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Sample records for therapeutic delay reduces

  1. Reducing Transmitted Vibration Using Delayed Hysteretic Suspension

    Directory of Open Access Journals (Sweden)

    Lahcen Mokni

    2011-01-01

    Full Text Available Previous numerical and experimental works show that time delay technique is efficient to reduce transmissibility of vibration in a single pneumatic chamber by controlling the pressure in the chamber. The present work develops an analytical study to demonstrate the effectiveness of such a technique in reducing transmitted vibrations. A quarter-car model is considered and delayed hysteretic suspension is introduced in the system. Analytical predictions based on perturbation analysis show that a delayed hysteretic suspension enhances vibration isolation comparing to the case where the nonlinear damping is delay-independent.

  2. Reducing Delay in Diagnosis: Multistage Recommendation Tracking.

    Science.gov (United States)

    Wandtke, Ben; Gallagher, Sarah

    2017-11-01

    The purpose of this study was to determine whether a multistage tracking system could improve communication between health care providers, reducing the risk of delay in diagnosis related to inconsistent communication and tracking of radiology follow-up recommendations. Unconditional recommendations for imaging follow-up of all diagnostic imaging modalities excluding mammography (n = 589) were entered into a database and tracked through a multistage tracking system for 13 months. Tracking interventions were performed for patients for whom completion of recommended follow-up imaging could not be identified 1 month after the recommendation due date. Postintervention compliance with the follow-up recommendation required examination completion or clinical closure (i.e., biopsy, limited life expectancy or death, or subspecialist referral). Baseline radiology information system checks performed 1 month after the recommendation due date revealed timely completion of 43.1% of recommended imaging studies at our institution before intervention. Three separate tracking interventions were studied, showing effectiveness between 29.0% and 57.8%. The multistage tracking system increased the examination completion rate to 70.5% (a 52% increase) and reduced the rate of unknown follow-up compliance and the associated risk of delay in diagnosis to 13.9% (a 74% decrease). Examinations completed after tracking intervention generated revenue of 4.1 times greater than the labor cost. Performing sequential radiology recommendation tracking interventions can substantially reduce the rate of unknown follow-up compliance and add value to the health system. Unknown follow-up compliance is a risk factor for delay in diagnosis, a form of preventable medical error commonly identified in malpractice claims involving radiologists and office-based practitioners.

  3. Delay generation methods with reduced memory requirements

    DEFF Research Database (Denmark)

    Tomov, Borislav Gueorguiev; Jensen, Jørgen Arendt

    2003-01-01

    Modern diagnostic ultrasound beamformers require delay information for each sample along the image lines. In order to avoid storing large amounts of focusing data, delay generation techniques have to be used. In connection with developing a compact beamformer architecture, recursive algorithms we...

  4. [Delayed-type hypersensitivity to heparin: diagnosis and therapeutic management].

    Science.gov (United States)

    Nosbaum, A; Pralong, P; Rozieres, A; Dargaud, Y; Nicolas, J-F; Bérard, F

    2012-05-01

    Heparin is widely used as an anticoagulant and is indicated in the prevention and treatment of thromboembolic disorders. Heparin-induced delayed-type hypersensitivity presents as eczematous lesions, either at the injection site or generally, and affects 7.5% of patients on heparin. This poses diagnostic and therapeutic issues, since an alternative anticoagulant treatment is essential and the risk of cross-reactivity may be as high as 80%, depending on the type of heparin used. If delayed-type hypersensitivity is suspected, heparin-induced thrombocytopenia must first be ruled out, and heparin should be stopped. Fondaparinux is currently the first-line alternative, with a risk of cross-reactivity estimated at only 10%. The switch from a low-molecular-weight heparin (LMWH) to another LMWH is no longer recommended. The use of unfractionated heparin, danaparoid or hirudin may be warranted in the event of recurrence with fondaparinux, and an immuno-allergological work-up is needed to specify the exact profile of cross-allergies. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  5. Thinking about Death Reduces Delay Discounting

    Science.gov (United States)

    Kelley, Nicholas J.; Schmeichel, Brandon J.

    2015-01-01

    The current study tested competing predictions regarding the effect of mortality salience on delay discounting. One prediction, based on evolutionary considerations, was that reminders of death increase the value of the present. Another prediction, based in part on construal level theory, was that reminders of death increase the value of the future. One-hundred eighteen participants thought about personal mortality or a control topic and then completed an inter-temporal choice task pitting the chance to gain $50 now against increasingly attractive rewards three months later. Consistent with the hypothesis inspired by construal theory, participants in the mortality salience condition traded $50 now for $66.67 in three months, whereas participants in the dental pain salience condition required $72.84 in three months in lieu of $50 now. Thus, participants in the mortality salience condition discounted future monetary gains less than other participants, suggesting that thoughts of death may increase the subjective value of the future. PMID:26630664

  6. Thinking about Death Reduces Delay Discounting.

    Directory of Open Access Journals (Sweden)

    Nicholas J Kelley

    Full Text Available The current study tested competing predictions regarding the effect of mortality salience on delay discounting. One prediction, based on evolutionary considerations, was that reminders of death increase the value of the present. Another prediction, based in part on construal level theory, was that reminders of death increase the value of the future. One-hundred eighteen participants thought about personal mortality or a control topic and then completed an inter-temporal choice task pitting the chance to gain $50 now against increasingly attractive rewards three months later. Consistent with the hypothesis inspired by construal theory, participants in the mortality salience condition traded $50 now for $66.67 in three months, whereas participants in the dental pain salience condition required $72.84 in three months in lieu of $50 now. Thus, participants in the mortality salience condition discounted future monetary gains less than other participants, suggesting that thoughts of death may increase the subjective value of the future.

  7. Therapeutic hypothermia reduces intestinal ischemia/reperfusion ...

    African Journals Online (AJOL)

    To investigate the effects of therapeutic hypothermia (TH) on the morphology and function of intestine after cardiac arrest and resuscitation, 45 male rats were randomly assigned into three groups: (1) normothermia group, animals underwent ventricular fibrillation (VF) and cardiopulmonary resuscitation (CPR) with the rectal ...

  8. Advanced access: reducing waiting and delays in primary care.

    Science.gov (United States)

    Murray, Mark; Berwick, Donald M

    2003-02-26

    Delay of care is a persistent and undesirable feature of current health care systems. Although delay seems to be inevitable and linked to resource limitations, it often is neither. Rather, it is usually the result of unplanned, irrational scheduling and resource allocation. Application of queuing theory and principles of industrial engineering, adapted appropriately to clinical settings, can reduce delay substantially, even in small practices, without requiring additional resources. One model, sometimes referred to as advanced access, has increasingly been shown to reduce waiting times in primary care. The core principle of advanced access is that patients calling to schedule a physician visit are offered an appointment the same day. Advanced access is not sustainable if patient demand for appointments is permanently greater than physician capacity to offer appointments. Six elements of advanced access are important in its application balancing supply and demand, reducing backlog, reducing the variety of appointment types, developing contingency plans for unusual circumstances, working to adjust demand profiles, and increasing the availability of bottleneck resources. Although these principles are powerful, they are counter to deeply held beliefs and established practices in health care organizations. Adopting these principles requires strong leadership investment and support.

  9. Relationship of diagnostic and therapeutic delay with survival in colorectal cancer: a review.

    Science.gov (United States)

    Ramos, Maria; Esteva, Magdalena; Cabeza, Elena; Campillo, Carlos; Llobera, Joan; Aguiló, Antonio

    2007-11-01

    Early diagnosis of colorectal cancer before the onset of symptoms improves survival. Once symptoms have occurred, however, the effect of delay on survival is unclear. We review here evidence on the relationship of diagnostic and therapeutic delay with survival in colorectal cancer. We conducted a systematic of Medline, Embase, Cancerlit and the Cochrane Database of Systematic Reviews to identify publications published between 1962 and 2006 dealing with delay, survival and colon cancer. A meta-analysis was performed based on the calculation of the relative risk (RR) and on a model of random effects. We identified 40 studies, representing 20,440 patients. Fourteen studies were excluded due to excessively restricted samples (e.g. exclusion of patients with intestinal obstruction, with tumours at stage C or D at the time of diagnosis, or who died 1-3 months after surgery); or because they studied only a portion of the delay. Of the 26 remaining studies, 20 showed no association between delay and survival. In contrast, four studies showed that delay was a factor contributing to better prognosis, and two showed that it contributed to poorer prognosis. There was no association between delay and survival when the colon and rectum were considered separately, when a multivariate analysis was performed, and when the effects of tumour stage and degree of differentiation were taken into account. To perform a meta-analysis, 18 additional studies were excluded, since the published articles did not specify the absolute numbers. In the remaining eight studies, the combined relative risk (RR) of delay was 0.92 (confidence interval (CI) 95%: 0.87-0.97). The results of the review suggest that there is no association between diagnostic and therapeutic delay and survival in colorectal cancer patients. Colon and rectum should be assessed separately, and it is necessary to adjust for other relevant variables such as tumour stage.

  10. Reduced turning frequency and delayed poultry manure addition reduces N loss from sugarcane compost.

    Science.gov (United States)

    Bryndum, S; Muschler, R; Nigussie, A; Magid, J; de Neergaard, A

    2017-07-01

    Composting is an effective method to recycle biodegradable waste as soil amendment in smallholder farming systems. Although all essential plant nutrients are found in compost, a substantial amount of nitrogen is lost during composting. This study therefore investigated the potential of reducing N losses by (i) delaying the addition of nitrogen-rich substrates (i.e. poultry manure), and (ii) reducing the turning frequency during composting. Furthermore, we tested the effect of compost application method on nitrogen mineralization. Sugarcane-waste was composted for 54days with addition of poultry manure at the beginning (i.e. early addition) or after 21days of composting (delayed addition). The compost pile was then turned either every three or nine days. Composts were subsequently applied to soil as (i) homogeneously mixed, or (ii) stratified, and incubated for 28days to test the effect of compost application on nitrogen mineralization. The results showed that delayed addition of poultry manure reduced total nitrogen loss by 33% and increased mineral nitrogen content by >200% compared with early addition. Similarly, less frequent turning reduced total N loss by 12% compared with frequent turning. Stratified placement of compost did not enhance N mineralization compared to a homogeneous mixing. Our results suggested that simple modifications of the composting process (i.e. delayed addition and/or turning frequency) could significantly reduce N losses and improve the plant-nutritional value of compost. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Lack of association between diagnostic and therapeutic delay and stage of colorectal cancer.

    Science.gov (United States)

    Ramos, Maria; Esteva, Magdalena; Cabeza, Elena; Llobera, Joan; Ruiz, Amador

    2008-03-01

    A recent review suggests that there is no association between diagnostic and therapeutic delays and survival in colorectal cancer patients. However, the effect of tumour stage on the relationship between delay and survival in CRC should be clarified. We review here the evidence on the relationship between diagnostic and therapeutic delays and stage in colorectal cancer. We conducted a systematic review of Medline, Embase, Cancerlit and the Cochrane Database of Systematic Reviews to identify publications published between 1965 and 2006 dealing with delay, stage and colorectal cancer. A meta-analysis was performed based on the estimation of the odds ratios (OR) and on a random effects model. We identified 50 studies, representing 18,649 patients. Thirty studies were excluded due to excessively restricted samples (e.g. exclusion of patients with intestinal obstruction or who died 1-3 months after surgery) or because they studied only a portion of the delay. Of the 37 remaining studies, great variability was noted in connection with the type of classification used for disease stage and the type of measurement used for the delay. Meta-analysis was performed based on 17 studies that included 5209 patients. The combined OR was 0.98 (95% confidence interval (CI): 0.76-1.25), suggesting a lack of association between delay and disease stage. In four studies, cancers of the colon and rectum were dealt with separately, and a meta-analysis was performed using the data for colon cancer (1001 patients) and for rectal cancer (799 patients). In both cases, the combined ORs overlapped 1.0, and showed opposite associations when studied separately: 0.86 (95% CI: 0.63-1.19) for the colon (i.e. more delay is associated with the earlier stage at diagnosis) and 1.93 (95% CI: 0.89-4.219) for the rectum (i.e. less delay is associated with the earlier stage). When colorectal cancers are taken as a whole, there appears to be no association between diagnostic delay and disease stage when

  12. Reducing therapeutic injection overuse through patients-prescribers ...

    African Journals Online (AJOL)

    Reducing therapeutic injection overuse through patients-prescribers Interaction Group Discussions in Kinondoni District, Dar es Salaam, Tanzania. ... Prescribed injections that complied with STG was low at baseline and did not significantly improve 3 months after (P>0.05, Χ2 test). Comprehensive studies and sensitization ...

  13. Reduced turning frequency and delayed poultry manure addition reduces N loss from sugarcane compost

    DEFF Research Database (Denmark)

    Bryndum, Sofie; Muschler, R.; Nigatu, Abebe Nigussie

    2017-01-01

    Composting is an effective method to recycle biodegradable waste as soil amendment in smallholder farming systems. Although all essential plant nutrients are found in compost, a substantial amount of nitrogen is lost during composting. This study therefore investigated the potential of reducing N...... losses by (i) delaying the addition of nitrogen-rich substrates (i.e. poultry manure), and (ii) reducing the turning frequency during composting. Furthermore, we tested the effect of compost application method on nitrogen mineralization. Sugarcane-waste was composted for 54days with addition of poultry...... manure at the beginning (i.e. early addition) or after 21days of composting (delayed addition). The compost pile was then turned either every three or nine days. Composts were subsequently applied to soil as (i) homogeneously mixed, or (ii) stratified, and incubated for 28days to test the effect...

  14. Sulfuretin has therapeutic activity against acquired lymphedema by reducing adipogenesis.

    Science.gov (United States)

    Roh, Kangsan; Kim, Suji; Kang, Hee; Ku, Jin-Mo; Park, Kye Won; Lee, Sukchan

    2017-07-01

    Acquired lymphedema is a pathological condition associated with lymphatic dysfunction caused by surgical treatments for cancer. Although global estimates of the prevalence of acquired lymphedema have been rising, there are currently no effective therapeutics available. Since adipose tissue accumulation is a clinical hallmark of lymphedema, we hypothesized that regulation of adipogenesis in lymphedematous tissue could be used as a therapeutic intervention against lymphedema. Toward this, we investigated the possibility of anti-adipogenic 30% ethanol Rhus verniciflua Stokes (RVS) extract as a potential lymphedema treatment. Oral administration of RVS extract ameliorated volumetric symptoms of lymphedema in a mouse model. RVS administration also reduced adipose tissue accumulation in lymphedematous tissue and downregulated expression of adipocyte markers, including Pparγ and Fabp4. Sulfuretin was identified as a major bioactive compound in the 30% ethanol RVS extract in liquid chromatography-mass spectrometry analysis. Similar to the activities of RVS, sulfuretin inhibited adipocyte differentiation in 3T3-L1 preadipocytes. Moreover, treatment with sulfuretin on lymphedema-induced mice reduced lymphedema volume, decreased the expression of adipogenic markers, but induced the expression of markers associated with lymphangiogenesis. Taken together, our data raise the possibility that sulfuretin might be used in therapeutic interventions against acquired lymphedema. Copyright © 2017. Published by Elsevier Ltd.

  15. Offload zone patient selection criteria to reduce ambulance offload delay

    NARCIS (Netherlands)

    Laan, Corine Maartje; Vanberkel, Peter T.; Boucherie, Richardus J.; Carter, Alix J.E.

    2016-01-01

    Emergency department overcrowding is a widespread problem and often leads to ambulance offload delay. If no bed is available when a patient arrives, the patient has to wait with the ambulance crew. A recent Canadian innovation is the offload zone—an area where multiple patients can wait with a

  16. Parecoxib reduces systemic inflammation and acute lung injury in burned animals with delayed fluid resuscitation.

    Science.gov (United States)

    Chong, Si Jack; Wong, Yong Chiat; Wu, Jian; Tan, Mui Hong; Lu, Jia; Moochhala, Shabbir M

    2014-01-01

    Burn injuries result in the release of proinflammatory mediators causing both local and systemic inflammation. Multiple organ dysfunctions secondary to systemic inflammation after severe burn contribute to adverse outcome, with the lungs being the first organ to fail. In this study, we evaluate the anti-inflammatory effects of Parecoxib, a parenteral COX-2 inhibitor, in a delayed fluid resuscitation burned rat model. Anaesthetized Sprague Dawley rats were inflicted with 45% total body surface area full-thickness scald burns and subsequently subjected to delayed resuscitation with Hartmann's solution. Parecoxib (0.1, 1.0, and 10 mg/kg) was delivered intramuscularly 20 min after injury followed by 12 h interval and the rats were sacrificed at 6 h, 24 h, and 48 h. Burn rats developed elevated blood cytokines, transaminase, creatinine, and increased lung MPO levels. Animals treated with 1 mg/kg Parecoxib showed significantly reduced plasma level of CINC-1, IL-6, PGEM, and lung MPO. Treatment of 1 mg/kg Parecoxib is shown to mitigate systemic and lung inflammation without significantly affecting other organs. At present, no specific therapeutic agent is available to attenuate the systemic inflammatory response secondary to burn injury. The results suggest that Parecoxib may have the potential to be used both as an analgesic and ameliorate the effects of lung injury following burn.

  17. Correlation between the different therapeutic properties of Chinese medicinal herbs and delayed luminescence.

    Science.gov (United States)

    Pang, Jingxiang; Fu, Jialei; Yang, Meina; Zhao, Xiaolei; van Wijk, Eduard; Wang, Mei; Fan, Hua; Han, Jinxiang

    2016-03-01

    In the practice and principle of Chinese medicine, herbal materials are classified according to their therapeutic properties. 'Cold' and 'heat' are the most important classes of Chinese medicinal herbs according to the theory of traditional Chinese medicine (TCM). In this work, delayed luminescence (DL) was measured for different samples of Chinese medicinal herbs using a sensitive photon multiplier detection system. A comparison of DL parameters, including mean intensity and statistic entropy, was undertaken to discriminate between the 'cold' and 'heat' properties of Chinese medicinal herbs. The results suggest that there are significant differences in mean intensity and statistic entropy and using this method combined with statistical analysis may provide novel parameters for the characterization of Chinese medicinal herbs in relation to their energetic properties. Copyright © 2015 John Wiley & Sons, Ltd.

  18. Candesartan reduces the hemorrhage associated with delayed tissue plasminogen activator treatment in rat embolic stroke.

    Science.gov (United States)

    Ishrat, Tauheed; Pillai, Bindu; Ergul, Adviye; Hafez, Sherif; Fagan, Susan C

    2013-12-01

    We have previously reported that angiotensin receptor blockade reduces reperfusion hemorrhage in a suture occlusion model of stroke, despite increasing matrix metalloproteinase (MMP-9) activity. We hypothesized that candesartan will also decrease hemorrhage associated with delayed (6 h) tissue plasminogen activator (tPA) administration after embolic stroke, widening the therapeutic time window of tPA. Adult male Wistar rats were subjected to embolic middle cerebral artery occlusion (eMCAO) and treated with either candesartan (1 mg/kg) alone early at 3 h, delayed tPA (10 mg/kg) alone at 6 h, the combination of candesartan and tPA, or vehicle control. Rats were sacrificed at 24 and 48 h post-eMCAO and brains perfused for evaluation of neurological deficits, cerebral hemorrhage in terms of hemoglobin content, occurrence rate of hemorrhage, infarct size, tissue MMP activity and protein expression. The combination therapy of candesartan and tPA after eMCAO reduced the brain hemorrhage, and improved neurological outcome compared with rats treated with tPA alone. Further, candesartan in combination with tPA increased activity of MMP-9 but decreased MMP-3, nuclear factor kappa-B and tumor necrosis factor-α expression and enhanced activation of endothelial nitric oxide synthase. An activation of MMP-9 alone is insufficient to cause increased hemorrhage in embolic stroke. Combination therapy with acute candesartan plus tPA may be beneficial in ameliorating tPA-induced hemorrhage after embolic stroke.

  19. Smart Telerobotic Surveillance System via Internet with Reduced Time Delay

    Directory of Open Access Journals (Sweden)

    Ashesh Vasalya

    2012-09-01

    Full Text Available This work provides an imperial solution to the problems faced by man while enduring hazardous tasks like handling and disposal of nuclear wastes, monitoring nuclear power plants, mining operations etc .which have to be aborted if expertise group running it is unavailable or on a run. This paper presents a distributed platform that allows the special group of user to control a gadget (possibly a robot through internet as a medium. An advanced version of this technology is capable of transmitting graphic images and other surrounding information as required, via internet back to the user to facilitate the effective monitoring of the existent situation using appropriate software tools. The project uses the SRV-1 Mobile Surveillance Robot which is a fully integrated system standard designed and other related technology for surveillance purposes. It is driven via web browser using JAVA based control applications with live video feeds. Specialised user group will be given separate account from where they can control and monitor the system even when they are not present at the site. End user will be connected to the gadget (robot through a central server which acts as a single channel for both sending and receiving information. But the subject of remote control over the internet has some possible anomalies namely network freezing, delay between host and recipient, congested network and many others. This system enables asynchronous object passing so that network bandwidth is used effectively and such parameters as the network condition and server states have less effect on the system. To resolve this issue, a fuzzy logic controller is used to control the robot’s motion along a predefined path with the necessary manipulation of the normal course. The robot was first modelled in Matlab Simulink and the fuzzy logic rules were optimized for the best results possible. In accordance with the fuzzy rules developed the fuzzy interference system generates the

  20. Quality Improvement Project to Reduce Delayed Vaccinations in Preterm Infants.

    Science.gov (United States)

    Cuna, Alain; Winter, Lindy

    2017-08-01

    Preterm infants are especially vulnerable to infectious diseases. Although vaccinations are a safe and effective measure to protect preterm infants from vaccine-preventable diseases, delays in vaccinations are not uncommon. The goal of this quality improvement project was to improve on time vaccinations of preterm infants hospitalized in the neonatal intensive care unit. The Plan-Do-Study-Act model of quality improvement was adopted to develop, test, and implement interventions aimed at improving timely vaccination of preterm infants. The primary outcome measure of interest was the rate of on time vaccination, which was defined as the proportion of medically eligible preterm infants who received vaccinations within 2 weeks of the recommended schedule. Baseline on time vaccination rate was only 36%. Following several Plan-Do-Study-Act cycles, a steady increase in on time vaccinations of eligible infants was observed, and a new baseline on time vaccination rate of 82% was achieved. Simple interventions implemented within the context of Plan-Do-Study-Act cycles are effective in improving timely vaccinations among preterm infants. Future research that focuses on vaccinations in preterm infants is needed to further reinforce the safety and efficacy of vaccines. Effective methods on how to disseminate and apply this knowledge to practice should also be studied.Video Abstract available at http://links.lww.com/ANC/A27.

  1. Music as a Therapeutic Assistant: Strategy to Reduce Work Stress

    Directory of Open Access Journals (Sweden)

    Dereck Sena de Lima

    2017-02-01

    Full Text Available Objective: to understand the influence of music as a therapeutic assistant in reducing work stress of nursing professionals in a basic health unit. Method: it is an exploratory and descriptive research with a quantitative approach, developed with 9 nursing professionals from UBS Integrated Nova Esperança in João Pessoa, Paraíba. Data collection began after approval of the Research Ethics Committee of the Health Sciences Center of the Federal University of Paraíba, nº. 0508/16, CAAE: 58741916.6.0000.5188. Results: we identified that 33.3% of nursing professionals presented signs of stress, of the 33.3% who presented stress, 100% demonstrated to be in the resistance phase, 100% of the nursing professionals evaluated the musical strategy in a positive way. Conclusion: the musical strategy received extremely positive evaluations by the participants of the research, about 100% of professionals said that listening to music can reduce work stress.

  2. A prompt plus delayed contingency procedure for reducing bathroom graffiti.

    Science.gov (United States)

    Watson, T S

    1996-01-01

    This study assessed the effectiveness of posting signs for reducing graffiti in three men's restrooms on a college campus using a multiple baseline across settings design. During baseline, graffiti increased almost daily in each of the three settings. Immediately following the intervention, no marks were made on any of the three walls. Results were maintained at 3-month follow-up. A possible explanation for the results is that the signs specified an altruistic contingency.

  3. Evaluation of the effectiveness of kinesiotaping in reducing delayed onset muscle soreness of the biceps brachii

    Directory of Open Access Journals (Sweden)

    Boguszewski Dariusz

    2016-07-01

    Full Text Available biological regeneration in athletes. The aim of this study was to evaluate the effectiveness of the application of lymphatic kinesiotaping in reducing delayed onset muscle soreness of biceps brachii.

  4. Evaluation of the effectiveness of kinesiotaping in reducing delayed onset muscle soreness of the biceps brachii

    National Research Council Canada - National Science Library

    Dariusz Boguszewski; Beata Oko; Jakub Grzegorz Adamczyk; Dariusz Białoszewski

    2016-01-01

    biological regeneration in athletes. The aim of this study was to evaluate the effectiveness of the application of lymphatic kinesiotaping in reducing delayed onset muscle soreness of biceps brachii...

  5. Proposed method of reducing ground vibration from delay blasting

    Energy Technology Data Exchange (ETDEWEB)

    Coursen, D.L. [Dynatec Explosives Consultants, Inc., Espanola, NM (United States)

    1995-12-31

    In the proposed method, the charges are elongated and arranged in one or more arrays. The orientation of each charge in an array, its velocity of propagation of explosion, and the velocity of propagation of vibration in the formation are such that, at an outlying location where vibration is to be reduced, the onset of vibration from the explosion of the first negligibly small increment of each charge arrives a finite time before that from the explosion of the last negligibly small increment of that charge. The charges of each array are fired in accurately-timed sequence, with the times between initiations chosen so that, at the outlying location, the onset of vibration from the explosion of the last small increment of each charge, except the last charge, arrives a negligibly small increment of time before the onset of vibration from the explosion of the first negligibly small increment of the succeeding charge. With such timing, vibration may be reduced at the widest range of locations by tilting the boreholes so that the terminal end of each charge is directly above or below the terminal end of the succeeding charge. With the proposed method, vibration can be expected to decrease with increasing charge length, decreasing velocity of propagation of explosion, increasing number of charges per array, decreasing reverberation time, increasing precision of initiation timing, and increasing homogeneity of the rock. Computer modeling of the resulting vibration from single arrays having a total duration of explosion longer than the reverberation time shows a starting transient and an ending transient with little or no vibration between them. For patterns containing more than one array, the modeling indicates that the recommended timing between arrays can largely eliminate the vibration from the starting and ending transients as well when they are dominated by a single frequency.

  6. Normative arguments from experts and peers reduce delay discounting

    Directory of Open Access Journals (Sweden)

    Nicole Senecal

    2012-09-01

    Full Text Available When making decisions that involve tradeoffs between the quality and timing of desirable outcomes, people consistently discount the value of future outcomes. A puzzling finding regarding such decisions is the extremely high rate at which people discount future monetary outcomes. Most economists would argue that decision-makers should turn down only rates of return that are lower than those available to them elsewhere. Yet the vast majority of studies find discount rates that are significantly higher than market interest rates (Frederick et al., 2002. Here we ask whether a lack of knowledge about the normative strategy can explain high discount rates. In an initial experiment, nearly half of subjects did not spontaneously cite elements of the normative strategy when asked how people should make intertemporal monetary decisions. In two follow-up experiments, after subjects read a ``financial guide'' detailing the normative strategy, discount rates declined by up to 85%, but were still higher than market interest rates. This decline persisted, though attenuated, for at least one month. In a final experiment, peer-generated advice influenced discount rates in a similar manner to ``expert'' advice, and arguments focusing on normative considerations were at least as effective as others. These studies show that part of the explanation for high discount rates is a lack of knowledge regarding the normative strategy, and they quantify how much discount rates are reduced in response to normative arguments. Given the high level of discounting that remains, however, there are other contributing factors to high discount rates that remain to be quantified.

  7. Normative arguments from experts and peers reduce delay discounting.

    Science.gov (United States)

    Senecal, Nicole; Wang, Teresa; Thompson, Elizabeth; Kable, Joseph W

    2012-09-01

    When making decisions that involve tradeoffs between the quality and timing of desirable outcomes, people consistently discount the value of future outcomes. A puzzling finding regarding such decisions is the extremely high rate at which people discount future monetary outcomes. Most economists would argue that decision-makers should only turn down rates of return that are lower than those available to them elsewhere. Yet the vast majority of studies find discount rates that are significantly higher than market interest rates (Frederick et al., 2002). Here we ask whether a lack of knowledge about the normative strategy can explain high discount rates. In an initial experiment, we find that nearly half of subjects do not spontaneously cite elements of the normative strategy when asked how people should make intertemporal monetary decisions. In two follow-up experiments, we find that after subjects read a "financial guide" detailing the normative strategy, discount rates declined by up to 85%, but were still higher than market interest rates. This decline persisted, though attenuated, for at least one month. In a final experiment, we find that peer-generated advice influences discount rates in a similar manner to "expert" advice, and that arguments focusing on normative considerations are at least as effective as others. These studies show that part of the explanation for high discount rates is a lack of knowledge regarding the normative strategy, and quantify how much discount rates are reduced in response to normative arguments. Given the high level of discounting that remains, however, there are other contributing factors to high discount rates that remain to be quantified.

  8. Episodic future thinking reduces delay discounting and energy intake in children.

    Science.gov (United States)

    Daniel, Tinuke Oluyomi; Said, Michele; Stanton, Christina M; Epstein, Leonard H

    2015-08-01

    Discounting of larger future rewards in favor of smaller immediate rewards is known as delay discounting. High delay discounting or a bias towards immediate gratification impedes self-regulation and is associated with maladaptive eating behaviors. Children in general show greater delay discounting than adults. Obese children in particular, have greater difficulty delaying gratification for edible rewards. Episodic future thinking (EFT) which is mental self-projection to pre-experience future events reduces delay discounting and reduces energy intake in overweight/obese adults. However, these EFT effects have not been examined in children. We evaluated the effects of EFT versus control episodic recent thinking (ERT) on delay discounting and ad libitum energy intake while thinking about episodic cues in 42 overweight/obese 9 to 14year olds. Results showed that EFT led to less delay discounting and lowered energy intake, and EFT had the greatest effect on reducing energy intake in children with a higher desire to restrict food intake. This suggests that EFT may be useful in pediatric obesity treatment programs to help children regulate energy intake. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Fast track diagnosis as a means of reducing diagnostic delay in cancer

    DEFF Research Database (Denmark)

    Larsen, Mette Bach; Vedsted, Peter; Olesen, Frede

    Background: Denmark has the highest morbidity and mortality from cancer in Western Europe, and studies suggest that Danish cancer patients are diagnosed at a later stage than patients in the other Nordic countries. To address this issue a Danish hospital has introduced fast track diagnosis...... of cancer and expanded services to the general practitioners. Objective: To investigate the diagnostic delay of cancer, patient and provider satisfaction and health economic aspects in two Danish regions with special emphasis on the possible benefits of fast track diagnosis. Methods: The study...... in diagnostic delay will be described in uni- and multivariate analysis models based on three types of delay (patient, doctors and system delay) and stratified by diagnosis. The second part of the analysis will focus on the possible benefits from fast track diagnosis in terms of reduced diagnostic delay...

  10. Reduced ultraviolet irradiation delays subsequent squamous cell carcinomas in hairless mice

    DEFF Research Database (Denmark)

    Togsverd-Bo, Katrine; Lerche, Catharina M; Poulsen, Thomas

    2009-01-01

    BACKGROUND: Ultraviolet (UV) radiation induces non-melanoma skin cancer (NMSC), and UV prophylaxis is essential to prevent skin cancer. It is unclear whether patients diagnosed with squamous cell carcinomas (SCC) may benefit from reduced UV exposures in terms of delaying the development of new...... tumors. The objective was to evaluate the significance of discontinued or reduced UV exposure for the development of subsequent skin tumors. METHODS: Seven groups of mice (n = 175) were irradiated with UV doses of 2 and 4 standard erythema doses (SED) that were continued, reduced or discontinued...... at the time of appearance of the first skin tumor. RESULTS: The development of new tumors was delayed, corresponding to the degree of reductions in UV dose in an inversely linear manner. Discontinuation of UV doses delayed the median times to the second tumor by 24 days (2 SED, P = 0.0549) and 33.5 days (4...

  11. New standardized nursing cooperation workflow to reduce stroke thrombolysis delays in patients with acute ischemic stroke

    Directory of Open Access Journals (Sweden)

    Zhou Y

    2017-05-01

    Full Text Available Yan Zhou,1 Zhuojun Xu,2 Jiali Liao,1 Fangming Feng,1 Lai Men,3 Li Xu,2 Yanan He,2 Gang Li2 1Nursing Department, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 2Department of Neurology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China; 3Paddington Dental Practice, London, UK Objective: We assessed the effectiveness of a new standardized nursing cooperation workflow in patients with acute ischemic stroke (AIS to reduce stroke thrombolysis delays.Patients and methods: AIS patients receiving conventional thrombolysis treatment from March to September 2015 were included in the control group, referred to as T0. The intervention group, referred to as T1 group, consisted of AIS patients receiving a new standardized nursing cooperation workflow for intravenous thrombolysis (IVT at the emergency department of Shanghai East Hospital (Shanghai, People’s Republic of China from October 2015 to March 2016. Information was collected on the following therapeutic techniques used: application or not of thrombolysis, computed tomography (CT time, and door-to-needle (DTN time. A nursing coordinator who helped patients fulfill the medical examinations and diagnosis was appointed to T1 group. In addition, a nurse was sent immediately from the stroke unit to the emergency department to aid the thrombolysis treatment.Results: The average value of the door-to-CT initiation time was 38.67±5.21 min in the T0 group, whereas it was 14.39±4.35 min in the T1 group; the average values of CT completion-to-needle time were 55.06±4.82 and 30.26±3.66 min; the average values of DTN time were 100.43±6.05 and 55.68±3.62 min, respectively; thrombolysis time was improved from 12.8% (88/689 in the T0 group to 32.5% (231/712 in the T1 group (all P<0.01. In addition, the new standardized nursing cooperation workflow decreased the National Institutes of Health Stroke Scale (NIHSS scores at 24 h (P<0

  12. Delayed umbilical cord clamping for reducing anaemia in low birthweight infants : implications for developing countries

    NARCIS (Netherlands)

    van Rheenen, Patrick F.; Gruschke, Sebastian; Brabin, Bernard J.

    BACKGROUND: Cheap and effective interventions are needed to reduce the risk of infant anaemia in developing countries. Delayed cord clamping (DCC) has been shown to be a simple, safe and cost-free delivery procedure that augments red cell mass in appropriate-for-gestational-age term and preterm

  13. Electromagnetic therapeutic coils design to reduce energy loss

    Directory of Open Access Journals (Sweden)

    Syrek Przemyslaw

    2016-01-01

    Full Text Available The article introduces the problem of power loss reduction in applicators used in magnetotherapy. To generate magnetic field whose distribution is optimal and to reduce the power loss, the authors establish a set of parameters to evaluate the model of device. Results make it possible to infer that the real power input necessary to operate the magnetic field generator properly may vary significantly depending on construction and localization. The issues raised in this paper should be treated as a basis for further discussion on the construction of applicators used, e.g., in Transcranial Magnetic Stimulation.

  14. Characterization of the therapeutic properties of Chinese herbal materials by measuring delayed luminescence and dendritic cell-based immunomodulatory response.

    Science.gov (United States)

    Sun, Mengmeng; Chang, Wen-Te; Van Wijk, Eduard; He, Min; Koval, Slavik; Lin, Ming-Kuem; Van Wijk, Roel; Hankemeier, Thomas; van der Greef, Jan; Wang, Mei

    2017-03-01

    Based on the traditional Chinese medicine theory, the Chinese pharmacopeia assigns a therapeutic description of "taste" to all herbs; thus, an herb's "taste" is valued in traditional Chinese medicine as a major ethnopharmacological category and reflects the herb's therapeutic properties. These properties guide the practitioner with respect to preparing a specific herbal formula in order to provide each patient with a personalized intervention. The key challenge in evidence-based medicine is to characterize herbal therapeutic properties from a multi-target, multi-dimensional systems pharmacology perspective. Here, we used delayed luminescence (DL, the slowly decaying emission of photons following excitation with light) as a rapid, direct, highly sensitive indicator to characterize the properties of herbal medicines. The DL parameters were able to reliably identify a specific category of herbal materials with the so-called "sweet" taste. To support the DL results and provide biological relevance to the DL results, we used a murine bone marrow-derived dendritic cell-based assay to examine the immunomodulatory effects of herbal extracts from various "taste" categories. Our results indicate that DL may serve as a robust and sensitive tool for evaluating the therapeutic properties of herbs based on the traditional Chinese medicine classification of "taste". Thus, DL provides a promising technological platform for investigating the properties of Chinese herbal medicines both qualitatively and quantitatively. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Genistein aglycone: a new therapeutic approach to reduce endometrial hyperplasia.

    Science.gov (United States)

    Bitto, Alessandra; Granese, Roberta; Triolo, Onofrio; Villari, Daniela; Maisano, Daniele; Giordano, Domenico; Altavilla, Domenica; Marini, Herbert; Adamo, Elena Bianca; Nicotina, Piero Antonio; D'Anna, Rosario; Squadrito, Francesco

    2010-09-01

    Endometrial hyperplasia without cytological atypia is commonly treated with progestins, but other treatment regimes may be available with equivalent efficacy and low side effects. A randomized double-blind, placebo and progesterone-controlled clinical trial to evaluate the effects of genistein aglycone in reducing endometrial hyperplasia. A group of 56 premenopausal women with non-atypical endometrial hyperplasia were enrolled and received: genistein aglycone (n=19; 54 mg/day); norethisterone acetate (n=19; 10 mg/day on days 16-25 of the menstrual cycle) or placebo (n=18) for 6 months. Hysteroscopy was performed with biopsies and symptomology assessed at baseline, 3 and 6 months of administration. The effect on estrogen (ER) and progesterone receptors (PR) expression in uterine biopsies were assessed after 3 and 6 months. For each treatment follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), sex hormone-binding globulin (SHBG) and progesterone (PG) levels were also evaluated. After 6 months, 42% of genistein aglycone-administered subjects had a significant improvement of symptoms (histologically confirmed in the 29%) compared to 47% of norethisterone acetate subjects (histologically confirmed in the 31%), but only 12% in the placebo group with 19% exhibiting worsening symptoms and increased endometrial thickness. No significant differences were noted for hormone levels for any treatment, but immunohistochemical analysis revealed significantly reduced staining for ER-alpha and PR and enhanced ER-beta1 staining in genistein-administered subjects associated with a complete regression of bleeding. These results suggest that genistein aglycone might be useful for the management of endometrial hyperplasia without atypia in women that cannot be treated with progestin. Copyright 2010 Elsevier GmbH. All rights reserved.

  16. Therapeutic ketosis with ketone ester delays central nervous system oxygen toxicity seizures in rats.

    Science.gov (United States)

    D'Agostino, Dominic P; Pilla, Raffaele; Held, Heather E; Landon, Carol S; Puchowicz, Michelle; Brunengraber, Henri; Ari, Csilla; Arnold, Patrick; Dean, Jay B

    2013-05-15

    Central nervous system oxygen toxicity (CNS-OT) seizures occur with little or no warning, and no effective mitigation strategy has been identified. Ketogenic diets (KD) elevate blood ketones and have successfully treated drug-resistant epilepsy. We hypothesized that a ketone ester given orally as R,S-1,3-butanediol acetoacetate diester (BD-AcAc(2)) would delay CNS-OT seizures in rats breathing hyperbaric oxygen (HBO(2)). Adult male rats (n = 60) were implanted with radiotelemetry units to measure electroencephalogram (EEG). One week postsurgery, rats were administered a single oral dose of BD-AcAc(2), 1,3-butanediol (BD), or water 30 min before being placed into a hyperbaric chamber and pressurized to 5 atmospheres absolute (ATA) O2. Latency to seizure (LS) was measured from the time maximum pressure was reached until the onset of increased EEG activity and tonic-clonic contractions. Blood was drawn at room pressure from an arterial catheter in an additional 18 animals that were administered the same compounds, and levels of glucose, pH, Po(2), Pco(2), β-hydroxybutyrate (BHB), acetoacetate (AcAc), and acetone were analyzed. BD-AcAc(2) caused a rapid (30 min) and sustained (>4 h) elevation of BHB (>3 mM) and AcAc (>3 mM), which exceeded values reported with a KD or starvation. BD-AcAc(2) increased LS by 574 ± 116% compared with control (water) and was due to the effect of AcAc and acetone but not BHB. BD produced ketosis in rats by elevating BHB (>5 mM), but AcAc and acetone remained low or undetectable. BD did not increase LS. In conclusion, acute oral administration of BD-AcAc(2) produced sustained ketosis and significantly delayed CNS-OT seizures by elevating AcAc and acetone.

  17. Design of therapeutic clothing for sensory stimulation of children with psychomotor delay.

    Science.gov (United States)

    Pires, Ângela; Miguel, Rui

    2012-01-01

    This research work was based on an experimental concept of functional clothing for children with psychomotor development limitations. No matter the analyzed pathology, all these children need sensorial stimulation because of their psychomotor difficulties, especially at fine motor skills level. The main objective was to develop functional and comfortable clothing with sensorial stimulation elements (colours, textures, fragrances, sounds, etc.). It is intended, on the one hand, to increase the autonomy of the children in what concerns the act of dressing/undressing and, on the other hand, to stimulate their learning, coordination and self-esteem. A study about the specific needs of these children concerning clothing was worked out, which consisted in inquiring their parents and therapists. Based on the inquiries results, bibliographic revision in the area of therapeutic/ interactive clothing and analysis of didactic and therapeutic material catalogues we developed a clothing prototype (sweat-shirt). The prototype was then tested by the children of the study sample and the test results were, once again, explained by the parents through the fulfilling of a prototype evaluation inquiry. This study supplied some important conclusions, more directed to the confirmation of the theme significance and to the definition of a methodology to be used in future research.

  18. Study of the Effectiveness of Vibration in Reduction of Delayed Onset Muscle Soreness Resulting after Therapeutic Exercise

    Directory of Open Access Journals (Sweden)

    Khayam-Bashi

    2009-07-01

    Full Text Available Introduction: Delayed Onset Muscle Soreness (DOMS is a common strain resulting during therapeutic exercise with eccentric contractions. This pain can result in loss of interest by the patient and eventually in cancellation of the routine. The purpose of the present study was to determine whether vibration could have an affect on delayed onset muscle soreness. We hypothesized that the vibration training would decrease DOMS. Methods: Subjects comprised of 30 male athletes aged 18-26 years. The athletes were involved in regular sports activities since at least three years. Subjects were assigned randomly into two VT (n=15 and Non-VT (n=15 groups. The measurements included the flexed knee angle (FANG, pressure pain threshold (PPT, muscle soreness (SOR of right quadriceps muscle and maximal isometric force (MIF of both quadriceps muscles together (Base-line. A vibrator was used to apply 50 Hz vibration on the left and right quadriceps muscles for 1 min in the VT group. Then both groups trained eccentric exercise. All parameters were determined again 24 hours post-exercise (After- activity. Results: All subjects showed a loss in MIF, decrease in PPT, FANG and increase in SOR 24h after eccentric exercise (p=0/000. But the parameters were statistically significantly different in the VT and Non-VT groups [MIF (p=0/000, PPT (p=0/001, FANG (p=0/02, SOR (p=0/003]. Conclusion: Therapeutic exercise with eccentric contractions results in DOMS, but vibration training before exercise is effective and beneficial in decreasing DOMS.

  19. On Reducing Delay in Mesh-Based P2P Streaming: A Mesh-Push Approach

    Science.gov (United States)

    Liu, Zheng; Xue, Kaiping; Hong, Peilin

    The peer-assisted streaming paradigm has been widely employed to distribute live video data on the internet recently. In general, the mesh-based pull approach is more robust and efficient than the tree-based push approach. However, pull protocol brings about longer streaming delay, which is caused by the handshaking process of advertising buffer map message, sending request message and scheduling of the data block. In this paper, we propose a new approach, mesh-push, to address this issue. Different from the traditional pull approach, mesh-push implements block scheduling algorithm at sender side, where the block transmission is initiated by the sender rather than by the receiver. We first formulate the optimal upload bandwidth utilization problem, then present the mesh-push approach, in which a token protocol is designed to avoid block redundancy; a min-cost flow model is employed to derive the optimal scheduling for the push peer; and a push peer selection algorithm is introduced to reduce control overhead. Finally, we evaluate mesh-push through simulation, the results of which show mesh-push outperforms the pull scheduling in streaming delay, and achieves comparable delivery ratio at the same time.

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

    Science.gov (United States)

    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.

  1. Delay-feedback control strategy for reducing CO2 emission of traffic flow system

    Science.gov (United States)

    Zhang, Li-Dong; Zhu, Wen-Xing

    2015-06-01

    To study the signal control strategy for reducing traffic emission theoretically, we first presented a kind of discrete traffic flow model with relative speed term based on traditional coupled map car-following model. In the model, the relative speed difference between two successive running cars is incorporated into following vehicle's acceleration running equation. Then we analyzed its stability condition with discrete control system stability theory. Third, we designed a delay-feedback controller to suppress traffic jam and decrease traffic emission based on modern controller theory. Last, numerical simulations are made to support our theoretical results, including the comparison of models' stability analysis, the influence of model type and signal control on CO2 emissions. The results show that the temporal behavior of our model is superior to other models, and the traffic signal controller has good effect on traffic jam suppression and traffic CO2 emission, which fully supports the theoretical conclusions.

  2. Delayed introduction of solid feeding reduces child overweight and obesity at 10 years.

    Science.gov (United States)

    Seach, K A; Dharmage, S C; Lowe, A J; Dixon, J B

    2010-10-01

    The function that the timing of introduction of solid foods may have in the development of child obesity has not been adequately explored, either as a potential confounder of the relationship between breastfeeding and child obesity, or as an independent modifiable risk factor. To determine the association between infant feeding practices and child overweight/obesity. Six hundred and twenty subjects were recruited antenatally from 1990 to 1994. A total of 18 telephone interviews over the first 2 years of life recorded infant feeding practices. At mean age of 10 years, height and weight were measured for 307 subjects. Multiple logistic regression was used to determine whether infant feeding practices (duration of exclusive and any breastfeeding, and age at introduction of solid foods) were associated with odds of being overweight/obese (internationally age- and sex-standardized body mass index category) at age 10 years, after adjustment for confounders. Delayed introduction of solid foods was associated with reduced odds of being overweight/obese at age 10 years, after controlling for socioeconomic status, parental smoking and childcare attendance (adjusted odds ratio (aOR)=0.903 per week, 95% CI=0.841-0.970, P=0.005). Antenatal parental smoking was associated with overweight/obesity at age 10 years (aOR=3.178, 95% CI=1.643-6.147, P=0.001). Duration of exclusive or any breastfeeding was not associated with the outcome. Delayed introduction of solids is associated with reduced odds of child overweight/obesity. Wider promotion of current infant feeding guidelines could have a significant impact on the rates of child overweight and obesity.

  3. EpiSweep: Computationally Driven Reengineering of Therapeutic Proteins to Reduce Immunogenicity While Maintaining Function.

    Science.gov (United States)

    Choi, Yoonjoo; Verma, Deeptak; Griswold, Karl E; Bailey-Kellogg, Chris

    2017-01-01

    Therapeutic proteins are yielding ever more advanced and efficacious new drugs, but the biological origins of these highly effective therapeutics render them subject to immune surveillance within the patient's body. When recognized by the immune system as a foreign agent, protein drugs elicit a coordinated response that can manifest a range of clinical complications including rapid drug clearance, loss of functionality and efficacy, delayed infusion-like allergic reactions, more serious anaphylactic shock, and even induced auto-immunity. It is thus often necessary to deimmunize an exogenous protein in order to enable its clinical application; critically, the deimmunization process must also maintain the desired therapeutic activity.To meet the growing need for effective, efficient, and broadly applicable protein deimmunization technologies, we have developed the EpiSweep suite of protein design algorithms. EpiSweep seamlessly integrates computational prediction of immunogenic T cell epitopes with sequence- or structure-based assessment of the impacts of mutations on protein stability and function, in order to select combinations of mutations that make Pareto optimal trade-offs between the competing goals of low immunogenicity and high-level function. The methods are applicable both to the design of individual functionally deimmunized variants as well as the design of combinatorial libraries enriched in functionally deimmunized variants. After validating EpiSweep in a series of retrospective case studies providing comparisons to conventional approaches to T cell epitope deletion, we have experimentally demonstrated it to be highly effective in prospective application to deimmunization of a number of different therapeutic candidates. We conclude that our broadly applicable computational protein design algorithms guide the engineer towards the most promising deimmunized therapeutic candidates, and thereby have the potential to accelerate development of new protein

  4. Therapeutic Hypothermia Reduces Oxidative Damage and Alters Antioxidant Defenses after Cardiac Arrest

    Science.gov (United States)

    Hackenhaar, Fernanda S.; Medeiros, Tássia M.; Heemann, Fernanda M.; Behling, Camile S.; Putti, Jordana S.; Mahl, Camila D.; Verona, Cleber; da Silva, Ana Carolina A.; Guerra, Maria C.; Gonçalves, Carlos A. S.; Oliveira, Vanessa M.; Riveiro, Diego F. M.; Vieira, Silvia R. R.

    2017-01-01

    After cardiac arrest, organ damage consequent to ischemia-reperfusion has been attributed to oxidative stress. Mild therapeutic hypothermia has been applied to reduce this damage, and it may reduce oxidative damage as well. This study aimed to compare oxidative damage and antioxidant defenses in patients treated with controlled normothermia versus mild therapeutic hypothermia during postcardiac arrest syndrome. The sample consisted of 31 patients under controlled normothermia (36°C) and 11 patients treated with 24 h mild therapeutic hypothermia (33°C), victims of in- or out-of-hospital cardiac arrest. Parameters were assessed at 6, 12, 36, and 72 h after cardiac arrest in the central venous blood samples. Hypothermic and normothermic patients had similar S100B levels, a biomarker of brain injury. Xanthine oxidase activity is similar between hypothermic and normothermic patients; however, it decreases posthypothermia treatment. Xanthine oxidase activity is positively correlated with lactate and S100B and inversely correlated with pH, calcium, and sodium levels. Hypothermia reduces malondialdehyde and protein carbonyl levels, markers of oxidative damage. Concomitantly, hypothermia increases the activity of erythrocyte antioxidant enzymes superoxide dismutase, glutathione peroxidase, and glutathione S-transferase while decreasing the activity of serum paraoxonase-1. These findings suggest that mild therapeutic hypothermia reduces oxidative damage and alters antioxidant defenses in postcardiac arrest patients. PMID:28553435

  5. Coping with persistent environmental problems: systemic delays in reducing eutrophication of the Baltic Sea

    Directory of Open Access Journals (Sweden)

    Riku Varjopuro

    2014-12-01

    Full Text Available In this paper we focus on systemic delays in the Baltic Sea that cause the problem of eutrophication to persist. These problems are demonstrated in our study by addressing three types of delays: (1 decision delay: the time it takes for an idea or perceived need to be launched as a policy; (2 implementation delay: the time from the launch of a policy to the actual implementation; (3 ecosystem delay: the time difference between the implementation and an actual measurable effects. A policy process is one characterized by delays. It may take years from problem identification to a decision to taking action and several years further for actual implementation. Ecosystem responses to measures illustrate that feedback can keep the ecosystem in a certain state and cause a delay in ecosystem response. These delays can operate on decadal scales. Our aim in this paper is to analyze these systemic delays and especially to discuss how the critical delays can be better addressed in marine protection policies by strengthening the adaptive capacity of marine protection. We conclude that the development of monitoring systems and reflexive, participatory analysis of dynamics involved in the implementation are keys to improve understanding of the systemic delays. The improved understanding is necessary for the adaptive management of a persistent environmental problem. In addition to the state of the environment, the monitoring and analysis should be targeted also at the implementation of policies to ensure that the societies are investing in the right measures.

  6. Experimental colitis delays and reduces the severity of collagen-induced arthritis in mice.

    Science.gov (United States)

    Hablot, Julie; Peyrin-Biroulet, Laurent; Kokten, Tunay; El Omar, Reine; Netter, Patrick; Bastien, Claire; Jouzeau, Jean-Yves; Sokol, Harry; Moulin, David

    2017-01-01

    Amongst extraintestinal manifestations (EIM) occurring in IBD patients, rheumatologic manifestations are the most frequent. Understanding the relationships between arthritis and colitis is a prerequisite to improving the management of these patients. Microbiota of patients with IBD or rheumatologic diseases, like spondyloarthritis (SpA) is modified compared to healthy individual. Thus, we have evaluated the impact of colitis in the development of arthritis in mice and we have analyzed microbiota changes. Collagen-induced arthritis (CIA) was induced at day 0 in DBA1 mice exposed or not to Dextran Sodium Sulfate (DSS) to induce colitis between day 14 and day 21. Animals were monitored regularly for arthritis and colitis severity (clinical score, hindpaw edema). Fecal microbiota was studied by 16S rRNA deep sequencing at critical time points (D14, D14, D21 & D41). At day 41, histological scoring of the intestines and ankles were performed at the end of experiment. Induction of colitis slightly delayed arthritis onset (2 ± 1 days of delay) and reduced its severity (5.75 ± 1.62 in arthritis only group vs 4.00 ± 1.48 in arthritis + colitis group (p = 0.02 at day 28) macroscopically and histologically. In contrast, colitis severity was not influenced by arthritis development. Induction of colitis promoted a modification of microbiota composition and a decrease of α-diversity. Fecal microbiota composition was different between "colitis" and "arthritis+colitis" groups during colitis development. Interestingly a milder decrease of bacterial diversity in the "arthritis+colitis" group was observed. Concomitant experimental colitis protects mice against collagen-induced arthritis and this is associated with changes in gut microbiome composition.

  7. Experimental colitis delays and reduces the severity of collagen-induced arthritis in mice

    Science.gov (United States)

    Hablot, Julie; Peyrin-Biroulet, Laurent; Kokten, Tunay; El Omar, Reine; Netter, Patrick; Bastien, Claire; Jouzeau, Jean-Yves; Sokol, Harry

    2017-01-01

    Amongst extraintestinal manifestations (EIM) occurring in IBD patients, rheumatologic manifestations are the most frequent. Understanding the relationships between arthritis and colitis is a prerequisite to improving the management of these patients. Microbiota of patients with IBD or rheumatologic diseases, like spondyloarthritis (SpA) is modified compared to healthy individual. Thus, we have evaluated the impact of colitis in the development of arthritis in mice and we have analyzed microbiota changes. Collagen-induced arthritis (CIA) was induced at day 0 in DBA1 mice exposed or not to Dextran Sodium Sulfate (DSS) to induce colitis between day 14 and day 21. Animals were monitored regularly for arthritis and colitis severity (clinical score, hindpaw edema). Fecal microbiota was studied by 16S rRNA deep sequencing at critical time points (D14, D14, D21 & D41). At day 41, histological scoring of the intestines and ankles were performed at the end of experiment. Induction of colitis slightly delayed arthritis onset (2 ± 1 days of delay) and reduced its severity (5.75 ± 1.62 in arthritis only group vs 4.00 ± 1.48 in arthritis + colitis group (p = 0.02 at day 28) macroscopically and histologically. In contrast, colitis severity was not influenced by arthritis development. Induction of colitis promoted a modification of microbiota composition and a decrease of α-diversity. Fecal microbiota composition was different between “colitis” and “arthritis+colitis” groups during colitis development. Interestingly a milder decrease of bacterial diversity in the “arthritis+colitis” group was observed. Concomitant experimental colitis protects mice against collagen-induced arthritis and this is associated with changes in gut microbiome composition. PMID:28926599

  8. Use of Insulated Covers over Product Crates to Reduce Losses in Amaranth during Shipping Delays

    Directory of Open Access Journals (Sweden)

    Lizanne Wheeler

    2015-12-01

    Full Text Available Amaranth is a leafy vegetable with high nutrient content which is sensitive to temperature and low relative humidity. Delays in shipment to market may result in significant losses, therefore improved packaging to minimize mechanical damage and reduce moisture loss are desirable. Amaranth was stored in three types of consumer packages, bunches, clamshells and thin plastic bags, within vented plastic crates. Pallet loads were either covered with insulated material or not, while awaiting transportation. Results indicated covering pallets improved the color and overall quality while reducing weight loss and wilting. Covered crates had a “good” (7.6/9.0 overall quality while uncovered averaged 5.5/9.0 or “moderate” quality. There were significant differences in consumer package type, with the bagged amaranth having almost “excellent” quality (8.8/9.0 compared to “good-fair” quality in clamshells (6.2/9.0 and “poor-fair” quality in the control bunches (4.7/9.0. Amaranth stored in thin plastic bags was better in quality and color, with less weight loss and wilting, however, temperatures at the end of six hours of storage were higher and this may lead to microbial growth. Storage of amaranth in thin bags or clamshell packages, within plastic crates covered with insulated pallet covers while awaiting shipping resulted in improved overall quality and color.

  9. Delayed intranasal delivery of hypoxic-preconditioned bone marrow mesenchymal stem cells enhanced cell homing and therapeutic benefits after ischemic stroke in mice.

    Science.gov (United States)

    Wei, Ning; Yu, Shan Ping; Gu, Xiaohuan; Taylor, Tammi M; Song, Denise; Liu, Xin-Feng; Wei, Ling

    2013-01-01

    Stem cell transplantation therapy has emerged as a potential treatment for ischemic stroke and other neurodegenerative diseases. Effective delivery of exogenous cells and homing of these cells to the lesion region, however, have been challenging issues that hinder the efficacy and efficiency of cell-based therapy. In the present investigation, we tested a delayed treatment of noninvasive and brain-targeted intranasal delivery of bone marrow mesenchymal stem cells (BMSCs) in a mouse focal cerebral ischemia model. The investigation tested the feasibility and effectiveness of intranasal delivery of BMSCs to the ischemic cortex. Hypoxia preconditioning (HP) of BMSCs was performed before transplantation in order to promote their survival, migration, and homing to the ischemic brain region after intranasal transplantation. Hoechst dye-labeled normoxic- or hypoxic-pretreated BMSCs (1 × 10(6) cells/animal) were delivered intranasally 24 h after stroke. Cells reached the ischemic cortex and deposited outside of vasculatures as early as 1.5 h after administration. HP-treated BMSCs (HP-BMSCs) showed a higher level of expression of proteins associated with migration, including CXC chemokine receptor type 4 (CXCR4), matrix metalloproteinase 2 (MMP-2), and MMP-9. HP-BMSCs exhibited enhanced migratory capacities in vitro and dramatically enhanced homing efficiency to the infarct cortex when compared with normoxic cultured BMSCs (N-BMSCs). Three days after transplantation and 4 days after stroke, both N-BMSCs and HP-BMSCs decreased cell death in the peri-infarct region; significant neuroprotection of reduced infarct volume was seen in mice that received HP-BMSCs. In adhesive removal test of sensorimotor functional assay performed 3 days after transplantation, HP-BMSC-treated mice performed significantly better than N-BMSC- and vehicle-treated animals. These data suggest that delayed intranasal administration of stem cells is feasible in the treatment of stroke and hypoxic

  10. Reducing therapeutic misconception: A randomized intervention trial in hypothetical clinical trials.

    Science.gov (United States)

    Christopher, Paul P; Appelbaum, Paul S; Truong, Debbie; Albert, Karen; Maranda, Louise; Lidz, Charles

    2017-01-01

    Participants in clinical trials frequently fail to appreciate key differences between research and clinical care. This phenomenon, known as therapeutic misconception, undermines informed consent to clinical research, but to date there have been no effective interventions to reduce it and concerns have been expressed that to do so might impede recruitment. We determined whether a scientific reframing intervention reduces therapeutic misconception without significantly reducing willingness to participate in hypothetical clinical trials. This prospective randomized trial was conducted from 2015 to 2016 to test the efficacy of an informed consent intervention based on scientific reframing compared to a traditional informed consent procedure (control) in reducing therapeutic misconception among patients considering enrollment in hypothetical clinical trials modeled on real-world studies for one of five disease categories. Patients with diabetes mellitus, hypertension, coronary artery disease, head/neck cancer, breast cancer, and major depression were recruited from medical clinics and a clinical research volunteer database. The primary outcomes were therapeutic misconception, as measured by a validated, ten-item Therapeutic Misconception Scale (range = 10-50), and willingness to participate in the clinical trial. 154 participants completed the study (age range, 23-87 years; 92.3% white, 56.5% female); 74 (48.1%) had been randomized to receive the experimental intervention. Therapeutic misconception was significantly lower (p = 0.004) in the scientific reframing group (26.4, 95% CI [23.7 to 29.1] compared to the control group (30.9, 95% CI [28.4 to 33.5], and remained so after controlling for education (p = 0.017). Willingness to participate in the hypothetical trial was not significantly different (p = 0.603) between intervention (52.1%, 95% CI [40.2% to 62.4%]) and control (56.3%, 95% CI [45.3% to 66.6%] groups. An enhanced educational intervention augmenting

  11. Reduced group delay dispersion in quantum dot passively mode-locked lasers operating at elevated temperature

    Science.gov (United States)

    Mee, J. K.; Raghunathan, R.; Murrell, D.; Braga, A.; Li, Y.; Lester, L. F.

    2014-09-01

    A detailed study of the pulse characteristics emitted from a monolithic Quantum Dot (QD) passively Mode-Locked Laser (MLL) has been performed using a state-of-the-art Frequency Resolved Optical Gating (FROG) pulse measurement system. While traditionally the time-domain pulse characteristics of semiconductor MLLs have been studied using digital sampling oscilloscope or intensity autocorrelation techniques, the FROG measurements allow for simultaneous characterization of time and frequency, which has been shown to be necessary and sufficient for true determination of mode-locked stability. In this paper, FROG pulse measurements are presented on a two-section QD MLL operating over wide temperature excursions. The FROG measurement allows for extraction of the temporal and spectral intensity and phase profiles from which the Group Delay Dispersion (GDD) can be determined. The magnitude of the GDD is found to decrease from 16.1 to 3.5 ps/nm when the temperature is increased from 20 to 50 oC, mirroring the trend of pulse width reduction at elevated temperature, which has been shown to correlate strongly with reduced unsaturated absorption. The possibility to further optimize pulse generation via intra-cavity dispersion compensation in a novel three-section MLL design is also examined, and shows strong potential toward providing valuable insight into the optimal cavity designs and operating parameters for QD MLLs.

  12. Delayed fertilization of anuran amphibian (Xenopus) eggs leads to reduced numbers of primordial germ cells

    Science.gov (United States)

    Wakahara, M.; Neff, A. W.; Malacinski, G. M.

    1984-01-01

    Several media were tested for the extent to which they promoted high fertilization efficiencies in ovulated, stripped Xenopus eggs. One medium was selected for maintaining eggs in a 'delayed fertilization' (DelF) condition. DelF eggs displayed several unusual characteristics, including shift of the center of gravity, prominent sperm entrance site, and occasional polyspermy. The frequency of normal pattern formation varied according to the length of time eggs were maintained in the DelF condition. Various developmental abnormalities were observed during gastrulation, neurulation, and organogenesis. Most abnormalities appeared, however, to be related to morphogenesis of the endoderm. Primordial germ cell (PGC) development was examined in DelF eggs which displayed normal external morphological features at the swimming tadpole stage. PGC counts were usually normal in short-duration (eg, 5 hr) DelF eggs, but frequently substantially reduced or completely diminished in longer-duration (eg, 25h) tadpoles. Six spawnings were compared and shown to exhibit considerable variability in fertility, morphogenesis, and PGC development. Yolk platelet shifts and developmental parameters were examined in two additional spawnings. The subcortical cytoplasm in which the germ plasm is normally localized appeared to be disrupted in longer duration DelF eggs. That observation may account for low PGC counts in DelF tadpoles.

  13. Development of an education campaign to reduce delays in pre-hospital response to stroke.

    Science.gov (United States)

    Caminiti, Caterina; Schulz, Peter; Marcomini, Barbara; Iezzi, Elisa; Riva, Silvia; Scoditti, Umberto; Zini, Andrea; Malferrari, Giovanni; Zedde, Maria Luisa; Guidetti, Donata; Montanari, Enrico; Baratti, Mario; Denti, Licia

    2017-06-24

    Systematic reviews call for well-designed trials with clearly described intervention components to support the effectiveness of educational campaigns to reduce patient delay in stroke presentation. We herein describe the systematic development process of a campaign aimed to increase stroke awareness and preparedness. Campaign development followed Intervention Mapping (IM), a theory- and evidence-based tool, and was articulated in two phases: needs assessment and intervention development. In phase 1, two cross-sectional surveys were performed, one aiming to measure stroke awareness in the target population and the other to analyze the behavioral determinants of prehospital delay. In phase 2, a matrix of proximal program objectives was developed, theory-based intervention methods and practical strategies were selected and program components and materials produced. In phase 1, the survey on 202 citizens highlighted underestimation of symptom severity, as in only 44% of stroke situations respondents would choose to call the emergency service (EMS). In the survey on 393 consecutive patients, 55% presented over 2 hours after symptom onset; major determinants were deciding to call the general practitioner first and the reaction of the first person the patient called. In phase 2, adult individuals were identified as the target of the intervention, both as potential "patients" and witnesses of stroke. The low educational level found in the patient survey called for a narrative approach in cartoon form. The family setting was chosen for the message because 42% of patients who presented within 2 hours had been advised by a family member to call EMS. To act on people's tendency to view stroke as an untreatable disease, it was decided to avoid fear-arousal appeals and use a positive message providing instructions and hope. Focus groups were used to test educational products and identify the most suitable sites for message dissemination. The IM approach allowed to develop a

  14. Exposure to intermittent hypoxia and sustained hypercapnia reduces therapeutic CPAP in participants with obstructive sleep apnea.

    Science.gov (United States)

    El-Chami, Mohamad; Sudan, Sukhesh; Lin, Ho-Sheng; Mateika, Jason H

    2017-07-06

    To determine if exposure to mild intermittent hypoxia leads to a reduction in the therapeutic continuous positive airway pressure required to eliminate breathing events. Ten male participants were treated with twelve 2-minute episodes of hypoxia (PETO2 ≈ 50 mmHg) separated by 2-minute intervals of normoxia in the presence of PETCO2 that was sustained 3 mmHg above baseline. During recovery from the last episode the positive airway pressure was reduced in a step-wise fashion until flow limitation was evident. The participants also completed a sham protocol under normocapnic conditions, which mimicked the timeframe of the intermittent hypoxia protocol. After exposure to intermittent hypoxia the therapeutic pressure was significantly reduced (i.e. 5 cmH2O) without evidence of flow limitation (103.4 ± 6.3 % of baseline, P = 0.5) or increases in upper airway resistance (95.6 ± 15.0 % of baseline, P = 0.6). In contrast, a similar decrease in pressure was accompanied by flow limitation (77.0 ± 1.8 % of baseline, P = 0.001) and an increase in upper airway resistance (167.2 ± 17.5 % of baseline, P = 0.01) after the sham protocol. Consistent with the initiation of long-term facilitation of upper airway muscle activity exposure to intermittent hypoxia reduced the therapeutic pressure required to eliminate apneic events which could improve treatment compliance. This possibility coupled with the potential beneficial effects of intermittent hypoxia on co-morbidities linked to sleep apnea suggests that mild intermittent hypoxia may have a multipronged therapeutic effect on sleep apnea. Copyright © 2017, Journal of Applied Physiology.

  15. A case study of mediated learning, delayed auditory feedback, and motor repatterning to reduce stuttering.

    Science.gov (United States)

    Radford, Nola T; Tanguma, Jesus; Gonzalez, Marcia; Nericcio, Mary Anne; Newman, Denis G

    2005-08-01

    A case study of DW, an 11-yr. old monolingual, English-speaking boy who exhibits stuttering, language delay, and ADHD is presented. DW experienced only limited improvement during stuttering therapy received in public schools, according to parents and the public school clinician. The purpose of this case study was to assess whether fluency treatment which incorporated Mediated Learning, Delayed Auditory Feedback, and Speech Motor Repatterning would enhance progress. Therapy was delivered in two treatments, with each treatment being 5 wk. of intense therapy, separated by one year. Treatment 1 of combined Mediated Learning and Delayed Auditory Feedback yielded improvement in fluency, judged by parents and the teacher to be clinically significant. The improved fluency was maintained for one year when DW was pretested for participation in Treatment 2, which combined Mediated Learning, Delayed Auditory Feedback, and Speech Motor Repatterning Exercises. As no conclusions are possible, further study is needed.

  16. The use of therapeutic plasma exchange to reduce serum bilirubin in a dog with kernicterus.

    Science.gov (United States)

    Tovar, Tricia; Deitschel, Sarah; Guenther, Christine

    2017-07-01

    To describe the use of a manual method of therapeutic plasma exchange to reduce total serum bilirubin, manage kernicterus, and halt progression of neurological dysfunction in a dog with immune-mediated hemolytic anemia (IMHA). A 5-year-old male neutered Lhasa Apso diagnosed with IMHA developed acute onset neurologic signs consistent with kernicterus. Manual therapeutic plasma exchange was performed in an attempt to reduce total serum bilirubin. The initial exchange was performed at a lower plasma exchange volume due to the dog's critical status and the dog's clinical signs progressed. More aggressive plasma exchange was performed that resulted in a reduction in total serum bilirubin and no further progression of neurologic signs. The dog was euthanized due to suspicion of permanent neurologic changes and need for further blood transfusions. Histopathology postmortem confirmed a diagnosis of kernicterus. Kernicterus secondary to hyperbilirubinemia is well described in people, but has rarely been reported in dogs. Therapeutic plasma exchange has been used for decades in people to rapidly decrease serum bilirubin when hyperbilirubinemia progresses to neurologic signs, but to the authors' knowledge this has not been described in a dog. © Veterinary Emergency and Critical Care Society 2017.

  17. Marine oil dietary supplementation reduces delayed onset muscle soreness after a 30 km run

    Directory of Open Access Journals (Sweden)

    Baum K

    2013-05-01

    Full Text Available Klaus Baum,1 Richard D Telford,2 Ross B Cunningham,3 1Trainingsinstitut Prof Baum, Köln, Germany; 2College of Medicine, Biology, and Environment, Australian National University, Canberra, ACT, Australia; 3The Fenner School of Environment and Society, Australian National University, Canberra, ACT, Australia Objective: Runners are prone to delayed onset muscle soreness (DOMS during long distance training. This especially holds for unaccustomed training volumes at moderate to high intensities. We investigated the effects of a marine oil complex, PCSO-524®, derived from the New Zealand green-lipped mussel (formulated as Lyprinol® and Omega XL® on DOMS after a 30 km training run. Methods: Initially, peak oxygen uptake of 32 distance runners (4 female, 28 male; median age 45 years, range 28–53 was measured on a treadmill with a 1.5 km hour-1 increase every 4 minutes starting from 8.5 km hour-1. At least 1-week after this initial test, they participated in a 30 km road run at a speed corresponding to about 70% of their individual peak oxygen uptake on a flat terrain. Before and after (0, 24, and 48 hours the run, blood concentration of creatine kinase (CK were measured and pain sensation was determined (pain scale from 0 = no pain to 10 = extremely painful. Runners were then matched in pairs based on maximal CK and peak oxygen uptake, and allocated randomly into two different groups. One group was supplemented with 400 mg per day of PCSO-524® for 11 weeks, the other group with an olive oil placebo. After that period, CK and pain sensations were remeasured following a second 30 km run at the same speed and on the same terrain. Results: The general pattern of soreness in the PCSO-524® supplemented group was reduced by 1.1 units (standard error 0.41 compared to the placebo (P < 0.05, the effects being greater in lesser trained runners (P < 0.05. CK levels were positively associated with pain sensation (P < 0.05, but trends toward lower CK in the

  18. Factors that hinder or enable maternal health strategies to reduce delays in rural and pastoralist areas in Ethiopia.

    Science.gov (United States)

    Jackson, Ruth; Tesfay, Fisaha Haile; Gebrehiwot, Tesfay Gebregzabher; Godefay, Hagos

    2017-02-01

    To document factors that hinder or enable strategies to reduce the first and second delays of the Three Delays in rural and pastoralist areas in Ethiopia. A key informant study was conducted with 44 Health Extension Workers in Afar Region, Kafa Zone (Southern Nation, Nationalities and Peoples' Region), and Adwa Woreda (Tigray Region). Health Extension Workers were trained to interview women and ask for stories about their recent experiences of birth. We interviewed the Health Extension Workers about their experiences referring women for Skilled Birth Attendance and Emergency Obstetric and Newborn Care. Data were analysed using thematic analysis. Themes related to reducing the first delay, such as the tradition of home birth, decision-making, distance and unavailability of transport, did not differ between the three locations. Themes related to reducing the second delay differed substantially. Health Extension Workers in Adwa Woreda were more likely to call ambulances due to support from the Health Development Army and a functioning referral system. In Kafa Zone, some Health Extension Workers were discouraged from calling ambulances as they were used for other purposes. In Afar Region, few Health Extension Workers were called to assist women as most women give birth at home with Traditional Birth Attendants unless they need to travel to health facilities for Emergency Obstetric and Newborn Care. Initiatives to reduce delays can improve access to maternal health services, especially when Health Extension Workers are supported by the Health Development Army and a functioning referral system, but district (woreda) health offices should ensure that ambulances are used as intended. © 2016 John Wiley & Sons Ltd.

  19. Decalogue of the Spanish Society of Arteriosclerosis to reduce therapeutic inertia.

    Science.gov (United States)

    Blasco, Mariano; Pérez-Martínez, Pablo; Lahoz, Carlos

    Therapeutic inertia (TI) is defined as the failure of the physician to initiate or intensify a treatment when the therapeutic goal has not been achieved. TI can be of 2types: inertia due to lack of prescription of drugs and inertia in the absence of control of a risk factor. The consequences of TI are poor control of risk factors, an increase in potentially preventable events and an increase in costs. There are factors of the doctor himself, the patient and the care organization that determine the presence of TI. Ten measures are proposed to reduce TI: to promote continuing education, to define clearly therapeutic objectives, to establish audits, to implement computerized medical records with alerts, to encourage research in this field, to disseminate clinical practice guidelines, to create motivational incentives, to organize care, to improve the doctor-patient relationship and to involve other health care providers. Copyright © 2017 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.

  20. Characterization of the therapeutic properties of Chinese herbal materials by measuring delayed luminescence and dendritic cell-based immunomodulatory response

    NARCIS (Netherlands)

    Sun, M.; Chang, W.T.; Wijk, E. van; He, M.; Koval, S.; Lin, M.K.; Van Wijk, R.; Hankemeier, T.; Greef, J. van der; Wang, M.

    2017-01-01

    Based on the traditional Chinese medicine theory, the Chinese pharmacopeia assigns a therapeutic description of “taste” to all herbs; thus, an herb's “taste” is valued in traditional Chinese medicine as a major ethnopharmacological category and reflects the herb's therapeutic properties. These

  1. Reduced Delay of Gratification and Effortful Control among Young Children with Autism Spectrum Disorders

    Science.gov (United States)

    Faja, Susan; Dawson, Geraldine

    2015-01-01

    We explored internal control of behavior using direct observation and parent report. Previous research has found that both the delay of gratification task and parent-reported effortful control predict later social ability and more positive outcomes in typically developing children. Children with autism spectrum disorder have previously been…

  2. Low-dose acarbose does not delay digestion of starch but reduces its bioavailability

    NARCIS (Netherlands)

    Wachters-Hagedoorn, R. E.; Priebe, M. G.; Heimweg, J. A. J.; Heiner, A. M.; Elzinga, H.; Stellaard, F.; Vonk, R. J.

    Aims Slowly digestible starch is associated with beneficial health effects. The glucose-lowering drug acarbose has the potential to retard starch digestion since it inhibits alpha-amylase and alpha-glucosidases. We tested the hypothesis that a low dose of acarbose delays the rate of digestion of

  3. [ManNAc, a new therapeutic agent to reduce Angptl4-induced proteinuria in MCD].

    Science.gov (United States)

    Clément, Lionel; Macé, Camille

    2016-01-01

    Current therapies used in minimal change disease (MCD) were originally designed to cure other diseases. They are only partially efficient, and present inconvenient side effects. Therefore, understanding the molecular mechanisms implicated in the pathogenesis of proteinuria in MCD could lead to new therapeutic strategies. A new experimental transgenic rat model of human MCD was generated. These NPHS2-Angptl4 transgenic rats over-express two different forms of the glycoprotein Angptl4 from the podocyte. The majority of the protein shows a lack of sialylation that is implicated in the pathogenesis of proteinuria. Supplementation of ManNAc, a precursor of sialic acid, significantly reduces albuminuria in those rats by increasing sialylation of the hyposialylated form of Angptl4. After treatment of the first episode of MCD with glucocorticoids in patients, ManNAc could be used as a maintenance drug, especially to reduce the frequency and intensity of relapse. ManNAc is a promising therapeutic agent for patients with MCD. © 2016 médecine/sciences – Inserm.

  4. A reduced-order, single-bubble cavitation model with applications to therapeutic ultrasound

    Science.gov (United States)

    Kreider, Wayne; Crum, Lawrence A.; Bailey, Michael R.; Sapozhnikov, Oleg A.

    2011-01-01

    Cavitation often occurs in therapeutic applications of medical ultrasound such as shock-wave lithotripsy (SWL) and high-intensity focused ultrasound (HIFU). Because cavitation bubbles can affect an intended treatment, it is important to understand the dynamics of bubbles in this context. The relevant context includes very high acoustic pressures and frequencies as well as elevated temperatures. Relative to much of the prior research on cavitation and bubble dynamics, such conditions are unique. To address the relevant physics, a reduced-order model of a single, spherical bubble is proposed that incorporates phase change at the liquid-gas interface as well as heat and mass transport in both phases. Based on the energy lost during the inertial collapse and rebound of a millimeter-sized bubble, experimental observations were used to tune and test model predictions. In addition, benchmarks from the published literature were used to assess various aspects of model performance. Benchmark comparisons demonstrate that the model captures the basic physics of phase change and diffusive transport, while it is quantitatively sensitive to specific model assumptions and implementation details. Given its performance and numerical stability, the model can be used to explore bubble behaviors across a broad parameter space relevant to therapeutic ultrasound. PMID:22088026

  5. Rate-Optimal Multiuser Scheduling with Reduced Feedback Load and Analysis of Delay Effects

    Directory of Open Access Journals (Sweden)

    Alouini Mohamed-Slim

    2006-01-01

    Full Text Available We propose a feedback algorithm for wireless networks that always collects feedback from the user with the best channel conditions and has a significant reduction in feedback load compared to full feedback. The algorithm is based on a carrier-to-noise threshold, and closed-form expressions for the feedback load as well as the threshold value that minimizes the feedback load have been found. We analyze two delay scenarios. The first scenario is where the scheduling decision is based on outdated channel estimates, and the second scenario is where both the scheduling decision and the adaptive modulation are based on outdated channel estimates.

  6. Reconciling Estimates of the Value to Firms of Reduced Regulatory Delay in the Marketing of Their New Drugs.

    Science.gov (United States)

    Wilmoth, Daniel R

    2015-12-01

    The prescription drug user fee program provides additional resources to the U.S. Food and Drug Administration at the expense of regulated firms. Those resources accelerate the review of new drugs. Faster approvals allow firms to realize profits sooner, and the program is supported politically by industry. However, published estimates of the value to firms of reduced regulatory delay vary dramatically. It is shown here that this variation is driven largely by differences in methods that correspond to differences in implicit assumptions about the effects of reduced delay. Theoretical modeling is used to derive an equation describing the relationship between estimates generated using different methods. The method likely to yield the most accurate results is identified. A reconciliation of published estimates yields a value to a firm for a one-year reduction in regulatory delay at the time of approval of about $60 million for a typical drug. Published 2015. This article is a U.S. Government work and is in the public domain in the U.S.A. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.

  7. Effect of erythromycin treatment delay on therapeutic outcome of experimental acute otitis media caused by Streptococcus pneumoniae.

    Science.gov (United States)

    Martínez-Marín, Carmina; Huelves, Lorena; del Prado, Gema; García-Cía, José I; Cenjor, Carlos; Ponte, Carmen; Granizo, Juan J; Soriano, Francisco

    2005-10-01

    To evaluate the effect of delayed administration of erythromycin in the course of acute otitis media caused by an erythromycin-susceptible Streptococcus pneumoniae strain in the gerbil model. The bacterium was inoculated by transbullar challenge in the middle ear (ME) and antibiotic treatment at different doses was administered at various times thereafter. When 2.5 mg/kg of erythromycin was administered as a single dose 2, 5, 18 or 21 h post-inoculation (pi) the bacterial eradication rate was 55, 40, 0 and 0%, respectively. A higher dose (5 mg/kg) administered also as a single dose 2, 5, 18 and 21 h pi achieved bacterial eradication rates of 62.5, 43.8, 0 and 0%, respectively. Using a very high dose (50 mg/kg) repeated three times at 3 h intervals (total dose 150 mg/kg) and starting the treatment 21 h pi only achieved bacterial eradication in 25% of cases. The concentration of erythromycin achieved in the ME 90 min after administration of 5 mg/kg 5 or 21 h pi was very similar (0.74 and 0.79 mg/L) but the ME half-life was longer (98.2 min) with the early administration as compared with the delayed form (47.5 min), which could partially explain the different results. Further experiments showed that the failures observed with the delayed administration were not related to the time elapsed from antibiotic administration to ME sampling or selection of antibiotic-resistant mutants. Bacteriological and clinical efficacies were significantly diminished if antibiotic administration was delayed.

  8. Investing in the future: stimulation of the medial prefrontal cortex reduces discounting of delayed rewards.

    Science.gov (United States)

    Cho, Sang Soo; Koshimori, Yuko; Aminian, Kelly; Obeso, Ignacio; Rusjan, Pablo; Lang, Anthony E; Daskalakis, Zafiris J; Houle, Sylvain; Strafella, Antonio P

    2015-02-01

    Generally, rewards that are received sooner are often preferred over future rewards, and the time between the choice and the reception of the reward is an important factor that influences our decisions, a phenomenon called delay discounting (DD). In DD, the medial prefrontal cortex (MePFC) and striatal dopamine neurotransmission both play an important role. We used repetitive transcranial magnetic stimulation (rTMS) to transiently activate the MePFC to evaluate its behavioral effect on the DD paradigm, and subsequently to measure its effect on striatal dopamine. Twenty-four right-handed young healthy subjects (11 females; age: 22.1±2.9 years) underwent DD following 10 Hz-rTMS of the MePFC and vertex stimulation (control condition). Thereafter, 11 subjects (5 females; age: 22.2±2.87 years) completed the PET study at rest using [(11)C]-(+)-PHNO following 10 Hz-rTMS of the MePFC and vertex. Modulation of the MePFC excitability influenced the subjective level of DD for delayed rewards and interfered with synaptic dopamine level in the striatum. The present study yielded findings that might reconcile the role of these areas in inter-temporal decision making and dopamine modulation, suggesting that the subjective sense of time and value of reward are critically controlled by these important regions.

  9. Mutation in ATG5 reduces autophagy and leads to ataxia with developmental delay.

    Science.gov (United States)

    Kim, Myungjin; Sandford, Erin; Gatica, Damian; Qiu, Yu; Liu, Xu; Zheng, Yumei; Schulman, Brenda A; Xu, Jishu; Semple, Ian; Ro, Seung-Hyun; Kim, Boyoung; Mavioglu, R Nehir; Tolun, Aslıhan; Jipa, Andras; Takats, Szabolcs; Karpati, Manuela; Li, Jun Z; Yapici, Zuhal; Juhasz, Gabor; Lee, Jun Hee; Klionsky, Daniel J; Burmeister, Margit

    2016-01-26

    Autophagy is required for the homeostasis of cellular material and is proposed to be involved in many aspects of health. Defects in the autophagy pathway have been observed in neurodegenerative disorders; however, no genetically-inherited pathogenic mutations in any of the core autophagy-related (ATG) genes have been reported in human patients to date. We identified a homozygous missense mutation, changing a conserved amino acid, in ATG5 in two siblings with congenital ataxia, mental retardation, and developmental delay. The subjects' cells display a decrease in autophagy flux and defects in conjugation of ATG12 to ATG5. The homologous mutation in yeast demonstrates a 30-50% reduction of induced autophagy. Flies in which Atg5 is substituted with the mutant human ATG5 exhibit severe movement disorder, in contrast to flies expressing the wild-type human protein. Our results demonstrate the critical role of autophagy in preventing neurological diseases and maintaining neuronal health.

  10. Reduced Mid1 expression and delayed neuromotor development in daDREAM transgenic mice

    Directory of Open Access Journals (Sweden)

    Mara eDierssen

    2012-05-01

    Full Text Available DREAM (downstream regulatory element antagonist modulator is a Ca2+-binding protein that binds DNA and represses transcription in a Ca2+-dependent manner. Previous work has shown a role for DREAM in cerebellar function regulating the expression of the sodium/calcium exchanger 3 (NCX3 in cerebellar granular neurons to control Ca2+ homeostasis and survival of these neurons. To achieve a global view of the genes regulated by DREAM in the cerebellum, we performed a genome-wide analysis in transgenic cerebellum expressing a Ca2+-insensitive/CREB-independent dominant active mutant DREAM (daDREAM. Here we show that DREAM regulates the expression of the midline 1 (Mid1 gene early after birth. As a consequence, daDREAM mice exhibit a significant shortening of the rostro-caudal axis of the cerebellum and a severe delay in neuromotor development early after birth. Our results indicate a role for DREAM in cerebellar function.

  11. Migratory delay leads to reduced passage success of Atlantic salmon smolts at a hydroelectric dam

    Science.gov (United States)

    Nyqvist, Daniel; Greenberg, L.; Goerig, E.; Calles, O.; Bergman, E.; Ardren, William R.; Castro-Santos, Theodore R.

    2017-01-01

    Passage of fish through hydropower dams is associated with mortality, delay, increased energy expenditure and migratory failure for migrating fish and the need for remedial measures for both upstream and downstream migration is widely recognised. A functional fish passage must ensure safe and timely passage routes that a substantial portion of migrating fish will use. Passage solutions must address not only the number or percentage of fish that successfully pass a barrier, but also the time it takes to pass. Here, we used radiotelemetry to study the functionality of a fish bypass for downstream-migrating wild-caught and hatchery-released Atlantic salmon smolts. We used time-to-event analysis to model the influence of fish characteristics and environmental variables on the rates of a series of events associated with dam passage. Among the modelled events were approach rate to the bypass entry zone, retention rates in both the forebay and the entry zone and passage rates. Despite repeated attempts, only 65% of the tagged fish present in the forebay passed the dam. Fish passed via the bypass (33%), via spill (18%) and via turbines (15%). Discharge was positively related to approach, passage and retention rates. We did not detect any differences between wild and hatchery fish. Even though individual fish visited the forebay and the entry zone on multiple occasions, most fish passed during the first exposures to these zones. This study underscores the importance of timeliness to passage success and the usefulness of time-to-event analysis for understanding factors governing passage performance.

  12. Delayed treatment with a novel neurotrophic compound reduces behavioral deficits in rabbit ischemic stroke.

    Science.gov (United States)

    Lapchak, Paul A; Schubert, David R; Maher, Pamela A

    2011-01-01

    Acute ischemic stroke is a major risk for morbidity and mortality in our aging population. Currently only one drug, the thrombolytic tissue plasminogen activator, is approved by the US Food and Drug Administration to treat stroke. Therefore, there is a need to develop new drugs that promote neuronal survival following stroke. We have synthesized a novel neuroprotective molecule called CNB-001 (a pyrazole derivative of curcumin) that has neurotrophic activity, enhances memory, and blocks cell death in multiple toxicity assays related to ischemic stroke. In this study, we tested the efficacy of CNB-001 in a rigorous rabbit ischemic stroke model and determined the molecular basis of its in vivo activity. CNB-001 has substantial beneficial properties in an in vitro ischemia assay and improves the behavioral outcome of rabbit ischemic stroke even when administered 1 h after the insult, a therapeutic window in this model comparable to tissue plasminogen activator. In addition, we elucidated the protein kinase pathways involved in neuroprotection. CNB-001 maintains the calcium-calmodulin-dependent kinase signaling pathways associated with neurotrophic growth factors that are critical for the maintenance of neuronal function. On the basis of its in vivo efficacy and novel mode of action, we conclude that CNB-001 has a great potential for the treatment of ischemic stroke as well as other CNS pathologies.

  13. Human microbiome as therapeutic intervention target to reduce cardiovascular disease risk

    NARCIS (Netherlands)

    Koopen, Annefleur M.; Groen, Albert K.; Nieuwdorp, Max

    2016-01-01

    Purpose of review The absolute burden of cardiovascular risk remains high despite currently available preventive and therapeutic options. In search for novel therapeutic leads, mounting evidence has linked the gut microbiota as well as their metabolites to the development of cardiometabolic

  14. Diagnostic and therapeutic delay of rheumatoid arthritis and its relationship with health care devices in Catalonia. The AUDIT study.

    Science.gov (United States)

    Corominas, Hèctor; Narváez, Javier; Díaz-Torné, César; Salvador, Georgina; Gomez-Caballero, María Eugenia; de la Fuente, Diana; Campoy, Ester; Roig-Vilaseca, Daniel; Clavaguera, Teresa; Morlà, Rosa; Torrente-Segarra, Vicenç; Arasa, Xavier; Gomez-Puerta, José Alfredo; Möller, Ingrid; Alegre, Cayetano; Graell, Eduard; Ponce, Andrés; Lisbona, María Pilar; Pérez-Garcia, Carolina; Fíguls, Ramon; Sirvent, Elena; Poca, Violan; Sanmartí, Raimon

    2016-01-01

    Diagnosis and therapy of patients with early onset rheumatoid arthritis (RA) is influenced by accessibility to specialized care devices. We attempted to analyze the impact of their availability. We analyzed time related to diagnosis delay measuring: 1) Time from first clinical symptoms to the first visit with the Rheumatologist; 2) Time from referral to the first visit of Rheumatology; 3) Time between first symptom until final diagnosis; 4) time between first symptom until the initiation of the first disease-modifying antirheumatic drug (DMARD). The presence of these 6 rheumatology devices was defined: 1) early arthritis monographic clinics, 2) RA monographic clinics, 3) Mechanisms for fast programming, 4) Algorithms for referral from primary care (PC), 5) rheumatology consultation services in PC and 6) consulting services in PC. The mean time from onset of symptoms to diagnosis or the establishment of a DMARD in RA patients in Catalonia is very long (11 months). Patients seen in rheumatology devices such as RA monographic clinics, rheumatology consultation in PC and specially in early arthritis clinics are treated early with DMARDs. the existence of monographic clinics or consulting in primary care centers is essential to improve early care of RA patients. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  15. Therapeutic interventions to reduce the risk of progression from prediabetes to type 2 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Portero McLellan KC

    2014-03-01

    Full Text Available Katia Cristina Portero McLellan,1 Kathleen Wyne,2 Evangelina Trejo Villagomez,2 Willa A Hsueh2 1Department of Public Health, School of Medicine, Sao Paulo State University, Botucatu, SP, Brazil; 2Division of Diabetes, Obesity and Lipids, Department of Medicine, The Methodist Hospital Diabetes and Metabolism Institute, and the Houston Methodist Research Institute, Weill Cornell Medical College, Houston, TX, USA Abstract: Clinical trials have demonstrated that it is possible to prevent diabetes through lifestyle modification, pharmacological intervention, and surgery. This review aims to summarize the effectiveness of these various therapeutic interventions in reducing the risk of progression of prediabetes to diabetes, and address the challenges to implement a diabetes prevention program at a community level. Strategies focusing on intensive lifestyle changes are not only efficient but cost-effective and/or cost-saving. Indeed, lifestyle intervention in people at high risk for type 2 diabetes mellitus (T2DM has been successful in achieving sustained behavioral changes and a reduction in diabetes incidence even after the counseling is stopped. Although prediabetes is associated with health and economic burdens, it has not been adequately addressed by interventions or regulatory agencies in terms of prevention or disease management. Lifestyle intervention strategies to prevent T2DM should be distinct for different populations around the globe and should emphasize sex, age, ethnicity, and cultural and geographical considerations to be feasible and to promote better compliance. The translation of diabetes prevention research at a population level, especially finding the most effective methods of preventing T2DM in various societies and cultural settings remains challenging, but must be accomplished to stop this worldwide epidemic. Keywords: lifestyle, T2DM, intervention, prevention

  16. Responses of Tree Seedlings near the Alpine Treeline to Delayed Snowmelt and Reduced Sky Exposure

    Directory of Open Access Journals (Sweden)

    Maaike Y. Bader

    2017-12-01

    Full Text Available Earlier snowmelt changes spring stress exposure and growing-season length, possibly causing shifts in plant species dominance. If such shifts involve trees, this may lead to changes in treeline position. We hypothesized that earlier snowmelt would negatively affect the performance of tree seedlings near the treeline due to higher spring stress levels, but less so if seedlings were protected from the main stress factors of night frosts and excess solar radiation. We exposed seedlings of five European treeline tree species: Larix decidua, Picea abies, Pinus cembra, Pinus uncinata, and Sorbus aucuparia to two snow-cover treatments (early and late melting, with about two weeks difference combined with reduced sky exposure during the day (shading or night (night warming, repeated in two years, at a site about 200 m below the regional treeline elevation. Physiological stress levels (as indicated by lower Fv/Fm in the first weeks after emergence from snow were higher in early-emerging seedlings. As expected, shade reduced stress, but contrary to expectation, night warming did not. However, early- and late-emerging seedlings did not differ overall in their growth or survival, and the interaction with shading was inconsistent between years. Overall, shading had the strongest effect, decreasing stress levels and mortality (in the early-emerging seedlings only, but also growth. A two-week difference in snow-cover duration did not strongly affect the seedlings, although even smaller differences have been shown to affect productivity in alpine and arctic tundra vegetation. Still, snowmelt timing cannot be discarded as important for regeneration in subalpine conditions, because (1 it is likely more critical in very snow-rich or snow-poor mountains or landscape positions; and (2 it can change (subalpine vegetation phenology and productivity, thereby affecting plant interactions, an aspect that should be considered in future studies.

  17. How does delayed testing reduce effects of implicit memory: context infusion or cuing with context?

    Science.gov (United States)

    Nelson, Douglas L; Goodmon, Leilani B; Ceo, David

    2007-07-01

    Studying a word implicitly activates related associates that affect its recall in the extralist cuing task. Recall is more likely when one of these associates becomes the test cue and when other associates of the studied word activate this associate. Context disruptions occurring between study and test reduce these effects, suggesting that implicitly activated memories are linked to context. The context infusion hypothesis assumes that context information spreads throughout a word's associative network during study, decreasing with distance from the studied word. Interactive cuing assumes that context is linked only to the studied word and that recall is based on retrieving information from the test cue and the context. The infusion hypothesis predicts that effects of disruptions will depend on link distance whereas interactive cuing predicts that distance will have no effect. The experiments evaluate these explanations by manipulating target-to-cue strength, associate-to-cue strength, and context disruption. Experiment 1 varies disruption by testing under the same or different conditions (room, modality, experimenter). Experiment 2 tests recall immediately or after 5 m, 10 m, or 20 m of multiplication. The results are inconsistent with context infusion and support the interactive cuing explanation.

  18. Therapeutic administration of a recombinant human monoclonal antibody reduces the severity of chikungunya virus disease in rhesus macaques.

    Directory of Open Access Journals (Sweden)

    Rebecca Broeckel

    2017-06-01

    Full Text Available Chikungunya virus (CHIKV is a mosquito-borne virus that causes a febrile syndrome in humans associated with acute and chronic debilitating joint and muscle pain. Currently no licensed vaccines or therapeutics are available to prevent or treat CHIKV infections. We recently isolated a panel of potently neutralizing human monoclonal antibodies (mAbs, one (4N12 of which exhibited prophylactic and post-exposure therapeutic activity against CHIKV in immunocompromised mice. Here, we describe the development of an engineered CHIKV mAb, designated SVIR001, that has similar antigen binding and neutralization profiles to its parent, 4N12. Because therapeutic administration of SVIR001 in immunocompetent mice significantly reduced viral load in joint tissues, we evaluated its efficacy in a rhesus macaque model of CHIKV infection. Rhesus macaques that were treated after infection with SVIR001 showed rapid elimination of viremia and less severe joint infiltration and disease compared to animals treated with SVIR002, an isotype control mAb. SVIR001 reduced viral burden at the site of infection and at distant sites and also diminished the numbers of activated innate immune cells and levels of pro-inflammatory cytokines and chemokines. SVIR001 therapy; however, did not substantively reduce the induction of CHIKV-specific B or T cell responses. Collectively, these results show promising therapeutic activity of a human anti-CHIKV mAb in rhesus macaques and provide proof-of-principle for its possible use in humans to treat active CHIKV infections.

  19. Glucagon-like peptide-1 analogue, liraglutide, delays onset and reduces severity of experimental autoimmune encephalitis in Lewis rats

    Directory of Open Access Journals (Sweden)

    Brian DellaValle

    2016-11-01

    Full Text Available AbstractIntroduction: Recent findings indicate that metabolic disturbances are involved in multiple sclerosis (MS pathology and influence the susceptibility to treatment, directing attention towards anti-diabetic drugs such as metformin and pioglitazone. Liraglutide, a drug of the glucagon-like peptide-1 (GLP-1 family, is also anti-diabetic and weight-reducing and is moreover, directly neuroprotective and anti-inflammatory in a broad spectrum of experimental models of brain disease. In this study we investigate the potential for this FDA-approved drug, liraglutide, as a treatment for MS by utilizing the experimental model, experimental autoimmune encephalitis (EAE.Methods: EAE was induced in 30 female Lewis rats that subsequently received twice-daily liraglutide (200 µg/kg s.c. or saline. Healthy controls were included (saline, n=6, liraglutide, n=7. Clinical score and weight were assessed daily by blinded observers. Animals were killed at peak disease severity (day 11 or if exceeding humane endpoint (clinical score ≥4. Protein levels of manganese superoxide dismutase (MnSOD, amyloid precursor protein (APP, and glial fibrillary acidic protein (GFAP were determined.Results: Liraglutide treatment delayed disease onset (group clinical score significantly >0 by two days and markedly reduced disease severity (median clinical score 2 vs. 5; p=0.0003. Fourteen of 15 (93% of vehicle-treated rats reached the humane endpoint (clinical score ≥4 by day 11 compared to 5 of 15 (33% of liraglutide-treated rats (p=0.0004. Liraglutide substantially increased the mitochondrial antioxidant MnSOD (p<0.01 and reduced the neurodegenerative marker APP (p=0.036 in the brain. GFAP levels were not significantly changed with drug treatment (p=0.09Conclusion: We demonstrate, for the first time, that liraglutide treatment delays onset of EAE in Lewis rats and is associated with improved protective capacity against oxidative stress. These data suggest GLP-1 receptor

  20. Delayed Treatment with Lidocaine Reduces Mouse Microglial Cell Injury and Cytokine Production After Stimulation with Lipopolysaccharide and Interferon γ

    Science.gov (United States)

    Jeong, Hae-Jeong; Lin, Daowei; Li, Liaoliao; Zuo, Zhiyi

    2012-01-01

    Background Neuroinflammation is an important pathological process for almost all acquired neurological diseases. Microglial cells play a critical role in neuroinflammation. We determined whether lidocaine, a local anesthetic with antiinflammatory property, protected microglial cells and attenuated cytokine production from activated microglial cells. Methods Mouse microglial cultures were incubated with or without 1 µg/ml lipopolysaccharide and 10 U/ml interferon γ (IFNγ) for 24 h in the presence or absence of lidocaine for 1 h started at 2, 3 or 4 h after the onset of lipopolysaccharide and IFNγ stimulation. Lactate dehydrogenase release and cytokine production were determined after the cells were stimulated by lipopolysaccharide and IFNγ for 24 h. Results Lidocaine dose-dependently reduced lipopolysaccharide and IFNγ-induced microglial cell injury as measured by lactate dehydrogenase release. This effect was apparent with lidocaine at 2 µg/ml (30.3 ± 5.8 and 23.1 ± 9.7%, respectively, for stimulation alone and the stimulation in the presence of lidocaine, n = 18, P = 0.025). Lidocaine applied at 2, 3 or 4 h after the onset of lipopolysaccharide and IFNγ stimulation reduced the cell injury. This lidocaine effect was not affected by the mitochondrial KATP channel inhibitor 5-hydroxydecanoate. Similar to lidocaine, QX314, a permanently charged lidocaine analog that usually does not permeate through the plasma membrane, reduced lipopolysaccharide and IFNγ-induced microglial cell injury. QX314 also attenuated the stimulation-induced interleukin-1β production. Conclusions Delayed treatment with lidocaine protects microglial cells and reduces cytokine production from these cells. These effects may involve action site(s) on the cell surface. PMID:22253275

  1. Decreased gut microbiota diversity, delayed Bacteroidetes colonisation and reduced Th1 responses in infants delivered by caesarean section.

    Science.gov (United States)

    Jakobsson, Hedvig E; Abrahamsson, Thomas R; Jenmalm, Maria C; Harris, Keith; Quince, Christopher; Jernberg, Cecilia; Björkstén, Bengt; Engstrand, Lars; Andersson, Anders F

    2014-04-01

    The early intestinal microbiota exerts important stimuli for immune development, and a reduced microbial exposure as well as caesarean section (CS) has been associated with the development of allergic disease. Here we address how microbiota development in infants is affected by mode of delivery, and relate differences in colonisation patterns to the maturation of a balanced Th1/Th2 immune response. The postnatal intestinal colonisation pattern was investigated in 24 infants, born vaginally (15) or by CS (nine). The intestinal microbiota were characterised using pyrosequencing of 16S rRNA genes at 1 week and 1, 3, 6, 12 and 24 months after birth. Venous blood levels of Th1- and Th2-associated chemokines were measured at 6, 12 and 24 months. Infants born through CS had lower total microbiota diversity during the first 2 years of life. CS delivered infants also had a lower abundance and diversity of the Bacteroidetes phylum and were less often colonised with the Bacteroidetes phylum. Infants born through CS had significantly lower levels of the Th1-associated chemokines CXCL10 and CXCL11 in blood. CS was associated with a lower total microbial diversity, delayed colonisation of the Bacteroidetes phylum and reduced Th1 responses during the first 2 years of life.

  2. Some new results on stability and synchronization for delayed inertial neural networks based on non-reduced order method.

    Science.gov (United States)

    Li, Xuanying; Li, Xiaotong; Hu, Cheng

    2017-12-01

    In this paper, without transforming the second order inertial neural networks into the first order differential systems by some variable substitutions, asymptotic stability and synchronization for a class of delayed inertial neural networks are investigated. Firstly, a new Lyapunov functional is constructed to directly propose the asymptotic stability of the inertial neural networks, and some new stability criteria are derived by means of Barbalat Lemma. Additionally, by designing a new feedback control strategy, the asymptotic synchronization of the addressed inertial networks is studied and some effective conditions are obtained. To reduce the control cost, an adaptive control scheme is designed to realize the asymptotic synchronization. It is noted that the dynamical behaviors of inertial neural networks are directly analyzed in this paper by constructing some new Lyapunov functionals, this is totally different from the traditional reduced-order variable substitution method. Finally, some numerical simulations are given to demonstrate the effectiveness of the derived theoretical results. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Ultrasound-guided peripheral venous access for therapeutic apheresis procedures reduces need for central venous catheters.

    Science.gov (United States)

    Salazar, Eric; Garcia, Salvador; Miguel, Robin; Segura, Francisco J; Ipe, Tina S; Leveque, Christopher

    2017-08-01

    Therapeutic and donor apheresis requires adequate vascular access to achieve inlet flow rates of ∼50-100 mL/min. While central dialysis-type venous catheters can usually provide such access, their use includes several associated risks. Some of these risks can be avoided or diminished if adequate peripheral venous access can be established. Some patients have adequate peripheral veins for apheresis that cannot be readily identified visually or by palpation. We hypothesized that ultrasound-guided peripheral venous access would benefit such patients and would lead to placement of fewer central venous catheters. The technique of ultrasound-guided peripheral access for apheresis has been in use at Houston Methodist Hospital since 2012. We performed a prospective review of patients undergoing inpatient and outpatient apheresis at Houston Methodist Hospital from July 1, 2015 to September 30, 2015, to assess its benefit. During this time, we performed 831 procedures on 186 patients, including 787 therapeutic plasma exchanges, three red blood cell exchanges, 41 peripheral stem cell collections. Ultrasound-guided vascular access was used for 68 procedures (8% of all procedures), including 62 therapeutic plasma exchanges, 4 peripheral stem cell collections, and 2 red blood cell changes. Use of ultrasound-guided peripheral access prevented the placement of central venous catheters in 37 (20%) patients, demonstrating its utility in a busy transfusion service. © 2016 Wiley Periodicals, Inc.

  4. Do delayed prescriptions reduce the use of antibiotics for the common cold? A single-blind controlled trial

    National Research Council Canada - National Science Library

    Arroll, B; Kenealy, T; Kerse, N

    2002-01-01

    To test the use of a delayed prescription compared with instructions to take antibiotics immediately in patients presenting to family physicians with upper respiratory tract infections (common colds...

  5. Reduced and delayed expression of GDF9 and BMP15 in ovarian tissues from women with polycystic ovary syndrome.

    Science.gov (United States)

    Wei, Li-Na; Huang, Rui; Li, Li-Lin; Fang, Cong; Li, Yi; Liang, Xiao-Yan

    2014-11-01

    Growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15) play crucial roles in follicular development and oocyte maturation. This study aimed to investigate and compare the expression of these proteins in ovarian tissues of women with and without polycystic ovary syndrome (PCOS). Ovarian tissues from 28 patients with PCOS and 26 normal ovulatory women were collected, and the expression of GDF9 and BMP15 in oocytes and granulosa cells was evaluated via immunohistochemical staining. GDF9 and BMP15 were first expressed in primordial follicles at very low levels, and their expression increased gradually with follicular development, reaching the highest levels in Graafian follicles. However, less GDF9 and BMP15 expression was observed in primordial, primary, and secondary follicles in ovarian tissues of PCOS patients compared with levels in the control tissues (P  0.05). The expression of GDF9 and BMP15 in ovarian tissues varies among the developmental stages in both oocytes and granulosa cells in human ovarian tissues. The expression of these proteins is reduced and delayed in the early follicular stage in PCOS ovarian tissues, and these differences in expression may be associated with aberrant follicular development in patients with PCOS.

  6. Fasting Reduces the Incidence of Delayed-Type Vomiting Associated with Doxorubicin Treatment in Dogs with Lymphoma1

    Science.gov (United States)

    Withers, Sita S.; Kass, Philip H.; Rodriguez, Carlos O.; Skorupski, Katherine A.; O’Brien, Danielle; Guerrero, Teri A.; Sein, Kristen D.; Rebhun, Robert B.

    2014-01-01

    Fasting reduces gastrointestinal cellular proliferation rates through G1 cycle blockade and can promote cellular protection of normal but not cancer cells through altered cell signaling including down-regulation of insulin-like growth factor 1 (IGF-1). Consequently, the purpose of this study was to determine the effects of fasting on delayed-type chemotherapy-induced nausea and vomiting in dogs receiving doxorubicin. This prospective randomized crossover study involved intended administration of two doses of doxorubicin. Cancer-bearing dogs were randomized to be fasted for 24 hours beginning at 6 P.M. the night before the first or second doxorubicin administration, and all treatments were administered within an hour before or after 12 P.M. Dogs were fed normally before the alternate dose. Circulating IGF-1 concentrations were determined from serum samples obtained immediately before each doxorubicin treatment. Data from 35 doses were available from 20 dogs enrolled. Dogs that were fasted exhibited a significantly lower incidence of vomiting, when compared to fed dogs (10% compared to 67%, P = .020). Furthermore, among the 15 dogs that completed crossover dosing, vomiting was abrogated in four of five dogs that experienced doxorubicin-induced vomiting when fed normally (P = .050). No differences in other gastrointestinal, constitutional, or bone marrow toxicities or serum IGF-1 levels were observed. PMID:24831580

  7. Therapeutic vaccination with recombinant adenovirus reduces splenic parasite burden in experimental visceral leishmaniasis.

    Science.gov (United States)

    Maroof, Asher; Brown, Najmeeyah; Smith, Barbara; Hodgkinson, Michael R; Maxwell, Alice; Losch, Florian O; Fritz, Ulrike; Walden, Peter; Lacey, Charles N J; Smith, Deborah F; Aebischer, Toni; Kaye, Paul M

    2012-03-01

    Therapeutic vaccines, when used alone or in combination therapy with antileishmanial drugs, may have an important place in the control of a variety of forms of human leishmaniasis. Here, we describe the development of an adenovirus-based vaccine (Ad5-KH) comprising a synthetic haspb gene linked to a kmp11 gene via a viral 2A sequence. In nonvaccinated Leishmania donovani-infected BALB/c mice, HASPB- and KMP11-specific CD8(+) T cell responses were undetectable, although IgG1 and IgG2a antibodies were evident. After therapeutic vaccination, antibody responses were boosted, and IFNγ(+)CD8(+) T cell responses, particularly to HASPB, became apparent. A single vaccination with Ad5-KH inhibited splenic parasite growth by ∼66%, a level of efficacy comparable to that observed in early stage testing of clinically approved antileishmanial drugs in this model. These studies indicate the usefulness of adenoviral vectors to deliver leishmanial antigens in a potent and host protective manner to animals with existing L. donovani infection.

  8. Therapeutic Vaccination With Recombinant Adenovirus Reduces Splenic Parasite Burden in Experimental Visceral Leishmaniasis

    Science.gov (United States)

    Maroof, Asher; Brown, Najmeeyah; Smith, Barbara; Hodgkinson, Michael R.; Maxwell, Alice; Losch, Florian O.; Fritz, Ulrike; Walden, Peter; Lacey, Charles N. J.; Smith, Deborah F.; Aebischer, Toni

    2012-01-01

    Therapeutic vaccines, when used alone or in combination therapy with antileishmanial drugs, may have an important place in the control of a variety of forms of human leishmaniasis. Here, we describe the development of an adenovirus-based vaccine (Ad5-KH) comprising a synthetic haspb gene linked to a kmp11 gene via a viral 2A sequence. In nonvaccinated Leishmania donovani–infected BALB/c mice, HASPB- and KMP11-specific CD8+ T cell responses were undetectable, although IgG1 and IgG2a antibodies were evident. After therapeutic vaccination, antibody responses were boosted, and IFNγ+CD8+ T cell responses, particularly to HASPB, became apparent. A single vaccination with Ad5-KH inhibited splenic parasite growth by ∼66%, a level of efficacy comparable to that observed in early stage testing of clinically approved antileishmanial drugs in this model. These studies indicate the usefulness of adenoviral vectors to deliver leishmanial antigens in a potent and host protective manner to animals with existing L. donovani infection. PMID:22301630

  9. Superoxide dismutase - a target for gene therapeutic approach to reduce oxidative stress in erectile dysfunction.

    Science.gov (United States)

    Deng, W; Bivalacqua, T J; Champion, H C; Hellstrom, W J; Murthy, Subramanyam N; Kadowitz, Philip J

    2010-01-01

    Erectile dysfunction (ED) is defined as the inability to attain and/or maintain penile erection sufficient for satisfactory sexual performance. Oxidative stress has been demonstrated to be involved in the pathophysiology of age- or diabetes-related ED. Superoxide dismutase (SOD), an antioxidant enzyme catalyzing the conversion of superoxide anion (O(2) (-)) to hydrogen peroxide (H(2)O(2)) and molecular oxygen (O(2)), is a promising therapeutic target for ED. In vivo gene therapy and adult stem cell-based ex vivo gene therapy are two attractive current gene therapies for the treatment of ED. In this chapter we describe the use of two potent gene transfer techniques to deliver the therapeutic gene extracellular superoxide dismutase (ecSOD) into the penis of aged or diabetic rats for therapy of ED: adenoviral-mediated intracavernosal ecSOD gene transfer for gene therapy of ED and ecSOD gene-modified marrow stromal cells, also known as mesenchymal stem cells, based stem cell and gene therapy.

  10. Antioxidant activity, delayed aging, and reduced amyloid-β toxicity of methanol extracts of tea seed pomace from Camellia tenuifolia.

    Science.gov (United States)

    Wei, Chia-Cheng; Yu, Chan-Wei; Yen, Pei-Ling; Lin, Huan-You; Chang, Shang-Tzen; Hsu, Fu-Lan; Liao, Vivian Hsiu-Chuan

    2014-11-05

    There is a growing interest in the exploitation of the residues generated by plants. This study explored the potential beneficial health effects from the main biowaste, tea seed pomace, produced when tea seed is processed. DPPH radical scavenging and total phenolic content assays were performed to evaluate the in vitro activities of the extracts. Caenorhabditis elegans was used as in vivo model to evaluate the beneficial health effects, including antioxidant activity, delayed aging, and reduced amyloid-β toxicity. Among all soluble fractions obtained from the extracts of tea seed pomace from Camellia tenuifolia, the methanol (MeOH)-soluble fraction has the best in vivo antioxidant activities. The MeOH-soluble extraction was further divided into six fractions by chromatography with a Diaion HP-20 column eluted with water/MeOH, and fraction 3 showed the best in vitro and in vivo antioxidant activities. Further analysis in C. elegans showed that the MeOH extract (fraction 3) of tea seed pomace significantly decreased intracellular reactive oxygen species, prolonged C. elegans lifespan, and reduced amyloid-β (Aβ) toxicity in transgenic C. elegans expressing human Aβ. Moreover, bioactivity-guided fractionation yielded two potent constituents from fraction 3 of the MeOH extract, namely, kaempferol 3-O-(2″-glucopyranosyl)-rutinoside and kaempferol 3-O-(2″-xylopyranosyl)-rutinoside, and both compounds exhibited excellent in vivo antioxidant activity. Taken together, MeOH extracts of tea seed pomace from C. tenuifolia have multiple beneficial health effects, suggesting that biowaste might be valuable to be explored for further development as nutraceutical products. Furthermore, the reuse of agricultural byproduct tea seed pomace also fulfills the environmental perspective.

  11. The use of cell phones and radio communication systems to reduce delays in getting help for pregnant women in low- and middle-income countries: a scoping review

    Directory of Open Access Journals (Sweden)

    Sunday O. Oyeyemi

    2015-09-01

    Full Text Available Background: Delays in getting medical help are important factors in the deaths of many pregnant women and unborn children in the low- and middle-income countries (LMIC. Studies have suggested that the use of cell phones and radio communication systems might reduce such delays. Objectives: We review the literature regarding the impact of cell phones and radio communication systems on delays in getting medical help by pregnant women in the LMIC. Design: Cochrane Library, PubMed, Maternity and Infant care (Ovid, Web of Science (ISI, and Google Scholar were searched for studies relating to the use of cell phones for maternal and child health services, supplemented with hand searches. We included studies in LMIC and in English involving the simple use of cell phones (or radio communication to either make calls or send text messages. Results: Fifteen studies met the inclusion criteria. All the studies, while of various designs, demonstrated positive contributory effects of cell phones or radio communication systems in reducing delays experienced by pregnant women in getting medical help. Conclusions: While the results suggested that cell phones could contribute in reducing delays, more studies of a longer duration are needed to strengthen the finding.

  12. The use of cell phones and radio communication systems to reduce delays in getting help for pregnant women in low- and middle-income countries: a scoping review.

    Science.gov (United States)

    Oyeyemi, Sunday O; Wynn, Rolf

    2015-01-01

    Delays in getting medical help are important factors in the deaths of many pregnant women and unborn children in the low- and middle-income countries (LMIC). Studies have suggested that the use of cell phones and radio communication systems might reduce such delays. We review the literature regarding the impact of cell phones and radio communication systems on delays in getting medical help by pregnant women in the LMIC. Cochrane Library, PubMed, Maternity and Infant care (Ovid), Web of Science (ISI), and Google Scholar were searched for studies relating to the use of cell phones for maternal and child health services, supplemented with hand searches. We included studies in LMIC and in English involving the simple use of cell phones (or radio communication) to either make calls or send text messages. Fifteen studies met the inclusion criteria. All the studies, while of various designs, demonstrated positive contributory effects of cell phones or radio communication systems in reducing delays experienced by pregnant women in getting medical help. While the results suggested that cell phones could contribute in reducing delays, more studies of a longer duration are needed to strengthen the finding.

  13. Transient inhibition of ROR-γt therapeutically limits intestinal inflammation by reducing TH17 cells and preserving ILC3

    Science.gov (United States)

    Withers, David R.; Hepworth, Matthew R.; Wang, Xinxin; Mackley, Emma C.; Halford, Emily E.; Dutton, Emma E.; Marriott, Clare L.; Brucklacher-Waldert, Verena; Veldhoen, Marc; Kelsen, Judith; Baldassano, Robert N.; Sonnenberg, Gregory F.

    2016-01-01

    RAR-related orphan receptor γt (ROR-γt) directs differentiation of pro-inflammatory T helper 17 (TH17) cells and is a potential therapeutic target in chronic autoimmune and inflammatory diseases1–3. However, ROR-γt-dependent group 3 innate lymphoid cells (ILC3s) provide essential immunity and tissue protection in the intestine4–11, suggesting that targeting ROR-γt could also result in impaired host defense to infection or enhanced tissue damage. Here, we demonstrate that transient chemical inhibition of ROR-γt in mice selectively reduces cytokine production from TH17 cells but not ILC3s in the context of intestinal infection with Citrobacter rodentium, resulting in preserved innate immunity. Transient genetic deletion of ROR-γt in mature ILC3s also did not impair cytokine responses in the steady state or during infection. Finally, pharmacologic inhibition of ROR-γt provided therapeutic benefit in mouse models of intestinal inflammation, and reduced the frequencies of TH17 cells but not ILC3s isolated from primary intestinal samples of individuals with inflammatory bowel disease (IBD). Collectively, these results reveal differential requirements for ROR-γt in the maintenance of TH17 cell versus ILC3 responses, and suggest that transient inhibition of ROR-γt is a safe and effective therapeutic approach during intestinal inflammation. PMID:26878233

  14. Delayed initiation but not gradual advancement of enteral formula feeding reduces the incidence of necrotizing enterocolitis (NEC in preterm pigs.

    Directory of Open Access Journals (Sweden)

    Nada Ghoneim

    Full Text Available Enteral formula feeding is a risk factor for necrotizing enterocolitis (NEC in premature infants, yet studies are conflicting regarding the safest timing for introduction and advancement of feeds. Our aim was to test the effects of early vs. late initiation and abrupt vs. gradual advancement of enteral feeding of an intact vs. hydrolyzed protein formula on NEC incidence and severity in preterm pigs. In Experiment 1, preterm pigs received total parenteral nutrition (TPN at birth with abrupt initiation of enteral formula feeds (50% full intake on d of life (DOL 2 (EA or 5 (LA while PN continued. Pigs were also fed formula containing either intact or hydrolyzed protein. In Experiment 2, preterm pigs received TPN at birth with enteral, hydrolyzed-protein formula feeds introduced on DOL 2 either abruptly (EA; 50% full feeds or gradually (EG; 10-50% full feeds over 5 d while PN continued. NEC incidence and severity were assessed based on macroscopic and histological scoring. In Experiment 1, NEC incidence (41% vs. 70%, P<0.05 and severity were reduced in LA vs. EA groups and LA was associated with a higher survival rate, daily weight gain and jejunum villus height. Piglets fed hydrolyzed vs. intact protein formula had lower stomach content weights and similar NEC incidence. In Experiment 2, NEC incidence and severity were not different between pigs the EG vs. EA group. Proinflammatory gene expression (IL-1β, IL-6 and S100A9 in the ileum was lower in both LA and EG vs. EA groups. In conclusion, delayed initiation but not gradual advancement of enteral feeding is protective against NEC in preterm pigs. Feeding hydrolyzed vs. intact protein formula improved gastric transit without affecting the NEC incidence.

  15. Delayed uterine fluid clearance and reduced uterine perfusion in bitches with endometrial hyperplasia and clinical management with postmating antibiotic.

    Science.gov (United States)

    England, G C W; Moxon, R; Freeman, S L

    2012-10-15

    In many species a transient uterine inflammatory response follows mating and is proposed to remove excess spermatozoa, bacteria, and other contaminants from the uterus. Similar events have been documented in the bitch involving increased uterine contractions, polymorphonuclear neutrophil influx and uterine artery vasodilation. Some healthy bitches with endometrial hyperplasia have increased numbers of uterine luminal polymorphonuclear neutrophils after mating and reduced fertility; it is purported that this represents a presumed postmating endometritis. This study used B-mode and Doppler ultrasonography at the time of mating to measure uterine contractions, clearance of ejaculated fluid, and uterine artery velocity in normal bitches and those with endometrial hyperplasia. Mating resulted in an increase in the number of uterine contractions, although fewer mating-induced contractions were noted in bitches with endometrial hyperplasia. Interestingly, uterine fluid cleared significantly more slowly after mating from the bitches with endometrial hyperplasia than the normal bitches (P = 0.01). In a further study, Doppler ultrasonography showed that in normal bitches there was a significant increase in uterine artery blood velocity (P = 0.04) and a decrease in the resistance index after mating (P = 0.04), indicating vasodilation. In bitches with endometrial hyperplasia the baseline resistance index was significantly higher than normal bitches (P = 0.05), and furthermore, although there was a significant decrease in resistance index after mating, in the bitches with endometrial hyperplasia this was of a smaller magnitude that in normal bitches. These findings indicate lower baseline uterine perfusion, and a blunted vasodilation response to mating in bitches with endometrial hyperplasia. Short-duration postmating administration of systemic antibiotic increased pregnancy rates in bitches with endometrial hyperplasia (P uterine vasodilatory response to mating and delaying

  16. Sequential application of non-pharmacological interventions reduces the severity of labour pain, delays use of pharmacological analgesia, and improves some obstetric outcomes: a randomised trial

    Directory of Open Access Journals (Sweden)

    Rubneide Barreto Silva Gallo

    2018-01-01

    Trial registration: NCT01389128. [Gallo RBS, Santana LS, Marcolin AC, Duarte G, Quintana SM (2018 Sequential application of non-pharmacological interventions reduces the severity of labour pain, delays use of pharmacological analgesia, and improves some obstetric outcomes: a randomised trial. Journal of Physiotherapy 64: 33–40

  17. A Reduced-Order Controller Considering High-Order Modal Information of High-Rise Buildings for AMD Control System with Time-Delay

    Directory of Open Access Journals (Sweden)

    Zuo-Hua Li

    2017-01-01

    Full Text Available Time-delays of control force calculation, data acquisition, and actuator response will degrade the performance of Active Mass Damper (AMD control systems. To reduce the influence, model reduction method is used to deal with the original controlled structure. However, during the procedure, the related hierarchy information of small eigenvalues will be directly discorded. As a result, the reduced-order model ignores the information of high-order mode, which will reduce the design accuracy of an AMD control system. In this paper, a new reduced-order controller based on the improved Balanced Truncation (BT method is designed to reduce the calculation time and to retain the abandoned high-order modal information. It includes high-order natural frequency, damping ratio, and vibration modal information of the original structure. Then, a control gain design method based on Guaranteed Cost Control (GCC algorithm is presented to eliminate the adverse effects of data acquisition and actuator response time-delays in the design process of the reduced-order controller. To verify its effectiveness, the proposed methodology is applied to a numerical example of a ten-storey frame and an experiment of a single-span four-storey steel frame. Both numerical and experimental results demonstrate that the reduced-order controller with GCC algorithm has an excellent control effect; meanwhile it can compensate time-delays effectively.

  18. Piroxicam fails to reduce myocellular enzyme leakage and delayed onset muscle soreness induced by isokinetic eccentric exercise

    Directory of Open Access Journals (Sweden)

    J-L. Croisier

    1996-01-01

    Full Text Available To test the hypothesis that delayed onset muscular soreness (DOMS following intense eccentric muscle contraction could be due to increased production of prostaglandin E2 (PGE2, ten healthy male subjects were studied. Using a double-blind randomized crossover design, each subject performed two isokinetic tests separated by a period of at least 6 weeks: once with placebo, and once with piroxicam (Feldene®. They were given one capsule containing either placebo or piroxicam (20 mg per day for 6 days with initial doses given starting 3 days prior to isokinetic testing. Exercise consisted of eight stages of five maximal contractions of the knee extensor and flexor muscle groups of both legs separated by 1 min rest phases, on a Kin Trex device at 60°/s angular velocity. The subjective presence and intensity of DOMS were evaluated using a visual analogue scale immediately after, and 24 and 48 h after each test. The mean plasma concentration of PGE2 measured at rest and after exercise was significantly lower in the group treated with piroxicam (p < 0.05. However, statistical analysis (two-way ANOVA test revealed that exercise did not cause any significant change of mean plasma PGE2 over time in either of the two groups. Eccentric work was followed by severe muscle pain in extensor and flexor muscle groups. Maximal soreness was noted 48 h postexercise. Serum creatine kinase activity and the serum concentration of myoglobin increased significantly, and reached peak values 48 h after exercise in both experimental conditions (p < 0.001. By paired t-test, it appeared that there were no significant differences in the serum levels of these two markers of muscle damage between the two groups at any time point. We conclude that: (1 oral administration of piroxicam fails to reduce muscle damage and DOMS caused by strenuous eccentric exercise; and (2 the hypothetical role of increased PGE2 production in eccentric exercise-induced muscle damage, DOMS, and reduced

  19. Therapeutic concentration of morphine reduces oxidative stress in glioma cell line

    Directory of Open Access Journals (Sweden)

    M.B. Almeida

    2014-05-01

    Full Text Available Morphine is a potent analgesic opioid used extensively for pain treatment. During the last decade, global consumption grew more than 4-fold. However, molecular mechanisms elicited by morphine are not totally understood. Thus, a growing literature indicates that there are additional actions to the analgesic effect. Previous studies about morphine and oxidative stress are controversial and used concentrations outside the range of clinical practice. Therefore, in this study, we hypothesized that a therapeutic concentration of morphine (1 μM would show a protective effect in a traditional model of oxidative stress. We exposed the C6 glioma cell line to hydrogen peroxide (H2O2 and/or morphine for 24 h and evaluated cell viability, lipid peroxidation, and levels of sulfhydryl groups (an indicator of the redox state of the cell. Morphine did not prevent the decrease in cell viability provoked by H2O2 but partially prevented lipid peroxidation caused by 0.0025% H2O2 (a concentration allowing more than 90% cell viability. Interestingly, this opioid did not alter the increased levels of sulfhydryl groups produced by exposure to 0.0025% H2O2, opening the possibility that alternative molecular mechanisms (a direct scavenging activity or the inhibition of NAPDH oxidase may explain the protective effect registered in the lipid peroxidation assay. Our results demonstrate, for the first time, that morphine in usual analgesic doses may contribute to minimizing oxidative stress in cells of glial origin. This study supports the importance of employing concentrations similar to those used in clinical practice for a better approximation between experimental models and the clinical setting.

  20. Nitroxyl (HNO): A Reduced Form of Nitric Oxide with Distinct Chemical, Pharmacological, and Therapeutic Properties

    OpenAIRE

    Shoman, Mai E; Aly, Omar M.

    2016-01-01

    Nitroxyl (HNO), the one-electron reduced form of nitric oxide (NO), shows a distinct chemical and biological profile from that of NO. HNO is currently being viewed as a vasodilator and positive inotropic agent that can be used as a potential treatment for heart failure. The ability of HNO to react with thiols and thiol containing proteins is largely used to explain the possible biological actions of HNO. Herein, we summarize different aspects related to HNO including HNO donors, chemistry, bi...

  1. Bulky Polar Additives That Greatly Reduce the Viscosity of Concentrated Solutions of Therapeutic Monoclonal Antibodies.

    Science.gov (United States)

    Larson, Alyssa M; Weight, Alisha K; Love, Kevin; Bonificio, Amanda; Wescott, Charles R; Klibanov, Alexander M

    2017-05-01

    The viscosity of concentrated aqueous solutions of 3 clinical monoclonal antibodies (mAbs), Erbitux®, Herceptin®, and Rituxan®, has been reduced up to over 10-fold by adding certain bulky polar additives instead of saline at isotonic levels. Because these additives are also found not to compromise mAbs' stability against aggregation induced by stresses, a drug-delivery modality switch from intravenous infusions to more convenient and inexpensive parenteral options like subcutaneous injections may become possible. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  2. Nitroxyl (HNO): A Reduced Form of Nitric Oxide with Distinct Chemical, Pharmacological, and Therapeutic Properties.

    Science.gov (United States)

    Shoman, Mai E; Aly, Omar M

    2016-01-01

    Nitroxyl (HNO), the one-electron reduced form of nitric oxide (NO), shows a distinct chemical and biological profile from that of NO. HNO is currently being viewed as a vasodilator and positive inotropic agent that can be used as a potential treatment for heart failure. The ability of HNO to react with thiols and thiol containing proteins is largely used to explain the possible biological actions of HNO. Herein, we summarize different aspects related to HNO including HNO donors, chemistry, biology, and methods used for its detection.

  3. Nitroxyl (HNO: A Reduced Form of Nitric Oxide with Distinct Chemical, Pharmacological, and Therapeutic Properties

    Directory of Open Access Journals (Sweden)

    Mai E. Shoman

    2016-01-01

    Full Text Available Nitroxyl (HNO, the one-electron reduced form of nitric oxide (NO, shows a distinct chemical and biological profile from that of NO. HNO is currently being viewed as a vasodilator and positive inotropic agent that can be used as a potential treatment for heart failure. The ability of HNO to react with thiols and thiol containing proteins is largely used to explain the possible biological actions of HNO. Herein, we summarize different aspects related to HNO including HNO donors, chemistry, biology, and methods used for its detection.

  4. Can a standard dose of eicosapentaenoic acid (EPA supplementation reduce the symptoms of delayed onset of muscle soreness?

    Directory of Open Access Journals (Sweden)

    Houghton David

    2012-01-01

    Full Text Available Abstract Background Unaccustomed exercise can result in delayed onset of muscle soreness (DOMS which can affect athletic performance. Although DOMS is a useful tool to identify muscle damage and remodelling, prolonged symptoms of DOMS may be associated with the over-training syndrome. In order to reduce the symptoms of DOMS numerous management strategies have been attempted with no significant effect on DOMS-associated cytokines surge. The present study aimed to investigate the acute and chronic effects of a 2 × 180 mg per day dose of eicosapentaenoic acid (EPA on interleukin-6 (IL-6 mediated inflammatory response and symptoms associated with DOMS. Methods Seventeen healthy non-smoking females (age 20.4 ± 2.1 years, height 161.2 ± 8.3 cm and mass 61.48 ± 7.4 kg were randomly assigned to either placebo (N = 10 or EPA (N = 7. Serum IL-6, isometric and isokinetic (concentric and eccentric strength, and rating of perceived exertion (RPE were recorded on four occasions: i-prior to supplementation, ii-immediately after three weeks of supplementation (basal effects, iii-48 hours following a single bout of resistance exercise (acute training response effects, and iv-48 hours following the last of a series of three bouts of resistance exercise (chronic training response effects. Results There was only a group difference in the degree of change in circulating IL-6 levels. In fact, relative to the first baseline, by the third bout of eccentric workout, the EPA group had 103 ± 60% increment in IL-6 levels whereas the placebo group only had 80 ± 26% incremented IL-6 levels (P = 0.020. We also describe a stable multiple linear regression model which included measures of strength and not IL-6 as predictors of RPE scale. Conclusion The present study suggests that in doubling the standard recommended dose of EPA, whilst this may still not be beneficial at ameliorating the symptoms of DOMS, it counter intuitively appears to enhance the cytokine response to

  5. Physico-Chemical, Biological and Therapeutic Characteristics of Electrolyzed Reduced Alkaline Water (ERAW

    Directory of Open Access Journals (Sweden)

    Marc Henry

    2013-12-01

    Full Text Available The consumption of alkaline reduced water produced by domestic electrolysis devices was approved in Japan in 1965 by the Ministry of Health, Labour and Welfare for the cure of gastro-intestinal disorders. Today, these devices are freely available in several countries and can be easily purchased without reserve. The commercial information included with the device recommends the consumption of 1–1.5 L of water per day, not only for gastro-intestinal disorders but also for numerous other illnesses such as diabetes, cancer, inflammation, etc. Academic research in Japan on this subject has been undergoing since 1990 only but has established that the active ingredient is dissolved dihydrogen that eliminates the free radical HO• in vivo. In addition, it was demonstrated that degradation of the electrodes during functioning of the device releases very reactive nanoparticles of platinum, the toxicity of which has not yet been clearly proven. This report recommends alerting health authorities of the uncontrolled availability of these devices used as health products, but which generate drug substances and should therefore be sold according to regulatory requirements.

  6. A New Strategy to Reduce Influenza Escape: Detecting Therapeutic Targets Constituted of Invariance Groups

    Directory of Open Access Journals (Sweden)

    Julie Lao

    2017-03-01

    Full Text Available The pathogenicity of the different flu species is a real public health problem worldwide. To combat this scourge, we established a method to detect drug targets, reducing the possibility of escape. Besides being able to attach a drug candidate, these targets should have the main characteristic of being part of an essential viral function. The invariance groups that are sets of residues bearing an essential function can be detected genetically. They consist of invariant and synthetic lethal residues (interdependent residues not varying or slightly varying when together. We analyzed an alignment of more than 10,000 hemagglutinin sequences of influenza to detect six invariance groups, close in space, and on the protein surface. In parallel we identified five potential pockets on the surface of hemagglutinin. By combining these results, three potential binding sites were determined that are composed of invariance groups located respectively in the vestigial esterase domain, in the bottom of the stem and in the fusion area. The latter target is constituted of residues involved in the spring-loaded mechanism, an essential step in the fusion process. We propose a model describing how this potential target could block the reorganization of the hemagglutinin HA2 secondary structure and prevent viral entry into the host cell.

  7. A TOTP-based enhanced route optimization procedure for mobile IPv6 to reduce handover delay and signalling overhead.

    Science.gov (United States)

    Shah, Peer Azmat; Hasbullah, Halabi B; Lawal, Ibrahim A; Aminu Mu'azu, Abubakar; Tang Jung, Low

    2014-01-01

    Due to the proliferation of handheld mobile devices, multimedia applications like Voice over IP (VoIP), video conferencing, network music, and online gaming are gaining popularity in recent years. These applications are well known to be delay sensitive and resource demanding. The mobility of mobile devices, running these applications, across different networks causes delay and service disruption. Mobile IPv6 was proposed to provide mobility support to IPv6-based mobile nodes for continuous communication when they roam across different networks. However, the Route Optimization procedure in Mobile IPv6 involves the verification of mobile node's reachability at the home address and at the care-of address (home test and care-of test) that results in higher handover delays and signalling overhead. This paper presents an enhanced procedure, time-based one-time password Route Optimization (TOTP-RO), for Mobile IPv6 Route Optimization that uses the concepts of shared secret Token, time based one-time password (TOTP) along with verification of the mobile node via direct communication and maintaining the status of correspondent node's compatibility. The TOTP-RO was implemented in network simulator (NS-2) and an analytical analysis was also made. Analysis showed that TOTP-RO has lower handover delays, packet loss, and signalling overhead with an increased level of security as compared to the standard Mobile IPv6's Return-Routability-based Route Optimization (RR-RO).

  8. A TOTP-Based Enhanced Route Optimization Procedure for Mobile IPv6 to Reduce Handover Delay and Signalling Overhead

    Directory of Open Access Journals (Sweden)

    Peer Azmat Shah

    2014-01-01

    Full Text Available Due to the proliferation of handheld mobile devices, multimedia applications like Voice over IP (VoIP, video conferencing, network music, and online gaming are gaining popularity in recent years. These applications are well known to be delay sensitive and resource demanding. The mobility of mobile devices, running these applications, across different networks causes delay and service disruption. Mobile IPv6 was proposed to provide mobility support to IPv6-based mobile nodes for continuous communication when they roam across different networks. However, the Route Optimization procedure in Mobile IPv6 involves the verification of mobile node’s reachability at the home address and at the care-of address (home test and care-of test that results in higher handover delays and signalling overhead. This paper presents an enhanced procedure, time-based one-time password Route Optimization (TOTP-RO, for Mobile IPv6 Route Optimization that uses the concepts of shared secret Token, time based one-time password (TOTP along with verification of the mobile node via direct communication and maintaining the status of correspondent node’s compatibility. The TOTP-RO was implemented in network simulator (NS-2 and an analytical analysis was also made. Analysis showed that TOTP-RO has lower handover delays, packet loss, and signalling overhead with an increased level of security as compared to the standard Mobile IPv6’s Return-Routability-based Route Optimization (RR-RO.

  9. Winter warming delays dormancy release, advances budburst, alters carbohydrate metabolism and reduces yield in a temperate shrub

    DEFF Research Database (Denmark)

    Pagter, Majken; Andersen, Uffe Brandt; Andersen, Lillie

    2015-01-01

    winter warming modifies phenological traits in a woody perennial known to have a large chilling requirement and to be sensitive to spring frost. Warming delayed dormancy release more in the cultivar ‘Narve Viking’ than in the cultivar ‘Titania’, but advanced budburst and flowering predominantly...

  10. New therapeutic approach: diphenyl diselenide reduces mitochondrial dysfunction in acetaminophen-induced acute liver failure.

    Directory of Open Access Journals (Sweden)

    Nélson R Carvalho

    Full Text Available The acute liver failure (ALF induced by acetaminophen (APAP is closely related to oxidative damage and depletion of hepatic glutathione, consequently changes in cell energy metabolism and mitochondrial dysfunction have been observed after APAP overdose. Diphenyl diselenide [(PhSe2], a simple organoselenium compound with antioxidant properties, previously demonstrated to confer hepatoprotection. However, little is known about the protective mechanism on mitochondria. The main objective of this study was to investigate the effects (PhSe2 to reduce mitochondrial dysfunction and, secondly, compare in the liver homogenate the hepatoprotective effects of the (PhSe2 to the N-acetylcysteine (NAC during APAP-induced ALF to validate our model. Mice were injected intraperitoneal with APAP (600 mg/kg, (PhSe2 (15.6 mg/kg, NAC (1200 mg/kg, APAP+(PhSe2 or APAP+NAC, where the (PhSe2 or NAC treatment were given 1 h following APAP. The liver was collected 4 h after overdose. The plasma alanine and aspartate aminotransferase activities increased after APAP administration. APAP caused a remarkable increase of oxidative stress markers (lipid peroxidation, reactive species and protein carbonylation and decrease of the antioxidant defense in the liver homogenate and mitochondria. APAP caused a marked loss in the mitochondrial membrane potential, the mitochondrial ATPase activity, and the rate of mitochondrial oxygen consumption and increased the mitochondrial swelling. All these effects were significantly prevented by (PhSe2. The effectiveness of (PhSe2 was similar at a lower dose than NAC. In summary, (PhSe2 provided a significant improvement to the mitochondrial redox homeostasis and the mitochondrial bioenergetics dysfunction caused by membrane permeability transition in the hepatotoxicity APAP-induced.

  11. Re: What is the best treatment to reduce the need for caesarean section in nulliparous women at term with delayed first stage of labour?

    DEFF Research Database (Denmark)

    Boie, Sidsel; Glavind, Julie; Uldbjerg, Niels

    2017-01-01

    The authors pose the question - What is the best treatment to reduce the need for caesarean section in nulliparous women at term with delayed first stage of labour? and state in their paper that "There is no consensus on the optimal dose regimen of oxytocin for delay in the first stage of labour...... in nulliparous women at term (37-42 weeks’ gestation) to reduce unplanned caesarean section and increase vaginal birth with minimal adverse events". However, they describe only low and high dose oxytocin regimens and fail to acknowledge that no oxytocin at all is associated with a spontaneous delivery just...... as often as when oxytocin is given (1,2) or that discontinuation of oxytocin once the active phase of labour is reached can result in higher spontaneous delivery rates than continuing oxytocin (3,4). The paper in its list of trials (box 2) only describes those addressing high and low dose oxytocin, which...

  12. Fast-track pathway for reduction of dislocated hip arthroplasty reduces surgical delay and length of stay

    DEFF Research Database (Denmark)

    Gromov, Kirill; Willendrup, Fatin; Palm, Henrik

    2015-01-01

    BACKGROUND AND PURPOSE: Dislocation is one of the most common complications following hip arthroplasty. Delay until reduction leads to pain for the patient, and may increase the risk of complications. We investigated the safety aspect of a fast-track pathway for dislocated hip arthroplasties...... and evaluated its effect on surgical delay and length of stay (LOS). PATIENTS AND METHODS: 402 consecutive and unselected dislocations (253 patients) were admitted at our institution between May 10, 2010 and September 31, 2013. The fast-track pathway for early reduction was introduced on January 9, 2011. Fast...... admitted through the fast-track pathway than in patients on regular pathway. Perioperative complications (1.6% vs. 3.7%) and complications during the hospital stay (11% vs. 15%) were also less, but not statistically significantly so. Only 1 patient admitted through fast-track pathway had a fracture instead...

  13. Altered joint tribology in osteoarthritis: Reduced lubricin synthesis due to the inflammatory process. New horizons for therapeutic approaches.

    Science.gov (United States)

    Szychlinska, M A; Leonardi, R; Al-Qahtani, M; Mobasheri, A; Musumeci, G

    2016-06-01

    Osteoarthritis (OA) is the most common form of joint disease. This review aimed to consolidate the current evidence that implicates the inflammatory process in the attenuation of synovial lubrication and joint tissue homeostasis in OA. Moreover, with these findings, we propose some evidence for novel therapeutic strategies for preventing and/or treating this complex disorder. The studies reviewed support that inflammatory mediators participate in the onset and progression of OA after joint injury. The flow of pro-inflammatory cytokines following an acute injury seems to be directly associated with altered lubricating ability in the joint tissue. The latter is associated with reduced level of lubricin, one of the major joint lubricants. Future research should focus on the development of new therapies that attenuate the inflammatory process and restore lubricin synthesis and function. This approach could support joint tribology and synovial lubrication leading to improved joint function and pain relief. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  14. Dietary restriction delays the secretion of senescence associated secretory phenotype by reducing DNA damage response in the process of renal aging.

    Science.gov (United States)

    Wang, Wenjuan; Cai, Guangyan; Chen, Xiangmei

    2017-09-13

    Dietary restriction (DR) has multiple and essential effects in protecting against DNA damage in model organisms. Persistent DNA damage plays a central role in the process of aging. Senescence-associated secretory phenotype (SASP), as a product of cellular aging, can accelerate the process of cellular senescence as a feedback. In this study, we directly observed whether a DR of 30% for 6months in aged rats could retard SASP by delaying the progression of DNA damage and also found the specific mechanism. The results revealed that a 30% DR could significantly improve renal pathology and some metabolic characteristics. The biomarkers and products of DNA damage were decreased in the process of renal aging on a 30% DR. A series of SASP, notably cytokine, chemokine, and growth factor, were obviously reduced by DR during renal aging. The phosphorylation levels of NF-κB and IκBα in aged kidneys of DR group were markedly reduced. These findings suggest that a 30% DR for 6months can delay renal aging and reduce the accumulation of SASP by retarding the progression of DNA damage and decreasing the transcription activity of NF-κB, thus providing a target to delay renal aging. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Reducing communication delays and improving quality of care with a tuberculosis laboratory information system in resource poor environments: a cluster randomized controlled trial.

    Science.gov (United States)

    Blaya, Joaquín A; Shin, Sonya S; Yagui, Martin; Contreras, Carmen; Cegielski, Peter; Yale, Gloria; Suarez, Carmen; Asencios, Luis; Bayona, Jaime; Kim, Jihoon; Fraser, Hamish S F

    2014-01-01

    Lost, delayed or incorrect laboratory results are associated with delays in initiating treatment. Delays in treatment for Multi-Drug Resistant Tuberculosis (MDR-TB) can worsen patient outcomes and increase transmission. The objective of this study was to evaluate the impact of a laboratory information system in reducing delays and the time for MDR-TB patients to culture convert (stop transmitting). 78 primary Health Centers (HCs) in Lima, Peru. Participants lived within the catchment area of participating HCs and had at least one MDR-TB risk factor. The study design was a cluster randomized controlled trial with baseline data. The intervention was the e-Chasqui web-based laboratory information system. Main outcome measures were: times to communicate a result; to start or change a patient's treatment; and for that patient to culture convert. 1671 patients were enrolled. Intervention HCs took significantly less time to receive drug susceptibility test (DST) (median 11 vs. 17 days, Hazard Ratio 0.67 [0.62-0.72]) and culture (5 vs. 8 days, 0.68 [0.65-0.72]) results. The time to treatment was not significantly different, but patients in intervention HCs took 16 days (20%) less time to culture convert (p = 0.047). The eChasqui system reduced the time to communicate results between laboratories and HCs and time to culture conversion. It is now used in over 259 HCs covering 4.1 million people. This is the first randomized controlled trial of a laboratory information system in a developing country for any disease and the only study worldwide to show clinical impact of such a system. ClinicalTrials.gov NCT01201941.

  16. Reducing communication delays and improving quality of care with a tuberculosis laboratory information system in resource poor environments: a cluster randomized controlled trial.

    Directory of Open Access Journals (Sweden)

    Joaquín A Blaya

    Full Text Available Lost, delayed or incorrect laboratory results are associated with delays in initiating treatment. Delays in treatment for Multi-Drug Resistant Tuberculosis (MDR-TB can worsen patient outcomes and increase transmission. The objective of this study was to evaluate the impact of a laboratory information system in reducing delays and the time for MDR-TB patients to culture convert (stop transmitting.78 primary Health Centers (HCs in Lima, Peru. Participants lived within the catchment area of participating HCs and had at least one MDR-TB risk factor. The study design was a cluster randomized controlled trial with baseline data. The intervention was the e-Chasqui web-based laboratory information system. Main outcome measures were: times to communicate a result; to start or change a patient's treatment; and for that patient to culture convert.1671 patients were enrolled. Intervention HCs took significantly less time to receive drug susceptibility test (DST (median 11 vs. 17 days, Hazard Ratio 0.67 [0.62-0.72] and culture (5 vs. 8 days, 0.68 [0.65-0.72] results. The time to treatment was not significantly different, but patients in intervention HCs took 16 days (20% less time to culture convert (p = 0.047.The eChasqui system reduced the time to communicate results between laboratories and HCs and time to culture conversion. It is now used in over 259 HCs covering 4.1 million people. This is the first randomized controlled trial of a laboratory information system in a developing country for any disease and the only study worldwide to show clinical impact of such a system.ClinicalTrials.gov NCT01201941.

  17. Implementing a Family Centered Program for Physically Impaired/Developmentally Delayed Preschool Children To Bridge the Therapeutic Gap between School and Home.

    Science.gov (United States)

    Kluger, Karen P.

    This practicum addresses the problem of limited interaction between physical therapists and families of developmentally delayed/physically impaired preschool-age children. A program was developed in which the physical therapist was videotaped handling and exercising a child, while explaining the purpose of the movements and instructing the parent…

  18. Infrared warming reduced winter wheat yields and some physiological parameters, which were mitigated by irrigation and worsened by delayed sowing.

    Directory of Open Access Journals (Sweden)

    Shibo Fang

    Full Text Available Winter wheat has a central role in ensuring the food security and welfare of 1.3 billion people in China. Extensive previous studies have concluded that winter wheat yields would decrease with higher temperatures, owing to warming-induced soil drying or shortening of phenophase. Temperature in China is predicted to increase by 1-5°C by 2100, which may greatly impact plant production and cause other negative effects. We performed a manipulative field experiment, creating diverse growth regimes for wheat by infrared radiation (IR warming day and night, including IR warming only (DW, IR warming + delayed sowing dates (DS, IR warming + increased irrigation (IW, and a control (CK. The results show that IR warming increased daily average wheat canopy and soil temperatures by 2.0°C and 2.3°C, respectively. DW was associated with an advanced maturity of 10 days and yield reduction of 8.2%. IR-warming effects on the photosynthetic apparatus of wheat varied with season as well as significant differences were found in the booting stage. DS represented a worsened situation, lowering yield per plant by 16.4%, with a significant decline in aboveground biomass and functional leaf area. Wheat under DS showed double-peak patterns of diurnal gas exchange during booting stages and, consequently, lower photosynthetic capacity with high transpiration for cooling. Significantly lower actual water use efficiency and intrinsic water use efficiency from jointing to anthesis stages were also found under DS. However, IW had no significant difference from CK, irrespective of yield and photosynthesis. Therefore, we concluded that delayed sowing date may not be a good choice for winter wheat, whereas a thoroughly-watered wheat agroecosystem should be promoted in the context of global warming.

  19. Hydroxychloroquine reduces heart rate by modulating the hyperpolarization-activated current If: Novel electrophysiological insights and therapeutic potential.

    Science.gov (United States)

    Capel, Rebecca A; Herring, Neil; Kalla, Manish; Yavari, Arash; Mirams, Gary R; Douglas, Gillian; Bub, Gil; Channon, Keith; Paterson, David J; Terrar, Derek A; Burton, Rebecca-Ann B

    2015-10-01

    Bradycardic agents are of interest for the treatment of ischemic heart disease and heart failure, as heart rate is an important determinant of myocardial oxygen consumption. The purpose of this study was to investigate the propensity of hydroxychloroquine (HCQ) to cause bradycardia. We assessed the effects of HCQ on (1) cardiac beating rate in vitro (mice); (2) the "funny" current (If) in isolated guinea pig sinoatrial node (SAN) myocytes (1, 3, 10 µM); (3) heart rate and blood pressure in vivo by acute bolus injection (rat, dose range 1-30 mg/kg), (4) blood pressure and ventricular function during feeding (mouse, 100 mg/kg/d for 2 wk, tail cuff plethysmography, anesthetized echocardiography). In mouse atria, spontaneous beating rate was significantly (P rate (17% ± 6%, 1 μM dose) and a dose-dependent reduction in If (13% ± 3% at 1 µM; 19% ± 2% at 3 µM). Effects were also observed on L-type calcium ion current (ICaL) (12% ± 4% reduction) and rapid delayed rectifier potassium current (IKr) (35% ± 4%) at 3 µM. Intravenous HCQ decreased heart rate in anesthetized rats (14.3% ± 1.1% at 15mg/kg; n = 6) without significantly reducing mean arterial blood pressure. In vivo feeding studies in mice showed no significant change in systolic blood pressure nor left ventricular function. We have shown that HCQ acts as a bradycardic agent in SAN cells, in atrial preparations, and in vivo. HCQ slows the rate of spontaneous action potential firing in the SAN through multichannel inhibition, including that of If. Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

  20. Outpatient Management of Delayed Graft Function Is Associated With Reduced Length of Stay Without an Increase in Adverse Events.

    Science.gov (United States)

    Muth, B L; Astor, B C; Turk, J; Mohamed, M; Parajuli, S; Kaufman, D B; Mandelbrot, D A; Djamali, A

    2016-05-01

    Delayed graft function (DGF) is a common and costly complication of kidney transplantation. In July 2011, we established a multidisciplinary DGF clinic managed by nurse practitioners to facilitate early discharge and intensive management of DGF in the outpatient setting. We compared length of stay, 30-day readmission, acute rejection, and patient/graft survival in 697 consecutive deceased donor kidney transplantations performed between July 2009 and July 2014. Patients were divided into three groups: no DGF (n = 487), DGF before implementation of the DGF clinic (n = 118), and DGF clinic (n = 92). Baseline characteristics including age, gender, panel reactive antibody, retransplantation rates, HLA mismatches, induction, and maintenance immunosuppression were not significantly different between pre- and post-DGF clinic groups. Length of stay was significantly longer in pre-DGF clinic (10.9 ± 6.2 vs. 6.1 ± 2.1 days, p management of DGF in a specialized clinic is associated with substantially shorter hospitalization and lower incidence of acute rejection without significant difference in 30-day readmission or patient and graft survival. © Copyright 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.

  1. Reduced cortical complexity in children with Prader-Willi Syndrome and its association with cognitive impairment and developmental delay.

    Directory of Open Access Journals (Sweden)

    Akvile Lukoshe

    Full Text Available BACKGROUND: Prader-Willi Syndrome (PWS is a complex neurogenetic disorder with symptoms involving not only hypothalamic, but also a global, central nervous system dysfunction. Previously, qualitative studies reported polymicrogyria in adults with PWS. However, there have been no quantitative neuroimaging studies of cortical morphology in PWS and no studies to date in children with PWS. Thus, our aim was to investigate and quantify cortical complexity in children with PWS compared to healthy controls. In addition, we investigated differences between genetic subtypes of PWS and the relationship between cortical complexity and intelligence within the PWS group. METHODS: High-resolution structural magnetic resonance images were acquired in 24 children with genetically confirmed PWS (12 carrying a deletion (DEL, 12 with maternal uniparental disomy (mUPD and 11 age- and sex-matched typically developing siblings as healthy controls. Local gyrification index (lGI was obtained using the FreeSurfer software suite. RESULTS: Four large clusters, two in each hemisphere, comprising frontal, parietal and temporal lobes, had lower lGI in children with PWS, compared to healthy controls. Clusters with lower lGI also had significantly lower cortical surface area in children with PWS. No differences in cortical thickness of the clusters were found between the PWS and healthy controls. lGI correlated significantly with cortical surface area, but not with cortical thickness. Within the PWS group, lGI in both hemispheres correlated with Total IQ and Verbal IQ, but not with Performance IQ. Children with mUPD, compared to children with DEL, had two small clusters with lower lGI in the right hemisphere. lGI of these clusters correlated with cortical surface area, but not with cortical thickness or IQ. CONCLUSIONS: These results suggest that lower cortical complexity in children with PWS partially underlies cognitive impairment and developmental delay, probably due to

  2. Cold snare polypectomy reduced delayed postpolypectomy bleeding compared with conventional hot polypectomy: a propensity score-matching analysis.

    Science.gov (United States)

    Yamashina, Takeshi; Fukuhara, Manabu; Maruo, Takanori; Tanke, Gensho; Marui, Saiko; Sada, Ryota; Taki, Mio; Ohara, Yoshiaki; Sakamoto, Azusa; Henmi, Shinichiro; Sawai, Yugo; Saito, Sumio; Nishijima, Norihiro; Nasu, Akihiro; Komekado, Hideyuki; Sekikawa, Akira; Asada, Masanori; Tumura, Takehiko; Kita, Ryuichi; Kimura, Toru; Osaki, Yukio

    2017-07-01

     Cold snare polypectomy (CSP) for small colorectal polyps has lower incidence of adverse events, especially delayed postpolypectomy bleeding (DPPB). However, few data are available on comparisons of the incidence of DPPB of CSP and hot polypectomy (HP). The aim of this study was to evaluate the incidence of DPPB after CSP and compare it with that of HP. A propensity score model was used as a secondary analysis.  This was a retrospective cohort study conducted in a single municipal hospital. We identified 539 patients with colorectal polyps from 2 mm to 11 mm in size who underwent CSP (804 polyps in 330 patients) or HP (530 polyps in 209 patients) between July 2013 and June 2015.  There were no cases of DPPB in the CSP group. Conversely, DPPB occurred in 4 patients (1.9 %) after HP, resulting in a significant difference between the CSP and HP groups (0.008 % vs 0 %, P  = 0.02). Propensity score-matching analysis created 402 matched pairs, yielding a significantly higher DPPB rate in the HP group than CSP group (0.02 % vs 0 %, P  = 0.04). However, significantly more patients in the CSP group had unclear horizontal margins that precluded assessment (83 vs 38 cases, P  < 0.001). The retrieval failure rate was significantly higher in the CSP group than in the HP group (3 % vs 0.7 %, P  = 0.01). DPPB was less frequent with CSP than HP, as selected by the propensity score-matching model. Our findings indicate that CSP is recommended polypectomy in daily clinical setting. However, special care should be taken during polyp retrieval and horizontal margin assessment, and these issues could be taken into account in follow-up after CSP.

  3. Reducing patient delay in Acute Coronary Syndrome (RAPiD): research protocol for a web-based randomized controlled trial examining the effect of a behaviour change intervention.

    Science.gov (United States)

    Farquharson, Barbara; Johnston, Marie; Smith, Karen; Williams, Brian; Treweek, Shaun; Dombrowski, Stephan U; Dougall, Nadine; Abhyankar, Purva; Grindle, Mark

    2017-05-01

    To evaluate the efficacy of a behaviour change technique-based intervention and compare two possible modes of delivery (text + visual and text-only) with usual care. Patient delay prevents many people from achieving optimal benefit of time-dependent treatments for acute coronary syndrome. Reducing delay would reduce mortality and morbidity, but interventions to change behaviour have had mixed results. Systematic inclusion of behaviour change techniques or a visual mode of delivery might improve the efficacy of interventions. A three-arm web-based, parallel randomized controlled trial of a theory-based intervention. The intervention comprises 12 behaviour change techniques systematically identified following systematic review and a consensus exercise undertaken with behaviour change experts. We aim to recruit n = 177 participants who have experienced acute coronary syndrome in the previous 6 months from a National Health Service Hospital. Consenting participants will be randomly allocated in equal numbers to one of three study groups: i) usual care, ii) usual care plus text-only behaviour change technique-based intervention or iii) usual care plus text + visual behaviour change technique-based intervention. The primary outcome will be the change in intention to phone an ambulance immediately with symptoms of acute coronary syndrome ≥15-minute duration, assessed using two randomized series of eight scenarios representing varied symptoms before and after delivery of the interventions or control condition (usual care). Funding granted January 2014. Positive results changing intentions would lead to a randomized controlled trial of the behaviour change intervention in clinical practice, assessing patient delay in the event of actual symptoms. Registered at ClinicalTrials.gov: NCT02820103. © 2016 John Wiley & Sons Ltd.

  4. Women-focused development intervention reduces delays in accessing emergency obstetric care in urban slums in Bangladesh: a cross-sectional study

    Directory of Open Access Journals (Sweden)

    Banu Morsheda

    2011-01-01

    Full Text Available Abstract Background Recognizing the burden of maternal mortality in urban slums, in 2007 BRAC (formally known as Bangladesh Rural Advancement Committee has established a woman-focused development intervention, Manoshi (the Bangla abbreviation of mother, neonate and child, in urban slums of Bangladesh. The intervention emphasizes strengthening the continuum of maternal, newborn and child care through community, delivery centre (DC and timely referral of the obstetric complications to the emergency obstetric care (EmOC facilities. This study aimed to assess whether Manoshi DCs reduces delays in accessing EmOC. Methods This cross-sectional study was conducted during October 2008 to January 2009 in the slums of Dhaka city among 450 obstetric complicated cases referred either from DCs of Manoshi or from their home to the EmOC facilities. Trained female interviewers interviewed at their homestead with structured questionnaire. Pearson's chi-square test, t-test and Mann-Whitney test were performed. Results The median time for making the decision to seek care was significantly longer among women who were referred from home than referred from DCs (9.7 hours vs. 5.0 hours, p Conclusions Manoshi program reduces the first delay for life-threatening conditions but not non-life-threatening complications even though providing financial assistance. Programme should give more emphasis on raising awareness through couple/family-based education about maternal complications and dispel fear of clinical care to accelerate seeking EmOC.

  5. The Power of the Virtual Ideal Self in Weight Control: Weight-Reduced Avatars Can Enhance the Tendency to Delay Gratification and Regulate Dietary Practices.

    Science.gov (United States)

    Kuo, Hsu-Chan; Lee, Chun-Chia; Chiou, Wen-Bin

    2016-02-01

    The tendency to discount larger future benefits in favor of smaller immediate gains (i.e., temporal discounting) is relevant to the issue of obesity. Successful weight loss requires individuals to sacrifice immediate culinary pleasures in favor of future health gains. Based on the notion that increasing the vividness of one's future self may mitigate temporal discounting and promote the ability to delay gratification, we examined whether viewing one's weight-reduced self (i.e., the ideal self) in a virtual environment can decrease temporal discounting and lead to better regulation of dietary practices. Seventy-six undergraduates who had reported an intention to lose weight were recruited to participate in a laboratory experiment and were randomly assigned to interact with either the weight-reduced self (experimental condition) or the present self (control condition) by looking into a dressing mirror in a virtual fitting room. A temporal-discounting task and a taste test were subsequently administered. Results showed that, compared with control participants, participants who viewed their weight-reduced avatars ate less ice cream in a taste test and were more likely to choose a sugar-free drink as a reward. The discounting rate mediated the association between the avatar manipulation and the amount of ice cream eaten in the subsequent taste test. Overall, our findings suggest that a computer-generated image of one's weight-reduced self may assist in resisting impulses that promote immediate gratification over delayed benefits. This research provides a new approach for controlling impulsive behavior such as dietary regulation and weight control.

  6. The role of transference work, the therapeutic alliance, and their interaction in reducing interpersonal problems among psychotherapy patients with Cluster C personality disorders.

    Science.gov (United States)

    Ryum, Truls; Stiles, Tore C; Svartberg, Martin; McCullough, Leigh

    2010-12-01

    The aim of the present study was to examine whether transference work, the therapeutic alliance, and their interaction predicted a reduction in interpersonal problems at treatment termination. Forty-nine patients with Cluster C personality disorders from a randomized controlled trial investigating the effectiveness of short-term dynamic psychotherapy and cognitive therapy were included. Transference work was measured with the Inventory of Therapeutic Strategies (Gaston & Ring, 1992), while the therapeutic alliance was measured with the Helping Alliance Questionnaire (Luborsky, Crits-Christoph, Alexander, Margolis & Cohen, 1983). Less emphasis on transference work predicted overall reduced interpersonal problems, whereas the effects of the therapeutic alliance did not reach statistical significance. An interaction effect was also demonstrated, indicating that greater emphasis on transference work performed on patients with lower therapeutic alliance ratings was associated with a smaller reduction in interpersonal problems at termination. However, the results also indicate that a low dose of transference work may be beneficial in reducing interpersonal problems. (PsycINFO Database Record (c) 2010 APA, all rights reserved).

  7. Treatment with immunosuppressive and anti-inflammatory agents delays onset of canine genetic narcolepsy and reduces symptom severity.

    Science.gov (United States)

    Boehmer, L N; Wu, M-F; John, J; Siegel, J M

    2004-08-01

    All Doberman pinschers and Labrador retrievers homozygous for a mutation of the hypocretin (orexin) receptor-2 (hcrtr2) gene develop narcolepsy under normal conditions. Degenerative changes and increased display of major histocompatibility complex class II antigens have been linked to symptom onset in genetically narcoleptic Doberman pinschers. This suggests that the immune system may contribute to neurodegenerative changes and narcoleptic symptomatology in these dogs. We therefore attempted to alter the course of canine genetic narcolepsy, as an initial test of principle, by administering a combination of three immunosuppressive and anti-inflammatory drugs chosen to suppress the immune response globally. Experimental dogs were treated with a combination of methylprednisolone, methotrexate and azathioprine orally starting within 3 weeks after birth, and raised in an environment that minimized pathogen exposure. Symptoms in treated and untreated animals were quantified using the food elicited cataplexy test (FECT), modified FECT and actigraphy. With drug treatment, time to cataplexy onset more than doubled, time spent in cataplexy during tests was reduced by more than 90% and nighttime sleep periods were consolidated. Short-term drug administration to control dogs did not reduce cataplexy symptoms, demonstrating that the drug regimen did not directly affect symptoms. Treatment was stopped at 6 months, after which experimental animals remained less symptomatic than controls until at least 2 years of age. This treatment is the first shown to affect symptom development in animal or human genetic narcolepsy. Our findings show that hcrtr2 mutation is not sufficient for the full symptomatic development of canine genetic narcolepsy and suggest that the immune system may play a role in the development of this disorder.

  8. Is it possible to improve compliance in hypertension and reduce therapeutic inertia of physicians by mandatory periodical examinations of workers?

    Science.gov (United States)

    Marcinkiewicz, Andrzej; Plewka, Michał; Hanke, Wojciech; Kałużny, Paweł; Wiszniewska, Marta; Lipińska-Ojrzanowska, Agnieszka; Walusiak-Skorupa, Jolanta

    2018-01-19

    case of occupational exposure to risk factors for CVD. The mean of age of the study participants amounted to 41.7 years (similar among both genders). A previous diagnosis of HT was declared by 20.1% patients. 11% of patients involved in the intervention did not comply with medical advice. The current HT therapy of all of the subjects with HT (100% of those with abnormal BP levels, who visited their GP) was modified. Prophylactic medical check-ups of workers permit improved compliance and medical surveillance over HT in patients an with uncontrolled clinical course of this disease. Obligations and periodical frequency of examinations encourage both patients and physicians to improve compliance and reduce the risk of therapeutic inertia.

  9. Simulations of drastically reduced SBS with laser pulses composed of a Spike Train of Uneven Duration and Delay (STUD pulses

    Directory of Open Access Journals (Sweden)

    Hüller Stefan

    2013-11-01

    Full Text Available By comparing the impact of established laser smoothing techniques like Random Phase Plates (RPP and Smoothing by Spectral Dispersion (SSD to the concept of “Spike Trains of Uneven Duration and Delay” (STUD pulses on the amplification of parametric instabilities in laser-produced plasmas, we show with the help of numerical simulations, that STUD pulses can drastically reduce instability growth by orders of magnitude. The simulation results, obtained with the code Harmony in a nonuniformly flowing mm-size plasma for the Stimulated Brillouin Scattering (SBS instability, show that the efficiency of the STUD pulse technique is due to the fact that successive re-amplification in space and time of parametrically excited plasma waves inside laser hot spots is minimized. An overall mean fluctuation level of ion acoustic waves at low amplitude is established because of the frequent change of the speckle pattern in successive spikes. This level stays orders of magnitude below the levels of ion acoustic waves excited in hot spots of RPP and SSD laser beams.

  10. Delayed post-ischaemic administration of xenon reduces brain damage in a rat model of global ischaemia.

    Science.gov (United States)

    Metaxa, V; Lagoudaki, R; Meditskou, S; Thomareis, O; Oikonomou, L; Sakadamis, A

    2014-01-01

    Xenon and nitrous oxide have been shown to be neuroprotective in vivo and in vitro, but mainly in models of focal cerebral ischaemia. This study aimed to investigate whether the two gases are able to attenuate cerebral injury after global cerebral ischaemia. Adult male Wistar rats underwent bilateral common carotid artery occlusion and were ventilated for 1 hour with 21% O₂/78% N₂. They were then randomized to three groups which continued to receive atmospheric air, 50% N2O/50% O₂ and 50% Xe/50% O₂ for an additional period of 45 minutes. The number of ischaemic neurons, the cortical volume loss and the immunochemical and molecular expression of c-fos and MMP-9 were evaluated. Xenon reduced the number of ischaemic neurons in the cortex and CA1 hippocampal region (p xenon. The molecular analysis revealed significant effects of N2O and xenon administration on c-fos and MMP-9 expression. The data indicate that N2O and xenon administration is neuroprotective 1 hour after bilateral common carotid artery occlusion. These findings provide valuable evidence on the beneficial role of N2O and xenon in global cerebral injury.

  11. Effects of feeding level and access to rooting material on behaviour of growing pigs in situations with reduced feeding space and delayed feeding

    DEFF Research Database (Denmark)

    Jensen, Margit Bak; Pedersen, Lene Juul

    2010-01-01

    Seventy-two pigs, housed in groups of four, were allocated to either (1) ad libitum feeding with access to wood chip, (2) restrictive feeding with access to wood chip or (3) restrictive feeding without access to wood chip. The effects of feeding level (treatment 1 vs. 2) and access to wood chip...... (treatment 2 vs. 3) were investigated in a normal situation, a competitive situation (reduced feeder space) and a conflict situation (delayed feeding). During normal days the pigs without access to wood chip manipulated the floor more, both on a 24 h basis and during the first hour after feed allocation......, but the level of manipulating floor in these pigs did not reach the level of manipulating wood chip among pigs on treatment 2. During normal days restrictively fed pigs spent less time feeding on a 24 h basis, but more time feeding during the first hour after feed allocation than ad libitum fed pigs. When...

  12. Reduced chance of hearing loss associated with Therapeutic Drug Monitoring of Aminoglycosides in the treatment of Multidrug Resistant Tuberculosis

    NARCIS (Netherlands)

    van Altena, R; Dijkstra, J.A.; van der Meer, M E; Borjas Howard, J F; Kosterink, J G W; van Soolingen, D; van der Werf, T S; Alffenaar, J W C

    Hearing loss and nephrotoxicity are associated with prolonged treatment duration and higher dosage of amikacin and kanamycin. In our Tuberculosis Center, we have employed therapeutic drug monitoring (TDM) targeting pre-set pharmacokinetic/pharmacodynamic (PK/PD) surrogate endpoints in an attempt to

  13. Hypothermic machine perfusion reduces delayed graft function and improves one-year graft survival of kidneys from expanded criteria donors: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Baoping Jiao

    Full Text Available BACKGROUND: Expanded criteria donors (ECDs are currently accepted as potential sources to increase the donor pool and to provide more chances of kidney transplantation for elderly recipients who would not survive long waiting periods. Hypothermic machine perfusion (HMP is designed to mitigate the deleterious effects of simple cold storage (CS on the quality of preserved organs, particularly when the donor is in a marginal status. METHODS: We compared the transplant outcomes in patients receiving ECD kidneys with either HMP or CS graft preservation. Articles from the MEDLINE, EMBASE and Cochrane Library databases were searched and all studies reporting outcomes from HMP versus CS methods of kidney preservation were included in this meta-analysis. The parameters analyzed included the incidence of delayed graft function (DGF, primary non-function (PNF and one-year graft and patient survival. RESULTS: A total of seven studies qualified for the review, involving 2374 and 8716 kidney grafts with HMP or CS preservation respectively, all from ECD donors. The incidence of delayed graft function (DGF was significantly reduced with an odd ratio(OR of 0.59 (95% CI 0.54-0.66, P<0.001 and one-year graft survival was significantly improved with an OR of 1.12 (95% CI 1.03-1.21, P = 0.005 in HMP preservation compared to CS. However, there was no difference in the incidence of PNF (OR 0.54, 95% CI 0.21-1.40, P = 0.20, and one-year patient survival (OR 0.98, 95% CI 0.94-1.02, P = 0.36 between HMP and CS preservation. CONCLUSIONS: HMP was associated with a reduced incidence of DGF and an with increased one-year graft survival, but it was not associated with the incidence of PNF and one-year patient survival.

  14. CHIP−/−-Mouse Liver: Adiponectin-AMPK-FOXO-Activation Overrides CYP2E1-Elicited JNK1-Activation, Delaying Onset of NASH: Therapeutic Implications

    Science.gov (United States)

    Kim, Sung-Mi; Grenert, James P.; Patterson, Cam; Correia, Maria Almira

    2016-01-01

    Genetic ablation of C-terminus of Hsc70-interacting protein (CHIP) E3 ubiquitin-ligase impairs hepatic cytochrome P450 CYP2E1 degradation. Consequent CYP2E1 gain of function accelerates reactive O2 species (ROS) production, triggering oxidative/proteotoxic stress associated with sustained activation of c-Jun NH2-terminal kinase (JNK)-signaling cascades, pro-inflammatory effectors/cytokines, insulin resistance, progressive hepatocellular ballooning and microvesicular steatosis. Despite this, little evidence of nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) was found in CHIP−/−-mice over the first 8–9-months of life. We herein document that this lack of tissue injury is largely due to the concurrent up-regulation and/or activation of the adiponectin-5′-AMP-activated protein kinase (AMPK)-forkhead box O (FOXO)-signaling axis stemming from at the least three synergistic features: Up-regulated expression of adipose tissue adiponectin and its hepatic adipoR1/adipoR2 receptors, stabilization of hepatic AMPKα1-isoform, identified herein for the first time as a CHIP-ubiquitination substrate (unlike its AMPKα2-isoform), as well as nuclear stabilization of FOXOs, well-known CHIP-ubiquitination targets. Such beneficial predominance of the adiponectin-AMPK-FOXO-signaling axis over the sustained JNK-elevation and injurious insulin resistance in CHIP−/−-livers apparently counteracts/delays rapid progression of the hepatic microvesicular steatosis to the characteristic macrovesicular steatosis observed in clinical NASH and/or rodent NASH-models. PMID:27406999

  15. Chitosan-Hyaluronate Hybrid Gel Intraarticular Injection Delays Osteoarthritis Progression and Reduces Pain in a Rat Meniscectomy Model as Compared to Saline and Hyaluronate Treatment

    Directory of Open Access Journals (Sweden)

    Shachar Patchornik

    2012-01-01

    Full Text Available Chitosan-Hyaluronate hybrid gel (CHHG is a self-forming thermo-responsive hydrogel. The current study was undertaken in order to assess the effect of CHHG on rat's surgically induced osteoarthritis. Methods. Thirteen rats were included in the study. In all rats weight-bearing was assessed using a Linton Incapacitance tester. All rats underwent bilateral medial partial meniscectomy. Four rats received a saline injection in the control knee and a 200-microliter injection of CHHG in the experimental knee. Five rats received a high-molecular weight hyaluronate injection to the control knee and a 200-microliter injection of CHHG in the experimental knee. Four rats underwent the same surgical procedure, allowed to recuperate for seven days and then CHHG and hyaluronate were injected. The animals were followed for 6 weeks. Two weeks after injection of a therapeutic substance the amount of weight-bearing on each knee was evaluated using a Linton Incapacitance meter. Results. Two weeks after induction of osteoarthritis there is less pain in the CHHG-treated knee than in the control-treated knee, as determined using a Lintron Incapacitance meter. After six-weeks the histological appearance of the CHHG-treated knee was superior to that of the controls. This is indicated by thicker cartilage remaining on the medial femoral condyle as well as less cyst formation in the CHHG-treated knee. Discussion. CHHG appears to delay progression of osteoarthritis and lessen pain in a rat surgically-induced knee osteoarthritis model. These results support other published results, indicating that there is an ameliorative effect of chitosan on human and rabbit osteoarthritis.

  16. Chitosan-Hyaluronate Hybrid Gel Intraarticular Injection Delays Osteoarthritis Progression and Reduces Pain in a Rat Meniscectomy Model as Compared to Saline and Hyaluronate Treatment

    Science.gov (United States)

    Patchornik, Shachar; Ram, Edward; Ben Shalom, Noah; Nevo, Zvi; Robinson, Dror

    2012-01-01

    Chitosan-Hyaluronate hybrid gel (CHHG) is a self-forming thermo-responsive hydrogel. The current study was undertaken in order to assess the effect of CHHG on rat's surgically induced osteoarthritis. Methods. Thirteen rats were included in the study. In all rats weight-bearing was assessed using a Linton Incapacitance tester. All rats underwent bilateral medial partial meniscectomy. Four rats received a saline injection in the control knee and a 200-microliter injection of CHHG in the experimental knee. Five rats received a high-molecular weight hyaluronate injection to the control knee and a 200-microliter injection of CHHG in the experimental knee. Four rats underwent the same surgical procedure, allowed to recuperate for seven days and then CHHG and hyaluronate were injected. The animals were followed for 6 weeks. Two weeks after injection of a therapeutic substance the amount of weight-bearing on each knee was evaluated using a Linton Incapacitance meter. Results. Two weeks after induction of osteoarthritis there is less pain in the CHHG-treated knee than in the control-treated knee, as determined using a Lintron Incapacitance meter. After six-weeks the histological appearance of the CHHG-treated knee was superior to that of the controls. This is indicated by thicker cartilage remaining on the medial femoral condyle as well as less cyst formation in the CHHG-treated knee. Discussion. CHHG appears to delay progression of osteoarthritis and lessen pain in a rat surgically-induced knee osteoarthritis model. These results support other published results, indicating that there is an ameliorative effect of chitosan on human and rabbit osteoarthritis. PMID:22611500

  17. A specific inhibitor of protein kinase CK2 delays gamma-H2Ax foci removal and reduces clonogenic survival of irradiated mammalian cells

    Directory of Open Access Journals (Sweden)

    Huber Peter E

    2011-02-01

    Full Text Available Abstract Background The protein kinase CK2 sustains multiple pro-survival functions in cellular DNA damage response and its level is tightly regulated in normal cells but elevated in cancers. Because CK2 is thus considered as potential therapeutic target, DNA double-strand break (DSB formation and rejoining, apoptosis induction and clonogenic survival was assessed in irradiated mammalian cells upon chemical inhibition of CK2. Methods MRC5 human fibroblasts and WIDR human colon carcinoma cells were incubated with highly specific CK2 inhibitor 4,5,6,7-tetrabromobenzotriazole (TBB, or mock-treated, 2 hours prior to irradiation. DSB was measured by pulsed-field electrophoresis (PFGE as well as gamma-H2AX foci formation and removal. Apoptosis induction was tested by DAPI staining and sub-G1 flow cytometry, survival was quantified by clonogenic assay. Results TBB treatment did not affect initial DNA fragmention (PFGE; up to 80 Gy or foci formation (1 Gy. While DNA fragment rejoining (PFGE was not inhibited by the drug, TBB clearly delayed gamma-H2AX foci disappearence during postirradiation incubation. No apoptosis induction could be detected for up to 38 hours for both cell lines and exposure conditions (monotherapies or combination, but TBB treatment at this moderately toxic concentration of 20 μM (about 40% survival enhanced radiation-induced cell killing in the clonogenic assay. Conclusions The data imply a role of CK2 in gamma-H2AX dephosporylation, most likely through its known ability to stimulate PP2A phosphatase, rather than DSB rejoining. The slight but definite clonogenic radiosensitization by TBB does apparently not result from interference with an apoptosis suppression function of CK2 in these cells but could reflect inhibitor-induced uncoupling of DNA damage response decay from break ligation.

  18. The small-molecule TNF-alpha modulator, UTL-5g, reduces side effects induced by cisplatin and enhances the therapeutic effect of cisplatin in vivo.

    Science.gov (United States)

    Shaw, JiaJiu; Chen, Ben; Huang, Wen-Hsin; Lee, An-Rong; Media, Joseph; Valeriote, Frederick A

    2011-01-01

    We investigated a small-molecule modulator of tumor necrosis factor alpha (TNF-alpha), UTL-5g (also referred to as GBL-5g), as a potential chemoprotective agent against cisplatin-induced side effects including nephrotoxicity, hepatotoxicity and hematotoxicity. Pretreatment of UTL-5g i.p. in BDF1 mice reduced the levels of blood urea nitrogen (BUN) and creatinine induced by cisplatin treatment. The levels of both aspartate transaminase (AST) and alanine transaminase (ALT) in these animals were also reduced by UTL-5g. Pretreatment of UTL-5g did not significantly affect the number of white blood cells (WBC) under current experimental conditions, yet it markedly increased blood platelet counts by more than threefold. Therapeutic assessment in SCID mice inoculated with human HCT-15 tumor cells showed that UTL-5g did not attenuate the anti-tumor effect of cisplatin but increased the therapeutic efficacy of cisplatin. The LD50 of UTL-5g was determined to be > 2,000 mg/kg by an acute toxicity study. In summary, our studies showed that 1) UTL-5g significantly reduces nephrotoxicity and hepatotoxicity induced by cisplatin in mice, presumably by lowering the levels of TNF-alpha, 2) UTL-5g markedly increased blood platelet counts in mice and 3) UTL-5g treatment increased the therapeutic efficacy of cisplatin against HCT-15 cells inoculated in SCID mice.

  19. p38 Mitogen activated protein kinase (MAPK): a new therapeutic target for reducing the risk of adverse pregnancy outcomes.

    Science.gov (United States)

    Menon, Ramkumar; Papaconstantinou, John

    2016-12-01

    Spontaneous preterm birth (PTB) and preterm premature rupture of the membranes (pPROM) remain as a major clinical and therapeutic problem for intervention and management. Current strategies, based on our knowledge of pathways of preterm labor, have only been effective, in part, due to major gaps in our existing knowledge of risks and risk specific pathways. Areas covered: Recent literature has identified physiologic aging of fetal tissues as a potential mechanistic feature of normal parturition. This process is affected by telomere dependent and p38 mitogen activated protein kinase (MAPK) induced senescence activation. Pregnancy associated risk factors can cause pathologic activation of this pathway that can cause oxidative stress induced p38 MAPK activation leading to senescence and premature aging of fetal tissues. Premature aging is associated with sterile inflammation capable of triggering preterm labor or preterm premature rupture of membranes. Preterm activation of p38MAPK can be considered as a key contributor to adverse pregnancies. Expert opinion: This review considers p38MAPK activation as a potential target for therapeutic interventions to prevent adverse pregnancy outcomes mediated by stress factors. In this review, we propose multiple strategies to prevent p38MAPK activation.

  20. Transient inhibition of ROR-γt therapeutically limits intestinal inflammation by reducing TH17 cells and preserving group 3 innate lymphoid cells.

    Science.gov (United States)

    Withers, David R; Hepworth, Matthew R; Wang, Xinxin; Mackley, Emma C; Halford, Emily E; Dutton, Emma E; Marriott, Clare L; Brucklacher-Waldert, Verena; Veldhoen, Marc; Kelsen, Judith; Baldassano, Robert N; Sonnenberg, Gregory F

    2016-03-01

    RAR-related orphan receptor-γt (ROR-γt) directs differentiation of proinflammatory T helper 17 (TH17) cells and is a potential therapeutic target in chronic autoimmune and inflammatory diseases. However, ROR-γt-dependent group 3 innate lymphoid cells ILC3s provide essential immunity and tissue protection in the intestine, suggesting that targeting ROR-γt could also result in impaired host defense after infection or enhanced tissue damage. Here, we demonstrate that transient chemical inhibition of ROR-γt in mice selectively reduces cytokine production from TH17 but not ILCs in the context of intestinal infection with Citrobacter rodentium, resulting in preserved innate immunity. Temporal deletion of Rorc (encoding ROR-γt) in mature ILCs also did not impair cytokine response in the steady state or during infection. Finally, pharmacologic inhibition of ROR-γt provided therapeutic benefit in mouse models of intestinal inflammation and reduced the frequency of TH17 cells but not ILCs isolated from primary intestinal samples of individuals with inflammatory bowel disease (IBD). Collectively, these results reveal differential requirements for ROR-γt in the maintenance of TH17 cell and ILC3 responses and suggest that transient inhibition of ROR-γt is a safe and effective therapeutic approach during intestinal inflammation.

  1. Reducing time delay in the thrombolysis of myocardial infarction: an internal quality improvement project. ARIAM Project Group. Analisis del Retraso en Infarto Agudo de Miocardio.

    Science.gov (United States)

    Saturno, P J; Felices, F; Segura, J; Vera, A; Rodriguez, J J

    2000-01-01

    The objectives of this study were to improve thrombolytic therapy in acute myocardial infarction by reducing the "door-to-needle" time in a 285-bed university hospital in Spain. A quality management approach was used involving all the relevant staff. Target standard was set at 35 minutes. Baseline data, intervention effect, and continuous monitoring were analyzed using x control charts. Analysis of baseline data showed a wide out-of-control variation and 72 minutes' average delay. Cause analysis revealed organizational and clinical problems that were subjected to intervention. Postintervention data showed a stable process, with an average of 30 minutes. Continuous monitoring showed further improvement in average time and predictable variation. The template of the current control chart has an average of 26 minutes. Quality management methods, particularly staff involvement in problem analysis and intervention design, and the use of control charts were useful to understand, solve, and continuously monitor an important clinical problem whose existence was evident only after it was measured.

  2. Neutralisation of uPA with a monoclonal antibody reduces plasmin formation and delays skin wound healing in tPA-deficient mice

    DEFF Research Database (Denmark)

    Jögi, Annika; Rønø, Birgitte; Lund, Ida K

    2010-01-01

    Proteolytic degradation by plasmin and metalloproteinases is essential for epidermal regeneration in skin wound healing. Plasminogen deficient mice have severely delayed wound closure as have mice simultaneously lacking the two plasminogen activators, urokinase-type plasminogen activator (u......PA) and tissue-type plasminogen activator (tPA). In contrast, individual genetic deficiencies in either uPA or tPA lead to wound healing kinetics with no or only slightly delayed closure of skin wounds....

  3. Delayed Puberty

    DEFF Research Database (Denmark)

    Kolby, Nanna; Busch, Alexander Siegfried; Juul, Anders

    2017-01-01

    Delayed puberty can be a source of great concern and anxiety, although it usually is caused by a self-limiting variant of the normal physiological timing named constitutional delay of growth and puberty (CDGP). Delayed puberty can, however, also be the first presentation of a permanent condition...... of diagnostic evaluation today remain in distinguishing the benign CDGP from underlying pathological causes such as hypogonadotropic hypogonadism (HH) and hypergonadotropic hypogonadism. Several techniques have been investigated for this purpose and are reviewed in this chapter; however, no single test is yet...

  4. Delayed growth

    Science.gov (United States)

    ... 4 years Developmental milestones record - 5 years Causes Constitutional growth delay refers to children who are small ... nutrition expert who can help you choose the right foods to offer your child. What to Expect ...

  5. Delayed Ejaculation

    Science.gov (United States)

    ... bladder rather than out of the penis Psychological causes of delayed ejaculation include: Depression, anxiety or other mental health conditions Relationship problems due to stress, poor communication or other concerns ...

  6. Delayed Ejaculation

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    ... of stress Delayed ejaculation Symptoms & causes Diagnosis & treatment Advertisement Mayo Clinic does not endorse companies or products. ... a Job Site Map About This Site Twitter Facebook Google YouTube Pinterest Mayo Clinic is a not- ...

  7. Interleukin 6 (IL-6) deficiency delays lupus nephritis in MRL-Faslpr mice: the IL-6 pathway as a new therapeutic target in treatment of autoimmune kidney disease in systemic lupus erythematosus.

    Science.gov (United States)

    Cash, Hannes; Relle, Manfred; Menke, Julia; Brochhausen, Christoph; Jones, Simon A; Topley, Nicholas; Galle, Peter R; Schwarting, Andreas

    2010-01-01

    To investigate the pathophysiological effect of interleukin 6 (IL-6) on lupus nephritis in MRL-Fas(lpr) mice. We generated IL-6-deficient MRL-Fas(lpr) mice using a backcross/intercross breeding scheme. Renal pathology was evaluated using immunohistochemistry detection for macrophages, lymphocytes, vascular cell adhesion molecule-1 (VCAM-1), and TUNEL (terminal deoxynucleotide transferase-mediated dUTP nick end-labeling) for apoptotic cells, and renal IgG and C3 deposition by immunofluorescence staining. Expression of inflammatory markers in the spleen was analyzed by quantitative real-time reverse transcription-polymerase chain reaction. Serum cytokine concentrations were detected by FACS analysis. IL-6 deficiency was highly effective in prolonging survival and ameliorating the clinical, immunological, and histological indicators of murine systemic lupus erythematosus. During the study period of 6 months, MRL-Fas(lpr) IL-6 -/- mice showed delayed onset of proteinuria and hematuria compared to IL-6-intact control mice. Survival rate was 100% in IL-6-deficient MRL-Fas(lpr) mice and 25% in the control group at 6 months of age. The absence of IL-6 resulted in significant reduction of infiltrating macrophages in the kidney (p kidneys of MRL-Fas(lpr) IL-6 -/- compared to IL-6-intact mice. We found elevated serum levels of IL-10 and interferon-gamma in IL-6-deficient mice, while splenic mRNA showed an overall downregulation of immunoregulatory genes. IL-6 is a strong promoter of lupus nephritis and may be a promising new therapeutic target in the treatment of human lupus nephritis.

  8. Therapeutic Nanodevices

    Science.gov (United States)

    Lee, Stephen; Ruegsegger, Mark; Barnes, Philip; Smith, Bryan; Ferrari, Mauro

    Therapeutic nanotechnology offers minimally invasive therapies with high densities of function concentrated in small volumes, features that may reduce patient morbidity and mortality. Unlike other areas of nanotechnology, novel physical properties associated with nanoscale dimensionality are not the raison d'être of therapeutic nanotechnology, whereas the aggregation of multiple biochemical (or comparably precise) functions into controlled nanoarchitectures is. Multifunctionality is a hallmark of emerging nanotherapeutic devices, and multifunctionality can allow nanotherapeutic devices to perform multistep work processes, with each functional component contributing to one or more nanodevice subroutine such that, in aggregate, subroutines sum to a cogent work process. Cannonical nanotherapeutic subroutines include tethering (targeting) to sites of disease, dispensing measured doses of drug (or bioactive compound), detection of residual disease after therapy and communication with an external clinician/operator. Emerging nanotherapeutics thus blur the boundaries between medical devices and traditional pharmaceuticals. Assembly of therapeutic nanodevices generally exploits either (bio)material self-assembly properties or chemoselective bioconjugation techniques, or both. Given the complexity, composition, and the necessity for their tight chemical and structural definition inherent in the nature of nanotherapeutics, their cost of goods (COGs) might exceed that of (already expensive) biologics. Early therapeutic nanodevices will likely be applied to disease states which exhibit significant unmet patient need (cancer and cardiovascular disease), while application to other disease states well-served by conventional therapy may await perfection of nanotherapeutic design and assembly protocols.

  9. Novel epigallocatechin-3-gallate (EGCG derivative as a new therapeutic strategy for reducing neuropathic pain after chronic constriction nerve injury in mice.

    Directory of Open Access Journals (Sweden)

    Xavier Xifró

    Full Text Available Neuropathic pain is common in peripheral nerve injury and often fails to respond to ordinary medication. Here, we investigated whether the two novel epigallocatechin-3-gallate (EGCG polyphenolic derivatives, compound 23 and 30, reduce the neuropathic pain in mice chronic constriction nerve injury (CCI. First, we performed a dose-response study to evaluate nociceptive sensation after administration of EGCG and its derivatives 23 and 30, using the Hargreaves test at 7 and 21 days after injury (dpi. We daily administered EGCG, 23 and 30 (10 to 100 mg/Kg; i.p. during the first week post-CCI. None of the doses of compound 23 caused significant pain diminution, whereas 50mg/kg was optimal for both EGCG and 30 to delay the latency of paw withdrawal. With 50 mg/Kg, we showed that EGCC prevented the thermal hyperalgesia from 7 to 21 dpi and compound 30 from 14 to 56 dpi. To evaluate the molecular mechanisms underpinning why EGCG and compound 30 differentially prevented the thermal hyperalgesia, we studied several biochemical parameters in the dorsal horn of the spinal cord at 14 and 56 dpi. We showed that the effect observed with EGCG and compound 30 was related to the inhibition of fatty acid synthase (FASN, a known target of these polyphenolic compounds. Additionally, we observed that EGCG and compound 30 reduced the expression of CCI-mediated inflammatory proteins and the nuclear localization of nuclear factor-kappa B at 14 dpi, but not at 56 dpi. We also strongly detected a decrease of synaptic plasma membrane levels of N-methyl-D-asparte receptor 2B in CCI-mice treated with compound 30 at 56 dpi. Altogether, compound 30 reduced the chronic thermal hyperalgesia induced by CCI better than the natural compound EGCG. Thus, our findings provide a rationale for the preclinical development of compound 30 as an agent to treat neuropathic pain.

  10. Implementation of uniform information on fetal movement in a Norwegian population reduced delayed reporting of decreased fetal movement and stillbirths in primiparous women - a clinical quality improvement

    Directory of Open Access Journals (Sweden)

    Stray-Pedersen Babill

    2010-01-01

    Full Text Available Abstract Background Delayed maternal reporting of decreased fetal movement (DFM is associated with adverse pregnancy outcomes. Inconsistent information on fetal activity to women during the antenatal period may result in delayed reporting of DFM. We aimed to evaluate an intervention of implementation of uniform information on fetal activity to women during the antenatal period. Methods In a prospective before-and-after study, singleton women presenting DFM in the third trimester across 14 hospitals in Norway were registered. Outcome measures were maternal behavior regarding reporting of DFM, concerns and stillbirth. In addition, cross-sectional studies of all women giving birth were undertaken to assess maternal concerns about fetal activity, and population-based data were obtained from the Medical Birth Registry Norway. Results Pre- and post-intervention cohorts included 19 407 and 46 143 births with 1 215 and 3 038 women with DFM respectively. Among primiparous women with DFM, a reduction in delayed reporting of DFM (≥48 hrs OR 0.61 (95% CI 0.47-0.81 and stillbirths OR 0.36 (95% CI 0.19-0.69 was shown in the post-intervention period. No difference was shown in rates of consultations for DFM or maternal concerns. Stillbirth rates and maternal behavior among women who were of non-Western origin, smokers, overweight or >34 years old were unchanged. Conclusions Uniform information on fetal activity provided to pregnant women was associated with a reduction in the number of primiparous women who delayed reporting of DFM and a reduction of the stillbirth rates for primiparous women reporting DFM. The information did not appear to increase maternal concerns or rate of consultation. Due to different imperfections in different clinical settings, further studies in other populations replicating these findings are required.

  11. Delayed Puberty

    DEFF Research Database (Denmark)

    Kolby, Nanna; Busch, Alexander Siegfried; Juul, Anders

    2017-01-01

    or a symptom of an underlying disease. The diagnosis delayed puberty is made if there are no signs of puberty at an age corresponding to 2 SD above the population mean age at pubertal onset, often translated into 14 years in boys. Delayed puberty among boys is a frequent presentation in pediatrics....... The underlying reasons for the large variation in the age at pubertal onset are not fully established; however, nutritional status and socioeconomic and environmental factors are known to be influencing, and a significant amount of influencing genetic factors have also been identified. The challenges...... of diagnostic evaluation today remain in distinguishing the benign CDGP from underlying pathological causes such as hypogonadotropic hypogonadism (HH) and hypergonadotropic hypogonadism. Several techniques have been investigated for this purpose and are reviewed in this chapter; however, no single test is yet...

  12. Field triage reduces treatment delay and improves long-term clinical outcome in patients with acute ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention

    DEFF Research Database (Denmark)

    Pedersen, Sune H; Galatius, Soren; Hansen, Peter R

    2009-01-01

    OBJECTIVES: We evaluated the independent impact of field triage on treatment delay and long-term clinical outcome in a large contemporary, consecutive population of ST-segment elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (pPCI). BACKGROUND...... by field triage and 821 by emergency departments. Baseline and angiographic variables were similar in the 2 populations. Patients admitted by field triage had a significantly shorter median door-to-balloon time compared with patients admitted by emergency department triage (83 min, interquartile range 67...... to 100 min vs. 103 min, interquartile range 80 to 135 min; ptriage patients, but only in 36% of nonfield-triage patients (p

  13. Development of reduced crude processing technology in delayed coking units; Desenvolvimento da tecnologia de processamento de residuo atmosferico em unidade de coqueamento retardado

    Energy Technology Data Exchange (ETDEWEB)

    Soares, Gloria Maria Gomes; Bartros, Francisco Carlos da Costa; Goncalves, Natalie Jorge; Pala, Danielle Marins; Nadolni, Aline Voigt [PETROBRAS, Rio de Janeiro, RJ (Brazil)

    2008-07-01

    Delayed Coking Technology can be described as thermal cracking of low value refinery residual streams into high-value products. This process has been applied in petroleum refining schemes in order to upgrade heavy and ultra-heavy crude oils. The typical feedstock is vacuum residue (VR). When we have an increasing medium distillates demand and refining schemes which have gas oil and VR excess, the simultaneous conversion of these streams becomes economically attractive, due mainly to the increase of diesel production. Thus, the processing of atmospheric residue (AR) in Delayed Coking Units (DCU) has fueled great interest for PETROBRAS. This work presents the results of industrial and pilot plant tests with AR and VR showing the increasing of diesel yields and decreasing of coke yields processing AR as feedstock. When we process all the AR in the DCU with high recycle rate we observe an increasing of 25% on refinery diesel production related to conventional schemes. The refining scheme of the new PETROBRAS refinery at Northeast of Brazil is based on this technology. This refinery will process heavy oils maximizing diesel production with minimum investment. (author)

  14. A reflection on choosing practice development as a framework to explore music as a therapeutic method to reduce anxiety in patients living with dementia in a ward setting

    Directory of Open Access Journals (Sweden)

    Alasdair Pithie

    2016-05-01

    Full Text Available Background: As a student nurse I chose to write my fourth year dissertation on the use of music as a therapeutic method to reduce anxiety in patients living with dementia. Music has been shown to have a positive effect on patients’ anxiety levels and improve their quality of life. A music therapy intervention could be beneficial but I realised I would need a framework that would enable me to implement the intervention in a ward setting, while offering practitioners and other participants a reasonable level of control and ownership. Discussion: Practice development was chosen because it is a person-centred framework, encouraging the learning of all those involved as well as those facilitating. It is inclusive and allows staff to adapt to the way new practices are introduced in a project. Change management theory was also considered as a framework but lacked many of the person-centred qualities required. Conclusions and implications for practice: Practice development provides the required characteristics for a project to introduce music into a care setting. Given that the methods of the project rely heavily on the involvement of staff and patients’ families, it is important to offer them a sense of ownership and control as an encouragement to take an interest and pride in its success. Furthermore, student nurses can benefit from being introduced to practice development because it will offer them a change theory that is person centred and inclusive.

  15. Delays in Motor Development in Children with Down Syndrome

    National Research Council Canada - National Science Library

    Malak, Roksana; Kostiukow, Anna; Krawczyk-Wasielewska, Agnieszka; Mojs, Ewa; Samborski, Włodzimierz

    2015-01-01

    Children with Down syndrome (DS) present with delays in motor development. The reduced size of the cerebrum, brain maturation disorders, and pathophysiological processes lead to motor development delay...

  16. Early MEK1/2 Inhibition after Global Cerebral Ischemia in Rats Reduces Brain Damage and Improves Outcome by Preventing Delayed Vasoconstrictor Receptor Upregulation

    DEFF Research Database (Denmark)

    Johansson, Sara Ellinor; Larsen, Stine Schmidt; Povlsen, Gro Klitgaard

    2014-01-01

    and 5-HT1B receptors, previously demonstrated in cerebral arteries after experimental global ischemia, are a key mechanism behind insufficient perfusion of the post-ischemic brain, proposing blockade of this receptor upregulation as a novel target for prevention of cerebral hypoperfusion and delayed...... neuronal cell death after global cerebral ischemia. The aim was to characterize the time-course of receptor upregulation and associated neuronal damage after global ischemia and investigate whether treatment with the MEK1/2 inhibitor U0126 can prevent cerebrovascular receptor upregulation and thereby...... improve functional outcome after global cerebral ischemia. Incomplete global cerebral ischemia was induced in Wistar rats and the time-course of enhanced contractile responses and the effect of U0126 in cerebral arteries were studied by wire myography and the neuronal cell death by TUNEL. The expression...

  17. Subcutaneous bortezomib in multiple myeloma patients induces similar therapeutic response rates as intravenous application but it does not reduce the incidence of peripheral neuropathy.

    Directory of Open Access Journals (Sweden)

    Jiri Minarik

    Full Text Available Subcutaneous (SC application of bortezomib has been recently introduced as a new application route in multiple myeloma (MM patients. We performed an analysis to compare the outcomes of bortezomib-based therapy in multiple myeloma (MM patients treated using either intravenous (IV or subcutaneous (SC route of administration.During January 2012 through December 2013, we performed a retrospective analysis of 446 patients with MM treated with bortezomib-based regimens (either once weekly - 63% or twice weekly - 27% in both, the first line setting, and in relapse, with separate analysis of patients undergoing autologous stem cell transplantation. We assessed the response rates and toxicity profiles in both, IV and SC route of bortezomib administration.The response rates in both IV and SC arm were similar with overall response rate 71.7% vs 70.7%, complete remissions in 13.9% vs 8.6%, very good partial remissions in 30.8% vs 34.5% and partial remissions in 27% vs 27.6%. The most frequent grade ≥ 3 toxicities were anemia, thrombocytopenia and neutropenia, with no significant differences between IV and SC group. There were no significant differences in the rate of peripheral neuropathy (PN. PN of any grade was present in 48% in the IV arm and in 41% in the SC arm. PN grade ≥ 2 was present in 20% vs 18% and PN grade ≥ 3 was present in 6% vs 4%.We conclude that subcutaneous application of bortezomib has similar therapeutic outcomes and toxicity profile as intravenous route of application. In our cohort there was no difference in the incidence of PN, suggesting that PN is dose dependent and might be reduced by lower intensity schemes rather than by the route of administration.

  18. Time Delay of CGM Sensors

    Science.gov (United States)

    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

  19. Effectiveness of a reduced dose of efavirenz plus 2 NRTIs as maintenance antiretroviral therapy with the guidance of therapeutic drug monitoring.

    Science.gov (United States)

    Yang, Shang-Ping; Liu, Wen-Chun; Lee, Kuan-Yeh; Wu, Bing-Ru; Su, Yi-Ching; Wu, Pei-Ying; Zhang, Jun-Yu; Luo, Yu-Zhen; Sun, Hsin-Yun; Chang, Sui-Yuan; Lin, Shu-Wen; Hung, Chien-Ching

    2014-01-01

    Wide inter-patient variation of plasma efavirenz (EFV) concentrations has been observed, and a substantial proportion of HIV-positive patients may have unnecessarily higher plasma EFV concentrations than recommended while receiving EFV-containing combination antiretroviral therapy (cART) at the currently recommended daily dose of 600 mg. A lower daily dose (400 mg) of EFV has recently been demonstrated to be as efficacious as the recommended 600 mg when combined with tenofovir/mtricitabine in a multinational clinical trial, with a lower incidence of adverse effects. We aimed to use a therapeutic drug monitoring (TDM)-guided strategy to optimize the EFV dose in HIV-positive Taiwanese patients. The plasma EFV concentrations at 12 hours (C12) after taking the previous dose were determined among HIV-positive adults who had received EFV-containing cART with viral suppression (plasma HIV RNA load (PVL) EFV C12 >2.0 mg/L, EFV (Stocrit, MSD) was reduced to half a tablet daily. Determinations of EFV C12 were repeated 4-12 weeks after switch using high-performance liquid chromatography. CYP2B6 G516T polymorphisms were determined using polymerase-chain-reaction restriction fragment-length polymorphism. Between April 2013 and June 2014, 111 patients (95.5% male; mean age, 39 years; 96.4% with PVL 2.0 mg/L were switched to a reduced dose (1/2# hs) of EFV; 45.5% of them had CYP2B6 G516T or TT genotypes; and 32.4% weighed 60 kg or less. The mean baseline EFV C12 before switch was 3.65 mg/L (interquartile range (IQR), 2.62-4.17) for 111 patients, which decreased to 1.96 mg/L (IQR, 1.53-2.33) for 64 patients who had completed follow-up of C12 EFV 4 weeks after switch, with a reduction of 49.4% (IQR, 38.9-57.0%). As of 10 July, 2014, all of the 38 patients (100%) who had completed at least one follow-up of PVL achieved undetectable PVL (EFV after a mean observation of 13 weeks (IQR, 7-15 weeks). Switch to cART containing a half tablet of EFV (1/2#) in HIV-positive Taiwanese patients

  20. Extra virgin olive oil intake delays the development of amyotrophic lateral sclerosis associated with reduced reticulum stress and autophagy in muscle of SOD1G93A mice.

    Science.gov (United States)

    Oliván, Sara; Martínez-Beamonte, Roberto; Calvo, Ana C; Surra, Joaquín C; Manzano, Raquel; Arnal, Carmen; Osta, Rosario; Osada, Jesús

    2014-08-01

    Amyotrophic lateral sclerosis is a neurodegenerative disease associated with mutations in antioxidant enzyme Cu/Zn-superoxide dismutase 1. Albeit there is no treatment for this disease, new insights related to an exacerbated lipid metabolism have been reported. In connection with the hypermetabolic lipid status, the hypothesis whether nature of dietary fat might delay the progression of the disease was tested by using a transgenic mouse that overexpresses the human SOD1G93A variant. For this purpose, SOD1G93A mice were assigned randomly to one of the following three experimental groups: (1) a standard chow diet (control, n=21), (2) a chow diet enriched with 20% (w/w) extra virgin olive oil (EVOO, n=22) and (3) a chow diet containing 20% palm oil (palm, n=20). They received the diets for 8 weeks and the progression of the disease was assessed. On the standard chow diet, average plasma cholesterol levels were lower than those mice receiving the high-fat diets. Mice fed an EVOO diet showed a significant higher survival and better motor performance than control mice. EVOO group mice survived longer and showed better motor performance and larger muscle fiber area than animals receiving palm. Moreover, the EVOO-enriched diet improved the muscle status as shown by expression of myogenic factors (Myod1 and Myog) and autophagy markers (LC3 and Beclin1), as well as diminished endoplasmic reticulum (ER) stress through decreasing Atf6 and Grp78. Our results demonstrate that EVOO may be effective in increasing survival rate, improving motor coordination together with a potential amelioration of ER stress, autophagy and muscle damage. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Combined lithium and valproate treatment delays disease onset, reduces neurological deficits and prolongs survival in an amyotrophic lateral sclerosis mouse model.

    Science.gov (United States)

    Feng, H-L; Leng, Y; Ma, C-H; Zhang, J; Ren, M; Chuang, D-M

    2008-08-26

    Lithium and valproic acid (VPA) are two primary drugs used to treat bipolar disorder, and have been shown to have neuroprotective properties in vivo and in vitro. A recent study demonstrated that combined treatment with lithium and VPA elicits synergistic neuroprotective effects against glutamate excitotoxicity in cultured brain neurons, and the synergy involves potentiated inhibition of glycogen synthase kinase-3 (GSK-3) activity through enhanced GSK-3 serine phosphorylation [Leng Y, Liang MH, Ren M, Marinova Z, Leeds P, Chuang DM (2008) Synergistic neuroprotective effects of lithium and valproic acid or other histone deacetylase inhibitors in neurons: roles of glycogen synthase kinase-3 inhibition. J Neurosci 28:2576-2588]. We therefore investigated the effects of lithium and VPA cotreatment on the disease symptom onset, survival time and neurological deficits in cooper zinc superoxide dismutase (SOD1) G93A mutant mice, a commonly used mouse model of amyotrophic lateral sclerosis (ALS). The G93A ALS mice received twice daily i.p. injections with LiCl (60 mg/kg), VPA (300 mg/kg) or lithium plus VPA, starting from the 30(th) day after birth and continuing until death. We found that combined treatment with lithium and VPA produced a greater and more consistent effect in delaying the onset of disease symptoms, prolonging the lifespan and decreasing the neurological deficit scores, compared with the results of monotreatment with lithium or VPA. Moreover, lithium in conjunction with VPA was more effective than lithium or VPA alone in enhancing the immunostaining of phospho-GSK-3beta(Ser9) in brain and lumbar spinal cord sections. To our knowledge, this is the first demonstration of enhanced neuroprotection by a combinatorial approach using mood stabilizers in a mouse ALS model. Our results suggest that clinical trials using lithium and VPA in combination for ALS patients are a rational strategy.

  2. User-centric video delay measurements

    NARCIS (Netherlands)

    A.J. Jansen (Jack); D.C.A. Bulterman (Dick)

    2013-01-01

    htmlabstractThe complexities and physical constraints associated with video transmission make the introduction of video playout delays unavoidable. Tuning systems to reduce delay requires an ability to effectively and easily gather delay metrics on a potentially wide range of systems. In order to

  3. Hot air treatment reduces postharvest decay and delays softening of cherry tomato by regulating gene expression and activities of cell wall-degrading enzymes.

    Science.gov (United States)

    Wei, Yingying; Zhou, Dandan; Wang, Zhenjie; Tu, Sicong; Shao, Xingfeng; Peng, Jing; Pan, Leiqing; Tu, Kang

    2017-09-25

    Fruit softening facilitates pathogen infection and postharvest decay, leading to the reduction of shelf-life. Hot air (HA) treatment at 38 °C for 12 h is effective in reducing postharvest disease and chilling injury of tomato fruit. To explore the effect and mechanism of HA treatment on reducing postharvest decay and softening of cherry tomato, fruit at the mature green stage were treated with HA and then stored at 20 °C for 15 days. Changes in natural decay incidence, firmness, cell wall compositions, activities and gene expression of cell wall-degrading enzymes of cherry tomatoes were assessed. HA treatment reduced natural decay incidence, postponed the firmness decline, inhibited the respiration rate and ethylene production, and retarded pectin solubilization and cellulose degradation of cherry tomatoes. Enzymatic activities and gene expression of pectin methylesterase, polygalacturonase, cellulase and β-galactosidase were inhibited by HA treatment. In addition, the gene expression of LeEXP1 was reduced, while LeEXT was up-regulated after HA treatment. Our findings suggested that HA treatment could inhibit cell wall degradation and postpone softening of cherry tomatoes by regulating gene expression and activities of cell wall-degrading enzymes, resulting in the reduction of postharvest decay. This article is protected by copyright. All rights reserved.

  4. Nanomedicine for therapeutic drug therapy: Approaches to increase the efficacy of drug therapy with nanoemulsion delivery and reduce the toxicity of quantum dots

    Science.gov (United States)

    Kambalapally, Swetha Reddy

    The advancement of nanotechnology has paved the way for novel nanoscale materials for use in a wide range of applications. The use of these nanomaterials in biomedicine facilitates the improvement of existing technologies for disease prevention and treatment through diagnostics, tumor detection, drug delivery, medical imaging and vaccine development. Nanotechnology delivery systems for therapeutic uses includes the formulation of nanoparticles in emulsions. These novel delivery systems can improve drug efficacy by their ability to enhance bioavailability, minimize drug side effects, decrease drug toxicity, provide targeted site delivery and increase circulation of the drug in the blood. Additionally, these delivery systems also improve the drug stability and encapsulation efficiency. In the Introduction, this thesis will describe a novel technique for the preparation of nanoemulsions which was utilized in drug delivery and diagnostic applications. This novel Phase Inversion Temperature (PIT) method is a solvent and polymer-free and low energy requiring emulsification method, typically utilizing oils stabilized by nonionic surfactants to prepare water in oil (W/O) emulsions. The correlation between the particle size, zeta potential and the emulsion stability is described. The use of this nanoemulsion delivery system for pharmaceuticals and nutraceuticals by utilizing in vitro systems was investigated. Using the PIT method, a self assembling nanoemulsion (SANE) of gamma Tocotrienols (gammaT3), a component of Vitamin E family has been demonstrated to reduce cholesterol accumulation in HepG-2 cells. The nanoemulsion is stable and the particle size is around 20 nm with a polydispersity index (PDI) of 0.065. The effect of the nano gammaT3 on the metabolism of cholesterol, HMG-CoA activity and Apo-B levels were evaluated in an in vitro system utilizing HepG2 cells. A new class of nanoparticles, Quantum dots (QDs) has shown immense potential as novel nanomaterials used as

  5. Early enteral nutrition prevents intra-abdominal hypertension and reduces the severity of severe acute pancreatitis compared with delayed enteral nutrition: a prospective pilot study.

    Science.gov (United States)

    Sun, Jia-Kui; Li, Wei-Qin; Ke, Lu; Tong, Zhi-Hui; Ni, Hai-Bin; Li, Gang; Zhang, Lu-Yao; Nie, Yao; Wang, Xin-Ying; Ye, Xiang-Hong; Li, Ning; Li, Jie-Shou

    2013-09-01

    To investigate the effects of early enteral nutrition (EEN) on intra-abdominal pressure (IAP) and disease severity in patients with severe acute pancreatitis (SAP). Enteral nutrition (EN) was started within 48 h after admission in the EEN group and from the 8th day in the delayed enteral nutrition (DEN) group. The IAP and intra-abdominal hypertension (IAH) incidence were recorded for 2 weeks. The caloric intake and feeding intolerance (FI) incidence were recorded daily after EN was started. The severity markers and clinical outcome variables were also recorded. Sixty patients were enrolled to this study. No difference about IAP was found. The IAH incidence of the EEN group was significantly lower than that of the DEN group from the 9th day (8/30 versus 18/30; P = 0.009) after admission. The FI incidence of the EEN group was higher than that of the DEN group during the initial 3 days of feeding (25/30 versus 12/30; P = 0.001; 22/30 versus 9/30; P = 0.001; 15/30 versus 4/30; P = 0.002). Patients with an IAP <15 mmHg had lower FI incidence than those with an IAP ≥15 mmHg on the 1st day (20/22 versus 17/38; P < 0.001), the 3rd day (11/13 versus 8/47; P < 0.001), and the 7th day (3/5 versus 3/55; P = 0.005) of feeding. The severity markers and clinical outcome variables of the EEN group were significantly improved. Early enteral nutrition did not increase IAP. In contrast, it might prevent the development of IAH. In addition, EEN might be not appropriate during the initial 3-4 days of SAP onset. Moreover, EN might be of benefit to patients with an IAP <15 mmHg. Early enteral nutrition could improve disease severity and clinical outcome, but did not decrease mortality of SAP.

  6. Moderately delayed post-insult treatment with normobaric hyperoxia reduces excitotoxin-induced neuronal degeneration but increases ischemia-induced brain damage

    Directory of Open Access Journals (Sweden)

    Haelewyn Benoit

    2011-04-01

    Full Text Available Abstract Background The use and benefits of normobaric oxygen (NBO in patients suffering acute ischemic stroke is still controversial. Results Here we show for the first time to the best of our knowledge that NBO reduces both NMDA-induced calcium influxes in vitro and NMDA-induced neuronal degeneration in vivo, but increases oxygen and glucose deprivation-induced cell injury in vitro and ischemia-induced brain damage produced by middle cerebral artery occlusion in vivo. Conclusions Taken together, these results indicate that NBO reduces excitotoxin-induced calcium influx and subsequent neuronal degeneration but favors ischemia-induced brain damage and neuronal death. These findings highlight the complexity of the mechanisms involved by the use of NBO in patients suffering acute ischemic stroke.

  7. Use of Cold-Water Immersion to Reduce Muscle Damage and Delayed-Onset Muscle Soreness and Preserve Muscle Power in Jiu-Jitsu Athletes.

    Science.gov (United States)

    Fonseca, Líllian Beatriz; Brito, Ciro J; Silva, Roberto Jerônimo S; Silva-Grigoletto, Marzo Edir; da Silva, Walderi Monteiro; Franchini, Emerson

    2016-07-01

    Cold-water immersion (CWI) has been applied widely as a recovery method, but little evidence is available to support its effectiveness. To investigate the effects of CWI on muscle damage, perceived muscle soreness, and muscle power recovery of the upper and lower limbs after jiu-jitsu training. Crossover study. Laboratory and field. A total of 8 highly trained male athletes (age = 24.0 ± 3.6 years, mass = 78.4 ± 2.4 kg, percentage of body fat = 13.1% ± 3.6%) completed all study phases. We randomly selected half of the sample for recovery using CWI (6.0°C ± 0.5°C) for 19 minutes; the other participants were allocated to the control condition (passive recovery). Treatments were reversed in the second session (after 1 week). We measured serum levels of creatine phosphokinase, lactate dehydrogenase (LDH), aspartate aminotransferase, and alanine aminotransferase enzymes; perceived muscle soreness; and recovery through visual analogue scales and muscle power of the upper and lower limbs at pretraining, postrecovery, 24 hours, and 48 hours. Athletes who underwent CWI showed better posttraining recovery measures because circulating LDH levels were lower at 24 hours postrecovery in the CWI condition (441.9 ± 81.4 IU/L) than in the control condition (493.6 ± 97.4 IU/L; P = .03). Estimated muscle power was higher in the CWI than in the control condition for both upper limbs (757.9 ± 125.1 W versus 695.9 ± 56.1 W) and lower limbs (53.7 ± 3.7 cm versus 35.5 ± 8.2 cm; both P values = .001). In addition, we observed less perceived muscle soreness (1.5 ± 1.1 arbitrary units [au] versus 3.1 ± 1.0 au; P = .004) and higher perceived recovery (8.8 ± 1.9 au versus 6.9 ± 1.7 au; P = .005) in the CWI than in the control condition at 24 hours postrecovery. Use of CWI can be beneficial to jiu-jitsu athletes because it reduces circulating LDH levels, results in less perceived muscle soreness, and helps muscle power recovery at 24 hours postrecovery.

  8. Ebola management centre proximity associated with reduced delays of healthcare of Ebola Virus Disease (EVD patients, Tonkolili, Sierra Leone, 2014-15.

    Directory of Open Access Journals (Sweden)

    Georgios Theocharopoulos

    Full Text Available Between August-December 2014, Ebola Virus Disease (EVD patients from Tonkolili District were referred for care to two Médecins Sans Frontières (MSF Ebola Management Centres (EMCs outside the district (distant EMCs. In December 2014, MSF opened an EMC in Tonkolili District (district EMC. We examined the effect of opening a district-based EMC on time to admission and number of suspect cases dead on arrival (DOA, and identified factors associated with fatality in EVD patients, residents in Tonkolili District. Residents of Tonkolili district who presented between 12 September 2014 and 23 February 2015 to the district EMC and the two distant EMCs were identified from EMC line-lists. EVD cases were confirmed by a positive Ebola PCR test. We calculated time to admission since the onset of symptoms, case-fatality and adjusted Risk Ratios (aRR using Binomial regression. Of 249 confirmed Ebola cases, 206 (83% were admitted to the distant EMCs and 43 (17% to the district EMC. Of them 110 (45% have died. Confirmed cases dead on arrival (n = 10 were observed only in the distant EMCs. The median time from symptom onset to admission was 6 days (IQR 4,8 in distant EMCs and 3 days (IQR 2,7 in the district EMC (p3 days after symptom onset in the distant compared with the district EMC, but were less likely (aRR = 0.8; 95%CI 0.6-1.0 to have a high viral load (cycle threshold ≤22. A fatal outcome was associated with a high viral load (aRR 2.6; 95%CI 1.8-3.6 and vomiting at first presentation (aRR 1.4; 95%CI 1.0-2.0. The opening of a district EMC was associated with earlier admission of cases to appropriate care facilities, an essential component of reducing EVD transmission. High viral load and vomiting at admission predicted fatality. Healthcare providers should consider the location of EMCs to ensure equitable access during Ebola outbreaks.

  9. Internet-based treatment for PTSD reduces distress and facilitates the development of a strong therapeutic alliance: a randomized controlled clinical trial

    Directory of Open Access Journals (Sweden)

    Maercker Andreas

    2007-04-01

    Full Text Available Abstract Background The present study was designed to evaluate the efficacy of an internet-based therapy (Interapy for Posttraumatic Stress Disorder (PTSD in a German speaking population. Also, the quality of the online therapeutic relationship, its development and its relevance as potential moderator of the treatment effects was investigated. Method Ninety-six patients with posttraumatic stress reactions were allocated at random to ten sessions of Internet-based cognitive behavioural therapy (CBT conducted over a 5-week period or a waiting list control group. Severity of PTSD was the primary outcome. Secondary outcome variables were depression, anxiety, dissociation and physical health. Follow-up assessments were conducted at the end of treatment and 3 months after treatment. Results From baseline to post-treatment assessment, PTSD severity and other psychopathological symptoms were significantly improved for the treatment group (intent-to-treat group × time interaction effect size d = 1.40. Additionally, patients of the treatment condition showed significantly greater reduction of co-morbid depression and anxiety as compared to the waiting list condition. These effects were sustained during the 3-months follow-up period. High ratings of the therapeutic alliance and low drop-out rates indicated that a positive and stable therapeutic relationship could be established online. Significant improvement of the online working alliance in the course of treatment and a substantial correlation between the quality of the online relationship at the end of treatment and treatment outcome emerged. Conclusion Interapy proved to be a viable treatment alternative for PTSD with large effect sizes and sustained treatment effects. A stable and positive online therapeutic relationship can be established through the Internet which improved during the treatment process. Trial registration Australian Clinical Trials Registry ACTRN012606000401550

  10. Antisense and sense expression of cDNA coding for CYP73A15, a class II cinnamate 4-hydroxylase, leads to a delayed and reduced production of lignin in tobacco

    Science.gov (United States)

    Blee, K.; Choi, J. W.; O'Connell, A. P.; Jupe, S. C.; Schuch, W.; Lewis, N. G.; Bolwell, G. P.

    2001-01-01

    A number of plant species contain the class II of genes encoding the cytochrome P450, CYP73, the cognate protein of which cinnamic acid 4-hydroxylase, is the second enzyme of the phenylpropanoid pathway. In order to begin to determine possible functionality, tobacco has been transformed with a truncated French bean class II cinnamate hydroxylase (CYP73A15) in the sense and antisense orientations. Signals for C4H protein could be detected in vascular tissue from wild-type plants using heterologous probes. The transformed plants showed a normal phenotype, even though detectable C4H protein was much reduced in tissue prints. Young propagated transformants displayed a range of reduced C4H activities, as well as either reduced or no phloroglucinol-stainable lignin. However, all mature tobacco plants showed the accumulation of lignin, even though its deposition was apparently delayed. This was not due to induction of tyrosine ammonia-lyase activity, which was not detected, but instead it is presumed due to sufficient C4H residual activity. Analysis of the lignin content of the plants showed reductions of up to 30% with a slightly reduced syringyl to guaiacyl ratio as compared to wild type. This reduction level was favourable in comparison with some other targets in the lignification pathway that have been manipulated including that of class I cinnamate 4-hydroxylase. It is proposed that the class II cinnamate 4-hydroxylase might also function in lignification in a number of species including French bean and tobacco, based on these data.

  11. Reducing C-17 Pilot Training Delays

    Science.gov (United States)

    2004-06-01

    divided into two main phases, the combined Computer Based Training (CBT) and simulator phase taught by Boeing employees , followed by the flight line...of Boeing employees were extremely helpful with this research, not all requested data was made available. Therefore, contractual and other...64 282 SUMMARY OF C-17 FLYING HOURS DATE 14-Mar-03 40 Appendix E – Refly Tracker Date Class # R efly A ttrition A R A ssaults G nd O ps G K

  12. Reducing start time delays in operating rooms

    NARCIS (Netherlands)

    Does, R.J.M.M.; Vermaat, T.M.B.; Verver, J.P.S.; Bisgaard, S.; van den Heuvel, J.

    2009-01-01

    Problem: Health care today is facing serious problems: quality of care does not meet patients’ needs and costs are exploding. Inefficient utilization of expensive operating rooms is one of the major problems in many hospitals worldwide. A benchmark study of 13 hospitals in the Netherlands and

  13. Immediate and delayed loading of two-piece reduced-diameter implants with locator-analog attachments in edentulous mandibles: One-year results from a randomized clinical trial examining clinical outcome and patient expectation.

    Science.gov (United States)

    Giannakopoulos, Nikolaos Nikitas; Ariaans, Kirsten; Eberhard, Lydia; Klotz, Anna-Luisa; Oh, Keunyoung; Kappel, Stefanie

    2017-08-01

    Prosthetic management of thin alveolar ridges in the edentulous mandibles of elderly patients, especially the time of loading, the number of implants needed, and patient expectations and perception, is a challenge in implant dentistry. Survival of conventionally and immediately loaded 2-piece reduced-diameter implants in the interforaminal region of the edentulous mandible supporting locator-analog attachments was evaluated. Prosthetic complications and peri-implant hygiene were also studied, and patient expectation and subjective evaluation of the treatment were documented. Twenty-five patients with adapted complete dentures received 4 reduced-diameter implants. All anterior implants were immediately loaded. Three months later, patients were allocated by randomization to 1 of 2 treatment groups: 2 locator-analog attachments on the anterior implants (Group A); or 4 locator-analog attachments (Group B). After another 3 months patient allocation was changed (crossover design) for the next 3 months. Questionnaires with Likert scales and numeric rating scales were used to assess patients' expectations and subjective overdenture-related variables, respectively. One implant was lost in the immediate-loading group. Survival was 98% and 100% for immediate and delayed loading, respectively. During 12-month observation, 8 complications required aftercare. At the beginning of treatment, patients' expectations were highly positive. Subjective assessment of overdenture-related variables 3 months after immediate loading of 2 implants revealed a statistically significant improvement for most of the variables studied; this was maintained 1 year later. In the subjective assessments, there were no statistically significant differences between Groups A and B. Immediate loading of reduced-diameter implants supporting locator-analog attachments resulted in high implant survival, few prosthetic complications, good oral hygiene, and improvement of subjective denture perception in the

  14. Caprylic acid reduces Salmonella Enteritidis populations in various segments of digestive tract and internal organs of 3- and 6-week-old broiler chickens, therapeutically

    NARCIS (Netherlands)

    Kollanoor-Johny, A.; Mattson, T.; Baskaran, S.A.; Amalaradjou, M.A.; Hoagland, T.A.; Darre, M.J.; Khan, M.I.; Schreiber, D.T.; Donoghue, A.M.; Donoghue, D.J.; Venkitanarayanan, K.

    2012-01-01

    We investigated the efficacy of feed supplemented with caprylic acid (CA), a natural, 8-carbon fatty acid for reducing Salmonella enterica serovar Enteritidis colonization in commercial broiler chickens. In separate 3- and 6-wk trials, 1-d-old straight-run broiler chicks (n = 70 birds/trial) were

  15. delayed presentation of blunt traumatic diaphragmatic heria

    African Journals Online (AJOL)

    Zinox

    the spleen and stomach. Through a left thoracotomy, the herniated organs were reduced and diaphragmatic defect closed with interrupted nylon sutures. A high index of suspicion would minimize the morbidity and mortality associated with delayed diagnosis. Keywords: Trauma, diaphragmatic hernia, delayed presentation.

  16. Facile synthesis of water-dispersible Cu2O nanocrystal-reduced graphene oxide hybrid as a promising cancer therapeutic agent

    Science.gov (United States)

    Hou, Chengyi; Quan, Haocheng; Duan, Yourong; Zhang, Qinghong; Wang, Hongzhi; Li, Yaogang

    2013-01-01

    We report a Cu2O nanocrystal-reduced graphene oxide hybrid that is dispersible in water and has anticancer activity under both visible and near-infrared light irradiation. In contrast to the highly efficient killing of both normal and cancer cells initiated by the photothermal effect, the photocatalytic effect of this material results in the selective killing of cancer cells under visible light irradiation. These results have implications for safe and widely applicable cancer therapy agents.We report a Cu2O nanocrystal-reduced graphene oxide hybrid that is dispersible in water and has anticancer activity under both visible and near-infrared light irradiation. In contrast to the highly efficient killing of both normal and cancer cells initiated by the photothermal effect, the photocatalytic effect of this material results in the selective killing of cancer cells under visible light irradiation. These results have implications for safe and widely applicable cancer therapy agents. Electronic supplementary information (ESI) available: Characterization of the over-reduced products and the photocatalytic activity of the CRGO. See DOI: 10.1039/c2nr32938g

  17. Therapeutic neuroprotective agents for amyotrophic lateral sclerosis

    Science.gov (United States)

    Pandya, Rachna S.; Zhu, Haining; Li, Wei; Bowser, Robert; Friedlander, Robert M.

    2014-01-01

    Amyotrophic lateral sclerosis (ALS) is a fatal chronic neurodegenerative disease whose hallmark is proteinaceous, ubiquitinated, cytoplasmic inclusions in motor neurons and surrounding cells. Multiple mechanisms proposed as responsible for ALS pathogenesis include dysfunction of protein degradation, glutamate excitotoxicity, mitochondrial dysfunction, apoptosis, oxidative stress, and inflammation. It is therefore essential to gain a better understanding of the underlying disease etiology and search for neuroprotective agents that might delay disease onset, slow progression, prolong survival, and ultimately reduce the burden of disease. Because riluzole, the only Food and Drug Administration (FDA)-approved treatment, prolongs the ALS patient’s life by only 3 months, new therapeutic agents are urgently needed. In this review, we focus on studies of various small pharmacological compounds targeting the proposed pathogenic mechanisms of ALS and discuss their impact on disease progression. PMID:23864030

  18. Delayed Orgasm and Anorgasmia

    OpenAIRE

    JENKINS, Lawrence C.; Mulhall, John P.

    2015-01-01

    Delayed orgasm/anorgasmia defined as the persistent or recurrent difficulty, delay in, or absence of attaining orgasm after sufficient sexual stimulation, which causes personal distress. Delayed orgasm and anorgasmia are associated with significant sexual dissatisfaction. A focused medical history can shed light on the potential etiologies; which include: medications, penile sensation loss, endocrinopathies, penile hyperstimulation and psychological etiologies, amongst others. Unfortunately, ...

  19. pH-Responsive therapeutic solid lipid nanoparticles for reducing P-glycoprotein-mediated drug efflux of multidrug resistant cancer cells.

    Science.gov (United States)

    Chen, Hsin-Hung; Huang, Wen-Chia; Chiang, Wen-Hsuan; Liu, Te-I; Shen, Ming-Yin; Hsu, Yuan-Hung; Lin, Sung-Chyr; Chiu, Hsin-Cheng

    2015-01-01

    administration of DOX-loaded SLNs show that the SLNs have no observable side effects. These results indicate that the C-PEG-SLN is a promising platform for the delivery of therapeutic agents for MDR cancer chemotherapy.

  20. Zinc transporter 8 (ZnT8 expression is reduced by ischemic insults: a potential therapeutic target to prevent ischemic retinopathy.

    Directory of Open Access Journals (Sweden)

    Michael Deniro

    Full Text Available The zinc (Zn(++ transporter ZnT8 plays a crucial role in zinc homeostasis. It's been reported that an acute decrease in ZnT8 levels impairs β cell function and Zn(++ homeostasis, which contribute to the pathophysiology of diabetes mellitus (DM. Although ZnT8 expression has been detected in the retinal pigment epithelium (RPE, its expression profile in the retina has yet to be determined. Furthermore, the link between diabetes and ischemic retinopathy is well documented; nevertheless, the molecular mechanism(s of such link has yet to be defined. Our aims were to; investigate the expression profile of ZnT8 in the retina; address the influence of ischemia on such expression; and evaluate the influence of YC-1; (3-(50-hydroxymethyl-20-furyl-1-benzyl indazole, a hypoxia inducible factor-1 (HIF-1 inhibitor, on the status of ZnT8 expression. We used real-time RT-PCR, immunohistochemistry, and Western blot in the mouse model of oxygen-induced retinopathy (OIR and Müller cells to evaluate the effects of ischemia/hypoxia and YC-1 on ZnT8 expression. Our data indicate that ZnT8 was strongly expressed in the outer nuclear layer (ONL, outer plexiform layer (OPL, ganglion cell layer (GCL, and nerve fiber layer (NFL, whereas the photoreceptor layer (PRL, inner nuclear layer (INL and inner plexiform layer (IPL showed moderate ZnT8 immunoreactivity. Furthermore, we demonstrate that retinal ischemic insult induces a significant downregulation of ZnT8 at the message and protein levels, YC-1 rescues the injured retina by restoring the ZnT8 to its basal homeostatic levels in the neovascular retinas. Our data indicate that ischemic retinopathy maybe mediated by aberrant Zn(++ homeostasis caused by ZnT8 downregulation, whereas YC-1 plays a neuroprotective role against ischemic insult. Therefore, targeting ZnT8 provides a therapeutic strategy to combat neovascular eye diseases.

  1. Peptides of presenilin-1 bind the amyloid precursor protein ectodomain and offer a novel and specific therapeutic approach to reduce ß-amyloid in Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Nazneen N Dewji

    Full Text Available β-Amyloid (Aβ accumulation in the brain is widely accepted to be critical to the development of Alzheimer's disease (AD. Current efforts at reducing toxic Aβ40 or 42 have largely focused on modulating γ-secretase activity to produce shorter, less toxic Aβ, while attempting to spare other secretase functions. In this paper we provide data that offer the potential for a new approach for the treatment of AD. The method is based on our previous findings that the production of Aβ from the interaction between the β-amyloid precursor protein (APP and Presenilin (PS, as part of the γ-secretase complex, in cell culture is largely inhibited if the entire water-soluble NH2-terminal domain of PS is first added to the culture. Here we demonstrate that two small, non-overlapping water-soluble peptides from the PS-1 NH2-terminal domain can substantially and specifically inhibit the production of total Aβ as well as Aβ40 and 42 in vitro and in vivo in the brains of APP transgenic mice. These results suggest that the inhibitory activity of the entire amino terminal domain of PS-1 on Aβ production is largely focused in a few smaller sequences within that domain. Using biolayer interferometry and confocal microscopy we provide evidence that peptides effective in reducing Aβ give a strong, specific and biologically relevant binding with the purified ectodomain of APP 695. Finally, we demonstrate that the reduction of Aβ by the peptides does not affect the catalytic activities of β- or γ-secretase, or the level of APP. P4 and P8 are the first reported protein site-specific small peptides to reduce Aβ production in model systems of AD. These peptides and their derivatives offer new potential drug candidates for the treatment of AD.

  2. Inhibition of ADAMTS-13 by Doxycycline Reduces von Willebrand Factor Degradation During Supraphysiological Shear Stress: Therapeutic Implications for Left Ventricular Assist Device-Associated Bleeding.

    Science.gov (United States)

    Bartoli, Carlo R; Kang, Jooeun; Restle, David J; Zhang, David M; Shabahang, Cameron; Acker, Michael A; Atluri, Pavan

    2015-11-01

    The aim of this study was to investigate a potential therapy for left ventricular assist device (LVAD)-associated bleeding. Nonsurgical bleeding is the most frequent complication of LVAD support. Recent evidence has demonstrated that supraphysiological shear stress from continuous-flow LVADs accelerates von Willebrand factor (vWF) metabolism by the action of a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS-13) (the vWF protease). An acquired vWF deficiency causes bleeding. This suggests that ADAMTS-13 is a clinical target to reduce vWF degradation. We tested the hypothesis that inhibition of ADAMTS-13 with doxycycline, an inexpensive, clinically approved drug, reduces vWF degradation during shear stress. Whole blood was collected from human donors (n = 15), and purified, recombinant ADAMTS-13 protein was obtained. An enzyme-linked immunosorbent assay (ELISA) was used to quantify the dose relationship between doxycycline and ADAMTS-13 activity prior to shear stress (n = 10). To determine the effect of shear stress, plasma and recombinant ADAMTS-13 were exposed to LVAD-like supraphysiological shear stress (approximately 175 dyne/cm(2)). vWF multimers and degradation fragments were characterized with electrophoresis and immunoblotting (n = 10). Förster resonance energy transfer was used to quantify plasma ADAMTS-13 activity (n = 10). An ELISA was used to quantify vWF:collagen binding activity. Platelet aggregometry was performed with adenosine 5'-diphosphate, collagen, and ristocetin (vWF-platelet pathway) agonism (n = 10). Doxycycline significantly decreased plasma ADAMTS-13 activity (p = 0.01) and the activity of recombinant human ADAMTS-13 protein by 21%. After plasma was exposed to shear stress, the same pattern of vWF degradation was observed as previously reported for LVAD patients, and vWF:collagen binding activity decreased significantly (p = 0.002). Doxycycline significantly decreased ADAMTS-13 activity (p = 0.04) and

  3. Permutation entropy with vector embedding delays

    Science.gov (United States)

    Little, Douglas J.; Kane, Deb M.

    2017-12-01

    Permutation entropy (PE) is a statistic used widely for the detection of structure within a time series. Embedding delay times at which the PE is reduced are characteristic timescales for which such structure exists. Here, a generalized scheme is investigated where embedding delays are represented by vectors rather than scalars, permitting PE to be calculated over a (D -1 ) -dimensional space, where D is the embedding dimension. This scheme is applied to numerically generated noise, sine wave and logistic map series, and experimental data sets taken from a vertical-cavity surface emitting laser exhibiting temporally localized pulse structures within the round-trip time of the laser cavity. Results are visualized as PE maps as a function of embedding delay, with low PE values indicating combinations of embedding delays where correlation structure is present. It is demonstrated that vector embedding delays enable identification of structure that is ambiguous or masked, when the embedding delay is constrained to scalar form.

  4. Lecithin as a therapeutic agent in ulcerative colitis.

    Science.gov (United States)

    Stremmel, Wolfgang; Gauss, Annika

    2013-01-01

    Lecithin [phosphatidylcholine (PC)] was shown to account for more than 70% of total phospholipids within the intestinal mucus layer. It is arranged in lamellar membranes (surfactant-like particles) and establishes a hydrophobic barrier preventing invasion of the colonic commensal microbiota. In ulcerative colitis (UC), the mucus PC content was demonstrated to be reduced by about 70%, irrespective of the presence of inflammation. This may be of primary pathogenetic significance allowing bacteria to enter the mucus and induce mucosal inflammation. Therefore, a new therapeutic strategy is being developed to substitute the missing mucus PC content in UC. Indeed, a delayed-release PC formulation was able to compensate the lack of PC and improve the inflammatory activity. In randomized controlled studies, delayed-release PC was proven to be clinically and endoscopically effective, which now awaits a phase III authority approval trial.

  5. Brain pyroglutamate amyloid-β is produced by cathepsin B and is reduced by the cysteine protease inhibitor E64d, representing a potential Alzheimer's disease therapeutic.

    Science.gov (United States)

    Hook, Gregory; Yu, Jin; Toneff, Thomas; Kindy, Mark; Hook, Vivian

    2014-01-01

    Pyroglutamate amyloid-β peptides (pGlu-Aβ) are particularly pernicious forms of amyloid-β peptides (Aβ) present in Alzheimer's disease (AD) brains. pGlu-Aβ peptides are N-terminally truncated forms of full-length Aβ peptides (flAβ(1-40/42)) in which the N-terminal glutamate is cyclized to pyroglutamate to generate pGlu-Aβ(3-40/42). β-secretase cleavage of amyloid-β precursor protein (AβPP) produces flAβ(1-40/42), but it is not yet known whether the β-secretase BACE1 or the alternative β-secretase cathepsin B (CatB) participate in the production of pGlu-Aβ. Therefore, this study examined the effects of gene knockout of these proteases on brain pGlu-Aβ levels in transgenic AβPPLon mice, which express AβPP isoform 695 and have the wild-type (wt) β-secretase activity found in most AD patients. Knockout or overexpression of the CatB gene reduced or increased, respectively, pGlu-Aβ(3-40/42), flAβ(1-40/42), and pGlu-Aβ plaque load, but knockout of the BACE1 gene had no effect on those parameters in the transgenic mice. Treatment of AβPPLon mice with E64d, a cysteine protease inhibitor of CatB, also reduced brain pGlu-Aβ(3-42), flAβ(1-40/42), and pGlu-Aβ plaque load. Treatment of neuronal-like chromaffin cells with CA074Me, an inhibitor of CatB, resulted in reduced levels of pGlu-Aβ(3-40) released from the activity-dependent, regulated secretory pathway. Moreover, CatB knockout and E64d treatment has been previously shown to improve memory deficits in the AβPPLon mice. These data illustrate the role of CatB in producing pGlu-Aβ and flAβ that participate as key factors in the development of AD. The advantages of CatB inhibitors, especially E64d and its derivatives, as alternatives to BACE1 inhibitors in treating AD patients are discussed.

  6. Therapeutic HIV Peptide Vaccine

    DEFF Research Database (Denmark)

    Fomsgaard, Anders

    2015-01-01

    Therapeutic vaccines aim to control chronic HIV infection and eliminate the need for lifelong antiretroviral therapy (ART). Therapeutic HIV vaccine is being pursued as part of a functional cure for HIV/AIDS. We have outlined a basic protocol for inducing new T cell immunity during chronic HIV-1...... infection directed to subdominant conserved HIV-1 epitopes restricted to frequent HLA supertypes. The rationale for selecting HIV peptides and adjuvants are provided. Peptide subunit vaccines are regarded as safe due to the simplicity, quality, purity, and low toxicity. The caveat is reduced immunogenicity...

  7. Prehospital delay in acute coronary syndrome--an analysis of the components of delay

    DEFF Research Database (Denmark)

    Ottesen, Michael Mundt; Dixen, Ulrik; Torp-Pedersen, Christian

    2004-01-01

    BACKGROUND: Prompt hospital admission is essential when treating acute coronary syndrome. Delay prior to admission is unnecessarily long. Therefore, a thorough scrutiny of the influence of characteristics, circumstantial and subjective variables on elements of prehospital delay among patients...... admitted with acute coronary syndrome is warranted. METHODS: A structured interview was conducted on 250 consecutive patients admitted alive with acute coronary syndrome. RESULTS: Median prehospital, decision, physician and transportation delays were 107, 74, 25 and 22 min, respectively. Women (n=77) had...... more frequently atypical symptoms and increased prehospital delay caused by prolonged physician and transportation delay. Physician delay among women and men were 69 and 16 min, respectively. Patients with prior myocardial infarction had reduced prehospital delay, which was caused by shorter decision...

  8. Therapeutic drug monitoring and receiver operating characteristic curve prediction may reduce the development of linezolid-associated thrombocytopenia in critically ill patients.

    Science.gov (United States)

    Dong, H-Y; Xie, J; Chen, L-H; Wang, T-T; Zhao, Y-R; Dong, Y-L

    2014-06-01

    To investigate the risk factors associated with the development of thrombocytopenia, and define the thresholds of efficacy and safety in critically ill patients who received linezolid therapy. A retrospective study was performed in critically ill patients treated with linezolid. Risk factors associated with thrombocytopenia were identified via medical records and trough levels (C(min)) measured during linezolid treatment. By establishing a logistic model, the risks were predicted by the receiver operating characteristic (ROC) curve and the thresholds of efficacy and safety were identified in the patients. Logistic analysis showed that, weight (OR = 0.906; 95% CI, 0.839-0.978; P = 0.011), baseline platelet count (OR = 0.989; 95% CI, 0.977-1.000; P = 0.049), C(min) (OR = 1.545; 95% CI, 1.203-1.983; P = 0.001), and APACHE II score (OR = 1.130; 95% CI, 1.003-1.273; P = 0.044) were significant factors for linezolid-associated thrombocytopenia. The area under the ROC curve of the combined predictor was larger based on the above factors. When the Youden index was the maximum, the best optimal cut-off point was 205.6 on the ROC curve; when C(min) ≥ 2 mg/L, the probability of bacterial eradication was more than 80%; when C(min) ≥ 6.3 mg/L, the probability of thrombocytopenia was more than 50 %. In clinical practice, when the calculating results of the combined predictor ≤205.6, the risk of the development of thrombocytopenia may be higher. Furthermore, maintenance of C(min) between 2 and 6.3 mg/L over time may be helpful in retaining appropriate efficacy and reducing the associated thrombocytopenia.

  9. Bioactive Antimicrobial Peptides as Therapeutics for Corneal Wounds and Infections

    Science.gov (United States)

    Griffith, Gina L.; Kasus-Jacobi, Anne; Pereira, H. Anne

    2017-01-01

    Significance: More than 2 million eye injuries and infections occur each year in the United States that leave civilians and military members with reduced or complete vision loss due to the lack of effective therapeutics. Severe ocular injuries and infections occur in varied settings including the home, workplace, and battlefields. In this review, we discuss the potential of developing antimicrobial peptides (AMPs) as therapeutics for the treatment of corneal wounds and infections for which the current treatment options are inadequate. Recent Advances: Standard-of-care employs the use of fluorescein dye for the diagnosis of ocular defects and is followed by the use of antibiotics and/or steroids to treat the infection and reduce inflammation. Recent advances for treating corneal wounds include the development of amniotic membrane therapies, wound chambers, and drug-loaded hydrogels. In this review, we will discuss an innovative approach using AMPs with the dual effect of promoting corneal wound healing and clearing infections. Critical Issues: An important aspect of treating ocular injuries is that treatments need to be effective and administered expeditiously. This is especially important for injuries that occur during combat and in individuals who demonstrate delayed wound healing. To overcome gaps in current treatment modalities, bioactive peptides based on naturally occurring cationic antimicrobial proteins are being investigated as new therapeutics. Future Directions: The development of new therapeutics that can treat ocular infections and promote corneal wound healing, including the healing of persistent corneal epithelial defects, would be of great clinical benefit. PMID:28616359

  10. Bioactive Antimicrobial Peptides as Therapeutics for Corneal Wounds and Infections.

    Science.gov (United States)

    Griffith, Gina L; Kasus-Jacobi, Anne; Pereira, H Anne

    2017-06-01

    Significance: More than 2 million eye injuries and infections occur each year in the United States that leave civilians and military members with reduced or complete vision loss due to the lack of effective therapeutics. Severe ocular injuries and infections occur in varied settings including the home, workplace, and battlefields. In this review, we discuss the potential of developing antimicrobial peptides (AMPs) as therapeutics for the treatment of corneal wounds and infections for which the current treatment options are inadequate. Recent Advances: Standard-of-care employs the use of fluorescein dye for the diagnosis of ocular defects and is followed by the use of antibiotics and/or steroids to treat the infection and reduce inflammation. Recent advances for treating corneal wounds include the development of amniotic membrane therapies, wound chambers, and drug-loaded hydrogels. In this review, we will discuss an innovative approach using AMPs with the dual effect of promoting corneal wound healing and clearing infections. Critical Issues: An important aspect of treating ocular injuries is that treatments need to be effective and administered expeditiously. This is especially important for injuries that occur during combat and in individuals who demonstrate delayed wound healing. To overcome gaps in current treatment modalities, bioactive peptides based on naturally occurring cationic antimicrobial proteins are being investigated as new therapeutics. Future Directions: The development of new therapeutics that can treat ocular infections and promote corneal wound healing, including the healing of persistent corneal epithelial defects, would be of great clinical benefit.

  11. Delays in thick targets

    CERN Document Server

    Bennett, J R J

    2002-01-01

    The delays in the emission of radioactive particles from a thick target bombarded by high-energy protons is discussed in relation to the basic physical processes of diffusion and effusion through the target and ioniser. The delay time, relative to the decay time, is crucial to the efficiency of particle release at the exit of the ioniser. The principles of minimizing the delay times are discussed with reference to a mathematical model of the process, and some experimental examples are given.

  12. Control of bifurcation-delay of slow passage effect by delayed self-feedback

    Science.gov (United States)

    Premraj, D.; Suresh, K.; Banerjee, Tanmoy; Thamilmaran, K.

    2017-01-01

    The slow passage effect in a dynamical system generally induces a delay in bifurcation that imposes an uncertainty in the prediction of the dynamical behaviors around the bifurcation point. In this paper, we investigate the influence of linear time-delayed self-feedback on the slow passage through the delayed Hopf and pitchfork bifurcations in a parametrically driven nonlinear oscillator. We perform linear stability analysis to derive the Hopf bifurcation point and its stability as a function of self-feedback time delay. Interestingly, the bifurcation-delay associated with Hopf bifurcation behaves differently in two different edges. In the leading edge of the modulating signal, it decreases with increasing self-feedback delay, whereas in the trailing edge, it behaves in an opposite manner. We also show that the linear time-delayed self-feedback can reduce bifurcation-delay in pitchfork bifurcation. These results are illustrated numerically and corroborated experimentally. We also propose a mechanistic explanation of the observed behaviors. In addition, we show that our observations are robust in the presence of noise. We believe that this study of interplay of two time delays of different origins will shed light on the control of bifurcation-delay and improve our knowledge of time-delayed systems.

  13. Delayed orgasm and anorgasmia.

    Science.gov (United States)

    Jenkins, Lawrence C; Mulhall, John P

    2015-11-01

    Delayed orgasm/anorgasmia defined as the persistent or recurrent difficulty, delay in, or absence of attaining orgasm after sufficient sexual stimulation, which causes personal distress. Delayed orgasm and anorgasmia are associated with significant sexual dissatisfaction. A focused medical history can shed light on the potential etiologies, which include medications, penile sensation loss, endocrinopathies, penile hyperstimulation, and psychological etiologies. Unfortunately, there are no excellent pharmacotherapies for delayed orgasm/anorgasmia, and treatment revolves largely around addressing potential causative factors and psychotherapy. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  14. DUI offenders delay license reinstatement: a problem?

    Science.gov (United States)

    Voas, Robert B; Tippetts, A Scott; McKnight, A Scott

    2010-07-01

    We examined the extent to which driving under the influence (DUI) offenders delay reinstatement, the reasons for that delay, and the relationship of the delay to recidivism. Analyzed were the driving records of 40 million drivers (3 million convicted of DUI) from 7 of the largest states spanning 7 to 14 years. License suspension effectively reduces, but does not eliminate, impaired driving. Apparently, many feel they can avoid apprehension for unlicensed driving; the limited research to date suggests that up to 75% of convicted offenders continue to drive and up to 84% delay reinstatement for 3 or more years. ANOVA and regression procedures were used to determine the relationship of prior driving record and sentence length to the DUI offender's delay in reinstatement. Meta-analysis was used to summarize results across the 7 states and survival analysis to determine the effect of the delay on recidivism. Forty-two percent of first offenders and 55% of multiple offenders convicted for DUI delay reinstatement for more than a year. For a third of the offenders, there were no records of their having reinstated within 5 years of becoming eligible. Both factors-more than one prior offense and the length of suspension imposed-were related to delay in reinstatement. Offenders who delayed reinstatement were more likely to recidivate both while they delayed before reinstating and after they reinstated. DUI offenders who delay reinstatement after they become eligible are high-risk drivers. Offenders who reinstate, however, have lower recidivism rates than those who do not. This suggests that encouraging reinstatement but with continued controls, as some states have provided through laws requiring interlocks as a condition of reinstatement, may be effective if they do not motivate extended delays.

  15. Factors Influencing Road Traffic Delay: Drivers' Perspectives And ...

    African Journals Online (AJOL)

    This study examined drivers' perception of road traffic delay attributes and factors influencing road traffic delay with a view to assessing loss of man hours along Lagos-Abeokuta Expressway. This view translated to policy statements that can tremendously reduce the road traffic delay in the study area. Primary data were ...

  16. A Translational Study of a New Therapeutic Approach for Acute Myocardial Infarction: Nanoparticle-Mediated Delivery of Pitavastatin into Reperfused Myocardium Reduces Ischemia-Reperfusion Injury in a Preclinical Porcine Model.

    Science.gov (United States)

    Ichimura, Kenzo; Matoba, Tetsuya; Nakano, Kaku; Tokutome, Masaki; Honda, Katsuya; Koga, Jun-Ichiro; Egashira, Kensuke

    2016-01-01

    There is an unmet need to develop an innovative cardioprotective modality for acute myocardial infarction, for which interventional reperfusion therapy is hampered by ischemia-reperfusion (IR) injury. We recently reported that bioabsorbable poly(lactic acid/glycolic acid) (PLGA) nanoparticle-mediated treatment with pitavastatin (pitavastatin-NP) exerts a cardioprotective effect in a rat IR injury model by activating the PI3K-Akt pathway and inhibiting inflammation. To obtain preclinical proof-of-concept evidence, in this study, we examined the effect of pitavastatin-NP on myocardial IR injury in conscious and anesthetized pig models. Eighty-four Bama mini-pigs were surgically implanted with a pneumatic cuff occluder at the left circumflex coronary artery (LCx) and telemetry transmitters to continuously monitor electrocardiogram as well as to monitor arterial blood pressure and heart rate. The LCx was occluded for 60 minutes, followed by 24 hours of reperfusion under conscious conditions. Intravenous administration of pitavastatin-NP containing ≥ 8 mg/body of pitavastatin 5 minutes before reperfusion significantly reduced infarct size; by contrast, pitavastatin alone (8 mg/body) showed no therapeutic effects. Pitavastatin-NP produced anti-apoptotic effects on cultured cardiomyocytes in vitro. Cardiac magnetic resonance imaging performed 4 weeks after IR injury revealed that pitavastatin-NP reduced the extent of left ventricle remodeling. Importantly, pitavastatin-NP exerted no significant effects on blood pressure, heart rate, or serum biochemistry. Exploratory examinations in anesthetized pigs showed pharmacokinetic analysis and the effects of pitavastatin-NP on no-reflow phenomenon. NP-mediated delivery of pitavastatin to IR-injured myocardium exerts cardioprotective effects on IR injury without apparent adverse side effects in a preclinical conscious pig model. Thus, pitavastatin-NP represents a novel therapeutic modality for IR injury in acute myocardial

  17. American Dream Delayed

    DEFF Research Database (Denmark)

    Khorunzhina, Natalia; Miller, Robert A.

    This paper investigates the delay in homeownership and a subsequent reduction in homeownership rate observed over the past decades. We focus on the delay in giving birth to children and increased labor market participation as contributing factors to homeownership dynamics for prime-age female hou...

  18. A protocol for a cluster-randomized controlled trial of a self-help psycho-education programme to reduce diagnosis delay in women with breast cancer symptoms in Indonesia

    NARCIS (Netherlands)

    H. Setyowibowo (Hari); M. Sijbrandij (Marit); A. Iskandarsyah (Aulia); J.A.M. Hunfeld (Joke); S.S. Sadarjoen (Sawitri); D.F. Badudu (Dharmayanti F.); D.R. Suardi (Dradjat); J. Passchier (Jan)

    2017-01-01

    markdownabstractBackground: Breast cancer (BC) is the most frequent cancer occurring in women across the world. Its mortality rate in low-middle income countries (LMICs) is higher than in high-income countries (HICs), and in Indonesia BC is the leading cause of cancer deaths among women. Delay in

  19. A protocol for a cluster-randomized controlled trial of a self-help psycho-education programme to reduce diagnosis delay in women with breast cancer symptoms in Indonesia

    NARCIS (Netherlands)

    Setyowibowo, H. (Hari); M. Sijbrandij (Marit); A. Iskandarsyah (Aulia); J.A.M. Hunfeld (Joke); S.S. Sadarjoen (Sawitri); Badudu, D.F. (Dharmayanti F.); D.R. Suardi (Dradjat); J. Passchier (Jan)

    2017-01-01

    textabstractBackground: Breast cancer (BC) is the most frequent cancer occurring in women across the world. Its mortality rate in low-middle income countries (LMICs) is higher than in high-income countries (HICs), and in Indonesia BC is the leading cause of cancer deaths among women. Delay in breast

  20. Delay Choice vs. Delay Maintenance: Different Measures of Delayed Gratification in Capuchin Monkeys (Cebus apella)

    OpenAIRE

    Addessi, Elsa; Paglieri, Fabio; Beran, Michael J.; Evans, Theodore A.; Macchitella, Luigi; De Petrillo, Francesca; Focaroli, Valentina

    2013-01-01

    Delaying gratification involves two components: (i) delay choice (selecting a delayed reward over an immediate one), and (ii) delay maintenance (sustaining the decision to delay gratification even if the immediate reward is available during the delay). In primates, two tasks most commonly have explored these components, the Intertemporal choice task and the Accumulation task. It is unclear whether these tasks provide equivalent measures of delay of gratification. Here, we compared the perform...

  1. Delayed Puberty (For Teens)

    Science.gov (United States)

    ... developed later than usual, too. This is called constitutional delay (or being a late bloomer), and it ... eventually — and even when you believe they're right — it's difficult to wait for something that can ...

  2. Delayed Sequence Intubation

    DEFF Research Database (Denmark)

    Weingart, Scott D; Trueger, N Seth; Wong, Nelson

    2015-01-01

    , patients were paralyzed and intubated. The primary outcome of this study was the difference in oxygen saturations after maximal attempts at preoxygenation before delayed sequence intubation compared with saturations just before intubation. Predetermined secondary outcomes and complications were also...... assessed. RESULTS: A total of 62 patients were enrolled: 19 patients required delayed sequence intubation to allow nonrebreather mask, 39 patients required it to allow NIPPV, and 4 patients required it for nasogastric tube placement. Saturations increased from a mean of 89.9% before delayed sequence...... intubation to 98.8% afterward, with an increase of 8.9% (95% confidence interval 6.4% to 10.9%). Thirty-two patients were in a predetermined group with high potential for critical desaturation (pre-delayed sequence intubation saturations ≤93%). All of these patients increased their saturations post...

  3. Delayed puberty in boys

    Science.gov (United States)

    ... Allan CA, McLachlan RI. Androgen deficiency disorders. In: Jameson JL, De Groot LJ, de Kretser DM, et ... 350. Haddad NG, Eugster EA. Delayed puberty. In: Jameson JL, De Groot LJ, de Kretser DM, et ...

  4. Therapeutic misadventure.

    Science.gov (United States)

    Langford, N J

    2010-10-01

    Therapeutic misadventure can be defined as an injury or an adverse event caused by medical management rather than by an underlying disease. Within the National Health Service there were over 86,000 reported adverse incidents in 2007. In the USA medication errors have been rated as the fourth highest cause of death. Unfortunately one of the greatest contributors to iatrogenic injury is human error. The potential types of misadventure are infinite. Medication errors are a major part of this, being responsible for over 70% of cases that cause serious harm. However, many medication errors caused by slips, lapses, technical errors and mistakes are preventable; intentional violations of safe operating procedures are not. While medication errors were tolerated by society in the past, the readiness to institute criminal proceedings against health-care professionals has increased greatly in the UK over the last decade. The medication process consists of writing prescriptions, dispensing the product, administering it and monitoring its effects. Prescription errors arise owing to incomplete information, lack of appropriate labelling, environmental factors and human blunders. Even with a perfect prescription the right medication must be dispensed and appropriately labelled. Dispensing errors are not uncommon and may be compounded by non-clinical considerations. Administration of a drug by injection is one of the most dangerous aspects of the medication process, especially in inexperienced hands. The final component of medication supply is monitoring the effect of the medication. With short courses of medication such monitoring is easy, but with long-term medication, particularly with potent drugs where the margin between efficacy and toxicity is small, active procedures may be required to ensure toxicity does not ensue. Despite the endeavour of health-care professions to stick to the rule of 'first, do no harm', in reality this is difficult to achieve all of the time. When

  5. Imaging of prehospital stroke therapeutics

    Science.gov (United States)

    Lin, Michelle P; Sanossian, Nerses; Liebeskind, David S

    2016-01-01

    Despite significant quality improvement efforts to streamline in-hospital acute stroke care in the conventional model, there remain inherent layers of treatment delays, which could be eliminated with prehospital diagnostics and therapeutics administered in a mobile stroke unit. Early diagnosis using Telestroke and neuroimaging while in the ambulance may enable targeted routing to hospitals with specialized care, which will likely improve patient outcomes. Key clinical trials in Telestroke, mobile stroke units with prehospital neuroimaging capability, prehospital ultrasound and co-administration of various classes of neuroprotectives, antiplatelets and antithrombin agents with intravenous thrombolysis are discussed in this article. PMID:26308602

  6. Keratinocyte-targeted overexpression of the glucocorticoid receptor delays cutaneous wound healing.

    Directory of Open Access Journals (Sweden)

    Ana Sanchis

    Full Text Available Delayed wound healing is one of the most common secondary adverse effects associated to the therapeutic use of glucocorticoid (GC analogs, which act through the ligand-dependent transcription factor GC-receptor (GR. GR function is exerted through DNA-binding-dependent and -independent mechanisms, classically referred to as transactivation (TA and transrepression (TR. Currently both TA and TR are thought to contribute to the therapeutical effects mediated by GR; however their relative contribution to unwanted side effects such as delayed wound healing is unknown. We evaluated skin wound healing in transgenic mice with keratinocyte-restricted expression of either wild type GR or a mutant GR that is TA-defective but efficient in TR (K5-GR and K5-GR-TR mice, respectively. Our data show that at days (d 4 and 8 following wounding, healing in K5-GR mice was delayed relative to WT, with reduced recruitment of granulocytes and macrophages and diminished TNF-α and IL-1β expression. TGF-β1 and Kgf expression was repressed in K5-GR skin whereas TGF-β3 was up-regulated. The re-epithelialization rate was reduced in K5-GR relative to WT, as was formation of granulation tissue. In contrast, K5-GR-TR mice showed delays in healing at d4 but re-established the skin breach at d8 concomitant with decreased repression of pro-inflammatory cytokines and growth factors relative to K5-GR mice. Keratinocytes from both transgenic mice closed in vitro wounds slower relative to WT, consistent with the in vivo defects in cell migration. Overall, the delay in the early stages of wound healing in both transgenic models is similar to that elicited by systemic treatment with dexamethasone. Wound responses in the transgenic keratinocytes correlated with reduced ERK activity both in vivo and in vitro. We conclude that the TR function of GR is sufficient for negatively regulating early stages of wound closure, while TA by GR is required for delaying later stages of healing.

  7. Improved delay-leaping simulation algorithm for biochemical reaction systems with delays.

    Science.gov (United States)

    Yi, Na; Zhuang, Gang; Da, Liang; Wang, Yifei

    2012-04-14

    In biochemical reaction systems dominated by delays, the simulation speed of the stochastic simulation algorithm depends on the size of the wait queue. As a result, it is important to control the size of the wait queue to improve the efficiency of the simulation. An improved accelerated delay stochastic simulation algorithm for biochemical reaction systems with delays, termed the improved delay-leaping algorithm, is proposed in this paper. The update method for the wait queue is effective in reducing the size of the queue as well as shortening the storage and access time, thereby accelerating the simulation speed. Numerical simulation on two examples indicates that this method not only obtains a more significant efficiency compared with the existing methods, but also can be widely applied in biochemical reaction systems with delays.

  8. [Achievement of therapeutic objectives].

    Science.gov (United States)

    Mantilla, Teresa

    2014-07-01

    Therapeutic objectives for patients with atherogenic dyslipidemia are achieved by improving patient compliance and adherence. Clinical practice guidelines address the importance of treatment compliance for achieving objectives. The combination of a fixed dose of pravastatin and fenofibrate increases the adherence by simplifying the drug regimen and reducing the number of daily doses. The good tolerance, the cost of the combination and the possibility of adjusting the administration to the patient's lifestyle helps achieve the objectives for these patients with high cardiovascular risk. Copyright © 2014 Sociedad Española de Arteriosclerosis y Elsevier España, S.L. All rights reserved.

  9. Delay of neutrophil apoptosis in acute coronary syndromes.

    Science.gov (United States)

    Garlichs, C D; Eskafi, S; Cicha, I; Schmeisser, A; Walzog, B; Raaz, D; Stumpf, C; Yilmaz, A; Bremer, J; Ludwig, J; Daniel, W G

    2004-05-01

    Apoptosis of polymorphonuclear neutrophils (PMN) is currently discussed as a key event in the control of inflammation. This study determined PMN apoptosis and its underlying mechanisms in controls (C), patients with stable (SAP) or unstable angina (UAP), and with acute myocardial infarction (AMI). Blood was drawn from 15 subjects of each C, SAP, UAP, and AMI. Apoptosis was measured by flow cytometry in isolated PMN (propidium iodide staining) and PMN from whole blood (CD16, FcgammaRIII). Serum cytokines were determined by enzyme-linked immunosorbent assay. Apoptosis of isolated PMN was delayed significantly in acute coronary syndromes (ACS) as compared with SAP or C (C, 51.2+/-12.6%; SAP, 44.9+/-13.6%; UAP, 28.4+/-10.1%; AMI, 20.3+/-8.5%; AMI or UAP vs. SAP or C, P<0.001). These results were confirmed by measurement of PMN apoptosis in cultured whole blood from patients and controls. Moreover, serum of patients with ACS markedly reduced apoptosis of PMN from healthy donors. Analysis of patients' sera revealed significantly elevated concentrations of tumor necrosis factor alpha, interferon-gamma (IFN-gamma), granulocyte macrophage-colony stimulating factor (GM-CSF), and interleukin (IL)-1beta in ACS (vs. C and SAP). IFN-gamma, GM-CSF, and IL-1beta significantly delayed PMN apoptosis in vitro. Furthermore, coincubation of PMN with adenosine 5'-diphosphate-activated platelets significantly inhibited PMN apoptosis as compared with coculture with unstimulated platelets. This study demonstrates a pronounced delay of PMN apoptosis in UAP and AMI, which may result from increased serum levels of IFN-gamma, GM-CSF, and IL-1beta and from enhanced platelet activation. Therapeutical modulation of these determinants of PMN lifespan may provide a new concept for the control of inflammation in ACS.

  10. Stripe delay filters

    OpenAIRE

    Zakharov, Alexander V.; Ilchenko, Mykhailo Ye.; Trubarov, Igor V.; Pinchuk, Ludmila S.

    2016-01-01

    There are considered constructions of microsized stripe delay filters, which are realized on a basis of ceramic materials with high dielectric permittivity. Delay time of non-minimal phase filters is 7–12 ns at frequencies of 1900 MHz with relative bandwidth of 3.6–3.85%. Filters dimensions are comparable with ones used in portable communication devices. Dimensions of researched three-resonator filter at frequency of 1900 MHz are 8.4×5×2 mm with material dielectric permittivity εr = 92, and 5...

  11. Eliminating common PACU delays.

    Science.gov (United States)

    Jenkins, Jamie

    2007-01-01

    This article discusses how one hospital identified patient flow delays in its PACU By using lean methods focused on eliminating waste, the team was able to improve patient flow. Lean thinking required the team to keep issues that were important to patients at top of mind. The improvements not only saved staff time, but they also helped the department prepare for the addition of six beds by focusing on methods to eliminate delays. The team, assigned by the vice president of surgical services, included a process engineer two decision support analysts, the PACU charge nurse, the nursing manager and ad hoc department nurses. The team recommended and implemented changes to improve operational effectiveness.

  12. Delay in the diagnosis of tuberculosis in Nepal

    Directory of Open Access Journals (Sweden)

    Enarson Don

    2009-07-01

    Full Text Available Abstract Background Identifying reasons for delay in diagnosis and treatment of tuberculosis is important for the health system to find ways to treat patients as early as possible, and hence reduce the suffering of patients and transmission of the disease. The objectives of this study was to assess the duration of delay in the diagnosis of tuberculosis and to investigate its determinants. Methods A cross-sectional survey was conducted using a structured questionnaire in 307 new tuberculosis patients registered by the National Tuberculosis Programme (NTP in all DOTS centres in Banke district of Nepal. Results The median patient delay was 50 days, the median health system delay was 18 days, and the median total delay was 60 days. Sputum smear negative participants had significantly lower risk of patient delay. Smokers using >5 cigarettes per day had higher risk of patient delay and health system delay. Conclusion Total delay in the diagnosis of tuberculosis in Banke district is shorter compared to other places in Nepal and neighbouring countries. The shorter delay for smear negative pulmonary tuberculosis raises suspicion that many of these patients are not examined according to the NTP manual before being diagnosed. Increasing public awareness of the disease and expansion of the facilities with assured quality could be helpful to reduce the delay in the diagnosis of tuberculosis.

  13. Delayed breast implant reconstruction

    DEFF Research Database (Denmark)

    Hvilsom, Gitte B.; Hölmich, Lisbet R.; Steding-Jessen, Marianne

    2012-01-01

    We evaluated the association between radiation therapy and severe capsular contracture or reoperation after 717 delayed breast implant reconstruction procedures (288 1- and 429 2-stage procedures) identified in the prospective database of the Danish Registry for Plastic Surgery of the Breast during...... reconstruction approaches other than implants should be seriously considered among women who have received radiation therapy....

  14. Permissible Delay in Payments

    Directory of Open Access Journals (Sweden)

    Yung-Fu Huang

    2007-01-01

    Full Text Available The main purpose of this paper wants to investigate the optimal retailer's lot-sizing policy with two warehouses under partially permissible delay in payments within the economic order quantity (EOQ framework. In this paper, we want to extend that fully permissible delay in payments to the supplier would offer the retailer partially permissible delay in payments. That is, the retailer must make a partial payment to the supplier when the order is received. Then the retailer must pay off the remaining balance at the end of the permissible delay period. In addition, we want to add the assumption that the retailer's storage space is limited. That is, the retailer will rent the warehouse to store these exceeding items when the order quantity is larger than retailer's storage space. Under these conditions, we model the retailer's inventory system as a cost minimization problem to determine the retailer's optimal cycle time and optimal order quantity. Three theorems are developed to efficiently determine the optimal replenishment policy for the retailer. Finally, numerical examples are given to illustrate these theorems and obtained a lot of managerial insights.

  15. Delayed visual maturation.

    OpenAIRE

    Harel, S; Holtzman, M; Feinsod, M

    1983-01-01

    Three infants, recognised as blind during the first 4 months of life, were found to be normal on neurological and ophthalmological examinations. Visual electro-diagnostic studies showed normal retinal responses, but delayed conduction velocities and impaired visually-evoked responses over the occipital cortex. After age 6 months, normal vision developed gradually and all abnormalities disappeared.

  16. Delayed visual maturation.

    Science.gov (United States)

    Harel, S; Holtzman, M; Feinsod, M

    1983-01-01

    Three infants, recognised as blind during the first 4 months of life, were found to be normal on neurological and ophthalmological examinations. Visual electro-diagnostic studies showed normal retinal responses, but delayed conduction velocities and impaired visually-evoked responses over the occipital cortex. After age 6 months, normal vision developed gradually and all abnormalities disappeared. PMID:6189454

  17. Causal Analysis of Railway Running Delays

    DEFF Research Database (Denmark)

    Cerreto, Fabrizio; Nielsen, Otto Anker; Harrod, Steven

    against service transit times and railway asset productivity. Methods to investigate the quality of supplement time allocation are necessary to reduce the behavioral response and the waste of resources. This is a preliminary study that investigates train delay data from the year 2014 supplied by Rail Net......Operating delays and network propagation are inherent characteristics of railway operations. These are traditionally reduced by provision of time supplements or “slack” in railway timetables and operating plans. Supplement allocation policies must trade off reliability in the service commitments...... Denmark (the Danish infrastructure manager). The statistical analysis of the data identifies the minimum running times and the scheduled running time supplements and investigates the evolution of train delays along given train paths. An improved allocation of time supplements would result in smaller...

  18. Frankincense--therapeutic properties.

    Science.gov (United States)

    Al-Yasiry, Ali Ridha Mustafa; Kiczorowska, Bożena

    2016-01-04

    Recently, increasing interest in natural dietary and therapeutic preparations used as dietary supplements has been observed. One of them is frankincense. This traditional medicine of the East is believed to have anti-inflammatory, expectorant, antiseptic, and even anxiolytic and anti-neurotic effects. The present study aims to verify the reported therapeutic properties of Boswellia resin and describe its chemical composition based on available scientific studies. The main component of frankincense is oil (60%). It contains mono- (13%) and diterpenes (40%) as well as ethyl acetate (21.4%), octyl acetate (13.4%) and methylanisole (7.6%). The highest biological activity among terpenes is characteristic of 11-keto-ß-acetyl-beta-boswellic acid, acetyl-11-keto-ß-boswellic acid and acetyl-α-boswellic acid. Contemporary studies have shown that resin indeed has an analgesic, tranquilising and anti-bacterial effects. From the point of view of therapeutic properties, extracts from Boswellia serrata and Boswellia carterii are reported to be particularly useful. They reduce inflammatory conditions in the course of rheumatism by inhibiting leukocyte elastase and degrading glycosaminoglycans. Boswellia preparations inhibit 5-lipoxygenase and prevent the release of leukotrienes, thus having an anti-inflammatory effect in ulcerative colitis, irritable bowel syndrome, bronchitis and sinusitis. Inhalation and consumption of Boswellia olibanum reduces the risk of asthma. In addition, boswellic acids have an antiproliferative effect on tumours. They inhibit proliferation of tumour cells of the leukaemia and glioblastoma subset. They have an anti-tumour effect since they inhibit topoisomerase I and II-alpha and stimulate programmed cell death (apoptosis).

  19. Frankincense – therapeutic properties

    Directory of Open Access Journals (Sweden)

    Ali Ridha Mustafa Al-Yasiry

    2016-01-01

    Full Text Available Recently, increasing interest in natural dietary and therapeutic preparations used as dietary supplements has been observed. One of them is frankincense. This traditional medicine of the East is believed to have anti-inflammatory, expectorant, antiseptic, and even anxiolytic and anti-neurotic effects. The present study aims to verify the reported therapeutic properties of Boswellia resin and describe its chemical composition based on available scientific studies. The main component of frankincense is oil (60%. It contains mono- (13% and diterpenes (40% as well as ethyl acetate (21.4%, octyl acetate (13.4% and methylanisole (7.6%. The highest biological activity among terpenes is characteristic of 11-keto-ß-acetyl-beta-boswellic acid, acetyl-11-keto-ß-boswellic acid and acetyl-α-boswellic acid. Contemporary studies have shown that resin indeed has an analgesic, tranquilising and anti-bacterial effects. From the point of view of therapeutic properties, extracts from Boswellia serrata and Boswellia carterii are reported to be particularly useful. They reduce inflammatory conditions in the course of rheumatism by inhibiting leukocyte elastase and degrading glycosaminoglycans. Boswellia preparations inhibit 5-lipoxygenase and prevent the release of leukotrienes, thus having an anti-inflammatory effect in ulcerative colitis, irritable bowel syndrome, bronchitis and sinusitis. Inhalation and consumption of Boswellia olibanum reduces the risk of asthma. In addition, boswellic acids have an antiproliferative effect on tumours. They inhibit proliferation of tumour cells of the leukaemia and glioblastoma subset. They have an anti-tumour effect since they inhibit topoisomerase I and II-alpha and stimulate programmed cell death (apoptosis.

  20. Delay compensation using Smith predictor for wireless network control system

    Directory of Open Access Journals (Sweden)

    Mahmoud Gamal

    2016-06-01

    In this paper, a delay compensation scheme using classical and adaptive Smith predictor is applied to wireless NCS. The Markov model is proposed to compute the estimated network delay used in the classical predictor. In the adaptive predictor, the channel delay statistics using shift register is proposed to update the estimated delay. To evaluate the proposed schemes, a DC-motor controller system based on IEEE 802.15.4 is built using True Time Matlab software. The system performance with and without the proposed delay compensation scheme is studied. It is also compared to other delay compensation schemes. The results show that the proposed scheme improves the NCS performance significantly and reduces the effect of the delay on the system.

  1. Delayed fluorescence in photosynthesis.

    Science.gov (United States)

    Goltsev, Vasilij; Zaharieva, Ivelina; Chernev, Petko; Strasser, Reto J

    2009-01-01

    Photosynthesis is a very efficient photochemical process. Nevertheless, plants emit some of the absorbed energy as light quanta. This luminescence is emitted, predominantly, by excited chlorophyll a molecules in the light-harvesting antenna, associated with Photosystem II (PS II) reaction centers. The emission that occurs before the utilization of the excitation energy in the primary photochemical reaction is called prompt fluorescence. Light emission can also be observed from repopulated excited chlorophylls as a result of recombination of the charge pairs. In this case, some time-dependent redox reactions occur before the excitation of the chlorophyll. This delays the light emission and provides the name for this phenomenon-delayed fluorescence (DF), or delayed light emission (DLE). The DF intensity is a decreasing polyphasic function of the time after illumination, which reflects the kinetics of electron transport reactions both on the (electron) donor and the (electron) acceptor sides of PS II. Two main experimental approaches are used for DF measurements: (a) recording of the DF decay in the dark after a single turnover flash or after continuous light excitation and (b) recording of the DF intensity during light adaptation of the photosynthesizing samples (induction curves), following a period of darkness. In this paper we review historical data on DF research and recent advances in the understanding of the relation between the delayed fluorescence and specific reactions in PS II. An experimental method for simultaneous recording of the induction transients of prompt and delayed chlorophyll fluorescence and decay curves of DF in the millisecond time domain is discussed.

  2. Delayed antibiotic prescriptions for respiratory infections.

    Science.gov (United States)

    Spurling, Geoffrey Kp; Del Mar, Chris B; Dooley, Liz; Foxlee, Ruth; Farley, Rebecca

    2017-09-07

    Concerns exist regarding antibiotic prescribing for respiratory tract infections (RTIs) owing to adverse reactions, cost, and antibacterial resistance. One proposed strategy to reduce antibiotic prescribing is to provide prescriptions, but to advise delay in antibiotic use with the expectation that symptoms will resolve first. This is an update of a Cochrane Review originally published in 2007, and updated in 2010 and 2013. To evaluate the effects on clinical outcomes, antibiotic use, antibiotic resistance, and patient satisfaction of advising a delayed prescription of antibiotics in respiratory tract infections. For this 2017 update we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library, Issue 4, 2017), which includes the Cochrane Acute Respiratory Infection Group's Specialised Register; Ovid MEDLINE (2013 to 25 May 2017); Ovid Embase (2013 to 2017 Week 21); EBSCO CINAHL Plus (1984 to 25 May 2017); Web of Science (2013 to 25 May 2017); WHO International Clinical Trials Registry Platform (1 September 2017); and ClinicalTrials.gov (1 September 2017). Randomised controlled trials involving participants of all ages defined as having an RTI, where delayed antibiotics were compared to immediate antibiotics or no antibiotics. We defined a delayed antibiotic as advice to delay the filling of an antibiotic prescription by at least 48 hours. We considered all RTIs regardless of whether antibiotics were recommended or not. We used standard Cochrane methodological procedures. Three review authors independently extracted and collated data. We assessed the risk of bias of all included trials. We contacted trial authors to obtain missing information. For this 2017 update we added one new trial involving 405 participants with uncomplicated acute respiratory infection. Overall, this review included 11 studies with a total of 3555 participants. These 11 studies involved acute respiratory infections including acute otitis media (three studies

  3. Non-inferiority of nitric oxide releasing intranasal spray compared to sub-therapeutic antibiotics to reduce incidence of undifferentiated fever and bovine respiratory disease complex in low to moderate risk beef cattle arriving at a commercial feedlot.

    Science.gov (United States)

    Regev-Shoshani, G; McMullin, B; Nation, N; Church, J S; Dorin, C; Miller, C

    2017-03-01

    an alternative strategy to reduce sub-therapeutic metaphylaxis antibiotic use in beef cattle production. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Diagnosis delay in Libyan female breast cancer

    Directory of Open Access Journals (Sweden)

    Ermiah Eramah

    2012-08-01

    Full Text Available Abstract Aims To study the diagnosis delay and its impact on stage of disease among women with breast cancer on Libya. Methods 200 women, aged 22 to 75 years with breast cancer diagnosed during 2008–2009 were interviewed about the period from the first symptoms to the final histological diagnosis of breast cancer. This period (diagnosis time was categorized into 3 periods: 6 months. If diagnosis time was longer than 3 months, the diagnosis was considered delayed (diagnosis delay. Consultation time was the time taken to visit the general practitioner after the first symptoms. Retrospective preclinical and clinical data were collected on a form (questionnaire during an interview with each patient and from medical records. Results The median of diagnosis time was 7.5 months. Only 30.0% of patients were diagnosed within 3 months after symptoms. 14% of patients were diagnosed within 3–6 months and 56% within a period longer than 6 months. A number of factors predicted diagnosis delay: Symptoms were not considered serious in 27% of patients. Alternative therapy (therapy not associated with cancer was applied in 13.0% of the patients. Fear and shame prevented the visit to the doctor in 10% and 4.5% of patients, respectively. Inappropriate reassurance that the lump was benign was an important reason for prolongation of the diagnosis time. Diagnosis delay was associated with initial breast symptom(s that did not include a lump (p  Diagnosis delay was associated with bigger tumour size (p Conclusions Diagnosis delay is very serious problem in Libya. Diagnosis delay was associated with complex interactions between several factors and with advanced stages. There is a need for improving breast cancer awareness and training of general practitioners to reduce breast cancer mortality by promoting early detection. The treatment guidelines should pay more attention to the early phases of breast cancer. Especially, guidelines for good practices in managing

  5. Pre-hospital and hospital delay in patients with non-ST elevation acute coronary syndromes in tertiary care

    Directory of Open Access Journals (Sweden)

    G.S. Youssef

    2017-09-01

    Conclusion: Pre-hospital delay was mainly patient-related. Hospital delay was mainly related to healthcare resources. Governmental measures to promote ambulance emergency services may reduce the pre-hospital delay, while improving the utilization of healthcare resources may reduce hospital delay.

  6. Therapeutic benefits of enhancing permeability barrier for atopic eczema

    Directory of Open Access Journals (Sweden)

    George Man

    2015-06-01

    Full Text Available The regulatory role of epidermal permeability barrier function in cutaneous inflammation has been well appreciated. While barrier disruption induces cutaneous inflammation, improvement of permeability barrier function alleviates inflammation. Studies have demonstrated that improvement of epidermal permeability barrier function not only prevents the development of atopic eczema, but also delays the relapse of these diseases. Moreover, enhancing the epidermal permeability barrier also alleviates atopic eczema. Furthermore, co-applications of barrier enhancing products with glucocorticoids can increase the therapeutic efficacy and reduce the adverse effects of glucocorticoids in the treatment of atopic eczema. Therefore, utilization of permeability barrier enhancing products alone or in combination with glucocorticoids could be a valuable approach in the treatment of atopic eczema. In this review, we discuss the benefits of improving the epidermal permeability barrier in the management of atopic eczema.

  7. Delayed crosslinker composition

    Energy Technology Data Exchange (ETDEWEB)

    Hodge, R.M.

    1989-01-10

    A crosslinker composition is described that can produce delayed crosslinking of an aqueous solution of a crosslinkable organic polymer. It consists of about 1% to about 10% by weight of an organic zirconium complex and about 2% to about 37% by weight organic hydroxycarboxylic acid selected from the group consisting of lactic, mandelic and hydroxyacetic acids the pH of the composition being no greater than 4.8.

  8. Delayed visual maturation.

    OpenAIRE

    Cole, G F; Hungerford, J.; Jones, R B

    1984-01-01

    Sixteen blind babies who were considered to be showing the characteristics of delayed visual maturation were studied prospectively. The diagnosis was made on clinical grounds, and the criteria for this are discussed. All of these infants developed visual responses between 4 and 6 months of age and had normal or near normal visual acuities by 1 year of age. Long term follow up, however, has shown neurological abnormalities in some of these children.

  9. Delayed visual maturation.

    Science.gov (United States)

    Fielder, A R; Russell-Eggitt, I R; Dodd, K L; Mellor, D H

    1985-01-01

    Fifty-three infants with delayed visual maturation (DVM) are presented. These have been classified according to their ocular and systemic features into three groups: DVM as an isolated anomaly, in association with mental retardation, and ocular abnormalities accompanied by DVM. The clinical features are discussed, particularly regarding the time and speed of visual improvement in the three groups. Infants with DVM who experienced difficulties in the perinatal period have an increased risk of developing permanent neurological sequelae.

  10. Delayed breast implant reconstruction

    DEFF Research Database (Denmark)

    Hvilsom, Gitte B.; Hölmich, Lisbet R.; Steding-Jessen, Marianne

    2011-01-01

    Studies of complications following reconstructive surgery with implants among women with breast cancer are needed. As the, to our knowledge, first prospective long-term study we evaluated the occurrence of complications following delayed breast reconstruction separately for one- and two-stage pro......Studies of complications following reconstructive surgery with implants among women with breast cancer are needed. As the, to our knowledge, first prospective long-term study we evaluated the occurrence of complications following delayed breast reconstruction separately for one- and two......-stage procedures. From the Danish Registry for Plastic Surgery of the Breast, which has prospectively registered data for women undergoing breast implantations since 1999, we identified 559 women without a history of radiation therapy undergoing 592 delayed breast reconstructions following breast cancer during...... the period 1999 to 2006; 239 one-stage procedures and 353 two-stage procedures. The postoperative course through November 2009 was evaluated by cumulative incidence adjusting for competing risks for the selected outcomes; hematoma, infection, seroma, implant rupture, severe capsular contracture (modified...

  11. Delay in atomic photoionization

    CERN Document Server

    Kheifets, A S

    2010-01-01

    We analyze the time delay between emission of photoelectrons from the outer valence $ns$ and $np$ sub-shells in noble gas atoms following absorption of an attosecond XUV pulse. By solving the time dependent Schr\\"odinger equation and carefully examining the time evolution of the photoelectron wave packet, we establish the apparent "time zero" when the photoelectron leaves the atom. Various processes such as elastic scattering of the photoelectron on the parent ion and many-electron correlation affect the quantum phase of the dipole transition matrix element, the energy dependence of which defines the emission timing. This qualitatively explains the time delay between photoemission from the $2s$ and $2p$ sub-shells of Ne as determined experimentally by attosecond streaking [{\\em Science} {\\bf 328}, 1658 (2010)]. However, with our extensive numerical modeling, we were only able to account for less than a half of the measured time delay of $21\\pm5$~as. We argue that the XUV pulse alone cannot produce such a larg...

  12. Time-Delay Interferometry

    Directory of Open Access Journals (Sweden)

    Massimo Tinto

    2014-08-01

    Full Text Available Equal-arm detectors of gravitational radiation allow phase measurements many orders of magnitude below the intrinsic phase stability of the laser injecting light into their arms. This is because the noise in the laser light is common to both arms, experiencing exactly the same delay, and thus cancels when it is differenced at the photo detector. In this situation, much lower level secondary noises then set the overall performance. If, however, the two arms have different lengths (as will necessarily be the case with space-borne interferometers, the laser noise experiences different delays in the two arms and will hence not directly cancel at the detector. In order to solve this problem, a technique involving heterodyne interferometry with unequal arm lengths and independent phase-difference readouts has been proposed. It relies on properly time-shifting and linearly combining independent Doppler measurements, and for this reason it has been called time-delay interferometry (TDI. This article provides an overview of the theory, mathematical foundations, and experimental aspects associated with the implementation of TDI. Although emphasis on the application of TDI to the Laser Interferometer Space Antenna (LISA mission appears throughout this article, TDI can be incorporated into the design of any future space-based mission aiming to search for gravitational waves via interferometric measurements. We have purposely left out all theoretical aspects that data analysts will need to account for when analyzing the TDI data combinations.

  13. Delay-Dependent Exponential Stability for Discrete-Time BAM Neural Networks with Time-Varying Delays

    Directory of Open Access Journals (Sweden)

    Yonggang Chen

    2008-01-01

    Full Text Available This paper considers the delay-dependent exponential stability for discrete-time BAM neural networks with time-varying delays. By constructing the new Lyapunov functional, the improved delay-dependent exponential stability criterion is derived in terms of linear matrix inequality (LMI. Moreover, in order to reduce the conservativeness, some slack matrices are introduced in this paper. Two numerical examples are presented to show the effectiveness and less conservativeness of the proposed method.

  14. Delayed haemolytic transfusion reactions in patients with sickle cell disease.

    OpenAIRE

    Cummins, D; Webb, G.; Shah, N; Davies, S C

    1991-01-01

    We describe two cases which illustrate the difficult diagnostic and therapeutic problems posed by delayed haemolytic transfusion reactions in patients with sickle-cell disease. The cases emphasize the need for meticulous phenotypic and serological assessment of sickle-cell patients prior to transfusion therapy.

  15. Sofalcone upregulates the nuclear factor (erythroid-derived 2)-like 2/heme oxygenase-1 pathway, reduces soluble fms-like tyrosine kinase-1, and quenches endothelial dysfunction: potential therapeutic for preeclampsia.

    Science.gov (United States)

    Onda, Kenji; Tong, Stephen; Nakahara, Anzu; Kondo, Mei; Monchusho, Hideaki; Hirano, Toshihiko; Kaitu'u-Lino, Tu'uhevaha; Beard, Sally; Binder, Natalie; Tuohey, Laura; Brownfoot, Fiona; Hannan, Natalie J

    2015-04-01

    Preeclampsia is a severe complication of pregnancy, characterized by hypertension, oxidative stress, and severe endothelial dysfunction. Antiangiogenic factors, soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin, play key pathophysiological roles in preeclampsia. Heme oxygenase-1 (HO-1) is a cytoprotective, antioxidant enzyme reported to be downregulated in preeclampsia. Studies propose that inducing HO-1 may also decrease sFlt-1 production. Sofalcone, a gastric antiulcer agent in clinical use, is known to induce HO-1 in gastric epithelium. We aimed to investigate whether sofalcone induces HO-1 and reduces sFlt-1 release from primary human placental and endothelial cells and blocks endothelial dysfunction in vitro. We isolated human trophoblasts and endothelial cells (human umbilical vein endothelial cells) and also used uterine microvascular cells. We investigated the effects of sofalcone on (1) HO-1 production, (2) activation of the nuclear factor (erythroid-derived 2)-like 2 pathway, (3) sFlt-1 and soluble endoglin release, (4) tumor necrosis factor α-induced monocyte adhesion and vascular cell adhesion molecule upregulation, and (5) endothelial tubule formation. Sofalcone potently increased HO-1 mRNA and protein in both primary trophoblasts and human umbilical vein endothelial cells. Furthermore, sofalcone treatment caused nuclear translocation of nuclear factor (erythroid-derived 2)-like 2 and transactivation of other nuclear factor (erythroid-derived 2)-like 2 responsive genes (NQO1, TXN, and GCLC). Importantly, sofalcone significantly decreased the secretion of sFlt-1 from primary human trophoblasts. Sofalcone potently suppressed endothelial dysfunction in 2 in vitro models, blocking tumor necrosis factor α-induced monocyte adhesion and vascular cell adhesion molecule 1 expression in human umbilical vein endothelial cells. These results indicate that in primary human tissues, sofalcone can potently activate antioxidant nuclear factor

  16. Current Vaccine Shortages and Delays

    Science.gov (United States)

    ... value="Submit" /> Related Links Vaccines & Immunizations Current Vaccine Shortages & Delays Recommend on Facebook Tweet Share Compartir ... vaccination are included in this update. Chart of Vaccines* in Delay or Shortage National Vaccine Supply Shortages ...

  17. Lag synchronization of chaotic systems with time-delayed linear ...

    Indian Academy of Sciences (India)

    ... delayed chaotic systems. Numerical simulations on time-delayed Lorenz and hyperchaotic Chen systems are also carried out to show the effectiveness of the proposed scheme. Note that under the scheme the chaotic system is controlled only at discrete time instants, and so it reduces the control cost in real applications.

  18. Don't Delay Questions on Campus Construction

    Science.gov (United States)

    Gainsboro, Dan

    2006-01-01

    Most campus building projects are high-stakes ventures that, if not correctly planned, may be accompanied by cost overruns, schedule delays, unhappy stakeholders, diminished political goodwill, delays in new programs, or even the forfeiture of a donor gift. The key to managing complexity, reducing risk, and saving time and money lies in one…

  19. Psoriasis is characterized by deficient negative immune regulation compared to transient delayed-type hypersensitivity reactions

    National Research Council Canada - National Science Library

    Gulati, Nicholas; Suárez-Fariñas, Mayte; Correa da Rosa, Joel; Krueger, James G

    2015-01-01

    Diphencyprone (DPCP) is a hapten that causes delayed-type hypersensitivity (DTH) reactions in human skin, and is used as a topical therapeutic for alopecia areata, warts, and cutaneous melanoma metastases...

  20. [Therapeutic strategies in the first psychotic episode].

    Science.gov (United States)

    Douki, S; Taktak, M J; Ben Zineb, S; Cheour, M

    1999-11-01

    A first psychotic episode includes a wide range of disorders with different outcomes: schizophrenia, bipolar disorder, schizophreniform disorder, schizoaffective disorder, drug-induced psychosis, brief reactive psychosis, organic psychoses and delusional disorder. The course and outcome of a first psychotic episode is greatly dependent on its initial management. Major clinical, etiopathogenic and therapeutic advances have been achieved in this field and have allowed specific management strategies to be adopted. The primary task of therapists involved in the management of patients who have experienced a first episode of psychosis is promotion of recovery and prevention of secondary morbidity, relapse and persistent disability. The main guidelines of an early psychosis management are:--to keep in mind that early psychosis is not early schizophrenia. Thus, clinicians and therapists should avoid an early diagnosis of schizophrenia. Diagnosis in early psychosis can be highly unstable. A diagnosis of schizophrenia, with its implications of pessimism, relapse and disability, does not contribute anything positive in terms of guiding treatment. On the contrary, such a diagnosis may damage the patient and family by stigmatizing them and affecting the way they are viewed and managed by healthcare professionals.--To integrate biological, psychological and social interventions: effective medications is useful in reducing the risk of relapse, but is not a guarantee against it. Psychological and social interventions can greatly help promote recovery.--To tailor the various strategies to met the needs of an individual: as an example, it is important to formulate appropriate strategies for the different stages of the illness (prodromal phase, acute phase, early recovery phase and late recovery phase) because patients have different therapeutic needs at each stage.--In the acute treatment, not to concentrate on short-term goals in indicating antipsychotic treatment: prescribing

  1. Plasminogen Deficiency Delays the Onset and Protects from Demyelination and Paralysis in Autoimmune Neuroinflammatory Disease.

    Science.gov (United States)

    Shaw, Maureen A; Gao, Zhen; McElhinney, Kathryn E; Thornton, Sherry; Flick, Matthew J; Lane, Adam; Degen, Jay L; Ryu, Jae Kyu; Akassoglou, Katerina; Mullins, Eric S

    2017-04-05

    Multiple sclerosis (MS) is a neuroinflammatory, demyelinating disease of the CNS. Fibrinogen deposition at sites of blood-brain barrier breakdown is a prominent feature of neuroinflammatory disease and contributes to disease severity. Plasminogen, the primary fibrinolytic enzyme, also modifies inflammatory processes. We used a murine model of MS, experimental autoimmune encephalomyelitis (EAE), to evaluate the hypothesis that the loss of plasminogen would exacerbate neuroinflammatory disease. However, contrary to initial expectations, EAE-challenged plasminogen-deficient (Plg-) mice developed significantly delayed disease onset and reduced disease severity compared with wild-type (Plg+) mice. Similarly, pharmacologic inhibition of plasmin activation with tranexamic acid also delayed disease onset. The T-cell response to immunization was similar between genotypes, suggesting that the contribution of plasminogen was downstream of the T-cell response. Spinal cords from EAE-challenged Plg- mice demonstrated significantly decreased demyelination and microglial/macrophage accumulation compared with Plg+ mice. Although fibrinogen-deficient mice or mice with combined deficiencies of plasminogen and fibrinogen had decreased EAE severity, they did not exhibit the delay in EAE disease onset, as seen in mice with plasminogen deficiency alone. Together, these data suggest that plasminogen and plasmin-mediated fibrinolysis is a key modifier of the onset of neuroinflammatory demyelination.SIGNIFICANCE STATEMENT Multiple sclerosis is a severe, chronic, demyelinating disease. Understanding the pathobiology related to the autoreactive T-cell and microglial/macrophage demyelinating response is critical to effectively target therapeutics. We describe for the first time that deficiency of plasminogen, the key fibrinolytic enzyme, delays disease onset and protects from the development of the paralysis associated with a murine model of multiple sclerosis, experimental autoimmune

  2. Delay Choice vs. Delay Maintenance: Different Measures of Delayed Gratification in Capuchin Monkeys (Cebus apella)

    Science.gov (United States)

    Addessi, Elsa; Paglieri, Fabio; Beran, Michael J.; Evans, Theodore A.; Macchitella, Luigi; De Petrillo, Francesca; Focaroli, Valentina

    2013-01-01

    Delaying gratification involves two components: (i) delay choice (selecting a delayed reward over an immediate one), and (ii) delay maintenance (sustaining the decision to delay gratification even if the immediate reward is available during the delay). In primates, two tasks most commonly have explored these components, the Intertemporal choice task and the Accumulation task. It is unclear whether these tasks provide equivalent measures of delay of gratification. Here, we compared the performance of the same capuchin monkeys, belonging to two study populations, between these tasks. We found only limited evidence of a significant correlation in performance. Consequently, in contrast to what is often assumed, our data provide only partial support to the hypothesis that these tasks provide equivalent measures of delay of gratification. PMID:23544770

  3. Delay choice versus delay maintenance: different measures of delayed gratification in capuchin monkeys (Cebus apella).

    Science.gov (United States)

    Addessi, Elsa; Paglieri, Fabio; Beran, Michael J; Evans, Theodore A; Macchitella, Luigi; De Petrillo, Francesca; Focaroli, Valentina

    2013-11-01

    Delaying gratification involves 2 components: (1) delay choice (selecting a delayed reward over an immediate one) and (2) delay maintenance (sustaining the decision to delay gratification even if the immediate reward is available during the delay). Two tasks most commonly have explored these components in primates: the intertemporal choice task and the accumulation task. It is unclear whether these tasks provide equivalent measures of delay of gratification. Here, we compared the performance on the intertemporal choice task and the accumulation task of capuchin monkeys (Cebus apella) belonging to 2 study populations. We found only limited evidence of a significant correlation in performance. Consequently, in contrast to what is often assumed, our data provide only partial support for the hypothesis that these tasks provide equivalent measures of delay of gratification.

  4. Delaying information search

    Directory of Open Access Journals (Sweden)

    Yaniv Shani

    2012-11-01

    Full Text Available In three studies, we examined factors that may temporarily attenuate information search. People are generally curious and dislike uncertainty, which typically encourages them to look for relevant information. Despite these strong forces that promote information search, people sometimes deliberately delay obtaining valuable information. We find they may do so when they are concerned that the information might interfere with future pleasurable activities. Interestingly, the decision to search or to postpone searching for information is influenced not only by the value and importance of the information itself but also by well-being maintenance goals related to possible detrimental effects that negative knowledge may have on unrelated future plans.

  5. The effect of different distractions on remembering delayed intentions.

    Science.gov (United States)

    Schaper, Philipp; Grundgeiger, Tobias

    2018-02-01

    In safety-critical domains, frequently intentions need to be delayed until an ongoing task is completed. Research using the delay-execute paradigm showed that interruptions during the delay cause forgetting. However, staff members often handle an initial distraction not by interrupting the ongoing task but by acknowledging the distraction or multitasking. In Experiments 1a and 1b, we observed that, compared to a no distraction condition, multitasking significantly decreased remembering of intentions and interrupting decreased remembering even further. In Experiment 2, interruptions with context change reduced remembering of intentions compared to uninterrupted delays, and at the same time, interruptions without context change improved memory performance compared to uninterrupted delays. However, improved memory performance resulted in decreased interrupting task performance. Theoretically, the results support the contextual cueing mechanism of delay-execute tasks. Considering safety-critical domains, multitasking, interruptions and context changes can contribute to forgetting of tasks.

  6. Epidemiology of delayed ejaculation

    Science.gov (United States)

    Di Sante, Stefania; Mollaioli, Daniele; Gravina, Giovanni Luca; Ciocca, Giacomo; Limoncin, Erika; Carosa, Eleonora; Lenzi, Andrea

    2016-01-01

    A large body of literature on diminished ejaculatory disorders has been generated without the use of a clear diagnostic definition. Many studies have not distinguished between the orgasm and ejaculation disorders leading to doubtful results. Delayed ejaculation (DE) is one of the diminished ejaculatory disorders, which range from varying delays in ejaculatory latency to a complete inability to ejaculate. The present review is aimed at providing a comprehensive overview of the current knowledge on the definition and epidemiology of diminished ejaculatory disorders. We focus on the acquired diseases, such as benign prostatic hyperplasia (BPH) and specific drug regimens that may cause an iatrogenic form of ejaculatory disorder. In addition, the impact of aging is discussed since the prevalence of DE appears to be moderately but positively related to age. Finally, we also focus on the importance of the hormonal milieu on male ejaculation. To date, evidence on the endocrine control of ejaculation is derived from small clinical trials, but the evidence suggests that hormones modulate the ejaculatory process by altering its overall latency. PMID:27652226

  7. Epidemiology of delayed ejaculation.

    Science.gov (United States)

    Di Sante, Stefania; Mollaioli, Daniele; Gravina, Giovanni Luca; Ciocca, Giacomo; Limoncin, Erika; Carosa, Eleonora; Lenzi, Andrea; Jannini, Emmanuele A

    2016-08-01

    A large body of literature on diminished ejaculatory disorders has been generated without the use of a clear diagnostic definition. Many studies have not distinguished between the orgasm and ejaculation disorders leading to doubtful results. Delayed ejaculation (DE) is one of the diminished ejaculatory disorders, which range from varying delays in ejaculatory latency to a complete inability to ejaculate. The present review is aimed at providing a comprehensive overview of the current knowledge on the definition and epidemiology of diminished ejaculatory disorders. We focus on the acquired diseases, such as benign prostatic hyperplasia (BPH) and specific drug regimens that may cause an iatrogenic form of ejaculatory disorder. In addition, the impact of aging is discussed since the prevalence of DE appears to be moderately but positively related to age. Finally, we also focus on the importance of the hormonal milieu on male ejaculation. To date, evidence on the endocrine control of ejaculation is derived from small clinical trials, but the evidence suggests that hormones modulate the ejaculatory process by altering its overall latency.

  8. Delayed Choice Quantum Cryptography

    Science.gov (United States)

    Jeffrey, Evan; Kwiat, Paul

    2002-05-01

    Quantum Cryptography has recently gained attention as a method of communication with security guaranteed by the laws of physics. In particular, according to quantum mechanics, any measurement of an unknown quantum state perturbs the state in an easily detectable manner. One practical difficulty in implementing quantum cryptography is that Alice must encode each bit in a random basis, and Bob must choose the correct basis to get a shared bit of the final key. This necessarily introduces at least a 50% loss of data rate, and higher in protocols that use more than two bases in order to be more sensitive to eavesdroppers. We show that Bob can solve this by storing his photon until Alice has send the basis to use, allowing him to measure in the correct basis 100% of the time, while preventing Eve from having that information in time to use it maliciously. Bob accomplishes this storage by means of an optical delay line -- a pair of mirrors arranged so that his photon makes many round trips through the cavity before emerging and entering the detector. By using mirrors with a slight astigmatism, hope to achieve hundreds of round trips and a few microseconds of delay time.

  9. Pseudotumoral delayed cerebral radionecrosis

    Energy Technology Data Exchange (ETDEWEB)

    Ciaudo-Lacroix, C.; Lapresle, J. (Centre Hospitalier de Bicetre, 94 - Le Kremlin-Bicetre (France))

    1985-01-01

    A 60 year-old woman with a scalp epithelioma underwent radiotherapy, the dose being 57 Gray. A first epileptic seizure occurred twenty months later. Neurological examination revealed signs of left hemisphere involvement. ..gamma..EG, angiography, CT scans, demonstrated a pseudotumoral avascular process. On account of the localisation, the patient being right-handed, no surgical procedure was performed. In spite of corticotherapy and anticonvulsive treatment, seizures recurred and neurological signs slowly progressed. The patient died, 22 months after the first seizure, of an associated disseminated carcinoma with cachexia. Neuropathological examination showed a massive lesion presenting all the features of delayed radionecrosis in the left hemisphere: situated mainly in the white matter; numerous vascular abnormalities; wide-spread demyelination; disappearance of oligoglial cells. The Authors recall the clinical and anatomical aspects of this condition for which the only successful treatment is surgical removal when location and size of the lesion permit. Finally, the mechanisms which have been proposed to explain this delayed cerebral radionecrosis are discussed.

  10. Delaying the international spread of pandemic influenza.

    Science.gov (United States)

    Cooper, Ben S; Pitman, Richard J; Edmunds, W John; Gay, Nigel J

    2006-06-01

    The recent emergence of hypervirulent subtypes of avian influenza has underlined the potentially devastating effects of pandemic influenza. Were such a virus to acquire the ability to spread efficiently between humans, control would almost certainly be hampered by limited vaccine supplies unless global spread could be substantially delayed. Moreover, the large increases that have occurred in international air travel might be expected to lead to more rapid global dissemination than in previous pandemics. To evaluate the potential of local control measures and travel restrictions to impede global dissemination, we developed stochastic models of the international spread of influenza based on extensions of coupled epidemic transmission models. These models have been shown to be capable of accurately forecasting local and global spread of epidemic and pandemic influenza. We show that under most scenarios restrictions on air travel are likely to be of surprisingly little value in delaying epidemics, unless almost all travel ceases very soon after epidemics are detected. Interventions to reduce local transmission of influenza are likely to be more effective at reducing the rate of global spread and less vulnerable to implementation delays than air travel restrictions. Nevertheless, under the most plausible scenarios, achievable delays are small compared with the time needed to accumulate substantial vaccine stocks.

  11. The role for decorin in delayed-type hypersensitivity

    National Research Council Canada - National Science Library

    Seidler, Daniela G; Mohamed, Negia A; Bocian, Carla; Stadtmann, Anika; Hermann, Sven; Schäfers, Klaus; Schäfers, Michael; Iozzo, Renato V; Zarbock, Alexander; Götte, Martin

    2011-01-01

    ... (oxazolone-mediated delayed-type hypersensitivity [DTH]) in decorin-deficient (Dcn(-/-)) and wild-type mice. Dcn(-/-) mice showed a reduced ear swelling 24 h after oxazolone treatment with a concurrent attenuation of leukocyte infiltration...

  12. Stability and delay sensitivity of neutral fractional-delay systems

    Science.gov (United States)

    Xu, Qi; Shi, Min; Wang, Zaihua

    2016-08-01

    This paper generalizes the stability test method via integral estimation for integer-order neutral time-delay systems to neutral fractional-delay systems. The key step in stability test is the calculation of the number of unstable characteristic roots that is described by a definite integral over an interval from zero to a sufficient large upper limit. Algorithms for correctly estimating the upper limits of the integral are given in two concise ways, parameter dependent or independent. A special feature of the proposed method is that it judges the stability of fractional-delay systems simply by using rough integral estimation. Meanwhile, the paper shows that for some neutral fractional-delay systems, the stability is extremely sensitive to the change of time delays. Examples are given for demonstrating the proposed method as well as the delay sensitivity.

  13. Rationale, design and organization of the delayed antibiotic prescription (DAP) trial: a randomized controlled trial of the efficacy and safety of delayed antibiotic prescribing strategies in the non-complicated acute respiratory tract infections in general practice

    Science.gov (United States)

    2013-01-01

    Background Respiratory tract infections are an important burden in primary care and it’s known that they are usually self-limited and that antibiotics only alter its course slightly. This together with the alarming increase of bacterial resistance due to increased use of antimicrobials calls for a need to consider strategies to reduce their use. One of these strategies is the delayed prescription of antibiotics. Methods Multicentric, parallel, randomised controlled trial comparing four antibiotic prescribing strategies in acute non-complicated respiratory tract infections. We will include acute pharyngitis, rhinosinusitis, acute bronchitis and acute exacerbation of chronic bronchitis or chronic obstructive pulmonary disease (mild to moderate). The therapeutic strategies compared are: immediate antibiotic treatment, no antibiotic treatment, and two delayed antibiotic prescribing (DAP) strategies with structured advice to use a course of antibiotics in case of worsening of symptoms or not improving (prescription given to patient or prescription left at the reception of the primary care centre 3 days after the first medical visit). Discussion Delayed antibiotic prescription has been widely used in Anglo-Saxon countries, however, in Southern Europe there has been little research about this topic. The DAP trial wil evaluate two different delayed strategies in Spain for the main respiratory infections in primary care. Trial registration This trial is registered with ClinicalTrials.gov, number http://NCT01363531. PMID:23682979

  14. Delayed cure bismaleimide resins

    Science.gov (United States)

    Adams, Johnnie E.; Jamieson, Donald R.

    1984-08-07

    Polybismaleimides prepared by delayed curing of bis-imides having the formula ##STR1## wherein R.sub.1 and R.sub.2 each independently is H, C.sub.1-4 -alkyl, C.sub.1-4 -alkoxy, Cl or Br, or R.sub.1 and R.sub.2 together form a fused 6-membered hydrocarbon aromatic ring, with the proviso that R.sub.1 and R.sub.2 are not t-butyl or t-butoxy; X is O, S or Se; n is 1-3; and the --(CH.sub.2).sub.n -- group, optionally, is substituted by 1-3 methyl groups or by fluorine.

  15. Delay tolerant networks

    CERN Document Server

    Gao, Longxiang; Luan, Tom H

    2015-01-01

    This brief presents emerging and promising communication methods for network reliability via delay tolerant networks (DTNs). Different from traditional networks, DTNs possess unique features, such as long latency and unstable network topology. As a result, DTNs can be widely applied to critical applications, such as space communications, disaster rescue, and battlefield communications. The brief provides a complete investigation of DTNs and their current applications, from an overview to the latest development in the area. The core issue of data forward in DTNs is tackled, including the importance of social characteristics, which is an essential feature if the mobile devices are used for human communication. Security and privacy issues in DTNs are discussed, and future work is also discussed.

  16. Synchronizing time delay systems using variable delay in coupling

    Energy Technology Data Exchange (ETDEWEB)

    Ambika, G., E-mail: g.ambika@iiserpune.ac.in [Indian Institute of Science Education and Research, Pune 411 021 (India); Amritkar, R.E., E-mail: amritkar@prl.res.in [Physical Research Laboratory, Ahmedabad 380 009 (India)

    2011-11-15

    Highlights: > Delay and anticipation in coupling function varies with system dynamics. > Delay or anticipation of the synchronized state is independent of system delay. > Stability analysis developed is quite general. > We demonstrate enhanced security in communication. > Generalized synchronization possible over a wide range of parameter mismatch. - Abstract: We present a mechanism for synchronizing time delay systems using one way coupling with a variable delay in coupling that is reset at finite intervals. We present the analysis of the error dynamics that helps to isolate regions of stability of the synchronized state in the parameter space of interest for single and multiple delays. We supplement this by numerical simulations in a standard time delay system like Mackey Glass system. This method has the advantage that it can be adjusted to be delay or anticipatory in synchronization with a time which is independent of the system delay. We demonstrate the use of this method in communication using the bi channel scheme. We show that since the synchronizing channel carries information from transmitter only at intervals of reset time, it is not susceptible to an easy reconstruction.

  17. The effects of therapeutic touch on pain.

    Science.gov (United States)

    Monroe, Carolyn Magdalen

    2009-06-01

    To better understand how Therapeutic Touch can be used in today's health care arena, this integrative literature review will examine current research that will help answer the question, Does Therapeutic Touch reduce pain? An extensive search was conducted of the online databases MEDLINE, CINAHL, Cochrane Library, EMBASE, PsychLIT, and PubMed to retrieve research articles published from 1997 to 2007. Seven studies that were conducted between 1997 and 2004 were found and only five of the seven were included as pertinent evidence to answer the question. All of the research that was reviewed to answer whether Therapeutic Touch could significantly reduce pain revealed a majority of statistically significant positive results for implementing this intervention. Because there are no identified risks to Therapeutic Touch as a pain relief measure, it is safe to recommend despite the limitations of current research. Therapeutic Touch should be considered among the many possible nursing interventions for the treatment of pain.

  18. Concurrent Delay in Construction Disputes

    DEFF Research Database (Denmark)

    Cavaleri, Sylvie Cécile

    Delay is one of the issues most frequently encountered in today’s construction industry; it causes significant economic damage to all parties involved. Construction contracts, standard and bespoke, almost invariably consider delay from a perspective of single liability. If the event causing...... solutions to the issue of concurrent delay in a comparative perspective between common and civil law systems, with an emphasis on Danish and English law....

  19. Location Estimation using Delayed Measurements

    DEFF Research Database (Denmark)

    Bak, Martin; Larsen, Thomas Dall; Nørgård, Peter Magnus

    1998-01-01

    When combining data from various sensors it is vital to acknowledge possible measurement delays. Furthermore, the sensor fusion algorithm, often a Kalman filter, should be modified in order to handle the delay. The paper examines different possibilities for handling delays and applies a new...... technique to a sensor fusion system for estimating the location of an autonomous guided vehicle. The system fuses encoder and vision measurements in an extended Kalman filter. Results from experiments in a real environment are reported...

  20. Modeling delay in genetic networks: from delay birth-death processes to delay stochastic differential equations.

    Science.gov (United States)

    Gupta, Chinmaya; López, José Manuel; Azencott, Robert; Bennett, Matthew R; Josić, Krešimir; Ott, William

    2014-05-28

    Delay is an important and ubiquitous aspect of many biochemical processes. For example, delay plays a central role in the dynamics of genetic regulatory networks as it stems from the sequential assembly of first mRNA and then protein. Genetic regulatory networks are therefore frequently modeled as stochastic birth-death processes with delay. Here, we examine the relationship between delay birth-death processes and their appropriate approximating delay chemical Langevin equations. We prove a quantitative bound on the error between the pathwise realizations of these two processes. Our results hold for both fixed delay and distributed delay. Simulations demonstrate that the delay chemical Langevin approximation is accurate even at moderate system sizes. It captures dynamical features such as the oscillatory behavior in negative feedback circuits, cross-correlations between nodes in a network, and spatial and temporal information in two commonly studied motifs of metastability in biochemical systems. Overall, these results provide a foundation for using delay stochastic differential equations to approximate the dynamics of birth-death processes with delay.

  1. Therapeutic efficacy of a respiratory syncytial virus fusion inhibitor.

    Science.gov (United States)

    Roymans, Dirk; Alnajjar, Sarhad S; Battles, Michael B; Sitthicharoenchai, Panchan; Furmanova-Hollenstein, Polina; Rigaux, Peter; Berg, Joke Van den; Kwanten, Leen; Ginderen, Marcia Van; Verheyen, Nick; Vranckx, Luc; Jaensch, Steffen; Arnoult, Eric; Voorzaat, Richard; Gallup, Jack M; Larios-Mora, Alejandro; Crabbe, Marjolein; Huntjens, Dymphy; Raboisson, Pierre; Langedijk, Johannes P; Ackermann, Mark R; McLellan, Jason S; Vendeville, Sandrine; Koul, Anil

    2017-08-01

    Respiratory syncytial virus is a major cause of acute lower respiratory tract infection in young children, immunocompromised adults, and the elderly. Intervention with small-molecule antivirals specific for respiratory syncytial virus presents an important therapeutic opportunity, but no such compounds are approved today. Here we report the structure of JNJ-53718678 bound to respiratory syncytial virus fusion (F) protein in its prefusion conformation, and we show that the potent nanomolar activity of JNJ-53718678, as well as the preliminary structure-activity relationship and the pharmaceutical optimization strategy of the series, are consistent with the binding mode of JNJ-53718678 and other respiratory syncytial virus fusion inhibitors. Oral treatment of neonatal lambs with JNJ-53718678, or with an equally active close analog, efficiently inhibits established acute lower respiratory tract infection in the animals, even when treatment is delayed until external signs of respiratory syncytial virus illness have become visible. Together, these data suggest that JNJ-53718678 is a promising candidate for further development as a potential therapeutic in patients at risk to develop respiratory syncytial virus acute lower respiratory tract infection.Respiratory syncytial virus causes lung infections in children, immunocompromised adults, and in the elderly. Here the authors show that a chemical inhibitor to a viral fusion protein is effective in reducing viral titre and ameliorating infection in rodents and neonatal lambs.

  2. Delayed visual maturation and autism.

    Science.gov (United States)

    Goodman, R; Ashby, L

    1990-09-01

    Three boys are described with a mixed developmental disorder, which so far appears to have a relatively good prognosis. Each boy presented in early infancy with visual unresponsiveness, which spontaneously resolved. This delayed visual maturation was accompanied or followed by severe autistic impairment, general developmental delay, hypotonia and clumsiness. Subsequent progress has been unexpectedly favourable, with striking improvements in language, play, social interest and social competence. Widespread, patchy delay in brain maturation could possibly account for this combination of delayed visual maturation and autism, with a good prognosis.

  3. Break-before-Make CMOS Inverter for Power-Efficient Delay Implementation

    Directory of Open Access Journals (Sweden)

    Janez Puhan

    2014-01-01

    Full Text Available A modified static CMOS inverter with two inputs and two outputs is proposed to reduce short-circuit current in order to increment delay and reduce power overhead where slow operation is required. The circuit is based on bidirectional delay element connected in series with the PMOS and NMOS switching transistors. It provides differences in the dynamic response so that the direct-path current in the next stage is reduced. The switching transistors are never ON at the same time. Characteristics of various delay element implementations are presented and verified by circuit simulations. Global optimization procedure is used to obtain the most power-efficient transistor sizing. The performance of the modified CMOS inverter chain is compared to standard implementation for various delays. The energy (charge per delay is reduced up to 40%. The use of the proposed delay element is demonstrated by implementing a low-power delay line and a leading-edge detector cell.

  4. The effects of three modalities on delayed onset muscle soreness.

    Science.gov (United States)

    Weber, M D; Servedio, F J; Woodall, W R

    1994-11-01

    Delayed onset muscle soreness is a common problem that can interfere with rehabilitation as well as activities of daily living. The purpose of this study was to test the impact of therapeutic massage, upper body ergometry, or microcurrent electrical stimulation on muscle soreness and force deficits evident following a high-intensity eccentric exercise bout. Forty untrained, volunteer female subjects were randomly assigned to one of three treatment groups or to a control group. Exercise consisted of high-intensity eccentric contractions of the elbow flexors. Resistance was reduced as subjects fatigued, until they reached exhaustion. Soreness rating was determined using a visual analog scale. Force deficits were determined by measures of maximal voluntary isometric contraction at 90 degrees of elbow flexion and peak torque for elbow flexion at 60 degrees/sec on a Cybex II isokinetic dynamometer. Maximal voluntary isometric contraction and peak torque were determined at the 0 hour (before exercise) and again at 24 and 48 hours postexercise. Treatments were applied immediately following exercise and again at 24 hours after exercise. The control group subjects rested following their exercise bout. Statistical analysis showed significant increases in soreness rating and significant decreases in force generated when the 0 hour was compared with 24- and 48-hour measures. Further analysis indicated no statistically significant differences between massage, microcurrent electrical stimulation, upper body ergometry, and control groups.

  5. Maternal voluntary physical activity attenuates delayed neurodevelopment in malnourished rats.

    Science.gov (United States)

    Fragoso, Jéssica; Lira, Allan de Oliveira; Chagas, Guilherme Souza; Lucena Cavalcanti, Carolina Cadete; Beserra, Renata; de Santana-Muniz, Gisélia; Bento-Santos, Adriano; Martins, Gerffeson; Pirola, Luciano; da Silva Aragão, Raquel; Leandro, Carol Góis

    2017-11-01

    What is the central question of this study? In the present study, a reproducible model of maternal voluntary physical activity was developed to evaluate the adaptive response of physical activity by attenuating the effects of maternal undernutrition on physical features, reflex ontogeny and growth trajectory of offspring during development. What is the main finding and its importance? Maternal physical activity may induce neuronal maturation of sensorimotor connections impacting on the patterns of locomotor activity in malnourished offspring. Thus, physical activity should be considered as a therapeutic means of countering the effects of maternal undernutrition, by providing a useful strategy for enhancing the neuronal activity of children born to mothers who experience a restricted diet during pregnancy. This study evaluated the effects of maternal voluntary physical activity during pregnancy and lactation on somatic growth (SG), reflex ontogeny (RO) and locomotor activity (LA) of rats whose mothers were protein restricted. Virgin female Wistar rats were divided into the following six groups: control, normal protein (C-NP, n = 4); control, low protein (C-LP, n = 4); inactive, normal protein (I-NP, n = 8); inactive, low protein (I-LP, n = 7); very active, normal protein (VA-NP, n = 8); and very active, low protein (VA-LP, n = 6). Voluntary physical activity was recorded daily in dams. The LP groups were fed an 8% casein diet, whereas control groups were fed a 17% casein diet during pregnancy and lactation. Offspring were evaluated in terms of SG (body weight and length, latero-lateral skull axis and anteroposterior head axis) and RO (palmar grasp, righting, free-fall righting, negative geotaxis, cliff avoidance, auditory startle response and vibrissa placing). The LA was evaluated at 23, 45 and 60 days old in the open field. Voluntary physical activity was reduced during pregnancy and lactation independent of the maternal diet. Pups from LP dams showed

  6. Delay of gratification and delay discounting in rats.

    Science.gov (United States)

    Reynolds, Brady; de Wit, Harriet; Richards, Jerry

    2002-09-30

    Delay discounting (DD) and delay of gratification (DG) are two measures of impulsive behavior often viewed as reflecting the same or equivalent processes. However, there are some key differences in the contingencies of reinforcement between the procedures that may have implications for understanding impulsivity. This study used DD and DG procedures to determine if differences in contingencies of reinforcement specified by DD and DG alters how much organisms discount the value of delayed reinforcers. Twenty-four water-deprived rats performed one of two Adjusting Amount procedures, which consisted of repeated choices between a fixed amount of water (250 &mgr;l) delivered after a delay (0, 4, 8, 16, or 32 s) and an adjusting, usually lesser amount delivered immediately. Half of the rats (n=12) performed a DD procedure designed to assess preference for immediate over delayed reinforcers in which they had discrete choices between the immediate and delayed amounts of water. A DG procedure was used for the other half of the rats (n=12). In the DG procedure rats also selected between immediate and delayed alternatives, but if they chose the delayed alternative they could switch to and receive the immediate alternative at any time during the delay to the larger reward. In the DD procedure switching responses were not reinforced but were still recorded and used for analyses. The DD functions of the two groups did not differ significantly. However, at the longer delays, the DG group made significantly fewer switching responses than the DD group. A possible role of response inhibition in the DG procedure is discussed.

  7. Strategic Attention Deployment for Delay of Gratification in Working and Waiting Situations.

    Science.gov (United States)

    Peake, Philip K.; Hebl, Michelle; Mischel, Walter

    2002-01-01

    Two studies examined whether effects of attention to rewards during a delay of gratification task in waiting situations affects preschoolers' ability to delay gratification in working situations. Findings show that when work provides distraction, attention on rewards reduces delay time whether working or waiting; when work is not engaging,…

  8. On minimizing the maximum broadcast decoding delay for instantly decodable network coding

    KAUST Repository

    Douik, Ahmed S.

    2014-09-01

    In this paper, we consider the problem of minimizing the maximum broadcast decoding delay experienced by all the receivers of generalized instantly decodable network coding (IDNC). Unlike the sum decoding delay, the maximum decoding delay as a definition of delay for IDNC allows a more equitable distribution of the delays between the different receivers and thus a better Quality of Service (QoS). In order to solve this problem, we first derive the expressions for the probability distributions of maximum decoding delay increments. Given these expressions, we formulate the problem as a maximum weight clique problem in the IDNC graph. Although this problem is known to be NP-hard, we design a greedy algorithm to perform effective packet selection. Through extensive simulations, we compare the sum decoding delay and the max decoding delay experienced when applying the policies to minimize the sum decoding delay and our policy to reduce the max decoding delay. Simulations results show that our policy gives a good agreement among all the delay aspects in all situations and outperforms the sum decoding delay policy to effectively minimize the sum decoding delay when the channel conditions become harsher. They also show that our definition of delay significantly improve the number of served receivers when they are subject to strict delay constraints.

  9. Therapeutic use exemption

    Science.gov (United States)

    Dvorak, J; Kirkendall, D; Vouillamoz, M

    2006-01-01

    Football players who have either physical symptoms or disease after injury may need to be treated with specific medicines that are on the list of prohibited substances. Therapeutic use exemption may be granted to such players, in accordance with strictly defined criteria—these are presented in this article. Procedures of how to request for an abbreviated or a standard therapeutic use exemption are explained, and data on therapeutic use exemptions (UEFA and FIFA, 2004 and 2005) are also presented. PMID:16799102

  10. Delayed Imatinib Treatment for Acute Spinal Cord Injury: Functional Recovery and Serum Biomarkers

    Science.gov (United States)

    Finn, Anja; Hao, Jingxia; Wellfelt, Katrin; Josephson, Anna; Svensson, Camilla I.; Wiesenfeld-Hallin, Zsuzsanna; Eriksson, Ulf; Abrams, Mathew

    2015-01-01

    Abstract With no currently available drug treatment for spinal cord injury, there is a need for additional therapeutic candidates. We took the approach of repositioning existing pharmacological agents to serve as acute treatments for spinal cord injury and previously found imatinib to have positive effects on locomotor and bladder function in experimental spinal cord injury when administered immediately after the injury. However, for imatinib to have translational value, it needs to have sustained beneficial effects with delayed initiation of treatment, as well. Here, we show that imatinib improves hind limb locomotion and bladder recovery when initiation of treatment was delayed until 4 h after injury and that bladder function was improved with a delay of up to 24 h. The treatment did not induce hypersensitivity. Instead, imatinib-treated animals were generally less hypersensitive to either thermal or mechanical stimuli, compared with controls. In an effort to provide potential biomarkers, we found serum levels of three cytokines/chemokines—monocyte chemoattractant protein-1, macrophage inflammatory protein (MIP)-3α, and keratinocyte chemoattractant/growth-regulated oncogene (interleukin 8)—to increase over time with imatinib treatment and to be significantly higher in injured imatinib-treated animals than in controls during the early treatment period. This correlated to macrophage activation and autofluorescence in lymphoid organs. At the site of injury in the spinal cord, macrophage activation was instead reduced by imatinib treatment. Our data strengthen the case for clinical trials of imatinib by showing that initiation of treatment can be delayed and by identifying serum cytokines that may serve as candidate markers of effective imatinib doses. PMID:25914996

  11. Exponential Stability of Stochastic Nonlinear Dynamical Price System with Delay

    Directory of Open Access Journals (Sweden)

    Wenli Zhu

    2013-01-01

    Full Text Available Based on Lyapunov stability theory, Itô formula, stochastic analysis, and matrix theory, we study the exponential stability of the stochastic nonlinear dynamical price system. Using Taylor's theorem, the stochastic nonlinear system with delay is reduced to an n-dimensional semilinear stochastic differential equation with delay. Some sufficient conditions of exponential stability and corollaries for such price system are established by virtue of Lyapunov function. The time delay upper limit is solved by using our theoretical results when the system is exponentially stable. Our theoretical results show that if the classical price Rayleigh equation is exponentially stable, so is its perturbed system with delay provided that both the time delay and the intensity of perturbations are small enough. Two examples are presented to illustrate our results.

  12. Delay dynamic equations with stability

    Directory of Open Access Journals (Sweden)

    Krueger Robert J

    2006-01-01

    Full Text Available We first give conditions which guarantee that every solution of a first order linear delay dynamic equation for isolated time scales vanishes at infinity. Several interesting examples are given. In the last half of the paper, we give conditions under which the trivial solution of a nonlinear delay dynamic equation is asymptotically stable, for arbitrary time scales.

  13. Registration Delay and Student Performance

    Science.gov (United States)

    Siefken, Jason

    2017-01-01

    Tracking the difference between the time a first-year student is allowed to register for a course and the time he or she does register for a course (a student's registration delay), we notice a negative correlation between registration delay and final grade in a course. The difference between a student who registers within the first two minutes…

  14. Delayed Reinforcement of Operant Behavior

    Science.gov (United States)

    Lattal, Kennon A.

    2010-01-01

    The experimental analysis of delay of reinforcement is considered from the perspective of three questions that seem basic not only to understanding delay of reinforcement but also, by implication, the contributions of temporal relations between events to operant behavior. The first question is whether effects of the temporal relation between…

  15. #FakeNobelDelayReasons

    CERN Document Server

    2013-01-01

    Tuesday’s hour-long delay of the Nobel Prize in Physics announcement was (and still is) quite the cause for speculation. But on the Twittersphere, it was simply the catalyst for some fantastic puns, so-bad-they're-good physics jokes and other shenanigans. Here are some of our favourite #FakeNobelDelayReasons.    

  16. Continuous generation of delayed light

    Science.gov (United States)

    Smartsev, Slava; Eger, David; Davidson, Nir; Firstenberg, Ofer

    2017-11-01

    We use a four-wave mixing process to read-out light from atomic coherence which is continuously written. The light is continuously generated after an effective delay, allowing the atomic coherence to evolve during the process. Contrary to slow-light delay, which depends on the medium optical depth, here the generation delay is determined solely by the intensive properties of the system, approaching the atomic coherence lifetime at the weak driving limit. The atomic evolution during the generation delay is further manifested in the spatial profile of the generated light due to atomic diffusion. Continuous generation of light with a long intrinsic delay can replace discrete write–read procedures when the atomic evolution is the subject of interest.

  17. Delayed radiation neuropathy

    Energy Technology Data Exchange (ETDEWEB)

    Nagashima, T.; Miyamoto, K.; Beppu, H.; Hirose, K.; Yamada, K. (Tokyo Metropolitan Neurological Hospital (Japan))

    1981-07-01

    A case of cervical plexus neuropathy was reported in association with chronic radio-dermatitis, myxedema with thyroid adenoma and epiglottic tumor. A 38-year-old man has noticed muscle weakness and wasting of the right shoulder girdle since age 33. A detailed history taking revealed a previous irradiation to the neck because of the cervical lymphadenopathy at age 10 (X-ray 3,000 rads), keroid skin change at age 19, obesity and edema since 26, and hoarseness at 34. Laryngoscopic examination revealed a tumor on the right vocal cord, diagnosed as benign papilloma by histological study. In addition, there were chronic radio-dermatitis around the neck, primary hypothyroidism with a benign functioning adenoma on the right lobe of the thyroid, the right phrenic nerve palsy and the right recurrent nerve palsy. All these lesions were considered to be the late sequellae of radiation to the neck in childhood. Other neurological signs were weakness and amyotrophy of the right shoulder girdle with patchy sensory loss, and areflexia of the right arm. Gross power was fairly well preserved in the right hand. EMG showed neurogenic changes in the tested muscles, suggesting a peripheral nerve lesion. Nerve conduction velocities were normal. No abnormal findings were revealed by myelography and spinal CT. The neurological findings of the patient were compatible with the diagnosis of middle cervical plexus palsy apparently due to late radiation effect. In the literature eight cases of post-radiation neuropathy with a long latency have been reported. The present case with the longest latency after the radiation should be included in the series of the reported cases of ''delayed radiation neuropathy.'' (author).

  18. Stability Tests of Positive Fractional Continuous-time Linear Systems with Delays

    Directory of Open Access Journals (Sweden)

    Tadeusz Kaczorek

    2013-06-01

    Full Text Available Necessary and sufficient conditions for the asymptotic stability of positive fractional continuous-time linear systems with many delays are established. It is shown that: 1 the asymptotic stability of the positive fractional system is independent of their delays, 2 the checking of the asymptotic stability of the positive fractional systems with delays can be reduced to checking of the asymptotic stability of positive standard linear systems without delays.

  19. Comparison of Efficacy of Eye Movement, Desensitization and Reprocessing and Cognitive Behavioral Therapy Therapeutic Methods for Reducing Anxiety and Depression of Iranian Combatant Afflicted by Post Traumatic Stress Disorder

    Science.gov (United States)

    Narimani, M.; Sadeghieh Ahari, S.; Rajabi, S.

    This research aims to determine efficacy of two therapeutic methods and compare them; Eye Movement, Desensitization and Reprocessing (EMDR) and Cognitive Behavioral Therapy (CBT) for reduction of anxiety and depression of Iranian combatant afflicted with Post traumatic Stress Disorder (PTSD) after imposed war. Statistical population of current study includes combatants afflicted with PTSD that were hospitalized in Isar Hospital of Ardabil province or were inhabited in Ardabil. These persons were selected through simple random sampling and were randomly located in three groups. The method was extended test method and study design was multi-group test-retest. Used tools include hospital anxiety and depression scale. This survey showed that exercise of EMDR and CBT has caused significant reduction of anxiety and depression.

  20. Delayed adverse reactions to blood donation.

    Science.gov (United States)

    Kamel, Hany; Tomasulo, Peter; Bravo, Marjorie; Wiltbank, Thomas; Cusick, Robin; James, Robert C; Custer, Brian

    2010-03-01

    Blood donation is safe, but a small proportion of donors have delayed and/or off-site reactions that have the potential to lead to serious injury. This retrospective study sought to identify risk factors for delayed reactions (DRs). The records of 793,293 allogeneic whole blood and apheresis donations in 2007 were assessed for vasovagal reactions. Donor demographic, biometric, and clinical measurements were captured. Incidents related to needle insertion and mild reactions were excluded. Based on the reaction onset time relative to the procedure end time, reactions were classified as delayed (>15 min) or immediate (Reactions were analyzed by multivariable logistic regression comparing donors with immediate reactions (IRs) or DRs to donors without reactions and comparing donors with DRs to IRs. The clinical consequences of off-site and on-site reactions are reported. The prevalence of reactions classified as moderate or severe was 41 in 10,000 donations; 24% of these reactions were delayed and 12% occurred off-site. DRs were associated with female sex (odds ratio [OR], 2.96; 95% confidence interval [CI], 2.21-3.96) and with low estimated blood volume (EBV; OR, 3.91; 96% CI, 2.84-5.51). Off-site reactions, particularly in female donors, were more likely to be associated with a fall, with head trauma, with other injury, and with the use of outside medical care. Low EBV, youth, and first-time donor status are major risk factors for IRs and DRs. Women are more likely than men to report DRs. Delayed and off-site reactions lead to potentially preventable morbidity. Understanding the physiologic basis of DRs may lead to the development of appropriate interventions to reduce their likelihood.

  1. Therapeutic Engagement as a Predictor of Retention in Adolescent Therapeutic Community Treatment

    Science.gov (United States)

    Abdel-Salam, Sami; Gunter, Whitney D.

    2014-01-01

    The adolescent drug problem places a huge toll on society and a heavy burden on the criminal justice system. Research regarding the benefits of therapeutic community (TC) treatment for adolescents has shown it to be effective. Despite the ability of therapeutic communities to lower drug relapse and reduce criminality, a great deal remains unknown…

  2. Chicanoizing the Therapeutic Community

    Science.gov (United States)

    Aron, William S.; And Others

    1974-01-01

    Focusing on the drug addiction problem and its antecedent conditions in a Chicano population, the article examines several therapeutic interventions suggested by these conditions and indicates how they might be incorporated into a drug addiction Therapeutic Community treatment program designed to meet the needs of Chicano drug addicts. (Author/NQ)

  3. Therapeutic Crisis Intervention.

    Science.gov (United States)

    Holden, Martha J.; Powers, Jane Levine

    1993-01-01

    Describes Therapeutic Crisis Intervention (TCI) program as providing staff with skills, knowledge, and confidence to manage child in crisis to bring about a "maximum amount of lasting response." Contends that, by applying principles of TCI training, direct care worker can attain therapeutic control and maintain dignity of both adult and child…

  4. Trends in Therapeutic Recreation.

    Science.gov (United States)

    Smith, Ralph W.

    1995-01-01

    Discusses the implications of the rapid, dramatic changes taking place in therapeutic recreation for individuals with physical disabilities. The article notes the impact of changes in managed care, examines programming trends in therapeutic recreation (adventure/outdoor education, competitive sports, handcycling, health enhancement activities, and…

  5. Delay of Gratification and Delay Discounting: A Unifying Feedback Model of Delay-Related Impulsive Behavior

    Science.gov (United States)

    Reynolds, Brady; Schiffbauer, Ryan

    2005-01-01

    Delay of Gratification (DG) and Delay Discounting (DD) represent two indices of impulsive behavior often treated as though they represent equivalent or the same underlying processes. However, there are key differences between DG and DD procedures, and between certain research findings with each procedure, that suggest they are not equivalent. In…

  6. Testing the Relations Among Family Disorganization, Delay Discounting, and Adolescent Alcohol Use: A Genetically Informed Study.

    Science.gov (United States)

    Wang, Frances L; Pandika, Danielle; Chassin, Laurie; Lee, Matthew; King, Kevin

    2016-04-01

    Delay discounting is a potential etiological factor in adolescents' alcohol use, making it important to understand its antecedents. Family disorganization might contribute to delay discounting, but few studies have tested this relation. Moreover, because delay discounting is heritable, the effects of family disorganization on delay discounting might be moderated by adolescents' genetic risk for delay discounting. Thus, the current study examined the role of family disorganization, in interaction with genetic risk, in predicting adolescents' delay discounting and subsequent alcohol use. Adolescents participated in 4 waves of data collection. Adolescents self-reported their family disorganization at T1, completed a delay discounting questionnaire at T3, and self-reported their alcohol use both at T2 (covariate) and T4 (outcome). Using results from an independent sample, we created a polygenic risk score consisting of dopaminergic genes to index genetic risk for delay discounting. Greater family disorganization predicted adolescents' greater delay discounting, but only for adolescents with low levels of genetic risk for delay discounting. Adolescents with high and mean levels of genetic risk for delay discounting showed elevated delay discounting regardless of their family's disorganization. Greater delay discounting prospectively predicted adolescents' greater alcohol use. Finally, the effects of family disorganization on adolescents' alcohol use were mediated through delay discounting, but only for adolescents with low levels of genetic risk. Results suggest multiple pathways to delay discounting. Although there are genetically influenced pathways to delay discounting, family disorganization might represent an environmental pathway to delay discounting (and subsequent alcohol use) for a subset of adolescents at low genetic risk. These findings reinforce the utility of family interventions for reducing adolescents' delay discounting and alcohol use, at least for a

  7. HAMLET treatment delays bladder cancer development.

    Science.gov (United States)

    Mossberg, Ann-Kristin; Hou, Yuchuan; Svensson, Majlis; Holmqvist, Bo; Svanborg, Catharina

    2010-04-01

    HAMLET is a protein-lipid complex that kills different types of cancer cells. Recently we observed a rapid reduction in human bladder cancer size after intravesical HAMLET treatment. In this study we evaluated the therapeutic effect of HAMLET in the mouse MB49 bladder carcinoma model. Bladder tumors were established by intravesical injection of MB49 cells into poly L-lysine treated bladders of C57BL/6 mice. Treatment groups received repeat intravesical HAMLET instillations and controls received alpha-lactalbumin or phosphate buffer. Effects of HAMLET on tumor size and putative apoptotic effects were analyzed in bladder tissue sections. Whole body imaging was used to study HAMLET distribution in tumor bearing mice compared to healthy bladder tissue. HAMLET caused a dose dependent decrease in MB49 cell viability in vitro. Five intravesical HAMLET instillations significantly decreased tumor size and delayed development in vivo compared to controls. TUNEL staining revealed selective apoptotic effects in tumor areas but not in adjacent healthy bladder tissue. On in vivo imaging Alexa-HAMLET was retained for more than 24 hours in the bladder of tumor bearing mice but not in tumor-free bladders or in tumor bearing mice that received Alexa-alpha-lactalbumin. Results show that HAMLET is active as a tumoricidal agent and suggest that topical HAMLET administration may delay bladder cancer development. Copyright (c) 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  8. Reporting therapeutic discourse in a therapeutic community.

    Science.gov (United States)

    Chapman, G E

    1988-03-01

    Research in nurses' communications has concentrated on nurse to patient interactions. Those few studies which focus on nurse to nurse communications seem to be generated by a pragmatic and normative concern with effective information sharing. In this paper, which describes one aspect of a larger case study of a hospital-based therapeutic community, the description and analysis of nurses' reports flows not from a normative model of professional practice, but rather an exploration of how professional practice is articulated as discourse in nurses' written accounts. Foucault's ideas about therapeutic discourse inform the theoretical framework of the research. Ethnomethodological concerns with the importance of documentary analysis provide the methodological rationale for examining nurses' 24-hour report documents, as official discourse, reflecting therapeutic practice in this setting. A content analysis of nurses' reports, collected over a period of 4 months, demonstrated the importance of domesticity and ordinary everyday activities in nurses' accounts of hospital life. Disruption to the 'life as usual' domesticity in the community seemed to be associated with admission to and discharge from the hospital when interpersonal and interactional changes between patients occur. It is suggested that nurses in general hospital wards and more orthodox psychiatric settings might usefully consider the impact of admissions and discharges on the group of patients they manage, and make this a discursive focus of their work.

  9. Time Delay in Molecular Photoionization

    CERN Document Server

    Hockett, P; Villeneuve, D M; Corkum, P B

    2015-01-01

    Time-delays in the photoionization of molecules are investigated. As compared to atomic ionization, the time-delays expected from molecular ionization present a much richer phenomenon, with a strong spatial dependence due to the anisotropic nature of the molecular scattering potential. We investigate this from a scattering theory perspective, and make use of molecular photoionization calculations to examine this effect in representative homonuclear and hetronuclear diatomic molecules, nitrogen and carbon monoxide. We present energy and angle-resolved maps of the Wigner delay time for single-photon valence ionization, and discuss the possibilities for experimental measurements.

  10. Therapeutic hypothermia for neonatal hypoxic-ischemic encephalopathy - where to from here?

    Directory of Open Access Journals (Sweden)

    Joanne O. Davidson

    2015-09-01

    Full Text Available Hypoxia-ischemia before or around the time of birth occurs in approximately 2/1000 live births and is associated with a high risk of death or lifelong disability. Therapeutic hypothermia is now well established as standard treatment for infants with moderate to severe hypoxic-ischemic encephalopathy but is only partially effective. There is compelling preclinical and clinical evidence that hypothermia is most protective when it is started as early as possible after hypoxia-ischemia. Further improvements in outcome from therapeutic hypothermia are very likely to arise from strategies to reduce the delay before starting treatment of affected infants. In this review we examine evidence that current protocols are reasonably close to the optimal depth and duration of cooling, but that the optimal rate of rewarming after hypothermia is unclear. The potential for combination treatments to augment hypothermic neuroprotection has considerable promise, particularly with endogenous targets such as melatonin and erythropoietin and noble gases such as xenon. We dissect the critical importance of preclinical studies using realistic delays in treatment and clinically relevant cooling protocols when examining combination treatment, and that for many strategies overlapping mechanisms of action can substantially attenuate any effects.

  11. Lay perceptions of malaria and therapeutic itinerary of resettled pregnant women in South Sudan.

    Science.gov (United States)

    Dræbel, Tania; Gueth Kueil, Bill

    2014-12-01

    Approximately 95% of South Sudan is malaria-endemic and transmission is high throughout the year. Annually, 2.3 million people are at risk of malarial infection, but children under 5 years, pregnant women and their unborn children are particularly at high risk. Appropriate policies for malarial prevention and control require a better understanding of the populations' malarial perceptions and treatment itinerary. A qualitative study was carried out to explore malarial lay perceptions and therapeutic itinerary among 30 resettled pregnant women in Unity State, South Sudan. The study showed that the therapeutic itinerary was prompted by fever and composed of five steps that were simultaneously or successively explored. The household and community constitute the first-line treatment options for fever. Interviewees relied on homemade remedies and concoctions, traditional healers' cures, magician's rituals and private formal and informal medicine vendors at the local market before seeking malarial diagnosis and treatment at the health centre. Improving capacities for proper identification and management of malarial fever at household and community level is a priority for reducing the delay in seeking timely and proper treatment. The formal health system may, in time, aspire to address the economic and cultural barriers within the system that contribute to delaying effective treatment-seeking. © The Author 2014. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  12. Impact of construal level manipulations on delay discounting.

    Directory of Open Access Journals (Sweden)

    Richard Yi

    Full Text Available Construal Level Theory states that psychologically proximal outcomes are construed concretely while psychologically distal outcomes are construed abstractly. Previous research suggests that the principles of Construal Level Theory can be applied to enhance self-control, as measured by delay discounting. The present studies replicate and expand on this work by examining whether theory-informed priming manipulations lead to delay discounting reductions in a repeated-measures design. Study 1 conceptually replicated previous work, with reduced delay discounting observed as a function of thinking abstractly. Studies 2 and 3 expanded on this work by reinterpreting (a preference for immediate outcomes as preference for outcomes that are construed concretely, and (b dispreference for delayed outcomes as dispreference for outcomes that are construed abstractly. Study 2 provided support for the first interpretation, as reduced delay discounting was observed as a function of thinking concretely about the future. Study 3 provided support for the second interpretation, as reduced delay discounting was observed as a function of thinking abstractly about the present. In studies 1 and 3, significant condition × order interactions were observed. In all three studies, the same impact of order of exposure to priming manipulation was observed, indicating specific carryover effects.

  13. Analysis and optimization of RC delay in vertical nanoplate FET

    Science.gov (United States)

    Woo, Changbeom; Ko, Kyul; Kim, Jongsu; Kim, Minsoo; Kang, Myounggon; Shin, Hyungcheol

    2017-10-01

    In this paper, we have analyzed short channel effects (SCEs) and RC delay with Vertical nanoplate FET (VNFET) using 3-D Technology computer-aided design (TCAD) simulation. The device is based on International Technology Road-map for Semiconductor (ITRS) 2013 recommendations, and it has initially gate length (LG) of 12.2 nm, channel thickness (Tch) of 4 nm, and spacer length (LSD) of 6 nm. To obtain improved performance by reducing RC delay, each dimension is adjusted (LG = 12.2 nm, Tch = 6 nm, LSD = 11.9 nm). It has each characteristic in this dimension (Ion/Ioff = 1.64 × 105, Subthreshold swing (S.S.) = 73 mV/dec, Drain-induced barrier lowering (DIBL) = 60 mV/V, and RC delay = 0.214 ps). Furthermore, with long shallow trench isolation (STI) length and thick insulator thickness (Ti), we can reduce RC delay from 0.214 ps to 0.163 ps. It is about a 23.8% reduction. Without decreasing drain current, there is a reduction of RC delay as reducing outer fringing capacitance (Cof). Finally, when source/drain spacer length is set to be different, we have verified RC delay to be optimum.

  14. Fundamentals of Delayed Coking Joint Industry Project

    Energy Technology Data Exchange (ETDEWEB)

    Michael Volk; Keith Wisecarver

    2004-09-26

    Delayed coking evolved steadily over the early to mid 1900s to enable refiners to convert high boiling, residual petroleum fractions to light products such as gasoline. Pound for pound, coking is the most energy intensive of any operation in a modern refinery. Large amounts of energy are required to heat the thick, poor-quality petroleum residuum to the 900 to 950 degrees F required to crack the heavy hydrocarbon molecules into lighter, more valuable products. One common misconception of delayed coking is that the product coke is a disadvantage. Although coke is a low valued (near zero economic value) byproduct, compared to transportation fuels, there is a significant worldwide trade and demand for coke as it is an economical fuel. Coke production has increased steadily over the last ten years, with further increases forecast for the foreseeable future. Current domestic production is near 111,000 tons per day. A major driving force behind this increase is the steady decline in crude quality available to refiners. Crude slates are expected to grow heavier with higher sulfur contents while environmental restrictions are expected to significantly reduce the demand for high-sulfur residual fuel oil. Light sweet crudes will continue to be available and in even greater demand than they are today. Refiners will be faced with the choice of purchasing light sweet crudes at a premium price, or adding bottom of the barrel upgrading capability, through additional new investments, to reduce the production of high-sulfur residual fuel oil and increase the production of low-sulfur distillate fuels. A second disadvantage is that liquid products from cokers frequently are unstable, i.e., they rapidly form gum and sediments. Because of intermediate investment and operating costs, delayed coking has increased in popularity among refiners worldwide. Based on the 2000 Worldwide Refining Survey published in the Oil and Gas, the delayed coking capacity for 101 refineries around the world

  15. Fundamentals of Delayed Coking Joint Industry Project

    Energy Technology Data Exchange (ETDEWEB)

    Michael Volk; Keith Wisecarver

    2003-09-26

    Delayed coking evolved steadily over the early to mid 1900s to enable refiners to convert high boiling, residual petroleum fractions to light products such as gasoline. Pound for pound, coking is the most energy intensive of any operation in a modern refinery. Large amounts of energy are required to heat the thick, poor-quality petroleum residuum to the 900 to 950 degrees F required to crack the heavy hydrocarbon molecules into lighter, more valuable products. One common misconception of delayed coking is that the product coke is a disadvantage. Although coke is a low valued (near zero economic value) byproduct, compared to transportation fuels, there is a significant worldwide trade and demand for coke as it is an economical fuel. Coke production has increased steadily over the last ten years, with further increases forecast for the foreseeable future. Current domestic production is near 111,000 tons per day. A major driving force behind this increase is the steady decline in crude quality available to refiners. Crude slates are expected to grow heavier with higher sulfur contents while environmental restrictions are expected to significantly reduce the demand for high-sulfur residual fuel oil. Light sweet crudes will continue to be available and in even greater demand than they are today. Refiners will be faced with the choice of purchasing light sweet crudes at a premium price, or adding bottom of the barrel upgrading capability, through additional new investments, to reduce the production of high-sulfur residual fuel oil and increase the production of low-sulfur distillate fuels. A second disadvantage is that liquid products from cokers frequently are unstable, i.e., they rapidly form gum and sediments. Because of intermediate investment and operating costs, delayed coking has increased in popularity among refiners worldwide. Based on the 2000 Worldwide Refining Survey published in the Oil and Gas, the delayed coking capacity for 101 refineries around the world

  16. [Therapeutic education for recurrent depressive disorder].

    Science.gov (United States)

    Carde, Soufiane; Hatif, Séverine; Samama, Diane; Charbonnel, Patricia; Jouvent, Roland

    2016-01-01

    Depression is a serious and recurrent condition which can become chronic. As a complement to other therapeutic approaches, therapeutic patient education (TPE) or psychoeducation is effective. TPE groups led by a multidisciplinary hospitalisation team in a psychiatric department are thereby integrated into the global care in order to reduce relapses and improve patients' quality of life. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  17. DELAYED PUBERTY: A LATE DIAGNOSIS

    Directory of Open Access Journals (Sweden)

    Helena Ferreira

    2017-04-01

    Discussion/Conclusion: We aimed to aware Crohn’s disease as one of the causes of pubertal and growth delay, highlighting the need for early diagnosis and therapy, in order to reach a favorable pubertal development.

  18. Delays and networked control systems

    CERN Document Server

    Hetel, Laurentiu; Daafouz, Jamal; Johansson, Karl

    2016-01-01

    This edited monograph includes state-of-the-art contributions on continuous time dynamical networks with delays. The book is divided into four parts. The first part presents tools and methods for the analysis of time-delay systems with a particular attention on control problems of large scale or infinite-dimensional systems with delays. The second part of the book is dedicated to the use of time-delay models for the analysis and design of Networked Control Systems. The third part of the book focuses on the analysis and design of systems with asynchronous sampling intervals which occur in Networked Control Systems. The last part of the book exposes several contributions dealing with the design of cooperative control and observation laws for networked control systems. The target audience primarily comprises researchers and experts in the field of control theory, but the book may also be beneficial for graduate students. .

  19. Parental Discipline and Delayed Gratification

    Science.gov (United States)

    Weller, Leonard; Berkowitz, Edith

    1975-01-01

    It was hypothesized that children brought up under coercive power would be more likely to exhibit immediate gratification, whereas children brought up under noncoercive power would be more likely to delay gratification. The hypothesis was confirmed. (Author)

  20. Fractional variational principles with delay

    Science.gov (United States)

    Baleanu, Dumitru; Maaraba Abdeljawad, Thabet; Jarad, Fahd

    2008-08-01

    The fractional variational principles within Riemann-Liouville fractional derivatives in the presence of delay are analyzed. The corresponding Euler-Lagrange equations are obtained and one example is analyzed in detail.

  1. Fractional variational principles with delay

    Energy Technology Data Exchange (ETDEWEB)

    Baleanu, Dumitru; Abdeljawad, Thabet Maaraba; Jarad, Fahd [Department of Mathematics and Computer Sciences, Faculty of Arts and Sciences, Cankaya University, 06530 Ankara (Turkey)], E-mail: dumitru@cankaya.edu.tr, E-mail: baleanu@venus.nipne.ro

    2008-08-08

    The fractional variational principles within Riemann-Liouville fractional derivatives in the presence of delay are analyzed. The corresponding Euler-Lagrange equations are obtained and one example is analyzed in detail.

  2. EAMJ Delayed April 10.indd

    African Journals Online (AJOL)

    2010-04-04

    Apr 4, 2010 ... INTRODUCTION. Breast cancer remains a leading cause of death of ... ABSTRACT. Objective: To determine the extent and nature of delayed presentation of patients .... symptomatic breast cancer: a systematic review. Lancet.

  3. In vivo early intervention and the therapeutic effects of 20(s-ginsenoside rg3 on hypertrophic scar formation.

    Directory of Open Access Journals (Sweden)

    Liying Cheng

    Full Text Available Intra-lesional injections of corticosteroids, interferon, and chemotherapeutic drugs are currently the most popular treatments of hypertrophic scar formation. However, these drugs can only be used after HS is formed, and not during the inflammatory phase of wound healing, which regulates the HS forming process.To investigate a new, effective, combining therapeutic and safe drug for early intervention and treatment for hypertrophic scars.Cell viability assay and flow cytometric analysis were studied in vitro. Animal studies were done to investigate the combining therapeutic effects of 20(S-ginsenoside Rg3 (Rg3 on the inflammatory phase of wound healing and HS formation.In vitro studies showed that Rg3 can inhibit HS fibroblasts proliferation and induce HSF apoptosis in a concentration-dependent manner. In vivo studies demonstrated that Rg3 can limit the exaggerated inflammation, and do not delay the wound healing process, which indicates that Rg3 could be used as an early intervention to reduce HS formation. Topical injection of 4 mg/mL Rg3 can reduce HS formation by 34%. Histological and molecular studies revealed that Rg3 injection inhibits fibroblasts proliferation thus reduced the accumulation of collagen fibers, and down-regulates VEGF expression in the HS tissue.Rg3 can be employed as an early intervention and a combining therapeutic drug to reduce inflammation and HS formation as well.

  4. A method for generation phage cocktail with great therapeutic potential.

    Directory of Open Access Journals (Sweden)

    Jingmin Gu

    Full Text Available BACKGROUND: Bacteriophage could be an alternative to conventional antibiotic therapy against multidrug-resistant bacteria. However, the emergence of resistant variants after phage treatment limited its therapeutic application. METHODOLOGY/PRINCIPAL FINDINGS: In this study, an approach, named "Step-by-Step" (SBS, has been established. This method takes advantage of the occurrence of phage-resistant bacteria variants and ensures that phages lytic for wild-type strain and its phage-resistant variants are selected. A phage cocktail lytic for Klebsiella pneumoniae was established by the SBS method. This phage cocktail consisted of three phages (GH-K1, GH-K2 and GH-K3 which have different but overlapping host strains. Several phage-resistant variants of Klebsiella pneumoniae were isolated after different phages treatments. The virulence of these variants was much weaker [minimal lethal doses (MLD>1.3×10(9 cfu/mouse] than that of wild-type K7 countpart (MLD = 2.5×10(3 cfu/mouse. Compared with any single phage, the phage cocktail significantly reduced the mutation frequency of Klebsiella pneumoniae and effectively rescued Klebsiella pneumoniae bacteremia in a murine K7 strain challenge model. The minimal protective dose (MPD of the phage cocktail which was sufficient to protect bacteremic mice from lethal K7 infection was only 3.0×10(4 pfu, significantly smaller (p<0.01 than that of single monophage. Moreover, a delayed administration of this phage cocktail was still effective in protection against K7 challenge. CONCLUSIONS/SIGNIFICANCE: Our data showed that the phage cocktail was more effective in reducing bacterial mutation frequency and in the rescue of murine bacteremia than monophage suggesting that phage cocktail established by SBS method has great therapeutic potential for multidrug-resistant bacteria infection.

  5. Systematics in delayed neutron yields

    Energy Technology Data Exchange (ETDEWEB)

    Ohsawa, Takaaki [Kinki Univ., Higashi-Osaka, Osaka (Japan). Atomic Energy Research Inst.

    1998-03-01

    An attempt was made to reproduce the systematic trend observed in the delayed neutron yields for actinides on the basis of the five-Gaussian representation of the fission yield together with available data sets for delayed neutron emission probability. It was found that systematic decrease in DNY for heavier actinides is mainly due to decrease of fission yields of precursors in the lighter side of the light fragment region. (author)

  6. Measuring information-transfer delays.

    Directory of Open Access Journals (Sweden)

    Michael Wibral

    Full Text Available In complex networks such as gene networks, traffic systems or brain circuits it is important to understand how long it takes for the different parts of the network to effectively influence one another. In the brain, for example, axonal delays between brain areas can amount to several tens of milliseconds, adding an intrinsic component to any timing-based processing of information. Inferring neural interaction delays is thus needed to interpret the information transfer revealed by any analysis of directed interactions across brain structures. However, a robust estimation of interaction delays from neural activity faces several challenges if modeling assumptions on interaction mechanisms are wrong or cannot be made. Here, we propose a robust estimator for neuronal interaction delays rooted in an information-theoretic framework, which allows a model-free exploration of interactions. In particular, we extend transfer entropy to account for delayed source-target interactions, while crucially retaining the conditioning on the embedded target state at the immediately previous time step. We prove that this particular extension is indeed guaranteed to identify interaction delays between two coupled systems and is the only relevant option in keeping with Wiener's principle of causality. We demonstrate the performance of our approach in detecting interaction delays on finite data by numerical simulations of stochastic and deterministic processes, as well as on local field potential recordings. We also show the ability of the extended transfer entropy to detect the presence of multiple delays, as well as feedback loops. While evaluated on neuroscience data, we expect the estimator to be useful in other fields dealing with network dynamics.

  7. Language Delays in Toddlers: Information for Parents

    Science.gov (United States)

    ... Stages Listen Español Text Size Email Print Share Language Delays in Toddlers: Information for Parents Page Content ... situation or repeats scripts from TV Delays in language Delays in language are the most common types ...

  8. [PLURAL THERAPEUTIC ITINERARIES].

    Science.gov (United States)

    Iorio, Silvia

    2015-01-01

    This article addresses the strategies employed by Nahua community of Mexixo to deal with health problems. Drawing on qualitative research, it discusses the choice of plural therapeutic itineraries, including the use of informal and formal healthcare.

  9. Stroke patients' delay of emergency treatment.

    Science.gov (United States)

    Hjelmblink, Finn; Holmström, Inger; Kjeldmand, Dorte

    2010-06-01

    Scand J Caring Sci; 2010; 24; 307-311 Stroke patients' delay of emergency treatment Treatment of stroke victims with fibrinolysis should take place within a time limit of 3 hours. In spite of comprehensive endeavours to reduce hospital arrival time, too many patients still delay arrival beyond this time limit. This qualitative case study explored the meaning of acute stroke and treatment to four patients with more than 24-hour delayed arrival. The setting of the study was the catchment area of a university hospital. Semi-structured interviews were analysed through the empirical psychological, phenomenological method. An essence was found which was constituted by four themes. The essence of stroke symptoms and treatment was: 'Threatened control of bodily function, autonomy and integrity'. When the patients fell ill they acted as if nothing had happened. They treated their body like a defective device. In encounters with physicians they demanded to be met as a person by a person; otherwise they rejected both the physician and her or his prescriptions. They did not involve their near ones in decision-making. The conclusions were the following: Health care information about how to act in cases of early stroke symptoms may need to imbue people with an understanding of how early treatment of neurological symptoms and preserved control of life are intimately connected. Furthermore emergency care of acute stroke patients might need to take place in an organisation where patients are sure to be met by physicians as a person by a person.

  10. Ability to delay gratification and BMI in preadolescence.

    Science.gov (United States)

    Bruce, Amanda S; Black, William R; Bruce, Jared M; Daldalian, Marina; Martin, Laura E; Davis, Ann M

    2011-05-01

    Delay of gratification tasks require an individual to forgo an immediate reward and wait for a more desirable delayed reward. This study used an ecologically valid measure of delayed gratification to test the hypothesis that preadolescents with higher BMI would be less likely to delay gratification. Healthy Hawks is a 12-week educational/behavioral obesity intervention at the University of Kansas Medical Center. Each week, children earn a point if they complete their goals worksheet. They can spend that point immediately on a small toy prize or save points to use on a larger prize. We retrospectively calculated the percentage of points saved over the 12 weeks for 59 children (28 females) ages 8-12 years old (mean = 10.29 ± 1.39). Spearman correlation revealed that higher BMI percentile was associated with reduced point savings (r = 0.33, P = 0.01). Similarly, obese preadolescents saved significantly fewer points than healthy weight (HW) and overweight preadolescents (t (57) = 3.14, P delay gratification than overweight and HW children. Even for nonfood rewards, preadolescent children with higher BMIs prefer the immediate reward over a delayed, larger reward. This has implications for developing specific strategies within obesity treatments aimed at improving delayed gratification.

  11. Stochastic Simulation of Delay-Induced Circadian Rhythms in Drosophila

    Directory of Open Access Journals (Sweden)

    Xu Zhouyi

    2009-01-01

    Full Text Available Circadian rhythms are ubiquitous in all eukaryotes and some prokaryotes. Several computational models with or without time delays have been developed for circadian rhythms. Exact stochastic simulations have been carried out for several models without time delays, but no exact stochastic simulation has been done for models with delays. In this paper, we proposed a detailed and a reduced stochastic model with delays for circadian rhythms in Drosophila based on two deterministic models of Smolen et al. and employed exact stochastic simulation to simulate circadian oscillations. Our simulations showed that both models can produce sustained oscillations and that the oscillation is robust to noise in the sense that there is very little variability in oscillation period although there are significant random fluctuations in oscillation peeks. Moreover, although average time delays are essential to simulation of oscillation, random changes in time delays within certain range around fixed average time delay cause little variability in the oscillation period. Our simulation results also showed that both models are robust to parameter variations and that oscillation can be entrained by light/dark circles. Our simulations further demonstrated that within a reasonable range around the experimental result, the rates that dclock and per promoters switch back and forth between activated and repressed sites have little impact on oscillation period.

  12. Choice between delayed food and immediate oxycodone in rats.

    Science.gov (United States)

    Secci, Maria E; Factor, Julie A; Schindler, Charles W; Panlilio, Leigh V

    2016-12-01

    The choice to seek immediate drug effects instead of more meaningful but delayed rewards is a defining feature of addiction. To develop a rodent model of this behavior, we allowed rats to choose between immediate intravenous delivery of the prescription opioid oxycodone (50 μg/kg) and delayed delivery of palatable food pellets. Rats preferred food at delays up to 30 s, but they chose oxycodone and food equally at 60-s delay and preferred oxycodone over food at 120-s delay. Comparison of food-drug choice, food-only, and drug-only conditions indicated that food availability decreased drug intake, but drug availability increased food intake. In the food-only condition, food was effective as a reinforcer even when delayed by 120 s. Pre-session feeding with chow slowed acquisition of food and drug self-administration, but did not affect choice. To establish procedures for testing potential anti-addiction medications, noncontingent pre-treatment with oxycodone or naltrexone (analogous to substitution and antagonist therapies, respectively) were tested on a baseline in which oxycodone was preferred over delayed food. Naltrexone pre-treatment decreased drug intake and increased food intake. Oxycodone pre-treatment decreased drug intake, but also produced extended periods with no food or drug responding. These findings show that the contingencies that induce preference for drugs over more meaningful but less immediate rewards in humans can be modeled in rodents, and they suggest that the model could be useful for assessing the therapeutic potential of treatments and exploring the underlying behavioral and neural mechanisms involved in addiction.

  13. Chirped-pulse programming of optical coherent transient true-time delays.

    Science.gov (United States)

    Merkel, K D; Babbitt, W R

    1998-04-01

    Programming an optical coherent transient true-time delay device with two frequency-chirped pulses provides a novel means of performing broadband (> >GHz) true-time delay with a wide dynamic range of delays with fine temporal resolution. We have demonstrated true-time delays exceeding 2micros with sub-100-ps resolution. Chirped-pulse programming has the advantages over the previously proposed brief pulse programming [Opt. Lett. 21 1102 (1996)] of reduced instantaneous power requirements and the ability to control the true-time delay by frequency shifting the programming pulses.

  14. Online Scheduling in Manufacturing A Cumulative Delay Approach

    CERN Document Server

    Suwa, Haruhiko

    2013-01-01

    Online scheduling is recognized as the crucial decision-making process of production control at a phase of “being in production" according to the released shop floor schedule. Online scheduling can be also considered as one of key enablers to realize prompt capable-to-promise as well as available-to-promise to customers along with reducing production lead times under recent globalized competitive markets. Online Scheduling in Manufacturing introduces new approaches to online scheduling based on a concept of cumulative delay. The cumulative delay is regarded as consolidated information of uncertainties under a dynamic environment in manufacturing and can be collected constantly without much effort at any points in time during a schedule execution. In this approach, the cumulative delay of the schedule has the important role of a criterion for making a decision whether or not a schedule revision is carried out. The cumulative delay approach to trigger schedule revisions has the following capabilities for the ...

  15. Fusion Kalman filtration with k-step delay sharing pattern

    Directory of Open Access Journals (Sweden)

    Duda Zdzisław

    2015-09-01

    Full Text Available A fusion hierarchical state filtration with k−step delay sharing pattern for a multisensor system is considered. A global state estimate depends on local state estimates determined by local nodes using local information. Local available information consists of local measurements and k−step delay global information - global estimate sent from a central node. Local estimates are transmitted to the central node to be fused. The synthesis of local and global filters is presented. It is shown that a fusion filtration with k−step delay sharing pattern is equivalent to the optimal centralized classical Kalman filtration when local measurements are transmitted to the center node and used to determine a global state estimate. It is proved that the k−step delay sharing pattern can reduce covariances of local state errors.

  16. Opportunities for Process Monitoring Techniques at Delayed Access Facilities

    Energy Technology Data Exchange (ETDEWEB)

    Curtis, Michael M.; Gitau, Ernest TN; Johnson, Shirley J.; Schanfein, Mark; Toomey, Christopher

    2013-09-20

    Except for specific cases where the International Atomic Energy Agency (IAEA) maintains a continuous presence at a facility (such as the Japanese Rokkasho Reprocessing Plant), there is always a period of time or delay between the moment a State is notified or aware of an upcoming inspection, and the time the inspector actually enters the material balance area or facility. Termed by the authors as “delayed access,” this period of time between inspection notice and inspector entrance to a facility poses a concern. Delayed access also has the potential to reduce the effectiveness of measures applied as part of the Safeguards Approach for a facility (such as short-notice inspections). This report investigates the feasibility of using process monitoring to address safeguards challenges posed by delayed access at a subset of facility types.

  17. Brain Pyroglutamate Amyloid-Beta is Produced by Cathepsin B and is Reduced by the Cysteine Protease Inhibitor E64d, Representing a Potential Alzheimer’s Disease Therapeutic

    Science.gov (United States)

    Hook, Gregory; Yu, Jin; Toneff, Thomas; Kindy, Mark; Hook, Vivian

    2014-01-01

    Pyroglutamate amyloid-β peptides (pGlu-Aβ) are particularly pernicious forms of amyloid-β peptides (Aβ) present in Alzheimer’s disease (AD) brains. pGlu-Aβ peptides are N-terminally truncated forms of full-length Aβ peptides (flAβ(1-40/42)) in which the N-terminal glutamate is cyclized to pyroglutamate to generate pGlu-Aβ(3-40/42). β-secretase cleavage of amyloid-β precursor protein (AβPP) produces flAβ(1-40/42), but it is not yet known whether the β-secretase BACE1 or the alternative β-secretase cathepsin B (CatB) participate in the production of pGlu-Aβ. Therefore, this study examined the effects of gene knockout of these proteases on brain pGlu-Aβ levels in transgenic AβPPLon mice, which express AβPP isoform 695 and have the wild-type (wt) β-secretase activity found in most AD patients. Knockout or overexpression of the CatB gene reduced or increased, respectively, pGlu-Aβ(3-40/42), flAβ(1-40/42), and pGlu-Aβ plaque load, but knockout of the BACE1 gene had no effect on those parameters in the transgenic mice. Treatment of AβPPLon mice with E64d, a cysteine protease inhibitor of CatB, also reduced brain pGlu-Aβ(3-42), flAβ(1-40/42), and pGlu-Aβ plaque load. Treatment of neuronal-like chromaffin cells with CA074Me, an inhibitor of CatB, resulted in reduced levels of pGlu-Aβ(3-40) released from the activity-dependent, regulated secretory pathway. Moreover, CatB knockout and E64d treatment has been previously shown to improve memory deficits in the AβPPLon mice. These data illustrate the role of CatB in producing pGlu-Aβ and flAβ that participate as key factors in the development of AD. The advantages of CatB inhibitors, especially E64d and its derivatives, as alternatives to BACE1 inhibitors in treating AD patients are discussed. PMID:24595198

  18. Targeting surface nucleolin with a multivalent pseudopeptide delays development of spontaneous melanoma in RET transgenic mice

    Directory of Open Access Journals (Sweden)

    Briand Jean-Paul

    2010-06-01

    Full Text Available Abstract Background The importance of cell-surface nucleolin in cancer biology was recently highlighted by studies showing that ligands of nucleolin play critical role in tumorigenesis and angiogenesis. By using a specific antagonist that binds the C-terminal tail of nucleolin, the HB-19 pseudopeptide, we recently reported that HB-19 treatment markedly suppressed the progression of established human breast tumor cell xenografts in the athymic nude mice without apparent toxicity. Methods The in vivo antitumoral action of HB-19 treatment was assessed on the spontaneous development of melanoma in the RET transgenic mouse model. Ten days old RET mice were treated with HB-19 in a prophylactic setting that extended 300 days. In parallel, the molecular basis for the action of HB-19 was investigated on a melanoma cell line (called TIII derived from a cutaneous nodule of a RET mouse. Results HB-19 treatment of RET mice caused a significant delay in the onset of cutaneous tumors, several-months delay in the incidence of large tumors, a lower frequency of cutaneous nodules, and a reduction of visceral metastatic nodules while displaying no toxicity to normal tissue. Moreover, microvessel density was significantly reduced in tumors recovered from HB-19 treated mice compared to corresponding controls. Studies on the melanoma-derived tumor cells demonstrated that HB-19 treatment of TIII cells could restore contact inhibition, impair anchorage-independent growth, and reduce their tumorigenic potential in mice. Moreover, HB-19 treatment caused selective down regulation of transcripts coding matrix metalloproteinase 2 and 9, and tumor necrosis factor-α in the TIII cells and in melanoma tumors of RET mice. Conclusions Although HB-19 treatment failed to prevent the development of spontaneous melanoma in the RET mice, it delayed for several months the onset and frequency of cutaneous tumors, and exerted a significant inhibitory effect on visceral metastasis

  19. Kant and therapeutic privilege.

    Science.gov (United States)

    Brown, Chris

    2008-08-01

    Given Kant's exceptionless moral prohibition on lying, one might suspect that he is committed to a similar prohibition on withholding diagnostic and prognostic information from patients. I confirm this suspicion by adapting arguments against therapeutic privilege from his arguments against lying. However, I show that all these arguments are importantly flawed and submit that they should be rejected. A more compelling Kantian take on informed consent and therapeutic privilege is achievable, I argue, by focusing on Kant's duty of beneficence, which requires us to aim at furthering others' ends. But I show that there are some cases in which furthering a patient's ends requires withholding material medical information from her. Although I concede that these cases are probably quite rare, I conclude that the best Kantian thinking agrees with that of therapeutic privilege's advocates.

  20. Stochastic modelling of train delays and delay propagation in stations

    NARCIS (Netherlands)

    Yuan, J.

    2006-01-01

    A trade-off exists between efficiently utilizing the capacity of railway networks and improving the reliability and punctuality of train operations. This dissertation presents a new analytical probability model based on blocking time theory which estimates the knock-on delays of trains caused by

  1. Justice Delayed is Justice Denied

    Directory of Open Access Journals (Sweden)

    Naomi Burstyner

    2014-10-01

    Full Text Available This paper explores issues in the justice system that are related to timeliness and its interconnectedness to the definition of delay, whilst considering the impact of delay on the experience of the justice system user.Historical acknowledgements recognise the perspective of the accused or the disputant, and suggest that for a person seeking justice, the time taken for resolution of their issue is critical to the justice experience of this person and can render their treatment wholly ‘unjust’ in circumstances where closure takes ‘too long’.

  2. Therapeutic Approaches for Preserving or Restoring Pancreatic β-Cell Function and Mass

    Directory of Open Access Journals (Sweden)

    Kyong Yeun Jung

    2014-12-01

    Full Text Available The goal for the treatment of patients with diabetes has today shifted from merely reducing glucose concentrations to preventing the natural decline in β-cell function and delay the progression of disease. Pancreatic β-cell dysfunction and decreased β-cell mass are crucial in the development of diabetes. The β-cell defects are the main pathogenesis in patients with type 1 diabetes and are associated with type 2 diabetes as the disease progresses. Recent studies suggest that human pancreatic β-cells have a capacity for increased proliferation according to increased demands for insulin. In humans, β-cell mass has been shown to increase in patients showing insulin-resistance states such as obesity or in pregnancy. This capacity might be useful for identifying new therapeutic strategies to reestablish a functional β-cell mass. In this context, therapeutic approaches designed to increase β-cell mass might prove a significant way to manage diabetes and prevent its progression. This review describes the various β-cell defects that appear in patients with diabetes and outline the mechanisms of β-cell failure. We also review common methods for assessing β-cell function and mass and methodological limitations in vivo. Finally, we discuss the current therapeutic approaches to improve β-cell function and increase β-cell mass.

  3. 49 CFR 236.563 - Delay time.

    Science.gov (United States)

    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. ...

  4. Lymphedema and Therapeutic Lymphangiogenesis

    Directory of Open Access Journals (Sweden)

    Yukihiro Saito

    2013-01-01

    Full Text Available Lymphedema is a disorder of the lymphatic vascular system characterized by impaired lymphatic return and swelling of the extremities. Lymphedema is divided into primary and secondary forms based on the underlying etiology. Despite substantial advances in both surgical and conservative techniques, therapeutic options for the management of lymphedema are limited. Although rarely lethal, lymphedema is a disfiguring and disabling condition with an associated decrease in the quality of life. The recent impressive expansion of knowledge on the molecular mechanisms governing lymphangiogenesis provides new possibilities for the treatment of lymphedema. This review highlights the lymphatic biology, the pathophysiology of lymphedema, and the therapeutic lymphangiogenesis using hepatocyte growth factor.

  5. Therapeutic development in psoriasis.

    Science.gov (United States)

    Sobell, Jeffrey M; Leonardi, Craig L

    2014-06-01

    Advances in molecular biology have provided the basis for development of new therapeutic approaches to psoriasis. New, more effective therapies target specific molecules in the inflammatory cascade involved in the pathogenesis of psoriasis.The biologic era of psoriasis therapy began with inhibitors of T-cell activation, tumor necrosis factor-α, and interleukin (IL)-12/23. Continued investigation has led to therapies and therapeutic candidates that target IL-17, IL-23, phosphodiesterase-4, and isomers of Janus kinase. 2014 by Frontline Medical Communications Inc.

  6. Mind-Body Interventions to Reduce Risk for Health Disparities Related to Stress and Strength Among African American Women: The Potential of Mindfulness-Based Stress Reduction, Loving-Kindness, and the NTU Therapeutic Framework

    Science.gov (United States)

    Woods-Giscombé, Cheryl L.; Black, Angela R.

    2011-01-01

    In the current article, the authors examine the potential role of mind-body interventions for preventing or reducing health disparities in a specific group—African American women. The authors first discuss how health disparities affect this group, including empirical evidence regarding the influence of biopsychosocial processes (e.g., psychological stress and social context) on disparate health outcomes. They also detail how African American women's unique stress experiences as a result of distinct sociohistorical and cultural experiences related to race and gender potentially widen exposure to stressors and influence stress responses and coping behaviors. Using two independent, but related, frameworks (Superwoman Schema [SWS] and the Strong Black Woman Script [SBW-S]), they discuss how, for African American women, stress is affected by “strength” (vis-à-vis resilience, fortitude, and self-sufficiency) and the emergent health-compromising behaviors related to strength (e.g., emotional suppression, extraordinary caregiving, and self-care postponement). The authors then describe the potential utility of three mind-body interventions—mindfulness-based stress reduction (MBSR), loving-kindness meditation (LKM), and NTU psychotherapy—for specifically targeting the stress-, strength-, and contextually related factors that are thought to influence disparate outcomes for African American women. Self-awareness, self-care, inter- and intrapersonal restorative healing and a redefinition of inner strength may manifest through developing a mindfulness practice to decrease stress-related responses; using LKM to cultivate compassion and forgiveness for self and others; and the balance of independence and interdependence as a grounding NTU principle for redefining strength. The authors conclude with a discussion of potential benefits for integrating key aspects of the interventions with recommendations for future research. PMID:21479157

  7. Therapeutic Recombinant Monoclonal Antibodies

    Science.gov (United States)

    Bakhtiar, Ray

    2012-01-01

    During the last two decades, the rapid growth of biotechnology-derived techniques has led to a myriad of therapeutic recombinant monoclonal antibodies with significant clinical benefits. Recombinant monoclonal antibodies can be obtained from a number of natural sources such as animal cell cultures using recombinant DNA engineering. In contrast to…

  8. Therapeutic HPV DNA vaccines

    Science.gov (United States)

    Lin, Ken; Roosinovich, Elena; Ma, Barbara; Hung, Chien-Fu

    2010-01-01

    It is now well established that most cervical cancers are causally associated with HPV infection. This realization has led to efforts to control HPV-associated malignancy through prevention or treatment of HPV infection. Currently, commercially available HPV vaccines are not designed to control established HPV infection and associated premalignant and malignant lesions. To treat and eradicate pre-existing HPV infections and associated lesions which remain prevalent in the U.S. and worldwide, effective therapeutic HPV vaccines are needed. DNA vaccination has emerged as a particularly promising form of therapeutic HPV vaccines due to its safety, stability and ability to induce antigen-specific immunity. This review focuses on improving the potency of therapeutic HPV vaccines through modification of dendritic cells (DCs) by [1] increasing the number of antigen-expressing/antigen-loaded DCs, [2] improving HPV antigen expression, processing and presentation in DCs, and [3] enhancing DC and T cell interaction. Continued improvement in therapeutic HPV DNA vaccines may ultimately lead to an effective DNA vaccine for the treatment of HPV-associated malignancies. PMID:20066511

  9. Livermore blasted for project delay

    CERN Multimedia

    1999-01-01

    In a 12 page report issued last week, a review committee set up by the University of California has concluded that mismanagement and poor planning are to blame for significant cost overruns and delays in the construction of NIF, the worlds largest laser (1 page).

  10. EAMJ Delayed April 10.indd

    African Journals Online (AJOL)

    2010-04-04

    Apr 4, 2010 ... Patient delay accounts for a large proportion of those who present with late stage disease especially ... Data collection: All patients diagnosed with breast cancer who certified the inclusion criteria were ..... Ingram, D.M., Huang, H.Y., Catchpole, B.N. and. Roberts, A. Do big breasts disadvantage women with.

  11. Diagnostic Delay in Rheumatoid Arthritis

    DEFF Research Database (Denmark)

    Mølbaek, Karen; Hørslev-Petersen, Kim; Primdahl, Jette

    2016-01-01

    BACKGROUND: To prevent joint damage among patients with rheumatoid arthritis (RA), there is a need to minimize delays from the onset of symptoms until the initiation of appropriate therapy. The present study explored the factors that have an impact on the time it takes for Danish patients with RA...

  12. Design flaw could delay collider

    CERN Multimedia

    Cho, Adrian

    2007-01-01

    "A magnet for the Large Hadron Collider (LHC) failed during a key test at the European particle physics laboratory CERN last week. Physicists and engineers will have to repair the damaged magnet and retrofit others to correct the underlynig design flaw, which could delay the start-up of the mammouth subterranean machine." (1,5 page)

  13. Delayed logistic population models revisited

    OpenAIRE

    Liz, Eduardo

    2014-01-01

    We discuss the global dynamics of some logistic models governed by delay-differential equations. We focus on models of exploited populations, and study the changes in the dynamics as the harvesting effort is increased. We get new results and highlight the link among different logistic equations usually employed in population models.

  14. Providing delay guarantees in Bluetooth

    NARCIS (Netherlands)

    Ait Yaiz, R.; Heijenk, Geert; Titsworth, F.

    2003-01-01

    Bluetooth polling, also referred to as Bluetooth MAC scheduling or intra-piconet scheduling, is the mechanism that schedules the traffic between the participants in a Bluetooth network. Hence, this mechanism is highly determining with respect to the delay packets experience in a Bluetooth network.

  15. Tooth formation - delayed or absent

    Science.gov (United States)

    ... tooth formation; Teeth - delayed or absent formation Images Tooth anatomy Development of baby teeth Development of permanent teeth References ... MO: Elsevier Mosby; 2016:chap 19. Tinanoff N. Development and developmental anomalies of the teeth. In: Kliegman RM, ... NIH MedlinePlus Magazine Read more ...

  16. Early-delayed radiation rhombencephalopathy

    Energy Technology Data Exchange (ETDEWEB)

    Nightingale, S.; Dawes, P.J.D.K.; Cartlidge, N.E.F. (Royal Victoria Infirmary, Newcastle upon Tyne (UK); Newcastle upon Tyne Univ. (UK). Newcastle General Hospital)

    1982-03-01

    A 37-year-old woman developed an early-delayed rhombencephalopathy 7 weeks after completing a course of radiotherapy to a glomus jugulare tumour. The clinical features, comprising nystagmus, skew strabismus, unilateral facial weakness, dysarthria and ataxia, are compared with four previously reported patients with this syndrome.

  17. Deconstructing delayed posttraumatic stress disorder

    NARCIS (Netherlands)

    Smid, G

    2011-01-01

    According to the Diagnostic and Statistical Manual of Mental Disorders, delayed posttraumatic stress disorder (PTSD) must be diagnosed in individuals fulfilling criteria for PTSD if the onset of symptoms is at least six months after the trauma. The purpose of this thesis was to establish the

  18. Therapeutic targets of brain insulin resistance in sporadic Alzheimer's disease.

    Science.gov (United States)

    de la Monte, Suzanne M

    2012-01-01

    Growing evidence supports roles for brain insulin and insulin-like growth factor (IGF) resistance and metabolic dysfunction in the pathogenesis of Alzheimer's disease (AD). Whether the underlying problem stems from a primary disorder of central nervous system (CNS) neurons and glia, or secondary effects of systemic diseases such as obesity, Type 2 diabetes, or metabolic syndrome, the end-results include impaired glucose utilization, mitochondrial dysfunction, increased oxidative stress, neuroinflammation, and the propagation of cascades that result in the accumulation of neurotoxic misfolded, aggregated, and ubiquitinated fibrillar proteins. This article reviews the roles of impaired insulin and IGF signaling to AD-associated neuronal loss, synaptic disconnection, tau hyperphosphorylation, amyloid-beta accumulation, and impaired energy metabolism, and discusses therapeutic strategies and lifestyle approaches that could be used to prevent, delay the onset, or reduce the severity of AD. Finally, it is critical to recognize that AD is heterogeneous and has a clinical course that fully develops over a period of several decades. Therefore, early and multi-modal preventive and treatment approaches should be regarded as essential.

  19. Fundamentals of Delayed Coking Joint Industry Project

    Energy Technology Data Exchange (ETDEWEB)

    Michael Volk Jr; Keith Wisecarver

    2005-10-01

    Delayed coking evolved steadily over the early to mid 1900s to enable refiners to convert high boiling, residual petroleum fractions to light products such as gasoline. Pound for pound, coking is the most energy intensive of any operation in a modern refinery. Large amounts of energy are required to heat the thick, poor-quality petroleum residuum to the 900 to 950 degrees F required to crack the heavy hydrocarbon molecules into lighter, more valuable products. One common misconception of delayed coking is that the product coke is a disadvantage. Although coke is a low valued (near zero economic value) byproduct, compared to transportation fuels, there is a significant worldwide trade and demand for coke as it is an economical fuel. Coke production has increased steadily over the last ten years, with further increases forecast for the foreseeable future. Current domestic production is near 111,000 tons per day. A major driving force behind this increase is the steady decline in crude quality available to refiners. Crude slates are expected to grow heavier with higher sulfur contents while environmental restrictions are expected to significantly reduce the demand for high-sulfur residual fuel oil. Light sweet crudes will continue to be available and in even greater demand than they are today. Refiners will be faced with the choice of purchasing light sweet crudes at a premium price, or adding bottom of the barrel upgrading capability, through additional new investments, to reduce the production of high-sulfur residual fuel oil and increase the production of low-sulfur distillate fuels. A second disadvantage is that liquid products from cokers frequently are unstable, i.e., they rapidly form gum and sediments. Because of intermediate investment and operating costs, delayed coking has increased in popularity among refiners worldwide. Based on the 2000 Worldwide Refining Survey published in the Oil and Gas, the delayed coking capacity for 101 refineries around the world

  20. A pulverização pré-colheita com ácido giberélico (GA3 e aminoetoxivinilglicina (AVG retarda a maturação e reduz as perdas de frutos na cultura do pessegueiro Preharvest spraying with gibberellic acid (GA3 and aminoethoxyvinilglycine (AVG delays fruit maturity and reduces fruit losses on peaches

    Directory of Open Access Journals (Sweden)

    Cassandro Vidal Talamini do Amarante

    2005-04-01

    mg L-1 delayed fruit maturity at harvest and during cold storage (4 weeks at 0-2ºC/90-95% RH, resulting in a better retention of skin background color, the least reduction of flesh firmness, the least increasing of acidity, and the least increasing of soluble solids content (ºBrix. The treatment with GA3 (100 mg L-1 was more effective than AVG (75 and 150 mg L-1 to delay fruit maturity. In addition, GA3 reduced the number of fruit with skin splitting and decay, increased the fruit average weight at harvest, and reduced the incidence of flesh browning after cold storage. The AVG increased fruit skin splitting.

  1. Recent Advances on Pathophysiology, Diagnostic and Therapeutic Insights in Cardiac Dysfunction Induced by Antineoplastic Drugs

    Directory of Open Access Journals (Sweden)

    Marilisa Molinaro

    2015-01-01

    Full Text Available Along with the improvement of survival after cancer, cardiotoxicity due to antineoplastic treatments has emerged as a clinically relevant problem. Potential cardiovascular toxicities due to anticancer agents include QT prolongation and arrhythmias, myocardial ischemia and infarction, hypertension and/or thromboembolism, left ventricular (LV dysfunction, and heart failure (HF. The latter is variable in severity, may be reversible or irreversible, and can occur soon after or as a delayed consequence of anticancer treatments. In the last decade recent advances have emerged in clinical and pathophysiological aspects of LV dysfunction induced by the most widely used anticancer drugs. In particular, early, sensitive markers of cardiac dysfunction that can predict this form of cardiomyopathy before ejection fraction (EF is reduced are becoming increasingly important, along with novel therapeutic and cardioprotective strategies, in the attempt of protecting cardiooncologic patients from the development of congestive heart failure.

  2. Robustness of delayed multistable systems with application to droop-controlled inverter-based microgrids

    Science.gov (United States)

    Efimov, Denis; Schiffer, Johannes; Ortega, Romeo

    2016-05-01

    Motivated by the problem of phase-locking in droop-controlled inverter-based microgrids with delays, the recently developed theory of input-to-state stability (ISS) for multistable systems is extended to the case of multistable systems with delayed dynamics. Sufficient conditions for ISS of delayed systems are presented using Lyapunov-Razumikhin functions. It is shown that ISS multistable systems are robust with respect to delays in a feedback. The derived theory is applied to two examples. First, the ISS property is established for the model of a nonlinear pendulum and delay-dependent robustness conditions are derived. Second, it is shown that, under certain assumptions, the problem of phase-locking analysis in droop-controlled inverter-based microgrids with delays can be reduced to the stability investigation of the nonlinear pendulum. For this case, corresponding delay-dependent conditions for asymptotic phase-locking are given.

  3. A review of nutritional intervention on delayed onset muscle soreness. Part I.

    Science.gov (United States)

    Kim, Jooyoung; Lee, Joohyung

    2014-12-01

    This review is focused on the effect of nutritional intervention on delayed onset muscle soreness (DOMS) that occurs after exercise. In general, high force eccentric contractions and/or unaccustomed exercise result in DOMS attributed to reduction in performance such as muscle strength and range of motion (ROM) for both athletes and non-athletes. Nutritional intervention is one of the preventive or therapeutic ways to reduce DOMS. Previous research studies have suggested the following nutrition intervention: caffeine, omega-3 fatty acids, taurine, polyphenols, and so on. Nutritional intervention with these nutrients before and after exercise was reported to be effective in reducing DOMS. These nutritional interventions have also been reported to affect inflammatory responses and oxidative stress leading to DOMS reduction. However, other studies have reported that these nutritional interventions have no effect on DOMS. It is suggested that intake of proper nutrition intervention can effectively reduce DOMS after exercise and quickly help an athlete return to exercise or training program. In addition, nutritional intervention may help both athletes and non-athletes who engage in physical therapy or rehabilitative programs after surgery or any injurious events.

  4. Prototype high speed optical delay line for stellar interferometry

    Science.gov (United States)

    Colavita, M. M.; Hines, B. E.; Shao, M.; Klose, G. J.; Gibson, B. V.

    1991-01-01

    The long baselines of the next-generation ground-based optical stellar interferometers require optical delay lines which can maintain nm-level path-length accuracy while moving at high speeds. NASA-JPL is currently designing delay lines to meet these requirements. The design is an enhanced version of the Mark III delay line, with the following key features: hardened, large diameter wheels, rather than recirculating ball bearings, to reduce mechanical noise; a friction-drive cart which bears the cable-dragging forces, and drives the optics cart through a force connection only; a balanced PZT assembly to enable high-bandwidth path-length control; and a precision aligned flexural suspension for the optics assembly to minimize bearing noise feedthrough. The delay line is fully programmable in position and velocity, and the system is controlled with four cascaded software feedback loops. Preliminary performance is a jitter in any 5 ms window of less than 10 nm rms for delay rates of up to 28 mm/s; total jitter is less than 10 nm rms for delay rates up to 20 mm/s.

  5. Swing Damping for Helicopter Slung Load Systems using Delayed Feedback

    DEFF Research Database (Denmark)

    Bisgaard, Morten; la Cour-Harbo, Anders; Bendtsen, Jan Dimon

    2009-01-01

    helicopters. The delayed feedback controller is added to actively reduce oscillations of the slung load by improving the damping of the slung load pendulum modes. Furthermore, it is intended for integration with a feedforward control scheme based on input shaping for concurrent avoidance and dampening...

  6. NORMAL-FORM IN A DELAY-INSENSITIVE ALGEBRA

    NARCIS (Netherlands)

    GROENBOOM, R; JOSEPHS, MB; LUCASSEN, PG; UDDING, JT; Furber, S; Edwards, M

    1993-01-01

    A process algebra is given for specifying delay-insensitive processes. We show in two steps that expressions in this algebra have a normal form, as a consequence of which the algebra is complete. First, the number of operators in process expressions is reduced by a set of rewrite laws. The resulting

  7. A systems thinking approach to eliminate delays on building ...

    African Journals Online (AJOL)

    It is obvious that the performance of firms and their market competitiveness hinge on project delivery time. Many approaches have been used to reduce the effect of the potential factors of delay on project delivery time. In this study, the system approach has been employed and validated. Inferential statistical analysis was ...

  8. [Therapeutic Aggressiveness and Liquid Oncology].

    Science.gov (United States)

    Barón Duarte, F J; Rodríguez Calvo, M S; Amor Pan, J R

    2017-01-01

    Aggressiveness criteria proposed in the scientific literature a decade ago provide a quality judgment and are a reference in the care of patients with advanced cancer, but their use is not generalized in the evaluation of Oncology Services. In this paper we analyze the therapeutic aggressiveness, according to standard criteria, in 1.001 patients with advanced cancer who died in our Institution between 2010 and 2013. The results seem to show that aggressiveness at the end of life is present more frequently than experts recommend. About 25% of patients fulfill at least one criterion of aggressiveness. This result could be explained by a liquid Oncology which does not prioritize the patient as a moral subject in the clinical appointment. Medical care is oriented to necessities and must be articulated in a model focused on dignity and communication. Its implementation through Advanced Care Planning, consideration of patient's values and preferences, and Limitation of therapeutic effort are ways to reduce aggressiveness and improve clinical practice at the end of life. We need to encourage synergic and proactive attitudes, adding the best of cancer research with the best clinical care for the benefit of human being, moral subject and main goal of Medicine.

  9. Multistage vector (MSV) therapeutics

    Science.gov (United States)

    Wolfram, Joy; Shen, Haifa; Ferrari, Mauro

    2015-01-01

    One of the greatest challenges in the field of medicine is obtaining controlled distribution of systemically administered therapeutic agents within the body. Indeed, biological barriers such as physical compartmentalization, pressure gradients, and excretion pathways adversely affect localized delivery of drugs to pathological tissue. The diverse nature of these barriers requires the use of multifunctional drug delivery vehicles that can overcome a wide range of sequential obstacles. In this review, we explore the role of multifunctionality in nanomedicine by primarily focusing on multistage vectors (MSVs). The MSV is an example of a promising therapeutic platform that incorporates several components, including a microparticle, nanoparticles, and small molecules. In particular, these components are activated in a sequential manner in order to successively address transport barriers. PMID:26264836

  10. Acylation of Therapeutic Peptides

    DEFF Research Database (Denmark)

    Trier, Sofie; Henriksen, Jonas Rosager; Jensen, Simon Bjerregaard

    Oral administration of therapeutic peptides could benefit millions of chronically ill people worldwide, through easier and less stigmatized therapy, and likely improve the long-term effects of currently widespread disease mismanagement. However, oral peptide delivery is a formidable task due......, but it is not widely studied in an oral context. As acylation furthermore increases interactions with the lipid membranes of mammalian cells, it offers several potential benefits for oral delivery of therapeutic peptides, and we hypothesize that tailoring the acylation may be used to optimize intestinal translocation...... to the harsh and selective gastrointestinal system, and development has lacked far behind injection therapy. Peptide acylation is a powerful tool to alter the pharmacokinetics, biophysical properties and chemical stability of injectable peptide drugs, primarily used to prolong blood circulation...

  11. Therapeutic use of cannabis.

    Science.gov (United States)

    de Vries, Kay; Green, Anita J

    Therapeutic cannabis use raises a number of dilemmas for nurses. This article examines the legal, political and ethical challenges raised by the use of cannabis by people with life-limiting or terminal illnesses in their own homes. (Throughout this paper, the term cannabis refers to illegal cannabis unless specified.) A literature review of databases from 1996 was conducted and internet material was also examined. Evidence on the therapeutic use of cannabis suggests it may produce improvements in quality of life, which has led to increased use among people with life-limiting illnesses. The cannabis used is usually obtained illegally, which can have consequences for both those who use it and nurses who provide treatment in the community.

  12. Leech Therapeutic Applications

    OpenAIRE

    Abdualkader, A. M.; A M Ghawi; Alaama, M.; M. Awang; A Merzouk

    2013-01-01

    Hematophagous animals including leeches have been known to possess biologically active compounds in their secretions, especially in their saliva. The blood-sucking annelids, leeches have been used for therapeutic purposes since the beginning of civilization. Ancient Egyptian, Indian, Greek and Arab physicians used leeches for a wide range of diseases starting from the conventional use for bleeding to systemic ailments, such as skin diseases, nervous system abnormalities, urinary and reproduct...

  13. Delay of Vehicle Motion in Traffic Dynamics

    CERN Document Server

    Bando, M; Nakanishi, K; Nakayama, A; Bando, Masako; Hasebe, Katsuya; Nakanishi, Ken; Nakayama, Akihiro

    1996-01-01

    We demonstrate that in Optimal Velocity Model (OVM) delay times of vehicles coming from the dynamical equation of motion of OVM almost explain the order of delay times observed in actual traffic flows without introducing explicit delay times. Delay times in various cases are estimated: the case of a leader vehicle and its follower, a queue of vehicles controlled by traffic lights and many-vehicle case of highway traffic flow. The remarkable result is that in most of the situation for which we can make a reasonable definition of a delay time, the obtained delay time is of order 1 second.

  14. Delayed Posthypoxic Leukoencephalopathy: Improvement with Antioxidant Therapy

    Directory of Open Access Journals (Sweden)

    Franklin King

    2015-12-01

    Full Text Available Introduction: Delayed posthypoxic leukoencephalopathy (DPHL may result from a variety of hypoxic insults, including respiratory depression from an opiate overdose. The underlying pathophysiological mechanism of DPHL remains uncertain. We describe a patient with a typical case of DPHL who responded clinically to antioxidant treatment. Methods: Clinical, serological, and radiographic investigations were undertaken in the evaluation of the patient. Results: A 63-year-old man developed altered mental status 10 days following recovery from an opiate overdose and aspiration pneumonia that required intubation. The clinical course and brain imaging were consistent with DPHL. Initiation of antioxidant therapy with vitamin E, vitamin C, B-complex vitamins, and coenzyme Q10 coincided with the prompt reversal of clinical deterioration. Conclusions: The potential therapeutic effect of antioxidants on DPHL needs to be explored in future cases. If this relationship indeed holds true, it would be consistent with the hypothesis that formation of reactive oxygen species during reperfusion plays a role in the pathophysiology of this disorder.

  15. Minimum Delay Moving Object Detection

    KAUST Repository

    Lao, Dong

    2017-01-08

    We present a general framework and method for detection of an object in a video based on apparent motion. The object moves relative to background motion at some unknown time in the video, and the goal is to detect and segment the object as soon it moves in an online manner. Due to unreliability of motion between frames, more than two frames are needed to reliably detect the object. Our method is designed to detect the object(s) with minimum delay, i.e., frames after the object moves, constraining the false alarms. Experiments on a new extensive dataset for moving object detection show that our method achieves less delay for all false alarm constraints than existing state-of-the-art.

  16. Minimum Delay Moving Object Detection

    KAUST Repository

    Lao, Dong

    2017-11-09

    We present a general framework and method for detection of an object in a video based on apparent motion. The object moves relative to background motion at some unknown time in the video, and the goal is to detect and segment the object as soon it moves in an online manner. Due to unreliability of motion between frames, more than two frames are needed to reliably detect the object. Our method is designed to detect the object(s) with minimum delay, i.e., frames after the object moves, constraining the false alarms. Experiments on a new extensive dataset for moving object detection show that our method achieves less delay for all false alarm constraints than existing state-of-the-art.

  17. Air congestion delay: a review

    Directory of Open Access Journals (Sweden)

    Daniel Alberto Pamplona

    2016-04-01

    Full Text Available This article is a literature review of the air congestion delay and its costs. Air congestion is a worldwide problem. Its existence brings costs for airlines and discomfort for passengers. With the increasing demand for air transport, the study of air congestion has attracted the attention of many researchers around the world. The cause for the delays is erroneously attributed only to the lack of infrastructure investments. The literature review shows that other factors such as population growth, increasing standards of living, lack of operational planning and environmental issues exercise decisive influence. Several studies have been conducted in order to analyze and propose solutions to this problem that affects society as a whole.

  18. Riluzole improves outcome following ischemia-reperfusion injury to the spinal cord by preventing delayed paraplegia.

    Science.gov (United States)

    Wu, Y; Satkunendrarajah, K; Fehlings, M G

    2014-04-18

    The spinal cord is vulnerable to ischemic injury due to trauma, vascular malformations and correction of thoracic aortic lesions. Riluzole, a sodium channel blocker and anti-glutamate drug has been shown to be neuroprotective in a model of ischemic spinal cord injury, although the effects in clinically relevant ischemia/reperfusion models are unknown. Here, we examine the effect of riluzole following ischemia-reperfusion injury to the spinal cord. Female rats underwent high thoracic aortic balloon occlusion to produce an ischemia/reperfusion injury. Tolerance to ischemia was evaluated by varying the duration of occlusion. Riluzole (8mg/kg) was injected intraperitoneally 4h after injury. Locomotor function (Basso, Beattie and Bresnahan (BBB) scale) was assessed at 4h, 1day, and 5days post-ischemia. Spinal cords were extracted and evaluated for neuronal loss using immunohistology (choline acetyltransferase (ChAT) and neuronal nuclei (NeuN)), inflammation (CD11b), astrogliosis (glial fibrillary acidic protein - GFAP) and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). Ischemic injury lasting between 5.5 and 6.75min resulted in delayed paraplegia, whereas longer ischemia induced immediate paraplegia. When riluzole was administered to rats that underwent 6min of occlusion, delayed paraplegia was prevented. The BBB score of riluzole-treated rats was 11.14±4.85 compared with 1.86±1.07 in control animals. Riluzole also reduced neuronal loss, infiltration of microglia/macrophages and astrogliosis in the ventral horn and intermediate zone of the gray matter. In addition, riluzole reduced apoptosis of neurons in the dorsal horn of the gray matter. Riluzole has a neuroprotective effect in a rat model of spinal cord injury/reperfusion when administered up to 4h post-injury, a clinically relevant therapeutic time window. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  19. Assembly delay line pulse generators

    CERN Multimedia

    CERN PhotoLab

    1971-01-01

    Assembly of six of the ten delay line pulse generators that will power the ten kicker magnet modules. One modulator part contains two pulse generators. Capacitors, inductances, and voltage dividers are in the oil tank on the left. Triggered high-pressure spark gap switches are on the platforms on the right. High voltage pulse cables to the kicker magnet emerge under the spark gaps. In the centre background are the assembled master gaps.

  20. ATLAS calibration delay chip study

    CERN Document Server

    Massol, N

    2003-01-01

    The delay chip is an ASIC developed to precisely adjust signals within the range of 0-24ns in steps of 1ns. In this note, we report the study of the characteristics of this chip like the linearity and the jitter. We describe the influence of temperature and supply voltage on its behavior. Finally, we study its dependency due to the variations in process on a whole production.

  1. Teriparatide Induced Delayed Persistent Hypercalcemia

    Directory of Open Access Journals (Sweden)

    Nirosshan Thiruchelvam

    2014-01-01

    Full Text Available Teriparatide, a recombinant PTH, is an anabolic treatment for osteoporosis that increases bone density. Transient hypercalcemia is a reported side effect of teriparatide that is seen few hours following administration of teriparatide and resolves usually within 16 hours of drug administration. Persistent hypercalcemia, although not observed in clinical trials, is rarely reported. The current case describes a rare complication of teriparatide induced delayed persistent hypercalcemia.

  2. Teriflunomide reduces behavioral, electrophysiological, and histopathological deficits in the Dark Agouti rat model of experimental autoimmune encephalomyelitis.

    Science.gov (United States)

    Merrill, Jean E; Hanak, Susan; Pu, Su-Fen; Liang, Jinjun; Dang, Chelsea; Iglesias-Bregna, Deborah; Harvey, Brian; Zhu, Bin; McMonagle-Strucko, Kathleen

    2009-01-01

    Teriflunomide is an orally available anti-inflammatory drug that prevents T and B cell proliferation and function by inhibition of dihydroorotate dehydrogenase. It is currently being developed for the treatment of multiple sclerosis (MS). We report here for the first time the anti-inflammatory effects of teriflunomide in the Dark Agouti rat model of experimental autoimmune encephalomyelitis (EAE). Neurological evaluation demonstrated that prophylactic dosing of teriflunomide at 3 and 10 mg/kg delayed disease onset and reduced maximal and cumulative scores. Therapeutic administration of teriflunomide at doses of 3 or 10 mg/kg at disease onset significantly reduced maximal and cumulative disease scores as compared to vehicle treated rats. Dosing teriflunomide at disease remission, at 3 and 10 mg/kg, reduced the cumulative scores for the remaining course of the disease. Teriflunomide at 10 mg/kg significantly reduced inflammation, demyelination, and axonal loss when dosed prophylactically or therapeutically. In electrophysiological somatosensory evoked potential studies, therapeutic administration of teriflunomide, at the onset of disease, prevented both a decrease in waveform amplitude and an increase in the latency to waveform initiation in EAE animals compared to vehicle. Therapeutic dosing with teriflunomide at disease remission prevented a decrease in evoked potential amplitude, prevented an increase in latency, and enhanced recovery time within the CNS.

  3. Moist Heat or Dry Heat for Delayed Onset Muscle Soreness

    OpenAIRE

    Petrofsky, Jerrold; Berk, Lee; Bains, Gurinder; Khowailed, Iman Akef; Hui, Timothy; Granado, Michael; Laymon, Mike; Lee, Haneul

    2013-01-01

    Background Heat is commonly used in physical therapy following exercise induced delayed onset muscle soreness (DOMS). Most heat modalities used in a clinical setting for DOMS are only applied for 5 to 20 minutes. This minimal heat exposure causes little, if any, change in deep tissue temperature. For this reason, long duration dry chemical heat packs are used at home to slowly and safely warm tissue and reduce potential heat damage while reducing pain associated from DOMS. Clinically, it has ...

  4. Minimum Delay Moving Object Detection

    KAUST Repository

    Lao, Dong

    2017-05-14

    This thesis presents a general framework and method for detection of an object in a video based on apparent motion. The object moves, at some unknown time, differently than the “background” motion, which can be induced from camera motion. The goal of proposed method is to detect and segment the object as soon it moves in an online manner. Since motion estimation can be unreliable between frames, more than two frames are needed to reliably detect the object. Observing more frames before declaring a detection may lead to a more accurate detection and segmentation, since more motion may be observed leading to a stronger motion cue. However, this leads to greater delay. The proposed method is designed to detect the object(s) with minimum delay, i.e., frames after the object moves, constraining the false alarms, defined as declarations of detection before the object moves or incorrect or inaccurate segmentation at the detection time. Experiments on a new extensive dataset for moving object detection show that our method achieves less delay for all false alarm constraints than existing state-of-the-art.

  5. Novel therapeutic mechanisms determine the effectiveness of lipid-core nanocapsules on melanoma models.

    Science.gov (United States)

    Drewes, Carine C; Fiel, Luana A; Bexiga, Celina G; Asbahr, Ana Carolina C; Uchiyama, Mayara K; Cogliati, Bruno; Araki, Koiti; Guterres, Sílvia S; Pohlmann, Adriana R; Farsky, Sandra P

    2016-01-01

    Melanoma is a severe metastatic skin cancer with poor prognosis and no effective treatment. Therefore, novel therapeutic approaches using nanotechnology have been proposed to improve therapeutic effectiveness. Lipid-core nanocapsules (LNCs), prepared with poly(ε-caprolactone), capric/caprylic triglyceride, and sorbitan monostearate and stabilized by polysorbate 80, are efficient as drug delivery systems. Here, we investigated the effects of acetyleugenol-loaded LNC (AcE-LNC) on human SK-Mel-28 melanoma cells and its therapeutic efficacies on melanoma induced by B16F10 in C57B6 mice. LNC and AcE-LNC had z-average diameters and zeta potential close to 210 nm and -10.0 mV, respectively. CytoViva(®) microscopy images showed that LNC and AcE-LNC penetrated into SK-Mel-28 cells, and remained in the cytoplasm. AcE-LNC in vitro treatment (18-90×10(9) particles/mL; 1 hour) induced late apoptosis and necrosis; LNC and AcE-LNC (3-18×10(9) particles/mL; 48 hours) treatments reduced cell proliferation and delayed the cell cycle. Elevated levels of nitric oxide were found in supernatant of LNC and AcE-LNC, which were not dependent on nitric oxide synthase expressions. Daily intraperitoneal or oral treatment (days 3-10 after tumor injection) with LNC or AcE-LNC (1×10(12) particles/day), but not with AcE (50 mg/kg/day, same dose as AcE-LNC), reduced the volume of the tumor; nevertheless, intraperitoneal treatment caused toxicity. Oral LNC treatment was more efficient than AcE-LNC treatment. Moreover, oral treatment with nonencapsulated capric/caprylic triglyceride did not inhibit tumor development, implying that nanocapsule supramolecular structure is important to the therapeutic effects. Together, data herein presented highlight the relevance of the supramolecular structure of LNCs to toxicity on SK-Mel-28 cells and to the therapeutic efficacy on melanoma development in mice, conferring novel therapeutic mechanisms to LNC further than a drug delivery system.

  6. A comparative study on the therapeutic effect of TRPV1, TRPA1, and TRPM8 agonists on swallowing dysfunction associated with aging and neurological diseases.

    Science.gov (United States)

    Alvarez-Berdugo, D; Rofes, L; Arreola, V; Martin, A; Molina, L; Clavé, P

    2017-08-11

    Oropharyngeal sensory impairment is a potential target to treat swallowing dysfunction in patients with oropharyngeal dysphagia (OD). To assess the therapeutic effect of stimulating oropharyngeal sensory afferents with TRPV1, TRPA1, or TRPM8 agonists vs increasing bolus viscosity in older and neurologic patients with OD by comparing four studies of similar experimental design. Swallow function of 142 older patients with impaired safety of swallow at nectar ([50-350] mPa·s) viscosity was evaluated with videofluoroscopy (VFS) while treated with TRPV1 (150 μmol/L), TRPV1/A1 (150 μmol/L and 1 mmol/L), or TRPM8 (1 mmol/L or 10 mmol/L) agonists or modified starch (MS) at spoon thick viscosity (>1750 mPa·s). TRPV1 stimulation with capsaicinoids reduced penetrations by 50%, pharyngeal residue by 80%, and LVC time by 24.38% and increased bolus velocity by 36.51%. TRPV1/A1 stimulation with piperine reduced penetrations by 56.32%, LVC time by 25.55% and increased bolus velocity by 23.63%. TRPM8 stimulation with menthol 1 mmol/L reduced penetrations by 37.5% while 10 mmol/L reduced LVC time by 18.44%. Thickeners reduced penetrations by 77.11%, but increased pharyngeal residue by 19.89%, delayed LVC by 41.73%, and reduced bolus velocity by 13.44%. Natural capsaicinoids have a stronger therapeutic effect on VFS signs and swallow response by stimulating TRPV1 than TRPV1/A1 or TRPM8 agonists. While TRP stimulants increased bolus velocity and reduced swallow response times, thickeners reduced bolus velocity and further delayed the swallow response. This study sets the bases to develop new pharmacologic strategies for older patients with OD, moving away from compensation toward the recovery of swallow function. © 2017 John Wiley & Sons Ltd.

  7. Causes of delay in door-to-balloon time in south-east Asian patients undergoing primary percutaneous coronary intervention.

    Directory of Open Access Journals (Sweden)

    Wen Jun Sim

    Full Text Available 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.

  8. Causes of delay in door-to-balloon time in south-east Asian patients undergoing primary percutaneous coronary intervention.

    Science.gov (United States)

    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.

  9. severe organophosphate poisoning with delayed cholinergic crisis

    African Journals Online (AJOL)

    Abrham

    2011-01-06

    Jan 6, 2011 ... CASE REPORT. SEVERE ORGANOPHOSPHATE POISONING WITH DELAYED. CHOLINERGIC CRISIS, INTERMEDIATE SYNDROME AND. ORGANOPHOSPHATE. INDUCED. DELAYED. POLYNEUROPATHY ON SUCCESSION. Aklilu Azazh. ABSTRACT. Organophosphate compounds are the organic ...

  10. Inhibitory effect of ramosetron on corticotropin releasing factor- and soybean oil-induced delays in gastric emptying in rats.

    Science.gov (United States)

    Hirata, Takuya; Keto, Yoshihiro; Yamano, Mayumi; Yokoyama, Toshihide; Sengoku, Takanori; Seki, Nobuo

    2012-09-01

    Symptoms of functional dyspepsia (FD) are highly prevalent in patients with irritable bowel syndrome (IBS). However, the effects of therapeutic agents for IBS on the pathophysiology of FD are unclear. In this study, therefore, we examined the effects of ramosetron, a serotonin 5-HT(3) receptor antagonist, on corticotropin releasing factor (CRF)- and soybean oil-induced delays in gastric emptying of rats, in comparison with anti-diarrheal agent and spasmolytics. The involvement of 5-HT and the 5-HT(3) receptor in delayed gastric emptying was also evaluated. Corticotropin releasing factor was administered intravenously to rats 10min before oral administration of 0.05% phenol red solution, and the amount remaining in the stomach was measured after 30min. Soybean oil was administered orally with glass beads, and the number of residual beads in the stomach was counted 1h later. Both CRF and soybean oil inhibited gastric emptying dose-dependently. Ramosetron and itopride, a gastro-prokinetic agent, significantly reduced both CRF- and soybean oil-induced delays in gastric emptying, while an anti-diarrheal agent and spasmolytics aggravated them. Pretreatment with p-chlorophenylalanine for 2days to reduced the synthesis of endogenous 5-HT diminished the effects of both CRF and soybean oil on gastric emptying. A 5-HT(3) receptor agonist m-chlorophenylbiguanide suppressed gastric emptying of both phenol red and glass beads, and those effects were reversed by ramosetron. These results suggest that CRF and soybean oil suppress gastric emptying in rats by activating 5-HT(3) receptors, and that by antagonizing these receptors, ramosetron may ameliorate symptoms of FD in clinical settings. © 2012 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.

  11. Therapeutic potential of paclitaxel-radiation treatment of a murine ovarian carcinoma.

    Science.gov (United States)

    Milas, L; Saito, Y; Hunter, N; Milross, C G; Mason, K A

    1996-08-01

    Paclitaxel has been shown to radiosensitize tumor cells in culture by arresting them in the most radiosensitive G2 and M cell cycle phases. In vivo preclinical studies are now necessary to obtain full insight into the radiopotentiating potential of this drug and its ability to increase the therapeutic gain of radiotherapy. We tested its ability to enhance the tumor radioresponse of an ovarian carcinoma and to influence the normal tissue radioresponse of recipient mice. Mice bearing 8-mm isotransplants of a syngeneic ovarian carcinoma, designated OCA-I, in their legs were treated with 40 mg/kg paclitaxel i.v., 14-60 Gy single-dose local tumor irradiation, or both; radiation was given under ambient conditions 1-96 h after paclitaxel. Tumor growth delay, tumor cure rate (TCD50 assay), and delay in tumor recurrences were measured. Normal tissue radioresponse was determined using jejunal crypt cell survival at 3.5 days after exposure of mice to 9-14 Gy single dose of total body irradiation; the mice were untreated or treated with 40 mg/kg i.v. paclitaxel 4-96 h before irradiation. Paclitaxel alone was effective against OCA-I, but its combination with irradiation produced supra-additive tumor growth delay. It also reduced TCD50 values and delayed tumor recurrences. The enhancement of tumor radioresponse ranged from 1.33 to 1.96; the value increased as the time between paclitaxel administration and tumor irradiation increased up to 48 h, but then decreased again at 96 h. In contrast, paclitaxel protected jejunum against radiation damage by factors of 1.03 to 1.07 when given 24-96 h before irradiation. It showed some potentiation of damage (by a factor of 1.07), but only when given 4 h before irradiation. Paclitaxel potentiated tumor radioresponse if given within 4 days before irradiation, whereas it caused radioprotection of normal tissue (jejunum) at that time. Therefore, paclitaxel significantly increased therapeutic gain and so has potential for use in combination with

  12. Delay Margin in Controlling a Furuta Pendulum

    OpenAIRE

    Hernández-Díez, José-Enrique; Niculescu, Silviu-Iulian; Méndez-Barrios, César-Fernando; González-Galván, Emilio-Jorge; Loredo-Flores, Ambrocio; Escareno, Juan-Antonio

    2017-01-01

    International audience; This paper focuses on the design of an LQR based control scheme for the stabilization of the Furuta Pendulum in its unstable equilibrium point at the upright position. More precisely, we are interested in characterizing the corresponding delay margin under the assumption that the feedback loop includes time-delay. The paper provides an explicit tool to compute the critical delay value in the state feedback loop and a delicate tuning to reach larger delay values. In ord...

  13. A Developmental Study on Delay of Gratification

    OpenAIRE

    Kobayashi, Sayoko; Mitsumoto, Takashi

    2009-01-01

    Two studies were conducted to investigate development of delay of gratification. In Study 1, the personal delay of gratification test, social delay of gratification inventory and personality inventory were administered to kindergarteners aged 3 to 6 years. The personal delay of gratification test included three reward pairs and subjects were instructed to choose between a less valuable reward which was immediately available and a more valuable reward which was available tomorrow. In the perso...

  14. An investigation of the effects of therapeutic touch plan on acute chemotherapy-induced nausea in women with breast cancer in Isfahan, Iran, 2012-2013.

    Science.gov (United States)

    Matourypour, Pegah; Zare, Zahra; Mehrzad, Valiolah; Musarezaie, Amir; Dehghan, Mojtaba; Vanaki, Zohre

    2015-01-01

    Nausea is the worst and most prevalent chemotherapy-induced complication experienced by 70-80% of patients despite mediation therapy. Reduction of nausea is one of the most important roles of oncologist nurses. Today, complementary therapies in addition to classic medicine, because of their lower costs, receive much attention. Nonetheless, their safety and effectiveness are not yet proven. The purpose of this research was to investigate the effect of therapeutic touch plan as a complementary therapy on acute nausea in women with breast cancer in 2012-2013 in Isfahan, Iran. A quasi-experimental, single-blind, randomized control trial with three groups (control, placebo and intervention) was performed at the Isfahan Seyedolshohada (AS) Teaching Hospital, Isfahan, in 2012-2013. The intervention was therapeutic touch plan on women with breast cancer, with the three groups receiving the same medicine regimen. Information was recorded by a checklist after infusion of chemotherapy drugs. Data analysis was performed by SPSS, ANOVA and Kruskal-Wallis tests. The ANOVA test showed that the therapeutic touch plan was significantly effective in reducing the duration of nausea compared with the control and placebo groups (P touch plan was significantly effective in delaying the onset of nausea compared with the control and placebo groups (P touch plan is effective in reducing acute chemotherapy-induced nausea; thus, education and implementation of the therapeutic touch plan is proposed for clinical nurses.

  15. An investigation of the effects of therapeutic touch plan on acute chemotherapy-induced nausea in women with breast cancer in Isfahan, Iran, 2012–2013

    Science.gov (United States)

    Matourypour, Pegah; Zare, Zahra; Mehrzad, Valiolah; Musarezaie, Amir; Dehghan, Mojtaba; Vanaki, Zohre

    2015-01-01

    Introduction: Nausea is the worst and most prevalent chemotherapy-induced complication experienced by 70–80% of patients despite mediation therapy. Reduction of nausea is one of the most important roles of oncologist nurses. Today, complementary therapies in addition to classic medicine, because of their lower costs, receive much attention. Nonetheless, their safety and effectiveness are not yet proven. The purpose of this research was to investigate the effect of therapeutic touch plan as a complementary therapy on acute nausea in women with breast cancer in 2012–2013 in Isfahan, Iran. Materials and Methods: A quasi-experimental, single-blind, randomized control trial with three groups (control, placebo and intervention) was performed at the Isfahan Seyedolshohada (AS) Teaching Hospital, Isfahan, in 2012–2013. The intervention was therapeutic touch plan on women with breast cancer, with the three groups receiving the same medicine regimen. Information was recorded by a checklist after infusion of chemotherapy drugs. Data analysis was performed by SPSS, ANOVA and Kruskal–Wallis tests. Results: The ANOVA test showed that the therapeutic touch plan was significantly effective in reducing the duration of nausea compared with the control and placebo groups (P touch plan was significantly effective in delaying the onset of nausea compared with the control and placebo groups (P touch plan is effective in reducing acute chemotherapy-induced nausea; thus, education and implementation of the therapeutic touch plan is proposed for clinical nurses. PMID:26430688

  16. Delayed effects of cortisol enhance fear memory of trace conditioning.

    Science.gov (United States)

    Cornelisse, Sandra; van Ast, Vanessa A; Joëls, Marian; Kindt, Merel

    2014-02-01

    Corticosteroids induce rapid non-genomic effects followed by slower genomic effects that are thought to modulate cognitive function in opposite and complementary ways. It is presently unknown how these time-dependent effects of cortisol affect fear memory of delay and trace conditioning. This distinction is of special interest because the neural substrates underlying these types of conditioning may be differently affected by time-dependent cortisol effects. Delay conditioning is predominantly amygdala-dependent, while trace conditioning additionally requires the hippocampus. Here, we manipulated the timing of cortisol action during acquisition of delay and trace fear conditioning, by randomly assigning 63 men to one of three possible groups: (1) receiving 10mg hydrocortisone 240 min (slow cort) or (2) 60 min (rapid cort) before delay and trace acquisition, or (3) placebo at both times, in a double-blind design. The next day, we tested memory for trace and delay conditioning. Fear potentiated startle responses, skin conductance responses and unconditioned stimulus expectancy scores were measured throughout the experiment. The fear potentiated startle data show that cortisol intake 240 min before actual fear acquisition (slow cort) uniquely strengthened subsequent trace conditioned memory. No effects of cortisol delivery 60 min prior to fear acquisition were found on any measure of fear memory. Our findings emphasize that slow, presumably genomic, but not more rapid effects of corticosteroids enhance hippocampal-dependent fear memories. On a broader level, our findings underline that basic experimental research and clinically relevant pharmacological treatments employing corticosteroids should acknowledge the timing of corticosteroid administration relative to the learning phase, or therapeutic intervention. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. [Therapeutic applications of digestive endoscopy].

    Science.gov (United States)

    Ortega, J A; Pérez, L; Madureri, V

    1976-01-01

    Endoscopy has proven useful as a diagnostic tool and recently many useful therapeutic possibilities have been proposed. The authors discuss their experience with therapeutic endoscopic procedures and present new ones for treatment of Acalasia and small sliding hiatal hernia.

  18. Therapeutic approaches to cellulite.

    Science.gov (United States)

    Green, Jeremy B; Cohen, Joel L; Kaufman, Joely; Metelitsa, Andrei I; Kaminer, Michael S

    2015-09-01

    Cellulite is a condition that affects the vast majority of women. Although it is of no danger to one's overall health, cellulite can be psychosocially debilitating. Consequently, much research has been devoted to understanding cellulite and its etiopathogenesis. With additional insights into the underlying causes of its clinical presentation, therapeutic modalities have been developed that offer hope to cellulite sufferers. This review examines evidence for topical treatments, noninvasive energy-based devices, and recently developed minimally invasive interventions that may finally provide a solution. ©2015 Frontline Medical Communications.

  19. [Is therapeutic deadlock inevitable?].

    Science.gov (United States)

    Vignat, Jean-Pierre

    2016-01-01

    Many long-term treatments appear to be an expression of therapeutic deadlock. The situation leads to a questioning of the concept of chronicity and the identification of the determining factors of situations which are apparently blocked, marked by the search for solutions taking a back seat to the taking of action. The interaction between patients' mental apparatus and the care apparatus lies at the heart of the question, interpreted from an institutional, collective and individual perspective, supported by the clinical and psychopathological approach, and the return to the prioritisation of the thought. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  20. Dynamic Cournot Duopoly Game with Delay

    Directory of Open Access Journals (Sweden)

    A. A. Elsadany

    2014-01-01

    Full Text Available The delay Cournot duopoly game is studied. Dynamical behaviors of the game are studied. Equilibrium points and their stability are studied. The results show that the delayed system has the same Nash equilibrium point and the delay can increase the local stability region.

  1. Synchronization analysis of coloured delayed networks under ...

    Indian Academy of Sciences (India)

    This paper investigates synchronization of coloured delayed networks under decentralized pinning intermittent control. To begin with, the time delays are taken into account in the coloured networks. In addition, we propose a decentralized pinning intermittent control for coloured delayed networks, which is different from that ...

  2. Academic Delay of Gratification and Academic Achievement

    Science.gov (United States)

    Bembenutty, Hefer

    2011-01-01

    The ability to delay gratification is the cornerstone of all academic achievement and education. It is by delaying gratification that learners can pursue long-term academic and career goals. In general, "delay of gratification" refers to an individual's ability to forgo immediate rewards for the sake of more valuable ones later (Mischel, 1996).…

  3. Delayed reinforcement and fixed-ratio performance.

    Science.gov (United States)

    Jarmolowicz, David P; Lattal, Kennon A

    2013-11-01

    Effects of delayed reinforcement on fixed-ratio (FR) maintained responding of pigeons were investigated. In Experiments 1-3, the delay of reinforcement was increased across successive sessions until pigeons paused for 300 s. Both signaled and unsignaled delays were studied across different conditions. Overall response rates and run rates (timed from the first to last response of a ratio) decreased and postreinforcement pauses increased as delays increased in each experiment. As delays increased, the likelihood of pausing during a ratio run also increased. When these measures were plotted as a function of obtained delays, signaled delays had less of an effect on the above measures than did unsignaled ones. In Experiment 2, delays had a greater effect on the above measures than did a control condition arranging equivalent interreinforcer intervals to those accompanying the delays. Experiments 3 and 4 examined the generality of the effects obtained in the first two experiments. In Experiment 3, delays imposed on FR or yoked-interval schedules had similar behavioral effects. In Experiment 4, effects similar to those found in Experiments 1-3 for 1, 10, and 20-s delays imposed on FR 50 schedules were found when the FR requirement increased across sessions. Despite the different contingencies relating response rate and reinforcement rates on interval and ratio schedules, delays of reinforcement generally affect performance on these schedules similarly. © Society for the Experimental Analysis of Behavior.

  4. Low-complexity controllers for time-delay systems

    CERN Document Server

    Özbay, Hitay; Bonnet, Catherine; Mounier, Hugues

    2014-01-01

    This volume in the newly established series Advances in Delays and Dynamics (ADD@S) provides a collection of recent results on the design and analysis of Low Complexity Controllers for Time Delay Systems. A widely used indirect method to obtain low order controllers for time delay systems is to design a controller for the reduced order model of the plant. In the dual indirect approach, an infinite dimensional controller is designed first for the original plant model; then, the controller is approximated by keeping track of the degradation in performance and stability robustness measures. The present volume includes new techniques used at different stages of the indirect approach. It also includes new direct design methods for fixed structure and low order controllers. On the other hand, what is meant by low complexity controller is not necessarily low order controller. For example, Smith predictor or similar type of controllers include a copy of the plant internally in the controller, so they are technically ...

  5. Boolean delay equations. II. Periodic and aperiodic solutions

    Science.gov (United States)

    Ghil, M.; Mullhaupt, A.

    1985-10-01

    Boolean delay equations (BDEs) are evolution equations for a vector of discrete variables x (t). The value of each component X i ( t), 0 or 1. depends on previous values of all components x j (t- t ij ), x i (t)=f i (x1( t- t i1),..., x n ( t - t in )). BDEs model the evolution of biological and physical systems with threshold behavior and nonlinear feedbacks. The delays model distinct interaction times between pairs of variables. In this paper, BDEs are studied by algebraic, analytic, and numerical methods. It is shown that solutions depend continuously on the initial data and on the delays. BDEs are classified into conservative and dissipative. All BDEs with rational delays only have periodic solutions only. But conservative BDEs with rationally unrelated delays have aperiodic solutions of increasing complexity. These solutions can be approximated arbitrarily well by periodic solutions of increasing period. Self-similarity and intermittency of aperiodic solutions is studied as a function of delay values, and certain number-theoretic questions related to resonances and diophantine approximation are raised. Period length is shown to be a lower semicontinuous function of the delays for a given BDE, and can be evaluated explicitly for linear equations. We prove that a BDE is structurable stable if and only if it has eventually periodic solutions of bounded period, and if the length of initial transients is bounded. It is shown that, for dissipative BDEs, asymptotic solution behavior is typically governed by a reduced BDE. Applications to climate dynamics and other problems are outlined.

  6. The Delay Phenomenon: A Compilation of Knowledge across Specialties.

    Science.gov (United States)

    Hamilton, Kristy; Wolfswinkel, Erik M; Weathers, William M; Xue, Amy S; Hatef, Daniel A; Izaddoost, Shayan; Hollier, Larry H

    2014-06-01

    Objective The purpose of this article is to review and integrate the available literature in different fields to gain a better understanding of the basic physiology and optimize vascular delay as a reconstructive surgery technique. Methods A broad search of the literature was performed using the Medline database. Two queries were performed using "vascular delay," a search expected to yield perspectives from the field of plastic and reconstructive surgery, and "ischemic preconditioning," (IPC) which was expected to yield research on the same topic in other fields. Results The combined searches yielded a total of 1824 abstracts. The "vascular delay" query yielded 76 articles from 1984 to 2011. The "ischemic preconditioning" query yielded 6534 articles, ranging from 1980 to 2012. The abstracts were screened for those from other specialties in addition to reconstructive surgery, analyzed potential or current uses of vascular delay in practice, or provided developments in understanding the pathophysiology of vascular delay. 70 articles were identified that met inclusion criteria and were applicable to vascular delay or ischemic preconditioning. Conclusion An understanding of IPC's implementation and mechanisms in other fields has beneficial implications for the field of reconstructive surgery in the context of the delay phenomenon. Despite an incomplete model of IPC's pathways, the anti-oxidative, anti-apoptotic and anti-inflammatory benefits of IPC are well recognized. The activation of angiogenic genes through IPC could allow for complex flap design, even in poorly vascularized regions. IPC's promotion of angiogenesis and reduction of endothelial dysfunction remain most applicable to reconstructive surgery in reducing graft-related complications and flap failure.

  7. H∞ Control of Four-Wheel-Independent-Drive Electric Vehicles with Random Time-Varying Delays

    Directory of Open Access Journals (Sweden)

    Gang Qin

    2015-01-01

    Full Text Available The random time-varying delays would reduce control performance and even deteriorate the EV system. To deal with random time-varying delays and achieve a real-time steady-state response, considering randomness of delay and a rapid response, an H∞-based delay-tolerant linear quadratic regulator (LQR control method based on Taylor series expansion is proposed in this paper. The results of cosimulations with Simulink and CarSim demonstrate the effectiveness of the proposed controller through the control performance of yaw rate, sideslip angle, and the running track. Moreover, the results of comparison with the other controller illustrate the strength of explicitly.

  8. Fetal neonatal hyperthyroidism: diagnostic and therapeutic approachment

    Science.gov (United States)

    Kurtoğlu, Selim; Özdemir, Ahmet

    2017-01-01

    Fetal and neonatal hyperthyroidism may occur in mothers with Graves’ disease. Fetal thyrotoxicosis manifestation is observed with the transition of TSH receptor stimulating antibodies to the fetus from the 17th–20th weeks of pregnancy and with the fetal TSH receptors becoming responsive after 20 weeks. The diagnosis is confirmed by fetal tachycardia, goiter and bone age advancement in pregnancy and maternal treatment is conducted in accordance. The probability of neonatal hyperthyroidism is high in the babies of mothers that have ongoing antithyroid requirement and higher antibody levels in the last months of pregnancy. Clinical manifestation may be delayed by 7–17 days because of the antithyroid drugs taken by the mother. Neonatal hyperthyroidism symptoms can be confused with sepsis and congenital viral infections. Herein, the diagnosis and therapeutic approach are reviewed in cases of fetal neonatal hyperthyroidism. PMID:28439194

  9. Mechanisms of Plasma Therapeutics

    Science.gov (United States)

    Graves, David

    2015-09-01

    In this talk, I address research directed towards biomedical applications of atmospheric pressure plasma such as sterilization, surgery, wound healing and anti-cancer therapy. The field has seen remarkable growth in the last 3-5 years, but the mechanisms responsible for the biomedical effects have remained mysterious. It is known that plasmas readily create reactive oxygen species (ROS) and reactive nitrogen species (RNS). ROS and RNS (or RONS), in addition to a suite of other radical and non-radical reactive species, are essential actors in an important sub-field of aerobic biology termed ``redox'' (or oxidation-reduction) biology. It is postulated that cold atmospheric plasma (CAP) can trigger a therapeutic shielding response in tissue in part by creating a time- and space-localized, burst-like form of oxy-nitrosative stress on near-surface exposed cells through the flux of plasma-generated RONS. RONS-exposed surface layers of cells communicate to the deeper levels of tissue via a form of the ``bystander effect,'' similar to responses to other forms of cell stress. In this proposed model of CAP therapeutics, the plasma stimulates a cellular survival mechanism through which aerobic organisms shield themselves from infection and other challenges.

  10. Therapeutic Uses of Exosomes

    Directory of Open Access Journals (Sweden)

    Zacharias E. Suntres

    2013-01-01

    Full Text Available Exosomes are membrane vesicles with a diameter of 40–100 nm that are secreted by many cell types into the extracellular milieu. Exosomes are found in cell culture supernatants and in different biological fluids and are known to be secreted by most cell types under normal and pathological conditions. Considerable research is focusing on the exploitation of exosomes in biological fluids for biomarkers in the diagnosis of disease. More recently, exosomes are being exploited for their therapeutic potential. Exosomes derived from dendritic cells, tumor cells, and malignant effusions demonstrate immunomodulatory functions and are able to present antigens to T-cells and stimulate antigen-specific T-cell responses. Exosomes have also been examined for their therapeutic potential in the treatment of infections such as toxoplasmosis, diphtheria, tuberculosis and atypical severe acute respiratory syndrome as well as autoimmune diseases. Attempts to find practical applications for exosomes continue to expand with the role of exosomes as a drug delivery system for the treatment of autoimmune/inflammatory diseases and cancers.

  11. Engineering therapeutic protein disaggregases.

    Science.gov (United States)

    Shorter, James

    2016-05-15

    Therapeutic agents are urgently required to cure several common and fatal neurodegenerative disorders caused by protein misfolding and aggregation, including amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), and Alzheimer's disease (AD). Protein disaggregases that reverse protein misfolding and restore proteins to native structure, function, and localization could mitigate neurodegeneration by simultaneously reversing 1) any toxic gain of function of the misfolded form and 2) any loss of function due to misfolding. Potentiated variants of Hsp104, a hexameric AAA+ ATPase and protein disaggregase from yeast, have been engineered to robustly disaggregate misfolded proteins connected with ALS (e.g., TDP-43 and FUS) and PD (e.g., α-synuclein). However, Hsp104 has no metazoan homologue. Metazoa possess protein disaggregase systems distinct from Hsp104, including Hsp110, Hsp70, and Hsp40, as well as HtrA1, which might be harnessed to reverse deleterious protein misfolding. Nevertheless, vicissitudes of aging, environment, or genetics conspire to negate these disaggregase systems in neurodegenerative disease. Thus, engineering potentiated human protein disaggregases or isolating small-molecule enhancers of their activity could yield transformative therapeutics for ALS, PD, and AD. © 2016 Shorter. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  12. Risk-factors for surgical delay following hip fracture.

    Science.gov (United States)

    Sanz-Reig, J; Salvador Marín, J; Ferrández Martínez, J; Orozco Beltrán, D; Martínez López, J F

    To identify pre-operative risk factors for surgical delay of more than 2 days after admission in patients older than 65 years with a hip fracture. A prospective observational study was conducted on 180 hip fractures in patients older than 65 years of age admitted to our hospital from January 2015 to April 2016. The data recorded included, patient demographics, day of admission, pre-fracture comorbidities, mental state, level of mobility and physical function, type of fracture, antiaggregant and anticoagulant medication, pre-operative haemoglobin value, type of treatment, and surgical delay. The mean age of the patients was 83.7 years. The mean Charlson Index was 2.8. The pre-fracture baseline co-morbidities were equal or greater than 2 in 70% of cases. Mean timing of surgery was 3.1 days. At the time of admission, 122 (67.7%) patients were fit for surgery, of which 80 (44.4%) underwent surgery within 2 days. A Charlson index greater than 2, anticoagulant therapy, and admission on Thursday to Saturday, were independently associated with a surgical delay greater than 2 days. The rate of hip fracture patients undergoing surgery within 2 days is low. Risk factors associated to surgical delay are non-modifiable. However, their knowledge should allow the development of protocols that can reduce surgical delay in this group of patients. Copyright © 2017 SECOT. Publicado por Elsevier España, S.L.U. All rights reserved.

  13. Delay in diagnosis of tuberculosis in Rawalpindi, Pakistan

    Directory of Open Access Journals (Sweden)

    Tahseen Sabira

    2011-05-01

    Full Text Available Abstract Background Delay in diagnosis and treatment of tuberculosis (TB may enhance the chances of morbidity and mortality and play a key role in continuous transmission of the bacilli. The objective of this study was to describe health care seeking behavior of suspected TB patients and initial diagnostic work up prior to consultation and diagnosis at National TB Center (NTC. Findings Interviews of 252 sputum smear positive patients were taken from NTC, Rawalpindi. The duration between on-set of symptoms and start of treatment was considered as the total delay and correlated with general characteristics of TB patients. The proportion of males and females were 49.6% and 50.4% with median age of 25 and 24 years respectively. A median delay of 56 days (8 weeks was observed which was significantly associated with age, cough and fever. More than 50% of the current patients had a history of contact with previously diagnosed TB patients. The majority of patients (63% visited health care providers within three weeks of appearance of symptoms but only thirty five percent were investigated for TB diagnosis. Conclusion Cough and fever are being ignored as likely symptoms of TB by patients as well as health care providers resulting in delay. Engaging private practitioners through public private mix (PPM approach for expansion of TB diagnosis and increasing public awareness could be more beneficial to reduce delay.

  14. Procrastination by pigeons: preference for larger, more delayed work requirements.

    Science.gov (United States)

    Mazur, J E

    1996-01-01

    In three experiments, pigeons chose between alternatives that required the completion of a small ratio schedule early in the trial or a larger ratio schedule later in the trial. Completion of the ratio requirement did not lead to an immediate reinforcer, but simply allowed the events of the trial to continue. In Experiment 1, the ratio requirements interrupted periods in which food was delivered on a variable-time schedule. In Experiments 2 and 3, each ratio requirement was preceded and followed by a delay, and only one reinforcer was delivered, at the end of each trial. Two of the experiments used an adjusting-ratio procedure in which the ratio requirement was increased and decreased over trials so as to estimate an indifference point--a ratio size at which the two alternatives were chosen about equally often. These experiments found clear evidence for "procrastination"--the choice of a larger but more delayed response requirement. In some cases, subjects chose the more delayed ratio schedule even when it was larger than the more immediate alternative by a factor of four or more. The results suggest that as the delay to the start of a ratio requirement is increased, it has progressively less effect on choice behavior, in much the same way that delaying a positive reinforcer reduces it effect on choice. PMID:8583195

  15. Effects of acute and chronic morphine on delay discounting in pigeons.

    Science.gov (United States)

    Eppolito, Amy K; France, Charles P; Gerak, Lisa R

    2013-05-01

    When reinforcers of different magnitudes are concurrently available, choice is greater for a large reinforcer; that choice can be reduced by delaying its delivery, a phenomenon called delay discounting and represented graphically by a delay curve in which choice is plotted as a function of delay to the large reinforcer. Morphine, administered acutely, can alter responding for large, delayed reinforcers. In this study, the impact of morphine tolerance, dependence and withdrawal on choice of delayed reinforcers was examined in six pigeons responding to receive a small amount of food delivered immediately or a larger amount delivered immediately or after delays that increased within sessions. Acutely, morphine decreased responding for the large reinforcer, and the effect was greater when morphine was administered immediately, rather than 6 hr, before sessions. During 8 weeks of daily administration, morphine produced differential effects across pigeons, shifting the delay curve downward in some and upward in others. In all pigeons, tolerance developed to the response-rate-decreasing effects of morphine but not to its effects on delay discounting. When chronic morphine treatment was discontinued, rate of responding decreased in four pigeons, indicating the emergence of withdrawal; choice of the large reinforcer increased, regardless of delay, in all pigeons, an effect that persisted for weeks. These data suggest that chronic morphine administration has long-lasting effects on choice behavior, which might impact vulnerability to relapse in opioid abusers. © Society for the Experimental Analysis of Behavior.

  16. Fourteen days oral administration of therapeutic dosage of some ...

    African Journals Online (AJOL)

    Fourteen days oral administration of therapeutic dosage of some antibiotics reduced serum testosterone in male rats. FO Awobajo, Y Raji, II Olatunji-Bello, FT Kunle-Alabi, AO Adesanya, TO Awobajo ...

  17. Delay Variation Model with Two Service Queues

    Directory of Open Access Journals (Sweden)

    Filip Rezac

    2010-01-01

    Full Text Available Delay in VoIP technology is very unpleasant issue and therefore a voice packets prioritization must be ensured. To maintain the high call quality a maximum information delivery time from the sender to the recipient is set to 150 ms. This paper focuses on the design of a mathematical model of end-to-end delay of a VoIP connection, in particular on a delay variation. It describes all partial delay components and mechanisms, their generation, facilities and mathematical formulations. A new approach to the delay variation model is presented and its validation has been done by experimention.

  18. Controllability of Nonlinear Fractional Delay Dynamical Systems

    Science.gov (United States)

    Nirmala, R. Joice; Balachandran, K.; Rodríguez-Germa, L.; Trujillo, J. J.

    2016-02-01

    This paper is concerned with controllability of nonlinear fractional delay dynamical systems with delay in state variables. The solution representations of fractional delay differential equations have been established by using the Laplace transform technique and the Mittag-Leffler function. Necessary and sufficient conditions for the controllability criteria of linear fractional delay systems are established. Further sufficient condition for the controllability of nonlinear fractional delay dynamical system are obtained by using the fixed point argument. Examples and numerical simulation are presented to illustrate the results.

  19. Fuzzy delay model based fault simulator for crosstalk delay fault test ...

    Indian Academy of Sciences (India)

    The delays of a logic gates or interconnect are affected by various fabrication process parameters and however accurate the delay models are, it is very difficult to model the process uncertainties. In this paper, the fuzzy delay model is employed for test generation of crosstalk delay faults in asynchronous sequential circuits.

  20. Large Deviations for Gaussian Diffusions with Delay

    Science.gov (United States)

    Azencott, Robert; Geiger, Brett; Ott, William

    2018-01-01

    Dynamical systems driven by nonlinear delay SDEs with small noise can exhibit important rare events on long timescales. When there is no delay, classical large deviations theory quantifies rare events such as escapes from metastable fixed points. Near such fixed points, one can approximate nonlinear delay SDEs by linear delay SDEs. Here, we develop a fully explicit large deviations framework for (necessarily Gaussian) processes X_t driven by linear delay SDEs with small diffusion coefficients. Our approach enables fast numerical computation of the action functional controlling rare events for X_t and of the most likely paths transiting from X_0 = p to X_T=q. Via linear noise local approximations, we can then compute most likely routes of escape from metastable states for nonlinear delay SDEs. We apply our methodology to the detailed dynamics of a genetic regulatory circuit, namely the co-repressive toggle switch, which may be described by a nonlinear chemical Langevin SDE with delay.

  1. Reasons for diagnostic delay in gynecological malignancies

    DEFF Research Database (Denmark)

    Vandborg, Mai Partridge; Christensen, René dePont Christensen; Kragstrup, Jakob

    2011-01-01

    Aim The primary aim of this study was to identify and describe different delay types in women with gynecologic cancer, and to analyze the relationship between diagnostic delay and a number of characteristics for patients, cancers and the health care system. Setting A cohort study of women newly......) and The Danish Gynecological Cancer Database (DGCD). 161 women were included; ovarian cancer: 63, endometrial cancer: 50, cervical cancer: 34 and vulvar cancer: 14. Outcome measures were different delay types counted in days and the influence of four clinical important variables: Presence of alarm symptoms, age...... (≤ or > 60 years), performance of gynecological examination by the GP and notification of cancer suspicion on first referral from GP’s on the diagnostic delay (short delay ≤90 days and long delay >90 days). Results Across cancer type a median total delay of 101 days was observed. The 10% of women...

  2. Cross delay line sensor characterization

    Energy Technology Data Exchange (ETDEWEB)

    Owens, Israel J [Los Alamos National Laboratory; Remelius, Dennis K [Los Alamos National Laboratory; Tiee, Joe J [Los Alamos National Laboratory; Buck, Steven E [Los Alamos National Laboratory; Whittemore, Stephen R [Los Alamos National Laboratory; Thompson, David C [Los Alamos National Laboratory; Shirey, Robert [Los Alamos National Laboratory

    2010-01-01

    There exists a wealth of information in the scientific literature on the physical properties and device characterization procedures for complementary metal oxide semiconductor (CMOS), charge coupled device (CCD) and avalanche photodiode (APD) format detectors. Numerous papers and books have also treated photocathode operation in the context of photomultiplier tube (PMT) operation for either non imaging applications or limited night vision capability. However, much less information has been reported in the literature about the characterization procedures and properties of photocathode detectors with novel cross delay line (XDL) anode structures. These allow one to detect single photons and create images by recording space and time coordinate (X, Y & T) information. In this paper, we report on the physical characteristics and performance of a cross delay line anode sensor with an enhanced near infrared wavelength response photocathode and high dynamic range micro channel plate (MCP) gain (> 10{sup 6}) multiplier stage. Measurement procedures and results including the device dark event rate (DER), pulse height distribution, quantum and electronic device efficiency (QE & DQE) and spatial resolution per effective pixel region in a 25 mm sensor array are presented. The overall knowledge and information obtained from XDL sensor characterization allow us to optimize device performance and assess capability. These device performance properties and capabilities make XDL detectors ideal for remote sensing field applications that require single photon detection, imaging, sub nano-second timing response, high spatial resolution (10's of microns) and large effective image format.

  3. PRECISION TIME-DELAY GENERATOR

    Science.gov (United States)

    Carr, B.J.; Peckham, V.D.

    1959-06-16

    A precision time-delay generator circuit with low jitter is described. The first thyratron has a series resonant circuit and a diode which is connected to the second thyratron. The first thyratron is triggered at the begin-ning of a time delay and a capacitor is discharged through the first thyratron and the diode, thereby, triggering the second thyratron. (T.R.H.) l6l9O The instrument described can measure pressures between sea level and 300,000 ft. The pressure- sensing transducer of the instrument is a small cylindrical tube with a thin foil of titanium-tritium fastened around the inside of the tube. Output is a digital signal which can be used for storage or telemetering more conveniently than an analog signal. (W.D.M.) l6l9l An experimental study was made on rolling contacts in the temperature range of 550 to 1000 deg F. Variables such as material composition, hardness, and operating conditions were investigated in a rolling test stand. Ball bearing tests were run to determine the effect of design parameters, bearing materials, lubricants, and operating conditions. (auth)

  4. Asymptotic Delay Analysis for Cross-Layer Delay-Based Routing in Ad Hoc Networks

    Directory of Open Access Journals (Sweden)

    Philippe Jacquet

    2007-01-01

    Full Text Available This paper addresses the problem of the evaluation of the delay distribution via analytical means in IEEE 802.11 wireless ad hoc networks. We show that the asymptotic delay distribution can be expressed as a power law. Based on the latter result, we present a cross-layer delay estimation protocol and we derive new delay-distribution-based routing algorithms, which are well adapted to the QoS requirements of real-time multimedia applications. In fact, multimedia services are not sensitive to average delays, but rather to the asymptotic delay distributions. Indeed, video streaming applications drop frames when they are received beyond a delay threshold, determined by the buffer size. Although delay-distribution-based routing is an NP-hard problem, we show that it can be solved in polynomial time when the delay threshold is large, because of the asymptotic power law distribution of the link delays.

  5. Nucleus accumbens core lesions retard instrumental learning and performance with delayed reinforcement in the rat.

    Science.gov (United States)

    Cardinal, Rudolf N; Cheung, Timothy H C

    2005-02-03

    Delays between actions and their outcomes severely hinder reinforcement learning systems, but little is known of the neural mechanism by which animals overcome this problem and bridge such delays. The nucleus accumbens core (AcbC), part of the ventral striatum, is required for normal preference for a large, delayed reward over a small, immediate reward (self-controlled choice) in rats, but the reason for this is unclear. We investigated the role of the AcbC in learning a free-operant instrumental response using delayed reinforcement, performance of a previously-learned response for delayed reinforcement, and assessment of the relative magnitudes of two different rewards. Groups of rats with excitotoxic or sham lesions of the AcbC acquired an instrumental response with different delays (0, 10, or 20 s) between the lever-press response and reinforcer delivery. A second (inactive) lever was also present, but responding on it was never reinforced. As expected, the delays retarded learning in normal rats. AcbC lesions did not hinder learning in the absence of delays, but AcbC-lesioned rats were impaired in learning when there was a delay, relative to sham-operated controls. All groups eventually acquired the response and discriminated the active lever from the inactive lever to some degree. Rats were subsequently trained to discriminate reinforcers of different magnitudes. AcbC-lesioned rats were more sensitive to differences in reinforcer magnitude than sham-operated controls, suggesting that the deficit in self-controlled choice previously observed in such rats was a consequence of reduced preference for delayed rewards relative to immediate rewards, not of reduced preference for large rewards relative to small rewards. AcbC lesions also impaired the performance of a previously-learned instrumental response in a delay-dependent fashion. These results demonstrate that the AcbC contributes to instrumental learning and performance by bridging delays between subjects

  6. Effects of methylphenidate on discounting of delayed rewards in attention deficit/hyperactivity disorder.

    Science.gov (United States)

    Shiels, Keri; Hawk, Larry W; Reynolds, Brady; Mazzullo, Rebecca J; Rhodes, Jessica D; Pelham, William E; Waxmonsky, James G; Gangloff, Brian P

    2009-10-01

    Impulsivity is a central component of attention deficit/hyperactivity disorder (ADHD). Delay discounting, or a preference for smaller, immediate rewards over larger, delayed rewards, is considered an important aspect of impulsivity, and delay-related impulsivity has been emphasized in etiological models of ADHD. In this study, we examined whether stimulant medication, an effective treatment for ADHD, reduced discounting of delayed experiential and hypothetical rewards among 49 children (ages 9-12 years) with ADHD. After a practice day, participants completed a 3-day double-blind placebo-controlled acute medication assessment. Active doses were long-acting methylphenidate (Concerta), with the nearest equivalents of 0.3 and 0.6 mg/kg TID immediate-release methylphenidate. On each testing day, participants completed experiential (real-world money in real time) and hypothetical discounting tasks. Relative to placebo, methylphenidate reduced discounting of delayed experiential rewards but not hypothetical rewards. Broadly consistent with etiological models that emphasize delay-related impulsivity among children with ADHD, these findings provide initial evidence that stimulant medication reduces delay discounting among those with the disorder. The results also draw attention to task parameters that may influence the sensitivity of various delay discounting measures to medication effects.

  7. Therapeutic and diagnostic nanomaterials

    CERN Document Server

    Devasena T

    2017-01-01

    This brief highlights nanoparticles used in the diagnosis and treatment of prominent diseases and toxic conditions. Ecofriendly methods which are ideal for the synthesis of medicinally valued nanoparticles are explained and the characteristic features of these particles projected. The role of these particles in the therapeutic field, and the induced biological changes in some diseases are discussed. The main focus is on inflammation, oxidative stress and cellular membrane integrity alterations. The effect of nanoparticles on these changes produced by various agents are highlighted using in vitro and in vivo models. The mechanism of nanoparticles in ameliorating the biological changes is supported by relevant images and data. Finally, the brief demonstrates recent developments on the use of nanoparticles in diagnosis or sensing of some biological materials and biologically hazardous environmental materials.

  8. Antibody Engineering and Therapeutics

    Science.gov (United States)

    Almagro, Juan Carlos; Gilliland, Gary L; Breden, Felix; Scott, Jamie K; Sok, Devin; Pauthner, Matthias; Reichert, Janice M; Helguera, Gustavo; Andrabi, Raiees; Mabry, Robert; Bléry, Mathieu; Voss, James E; Laurén, Juha; Abuqayyas, Lubna; Barghorn, Stefan; Ben-Jacob, Eshel; Crowe, James E; Huston, James S; Johnston, Stephen Albert; Krauland, Eric; Lund-Johansen, Fridtjof; Marasco, Wayne A; Parren, Paul WHI; Xu, Kai Y

    2014-01-01

    The 24th Antibody Engineering & Therapeutics meeting brought together a broad range of participants who were updated on the latest advances in antibody research and development. Organized by IBC Life Sciences, the gathering is the annual meeting of The Antibody Society, which serves as the scientific sponsor. Preconference workshops on 3D modeling and delineation of clonal lineages were featured, and the conference included sessions on a wide variety of topics relevant to researchers, including systems biology; antibody deep sequencing and repertoires; the effects of antibody gene variation and usage on antibody response; directed evolution; knowledge-based design; antibodies in a complex environment; polyreactive antibodies and polyspecificity; the interface between antibody therapy and cellular immunity in cancer; antibodies in cardiometabolic medicine; antibody pharmacokinetics, distribution and off-target toxicity; optimizing antibody formats for immunotherapy; polyclonals, oligoclonals and bispecifics; antibody discovery platforms; and antibody-drug conjugates. PMID:24589717

  9. Therapeutic applications of melatonin

    Science.gov (United States)

    2013-01-01

    Melatonin is a methoxyindole synthesized within the pineal gland. The hormone is secreted during the night and appears to play multiple roles within the human organism. The hormone contributes to the regulation of biological rhythms, may induce sleep, has strong antioxidant action and appears to contribute to the protection of the organism from carcinogenesis and neurodegenerative disorders. At a therapeutic level as well as in prevention, melatonin is used for the management of sleep disorders and jet lag, for the resynchronization of circadian rhythms in situations such as blindness and shift work, for its preventive action in the development of cancer, as additive therapy in cancer and as therapy for preventing the progression of Alzheimer’s disease and other neurodegenerative disorders. PMID:23515203

  10. Microfabricated therapeutic actuators

    Science.gov (United States)

    Lee, Abraham P.; Northrup, M. Allen; Ciarlo, Dino R.; Krulevitch, Peter A.; Benett, William J.

    1999-01-01

    Microfabricated therapeutic actuators are fabricated using a shape memory polymer (SMP), a polyurethane-based material that undergoes a phase transformation at a specified temperature (Tg). At a temperature above temperature Tg material is soft and can be easily reshaped into another configuration. As the temperature is lowered below temperature Tg the new shape is fixed and locked in as long as the material stays below temperature Tg. Upon reheating the material to a temperature above Tg, the material will return to its original shape. By the use of such SMP material, SMP microtubing can be used as a release actuator for the delivery of embolic coils through catheters into aneurysms, for example. The microtubing can be manufactured in various sizes and the phase change temperature Tg is determinate for an intended temperature target and intended use.

  11. Therapeutic effects of reading

    Directory of Open Access Journals (Sweden)

    Agustín HIDALGO

    2017-06-01

    Full Text Available Reading is an act that requires isolation and loneliness, which allows rewriting the narratives through the identification between the reader and the character, the involvement in the fact narrated and singular recreation by every single reader. The act of reading allows stepping aside from reality. The reading as well as the writing perform the therapeutic effect of helping to understand the illness and to know experiences of others patients that can be useful for the accompaniment, overcoming and/or making decisions. There is not a concrete literary that could be universally recommend to every patient, but all the genre can be useful to some patient. However, poetry, novel and autobiographies are frequently referred as the manuscripts that provide help and consolation.

  12. Antiviral Polymer Therapeutics

    DEFF Research Database (Denmark)

    Smith, Anton Allen Abbotsford

    2014-01-01

    polymerized in a controlled manner with carrier monomers of historically proven biocompatible polymers. The carrier polymers, the loading of ribavirin as well as the size of the polymer were varied systematically with the aid of an automated synthesis platform. These polymers were tested in a cellular assay...... of reversible-addition-fragmentation chain transfer polymerization, which not only controls the size of polymer, but also allows the introduction of a terminal amine on the polymer which can be used for further conjugation. This has allowed for not only fluorescent labeling of the polymer, but also protein......The field of drug delivery is in essence an exercise in engineered pharmacokinetics. Methods of doing so have been developed through the introduction of a vehicle carrying the drug, either by encapsulation or covalent attachment. The emergence of polymer therapeutics in anticancer therapy has...

  13. Patient Related Factors Associated with Delayed Reporting in Oral Cavity and Oropharyngeal Cancer

    Directory of Open Access Journals (Sweden)

    Mohammad Akram

    2014-01-01

    Conclusions: The results of this study provide guidance towards interventions to reduce patient delay. Interventions should target the rural, older age group and lower socioeconomic population for educating them and to change their psychosocial behavior for oral and oropharyngeal cancer.

  14. Therapeutic Approaches in CLIPPERS.

    Science.gov (United States)

    Taieb, Guillaume; Allou, Thibaut; Labauge, Pierre

    2017-05-01

    CLIPPERS for chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids, is a steroid-sensitive and steroid-dependent brainstem inflammatory disease of unknown origin. Since its first description in 2010, about 60 cases have been reported throughout the world. The mean age at onset is 50 years and men seem to be more frequently affected. In patients without chronic corticosteroid therapy or immunosuppressive agents, the disease had a relapsing remitting course, and the mean annualized relapse rate was 0.5. During attacks, although clinical and radiological improvement after high doses of corticosteroids was systematically observed, patients could display subsequent disability and hindbrain atrophy. Since no progressive course was observed, clinical and radiological sequelae were correlated with previous severe attacks. Therefore, maintaining the disease in remission may prevent the accumulation of disability. In the literature, no relapse occurred when chronic corticosteroid therapy was maintained above 20 mg per day. However, steroids side effects led to propose corticosteroid-sparing therapies. Unfortunately, no controlled therapy studies for CLIPPERS have been performed yet, and no therapeutic recommendations exist. Using the PubMed database, all articles having the following keywords "chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids" and "CLIPPERS" have been analysed. Considering that the mean annual relapse rate was 0.5, and that no relapse occurred when corticosteroid therapy was maintained above 20 mg per day, the therapeutic efficiency of corticosteroid-sparing agents was considered as "probable" when patients had a relapse-free period ≥24 months, in the absence of concomitant corticosteroid therapy. Corticosteroid-sparing agents whose efficiency is "probable" are methotrexate in two cases, cyclophosphamide in one case and hydroxychloroquine in one case. Considering the

  15. Poly[ADP-ribose] polymerase-1 expression is related to cold ischemia, acute tubular necrosis, and delayed renal function in kidney transplantation.

    Directory of Open Access Journals (Sweden)

    Francisco O'Valle

    Full Text Available UNLABELLED: Cold ischemia time especially impacts on outcomes of expanded-criteria donor (ECD transplantation. Ischemia-reperfusion (IR injury produces excessive poly[ADP-Ribose] Polymerase-1 (PARP-1 activation. The present study explored the hypothesis that increased tubular expression of PARP-1 contributes to delayed renal function in suboptimal ECD kidney allografts and in non-ECD allografts that develop posttransplant acute tubular necrosis (ATN. MATERIALS AND METHODS: Nuclear PARP-1 immunohistochemical expression was studied in 326 paraffin-embedded renal allograft biopsies (193 with different degrees of ATN and 133 controls and in murine Parp-1 knockout model of IR injury. RESULTS: PARP-1 expression showed a significant relationship with cold ischemia time (r coefficient = 0.603, time to effective diuresis (r = 0.770, serum creatinine levels at biopsy (r = 0.649, and degree of ATN (r = 0.810 (p = 0.001, Pearson test. In the murine IR model, western blot showed an increase in PARP-1 that was blocked by Parp-1 inhibitor. Immunohistochemical study of PARP-1 in kidney allograft biopsies would allow early detection of possible delayed renal function, and the administration of PARP-1 inhibitors may offer a therapeutic option to reduce damage from IR in donor kidneys by preventing or minimizing ATN. In summary, these results suggest a pivotal role for PARP-1 in the ATN of renal transplantation. We propose the immunohistochemical assessment of PARP-1 in kidney allograft biopsies for early detection of a possible delayed renal function.

  16. The delaying effect of stigma on mental health help-seeking in Sri Lanka.

    Science.gov (United States)

    Fernando, Sunera M; Deane, Frank P; McLeod, Hamish J

    2017-03-01

    Mental health stigma has been associated with delays in seeking treatment. To describe perceived stigma experienced by patients and carers in Sri Lanka and to determine the effects of stigma on help-seeking delay. Survey of outpatients and family carers (n = 118 dyads) attending two psychiatric hospitals in Sri Lanka, using the Disclosure and Discrimination subscales of the Stigma Scale. Stigma was positively related to help-seeking delay for carers but not patients. Public stigma experienced by carers accounted for 23% of the variance in help-seeking delay. Reducing stigma may reduce help-seeking delays during the course of treatment. © 2016 John Wiley & Sons Australia, Ltd.

  17. Targeting Glutamatergic Signaling for the Development of Novel Therapeutics for Mood Disorders

    Science.gov (United States)

    Machado-Vieira, R.; Salvadore, G.; Ibrahim, L.; DiazGranados, N.; Zarate, C.A.

    2009-01-01

    There have been no recent advances in drug development for mood disorders in terms of identifying drug targets that are mechanistically distinct from existing ones. As a result, existing antidepressants are based on decades-old notions of which targets are relevant to the mechanisms of antidepressant action. Low rates of remission, a delay of onset of therapeutic effects, continual residual depressive symptoms, relapses, and poor quality of life are unfortunately common in patients with mood disorders. Offering alternative options is requisite in order to reduce the individual and societal burden of these diseases. The glutamatergic system is a promising area of research in mood disorders, and likely to offer new possibilities in therapeutics. There is increasing evidence that mood disorders are associated with impairments in neuroplasticity and cellular resilience, and alterations of the glutamatergic system are known to play a major role in cellular plasticity and resilience. Existing antidepressants and mood stabilizers have prominent effects on the glutamate system, and modulating glutamatergic ionotropic or metabotropic receptors results in antidepressant-like properties in animal models. Several glutamatergic modulators targeting various glutamate components are currently being studied in the treatment of mood disorders, including release inhibitors of glutamate, N-methyl-D-aspartate (NMDA) antagonists, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) throughput enhancers, and glutamate transporter enhancers. This paper reviews the currently available knowledge regarding the role of the glutamatergic system in the etiopathogenesis of mood disorders and putative glutamate modulators. PMID:19442176

  18. Effects of prophylactic and therapeutic teriflunomide in transcranial magnetic stimulation-induced motor-evoked potentials in the dark agouti rat model of experimental autoimmune encephalomyelitis.

    Science.gov (United States)

    Iglesias-Bregna, Deborah; Hanak, Susan; Ji, Zhongqi; Petty, Margaret; Liu, Li; Zhang, Donghui; McMonagle-Strucko, Kathleen

    2013-10-01

    Teriflunomide is a once-daily oral immunomodulatory agent recently approved in the United States for the treatment of relapsing multiple sclerosis (RMS). This study investigated neurophysiological deficits in descending spinal cord motor tracts during experimental autoimmune encephalomyelitis (EAE; a model of multiple sclerosis) and the functional effectiveness of prophylactic or therapeutic teriflunomide treatment in preventing the debilitating paralysis observed in this model. Relapsing-remitting EAE was induced in Dark Agouti rats using rat spinal cord homogenate. Animals were treated with oral teriflunomide (10 mg/kg daily) prophylactically, therapeutically, or with vehicle (control). Transcranial magnetic motor-evoked potentials were measured throughout the disease to provide quantitative assessment of the neurophysiological status of descending motor tracts. Axonal damage was quantified histologically by silver staining. Both prophylactic and therapeutic teriflunomide treatment significantly reduced maximum EAE disease scores (P teriflunomide treatment regimens prevented a delay in wave-form latency and a decrease in wave-form amplitude compared with that observed in vehicle-treated animals. A significant reduction in axonal loss was observed with both teriflunomide treatment regimens compared with vehicle (P teriflunomide can prevent the deficits observed in this animal model in descending spinal cord motor tracts. The mechanism behind reduced axonal loss and improved motor function may be primarily the reduced inflammation and consequent demyelination observed in these animals through the known effects of teriflunomide on impairing proliferation of stimulated T cells. These findings may have significant implications for patients with RMS.

  19. Effects of delayed and extended antioxidant treatment on acute acoustic trauma.

    Science.gov (United States)

    Choi, Chul-Hee; Chen, Kejian; Du, Xiaoping; Floyd, Robert A; Kopke, Richard D

    2011-10-01

    Hair cell death caused by acute acoustic trauma (AAT) reaches a secondary maximum at 7-10 days after noise exposure due to a second oxidative stress. Therefore, this study tested the effects of a combination of hydroxylated alpha-phenyl-tert-butylnitrone (4-OHPBN), N-acetyl-L-cysteine (NAC) and acetyl-L-carnitine (ALCAR) on AAT when the duration of treatment was extended over the period of 7-10 days after noise exposure as well as when the initial treatment was delayed 24 to 48 h after noise exposure. Thirty chinchilla were exposed to a 105 dB octave-band noise centred at 4 kHz for 6 h and received the following treatments: (1) noise + saline (2-5) 4-OHPBN (20 mg/kg) + NAC (50 mg/kg) + ALCAR (20 mg/kg) intraperitoneally injected beginning 24 or 48 h after noise exposure twice daily for the next 2, 8 or 9 days. Auditory brainstem response (ABR) threshold shifts, outer hair cell (OHC) counts and organ of Corti immunohistochemistry were analyzed. The combination administration decreased ABR threshold shifts, inhibited OHC loss and reduced 4-hydroxynonenal (4-HNE) immunostaining. Significant decreases in the threshold shifts and reduction in OHC loss were observed with a shorter delay before starting treatment (24 h) and longer duration (9 days) treatment. These results demonstrate that the administration of antioxidant drugs extended up to 10 days after noise exposure can effectively treat AAT in a chinchilla model. This may provide significant and potentially clinically important information about the effective therapeutic window for AAT treatment. © 2011 Informa UK, Ltd.

  20. AAV serotype-1 mediates early onset of gene expression in mouse hearts and results in better therapeutic effect.

    Science.gov (United States)

    Su, H; Huang, Y; Takagawa, J; Barcena, A; Arakawa-Hoyt, J; Ye, J; Grossman, W; Kan, Y W

    2006-11-01

    Adeno-associated viral vectors (AAV) are attractive tool for gene therapy for coronary artery disease. However, gene expression in myocardium mediated by AAV serotype 2 (AAV2) does not peak until 4-6 weeks after gene transfer. This delayed gene expression may reduce its therapeutic potential for acute cardiac infarction. To determine whether earlier gene expression and better therapeutic effect could be achieved using a different serotype, CMV promoter driving the EPO gene (AAV-EPO) was packaged into AAV serotypes 1-5 capsids and injected into mouse myocardium. EPO expression was studied by measuring the hematocrits and EPO mRNA. After we found that AAV1 mediates the highest gene expression after 4 days of gene transduction, AAV-LacZ (CMV promoter driving LacZ gene expression) and MLCVEGF (hypoxia-inducible and cardiac-specific VEGF expression) were packaged into AAV1 and 2 capsids. LacZ expression was detected in AAV1-LacZ but not in AAV2-LacZ-injected hearts 1 day after vector injection. Compared to AAV2-MLCVEGF that mediated no significant VEGF expression, AAV1-MLCVEGF mediated 13.7-fold induction of VEGF expression in ischemic hearts 4 days after gene transduction and resulted in more neovasculatures, better cardiac function and less myocardial fibrosis. Thus, AAV1 mediates earlier and higher transgene expression in myocardium and better therapeutic effects.

  1. A Delayed Promotion Policy for Parity Games

    Directory of Open Access Journals (Sweden)

    Massimo Benerecetti

    2016-09-01

    Full Text Available Parity games are two-player infinite-duration games on graphs that play a crucial role in various fields of theoretical computer science. Finding efficient algorithms to solve these games in practice is widely acknowledged as a core problem in formal verification, as it leads to efficient solutions of the model-checking and satisfiability problems of expressive temporal logics, e.g., the modal muCalculus. Their solution can be reduced to the problem of identifying sets of positions of the game, called dominions, in each of which a player can force a win by remaining in the set forever. Recently, a novel technique to compute dominions, called priority promotion, has been proposed, which is based on the notions of quasi dominion, a relaxed form of dominion, and dominion space. The underlying framework is general enough to accommodate different instantiations of the solution procedure, whose correctness is ensured by the nature of the space itself. In this paper we propose a new such instantiation, called delayed promotion, that tries to reduce the possible exponential behaviours exhibited by the original method in the worst case. The resulting procedure not only often outperforms the original priority promotion approach, but so far no exponential worst case is known.

  2. Therapeutic Effect of Caffeine Treatment Immediately Following Neonatal Hypoxic-Ischemic Injury on Spatial Memory in Male Rats

    Directory of Open Access Journals (Sweden)

    R. Holly Fitch

    2013-03-01

    Full Text Available Hypoxia Ischemia (HI refers to the disruption of blood and/or oxygen delivery to the brain. Term infants suffering perinatal complications that result in decreased blood flow and/or oxygen delivery to the brain are at risk for HI. Among a variety of developmental delays in this population, HI injured infants demonstrate subsequent memory deficits. The Rice-Vannucci rodent HI model can be used to explore behavioral deficits following early HI events, as well as possible therapeutic agents to help reduce deleterious outcomes. Caffeine is an adenosine receptor antagonist that has recently shown promising results as a therapeutic agent following HI injury. The current study sought to investigate the therapeutic benefit of caffeine following early HI injury in male rats. On post-natal day (P 7, HI injury was induced (cauterization of the right common carotid artery, followed by two hours of 8% oxygen. Male sham animals received only a midline incision with no manipulation of the artery followed by room air exposure for two hours. Subsets of HI and sham animals then received either an intraperitoneal (i.p. injection of caffeine (10 mg/kg, or vehicle (sterile saline immediately following hypoxia. All animals later underwent testing on the Morris Water Maze (MWM from P90 to P95. Results show that HI injured animals (with no caffeine treatment displayed significant deficits on the MWM task relative to shams. These deficits were attenuated by caffeine treatment when given immediately following the induction of HI. We also found a reduction in right cortical volume (ipsilateral to injury in HI saline animals as compared to shams, while right cortical volume in the HI caffeine treated animals was intermediate. These findings suggest that caffeine is a potential therapeutic agent that could be used in HI injured infants to reduce brain injury and preserve subsequent cognitive function.

  3. Caloric intake and Alzheimer's disease. Experimental approaches and therapeutic implications.

    Science.gov (United States)

    Pasinetti, Giulio Maria; Zhao, Zhong; Qin, Weiping; Ho, Lap; Shrishailam, Yemul; Macgrogan, Donal; Ressmann, Wendy; Humala, Nelson; Liu, Xunxian; Romero, Carmen; Stetka, Breton; Chen, Linghong; Ksiezak-Reding, Hanna; Wang, Jun

    2007-01-01

    Alzheimer's disease (AD) is a rapidly growing public health concern with potentially devastating effects. Presently, there are no known cures or effective preventive strategies. While genetic factors are relevant in early-onset cases, they appear to play less of a role in late-onset sporadic AD cases, the most common form of AD. Due to the fact that the disease typically strikes very late in life, delaying symptoms could be as good as a cure for many people. For example, it is now widely accepted that if the onset of the disease could be delayed by even 5 years, the incidence could be cut in half. Both clinical and epidemiological evidence suggests that modification of lifestyle factors such as nutrition may prove crucial to AD management given the mounting experimental evidence suggesting that brain cells are remarkably responsive to "what somebody is doing". Among other nongenetic factors influencing AD, recent studies strongly support the evidence that caloric intake may play a role in the relative risk for AD clinical dementia. Indeed, the effect of diet in AD has been an area of research that has produced promising results, at least experimentally. Most importantly, as mechanistic pathways are defined and their biochemical functions scrutinized, the evidence supporting a direct link between nutrition and AD neuropathology continues to grow. Our work, as well as that of others, has recently resulted in the development of experimental dietary regimens that might promote, attenuate or even reverse features of AD. Most remarkably, while we found that high caloric intake based on saturated fat promotes AD type Beta-amyloidosis, conversely we found that dietary restriction based on reduced carbohydrate intake is able to prevent it. This evidence is very exciting and is, in part, consistent with current epidemiological studies suggesting that obesity and diabetes are associated with a >4-fold increased risk of developing AD. The clarification of the mechanisms

  4. Delay discounting of food and remifentanil in rhesus monkeys.

    Science.gov (United States)

    Maguire, David R; Gerak, Lisa R; France, Charles P

    2013-09-01

    Drug abuse can be conceptualized as choice between drug and nondrug reinforcers in which drug choice is excessive; factors impacting drug taking can be examined using procedures in which subjects choose between drug and an alternative reinforcer. This experiment examined the effects of delayed reinforcement on choice between food and the mu-opioid receptor agonist remifentanil. Rhesus monkeys responded under a concurrent fixed-ratio 5, fixed-ratio 5 schedule in which responding on one lever delivered one food pellet and responding on another lever delivered an i.v. infusion. With no delay, monkeys responded predominantly for food rather than saline or small doses of remifentanil; as the dose of remifentanil increased (0.1-1.0 μg/kg/infusion), monkeys responded more for drug. Delaying delivery (30-240 s) of 0.32 and not 1.0 μg/kg/infusion of remifentanil (food delivered immediately) decreased responding for drug and increased responding for food, resulting in a rightward shift in the remifentanil dose-effect curve. Delaying delivery of food (60-240 s) when doses of remifentanil smaller than 0.32 μg/kg/infusion (but not saline) were available decreased responding for food and increased responding for drug, resulting in a leftward shift in the remifentanil dose-effect curve. These results provide evidence that delaying the delivery of a mu-opioid receptor agonist reduces its potency as a positive reinforcer; more importantly, delaying the delivery of an alternative nondrug reinforcer (e.g., food) enhances the reinforcing potency of the agonist. Thus, understanding the factors that control substance abuse requires examination of contingencies for both drug and nondrug reinforcers.

  5. Is "Delayed Umbilical Cord Clamping" Beneficial for Premature Newborns?

    Directory of Open Access Journals (Sweden)

    Amir-Mohammad Armanian

    2017-05-01

    Full Text Available Background: The appropriate moment for clamping the umbilical cord is controversial. Immediate cord clamping (ICC is an item of active management of the third stage of labor (AMTSL. Unclamped umbilical cord may cause inconvenience in preterm neonates because they commonly need some levels of emergent services. Some studies revealed delayed cord clamping (DCC of preterm neonates results in better health conditions like lower rates of respiratory distress syndrome (RDS, less morbidities in labor room and lower risk of postpartum hemorrhage. The aim of the present study was to determine the effect of delayed umbilical cord clamping on premature neonatal outcomes. Materials and Methods: In this single‑center randomized control trial study, sixty premature neonates (gestational age ≤ 34 weeks were randomly assigned to ICC (cord clamped at 5–10 seconds or DCC (30–45 seconds groups and followed up in neonatal intensive care unit (NICU. Primary outcomes were 1st and 5th minute Apgar score, average of level of hematocrit after birth, intra ventricle hemorrhage and need some levels of resuscitation. Results: Differences in demographic characteristics were not statistically significant. After birth, neonates who had delayed clamping had significantly higher mean hematocrit after at 4-hour of birth (49.58+5.15gr/dl vs. 46.58+5.40gr/dlin DCC vs. ICC groups, respectively (P=0.031. Delayed cord clamping reduced the duration of need to nasal continues positive airway pressure (NCPAP (86.7% and 60.0% in ICC and DCC groups, respectively, P= 0.039. Attractively, the results showed lower incidence of clinical sepsis in delayed cord clamping neonates (53.3% vs. 23.3% in ICC and DCC groups, respectively, P=0.033. Conclusion: Prematurity complications might decrease by delay umbilical cord clamping which improve the hematocrit, duration of need to NCPAP and incidence of clinical sepsis. Furthermore, DCC may have no negative impact on neonatal resuscitation.

  6. Analysis and control of issues that delay pharmaceutical projects

    Directory of Open Access Journals (Sweden)

    Nallam Sai Nandeswara Rao

    2015-10-01

    Full Text Available Every project will have certain objectives and service levels to be achieved. The success of a project depends on several dimensions like time, cost/budget, quality, etc. and managing a project involves completing the project within time, within budget and with quality to satisfy the users. Because of the significance of health, pharmaceutical companies realized the importance of project management methods and techniques to make available the life saving drugs in time to the needy patients and hospitals. In literature, there is meager information about pharmaceutical project management oriented towards analysis of issues and factors that contribute to the failure or success of projects. This study attempts to analyse different issues that contribute to time delays in pharmaceutical product-based projects, group them under a finite set of prominent factors and identify remedial measures to control those delays. The feedback of project people of some big pharmaceutical firms of Indian sub-continent was collected for this purpose. Exploratory factor analysis (EFA has been used to reduce the reasons for time delays to a limited number of prominent factors and the EFA model has been further examined by confirmatory factor analysis (CFA for its validation. Remedial measures under each factor of time delays have been gathered and a framework designed to mitigate the time delays in pharmaceutical projects. The derived factors that delay the pharmaceutical projects include resource, monitoring & control, scheduling and planning problems. Important remedial measures like blended resource approach, estimation and forecast of shortage of labour and skills, regular quality training, etc. have been recommended.

  7. A human type 5 adenovirus-based Trypanosoma cruzi therapeutic vaccine re-programs immune response and reverses chronic cardiomyopathy.

    Directory of Open Access Journals (Sweden)

    Isabela Resende Pereira

    2015-01-01

    Full Text Available Chagas disease (CD, caused by the protozoan Trypanosoma cruzi, is a prototypical neglected tropical disease. Specific immunity promotes acute phase survival. Nevertheless, one-third of CD patients develop chronic chagasic cardiomyopathy (CCC associated with parasite persistence and immunological unbalance. Currently, the therapeutic management of patients only mitigates CCC symptoms. Therefore, a vaccine arises as an alternative to stimulate protective immunity and thereby prevent, delay progression and even reverse CCC. We examined this hypothesis by vaccinating mice with replication-defective human Type 5 recombinant adenoviruses (rAd carrying sequences of amastigote surface protein-2 (rAdASP2 and trans-sialidase (rAdTS T. cruzi antigens. For prophylactic vaccination, naïve C57BL/6 mice were immunized with rAdASP2+rAdTS (rAdVax using a homologous prime/boost protocol before challenge with the Colombian strain. For therapeutic vaccination, rAdVax administration was initiated at 120 days post-infection (dpi, when mice were afflicted by CCC. Mice were analyzed for electrical abnormalities, immune response and cardiac parasitism and tissue damage. Prophylactic immunization with rAdVax induced antibodies and H-2Kb-restricted cytotoxic and interferon (IFNγ-producing CD8+ T-cells, reduced acute heart parasitism and electrical abnormalities in the chronic phase. Therapeutic vaccination increased survival and reduced electrical abnormalities after the prime (analysis at 160 dpi and the boost (analysis at 180 and 230 dpi. Post-therapy mice exhibited less heart injury and electrical abnormalities compared with pre-therapy mice. rAdVax therapeutic vaccination preserved specific IFNγ-mediated immunity but reduced the response to polyclonal stimuli (anti-CD3 plus anti-CD28, CD107a+ CD8+ T-cell frequency and plasma nitric oxide (NO levels. Moreover, therapeutic rAdVax reshaped immunity in the heart tissue as reduced the number of perforin+ cells

  8. Optimal therapies of a virus replication model with pharmacological delays based on reverse transcriptase inhibitors and protease inhibitors

    Science.gov (United States)

    Pei, Yongzhen; Li, Changguo; Liang, Xiyin

    2017-11-01

    A short delay in the pharmacological effect on account of the time required for drug absorption, distribution, and penetration into target cells after application of any anti-viral drug, is defined by the pharmacological delay (Herz et al 1996 Proc. Natl Acad. Sci. USA 93 7247-51). In this paper, a virus replication model with Beddington-DeAngelis incidence rate and the pharmacological and intracellular delays is presented to describe the treatment to cure the virus infection. The optimal controls represent the efficiency of reverse transcriptase inhibitors and protease inhibitors in suppressing viral production and prohibiting new infections. Due to the fact that both the control and state variables contain delays, we derive a necessary conditions for our optimal problem. Based on these results, numerical simulations are implemented not only to show the optimal therapeutic schedules for different infection and release rates, but also to compare the effective of three treatment programs. Furthermore, comparison of therapeutic effects under different maximum tolerable dosages is shown. Our research indicates that (1) the proper and specific treatment program should be determined according to the infection rates of different virus particles; (2) the optimal combined drug treatment is the most efficient; (3) the appropriate proportion of medicament must be formulated during the therapy due to the non-monotonic relationship between maximum tolerable dosages and therapeutic effects; (4) the therapeutic effect is advantageous when the pharmacological delay is considered.

  9. [Nuclear transfer and therapeutic cloning].

    Science.gov (United States)

    Xu, Xiao-Ming; Lei, An-Min; Hua, Jin-Lian; Dou, Zhong-Ying

    2005-03-01

    Nuclear transfer and therapeutic cloning have widespread and attractive prospects in animal agriculture and biomedical applications. We reviewed that the quality of oocytes and nuclear reprogramming of somatic donor cells were the main reasons of the common abnormalities in cloned animals and the low efficiency of cloning and showed the problems and outlets in therapeutic cloning, such as some basic problems in nuclear transfer affected clinical applications of therapeutic cloning. Study on isolation and culture of nuclear transfer embryonic stem (ntES) cells and specific differentiation of ntES cells into important functional cells should be emphasized and could enhance the efficiency. Adult stem cells could help to cure some great diseases, but could not replace therapeutic cloning. Ethics also impeded the development of therapeutic cloning. It is necessary to improve many techniques and reinforce the research of some basic theories, then somatic nuclear transfer and therapeutic cloning may apply to agriculture reproduction and benefit to human life better.

  10. Reducing Attendance Time in LR-EPONs With Differentiated Services

    KAUST Repository

    Elrasad, Amr

    2015-04-09

    This work presents a novel on-the-fly void filling scheme for Long-Reach EPON called Size Controlled Batch Void Filling (SCBVF). SCBVF aims at reducing the time between consecutive bandwidth grants (attendance time) and hence reducing the average delay for delay-sensitive traffic.

  11. Delay Discounting of Losses in Alcohol Use Disorders and Antisocial Psychopathology: Effects of a Working Memory Load.

    Science.gov (United States)

    Gerst, Kyle R; Gunn, Rachel L; Finn, Peter R

    2017-10-01

    Alcohol use disorders (AUDs) are associated with increased discounting of delayed rewards and reduced executive working memory (eWM) capacity. This association is amplified when comorbid with antisocial psychopathology (AP). Furthermore, recent studies suggest that reduced WM capacity is associated with disinhibited decisions reflected by increased impulsive decision making on the delay discounting of rewards task. While discounting of delayed rewards is well studied, the discounting of delayed losses has received significantly less experimental attention. The current study investigated (i) the rate of discounting of delayed losses in individuals with AUD only (n = 61), AUD with comorbid AP (n = 79) and healthy controls (n = 64); (ii) the relationship between eWM capacity and discounting of delayed losses; and (iii) the effect of a WM load on discounting of delayed losses. Discounting performance was assessed using a computerized discounting of delayed losses task. Results showed that the AUD-only and AUD-AP groups had higher rates of discounting of delayed losses and lower eWM capacity compared to the control groups. Lower individual eWM capacity was associated with increased discounting of delayed losses. However, WM load did not increase discounting rates overall. These results support the hypothesis that greater discounting of delayed losses is associated with AUD and comorbid AP problems and lower individual eWM capacity. Copyright © 2017 by the Research Society on Alcoholism.

  12. Temperature Dependent Wire Delay Estimation in Floorplanning

    DEFF Research Database (Denmark)

    Winther, Andreas Thor; Liu, Wei; Nannarelli, Alberto

    2011-01-01

    Due to large variations in temperature in VLSI circuits and the linear relationship between metal resistance and temperature, the delay through wires of the same length can be different. Traditional thermal aware floorplanning algorithms use wirelength to estimate delay and routability....... In this work, we show that using wirelength as the evaluation metric does not always produce a floorplan with the shortest delay. We propose a temperature dependent wire delay estimation method for thermal aware floorplanning algorithms, which takes into account the thermal effect on wire delay. The experiment...... results show that a shorter delay can be achieved using the proposed method. In addition, we also discuss the congestion and reliability issues as they are closely related to routing and temperature....

  13. Memorized discrete systems and time-delay

    CERN Document Server

    Luo, Albert C J

    2017-01-01

    This book examines discrete dynamical systems with memory—nonlinear systems that exist extensively in biological organisms and financial and economic organizations, and time-delay systems that can be discretized into the memorized, discrete dynamical systems. It book further discusses stability and bifurcations of time-delay dynamical systems that can be investigated through memorized dynamical systems as well as bifurcations of memorized nonlinear dynamical systems, discretization methods of time-delay systems, and periodic motions to chaos in nonlinear time-delay systems. The book helps readers find analytical solutions of MDS, change traditional perturbation analysis in time-delay systems, detect motion complexity and singularity in MDS; and determine stability, bifurcation, and chaos in any time-delay system.

  14. Time Delay Estimation Algoritms for Echo Cancellation

    Directory of Open Access Journals (Sweden)

    Boris Simak

    2011-01-01

    Full Text Available The following case study describes how to eliminate echo in a VoIP network using delay estimation algorithms. It is known that echo with long transmission delays becomes more noticeable to users. Thus, time delay estimation, as a part of echo cancellation, is an important topic during transmission of voice signals over packetswitching telecommunication systems. An echo delay problem associated with IP-based transport networks is discussed in the following text. The paper introduces the comparative study of time delay estimation algorithm, used for estimation of the true time delay between two speech signals. Experimental results of MATLab simulations that describe the performance of several methods based on cross-correlation, normalized crosscorrelation and generalized cross-correlation are also presented in the paper.

  15. Dynamics of Nonlinear Time-Delay Systems

    CERN Document Server

    Lakshmanan, Muthusamy

    2010-01-01

    Synchronization of chaotic systems, a patently nonlinear phenomenon, has emerged as a highly active interdisciplinary research topic at the interface of physics, biology, applied mathematics and engineering sciences. In this connection, time-delay systems described by delay differential equations have developed as particularly suitable tools for modeling specific dynamical systems. Indeed, time-delay is ubiquitous in many physical systems, for example due to finite switching speeds of amplifiers in electronic circuits, finite lengths of vehicles in traffic flows, finite signal propagation times in biological networks and circuits, and quite generally whenever memory effects are relevant. This monograph presents the basics of chaotic time-delay systems and their synchronization with an emphasis on the effects of time-delay feedback which give rise to new collective dynamics. Special attention is devoted to scalar chaotic/hyperchaotic time-delay systems, and some higher order models, occurring in different bran...

  16. Therapeutic vaccines for leishmaniasis.

    Science.gov (United States)

    Khamesipour, Ali

    2014-11-01

    Numerous therapeutic strategies are used to treat leishmaniasis. The treatment of cutaneous leishmaniasis (CL) is solely depends on antimonate derivatives with safety issues and questionable efficacy and there is no fully effective modality to treat CL caused by Leishmania tropica and Leishmania braziliensis. There is no prophylactic vaccine available against any form of leishmaniasis. Immunotherapy for CL has a long history; immunotherapy trials of first and second generation vaccines showed promising results. The current article briefly covers the prophylactic vaccines and explains different immunotherapy strategies that have been used to treat leishmaniasis. This paper does not include experimental vaccines and only lays emphasis on human trials and those vaccines which reached human trials. Immunotherapy is currently used to successfully treat several disorders; Low cost, limited side effects and no possibility to develop resistance make immunotherapy a valuable choice especially for infectious disease with chemotherapy problems. Efforts are needed to explore the immunological surrogate marker(s) of cure and protection in leishmaniasis and overcome the difficulties in standardization of crude Leishmania vaccines. One of the reasons for anti-leishmaniasis vaccine failure is lack of an appropriate adjuvant. So far, not enough attention has been paid to develop vaccines for immunotherapy of leishmaniasis.

  17. Kinetoplastida: new therapeutic strategies

    Directory of Open Access Journals (Sweden)

    Croft S.L.

    2008-09-01

    Full Text Available New formulations and therapeutic switching of the established drugs, amphotericin B and paromomycin, together with the discovery of miltefosine, have significantly improved the opportunities for treatment of visceral leishmaniasis (VL chemotherapy. However, for human African trypanosomiasis (HAT, Chagas disease and cutaneous leishmaniases there has been limited progress. For HAT, a novel diamidine, parfuramidine, is in phase III clinical trial for early-stage disease, but for the treatment of late-stage disease there are no new drugs and combinations of eflornithine with melarsoprol or nifurtimox have been the focus of clinical studies. For Chagas disease, different classes of compounds that have validated biochemical targets, sterol biosynthesis methylases and cysteine proteases, are in various stages of development. The genome sequences that are now available for the pathogens that cause the leishmaniases and trypanosomiases, and new methods for rapid validation of targets, are part of the solution to discover new drugs. The integration of medicinal chemistry, pharmacokinetics, project planning and interaction with the pharma/biotech sector are essential if progress is to be made. Although there are financial constraints, the appearance of new funding sources and not-for-profit product development partnerships offers hope for drug development.

  18. Therapeutic uses of magnesium.

    Science.gov (United States)

    Guerrera, Mary P; Volpe, Stella Lucia; Mao, Jun James

    2009-07-15

    Magnesium is an essential mineral for optimal metabolic function. Research has shown that the mineral content of magnesium in food sources is declining, and that magnesium depletion has been detected in persons with some chronic diseases. This has led to an increased awareness of proper magnesium intake and its potential therapeutic role in a number of medical conditions. Studies have shown the effectiveness of magnesium in eclampsia and preeclampsia, arrhythmia, severe asthma, and migraine. Other areas that have shown promising results include lowering the risk of metabolic syndrome, improving glucose and insulin metabolism, relieving symptoms of dysmenorrhea, and alleviating leg cramps in women who are pregnant. The use of magnesium for constipation and dyspepsia are accepted as standard care despite limited evidence. Although it is safe in selected patients at appropriate dosages, magnesium may cause adverse effects or death at high dosages. Because magnesium is excreted renally, it should be used with caution in patients with kidney disease. Food sources of magnesium include green leafy vegetables, nuts, legumes, and whole grains.

  19. Leech Therapeutic Applications

    Science.gov (United States)

    Abdualkader, A. M.; Ghawi, A. M.; Alaama, M.; Awang, M.; Merzouk, A.

    2013-01-01

    Hematophagous animals including leeches have been known to possess biologically active compounds in their secretions, especially in their saliva. The blood-sucking annelids, leeches have been used for therapeutic purposes since the beginning of civilization. Ancient Egyptian, Indian, Greek and Arab physicians used leeches for a wide range of diseases starting from the conventional use for bleeding to systemic ailments, such as skin diseases, nervous system abnormalities, urinary and reproductive system problems, inflammation, and dental problems. Recently, extensive researches on leech saliva unveiled the presence of a variety of bioactive peptides and proteins involving antithrombin (hirudin, bufrudin), antiplatelet (calin, saratin), factor Xa inhibitors (lefaxin), antibacterial (theromacin, theromyzin) and others. Consequently, leech has made a comeback as a new remedy for many chronic and life-threatening abnormalities, such as cardiovascular problems, cancer, metastasis, and infectious diseases. In the 20th century, leech therapy has established itself in plastic and microsurgery as a protective tool against venous congestion and served to salvage the replanted digits and flaps. Many clinics for plastic surgery all over the world started to use leeches for cosmetic purposes. Despite the efficacious properties of leech therapy, the safety, and complications of leeching are still controversial. PMID:24019559

  20. [In chronic hepatitis C, delays between diagnosis and treatment are linked to the doctor-patient relationship].

    Science.gov (United States)

    Enel, Catherine; Minello, Anne; Jooste, Valérie; Pinoit, Jean-Michel; Hillon, Patrick

    2009-05-01

    An epidemiological survey conducted in Côte d'Or and Doubs in 2004 showed that out of 1,251 patients carrying HCV, only 1 in 4 was treated whereas 1 in 6 evades medical care after diagnosis. A study carried out in Burgundy in 2006-2008 aimed to identify the key factors underlying insufficiency in medical care of hepatitis C. Semi-structured in-depth interviews were conducted with 25 medical doctors. They covered the frequency with which doctors were confronted with hepatitis C and the difficulties encountered in its management. The interviews with patients explored the circumstances of diagnosis, therapeutic route, perceptions regarding infection and its treatment and relationships with healthcare providers. The study showed a variability in delays between diagnosis and treatment that can be explained by the functioning of the doctor-patient relationship, and the choices of medical strategies. To prevent more efficiently hepatitis C complications, treatment acceptance by patients needs to be improved and doctors' hesitations in prescribing it lessened. Efforts should also be made to reduce the iatrogenic side effects of the treatment, and improve general practitioners' training with respect to viral hepatitis, and interaction between the medical specialities involved, in order to develop greater consensus in therapeutic strategies to be adopted.

  1. Delayed leaf senescence induces extreme drought tolerance in crop plants

    OpenAIRE

    Rivero, Rosa; Peleg, Zvi; Szczerba, Mark; Tumimbang, Ellen; Jauregui, Rosa N; Liu, Li; Blumwald, Eduardo

    2009-01-01

    Drought, the most prominent threat to agricultural production worldwide, accelerates leaf senescence, leading to a decrease in canopy size, loss in photosynthesis and reduced yields. On the basis of the assumption that senescence is a type of cell death program that could be inappropriately activated during drought, we hypothesized that it may be possible to enhance drought tolerance by delaying drought-induced leaf senescence through the stress-induced synthesis of cytokinins. We generated m...

  2. Lyapunov exponents for complex systems with delayed feedback

    CERN Document Server

    Dailyudenko, V F

    2003-01-01

    Analytical and numerical analysis is implemented for two methods of Lyapunov exponents calculation. The first is based on successive multiplication of functional matrixes corresponding to discrete transformations and calculation of eigenvalues for the obtained matrix. The second approach is based on successive orthogonalization of multiplied matrixes using QR-decomposition. The analytical model for describing functional maps of discrete iterations derived from delay differential equation is proposed, which implements representation of the product matrix through matrixes of canonical form that reduces calculation complexity.

  3. The Gist of Delay of Gratification: Understanding and Predicting Problem Behaviors.

    Science.gov (United States)

    Reyna, Valerie F; Wilhelms, Evan A

    2017-04-01

    Delay of gratification captures elements of temptation and self-denial that characterize real-life problems with money and other problem behaviors such as unhealthy risk taking. According to fuzzy-trace theory, decision makers mentally represent social values such as delay of gratification in a coarse but meaningful form of memory called "gist." Applying this theory, we developed a gist measure of delay of gratification that does not involve quantitative trade-offs (as delay discounting does) and hypothesize that this construct explains unique variance beyond sensation seeking and inhibition in accounting for problem behaviors. Across four studies, we examine this Delay-of-gratification Gist Scale by using principal components analyses and evaluating convergent and divergent validity with other potentially related scales such as Future Orientation, Propensity to Plan, Time Perspectives Inventory, Spendthrift-Tightwad, Sensation Seeking, Cognitive Reflection, Barratt Impulsiveness, and the Monetary Choice Questionnaire (delay discounting). The new 12-item measure captured a single dimension of delay of gratification, correlated as predicted with other scales, but accounted for unique variance in predicting such outcomes as overdrawing bank accounts, substance abuse, and overall subjective well-being. Results support a theoretical distinction between reward-related approach motivation, including sensation seeking, and inhibitory faculties, including cognitive reflection. However, individuals' agreement with the qualitative gist of delay of gratification, as expressed in many cultural traditions, could not be reduced to such dualist distinctions nor to quantitative conceptions of delay discounting, shedding light on mechanisms of self-control and risk taking.

  4. Therapeutic cloning in the mouse

    Science.gov (United States)

    Mombaerts, Peter

    2003-01-01

    Nuclear transfer technology can be applied to produce autologous differentiated cells for therapeutic purposes, a concept termed therapeutic cloning. Countless articles have been published on the ethics and politics of human therapeutic cloning, reflecting the high expectations from this new opportunity for rejuvenation of the aging or diseased body. Yet the research literature on therapeutic cloning, strictly speaking, is comprised of only four articles, all in the mouse. The efficiency of derivation of embryonic stem cell lines via nuclear transfer is remarkably consistent among these reports. However, the efficiency is so low that, in its present form, the concept is unlikely to become widespread in clinical practice. PMID:12949262

  5. Delay discounting of the mu opioid receptor agonist remifentanil in rhesus monkeys

    Science.gov (United States)

    Maguire, David R.; Gerak, Lisa R.; France, Charles P.

    2015-01-01

    Although increased impulsivity (delay discounting) is an important risk factor for drug abuse, the impact of delay on drug taking has received relatively little attention. This study examined delay discounting of the mu opioid receptor agonist remifentanil in rhesus monkeys (n=4) responding for intravenous (i.v.) infusions under a concurrent choice procedure. Dose-effect curves for remifentanil were determined by varying the dose available on one lever (0.001-0.32 μg/kg/infusion) while keeping the dose available on the other lever (0.1 μg/kg/infusion) the same. Dose-effect curves were determined when both infusions were delivered immediately and when delivery of the fixed dose was delayed (15-180 s). When both doses of remifentanil were delivered immediately, monkeys chose the large dose. Delaying delivery of the fixed dose reduced choice of that dose and increased choice of small immediately available doses. Extending previous studies these results show that the effects of delay on choice between two doses of a mu opioid receptor agonist are consistent with hyperbolic discounting. Delaying delivery of a preferred reinforcer (e.g., large dose of drug) reduces its effectiveness and increases the effectiveness of small immediately available doses. This effect of delay, particularly on drug self-administration, might contribute to drug abuse. PMID:26397761

  6. Delay discounting of the μ-opioid receptor agonist remifentanil in rhesus monkeys.

    Science.gov (United States)

    Maguire, David R; Gerak, Lisa R; France, Charles P

    2016-04-01

    Although increased impulsivity (delay discounting) is an important risk factor for drug abuse, the impact of delay on drug taking has received relatively little attention. This study examined delay discounting of the μ-opioid receptor agonist remifentanil in rhesus monkeys (n=4) responding for intravenous infusions under a concurrent choice procedure. Dose-effect curves for remifentanil were determined by varying the dose available on one lever (0.001-0.32 μg/kg/infusion) while keeping the dose available on the other lever (0.1 μg/kg/infusion) the same. Dose-effect curves were determined when both infusions were delivered immediately and when delivery of the fixed dose was delayed (15-180 s). When both doses of remifentanil were delivered immediately, monkeys chose the large dose. Delaying delivery of the fixed dose reduced choice of that dose and increased choice of small immediately available doses. Extending previous studies, these results show that the effects of delay on choice between two doses of a μ-opioid receptor agonist are consistent with hyperbolic discounting. Delaying delivery of a preferred reinforcer (e.g. large dose of drug) reduces its effectiveness and increases the effectiveness of small immediately available doses. This effect of delay, particularly on drug self-administration, might contribute to drug abuse.

  7. Stochastic modeling of biochemical systems with multistep reactions using state-dependent time delay

    Science.gov (United States)

    Wu, Qianqian; Tian, Tianhai

    2016-08-01

    To deal with the growing scale of molecular systems, sophisticated modelling techniques have been designed in recent years to reduce the complexity of mathematical models. Among them, a widely used approach is delayed reaction for simplifying multistep reactions. However, recent research results suggest that a delayed reaction with constant time delay is unable to describe multistep reactions accurately. To address this issue, we propose a novel approach using state-dependent time delay to approximate multistep reactions. We first use stochastic simulations to calculate time delay arising from multistep reactions exactly. Then we design algorithms to calculate time delay based on system dynamics precisely. To demonstrate the power of proposed method, two processes of mRNA degradation are used to investigate the function of time delay in determining system dynamics. In addition, a multistep pathway of metabolic synthesis is used to explore the potential of the proposed method to simplify multistep reactions with nonlinear reaction rates. Simulation results suggest that the state-dependent time delay is a promising and accurate approach to reduce model complexity and decrease the number of unknown parameters in the models.

  8. Stability investigation of quadratic systems with delay

    Directory of Open Access Journals (Sweden)

    Vladimir Davydov

    2000-01-01

    Full Text Available Systems of differential equations with quadratic right-hand sides with delay are considered in the paper. Compact matrix notation form is proposed for the systems of such type. Stability investigations are performed by Lyapunov's second method with functions of quadratic form. Stability conditions of quadratic systems with delay, uniformly by argument deviation, and with delay depending on the system's parameters are derived. A guaranteed radius of the ball of asymptotic stability region for zero solution is obtained.

  9. Therapeutic outcomes of retinal hemangioblastomas.

    Science.gov (United States)

    Kim, Hyesun; Yi, Jeong H; Kwon, Hee J; Lee, Christopher S; Lee, Sung C

    2014-12-01

    To report the results of treatments and therapeutic complications of retinal hemangioblastomas (RH). Retrospective consecutive case series. Data from 32 patients (37 eyes) with RH were reviewed for characteristics of RH and treatment outcomes. Among 32 patients, we identified 73 RHs in 37 eyes. At baseline, 24 of 37 eyes (65%) had 20/50 visual acuity or better, 8 eyes (22%) had intermediate vision (20/400-20/50), and 5 eyes (13%) had poor vision (≤20/400). Seven RHs (9.6%) were located in the juxtapapillary area, and 66 RHs (90.4%) were located in peripheral area. Small RHs (54.8%; thermotherapy, and large RHs (20.5%; >3.0 mm in size) were treated with a combination of transpupillary thermotherapy and cryotherapy. After treatment, 90% of small RHs regressed, whereas only 67% of large RHs regressed (P = 0.044). Peripheral RHs showed better response to treatment than juxtapapillary RHs (P = 0.010). Treatment-related complications occurred in 5 eyes (14%), and 1-step combination therapy was applied more frequently in the complication group (P = 0.048). Small RHs in peripheral areas may require aggressive treatment because they respond well to treatment. In larger RHs, staged treatment could reduce treatment-related complications. Transpupillary thermotherapy could be an effective method in tumor regression for moderate-to-large-sized RHs showing tumor regression rate of 70%.

  10. Pelvic Actinomycosis; the Disease for Which Diagnostic and Therapeutic Delay is Still Being Experienced

    Directory of Open Access Journals (Sweden)

    Dinc Suren

    2014-03-01

    Full Text Available Actinomyces is a gram-positive bacteria, which presents as a normal flora member at mucosal areas. Because of its unexpected localization, malignancy is the clinical prediagnosis for more than half of the pelvic cases, and unnecessary extended surgery is performed in these patients. In this report, we present a case of a premenopausal woman with an abdominal mass, who had a pre-operative diagnosis of malignancy, but a post-operative histopathologic diagnosis of pelvic Actinomycosis. Although the clinical appearance resembles a malignancy, for the patient with intrauterine device (IUD history, distinctive aspect of the pelvic Actinomycosis should absolutely be considered. After the diagnosis is established, the infection source IUD should be removed and long term high dose penicillin therapy should be administered.  Surgery should be considered only if malignancy cannot be certainly excluded, if abscess drainage is necessary and if necrotic tissues and sinuses should be removed

  11. Food reinforcement, delay discounting and obesity.

    Science.gov (United States)

    Epstein, Leonard H; Salvy, Sarah J; Carr, Katelyn A; Dearing, Kelly K; Bickel, Warren K

    2010-07-14

    Choice is a central construct in behavioral economics, with choice research divided into choice of concurrent alternative reinforcers, which is conceptualized as relative reinforcing value, or choice of small immediate versus larger delayed rewards, usually of the same commodity, which is conceptualized as delay of gratification and delay discounting. Relative reinforcing value, delay of gratification and delay discounting paradigms can be used to study obesity, which involves strong motivation to obtain and consume food reinforcers. Strong food reinforcement and difficulties in delay of gratification are risk factors for child weight gain, and both are related to individual differences in overweight/obesity. Delay discounting interacts with food reinforcement to predict energy intake. We provide a selective review of research on each of these areas, and argue that the division of choice into reinforcing value versus delay discounting is based on an arbitrary definition based on the temporality of choices. We present a model that integrates reinforcing value and delay discounting approaches. Implications of this theoretical approach to better understand excess energy intake and obesity are discussed. The paper represents an invited review by a symposium, award winner or keynote speaker at the Society for the Study of Ingestive Behavior [SSIB] Annual Meeting in Portland, July 2009. 2010 Elsevier Inc. All rights reserved.

  12. Group Delay of High Q Antennas

    DEFF Research Database (Denmark)

    Bahramzy, Pevand; Pedersen, Gert Frølund

    2013-01-01

    become an issue, when working with high Q antennas, because of the steep phase shift over the frequency. In this paper, it is measured how large group delay variations can become, when going from a low Q antenna to a high Q antenna. The group delay of a low Q antenna is shown to be around 1.3 ns, whereas...... a high Q antenna has group delay of around 22 ns. It is due to this huge group delay variation characteristics of high Q antennas, that signal distortion might occur in the radio system with high Q antennas....

  13. Treatment delay among pulmonary tuberculosis patients in pastoralist communities in Bale Zone, Southeast Ethiopia

    Science.gov (United States)

    2012-01-01

    Background Tuberculosis (TB) is a major public health problem in Africa with Ethiopia being the most affected. Treatment delay is an important indicator of access to TB diagnosis and treatment. However, little is known about factors associated with treatment delay of pulmonary TB among pastoralists. Health facility based cross sectional study was conducted on 129 pulmonary TB patients in pastoralist community. The study was conducted in three health centers and a hospital. Time between onset of TB symptoms and first visit to a professional health care provider (patient delay), and the time between first visits to the professional health care provider to the date of diagnosis (provider's delay) were analyzed using SPSS 16.0 statistical software. Findings A total of 129 new smear positive pulmonary TB patients participated in the study. The median total delay was 97 days. The median patient and health provider delays were 63 and 34 days, respectively. Ninety six percent of the patients were delayed for more than the twenty one days cutoff point. Patient delay was positively associated with first visit to traditional healer/private clinic/drug shop, rural residence, being illiterate, living in more than 10 kilometers from health facility; severity of illness at first presentation to health facility. Provider delay was positively associated with rural residence, being illiterate, patient with good functional status, patients in contact with more than two health providers, and place of first visit being traditional healer/private clinic/drug shop. Conclusions This study showed that majority of smear positive patients delayed either for diagnosis or treatment, thus continue to serve as reservoirs of infection. This indicates that there is a need for intervention to decrease patient and provider delays. Effort to reduce delays in pastoralist communities should focus on improving access to services in rural communities, engaging traditional and private health providers and

  14. Treatment delay among pulmonary tuberculosis patients in pastoralist communities in Bale Zone, Southeast Ethiopia

    Directory of Open Access Journals (Sweden)

    Hussen Awol

    2012-06-01

    Full Text Available Abstract Background Tuberculosis (TB is a major public health problem in Africa with Ethiopia being the most affected. Treatment delay is an important indicator of access to TB diagnosis and treatment. However, little is known about factors associated with treatment delay of pulmonary TB among pastoralists. Health facility based cross sectional study was conducted on 129 pulmonary TB patients in pastoralist community. The study was conducted in three health centers and a hospital. Time between onset of TB symptoms and first visit to a professional health care provider (patient delay, and the time between first visits to the professional health care provider to the date of diagnosis (provider's delay were analyzed using SPSS 16.0 statistical software. Findings A total of 129 new smear positive pulmonary TB patients participated in the study. The median total delay was 97 days. The median patient and health provider delays were 63 and 34 days, respectively. Ninety six percent of the patients were delayed for more than the twenty one days cutoff point. Patient delay was positively associated with first visit to traditional healer/private clinic/drug shop, rural residence, being illiterate, living in more than 10 kilometers from health facility; severity of illness at first presentation to health facility. Provider delay was positively associated with rural residence, being illiterate, patient with good functional status, patients in contact with more than two health providers, and place of first visit being traditional healer/private clinic/drug shop. Conclusions This study showed that majority of smear positive patients delayed either for diagnosis or treatment, thus continue to serve as reservoirs of infection. This indicates that there is a need for intervention to decrease patient and provider delays. Effort to reduce delays in pastoralist communities should focus on improving access to services in rural communities, engaging traditional and

  15. Therapeutic applications of collagenase (metalloproteases: A review

    Directory of Open Access Journals (Sweden)

    Hamzeh Alipour

    2016-11-01

    Full Text Available Non-invasive therapeutic methods have recently been used in medical sciences. Enzymes have shown high activity at very low concentrations in laboratories and pharmaceutical, enabling them to play crucial roles in different biological phenomena related to living organism, especially human medicine. Recently, using the therapeutic methods based on non-invasive approaches has been emphasized in medical society. Researchers have focused on producing medicines and tools reducing invasive procedures in medical. Collagenases are proteins which catalyze chemical processes and break the peptide bonds in collagen. Collagen may be generated more than the required amount or produced in unsuitable sites or may not degrade after a certain time. In such cases, using an injectable collagenase or its ointment can be helpful in collagen degradation. In both in vitro and in vivo tests, it has been revealed that collagenases have several therapeutic properties in wound healing, burns, nipple pain and some diseases including intervertebral disc herniation, keloid, cellulite, lipoma among others. This review describes the therapeutic application of collagenase in medical sciences and the process for its production using novel methods, paving the way for more effective and safe applications of collagenases.

  16. Delayed presentation of cervical facet dislocations.

    Science.gov (United States)

    Basu, Saumyajit; Malik, Farid H; Ghosh, Jay Deep; Tikoo, Agnivesh

    2011-12-01

    To review treatment outcomes of 19 patients with delayed presentation of cervical facet dislocations. Records of 17 men and 2 women aged 21 to 63 (mean, 39) years who presented with unilateral (n=14) or bilateral (n=5) cervical facet dislocation after a delay of 7 to 21 (mean, 14) days were reviewed. The most common level of dislocation was C5-C6 (n=9), followed by C4-C5 (n=6), C3- C4 (n=2), and C6-C7 (n=2). The neurological status was graded according to the Frankel classification. One patient (with bilateral facet dislocation) had complete quadriplegia (grade A), 11 had incomplete spinal cord injury (grades C and D), and 7 had nerve root injury. Closed reduction using continuous skull traction for 2 days was attempted. In patients achieving closed reduction, only anterior discectomy and fusion was performed. Those who failed closed reduction underwent posterior partial/complete facetectomy and fixation. If there was traumatic disk prolapse, anterior decompression and fusion was then performed. The mean follow-up was 46 (range, 12- 108) months. 10 of 14 patients with unilateral facet dislocation were reduced with traction and then underwent anterior discectomy and fusion. The remaining 4 patients who failed closed reduction underwent posterior facetectomy and fixation; 3 of them had traumatic disk prolapse and thus also underwent anterior discectomy and fusion with cage and plate. Four of the 5 patients with bilateral facet dislocations failed closed reduction and underwent posterior facetectomy and lateral mass fixation, as well as anterior surgery. The remaining patient achieved reduction after traction and hence underwent only anterior discectomy and fusion. All patients achieved pain relief and sufficient neck movement for normal activities. All 7 patients with nerve root injury improved completely; 9 of the 11 patients with incomplete spinal cord injury improved by one Frankel grade, and the remaining 2 by 2 grades. The patient with complete quadriplegia

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

    Science.gov (United States)

    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.

  18. Purinergic Signalling: Therapeutic Developments

    Directory of Open Access Journals (Sweden)

    Geoffrey Burnstock

    2017-09-01

    Full Text Available Purinergic signalling, i.e., the role of nucleotides as extracellular signalling molecules, was proposed in 1972. However, this concept was not well accepted until the early 1990’s when receptor subtypes for purines and pyrimidines were cloned and characterised, which includes four subtypes of the P1 (adenosine receptor, seven subtypes of P2X ion channel receptors and 8 subtypes of the P2Y G protein-coupled receptor. Early studies were largely concerned with the physiology, pharmacology and biochemistry of purinergic signalling. More recently, the focus has been on the pathophysiology and therapeutic potential. There was early recognition of the use of P1 receptor agonists for the treatment of supraventricular tachycardia and A2A receptor antagonists are promising for the treatment of Parkinson’s disease. Clopidogrel, a P2Y12 antagonist, is widely used for the treatment of thrombosis and stroke, blocking P2Y12 receptor-mediated platelet aggregation. Diquafosol, a long acting P2Y2 receptor agonist, is being used for the treatment of dry eye. P2X3 receptor antagonists have been developed that are orally bioavailable and stable in vivo and are currently in clinical trials for the treatment of chronic cough, bladder incontinence, visceral pain and hypertension. Antagonists to P2X7 receptors are being investigated for the treatment of inflammatory disorders, including neurodegenerative diseases. Other investigations are in progress for the use of purinergic agents for the treatment of osteoporosis, myocardial infarction, irritable bowel syndrome, epilepsy, atherosclerosis, depression, autism, diabetes, and cancer.

  19. Rose Essential Oil Delayed Alzheimer's Disease-Like Symptoms by SKN-1 Pathway in C. elegans.

    Science.gov (United States)

    Zhu, Shuqian; Li, Hongyu; Dong, Juan; Yang, Wenqi; Liu, Ting; Wang, Yu; Wang, Xin; Wang, Meizhu; Zhi, Dejuan

    2017-10-11

    There are no effective medications for delaying the progress of Alzheimer's disease (AD), the most common neurodegenerative disease in the world. In this study, our results with C. elegans showed that rose essential oil (REO) significantly inhibited AD-like symptoms of worm paralysis and hypersensivity to exogenous 5-HT in a dose-dependent manner. Its main components of β-citronellol and geraniol acted less effectively than the oil itself. REO significantly suppressed Aβ deposits and reduced the Aβ oligomers to alleviate the toxicity induced by Aβ overexpression. Additionally, the inhibitory effects of REO on worm paralysis phenotype were abrogated only after skn-1 RNAi but not daf-16 and hsf-1 RNAi. REO markedly activated the expression of gst-4 gene, which further supported SKN-1 signaling pathway was involved in the therapeutic effect of REO on AD C. elegans. Our results provided direct evidence on REO for treating AD on an organism level and relative theoretical foundation for reshaping medicinal products of REO in the future.

  20. Therapeutical aspect of trichomoniasis

    Directory of Open Access Journals (Sweden)

    Vukićević Jelica

    2003-01-01

    Full Text Available Trichomoniasis is frequent, parasitic and sexually transmitted infection of genitourinary tract. It is treated by metronidazole (5-nitroimidazole according to protocol recommended by Center for Disease Control (CDC formerly called: Communicable Disease Center [19]. The resistance of Trichomonas vaginalis (TV strains to metronidazole (MND was described in USA in 1960, and later on in many European countries [8, 9, 10, 11, 12, 13]. In these cases, due to persistent trichomonas infection, it is necessary to repeat MND treatment with moderate modification of dose and/or length of its application. Nevertheless, oncogenic and toxic effects of MND have to be taken into consideration. OBJECT The aim of this study was to investigate and analyze the incidence of TV in STD and lower susceptibility of certain TV strains to MND were analyzed. MATERIAL AND METHODS In three-year period (1999-2001 612 patients (244 females and 368 males suspected of STD were examined clinically and microbiologically at the Institute of Dermatovenereology in Belgrade. The patients detected for TV were treated according to CDC protocol. The affected were considered cured if there was no manifest clinical infection, and no TV verified by microbiological test. Results TV was isolated in 216 patients (35.29 % of all subjects. Trichomonas infection was found in 90 (36.88 % out of 244 tested females and in 126 (32.34 % of 368 males. Clinically manifested infection, with extensive urethral and vaginal secretion, was recorded in 161 patients, while the asymptomatic form was found in 55 subjects. This result indicates the predominance of manifested trichomonas infections (75.54 % of cases. The difference of distribution of clinical forms of trichomoniasis, in relation to sex, was not statistically significant (c2=0.854; p>0.05. The patients with verified trichomonas infection were treated by metronidazole according to CDC protocol. The recommended therapeutical scheme consisted of three

  1. The Mind-Tranquilizing and Menstruation-Regulating Method for Acupuncture Treatment of Delayed Menstrual Cycle——A Clinical Controlled Study

    Institute of Scientific and Technical Information of China (English)

    CAI Xue-mei; WU Jie

    2009-01-01

    To compare the therapeutic effects of the mind-tranquilizing and menstruation-regulating acupuncture method with the routine acupuncture method in treating delayed menstrual cycle. Methods: 40 patients with delayed menstrual cycle were randomly divided into a treatment group of 23 cases (treated by the mind-tranquilizing and menstruation-regulating acupuncture method),and a control group of 17 cases (treated by the routine acupuncture method for delayed menstrual cycle due to stagnation of the liver-qi). The treatment involved three menstrual cycles. The evaluations were done by scoring the symptoms before treatment and at the end of each menstrual cycle. Results: After treatment,significant differences were found between the two groups in the therapeutic effects (P<0.05). Conclusion: The therapeutic effect of the mind-tranquilizing and menstruation-regulating acupuncture method is significantly superior to that of the routine acupuncture method for delayed menstrual cycle.

  2. Natural Compounds as a Therapeutic Intervention following Traumatic Brain Injury: The Role of Phytochemicals.

    Science.gov (United States)

    Scheff, Stephen W; Ansari, Mubeen A

    2017-04-15

    There has been a tremendous focus on the discovery and development of neuroprotective agents that might have clinical relevance following traumatic brain injury (TBI). This type of brain injury is very complex and is divided into two major components. The first component, a primary injury, occurs at the time of impact and is the result of the mechanical insult itself. This primary injury is thought to be irreversible and resistant to most treatments. A second component or secondary brain injury, is defined as cellular damage that is not immediately obvious after trauma, but that develops after a delay of minutes, hours, or even days. This injury appears to be amenable to treatment. Because of the complexity of the secondary injury, any type of therapeutic intervention needs to be multi-faceted and have the ability to simultaneously modulate different cellular changes. Because of diverse pharmaceutical interactions, combinations of different drugs do not work well in concert and result in adverse physiological conditions. Research has begun to investigate the possibility of using natural compounds as a therapeutic intervention following TBI. These compounds normally have very low toxicity and have reduced interactions with other pharmaceuticals. In addition, many natural compounds have the potential to target numerous different components of the secondary injury. Here, we review 33 different plant-derived natural compounds, phytochemicals, which have been investigated in experimental animal models of TBI. Some of these phytochemicals appear to have potential as possible therapeutic interventions to offset key components of the secondary injury cascade. However, not all studies have used the same scientific rigor, and one should be cautious in the interpretation of studies using naturally occurring phytochemical in TBI research.

  3. Surgery for hip fractures: Does surgical delay affect outcomes?

    Directory of Open Access Journals (Sweden)

    Nicole Simunovic

    2011-01-01

    Full Text Available Hip fractures are associated with a high rate of mortality and profound temporary and sometimes permanent impairment of quality of life. Current guidelines indicate that surgeons should perform surgery for a hip fracture within 24 hours of injury because earlier surgery is associated with better functional outcome and lower rates of perioperative complications and mortality. Proponents of early treatment argue that this approach minimizes the length of time a patient is confined to bed rest, thereby reducing the risk for associated complications, such as pressure sores, deep vein thrombosis, and urinary tract infections. Those favoring delaying surgery beyond the guideline recommendations believe that this approach is required to medically optimize patients, and therefore decrease the risk for perioperative complications. Further challenges to resolving this debate is the lack of an accepted definition of what should constitute an "unacceptable delay" for hip fracture surgery and the fact that outcomes associated with surgical delay are based on observational data alone (i.e., not randomized controlled trials. The effect of preoperative timing on mortality and other patient-important outcomes across various age groups remains controversial and warrants a large randomized controlled trial to offer clear insights into the effects associated with early versus delayed surgery among hip fracture patients.

  4. A Novel Message Scheduling Framework for Delay Tolerant Networks Routing

    KAUST Repository

    Elwhishi, Ahmed

    2013-05-01

    Multicopy routing strategies have been considered the most applicable approaches to achieve message delivery in Delay Tolerant Networks (DTNs). Epidemic routing and two-hop forwarding routing are two well-reported approaches for delay tolerant networks routing which allow multiple message replicas to be launched in order to increase message delivery ratio and/or reduce message delivery delay. This advantage, nonetheless, is at the expense of additional buffer space and bandwidth overhead. Thus, to achieve efficient utilization of network resources, it is important to come up with an effective message scheduling strategy to determine which messages should be forwarded and which should be dropped in case of buffer is full. This paper investigates a new message scheduling framework for epidemic and two-hop forwarding routing in DTNs, such that the forwarding/dropping decision can be made at a node during each contact for either optimal message delivery ratio or message delivery delay. Extensive simulation results show that the proposed message scheduling framework can achieve better performance than its counterparts.

  5. Celiac disease diagnosis still significantly delayed - Doctor's but not patients' delay responsive for the increased total delay in women.

    Science.gov (United States)

    Vavricka, Stephan R; Vadasz, Nina; Stotz, Matthias; Lehmann, Romina; Studerus, Diana; Greuter, Thomas; Frei, Pascal; Zeitz, Jonas; Scharl, Michael; Misselwitz, Benjamin; Pohl, Daniel; Fried, Michael; Tutuian, Radu; Fasano, Alessio; Schoepfer, Alain M; Rogler, Gerhard; Biedermann, Luc

    2016-10-01

    There is insufficient data on diagnostic delay and associated factors in celiac disease (CeD) as well as on its potential impact on the course of disease. Specifically taking its two components - patients' and doctors' delay - into account, we performed a large systematic patient survey study among unselected CeD patients in Switzerland. We found a mean/median total diagnostic delay of 87/24 months (IQR 5-96), with a range from 0 up to 780 months and roughly equal fractions of patients' and doctors' delay. Both mean/median total (93.1/24 vs. 60.2/12, pwomen is due to doctors' but not patients' delay and cannot be explained by antecedent IBS prior to establishing the CeD diagnosis. Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  6. Socio-demographic factors, comorbidity and diagnostic delay among women diagnosed with cervical, endometrial or ovarian cancer

    DEFF Research Database (Denmark)

    Robinson, Kirstine Magtengaard; Christensen, K B; Ottesen, B

    2011-01-01

    patient delays were associated with diagnosis with a greater risk of experiencing long delays among women diagnosed with cervical and endometrial cancer as opposed to ovarian cancer. The risk of experiencing long GP referral delays was associated with residential area, with a greater risk of long delays...... diagnosed with cervical and endometrial cancer as opposed to ovarian cancer, and with working as opposed to being retired. In conclusion, this study found that socio-demographic factors and comorbidity play a role in the probability of experiencing long delays. If delays in diagnosis are to be reduced......This study investigates the association between socio-demographic factors, comorbidity and diagnostic delay among gynaecological cancer patients. A questionnaire was sent to 1052 women diagnosed with cervical, endometrial or ovarian cancer between October 2006 and December 2007 in Denmark. Long...

  7. Prospective strategies to delay the evolution of anti-malarial drug resistance: weighing the uncertainty

    Directory of Open Access Journals (Sweden)

    McKenzie F Ellis

    2010-07-01

    Full Text Available Abstract Background The evolution of drug resistance in malaria parasites highlights a need to identify and evaluate strategies that could extend the useful therapeutic life of anti-malarial drugs. Such strategies are deployed to best effect before resistance has emerged, under conditions of great uncertainty. Methods Here, the emergence and spread of resistance was modelled using a hybrid framework to evaluate prospective strategies, estimate the time to drug failure, and weigh uncertainty. The waiting time to appearance was estimated as the product of low mutation rates, drug pressure, and parasite population sizes during treatment. Stochastic persistence and the waiting time to establishment were simulated as an evolving branching process. The subsequent spread of resistance was simulated in simple epidemiological models. Results Using this framework, the waiting time to the failure of artemisinin combination therapy (ACT for malaria was estimated, and a policy of multiple first-line therapies (MFTs was evaluated. The models quantify the effects of reducing drug pressure in delaying appearance, reducing the chances of establishment, and slowing spread. By using two first-line therapies in a population, it is possible to reduce drug pressure while still treating the full complement of cases. Conclusions At a global scale, because of uncertainty about the time to the emergence of ACT resistance, there was a strong case for MFTs to guard against early failure. Our study recommends developing operationally feasible strategies for implementing MFTs, such as distributing different ACTs at the clinic and for home-based care, or formulating different ACTs for children and adults.

  8. Improve the Communication, Decrease the Distance: The Investigation into Problematic Communication and Delays in Inter-Hospital Transfer of Rural Trauma Patients

    Science.gov (United States)

    Avtgis, Theodore A.; Polack, E. Phillips; Martin, Matthew M.; Rossi, Daniel

    2010-01-01

    Time delays in the treatment and transfer of trauma patients is a contributing factor responsible for many fatalities. Time delays are more characteristic of rural trauma systems due to factors such as greater distance, and delays in accident reporting. Efforts to reduce the trauma transfer process have resulted in many changes in protocol and use…

  9. READING PHILEMON AS THERAPEUTIC NARRATIVE

    African Journals Online (AJOL)

    2010-03-29

    Mar 29, 2010 ... Contrary to an initial impression, the narrative therapeutic approach does not emerge from a completely psychological ... Furthermore, a narrative therapeutic reading does not exist in a vacuum, therefore this investigation ..... converted to Christianity, Philemon supported other believers in various ways ...

  10. Suspended animation for delayed resuscitation.

    Science.gov (United States)

    Safar, Peter J; Tisherman, Samuel A

    2002-04-01

    'Suspended animation for delayed resuscitation' is a new concept for attempting resuscitation from cardiac arrest of patients who currently (totally or temporarily) cannot be resuscitated, such as traumatic exsanguination cardiac arrest. Suspended animation means preservation of the viability of brain and organism during cardiac arrest, until restoration of stable spontaneous circulation or prolonged artificial circulation is possible. Suspended animation for exsanguination cardiac arrest of trauma victims would have to be induced within the critical first 5 min after the start of cardiac arrest no-flow, to buy time for transport and resuscitative surgery (hemostasis) performed during no-flow. Cardiac arrest is then reversed with all-out resuscitation, usually requiring cardiopulmonary bypass. Suspended animation has been explored and documented as effective in dogs in terms of long-term survival without brain damage after very prolonged cardiac arrest. In the 1990s, the Pittsburgh group achieved survival without brain damage in dogs after cardiac arrest of up to 90 min no-flow at brain (tympanic) temperature of 10 degrees C, with functionally and histologically normal brains. These studies used emergency cardiopulmonary bypass with heat exchanger or a single hypothermic saline flush into the aorta, which proved superior to pharmacologic strategies. For the large number of normovolemic sudden cardiac death victims, which currently cannot be resuscitated, more research in large animals is needed.

  11. Telepresence, time delay, and adaptation

    Science.gov (United States)

    Held, Richard; Durlach, Nathaniel

    1989-01-01

    Displays are now being used extensively throughout the society. More and more time is spent watching television, movies, computer screens, etc. Furthermore, in an increasing number of cases, the observer interacts with the display and plays the role of operator as well as observer. To a large extent, the normal behavior in the normal environment can also be thought of in these same terms. Taking liberties with Shakespeare, it might be said, all the world's a display and all the individuals in it are operators in and on the display. Within this general context of interactive display systems, a discussion is began with a conceptual overview of a particular class of such systems, namely, teleoperator systems. The notion is considered of telepresence and the factors that limit telepresence, including decorrelation between the: (1) motor output of the teleoperator as sensed directly via the kinesthetic/tactual system, and (2) the motor output of the teleoperator as sensed indirectly via feedback from the slave robot, i.e., via a visual display of the motor actions of the slave robot. Finally, the deleterious effect of time delay (a particular decorrelation) on sensory-motor adaptation (an important phenomenon related to telepresence) is examined.

  12. Clinical applications of therapeutic phlebotomy

    Directory of Open Access Journals (Sweden)

    Kim KH

    2016-07-01

    Full Text Available Kyung Hee Kim,1 Ki Young Oh,2 1Department of Laboratory Medicine, Gachon University Gil Medical Center, Incheon, 2Department of Physical Medicine and Rehabilitation, Soonchunhyang University, Cheonan Hospital, Cheonan, South Korea Abstract: Phlebotomy is the removal of blood from the body, and therapeutic phlebotomy is the preferred treatment for blood disorders in which the removal of red blood cells or serum iron is the most efficient method for managing the symptoms and complications. Therapeutic phlebotomy is currently indicated for the treatment of hemochromatosis, polycythemia vera, porphyria cutanea tarda, sickle cell disease, and nonalcoholic fatty liver disease with hyperferritinemia. This review discusses therapeutic phlebotomy and the related disorders and also offers guidelines for establishing a therapeutic phlebotomy program. Keywords: therapeutic phlebotomy, hemochromatosis, polycythemia vera, porphyria cutanea tarda, sickle cell disease, nonalcoholic fatty liver disease

  13. Rethinking Therapeutic Misconception in Biobanking

    DEFF Research Database (Denmark)

    Tupasela, Aaro; Snell, Karoliina; Cañada, Jose

    2017-01-01

    Some authors have noted that in biobank research participants may be guided by what is called therapeutic misconception, whereby participants attribute therapeutic intent to research procedures.This article argues that the notion of therapeutic misconception is increasingly less justified when...... evaluating biobanks. We present four examples taken from recent developments in biobanking to argue why the notion of therapeutic misconception is problematic in that biobanking practices are increasingly seeking to bridge research and treatment in diff erent ways. In this article we explore examples where...... underpinnings for the need to separate research and treatment, and thus the notion of therapeutic misconception in the fi rst place. We call this tension between research and treatment ambivalent research advancement to highlight the difficulties that various actors have in managing such shifts within...

  14. Delay Banking for Managing Air Traffic

    Science.gov (United States)

    Green, Steve

    2008-01-01

    Delay banking has been invented to enhance air-traffic management in a way that would increase the degree of fairness in assigning arrival, departure, and en-route delays and trajectory deviations to aircraft impacted by congestion in the national airspace system. In delay banking, an aircraft operator (airline, military, general aviation, etc.) would be assigned a numerical credit when any of their flights are delayed because of an air-traffic flow restriction. The operator could subsequently bid against other operators competing for access to congested airspace to utilize part or all of its accumulated credit. Operators utilize credits to obtain higher priority for the same flight, or other flights operating at the same time, or later, in the same airspace, or elsewhere. Operators could also trade delay credits, according to market rules that would be determined by stakeholders in the national airspace system. Delay banking would be administered by an independent third party who would use delay banking automation to continually monitor flights, allocate delay credits, maintain accounts of delay credits for participating airlines, mediate bidding and the consumption of credits of winning bidders, analyze potential transfers of credits within and between operators, implement accepted transfers, and ensure fair treatment of all participating operators. A flow restriction can manifest itself in the form of a delay in assigned takeoff time, a reduction in assigned airspeed, a change in the position for the aircraft in a queue of all aircraft in a common stream of traffic (e.g., similar route), a change in the planned altitude profile for an aircraft, or change in the planned route for the aircraft. Flow restrictions are typically imposed to mitigate traffic congestion at an airport or in a region of airspace, particularly congestion due to inclement weather, or the unavailability of a runway or region of airspace. A delay credit would be allocated to an operator of a

  15. Reduction of channel zapping delay in IPTV services

    Directory of Open Access Journals (Sweden)

    F. Moumtadi

    2008-07-01

    Full Text Available This paper analyses the existing delay within an IPTV system when a user selects an other channel, and a new algorithm is used to reduce it. Based on the adjacent groups method, which reduces the time acquisition of a new channel placing the order not only for that channel but also for the adjacent channels. There are two principles under coonsideration, one that there exists a sufficient bandwidht, and the other, a multicast transmission (Chunglae, 2004. At the end of the paper, the obtained results are compared against the present ones and the possibilities of the algorithm are determined.

  16. Synchronization of Switched Neural Networks With Communication Delays via the Event-Triggered Control.

    Science.gov (United States)

    Wen, Shiping; Zeng, Zhigang; Chen, Michael Z Q; Huang, Tingwen

    2017-10-01

    This paper addresses the issue of synchronization of switched delayed neural networks with communication delays via event-triggered control. For synchronizing coupled switched neural networks, we propose a novel event-triggered control law which could greatly reduce the number of control updates for synchronization tasks of coupled switched neural networks involving embedded microprocessors with limited on-board resources. The control signals are driven by properly defined events, which depend on the measurement errors and current-sampled states. By using a delay system method, a novel model of synchronization error system with delays is proposed with the communication delays and event-triggered control in the unified framework for coupled switched neural networks. The criteria are derived for the event-triggered synchronization analysis and control synthesis of switched neural networks via the Lyapunov-Krasovskii functional method and free weighting matrix approach. A numerical example is elaborated on to illustrate the effectiveness of the derived results.

  17. Directly Solving Special Second Order Delay Differential Equations Using Runge-Kutta-Nyström Method

    Directory of Open Access Journals (Sweden)

    M. Mechee

    2013-01-01

    Full Text Available Runge-Kutta-Nyström (RKN method is adapted for solving the special second order delay differential equations (DDEs. The stability polynomial is obtained when this method is used for solving linear second order delay differential equation. A standard set of test problems is solved using the method together with a cubic interpolation for evaluating the delay terms. The same set of problems is reduced to a system of first order delay differential equations and then solved using the existing Runge-Kutta (RK method. Numerical results show that the RKN method is more efficient in terms of accuracy and computational time when compared to RK method. The methods are applied to a well-known problem involving delay differential equations, that is, the Mathieu problem. The numerical comparison shows that both methods are in a good agreement.

  18. Phase models and clustering in networks of oscillators with delayed coupling

    Science.gov (United States)

    Campbell, Sue Ann; Wang, Zhen

    2018-01-01

    We consider a general model for a network of oscillators with time delayed coupling where the coupling matrix is circulant. We use the theory of weakly coupled oscillators to reduce the system of delay differential equations to a phase model where the time delay enters as a phase shift. We use the phase model to determine model independent existence and stability results for symmetric cluster solutions. Our results extend previous work to systems with time delay and a more general coupling matrix. We show that the presence of the time delay can lead to the coexistence of multiple stable clustering solutions. We apply our analytical results to a network of Morris Lecar neurons and compare these results with numerical continuation and simulation studies.

  19. On Delay and Security in Network Coding

    Science.gov (United States)

    Dikaliotis, Theodoros K.

    2013-01-01

    In this thesis, delay and security issues in network coding are considered. First, we study the delay incurred in the transmission of a fixed number of packets through acyclic networks comprised of erasure links. The two transmission schemes studied are routing with hop-by-hop retransmissions, where every node in the network simply stores and…

  20. Delayed-proton and -alpha emission

    CERN Document Server

    Feix, W

    1981-01-01

    Delayed-proton and delayed-alpha spectra and their branching ratios are theoretically studied for neutron deficient heavy nuclei, /sup 114,116/Cs. The results exhibit a strong model dependence of the analysis. This implies a difficulty of deducing details of the beta - strength function of the precursors from such an analysis. (0 refs).

  1. Programmable delay circuit for sparker signal analysis

    Digital Repository Service at National Institute of Oceanography (India)

    Pathak, D.

    on it to classify the seafloor sediment properties. A specific purpose oriented programmable delay circuit was developed to generate the necessary delay so that the A/D conversion could start just before the arrival of the echo from the water bottom interface...

  2. Performance Evaluation of Blind Tropospheric Delay correction ...

    African Journals Online (AJOL)

    Tropospheric delay is a major error source in positioning by Global Navigation Satellite Systems (GNSS). Many techniques are available for tropospheric delay mitigation consisting of surface meteorological models and global empirical models. Surface meteorological models need surface meteorological data to give high ...

  3. Government delays release of medical marijuana supply.

    Science.gov (United States)

    Scanlon, Liz

    2002-07-01

    The federal government's initiative to make marijuana available for medical use continues to run into problems and delays. In a recent development, the first crop produced by the government's designated grower turned out to be too impure to use. The delays have led to the launch of a lawsuit against the federal government.

  4. Discounting of Delayed Rewards Is Not Hyperbolic

    Science.gov (United States)

    Luhmann, Christian C.

    2013-01-01

    Delay discounting refers to decision-makers' tendency to value immediately available goods more than identical goods available only after some delay. In violation of standard economic theory, decision-makers frequently exhibit dynamic inconsistency; their preferences change simply due to the passage of time. The standard explanation for this…

  5. [Delayed asthma bronchiale due to epoxy resin].

    Science.gov (United States)

    Authried, Georg; Al-Asadi, Haifaa; Møller, Ulla; Sherson, David Lee

    2013-10-28

    Epoxy resin is a low molecular weight agent, which can cause both acute and delayed allergic reactions. However, it is known causing skin reactions with direct or airborne contact. Rarely it can cause airway reactions like asthma bronchiale. We describe a case of a windmill worker who developed delayed asthma bronchiale due to airborne contact with epoxy resin.

  6. Delaying gratification depends on social trust

    Directory of Open Access Journals (Sweden)

    Laura eMichaelson

    2013-06-01

    Full Text Available Delaying gratification is hard, yet predictive of important life outcomes, such as academic achievement and physical health. Prominent theories focus on the role of self-control, hypersensitivity to immediate rewards, and the cost of time spent waiting. However, delaying gratification may also require trust in people delivering future rewards as promised. To test the role of social trust, participants were presented with character vignettes and faces that varied in trustworthiness, and then chose between hypothetical smaller immediate or larger delayed rewards from those characters. Across two experiments, participants were less willing to wait for delayed rewards from less trustworthy characters, and perceived trustworthiness predicted willingness to delay gratification. These findings provide the first demonstration of a causal role for social trust in willingness to delay gratification, independent of other relevant factors, such as self-control or reward history. Thus, delaying gratification requires choosing not only a later reward, but a reward that is potentially less likely to be delivered, when there is doubt about the person promising it. Implications of this work include the need to revise prominent theories of delay of gratification, and new directions for interventions with populations characterized by impulsivity.

  7. Test Anxiety and Academic Delay of Gratification

    Science.gov (United States)

    Bembenutty, Hefer

    2009-01-01

    The present study examined the relationship between college students' willingness to delay gratification, motivation, self-regulation of learning, and their level of test anxiety (N = 364). Academic delay of gratification refers to students' postponement of immediately available opportunities to satisfy impulses in favor of pursuing academic…

  8. Delaying gratification depends on social trust.

    Science.gov (United States)

    Michaelson, Laura; de la Vega, Alejandro; Chatham, Christopher H; Munakata, Yuko

    2013-01-01

    Delaying gratification is hard, yet predictive of important life outcomes, such as academic achievement and physical health. Prominent theories focus on the role of self-control, hypersensitivity to immediate rewards, and the cost of time spent waiting. However, delaying gratification may also require trust in people delivering future rewards as promised. To test the role of social trust, participants were presented with character vignettes and faces that varied in trustworthiness, and then choose between hypothetical smaller immediate or larger delayed rewards from those characters. Across two experiments, participants were less willing to wait for delayed rewards from less trustworthy characters, and perceived trustworthiness predicted willingness to delay gratification. These findings provide the first demonstration of a causal role for social trust in willingness to delay gratification, independent of other relevant factors, such as self-control or reward history. Thus, delaying gratification requires choosing not only a later reward, but a reward that is potentially less likely to be delivered, when there is doubt about the person promising it. Implications of this work include the need to revise prominent theories of delay of gratification, and new directions for interventions with populations characterized by impulsivity.

  9. Recursive Delay Calculation Unit for Parametric Beamformer

    DEFF Research Database (Denmark)

    Nikolov, Svetoslav; Jensen, Jørgen Arendt; Tomov, Borislav Gueorguiev

    2006-01-01

    This paper presents a recursive approach for parametric delay calculations for a beamformer. The suggested calculation procedure is capable of calculating the delays for any image line defined by an origin and arbitrary direction. It involves only add and shift operations making it suitable...

  10. History and definition of delayed cerebral ischemia.

    Science.gov (United States)

    Macdonald, R Loch

    2013-01-01

    A list of the vasospasm meetings is provided. The early descriptions of angiographic vasospasm and delayed cerebral ischemia are presented. Selected advances in knowledge in the field and some controversies are described. A proposal for definitions of neurological deterioration due to delayed cerebral ischemia, of cerebral infarction, and of vasospasm is reviewed.

  11. Space object tracking with delayed measurements

    Science.gov (United States)

    Chen, Huimin; Shen, Dan; Chen, Genshe; Blasch, Erik; Pham, Khanh

    2010-04-01

    This paper is concerned with the nonlinear filtering problem for tracking a space object with possibly delayed measurements. In a distributed dynamic sensing environment, due to limited communication bandwidth and long distances between the earth and the satellites, it is possible for sensor reports to be delayed when the tracking filter receives them. Such delays can be complete (the full observation vector is delayed) or partial (part of the observation vector is delayed), and with deterministic or random time lag. We propose an approximate approach to incorporate delayed measurements without reprocessing the old measurements at the tracking filter. We describe the optimal and suboptimal algorithms for filter update with delayed measurements in an orbital trajectory estimation problem without clutter. Then we extend the work to a single object tracking under clutter where probabilistic data association filter (PDAF) is used to replace the recursive linear minimum means square error (LMMSE) filter and delayed measurements with arbitrary lags are be handled without reprocessing the old measurements. Finally, we demonstrate the proposed algorithms in realistic space object tracking scenarios using the NASA General Mission Analysis Tool (GMAT).

  12. ANALYSING SURFACE MOVEMENT DELAYS IN AN AIRPORT

    Directory of Open Access Journals (Sweden)

    Volodymyr Kharchenko

    2014-07-01

    Full Text Available Queuing effect can be in the different components of ground operations. Causes of surface – movement delays are long taxi – in and taxi – out operations during departure and arrival of aircraft. Surface movement delays in an airport are analyzed

  13. Congenital rubella syndrome and delayed manifestations

    DEFF Research Database (Denmark)

    Dammeyer, Jesper Herup

    2010-01-01

    Objective: Several hypotheses of different medical and psychological delayed manifestations among people who have congenital rubella syndrome (CRS) have been discussed. This study tests some of these hypotheses of delayed manifestations. Methods: Gathering information about 35 individuals who hav...... which people with CRS face must primarily be understood in relation to congenital deafblindness and dual sensory and communicative deprivation....

  14. Analyzing delay causes in Egyptian construction projects

    Directory of Open Access Journals (Sweden)

    Mohamed M. Marzouk

    2014-01-01

    Full Text Available Construction delays are common problems in civil engineering projects in Egypt. These problems occur frequently during project life-time leading to disputes and litigation. Therefore, it is essential to study and analyze causes of construction delays. This research presents a list of construction delay causes retrieved from literature. The feedback of construction experts was obtained through interviews. Subsequently, a questionnaire survey was prepared. The questionnaire survey was distributed to thirty-three construction experts who represent owners, consultants, and contractor’s organizations. Frequency Index, Severity Index, and Importance Index are calculated and according to the highest values of them the top ten delay causes of construction projects in Egypt are determined. A case study is analyzed and compared to the most important delay causes in the research. Statistical analysis is carried out using analysis of variance ANOVA method to test delay causes, obtained from the survey. The test results reveal good correlation between groups while there is significant difference between them for some delay causes and finally roadmap for prioritizing delay causes groups is presented.

  15. Analyzing delay causes in Egyptian construction projects.

    Science.gov (United States)

    Marzouk, Mohamed M; El-Rasas, Tarek I

    2014-01-01

    Construction delays are common problems in civil engineering projects in Egypt. These problems occur frequently during project life-time leading to disputes and litigation. Therefore, it is essential to study and analyze causes of construction delays. This research presents a list of construction delay causes retrieved from literature. The feedback of construction experts was obtained through interviews. Subsequently, a questionnaire survey was prepared. The questionnaire survey was distributed to thirty-three construction experts who represent owners, consultants, and contractor's organizations. Frequency Index, Severity Index, and Importance Index are calculated and according to the highest values of them the top ten delay causes of construction projects in Egypt are determined. A case study is analyzed and compared to the most important delay causes in the research. Statistical analysis is carried out using analysis of variance ANOVA method to test delay causes, obtained from the survey. The test results reveal good correlation between groups while there is significant difference between them for some delay causes and finally roadmap for prioritizing delay causes groups is presented.

  16. Adding 5 h delayed xenon to delayed hypothermia treatment improves long-term function in neonatal rats surviving to adulthood.

    Science.gov (United States)

    Liu, Xun; Dingley, John; Scull-Brown, Emma; Thoresen, Marianne

    2015-06-01

    We previously reported that combining immediate hypothermia with immediate or 2 h delayed inhalation of an inert gas, xenon, gave additive neuroprotection in rats after a hypoxic-ischemic insult, compared to hypothermia alone. Defining the therapeutic time window for this new combined intervention is crucial in clinical practice when immediate treatment is not always feasible. The aim of this study is to investigate whether combined hypothermia and xenon still provide neuroprotection in rats after a 5 h delay for both hypothermia and xenon. Seven-day-old Wistar rat pups underwent a unilateral hypoxic-ischemic insult. Pups received 5 h of treatment starting 5 h after the insult randomized between normothermia, hypothermia, or hypothermia with 50% xenon. Surviving pups were tested for fine motor function through weeks 8-10 before being euthanized at week 11. Their hemispheric and hippocampal areas were assessed. Both delayed hypothermia-xenon and hypothermia-only treated groups had significantly less brain tissue loss than those which underwent normothermia. The functional performance after 1 wk and adulthood was significantly better after hypothermia-xenon treatment as compared to the hypothermia-only or normothermia groups. Adding 50% xenon to 5 h delayed hypothermia significantly improved functional outcome as compared to delayed hypothermia alone despite similar reductions in brain area.

  17. Stochastic two-delay differential model of delayed visual feedback effects on postural dynamics

    NARCIS (Netherlands)

    Boulet, J.; Balasubramaniam, R.; Daffertshofer, A.; Longtin, A.

    2010-01-01

    We report on experiments and modelling involving the 'visuo-postural control loop' in the upright stance. We experimentally manipulated an artificial delay to the visual feedback during standing, presented at delays ranging from 0 to 1 s in increments of 250 ms. Using stochastic delay differential

  18. DELAYED EFFECTS OF RADIATION ON THE HUMAN CENTRAL NERVOUS SYSTEM. EARLY AND LATE DELAYED REACTIONS,

    Science.gov (United States)

    Two cases of delayed effects of radiation on the central nervous system of man are reported. One demonstrates the rare early delayed reaction which...involvement. This patient is an extreme example of the well-documented late delayed effects of radiation and is presented for contrast with the patient in

  19. Predictive and therapeutic markers in ovarian cancer

    Science.gov (United States)

    Gray, Joe W.; Guan, Yinghui; Kuo, Wen-Lin; Fridlyand, Jane; Mills, Gordon B.

    2013-03-26

    Cancer markers may be developed to detect diseases characterized by increased expression of apoptosis-suppressing genes, such as aggressive cancers. Genes in the human chromosomal regions, 8q24, 11q13, 20q11-q13, were found to be amplified indicating in vivo drug resistance in diseases such as ovarian cancer. Diagnosis and assessment of amplification levels certain genes shown to be amplified, including PVT1, can be useful in prediction of poor outcome of patient's response and drug resistance in ovarian cancer patients with low survival rates. Certain genes were found to be high priority therapeutic targets by the identification of recurrent aberrations involving genome sequence, copy number and/or gene expression are associated with reduced survival duration in certain diseases and cancers, specifically ovarian cancer. Therapeutics to inhibit amplification and inhibitors of one of these genes, PVT1, target drug resistance in ovarian cancer patients with low survival rates is described.

  20. Implications for Therapeutic Intervention

    Directory of Open Access Journals (Sweden)

    A. L. Hof

    2001-01-01

    Full Text Available Patients with an upper motor neurone syndrome (CP suffer from many disabling primary symptoms: spasms, weakness, and loss of dexterity. These primary ‘neurogenic’ symptoms often lead to secondary disabilities, muscle contractures, and tertiary effects, bone deformations. A common symptom of CP is hypertonia, with. the consequence that the involved muscles remain in an excessively shortened length for most of the time. As a normal reaction of the muscle tissue, the number of sarcomeres is reduced and the muscle fibers shorten permanently: a contracture develops. A possible second type of contracture is that normal muscle lengthening along with bone growth is affected. Current treatments for the secondary effects include (1 reduction of muscle force, (2lengthening of the muscle fibers by serial plaster casts, and (3surgical lengthening of tendons or aponeurosis. The choice of treatment depends on the cause of the functional deficit. Bone tissue also adapts itself to abnormal forces, especially in the growth period. The hypertonias or contractures of CP so may give rise to bone malformations that interfere with function (e.g. femur endorotation or may reduce the action of muscles by changing the lever arm (e.g. ankle varus. Although prevention should always be preferred, a timely surgical intervention cannot always be avoided. The differences in treatment for the various groups require and justify an extensive laboratory investigation, including EMG recordings in gait, measurement of passive elastic properties, and long-term observation of the hypertonia.