of-freedom setup and illustrate the stabilization behaviour of the proposed controller when time delay is present in the communication channel.

Typical teleoperator time delay profiles, phase 2. [remotely controlled manipulator arms

NASA Technical Reports Server (NTRS)

Wetherington, R. D.; Walsh, J. R.

1974-01-01

The results of the second phase of a study on time delays in communications systems applicable to the teleoperator program are presented. Estimates of the maximum time delays that will be encountered and presents time delay profiles are given for (1) ground control to teleoperator in low earth orbit, (2) ground control to teleoperator in geosynchronous orbit, and (3) low earth orbit control to teleoperator in low earth orbit.

VARIABLE TIME DELAY MEANS

DOEpatents

Clemensen, R.E.

1959-11-01

An electrically variable time delay line is described which may be readily controlled simuitaneously with variable impedance matching means coupied thereto such that reflections are prevented. Broadly, the delay line includes a signal winding about a magnetic core whose permeability is electrically variable. Inasmuch as the inductance of the line varies directly with the permeability, the time delay and characteristic impedance of the line both vary as the square root of the permeability. Consequently, impedance matching means may be varied similariy and simultaneously w:th the electrically variable permeability to match the line impedance over the entire range of time delay whereby reflections are prevented.

Simulator study of the effect of visual-motion time delays on pilot tracking performance with an audio side task

NASA Technical Reports Server (NTRS)

Riley, D. R.; Miller, G. K., Jr.

1978-01-01

The effect of time delay was determined in the visual and motion cues in a flight simulator on pilot performance in tracking a target aircraft that was oscillating sinusoidally in altitude only. An audio side task was used to assure the subject was fully occupied at all times. The results indicate that, within the test grid employed, about the same acceptable time delay (250 msec) was obtained for a single aircraft (fighter type) by each of two subjects for both fixed-base and motion-base conditions. Acceptable time delay is defined as the largest amount of delay that can be inserted simultaneously into the visual and motion cues before performance degradation occurs. A statistical analysis of the data was made to establish this value of time delay. Audio side task provided quantitative data that documented the subject's work level.

Wigner time delay and spin-orbit activated confinement resonances

NASA Astrophysics Data System (ADS)

Keating, D. A.; Deshmukh, P. C.; Manson, S. T.

2017-09-01

A study of the photoionization of spin-orbit split subshells of high-Z atoms confined in C60 has been performed using the relativistic-random-phase approximation. Specifically, Hg@C60 5p, Rn@C60 6p and Ra@C60 5d were investigated and the near-threshold confinement resonances in the j = l - 1/2 channels were found to engender structures in the j = l + 1/2 cross sections via correlation in the form of interchannel coupling. These structures are termed spin-orbit induced confinement resonances and they are found to profoundly influence the Wigner time delay spectrum resulting in time delays of tens or hundreds of attoseconds along with dramatic swings in time delay over small energy intervals. Pronounced relativistic effects in time delay are also found. These structures, including their manifestation in time delay spectra, are expected to be general phenomena in the photoionization of spin-orbit doublets in confined high-Z atoms.

Synchronization in a chaotic neural network with time delay depending on the spatial distance between neurons

NASA Astrophysics Data System (ADS)

Tang, Guoning; Xu, Kesheng; Jiang, Luoluo

2011-10-01

The synchronization is investigated in a two-dimensional Hindmarsh-Rose neuronal network by introducing a global coupling scheme with time delay, where the length of time delay is proportional to the spatial distance between neurons. We find that the time delay always disturbs synchronization of the neuronal network. When both the coupling strength and length of time delay per unit distance (i.e., enlargement factor) are large enough, the time delay induces the abnormal membrane potential oscillations in neurons. Specifically, the abnormal membrane potential oscillations for the symmetrically placed neurons form an antiphase, so that the large coupling strength and enlargement factor lead to the desynchronization of the neuronal network. The complete and intermittently complete synchronization of the neuronal network are observed for the right choice of parameters. The physical mechanism underlying these phenomena is analyzed.

Dissipativity and stability analysis of fractional-order complex-valued neural networks with time delay.

PubMed

Velmurugan, G; Rakkiyappan, R; Vembarasan, V; Cao, Jinde; Alsaedi, Ahmed

2017-02-01

As we know, the notion of dissipativity is an important dynamical property of neural networks. Thus, the analysis of dissipativity of neural networks with time delay is becoming more and more important in the research field. In this paper, the authors establish a class of fractional-order complex-valued neural networks (FCVNNs) with time delay, and intensively study the problem of dissipativity, as well as global asymptotic stability of the considered FCVNNs with time delay. Based on the fractional Halanay inequality and suitable Lyapunov functions, some new sufficient conditions are obtained that guarantee the dissipativity of FCVNNs with time delay. Moreover, some sufficient conditions are derived in order to ensure the global asymptotic stability of the addressed FCVNNs with time delay. Finally, two numerical simulations are posed to ensure that the attention of our main results are valuable. Copyright © 2016 Elsevier Ltd. All rights reserved.

Determining delayed admission to intensive care unit for mechanically ventilated patients in the emergency department.

PubMed

Hung, Shih-Chiang; Kung, Chia-Te; Hung, Chih-Wei; Liu, Ber-Ming; Liu, Jien-Wei; Chew, Ghee; Chuang, Hung-Yi; Lee, Wen-Huei; Lee, Tzu-Chi

2014-08-23

The adverse effects of delayed admission to the intensive care unit (ICU) have been recognized in previous studies. However, the definitions of delayed admission varies across studies. This study proposed a model to define "delayed admission", and explored the effect of ICU-waiting time on patients' outcome. This retrospective cohort study included non-traumatic adult patients on mechanical ventilation in the emergency department (ED), from July 2009 to June 2010. The primary outcomes measures were 21-ventilator-day mortality and prolonged hospital stays (over 30 days). Models of Cox regression and logistic regression were used for multivariate analysis. The non-delayed ICU-waiting was defined as a period in which the time effect on mortality was not statistically significant in a Cox regression model. To identify a suitable cut-off point between "delayed" and "non-delayed", subsets from the overall data were made based on ICU-waiting time and the hazard ratio of ICU-waiting hour in each subset was iteratively calculated. The cut-off time was then used to evaluate the impact of delayed ICU admission on mortality and prolonged length of hospital stay. The final analysis included 1,242 patients. The time effect on mortality emerged after 4 hours, thus we deduced ICU-waiting time in ED > 4 hours as delayed. By logistic regression analysis, delayed ICU admission affected the outcomes of 21 ventilator-days mortality and prolonged hospital stay, with odds ratio of 1.41 (95% confidence interval, 1.05 to 1.89) and 1.56 (95% confidence interval, 1.07 to 2.27) respectively. For patients on mechanical ventilation at the ED, delayed ICU admission is associated with higher probability of mortality and additional resource expenditure. A benchmark waiting time of no more than 4 hours for ICU admission is recommended.

Microlensing makes lensed quasar time delays significantly time variable

NASA Astrophysics Data System (ADS)

Tie, S. S.; Kochanek, C. S.

2018-01-01

The time delays of gravitationally lensed quasars are generally believed to be unique numbers whose measurement is limited only by the quality of the light curves and the models for the contaminating contribution of gravitational microlensing to the light curves. This belief is incorrect - gravitational microlensing also produces changes in the actual time delays on the ∼day(s) light-crossing time-scale of the emission region. This is due to a combination of the inclination of the disc relative to the line of sight and the differential magnification of the temperature fluctuations producing the variability. We demonstrate this both mathematically and with direct calculations using microlensing magnification patterns. Measuring these delay fluctuations can provide a physical scale for microlensing observations, removing the need for priors on either the microlens masses or the component velocities. That time delays in lensed quasars are themselves time variable likely explains why repeated delay measurements of individual lensed quasars appear to vary by more than their estimated uncertainties. This effect is also a new important systematic problem for attempts to use time delays in lensed quasars for cosmology or to detect substructures (satellites) in lens galaxies.

Long-time behavior for suspension bridge equations with time delay

NASA Astrophysics Data System (ADS)

Park, Sun-Hye

2018-04-01

In this paper, we consider suspension bridge equations with time delay of the form u_{tt}(x,t) + Δ ^2 u (x,t) + k u^+ (x,t) + a_0 u_t (x,t) + a_1 u_t (x, t- τ ) + f(u(x,t)) = g(x). Many researchers have studied well-posedness, decay rates of energy, and existence of attractors for suspension bridge equations without delay effects. But, as far as we know, there is no work about suspension equations with time delay. In addition, there are not many studies on attractors for other delayed systems. Thus we first provide well-posedness for suspension equations with time delay. And then show the existence of global attractors and the finite dimensionality of the attractors by establishing energy functionals which are related to the norm of the phase space to our problem.

Robust outer synchronization between two nonlinear complex networks with parametric disturbances and mixed time-varying delays

NASA Astrophysics Data System (ADS)

Zhang, Chuan; Wang, Xingyuan; Luo, Chao; Li, Junqiu; Wang, Chunpeng

2018-03-01

In this paper, we focus on the robust outer synchronization problem between two nonlinear complex networks with parametric disturbances and mixed time-varying delays. Firstly, a general complex network model is proposed. Besides the nonlinear couplings, the network model in this paper can possess parametric disturbances, internal time-varying delay, discrete time-varying delay and distributed time-varying delay. Then, according to the robust control strategy, linear matrix inequality and Lyapunov stability theory, several outer synchronization protocols are strictly derived. Simple linear matrix controllers are designed to driver the response network synchronize to the drive network. Additionally, our results can be applied on the complex networks without parametric disturbances. Finally, by utilizing the delayed Lorenz chaotic system as the dynamics of all nodes, simulation examples are given to demonstrate the effectiveness of our theoretical results.

Fixed-base simulator study of the effect of time delays in visual cues on pilot tracking performance

NASA Technical Reports Server (NTRS)

Queijo, M. J.; Riley, D. R.

1975-01-01

Factors were examined which determine the amount of time delay acceptable in the visual feedback loop in flight simulators. Acceptable time delays are defined as delays which significantly affect neither the results nor the manner in which the subject 'flies' the simulator. The subject tracked a target aircraft as it oscillated sinusoidally in a vertical plane only. The pursuing aircraft was permitted five degrees of freedom. Time delays of from 0.047 to 0.297 second were inserted in the visual feedback loop. A side task was employed to maintain the workload constant and to insure that the pilot was fully occupied during the experiment. Tracking results were obtained for 17 aircraft configurations having different longitudinal short-period characteristics. Results show a positive correlation between improved handling qualities and a longer acceptable time delay.

Pleiotropic activity of systemically delivered angiogenin in the SOD1G93A mouse model.

PubMed

Crivello, Martin; O'Riordan, Saidhbhe L; Woods, Ina; Cannon, Sarah; Halang, Luise; Coughlan, Karen S; Hogg, Marion C; Lewandowski, Sebastian A; Prehn, Jochen H M

2018-05-01

Loss-of-function mutations in the angiogenin (ANG) gene have been identified in familial and sporadic ALS patients. Previous work from our group identified human ANG (huANG) to protect motoneurons in vitro, and provided proof-of-concept that daily intraperitoneal (i.p.) huANG injections post-symptom onset increased lifespan and delayed disease progression in SOD1 G93A mice. huANG's mechanism of action remains less well understood. Here, we implemented a preclinical in vivo design to validate our previous results, provide pharmacokinetic and protein distribution data after systemic administration, and explore potential pleiotropic activities of huANG in vivo. SOD1 G93A mice (n = 45) and non-transgenic controls (n = 31) were sex- age- and litter-matched according to the 2010 European ALS/MND group guidelines, and treated with huANG (1 μg, i.p., 3 times/week) or vehicle from 90 days on. huANG treatment increased survival and delayed motor dysfunction as assessed by rotarod in SOD1 G93A mice. Increased huANG serum levels were detectable 2 and 24 h after i.p. injection equally in transgenic and non-transgenic mice. Exogenous huANG localized to spinal cord astrocytes, supporting a glia-mediated, paracrine mechanism of action; uptake into endothelial cells was also observed. 1 μg huANG or vehicle were administered from 90 to 115 days of age for histological analysis. Vehicle-treated SOD1 G93A mice showed decreased motoneuron numbers and vascular length per ventral horn area, while huANG treatment resulted in improved vascular network maintenance and motoneuron survival. Our data suggest huANG represents a new class of pleiotropic ALS therapeutic that acts on the spinal cord vasculature and glia to delay motoneuron degeneration and disease progression. Copyright © 2018 Elsevier Ltd. All rights reserved.

Delayed Onset and Reduced Cognitive Deficits through Pre-Conditioning with 3-Nitropropionic Acid is Dependent on Sex and CAG Repeat Length in the R6/2 Mouse Model of Huntington's Disease.

PubMed

Skillings, Elizabeth A; Morton, A Jennifer

2016-01-01

Impairments in energy metabolism are implicated in Huntington's disease (HD) pathogenesis. Reduced levels of the mitochondrial enzyme succinate dehydrogenase (SDH), the main element of complex II, are observed post mortem in the brains of HD patients, and energy metabolism defects have been identified in both presymptomatic and symptomatic HD patients. Chemical preconditioning with 3-nitropropionic acid (3-NP), an irreversible inhibitor of SDH, has been shown to increase tolerance against experimental hypoxia in both heart and brain. Here we studied the effect of chronic preconditioning in the R6/2 mouse model of HD using mice carrying CAG repeat lengths of either 250 or 400 repeats. Both are transgenic fragment models, with 250CAG mice having a more rapid disease progression than 400CAG mice. Low doses of 3-NP (24 mg/kg) were administered via the drinking water and the effect on phenotype progression and cognition function assessed. After 3-NP treatment there were significant improvements in all aspects of the behavioural phenotype, apart from body weight, with timing and magnitude of improvements dependent on both CAG repeat length and sex. Specifically, a delay in the deterioration of general health (as shown by delayed onset of glycosuria and increased survival) was seen in both male and female 400CAG mice and in female 250CAG mice and was consistent with improved appearance of 3-NP treated R6/2 mice. Male 250CAG mice showed improvements but these were short term, and 3-NP treatment eventually had deleterious effects on their survival rate. When cognitive performance of 250CAG mice was assessed using a two-choice discrimination touchscreen task, we found that female mice showed significant improvements. Together, our results support the idea that energy metabolism contributes to the pathogenesis of HD, and suggest that improving energy deficits might be a therapeutically useful target.

Glutathione transferases P1/P2 regulate the timing of signaling pathway activations and cell cycle progression during mouse liver regeneration

PubMed Central

Pajaud, J; Ribault, C; Ben Mosbah, I; Rauch, C; Henderson, C; Bellaud, P; Aninat, C; Loyer, P; Morel, F; Corlu, A

2015-01-01

Glutathione transferases (GST) are phase II enzymes catalyzing the detoxification of endogenous noxious compounds and xenobiotics. They also regulate phosphorylation activities of MAPKinases in a catalytic-independent manner. Previous studies have demonstrated the regulation of JNK-dependent pathway by GSTP1/2. Considering the crucial role of JNK in the early steps of the hepatocyte cell cycle, we sought to determine whether GSTP1/2 were essential for hepatocyte proliferation following partial hepatectomy (PH). Using a conventional double knockout mouse model for the Gstp1 and Gstp2 genes, we found that the lack of GSTP1/P2 reduced the rate of DNA replication and mitotic index during the first wave of hepatocyte proliferation. The lowered proliferation was associated with the decrease in TNFalpha and IL-6 plasma concentrations, reduced hepatic HGF expression and delayed and/or altered activation of STAT3, JNK and ERK1/2 signaling pathways. In addition, the expression and/or activation of cell cycle regulators such as Cyclin D1, CDK4, E2F1 and MCM7 was postponed demonstrating that the absence of GSTP1/2 delayed the entry into and progression through the G1 phase of the cell cycle and impaired the synchrony of proliferation in hepatocytes following PH. Furthermore, while JNK and its downstream targets c-Jun and ATF2 were activated during the early steps of the liver regeneration in wild-type animals, the constitutively active JNK found in the quiescent liver of Gstp1/2 knockout mice underwent a decrease in its activity after PH. Transient induction of antioxidant enzymes and nitric oxide synthase were also delayed or repressed during the regenerative response. Altogether our results demonstrate that GSTP1/2 are a critical regulators of hepatocyte proliferation in the initial phases of liver regeneration. PMID:25590808

A comprehensive review of prehospital and in-hospital delay times in acute stroke care.

PubMed

Evenson, K R; Foraker, R E; Morris, D L; Rosamond, W D

2009-06-01

The purpose of this study was to systematically review and summarize prehospital and in-hospital stroke evaluation and treatment delay times. We identified 123 unique peer-reviewed studies published from 1981 to 2007 of prehospital and in-hospital delay time for evaluation and treatment of patients with stroke, transient ischemic attack, or stroke-like symptoms. Based on studies of 65 different population groups, the weighted Poisson regression indicated a 6.0% annual decline (P<0.001) in hours/year for prehospital delay, defined from symptom onset to emergency department arrival. For in-hospital delay, the weighted Poisson regression models indicated no meaningful changes in delay time from emergency department arrival to emergency department evaluation (3.1%, P=0.49 based on 12 population groups). There was a 10.2% annual decline in hours/year from emergency department arrival to neurology evaluation or notification (P=0.23 based on 16 population groups) and a 10.7% annual decline in hours/year for delay time from emergency department arrival to initiation of computed tomography (P=0.11 based on 23 population groups). Only one study reported on times from arrival to computed tomography scan interpretation, two studies on arrival to drug administration, and no studies on arrival to transfer to an in-patient setting, precluding generalizations. Prehospital delay continues to contribute the largest proportion of delay time. The next decade provides opportunities to establish more effective community-based interventions worldwide. It will be crucial to have effective stroke surveillance systems in place to better understand and improve both prehospital and in-hospital delays for acute stroke care.

Effects of time delay and pitch control sensitivity in the flared landing

NASA Technical Reports Server (NTRS)

Berthe, C. J.; Chalk, C. R.; Wingarten, N. C.; Grantham, W.

1986-01-01

Between December 1985 and January 1986, a flared landing program was conducted, using the USAF Total In-Flight simulator airplane, to examine time delay effects in a formal manner. Results show that as pitch sensitivity is increased, tolerance to time delay decreases. With the proper selection of pitch sensitivity, Level I performance was maintained with time delays ranging from 150 milliseconds to greater than 300 milliseconds. With higher sensitivity, configurations with Level I performance at 150 milliseconds degraded to level 2 at 200 milliseconds. When metrics of time delay and pitch sensitivity effects are applied to enhance previously developed predictive criteria, the result is an improved prediction technique which accounts for significant closed loop items.

Exact synchronization bound for coupled time-delay systems.

PubMed

Senthilkumar, D V; Pesquera, Luis; Banerjee, Santo; Ortín, Silvia; Kurths, J

2013-04-01

We obtain an exact bound for synchronization in coupled time-delay systems using the generalized Halanay inequality for the general case of time-dependent delay, coupling, and coefficients. Furthermore, we show that the same analysis is applicable to both uni- and bidirectionally coupled time-delay systems with an appropriate evolution equation for their synchronization manifold, which can also be defined for different types of synchronization. The exact synchronization bound assures an exponential stabilization of the synchronization manifold which is crucial for applications. The analytical synchronization bound is independent of the nature of the modulation and can be applied to any time-delay system satisfying a Lipschitz condition. The analytical results are corroborated numerically using the Ikeda system.

Time delay induced different synchronization patterns in repulsively coupled chaotic oscillators

NASA Astrophysics Data System (ADS)

Yao, Chenggui; Yi, Ming; Shuai, Jianwei

2013-09-01

Time delayed coupling plays a crucial role in determining the system's dynamics. We here report that the time delay induces transition from the asynchronous state to the complete synchronization (CS) state in the repulsively coupled chaotic oscillators. In particular, by changing the coupling strength or time delay, various types of synchronous patterns, including CS, antiphase CS, antiphase synchronization (ANS), and phase synchronization, can be generated. In the transition regions between different synchronous patterns, bistable synchronous oscillators can be observed. Furthermore, we show that the time-delay-induced phase flip bifurcation is of key importance for the emergence of CS. All these findings may light on our understanding of neuronal synchronization and information processing in the brain.

Stability analysis of fractional-order Hopfield neural networks with time delays.

PubMed

Wang, Hu; Yu, Yongguang; Wen, Guoguang

2014-07-01

This paper investigates the stability for fractional-order Hopfield neural networks with time delays. Firstly, the fractional-order Hopfield neural networks with hub structure and time delays are studied. Some sufficient conditions for stability of the systems are obtained. Next, two fractional-order Hopfield neural networks with different ring structures and time delays are developed. By studying the developed neural networks, the corresponding sufficient conditions for stability of the systems are also derived. It is shown that the stability conditions are independent of time delays. Finally, numerical simulations are given to illustrate the effectiveness of the theoretical results obtained in this paper. Copyright © 2014 Elsevier Ltd. All rights reserved.

Influence of coal particles on ignition delay times of methane-air mixture

NASA Astrophysics Data System (ADS)

Fedorov, A. V.; Tropin, D. A.

2018-03-01

The results of numerical investigation of the ignition of a stoichiometric methane-air mixture in the presence of carbon particles with diameters of 20-52 μm in the temperature range 950-1150 K and pressures of 1.5-2.0 MPa are presented. The calculated data of the ignition delay times of coal particles in the coal particles/air mixture and of the ignition delay times of methane and coal particles in the methane/coal particles /air mixture are compared with the experimental ones. A satisfactory agreement of the data on the coal particles ignition delay times and methane ignition delay times in all the mixtures considered is shown.

Stochastic parameter estimation in nonlinear time-delayed vibratory systems with distributed delay

NASA Astrophysics Data System (ADS)

Torkamani, Shahab; Butcher, Eric A.

2013-07-01

The stochastic estimation of parameters and states in linear and nonlinear time-delayed vibratory systems with distributed delay is explored. The approach consists of first employing a continuous time approximation to approximate the delayed integro-differential system with a large set of ordinary differential equations having stochastic excitations. Then the problem of state and parameter estimation in the resulting stochastic ordinary differential system is represented as an optimal filtering problem using a state augmentation technique. By adapting the extended Kalman-Bucy filter to the augmented filtering problem, the unknown parameters of the time-delayed system are estimated from noise-corrupted, possibly incomplete measurements of the states. Similarly, the upper bound of the distributed delay can also be estimated by the proposed technique. As an illustrative example to a practical problem in vibrations, the parameter, delay upper bound, and state estimation from noise-corrupted measurements in a distributed force model widely used for modeling machine tool vibrations in the turning operation is investigated.

Optical resonators for true-time-delay beam steering

NASA Astrophysics Data System (ADS)

Gesell, Leslie H.; Evanko, Stephen M.

1996-06-01

Conventional true time delay beamforming and steering devices rely on switching between various lengths of delay line. Therefore only discrete delays are possible. Proposed is a new photonics concept for true time delay beamforming which provides a finely controlled continuum of delays with switching speeds on the order of 10's of nanoseconds or faster. The architecture uses an array of waveguide cavities with different resonate frequencies to channelize the signal. Each spectral component of the signal is phase shifted by an amount proportional to the frequency of that component and the desired time delay. These phase shifted spectral components are then summed to obtain the delayed signal. This paper provides an overview of the results of a Phase I SBIR contract where this concept has been refined and analyzed. The parameters for an operational system are determined and indication of the feasibility of this approach is given. Among the issues addressed are the requirements of the resonators and the methods necessary to implement fiber optic Bragg gratings as these resonators.

Satellite Analysis of Ocean Biogeochemistry and Mesoscale Variability in the Sargasso Sea

NASA Technical Reports Server (NTRS)

Siegel, D. A.; Micheals, A. F.; Nelson, N. B.

1997-01-01

The objective of this study was to analyze the impact of spatial variability on the time-series of biogeochemical measurements made at the U.S. JGOFS Bermuda Atlantic Time-series Study (BATS) site. Originally the study was planned to use SeaWiFS as well as AVHRR high-resolution data. Despite the SeaWiFS delays we were able to make progress on the following fronts: (1) Operational acquisition, processing, and archive of HRPT data from a ground station located in Bermuda; (2) Validation of AVHRR SST data using BATS time-series and spatial validation cruise CTD data; (3) Use of AVHRR sea surface temperature imagery and ancillary data to assess the impact of mesoscale spatial variability on P(CO2) and carbon flux in the Sargasso Sea; (4) Spatial and temporal extent of tropical cyclone induced surface modifications; and (5) Assessment of eddy variability using TOPEX/Poseidon data.

Enzalutamide in metastatic prostate cancer before chemotherapy.

PubMed

Beer, Tomasz M; Armstrong, Andrew J; Rathkopf, Dana E; Loriot, Yohann; Sternberg, Cora N; Higano, Celestia S; Iversen, Peter; Bhattacharya, Suman; Carles, Joan; Chowdhury, Simon; Davis, Ian D; de Bono, Johann S; Evans, Christopher P; Fizazi, Karim; Joshua, Anthony M; Kim, Choung-Soo; Kimura, Go; Mainwaring, Paul; Mansbach, Harry; Miller, Kurt; Noonberg, Sarah B; Perabo, Frank; Phung, De; Saad, Fred; Scher, Howard I; Taplin, Mary-Ellen; Venner, Peter M; Tombal, Bertrand

2014-07-31

Enzalutamide is an oral androgen-receptor inhibitor that prolongs survival in men with metastatic castration-resistant prostate cancer in whom the disease has progressed after chemotherapy. New treatment options are needed for patients with metastatic prostate cancer who have not received chemotherapy, in whom the disease has progressed despite androgen-deprivation therapy. In this double-blind, phase 3 study, we randomly assigned 1717 patients to receive either enzalutamide (at a dose of 160 mg) or placebo once daily. The coprimary end points were radiographic progression-free survival and overall survival. The study was stopped after a planned interim analysis, conducted when 540 deaths had been reported, showed a benefit of the active treatment. The rate of radiographic progression-free survival at 12 months was 65% among patients treated with enzalutamide, as compared with 14% among patients receiving placebo (81% risk reduction; hazard ratio in the enzalutamide group, 0.19; 95% confidence interval [CI], 0.15 to 0.23; P<0.001). A total of 626 patients (72%) in the enzalutamide group, as compared with 532 patients (63%) in the placebo group, were alive at the data-cutoff date (29% reduction in the risk of death; hazard ratio, 0.71; 95% CI, 0.60 to 0.84; P<0.001). The benefit of enzalutamide was shown with respect to all secondary end points, including the time until the initiation of cytotoxic chemotherapy (hazard ratio, 0.35), the time until the first skeletal-related event (hazard ratio, 0.72), a complete or partial soft-tissue response (59% vs. 5%), the time until prostate-specific antigen (PSA) progression (hazard ratio, 0.17), and a rate of decline of at least 50% in PSA (78% vs. 3%) (P<0.001 for all comparisons). Fatigue and hypertension were the most common clinically relevant adverse events associated with enzalutamide treatment. Enzalutamide significantly decreased the risk of radiographic progression and death and delayed the initiation of chemotherapy in men with metastatic prostate cancer. (Funded by Medivation and Astellas Pharma; PREVAIL ClinicalTrials.gov number, NCT01212991.).

Stability analysis for discrete-time stochastic memristive neural networks with both leakage and probabilistic delays.

PubMed

Liu, Hongjian; Wang, Zidong; Shen, Bo; Huang, Tingwen; Alsaadi, Fuad E

2018-06-01

This paper is concerned with the globally exponential stability problem for a class of discrete-time stochastic memristive neural networks (DSMNNs) with both leakage delays as well as probabilistic time-varying delays. For the probabilistic delays, a sequence of Bernoulli distributed random variables is utilized to determine within which intervals the time-varying delays fall at certain time instant. The sector-bounded activation function is considered in the addressed DSMNN. By taking into account the state-dependent characteristics of the network parameters and choosing an appropriate Lyapunov-Krasovskii functional, some sufficient conditions are established under which the underlying DSMNN is globally exponentially stable in the mean square. The derived conditions are made dependent on both the leakage and the probabilistic delays, and are therefore less conservative than the traditional delay-independent criteria. A simulation example is given to show the effectiveness of the proposed stability criterion. Copyright © 2018 Elsevier Ltd. All rights reserved.

14 CFR 417.221 - Time delay analysis.

Code of Federal Regulations, 2012 CFR

2012-01-01

... occurs; (2) A flight safety official's decision and reaction time, including variation in human response... 14 Aeronautics and Space 4 2012-01-01 2012-01-01 false Time delay analysis. 417.221 Section 417... OF TRANSPORTATION LICENSING LAUNCH SAFETY Flight Safety Analysis § 417.221 Time delay analysis. (a...

14 CFR 417.221 - Time delay analysis.

Code of Federal Regulations, 2014 CFR

2014-01-01

... occurs; (2) A flight safety official's decision and reaction time, including variation in human response... 14 Aeronautics and Space 4 2014-01-01 2014-01-01 false Time delay analysis. 417.221 Section 417... OF TRANSPORTATION LICENSING LAUNCH SAFETY Flight Safety Analysis § 417.221 Time delay analysis. (a...

14 CFR 417.221 - Time delay analysis.

Code of Federal Regulations, 2013 CFR

2013-01-01

... occurs; (2) A flight safety official's decision and reaction time, including variation in human response... 14 Aeronautics and Space 4 2013-01-01 2013-01-01 false Time delay analysis. 417.221 Section 417... OF TRANSPORTATION LICENSING LAUNCH SAFETY Flight Safety Analysis § 417.221 Time delay analysis. (a...

Symmetry, Hopf bifurcation, and the emergence of cluster solutions in time delayed neural networks.

PubMed

Wang, Zhen; Campbell, Sue Ann

2017-11-01

We consider the networks of N identical oscillators with time delayed, global circulant coupling, modeled by a system of delay differential equations with Z N symmetry. We first study the existence of Hopf bifurcations induced by the coupling time delay and then use symmetric Hopf bifurcation theory to determine how these bifurcations lead to different patterns of symmetric cluster oscillations. We apply our results to a case study: a network of FitzHugh-Nagumo neurons with diffusive coupling. For this model, we derive the asymptotic stability, global asymptotic stability, absolute instability, and stability switches of the equilibrium point in the plane of coupling time delay (τ) and excitability parameter (a). We investigate the patterns of cluster oscillations induced by the time delay and determine the direction and stability of the bifurcating periodic orbits by employing the multiple timescales method and normal form theory. We find that in the region where stability switching occurs, the dynamics of the system can be switched from the equilibrium point to any symmetric cluster oscillation, and back to equilibrium point as the time delay is increased.

Improving quality of life in multiple sclerosis: an unmet need.

PubMed

Zwibel, Howard L; Smrtka, Jennifer

2011-05-01

Multiple sclerosis (MS) affects approximately 400,000 people in the United States and 2.1 million people worldwide. It is the most common chronic, non-traumatic neurological disorder afflicting young people during their peak productive ages. MS can diminish quality of life (QOL) by interfering with the ability to work, pursue leisure activities, and carry on usual life roles. Symptoms that affect QOL may include impaired mobility, fatigue, depression, pain, spasticity, cognitive impairment, sexual dysfunction, bowel and bladder dysfunction, vision and hearing problems, seizures, and sDwallowing and breathing difficulties. Direct medical costs of MS in the United States are estimated in excess of $10 billion per year. Indirect costs of MS include costs of reduced employment or unemployment, assistive equipment, disability related home modifications, and paid and unpaid personal care. Although direct medical costs predominate in the earlier stages of MS, indirect costs of productivity loss are responsible for higher costs later. Disease-modifying therapies (DMTs) lessen symptoms, reduce relapses, and delay disability progression. Unfortunately, many DMTs might produce only modest improvements in QOL. Although symptom-specific therapies do not delay disease progression, they may delay unemployment and dependency, thereby reducing indirect costs.

Spectroscopy of the UO+2 cation and the delayed ionization of UO2.

PubMed

Merritt, Jeremy M; Han, Jiande; Heaven, Michael C

2008-02-28

Vibronically resolved spectra for the UO+2 cation have been recorded using the pulsed field ionization zero electron kinetic energy (PFI-ZEKE) technique. For the ground state, long progressions in both the bending and symmetric stretch vibrations were observed. Bend and stretch progressions of the first electronically excited state were also observed, and the origin was found at an energy of 2678 cm(-1) above the ground state zero-point level. This observation is consistent with a recent theoretical prediction [Infante et al., J. Chem. Phys. 127, 124308 (2007)]. The ionization energy for UO2, derived from the PFI-ZEKE spectrum, namely, 6.127(1) eV, is in excellent agreement with the value obtained from an earlier photoionization efficiency measurement. Delayed ionization of UO2 in the gas phase has been reported previously [Han et al., J. Chem. Phys. 120, 5155 (2004)]. Here, we extend the characterization of the delayed ionization process by performing a quantitative study of the ionization rate as a function of the energy above the ionization threshold. The ionization rate was found to be 5 x 10(6) s(-1) at threshold, and increased linearly with increasing energy in the range investigated (0-1200 cm(-1)).

75 FR 41920 - Agency Information Collection; Activity Under OMB Review; Airline Service Quality Performance...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-19

... and analyze air traffic delays. Wheels-up and wheels-down times are used in conjunction with departure and arrival times to show the extent of ground delays. Actual elapsed flight time, wheels-down minus wheels- up time, is compared to scheduled elapsed flight time to identify airborne delays. The reporting...

High resolution digital delay timer

DOEpatents

Martin, Albert D.

1988-01-01

Method and apparatus are provided for generating an output pulse following a trigger pulse at a time delay interval preset with a resolution which is high relative to a low resolution available from supplied clock pulses. A first lumped constant delay (20) provides a first output signal (24) at predetermined interpolation intervals corresponding to the desired high resolution time interval. Latching circuits (26, 28) latch the high resolution data (24) to form a first synchronizing data set (60). A selected time interval has been preset to internal counters (142, 146, 154) and corrected for circuit propagation delay times having the same order of magnitude as the desired high resolution. Internal system clock pulses (32, 34) count down the counters to generate an internal pulse delayed by an interval which is functionally related to the preset time interval. A second LCD (184) corrects the internal signal with the high resolution time delay. A second internal pulse is then applied to a third LCD (74) to generate a second set of synchronizing data (76) which is complementary with the first set of synchronizing data (60) for presentation to logic circuits (64). The logic circuits (64) further delay the internal output signal (72) to obtain a proper phase relationship of an output signal (80) with the internal pulses (32, 34). The final delayed output signal (80) thereafter enables the output pulse generator (82) to produce the desired output pulse (84) at the preset time delay interval following input of the trigger pulse (10, 12).

Analyzing Double Delays at Newark Liberty International Airport

NASA Technical Reports Server (NTRS)

Evans, Antony D.; Lee, Paul

2016-01-01

When weather or congestion impacts the National Airspace System, multiple different Traffic Management Initiatives can be implemented, sometimes with unintended consequences. One particular inefficiency that is commonly identified is in the interaction between Ground Delay Programs (GDPs) and time based metering of internal departures, or TMA scheduling. Internal departures under TMA scheduling can take large GDP delays, followed by large TMA scheduling delays, because they cannot be easily fitted into the overhead stream. In this paper we examine the causes of these double delays through an analysis of arrival operations at Newark Liberty International Airport (EWR) from June to August 2010. Depending on how the double delay is defined between 0.3 percent and 0.8 percent of arrivals at EWR experienced double delays in this period. However, this represents between 21 percent and 62 percent of all internal departures in GDP and TMA scheduling. A deep dive into the data reveals that two causes of high internal departure scheduling delays are upstream flights making up time between their estimated departure clearance times (EDCTs) and entry into time based metering, which undermines the sequencing and spacing underlying the flight EDCTs, and high demand on TMA, when TMA airborne metering delays are high. Data mining methods (currently) including logistic regression, support vector machines and K-nearest neighbors are used to predict the occurrence of double delays and high internal departure scheduling delays with accuracies up to 0.68. So far, key indicators of double delay and high internal departure scheduling delay are TMA virtual runway queue size, and the degree to which estimated runway demand based on TMA estimated times of arrival has changed relative to the estimated runway demand based on EDCTs. However, more analysis is needed to confirm this.

Determination of Relevant Neuron–Neuron Connections for Neural Prosthetics Using Time-Delayed Mutual Information: Tutorial and Preliminary Results

PubMed Central

Taghva, Alexander; Song, Dong; Hampson, Robert E.; Deadwyler, Sam A.; Berger, Theodore W.

2013-01-01

BACKGROUND Identification of functional dependence among neurons is a necessary component in both the rational design of neural prostheses as well as in the characterization of network physiology. The objective of this article is to provide a tutorial for neurosurgeons regarding information theory, specifically time-delayed mutual information, and to compare time-delayed mutual information, an information theoretic quantity based on statistical dependence, with cross-correlation, a commonly used metric for this task in a preliminary analysis of rat hippocampal neurons. METHODS Spike trains were recorded from rats performing delayed nonmatch-to-sample task using an array of electrodes surgically implanted into the hippocampus of each hemisphere of the brain. In addition, spike train simulations of positively correlated neurons, negatively correlated neurons, and neurons correlated by nonlinear functions were generated. These were evaluated by time-delayed mutual information (MI) and cross-correlation. RESULTS Application of time-delayed MI to experimental data indicated the optimal bin size for information capture in the CA3-CA1 system was 40 ms, which may provide some insight into the spatiotemporal nature of encoding in the rat hippocampus. On simulated data, time-delayed MI showed peak values at appropriate time lags in positively correlated, negatively correlated, and complexly correlated data. Cross-correlation showed peak and troughs with positively correlated and negatively correlated data, but failed to capture some higher order correlations. CONCLUSIONS Comparison of time-delayed MI to cross-correlation in identification of functionally dependent neurons indicates that the methods are not equivalent. Time-delayed MI appeared to capture some interactions between CA3-CA1 neurons at physiologically plausible time delays missed by cross-correlation. It should be considered as a method for identification of functional dependence between neurons and may be useful in the development of neural prosthetics. PMID:22120279

Determination of relevant neuron-neuron connections for neural prosthetics using time-delayed mutual information: tutorial and preliminary results.

PubMed

Taghva, Alexander; Song, Dong; Hampson, Robert E; Deadwyler, Sam A; Berger, Theodore W

2012-12-01

Identification of functional dependence among neurons is a necessary component in both the rational design of neural prostheses as well as in the characterization of network physiology. The objective of this article is to provide a tutorial for neurosurgeons regarding information theory, specifically time-delayed mutual information, and to compare time-delayed mutual information, an information theoretic quantity based on statistical dependence, with cross-correlation, a commonly used metric for this task in a preliminary analysis of rat hippocampal neurons. Spike trains were recorded from rats performing delayed nonmatch-to-sample task using an array of electrodes surgically implanted into the hippocampus of each hemisphere of the brain. In addition, spike train simulations of positively correlated neurons, negatively correlated neurons, and neurons correlated by nonlinear functions were generated. These were evaluated by time-delayed mutual information (MI) and cross-correlation. Application of time-delayed MI to experimental data indicated the optimal bin size for information capture in the CA3-CA1 system was 40 ms, which may provide some insight into the spatiotemporal nature of encoding in the rat hippocampus. On simulated data, time-delayed MI showed peak values at appropriate time lags in positively correlated, negatively correlated, and complexly correlated data. Cross-correlation showed peak and troughs with positively correlated and negatively correlated data, but failed to capture some higher order correlations. Comparison of time-delayed MI to cross-correlation in identification of functionally dependent neurons indicates that the methods are not equivalent. Time-delayed MI appeared to capture some interactions between CA3-CA1 neurons at physiologically plausible time delays missed by cross-correlation. It should be considered as a method for identification of functional dependence between neurons and may be useful in the development of neural prosthetics. Copyright © 2012 Elsevier Inc. All rights reserved.

Reduced order modelling in searches for continuous gravitational waves - I. Barycentring time delays

NASA Astrophysics Data System (ADS)

Pitkin, M.; Doolan, S.; McMenamin, L.; Wette, K.

2018-06-01

The frequencies and phases of emission from extra-solar sources measured by Earth-bound observers are modulated by the motions of the observer with respect to the source, and through relativistic effects. These modulations depend critically on the source's sky-location. Precise knowledge of the modulations are required to coherently track the source's phase over long observations, for example, in pulsar timing, or searches for continuous gravitational waves. The modulations can be modelled as sky-location and time-dependent time delays that convert arrival times at the observer to the inertial frame of the source, which can often be the Solar system barycentre. We study the use of reduced order modelling for speeding up the calculation of this time delay for any sky-location. We find that the time delay model can be decomposed into just four basis vectors, and with these the delay for any sky-location can be reconstructed to sub-nanosecond accuracy. When compared to standard routines for time delay calculation in gravitational wave searches, using the reduced basis can lead to speed-ups of 30 times. We have also studied components of time delays for sources in binary systems. Assuming eccentricities <0.25, we can reconstruct the delays to within 100 s of nanoseconds, with best case speed-ups of a factor of 10, or factors of two when interpolating the basis for different orbital periods or time stamps. In long-duration phase-coherent searches for sources with sky-position uncertainties, or binary parameter uncertainties, these speed-ups could allow enhancements in their scopes without large additional computational burdens.

Evaluation of the use of oseltamivir prophylaxis in the control of influenza outbreaks in long-term care facilities in Alberta, Canada: a retrospective provincial database analysis

PubMed Central

Ye, Ming; Jacobs, Angela; Khan, Muhammad Naeem; Jaipaul, Joy; Oda, Joanna; Johnson, Marcia; Doroshenko, Alexander

2016-01-01

Objectives To evaluate the impact of oseltamivir prophylaxis in the management and control of influenza outbreaks in long-term care facilities in Alberta, Canada. Setting and participants Long-term care facilities where 127 influenza outbreaks were reported to public health authorities in Alberta, Canada, during two influenza seasons from 2013 to 2015. Design and outcome measures Using routinely collected surveillance and administrative data, we examined the association between decision-making time for oseltamivir recommendation as prophylaxis strategy for influenza outbreaks in long-term care facilities (explanatory variable) and the duration of an influenza outbreak, the postprophylaxis risk of influenza-like illness and hospitalisation among residents of long-term care facilities in Alberta (outcome variables) using multivariable linear and Poisson regression models. Results Oseltamivir prophylaxis decision-making time was positively associated with the postintervention duration of an outbreak, with a 1-day delay in making decision on oseltamivir prophylaxis associated with 2.22 (95% CI 1.37 to 3.06) more days of the duration of an outbreak after controlling for potential confounding effect of the number of residents at risk at intervention, outbreak progression time, prevalence of influenza-like illness during outbreak progression, facility location, presence of mixed strain and based on optimal timing of oseltamivir prophylaxis. Although not statistically significant, a 1-day delay in making decision on oseltamivir prophylaxis was associated with a 5% (95% CI −1% to 11%) increase in the postintervention risk of influenza-like illness, and a 6% (95% CI −8% to 22%) increase in the postintervention risk of hospitalisation after controlling for the same potential confounders. Conclusions Our study demonstrated benefits of using oseltamivir prophylaxis to shorten the duration of influenza outbreaks; however, there were no significant differences in the influenza-like illness and hospitalisation risk occurring after the intervention. Surveillance data may offer means of rapid evaluation of oseltamivir prophylaxis in long-term care facilities as a public health measure. PMID:27381211

Evaluation of the use of oseltamivir prophylaxis in the control of influenza outbreaks in long-term care facilities in Alberta, Canada: a retrospective provincial database analysis.

PubMed

Ye, Ming; Jacobs, Angela; Khan, Muhammad Naeem; Jaipaul, Joy; Oda, Joanna; Johnson, Marcia; Doroshenko, Alexander

2016-07-05

To evaluate the impact of oseltamivir prophylaxis in the management and control of influenza outbreaks in long-term care facilities in Alberta, Canada. Long-term care facilities where 127 influenza outbreaks were reported to public health authorities in Alberta, Canada, during two influenza seasons from 2013 to 2015. Using routinely collected surveillance and administrative data, we examined the association between decision-making time for oseltamivir recommendation as prophylaxis strategy for influenza outbreaks in long-term care facilities (explanatory variable) and the duration of an influenza outbreak, the postprophylaxis risk of influenza-like illness and hospitalisation among residents of long-term care facilities in Alberta (outcome variables) using multivariable linear and Poisson regression models. Oseltamivir prophylaxis decision-making time was positively associated with the postintervention duration of an outbreak, with a 1-day delay in making decision on oseltamivir prophylaxis associated with 2.22 (95% CI 1.37 to 3.06) more days of the duration of an outbreak after controlling for potential confounding effect of the number of residents at risk at intervention, outbreak progression time, prevalence of influenza-like illness during outbreak progression, facility location, presence of mixed strain and based on optimal timing of oseltamivir prophylaxis. Although not statistically significant, a 1-day delay in making decision on oseltamivir prophylaxis was associated with a 5% (95% CI -1% to 11%) increase in the postintervention risk of influenza-like illness, and a 6% (95% CI -8% to 22%) increase in the postintervention risk of hospitalisation after controlling for the same potential confounders. Our study demonstrated benefits of using oseltamivir prophylaxis to shorten the duration of influenza outbreaks; however, there were no significant differences in the influenza-like illness and hospitalisation risk occurring after the intervention. Surveillance data may offer means of rapid evaluation of oseltamivir prophylaxis in long-term care facilities as a public health measure. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Circadian polymorphisms in night owls, in bipolars, and in non-24-hour sleep cycles.

PubMed

Kripke, Daniel F; Klimecki, Walter T; Nievergelt, Caroline M; Rex, Katharine M; Murray, Sarah S; Shekhtman, Tatyana; Tranah, Gregory J; Loving, Richard T; Lee, Heon-Jeong; Rhee, Min Kyu; Shadan, Farhad F; Poceta, J Steven; Jamil, Shazia M; Kline, Lawrence E; Kelsoe, John R

2014-10-01

People called night owls habitually have late bedtimes and late times of arising, sometimes suffering a heritable circadian disturbance called delayed sleep phase syndrome (DSPS). Those with DSPS, those with more severe progressively-late non-24-hour sleep-wake cycles, and those with bipolar disorder may share genetic tendencies for slowed or delayed circadian cycles. We searched for polymorphisms associated with DSPS in a case-control study of DSPS research participants and a separate study of Sleep Center patients undergoing polysomnography. In 45 participants, we resequenced portions of 15 circadian genes to identify unknown polymorphisms that might be associated with DSPS, non-24-hour rhythms, or bipolar comorbidities. We then genotyped single nucleotide polymorphisms (SNPs) in both larger samples, using Illumina Golden Gate assays. Associations of SNPs with the DSPS phenotype and with the morningness-eveningness parametric phenotype were computed for both samples, then combined for meta-analyses. Delayed sleep and "eveningness" were inversely associated with loci in circadian genes NFIL3 (rs2482705) and RORC (rs3828057). A group of haplotypes overlapping BHLHE40 was associated with non-24-hour sleep-wake cycles, and less robustly, with delayed sleep and bipolar disorder (e.g., rs34883305, rs34870629, rs74439275, and rs3750275 were associated with n=37, p=4.58E-09, Bonferroni p=2.95E-06). Bright light and melatonin can palliate circadian disorders, and genetics may clarify the underlying circadian photoperiodic mechanisms. After further replication and identification of the causal polymorphisms, these findings may point to future treatments for DSPS, non-24-hour rhythms, and possibly bipolar disorder or depression.

A novel method for rapid and non-invasive detection of plants senescence using delayed fluorescence technique

NASA Astrophysics Data System (ADS)

Zhang, Lingrui; Xing, Da; Wang, Junsheng; Zeng, Lizhang; Li, Qiang

2007-05-01

Plants senescence is a phase of plants ontogeny marked by declining photosynthetic activity that is paralleled by a decline in chloroplast function. The photosystem II ( PSII ) in a plant is considered the primary site where light-induced delayed fluorescence (DF) is produced. With the leaves of Catharanthus roseus (Catharanthus roseus (L.) G.Don) as testing models, we have studied the effects of plants senescence induced by dark and/or exogenous hormones treatments on characteristics of DF by using a home-made portable DF detection system, which can enable various DF parameters, such as DF decay kinetic curve and DF intensity, to be rapidly produced for the plants in a short time. The results show that the changes in DF intensity of green plants can truly reflect the changes in photosynthetic capacity and chlorophyll content. Therefore, DF may be used an important means of evaluating in vivo plants senescence physiology. The changes in DF intensity may provide a new approach for the rapid and early detection of plants senescence caused by age or other senescence-related factors. DF technique could be potential useful for high throughput screening and less time-consuming and automated identifying the interesting mutants with genetic modifications that change plants senescence progress.

Delayed Induction of Human NTE (PNPLA6) Rescues Neurodegeneration and Mobility Defects of Drosophila swiss cheese (sws) Mutants.

PubMed

Sujkowski, Alyson; Rainier, Shirley; Fink, John K; Wessells, Robert J

2015-01-01

Human PNPLA6 gene encodes Neuropathy Target Esterase protein (NTE). PNPLA6 gene mutations cause hereditary spastic paraplegia (SPG39 HSP), Gordon-Holmes syndrome, Boucher-Neuhäuser syndromes, Laurence-Moon syndrome, and Oliver-McFarlane syndrome. Mutations in the Drosophila NTE homolog swiss cheese (sws) cause early-onset, progressive behavioral defects and neurodegeneration characterized by vacuole formation. We investigated sws5 flies and show for the first time that this allele causes progressive vacuolar formation in the brain and progressive deterioration of negative geotaxis speed and endurance. We demonstrate that inducible, neuron-specific expression of full-length human wildtype NTE reduces vacuole formation and substantially rescues mobility. Indeed, neuron-specific expression of wildtype human NTE is capable of rescuing mobility defects after 10 days of adult life at 29°C, when significant degeneration has already occurred, and significantly extends longevity of mutants at 25°C. These results raise the exciting possibility that late induction of NTE function may reduce or ameliorate neurodegeneration in humans even after symptoms begin. In addition, these results highlight the utility of negative geotaxis endurance as a new assay for longitudinal tracking of degenerative phenotypes in Drosophila.

PubMed Central

DE LOS ANGELES BEYTÍA, MARIA; VRY, JULIA; KIRSCHNER, JANBERND

2012-01-01

Duchenne muscular dystrophy (DMD) is a disease linked to the X-chromosome which affects 1 in 3,600-6,000 newborn males. It is manifested by the absence of the dystrophin protein in muscle fibres, which causes progressive damage leading to death in the third decade of life. The only medication so far shown to be effective in delaying the progression of this illness are corticosteroids, which have been shown to increase muscle strength in randomised controlled studies; long-term studies have demonstrated that they prolong walking time and retard the progression of respiratory dysfunction, dilated cardiomyopathy and scoliosis. Several potential drugs are now being investigated. Genetic therapy, involving the insertion of a dystrophin gene through a vector, has proven effective in animals but not humans. Currently under clinical study is Ataluren, a molecule that binds with ribosomes and may allow the insertion of an aminoacid in the premature termination codon, and exon-skipping, which binds with RNA and excludes specific sites of RNA splicing, producing a dystrophin that is smaller but functional. There are also studies attempting to modulate other muscular proteins, such as myostatin and utrophin, to reduce symptoms. This paper does not address cardiomyopathy treatment in DMD patients. PMID:22655510

Longitudinal Outcomes of Start Time Delay on Sleep, Behavior, and Achievement in High School

PubMed Central

Thacher, Pamela V.; Onyper, Serge V.

2016-01-01

Study Objectives: To establish whether sleep, health, mood, behavior, and academics improved after a 45-minute delay in high school start time, and whether changes persisted longitudinally. Methods: We collected data from school records and student self-report across a number of domains at baseline (May 2012) and at two follow-up time points (November 2012 and May 2013), at a public high school in upstate New York. Students enrolled during academic years (AY) 2011–2012 and 2012–2013 completed the Pittsburgh Sleep Quality Index; the DASS-21; the “Owl-Lark” Scale; the Daytime Sleepiness Index; and a brief self-report of health. Reports from school records regarding attendance, tardiness, disciplinary violations, and academic performance were collected for AY 2010–2011 through 2013–2014. Results: Students delayed but did not extend their sleep period; we found lasting improvements in tardiness and disciplinary violations after the start-time delay, but no changes to other variables. At the first follow-up, students reported 20 minutes longer sleep, driven by later rise times and stable bed times. At the second follow-up, students maintained later rise times but delayed bedtimes, returning total sleep to baseline levels. A delay in rise time, paralleling the delay in the start time that occurred, resulted in less tardiness and decreased disciplinary incidents, but larger improvements to sleep patterns may be necessary to affect health, attendance, sleepiness, and academic performance. Conclusions: Later start times improved tardiness and disciplinary issues at this school district. A delay in start time may be a necessary but not sufficient means to increase sleep time and may depend on preexisting individual differences. Commentary: A commentary on this article appears in this issue on page 267. Citation: Thacher PV, Onyper SV. Longitudinal outcomes of start time delay on sleep, behavior, and achievement in high school. SLEEP 2016;39(2):271–281. PMID:26446106

Stability and Bifurcation Analysis in a Maglev System with Multiple Delays

NASA Astrophysics Data System (ADS)

Zhang, Lingling; Huang, Jianhua; Huang, Lihong; Zhang, Zhizhou

This paper considers the time-delayed feedback control for Maglev system with two discrete time delays. We determine constraints on the feedback time delays which ensure the stability of the Maglev system. An algorithm is developed for drawing a two-parametric bifurcation diagram with respect to two delays τ1 and τ2. Direction and stability of periodic solutions are also determined using the normal form method and center manifold theory by Hassard. The complex dynamical behavior of the Maglev system near the domain of stability is confirmed by exhaustive numerical simulation.

PRECISION TIME-DELAY CIRCUIT

DOEpatents

Creveling, R.

1959-03-17

A tine-delay circuit which produces a delay time in d. The circuit a capacitor, an te back resistance, connected serially with the anode of the diode going to ground. At the start of the time delay a negative stepfunction is applied to the series circuit and initiates a half-cycle transient oscillatory voltage terminated by a transient oscillatory voltage of substantially higher frequency. The output of the delay circuit is taken at the junction of the inductor and diode where a sudden voltage rise appears after the initiation of the higher frequency transient oscillations.

Academic delay of gratification, self-efficacy, and time management among academically unprepared college students.

PubMed

Bembenutty, Héfer

2009-04-01

This study examined the associations between academic delay of gratification, self-efficacy beliefs, and time management among academically unprepared college students participating in a summer-immersion program. This study also examined whether the relation of self-efficacy with time management is mediated by academic delay of gratification. Analysis indicated that self-efficacy was directly associated with time management, as delay of gratification served to mediate this effect partially. Self-efficacy emerged as the strongest positive predictor of academic achievement.

Time delay in atomic photoionization with circularly polarized light

NASA Astrophysics Data System (ADS)

Ivanov, I. A.; Kheifets, A. S.

2013-03-01

We study time delay in atomic photoionization by circularly polarized light. By considering the Li atom in an excited 2p state, we demonstrate a strong time-delay asymmetry between the photoemission of the target electrons that are co- and counter-rotating with the electromagnetic field in the polarization plane. In addition, we observe the time-delay sensitivity to the polar angle of the photoelectron emission in the polarization plane. This modulation depends on the shape and duration of the electromagnetic pulse.

Generating chaos for discrete time-delayed systems via impulsive control.

PubMed

Guan, Zhi-Hong; Liu, Na

2010-03-01

Generating chaos for a class of discrete time-delayed systems via impulsive control is investigated in this paper. With the augmented matrix method, the time-delay impulsive systems can be transformed into a new class of linear discrete impulsive systems. Based on the largest Lyapunov exponent and the boundedness of the systems, some theoretical results about the chaotification for the discrete impulsive systems with time delay are derived and an example is given to visualize the satisfactory control performance.

Insensitivity of synchronization to network structure in chaotic pendulum systems with time-delay coupling.

PubMed

Yao, Chenggui; Zhan, Meng; Shuai, Jianwei; Ma, Jun; Kurths, Jürgen

2017-12-01

It has been generally believed that both time delay and network structure could play a crucial role in determining collective dynamical behaviors in complex systems. In this work, we study the influence of coupling strength, time delay, and network topology on synchronization behavior in delay-coupled networks of chaotic pendulums. Interestingly, we find that the threshold value of the coupling strength for complete synchronization in such networks strongly depends on the time delay in the coupling, but appears to be insensitive to the network structure. This lack of sensitivity was numerically tested in several typical regular networks, such as different locally and globally coupled ones as well as in several complex networks, such as small-world and scale-free networks. Furthermore, we find that the emergence of a synchronous periodic state induced by time delay is of key importance for the complete synchronization.

Determining collective barrier operation skew in a parallel computer

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

Faraj, Daniel A.

2015-11-24

Determining collective barrier operation skew in a parallel computer that includes a number of compute nodes organized into an operational group includes: for each of the nodes until each node has been selected as a delayed node: selecting one of the nodes as a delayed node; entering, by each node other than the delayed node, a collective barrier operation; entering, after a delay by the delayed node, the collective barrier operation; receiving an exit signal from a root of the collective barrier operation; and measuring, for the delayed node, a barrier completion time. The barrier operation skew is calculated by:more » identifying, from the compute nodes' barrier completion times, a maximum barrier completion time and a minimum barrier completion time and calculating the barrier operation skew as the difference of the maximum and the minimum barrier completion time.« less

Effects of time delays on stability and Hopf bifurcation in a fractional ring-structured network with arbitrary neurons

NASA Astrophysics Data System (ADS)

Huang, Chengdai; Cao, Jinde; Xiao, Min; Alsaedi, Ahmed; Hayat, Tasawar

2018-04-01

This paper is comprehensively concerned with the dynamics of a class of high-dimension fractional ring-structured neural networks with multiple time delays. Based on the associated characteristic equation, the sum of time delays is regarded as the bifurcation parameter, and some explicit conditions for describing delay-dependent stability and emergence of Hopf bifurcation of such networks are derived. It reveals that the stability and bifurcation heavily relies on the sum of time delays for the proposed networks, and the stability performance of such networks can be markedly improved by selecting carefully the sum of time delays. Moreover, it is further displayed that both the order and the number of neurons can extremely influence the stability and bifurcation of such networks. The obtained criteria enormously generalize and improve the existing work. Finally, numerical examples are presented to verify the efficiency of the theoretical results.

Determining collective barrier operation skew in a parallel computer

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

Faraj, Daniel A.

Determining collective barrier operation skew in a parallel computer that includes a number of compute nodes organized into an operational group includes: for each of the nodes until each node has been selected as a delayed node: selecting one of the nodes as a delayed node; entering, by each node other than the delayed node, a collective barrier operation; entering, after a delay by the delayed node, the collective barrier operation; receiving an exit signal from a root of the collective barrier operation; and measuring, for the delayed node, a barrier completion time. The barrier operation skew is calculated by:more » identifying, from the compute nodes' barrier completion times, a maximum barrier completion time and a minimum barrier completion time and calculating the barrier operation skew as the difference of the maximum and the minimum barrier completion time.« less

Delay-dependent coupling for a multi-agent LTI consensus system with inter-agent delays

NASA Astrophysics Data System (ADS)

Qiao, Wei; Sipahi, Rifat

2014-01-01

Delay-dependent coupling (DDC) is considered in this paper in a broadly studied linear time-invariant multi-agent consensus system in which agents communicate with each other under homogeneous delays, while attempting to reach consensus. The coupling among the agents is designed here as an explicit parameter of this delay, allowing couplings to autonomously adapt based on the delay value, and in order to guarantee stability and a certain degree of robustness in the network despite the destabilizing effect of delay. Design procedures, analysis of convergence speed of consensus, comprehensive numerical studies for the case of time-varying delay, and limitations are presented.

Delay correlation analysis and representation for vital complaint VHDL models

DOEpatents

Rich, Marvin J.; Misra, Ashutosh

2004-11-09

A method and system unbind a rise/fall tuple of a VHDL generic variable and create rise time and fall time generics of each generic variable that are independent of each other. Then, according to a predetermined correlation policy, the method and system collect delay values in a VHDL standard delay file, sort the delay values, remove duplicate delay values, group the delay values into correlation sets, and output an analysis file. The correlation policy may include collecting all generic variables in a VHDL standard delay file, selecting each generic variable, and performing reductions on the set of delay values associated with each selected generic variable.

Pneumatic shutoff and time-delay valve operates at controlled rate

NASA Technical Reports Server (NTRS)

Horning, J. L.; Tomlinson, L. E.

1966-01-01

Shutoff and time delay valve, which incorporates a metering spool that moves at constant velocity under pneumatic pressure and spring compression, increases fluid-flow area at a uniform rate. Diaphragm areas, control cavity volume, and bleed-orifice size may be varied to give any desired combination of time delay and spool travel time.

The phantom robot - Predictive displays for teleoperation with time delay

NASA Technical Reports Server (NTRS)

Bejczy, Antal K.; Kim, Won S.; Venema, Steven C.

1990-01-01

An enhanced teleoperation technique for time-delayed bilateral teleoperator control is discussed. The control technique selected for time delay is based on the use of a high-fidelity graphics phantom robot that is being controlled in real time (without time delay) against the static task image. Thus, the motion of the phantom robot image on the monitor predicts the motion of the real robot. The real robot's motion will follow the phantom robot's motion on the monitor with the communication time delay implied in the task. Real-time high-fidelity graphics simulation of a PUMA arm is generated and overlaid on the actual camera view of the arm. A simple camera calibration technique is used for calibrated graphics overlay. A preliminary experiment is performed with the predictive display by using a very simple tapping task. The results with this simple task indicate that predictive display enhances the human operator's telemanipulation task performance significantly during free motion when there is a long time delay. It appears, however, that either two-view or stereoscopic predictive displays are necessary for general three-dimensional tasks.

Detection and characterization of Budd-Chiari syndrome with inferior vena cava obstruction: Comparison of fixed and flexible delayed scan time of computed tomography venography.

PubMed

Zhou, Peng-Li; Wu, Gang; Han, Xin-Wei; Bi, Yong-Hua; Zhang, Wen-Guang; Wu, Zheng-Yang

2017-06-01

To compare the results of computed tomography venography (CTV) with a fixed and a flexible delayed scan time for Budd-Chiari syndrome (BCS) with inferior vena cava (IVC) obstruction. A total of 209 consecutive BCS patients with IVC obstruction underwent either a CTV with a fixed delayed scan time of 180s (n=87) or a flexible delayed scan time for good image quality according to IVC blood flow in color Doppler ultrasonography (n=122). The IVC blood flow velocity was measured using a color Doppler ultrasound prior to CT scan. Image quality was classified as either good, moderate, or poor. Image quality, surrounding structures and the morphology of the IVC obstruction were compared between the two groups using a χ 2 -test or paired or unpaired t-tests as appropriate. Inter-observer agreement was assessed using Kappa statistics. There was no significant difference in IVC blood flow velocity between the two groups. Overall image quality, surrounding structures and IVC obstruction morphology delineation on the flexible delayed scan time of CTV images were rated better relative to those obtained by fixed delayed scan time of CTV images (p<0.001). Evaluation of CTV data sets was significantly facilitated with flexible delayed scan time of CTV. There were no significant differences in Kappa statistics between Group A and Group B. The flexible delayed scan time of CTV was associated with better detection and more reliable characterization of BCS with IVC obstruction compared to a fixed delayed scan time. Copyright © 2017 Elsevier B.V. All rights reserved.

Toxicological and histopathological effects of boric acid on Atta sexdens rubropilosa (Hymenoptera: Formicidae) workers.

PubMed

Sumida, Simone; Silva-Zacarin, Elaine C M; Decio, Pâmela; Malaspina, Osmar; Bueno, Fabiana C; Bueno, Odair C

2010-06-01

The current study compared the toxicity of different concentrations of boric acid in adult workers of Atta sexdens rubropilosa Forel (Hymenoptera: Formicidae), with toxicological bioassays, and examining the dose-dependent and time-dependent histopathological changes, of the midgut, Malpighian tubules, and postpharyngeal glands. Our results revealed the importance of conducting toxicological bioassays combined with morphological analyses of the organs of ants chronically exposed to insecticides used in commercial ant baits. In vitro bioassays showed that boric acid significantly decreases the survivorship of workers regardless of concentration, whereas the morphological data suggested progressive dose-dependent and time-dependent changes in the organs examined, which were evident in the midgut. The midgut is the first organ to be affected, followed by the postpharyngeal gland and Malpighian tubules. This sequence is in agreement with the absorption pathway of this chemical compound in the midgut, its transference to the hemolymph, possibly reaching the postpharyngeal glands, and excretion by the Malpighian tubules. These progressive changes might be due to the cumulative and delayed effect of boric acid. Our findings provide important information for the understanding of the action of boric acid in ant baits in direct and indirect target organs.

A case-control study relating railroad worker mortality to diesel exhaust exposure using a threshold regression model.

PubMed

Lee, Mei-Ling Ting; Whitmore, G A; Laden, Francine; Hart, Jaime E; Garshick, Eric

2009-01-01

A case-control study of lung cancer mortality in U.S. railroad workers in jobs with and without diesel exhaust exposure is reanalyzed using a new threshold regression methodology. The study included 1256 workers who died of lung cancer and 2385 controls who died primarily of circulatory system diseases. Diesel exhaust exposure was assessed using railroad job history from the US Railroad Retirement Board and an industrial hygiene survey. Smoking habits were available from next-of-kin and potential asbestos exposure was assessed by job history review. The new analysis reassesses lung cancer mortality and examines circulatory system disease mortality. Jobs with regular exposure to diesel exhaust had a survival pattern characterized by an initial delay in mortality, followed by a rapid deterioration of health prior to death. The pattern is seen in subjects dying of lung cancer, circulatory system diseases, and other causes. The unique pattern is illustrated using a new type of Kaplan-Meier survival plot in which the time scale represents a measure of disease progression rather than calendar time. The disease progression scale accounts for a healthy-worker effect when describing the effects of cumulative exposures on mortality.

Wait Times Experienced by Lung Cancer Patients in the BC Southern Interior to Obtain Oncologic Care: Exploration of the Intervals from First Abnormal Imaging to Oncologic Treatment

PubMed Central

Chowdhury, Rezwan; Boyce, Andrew; Halperin, Ross

2015-01-01

Background: Lung cancer is associated with rapid disease progression, which can significantly progress over a duration of four to eight weeks. This study examines the time interval lung cancer patients from the interior of British Columbia (BC) experience while undergoing diagnostic evaluation, biopsy, staging, and preparation for treatment. Methods: A chart review of lung cancer patients (n=231) referred to the BC Cancer Agency Centre for the Southern Interior between January 1, 2010 and December 31, 2011 was performed. Time zero was defined as the date of the first abnormal chest imaging. Time intervals, expressed as median averages, to specialist consult, biopsy, oncologic referral, initial oncology consultation, and commencement of oncologic treatment were obtained. Results: The median time interval from first abnormal chest imaging to a specialist consultation was 18 days (interquartile range, IQR, 7-36). An additional nine days elapsed prior to biopsy in the form of bronchoscopy, CT-guided biopsy, or sputum cytology (median; IQR, 3-21); if lobectomy was required, 18 days elapsed (median; IQR, 9-28). Eight days were required for pathologic diagnosis and subsequent referral to the cancer centre (median; IQR, 3-16.5). Once referral was received, 10 days elapsed prior to consultation with either a medical or radiation oncologist (median, IQR 5-18). Finally, eight days was required for initiation of radiation and/or chemotherapy (median; IQR, 1-15). The median wait time from detection of lung cancer on imaging to oncologic treatment in the form of radiation and/or chemotherapy was 65.5 days (IQR, 41.5-104.3).  Interpretation: Patients in the BC Southern Interior experience considerable delays in accessing lung cancer care. During this time, the disease has the potential to significantly progress and it is possible that a subset of patients may lose their opportunity for curative intent treatment. PMID:26543688

Evidence for Sequential and Increasing Activation of Replication Origins along Replication Timing Gradients in the Human Genome

PubMed Central

Guilbaud, Guillaume; Rappailles, Aurélien; Baker, Antoine; Chen, Chun-Long; Arneodo, Alain; Goldar, Arach; d'Aubenton-Carafa, Yves; Thermes, Claude; Audit, Benjamin; Hyrien, Olivier

2011-01-01

Genome-wide replication timing studies have suggested that mammalian chromosomes consist of megabase-scale domains of coordinated origin firing separated by large originless transition regions. Here, we report a quantitative genome-wide analysis of DNA replication kinetics in several human cell types that contradicts this view. DNA combing in HeLa cells sorted into four temporal compartments of S phase shows that replication origins are spaced at 40 kb intervals and fire as small clusters whose synchrony increases during S phase and that replication fork velocity (mean 0.7 kb/min, maximum 2.0 kb/min) remains constant and narrowly distributed through S phase. However, multi-scale analysis of a genome-wide replication timing profile shows a broad distribution of replication timing gradients with practically no regions larger than 100 kb replicating at less than 2 kb/min. Therefore, HeLa cells lack large regions of unidirectional fork progression. Temporal transition regions are replicated by sequential activation of origins at a rate that increases during S phase and replication timing gradients are set by the delay and the spacing between successive origin firings rather than by the velocity of single forks. Activation of internal origins in a specific temporal transition region is directly demonstrated by DNA combing of the IGH locus in HeLa cells. Analysis of published origin maps in HeLa cells and published replication timing and DNA combing data in several other cell types corroborate these findings, with the interesting exception of embryonic stem cells where regions of unidirectional fork progression seem more abundant. These results can be explained if origins fire independently of each other but under the control of long-range chromatin structure, or if replication forks progressing from early origins stimulate initiation in nearby unreplicated DNA. These findings shed a new light on the replication timing program of mammalian genomes and provide a general model for their replication kinetics. PMID:22219720

Impact of geographic distance on appraisal delay for active TB treatment seeking in Uganda: a network analysis of the Kawempe Community Health Cohort Study.

PubMed

Fluegge, Kyle; Malone, LaShaunda L; Nsereko, Mary; Okware, Brenda; Wejse, Christian; Kisingo, Hussein; Mupere, Ezekiel; Boom, W Henry; Stein, Catherine M

2018-06-26

Appraisal delay is the time a patient takes to consider a symptom as not only noticeable, but a sign of illness. The study's objective was to determine the association between appraisal delay in seeking tuberculosis (TB) treatment and geographic distance measured by network travel (driving and pedestrian) time (in minutes) and distance (Euclidean and self-reported) (in kilometers) and to identify other risk factors from selected covariates and how they modify the core association between delay and distance. This was part of a longitudinal cohort study known as the Kawempe Community Health Study based in Kampala, Uganda. The study enrolled households from April 2002 to July 2012. Multivariable interval regression with multiplicative heteroscedasticity was used to assess the impact of time and distance on delay. The delay interval outcome was defined using a comprehensive set of 28 possible self-reported symptoms. The main independent variables were network travel time (in minutes) and Euclidean distance (in kilometers). Other covariates were organized according to the Andersen utilization conceptual framework. A total of 838 patients with both distance and delay data were included in the network analysis. Bivariate analyses did not reveal a significant association of any distance metric with the delay outcome. However, adjusting for patient characteristics and cavitary disease status, the multivariable model indicated that each minute of driving time to the clinic significantly (p = 0.02) and positively predicted 0.25 days' delay. At the median distance value of 47 min, this represented an additional delay of about 12 (95% CI: [3, 21]) days to the mean of 40 days (95% CI: [25, 56]). Increasing Euclidean distance significantly predicted (p = 0.02) reduced variance in the delay outcome, thereby increasing precision of the mean delay estimate. At the median Euclidean distance of 2.8 km, the variance in the delay was reduced by more than 25%. Of the four geographic distance measures, network travel driving time was a better and more robust predictor of mean delay in this setting. Including network travel driving time with other risk factors may be important in identifying populations especially vulnerable to delay.

Operating room efficiency improvement after implementation of a postoperative team assessment.

PubMed

Porta, Christopher R; Foster, Andrew; Causey, Marlin W; Cordier, Patricia; Ozbirn, Roger; Bolt, Stephen; Allison, Dennis; Rush, Robert

2013-03-01

Operating room time is highly resource intensive, and delays can be a source of lost revenue and surgeon frustration. Methods to decrease these delays are important not only for patient care, but to maximize operating room resource utilization. The purpose of this study was to determine the root cause of operating room delays in a standardized manner to help improve overall operating room efficiency. We performed a single-center prospective observational study analyzing operating room utilization and efficiency after implementing an executive-driven standardized postoperative team debriefing system from January 2010 to December 2010. A total of 11,342 procedures were performed over the 1-y study period (elective 86%, urgent 11%, and emergent 3%), with 1.3 million min of operating room time, 865,864 min of surgeon operative time (62.5%), and 162,958 min of anesthesia time (11.8%). Overall, the average operating room delay was 18 min and varied greatly based on the surgical specialty. The longest delays were due to need for radiology (40 min); other significant delays were due to supply issues (22.7 min), surgeon issues (18 min), nursing issues (14 min), and room turnover (14 min). Over the 1-y period, there was a decrease in mean delay duration, averaging a decrease in delay of 0.147 min/mo with an overall 9% decrease in the mean delay times. With regard to overall operating room utilization, there was a 39% decrease in overall un-utilized available OR time that was due to delays, improving efficiency by 2334 min (212 min/mo). During this study interval no sentinel events occurred in the operating room. A standardized postoperative debrief tracking system is highly beneficial in identifying and reducing overall operative delays and improving operating room utilization. Published by Elsevier Inc.

Time-delayed directional beam phased array antenna

DOEpatents

Fund, Douglas Eugene; Cable, John William; Cecil, Tony Myron

2004-10-19

An antenna comprising a phased array of quadrifilar helix or other multifilar antenna elements and a time-delaying feed network adapted to feed the elements. The feed network can employ a plurality of coaxial cables that physically bridge a microstrip feed circuitry to feed power signals to the elements. The cables provide an incremental time delay which is related to their physical lengths, such that replacing cables having a first set of lengths with cables having a second set of lengths functions to change the time delay and shift or steer the antenna's main beam. Alternatively, the coaxial cables may be replaced with a programmable signal processor unit adapted to introduce the time delay using signal processing techniques applied to the power signals.

Health span approximates life span among many supercentenarians: compression of morbidity at the approximate limit of life span.

PubMed

Andersen, Stacy L; Sebastiani, Paola; Dworkis, Daniel A; Feldman, Lori; Perls, Thomas T

2012-04-01

We analyze the relationship between age of survival, morbidity, and disability among centenarians (age 100-104 years), semisupercentenarians (age 105-109 years), and supercentenarians (age 110-119 years). One hundred and four supercentenarians, 430 semisupercentenarians, 884 centenarians, 343 nonagenarians, and 436 controls were prospectively followed for an average of 3 years (range 0-13 years). The older the age group, generally, the later the onset of diseases, such as cancer, cardiovascular disease, dementia, and stroke, as well as of cognitive and functional decline. The hazard ratios for these individual diseases became progressively less with older and older age, and the relative period of time spent with disease was lower with increasing age group. We observed a progressive delay in the age of onset of physical and cognitive function impairment, age-related diseases, and overall morbidity with increasing age. As the limit of human life span was effectively approached with supercentenarians, compression of morbidity was generally observed.

Health Span Approximates Life Span Among Many Supercentenarians: Compression of Morbidity at the Approximate Limit of Life Span

PubMed Central

Andersen, Stacy L.; Sebastiani, Paola; Dworkis, Daniel A.; Feldman, Lori

2012-01-01

We analyze the relationship between age of survival, morbidity, and disability among centenarians (age 100–104 years), semisupercentenarians (age 105–109 years), and supercentenarians (age 110–119 years). One hundred and four supercentenarians, 430 semisupercentenarians, 884 centenarians, 343 nonagenarians, and 436 controls were prospectively followed for an average of 3 years (range 0–13 years). The older the age group, generally, the later the onset of diseases, such as cancer, cardiovascular disease, dementia, and stroke, as well as of cognitive and functional decline. The hazard ratios for these individual diseases became progressively less with older and older age, and the relative period of time spent with disease was lower with increasing age group. We observed a progressive delay in the age of onset of physical and cognitive function impairment, age-related diseases, and overall morbidity with increasing age. As the limit of human life span was effectively approached with supercentenarians, compression of morbidity was generally observed. PMID:22219514

Evaluation and Management of Diabetes Mellitus

PubMed Central

Nguyen, Quang; Nguyen, Loida; Felicetta, James

2008-01-01

Diabetes mellitus is a major public health problem with tremendous medical and economic burdens. It is the seventh leading cause of death and the number one cause of end-stage renal disease, adult blindness, impotence, and nontraumatic lower-limb amputation in the United States. People with diabetes are 2 to 4 times more likely to suffer from stroke or from cardiovascular disease, and are twice as likely to die compared with age-matched individuals without diabetes. Diabetes cost the United States around $174 billion in 2007, $58 billion of which was related to disability, work loss, and early mortality. Although there is currently no known cure for diabetes, much progress has been made over the past 2 decades to improve the diagnosis and management of diabetes. Evidence has shown that applying aggressive interventions early can prevent or delay progression to microvascular complications that increase the mortality rate in diabetes. The authors review the guidelines for optimal evaluation of diabetes mellitus and discuss the current and emerging therapeutic options available in the United States. PMID:25126259

Methane oxidation behind reflected shock waves: Ignition delay times measured by pressure and flame band emission

NASA Technical Reports Server (NTRS)

Brabbs, T. A.; Robertson, T. F.

1986-01-01

Ignition delay data were recorded for three methane-oxygen-argon mixtures (phi = 0.5, 1.0, 2.0) for the temperature range 1500 to 1920 K. Quiet pressure trances enabled us to obtain delay times for the start of the experimental pressure rise. These times were in good agreement with those obtained from the flame band emission at 3700 A. The data correlated well with the oxygen and methane dependence of Lifshitz, but showed a much stronger temperature dependence (phi = 0.5 delta E = 51.9, phi = 1.0 delta = 58.8, phi = 2.0 delta E = 58.7 Kcal). The effect of probe location on the delay time measurement was studied. It appears that the probe located 83 mm from the reflecting surface measured delay times which may not be related to the initial temperature and pressure. It was estimated that for a probe located 7 mm from the reflecting surface, the measured delay time would be about 10 microseconds too short, and it was suggested that delay times less than 100 microsecond should not be used. The ignition period was defined as the time interval between start of the experimental pressure rise and 50 percent of the ignition pressure. This time interval was measured for three gas mixtures and found to be similar (40 to 60 micro sec) for phi = 1.0 and 0.5 but much longer (100 to 120) microsecond for phi = 2.0. It was suggested that the ignition period would be very useful to the kinetic modeler in judging the agreement between experimental and calculated delay times.

21 CFR 310.532 - Drug products containing active ingredients offered over-the-counter (OTC) to relieve the...

Code of Federal Regulations, 2012 CFR

2012-04-01

... of benign prostatic hypertrophy, e.g., urinary urgency and frequency, excessive urinating at night... delay diagnosis and treatment of progressive obstruction and secondary infections. Based on evidence...

21 CFR 310.532 - Drug products containing active ingredients offered over-the-counter (OTC) to relieve the...

Code of Federal Regulations, 2014 CFR

2014-04-01

... of benign prostatic hypertrophy, e.g., urinary urgency and frequency, excessive urinating at night... delay diagnosis and treatment of progressive obstruction and secondary infections. Based on evidence...

21 CFR 310.532 - Drug products containing active ingredients offered over-the-counter (OTC) to relieve the...

Code of Federal Regulations, 2013 CFR

2013-04-01

... of benign prostatic hypertrophy, e.g., urinary urgency and frequency, excessive urinating at night... delay diagnosis and treatment of progressive obstruction and secondary infections. Based on evidence...

47 CFR 22.313 - Station identification.

Code of Federal Regulations, 2014 CFR

2014-10-01

... Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES PUBLIC MOBILE SERVICES... delayed to avoid interrupting the continuity of any public communication in progress, provided that station identification is transmitted at the conclusion of that public communication. (c) Station...

47 CFR 22.313 - Station identification.

Code of Federal Regulations, 2012 CFR

2012-10-01

... Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES PUBLIC MOBILE SERVICES... delayed to avoid interrupting the continuity of any public communication in progress, provided that station identification is transmitted at the conclusion of that public communication. (c) Station...

47 CFR 22.313 - Station identification.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES PUBLIC MOBILE SERVICES... delayed to avoid interrupting the continuity of any public communication in progress, provided that station identification is transmitted at the conclusion of that public communication. (c) Station...

47 CFR 22.313 - Station identification.

Code of Federal Regulations, 2013 CFR

2013-10-01

... Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES PUBLIC MOBILE SERVICES... delayed to avoid interrupting the continuity of any public communication in progress, provided that station identification is transmitted at the conclusion of that public communication. (c) Station...

47 CFR 22.313 - Station identification.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES PUBLIC MOBILE SERVICES... delayed to avoid interrupting the continuity of any public communication in progress, provided that station identification is transmitted at the conclusion of that public communication. (c) Station...

Longitudinal Outcomes of Start Time Delay on Sleep, Behavior, and Achievement in High School.

PubMed

Thacher, Pamela V; Onyper, Serge V

2016-02-01

To establish whether sleep, health, mood, behavior, and academics improved after a 45-minute delay in high school start time, and whether changes persisted longitudinally. We collected data from school records and student self-report across a number of domains at baseline (May 2012) and at two follow-up time points (November 2012 and May 2013), at a public high school in upstate New York. Students enrolled during academic years (AY) 2011-2012 and 2012-2013 completed the Pittsburgh Sleep Quality Index; the DASS-21; the "Owl-Lark" Scale; the Daytime Sleepiness Index; and a brief self-report of health. Reports from school records regarding attendance, tardiness, disciplinary violations, and academic performance were collected for AY 2010-2011 through 2013-2014. Students delayed but did not extend their sleep period; we found lasting improvements in tardiness and disciplinary violations after the start-time delay, but no changes to other variables. At the first follow-up, students reported 20 minutes longer sleep, driven by later rise times and stable bed times. At the second follow-up, students maintained later rise times but delayed bedtimes, returning total sleep to baseline levels. A delay in rise time, paralleling the delay in the start time that occurred, resulted in less tardiness and decreased disciplinary incidents, but larger improvements to sleep patterns may be necessary to affect health, attendance, sleepiness, and academic performance. Later start times improved tardiness and disciplinary issues at this school district. A delay in start time may be a necessary but not sufficient means to increase sleep time and may depend on preexisting individual differences. A commentary on this article appears in this issue on page 267. © 2016 Associated Professional Sleep Societies, LLC.

Delays in Reducing Waterborne and Water-related Infectious Diseases in China under Climate Change

DOE PAGES

Hodges, Maggie; Belle, Jessica; Carlton, Elizabeth; ...

2014-11-02

Despite China’s rapid progress improving water, sanitation and hygiene (WSH) infrastructure and access, in 2011, 471 million people lacked access to improved sanitation, and 401 million people lacked access to household piped water. Infectious diseases are sensitive to changes in climate, particularly temperature, and WSH conditions. To explore possible impacts of climate change on these diseases in China in 2020 and 2030, we coupled estimates of the temperature sensitivity of diarrheal disease and three vector-borne diseases, temperature projections from global climate models using four emissions pathways, WSH-infrastructure development scenarios and projected demographic changes. By 2030, the projected impacts would delaymore » China’s historically rapid progress toward reducing the burden of WSH-attributable infectious disease by 8-85 months. This developmental delay provides a key summary measure of the impact of climate change in China, and in other societies undergoing rapid social, economic, and environmental change.« less

Delays in Reducing Waterborne and Water-related Infectious Diseases in China under Climate Change

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

Hodges, Maggie; Belle, Jessica; Carlton, Elizabeth

Despite China’s rapid progress improving water, sanitation and hygiene (WSH) infrastructure and access, in 2011, 471 million people lacked access to improved sanitation, and 401 million people lacked access to household piped water. Infectious diseases are sensitive to changes in climate, particularly temperature, and WSH conditions. To explore possible impacts of climate change on these diseases in China in 2020 and 2030, we coupled estimates of the temperature sensitivity of diarrheal disease and three vector-borne diseases, temperature projections from global climate models using four emissions pathways, WSH-infrastructure development scenarios and projected demographic changes. By 2030, the projected impacts would delaymore » China’s historically rapid progress toward reducing the burden of WSH-attributable infectious disease by 8-85 months. This developmental delay provides a key summary measure of the impact of climate change in China, and in other societies undergoing rapid social, economic, and environmental change.« less

Design of surface acoustic wave filters for the multiplex transmission system of multilevel inverter circuits

NASA Astrophysics Data System (ADS)

Kubo, Keita; Kanai, Nanae; Kobayashi, Fumiya; Goka, Shigeyoshi; Wada, Keiji; Kakio, Shoji

2017-07-01

We designed surface acoustic wave (SAW) filters for a multiplex transmission system of multilevel inverter circuits, and applied them to a single-phase three-level inverter. To reduce the transmission delay time of the SAW filters, a four-channel SAW filter array was fabricated and its characteristics were measured. The delay time of the SAW filters was <350 ns, and the delay time difference was reduced to ≤184 ns, less than half that previously reported. The SAW filters withstood up to 990 V, which is sufficient for the inverters used in most domestic appliances. A single-phase three-level inverter with the fabricated SAW filters worked with a total delay time shorter than our target delay time of 2.5 µs. The delay time difference of the proposed system was 0.26 µs, which is sufficient for preventing the inverter circuit from short-circuiting. The SAW filters controlled a multilevel inverter system with simple signal wiring and high dielectric withstanding voltages.

Effects of FDA approved medications for Alzheimer’s disease on clinical progression

PubMed Central

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

2011-01-01

Background Observational studies suggest cholinesterase inhibitors and/or memantine may delay clinical progression of Alzheimer’s disease (AD) in 40% of individuals taking the medications. Given this response and existence of side effects, we sought to quantify medication use and benefits in a population-based study of incident AD cases. Methods The Cache County Dementia Progression study (DPS) enrolled and followed a cohort of 327 incident AD cases up to 9 years. Drug exposure was expressed using a persistency index (PI), calculated as total years of drug use divided by total years of observation. Linear mixed effects models examined PI, and interactions with sex and APOE ε4, as predictors of clinical progression on the Mini-Mental State Exam (MMSE) and Clinical Dementia Rating-Sum of Boxes (CDR-Sum). Results Sixty-nine participants (21.1%) ever used cholinesterase inhibitors or memantine. There was a strong three-way interaction between PI, sex, and time. Among women, a higher PI (i.e. greater duration of use) of cholinesterase inhibitors was associated with slower progression on the MMSE and CDR-Sum, particularly among those with an APOE ε4 allele. In contrast, higher PI was associated with faster progression in males. Conclusion A low percentage of individuals with AD in the community are taking cholinesterase inhibitors or memantine. This study suggests that women, particularly those with an APOE ε4 allele, may receive the most benefit from these medications. With the newly approved increased dose of donepezil, it will be imperative to determine whether a higher dose is needed in men or whether other factors warrant consideration. PMID:22301194

The role of luteinizing hormone-releasing hormone in the diagnosis of constitutional delayed puberty

PubMed Central

Sagel, Julius; Distiller, Larry A.; Joffe, Barry I.

1975-01-01

The presumptive diagnosis of constitutional delayed adolescence is difficult to substantiate. Clinical examination and routine biochemical testing are not sufficient to exclude isolated gonadotrophin deficiency. Seven males are reported who presented with delayed puberty. These patients were given 100 μg luteinizing hormone-releasing hormone (LH-RH) intravenously, and the luteinizing hormone (LH) and follicle stimulating hormone (FSH) responses were measured. Three of four males who were completely prepubertal (Stage 1) had a normal adult male response. These three patients have progressed further into puberty several months after this diagnostic test. The fourth patient in stage 1 puberty had a prepubertal LH response. A year later the response became adult in type, and 3 months thereafter stage 2 puberty was evident. The LH response to LH-RH thus appears to have some prognostic value in the assessment of males presenting with delayed puberty. PMID:1105498

Incorporating time-delays in S-System model for reverse engineering genetic networks.

PubMed

Chowdhury, Ahsan Raja; Chetty, Madhu; Vinh, Nguyen Xuan

2013-06-18

In any gene regulatory network (GRN), the complex interactions occurring amongst transcription factors and target genes can be either instantaneous or time-delayed. However, many existing modeling approaches currently applied for inferring GRNs are unable to represent both these interactions simultaneously. As a result, all these approaches cannot detect important interactions of the other type. S-System model, a differential equation based approach which has been increasingly applied for modeling GRNs, also suffers from this limitation. In fact, all S-System based existing modeling approaches have been designed to capture only instantaneous interactions, and are unable to infer time-delayed interactions. In this paper, we propose a novel Time-Delayed S-System (TDSS) model which uses a set of delay differential equations to represent the system dynamics. The ability to incorporate time-delay parameters in the proposed S-System model enables simultaneous modeling of both instantaneous and time-delayed interactions. Furthermore, the delay parameters are not limited to just positive integer values (corresponding to time stamps in the data), but can also take fractional values. Moreover, we also propose a new criterion for model evaluation exploiting the sparse and scale-free nature of GRNs to effectively narrow down the search space, which not only reduces the computation time significantly but also improves model accuracy. The evaluation criterion systematically adapts the max-min in-degrees and also systematically balances the effect of network accuracy and complexity during optimization. The four well-known performance measures applied to the experimental studies on synthetic networks with various time-delayed regulations clearly demonstrate that the proposed method can capture both instantaneous and delayed interactions correctly with high precision. The experiments carried out on two well-known real-life networks, namely IRMA and SOS DNA repair network in Escherichia coli show a significant improvement compared with other state-of-the-art approaches for GRN modeling.

Interrelationships between marijuana demand and discounting of delayed rewards: Convergence in behavioral economic methods.

PubMed

Aston, Elizabeth R; Metrik, Jane; Amlung, Michael; Kahler, Christopher W; MacKillop, James

2016-12-01

Distinct behavioral economic domains, including high perceived drug value (demand) and delay discounting (DD), have been implicated in the initiation of drug use and the progression to dependence. However, it is unclear whether frequent marijuana users conform to a "reinforcer pathology" addiction model wherein marijuana demand and DD jointly increase risk for problematic marijuana use and cannabis dependence (CD). Participants (n=88, 34% female, 14% cannabis dependent) completed a marijuana purchase task at baseline. A delay discounting task was completed following placebo marijuana cigarette (0% THC) administration during a separate experimental session. Marijuana demand and DD were quantified using area under the curve (AUC). In multiple regression models, demand uniquely predicted frequency of marijuana use while DD did not. In contrast, DD uniquely predicted CD symptom count while demand did not. There were no significant interactions between demand and DD in either model. These findings suggest that frequent marijuana users exhibit key constituents of the reinforcer pathology model: high marijuana demand and steep discounting of delayed rewards. However, demand and DD appear to be independent rather than synergistic risk factors for elevated marijuana use and risk for progression to CD. Findings also provide support for using AUC as a singular marijuana demand metric, particularly when also examining other behavioral economic constructs that apply similar statistical approaches, such as DD, to support analytic methodological convergence. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Sirtuin 7 promotes cellular survival following genomic stress by attenuation of DNA damage, SAPK activation and p53 response

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

Kiran, Shashi; Oddi, Vineesha; Ramakrishna, Gayatri, E-mail: gayatrirama1@gmail.com

2015-02-01

Maintaining the genomic integrity is a constant challenge in proliferating cells. Amongst various proteins involved in this process, Sirtuins play a key role in DNA damage repair mechanisms in yeast as well as mammals. In the present work we report the role of one of the least explored Sirtuin viz., SIRT7, under conditions of genomic stress when treated with doxorubicin. Knockdown of SIRT7 sensitized osteosarcoma (U2OS) cells to DNA damage induced cell death by doxorubicin. SIRT7 overexpression in NIH3T3 delayed cell cycle progression by causing delay in G1 to S transition. SIRT7 overexpressing cells when treated with low dose ofmore » doxorubicin (0.25 µM) showed delayed onset of senescence, lesser accumulation of DNA damage marker γH2AX and lowered levels of growth arrest markers viz., p53 and p21 when compared to doxorubicin treated control GFP expressing cells. Resistance to DNA damage following SIRT7 overexpression was also evident by EdU incorporation studies where cellular growth arrest was significantly delayed. When treated with higher dose of doxorubicin (>1 µM), SIRT7 conferred resistance to apoptosis by attenuating stress activated kinases (SAPK viz., p38 and JNK) and p53 response thereby shifting the cellular fate towards senescence. Interestingly, relocalization of SIRT7 from nucleolus to nucleoplasm together with its co-localization with SAPK was an important feature associated with DNA damage. SIRT7 mediated resistance to doxorubicin induced apoptosis and senescence was lost when p53 level was restored by nutlin treatment. Overall, we propose SIRT7 attenuates DNA damage, SAPK activation and p53 response thereby promoting cellular survival under conditions of genomic stress. - Highlights: • Knockdown of SIRT7 sensitized cells to DNA damage induced apoptosis. • SIRT7 delayed onset of premature senescence by attenuating DNA damage response. • Overexpression of SIRT7 delayed cell cycle progression by delaying G1/S transition. • Upon DNA damage SIRT7 attenuated p38/JNK activation and also p53 response. • Overall, SIRT7 promoted cellular survival in conditions of genomic stress.« less

IDENTIFYING ANOMALIES IN GRAVITATIONAL LENS TIME DELAYS

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

Congdon, Arthur B.; Keeton, Charles R.; Nordgren, C. Erik, E-mail: acongdon@jpl.nasa.go, E-mail: keeton@physics.rutgers.ed, E-mail: nordgren@sas.upenn.ed

2010-02-01

We examine the ability of gravitational lens time delays to reveal complex structure in lens potentials. In a previous paper, we predicted how the time delay between the bright pair of images in a 'fold' lens scales with the image separation, for smooth lens potentials. Here we show that the proportionality constant increases with the quadrupole moment of the lens potential, and depends only weakly on the position of the source along the caustic. We use Monte Carlo simulations to determine the range of time delays that can be produced by realistic smooth lens models consisting of isothermal ellipsoid galaxiesmore » with tidal shear. We can then identify outliers as 'time delay anomalies'. We find evidence for anomalies in close image pairs in the cusp lenses RX J1131 - 1231 and B1422+231. The anomalies in RX J1131 - 1231 provide strong evidence for substructure in the lens potential, while at this point the apparent anomalies in B1422+231 mainly indicate that the time delay measurements need to be improved. We also find evidence for time delay anomalies in larger-separation image pairs in the fold lenses, B1608+656 and WFI 2033 - 4723, and the cusp lens RX J0911+0551. We suggest that these anomalies are caused by some combination of substructure and a complex lens environment. Finally, to assist future monitoring campaigns we use our smooth models with shear to predict the time delays for all known four-image lenses.« less

Identifying Anomalies in Gravitational Lens Time Delays

NASA Astrophysics Data System (ADS)

Congdon, Arthur B.; Keeton, Charles R.; Nordgren, C. Erik

2010-02-01

We examine the ability of gravitational lens time delays to reveal complex structure in lens potentials. In a previous paper, we predicted how the time delay between the bright pair of images in a "fold" lens scales with the image separation, for smooth lens potentials. Here we show that the proportionality constant increases with the quadrupole moment of the lens potential, and depends only weakly on the position of the source along the caustic. We use Monte Carlo simulations to determine the range of time delays that can be produced by realistic smooth lens models consisting of isothermal ellipsoid galaxies with tidal shear. We can then identify outliers as "time delay anomalies." We find evidence for anomalies in close image pairs in the cusp lenses RX J1131 - 1231 and B1422+231. The anomalies in RX J1131 - 1231 provide strong evidence for substructure in the lens potential, while at this point the apparent anomalies in B1422+231 mainly indicate that the time delay measurements need to be improved. We also find evidence for time delay anomalies in larger-separation image pairs in the fold lenses, B1608+656 and WFI 2033 - 4723, and the cusp lens RX J0911+0551. We suggest that these anomalies are caused by some combination of substructure and a complex lens environment. Finally, to assist future monitoring campaigns we use our smooth models with shear to predict the time delays for all known four-image lenses.

COSMOGRAIL XVII: Time Delays for the Quadruply Imaged Quasar PG 1115+080

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

Bonvin, V.; et al.

We present time-delay estimates for the quadruply imaged quasar PG 1115+080. Our resuls are based on almost daily observations for seven months at the ESO MPIA 2.2m telescope at La Silla Observatory, reaching a signal-to-noise ratio of about 1000 per quasar image. In addition, we re-analyse existing light curves from the literature that we complete with an additional three seasons of monitoring with the Mercator telescope at La Palma Observatory. When exploring the possible source of bias we consider the so-called microlensing time delay, a potential source of systematic error so far never directly accounted for in previous time-delay publications.more » In fifteen years of data on PG 1115+080, we find no strong evidence of microlensing time delay. Therefore not accounting for this effect, our time-delay estimates on the individual data sets are in good agreement with each other and with the literature. Combining the data sets, we obtain the most precise time-delay estimates to date on PG 1115+080, with Dt(AB) = 8.3+1.5-1.6 days (18.7% precision), Dt(AC) = 9.9+1.1-1.1 days (11.1%) and Dt(BC) = 18.8+1.6-1.6 days (8.5%). Turning these time delays into cosmological constraints is done in a companion paper that makes use of ground-based Adaptive Optics (AO) with the Keck telescope.« less

Nuclear reactor with internal thimble-type delayed neutron detection system

DOEpatents

Gross, Kenny C.; Poloncsik, John; Lambert, John D. B.

1990-01-01

This invention teaches improved apparatus for the method of detecting a breach in cladded fuel used in a nuclear reactor. The detector apparatus is located in the primary heat exchanger which conveys part of the reactor coolant past at least three separate delayed-neutron detectors mounted in this heat exchanger. The detectors are spaced apart such that the coolant flow time from the core to each detector is different, and these differences are known. The delayed-neutron activity at the detectors is a function of the delay time after the reaction in the fuel until the coolant carrying the delayed-neutron emitter passes the respective detector. This time delay is broken down into separate components including an isotopic holdup time required for the emitter to move through the fuel from the reaction to the coolant at the breach, and two transit times required for the emitter now in the coolant to flow from the breach to the detector loop and then via the loop to the detector. At least two of these time components are determined during calibrated operation of the reactor. Thereafter during normal reactor operation, repeated comparisons are made by the method of regression approximation of the third time component for the best-fit line correlating measured delayed-neutron activity against activity that is approximated according to specific equations. The equations use these time-delay components and known parameter values of the fuel and of the part and emitting daughter isotopes.

The interaction of hydroxyurea and ionizing radiation in human cervical carcinoma cells.

PubMed

Kuo, M L; Kunugi, K A; Lindstrom, M J; Kinsella, T J

1997-01-01

The results from prior in vitro and in vivo studies and recent phase 3 clinical trials suggest a significant potential role for hydroxyurea (HU) as a clinical radiosensitizer for cervix cancer. However, a detailed study of possible cellular mechanisms of radiosensitization in human cervix cancer cells as a consequence of dose and timing of HU and ionizing radiation (IR) has not been performed. This in vitro study analyses the interactions of HU and IR in a human cervical carcinoma cell line, Caski. Exponentially growing Caski cells were continuously exposed to clinically achievable but minimally cytotoxic concentrations of HU (0.3-3.0 mM) for various time intervals (6, 12, 18, 24, and 30 hours) up to one population doubling time either prior to or immediately following IR (2-8 Gy). The radiation survival data were analyzed using our modification of the linear-quadratic model to test for an interaction (greater than additive). The effects of HU alone, IR alone, and the combination on cell cycle progression and on apoptotic cell death in exponentially growing Caski cells were measured. We report a significant HU-IR interaction (radiosensitization) based on the sequence of HU exposure (post- > pre-IR) and with increasing concentrations of HU (0.3-3.0 mM), but no effect on radiosensitization with the duration of exposure to HU for up to one cell population doubling (6-30 hours). HU concentration has a significant effect on both alpha and beta linear-quadratic values in the post-IR sequences. Exposures of exponentially growing Caski cells to 1 mM and 3 mM HU alone result in a complete block in early S phase throughout the 30-hour exposure, while 0.3 mM HU causes a transient early S-phase block over the initial 12 to 18 hours of exposure. HU alone has no effect on cell cycle progression in G1 or G2/M populations but results in a large apoptotic population (31% following 1 mM HU x 30 hours), which appears to be the principal mechanism of drug cytotoxicity in these cells. IR alone (4 or 6 Gy) results in a significant G2 delay for 6 to 18 hours following IR but no G1 delay and a small apoptotic population at 30 hours post-IR (5.4% vs 2.1% in non-IR controls). The use of HU (0.3 or 1.0 mM) following IR (4 or 6 Gy) results in a significantly larger G2 delay compared with IR alone, but with only an additive effect on the apoptotic population. These in vitro data demonstrate that radiosensitization of Caski cells is more significant with post-IR exposures to clinically achievable concentrations of HU. This HU-IR interaction is associated with an increased G2 delay, suggesting a reduction in IR damage repair. However, this interaction appears to be independent of the cytotoxicity (principally by apoptosis) from HU alone.

Time and decision making: differential contribution of the posterior insular cortex and the striatum during a delay discounting task.

PubMed

Wittmann, Marc; Leland, David S; Paulus, Martin P

2007-06-01

Delay discounting refers to the fact that an immediate reward is valued more than the same reward if it occurs some time in the future. To examine the neural substrates underlying this process, we studied 13 healthy volunteers who repeatedly had to decide between an immediate and parametrically varied delayed hypothetical reward using a delay discounting task during event-related functional magnetic resonance imaging. Subject's preference judgments resulted in different discounting slopes for shorter (<1 year) and for longer (> or =1 year) delays. Neural activation associated with the shorter delays relative to the longer delays was associated with increased activation in the head of the left caudate nucleus and putamen. When individuals selected the delayed relative to the immediate reward, a strong activation was found in bilateral posterior insular cortex. Several brain areas including the left caudate nucleus showed a correlation between the behaviorally determined discounting and brain activation for the contrast of intervals with delays <1 and > or =1 year. These results suggest that (1) the posterior insula, which is a critical component of the decision-making neural network, is involved in delaying gratification and (2) the degree of neural activation in the striatum, which plays a fundamental role in reward prediction and in time estimation, may code for the time delay.

Light exposure during storage preserving soluble sugar and l-ascorbic acid content of minimally processed romaine lettuce (Lactuca sativa L.var. longifolia).

PubMed

Zhan, Lijuan; Hu, Jinqiang; Ai, Zhilu; Pang, Lingyun; Li, Yu; Zhu, Meiyun

2013-01-01

Minimally processed romaine lettuce (MPRL) leaves were stored in light condition (2500lux) or darkness at 4°C for 7d. Light exposure significantly delayed the degradation of chlorophyll and decrease of glucose, reducing sugar, and sucrose content, and thus preserved more total soluble solid (TSS) content at the end of storage in comparison with darkness. While, it did not influenced starch content that progressively decreased over time. The l-ascorbic acid (AA) accumulated in light-stored leaves, but deteriorated in dark-stored leaves during storage. The dehydroascorbic acid (DHA) increased in all leaves stored in both light and dark condition, of which light condition resulted in less DHA than darkness. In addition, the fresh weight loss and dry matter significantly increased and these increases were accelerated by light exposure. Conclusively, light exposure in applied intensity effectively alleviated MPRL quality deterioration by delaying the decreases of pigments, soluble sugar, TSS content and accumulating AA. Copyright © 2012 Elsevier Ltd. All rights reserved.

An essential role for the RNA-binding protein Smaug during the Drosophila maternal-to-zygotic transition.

PubMed

Benoit, Beatrice; He, Chun Hua; Zhang, Fan; Votruba, Sarah M; Tadros, Wael; Westwood, J Timothy; Smibert, Craig A; Lipshitz, Howard D; Theurkauf, William E

2009-03-01

Genetic control of embryogenesis switches from the maternal to the zygotic genome during the maternal-to-zygotic transition (MZT), when maternal mRNAs are destroyed, high-level zygotic transcription is initiated, the replication checkpoint is activated and the cell cycle slows. The midblastula transition (MBT) is the first morphological event that requires zygotic gene expression. The Drosophila MBT is marked by blastoderm cellularization and follows 13 cleavage-stage divisions. The RNA-binding protein Smaug is required for cleavage-independent maternal transcript destruction during the Drosophila MZT. Here, we show that smaug mutants also disrupt syncytial blastoderm stage cell-cycle delays, DNA replication checkpoint activation, cellularization, and high-level zygotic expression of protein coding and micro RNA genes. We also show that Smaug protein levels increase through the cleavage divisions and peak when the checkpoint is activated and zygotic transcription initiates, and that transgenic expression of Smaug in an anterior-to-posterior gradient produces a concomitant gradient in the timing of maternal transcript destruction, cleavage cell cycle delays, zygotic gene transcription, cellularization and gastrulation. Smaug accumulation thus coordinates progression through the MZT.

Parturition dysfunction in obesity: time to target the pathobiology.

PubMed

Carlson, Nicole S; Hernandez, Teri L; Hurt, K Joseph

2015-12-18

Over a third of women of childbearing age in the United States are obese, and during pregnancy they are at increased risk for delayed labor onset and slow labor progress that often results in unplanned cesarean delivery. The biology behind this dysfunctional parturition is not well understood. Studies of obesity-induced changes in parturition physiology may facilitate approaches to optimize labor in obese women. In this review, we summarize known and proposed biologic effects of obesity on labor preparation, contraction/synchronization, and endurance, drawing on both clinical observation and experimental data. We present evidence from human and animal studies of interactions between obesity and parturition signaling in all elements of the birth process, including: delayed cervical ripening, prostaglandin insensitivity, amniotic membrane strengthening, decreased myometrial oxytocin receptor expression, decreased myocyte action potential initiation and contractility, decreased myocyte gap junction formation, and impaired myocyte neutralization of reactive oxygen species. We found convincing clinical data on the effect of obesity on labor initiation and successful delivery, but few studies on the underlying pathobiology. We suggest research opportunities and therapeutic interventions based on plausible biologic mechanisms.

Zooming in on children's behavior during delay of gratification: Disentangling impulsigenic and volitional processes underlying self-regulation.

PubMed

Neuenschwander, Regula; Blair, Clancy

2017-02-01

When delaying gratification, both motivational and regulatory processes are likely to be at play; however, the relative contributions of motivational and regulatory influences on delay behavior are unclear. By examining behavioral responses during a delay task, this study sought to examine the motivational (anticipatory behavior) and regulatory mechanisms (executive function and self-control strategies) underlying children's self-regulation. The participants, 65 5- to 9-year-old children (M age =7.19years, SD=0.89), were video-recorded during a delay procedure and later coded for anticipatory behaviors (e.g., gazing intensely at the tablet) and self-control strategies. Children also completed two executive function (EF) tasks. We found that anticipatory behavior was curvilinearly related to delay time. Children showing either very low or very high levels of anticipatory behavior were not able to wait the entire time. Furthermore, our results indicated that anticipatory behavior interacted with EF to predict delay time. Specifically, anticipatory behavior was negatively related to delay time only if EF abilities were low. Finally, self-control strategies also interacted with EF to predict children's ability to delay. Spontaneous engagement in self-control strategies such as fidgeting and engagement in alternative activities were beneficial for children with low EF but were unrelated to delay time for children with high EF. Results indicate the value of examining motivational and regulatory influences on delay behavior. Lapses in self-regulation may be due to the combination of powerful impulsigenic (i.e., anticipatory behavior) and weak volitional processes (i.e., EF, self-control strategies). Copyright © 2016. Published by Elsevier Inc.

Finite-time resilient decentralized control for interconnected impulsive switched systems with neutral delay.

PubMed

Ren, Hangli; Zong, Guangdeng; Hou, Linlin; Yang, Yi

2017-03-01

This paper is concerned with the problem of finite-time control for a class of interconnected impulsive switched systems with neutral delay in which the time-varying delay appears in both the state and the state derivative. The concepts of finite-time boundedness and finite-time stability are respectively extended to interconnected impulsive switched systems with neutral delay for the first time. By applying the average dwell time method, sufficient conditions are first derived to cope with the problem of finite-time boundedness and finite-time stability for interconnected impulsive switched systems with neutral delay. In addition, the purpose of finite-time resilient decentralized control is to construct a resilient decentralized state-feedback controller such that the closed-loop system is finite-time bounded and finite-time stable. All the conditions are formulated in terms of linear matrix inequalities to ensure finite-time boundedness and finite-time stability of the given system. Finally, an example is presented to illustrate the effectiveness of the proposed approach. Copyright © 2017 ISA. Published by Elsevier Ltd. All rights reserved.

Method and apparatus for measuring the intensity and phase of an ultrashort light pulse

DOEpatents

Kane, Daniel J.; Trebino, Rick P.

1998-01-01

The pulse shape I(t) and phase evolution x(t) of ultrashort light pulses are obtained using an instantaneously responding nonlinear optical medium to form a signal pulse. A light pulse, such a laser pulse, is split into a gate pulse and a probe pulse, where the gate pulse is delayed relative to the probe pulse. The gate pulse and the probe pulse are combined within an instantaneously responding optical medium to form a signal pulse functionally related to a temporal slice of the gate pulse corresponding to the time delay of the probe pulse. The signal pulse is then input to a wavelength-selective device to output pulse field information comprising intensity vs. frequency for a first value of the time delay. The time delay is varied over a range of values effective to yield an intensity plot of signal intensity vs. wavelength and delay. In one embodiment, the beams are overlapped at an angle so that a selected range of delay times is within the intersection to produce a simultaneous output over the time delays of interest.

Radar wideband digital beamforming based on time delay and phase compensation

NASA Astrophysics Data System (ADS)

Fu, Wei; Jiang, Defu

2018-07-01

In conventional phased array radars, analogue time delay devices and phase shifters have been used for wideband beamforming. These methods suffer from insertion losses, gain mismatches and delay variations, and they occupy a large chip area. To solve these problems, a compact architecture of digital array antennas based on subarrays was considered. In this study, the receiving beam patterns of wideband linear frequency modulation (LFM) signals were constructed by applying analogue stretch processing via mixing with delayed reference signals at the subarray level. Subsequently, narrowband digital time delaying and phase compensation of the tone signals were implemented with reduced arithmetic complexity. Due to the differences in amplitudes, phases and time delays between channels, severe performance degradation of the beam patterns occurred without corrections. To achieve good beamforming performance, array calibration was performed in each channel to adjust the amplitude, frequency and phase of the tone signal. Using a field-programmable gate array, wideband LFM signals and finite impulse response filters with continuously adjustable time delays were implemented in a polyphase structure. Simulations and experiments verified the feasibility and effectiveness of the proposed digital beamformer.

77 FR 33718 - Taking and Importing Marine Mammals: Taking Marine Mammals Incidental to Navy Training Exercises...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-07

...). Here, the Navy identifies the distance that a marine mammal is likely to travel during the time... typically travel within a given time-delay period (Table 1). Based on acoustic propagation modeling... Speed and Length of Time-Delay Potential Species group Swim speed Time-delay (min) distance traveled (yd...

Acute and Chronic Kidney Injury in a Non-Human Primate Model of Partial-Body Irradiation with Bone Marrow Sparing.

PubMed

Cohen, Eric P; Hankey, Kim G; Bennett, Alexander W; Farese, Ann M; Parker, George A; MacVittie, Thomas J

2017-12-01

The development of medical countermeasures against acute and delayed multi-organ injury requires animal models predictive of the human response to radiation and its treatment. Late chronic injury is a well-known feature of radiation nephropathy, but acute kidney injury has not been reported in an appropriate animal model. We have established a single-fraction partial-body irradiation model with minimal marrow sparing in non-human primates. Subject-based medical management was used including parenteral fluids according to prospective morbidity criteria. We show herein that 10 or 11 Gy exposures caused both acute and chronic kidney injury. Acute and chronic kidney injury appear to be dose-independent between 10 and 11 Gy. Acute kidney injury was identified during the first 50 days postirradiation and appeared to resolve before the occurrence of chronic kidney injury, which was progressively more severe up to 180 days postirradiation, which was the end of the study. These findings show that mitigation of the acute radiation syndrome by medical management will unmask delayed late effects that occur months after partial-body irradiation. They further emphasize that both acute and chronic changes in kidney function must be taken into account in the use and timing of mitigators and medical management for acute radiation syndrome and delayed effects of acute radiation exposure (DEARE).

Dysphagia Causes Symptom Fluctuations after Oral L-DOPA Treatment in a Patient with Parkinson Disease.

PubMed

Sato, Hiromasa; Yamamoto, Toshiyuki; Sato, Masako; Furusawa, Yoshihiko; Murata, Miho

2018-01-01

The causes of "delayed-on" and "no-on" phenomena in Parkinson disease (PD) are thought to have some impact on the progress of L-DOPA from the time of ingestion until it reaches the brain and is converted to dopamine. Dysphagia can cause fluctuating symptom expression in L-DOPA therapy for PD. A 69-year-old man with PD presented with "delayed-on" and "no-on" phenomena. The patient developed a gait disorder at age 60 years, and he began coughing on his food during breakfast at age 64 years. Even though he was independent in daily life, he could not eat because of dysphagia in an "off" state. Videofluoroscopic examination of swallowing in an "off" state revealed bradykinesia of the tongue and the retention of tablets in the epiglottic vallecula. We trained him to keep his tongue in strong contact with the upper incisors before swallowing. After rehabilitation of dysphagia, the frequency of "delayed-on" and "no-on" phenomena decreased, and his peak L-DOPA plasma concentration was elevated. Additionally, transdermal rotigotine (RTG) was initiated at a maintenance dose of 9.0 mg. The patient reported improvement in swallowing, and the frequency of "no-on" phenomena decreased. In PD patients, the "no-on" phenomenon can be caused by posterior contractile dysfunction of the tongue, and it can be improved with training of the tongue and transdermal RTG administration.

Oedema-based model for diffuse low-grade gliomas: application to clinical cases under radiotherapy.

PubMed

Badoual, M; Gerin, C; Deroulers, C; Grammaticos, B; Llitjos, J-F; Oppenheim, C; Varlet, P; Pallud, J

2014-08-01

Diffuse low-grade gliomas are characterized by slow growth. Despite appropriate treatment, they change inexorably into more aggressive forms, jeopardizing the patient's life. Optimizing treatments, for example with the use of mathematical modelling, could help to prevent tumour regrowth and anaplastic transformation. Here, we present a model of the effect of radiotherapy on such tumours. Our objective is to explain observed delay of tumour regrowth following radiotherapy and to predict its duration. We have used a migration-proliferation model complemented by an equation describing appearance and draining of oedema. The model has been applied to clinical data of tumour radius over time, for a population of 28 patients. We were able to show that draining of oedema accounts for regrowth delay after radiotherapy and have been able to fit the clinical data in a robust way. The model predicts strong correlation between high proliferation coefficient and low progression-free gain of lifetime, due to radiotherapy among the patients, in agreement with clinical studies. We argue that, with reasonable assumptions, it is possible to predict (precision ~20%) regrowth delay after radiotherapy and the gain of lifetime due to radiotherapy. Our oedema-based model provides an early estimation of individual duration of tumour response to radiotherapy and thus, opens the door to the possibility of personalized medicine. © 2014 John Wiley & Sons Ltd.

Targeting Protein Quality Control Mechanisms by Natural Products to Promote Healthy Ageing.

PubMed

Wedel, Sophia; Manola, Maria; Cavinato, Maria; Trougakos, Ioannis P; Jansen-Dürr, Pidder

2018-05-19

Organismal ageing is associated with increased chance of morbidity or mortality and it is driven by diverse molecular pathways that are affected by both environmental and genetic factors. The progression of ageing correlates with the gradual accumulation of stressors and damaged biomolecules due to the time-dependent decline of stress resistance and functional capacity, which eventually compromise cellular homeodynamics. As protein machines carry out the majority of cellular functions, proteome quality control is critical for cellular functionality and is carried out through the curating activity of the proteostasis network (PN). Key components of the PN are the two main degradation machineries, namely the ubiquitin-proteasome and autophagy-lysosome pathways along with several stress-responsive pathways, such as that of nuclear factor erythroid 2-related factor 2 (Nrf2), which mobilises cytoprotective genomic responses against oxidative and/or xenobiotic damage. Reportedly, genetic or dietary interventions that activate components of the PN delay ageing in evolutionarily diverse organisms. Natural products (extracts or pure compounds) represent an extraordinary inventory of highly diverse structural scaffolds that offer promising activities towards meeting the challenge of increasing healthspan and/or delaying ageing (e.g., spermidine, quercetin or sulforaphane). Herein, we review those natural compounds that have been found to activate proteostatic and/or anti-stress cellular responses and hence have the potential to delay cellular senescence and/or in vivo ageing.

Biophysical modelling of early and delayed radiation damage at chromosome level

NASA Astrophysics Data System (ADS)

Andreev, S.; Eidelman, Y.

Exposure by ionising radiation increases cancer risk in human population Cancer is thought to originate from an altered expression of certain number of specific genes It is now widely recognised that chromosome aberrations CA are involved in stable change in expression of genes by gain or loss of their functions Thus CA can contribute to initiation or progression of cancer Therefore understanding mechanisms of CA formation in the course of cancer development might be valuable tool for quantification and prognosis of different stages of radiation carcinogenesis Early CA are defined as aberrations induced in first post-irradiation mitotic cycle The present work describes the original biophysical technique for early CA modelling It includes the following simulation steps the ionising particle track structure the structural organisation of all chromosomes in G 0 G 1 cell nucleus spatial distribution of radiation induced DNA double-strand breaks dsb within chromosomes dsb rejoining and misrejoining modelling cell cycle taking into account mitotic delay which results in complex time dependence of aberrant cells in first mitosis The results on prediction of dose-response curves for simple and complex CA measured in cells undergoing first division cycle are presented in comparison with recent experimental data There is increasing evidence that CA are also observed in descendents of irradiated cells many generations after direct DNA damage These delayed CA or chromosome instability CI are thought to be a manifestation of genome

An active balance board system with real-time control of stiffness and time-delay to assess mechanisms of postural stability.

PubMed

Cruise, Denise R; Chagdes, James R; Liddy, Joshua J; Rietdyk, Shirley; Haddad, Jeffrey M; Zelaznik, Howard N; Raman, Arvind

2017-07-26

Increased time-delay in the neuromuscular system caused by neurological disorders, concussions, or advancing age is an important factor contributing to balance loss (Chagdes et al., 2013, 2016a,b). We present the design and fabrication of an active balance board system that allows for a systematic study of stiffness and time-delay induced instabilities in standing posture. Although current commercial balance boards allow for variable stiffness, they do not allow for manipulation of time-delay. Having two controllable parameters can more accurately determine the cause of balance deficiencies, and allows us to induce instabilities even in healthy populations. An inverted pendulum model of human posture on such an active balance board predicts that reduced board rotational stiffness destabilizes upright posture through board tipping, and limit cycle oscillations about the upright position emerge as feedback time-delay is increased. We validate these two mechanisms of instability on the designed balance board, showing that rotational stiffness and board time-delay induced the predicted postural instabilities in healthy, young adults. Although current commercial balance boards utilize control of rotational stiffness, real-time control of both stiffness and time-delay on an active balance board is a novel and innovative manipulation to reveal balance deficiencies and potentially improve individualized balance training by targeting multiple dimensions contributing to standing balance. Copyright © 2017 Elsevier Ltd. All rights reserved.

Maturation delay for the predators can enhance stable coexistence for a class of prey-predator models.

PubMed

Banerjee, Malay; Takeuchi, Yasuhiro

2017-01-07

Maturation time delay for the predators is introduced in prey-predator models to implicitly model the stage-structure of predators. Most of the prey-predator models with maturation delay are known to exhibit destabilization of coexistence steady-state. Discrete time delay induced destabilization is a common finding, however, this is due to the introduction of time delay with lack of ecological justification. The main objective of the present work is to show the stabilizing role of maturation delay for a class of delayed prey-predator model. To be specific, we consider prey-predator models with strong and weak Allee effects in prey growth and Michaelis-Menten type functional response. We provide ecological justification for the introduction of maturation delay parameter in predator's growth equation. We obtain the conditions for stable and oscillatory coexistence of prey and their specialist predator in case of strong as well as weak Allee effect for non-delayed and delayed models. Apart from the analytical results for the models under consideration, we perform extensive numerical simulations to construct the relevant bifurcation diagrams. Our analytical and supportive numerical findings reveal that delay is not always a destabilizing factor rather the stable coexistence in the presence of time delay depends upon the formulation of the delayed model. The biological implications of the current investigation are provided in the conclusion section. We also explain the validity of obtained results for other types of prey-predator models with a specialist predator. Copyright © 2016 Elsevier Ltd. All rights reserved.

Oscillatory dynamics of an intravenous glucose tolerance test model with delay interval

NASA Astrophysics Data System (ADS)

Shi, Xiangyun; Kuang, Yang; Makroglou, Athena; Mokshagundam, Sriprakash; Li, Jiaxu

2017-11-01

Type 2 diabetes mellitus (T2DM) has become prevalent pandemic disease in view of the modern life style. Both diabetic population and health expenses grow rapidly according to American Diabetes Association. Detecting the potential onset of T2DM is an essential focal point in the research of diabetes mellitus. The intravenous glucose tolerance test (IVGTT) is an effective protocol to determine the insulin sensitivity, glucose effectiveness, and pancreatic β-cell functionality, through the analysis and parameter estimation of a proper differential equation model. Delay differential equations have been used to study the complex physiological phenomena including the glucose and insulin regulations. In this paper, we propose a novel approach to model the time delay in IVGTT modeling. This novel approach uses two parameters to simulate not only both discrete time delay and distributed time delay in the past interval, but also the time delay distributed in a past sub-interval. Normally, larger time delay, either a discrete or a distributed delay, will destabilize the system. However, we find that time delay over a sub-interval might not. We present analytically some basic model properties, which are desirable biologically and mathematically. We show that this relatively simple model provides good fit to fluctuating patient data sets and reveals some intriguing dynamics. Moreover, our numerical simulation results indicate that our model may remove the defect in well known Minimal Model, which often overestimates the glucose effectiveness index.

Neratinib Plus Paclitaxel vs Trastuzumab Plus Paclitaxel in Previously Untreated Metastatic ERBB2-Positive Breast Cancer: The NEfERT-T Randomized Clinical Trial.

PubMed

Awada, Ahmad; Colomer, Ramon; Inoue, Kenichi; Bondarenko, Igor; Badwe, Rajendra A; Demetriou, Georgia; Lee, Soo-Chin; Mehta, Ajay O; Kim, Sung-Bae; Bachelot, Thomas; Goswami, Chanchal; Deo, Suryanarayan; Bose, Ron; Wong, Alvin; Xu, Feng; Yao, Bin; Bryce, Richard; Carey, Lisa A

2016-12-01

Efficacious ERBB2 (formerly HER2 or HER2/neu)-directed treatments, in addition to trastuzumab and lapatinib, are needed. To determine whether neratinib, an irreversible pan-ERBB tyrosine kinase inhibitor, plus paclitaxel improves progression-free survival compared with trastuzumab plus paclitaxel in the first-line treatment of recurrent and/or metastatic ERBB2-positive breast cancer. In the randomized, controlled, open-label NEfERT-T trial conducted from August 2009 to December 2014 at 188 centers in 34 countries in Europe, Asia, Africa, and North America, 479 women with previously untreated recurrent and/or metastatic ERBB2-positive breast cancer were randomized to 1 of 2 treatment arms (neratinib-paclitaxel [n = 242] or trastuzumab-paclitaxel [n = 237]). Women with asymptomatic central nervous system metastases were eligible, and randomization was stratified by prior trastuzumab and lapatinib exposure, hormone-receptor status, and region. Women received neratinib (240 mg/d orally) or trastuzumab (4 mg/kg then 2 mg/kg weekly), each combined with paclitaxel (80 mg/m2 on days 1, 8, and 15 every 28 days). Primary prophylaxis for diarrhea was not mandatory. The primary outcome was progression-free survival. Secondary end points were response rate, clinical benefit rate, duration of response, frequency, and time to symptomatic and/or progressive central nervous system lesions, and safety. The intent-to-treat population comprised 479 women 18 years or older (neratinib-paclitaxel, n = 242; trastuzumab-paclitaxel, n = 237) randomized and stratified in their respective treatment arms by prior trastuzumab and lapatinib exposure, hormone-receptor status, and region. Median progression-free survival was 12.9 months (95% CI, 11.1-14.9) with neratinib-paclitaxel and 12.9 months (95% CI, 11.1-14.8) with trastuzumab-paclitaxel (hazard ratio [HR], 1.02; 95% CI, 0.81-1.27; P =.89). With neratinib-paclitaxel, the incidence of central nervous system recurrences was lower (relative risk, 0.48; 95% CI, 0.29-0.79; P = .002) and time to central nervous system metastases delayed (HR, 0.45; 95% CI, 0.26-0.78; P = .004). Common grade 3 to 4 adverse events were diarrhea (73 of 240 patients [30.4%] with neratinib-paclitaxel and 9 of 234 patients [3.8%] with trastuzumab-paclitaxel), neutropenia (31 patients [12.9%] vs 34 patients [14.5%]) and leukopenia (19 patients [7.9%] vs 25 patients [10.7%]); no grade 4 diarrhea was observed. In first-line ERBB2-positive metastatic breast cancer, neratinib-paclitaxel was not superior to trastuzumab-paclitaxel in terms of progression-free survival. In spite of similar overall efficacy, neratinib-paclitaxel may delay the onset and reduce the frequency of central nervous system progression, a finding that requires a larger study to confirm. clinicaltrials.gov Identifier: NCT00915018.

Modeling of synchronization behavior of bursting neurons at nonlinearly coupled dynamical networks.

PubMed

Çakir, Yüksel

2016-01-01

Synchronization behaviors of bursting neurons coupled through electrical and dynamic chemical synapses are investigated. The Izhikevich model is used with random and small world network of bursting neurons. Various currents which consist of diffusive electrical and time-delayed dynamic chemical synapses are used in the simulations to investigate the influences of synaptic currents and couplings on synchronization behavior of bursting neurons. The effects of parameters, such as time delay, inhibitory synaptic strengths, and decay time on synchronization behavior are investigated. It is observed that in random networks with no delay, bursting synchrony is established with the electrical synapse alone, single spiking synchrony is observed with hybrid coupling. In small world network with no delay, periodic bursting behavior with multiple spikes is observed when only chemical and only electrical synapse exist. Single-spike and multiple-spike bursting are established with hybrid couplings. A decrease in the synchronization measure is observed with zero time delay, as the decay time is increased in random network. For synaptic delays which are above active phase period, synchronization measure increases with an increase in synaptic strength and time delay in small world network. However, in random network, it increases with only an increase in synaptic strength.

Effects of delayed polymerization time and bracket manipulation on orthodontic resin modified glass ionomer adhesive

NASA Astrophysics Data System (ADS)

Gilbert, Danielle Wiggins

This study examined the effect of varying delayed polymerization times in combination with bracket manipulation on shear bond strength (SBS), degree of conversion (DC), and adhesive remnant index (ARI) score when using a resin modified glass ionomer (RMGI) adhesive. Specimens were divided into three groups of clinically relevant delay times (0.5, 2, and 4-min) to simulate the delay that frequently occurs between bracket placement and manipulation and subsequent light curing. Based on an analysis of variance (alpha=.05), the SBS was not significantly different between the three groups. While one of the goals of this study was to be the first study to quantify DC of RMGI using Raman microspectroscopy, several challenges, including weak peak signal with and without fluorescence, were encountered and as a result, DC could not be determined. A significant difference (p<0.05) in ARI score was detected between the 0.5-min and 4.0-min delay groups with more adhesive remaining on the bracket with increasing delay time. A Spearman correlation between SBS and ARI indicated no positive association between SBS and ARI measures across delay times. The results of this study suggest that clinically relevant delay times of 0.5, 2, and 4-min do not negatively impact the SBS of a RMGI adhesive. However, with increasing delay time, the results suggest that more adhesive might remain on the bracket during debonding. With more adhesive remaining on the bracket, this could be beneficial in that less adhesive needs to be removed from enamel by grinding at the time of bracket removal when orthodontic treatment is completed.