WorldWideScience

Sample records for rapid apoptotic response

  1. Apoptotic response of malignant rhabdoid tumor cells

    Directory of Open Access Journals (Sweden)

    Nocentini Silvano

    2003-07-01

    Full Text Available Abstract Background Malignant rhabdoid tumors (MRTs are extremely aggressive and resist current radio- and chemotherapic treatments. To gain insight into the dysfunctions of MRT cells, the apoptotic response of a model cell line, MON, was analyzed after exposure to several genotoxic and non-genotoxic agents employed separately or in association. Results Fluorescence microscopy of chromatin morphology and electrophoretic analysis of internucleosomal DNA fragmentation revealed that MON cells were, comparatively to HeLa cells, resistant to apoptosis after treatment with etoposide, cisplatin (CisPt or X-rays, but underwent some degree of apoptosis after ultraviolet (UV C irradiation. Concomitant treatment of MON cells with X-rays or vinblastine and the phosphatidylinositol 3-kinase (PI3-K inhibitor wortmannin resulted in synergistic induction of apoptosis. Western blot analysis showed that the p53 protein was upregulated in MON cells after exposure to all the different agents tested, singly or in combination. In treated cells, the p53 downstream effectors p21WAF1/CIP1, Mdm2 and Bax were induced with some inconsistency with regard to the accumulation of p53. Poly ADP-ribose polymerase (PARP cleavage, indicative of ongoing apoptosis, occurred in UVC-irradiated cells and, especially, in cells treated with combinations of X-rays or vinblastine with wortmannin. However, there was moderate or no PARP cleavage in cells treated with CisPt, X-rays, vinblastine or wortmannin singly or with the combinations X-rays plus CisPt or vinblastine and CisPt plus vinblastine or wortmannin. The synergistic effect on the induction of apoptosis exerted by some agent combinations corresponded with synergy in respect of MON cell growth inhibition. Conclusion These results suggest abnormalities in the p53 pathway and apoptosis control in MRT cells. The Ras/PI3-K/AKT signaling pathway might also be deregulated in these cells by generating an excess of survival factors. These

  2. Apoptotic cell responses in the splenic marginal zone: A paradigm for immunologic reactions to apoptotic antigens with implications for autoimmunity

    Science.gov (United States)

    McGaha, Tracy L.; Karlsson, Mikael C.I.

    2015-01-01

    Summary Apoptotic cells drive innate regulatory responses that result in tolerogenic immunity. This is a critical aspect of cell physiology as apoptotic cells expose potentially dangerous nuclear antigens on the surface in apoptotic blebs, and failure in their recognition, phagocytosis, or destruction can cause dramatic autoimmunity in experimental models and is linked to development and progression of systemic pathology in man. The marginal zone is a specialized splenic environment that serves as a transitional site from circulation to peripheral lymphoid structures. The marginal zone serves a key role in trapping of particulates and initiation of innate responses against systemic microbial pathogens. However in recent years it has become clear the marginal zone is also important for initiation of immune tolerance to apoptotic cells, driving a coordinated response involving multiple phagocyte and lymphocyte subsets. Recent reports linking defects in splenic macrophage function to SLE in a manner analogous to marginal zone macrophages in lupus-prone mice provides an impetus to better understand the mechanistic basis of the apoptotic cell response in the marginal zone and its general applicability to apoptotic cell-driven tolerance at other tissue sites. In this review we discuss immune responses to apoptotic cells in the spleen in general and the marginal zone in particular, the relationship of these responses to autoimmune disease, and comparisons to apoptotic cell immunity in humans. PMID:26683143

  3. PDT-apoptotic tumor cells induce macrophage immune response

    Science.gov (United States)

    Zhou, Fei-fan; Xing, Da; Chen, Wei R.

    2008-02-01

    Photodynamic therapy (PDT) functions as a cancer therapy through two major cell death mechanisms: apoptosis and necrosis. Immunological responses induced by PDT has been mainly associated with necrosis while apoptosis associated immune responses have not fully investigated. Heat shock proteins (HSPs) play an important role in regulating immune responses. In present study, we studied whether apoptotic tumor cells could induce immune response and how the HSP70 regulates immune response. The endocytosis of tumor cells by the activated macrophages was observed at single cell level by LSM. The TNF-α release of macrophages induced by co-incubated with PDT-apoptotic tumor cells was detected by ELISA. We found that apoptotic tumor cells treated by PDT could activate the macrophages, and the immune effect decreased evidently when HSP70 was blocked. These findings not only show that apoptosis can induce immunological responses, but also show HSP70 may serves as a danger signal for immune cells and induce immune responses to regulate the efficacy of PDT.

  4. High-Fat Diet Feeding Causes Rapid, Non-apoptotic Cleavage of Caspase-3 in Astrocytes

    Science.gov (United States)

    Guyenet, Stephan J.; Nguyen, Hong T.; Hwang, Bang H.; Schwartz, Michael W.; Baskin, Denis G.; Thaler, Joshua P.

    2013-01-01

    Astrocytes respond to multiple forms of central nervous system (CNS) injury by entering a reactive state characterized by morphological changes and a specific pattern of altered protein expression. Termed astrogliosis, this response has been shown to strongly influence the injury response and functional recovery of CNS tissues. This pattern of CNS inflammation and injury associated with astrogliosis has recently been found to occur in the energy homeostasis centers of the hypothalamus during diet-induced obesity (DIO) in rodent models, but the characterization of the astrocyte response remains incomplete. Here, we report that astrocytes in the mediobasal hypothalamus respond robustly and rapidly to purified high-fat diet (HFD) feeding by cleaving caspase-3, a protease whose cleavage is often associated with apoptosis. Although obesity develops in HFD-fed rats by day 14, caspase-3 cleavage occurs by day 3, prior to the development of obesity, suggesting the possibility that it could play a causal role in the hypothalamic neuropathology and fat gain observed in DIO. Caspase-3 cleavage is not associated with an increase in the rate of apoptosis, as determined by TUNEL staining, suggesting it plays a non-apoptotic role analogous to the response to excitotoxic neuron injury. Our results indicate that astrocytes in the mediobasal hypothalamus respond rapidly and robustly to HFD feeding, activating caspase-3 in the absence of apoptosis, a process that has the potential to influence the course of DIO. PMID:23548599

  5. Rapid response manufacturing (RRM)

    Energy Technology Data Exchange (ETDEWEB)

    Cain, W.D. [Lockheed Martin Energy Systems, Inc., Oak Ridge, TN (United States); Waddell, W.L. [National Centers for Manufacturing Sciences, Ann Arbor, MI (United States)

    1997-02-18

    US industry is fighting to maintain its competitive edge in the global market place. Today markets fluctuate rapidly. Companies, to survive, have to be able to respond with quick-to-market, improved, high quality, cost efficient products. The way products are developed and brought to market can be improved and made more efficient through the proper incorporation of emerging technologies. The RRM project was established to leverage the expertise and resources of US private industries and federal agencies to develop, integrate, and deploy new technologies that meet critical needs for effective product realization. The RRM program addressed a needed change in the US Manufacturing infrastructure that will ensure US competitiveness in world market typified by mass customization. This project provided the effort needed to define, develop and establish a customizable infrastructure for rapid response product development design and manufacturing. A major project achievement was the development of a broad-based framework for automating and integrating the product and process design and manufacturing activities involved with machined parts. This was accomplished by coordinating and extending the application of feature-based product modeling, knowledge-based systems, integrated data management, and direct manufacturing technologies in a cooperative integrated computing environment. Key technological advancements include a product model that integrates product and process data in a consistent, minimally redundant manner, an advanced computer-aided engineering environment, knowledge-based software aids for design and process planning, and new production technologies to make products directly from design application software.

  6. Building a rapid response team.

    Science.gov (United States)

    Halvorsen, Lisa; Garolis, Salomeja; Wallace-Scroggs, Allyson; Stenstrom, Judy; Maunder, Richard

    2007-01-01

    The use of rapid response teams is a relatively new approach for decreasing or eliminating codes in acute care hospitals. Based on the principles of a code team for cardiac and/or respiratory arrest in non-critical care units, the rapid response teams have specially trained nursing, respiratory, and medical personnel to respond to calls from general care units to assess and manage decompensating or rapidly changing patients before their conditions escalate to a full code situation. This article describes the processes used to develop a rapid response team, clinical indicators for triggering a rapid response team call, topics addressed in an educational program for the rapid response team members, and methods for evaluating effectiveness of the rapid response team.

  7. Apoptotic neutrophils augment the inflammatory response to Mycobacterium tuberculosis infection in human macrophages.

    Directory of Open Access Journals (Sweden)

    Henrik Andersson

    Full Text Available Macrophages in the lung are the primary cells being infected by Mycobacterium tuberculosis (Mtb during the initial manifestation of tuberculosis. Since the adaptive immune response to Mtb is delayed, innate immune cells such as macrophages and neutrophils mount the early immune protection against this intracellular pathogen. Neutrophils are short-lived cells and removal of apoptotic cells by resident macrophages is a key event in the resolution of inflammation and tissue repair. Since anti-inflammatory activity is not compatible with effective immunity to intracellular pathogens, we therefore investigated how uptake of apoptotic neutrophils modulates the function of Mtb-activated human macrophages. We show that Mtb infection exerts a potent proinflammatory activation of human macrophages with enhanced gene activation and release of proinflammatory cytokines and that this response was augmented by apoptotic neutrophils. The enhanced macrophage response is linked to apoptotic neutrophil-driven activation of the NLRP3 inflammasome and subsequent IL-1β signalling. We also demonstrate that apoptotic neutrophils not only modulate the inflammatory response, but also enhance the capacity of infected macrophages to control intracellular growth of virulent Mtb. Taken together, these results suggest a novel role for apoptotic neutrophils in the modulation of the macrophage-dependent inflammatory response contributing to the early control of Mtb infection.

  8. Small GTPase CDC-42 promotes apoptotic cell corpse clearance in response to PAT-2 and CED-1 in C. elegans.

    Science.gov (United States)

    Neukomm, L J; Zeng, S; Frei, A P; Huegli, P A; Hengartner, M O

    2014-06-01

    The rapid clearance of dying cells is important for the well-being of multicellular organisms. In C. elegans, cell corpse removal is mainly mediated by three parallel engulfment signaling cascades. These pathways include two small GTPases, MIG-2/RhoG and CED-10/Rac1. Here we present the identification and characterization of CDC-42 as a third GTPase involved in the regulation of cell corpse clearance. Genetic analyses performed by both loss of cdc-42 function and cdc-42 overexpression place cdc-42 in parallel to the ced-2/5/12 signaling module, in parallel to or upstream of the ced-10 module, and downstream of the ced-1/6/7 module. CDC-42 accumulates in engulfing cells at membranes surrounding apoptotic corpses. The formation of such halos depends on the integrins PAT-2/PAT-3, UNC-112 and the GEF protein UIG-1, but not on the canonical ced-1/6/7 or ced-2/5/12 signaling modules. Together, our results suggest that the small GTPase CDC-42 regulates apoptotic cell engulfment possibly upstream of the canonical Rac GTPase CED-10, by polarizing the engulfing cell toward the apoptotic corpse in response to integrin signaling and ced-1/6/7 signaling in C. elegans.

  9. Cryopreserved ECP-treated lymphocytes maintain apoptotic response and anti-proliferative effect.

    Science.gov (United States)

    Radwanski, Katherine; Heber, Cheryl; Min, Kyungyoon

    2015-06-01

    The ability to cryopreserve a portion of the cells treated during extracorporeal photopheresis (ECP) would improve therapy logistics, particularly for pediatric patients, by allowing multiple therapeutic doses to be collected from a single apheresis session. However, the effect of cryopreservation on ECP-treated cells is unknown (e.g., ECP-induced lymphocyte apoptosis and inhibition of proliferation). Mononuclear cell (MNC) apheresis products collected from healthy subjects were ECP-treated using offline methods. Fresh samples of ECP-treated and control cells were placed immediately in culture. The remainder of the cells were frozen in cryovials (n = 8) or cryobags (n = 8) at -80°C. After 1 week of -80°C storage, ECP-treated and control cells were thawed rapidly and samples were placed in culture. Lymphocyte apoptosis was assessed by phosphatidylserine exposure using Annexin V/7-AAD labeling. Lymphocyte proliferation after 3 days culture was measured using the carboxyfluorescein succinimidyl ester labeling technique. On Day 0, apoptosis levels were 80% in fresh and cryopreserved ECP-treated cells but remained near constant in both control groups. Inhibition of lymphocyte proliferation was >95% in all ECP-treated cells with no significant difference between fresh and cryopreserved cells (P = 0.12). Cryopreservation did not impair the apoptotic response or anti-proliferative effect of ECP-treated lymphocytes, thereby demonstrating early feasibility of this approach. © 2014 Wiley Periodicals, Inc.

  10. p63 mediates an apoptotic response to pharmacological and disease-related ER stress in the developing epidermis.

    Science.gov (United States)

    Pyati, Ujwal J; Gjini, Evisa; Carbonneau, Seth; Lee, Jeong-Soo; Guo, Feng; Jette, Cicely A; Kelsell, David P; Look, A Thomas

    2011-09-13

    Endoplasmic reticulum (ER) stress triggers tissue-specific responses that culminate in either cellular adaptation or apoptosis, but the genetic networks distinguishing these responses are not well understood. Here we demonstrate that ER stress induced in the developing zebrafish causes rapid apoptosis in the brain, spinal cord, tail epidermis, lens, and epiphysis. Focusing on the tail epidermis, we uncover an apoptotic response that depends on Puma, but not on p53 or Chop. puma is transcriptionally activated during this ER stress response in a p53-independent manner, and is an essential mediator of epidermal apoptosis. We demonstrate that the p63 transcription factor is upregulated to initiate this apoptotic pathway and directly activates puma transcription in response to ER stress. We also show that a mutation of human Connexin 31, which causes erythrokeratoderma variabilis, induces ER stress and p63-dependent epidermal apoptosis in the zebrafish embryo, thus implicating this pathway in the pathogenesis of inherited disease. Copyright © 2011 Elsevier Inc. All rights reserved.

  11. Silver nanoparticle exposure causes apoptotic response in the earthworm Lumbricus terrestris (Oligochaeta).

    Science.gov (United States)

    Lapied, Emmanuel; Moudilou, Elara; Exbrayat, Jean-Marie; Oughton, Deborah Helen; Joner, Erik Jautris

    2010-08-01

    In terrestrial ecotoxicology there is a serious lack of data for potential hazards posed by engineered nanoparticles (ENPs). This is partly due to complex interactions between ENPs and the soil matrix, but also to the lack of suitable toxicological end points in organisms that are exposed to ENPs in a relevant manner. Earthworms are key organisms in terrestrial ecosystems, but so far only physiological end points of low sensitivity have been used in ecotoxicity studies with ENPs. We exposed the earthworm Lumbricus terrestris to silver nanoparticles and measured their impact on apoptosis in different tissues. Increased apoptotic activity was detected in a range of tissues both at acute and sublethal concentrations (down to 4 mg/kg soil). Comparing exposure in water and soil showed reduced bioavailability in soil reflected in the apoptotic response. Apoptosis appears to be a sensitive end point and potentially a powerful tool for quantifying environmental hazards of ENPs.

  12. Persistent inhibition of ABL tyrosine kinase causes enhanced apoptotic response to TRAIL and disrupts the pro-apoptotic effect of chloroquine.

    Directory of Open Access Journals (Sweden)

    Priya Sridevi

    Full Text Available TNF-Related Apoptosis Inducing Ligand (TRAIL binds to and activates death receptors to stimulate caspase-8 and apoptosis with higher efficiency in cancer than normal cells but the development of apoptosis resistance has limited its clinical efficacy. We found that stable, but not transient knockdown of the ABL tyrosine kinase enhanced the apoptotic response to TRAIL. Re-expression of Abl, but not its nuclear import- or kinase-defective mutant, in the ABL-knockdown cells re-established apoptosis suppression. TRAIL is known to stimulate caspase-8 ubiquitination (Ub-C8, which can facilitate caspase-8 activation or degradation by the lysosomes. In the ABL-knockdown cells, we found a higher basal level of Ub-C8 that was not further increased by lysosomal inhibition. Re-expression of Abl in the ABL-knockdown cells reduced the basal Ub-C8, correlating with apoptosis suppression. We found that lysosomal inhibition by chloroquine (CQ could also enhance TRAIL-induced apoptosis. However, this pro-apoptotic effect of CQ was lost in the ABL-knockdown cells but restored by Abl re-expression. Interestingly, kinase inhibition at the time of TRAIL stimulation was not sufficient to enhance apoptosis. Instead, persistent treatment for several days with imatinib, an ABL kinase inhibitor, was required to cause the enhanced and the CQ-insensitive apoptotic response to TRAIL. Together, these results show that persistent loss of nuclear ABL tyrosine kinase function can sensitize cells to TRAIL and suggest that long-term exposure to the FDA-approved ABL kinase inhibitors may potentiate apoptotic response to TRAIL-based cancer therapy.

  13. Melatonin modulates inflammatory response and suppresses burn-induced apoptotic injury

    Directory of Open Access Journals (Sweden)

    Ganka Bekyarova

    2017-04-01

    Full Text Available Introduction: Melatonin, the principal secretory product of the pineal gland, has antioxidant functions as a potent antioxidant and free radical scavenger. Objectives of the present study were to investigate the effect of melatonin against inflammatory response, burn-induced oxidative damage and apoptotic changes of rat liver. Methods: Melatonin (10 mg /kg, i.p. was applied immediately after 30% of total body surface area (TBSA burns on male Wistar rats. The level of malondialdehyde (MDA as a marker of an oxidative stress was quantified by thiobarbituric method. Hepatic TNFα and IL-10 as inflammatory markers were assayed by ELISA. Using light immunоchistochemistry the expression Ki67 proliferative marker was investigated. Results: Hepatic MDA and TNF-α levels increased significantly following burns without any change in IL-10 level. Intracellular vacuolization, hepatic cell degeneration and apoptosis occurred in rats after burns. The number of apoptotic cells was increased whereas no significant increase in Ki67 proliferative marker. Melatonin decreased the MDA and TNF-α content and increased the IL-10 level. It also limited the degenerative changes and formation of apoptotic cells in rat liver but did not increase expression of the marker of proliferation. In conclusion, our data show that melatonin relieves burn-induced hepatic damage associated with modulation of the proinflammatory/anti-inflammatory balance, mitigation of lipid peroxidation and hepatic apoptosis.

  14. Pineapple bromelain induces autophagy, facilitating apoptotic response in mammary carcinoma cells.

    Science.gov (United States)

    Bhui, Kulpreet; Tyagi, Shilpa; Prakash, Bharti; Shukla, Yogeshwer

    2010-01-01

    Bromelain, from pineapple, possesses potent anticancer effects. We investigated autophagic phenomenon in mammary carcinoma cells (estrogen receptor positive and negative) under bromelain treatment and also illustrated the relationship between autophagy and apoptosis in MCF-7 cells. MCF-7 cells exposed to bromelain showed delayed growth inhibitory response and induction of autophagy, identified by monodansylcadaverine localization. It was succeeded by apoptotic cell death, evident by sub-G1 cell fraction and apoptotic features like chromatin condensation and nuclear cleavage. 3-Methyladenine (MA, autophagy inhibitor) pretreatment reduced the bromelain-induced autophagic level, also leading to decline in apoptotic population, indicating that here autophagy facilitates apoptosis. However, addition of caspase-9 inhibitor Z-LEHD-FMK augmented the autophagy levels, inhibited morphological apoptosis but did not prevent cell death. Next, we found that bromelain downregulated the phosphorylation of extracellular signal-regulated kinase ½ (ERK½), whereas that of c-jun N-terminal kinase (JNK) and p38 kinase were upregulated. Also, MA had no influence on bromelain-suppressed ERK½ activation, yet, it downregulated JNK and p38 activation. Also, addition of mitogen-activated protein kinase (MAPK) inhibitors enhanced the autophagic ratios, which suggested the role of MAP kinases in bromelain-induced autophagy. All three MAPKs were seen to be constantly activated over the time. Bromelain was seen to induce the expressions of autophagy-related proteins, light chain 3 protein B II (LC3BII), and beclin-1. Using ERK½ inhibitor, expressions of LC3BII and beclin-1 increased, whereas p38 and JNK inhibitors decreased this protein expression, indicating that bromelain-induced autophagy was positively regulated by p38 and JNK but negatively regulated by ERK½. Autophagy-inducing property of bromelain can be further exploited in breast cancer therapy. Copyright © 2010 International Union

  15. The response of apoptotic and proteolytic systems to repeated heat stress in atrophied rat skeletal muscle.

    Science.gov (United States)

    Yoshihara, Toshinori; Sugiura, Takao; Yamamoto, Yuki; Shibaguchi, Tsubasa; Kakigi, Ryo; Naito, Hisashi

    2015-10-01

    We examined the effect of repeated heat stress on muscle atrophy, and apoptotic and proteolytic regulation in unloaded rat slow- and fast-type skeletal muscles. Forty male Wistar rats (11 week-old) were divided into control (CT), hindlimb unweighting (HU), intermittent weight-bearing during HU (HU + IWB), and intermittent weight-bearing with heat stress during HU (41-41.5°C for 30 min; HU + IWB + HS) groups. The HU + IWB + HS and HU + IWB groups were released from unloading for 1 h every second day, during which the HU + IWB + HS group underwent the heating. Our results revealed that repeated bouts of heat stress resulted in protection against disuse muscle atrophy in both soleus and plantaris muscles. This heat stress-induced protection against disuse-induced muscular atrophy may be partially due to reduced apoptotic activation in both muscles, and decreased ubiquitination in only the soleus muscle. We concluded that repeated heat stress attenuated skeletal muscle atrophy via suppressing apoptosis but the response to proteolytic systems depend on the muscle phenotype. © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  16. Modulation of apoptotic response by LAR family phosphatases-cIAP1 signaling during urinary tract morphogenesis.

    Science.gov (United States)

    Stewart, Katherine; Tang, You Chi; Shafer, Maxwell E R; Graham-Paquin, Adda-Lee; Bouchard, Maxime

    2017-10-24

    The elimination of unwanted cells by apoptosis is necessary for tissue morphogenesis. However, the cellular control of morphogenetic apoptosis is poorly understood, notably the modulation of cell sensitivity to apoptotic stimuli. Ureter maturation, the process by which the ureter is displaced to the bladder wall, represents an exquisite example of morphogenetic apoptosis, requiring the receptor protein tyrosine phosphatases (RPTPs): LAR and RPTPσ. Here we show that LAR-RPTPs act through cellular inhibitor of apoptosis protein 1 (cIAP1) to modulate caspase 3,7-mediated ureter maturation. Pharmacologic or genetic inactivation of cIAP1 reverts the apoptotic deficit of LAR-RPTP-deficient embryos. Moreover, Birc2 (cIAP1) inactivation generates excessive apoptosis leading to vesicoureteral reflux in newborns, which underscores the importance of apoptotic modulation during urinary tract morphogenesis. We finally demonstrate that LAR-RPTP deficiency increases cIAP1 stability during apoptotic cell death. Together these results identify a mode of cIAP1 regulation playing a critical role in the cellular response to apoptotic pathway activation in the embryo. Published under the PNAS license.

  17. Rapid Response Flood Water Mapping

    Science.gov (United States)

    Policelli, Fritz; Brakenridge, G. R.; Coplin, A.; Bunnell, M.; Wu, L.; Habib, Shahid; Farah, H.

    2010-01-01

    Since the beginning of operation of the MODIS instrument on the NASA Terra satellite at the end of 1999, an exceptionally useful sensor and public data stream have been available for many applications including the rapid and precise characterization of terrestrial surface water changes. One practical application of such capability is the near-real time mapping of river flood inundation. We have developed a surface water mapping methodology based on using only bands 1 (620-672 nm) and 2 (841-890 nm). These are the two bands at 250 m, and the use of only these bands maximizes the resulting map detail. In this regard, most water bodies are strong absorbers of incoming solar radiation at the band 2 wavelength: it could be used alone, via a thresholding procedure, to separate water (dark, low radiance or reflectance pixels) from land (much brighter pixels) (1, 2). Some previous water mapping procedures have in fact used such single band data from this and other sensors that include similar wavelength channels. Adding the second channel of data (band 1), however, allows a band ratio approach which permits sediment-laden water, often relatively light at band 2 wavelengths, to still be discriminated, and, as well, provides some removal of error by reducing the number of cloud shadow pixels that would otherwise be misclassified as water.

  18. Thiamine deficiency activates hypoxia inducible factor-1α to facilitate pro-apoptotic responses in mouse primary astrocytes.

    Directory of Open Access Journals (Sweden)

    Kristy Zera

    Full Text Available Thiamine is an essential enzyme cofactor required for proper metabolic function and maintenance of metabolism and energy production in the brain. In developed countries, thiamine deficiency (TD is most often manifested following chronic alcohol consumption leading to impaired mitochondrial function, oxidative stress, inflammation and excitotoxicity. These biochemical lesions result in apoptotic cell death in both neurons and astrocytes. Comparable histological injuries in patients with hypoxia/ischemia and TD have been described in the thalamus and mammillary bodies, suggesting a congruency between the cellular responses to these stresses. Consistent with hypoxia/ischemia, TD stabilizes and activates Hypoxia Inducible Factor-1α (HIF-1α under physiological oxygen levels. However, the role of TD-induced HIF-1α in neurological injury is currently unknown. Using Western blot analysis and RT-PCR, we have demonstrated that TD induces HIF-1α expression and activity in primary mouse astrocytes. We observed a time-dependent increase in mRNA and protein expression of the pro-apoptotic and pro-inflammatory HIF-1α target genes MCP1, BNIP3, Nix and Noxa during TD. We also observed apoptotic cell death in TD as demonstrated by PI/Annexin V staining, TUNEL assay, and Cell Death ELISA. Pharmacological inhibition of HIF-1α activity using YC1 and thiamine repletion both reduced expression of pro-apoptotic HIF-1α target genes and apoptotic cell death in TD. These results demonstrate that induction of HIF-1α mediated transcriptional up-regulation of pro-apoptotic/inflammatory signaling contributes to astrocyte cell death during thiamine deficiency.

  19. Thiamine deficiency activates hypoxia inducible factor-1α to facilitate pro-apoptotic responses in mouse primary astrocytes.

    Science.gov (United States)

    Zera, Kristy; Zastre, Jason

    2017-01-01

    Thiamine is an essential enzyme cofactor required for proper metabolic function and maintenance of metabolism and energy production in the brain. In developed countries, thiamine deficiency (TD) is most often manifested following chronic alcohol consumption leading to impaired mitochondrial function, oxidative stress, inflammation and excitotoxicity. These biochemical lesions result in apoptotic cell death in both neurons and astrocytes. Comparable histological injuries in patients with hypoxia/ischemia and TD have been described in the thalamus and mammillary bodies, suggesting a congruency between the cellular responses to these stresses. Consistent with hypoxia/ischemia, TD stabilizes and activates Hypoxia Inducible Factor-1α (HIF-1α) under physiological oxygen levels. However, the role of TD-induced HIF-1α in neurological injury is currently unknown. Using Western blot analysis and RT-PCR, we have demonstrated that TD induces HIF-1α expression and activity in primary mouse astrocytes. We observed a time-dependent increase in mRNA and protein expression of the pro-apoptotic and pro-inflammatory HIF-1α target genes MCP1, BNIP3, Nix and Noxa during TD. We also observed apoptotic cell death in TD as demonstrated by PI/Annexin V staining, TUNEL assay, and Cell Death ELISA. Pharmacological inhibition of HIF-1α activity using YC1 and thiamine repletion both reduced expression of pro-apoptotic HIF-1α target genes and apoptotic cell death in TD. These results demonstrate that induction of HIF-1α mediated transcriptional up-regulation of pro-apoptotic/inflammatory signaling contributes to astrocyte cell death during thiamine deficiency.

  20. Visualization of proteolytic activity associated with the apoptotic response in cancer cells

    Science.gov (United States)

    Tice, Brian George

    Caspases execute programmed cell death, where low levels of caspase activity are linked to cancer. Chemotherapies utilize induction of apoptosis as a key mechanism for cancer treatment, where caspase-3 is a major player involved in dismantling these aberrant cells. The ability to sensitively measure the initial caspase-3 cleavage events during apoptosis is important for understanding the initiation of this complex cellular process, however, current ensemble methods are not sensitive enough to measure single cleavage events in cells. By utilizing the optical properties of plasmon coupling, peptide-linked gold nanoparticles were developed to enable single molecule imaging of caspase-3 activity in two different cancer systems. Au crown nanoparticles were assembled in a multimeric fashion to overcome the high and heterogeneous background scattering of live cells. In a colon cancer (SW620) cell line challenged with tumor necrosis factor-alpha (TNF-alpha), single molecule trajectories show early stage caspase-3 activation within minutes, which was not detectable by ensemble assays until 23 hours. Variability in caspase-3 activation among the population of cells was identified and likely a result of each cell's specific resistance to death receptor-induced apoptosis. Following these studies, improvements by way of sensitivity and selectivity were tailored into an improved nanosensor construct. Au nanoshell dimers were prepared as a comparably bright construct with 1) reduced heterogeneity compared to the synthesis of the crown nanoparticles and 2) a peptide sequence highly selective for caspase-3. Chronic myeloid leukemia (CML) K562 cells were assessed for their early apoptotic response upon treatment with dasatinib, a clinically approved tyrosine kinase inhibitor that specifically targets BCR-ABL. It has been demonstrated that inhibition of BCR-ABL by dasatinib commits K562 cells to apoptosis. Single molecule experiments with Au nanoshell dimers show caspase-3 activation

  1. Rapid response systems in The Netherlands

    NARCIS (Netherlands)

    Ludikhuize, Jeroen; Hamming, Annette; de Jonge, Evert; Fikkers, Bernard G.

    2011-01-01

    Sixty-three (approximately 80%) of the 81 hospitals that responded to a survey sent to all hospitals in The Netherlands with nonpediatric intensive care units had a rapid response system (RRS) in place or were in the final process of starting one. Among many other findings regarding RRS

  2. Hederagenin Supplementation Alleviates the Pro-Inflammatory and Apoptotic Response to Alcohol in Rats.

    Science.gov (United States)

    Kim, Gyeong-Ji; Song, Da Hye; Yoo, Han Seok; Chung, Kang-Hyun; Lee, Kwon Jai; An, Jeung Hee

    2017-01-06

    In this study, we determined the effects of hederagenin isolated from Akebia quinata fruit on alcohol-induced hepatotoxicity in rats. Specifically, we investigated the hepatoprotective, anti-inflammatory, and anti-apoptotic effects of hederagenin, as well as the role of AKT and mitogen-activated protein kinase (MAPK) signaling pathways in ethanol-induced liver injury. Experimental animals were randomly divided into three groups: normal (sham), 25% ethanol, and 25% ethanol + hederagenin (50 mg/kg/day). Each group was orally administered the respective treatments once per day for 21 days. Acetaldehyde dehydrogenase-2 mRNA expression was higher and alcohol dehydrogenase mRNA expression was lower in the ethanol + hederagenin group than those in the ethanol group. Pro-inflammatory cytokines, including TNF-α, IL-6, and cyclooxygenase-2, significantly increased in the ethanol group, but these increases were attenuated by hederagenin. Moreover, Western blot analysis showed increased expression of the apoptosis-associated protein, Bcl-2, and decreased expression of Bax and p53 after treatment with hederagenin. Hederagenin treatment attenuated ethanol-induced increases in activated p38 MAPK and increased the levels of phosphorylated AKT and ERK. Hederagenin alleviated ethanol-induced liver damage through anti-inflammatory and anti-apoptotic activities. These results suggest that hederagenin is a potential candidate for preventing alcoholic liver injury.

  3. Hederagenin Supplementation Alleviates the Pro-Inflammatory and Apoptotic Response to Alcohol in Rats

    Directory of Open Access Journals (Sweden)

    Gyeong-Ji Kim

    2017-01-01

    Full Text Available In this study, we determined the effects of hederagenin isolated from Akebia quinata fruit on alcohol-induced hepatotoxicity in rats. Specifically, we investigated the hepatoprotective, anti-inflammatory, and anti-apoptotic effects of hederagenin, as well as the role of AKT and mitogen-activated protein kinase (MAPK signaling pathways in ethanol-induced liver injury. Experimental animals were randomly divided into three groups: normal (sham, 25% ethanol, and 25% ethanol + hederagenin (50 mg/kg/day. Each group was orally administered the respective treatments once per day for 21 days. Acetaldehyde dehydrogenase-2 mRNA expression was higher and alcohol dehydrogenase mRNA expression was lower in the ethanol + hederagenin group than those in the ethanol group. Pro-inflammatory cytokines, including TNF-α, IL-6, and cyclooxygenase-2, significantly increased in the ethanol group, but these increases were attenuated by hederagenin. Moreover, Western blot analysis showed increased expression of the apoptosis-associated protein, Bcl-2, and decreased expression of Bax and p53 after treatment with hederagenin. Hederagenin treatment attenuated ethanol-induced increases in activated p38 MAPK and increased the levels of phosphorylated AKT and ERK. Hederagenin alleviated ethanol-induced liver damage through anti-inflammatory and anti-apoptotic activities. These results suggest that hederagenin is a potential candidate for preventing alcoholic liver injury.

  4. Apoptotic responses of zebrafish (Danio rerio) after exposure with microcystin-LR under different ambient temperatures.

    Science.gov (United States)

    Ji, Wei; Liang, Hualei; Zhou, Wenshan; Zhang, Xuezhen

    2013-08-01

    Microcystins (MCs) can cause evident hepatic apoptosis. In vitro studies indicated that uptake of MC by isolated hepatocytes was dramatically reduced as ambient temperature dropped, and some studies presented a hypothesis that differences in core body temperatures in animals result in diverse uptake of MC, as well as different toxic effects. Thus far, however, few in vivo studies have been conducted to investigate the effects of temperature on MC-induced hepatocyte apoptosis in fish, a typical poikilotherm. In the present study, zebrafish were treated with MC-LR, an MC metabolite, at three water temperatures (12, 22 and 32 °C), and evident differences in apoptotic profiles were observed. Damage to liver ultrastructures revealed temperature-dependent early-stage patterns of apoptosis. Flow-cytometric analysis indicated that hepatocyte apoptotic rates varied with a temperature-dependent effect. The transcription levels of some apoptosis-related genes were determined using quantitative real-time polymerase chain reaction, and significantly elevated gene expressions of P53, Bcl-2, Bax and caspase-3 were found in the 12 and 32 °C groups. Results of the present study indicate that different ambient temperatures can lead to various toxic effects of MCs on hepatic apoptosis in fish. Copyright © 2012 John Wiley & Sons, Ltd.

  5. Market design for rapid demand response

    DEFF Research Database (Denmark)

    Nielsen, Kurt; Tamirat, Tseganesh Wubale

    We suggest a market design for rapid demand response in electricity markets. The solution consists of remotely controlled switches, meters, forecasting models as well as a flexible auction market to set prices and select endusers job by job. The auction market motivates truth-telling and makes...... it simple to involve the endusers in advance and to activate demand response immediately. The collective solution is analyzed and economic simulations are conducted for the case of Kenya. Kenya has been su ering from unreliable electricity supply for many years and companies and households have learned...... as the Transmission System Operator (TSO) requests demand response and the winning endusers are disconnected immediately if the TSO accepts the result of the auction. The endusers are compensated with a uniform auction price job by job and the Aggregator receives part of the surplus. The simulation captures...

  6. Rapid Response Manufacturing (RRM). Final CRADA report

    Energy Technology Data Exchange (ETDEWEB)

    Cain, W.D. [Lockheed Martin Energy Systems, Inc., Oak Ridge, TN (United States); Waddell, W.L. [National Centers for Manufacturing Sciences, Ann Arbor, MI (United States)

    1997-08-28

    A major accomplishment of the Rapid Response Manufacturing (RRM) project was the development of a broad-based generic framework for automating and integrating the design-to-manufacturing activities associated with machined part products. Key components of the framework are a manufacturing model that integrates product and process data in a consistent, minimally redundant manner, an advanced computer-aided engineering working environment, knowledge-based software systems for design, process planning, and manufacturing and new production technologies for making products directly from design application software.

  7. Rapid response manufacturing (RRM). Final CRADA report

    Energy Technology Data Exchange (ETDEWEB)

    Cain, W.D. [Lockheed Martin Energy Systems, Inc., Oak Ridge, TN (United States); Waddell, W.L. [National Centers for Manufacturing Sciences, Ann Arbor, MI (United States)

    1998-02-10

    US industry is fighting to maintain its competitive edge in the global market place. Markets fluctuate rapidly. Companies have to be able to respond quickly with improved, high quality, cost efficient products. Because companies and their suppliers are geographically distributed, rapid product realization is dependent on the development of a secure integrated concurrent engineering environment operating across multiple business entities. The way products are developed and brought to market can be improved and made more efficient through the proper incorporation of emerging technologies implemented in a secure environment. This documents the work done under this CRADA to develop capabilities, which permit the effective application, incorporation, and use of advanced technologies in a secure environment to facilitate the product realization process. Lockheed Martin Energy Systems (LMES), through a CRADA with the National Center for Manufacturing Sciences (NCMS), worked within a consortium of major industrial firms--Ford, General Motors, Texas Instruments, United Technologies, and Eastman Kodak--and several small suppliers of advanced manufacturing technology--MacNeal-Schwendler Corp., Teknowledge Corp., Cimplex Corp., Concentra, Spatial Technology, and Structural Dynamics Research Corp. (SDRC)--to create infrastructure to support the development and implementation of secure engineering environments for Rapid Response Manufacturing. The major accomplishment achieved under this CRADA was the demonstration of a prototypical implementation of a broad-based generic framework for automating and integrating the design-to-manufacturing activities associated with machined parts in a secure NWC compliant environment. Specifically, methods needed to permit the effective application, incorporation, and use of advanced technologies in a secure environment to facilitate the product realization process were developed and demonstrated. An important aspect of this demonstration was

  8. Rapid response oxygen-sensing nanofibers

    Energy Technology Data Exchange (ETDEWEB)

    Xue, Ruipeng [Department of Materials Science and Engineering, The Ohio State University, Columbus, OH 43210 (United States); Behera, Prajna; Viapiano, Mariano S. [Department of Neurosurgery, Brigham and Women' s Hospital, Harvard Medical School, Boston, MA 02115 (United States); Lannutti, John J., E-mail: lannutti.1@osu.edu [Department of Materials Science and Engineering, The Ohio State University, Columbus, OH 43210 (United States)

    2013-08-01

    Molecular oxygen has profound effects on cell and tissue viability. Relevant sensor forms that can rapidly determine dissolved oxygen levels under biologically relevant conditions provide critical metabolic information. Using 0.5 μm diameter electrospun polycaprolactone (PCL) fiber containing an oxygen-sensitive probe, tris (4,7-diphenyl-1,10-phenanthroline) ruthenium(II) dichloride, we observed a response time of 0.9 ± 0.12 s while the t{sub 95} for the corresponding film was more than two orders of magnitude greater. Interestingly, the response and recovery times of slightly larger diameter PCL fibers were 1.79 ± 0.23 s and 2.29 ± 0.13 s, respectively, while the recovery time was not statistically different likely due to the more limited interactions of nitrogen with the polymer matrix. A more than 10-fold increase in PCL fiber diameter reduces oxygen sensitivity while having minor effects on response time; conversely, decreases in fiber diameter to less than 0.5 μm would likely decrease response times even further. In addition, a 50 °C heat treatment of the electrospun fiber resulted in both increased Stern–Volmer slope and linearity likely due to secondary recrystallization that further homogenized the probe microenvironment. At exposure times up to 3600 s in length, photobleaching was observed but was largely eliminated by the use of either polyethersulfone (PES) or a PES–PCL core–shell composition. However, this resulted in 2- and 3-fold slower response times. Finally, even the non-core shell compositions containing the Ru oxygen probe result in no apparent cytotoxicity in representative glioblastoma cell populations. Highlights: • Nanofiber-based structures can self-report localized oxygen concentrations. • Ideal for tissue engineering as they allow close interaction of cells. • Nanofiber-incorporated oxygen-sensitive probes provide a perfectly linear response. • Photobleaching is largely eliminated by the use of PES–PCL core

  9. APOMAB, a La-specific monoclonal antibody, detects the apoptotic tumor response to life-prolonging and DNA-damaging chemotherapy.

    Directory of Open Access Journals (Sweden)

    Fares Al-Ejeh

    ability of radiolabeled DAB4 to rapidly assess the apoptotic tumor response and, consequently, to potentially predict extended survival justifies its future clinical development as a radioimmunoscintigraphic agent. This article is part I of a two-part series providing proof-of-concept for the the diagnostic and therapeutic use of a La-specific monoclonal antibody, the DAB4 clone of which is represented by the registered trademark, APOMAB.

  10. Rapid Response in Psychological Treatments for Binge-Eating Disorder

    Science.gov (United States)

    Hilbert, Anja; Hildebrandt, Thomas; Agras, W. Stewart; Wilfley, Denise E.; Wilson, G. Terence

    2015-01-01

    Objective Analysis of short- and long-term effects of rapid response across three different treatments for binge-eating disorder (BED). Method In a randomized clinical study comparing interpersonal psychotherapy (IPT), cognitive-behavioral guided self-help (CBTgsh), and behavioral weight loss (BWL) treatment in 205 adults meeting DSM-IV criteria for BED, the predictive value of rapid response, defined as ≥ 70% reduction in binge-eating by week four, was determined for remission from binge-eating and global eating disorder psychopathology at posttreatment, 6-, 12-, 18-, and 24-month follow-up. Results Rapid responders in CBTgsh, but not in IPT or BWL, showed significantly greater rates of remission from binge-eating than non-rapid responders, which was sustained over the long term. Rapid and non-rapid responders in IPT and rapid responders in CBTgsh showed a greater remission from binge-eating than non-rapid responders in CBTgsh and BWL. Rapid responders in CBTgsh showed greater remission from binge-eating than rapid responders in BWL. Although rapid responders in all treatments had lower global eating disorder psychopathology than non-rapid responders in the short term, rapid responders in CBTgsh and IPT were more improved than those in BWL and non-rapid responders in each treatment. Rapid responders in BWL did not differ from non-rapid responders in CBTgsh and IPT. Conclusions Rapid response is a treatment-specific positive prognostic indicator of sustained remission from binge-eating in CBTgsh. Regarding an evidence-based stepped care model, IPT, equally efficacious for rapid and non-rapid responders, could be investigated as a second-line treatment in case of non-rapid response to first-line CBTgsh. PMID:25867446

  11. Rapid response learning of brand logo priming: Evidence that brand priming is not dominated by rapid response learning.

    Science.gov (United States)

    Boehm, Stephan G; Smith, Ciaran; Muench, Niklas; Noble, Kirsty; Atherton, Catherine

    2017-08-31

    Repetition priming increases the accuracy and speed of responses to repeatedly processed stimuli. Repetition priming can result from two complementary sources: rapid response learning and facilitation within perceptual and conceptual networks. In conceptual classification tasks, rapid response learning dominates priming of object recognition, but it does not dominate priming of person recognition. This suggests that the relative engagement of network facilitation and rapid response learning depends on the stimulus domain. Here, we addressed the importance of the stimulus domain for rapid response learning by investigating priming in another domain, brands. In three experiments, participants performed conceptual decisions for brand logos. Strong priming was present, but it was not dominated by rapid response learning. These findings add further support to the importance of the stimulus domain for the relative importance of network facilitation and rapid response learning, and they indicate that brand priming is more similar to person recognition priming than object recognition priming, perhaps because priming of both brands and persons requires individuation.

  12. The Linker Histone H1.2 Is an Intermediate in the Apoptotic Response to Cytokine Deprivation in T-Effectors

    Directory of Open Access Journals (Sweden)

    Megha Garg

    2014-01-01

    Full Text Available Tissue homeostasis is a dynamic process involving proliferation and the removal of redundant or damaged cells. This is exemplified in the coordinated deletion—triggered by limiting trophic factors/cytokines in the extracellular milieu—of differentiated T cells overproduced during the mammalian immune response. However, mechanisms by which extracellular cues are perceived and transduced as apoptotic triggers remain incompletely understood. T-effectors are dependent on cytokines for survival and undergo apoptosis following cytokine withdrawal. Here we report that leptomycin B (LMB, an inhibitor of nuclear export machinery, protected T-effectors from apoptosis implicating a nuclear intermediate in the apoptotic pathway. Evidence is presented that the linker histone H1.2 localizes to the cytoplasm, by a mechanism sensitive to regulation by LMB, to activate apoptotic signaling culminating in nuclear and mitochondrial damage in T-effectors in response to cytokine deprivation. H1.2 is detected in a complex with the proapoptotic mitochondrial resident Bak and its subcellular localization regulated by Jun-N-terminal kinase (JNK, an intermediate in the apoptotic cascade in T-effectors. These data suggest that metabolic stressors may impinge on H1.2 dynamics favoring its activity at the mitochondrion, thereby functioning as a molecular switch for T-effector apoptosis.

  13. Distinct Dasatinib-Induced Mechanisms of Apoptotic Response and Exosome Release in Imatinib-Resistant Human Chronic Myeloid Leukemia Cells

    Directory of Open Access Journals (Sweden)

    Juan Liu

    2016-04-01

    Full Text Available Although dasatinib is effective in most imatinib mesylate (IMT-resistant chronic myeloid leukemia (CML patients, the underlying mechanism of its effectiveness in eliminating imatinib-resistant cells is only partially understood. This study investigated the effects of dasatinib on signaling mechanisms driving-resistance in imatinib-resistant CML cell line K562 (K562RIMT. Compared with K562 control cells, exsomal release, the phosphoinositide 3-kinase (PI3K/protein kinase B (Akt/ mammalian target of rapamycin (mTOR signaling and autophagic activity were increased significantly in K562RIMT cells and mTOR-independent beclin-1/Vps34 signaling was shown to be involved in exosomal release in these cells. We found that Notch1 activation-mediated reduction of phosphatase and tensin homolog (PTEN was responsible for the increased Akt/mTOR activities in K562RIMT cells and treatment with Notch1 γ-secretase inhibitor prevented activation of Akt/mTOR. In addition, suppression of mTOR activity by rapamycin decreased the level of activity of p70S6K, induced upregulation of p53 and caspase 3, and led to increase of apoptosis in K562RIMT cells. Inhibition of autophagy by spautin-1 or beclin-1 knockdown decreased exosomal release, but did not affect apoptosis in K562RIMT cells. In summary, in K562RIMT cells dasatinib promoted apoptosis through downregulation of Akt/mTOR activities, while preventing exosomal release and inhibiting autophagy by downregulating expression of beclin-1 and Vps34. Our findings reveal distinct dasatinib-induced mechanisms of apoptotic response and exosomal release in imatinib-resistant CML cells.

  14. Norepinephrine-induced apoptotic and hypertrophic responses in H9c2 cardiac myoblasts are characterized by different repertoire of reactive oxygen species generation

    Directory of Open Access Journals (Sweden)

    Anita Thakur

    2015-08-01

    Full Text Available Despite recent advances, the role of ROS in mediating hypertrophic and apoptotic responses in cardiac myocytes elicited by norepinephrine (NE is rather poorly understood. We demonstrate through our experiments that H9c2 cardiac myoblasts treated with 2 µM NE (hypertrophic dose generate DCFH-DA positive ROS only for 2 h; while those treated with 100 µM NE (apoptotic dose sustains generation for 48 h, followed by apoptosis. Though the levels of DCFH fluorescence were comparable at early time points in the two treatment sets, its quenching by DPI, catalase and MnTmPyP suggested the existence of a different repertoire of ROS. Both doses of NE also induced moderate levels of H2O2 but with different kinetics. Sustained but intermittent generation of highly reactive species detectable by HPF was seen in both treatment sets but no peroxynitrite was generated in either conditions. Sustained generation of hydroxyl radicals with no appreciable differences were noticed in both treatment sets. Nevertheless, despite similar profile of ROS generation between the two conditions, extensive DNA damage as evident from the increase in 8-OH-dG content, formation of γ-H2AX and PARP cleavage was seen only in cells treated with the higher dose of NE. We therefore conclude that hypertrophic and apoptotic doses of NE generate distinct but comparable repertoire of ROS/RNS leading to two very distinct downstream responses.

  15. Rapid response in psychological treatments for binge eating disorder.

    Science.gov (United States)

    Hilbert, Anja; Hildebrandt, Thomas; Agras, W Stewart; Wilfley, Denise E; Wilson, G Terence

    2015-06-01

    Analysis of short- and long-term effects of rapid response across 3 different treatments for binge eating disorder (BED). In a randomized clinical study comparing interpersonal psychotherapy (IPT), cognitive-behavioral therapy guided self-help (CBTgsh), and behavioral weight loss (BWL) treatment in 205 adults meeting Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV; APA, 1994) criteria for BED, the predictive value of rapid response, defined as ≥70% reduction in binge eating by Week 4, was determined for remission from binge eating and global eating disorder psychopathology at posttreatment, 6-, 12-, 18-, and 24-month follow-ups. Rapid responders in CBTgsh, but not in IPT or BWL, showed significantly greater rates of remission from binge eating than nonrapid responders, which was sustained over the long term. Rapid and nonrapid responders in IPT and rapid responders in CBTgsh showed a greater remission from binge eating than nonrapid responders in CBTgsh and BWL. Rapid responders in CBTgsh showed greater remission from binge eating than rapid responders in BWL. Although rapid responders in all treatments had lower global eating disorder psychopathology than nonrapid responders in the short term, rapid responders in CBTgsh and IPT were more improved than those in BWL and nonrapid responders in each treatment. Rapid responders in BWL did not differ from nonrapid responders in CBTgsh and IPT. Rapid response is a treatment-specific positive prognostic indicator of sustained remission from binge eating in CBTgsh. Regarding an evidence-based, stepped-care model, IPT, equally efficacious for rapid and nonrapid responders, could be investigated as a second-line treatment in case of nonrapid response to first-line CBTgsh. (c) 2015 APA, all rights reserved).

  16. 3D printed rapid disaster response

    Science.gov (United States)

    Lacaze, Alberto; Murphy, Karl; Mottern, Edward; Corley, Katrina; Chu, Kai-Dee

    2014-05-01

    Under the Department of Homeland Security-sponsored Sensor-smart Affordable Autonomous Robotic Platforms (SAARP) project, Robotic Research, LLC is developing an affordable and adaptable method to provide disaster response robots developed with 3D printer technology. The SAARP Store contains a library of robots, a developer storefront, and a user storefront. The SAARP Store allows the user to select, print, assemble, and operate the robot. In addition to the SAARP Store, two platforms are currently being developed. They use a set of common non-printed components that will allow the later design of other platforms that share non-printed components. During disasters, new challenges are faced that require customized tools or platforms. Instead of prebuilt and prepositioned supplies, a library of validated robots will be catalogued to satisfy various challenges at the scene. 3D printing components will allow these customized tools to be deployed in a fraction of the time that would normally be required. While the current system is focused on supporting disaster response personnel, this system will be expandable to a range of customers, including domestic law enforcement, the armed services, universities, and research facilities.

  17. Early applied electric field stimulation attenuates secondary apoptotic responses and exerts neuroprotective effects in acute spinal cord injury of rats.

    Science.gov (United States)

    Zhang, C; Zhang, G; Rong, W; Wang, A; Wu, C; Huo, X

    2015-04-16

    the inhibition of secondary apoptotic responses after SCI. These findings support further investigation of the future clinical application of EFS after SCI. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  18. Agile Science Planning: Rapid Response Re-planning Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Develop autonomous rapid response to science observations in missions targeting small bodies in fly-by mode where observing and reaction time is precious.

  19. Turnbull - Early Detection and Rapid Response Team 2007

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — Biocontrol agents and chemicals to facilitate the rapid response phase of the project will be purchased and applied and a Washington Service Corps AmeriCorps member...

  20. Adsorption of Chloroform by the Rapid Response System Filter

    National Research Council Canada - National Science Library

    Karwacki, Christopher

    1997-01-01

    Adsorption equilibria and dynamic breakthrough data were measured to determine the adsorption capacity and effect of purge air on the desorption of chloroform from activated carbon simulating the Rapid Response System (RRS) filter...

  1. Rapid Detection of Cellular Response to Biological Agents

    National Research Council Canada - National Science Library

    Williams, Bryan R

    2005-01-01

    Our program objective is to develop simple and rapid methods for detecting at a cellular level, individual responses to environmental stresses elaborated by exposure to infectious agents such as bacteria and viruses...

  2. Rapid Detection of Cellular Responses to Biological Agents

    National Research Council Canada - National Science Library

    Williams, Bryan

    2004-01-01

    Our program objective is to develop simple and rapid methods for detecting, at a cellular level, individual responses to environmental stresses elaborated by exposure to infectious agents such as bacteria and viruses...

  3. Rapid Detection of Cellular Responses to Biological Agents

    National Research Council Canada - National Science Library

    Williams, Bryan

    2003-01-01

    Our program objective is to develop simple and rapid methods for detecting, at a cellular level, individual responses to environmental stresses elaborated by exposure to infectious agents such as bacteria and viruses...

  4. Turnbull - Early Detection and Rapid Response Team 2010

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — Funding from this grant will allow for the purchase of biocontrol agents and chemicals to facilitate the rapid response phase of the project and to provide funds to...

  5. Turnbull - Early Detection and Rapid Response Team 2008

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — Funding from this grant will allow for the purchase of biocontrol agents and chemicals to facilitate the rapid response phase of the project and to provide match for...

  6. Lessons learned from Rapid Response Research on wildland fires

    Science.gov (United States)

    Leigh Lentile; Penny Morgan; Colin Hardy; Andrew Hudak; Robert Means; Roger Ottmar; Peter Robichaud; Elaine Sutherland; Frederick Way; Sarah Lewis

    2007-01-01

    In recent years, more researchers are collecting data either on active wildfires or immediately after wildfire occurrence. Known as Rapid Response Research, this important undertaking provides real-time information, useful data, and improved tools for managers.

  7. iNKT Cells Are Responsible for the Apoptotic Reduction of Basophils That Mediate Th2 Immune Responses Elicited by Papain in Mice Following γPGA Stimulation.

    Directory of Open Access Journals (Sweden)

    Hyun Jung Park

    Full Text Available Recent studies have demonstrated that Bacillus subtilis-derived poly-gamma glutamic acid (γPGA treatment suppresses the development of allergic diseases such as atopic dermatitis (AD. Although basophils, an innate immune cell, are known to play critical roles in allergic immune responses and repeated long-term administration of γPGA results in decreased splenic basophils in an AD murine model, the underlying mechanisms by which γPGA regulates basophil frequency remain unclear. To investigate how γPGA modulates basophils, we employed basophil-mediated Th2 induction in vivo model elicited by the allergen papain protease. Repeated injection of γPGA reduced the abundance of basophils and their production of IL4 in mice, consistent with our previous study using NC/Nga AD model mice. The depletion of basophils by a single injection of γPGA was dependent on the TLR4/DC/IL12 axis. CD1d-dependent Vα14 TCR invariant natural killer T (iNKT cells are known to regulate a variety of immune responses, such as allergy. Because iNKT cell activation is highly sensitive to IL12 produced by DCs, we evaluated whether the effect of γPGA on basophils is mediated by iNKT cell activation. We found that in vivo γPGA treatment did not induce the reduction of basophils in iNKT cell-deficient CD1d KO mice, suggesting the critical role of iNKT cells in γPGA-mediated basophil depletion at the early time points. Furthermore, increased apoptotic basophil reduction triggered by iNKT cells upon γPGA stimulation was mainly attributed to Th1 cytokines such as IFNγ and TNFα, consequently resulting in inhibition of papain-induced Th2 differentiation via diminishing basophil-derived IL4. Taken together, our results clearly demonstrate that γPGA-induced iNKT cell polarization toward the Th1 phenotype induces apoptotic basophil depletion, leading to the suppression of Th2 immune responses. Thus, elucidation of the crosstalk between innate immune cells will contribute to

  8. Rapid Response Teams: Is it Time to Reframe the Questions of Rapid Response Team Measurement?

    Science.gov (United States)

    Salvatierra, Gail G; Bindler, Ruth C; Daratha, Kenn B

    2016-11-01

    The purpose of this article is to present an overview of rapid response team (RRT) history in the United States, provide a review of prior RRT effectiveness research, and propose the reframing of four new questions of RRT measurement that are designed to better understand RRTs in the context of contemporary nursing practice as well as patient outcomes. RRTs were adopted in the United States because of their intuitive appeal, and despite a lack of evidence for their effectiveness. Subsequent studies used mortality and cardiac arrest rates to measure whether or not RRTs "work." Few studies have thoroughly examined the effect of RRTs on nurses and on nursing practice. An extensive literature review provided the background. Suppositions and four critical, unanswered questions arising from the literature are suggested. The results of RRT effectiveness, which have focused on patient-oriented outcomes, have been ambiguous, contradictory, and difficult to interpret. Additionally, they have not taken into account the multiple ways in which these teams have impacted nurses and nursing practice as well as patient outcomes. What happens in terms of RRT process and utilization is likely to have a major impact on nurses and nursing care on general medical and surgical wards. What that impact will be depends on what we can learn from measuring with an expanded yardstick, in order to answer the question, "Do RRTs work?" Evidence for the benefits of RRTs depends on proper framing of questions relating to their effectiveness, including the multiple ways RRTs contribute to nursing efficacy. © 2016 Sigma Theta Tau International.

  9. Investigation of DNA damage response and apoptotic gene methylation pattern in sporadic breast tumors using high throughput quantitative DNA methylation analysis technology

    Directory of Open Access Journals (Sweden)

    Prakash Neeraj

    2010-11-01

    Full Text Available Abstract Background- Sporadic breast cancer like many other cancers is proposed to be a manifestation of abnormal genetic and epigenetic changes. For the past decade our laboratory has identified genes involved in DNA damage response (DDR, apoptosis and immunesurvelliance pathways to influence sporadic breast cancer risk in north Indian population. Further to enhance our knowledge at the epigenetic level, we performed DNA methylation study involving 17 gene promoter regions belonging to DNA damage response (DDR and death receptor apoptotic pathway in 162 paired normal and cancerous breast tissues from 81 sporadic breast cancer patients, using a high throughput quantitative DNA methylation analysis technology. Results- The study identified five genes with statistically significant difference between normal and tumor tissues. Hypermethylation of DR5 (P = 0.001, DCR1 (P = 0.00001, DCR2 (P = 0.0000000005 and BRCA2 (P = 0.007 and hypomethylation of DR4 (P = 0.011 in sporadic breast tumor tissues suggested a weak/aberrant activation of the DDR/apoptotic pathway in breast tumorigenesis. Negative correlation was observed between methylation status and transcript expression levels for TRAIL, DR4, CASP8, ATM, CHEK2, BRCA1 and BRCA2 CpG sites. Categorization of the gene methylation with respect to the clinicopathological parameters showed an increase in aberrant methylation pattern in advanced tumors. These uncharacteristic methylation patterns corresponded with decreased death receptor apoptosis (P = 0.047 and DNA damage repair potential (P = 0.004 in advanced tumors. The observation of BRCA2 -26 G/A 5'UTR polymorphism concomitant with the presence of methylation in the promoter region was novel and emerged as a strong candidate for susceptibility to sporadic breast tumors. Conclusion- Our study indicates that methylation of DDR-apoptotic gene promoters in sporadic breast cancer is not a random phenomenon. Progressive epigenetic alterations in advancing

  10. DdrO is an essential protein that regulates the radiation desiccation response and the apoptotic-like cell death in the radioresistant Deinococcus radiodurans bacterium.

    Science.gov (United States)

    Devigne, Alice; Ithurbide, Solenne; Bouthier de la Tour, Claire; Passot, Fanny; Mathieu, Martine; Sommer, Suzanne; Servant, Pascale

    2015-06-01

    Deinococcus radiodurans is known for its extreme radioresistance. Comparative genomics identified a radiation-desiccation response (RDR) regulon comprising genes that are highly induced after DNA damage and containing a conserved motif (RDRM) upstream of their coding region. We demonstrated that the RDRM sequence is involved in cis-regulation of the RDR gene ddrB in vivo. Using a transposon mutagenesis approach, we showed that, in addition to ddrO encoding a predicted RDR repressor and irrE encoding a positive regulator recently shown to cleave DdrO in Deinococcus deserti, two genes encoding α-keto-glutarate dehydrogenase subunits are involved in ddrB regulation. In wild-type cells, the DdrO cell concentration decreased transiently in an IrrE-dependent manner at early times after irradiation. Using a conditional gene inactivation system, we showed that DdrO depletion enhanced expression of three RDR proteins, consistent with the hypothesis that DdrO acts as a repressor of the RDR regulon. DdrO-depleted cells loose viability and showed morphological changes evocative of an apoptotic-like response, including membrane blebbing, defects in cell division and DNA fragmentation. We propose that DNA repair and apoptotic-like death might be two responses mediated by the same regulators, IrrE and DdrO, but differently activated depending on the persistence of IrrE-dependent DdrO cleavage. © 2015 John Wiley & Sons Ltd.

  11. Reward prospect rapidly speeds up response inhibition via reactive control.

    Science.gov (United States)

    Boehler, Carsten N; Schevernels, Hanne; Hopf, Jens-Max; Stoppel, Christian M; Krebs, Ruth M

    2014-06-01

    Response inhibition is an important cognitive-control function that allows for already-initiated or habitual behavioral responses to be promptly withheld when needed. A typical paradigm to study this function is the stop-signal task. From this task, the stop-signal response time (SSRT) can be derived, which indexes how rapidly an already-initiated response can be canceled. Typically, SSRTs range around 200 ms, identifying response inhibition as a particularly rapid cognitive-control process. Even so, it has recently been shown that SSRTs can be further accelerated if successful response inhibition is rewarded. Since this earlier study effectively ruled out differential preparatory (proactive) control adjustments, the reward benefits likely relied on boosted reactive control. Yet, given how rapidly such control processes would need to be enhanced, alternative explanations circumventing reactive control are important to consider. We addressed this question with an fMRI study by gauging the overlap of the brain networks associated with reward-related and response-inhibition-related processes in a reward-modulated stop-signal task. In line with the view that reactive control can indeed be boosted swiftly by reward availability, we found that the activity in key brain areas related to response inhibition was enhanced for reward-related stop trials. Furthermore, we observed that this beneficial reward effect was triggered by enhanced connectivity between task-unspecific (reward-related) and task-specific (inhibition-related) areas in the medial prefrontal cortex (mPFC). The present data hence suggest that reward information can be translated very rapidly into behavioral benefits (here, within ~200 ms) through enhanced reactive control, underscoring the immediate responsiveness of such control processes to reward availability in general.

  12. Neurotransmitters and neuronal apoptotic cell death of chronically aluminum intoxicated Nile catfish (Clarias gariepinus) in response to ascorbic acid supplementation.

    Science.gov (United States)

    Khalil, Samah R; Hussein, Mohamed M A

    2015-12-01

    Few studies have been carried out to assess the neurotoxic effect of aluminum (Al) on the aquatic creatures. This study aims to evaluate the neurotoxic effects of long term Al exposure on the Nile catfish (Clarias gariepinus) and the potential ameliorative influence of ascorbic acid (ASA) over a 180 days exposure period. Forty eight Nile catfish were divided into four groups: control group, placed in clean water, ASA exposed group (5mg/l), AlCl3 received group (28.96 μg/l; 1/20 LC50), and group received AlCl3 concomitantly with ASA. Brain tissue was examined by using flow cytometry to monitor the apoptotic cell population, HPLC analysis for the quantitative estimation of brain monoamine neurotransmitters [serotonin (5-HT), dopamine (DA), norepinephrine (NE)]. The amino acid neurotransmitters [serum taurine, glycine, aspartate and glutamine and brain gamma aminobutyric acid (GABA)] levels were assessed, plus changes in brain tissue structure using light microscopy. The concentration of Al in both brain tissue and serum was determined by using atomic absorption spectrophotometery. The Al content in serum and brain tissue were both elevated and Al exposure induced an increase in the number of apoptotic cells, a marked reduction of the monoamine and amino acids neurotransmitters levels and changes in tissue morphology. ASA supplementation partially abolished the effects of AL on the reduced neurotransmitter, the degree of apoptosis and restored the morphological changes to the brain. Overall, our results indicate that, ASA is a promising neuroprotective agent against for Al-induced neurotoxicity in the Nile catfish. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Modulation of the Unfolded Protein Response by Tauroursodeoxycholic Acid Counteracts Apoptotic Cell Death and Fibrosis in a Mouse Model for Secondary Biliary Liver Fibrosis.

    Science.gov (United States)

    Paridaens, Annelies; Raevens, Sarah; Devisscher, Lindsey; Bogaerts, Eliene; Verhelst, Xavier; Hoorens, Anne; Van Vlierberghe, Hans; van Grunsven, Leo A; Geerts, Anja; Colle, Isabelle

    2017-01-20

    The role of endoplasmic reticulum stress and the unfolded protein response (UPR) in cholestatic liver disease and fibrosis is not fully unraveled. Tauroursodeoxycholic acid (TUDCA), a hydrophilic bile acid, has been shown to reduce endoplasmic reticulum (ER) stress and counteract apoptosis in different pathologies. We aimed to investigate the therapeutic potential of TUDCA in experimental secondary biliary liver fibrosis in mice, induced by common bile duct ligation. The kinetics of the hepatic UPR and apoptosis during the development of biliary fibrosis was studied by measuring markers at six different timepoints post-surgery by qPCR and Western blot. Next, we investigated the therapeutic potential of TUDCA, 10 mg/kg/day in drinking water, on liver damage (AST/ALT levels) and fibrosis (Sirius red-staining), in both a preventive and therapeutic setting. Common bile duct ligation resulted in the increased protein expression of CCAAT/enhancer-binding protein homologous protein (CHOP) at all timepoints, along with upregulation of pro-apoptotic caspase 3 and 12, tumor necrosis factor receptor superfamily, member 1A (TNFRsf1a) and Fas-Associated protein with Death Domain (FADD) expression. Treatment with TUDCA led to a significant reduction of liver fibrosis, accompanied by a slight reduction of liver damage, decreased hepatic protein expression of CHOP and reduced gene and protein expression of pro-apoptotic markers. These data indicate that TUDCA exerts a beneficial effect on liver fibrosis in a model of cholestatic liver disease, and suggest that this effect might, at least in part, be attributed to decreased hepatic UPR signaling and apoptotic cell death.

  14. Montelukast targeting the cysteinyl leukotriene receptor 1 ameliorates Aβ1-42-induced memory impairment and neuroinflammatory and apoptotic responses in mice.

    Science.gov (United States)

    Lai, Jin'e; Hu, Meng; Wang, Hao; Hu, Mei; Long, Yan; Miao, Ming-xing; Li, Jia-chang; Wang, Xiao-bing; Kong, Ling-yi; Hong, Hao

    2014-04-01

    Montelukast, known as a cysteinyl leukotriene receptor 1 (CysLT1R) antagonist, is currently used for treatment of inflammatory diseases such as asthma. Here, we investigated effects of montelukast on neuroinflammatory, apoptotic responses, and memory performance following intracerebral infusions of amyloid-β (Aβ). The data demonstrated that intracerebroventrical infusions of aggregated Aβ1-42 (410 pmol/mouse) produced deficits in learning ability and memory, as evidenced by increase in escape latency during acquisition trials and decreases in exploratory activities in the probe trial in Morris water maze (MWM) task, and by decrease in the number of correct choices and increase in latency to enter the shock-free compartment in Y-maze test, and caused significant increases in pro-inflammatory cytokines such as NF-κB p65, TNF-α and IL-1β as well as pro-apoptotic molecule caspase-3 activation and anti-apoptotic protein Bcl-2 downregulation in hippocampus and cortex. Interestingly, this treatment resulted in upregulation of protein or mRNA of CysLT1R in both hippocampus and cortex. Blockade of CysLT1R by repeated treatment with montelukast (1 or 2 mg/kg, ig, 4 weeks) reduced Aβ1-42-induced CysLT1R expression and also suppressed Aβ1-42-induced increments of NF-κB p65, TNF-α, IL-1β and caspase-3 activation, and Bcl-2 downregulation in the hippocampus and cortex. Correspondingly, montelukast treatment significantly improved Aβ1-42-induced memory impairment in mice, but had little effect on normal mice. Our results show that montelukast may ameliorate Aβ1-42-induced memory impairment via inhibiting neuroinflammation and apoptosis mediated by CysLT1R signaling, suggesting that CysLT1R antagonism represents a novel treatment strategy for Alzheimer's disease. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Dual response of human leukemia U937 cells to hypertonic shrinkage: initial regulatory volume increase (RVI) and delayed apoptotic volume decrease (AVD).

    Science.gov (United States)

    Yurinskaya, Valentina E; Moshkov, Alexey V; Wibberley, Anna V; Lang, Florian; Model, Michael A; Vereninov, Alexey A

    2012-01-01

    Osmotic cell shrinkage is a powerful trigger of suicidal cell death or apoptosis, which is paralleled and enforced by apoptotic volume decrease (AVD). Cells counteract cell shrinkage by volume regulatory increase (RVI). The present study explored the response of human U937 cells to hypertonic solution thus elucidating the relationship between RVI and AVD. Cell water, concentration of monovalent ions and the appearance of apoptotic markers were followed for 0.5-4 h after the cells were transferred to a hypertonic medium. Intracellular water, K+, Na+, and Cl- content, ouabain-sensitive and -resistant Rb+ influxes were determined by measurement of the cell buoyant density in Percoll density gradient, flame emission analysis and 36Cl- assay, respectively. Fluorescent microscopy of live cells stained by acridine orange and ethidium bromide was used to verify apoptosis. After 2-4 h incubation in hypertonic media the cell population was split into light (L) and heavy (H) fractions. According to microscopy and analysis of monovalent ions the majority of cells in the L population were healthy, while the H fractions were enriched with apoptotic cells. The density of L cells was decreasing with time, while the density of H cells was increasing, thus reflecting the opposite effects of RVI and AVD. At the same time, some of the cells were shifting from L to H fractions, indicating that apoptosis was gradually extending to cells that were previously displaying normal RVI. The findings suggest that apoptosis can develop in cells capable of RVI. Copyright © 2012 S. Karger AG, Basel.

  16. Response of some elite cocoyam varieties to cocoyam rapid ...

    African Journals Online (AJOL)

    The experiment on the response of some elite cocoyam varieties to cocoyam rapid multiplication technology was carried out in 2012 and 2013 at the Research field of the National Root Crops Research Institute Umudike. Treatment comprised M1, M2 (microcormels from colocasia spp and Xanthosoma spp respectively); ...

  17. Performance of the efferent limb of a rapid response system

    DEFF Research Database (Denmark)

    Sørensen, Emilie M; Petersen, Asger

    2015-01-01

    AIM: To determine the distribution of outcomes following a medical emergency team (MET) call using a modified version of the multidisciplinary audit and evaluation of outcomes of rapid response (MAELOR) tool, and to evaluate its usefulness in monitoring the performance of the efferent limb...

  18. Critical involvement of the ATM-dependent DNA damage response in the apoptotic demise of HIV-1-elicited syncytia.

    Directory of Open Access Journals (Sweden)

    Jean-Luc Perfettini

    Full Text Available DNA damage can activate the oncosuppressor protein ataxia telangiectasia mutated (ATM, which phosphorylates the histone H2AX within characteristic DNA damage foci. Here, we show that ATM undergoes an activating phosphorylation in syncytia elicited by the envelope glycoprotein complex (Env of human immunodeficiency virus-1 (HIV-1 in vitro. This was accompanied by aggregation of ATM in discrete nuclear foci that also contained phospho-histone H2AX. DNA damage foci containing phosphorylated ATM and H2AX were detectable in syncytia present in the brain or lymph nodes from patients with HIV-1 infection, as well as in a fraction of blood leukocytes, correlating with viral status. Knockdown of ATM or of its obligate activating factor NBS1 (Nijmegen breakage syndrome 1 protein, as well as pharmacological inhibition of ATM with KU-55933, inhibited H2AX phosphorylation and prevented Env-elicited syncytia from undergoing apoptosis. ATM was found indispensable for the activation of MAP kinase p38, which catalyzes the activating phosphorylation of p53 on serine 46, thereby causing p53 dependent apoptosis. Both wild type HIV-1 and an HIV-1 mutant lacking integrase activity induced syncytial apoptosis, which could be suppressed by inhibiting ATM. HIV-1-infected T lymphoblasts from patients with inactivating ATM or NBS1 mutations also exhibited reduced syncytial apoptosis. Altogether these results indicate that apoptosis induced by a fusogenic HIV-1 Env follows a pro-apoptotic pathway involving the sequential activation of ATM, p38MAPK and p53.

  19. Rapid climate change and society: assessing responses and thresholds.

    Science.gov (United States)

    Niemeyer, Simon; Petts, Judith; Hobson, Kersty

    2005-12-01

    Assessing the social risks associated with climate change requires an understanding of how humans will respond because it affects how well societies will adapt. In the case of rapid or dangerous climate change, of particular interest is the potential for these responses to cross thresholds beyond which they become maladaptive. To explore the possibility of such thresholds, a series of climate change scenarios were presented to U.K. participants whose subjective responses were recorded via interviews and surveyed using Q methodology. The results indicate an initially adaptive response to climate warming followed by a shift to maladaptation as the magnitude of change increases. Beyond this threshold, trust in collective action and institutions was diminished, negatively impacting adaptive capacity. Climate cooling invoked a qualitatively different response, although this may be a product of individuals being primed for warming because it has dominated public discourse. The climate change scenarios used in this research are severe by climatological standards. In reality, the observed responses might occur at a lower rate of change. Whatever the case, analysis of subjectivity has revealed potential for maladaptive human responses, constituting a dangerous or rapid climate threshold within the social sphere.

  20. Rapid Response Fault Drilling Past, Present, and Future

    Directory of Open Access Journals (Sweden)

    Demian M. Saffer

    2009-09-01

    Full Text Available New information about large earthquakes can be acquired by drilling into the fault zone quickly following a large seismic event. Specifically, we can learn about the levels of friction and strength of the fault which determine the dynamic rupture, monitor the healing process of the fault, record the stress changes that trigger aftershocks and capture important physical and chemical properties of the fault that control the rupture process. These scientific and associated technical issues were the focus of a three-day workshop on Rapid Response Fault Drilling: Past, Present, and Future, sponsored by the International Continental Scientific Drilling Program (ICDP and the Southern California Earthquake Center (SCEC. The meeting drewtogether forty-four scientists representing ten countries in Tokyo, Japan during November 2008. The group discussed the scientific problems and how they could be addressed through rapid response drilling. Focused talks presented previous work on drilling after large earthquakes and in fault zones in general, as well as the state of the art of experimental techniques and measurement strategies. Detailed discussion weighed the tradeoffs between rapid drilling andthe ability to satisfy a diverse range of scientific objectives. Plausible drilling sites and scenarios were evaluated. This is a shortened summary of the workshop report that discusses key scientific questions, measurement strategies, and recommendations. This report can provide a starting point for quickly mobilizing a drilling program following future large earthquakes. The full report can be seen at http://www.pmc.ucsc.edu/~rapid/.

  1. Rapid-Response Impulsivity: Definitions, Measurement Issues, and Clinical Implications

    OpenAIRE

    Hamilton, Kristen R.; Littlefield, Andrew K.; Anastasio, Noelle C.; Cunningham, Kathryn A.; Fink, Latham H.; Wing, Victoria C.; Mathias, Charles W.; Lane, Scott D; Schutz, Christian; Swann, Alan C.; Lejuez, C.W.; Clark, Luke; Moeller, F. Gerard; Potenza, Marc N.

    2015-01-01

    Impulsivity is a multi-faceted construct that is a core feature of multiple psychiatric conditions and personality disorders. However, progress in understanding and treating impulsivity in the context of these conditions is limited by a lack of precision and consistency in its definition and assessment. Rapid-response-impulsivity (RRI) represents a tendency toward immediate action that occurs with diminished forethought and is out of context with the present demands of the environment. Expert...

  2. Nicolaus Copernicus and the rapid vascular responses to aldosterone.

    Science.gov (United States)

    Barton, Matthias; Meyer, Matthias R

    2015-08-01

    For decades, rapid steroid responses initiated by membrane receptors have been a primary research focus. G protein-coupled estrogen receptor (GPER) is activated by 17β-estradiol and participates in functional crosstalk with other steroid receptors. With reference to the physician and astronomer Nicolaus Copernicus (1473-1543), who used rigorous scientific approaches to shift paradigms and change dogma, we discuss whether GPER can also be considered an aldosterone receptor. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Onboard Radar Processing Development for Rapid Response Applications

    Science.gov (United States)

    Lou, Yunling; Chien, Steve; Clark, Duane; Doubleday, Josh; Muellerschoen, Ron; Wang, Charles C.

    2011-01-01

    We are developing onboard processor (OBP) technology to streamline data acquisition on-demand and explore the potential of the L-band SAR instrument onboard the proposed DESDynI mission and UAVSAR for rapid response applications. The technology would enable the observation and use of surface change data over rapidly evolving natural hazards, both as an aid to scientific understanding and to provide timely data to agencies responsible for the management and mitigation of natural disasters. We are adapting complex science algorithms for surface water extent to detect flooding, snow/water/ice classification to assist in transportation/ shipping forecasts, and repeat-pass change detection to detect disturbances. We are near completion of the development of a custom FPGA board to meet the specific memory and processing needs of L-band SAR processor algorithms and high speed interfaces to reformat and route raw radar data to/from the FPGA processor board. We have also developed a high fidelity Matlab model of the SAR processor that is modularized and parameterized for ease to prototype various SAR processor algorithms targeted for the FPGA. We will be testing the OBP and rapid response algorithms with UAVSAR data to determine the fidelity of the products.

  4. Metastasized lung cancer suppression by Morinda citrifolia (Noni) leaf compared to Erlotinib via anti-inflammatory, endogenous antioxidant responses and apoptotic gene activation.

    Science.gov (United States)

    Lim, Swee-Ling; Mustapha, Noordin M; Goh, Yong-Meng; Bakar, Nurul Ain Abu; Mohamed, Suhaila

    2016-05-01

    Metastasized lung and liver cancers cause over 2 million deaths annually, and are amongst the top killer cancers worldwide. Morinda citrifolia (Noni) leaves are traditionally consumed as vegetables in the tropics. The macro and micro effects of M. citrifolia (Noni) leaves on metastasized lung cancer development in vitro and in vivo were compared with the FDA-approved anti-cancer drug Erlotinib. The extract inhibited the proliferation and induced apoptosis in A549 cells (IC50 = 23.47 μg/mL) and mouse Lewis (LL2) lung carcinoma cells (IC50 = 5.50 μg/mL) in vitro, arrested cancer cell cycle at G0/G1 phases and significantly increased caspase-3/-8 without changing caspase-9 levels. The extract showed no toxicity on normal MRC5 lung cells. Non-small-cell lung cancer (NSCLC) A549-induced BALB/c mice were fed with 150 and 300 mg/kg M. citrifolia leaf extract and compared with Erlotinib (50 mg/kg body weight) for 21 days. It significantly increased the pro-apoptotic TRP53 genes, downregulated the pro-tumourigenesis genes (BIRC5, JAK2/STAT3/STAT5A) in the mice tumours, significantly increased the anti-inflammatory IL4, IL10 and NR3C1 expression in the metastasized lung and hepatic cancer tissues and enhanced the NFE2L2-dependent antioxidant responses against oxidative injuries. The extract elevated serum neutrophils and reduced the red blood cells, haemoglobin, corpuscular volume and cell haemoglobin concentration in the lung cancer-induced mammal. It suppressed inflammation and oedema, and upregulated the endogenous antioxidant responses and apoptotic genes to suppress the cancer. The 300 mg/kg extract was more effective than the 50 mg/kg Erlotinib for most of the parameters measured.

  5. Systems analysis of ATF3 in stress response and cancer reveals opposing effects on pro-apoptotic genes in p53 pathway.

    Directory of Open Access Journals (Sweden)

    Yujiro Tanaka

    Full Text Available Stress-inducible transcription factors play a pivotal role in cellular adaptation to environment to maintain homeostasis and integrity of the genome. Activating transcription factor 3 (ATF3 is induced by a variety of stress and inflammatory conditions and is over-expressed in many kinds of cancer cells. However, molecular mechanisms underlying pleiotropic functions of ATF3 have remained elusive. Here we employed systems analysis to identify genome-wide targets of ATF3 that is either induced by an alkylating agent methyl methanesulfonate (MMS or over-expressed in a prostate tumour cell line LNCaP. We show that stress-induced and cancer-associated ATF3 is recruited to 5,984 and 1,423 targets, respectively, in the human genome, 89% of which are common. Notably, ATF3 targets are highly enriched for not only ATF/CRE motifs but also binding sites of several other stress-inducible transcription factors indicating an extensive network of stress response factors in transcriptional regulation of target genes. Further analysis of effects of ATF3 knockdown on these targets revealed that stress-induced ATF3 regulates genes in metabolic pathways, cell cycle, apoptosis, cell adhesion, and signalling including insulin, p53, Wnt, and VEGF pathways. Cancer-associated ATF3 is involved in regulation of distinct sets of genes in processes such as calcium signalling, Wnt, p53 and diabetes pathways. Notably, stress-induced ATF3 binds to 40% of p53 targets and activates pro-apoptotic genes such as TNFRSF10B/DR5 and BBC3/PUMA. Cancer-associated ATF3, by contrast, represses these pro-apoptotic genes in addition to CDKN1A/p21. Taken together, our data reveal an extensive network of stress-inducible transcription factors and demonstrate that ATF3 has opposing, cell context-dependent effects on p53 target genes in DNA damage response and cancer development.

  6. 20 CFR 665.300 - What are rapid response activities and who is responsible for providing them?

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false What are rapid response activities and who is responsible for providing them? 665.300 Section 665.300 Employees' Benefits EMPLOYMENT AND TRAINING... INVESTMENT ACT Rapid Response Activities § 665.300 What are rapid response activities and who is responsible...

  7. (99m)Tc-Annexin A5 quantification of apoptotic tumor response: a systematic review and meta-analysis of clinical imaging trials.

    Science.gov (United States)

    Belhocine, Tarik Z; Blankenberg, Francis G; Kartachova, Marina S; Stitt, Larry W; Vanderheyden, Jean-Luc; Hoebers, Frank J P; Van de Wiele, Christophe

    2015-12-01

    uptake following treatment was considered a significant threshold for an apoptotic tumor response (partial response, complete response). In three other phase I/II clinical trials, increases of ≥28%, ≥42% and ≥47% in uptake following treatment were found to be the mean cut-off levels in responders. In a phase II/III multicenter clinical trial, an increase of ≥23% in uptake following treatment was found to be the minimum cut-off level for a tumor response. In one clinical trial, no significant difference in (99m)Tc-annexin A5 uptake in terms of %ID was found in healthy tissues after chemotherapy compared to baseline. In two other clinical trials, intraobserver and interobserver measurements of (99m)Tc-annexin A5 tumor uptake were found to be reproducible (mean difference analysis demonstrated a pooled positive PPV of 100% (95% CI 92 - 100%) and a pooled NPV of 70% (95% CI 55 - 82%) for prediction of a tumor response after the first course of chemotherapy and/or radiotherapy in terms of ΔU%. In a symmetric sROC analysis, the AUC was 0.919 and the Q* index was 85.21 %. Quantitative (99m)Tc-annexin A5 imaging has been investigated in clinical trials for the assessment of apoptotic tumor responses. This meta-analysis showed a high pooled PPV and a moderate pooled NPV with ΔU cut-off values ranging between 20% and 30%. Standardization of quantification and harmonization of results are required for high-quality clinical research. A standardized uptake value score (SUV, ΔSUV) using quantitative SPECT/CT imaging may be a promising approach to the simple, reproducible and semiquantitative assessment of apoptotic tumor changes.

  8. Forecasting wildlife response to rapid warming in the Alaskan Arctic

    Science.gov (United States)

    Van Hemert, Caroline R.; Flint, Paul L.; Udevitz, Mark S.; Koch, Joshua C.; Atwood, Todd C.; Oakley, Karen L.; Pearce, John M.

    2015-01-01

    Arctic wildlife species face a dynamic and increasingly novel environment because of climate warming and the associated increase in human activity. Both marine and terrestrial environments are undergoing rapid environmental shifts, including loss of sea ice, permafrost degradation, and altered biogeochemical fluxes. Forecasting wildlife responses to climate change can facilitate proactive decisions that balance stewardship with resource development. In this article, we discuss the primary and secondary responses to physical climate-related drivers in the Arctic, associated wildlife responses, and additional sources of complexity in forecasting wildlife population outcomes. Although the effects of warming on wildlife populations are becoming increasingly well documented in the scientific literature, clear mechanistic links are often difficult to establish. An integrated science approach and robust modeling tools are necessary to make predictions and determine resiliency to change. We provide a conceptual framework and introduce examples relevant for developing wildlife forecasts useful to management decisions.

  9. Response variability in rapid automatized naming predicts reading comprehension.

    Science.gov (United States)

    Li, James J; Cutting, Laurie E; Ryan, Matthew; Zilioli, Monica; Denckla, Martha B; Mahone, E Mark

    2009-10-01

    A total of 37 children ages 8 to 14 years, screened for word-reading difficulties (23 with attention-deficit/hyperactivity disorder, ADHD; 14 controls) completed oral reading and rapid automatized naming (RAN) tests. RAN trials were segmented into pause and articulation time and intraindividual variability. There were no group differences on reading or RAN variables. Color- and letter-naming pause times and number-naming articulation time were significant predictors of reading fluency. In contrast, number and letter pause variability were predictors of comprehension. Results support analysis of subcomponents of RAN and add to literature emphasizing intraindividual variability as a marker for response preparation, which has relevance to reading comprehension.

  10. Rapid flow-induced responses in endothelial cells

    Science.gov (United States)

    Stamatas, G. N.; McIntire, L. V.

    2001-01-01

    Endothelial cells alter their morphology, growth rate, and metabolism in response to fluid shear stress. To study rapid flow-induced responses in the 3D endothelial cell morphology and calcium distribution, coupled fluorescence microscopy with optical sectioning, digital imaging, and numerical deconvolution techniques have been utilized. Results demonstrate that within the first minutes of flow application nuclear calcium is increasing. In the same time frame whole cell height and nuclear height are reduced by about 1 microm. Whole cell height changes may facilitate reduction of shear stress gradients on the luminal surface, whereas nuclear structural changes may be important for modulating endothelial growth rate and metabolism. To study the role of the cytoskeleton in these responses, endothelial cells have been treated with specific disrupters (acrylamide, cytochalasin D, and colchicine) of each of the cytoskeleton elements (intermediate filaments, microfilaments, and microtubules, respectively). None of these compounds had any effect on the shear-induced calcium response. Cytochalasin D and acrylamide did not affect the shear-induced nuclear morphology changes. Colchicine, however, completely abrogated the response, indicating that microtubules may be implicated in force transmission from the plasma membrane to the nucleus. A pedagogical model based on tensegrity theory principles is presented that is consistent with the results on the 3D endothelial morphology.

  11. Non-conventional apoptotic response to ionising radiation mediated by N-methyl D-aspartate receptors in immature neuronal cells.

    Science.gov (United States)

    Samari, Nada; De Saint-Georges, Louis; Pani, Giuseppe; Baatout, Sarah; Leyns, Luc; Benotmane, Mohammed Abderrafi

    2013-03-01

    During cortical development, N-methyl D-aspartate (NMDA) receptors are highly involved in neuronal maturation and synapse establishment. Their implication in the phenomenon of excitotoxicity has been extensively described in several neurodegenerative diseases due to the permissive entry of Ca2+ ions and massive accumulation in the intracellular compartment, which is highly toxic to cells. Ionising radiation is also a source of stress to the cells, particularly immature neurons. Their capacity to induce cell death has been described for various cell types either by directly damaging the DNA or indirectly through the generation of reactive oxygen species responsible for the activation of a battery of stress response effectors leading in certain cases, to cell death. In this study, in order to determine whether a link exists between NMDA receptors-mediated excitotoxicity and radiation-induced cell death, we evaluated radiation-induced cell death in vitro and in vivo in maturing neurons during the fetal period. Cell death induction was assessed by TUNEL, caspase-3 activity and DNA ladder assays, with or without the administration of dizocilpine (MK-801), a non-competitive NMDA receptor antagonist which blocks neuronal Ca2+ influx. To further investigate the possible involvement of Ca2+-dependent enzyme activation, known to occur at high Ca2+ concentrations, we examined the protective effect of a calpain inhibitor on cell death induced by radiation. Doses ranging from 0.2 to 0.6 Gy of X-rays elicited a clear apoptotic response that was prevented by the injection of dizocilpine (MK-801) or calpain inhibitor. These data demonstrate the involvement of NMDA receptors in radiation-induced neuronal death by the activation of downstream effectors, including calpain-related pathways. An increased apoptotic process elicited by radiation, occurring independently of the normal developmental scheme, may eliminate post-mitotic but immature neuronal cells and deeply impair the

  12. Oxidative stress alters base excision repair pathway and increases apoptotic response in apurinic/apyrimidinic endonuclease 1/redox factor-1 haploinsufficient mice.

    Science.gov (United States)

    Unnikrishnan, Archana; Raffoul, Julian J; Patel, Hiral V; Prychitko, Thomas M; Anyangwe, Njwen; Meira, Lisiane B; Friedberg, Errol C; Cabelof, Diane C; Heydari, Ahmad R

    2009-06-01

    Apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) is the redox regulator of multiple stress-inducible transcription factors, such as NF-kappaB, and the major 5'-endonuclease in base excision repair (BER). We utilized mice containing a heterozygous gene-targeted deletion of APE1/Ref-1 (Apex(+/-)) to determine the impact of APE1/Ref-1 haploinsufficiency on the processing of oxidative DNA damage induced by 2-nitropropane (2-NP) in the liver tissue of mice. APE1/Ref-1 haploinsufficiency results in a significant decline in NF-kappaB DNA-binding activity in response to oxidative stress in liver. In addition, loss of APE1/Ref-1 increases the apoptotic response to oxidative stress, in which significant increases in GADD45g expression, p53 protein stability, and caspase activity are observed. Oxidative stress displays a differential impact on monofunctional (UNG) and bifunctional (OGG1) DNA glycosylase-initiated BER in the liver of Apex(+/-) mice. APE1/Ref-1 haploinsufficiency results in a significant decline in the repair of oxidized bases (e.g., 8-OHdG), whereas removal of uracil is increased in liver nuclear extracts of mice using an in vitro BER assay. Apex(+/-) mice exposed to 2-NP displayed a significant decline in 3'-OH-containing single-strand breaks and an increase in aldehydic lesions in their liver DNA, suggesting an accumulation of repair intermediates of failed bifunctional DNA glycosylase-initiated BER.

  13. Rapid Prototyping of Simulated VIIRS Data in the SERVIR Fire Rapid Response System

    Science.gov (United States)

    Easson, G.; Kuszmaul, J. S.; Yarbrough, L. D.; Irwin, D.; Cherrington, E.

    2006-12-01

    A rapid prototyping capability experiment has been established involving the application of the SERVIR (Sistema Regional de Visualización y Monitoreo) decision support tool, which is NASA's and its partner agencies' tool to monitor groundcover and climatic conditions in Mesoamerica. As an information system, the SERVIR tool processes data products from multiple sources and the outcome is visualized through interactive digital maps, standard view map outputs or 3D real-time visualization. The focus of this research is one of the SERVIR Fire Rapid Response products known as the MODIS SERVIR Fire Extent Product, which was developed to meet the requirements of the Guatemalan Park Service. The credibility of SERVIR's monitoring tools currently depends upon NASA's MODIS data, which is nearing the end of its availability. This will make it necessary to transition to the planned replacement sensor, VIIRS. The impact of this transition on the performance of SERVIR's fire detection tools is the current focus of our investigation. A quantitative assessment of fire conditions in Guatemala is made using MODIS data and is compared to the anticipated performance using simulated data that would have been produced by a VIIRS-like sensor. Using a low-density geospatial database, the comparison is made for a number of dates from the 2003 Guatemalan fire season, where ground validation data is available. A comparative assessment is also made using the kappa statistic applied to the land classifications resulting from both the MODIS- and VIIRS- based fire detection algorithms.

  14. Rapid amygdala responses during trace fear conditioning without awareness.

    Directory of Open Access Journals (Sweden)

    Nicholas L Balderston

    Full Text Available The role of consciousness in learning has been debated for nearly 50 years. Recent studies suggest that conscious awareness is needed to bridge the gap when learning about two events that are separated in time, as is true for trace fear conditioning. This has been repeatedly shown and seems to apply to other forms of classical conditioning as well. In contrast to these findings, we show that individuals can learn to associate a face with the later occurrence of a shock, even if they are unable to perceive the face. We used a novel application of magnetoencephalography (MEG to non-invasively record neural activity from the amygdala, which is known to be important for fear learning. We demonstrate rapid (∼ 170-200 ms amygdala responses during the stimulus free period between the face and the shock. These results suggest that unperceived faces can serve as signals for impending threat, and that rapid, automatic activation of the amygdala contributes to this process. In addition, we describe a methodology that can be applied in the future to study neural activity with MEG in other subcortical structures.

  15. Rapid amygdala responses during trace fear conditioning without awareness.

    Science.gov (United States)

    Balderston, Nicholas L; Schultz, Douglas H; Baillet, Sylvain; Helmstetter, Fred J

    2014-01-01

    The role of consciousness in learning has been debated for nearly 50 years. Recent studies suggest that conscious awareness is needed to bridge the gap when learning about two events that are separated in time, as is true for trace fear conditioning. This has been repeatedly shown and seems to apply to other forms of classical conditioning as well. In contrast to these findings, we show that individuals can learn to associate a face with the later occurrence of a shock, even if they are unable to perceive the face. We used a novel application of magnetoencephalography (MEG) to non-invasively record neural activity from the amygdala, which is known to be important for fear learning. We demonstrate rapid (∼ 170-200 ms) amygdala responses during the stimulus free period between the face and the shock. These results suggest that unperceived faces can serve as signals for impending threat, and that rapid, automatic activation of the amygdala contributes to this process. In addition, we describe a methodology that can be applied in the future to study neural activity with MEG in other subcortical structures.

  16. Rapid screening of radioactivity in food for emergency response.

    Science.gov (United States)

    Bari, A; Khan, A J; Semkow, T M; Syed, U-F; Roselan, A; Haines, D K; Roth, G; West, L; Arndt, M

    2011-06-01

    This paper describes the development of methods for the rapid screening of gross alpha (GA) and gross beta (GB) radioactivity in liquid foods, specifically, Tang drink mix, apple juice, and milk, as well as screening of GA, GB, and gamma radioactivity from surface deposition on apples. Detailed procedures were developed for spiking of matrices with (241)Am (alpha radioactivity), (90)Sr/(90)Y (beta radioactivity), and (60)Co, (137)Cs, and (241)Am (gamma radioactivity). Matrix stability studies were performed for 43 days after spiking. The method for liquid foods is based upon rapid digestion, evaporation, and flaming, followed by gas proportional (GP) counting. For the apple matrix, surface radioactivity was acid-leached, followed by GP counting and/or gamma spectrometry. The average leaching recoveries from four different apple brands were between 63% and 96%, and have been interpreted on the basis of ion transport through the apple cuticle. The minimum detectable concentrations (MDCs) were calculated from either the background or method-blank (MB) measurements. They were found to satisfy the required U.S. FDA's Derived Intervention Levels (DILs) in all but one case. The newly developed methods can perform radioactivity screening in foods within a few hours and have the potential to capacity with further automation. They are especially applicable to emergency response following accidental or intentional contamination of food with radioactivity. Published by Elsevier Ltd.

  17. Brief, Rapid Response, Parenting Interventions Within Primary Care Settings.

    Science.gov (United States)

    Bultas, Margaret W; McMillin, Stephen Edward; Broom, Matthew A; Zand, Debra H

    2015-08-20

    Opportunities created by the Patient Protection and Affordable Care Act along with the increased prevalence of pediatric behavioral and mental health concerns provide new challenges for pediatric health care providers. To address these matters, providers need to change the manner by which they provide health care to families. A novel approach is providing brief, rapid response, evidence-based parenting interventions within the pediatric primary care setting. Family-focused parenting programs support the American Academy of Pediatrics recommendations of improving mental health via supports in pediatric primary care to maximize the social and psychological well-being of families. A considerable body of research indicates that parenting interventions reduce the severity and frequency of disruptive behavior disorders in children and provide support to parent by bolstering parental resilience and improving overall family functioning. Providing these services within the pediatric primary care setting addresses the need for fully integrated health services that are family-centered and easily accessible.

  18. Rapid enzymatic response to compensate UV radiation in copepods.

    Directory of Open Access Journals (Sweden)

    María Sol Souza

    Full Text Available Ultraviolet radiation (UVR causes physical damage to DNA, carboxylation of proteins and peroxidation of lipids in copepod crustaceans, ubiquitous and abundant secondary producers in most aquatic ecosystems. Copepod adaptations for long duration exposures include changes in behaviour, changes in pigmentation and ultimately changes in morphology. Adaptations to short-term exposures are little studied. Here we show that short-duration exposure to UVR causes the freshwater calanoid copepod, Eudiaptomus gracilis, to rapidly activate production of enzymes that prevent widespread collateral peroxidation (glutathione S-transferase, GST, that regulate apoptosis cell death (Caspase-3, Casp-3, and that facilitate neurotransmissions (cholinesterase-ChE. None of these enzyme systems is alone sufficient, but they act in concert to reduce the stress level of the organism. The interplay among enzymatic responses provides useful information on how organisms respond to environmental stressors acting on short time scales.

  19. Applying Bayesian belief networks in rapid response situations

    Energy Technology Data Exchange (ETDEWEB)

    Gibson, William L [Los Alamos National Laboratory; Deborah, Leishman, A. [Los Alamos National Laboratory; Van Eeckhout, Edward [Los Alamos National Laboratory

    2008-01-01

    The authors have developed an enhanced Bayesian analysis tool called the Integrated Knowledge Engine (IKE) for monitoring and surveillance. The enhancements are suited for Rapid Response Situations where decisions must be made based on uncertain and incomplete evidence from many diverse and heterogeneous sources. The enhancements extend the probabilistic results of the traditional Bayesian analysis by (1) better quantifying uncertainty arising from model parameter uncertainty and uncertain evidence, (2) optimizing the collection of evidence to reach conclusions more quickly, and (3) allowing the analyst to determine the influence of the remaining evidence that cannot be obtained in the time allowed. These extended features give the analyst and decision maker a better comprehension of the adequacy of the acquired evidence and hence the quality of the hurried decisions. They also describe two example systems where the above features are highlighted.

  20. Time course of apoptotic tumor response after a single dose of chemotherapy: comparison with 99mTc-annexin V uptake and histologic findings in an experimental model.

    Science.gov (United States)

    Takei, Toshiki; Kuge, Yuji; Zhao, Songji; Sato, Masayuki; Strauss, H William; Blankenberg, Francis G; Tait, Jonathan F; Tamaki, Nagara

    2004-12-01

    In tumors the process of apoptosis occurs over an interval of time after chemotherapy. To determine the best timing for detecting apoptosis in vivo with (99m)Tc-annexin V after chemotherapy, we examined the changes in (99m)Tc-annexin V accumulation over time in comparison with those of caspase-3 and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) expression level after cyclophosphamide treatment in an experimental model. Hydrazinonicotinamide (HYNIC)-annexin V was labeled with (99m)Tc ((99m)Tc-annexin V). Rats were inoculated with allogenic hepatoma cells (KDH-8) into the left calf muscle. Eleven days after the inoculation, the rats were randomly divided into the group receiving a single dose of cyclophosphamide (150 mg/kg intraperitoneally) and the control group. (99m)Tc-Annexin V (18.5 MBq [0.5 mCi] per rat) was injected intravenously in the rats 4, 12, and 20 h after the treatment and also to the control rats (n = 5 in each group). Radioactivity in tissues was determined 6 h after (99m)Tc-annexin V injection. Immunostaining of caspase-3 and TUNEL were performed to detect apoptosis, and the rates of positively stained cells were calculated. (99m)Tc-Annexin V accumulation in tumors significantly increased at 20 h (0.077 +/- 0.007 [%ID/g] x kg, where %ID/g = percentage injected dose per gram) but not at 4 or 12 h (0.048 +/- 0.008 and 0.052 +/- 0.014 [%ID/g] x kg, respectively) after cyclophosphamide treatment. (99m)Tc-Annexin V accumulation in tumors and the rate of apoptotic cells determined by caspase-3 immunostaining and TUNEL were significantly higher in treated rats 20 h after cyclophosphamide treatment as compared with control rats. The effective detection of apoptotic tumor response with (99m)Tc-annexin V required 20 h after cyclophosphamide treatment in an experimental model. The present results provide an important basis for determining the best timing of annexin V imaging after the start of chemotherapy

  1. Raf induces TGFβ production while blocking its apoptotic but not invasive responses: a mechanism leading to increased malignancy in epithelial cells

    Science.gov (United States)

    Lehmann, Kerstin; Janda, Elzbieta; Pierreux, Christophe E.; Rytömaa, Marjatta; Schulze, Almut; McMahon, Martin; Hill, Caroline S.; Beug, Hartmut; Downward, Julian

    2000-01-01

    c-Raf-1 is a major effector of Ras proteins, responsible for activation of the ERK MAP kinase pathway and a critical regulator of both normal growth and oncogenic transformation. Using an inducible form of Raf in MDCK cells, we have shown that sustained activation of Raf alone is able to induce the transition from an epithelial to a mesenchymal phenotype. Raf promoted invasive growth in collagen gels, a characteristic of malignant cells; this was dependent on the operation of an autocrine loop involving TGFβ, whose secretion was induced by Raf. TGFβ induced growth inhibition and apoptosis in normal MDCK cells: Activation of Raf led to inhibition of the ability of TGFβ to induce apoptosis but not growth retardation. ERK has been reported previously to inhibit TGFβ signaling via phosphorylation of the linker region of Smads, which prevents their translocation to the nucleus. However, we found no evidence in this system that ERK can significantly influence the function of Smad2, Smad3, and Smad4 at the level of nuclear translocation, DNA binding, or transcriptional activation. Instead, strong activation of Raf caused a broad protection of these cells from various apoptotic stimuli, allowing them to respond to TGFβ with increased invasiveness while avoiding cell death. The Raf–MAP kinase pathway thus synergizes with TGFβ in promoting malignancy but does not directly impair TGFβ-induced Smad signaling. PMID:11040215

  2. Raf induces TGFbeta production while blocking its apoptotic but not invasive responses: a mechanism leading to increased malignancy in epithelial cells.

    Science.gov (United States)

    Lehmann, K; Janda, E; Pierreux, C E; Rytömaa, M; Schulze, A; McMahon, M; Hill, C S; Beug, H; Downward, J

    2000-10-15

    c-Raf-1 is a major effector of Ras proteins, responsible for activation of the ERK MAP kinase pathway and a critical regulator of both normal growth and oncogenic transformation. Using an inducible form of Raf in MDCK cells, we have shown that sustained activation of Raf alone is able to induce the transition from an epithelial to a mesenchymal phenotype. Raf promoted invasive growth in collagen gels, a characteristic of malignant cells; this was dependent on the operation of an autocrine loop involving TGFbeta, whose secretion was induced by Raf. TGFbeta induced growth inhibition and apoptosis in normal MDCK cells: Activation of Raf led to inhibition of the ability of TGFbeta to induce apoptosis but not growth retardation. ERK has been reported previously to inhibit TGFbeta signaling via phosphorylation of the linker region of Smads, which prevents their translocation to the nucleus. However, we found no evidence in this system that ERK can significantly influence the function of Smad2, Smad3, and Smad4 at the level of nuclear translocation, DNA binding, or transcriptional activation. Instead, strong activation of Raf caused a broad protection of these cells from various apoptotic stimuli, allowing them to respond to TGFbeta with increased invasiveness while avoiding cell death. The Raf-MAP kinase pathway thus synergizes with TGFbeta in promoting malignancy but does not directly impair TGFbeta-induced Smad signaling.

  3. Rapid response to syphilis outbreak among female sex workers

    Directory of Open Access Journals (Sweden)

    Shaily B Surti

    2017-01-01

    Full Text Available Background: Outbreak of syphilis, i.e., 16 cases of rapid plasma reagin (RPR reactive cases of syphilis was reported in Community Based Organization (CBO Sahyog of Surat, India, from April to August 2014. The aim of the study was to find risk factors and take immediate actions to prevent spread. Materials and Methods: Outbreak investigation of 16 Female Sex Workers of CBO Sahyog in Surat who were found Rapid Plasma Reagin (RPR and Treponema Pallidum Hemagglutination Assay (TPHA positive from April to August 2014; was carried out. Clinico-epidemiological and laboratory-based evidence for different sexually transmitted infections (STIs conducted at Government Medical College, New Civil Hospital, Surat. Root cause analysis (RCA of index case was carried out. Results: Desk review for the past 3 years data of STI revealed total STI cases as 88 (2011, 95 (2012, and 130 (2013, of which 4, 2, and 2 found RPR reactive, respectively. Data from April to August 2014 revealed 16 RPR reactive cases and confirmed by TPHA. On examination, one had ulcerative cervical lesion, rest did not have any symptoms of syphilis. Eleven had vaginal/cervical discharge, 11 had lower abdominal pain. A total of 11 had unprotected sex, 7 encountered condom tear in the past 6 months, and 5 reported sexual violence. Seven had sexual activity under influence of alcohol. Laboratory investigation revealed two as HIV-positive. RPR reactivity reported highest (9 out of 16 from same area of hotspot. RCA of probable index case revealed factors responsible as violence and nonuse of condoms. Conclusions: Outbreak investigation revealed one probable index case. All 16 treated with injection Penidure. Violence or condom tear is responsible for the spread. Crisis management team should be strengthened.

  4. The expression of immediate early response gene X-1 in preeclampsia placenta and its pro-apoptotic role in preeclampsia.

    Science.gov (United States)

    Han, Liping; Zhang, Xiaoxue; Geng, Lina; Li, Mengmeng; Zhang, Yi; Wu, Mei X

    2013-05-01

    The stress-inducible immediate early response gene X-1 (IEX-1) regulates cell proliferation and apoptosis in a cell type and stimulus-dependent manner. The aim of this study was to investigate IEX-1 expression in preeclampsia placenta and human umbilical vein endothelial cells (HUVECs) cultured in the serum isolated from preeclampsia patients, to explore its relationship with the pathogenesis of preeclampsia. Thirty preeclampsia patients with 10 cases in the moderate group, 20 cases in the severe group (PE group) and 20 cases of normal pregnant women (control group) were randomly obtained. Reverse transcriptase-polymerase chain reaction and immunohistochemistry showed that IEX-1 expression was significantly higher in preeclampsia patients than in normal pregnant women (p preeclampsia (p preeclampsia group was colored more obviously, and the color was strengthened in correlation with the severity of the disease using immunocytochemial method. Flow cytometry and MTT revealed that the serum isolated from preeclampsia patients appeared to promote IEX-1 expression in cytoplasm of HUVECs, inhibited the proliferation and promoted the apoptosis of HUVECs when compared to the serum of normal pregnant women. Our study demonstrates a correlation of IEX-1 expression levels with the severity of preeclampsia. Given a well-known function of IEX-1 in regulation of apoptosis, IEX-1 may be important in the pathogenesis of preeclampsia by regulating placental villous trophoblast and decidual cell apoptosis as well as participation in endothelial cell injury process.

  5. Ganoderma atrum polysaccharide induces anti-tumor activity via the mitochondrial apoptotic pathway related to activation of host immune response.

    Science.gov (United States)

    Li, Wen-Juan; Chen, Yi; Nie, Shao-Ping; Xie, Ming-Yong; He, Ming; Zhang, Shen-Shen; Zhu, Ke-Xue

    2011-03-01

    Ganoderma atrum polysaccharide (PSG-1), the major active ingredient isolated from Ganoderma atrum, has been suggested as a candidate for cancer therapy. The aim of this study was to investigate the anti-tumor effect of PSG-1 using sarcoma 180 (S-180) transplanted mice and further to examine the molecular mechanisms of PSG-1-induced anti-tumor effect. Results showed that PSG-1 significantly inhibited tumor growth in S-180-bearing mice. PSG-1-induced tumor apoptosis was associated with the alteration of Bcl-2 family proteins, increase of reactive oxygen species generation, loss of mitochondrial membrane potential (Δψ(m) ), release of cytochrome c from the mitochondria into cytosol, and activation of caspase-3 and -9. Elevation of immune function was also shown during PSG-1-induced tumor apoptosis, as evidenced by increase of spleen and thymus indexes, lymphocyte proliferation, concentrations of tumor necrosis factor (TNF)-α, and interleukin-2 in serum. Furthermore, the combined treatment of PSG-1 and cyclophosphamide (CTX) results in an enhancement of the anti-tumor effect of CTX alone via increased host immune response. These results suggested that PSG-1 had a potent anti-tumor activity by induction of tumor apoptosis through mitochondrial pathways, and immunoenhancement effect of PSG-1 was related to its anti-tumor effect. In addition, PSG-1 enhanced CTX-induced anti-tumor activity in S-180-bearing mice. Copyright © 2010 Wiley-Liss, Inc.

  6. Harnessing Apoptotic Cell Clearance to Treat Autoimmune Arthritis

    OpenAIRE

    Philippe Saas; Francis Bonnefoy; Eric Toussirot; Sylvain Perruche

    2017-01-01

    Early-stage apoptotic cells possess immunomodulatory properties. Proper apoptotic cell clearance during homeostasis has been shown to limit subsequent immune responses. Based on these observations, early-stage apoptotic cell infusion has been used to prevent unwanted inflammatory responses in different experimental models of autoimmune diseases or transplantation. Moreover, this approach has been shown to be feasible without any toxicity in patients undergoing allogeneic hematopoietic cell tr...

  7. Preclinical Evaluation of 18F-ML-10 to Determine Timing of Apoptotic Response to Chemotherapy in Solid Tumors

    Science.gov (United States)

    Demirci, Emre; Ahmed, Rafay; Ocak, Meltem; Latoche, Joseph; Radelet, April; DeBlasio, Nicole; Mason, N. Scott

    2017-01-01

    Purpose: We investigated 2-(5-fluoro-pentyl)-2-methyl-malonic acid (18F-ML-10) positron emission tomography (PET) imaging of apoptosis posttherapy to determine optimal timing for predicting chemotherapy response in a mouse head/neck xenograft cancer model. Procedures: BALB/c nude mice (4-8 weeks old) were implanted with UM-SCC-22B tumors. The treatment group received 2 doses of doxorubicin (10 mg/kg, days 0, 2). Small animal 18F-ML-10 PET/computed tomography was performed before and on days 1, 3, and 7 postchemotherapy. Using regions of interest around tumors, 18F-ML-10 uptake change was measured as %ID/g and uptake relative to liver. Terminal Uridine Nick-End Labeling (TUNEL) immunohistochemistry assay was performed using tumor samples of baseline and on days 1, 3, and 7 posttreatment. Results: Treated mice demonstrated increased 18F-ML-10 uptake compared to baseline and controls, and 10 of 13 mice showed tumor volume decreases. All control mice showed tumor volume increases. Tumor-to-liver (T/L) ratios from the control group mice did not show significant change from baseline (P > .05); however, T/L ratios of the treatment group showed significant 18F-ML-10 uptake differences from baseline compared to days 3 and 7 posttreatment (P < .05), but no significant difference at 1 day posttreatment. Conclusion: 2-(5-Fluoro-pentyl)-2-methyl-malonic acid PET imaging has the potential for early assessment of treatment-induced apoptosis. Timing and image analysis strategies may require optimization, depending on the type of tumor and cancer treatment. PMID:28654376

  8. Preclinical Evaluation of 18F-ML-10 to Determine Timing of Apoptotic Response to Chemotherapy in Solid Tumors

    Directory of Open Access Journals (Sweden)

    Emre Demirci MD

    2017-01-01

    Full Text Available Purpose: We investigated 2-(5-fluoro-pentyl-2-methyl-malonic acid (18F-ML-10 positron emission tomography (PET imaging of apoptosis posttherapy to determine optimal timing for predicting chemotherapy response in a mouse head/neck xenograft cancer model. Procedures: BALB/c nude mice (4-8 weeks old were implanted with UM-SCC-22B tumors. The treatment group received 2 doses of doxorubicin (10 mg/kg, days 0, 2. Small animal 18F-ML-10 PET/computed tomography was performed before and on days 1, 3, and 7 postchemotherapy. Using regions of interest around tumors, 18F-ML-10 uptake change was measured as %ID/g and uptake relative to liver. Terminal Uridine Nick-End Labeling (TUNEL immunohistochemistry assay was performed using tumor samples of baseline and on days 1, 3, and 7 posttreatment. Results: Treated mice demonstrated increased 18F-ML-10 uptake compared to baseline and controls, and 10 of 13 mice showed tumor volume decreases. All control mice showed tumor volume increases. Tumor-to-liver (T/L ratios from the control group mice did not show significant change from baseline (P > .05; however, T/L ratios of the treatment group showed significant 18F-ML-10 uptake differences from baseline compared to days 3 and 7 posttreatment (P < .05, but no significant difference at 1 day posttreatment. Conclusion: 2-(5-Fluoro-pentyl-2-methyl-malonic acid PET imaging has the potential for early assessment of treatment-induced apoptosis. Timing and image analysis strategies may require optimization, depending on the type of tumor and cancer treatment.

  9. Thymidylate synthase inhibition induces p53-dependent and p53-independent apoptotic responses in human urinary bladder cancer cells.

    Science.gov (United States)

    Stravopodis, Dimitrios J; Karkoulis, Panagiotis K; Konstantakou, Eumorphia G; Melachroinou, Sophia; Thanasopoulou, Angeliki; Aravantinos, Gerasimos; Margaritis, Lukas H; Anastasiadou, Ema; Voutsinas, Gerassimos E

    2011-02-01

    In search for more effective clinical protocols, the antimetabolite drug 5-fluorouracil (5-FU) has been successfully included in new regimens of bladder cancer combination chemotherapy. In the present study, we have investigated the effects of 5-FU treatment on apoptosis induction in wild-type and mutant p53 urinary bladder cancer cells. We have used MTT-based assays, FACS analysis, Western blotting and semi-quantitative RT-PCR in RT4 and RT112 (grade I, wild-type p53), as well as in T24 (grade III, mutant p53) and TCCSUP (grade IV, mutant p53) human urinary bladder cancer cell lines. In the urothelial bladder cancer cell lines RT4 and T24, 5-FU-induced TS inhibition proved to be associated with cell type-dependent (a) sensitivity to the drug, (b) Caspase-mediated apoptosis, (c) p53 stabilization and activation, as well as Rb phosphorylation and E2F1 expression and (d) transcriptional regulation of p53 target genes and their cognate proteins, while an E2F-dependent transcriptional network did not seem to be critically engaged in such type of responses. We have shown that in the wild-type p53 context of RT4 cells, 5-FU-triggered apoptosis was prominently efficient and mainly regulated by p53-dependent mechanisms, whereas the mutant p53 environment of T24 cells was able to provide notable levels of resistance to apoptosis, basically ascribed to E2F-independent, and still unidentified, pathways. Nevertheless, the differential vulnerability of RT4 and T24 cells to 5-FU administration could also be associated with cell-type-specific transcriptional expression patterns of certain genes critically involved in 5-FU metabolism.

  10. Characterization of the apoptotic response induced by the cyanine dye D112: a potentially selective anti-cancer compound.

    Directory of Open Access Journals (Sweden)

    Ning Yang

    Full Text Available Chemotherapeutic drugs that are used in anti-cancer treatments often cause the death of both cancerous and noncancerous cells. This non-selective toxicity is the root cause of untoward side effects that limits the effectiveness of therapy. In order to improve chemotherapeutic options for cancer patients, there is a need to identify novel compounds with higher discrimination for cancer cells. In the past, methine dyes that increase the sensitivity of photographic emulsions have been investigated for anti-cancer properties. In the 1970's, Kodak Laboratories initiated a screen of approximately 7000 dye structural variants for selective toxicity. Among these, D112 was identified as a promising compound with elevated toxicity against a colon cancer cell line in comparison to a non-transformed cell line. Despite these results changing industry priorities led to a halt in further studies on D112. We decided to revive investigations on D112 and have further characterized D112-induced cellular toxicity. We identified that in response to D112 treatment, the T-cell leukemia cell line Jurkat showed caspase activation, mitochondrial depolarization, and phosphatidylserine externalization, all of which are hallmarks of apoptosis. Chemical inhibition of caspase enzymatic activity and blockade of the mitochondrial pathway through Bcl-2 expression inhibited D112-induced apoptosis. At lower concentrations, D112 induced growth arrest. To gain insight into the molecular mechanism of D112 induced mitochondrial dysfunction, we analyzed the intracellular localization of D112, and found that D112 associated with mitochondria. Interestingly, in the cell lines that we tested, D112 showed increased toxicity toward transformed versus non-transformed cells. Results from this work identify D112 as a potentially interesting molecule warranting further investigation.

  11. The Deployable Operations Group: A Model for a National Unified Interagency Rapid Response Command

    National Research Council Canada - National Science Library

    Cooper, Eric M

    2008-01-01

    .... Since the attacks, nationwide preparedness efforts have established numerous federal rapid response teams, which are coordinated during a federal interagency response under the National Incident Management System...

  12. Detection of apoptotic tumor response in vivo after a single dose of chemotherapy with 99mTc-annexin V.

    Science.gov (United States)

    Mochizuki, Takafumi; Kuge, Yuji; Zhao, Songji; Tsukamoto, Eriko; Hosokawa, Masuo; Strauss, H William; Blankenberg, Francis G; Tait, Jonathan F; Tamaki, Nagara

    2003-01-01

    tumor response, although further testing, including clinical evaluation, is required.

  13. {sup 99m}Tc-Annexin A5 quantification of apoptotic tumor response: a systematic review and meta-analysis of clinical imaging trials

    Energy Technology Data Exchange (ETDEWEB)

    Belhocine, Tarik Z. [Western University, Biomedical Imaging Research Centre (BIRC), London, Ontario (Canada); Blankenberg, Francis G. [Lucile Salter Packard Children' s Hospital, Stanford, Division of Pediatric Radiology, Department of Radiology, Palo Alto, CA (United States); Kartachova, Marina S. [Medical Center Alkmaar, Department of Nuclear Medicine, Alkmaar (Netherlands); Stitt, Larry W. [LW Stitt Statistical Services, London, Ontario (Canada); Vanderheyden, Jean-Luc [JLVMI Consulting LLC, Waukesha, WI (United States); Hoebers, Frank J.P. [Maastricht University Medical Centre, Department of Radiation Oncology (MAASTRO Clinic), GROW School for Oncology and Developmental Biology, Maastricht (Netherlands); Wiele, Christophe van de [University Hospital Ghent, Department of Nuclear Medicine and Radiology, Ghent (Belgium)

    2015-12-15

    , an increase of ≥25 % in uptake following treatment was considered a significant threshold for an apoptotic tumor response (partial response, complete response). In three other phase I/II clinical trials, increases of ≥28 %, ≥42 % and ≥47 % in uptake following treatment were found to be the mean cut-off levels in responders. In a phase II/III multicenter clinical trial, an increase of ≥23 % in uptake following treatment was found to be the minimum cut-off level for a tumor response. In one clinical trial, no significant difference in {sup 99m}Tc-annexin A5 uptake in terms of %ID was found in healthy tissues after chemotherapy compared to baseline. In two other clinical trials, intraobserver and interobserver measurements of {sup 99m}Tc-annexin A5 tumor uptake were found to be reproducible (mean difference <5 %, kappa = 0.90 and 0.82, respectively) and to be highly correlated with treatment outcome (Spearman r = 0.99, p < 0.0001). The meta-analysis demonstrated a pooled positive PPV of 100 % (95 % CI 92 - 100 %) and a pooled NPV of 70 % (95 % CI 55 - 82 %) for prediction of a tumor response after the first course of chemotherapy and/or radiotherapy in terms of ΔU%. In a symmetric sROC analysis, the AUC was 0.919 and the Q* index was 85.21 %. Quantitative {sup 99m}Tc-annexin A5 imaging has been investigated in clinical trials for the assessment of apoptotic tumor responses. This meta-analysis showed a high pooled PPV and a moderate pooled NPV with ΔU cut-off values ranging between 20 % and 30 %. Standardization of quantification and harmonization of results are required for high-quality clinical research. A standardized uptake value score (SUV, ΔSUV) using quantitative SPECT/CT imaging may be a promising approach to the simple, reproducible and semiquantitative assessment of apoptotic tumor changes. (orig.)

  14. Epidemiology and Clinical Characteristics of Rapid Response Team Activations

    Directory of Open Access Journals (Sweden)

    Sei Won Kim

    2017-05-01

    Full Text Available Background To ensure patient safety and improvements in the quality of hospital care, rapid response teams (RRTs have been implemented in many countries, including Korea. The goal of an RRT is early identification and response to clinical deterioration in patients. However, there are differences in RRT systems among hospitals and limited data are available. Methods In Seoul St. Mary’s Hospital, the St. Mary’s Advanced Life Support Team was implemented in June 2013. We retrospectively reviewed the RRT activation records of 287 cases from June 2013 to December 2016. Results The median response time and median modified early warning score were 8.6 minutes (interquartile range, 5.6 to 11.6 minutes and 5.0 points (interquartile range, 4.0 to 7.0 points, respectively. Residents (35.8% and nurses (59.1% were the main activators of the RRT. Interestingly, postoperative patients account for a large percentage of the RRT activation cases (69.3%. The survival rate was 83.6% and survival was mainly associated with malignancy, Acute Physiology and Chronic Health Evaluation-II score, and the time from admission to RRT activation. RRT activation with screening showed a better outcome compared to activation via a phone call in terms of the intensive care unit admission rate and length of hospital stay after RRT activation. Conclusions Malignancy was the most important factor related to survival. In addition, RRT activation with patient screening showed a better outcome compared to activation via a phone call. Further studies are needed to determine the effective screening criteria and improve the quality of the RRT system.

  15. Sensor Webs: Autonomous Rapid Response to Monitor Transient Science Events

    Science.gov (United States)

    Mandl, Dan; Grosvenor, Sandra; Frye, Stu; Sherwood, Robert; Chien, Steve; Davies, Ashley; Cichy, Ben; Ingram, Mary Ann; Langley, John; Miranda, Felix

    2005-01-01

    To better understand how physical phenomena, such as volcanic eruptions, evolve over time, multiple sensor observations over the duration of the event are required. Using sensor web approaches that integrate original detections by in-situ sensors and global-coverage, lower-resolution, on-orbit assets with automated rapid response observations from high resolution sensors, more observations of significant events can be made with increased temporal, spatial, and spectral resolution. This paper describes experiments using Earth Observing 1 (EO-1) along with other space and ground assets to implement progressive mission autonomy to identify, locate and image with high resolution instruments phenomena such as wildfires, volcanoes, floods and ice breakup. The software that plans, schedules and controls the various satellite assets are used to form ad hoc constellations which enable collaborative autonomous image collections triggered by transient phenomena. This software is both flight and ground based and works in concert to run all of the required assets cohesively and includes software that is model-based, artificial intelligence software.

  16. The Simulation-Based Assessment of Pediatric Rapid Response Teams.

    Science.gov (United States)

    Fehr, James J; McBride, Mary E; Boulet, John R; Murray, David J

    2017-09-01

    To create scenarios of simulated decompensating pediatric patients to train pediatric rapid response teams (RRTs) and to determine whether the scenario scores provide a valid assessment of RRT performance with the hypothesis that RRTs led by intensivists-in-training would be better prepared to manage the scenarios than teams led by nurse practitioners. A set of 10 simulated scenarios was designed for the training and assessment of pediatric RRTs. Pediatric RRTs, comprising a pediatric intensive care unit (PICU) registered nurse and respiratory therapist, led by a PICU intensivist-in-training or a pediatric nurse practitioner, managed 7 simulated acutely decompensating patients. Two raters evaluated the scenario performances and psychometric analyses of the scenarios were performed. The teams readily managed scenarios such as supraventricular tachycardia and opioid overdose but had difficulty with more complicated scenarios such as aortic coarctation or head injury. The management of any particular scenario was reasonably predictive of overall team performance. The teams led by the PICU intensivists-in-training outperformed the teams led by the pediatric nurse practitioners. Simulation provides a method for RRTs to develop decision-making skills in managing decompensating pediatric patients. The multiple scenario assessment provided a moderately reliable team score. The greater scores achieved by PICU intensivist-in-training-led teams provides some evidence to support the validity of the assessment. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. The Wallops Flight Facility Rapid Response Range Operations Initiative

    Science.gov (United States)

    Underwood, Bruce E.; Kremer, Steven E.

    2004-01-01

    becomes how can a launch site provide acceptably responsive mission services to a particular customer without dedicating extensive resources and while continuing to serve other projects? NASA's Wallops Flight Facility (WFF) is pursuing solutions to exactly this challenge. NASA, in partnership with the Virginia Commercial Space Flight Authority, has initiated the Rapid Response Range Operations Initiative (R3Ops). R3Ops is a multi-phased effort to incrementally establish and demonstrate increasingly responsive launch operations, with an ultimate goal of providing ELV-class services in a maximum of 7-10 days from initial notification routinely, and shorter schedules possible with committed resources. This target will be pursued within the reality of simultaneous concurrent programs, and ideally, largely independent of specialized flight system configurations. WFF has recently completed Phase 1 of R3Ops, an in-depth collection (through extensive expert interviews) and software modeling of individual steps by various range disciplines. This modeling is now being used to identify existing inefficiencies in current procedures, to identify bottlenecks, and show interdependencies. Existing practices are being tracked to provide a baseline to benchmark against as new procedures are implemented. This paper will describe in detail the philosophies behind WFF's R3Ops, the data collected and modeled in Phase 1, and strategies for meeting responsive launch requirements in a multi-user range environment planned for subsequent phases of this initiative.

  18. Stigma in Canada: Results From a Rapid Response Survey

    Science.gov (United States)

    Stuart, Heather; Patten, Scott B; Koller, Michelle; Modgill, Geeta; Liinamaa, Tiina

    2014-01-01

    Objective: Our paper presents findings from the first population survey of stigma in Canada using a new measure of stigma. Empirical objectives are to provide a descriptive profile of Canadian’s expectations that people will devalue and discriminate against someone with depression, and to explore the relation between experiences of being stigmatized in the year prior to the survey among people having been treated for a mental illness with a selected number of sociodemographic and mental health–related variables. Method: Data were collected by Statistics Canada using a rapid response format on a representative sample of Canadians (n = 10 389) during May and June of 2010. Public expectations of stigma and personal experiences of stigma in the subgroup receiving treatment for a mental illness were measured. Results: Over one-half of the sample endorsed 1 or more of the devaluation discrimination items, indicating that they believed Canadians would stigmatize someone with depression. The item most frequently endorsed concerned employers not considering an application from someone who has had depression. Over one-third of people who had received treatment in the year prior to the survey reported discrimination in 1 or more life domains. Experiences of discrimination were strongly associated with perceptions that Canadians would devalue someone with depression, younger age (12 to 15 years), and self-reported poor general mental health. Conclusions: The Mental Health Experiences Module reflects an important partnership between 2 national organizations that will help Canada fulfill its monitoring obligations under the United Nations Convention on the Rights of Persons with Disabilities and provide a legacy to researchers and policy-makers who are interested in monitoring changes in stigma over time. PMID:25565699

  19. Spectrophotometric Rapid-Response Classification of Near-Earth Objects

    Science.gov (United States)

    Mommert, Michael; Trilling, David; Butler, Nat; Axelrod, Tim; Moskovitz, Nick; Jedicke, Robert; Pichardo, Barbara; Reyes-Ruiz, Mauricio

    2015-08-01

    Small NEOs are, as a whole, poorly characterized, and we know nothing about the physical properties of the majority of all NEOs. The rate of NEO discoveries is increasing each year, and projects to determine the physical properties of NEOs are lagging behind. NEOs are faint, and generally even fainter by the time that follow-up characterizations can be made days or weeks after their discovery. There is a need for a high-throughput, high-efficiency physical characterization strategy in which hundreds of faint NEOs can be characterized each year. Broadband photometry in the near-infrared is sufficiently diagnostic to assign taxonomic types, and hence constrain both the individual and ensemble properties of NEOs.We present results from our rapid response near-infrared spectrophotometric characterization program of NEOs. We are using UKIRT (on Mauna Kea) and the RATIR instrument on the 1.5m telescope at the San Pedro Martir Observatory (Mexico) to allow us to make observations most nights of the year in robotic/queue mode. We derive taxonomic classifications for our targets using machine-learning techniques that are trained on a large sample of measured asteroid spectra. For each target we assign a probability for it to belong to a number of different taxa. Target selection, observation, data reduction, and analysis are highly automated, requiring only a minimum of user interaction, making this technique powerful and fast. Our targets are NEOs that are generally too faint for other characterization techniques, or would require many hours of large telescope time.

  20. Effectiveness Analysis of a Part-Time Rapid Response System During Operation Versus Nonoperation.

    Science.gov (United States)

    Kim, Youlim; Lee, Dong Seon; Min, Hyunju; Choi, Yun Young; Lee, Eun Young; Song, Inae; Park, Jong Sun; Cho, Young-Jae; Jo, You Hwan; Yoon, Ho Il; Lee, Jae Ho; Lee, Choon-Taek; Do, Sang Hwan; Lee, Yeon Joo

    2017-06-01

    To evaluate the effect of a part-time rapid response system on the occurrence rate of cardiopulmonary arrest by comparing the times of rapid response system operation versus nonoperation. Retrospective cohort study. A 1,360-bed tertiary care hospital. Adult patients admitted to the general ward were screened. Data were collected over 36 months from rapid response system implementation (October 2012 to September 2015) and more than 45 months before rapid response system implementation (January 2009 to September 2012). None. The rapid response system operates from 7 AM to 10 PM on weekdays and from 7 AM to 12 PM on Saturdays. Primary outcomes were the difference of cardiopulmonary arrest incidence between pre-rapid response system and post-rapid response system periods and whether the rapid response system operating time affects the cardiopulmonary arrest incidence. The overall cardiopulmonary arrest incidence (per 1,000 admissions) was 1.43. Although the number of admissions per month and case-mix index were increased (3,555.18 vs 4,564.72, p times (0.82 vs 0.49/1,000 admissions; p = 0.001) but remained similar during rapid response system nonoperating times (0.77 vs 0.73/1,000 admissions; p = 0.729). The implementation of a part-time rapid response system reduced the cardiopulmonary arrest incidence based on the reduction of cardiopulmonary arrest during rapid response system operating times. Further analysis of the cost effectiveness of part-time rapid response system is needed.

  1. Rapid Response Measurements of Hurricane Waves and Storm Surge

    Science.gov (United States)

    Gravois, U.

    2010-12-01

    Andrew (1992), Katrina (2005), and Ike (2008) are recent examples of extensive damage that resulted from direct hurricane landfall. Some of the worst damages from these hurricanes are caused by wind driven waves and storm surge flooding. The potential for more hurricane disasters like these continues to increase as a result of population growth and real estate development in low elevation coastal regions. Observational measurements of hurricane waves and storm surge play an important role in future mitigation efforts, yet permanent wave buoy moorings and tide stations are more sparse than desired. This research has developed a rapid response method using helicopters to install temporary wave and surge gauges ahead of hurricane landfall. These temporary installations, with target depths from 10-15 m and 1-7 km offshore depending on the local shelf slope, increase the density of measurement points where the worst conditions are expected. The method has progressed to an operational state and has successfully responded to storms Ernesto (2006), Noel (2007), Fay (2008), Gustav (2008), Hanna (2008) and Ike (2008). The temporary gauges are pressure data loggers that measure at 1 Hz continuously for 12 days and are post-processed to extract surge and wave information. For the six storms studied, 45 out of 49 sensors were recovered by boat led scuba diver search teams, with 43 providing useful data for an 88 percent success rate. As part of the 20 sensor Hurricane Gustav response, sensors were also deployed in lakes and bays inLouisiana, east of the Mississippi river delta. Gustav was the largest deployment to date. Generally efforts were scaled back for storms that were not anticipated to be highly destructive. For example, the cumulative total of sensors deployed for Ernesto, Noel, Fay and Hanna was only 20. Measurement locations for Gustav spanned over 800 km of exposed coastline from Louisiana to Florida with sensors in close proximity to landfall near Cocodrie

  2. Apoptotic signaling in mouse odontogenesis.

    Science.gov (United States)

    Matalova, Eva; Svandova, Eva; Tucker, Abigail S

    2012-01-01

    Apoptosis is an important morphogenetic event in embryogenesis as well as during postnatal life. In the last 2 decades, apoptosis in tooth development (odontogenesis) has been investigated with gradually increasing focus on the mechanisms and signaling pathways involved. The molecular machinery responsible for apoptosis exhibits a high degree of conservation but also organ and tissue specific patterns. This review aims to discuss recent knowledge about apoptotic signaling networks during odontogenesis, concentrating on the mouse, which is often used as a model organism for human dentistry. Apoptosis accompanies the entire development of the tooth and corresponding remodeling of the surrounding bony tissue. It is most evident in its role in the elimination of signaling centers within developing teeth, removal of vestigal tooth germs, and in odontoblast and ameloblast organization during tooth mineralization. Dental apoptosis is caspase dependent and proceeds via mitochondrial mediated cell death with possible amplification by Fas-FasL signaling modulated by Bcl-2 family members.

  3. Rapid Response Predicts Treatment Outcomes in Binge Eating Disorder: Implications for Stepped Care

    Science.gov (United States)

    Masheb, Robin M.; Grilo, Carlos M.

    2007-01-01

    The authors examined rapid response in 75 overweight patients with binge eating disorder (BED) who participated in a randomized clinical trial of guided self-help treatments (cognitive-behavioral therapy [CBTgsh] and behavioral weight loss [BWLgsh]). Rapid response, defined as a 65% or greater reduction in binge eating by the 4th treatment week,…

  4. Science Partnerships Enabling Rapid Response: Designing a Strategy for Improving Scientific Collaboration during Crisis Response

    Science.gov (United States)

    Mease, L.; Gibbs, T.; Adiseshan, T.

    2014-12-01

    The 2010 Deepwater Horizon disaster required unprecedented engagement and collaboration with scientists from multiple disciplines across government, academia, and industry. Although this spurred the rapid advancement of valuable new scientific knowledge and tools, it also exposed weaknesses in the system of information dissemination and exchange among the scientists from those three sectors. Limited government communication with the broader scientific community complicated the rapid mobilization of the scientific community to assist with spill response, evaluation of impact, and public perceptions of the crisis. The lessons and new laws produced from prior spills such as Exxon Valdez were helpful, but ultimately did not lead to the actions necessary to prepare a suitable infrastructure that would support collaboration with non-governmental scientists. As oil demand pushes drilling into increasingly extreme environments, addressing the challenge of effective, science-based disaster response is an imperative. Our study employs a user-centered design process to 1) understand the obstacles to and opportunity spaces for effective scientific collaboration during environmental crises such as large oil spills, 2) identify possible tools and strategies to enable rapid information exchange between government responders and non-governmental scientists from multiple relevant disciplines, and 3) build a network of key influencers to secure sufficient buy-in for scaled implementation of appropriate tools and strategies. Our methods include user ethnography, complex system mapping, individual and system behavioral analysis, and large-scale system design to identify and prototype a solution to this crisis collaboration challenge. In this talk, we will present out insights gleaned from existing analogs of successful scientific collaboration during crises and our initial findings from the 60 targeted interviews we conducted that highlight key collaboration challenges that government

  5. [Responses of tomato leaf photosynthesis to rapid water stress].

    Science.gov (United States)

    Han, Guo-Jun; Chen, Nian-lai; Huang, Hai-xia; Zhang, Ping; Zhang, Kai; Guo, Yan-hong

    2013-04-01

    By using polyethylene glycol (PEG-6000) solution to regulate the water potential of tomato (Lycopersicon esculentum) rhizosphere to simulate water stress, this paper studied the dynamic changes of net photosynthetic rate, dark respiratory rate and CO2 compensatory concentration of detached tomato leaves in the process of photosynthetic induction. Under 1000 micromol m-2 s-1 of light induction, the time required to reach the maximum net photosynthetic rate of water-stressed tomato leaves was shortened by 1/3, while the stomatal conductance was increased by 1.5 times, as compared to the non-stress control. Also, the light saturation point (LSP) of water-stressed tomato leaves was lowered by 65% to 85%, and the light compensation point (LCP) was increased by 75% to 100%, suggesting that the effective range of light utilized by tomato leaves was reduced. Furthermore, water stress decreased the maximum photosynthetic capacity of tomato leaves by 40%, but increased the dark respiration rate by about 45% . It was suggested that rapid water stress made the stomata of tomato leaves quickly opened, without initial photosynthetic induction stage. In conclusion, water stress could induce the decrease of plant light-energy use efficiency and potential, being the main reason for the decrease of plant productivity, and stomatal regulation could be the main physiological mechanism of tomato plants to adapt to rapid water stress.

  6. Rapid Time Response: A solution for Manufacturing Issue

    Directory of Open Access Journals (Sweden)

    Norazlin N.

    2017-01-01

    Full Text Available Respond time in manufacturing give the major impact that able to contribute too many manufacturing issues. Based on two worst case scenario occurred where Toyota in 2009 made a massive vehicles call due to car complexity of 11 major models and over 9 million vehicles. The recalls cost at least $2 billion in cost of repair, lost deals and result in lost 5% of its market share in United State of America, while A380 was reported on missing target in new production and leads to delayed market entry due to their weak product life cycle management (PLM. These cases give a sign to all industries to possess and optimize the facilities for better traceability in shortest time period. In Industry 4.0, the traceability and time respond become the factors for high performance manufacturing and rapid time respond able to expedite the traceability process and strengthen the communication level between man, machine and management. The round trip time (RTT experiment gives variant time respond between two difference operating system for intra and inter-platform signal. If this rapid time respond is adopted in any manufacturing process, the delay in traceability on every issue that lead to losses can be successfully avoided.

  7. l-Theanine prevents ETEC-induced liver damage by reducing intrinsic apoptotic response and inhibiting ERK1/2 and JNK1/2 signaling pathways.

    Science.gov (United States)

    Gong, Zhihua; Liu, Qiuling; Lin, Ling; Deng, Yanli; Cai, Shuxian; Liu, Zunying; Zhang, Sheng; Xiao, Wenjun; Xiong, Shuo; Chen, Dong

    2018-01-05

    l-Theanine (LTA; γ-glutamylethylamide), a peculiar non-protein-derived amino acid isolated from tea, is widely used as a functional ingredient and dietary supplement. l-Theanine has been confirmed to have hepatoprotective effects, but the underlying mechanism remains unknown. This study investigated the protective effect of l-Theanine-in vivo, using an enterotoxigenic Escherichia coli (ETEC)-infected mouse model. l-Theanine significantly decreased the elevated serum activities of both aspartate aminotransferase (AST) and alanine aminotransferase (ALT), two biomarkers of hepatic impairment. This was consistent with histopathological images from the microscopic observation of liver tissue. In addition, l-theanine significantly increased the mRNA and protein expression of Bcl-2 and decreased the expression of Bax, anti- and pro-apoptotic molecules, respectively, compared with levels in the ETEC control group. The expression of cleaved caspase-3 protein in the group pre-treated with l-theanine was significantly lower than that in the ETEC group. Additionally, decreases in extracellular signal-regulated kinase (ERK1/2) and c-Jun NH 2 -terminal kinase(JNK1/2) MAPK phosphorylation were observed in the l-theanine pre-treated group. Our study demonstrates that l-theanine possesses anti-apoptotic activity, which can be attributed to suppression of the intrinsic mitochondria-mediated apoptosis and MAPK phosphorylation signaling pathways. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Robust Research and Rapid Response: The Plum Pox Virus Story

    Science.gov (United States)

    Alter, Theodore R.; Bridger, Jeffrey C.; Travis, James W.

    2004-01-01

    Universities are frequently criticized for being unresponsive to the needs of their stakeholders. In response to this perception, many institutions of higher learning have taken steps to become more productively engaged with the people, organizations, and communities they serve. In this article, we analyze the process of engagement by focusing on…

  9. Rapid response to climate change in a marginal sea.

    Science.gov (United States)

    Schroeder, K; Chiggiato, J; Josey, S A; Borghini, M; Aracri, S; Sparnocchia, S

    2017-06-22

    The Mediterranean Sea is a mid-latitude marginal sea, particularly responsive to climate change as reported by recent studies. The Sicily Channel is a choke point separating the sea in two main basins, the Eastern Mediterranean Sea and the Western Mediterranean Sea. Here, we report and analyse a long-term record (1993-2016) of the thermohaline properties of the Intermediate Water that crosses the Sicily Channel, showing increasing temperature and salinity trends much stronger than those observed at intermediate depths in the global ocean. We investigate the causes of the observed trends and in particular determine the role of a changing climate over the Eastern Mediterranean, where the Intermediate Water is formed. The long-term Sicily record reveals how fast the response to climate change can be in a marginal sea like the Mediterranean Sea compared to the global ocean, and demonstrates the essential role of long time series in the ocean.

  10. Dissociation of rapid response learning and facilitation in perceptual and conceptual networks of person recognition.

    Science.gov (United States)

    Valt, Christian; Klein, Christoph; Boehm, Stephan G

    2015-08-01

    Repetition priming is a prominent example of non-declarative memory, and it increases the accuracy and speed of responses to repeatedly processed stimuli. Major long-hold memory theories posit that repetition priming results from facilitation within perceptual and conceptual networks for stimulus recognition and categorization. Stimuli can also be bound to particular responses, and it has recently been suggested that this rapid response learning, not network facilitation, provides a sound theory of priming of object recognition. Here, we addressed the relevance of network facilitation and rapid response learning for priming of person recognition with a view to advance general theories of priming. In four experiments, participants performed conceptual decisions like occupation or nationality judgments for famous faces. The magnitude of rapid response learning varied across experiments, and rapid response learning co-occurred and interacted with facilitation in perceptual and conceptual networks. These findings indicate that rapid response learning and facilitation in perceptual and conceptual networks are complementary rather than competing theories of priming. Thus, future memory theories need to incorporate both rapid response learning and network facilitation as individual facets of priming. © 2014 The British Psychological Society.

  11. Rapid Response Risk Assessment in New Project Development

    Science.gov (United States)

    Graber, Robert R.

    2010-01-01

    A capability for rapidly performing quantitative risk assessments has been developed by JSC Safety and Mission Assurance for use on project design trade studies early in the project life cycle, i.e., concept development through preliminary design phases. A risk assessment tool set has been developed consisting of interactive and integrated software modules that allow a user/project designer to assess the impact of alternative design or programmatic options on the probability of mission success or other risk metrics. The risk and design trade space includes interactive options for selecting parameters and/or metrics for numerous design characteristics including component reliability characteristics, functional redundancy levels, item or system technology readiness levels, and mission event characteristics. This capability is intended for use on any project or system development with a defined mission, and an example project will used for demonstration and descriptive purposes, e.g., landing a robot on the moon. The effects of various alternative design considerations and their impact of these decisions on mission success (or failure) can be measured in real time on a personal computer. This capability provides a high degree of efficiency for quickly providing information in NASA s evolving risk-based decision environment

  12. Development of Multiple Big Data Analytics Platforms with Rapid Response

    Directory of Open Access Journals (Sweden)

    Bao Rong Chang

    2017-01-01

    Full Text Available The crucial problem of the integration of multiple platforms is how to adapt for their own computing features so as to execute the assignments most efficiently and gain the best outcome. This paper introduced the new approaches to big data platform, RHhadoop and SparkR, and integrated them to form a high-performance big data analytics with multiple platforms as part of business intelligence (BI to carry out rapid data retrieval and analytics with R programming. This paper aims to develop the optimization for job scheduling using MSHEFT algorithm and implement the optimized platform selection based on computing features for improving the system throughput significantly. In addition, users would simply give R commands rather than run Java or Scala program to perform the data retrieval and analytics in the proposed platforms. As a result, according to performance index calculated for various methods, although the optimized platform selection can reduce the execution time for the data retrieval and analytics significantly, furthermore scheduling optimization definitely increases the system efficiency a lot.

  13. Changes in Sensory Evoked Responses Coincide with Rapid Improvement in Speech Identification Performance

    Science.gov (United States)

    Alain, Claude; Campeanu, Sandra; Tremblay, Kelly

    2010-01-01

    Perceptual learning is sometimes characterized by rapid improvements in performance within the first hour of training (fast perceptual learning), which may be accompanied by changes in sensory and/or response pathways. Here, we report rapid physiological changes in the human auditory system that coincide with learning during a 1-hour test session…

  14. Pre-apoptotic response to therapeutic DNA damage involves protein modulation of Mcl-1, Hdm2 and Flt3 in acute myeloid leukemia cells

    Directory of Open Access Journals (Sweden)

    Hovland Randi

    2007-05-01

    Full Text Available Abstract Background Acute myeloid leukemia (AML cells are characterized by non-mutated TP53, high levels of Hdm2, and frequent mutation of the Flt3 receptor tyrosine kinase. The juxtamembrane mutation of FLT3 is the strongest independent marker for disease relapse and is associated with elevated Bcl-2 protein and p53 hyper-phosphorylation in AML. DNA damage forms the basic mechanism of cancer cell eradication in current therapy of AML. Hdm2 and pro-apoptotic Bcl-2 members are among the most intensely induced genes immediately after chemotherapy and Hdm2 is proposed a role in receptor tyrosine kinase regulation. Thus we examined the DNA damage related modulation of these proteins in relation to FLT3 mutational status and induction of apoptosis. Results Within one hour after exposure to ionizing radiation (IR, the AML cells (NB4, MV4-11, HL-60, primary AML cells showed an increase in Flt3 protein independent of mRNA levels, while the Hdm2 protein decreased. The FLT3 mutant MV4-11 cells were resistant to IR accompanied by presence of both Mcl-1 and Hdm2 protein three hours after IR. In contrast, the FLT3 wild type NB4 cells responded to IR with apoptosis and pre-apoptotic Mcl-1 down regulation. Daunorubicin (DNR induced continuing down regulation of Hdm2 and Mcl-1 in both cell lines followed by apoptosis. Conclusion Both IR and DNR treatment resulted in concerted protein modulations of Mcl-1, Hdm2 and Flt3. Cell death induction was associated with persistent attenuation of Mcl-1 and Hdm2. These observations suggest that defining the pathway(s modulating Flt3, Hdm2 and Mcl-1 may propose new strategies to optimize therapy for the relapse prone FLT3 mutated AML patients.

  15. Rapid IV Versus Oral Rehydration: Responses to Subsequent Exercise Heat Stress

    National Research Council Canada - National Science Library

    Kenefick, Robert W; O'Moore, Kathleen M; Mahood, Nicholas V; Castellani, John W

    2006-01-01

    This study sought to determine the effect of rapid intravenous (IV) versus oral (ORAL) rehydration immediately after dehydration, on cardiovascular, thermoregulatory, and perceptual responses during subsequent exercise in the heat.

  16. Rapid Calculation of EMI Responses of Metallic Objects and Implementation in Inversion Schemes

    National Research Council Canada - National Science Library

    Paulsen, Keith

    2003-01-01

    .... Nonetheless, signal inversion schemes are impeded by a lack of rapid means for calculating the responses of possible target types in a great variety of depths and dispositions relative to the sensor...

  17. Rapid adaptive responses to climate change in corals

    KAUST Repository

    Torda, Gergely

    2017-09-01

    Pivotal to projecting the fate of coral reefs is the capacity of reef-building corals to acclimatize and adapt to climate change. Transgenerational plasticity may enable some marine organisms to acclimatize over several generations and it has been hypothesized that epigenetic processes and microbial associations might facilitate adaptive responses. However, current evidence is equivocal and understanding of the underlying processes is limited. Here, we discuss prospects for observing transgenerational plasticity in corals and the mechanisms that could enable adaptive plasticity in the coral holobiont, including the potential role of epigenetics and coral-associated microbes. Well-designed and strictly controlled experiments are needed to distinguish transgenerational plasticity from other forms of plasticity, and to elucidate the underlying mechanisms and their relative importance compared with genetic adaptation.

  18. Biological and psychological responses to two rapid shiftwork schedules.

    Science.gov (United States)

    Lac, G; Chamoux, A

    2004-10-10

    This study presents the biological responses to shiftwork in two groups of workers with different shiftwork rotas. Biological responses were studied by recording the heart rate and the changes in the circadian profile of salivary cortisol over 24 h (RIA assays). Various items were recorded through questionnaires aimed at determining self appreciation of sleep quantity, stress, health, satisfaction at work and in private lives. Thirty two male subjects aged from 23 to 56, working for the same company, having given their informed consent, took part in the study. The study was carried out under realistic conditions (at the work place) under the control of an occupational physician. Sixteen day-workers (8 am-6 pm) served as a reference group. Eight shiftworkers included in alternate schedules (morning M 4 am-12 am, evening E 12 am-8 pm, night N 8 pm-4 am) according to a system M, S, N 3/2, (3 work, 2 rest) and eight according to a system 7/5 (3M/2S/2N/5R, 2/3/2/5, 2/2/3/5) constituted the groups of shiftworkers respectively named 3/2 and 7/5. All subjects had comparable ages and BMIs. Shiftworkers expressed a higher stress level and frequency of health problems and a lower satisfaction at work than the control. Among the three groups, the 7/5 group had the best health and fitness score and was in need of less sleep. Heart rate was not affected by shift work. Conversely, consistent changes appeared in cortisol circadian profiles, the greatest changes appearing for the night shift and among the two groups of shiftworkers, more particularly for the 7/5 group. These changes correlated with self-perceived constraints of work and showed the difficulties of adaptation to shiftwork.

  19. Label-free, rapid and quantitative phenotyping of stress response in E. coli via ramanome

    OpenAIRE

    Lin Teng; Xian Wang; Xiaojun Wang; Honglei Gou; Lihui Ren; Tingting Wang; Yun Wang; Yuetong Ji; Huang, Wei E.; Jian Xu

    2016-01-01

    Rapid profiling of stress-response at single-cell resolution yet in a label-free, non-disruptive and mechanism-specific manner can lead to many new applications. We propose a single-cell-level biochemical fingerprinting approach named "ramanome", which is the collection of Single-cell Raman Spectra (SCRS) from a number of cells randomly selected from an isogenic population at a given time and condition, to rapidly and quantitatively detect and characterize stress responses of cellular populat...

  20. Glyphosate resistance in Ambrosia trifida: Part 2. Rapid response physiology and non-target-site resistance.

    Science.gov (United States)

    Moretti, Marcelo L; Van Horn, Christopher R; Robertson, Renae; Segobye, Kabelo; Weller, Stephen C; Young, Bryan G; Johnson, William G; Douglas Sammons, R; Wang, Dafu; Ge, Xia; d' Avignon, André; Gaines, Todd A; Westra, Philip; Green, Amanda C; Jeffery, Taylor; Lespérance, Mackenzie A; Tardif, François J; Sikkema, Peter H; Christopher Hall, J; McLean, Michael D; Lawton, Mark B; Schulz, Burkhard

    2017-03-08

    The glyphosate-resistant rapid response (GR RR) resistance mechanism in Ambrosia trifida is not due to target-site resistance (TSR) mechanisms. This study explores the physiology of the rapid response and the possibility of reduced translocation and vacuolar sequestration as non-target-site resistance (NTSR) mechanisms. GR RR leaf discs accumulated hydrogen peroxide within minutes of glyphosate exposure, but only in mature leaf tissue. The rapid response required energy either as light or exogenous sucrose. The combination of phenylalanine and tyrosine inhibited the rapid response in a dose-dependent manner. Reduced glyphosate translocation was observed in GR RR, but only when associated with tissue death caused by the rapid response. Nuclear magnetic resonance studies indicated that glyphosate enters the cytoplasm and reaches chloroplasts, and it is not moved into the vacuole of GR RR, GR non-rapid response or glyphosate-susceptible A. trifida. The GR RR mechanism of resistance is not associated with vacuole sequestration of glyphosate, and the observed reduced translocation is likely a consequence of rapid tissue death. Rapid cell death was inhibited by exogenous application of aromatic amino acids phenylalanine and tyrosine. The mechanism by which these amino acids inhibit rapid cell death in the GR RR phenotype remains unknown, and it could involve glyphosate phytotoxicity or other agents generating reactive oxygen species. Implications of these findings are discussed. The GR RR mechanism is distinct from the currently described glyphosate TSR or NTSR mechanisms in other species. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  1. Stimulus and response priming in rapid serial visual presentation : Evidence for a dissociation

    NARCIS (Netherlands)

    Akyürek, Elkan G.; Hommel, Bernhard

    2007-01-01

    Two experiments investigated the capacity demands of stimulus and response priming in a rapid serial visual presentation (RSVP) task. Three targets were presented in a stream of visual symbols: The first two (T1 and T2) required an unspeeded manual response at the end of the trial, but the third

  2. Role of CX3CL1 in the chemotactic migration of all-trans retinoic acid-treated acute promyelocytic leukemic cells toward apoptotic cells

    Directory of Open Access Journals (Sweden)

    Wen-Hui Tsai

    2014-07-01

    Conclusion: CX3CL1, in either the free or MP form, is released rapidly by apoptotic ATRA-NB4 cells after induction of apoptosis to mediate the chemoattraction of living ATRA-NB4 cells toward apoptotic cells.

  3. Thrombospondin-1 induces differential response in human corneal and conjunctival epithelial cells lines under in vitro inflammatory and apoptotic conditions.

    Science.gov (United States)

    Soriano-Romaní, Laura; García-Posadas, Laura; López-García, Antonio; Paraoan, Luminita; Diebold, Yolanda

    2015-05-01

    Recently, thrombospondin-1 (TSP-1) has been reported to be critical for maintaining a healthy ocular surface. The purpose of the study was to characterize the expression of TSP-1 and of its receptors CD36 and CD47 in corneal and conjunctival epithelial cells and determine the effect of exogenous TSP-1 treatment on these cells, following the induction of inflammation- and apoptosis-related changes. The expression of TSP-1, CD36 and CD47 by corneal and conjunctival cell lines was firstly characterized by ELISA, immunofluorescence analysis, Western blotting and reverse transcription polymerase chain reaction (RT-PCR). Benzalkonium chloride (BAC) exposure for 5 or 15 min was used as pro-inflammatory and pro-apoptotic stimulus for corneal or conjunctival epithelial cells, respectively. To analyze inflammation and apoptosis-related changes, IL-6 and TGF-β2 secretion determined by ELISA was used as inflammatory markers, while activated caspase-3/7 levels and cell viability, determined by CellEvent™ Caspase-3/7 Green Detection Reagent and XTT cytotoxicity assay, respectively, were used as apoptotic markers. Changes in CD36 and CD47 mRNA expression were quantified by real time RT-PCR. Corneal epithelial cells secreted and expressed higher protein levels of TSP-1 than conjunctival epithelial cells, although TSP-1 mRNA expression levels were similar and had lower CD36 and CD47, both at protein and mRNA levels. Both cell lines responded to exogenous TSP-1 treatment increasing CD36 at protein and mRNA levels. Blocking experiments revealed a predominance of TSP-1/CD47 rather than TSP-1/CD36 interactions to up-regulate CD36 levels in conjunctival epithelial cells, but not in corneal epithelial cells. BAC exposure increased IL-6 secretion and caspase-3/7 levels and decreased cell viability in both, corneal and conjunctival epithelial cells. Moreover, BAC exposure increased latent TGF-β2 levels in conjunctival epithelial cells. Interestingly, CD36 mRNA expression was down

  4. The combined treatment with novel platinum(II) complex and anti-MUC1 increases apoptotic response in MDA-MB-231 breast cancer cells.

    Science.gov (United States)

    Gornowicz, Agnieszka; Bielawska, Anna; Czarnomysy, Robert; Gabryel-Porowska, Halina; Muszyńska, Anna; Bielawski, Krzysztof

    2015-10-01

    New strategy of cancer's targeting treatment is combining monoclonal antibodies with chemotherapeutic agents. An important goal of targeted therapy appears to be a transmembrane glycoprotein type I-mucin 1 (MUC1), which is overexpressed in tumors of epithelial origin, especially in breast cancer. The goal of the study was to check the effect of monoclonal antibody against MUC1 with novel platinum(II) complex (Pt12) on selected aspects of apoptosis in human MDA-MB-231 breast cancer cells. The number of apoptotic and necrotic cells was measured using annexin V binding assay. The decrease of mitochondrial membrane potential (MMP) and DNA fragmentation was analyzed. Finally, the influence of novel platinum(II) complex (Pt12) used with anti-MUC1 on the concentration of selected markers of apoptosis such as Bax, caspase-8, -9, and caspase-3 was performed using ELISA. The results from combined treatment were compared with those obtained using monotherapy. In our study, we proved that anti-MUC1 used in combination with Pt12 strongly induced apoptosis in MDA-MB-231 breast cancer cell line. The effect was stronger than treatment with Pt12, cisplatin, anti-MUC1, and anti-MUC1 used with cisplatin. We also observed the highest decrease of MMP and the strongest DNA fragmentation after such a combined treatment. The results obtained from ELISA showed increased concentration of Bax, caspases-8, -9, -3 compared to monotherapy. Our study proved that Pt12 together with anti-MUC1 strongly induced apoptosis in estrogen-negative breast cancer cell line (MDA-MB-231). The apoptosis may go through extrinsic pathway associated with caspase-8 as well as intrinsic pathway connected with caspase-9.

  5. Rapid response seismic networks in Europe: lessons learnt from the L'Aquila earthquake emergency

    Directory of Open Access Journals (Sweden)

    Angelo Strollo

    2011-08-01

    Full Text Available

    The largest dataset ever recorded during a normal fault seismic sequence was acquired during the 2009 seismic emergency triggered by the damaging earthquake in L'Aquila (Italy. This was possible through the coordination of different rapid-response seismic networks in Italy, France and Germany. A seismic network of more than 60 stations recorded up to 70,000 earthquakes. Here, we describe the different open-data archives where it is possible to find this unique set of data for studies related to hazard, seismotectonics and earthquake physics. Moreover, we briefly describe some immediate and direct applications of emergency seismic networks. At the same time, we note the absence of communication platforms between the different European networks. Rapid-response networks need to agree on common strategies for network operations. Hopefully, over the next few years, the European Rapid-Response Seismic Network will became a reality.

  6. An in vivo root hair assay for determining rates of apoptotic-like programmed cell death in plants

    Directory of Open Access Journals (Sweden)

    Hogg Bridget V

    2011-12-01

    Full Text Available Abstract In Arabidopsis thaliana we demonstrate that dying root hairs provide an easy and rapid in vivo model for the morphological identification of apoptotic-like programmed cell death (AL-PCD in plants. The model described here is transferable between species, can be used to investigate rates of AL-PCD in response to various treatments and to identify modulation of AL-PCD rates in mutant/transgenic plant lines facilitating rapid screening of mutant populations in order to identify genes involved in AL-PCD regulation.

  7. The rapid response team nurse's role in end-of-life discussions during critical situations.

    Science.gov (United States)

    Bouley, Gary

    2011-01-01

    Rapid response teams have been in existence in hospitals over the past decade. This team call may offer life-saving interventions that save lives but, in some cases, may prolong the dying process. There are times in which the rapid response team nurse and the intensive care nurses need to have an understanding of the families' perception of what is occurring and manage this situation through communication, empathy, and information sharing. The nurse must be involved during discussions surrounding end-of-life decisions. The nurse also has a role in supporting the family through this difficult time of making a decision to withhold life-supporting measures.

  8. Rapid response to changing environments during biological invasions: DNA methylation perspectives.

    Science.gov (United States)

    Huang, Xuena; Li, Shiguo; Ni, Ping; Gao, Yangchun; Jiang, Bei; Zhou, Zunchun; Zhan, Aibin

    2017-12-01

    Dissecting complex interactions between species and their environments has long been a research hot spot in the fields of ecology and evolutionary biology. The well-recognized Darwinian evolution has well-explained long-term adaptation scenarios; however, "rapid" processes of biological responses to environmental changes remain largely unexplored, particularly molecular mechanisms such as DNA methylation that have recently been proposed to play crucial roles in rapid environmental adaptation. Invasive species, which have capacities to successfully survive rapidly changing environments during biological invasions, provide great opportunities to study molecular mechanisms of rapid environmental adaptation. Here, we used the methylation-sensitive amplified polymorphism (MSAP) technique in an invasive model ascidian, Ciona savignyi, to investigate how species interact with rapidly changing environments at the whole-genome level. We detected quite rapid DNA methylation response: significant changes of DNA methylation frequency and epigenetic differentiation between treatment and control groups occurred only after 1 hr of high-temperature exposure or after 3 hr of low-salinity challenge. In addition, we detected time-dependent hemimethylation changes and increased intragroup epigenetic divergence induced by environmental stresses. Interestingly, we found evidence of DNA methylation resilience, as most stress-induced DNA methylation variation maintained shortly (~48 hr) and quickly returned back to the control levels. Our findings clearly showed that invasive species could rapidly respond to acute environmental changes through DNA methylation modifications, and rapid environmental changes left significant epigenetic signatures at the whole-genome level. All these results provide fundamental background to deeply investigate the contribution of DNA methylation mechanisms to rapid contemporary environmental adaptation. © 2017 John Wiley & Sons Ltd.

  9. Normal Evoked Response to Rapid Sequences of Tactile Pulses in Autism Spectrum Disorders

    Directory of Open Access Journals (Sweden)

    Santosh Ganesan

    2016-09-01

    Full Text Available Autism spectrum disorder (ASD is a developmental disorder diagnosed behaviorally, with many documented neurophysiological abnormalities in cortical response properties. While abnormal sensory processing is not considered core to the disorder, most ASD individuals report sensory processing abnormalities. Yet, the neurophysiological correlates of these abnormalities have not been fully mapped. In the auditory domain, studies have shown that cortical responses in the early auditory cortex in ASD are abnormal in multiple ways. In particular, it has been shown that individuals with ASD who were also language impaired, have abnormal cortical auditory evoked responses to rapid, but not slow, sequences of tones. Here, we tested the somatosensory domain in ASD for abnormalities in rapid processing of tactile pulses, to determine whether abnormalities there parallel those observed in the auditory domain. Specifically, we tested the somatosensory cortex response to a sequence of two tactile pulses with different (short and long temporal separation. We analyzed the responses in cortical space, in primary somatosensory cortex. As expected, we found no group difference in the evoked response to pulses with long temporal separation. Contrary to findings in the auditory domain and to our hypothesis, we also found no group differences in the evoked responses to the sequence with a short temporal separation. These results suggest that rapid temporal processing deficits in ASD are not generalized across multiple sensory domains, and are unlikely to underlie the behavioral somatosensory abnormalities observed in ASD.

  10. Polyethylene glycol-functionalized poly (Lactic Acid-co-Glycolic Acid and graphene oxide nanoparticles induce pro-inflammatory and apoptotic responses in Candida albicans-infected vaginal epithelial cells.

    Directory of Open Access Journals (Sweden)

    R Doug Wagner

    Full Text Available Mucous-penetrating nanoparticles consisting of poly lactic acid-co-glycolic acid (PLGA-polyethylene glycol (PEG could improve targeting of microbicidal drugs for sexually transmitted diseases by intravaginal inoculation. Nanoparticles can induce inflammatory responses, which may exacerbate the inflammation that occurs in the vaginal tracts of women with yeast infections. This study evaluated the effects of these drug-delivery nanoparticles on VK2(E6/E7 vaginal epithelial cell proinflammatory responses to Candida albicans yeast infections. Vaginal epithelial cell monolayers were infected with C. albicans and exposed to 100 μg/ml 49.5 nm PLGA-PEG nanospheres or 20 μg/ml 1.1 x 500 nm PEG-functionalized graphene oxide (GO-PEG sheets. The cells were assessed for changes in mRNA and protein expression of inflammation-related genes by RT-qPCR and physiological markers of cell stress using high content analysis and flow cytometry. C. albicans exposure suppressed apoptotic gene expression, but induced oxidative stress in the cells. The nanomaterials induced cytotoxicity and programmed cell death responses alone and with C. albicans. PLGA-PEG nanoparticles induced mRNA expression of apoptosis-related genes and induced poly (ADP-ribose polymerase (PARP cleavage, increased BAX/BCL2 ratios, and chromatin condensation indicative of apoptosis. They also induced autophagy, endoplasmic reticulum stress, and DNA damage. They caused the cells to excrete inflammatory recruitment molecules chemokine (C-X-C motif ligand 1 (CXCL1, interleukin-1α (IL1A, interleukin-1β (IL1B, calprotectin (S100A8, and tumor necrosis factor α (TNF. GO-PEG nanoparticles induced expression of necrosis-related genes and cytotoxicity. They reduced autophagy and endoplasmic reticulum stress, and apoptotic gene expression responses. The results show that stealth nanoparticle drug-delivery vehicles may cause intracellular damage to vaginal epithelial cells by several mechanisms and that

  11. Value and challenges of conducting rapid response research on wildland fires

    Science.gov (United States)

    L. Lentile; P. Morgan; C. Hardy; A. Hudak; R. Means; R. Ottmar; P. Robichaud; E. Kennedy Sutherland; J. Szymoniak; F. Way; J. Fites-Kaufman; S. Lewis; E. Mathews; H. Shovik; K. Ryan

    2007-01-01

    Rapid Response Research is conducted during and immediately after wildland fires, in coordination with fire management teams, in order to collect information that can best be garnered in situ and in real-time. This information often includes fire behavior and fire effects data, which can be used to generate practical tools such as predictive fire models for managers....

  12. Financial consequences of the implementation of a rapid response system on a surgical ward

    NARCIS (Netherlands)

    Simmes, F.; Schoonhoven, L.; Mintjes, J.; Adang, E.M.; Hoeven, J.G. van der

    2014-01-01

    RATIONALE, AIMS AND OBJECTIVES: Rapid response systems (RRSs) are recommended by the Institute for Healthcare Improvement and implemented worldwide. Our study on the effects of an RRS showed a non-significant decrease in cardiac arrest and/or unexpected death from 0.5% to 0.25%. Unplanned intensive

  13. Voortekenen van verandering : Ervaringen met het implementeren van een rapid response-systeem

    NARCIS (Netherlands)

    Lex Smetsers; Hans van der Hoeven; Friede Simmes; Michael Edwards; Daan Sep; Maurice Peters

    2008-01-01

    Snel inspelen op veranderingen in de vitale functies van patiënten, levert een hoop winst op. Minder sterfgevallen en ook minder blijvende schade. In het UMC St Radboud heeft men dit streven met een rapid response-systeem in praktijk gebracht.

  14. Outcomes Associated With the Nationwide Introduction of Rapid Response Systems in The Netherlands

    NARCIS (Netherlands)

    Ludikhuize, Jeroen; Brunsveld-Reinders, Anja H.; Dijkgraaf, Marcel G. W.; Smorenburg, Susanne M.; de Rooij, Sophia E. J. A.; Adams, Rob; de Maaijer, Paul F.; Fikkers, Bernard G.; Tangkau, Peter; de Jonge, Evert; van Putten, M. A.; Kerkhoven, C.; Braber, A.; Schoonderbeek, F. J.; Kors, B. M.; Sep, D. P.; Vermeijden, J. W.; van der Weijden, P. K. C.; Koenders, S.; Meertens, M.; Brunsveld-Reinders, A. H.; Hoeksema, M.

    2015-01-01

    To describe the effect of implementation of a rapid response system on the composite endpoint of cardiopulmonary arrest, unplanned ICU admission, or death. Pragmatic prospective Dutch multicenter before-after trial, Cost and Outcomes analysis of Medical Emergency Teams trial. Twelve hospitals

  15. Outcomes Associated With the Nationwide Introduction of Rapid Response Systems in The Netherlands

    NARCIS (Netherlands)

    Ludikhuize, J.; Brunsveld-Reinders, A.H.; Dijkgraaf, M.G.; Smorenburg, S.M.; Rooij, S.E. De; Adams, R.; Maaijer, P.F. de; Fikkers, B.G.; Tangkau, P.; Jonge, E. de

    2015-01-01

    OBJECTIVE: To describe the effect of implementation of a rapid response system on the composite endpoint of cardiopulmonary arrest, unplanned ICU admission, or death. DESIGN: Pragmatic prospective Dutch multicenter before-after trial, Cost and Outcomes analysis of Medical Emergency Teams trial.

  16. 77 FR 35962 - Utilizing Rapidly Deployable Aerial Communications Architecture in Response to an Emergency

    Science.gov (United States)

    2012-06-15

    ... COMMISSION Utilizing Rapidly Deployable Aerial Communications Architecture in Response to an Emergency AGENCY... seeks comment on the role of deployable aerial communications architecture (DACA) in facilitating... eRulemaking Portal, or (3) by filing paper copies. Comments and reply comments may be filed...

  17. Cortical evoked potentials in response to rapid balloon distension of the rectum and anal canal

    DEFF Research Database (Denmark)

    Haas, S; Brock, C; Krogh, K

    2014-01-01

    BACKGROUND: Neurophysiological evaluation of anorectal sensory function is hampered by a paucity of methods. Rapid balloon distension (RBD) has been introduced to describe the cerebral response to rectal distension, but it has not successfully been applied to the anal canal. METHODS: Nineteen...

  18. Evaluation of a hospice rapid response community service: a controlled evaluation

    Directory of Open Access Journals (Sweden)

    Butler Claire

    2012-07-01

    Full Text Available Abstract Background While most people faced with a terminal illness would prefer to die at home, less than a third in England are enabled to do so with many dying in National Health Service hospitals. Patients are more likely to die at home if their carers receive professional support. Hospice rapid response teams, which provide specialist palliative care at home on a 24/7 on-call basis, are proposed as an effective way to help terminally ill patients die in their preferred place, usually at home. However, the effectiveness of rapid response teams has not been rigorously evaluated in terms of patient, carer and cost outcomes. Methods/Design The study is a pragmatic quasi-experimental controlled trial. The primary outcome for the quantitative evaluation for patients is dying in their preferred place of death. Carers’ quality of life will be evaluated using postal questionnaires sent at patient intake to the hospice service and eight months later. Carers’ perceptions of care received and the patient’s death will be assessed in one to one interviews at 6 to 8 months post bereavement. Service utilisation costs including the rapid response intervention will be compared to those of usual care. Discussion The study will contribute to the development of the evidence base on outcomes for patients and carers and costs of hospice rapid response teams operating in the community. Trial registration: Current controlled trials ISRCTN32119670.

  19. Early Detection Rapid Response Program Targets New Noxious Weed Species in Washington State

    Science.gov (United States)

    Andreas, Jennifer E.; Halpern, Alison D.; DesCamp, Wendy C.; Miller, Timothy W.

    2015-01-01

    Early detection, rapid response is a critical component of invasive plant management. It can be challenging, however, to detect new invaders before they become established if landowners cannot identify species of concern. In order to increase awareness, eye-catching postcards were developed in Washington State as part of a noxious weed educational…

  20. Cytostatic and apoptotic effects of paclitaxel in human ovarian tumors.

    Science.gov (United States)

    Millenbaugh, N J; Gan, Y; Au, J L

    1998-01-01

    The present study evaluated the cytostatic and apoptotic effects of a 24-hr paclitaxel treatment in ovarian tumors. Three-dimensional histocultures of surgical specimens from patients (n = 17) were used. The cytostatic effect was measured by inhibition of 96-hr cumulative DNA precursor incorporation and induction of apoptosis was determined by morphological changes. Paclitaxel produced partial inhibition of DNA precursor incorporation in about 40% of tumors (maximum inhibition of approximately 30%) and induced apoptosis in about 90% of tumors (maximum apoptotic index of approximately 15%). In responsive tumors, maximum cytostatic and apoptotic effects were achieved at < or = 1 microM with no further enhancement by increasing the drug concentration to 10 microM. In individual tumors, the apoptotic effect inversely correlated with cytostatic effect (r2 = 0.27, p = 0.031), and the maximal apoptotic index correlated with the LI for the untreated controls (r2 = 0.38, p < 0.01). More than 95% of apoptotic cells after paclitaxel treatment were labeled with DNA precursor. The incomplete cytostatic and apoptotic effects of paclitaxel and the link between DNA synthesis and apoptosis in ovarian tumors are similar to our previous findings in other human solid tumors. These findings suggest that (a) apoptosis is the major paclitaxel effect in advanced ovarian tumors, (b) tumor sensitivity to drug-induced cytostatic effect is opposite to sensitivity to apoptotic effect, (c) paclitaxel-induced apoptosis increases with increased cell proliferation and is completed after DNA synthesis, and (d) further increasing the dose to elevate plasma concentration beyond 1 microM may not improve treatment outcome.

  1. Response selection difficulty modulates the behavioral impact of rapidly learnt action effects.

    Directory of Open Access Journals (Sweden)

    Uta eWolfensteller

    2014-12-01

    Full Text Available It is well established that we can pick up action effect associations when acting in a free-choice intentional mode. However, it is less clear whether and when action effect associations are learnt and actually affect behavior if we are acting in a forced-choice mode, applying a specific stimulus-response (S-R rule. In the present study, we investigated whether response selection difficulty imposed by S-R rules influences the initial rapid learning and the behavioral expression of previously learnt but weakly practiced action effect associations when those are re-activated by effect exposure. Experiment 1 showed that the rapid acquisition of action effect associations is not directly influenced by response selection difficulty. By contrast, the behavioral expression of re-activated action effect associations is prevented when actions are directly activated by highly over-learnt response cues and thus response selection difficulty is low. However, all three experiments showed that if response selection difficulty is sufficiently high during re-activation, the same action effect associations do influence behavior. Experiment 2 and 3 revealed that the effect of response selection difficulty cannot be fully reduced to giving action effects more time to prime an action, but seems to reflect competition during response selection. Finally, the present data suggest that when multiple novel rules are rapidly learnt in succession, which requires a lot of flexibility, action effect associations continue to influence behavior only if response selection difficulty is sufficiently high. Thus, response selection difficulty might modulate the impact of experiencing multiple learning episodes on action effect expression and learning, possibly via inducing different strategies.

  2. A nationwide web-based automated system for early outbreak detection and rapid response in China

    Directory of Open Access Journals (Sweden)

    Yilan Liao

    2011-03-01

    Full Text Available Timely reporting, effective analyses and rapid distribution of surveillance data can assist in detecting the aberration of disease occurrence and further facilitate a timely response. In China, a new nationwide web-based automated system for outbreak detection and rapid response was developed in 2008. The China Infectious Disease Automated-alert and Response System (CIDARS was developed by the Chinese Center for Disease Control and Prevention based on the surveillance data from the existing electronic National Notifiable Infectious Diseases Reporting Information System (NIDRIS started in 2004. NIDRIS greatly improved the timeliness and completeness of data reporting with real time reporting information via the Internet. CIDARS further facilitates the data analysis, aberration detection, signal dissemination, signal response and information communication needed by public health departments across the country. In CIDARS, three aberration detection methods are used to detect the unusual occurrence of 28 notifiable infectious diseases at the county level and to transmit that information either in real-time or on a daily basis. The Internet, computers and mobile phones are used to accomplish rapid signal generation and dissemination, timely reporting and reviewing of the signal response results. CIDARS has been used nationwide since 2008; all Centers for Disease Control and Prevention (CDC in China at the county, prefecture, provincial and national levels are involved in the system. It assists with early outbreak detection at the local level and prompts reporting of unusual disease occurrences or potential outbreaks to CDCs throughout the country.

  3. Label-free, rapid and quantitative phenotyping of stress response in E. coli via ramanome.

    Science.gov (United States)

    Teng, Lin; Wang, Xian; Wang, Xiaojun; Gou, Honglei; Ren, Lihui; Wang, Tingting; Wang, Yun; Ji, Yuetong; Huang, Wei E; Xu, Jian

    2016-10-19

    Rapid profiling of stress-response at single-cell resolution yet in a label-free, non-disruptive and mechanism-specific manner can lead to many new applications. We propose a single-cell-level biochemical fingerprinting approach named "ramanome", which is the collection of Single-cell Raman Spectra (SCRS) from a number of cells randomly selected from an isogenic population at a given time and condition, to rapidly and quantitatively detect and characterize stress responses of cellular population. SCRS of Escherichia coli cells are sensitive to both exposure time (eight time points) and dosage (six doses) of ethanol, with detection time as early as 5 min and discrimination rate of either factor over 80%. Moreover, the ramanomes upon six chemical compounds from three categories, including antibiotics of ampicillin and kanamycin, alcohols of ethanol and n-butanol and heavy metals of Cu(2+) and Cr(6+), were analyzed and 31 marker Raman bands were revealed which distinguish stress-responses via cytotoxicity mechanism and variation of inter-cellular heterogeneity. Furthermore, specificity, reproducibility and mechanistic basis of ramanome were validated by tracking stress-induced dynamics of metabolites and by contrasting between cells with and without genes that convey stress resistance. Thus ramanome enables rapid prediction and mechanism-based screening of cytotoxicity and stress-response programs at single-cell resolution.

  4. Early warning systems and rapid response to the deteriorating patient in hospital: A realist evaluation.

    Science.gov (United States)

    McGaughey, Jennifer; O'Halloran, Peter; Porter, Sam; Trinder, John; Blackwood, Bronagh

    2017-12-01

    To test the Rapid Response Systems programme theory against actual practice components of the Rapid Response Systems implemented to identify those contexts and mechanisms which have an impact on the successful achievement of desired outcomes in practice. Rapid Response Systems allow deteriorating patients to be recognized using Early Warning Systems, referred early via escalation protocols and managed at the bedside by competent staff. Realist evaluation. The research design was an embedded multiple case study approach of four wards in two hospitals in Northern Ireland which followed the principles of Realist Evaluation. We used various mixed methods including individual and focus group interviews, observation of nursing practice between June-November 2010 and document analysis of Early Warning Systems audit data between May-October 2010 and hospital acute care training records over 4.5 years from 2003-2008. Data were analysed using NiVivo8 and SPPS. A cross-case analysis highlighted similar patterns of factors which enabled or constrained successful recognition, referral and response to deteriorating patients in practice. Key enabling factors were the use of clinical judgement by experienced nurses and the empowerment of nurses as a result of organizational change associated with implementation of Early Warning System protocols. Key constraining factors were low staffing and inappropriate skill mix levels, rigid implementation of protocols and culturally embedded suboptimal communication processes. Successful implementation of Rapid Response Systems was dependent on adopting organizational and cultural changes that facilitated staff empowerment, flexible implementation of protocols and ongoing experiential learning. © 2017 John Wiley & Sons Ltd.

  5. Multiple mucin depleted foci, high proliferation and low apoptotic response in the onset of colon carcinogenesis of the PIRC rat, mutated in Apc.

    Science.gov (United States)

    Femia, Angelo Pietro; Luceri, Cristina; Soares, Paulo Victoria; Lodovici, Maura; Caderni, Giovanna

    2015-03-15

    PIRC rats (F344/NTac-Apc (am1137) ) mutated in the Apc gene spontaneously develop colon tumors thus mimicking familial adenomatous polyposis (FAP) and sporadic colorectal cancer (CRC) more closely than Apc-based rodent models developing tumors mostly in the small intestine. To understand whether microscopic dysplastic lesions precede the development of macroscopic tumors, PIRC rat colon was examined for the presence of mucin depleted foci (MDF), microadenomas of the rodent and human colon. Few MDF (about 4/animal) were already present in 1-month-old rats and their number rapidly increases to about 250 in 8-month-old rats. These lesions showed Wnt signaling activation (nuclear β-catenin accumulation) and were dramatically decreased by sulindac (320 ppm), a drug with chemopreventive activity (MDF/rat at 4 months: 156 ± 8 and 38 ± 6 in controls and sulindac-treated rats, respectively, means ± SE, p rats. Colon proliferation (PCNA expression) was significantly higher in PIRC rats. Notably, PIRC rat NM showed resistance to apoptosis since it sustained proliferation and had lower apoptosis after a cytotoxic insult with 1,2 dimethylhydrazine. Gene expression of Myc, p21, Birc5, Ogg1, Apex1 and Sod2 were significantly up-regulated in the NM of PIRC rat. The overall results put forward PIRC rat as useful model of colon carcinogenesis, either to study the process itself or to test in vivo chemopreventive agents in both short- and long-term studies. © 2014 UICC.

  6. Cytoprotective effect of autophagy on phagocytosis of apoptotic cells by macrophages.

    Science.gov (United States)

    Zhou, Pei; Tan, Yu-Zhen; Wang, Hai-Jie; Li, Ting; He, Tao; Yu, Ying; Zhang, Jian; Zhang, Dan

    2016-11-01

    Clearance of the apoptotic cells by phagocytes plays pivotal roles in maintenance of tissue homeostasis, promotion of immunological tolerance and anti-inflammatory response. Recent studies show that autophagy is involved in phagocytosis of the apoptotic cells. However, contribution of autophagy to phagocytosis of the apoptotic cells by macrophages is not clearly defined. Here, we assessed cytoprotective effect of autophagy on clearance of the apoptotic cells. Apoptosis of murine splenic lymphocytes and human T-cell leukemia cells was induced with cyclophosphamide. After engulfment of the apoptotic cells, expression of Belin-1 and LC3 in macrophages was upregulated, the number of MDC-positive vesicles, LC3-positive autophagosomes and autophagic ultrastructures increased significantly. Autophagosome was fused with phagosome containing fragments of the nuclei or other debris of the apoptotic cells to form amphisome. Some cells in macrophages phagocytosing the apoptotic cells became apoptotic. After autophagy of macrophages was inhibited with 3-MA, viability and survival of macrophages reduced, phagocytosis of the apoptotic cells by macrophages deceased significantly. These results demonstrate that autophagy plays an important role in promoting clearance of the apoptotic cells by protecting macrophages from apoptosis during phagocytosis as well as degrading the contents of phagosomes via amphisome formation. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Sustaining Health Care Interventions to Achieve Quality Care: What We Can Learn From Rapid Response Teams.

    Science.gov (United States)

    Stolldorf, Deonni P

    Rapid response team (RRT) adoption and implementation are associated with improved quality of care of patients who experience an unanticipated medical emergency. The sustainability of RRTs is vital to achieve long-term benefits of these teams for patients, staff, and hospitals. Factors required to achieve RRT sustainability remain unclear. This study examined the relationship between sustainability elements and RRT sustainability in hospitals that have previously implemented RRTs.

  8. Nurses' perceptions of simulation-based interprofessional training program for rapid response and code blue events.

    Science.gov (United States)

    Wehbe-Janek, Hania; Lenzmeier, Carissa R; Ogden, Paul E; Lambden, Mary Pat; Sanford, Pamela; Herrick, Judy; Song, Juhee; Pliego, Jose F; Colbert, Colleen Y

    2012-01-01

    Following completion of an interprofessional simulation program for rapid response and code blue events, we explored hospital unit nurses' perspectives of the training, through a mixed-methods analysis. The results of this study advocate for the use of simulation training in preparing nurses and promoting communication among team members, effective teamwork, and early recognition of clinically deteriorating patients. This study provides support for the implementation and continued use of simulation interprofessional programs in hospital settings.

  9. Rapid Adjustments Cause Weak Surface Temperature Response to Increased Black Carbon Concentrations

    Science.gov (United States)

    Stjern, Camilla Weum; Samset, Bjørn Hallvard; Myhre, Gunnar; Forster, Piers M.; Hodnebrog, Øivind; Andrews, Timothy; Boucher, Olivier; Faluvegi, Gregory; Iversen, Trond; Kasoar, Matthew; Kharin, Viatcheslav; Kirkevâg, Alf; Lamarque, Jean-François; Olivié, Dirk; Richardson, Thomas; Shawki, Dilshad; Shindell, Drew; Smith, Christopher J.; Takemura, Toshihiko; Voulgarakis, Apostolos

    2017-11-01

    We investigate the climate response to increased concentrations of black carbon (BC), as part of the Precipitation Driver Response Model Intercomparison Project (PDRMIP). A tenfold increase in BC is simulated by nine global coupled-climate models, producing a model median effective radiative forcing of 0.82 (ranging from 0.41 to 2.91) W m-2, and a warming of 0.67 (0.16 to 1.66) K globally and 1.24 (0.26 to 4.31) K in the Arctic. A strong positive instantaneous radiative forcing (median of 2.10 W m-2 based on five of the models) is countered by negative rapid adjustments (-0.64 W m-2 for the same five models), which dampen the total surface temperature signal. Unlike other drivers of climate change, the response of temperature and cloud profiles to the BC forcing is dominated by rapid adjustments. Low-level cloud amounts increase for all models, while higher-level clouds are diminished. The rapid temperature response is particularly strong above 400 hPa, where increased atmospheric stabilization and reduced cloud cover contrast the response pattern of the other drivers. In conclusion, we find that this substantial increase in BC concentrations does have considerable impacts on important aspects of the climate system. However, some of these effects tend to offset one another, leaving a relatively small median global warming of 0.47 K per W m-2—about 20% lower than the response to a doubling of CO2. Translating the tenfold increase in BC to the present-day impact of anthropogenic BC (given the emissions used in this work) would leave a warming of merely 0.07 K.

  10. A rapid challenge protocol for determination of non-specific bronchial responsiveness

    DEFF Research Database (Denmark)

    Madsen, F; Nielsen, N H; Holstein-Rathlou, N H

    1986-01-01

    A rapid method for determination of non-specific bronchial hyperreactivity was developed. Resistance to breathing was determined by a modified expiratory airway interrupter technique and combined with a dosimeter-controlled nebulizer which made continuous determination of response possible during...... well to a non-cumulative standard protocol and could be terminated either within 10 min or within 20 inhalations. The results of this new challenge procedure enables us to predict the responsiveness to inhaled histamine precisely enough to separate patients into hyperreactive or normal reactive...

  11. Rapid bedrock uplift in the Antarctic Peninsula explained by viscoelastic response to recent ice unloading

    DEFF Research Database (Denmark)

    Nield, Grace A.; Barletta, Valentina Roberta; Bordoni, Andrea

    2014-01-01

    Since 1995 several ice shelves in the Northern Antarctic Peninsula have collapsed and triggered ice-mass unloading, invoking a solid Earth response that has been recorded at continuous GPS (cGPS) stations. A previous attempt to model the observation of rapid uplift following the 2002 breakup......×1017–2×1018 Pas – much lower than previously suggested for this region. Combining the LARISSA time series with the Palmer cGPS time series offers a rare opportunity to study the time-evolution of the low-viscosity solid Earth response to a well-captured ice unloading event....

  12. Rapid adaptive evolution of photoperiodic response during invasion and range expansion across a climatic gradient.

    Science.gov (United States)

    Urbanski, Jennifer; Mogi, Motoyoshi; O'Donnell, Deborah; DeCotiis, Mark; Toma, Takako; Armbruster, Peter

    2012-04-01

    Abstract Understanding the mechanisms of adaptation to spatiotemporal environmental variation is a fundamental goal of evolutionary biology. This issue also has important implications for anticipating biological responses to contemporary climate warming and determining the processes by which invasive species are able to spread rapidly across broad geographic ranges. Here, we compare data from a historical study of latitudinal variation in photoperiodic response among Japanese and U.S. populations of the invasive Asian tiger mosquito Aedes albopictus with contemporary data obtained using comparable methods. Our results demonstrated rapid adaptive evolution of the photoperiodic response during invasion and range expansion across ∼15° of latitude in the United States. In contrast to the photoperiodic response, size-based morphological traits implicated in climatic adaptation in a wide range of other insects did not show evidence of adaptive variation in Ae. albopictus across either the U.S. (invasive) or Japanese (native) range. These results show that photoperiodism has been an important adaptation to climatic variation across the U.S. range of Ae. albopictus and, in conjunction with previous studies, strongly implicate the photoperiodic control of seasonal development as a critical evolutionary response to ongoing contemporary climate change. These results also emphasize that photoperiodism warrants increased attention in studies of the evolution of invasive species.

  13. Rapid effects of olopatadine hydrochloride on the histamine-induced skin responses.

    Science.gov (United States)

    Morita, Keisuke; Koga, Tetsuya; Moroi, Yoichi; Urabe, Kazunori; Furue, Masutaka

    2002-11-01

    Olopatadine hydrochloride is one of the second-generation nonsedating antihistamines that are used for treating allergic disorders such as urticaria, rhinitis, and atopic dermatitis. We examined the inhibitory effects of this drug on the flare and wheal responses induced by histamine iontophoresis at 30, 60, and 90 min after oral administration in a double-blind, cross-over, and placebo-controlled study. Olopatadine hydrochloride significantly inhibited the histamine-induced flare and wheal responses as early as 60 min after oral administration when compared with placebo. Significant inihibitory effects of olopatadine hydrochloride on the itch responses were seen at 90 min after administration. Thus, olopatadine hydrochloride exhibited a very rapid and potent antihistamine effect on the histamine-induced skin responses.

  14. Establishing a rapid response team (RRT) in an academic hospital: one year's experience.

    Science.gov (United States)

    King, Emmanuel; Horvath, Rebecca; Shulkin, David J

    2006-09-01

    Rapid response teams and medical emergency teams have been utilized to rapidly manage seriously ill patients at risk of cardiopulmonary arrest and other high-risk conditions but have not been extensively described in the American medical literature. To describe a full year's experience of implementing a rapid response team (RRT) in an academic medical center. Retrospective analysis of our hospital's RRT database and description of the implementation process from July 2004 to July 2005. Urban, academic medical center. The RRT system was activated for 307 potentially unstable patients. The most common reasons for an RRT activation were cardiac, respiratory, and neurological conditions. At least 37% of RRT calls were for off-unit inpatients and to outpatient/common areas frequented by outpatients and visitors, whereas at least 42% occurred in inpatient units. Most RRT calls, 82.9%, occurred during daytime hours. In the opinion of RRT leaders 98% of the evaluated calls were appropriate and 85% of the RRT responses resulted in the prevention of further clinical deterioration. An RRT was introduced into an academic medical center, and the results suggested it is capable of preventing clinical deterioration in unstable patients and may have the potential to decrease the frequency of cardiac arrests. The RRT also may fill a gap in patient safety by enabling rapid triage and expedited treatment of off-unit inpatients, outpatients, and visitors. The keys to the early success of our implementation of an RRT were multidisciplinary input and improvements made in real time. (c) 2006 Society of Hospital Medicine.

  15. Urgent Need to Orient Public Health Response to Rapid Nutrition Transition

    Directory of Open Access Journals (Sweden)

    Umesh Kapil

    2012-01-01

    Full Text Available India is currently undergoing a rapid transition on economic, demographic, epidemiologic, nutrition, and sociological fronts. There is evidence of a decline in undernutrition with a simultaneous escalation in overnutrition and associated non-communicable diseases (NCDs. However, the current concern and national policy response for tackling malnutrition in India is still primarily restricted to undernutrition diagnosed on the basis of body size (anthropometry. A complex range of interacting factors have been linked to the rising trend of overnutrition and associated NCDs from a global perspective. The burden of overnutrition and associated morbidities is rapidly escalating to alarming proportions, particularly in urban areas and high socio-economic status groups. The poor are not spared from this transition. It is predicted that a more rapid transition may occur amongst poor populations in future with higher economic development. The need of the hour is to launch an integrated public health response to the dual burden beginning from pregnancy and early life. This will obviously require careful deliberation of the strategy and interventions, and a multi-sectoral approach, especially involving the health, women and child development, nutrition, education, agriculture, food processing, trade, architecture, water supply and sanitation, community and non-governmental organizations.

  16. Calcein+/PI- as an early apoptotic feature in Leishmania.

    Science.gov (United States)

    Basmaciyan, Louise; Azas, Nadine; Casanova, Magali

    2017-01-01

    Although leishmaniases are responsible for high morbidity and mortality all over the world, no really satisfying treatment exists. Furthermore, the corresponding parasite Leishmania undergoes a very characteristic form of programmed cell death. Indeed, different stimuli can induce morphological and biochemical apoptotic-like features. However, the key proteins involved in mammal apoptosis, such as caspases and death receptors, are not encoded in the genome of this parasite. Currently, little is known about Leishmania apoptosis, notably owing to the lack of specific tools for programmed cell death analysis in these parasites. Furthermore, there is a need for a better understanding of Leishmania programmed cell death in order (i) to better understand the role of apoptosis in unicellular organisms, (ii) to better understand apoptosis in general through the study of an ancestral eukaryote, and (iii) to identify new therapeutic targets against leishmaniases. To advance understanding of apoptosis in Leishmania, in this study we developed a new tool based on the quantification of calcein and propidium iodide by flow cytometry. This double labeling can be employed to distinguish early apoptosis, late apoptosis and necrosis in Leishmania live cells with a very simple and rapid assay. This paper should, therefore, be of interest for people working on Leishmania and related parasites.

  17. Initiation of a Multidisciplinary, Rapid Response Team to Massive and Submassive Pulmonary Embolism.

    Science.gov (United States)

    Carroll, Brett J; Pemberton, Heather; Bauer, Kenneth A; Chu, Louis M; Weinstein, Jeffrey L; Levarge, Barbara L; Pinto, Duane S

    2017-10-15

    Pulmonary embolism (PE) can result in rapid clinical decompensation in many patients. With increasing patient complexity and advanced treatment options for PE, multidisciplinary, rapid response teams can optimize risk stratification and expedite management strategies. The Massive And Submassive Clot On-call Team (MASCOT) was created at our institution, which comprised specialists from cardiology, pulmonology, hematology, interventional radiology, and cardiac surgery. MASCOT offers rapid consultation 24 hours a day with a web-based conference call to review patient data and discuss management of patients with high-risk PE. We reviewed patient data collected from MASCOT's registry to analyze patient clinical characteristics and outcomes and describe the composition and operation of the team. Between August 2015 and September 2016, MASCOT evaluated 72 patients. Seventy of the 72 patients were admitted to our institution, accounting for 32% of all patients discharged with a primary diagnosis of PE. Average age was 62 ± 17 years with a female predominance (63%). Active malignancy (31%), recent surgery or trauma (21%), and recent hospitalization (24%) were common. PE clinical severity was massive in 16% and submassive in 83%. Patients were managed with anticoagulation alone in 65% (n = 46), systemic fibrinolysis in 11% (n = 8), catheter-directed therapy in 18% (n = 13), extracorporeal membrane oxygenation in 3% (n = 2), and an inferior vena cava filter was placed in 15% (n = 11). Thirteen percent (n = 9) experienced a major bleed with no intracranial hemorrhage. Survival to discharge was 89% (64% with massive PE and 93% with submassive PE). In conclusion, multidisciplinary, rapid response PE teams offer a unique coordinated approach to patient care. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Scopolamine rapidly increases mammalian target of rapamycin complex 1 signaling, synaptogenesis, and antidepressant behavioral responses.

    Science.gov (United States)

    Voleti, Bhavya; Navarria, Andrea; Liu, Rong-Jian; Banasr, Mounira; Li, Nanxin; Terwilliger, Rose; Sanacora, Gerard; Eid, Tore; Aghajanian, George; Duman, Ronald S

    2013-11-15

    Clinical studies report that scopolamine, an acetylcholine muscarinic receptor antagonist, produces rapid antidepressant effects in depressed patients, but the mechanisms underlying the therapeutic response have not been determined. The present study examines the role of the mammalian target of rapamycin complex 1 (mTORC1) and synaptogenesis, which have been implicated in the rapid actions of N-methyl-D-aspartate receptor antagonists. The influence of scopolamine on mTORC1 signaling was determined by analysis of the phosphorylated and activated forms of mTORC1 signaling proteins in the prefrontal cortex (PFC). The numbers and function of spine synapses were analyzed by whole cell patch clamp recording and two-photon image analysis of PFC neurons. The actions of scopolamine were examined in the forced swim test in the absence or presence of selective mTORC1 and glutamate receptor inhibitors. The results demonstrate that a single, low dose of scopolamine rapidly increases mTORC1 signaling and the number and function of spine synapses in layer V pyramidal neurons in the PFC. Scopolamine administration also produces an antidepressant response in the forced swim test that is blocked by pretreatment with the mTORC1 inhibitor or by a glutamate alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor antagonist. Taken together, the results demonstrate that the antidepressant actions of scopolamine require mTORC1 signaling and are associated with increased glutamate transmission, and synaptogenesis, similar to N-methyl-D-aspartate receptor antagonists. These findings provide novel targets for safer and more efficacious rapid-acting antidepressant agents. © 2013 Society of Biological Psychiatry.

  19. Rapid Response Team Calls and Unplanned Transfers to the Pediatric Intensive Care Unit in a Pediatric Hospital.

    Science.gov (United States)

    Humphreys, Stacey; Totapally, Balagangadhar R

    2016-01-01

    Variability in disposition of children according to the time of rapid response calls is unknown. To evaluate times and disposition of rapid response alerts and outcomes for children transferred from acute care to intensive care. Deidentified data on demographics, time and disposition of the child after activation of a rapid response, time of transfer to intensive care, and patient outcomes were reviewed retrospectively. Data for rapid-response patients on time of activation of the response and unplanned transfers to the intensive care unit were compared with data on other patients admitted to the unit. Of 542 rapid responses activated, 321 (59.2%) were called during the daytime. Out of all rapid response activations, 323 children (59.6%) were transferred to intensive care, 164 (30.3%) remained on the general unit, and 19 (3.5%) required resuscitation. More children were transferred to intensive care after rapid response alerts (P = .048) during the daytime (66%) than at night (59%). During the same period, 1313 patients were transferred to intensive care from acute care units. Age, sex, risk of mortality, length of stay, and mortality rate did not differ according to the time of transfer. Mortality among unplanned transfers (3.8%) was significantly higher (P intensive care patients (1.4%). Only 25% of transfers from acute care units to the intensive care unit occurred after activation of a rapid response team. Most rapid responses were called during daytime hours. Mortality was significantly higher among unplanned transfers from acute care than among other intensive care admissions. ©2016 American Association of Critical-Care Nurses.

  20. Avoiding math on a rapid timescale: Emotional responsivity and anxious attention in math anxiety.

    Science.gov (United States)

    Pizzie, Rachel G; Kraemer, David J M

    2017-11-01

    Math anxiety (MA) is characterized by negative feelings towards mathematics, resulting in avoidance of math classes and of careers that rely on mathematical skills. Focused on a long timescale, this research may miss important cognitive and affective processes that operate moment-to-moment, changing rapid reactions even when a student simply sees a math problem. Here, using fMRI with an attentional deployment paradigm, we show that MA influences rapid spontaneous emotional and attentional responses to mathematical stimuli upon brief presentation. Critically, participants viewed but did not attempt to solve the problems. Indicating increased threat reactivity to even brief presentations of math problems, increased MA was associated with increased amygdala response during math viewing trials. Functionally and anatomically defined amygdala ROIs yielded similar results, indicating robustness of the finding. Similar to the pattern of vigilance and avoidance observed in specific phobia, behavioral results of the attentional paradigm demonstrated that MA is associated with attentional disengagement for mathematical symbols. This attentional avoidance is specific to math stimuli; when viewing negatively-valenced images, MA is correlated with attentional engagement, similar to other forms of anxiety. These results indicate that even brief exposure to mathematics triggers a neural response related to threat avoidance in highly MA individuals. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Glyphosate resistance in Ambrosia trifida: Part 1. Novel rapid cell death response to glyphosate.

    Science.gov (United States)

    Van Horn, Christopher R; Moretti, Marcelo L; Robertson, Renae R; Segobye, Kabelo; Weller, Stephen C; Young, Bryan G; Johnson, William G; Schulz, Burkhard; Green, Amanda C; Jeffery, Taylor; Lespérance, Mackenzie A; Tardif, François J; Sikkema, Peter H; Hall, J Christopher; McLean, Michael D; Lawton, Mark B; Sammons, R Douglas; Wang, Dafu; Westra, Philip; Gaines, Todd A

    2017-03-07

    Glyphosate-resistant (GR) Ambrosia trifida is now present in the midwestern United States and in southwestern Ontario, Canada. Two distinct GR phenotypes are known, including a rapid response (GR RR) phenotype, which exhibits cell death within hours after treatment, and a non-rapid response (GR NRR) phenotype. The mechanisms of resistance in both GR RR and GR NRR remain unknown. Here, we present a description of the RR phenotype and an investigation of target-site mechanisms on multiple A. trifida accessions. Glyphosate resistance was confirmed in several accessions, and whole-plant levels of resistance ranged from 2.3- to 7.5-fold compared with glyphosate-susceptible (GS) accessions. The two GR phenotypes displayed similar levels of resistance, despite having dramatically different phenotypic responses to glyphosate. Glyphosate resistance was not associated with mutations in EPSPS sequence, increased EPSPS copy number, EPSPS quantity, or EPSPS activity. These encompassing results suggest that resistance to glyphosate in these GR RR A. trifida accessions is not conferred by a target-site resistance mechanism. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  2. A Stimuli-Responsive, Binary Reagent System for Rapid Isolation of Protein Biomarkers.

    Science.gov (United States)

    Nehilla, Barrett J; Hill, John J; Srinivasan, Selvi; Chen, Yen-Chi; Schulte, Thomas H; Stayton, Patrick S; Lai, James J

    2016-11-01

    Magnetic microbeads exhibit rapid separation characteristics and are widely employed for biomolecule and cell isolations in research laboratories, clinical diagnostics assays, and cell therapy manufacturing. However, micrometer particle diameters compromise biomarker recognition, which leads to long incubation times and significant reagent demands. Here, a stimuli-responsive binary reagent system is presented that combines the nanoscale benefits of efficient biomarker recognition and the microscale benefits of rapid magnetic separation. This system comprises magnetic nanoparticles and polymer-antibody (Ab) conjugates that transition from hydrophilic nanoscale reagents to microscale aggregates in response to temperature stimuli. The binary reagent system was benchmarked against Ab-labeled Dynabeads in terms of biomarker isolation kinetics, assay speed, and reagent needs. Surface plasmon resonance (SPR) measurements showed that polymer conjugation did not significantly alter the Ab's binding affinity or kinetics. ELISA analysis showed that the unconjugated Ab, polymer-Ab conjugates, and Ab-labeled Dynabeads exhibited similar equilibrium dissociation constants (K d ), ∼2 nM. However, the binary reagent system isolated HIV p24 antigen from spiked serum specimens (150 pg/mL) much more quickly than Dynabeads, which resulted in shorter binding times by tens of minutes, or about 30-50% shorter overall assay times. The binary reagent system showed improved performance because the Ab molecules were not conjugated to large, solid microparticle surfaces. This stimuli-responsive binary reagent system illustrates the potential advantages of nanoscale reagents in molecule and cell isolations for both research and clinical applications.

  3. Efficient 3D frequency response modeling with spectral accuracy by the rapid expansion method

    KAUST Repository

    Chu, Chunlei

    2012-07-01

    Frequency responses of seismic wave propagation can be obtained either by directly solving the frequency domain wave equations or by transforming the time domain wavefields using the Fourier transform. The former approach requires solving systems of linear equations, which becomes progressively difficult to tackle for larger scale models and for higher frequency components. On the contrary, the latter approach can be efficiently implemented using explicit time integration methods in conjunction with running summations as the computation progresses. Commonly used explicit time integration methods correspond to the truncated Taylor series approximations that can cause significant errors for large time steps. The rapid expansion method (REM) uses the Chebyshev expansion and offers an optimal solution to the second-order-in-time wave equations. When applying the Fourier transform to the time domain wavefield solution computed by the REM, we can derive a frequency response modeling formula that has the same form as the original time domain REM equation but with different summation coefficients. In particular, the summation coefficients for the frequency response modeling formula corresponds to the Fourier transform of those for the time domain modeling equation. As a result, we can directly compute frequency responses from the Chebyshev expansion polynomials rather than the time domain wavefield snapshots as do other time domain frequency response modeling methods. When combined with the pseudospectral method in space, this new frequency response modeling method can produce spectrally accurate results with high efficiency. © 2012 Society of Exploration Geophysicists.

  4. Rapid response predicts 12-month post-treatment outcomes in binge-eating disorder: theoretical and clinical implications

    Science.gov (United States)

    Grilo, C. M.; White, M. A.; Wilson, G. T.; Gueorguieva, R.; Masheb, R. M.

    2011-01-01

    Background We examined rapid response in obese patients with binge-eating disorder (BED) in a clinical trial testing cognitive behavioral therapy (CBT) and behavioral weight loss (BWL). Method Altogether, 90 participants were randomly assigned to CBT or BWL. Assessments were performed at baseline, throughout and post-treatment and at 6- and 12-month follow-ups. Rapid response, defined as ≥70% reduction in binge eating by week four, was determined by receiver operating characteristic curves and used to predict outcomes. Results Rapid response characterized 57% of participants (67% of CBT, 47% of BWL) and was unrelated to most baseline variables. Rapid response predicted greater improvements across outcomes but had different prognostic significance and distinct time courses for CBT versus BWL. Patients receiving CBT did comparably well regardless of rapid response in terms of reduced binge eating and eating disorder psychopathology but did not achieve weight loss. Among patients receiving BWL, those without rapid response failed to improve further. However, those with rapid response were significantly more likely to achieve binge-eating remission (62% v. 13%) and greater reductions in binge-eating frequency, eating disorder psychopathology and weight loss. Conclusions Rapid response to treatment in BED has prognostic significance through 12-month follow-up, provides evidence for treatment specificity and has clinical implications for stepped-care treatment models for BED. Rapid responders who receive BWL benefit in terms of both binge eating and short-term weight loss. Collectively, these findings suggest that BWL might be a candidate for initial intervention in stepped-care models with an evaluation of progress after 1 month to identify non-rapid responders who could be advised to consider a switch to a specialized treatment. PMID:21923964

  5. Rapid post-earthquake modelling of coseismic landslide intensity and distribution for emergency response decision support

    Directory of Open Access Journals (Sweden)

    T. R. Robinson

    2017-09-01

    Full Text Available Current methods to identify coseismic landslides immediately after an earthquake using optical imagery are too slow to effectively inform emergency response activities. Issues with cloud cover, data collection and processing, and manual landslide identification mean even the most rapid mapping exercises are often incomplete when the emergency response ends. In this study, we demonstrate how traditional empirical methods for modelling the total distribution and relative intensity (in terms of point density of coseismic landsliding can be successfully undertaken in the hours and days immediately after an earthquake, allowing the results to effectively inform stakeholders during the response. The method uses fuzzy logic in a GIS (Geographic Information Systems to quickly assess and identify the location-specific relationships between predisposing factors and landslide occurrence during the earthquake, based on small initial samples of identified landslides. We show that this approach can accurately model both the spatial pattern and the number density of landsliding from the event based on just several hundred mapped landslides, provided they have sufficiently wide spatial coverage, improving upon previous methods. This suggests that systematic high-fidelity mapping of landslides following an earthquake is not necessary for informing rapid modelling attempts. Instead, mapping should focus on rapid sampling from the entire affected area to generate results that can inform the modelling. This method is therefore suited to conditions in which imagery is affected by partial cloud cover or in which the total number of landslides is so large that mapping requires significant time to complete. The method therefore has the potential to provide a quick assessment of landslide hazard after an earthquake and may therefore inform emergency operations more effectively compared to current practice.

  6. Rapid post-earthquake modelling of coseismic landslide intensity and distribution for emergency response decision support

    Science.gov (United States)

    Robinson, Tom R.; Rosser, Nicholas J.; Densmore, Alexander L.; Williams, Jack G.; Kincey, Mark E.; Benjamin, Jessica; Bell, Heather J. A.

    2017-09-01

    Current methods to identify coseismic landslides immediately after an earthquake using optical imagery are too slow to effectively inform emergency response activities. Issues with cloud cover, data collection and processing, and manual landslide identification mean even the most rapid mapping exercises are often incomplete when the emergency response ends. In this study, we demonstrate how traditional empirical methods for modelling the total distribution and relative intensity (in terms of point density) of coseismic landsliding can be successfully undertaken in the hours and days immediately after an earthquake, allowing the results to effectively inform stakeholders during the response. The method uses fuzzy logic in a GIS (Geographic Information Systems) to quickly assess and identify the location-specific relationships between predisposing factors and landslide occurrence during the earthquake, based on small initial samples of identified landslides. We show that this approach can accurately model both the spatial pattern and the number density of landsliding from the event based on just several hundred mapped landslides, provided they have sufficiently wide spatial coverage, improving upon previous methods. This suggests that systematic high-fidelity mapping of landslides following an earthquake is not necessary for informing rapid modelling attempts. Instead, mapping should focus on rapid sampling from the entire affected area to generate results that can inform the modelling. This method is therefore suited to conditions in which imagery is affected by partial cloud cover or in which the total number of landslides is so large that mapping requires significant time to complete. The method therefore has the potential to provide a quick assessment of landslide hazard after an earthquake and may therefore inform emergency operations more effectively compared to current practice.

  7. [Rapid Response obstetrics Team at Instituto Mexicano del Seguro Social,enabling factors].

    Science.gov (United States)

    Dávila-Torres, Javier; González-Izquierdo, José de Jesús; Ruíz-Rosas, Roberto Aguli; Cruz-Cruz, Polita Del Rocío; Hernández-Valencia, Marcelino

    2015-01-01

    There are barriers and enablers for the implementation of Rapid Response Teams in obstetric hospitals. The enabling factors were determined at Instituto Mexicano del Seguro Social (IMSS) MATERIAL AND METHODS: An observational, retrospective study was conducted by analysing the emergency obstetric reports sent by mobile technology and e-mail to the Medical Care Unit of the IMSS in 2013. Frequency and mean was obtained using the Excel 2010 program for descriptive statistics. A total of 164,250 emergency obstetric cases were reported, and there was a mean of 425 messages per day, of which 32.2% were true obstetric emergencies and required the Rapid Response team. By e-mail, there were 73,452 life threatening cases (a mean of 6 cases per day). A monthly simulation was performed in hospitals (480 in total). Enabling factors were messagés synchronisation among the participating personnel,the accurate record of the obstetrics, as well as the simulations performed by the operational staff. The most common emergency was pre-eclampsia-eclampsia with 3,351 reports, followed by obstetric haemorrhage with 2,982 cases. The enabling factors for the implementation of a rapid response team at IMSS were properly timed communication between the central delegation teams, as they allowed faster medical and administrative management and participation of hospital medical teams in the process. Mobile technology has increased the speed of medical and administrative management in emergency obstetric care. However, comparative studies are needed to determine the statistical significance. Published by Masson Doyma México S.A.

  8. The regulation of apoptotic cell death

    Directory of Open Access Journals (Sweden)

    G.P. Amarante-Mendes

    1999-09-01

    Full Text Available Apoptosis is a fundamental biological phenomenon in which the death of a cell is genetically and biochemically regulated. Different molecules are involved in the regulation of the apoptotic process. Death receptors, coupled to distinct members of the caspases as well as other adapter molecules, are involved in the initiation of the stress signals (The Indictment. Members of the Bcl-2 family control at the mitochondrial level the decision between life and death (The Judgement. The effector caspases are responsible for all morphological and biochemical changes related to apoptosis including the "eat-me" signals perceived by phagocytes and neighboring cells (The Execution. Finally, apoptosis would have little biological significance without the recognition and removal of the dying cells (The Burial.

  9. The regulation of apoptotic cell death

    Directory of Open Access Journals (Sweden)

    Amarante-Mendes G.P.

    1999-01-01

    Full Text Available Apoptosis is a fundamental biological phenomenon in which the death of a cell is genetically and biochemically regulated. Different molecules are involved in the regulation of the apoptotic process. Death receptors, coupled to distinct members of the caspases as well as other adapter molecules, are involved in the initiation of the stress signals (The Indictment. Members of the Bcl-2 family control at the mitochondrial level the decision between life and death (The Judgement. The effector caspases are responsible for all morphological and biochemical changes related to apoptosis including the "eat-me" signals perceived by phagocytes and neighboring cells (The Execution. Finally, apoptosis would have little biological significance without the recognition and removal of the dying cells (The Burial.

  10. Rapid evolutionary responses of life history traits to different experimentally-induced pollutions in Caenorhabditis elegans.

    Science.gov (United States)

    Dutilleul, Morgan; Bonzom, Jean-Marc; Lecomte, Catherine; Goussen, Benoit; Daian, Fabrice; Galas, Simon; Réale, Denis

    2014-12-10

    Anthropogenic disturbances can lead to intense selection pressures on traits and very rapid evolutionary changes. Evolutionary responses to environmental changes, in turn, reflect changes in the genetic structure of the traits, accompanied by a reduction of evolutionary potential of the populations under selection. Assessing the effects of pollutants on the evolutionary responses and on the genetic structure of populations is thus important to understanding the mechanisms that entail specialization to novel environmental conditions or resistance to novel stressors. Using an experimental evolution approach we exposed Caenorhabditis elegans populations to uranium, salt and alternating uranium-salt environments over 22 generations. We analyzed the changes in the average values of life history traits and the consequences at the demographic level in these populations. We also estimated the phenotypic and genetic (co)variance structure of these traits at different generations. Compared to populations in salt, populations in uranium showed a reduction of the stability of their trait structure and a higher capacity to respond by acclimation. However, the evolutionary responses of traits were generally lower for uranium compared to salt treatment; and the evolutionary responses to the alternating uranium-salt environment were between those of constant environments. Consequently, at the end of the experiment, the population rate of increase was higher in uranium than in salt and intermediate in the alternating environment. Our multigenerational experiment confirmed that rapid adaptation to different polluted environments may involve different evolutionary responses resulting in demographic consequences. These changes are partly explained by the effects of the pollutants on the genetic (co)variance structure of traits and the capacity of acclimation to novel conditions. Finally, our results in the alternating environment may confirm the selection of a generalist type in this

  11. Factors Leading to Rapid Response Team Interventions in Adult Medical-Surgical Patients.

    Science.gov (United States)

    Tarver, Christine M; Stuenkel, Diane

    2016-01-01

    The effectiveness of a Rapid Response Team Intervention (RRTI) in preventing transfer to a higher level of care and decreasing in-hospital mortality has not been firmly established. This retrospective exploratory study examined differences between medical-surgical patients who had an RRTI and those who did not. Results yielded 5 statistically significant differences (P ≤ .05) between the 2 groups as well as a large variation (range, 0-238 minutes; SD = 87.73 minutes) between time of documentation of RRTI criteria to time in calling an RRTI.

  12. Biochemical identification of a neutral sphingomyelinase 1 (NSM1)-like enzyme as the major NSM activity in the DT40 B-cell line: absence of a role in the apoptotic response to endoplasmic reticulum stress.

    Science.gov (United States)

    Fensome, Amanda C; Josephs, Michelle; Katan, Matilda; Rodrigues-Lima, Fernando

    2002-01-01

    DT40 cells have approx. 10-fold higher Mg2+-dependent neutral sphingomyelinase (NSM) activity in comparison with other B-cell lines and contain very low acidic sphingomyelinase activity. Purification of this activity from DT40 cell membranes suggested the presence of one major NSM isoform. Although complete purification of this isoform could not be achieved, partially purified fractions were examined further with regard to the known characteristics of previously partially purified NSMs and the two cloned enzymes exhibiting in vitro NSM activity (NSM1 and NSM2). For a direct comparative study, highly purified brain preparations, purified NSM1 protein and Bacillus cereus enzyme were used. Analysis of the enzymic properties of the partially purified DT40 NSM, such as cation dependence, substrate specificity, redox regulation and stimulation by phosphatidylserine, together with the localization of this enzyme to the endoplasmic reticulum (ER), suggested that this NSM from DT40 cells corresponds to NSM1. Further studies aimed to correlate presence of the high levels of this NSM1-like activity in DT40 cells with the ability of these cells to accumulate ceramide and undergo apoptosis. When DT40 cells were stimulated to apoptose by a variety of agents, including the ER stress, an increase in endogenous ceramide levels was observed. However, these responses were not enhanced compared with another B-cell line (Nalm-6), characterized by low sphingomyelinase activity. In addition, DT40 cells were not more susceptible to ceramide accumulation and apoptosis when exposed to the ER stress compared with other apoptotic agents. Inhibition of de novo synthesis of ceramide partially inhibited its accumulation, indicating that the ceramide production in DT40 cells could be complex and, under some conditions, could involve both sphingomyelin hydrolysis and ceramide synthesis. PMID:12071841

  13. Evaluation of preventive and therapeutic activity of novel non-steroidal anti-inflammatory drug, CG100649, in colon cancer: Increased expression of TNF-related apoptosis-inducing ligand receptors enhance the apoptotic response to combination treatment with TRAIL.

    Science.gov (United States)

    Woo, Jong Kyu; Kang, Ju-Hee; Jang, Yeong-Su; Ro, Seonggu; Cho, Joong Myung; Kim, Hwan-Mook; Lee, Sang-Jin; Oh, Seung Hyun

    2015-04-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) have been suggested as the potential new class of preventive or therapeutic antitumor agents. The aim of the present study was to evaluate the antitumor activity of the novel NSAID, CG100649. CG100649 is a novel NSAID dual inhibitor for COX-2 and carbonic anhydrase (CA)-I/-II. In the present study, we investigated the alternative mechanism by which CG100649 mediated suppression of the colon cancer growth and development. The anchorage‑dependent and -independent clonogenic assay showed that CG100649 inhibited the clonogenicity of human colon cancer cells. The flow cytometric analysis showed that CG100649 induced the G2/M cell cycle arrest in colon cancer cells. Animal studies showed that CG100649 inhibited the tumor growth in colon cancer xenograft in nude mice. Furthermore, quantitative PCR and FACS analysis demonstrated that CG100649 upregulated the expression of TNF-related apoptosis-inducing ligand (TRAIL) receptors (DR4 and DR5) but decreased the expression of decoy receptors (DcR1 and DcR2) in colon cancer cells. The results showed that CG100649 treatment sensitized TRAIL‑mediated growth suppression and apoptotic cell death. The combination treatment resulted in significant repression of the intestinal polyp formation in APCmin/+ mice. Our data clearly demonstrated that CG100649 contains preventive and therapeutic activity for colon cancer. The present study may be useful for identification of the potential benefit of the NSAID CG100649, for the achievement of a better treatment response in colon cancer.

  14. Rapid effects of diverse toxic water pollutants on chlorophyll a fluorescence: variable responses among freshwater microalgae.

    Science.gov (United States)

    Choi, Chang Jae; Berges, John A; Young, Erica B

    2012-05-15

    Chlorophyll a fluorescence of microalgae is a compelling indicator of toxicity of dissolved water contaminants, because it is easily measured and responds rapidly. While different chl a fluorescence parameters have been examined, most studies have focused on single species and/or a narrow range of toxins. We assessed the utility of one chl a fluorescence parameter, the maximum quantum yield of PSII (F(v)/F(m)), for detecting effects of nine environmental pollutants from a range of toxin classes on 5 commonly found freshwater algal species, as well as the USEPA model species, Pseudokirchneriella subcapitata. F(v)/F(m) declined rapidly over glyphosate (glyphosate increased exponentially with concentration. F(v)/F(m) provides a sensitive and easily-measured parameter for rapid and cost-effective detection of effects of many dissolved toxins. Field-portable fluorometers will facilitate field testing, however distinct responses between different species may complicate net F(v)/F(m) signal from a community. Copyright © 2012 Elsevier Ltd. All rights reserved.

  15. Early Flood Detection for Rapid Humanitarian Response: Harnessing Near Real-Time Satellite and Twitter Signals

    Directory of Open Access Journals (Sweden)

    Brenden Jongman

    2015-10-01

    Full Text Available Humanitarian organizations have a crucial role in response and relief efforts after floods. The effectiveness of disaster response is contingent on accurate and timely information regarding the location, timing and impacts of the event. Here we show how two near-real-time data sources, satellite observations of water coverage and flood-related social media activity from Twitter, can be used to support rapid disaster response, using case-studies in the Philippines and Pakistan. For these countries we analyze information from disaster response organizations, the Global Flood Detection System (GFDS satellite flood signal, and flood-related Twitter activity analysis. The results demonstrate that these sources of near-real-time information can be used to gain a quicker understanding of the location, the timing, as well as the causes and impacts of floods. In terms of location, we produce daily impact maps based on both satellite information and social media, which can dynamically and rapidly outline the affected area during a disaster. In terms of timing, the results show that GFDS and/or Twitter signals flagging ongoing or upcoming flooding are regularly available one to several days before the event was reported to humanitarian organizations. In terms of event understanding, we show that both GFDS and social media can be used to detect and understand unexpected or controversial flood events, for example due to the sudden opening of hydropower dams or the breaching of flood protection. The performance of the GFDS and Twitter data for early detection and location mapping is mixed, depending on specific hydrological circumstances (GFDS and social media penetration (Twitter. Further research is needed to improve the interpretation of the GFDS signal in different situations, and to improve the pre-processing of social media data for operational use.

  16. Findings of the first ANZICS conference on the role of intensive care in Rapid Response Teams.

    Science.gov (United States)

    Jones, D; Hicks, P; Currey, J; Holmes, J; Fennessy, G J; Hillman, K; Psirides, A; Rai, S; Singh, M Y; Pilcher, D V; Bhonagiri, D; Hart, G K; Fugaccia, E

    2015-05-01

    Rapid Response Teams (RRTs) are specialised teams introduced into hospitals to improve the outcomes of deteriorating ward patients. Although Rapid Response Systems (RRSs) were developed by the intensive care unit (ICU) community, there is variability in their delivery, and consultant involvement, supervision and leadership appears to be relatively infrequent. In July 2014, the Australian and New Zealand Intensive Care Society (ANZICS) convened the first conference on the role of intensive care medicine in RRTs in Australia and New Zealand. The conference explored RRSs in the broader role of patient safety, resourcing and staffing of RRTs, effect on ICU workload, different RRT models, the outcomes of RRT patients and original research projects in the area of RRSs. Issues around education and training of both ICU registrars and nurses were examined, and the role of team training explored. Measures to assess the effectiveness of the RRS and RRT at the level of health system and hospital, team performance and team effectiveness were discussed, and the need to develop a bi-national ANZICS RRT patient database was presented. Strategies to prevent patient deterioration in the 'pre-RRT' period were discussed, including education of ward nurses and doctors, as well as an overarching governance structure. The role of the ICU in deteriorating ward patients was debated and an integrated model of acute care presented. This article summarises the findings of the conference and presents recommendations on the role of intensive care medicine in RRTs in Australia and New Zealand.

  17. Response time distributions in rapid chess: A large-scale decision making experiment

    Directory of Open Access Journals (Sweden)

    Mariano Sigman

    2010-10-01

    Full Text Available Rapid chess provides an unparalleled laboratory to understand decision making in a natural environment. In a chess game, players choose consecutively around 40 moves in a finite time budget. The goodness of each choice can be determined quantitatively since current chess algorithms estimate precisely the value of a position. Web-based chess produces vast amounts of data, millions of decisions per day, incommensurable with traditional psychological experiments. We generated a database of response times and position value in rapid chess games. We measured robust emergent statistical observables: 1 Response time (RT distributions are long-tailed and show qualitatively distinct forms at different stages of the game, 2 RT of successive moves are highly correlated both for intra- and inter-player moves. These findings have theoretical implications since they deny two basic assumptions of sequential decision making algorithms: RTs are not stationary and can not be generated by a state function. Our results also have practical implications. First, we characterized the capacity of blunders and score fluctuations to predict a player strength, which is yet an open problem in chess softwares. Second, we show that the winning likelihood can be reliably estimated from a weighted combination of remaining times and position evaluation.

  18. Rapid host immune response and viral dynamics in herpes simplex virus-2 infection

    Science.gov (United States)

    Schiffer, Joshua T; Corey, Lawrence

    2014-01-01

    Herpes Simplex Virus-2 (HSV-2) is episodically shed throughout the human genital tract. While high viral load correlates with development of genital ulcers, shedding also commonly occurs even when ulcers are not present, allowing for silent transmission during coitus and contributing to high seroprevalence of HSV-2 worldwide. Frequent viral reactivation occurs despite diverse and complementary host and viral mechanisms within ganglionic tissue that predispose towards latency, suggesting that viral replication may be constantly occurring in a small minority of neurons within the ganglia. Within genital mucosa, the in vivo expansion and clearance rates of HSV-2 are extremely rapid. Resident dendritic cells and memory HSV-specific T cells persist at prior sites of genital tract reactivation, and in conjunction with prompt innate recognition of infected cells, lead to rapid containment of infected cells. Shedding episodes vary greatly in duration and severity within a single person over time: this heterogeneity appears best explained by variation in the densities of host immunity across the genital tract. The fact that immune responses usually control viral replication in genital skin prior to development of lesions provides optimism that enhancing such responses could lead to effective vaccines and immunotherapies. PMID:23467247

  19. [Effectiveness of a Rapid Response Team (RRT) in a case of ruptured ectopic pregnancy].

    Science.gov (United States)

    Campechano-López, José Miguel; Carranza-Bernal, María Lourdes; Juanico-Morales, Guillermina; Reyes-Gil, María Rayo

    2016-01-01

    An ectopic pregnancy happens when a fertilized egg attaches somewhere outside the endometrial surface. This sort of pregnancy has an estimated incidence of 1.6 to 2 each 100 births. The main objective was to expose the effective answer of a Rapid Response Team in a case of ruptured cervical ectopic pregnancy. We also describe a clinical case of this sort of pregnancy. 37-year-old female with a two-month history of amenorrhea. The patient entered the Labor & Delivery department with hypovolemic shock secondary to vaginal bleeding. The Código Mater (Mater Code) was activated and the Rapid Response Team arrived to the L&D department. This team performed pelvic examination and detected tissue in cervix with mild bleeding. The pelvic ultrasound displayed the presence of gas and the endometrium status was normal (no gestational sac was detected). The immunologic test for pregnancy was positive. It was diagnosed cervical ectopic pregnancy and hypovolemic shock. Providing timely access to care with standardized criteria by interdisciplinary teams in all the cases of obstetric emergency avoids maternal deaths related to obstetric hemorrhage.

  20. A UAV BASED CLOSE-RANGE RAPID AERIAL MONITORING SYSTEM FOR EMERGENCY RESPONSES

    Directory of Open Access Journals (Sweden)

    K. Choi

    2012-09-01

    Full Text Available As the occurrences and scales of disasters and accidents have been increased due to the global warming, the terrorists' attacks, and many other reasons, the demand for rapid responses for the emergent situations also has been thus ever-increasing. These emergency responses are required to be customized to each individual site for more effective management of the emergent situations. These requirements can be satisfied with the decisions based on the spatial changes on the target area, which should be detected immediately or in real-time. Aerial monitoring without human operators is an appropriate means because the emergency areas are usually inaccessible. Therefore, a UAV is a strong candidate as the platform for the aerial monitoring. In addition, the sensory data from the UAV system usually have higher resolution than other system because the system can operate at a lower altitude. If the transmission and processing of the data could be performed in real-time, the spatial changes of the target area can be detected with high spatial and temporal resolution by the UAV rapid mapping systems. As a result, we aim to develop a rapid aerial mapping system based on a UAV, whose key features are the effective acquisition of the sensory data, real-time transmission and processing of the data. In this paper, we will introduce the general concept of our system, including the main features, intermediate results, and explain our real-time sensory data georeferencing algorithm which is a core for prompt generation of the spatial information from the sensory data.

  1. Apoptotic engulfment pathway and schizophrenia.

    LENUS (Irish Health Repository)

    Chen, Xiangning

    2009-01-01

    BACKGROUND: Apoptosis has been speculated to be involved in schizophrenia. In a previously study, we reported the association of the MEGF10 gene with the disease. In this study, we followed the apoptotic engulfment pathway involving the MEGF10, GULP1, ABCA1 and ABCA7 genes and tested their association with the disease. METHODOLOGY\\/PRINCIPAL FINDINGS: Ten, eleven and five SNPs were genotyped in the GULP1, ABCA1 and ABCA7 genes respectively for the ISHDSF and ICCSS samples. In all 3 genes, we observed nominally significant associations. Rs2004888 at GULP1 was significant in both ISHDSF and ICCSS samples (p = 0.0083 and 0.0437 respectively). We sought replication in independent samples for this marker and found highly significant association (p = 0.0003) in 3 Caucasian replication samples. But it was not significant in the 2 Chinese replication samples. In addition, we found a significant 2-marker (rs2242436 * rs3858075) interaction between the ABCA1 and ABCA7 genes in the ISHDSF sample (p = 0.0022) and a 3-marker interaction (rs246896 * rs4522565 * rs3858075) amongst the MEGF10, GULP1 and ABCA1 genes in the ICCSS sample (p = 0.0120). Rs3858075 in the ABCA1 gene was involved in both 2- and 3-marker interactions in the two samples. CONCLUSIONS\\/SIGNIFICANCE: From these data, we concluded that the GULP1 gene and the apoptotic engulfment pathway are involved in schizophrenia in subjects of European ancestry and multiple genes in the pathway may interactively increase the risks to the disease.

  2. Nisqually - Early Detection Rapid Response, Monitoring and Mapping of High Priority Invasive Species with Nisqually NWRC Weed Warriors 2008

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This project will continue a successful program of early detection and rapid response, monitoring and mapping of invasive species on Nisqually NWRC by Weed Warrior...

  3. Nisqually - Early Detection Rapid Response, Monitoring and Mapping of High Priority Invasive Species with Nisqually NWRC Weed Warriors 2007

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This project continues a successful program of early detection and rapid response, monitoring and mapping of invasive species on Nisqually NWRC (NNWRC) by Weed...

  4. Exploring interprofessional practices in rapid response systems: a case study protocol.

    Science.gov (United States)

    Allen, Emily; Jackson, Debra; Elliott, Doug

    2015-01-01

    To describe the development of a proposed case study protocol investigating interprofessional relationships in a rapid response system (RRS) in a socioculturally complex clinical environment. Suboptimal care of deteriorating ward patients remains a concern for many acute healthcare organisations. Despite the advent of RRSs, emergency response teams are not always used to their full potential. How and why interprofessional relationships influence practices associated with the care and management of ward patients at risk of clinical deterioration requires investigation. Theoretical and empirical literature describing case study research and RRSs. Review methods An integrative review approach of the literature, focusing on key terms relating to 'case study research' and 'rapid response system', provided context and informed development of the study protocol. A single-site mixed-method instrumental case study protocol was developed using methodological triangulation and a multi-level model to examine interprofessional relationships between a broad range of stakeholders. Concurrent data collection and analysis will occur using document review of clinical scenarios, non-participant observations and semi-structured interviews. Case study research is an effective method for investigating socioculturally complex clinical environments. A strength of this approach is the flexibility in the choice of methods, which allows the researcher to build the design most suitable for the subjects or phenomena being investigated. Although this flexibility may be considered a potential weakness, rigour can be achieved by application of the strategies described. Findings from this research will provide rich descriptive insights into RRS relationships and healthcare professional practices during day-to-day management of acute ward patients at risk of or experiencing clinical deterioration. Description of this structured case study research approach will also inform other researchers.

  5. Drug-Related Hyponatremic Encephalopathy: Rapid Clinical Response Averts Life-Threatening Acute Cerebral Edema.

    Science.gov (United States)

    Siegel, Arthur J; Forte, Sophie S; Bhatti, Nasir A; Gelda, Steven E

    2016-03-09

    Drug-induced hyponatremia characteristically presents with subtle psychomotor symptoms due to its slow onset, which permits compensatory volume adjustment to hypo-osmolality in the central nervous system. Due mainly to the syndrome of inappropriate antidiuretic hormone secretion (SIADH), this condition readily resolves following discontinuation of the responsible pharmacological agent. Here, we present an unusual case of life-threatening encephalopathy due to adverse drug-related effects, in which a rapid clinical response facilitated emergent treatment to avert life-threatening acute cerebral edema. A 63-year-old woman with refractory depression was admitted for inpatient psychiatric care with a normal physical examination and laboratory values, including a serum sodium [Na+] of 144 mEq/L. She had a grand mal seizure and became unresponsive on the fourth day of treatment with the dual serotonin and norepinephrine reuptake inhibitor [SNRI] duloxetine while being continued on a thiazide-containing diuretic for a hypertensive disorder. Emergent infusion of intravenous hypertonic (3%) saline was initiated after determination of a serum sodium [Na+] of 103 mEq/L with a urine osmolality of 314 mOsm/kg H20 and urine [Na+] of 12 mEq/L. Correction of hyposmolality in accordance with current guidelines resulted in progressive improvement over several days, and she returned to her baseline mental status. Seizures with life-threatening hyponatremic encephalopathy in this case likely resulted from co-occurring SIADH and sodium depletion due to duloxetine and hydrochlorothiazide, respectively. A rapid clinical response expedited diagnosis and emergent treatment to reverse life-threatening acute cerebral edema and facilitate a full recovery without neurological complications.

  6. Murine Neonates Infected with Yersinia enterocolitica Develop Rapid and Robust Proinflammatory Responses in Intestinal Lymphoid Tissues

    Science.gov (United States)

    Siefker, David T.; Echeverry, Andrea; Brambilla, Roberta; Fukata, Masayuki; Schesser, Kurt

    2014-01-01

    Neonatal animals are generally very susceptible to infection with bacterial pathogens. However, we recently reported that neonatal mice are highly resistant to orogastric infection with Yersinia enterocolitica. Here, we show that proinflammatory responses greatly exceeding those in adults arise very rapidly in the mesenteric lymph nodes (MLN) of neonates. High-level induction of proinflammatory gene expression occurred in the neonatal MLN as early as 18 h postinfection. Marked innate phagocyte recruitment was subsequently detected at 24 h postinfection. Enzyme-linked immunosorbent spot assay (ELISPOT) analyses indicated that enhanced inflammation in neonatal MLN is contributed to, in part, by an increased frequency of proinflammatory cytokine-secreting cells. Moreover, both CD11b+ and CD11b− cell populations appeared to play a role in proinflammatory gene expression. The level of inflammation in neonatal MLN was also dependent on key bacterial components. Y. enterocolitica lacking the virulence plasmid failed to induce innate phagocyte recruitment. In contrast, tumor necrosis factor alpha (TNF-α) protein expression and neutrophil recruitment were strikingly higher in neonatal MLN after infection with a yopP-deficient strain than with wild-type Y. enterocolitica, whereas only modest increases occurred in adults. This hyperinflammatory response was associated with greater colonization of the spleen and higher mortality in neonates, while there was no difference in mortality among adults. This model highlights the dynamic levels of inflammation in the intestinal lymphoid tissues and reveals the protective (wild-type strain) versus harmful (yopP-deficient strain) consequences of inflammation in neonates. Moreover, these results reveal that the neonatal intestinal lymphoid tissues have great potential to rapidly mobilize innate components in response to infection with bacterial enteropathogens. PMID:24478090

  7. Apoptotic Potential of Artemsia sieberia Besser (Asteraceae ...

    African Journals Online (AJOL)

    fraction of A. sieberi against seven cancer cell lines (Colo20, HCT116, DLD, MCF7, Jurkat, HepG2 and. L929). Methods: A. .... Apoptotic morphology was confirmed by nuclear condensation, and round apoptotic bodies (white arrows). Annexin V/PI staining is a ... sieberia and its dichloromethane fraction affected. HepG2 cell ...

  8. Rapid stimulus-evoked astrocyte Ca2+ elevations and hemodynamic responses in mouse somatosensory cortex in vivo

    DEFF Research Database (Denmark)

    Lind, Barbara Lykke; Brazhe, Alexey; Jessen, Sanne Barsballe

    2013-01-01

    Increased neuron and astrocyte activity triggers increased brain blood flow, but controversy exists over whether stimulation-induced changes in astrocyte activity are rapid and widespread enough to contribute to brain blood flow control. Here, we provide evidence for stimulus-evoked Ca(2+) elevat...... brief Ca(2+) responses with a rapid onset in vivo, fast enough to initiate hemodynamic responses or influence synaptic activity.......Increased neuron and astrocyte activity triggers increased brain blood flow, but controversy exists over whether stimulation-induced changes in astrocyte activity are rapid and widespread enough to contribute to brain blood flow control. Here, we provide evidence for stimulus-evoked Ca(2......+) elevations with rapid onset and short duration in a large proportion of cortical astrocytes in the adult mouse somatosensory cortex. Our improved detection of the fast Ca(2+) signals is due to a signal-enhancing analysis of the Ca(2+) activity. The rapid stimulation-evoked Ca(2+) increases identified...

  9. Rapid shelf-wide cooling response of a stratified coastal ocean to hurricanes

    Science.gov (United States)

    Seroka, Greg; Miles, Travis; Xu, Yi; Kohut, Josh; Schofield, Oscar; Glenn, Scott

    2017-06-01

    Large uncertainty in the predicted intensity of tropical cyclones (TCs) persists compared to the steadily improving skill in the predicted TC tracks. This intensity uncertainty has its most significant implications in the coastal zone, where TC impacts to populated shorelines are greatest. Recent studies have demonstrated that rapid ahead-of-eye-center cooling of a stratified coastal ocean can have a significant impact on hurricane intensity forecasts. Using observation-validated, high-resolution ocean modeling, the stratified coastal ocean cooling processes observed in two U.S. Mid-Atlantic hurricanes were investigated: Hurricane Irene (2011)—with an inshore Mid-Atlantic Bight (MAB) track during the late summer stratified coastal ocean season—and Tropical Storm Barry (2007)—with an offshore track during early summer. For both storms, the critical ahead-of-eye-center depth-averaged force balance across the entire MAB shelf included an onshore wind stress balanced by an offshore pressure gradient. This resulted in onshore surface currents opposing offshore bottom currents that enhanced surface to bottom current shear and turbulent mixing across the thermocline, resulting in the rapid cooling of the surface layer ahead-of-eye-center. Because the same baroclinic and mixing processes occurred for two storms on opposite ends of the track and seasonal stratification envelope, the response appears robust. It will be critical to forecast these processes and their implications for a wide range of future storms using realistic 3-D coupled atmosphere-ocean models to lower the uncertainty in predictions of TC intensities and impacts and enable coastal populations to better respond to increasing rapid intensification threats in an era of rising sea levels.

  10. Rapid shelf‐wide cooling response of a stratified coastal ocean to hurricanes

    Science.gov (United States)

    Miles, Travis; Xu, Yi; Kohut, Josh; Schofield, Oscar; Glenn, Scott

    2017-01-01

    Abstract Large uncertainty in the predicted intensity of tropical cyclones (TCs) persists compared to the steadily improving skill in the predicted TC tracks. This intensity uncertainty has its most significant implications in the coastal zone, where TC impacts to populated shorelines are greatest. Recent studies have demonstrated that rapid ahead‐of‐eye‐center cooling of a stratified coastal ocean can have a significant impact on hurricane intensity forecasts. Using observation‐validated, high‐resolution ocean modeling, the stratified coastal ocean cooling processes observed in two U.S. Mid‐Atlantic hurricanes were investigated: Hurricane Irene (2011)—with an inshore Mid‐Atlantic Bight (MAB) track during the late summer stratified coastal ocean season—and Tropical Storm Barry (2007)—with an offshore track during early summer. For both storms, the critical ahead‐of‐eye‐center depth‐averaged force balance across the entire MAB shelf included an onshore wind stress balanced by an offshore pressure gradient. This resulted in onshore surface currents opposing offshore bottom currents that enhanced surface to bottom current shear and turbulent mixing across the thermocline, resulting in the rapid cooling of the surface layer ahead‐of‐eye‐center. Because the same baroclinic and mixing processes occurred for two storms on opposite ends of the track and seasonal stratification envelope, the response appears robust. It will be critical to forecast these processes and their implications for a wide range of future storms using realistic 3‐D coupled atmosphere‐ocean models to lower the uncertainty in predictions of TC intensities and impacts and enable coastal populations to better respond to increasing rapid intensification threats in an era of rising sea levels. PMID:28944132

  11. Metagenomic analysis of a permafrost microbial community reveals a rapid response to thaw

    Science.gov (United States)

    MacKelprang, R.; Waldrop, M.P.; Deangelis, K.M.; David, M.M.; Chavarria, K.L.; Blazewicz, S.J.; Rubin, E.M.; Jansson, J.K.

    2011-01-01

    Permafrost contains an estimated 1672????????Pg carbon (C), an amount roughly equivalent to the total currently contained within land plants and the atmosphere. This reservoir of C is vulnerable to decomposition as rising global temperatures cause the permafrost to thaw. During thaw, trapped organic matter may become more accessible for microbial degradation and result in greenhouse gas emissions. Despite recent advances in the use of molecular tools to study permafrost microbial communities, their response to thaw remains unclear. Here we use deep metagenomic sequencing to determine the impact of thaw on microbial phylogenetic and functional genes, and relate these data to measurements of methane emissions. Metagenomics, the direct sequencing of DNA from the environment, allows the examination of whole biochemical pathways and associated processes, as opposed to individual pieces of the metabolic puzzle. Our metagenome analyses reveal that during transition from a frozen to a thawed state there are rapid shifts in many microbial, phylogenetic and functional gene abundances and pathways. After one week of incubation at 5 ??C, permafrost metagenomes converge to be more similar to each other than while they are frozen. We find that multiple genes involved in cycling of C and nitrogen shift rapidly during thaw. We also construct the first draft genome from a complex soil metagenome, which corresponds to a novel methanogen. Methane previously accumulated in permafrost is released during thaw and subsequently consumed by methanotrophic bacteria. Together these data point towards the importance of rapid cycling of methane and nitrogen in thawing permafrost. ?? 2011 Macmillan Publishers Limited. All rights reserved.

  12. Rapid shelf-wide cooling response of a stratified coastal ocean to hurricanes.

    Science.gov (United States)

    Seroka, Greg; Miles, Travis; Xu, Yi; Kohut, Josh; Schofield, Oscar; Glenn, Scott

    2017-06-01

    Large uncertainty in the predicted intensity of tropical cyclones (TCs) persists compared to the steadily improving skill in the predicted TC tracks. This intensity uncertainty has its most significant implications in the coastal zone, where TC impacts to populated shorelines are greatest. Recent studies have demonstrated that rapid ahead-of-eye-center cooling of a stratified coastal ocean can have a significant impact on hurricane intensity forecasts. Using observation-validated, high-resolution ocean modeling, the stratified coastal ocean cooling processes observed in two U.S. Mid-Atlantic hurricanes were investigated: Hurricane Irene (2011)-with an inshore Mid-Atlantic Bight (MAB) track during the late summer stratified coastal ocean season-and Tropical Storm Barry (2007)-with an offshore track during early summer. For both storms, the critical ahead-of-eye-center depth-averaged force balance across the entire MAB shelf included an onshore wind stress balanced by an offshore pressure gradient. This resulted in onshore surface currents opposing offshore bottom currents that enhanced surface to bottom current shear and turbulent mixing across the thermocline, resulting in the rapid cooling of the surface layer ahead-of-eye-center. Because the same baroclinic and mixing processes occurred for two storms on opposite ends of the track and seasonal stratification envelope, the response appears robust. It will be critical to forecast these processes and their implications for a wide range of future storms using realistic 3-D coupled atmosphere-ocean models to lower the uncertainty in predictions of TC intensities and impacts and enable coastal populations to better respond to increasing rapid intensification threats in an era of rising sea levels.

  13. Abnormalities in Alternative Splicing of Apoptotic Genes and Cardiovascular Diseases

    Directory of Open Access Journals (Sweden)

    Zodwa Dlamini

    2015-11-01

    Full Text Available Apoptosis is required for normal heart development in the embryo, but has also been shown to be an important factor in the occurrence of heart disease. Alternative splicing of apoptotic genes is currently emerging as a diagnostic and therapeutic target for heart disease. This review addresses the involvement of abnormalities in alternative splicing of apoptotic genes in cardiac disorders including cardiomyopathy, myocardial ischemia and heart failure. Many pro-apoptotic members of the Bcl-2 family have alternatively spliced isoforms that lack important active domains. These isoforms can play a negative regulatory role by binding to and inhibiting the pro-apoptotic forms. Alternative splicing is observed to be increased in various cardiovascular diseases with the level of alternate transcripts increasing elevated in diseased hearts compared to healthy subjects. In many cases these isoforms appear to be the underlying cause of the disease, while in others they may be induced in response to cardiovascular pathologies. Regardless of this, the detection of alternate splicing events in the heart can serve as useful diagnostic or prognostic tools, while those splicing events that seem to play a causative role in cardiovascular disease make attractive future drug targets.

  14. Rapid health response, assessment, and surveillance after a tsunami--Thailand, 2004-2005.

    Science.gov (United States)

    2005-01-28

    On December 26, 2004, an earthquake triggered a devastating tsunami that caused an estimated 225,000 deaths in eight countries (India, Indonesia, Malaysia, Maldives, Seychelles, Somalia, Sri Lanka, and Thailand) on two continents. In Thailand, six provinces (Krabi, Phang-Nga, Phuket, Ranong, Satun, and Trang) were impacted, including prominent international tourist destinations. The Thai Ministry of Public Health (MOPH) responded with rapid mobilization of local and nonlocal clinicians, public health practitioners, and medical supplies; assessment of health-care needs; identification of the dead, injured, and missing; and active surveillance of syndromic illness. The MOPH response was augmented by technical assistance from the Thai MOPH-U.S. CDC Collaboration (TUC) and the Armed Forces Research Institute of Medical Sciences (AFRIMS), with support from the office of the World Health Organization (WHO) representative to Thailand. This report summarizes these activities. The experiences in Thailand underscore the value of written and rehearsed disaster plans, capacity for rapid mobilization, local coordination of relief activities, and active public health surveillance.

  15. Three-year-olds' rapid facial electromyographic responses to emotional facial expressions and body postures.

    Science.gov (United States)

    Geangu, Elena; Quadrelli, Ermanno; Conte, Stefania; Croci, Emanuela; Turati, Chiara

    2016-04-01

    Rapid facial reactions (RFRs) to observed emotional expressions are proposed to be involved in a wide array of socioemotional skills, from empathy to social communication. Two of the most persuasive theoretical accounts propose RFRs to rely either on motor resonance mechanisms or on more complex mechanisms involving affective processes. Previous studies demonstrated that presentation of facial and bodily expressions can generate rapid changes in adult and school-age children's muscle activity. However, to date there is little to no evidence to suggest the existence of emotional RFRs from infancy to preschool age. To investigate whether RFRs are driven by motor mimicry or could also be a result of emotional appraisal processes, we recorded facial electromyographic (EMG) activation from the zygomaticus major and frontalis medialis muscles to presentation of static facial and bodily expressions of emotions (i.e., happiness, anger, fear, and neutral) in 3-year-old children. Results showed no specific EMG activation in response to bodily emotion expressions. However, observing others' happy faces led to increased activation of the zygomaticus major and decreased activation of the frontalis medialis, whereas observing others' angry faces elicited the opposite pattern of activation. This study suggests that RFRs are the result of complex mechanisms in which both affective processes and motor resonance may play an important role. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Monitoring and evaluation of disaster response efforts undertaken by local health departments: a rapid realist review.

    Science.gov (United States)

    Gossip, Kate; Gouda, Hebe; Lee, Yong Yi; Firth, Sonja; Bermejo, Raoul; Zeck, Willibald; Jimenez Soto, Eliana

    2017-06-29

    Local health departments are often at the forefront of a disaster response, attending to the immediate trauma inflicted by the disaster and also the long term health consequences. As the frequency and severity of disasters are projected to rise, monitoring and evaluation (M&E) efforts are critical to help local health departments consolidate past experiences and improve future response efforts. Local health departments often conduct M&E work post disaster, however, many of these efforts fail to improve response procedures. We undertook a rapid realist review (RRR) to examine why M&E efforts undertaken by local health departments do not always result in improved disaster response efforts. We aimed to complement existing frameworks by focusing on the most basic and pragmatic steps of a M&E cycle targeted towards continuous system improvements. For these purposes, we developed a theoretical framework that draws on the quality improvement literature to 'frame' the steps in the M&E cycle. This framework encompassed a M&E cycle involving three stages (i.e., document and assess, disseminate and implement) that must be sequentially completed to learn from past experiences and improve future disaster response efforts. We used this framework to guide our examination of the literature and to identify any context-mechanism-outcome (CMO) configurations which describe how M&E may be constrained or enabled at each stage of the M&E cycle. This RRR found a number of explanatory CMO configurations that provide valuable insights into some of the considerations that should be made when using M&E to improve future disaster response efforts. Firstly, to support the accurate documentation and assessment of a disaster response, local health departments should consider how they can: establish a culture of learning within health departments; use embedded training methods; or facilitate external partnerships. Secondly, to enhance the widespread dissemination of lessons learned and facilitate

  17. Plaque-Like Sclerodermiform Localized Mucinosis Rapidly Responsive to Topical Tacrolimus

    Directory of Open Access Journals (Sweden)

    R. Schmaltz

    2010-08-01

    Full Text Available We report the successful treatment of plaque-like sclerodermiform mucinosis using tacrolimus ointment topically. We present a 70-year-old male with a large chronic erythema and hardening of the nuchal skin and shoulder area. Subjective symptoms were a moderate pruritus and a rather disabling stiffness. A biopsy specimen revealed typical features of lichen myxedematosus. In a subsequent clinical examination, no associated illnesses such as hypothyroidism or gammopathy were found. Since no established therapy exists for this condition, and as there was a lack of response to potent topical glucocorticosteroids, tacrolimus 0.03% ointment was used off-label twice daily. Surprisingly, this resulted in a rapid, almost complete clearance of the skin within three weeks of treatment.

  18. A participatory action research pilot study of urban health disparities using rapid assessment response and evaluation.

    Science.gov (United States)

    Brown, David Richard; Hernández, Agueda; Saint-Jean, Gilbert; Evans, Siân; Tafari, Ida; Brewster, Luther G; Celestin, Michel J; Gómez-Estefan, Carlos; Regalado, Fernando; Akal, Siri; Nierenberg, Barry; Kauschinger, Elaine D; Schwartz, Robert; Page, J Bryan

    2008-01-01

    Healthy People 2010 made it a priority to eliminate health disparities. We used a rapid assessment response and evaluation (RARE) to launch a program of participatory action research focused on health disparities in an urban, disadvantaged Black community serviced by a major south Florida health center. We formed partnerships with community members, identified local health disparities, and guided interventions targeting health disparities. We describe the RARE structure used to triangulate data sources and guide intervention plans as well as findings and conclusions drawn from scientific literature and epidemiological, historic, planning, clinical, and ethnographic data. Disenfranchisement and socioeconomic deprivation emerged as the principal determinants of local health disparities and the most appropriate targets for intervention.

  19. Rapid response team composition effects on outcomes for adult hospitalised patients: A systematic review.

    Science.gov (United States)

    Daniele, Rose Mary; Bova, Ann Marie; LeGar, Michelle; Smith, Pauline J; Shortridge-Baggett, Lillie M

    2011-01-01

    Utilisation of a rapid response team (RRT) in a hospital setting has been documented in the literature. RRTs were formed to intervene quickly when the hospitalised patient first shows signs of deterioration. The purpose was to prevent failure to rescue, leading to intensive care unit transfers, cardiac arrest and mortality. To date, however, there is a lack of evidence to support the effectiveness of this intervention. The focused question, subsequent systematic review and data analysis are presented. To synthesise the best available research evidence on the impact of rapid response team composition on cardiopulmonary arrest outside the intensive care unit (ICU), unplanned transfers to ICU, in-hospital mortality, length of hospital stay in hospitalised non-ICU adult medical-surgical patients and staff satisfaction. Published and unpublished literature were searched. The databases searched for studies from 1989 to 2010 were CINAHL, EMBASE, Google Scholar, Mednar, New York Academy of Medicine, Proquest and PubMed. Reference lists of included studies were hand searched. Initial keywords searched were rapid response team, rapid response system, medical emergency team, medical emergency system and team composition. The studies included in the systematic review were randomized controlled trials (RCTs). In absence of sufficient RCTs, quasi-experimental studies, cohort studies, observational and control trials without randomization were included. Types of participants were adults (18 years and older) hospitalised in an acute care setting, not requiring the specialized care and management of an ICU. Hospitalised paediatric patients, ICU patients, hospice or palliative care patients were excluded. JBI MAStARI Critical Appraisal Tools were used for the methodological assessment of identified studies. Data were collected specifically related to RRT intervention, study methods and design, randomization, length of intervention, data collection points and inclusion criteria

  20. ER Stress Causes Rapid Loss of Intestinal Epithelial Stemness through Activation of the Unfolded Protein Response

    Directory of Open Access Journals (Sweden)

    Jarom Heijmans

    2013-04-01

    Full Text Available Stem cells generate rapidly dividing transit-amplifying cells that have lost the capacity for self-renewal but cycle for a number of times until they exit the cell cycle and undergo terminal differentiation. We know very little of the type of signals that trigger the earliest steps of stem cell differentiation and mediate a stem cell to transit-amplifying cell transition. We show that in normal intestinal epithelium, endoplasmic reticulum (ER stress and activity of the unfolded protein response (UPR are induced at the transition from stem cell to transit-amplifying cell. Induction of ER stress causes loss of stemness in a Perk-eIF2α-dependent manner. Inhibition of Perk-eIF2α signaling results in stem cell accumulation in organoid culture of primary intestinal epithelium. Our findings show that the UPR plays an important role in the regulation of intestinal epithelial stem cell differentiation.

  1. Reactive oxygen species regulatory mechanisms associated with rapid response of MC3T3-E1 cells for vibration stress

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Ling; Gan, Xueqi; Zhu, Zhuoli; Yang, Yang; He, Yuting; Yu, Haiyang, E-mail: yhyang6812@scu.edu.cn

    2016-02-12

    Although many previous studies have shown that refractory period-dependent memory effect of vibration stress is anabolic for skeletal homeostasis, little is known about the rapid response of osteoblasts simply derived from vibration itself. In view of the potential role of reactive oxygen species (ROS) in mediating differentiated activity of osteoblasts, whether and how ROS regulates the rapid effect of vibration deserve to be demonstrated. Our findings indicated that MC3T3-E1 cells underwent decreased gene expression of Runx2, Col-I and ALP and impaired ALP activity accompanied by increased mitochondrial fission immediately after vibration loading. Moreover, we also revealed the involvement of ERK-Drp1 signal transduction in ROS regulatory mechanisms responsible for the rapid effect of vibration stress. - Highlights: • ROS contributed to the rapid response of MC3T3-E1 cells for vibration stress. • Imbalance of mitochondrial dynamics were linked to the LMHFV-derived rapid response. • The role of ERK-Drp1 signal pathway in the LMHFV-derived osteoblast rapid response.

  2. Condition Help: A Patient- and Family-Initiated Rapid Response System.

    Science.gov (United States)

    Eden, Elizabeth L; Rack, Laurie L; Chen, Ling-Wan; Bump, Gregory M

    2017-03-01

    Rapid response teams (RRTs) help in delivering safe, timely care. Typically they are activated by clinicians using specific parameters. Allowing patients and families to activate RRTs is a novel intervention. The University of Pittsburgh Medical Center developed and implemented a patient- and family-initiated rapid response system called Condition Help (CH). When the CH system is activated, a patient care liaison or an on-duty administrator meets bedside with the unit charge nurse to address the patient's concerns. In this study, we collected demographic data, call reasons, call designations (safety or nonsafety), and outcome information for all CH calls made during the period January 2012 through June 2015. Two hundred forty patients/family members made 367 CH calls during the study period. Most calls were made by patients (76.8%) rather than family members (21.8%). Of the 240 patients, 43 (18%) made multiple calls; their calls accounted for 46.3% of all calls (170/367). Inadequate pain control was the reason for the call in most cases (48.2%), followed by dissatisfaction with staff (12.5%). The majority of calls involved nonsafety issues (83.4%) rather than safety issues (11.4%). In 41.4% of cases, a change in care was made. Patient- and family-initiated RRTs are designed to engage patients and families in providing safer care. In the CH system, safety issues are identified, but the majority of calls involve nonsafety issues. Journal of Hospital Medicine 2017;12:157-161.

  3. Effect of a 2-tier rapid response system on patient outcome and staff satisfaction.

    Science.gov (United States)

    Aitken, Leanne M; Chaboyer, Wendy; Vaux, Amanda; Crouch, Shannon; Burmeister, Elizabeth; Daly, Michael; Joyce, Chris

    2015-08-01

    Rapid response systems (RRS) have been recommended as a strategy to prevent and treat deterioration in acute care patients. Questions regarding the most effective characteristics of RRS and strategies for implementing these systems remain. The aims of this study were to (i) describe the structures and processes used to implement a 2-tier RRS, (ii) determine the comparative prevalence of deteriorating patients and incidence of unplanned intensive care unit (ICU) admission and cardiac arrest prior to and after implementation of the RRS, and (iii) determine clinician satisfaction with the RRS. A quasi-experimental pre-test, post-test design was used to assess patient related outcomes and clinician satisfaction prior to and after implementation of a 2-tier RRS in a tertiary metropolitan hospital. Primary components of the RRS included an ICU Outreach Nurse and a Rapid Response Team. Prevalence of deteriorating patients was assessed through a point prevalence assessment and chart audit. Incidence of unplanned admission to ICU and cardiac arrests were accessed from routine hospital databases. Clinician satisfaction was measured through surveys. Prevalence of patients who met medical emergency call criteria without current treatment reduced from 3% prior to RRS implementation to 1% after implementation; a similar reduction from 9% to 3% was identified on chart review. The number of unplanned admissions to ICU increased slightly from 17.4/month prior to RRS implementation to 18.1/month after implementation (p=0.45) while cardiac arrests reduced slightly from 7.5/month to 5.6/month (p=0.22) but neither of these changes were statistically significant. Staff satisfaction with the RRS was generally high. The 2-tier RRS was accessed by staff to assist with care of deteriorating patients in a large, tertiary hospital. High levels of satisfaction have been reported by clinical staff. Copyright © 2014 Australian College of Critical Care Nurses Ltd. Published by Elsevier Ltd. All

  4. Critical role of CCL22/CCR4 axis in the maintenance of immune homeostasis during apoptotic cell clearance by splenic CD8α(+) CD103(+) dendritic cells.

    Science.gov (United States)

    Hao, Shengyu; Han, Xiaolei; Wang, Dan; Yang, Yang; Li, Qiuting; Li, Xiangzhi; Qiu, Chun-Hong

    2016-06-01

    Macrophages and dendritic cells (DCs) in murine spleen are essential for the maintenance of immune homeostasis by elimination of blood-borne foreign particles and organisms. It has been reported that splenic DCs, especially CD8α(+) CD103(+) DCs, are responsible for tolerance to apoptosis-associated antigens. However, the molecular mechanism by which these DCs maintain immune homeostasis by blood-borne apoptotic cell clearance remains elusive. Here, we found that the CCL22/CCR4 axis played a critical role in the maintenance of immune homeostasis during apoptotic cell clearance by splenic CD8α(+) CD103(+) DCs. The present results revealed that systemic administration of apoptotic cells rapidly induced a large number of CCL22 and CCR4(+) regulatory T (Treg) cells in the spleen of C57BL/6J mice. Further study demonstrated that CD8α(+) CD103(+) DCs dominantly produce much higher CCL22 than CD8α(+) CD103(-) DCs. Moreover, the transient deletion of CD8α(+) CD103(+) DCs caused a decrease in CCL22 levels together with CCR4(+) Treg cell percentage. Subsequently, the levels of some pro-inflammatory cytokines, such as interleukin-17 and interferon-γ in the spleen with the absence of CD8α(+) CD103(+) DCs increased in response to the administration of apoptotic cells. Hence, intravenous injection of apoptotic cells induced a subsequent increase in CCL22 expression and CCR4(+) Treg cells, which contribute to the maintenance of immune homeostasis at least partially by splenic CD8α(+) CD103(+) DCs. © 2016 John Wiley & Sons Ltd.

  5. Levels of pro-apoptotic regulator Bad and anti-apoptotic regulator Bcl-xL determine the type of the apoptotic logic gate.

    Science.gov (United States)

    Bogdał, Marta N; Hat, Beata; Kochańczyk, Marek; Lipniacki, Tomasz

    2013-07-24

    Apoptosis is a tightly regulated process: cellular survive-or-die decisions cannot be accidental and must be unambiguous. Since the suicide program may be initiated in response to numerous stress stimuli, signals transmitted through a number of checkpoints have to be eventually integrated. In order to analyze possible mechanisms of the integration of multiple pro-apoptotic signals, we constructed a simple model of the Bcl-2 family regulatory module. The module collects upstream signals and processes them into life-or-death decisions by employing interactions between proteins from three subgroups of the Bcl-2 family: pro-apoptotic multidomain effectors, pro-survival multidomain restrainers, and pro-apoptotic single domain BH3-only proteins. Although the model is based on ordinary differential equations (ODEs), it demonstrates that the Bcl-2 family module behaves akin to a Boolean logic gate of the type dependent on levels of BH3-only proteins (represented by Bad) and restrainers (represented by Bcl-xL). A low level of pro-apoptotic Bad or a high level of pro-survival Bcl-xL implies gate AND, which allows for the initiation of apoptosis only when two stress stimuli are simultaneously present: the rise of the p53 killer level and dephosphorylation of kinase Akt. In turn, a high level of Bad or a low level of Bcl-xL implies gate OR, for which any of these stimuli suffices for apoptosis. Our study sheds light on possible signal integration mechanisms in cells, and spans a bridge between modeling approaches based on ODEs and on Boolean logic. In the proposed scheme, logic gates switching results from the change of relative abundances of interacting proteins in response to signals and involves system bistability. Consequently, the regulatory system may process two analogous inputs into a digital survive-or-die decision.

  6. The Climate Science Rapid Response Team - A Model for Science Communication

    Science.gov (United States)

    Mandia, S. A.; Abraham, J. A.; Weymann, R.; Ashley, M.

    2011-12-01

    In recent years, there have been many independent initiatives which have commenced with the goal of improving communication between scientists and the larger public. These initiatives have often been motivated by the recognition that concerns amongst scientists related to the pending threats of climate change are not universally shared by the general public. Multiple studies have conclusively demonstrated that while the vast majority of climate scientists are in broad agreement that human-emitted greenhouse gases are causing increases in the Earth's temperature, the larger public is divided. Often, this divide mirrors divides on other political, societal, economic, or scientific issues. One unique approach to improve the conveyance of the state of climate-change science to the public is reflected by a self-organized effort of scientists themselves. This approach has lead to the formation of the Climate Science Rapid Response Team (CSRRT). The mission of this organization is to provide accurate and rapid information on any climate-science topic to general media and governmental inquirers. The CSRRT currently consists of approximately 135 world-class climate scientists whose members cover the sub-disciplines of climate change and include not only the natural sciences but also economics and policy. Since its formation, the CSRRT has fielded approximately four inquires each week from institutions that include The Associated Press, ABC, CBS, CNN, BBC, New York Times, Time of London, National Public Radio, The Guardian, The Washington Post, the Los Angeles Times, the Chicago Tribune, and the U.S. Congress, among others. Members of the CSRRT have been asked to provide quotations for news stories; they have also been asked to give radio, television, or print-media interviews. Some members of the CSRRT have undergone media training to help encourage the use of jargon-free language so that clear communication with the broader public can be more successful. The response from

  7. Rapid maize leaf and immature ear responses to UV-B radiation

    Directory of Open Access Journals (Sweden)

    Paula eCasati

    2011-07-01

    Full Text Available Because of their sessile lifestyle, plants have evolved adaptations to environmental factors, including UV-B present in solar radiation. To gain a better understanding of the initial events in UV-B acclimation, we have analyzed a 10min to 1h time course of transcriptome responses in irradiated and shielded leaves, and immature maize ears to unravel the systemic physiological and developmental responses in exposed and shielded organs. After 10 min of UV-B exposure, 262 transcripts are changed by at least 2-fold in irradiated leaves, and this number doubles after 1h. Indicative of the rapid modulation of transcription, 130 transcripts are only changed after 10 min. This is true not only in irradiated leaves, but also in shielded tissues. After 10 min of exposure, the overlap in transcriptome changes in irradiated and shielded organs is significant; however, after 30 min of UV-B, there are only 2 transcripts showing similar UV-B regulation between the three organs; 35 are similarly regulated in both IL and SL. Therefore, at longer irradiation times, there is more specificity of responses, and these are organ-specific. We suggest that early signaling in different tissues may be elicited by common signaling pathways, while at longer exposure times responses become more specific. To identify metabolites as possible signaling molecules, we looked for compounds that increased within 5-90 min in both irradiated and shielded leaves, to explain the kinetics of profound transcript changes within 1h. We found that myoinositol is one such candidate metabolite; and we also demonstrate that if 0.1mM myoinositol is applied to leaves of greenhouse maize, some metabolites that are changed by UV-B are also changed similarly by the chemical treatment. Therefore, this metabolite can partially mimic UV irradiation.

  8. Regulation of apoptotic pathways by Stylophora pistillata (Anthozoa, Pocilloporidae) to survive thermal stress and bleaching.

    Science.gov (United States)

    Kvitt, Hagit; Rosenfeld, Hanna; Zandbank, Keren; Tchernov, Dan

    2011-01-01

    Elevated seawater temperatures are associated with coral bleaching events and related mortality. Nevertheless, some coral species are able to survive bleaching and recover. The apoptotic responses associated to this ability were studied over 3 years in the coral Stylophora pistillata from the Gulf of Eilat subjected to long term thermal stress. These include caspase activity and the expression profiles of the S. pistillata caspase and Bcl-2 genes (StyCasp and StyBcl-2-like) cloned in this study. In corals exposed to thermal stress (32 or 34°C), caspase activity and the expression levels of the StyBcl-2-like gene increased over time (6-48 h) and declined to basal levels within 72 h of thermal stress. Distinct transcript levels were obtained for the StyCasp gene, with stimulated expression from 6 to 48 h of 34°C thermal stress, coinciding with the onset of bleaching. Increased cell death was detected in situ only between 6 to 48 h of stress and was limited to the gastroderm. The bleached corals survived up to one month at 32°C, and recovered back symbionts when placed at 24°C. These results point to a two-stage response in corals that withstand thermal stress: (i) the onset of apoptosis, accompanied by rapid activation of anti-oxidant/anti-apoptotic mediators that block the progression of apoptosis to other cells and (ii) acclimatization of the coral to the chronic thermal stress alongside the completion of symbiosis breakdown. Accordingly, the coral's ability to rapidly curb apoptosis appears to be the most important trait affecting the coral's thermotolerance and survival.

  9. Regulation of apoptotic pathways by Stylophora pistillata (Anthozoa, Pocilloporidae to survive thermal stress and bleaching.

    Directory of Open Access Journals (Sweden)

    Hagit Kvitt

    Full Text Available Elevated seawater temperatures are associated with coral bleaching events and related mortality. Nevertheless, some coral species are able to survive bleaching and recover. The apoptotic responses associated to this ability were studied over 3 years in the coral Stylophora pistillata from the Gulf of Eilat subjected to long term thermal stress. These include caspase activity and the expression profiles of the S. pistillata caspase and Bcl-2 genes (StyCasp and StyBcl-2-like cloned in this study. In corals exposed to thermal stress (32 or 34°C, caspase activity and the expression levels of the StyBcl-2-like gene increased over time (6-48 h and declined to basal levels within 72 h of thermal stress. Distinct transcript levels were obtained for the StyCasp gene, with stimulated expression from 6 to 48 h of 34°C thermal stress, coinciding with the onset of bleaching. Increased cell death was detected in situ only between 6 to 48 h of stress and was limited to the gastroderm. The bleached corals survived up to one month at 32°C, and recovered back symbionts when placed at 24°C. These results point to a two-stage response in corals that withstand thermal stress: (i the onset of apoptosis, accompanied by rapid activation of anti-oxidant/anti-apoptotic mediators that block the progression of apoptosis to other cells and (ii acclimatization of the coral to the chronic thermal stress alongside the completion of symbiosis breakdown. Accordingly, the coral's ability to rapidly curb apoptosis appears to be the most important trait affecting the coral's thermotolerance and survival.

  10. "Identifying the hospitalised patient in crisis"-A consensus conference on the afferent limb of Rapid Response Systems

    DEFF Research Database (Denmark)

    Devita, M.A.; Smith, G.B.; Adam, S.K.

    2010-01-01

    Background: Most reports of Rapid Response Systems (RRS) focus on the efferent, response component of the system, although evidence suggests that improved vital sign monitoring and recognition of a clinical crisis may have outcome benefits. There is no consensus regarding how best to detect patie...

  11. "Identifying the hospitalised patient in crisis"--a consensus conference on the afferent limb of rapid response systems

    DEFF Research Database (Denmark)

    DeVita, Michael A; Smith, Gary B; Adam, Sheila K

    2010-01-01

    Most reports of Rapid Response Systems (RRS) focus on the efferent, response component of the system, although evidence suggests that improved vital sign monitoring and recognition of a clinical crisis may have outcome benefits. There is no consensus regarding how best to detect patient deteriora...

  12. 46. Nurses perception of rapid response team in a tertiary hospital in Saudi Arabia

    Directory of Open Access Journals (Sweden)

    Emad Mraweh Mustafa

    2015-10-01

    Full Text Available For the last 30 years, the goal of improving the survival rate for patients post cardiopulmonary arrest has remained unattainable. This apparent failure to rescue opened the door to devise new strategies to improve patient outcomes at the onset of subtle deterioration, rather than at the point of cardiac arrest. Institute for Healthcare Improvement (IHI introduced the Rapid Response Team (RRT as one of the six preventative steps to save lives. Nurses’ perceptions of the RRT influenced by the content and process support provided. Nurses are responsible to detect the early signs of deterioration, and activate the RRT service. The aim of this cross sectional descriptive study was to examine nurses’ perceptions about the effect of the RRT and perceived content and process support in managing patient deterioration by using mental model maintenance and building at individual, group and hospital levels in a tertiary hospital in the Kingdom of Saudi Arabia. 300 nurses were recruited using a convenience sampling method. The study findings showed that the overall perceptions about the RRT were high. There was a significant positive correlation between the frequent utilization of the RRT and the perceived content support. The analysis of the open ended questions indicated that there were more advantages to have the RRT service than disadvantages. This study suggested that RRT service is influential in improving nurses’ perceptions about managing Patients’ deterioration. Training program about RRT utilization should include both content and process support, which may enhance building and maintaining mental model.

  13. Innate lymphoid cells: models of plasticity for immune homeostasis and rapid responsiveness in protection.

    Science.gov (United States)

    Almeida, F F; Belz, G T

    2016-09-01

    Innate lymphoid cells (ILCs) have stormed onto the immune landscape as "newly discovered" cell types. These tissue-resident sentinels are enriched at mucosal surfaces and engage in complex cross talk with elements of the adaptive immune system and microenvironment to orchestrate immune homeostasis. Many parallels exist between innate cells and T cells leading to the initial partitioning of ILCs into rather rigid subsets that reflect their "adaptive-like" effector cytokines profiles. ILCs themselves, however, have unique attributes that are only just beginning to be elucidated. These features result in complementarity with, rather than complete duplication of, functions of the adaptive immune system. Key transcription factors determine the pathway of differentiation of progenitors towards an ILC1, ILC2, or ILC3 subset. Once formed, flexibility in the responses of these subsets to stimuli unexpectedly allows transdifferentation between the different subsets and the acquisition of altered phenotypes and function. This provides a mechanism for rapid innate immune responsiveness. Here, we discuss the models of differentiation for maintenance and activation of tissue-resident ILCs in maintaining immune homeostasis and protection.

  14. Rapid-response Sensor Networks Leveraging Open Standards and the Internet of Things

    Science.gov (United States)

    Bermudez, L. E.; Lieberman, J. E.; Lewis, L.; Botts, M.; Liang, S.

    2016-12-01

    New sensor technologies provide an unparalleled capability to collect large numbers of diverse observations about the world around us. Networks of such sensors are especially effective for capturing and analyzing unexpected, fast moving events if they can be deployed with a minimum of time, effort, and cost. A rapid-response sensing and processing capability is extremely important in quickly unfolding events not only to collect data for future research.but also to support response efforts that may be needed by providing up-to-date knowledge of the situation. A recent pilot activity coordinated by the Open Geospatial Consortium combined Sensor Web Enablement (SWE) standards with Internet of Things (IoT) practices to understand better how to set up rapid-response sensor networks in comparable event situations involving accidents or disasters. The networks included weather and environmental sensors, georeferenced UAV and PTZ imagery collectors, and observations from "citizen sensors", as well as virtual observations generated by predictive models. A key feature of each "SWE-IoT" network was one or more Sensor Hubs that connected local, often proprietary sensor device protocols to a common set of standard SWE data types and standard Web interfaces on an IP-based internetwork. This IoT approach provided direct, common, interoperable access to all sensor readings from anywhere on the internetwork of sensors, Hubs, and applications. Sensor Hubs also supported an automated discovery protocol in which activated Hubs registered themselves with a canonical catalog service. As each sensor (wireless or wired) was activated within range of an authorized Hub, it registered itself with that Hub, which in turn registered the sensor and its capabilities with the catalog. Sensor Hub functions were implemented in a range of component types, from personal devices such as smartphones and Raspberry Pi's to full cloud-based sensor services platforms. Connected into a network

  15. Two-Step Engulfment of Apoptotic Cells

    Science.gov (United States)

    Toda, Satoshi; Hanayama, Rikinari

    2012-01-01

    Apoptotic cells expose phosphatidylserine on their surface as an “eat me” signal, and macrophages respond by engulfing them. Although several molecules that specifically bind phosphatidylserine have been identified, the molecular mechanism that triggers engulfment remains elusive. Here, using a mouse pro-B cell line, Ba/F3, that grows in suspension, we reconstituted the engulfment of apoptotic cells. The parental Ba/F3 cells did not engulf apoptotic cells. Ba/F3 transformants expressing T cell immunoglobulin- and mucin-domain-containing molecule 4 (Tim4), a type I membrane protein that specifically binds phosphatidylserine, efficiently bound apoptotic cells in a phosphatidylserine-dependent manner but did not engulf them. However, Ba/F3 transformants expressing both Tim4 and the integrin αvβ3 complex bound to and engulfed apoptotic cells in the presence of milk fat globule epidermal growth factor factor VIII (MFG-E8), a secreted protein that can bind phosphatidylserine and integrin αvβ3. These results indicate that the engulfment of apoptotic cells proceeds in two steps: Tim4 tethers apoptotic cells, and the integrin αvβ3 complex mediates engulfment in coordination with MFG-E8. A similar two-step engulfment of apoptotic cells was observed with mouse resident peritoneal macrophages. Furthermore, the Tim4/integrin-mediated engulfment by the Ba/F3 cells was enhanced in cells expressing Rac1 and Rab5, suggesting that this system well reproduces the engulfment of apoptotic cells by macrophages. PMID:22037761

  16. UMTS rapid response real-time seismic networks: implementation and strategies at INGV

    Science.gov (United States)

    Govoni, Aladino; Margheriti, Lucia; Moretti, Milena; Lauciani, Valentino; Sensale, Gianpaolo; Bucci, Augusto; Criscuoli, Fabio

    2015-04-01

    The benefits of portable real-time seismic networks are several and well known. During the management of a temporary experiment from the real-time data it is possible to detect and fix rapidly problems with power supply, time synchronization, disk failures and, most important, seismic signal quality degradation due to unexpected noise sources or sensor alignment/tampering. This usually minimizes field maintenance trips and maximizes both the quantity and the quality of the acquired data. When the area of the temporary experiment is not well monitored by the local permanent network, the real-time data from the temporary experiment can be fed to the permanent network monitoring system improving greatly both the real-time hypocentral locations and the final revised bulletin. All these benefits apply also in case of seismic crises when rapid deployment stations can significantly contribute to the aftershock analysis. Nowadays data transmission using meshed radio networks or satellite systems is not a big technological problem for a permanent seismic network where each site is optimized for the device power consumption and is usually installed by properly specialized technicians that can configure transmission devices and align antennas. This is not usually practical for temporary networks and especially for rapid response networks where the installation time is the main concern. These difficulties are substantially lowered using the now widespread UMTS technology for data transmission. A small (but sometimes power hungry) properly configured device with an omnidirectional antenna must be added to the station assembly. All setups are usually configured before deployment and this allows for an easy installation also by untrained personnel. We describe here the implementation of a UMTS based portable seismic network for both temporary experiments and rapid response applications developed at INGV. The first field experimentation of this approach dates back to the 2009 L

  17. Clinical review criteria and medical emergency teams: evaluating a two-tier rapid response system.

    Science.gov (United States)

    Bingham, Gordon; Fossum, Mariann; Barratt, Macey; Bucknall, Tracey

    2015-09-01

    To assess the prevalence of patients fulfilling clinical review criteria (CRC), to determine activation rates for CRC assessments, to compare baseline characteristics and outcomes of patients who fulfilled CRC with patients who did not, and to identify the documented nursing actions in response to CRC values. A cross-sectional study using a retrospective medical record audit, in a universityaffiliated, tertiary referral hospital with a two-tier rapid response system in Melbourne, Australia. We used a convenience sample of hospital inpatients on general medical, surgical and specialist service wards admitted during a 24-hour period in 2013. Medical emergency team (MET) or code blue activation, unplanned intensive care unit admissions, hospital length of stay and inhospital mortality. For patients who fulfilled CRC or MET criteria during the 24- hour period, the specific criteria fulfilled, escalation treatments and outcomes were collected. Of the sample (N = 422), 81 patients (19%) fulfilled CRC on 109 occasions. From 109 CRC events, 66 patients (81%) had at least one observation fulfilling CRC, and 15 patients (18%) met CRC on multiple occasions. The documented escalation rate was 58 of 109 events (53%). The number of patients who fulfilled CRC and subsequent MET call activation criteria within 24 hours was significantly greater than the number who did not meet CRC (P CRC during the study period; these patients were about four times more likely to also fulfil MET call criteria. Contrary to hospital policy, escalation was not documented for about half the patients meeting CRC values. Despite the clarity of escalation procedures on the graphic observation chart, escalation remains an ongoing problem. Further research is needed on the impact on patient outcomes over time and to understand factors influencing staff response.

  18. Using rapid assessment and response to operationalise physical activity strategic health communication campaigns in Tonga.

    Science.gov (United States)

    Turk, Tahir; Latu, Netina; Cocker-Palu, Elizabeth; Liavaa, Villiami; Vivili, Paul; Gloede, Sara; Simons, Allison

    2013-04-01

    The aim of the present study was to identify stakeholder and program beneficiary needs and wants in relation to a netball communication strategy in Tonga. In addition, the study aimed to more clearly identify audience segments for targeting of communication campaigns and to identify any barriers or benefits to engaging in the physical activity program. A rapid assessment and response (RAR) methodology was used. The elicitation research encompassed qualitative fieldwork approaches, including semistructured interviews with key informants and focus group discussions with program beneficiaries. Desk research of secondary data sources supported in-field findings. A number of potential barriers to behavioural compliance existed, including cultural factors, gender discrimination, socioeconomic factors, stigmatising attitudes, the threat of domestic violence, infrastructure and training issues. Factors contributing to participation in physical activity included the fun and social aspects of the sport, incentives (including career opportunities, highlighting the health benefits of the activity and the provision of religious and cultural sanctions by local leaders towards the increased physical activity of women. The consultative approach of RAR provided a more in-depth understanding of the need for greater levels of physical activity and opportunities for engagement by all stakeholders. The approach facilitated opportunities for the proposed health behaviours to be realised through the communication strategy. Essential insights for the strategy design were identified from key informants, as well as ensuring future engagement of these stakeholders into the strategy. So what? The expanded use of RAR to inform the design of social marketing interventions is a practical approach to data collection for non-communicable diseases and other health issues in developing countries. The approach allows for the rapid mobilisation of scarce resources for the implementation of more

  19. Effect of PDT-treated apoptotic cells on macrophages

    Science.gov (United States)

    Song, Sheng; Xing, Da; Zhou, Fei-fan; Chen, Wei R.

    2009-02-01

    Recently, the long-term immunological effects of photodynamic therapy have attracted much attention. PDT induced immune response was mainly initiated through necrotic cells and apoptotic cells, as well as immune cells such as macrophages. Nitric oxide (NO) as an important regulatory factor in signal transfer between cells has been wildly studied for generation, development, and metastasis of tumors. NO synthase is a key enzyme in nitric oxide synthesis. However, inducible nitric oxide synthase (iNOS) is usually activated under pathological conditions, such as stress and cancer, which can produce high levels of nitric oxide and contribute to tumor cytotoxicity. In addition, increased NO production by iNOS has been associated with the host immune response and cell apoptosis, which play an important role in many carcinogenesis and anti-carcinoma mechanisms. This study focuses on the NO production in macrophages, induced by mouse breast carcinoma apoptotic cells treated by PDT in vitro, and on the effects of immune response induced by apoptotic cells in tumor cells growth.

  20. Rapid Responsiveness to Practice Predicts Longer-Term Retention of Upper Extremity Motor Skill in Non-Demented Older Adults.

    Science.gov (United States)

    Schaefer, Sydney Y; Duff, Kevin

    2015-01-01

    Skill acquisition is a form of motor learning that may provide key insights into the aging brain. Although previous work suggests that older adults learn novel motor tasks slower and to a lesser extent than younger adults, we have recently demonstrated no significant effect of chronological age on the rates and amounts of skill acquisition, nor on its long-term retention, in adults over the age of 65. To better understand predictors of skill acquisition in non-demented older adults, we now explore the relationship between early improvements in motor performance due to practice (i.e., rapid responsiveness) and longer-term retention of an upper extremity motor skill, and whether the extent of rapid responsiveness was associated with global cognitive status. Results showed significant improvements in motor performance within the first five (of 150) trials, and that this "rapid responsiveness" was predictive of skill retention 1 month later. Notably, the extent of rapid responsiveness was not dependent on global cognitive status, as measured by the Montreal Cognitive Assessment (MoCA). Thus, rapid responsiveness appears to be an important variable in longer-term neurorehabilitative efforts with older adults, regardless of their cognitive status.

  1. Rapid Weight Loss Elicits Harmful Biochemical and Hormonal Responses in Mixed Martial Arts Athletes.

    Science.gov (United States)

    Coswig, Victor Silveira; Fukuda, David Hideyoshi; Del Vecchio, Fabrício Boscolo

    2015-10-01

    The purpose of this study was to compare biochemical and hormonal responses between mixed martial arts (MMA) competitors with minimal prefight weight loss and those undergoing rapid weight loss (RWL). Blood samples were taken from 17 MMA athletes (Mean± SD; age: 27.4 ±5.3yr; body mass: 76.2 ± 12.4kg; height: 1.71 ± 0.05m and training experience: 39.4 ± 25 months) before and after each match, according to the official events rules. The no rapid weight loss (NWL, n = 12) group weighed in on the day of the event (~30 min prior fight) and athletes declared not having used RWL strategies, while the RWL group (n = 5) weighed in 24 hr before the event and the athletes claimed to have lost 7.4 ± 1.1kg, approximately 10% of their body mass in the week preceding the event. Results showed significant (p < .05) increases following fights, regardless of group, in lactate, glucose, lactate dehydrogenase (LDH), creatinine, and cortisol for all athletes. With regard to group differences, NWL had significantly (p < .05) greater creatinine levels (Mean± SD; pre to post) (NWL= 101.6 ± 15-142.3 ± 22.9μmol/L and RWL= 68.9 ± 10.6-79.5 ± 15.9μmol/L), while RWL had higher LDH (median [interquartile range]; pre to post) (NWL= 211.5[183-236] to 231[203-258]U/L and RWL= 390[370.5-443.5] to 488[463.5-540.5]U/L) and AST (NWL= 30[22-37] to 32[22-41]U/L and 39[32.5-76.5] to 72[38.5-112.5] U/L) values (NWL versus RWL, p < .05). Post hoc analysis showed that AST significantly increased in only the RWL group, while creatinine increased in only the NWL group. The practice of rapid weight loss showed a negative impact on energy availability and increased both muscle damage markers and catabolic expression in MMA fighters.

  2. An improved non-contact thermometer and hygrometer with rapid response

    Science.gov (United States)

    Underwood, R.; Gardiner, T.; Finlayson, A.; Bell, S.; de Podesta, M.

    2017-02-01

    Previously (Underwood et al 2015 Meteorol. Appl. 22 830) we reported first tests of a device capable of simultaneous, non-contact, temperature and humidity (NCTAH) measurements in air. The device used an acoustic thermometer and a tuneable diode laser absorption spectrometer (TDLAS), a combination which should be capable of an extremely rapid response to changes in humidity as it does not require moisture in a solid-state matrix to equilibrate with the surrounding air. In this paper we report recent developments of the instrument focussed on reducing its response time so that it can be used as a reference instrument for assessing the response time of conventional humidity sensors. In addition, the interdependence of the temperature and humidity estimates is now accounted for in real-time using an iterative procedure, which eliminates the need for data post-processing. The TDLAS measures water molecule number density based on the transmission of an infrared beam (approximate wavelength 1360 nm) through a 0.6 m path length. The acoustic thermometer is based around a fixed-path acoustic interferometer. The improved NCTAH device now produces estimates of the water molecule number density every 20 ms and the temperature output displays an RC filter-like response, with a time constant of approximately 30 ms. The instrument has been tested in a climatic chamber through a temperature range of  -40 °C to  +40 °C and a dew point range of  -43 °C to  +38 °C, at atmospheric pressure, comparing the instrument readings with those from a calibrated hygrometer and four platinum resistance thermometers. In steady-state conditions, the instrument readings are in good agreement with the conventional sensors, with temperature differences less than 1 °C (repeatability 0.1 °C), and humidity differences mostly within 5% of mixing ratio. Under transient conditions, we demonstrate how the instrument can be used to evaluate the response times of conventional

  3. A volcano-seismic event spotting system for the use in rapid response systems

    Science.gov (United States)

    Hammer, Conny; Ohrnberger, Matthias

    2010-05-01

    The classification of seismic signals of volcanic origin is an important task in monitoring active volcanoes. The number and size of certain types of seismic events usually increase before periods of volcanic crisis and can be used to quantify the volcanic activity. Due to the advantage of providing consistent, objective and time-invariant results automatic classification systems are preferred. Most automatic classification systems are trained in a supervised fashion from a sufficiently large pre-classified data set. The setup of an automatic classification system thus requires the pre-existence of these training data. For a rapid volcano-response team, however, the situation is often different. In the worst case, no prior observations exist (e.g. re-awakening of a dormant volcano). More frequently, archive data exist for a particular observatory network, but no record of seismicity for a high volcanic activity level exists and new seismicity patterns occur. Usually, the networks are additionally sparse and new equipment will be installed for better surveillance during the actual crisis. For the new recording sites again no prior example data is available. Finally, due to the imminent crisis there might be no time for the time-consuming and tedious process of preparing a training data set. For all these reasons a classification system which allows a "learning-while-recording" approach would be very advantageous for use in rapid response systems. Within this study, we show a novel seismic event spotting approach in order to reduce the dependency on the existence of previously acquired data bases and classification schemes. One main goal is therefore to provide the observatory staff with a robust event classification system based on a minimum number of reference waveforms and thus allowing for a fast build-up of a volcanic signal classification scheme as early as interesting events have been identified. For implementation issues we make use of the Hidden Markov

  4. Rapid-Response Characterization of Near-Earth Asteroids Using KMTNet-SAAO

    Science.gov (United States)

    Erasmus, Nicolas; Mommert, Michael; Trilling, David E.; Sickafoose, Amanda A.; van Gend, Carel; Hora, Joseph L.; Worters, Hannah L.

    2017-10-01

    We present here VRI spectrophotometry of 39 near-Earth asteroids (NEAs) observed with the Sutherland, South Africa, node of the Korea Microlensing Telescope Network (KMTNet). Of the 39 NEAs, 19 were targeted, but because of KMTNet’s large 2 deg × 2 deg field of view, 20 serendipitous NEAs were also captured in the observing fields. Our rapid-response approach meant targeted observations were performed within 44 days (median: 16 days, min: 4 days) of each NEA’s discovery date. Our broadband spectrophotometry is reliable enough to distinguish among four asteroid taxonomies and we were able to confidently categorize 31 of the 39 observed targets as either a S-, C-, X- or D-type asteroid. Our data suggest that the ratio between “stony” S-type NEAs and “not- stony” (C+X+D)-type NEAs, with H magnitudes between 15 and 25, is roughly 1:1. Additionally, we report ~1-hour light curve data for each NEA. Of the 39 targets, we were able to resolve the complete rotation period and amplitude for six and place lower limits for the remaining targets.Based on the success of this pilot study we plan to continue KMTNet observations but also make use of Lesedi, a new 1-meter remotely-operable telescope also situated in Sutherland, to perform similar spectrophotometric observations in the future. As before, we plan to target newly discovered NEAs in order to continue the rapid-response approach. With Lesedi, observations will take place throughout the year and we plan to include smaller NEAs (larger H magnitudes) in our sample. We will also increase the observed duration of each NEA to 2-3 hours so we are more likely to observe a complete rotation period for our observed NEAs.This study was facilitated by observations made at the South African Astronomical Observatory (SAAO) and this work is partially supported by the South African National Research Foundation (NRF). This work is supported in part by the National Aeronautics and Space Administration (NASA) under grant

  5. Interactive terrain visualization enables virtual field work during rapid scientific response to the 2010 Haiti earthquake

    Science.gov (United States)

    Cowgill, Eric; Bernardin, Tony S.; Oskin, Michael E.; Bowles, Christopher; Yikilmaz, M. Burak; Kreylos, Oliver; Elliott, Austin J.; Bishop, Scott; Gold, Ryan D.; Morelan, Alexander; Bawden, Gerald W.; Hamann, Bernd; Kellogg, Louise

    2012-01-01

    The moment magnitude (Mw) 7.0 12 January 2010 Haiti earthquake is the first major earthquake for which a large-footprint LiDAR (light detection and ranging) survey was acquired within several weeks of the event. Here, we describe the use of virtual reality data visualization to analyze massive amounts (67 GB on disk) of multiresolution terrain data during the rapid scientific response to a major natural disaster. In particular, we describe a method for conducting virtual field work using both desktop computers and a 4-sided, 22 m3 CAVE immersive virtual reality environment, along with KeckCAVES (Keck Center for Active Visualization in the Earth Sciences) software tools LiDAR Viewer, to analyze LiDAR point-cloud data, and Crusta, for 2.5 dimensional surficial geologic mapping on a bare-earth digital elevation model. This system enabled virtual field work that yielded remote observations of the topographic expression of active faulting within an ∼75-km-long section of the eastern Enriquillo–Plantain Garden fault spanning the 2010 epicenter. Virtual field observations indicated that the geomorphic evidence of active faulting and ancient surface rupture varies along strike. Landform offsets of 6–50 m along the Enriquillo–Plantain Garden fault east of the 2010 epicenter and closest to Port-au-Prince attest to repeated recent surface-rupturing earthquakes there. In the west, the fault trace is well defined by displaced landforms, but it is not as clear as in the east. The 2010 epicenter is within a transition zone between these sections that extends from Grand Goâve in the west to Fayette in the east. Within this transition, between L'Acul (lat 72°40′W) and the Rouillone River (lat 72°35′W), the Enriquillo–Plantain Garden fault is undefined along an embayed low-relief range front, with little evidence of recent surface rupture. Based on the geometry of the eastern and western faults that show evidence of recent surface rupture, we propose that the 2010

  6. Apoptotic Bodies: Selective Detection in Extracellular Vesicles.

    Science.gov (United States)

    Hauser, Paul; Wang, Sha; Didenko, Vladimir V

    2017-01-01

    Normal and dying cells release various types of membrane-bound vesicles including microvesicles, exosomes, and apoptotic bodies. These vesicles play important roles in intercellular communication and signal transduction. However, their diverse forms and subtypes fluctuate in size and other properties. In result current purification approaches do not fully discriminate between different categories of extracellular vesicles. Here, we present a fluorescence technique that specifically identifies apoptotic bodies in preparations of microvesicles, exosomes, and other extracellular vesicles.The approach exclusively labels the vesicles that contain DNA with 5'PO 4 blunt-ended DNA breaks, such as those produced by the apoptotic CAD nuclease during apoptotic DNA degradation. The technique can be useful in studies of apoptosis involving microvesicles and exosomes.

  7. Using Simulation to Develop Care Models for Rapid Response and Code Teams at a Satellite Facility.

    Science.gov (United States)

    Rule, Amy R L; Snider, Julie; Marshall, Cheryl; Kramer, Kathleen; Geis, Gary L; Tegtmeyer, Ken; Gosdin, Craig H

    2017-12-01

    Our institution recently completed an expansion of an acute care inpatient unit within a satellite hospital that does not include an on-site ICU or PICU. Because of expected increases in volume and acuity, new care models for Rapid Response Teams (RRTs) and Code Blue Teams were necessary. Using simulation-based training, our objectives were to define the optimal roles and responsibilities for team members (including ICU physicians via telemedicine), refine the staffing of RRTs and code Teams, and identify latent safety threats (LSTs) before opening the expanded inpatient unit. The laboratory-based intervention consisted of 8 scenarios anticipated to occur at the new campus, with each simulation followed by an iterative debriefing process and a 30-minute safety talk delivered within 4-hour interprofessional sessions. In situ sessions were delivered after construction and before patients were admitted. A total of 175 clinicians completed a 4-hour course in 17 sessions. Over 60 clinicians participated during 2 in situ sessions before the opening of the unit. Eleven team-level knowledge deficits, 19 LSTs, and 25 system-level issues were identified, which directly informed changes and refinements in care models at the bedside and via telemedicine consultation. Simulation-based training can assist in developing staffing models, refining the RRT and code processes, and identify LSTs in a new pediatric acute care unit. This training model could be used as a template for other facilities looking to expand pediatric acute care at outlying smaller, more resource-limited facilities to evaluate new teams and environments before patient exposure. Copyright © 2017 by the American Academy of Pediatrics.

  8. Tachyphylaxis of human forearm vascular responses does not occur rapidly after exposure to isoproterenol.

    Science.gov (United States)

    Stein, C M; Nelson, R; Deegan, R; He, H; Inagami, T; Frazer, M; Badr, K F; Wood, M; Wood, A J

    1995-06-01

    In vitro and limited in vivo data suggest that rapid desensitization of beta-adrenoceptor responses occurs after exposure to agonist. Tachyphylaxis to a beta-adrenoceptor agonist would represent a potentially important mechanism for the short-term regulation of vascular tone. The effects of a 4-hour infusion of 400 ng/min intra-arterial isoproterenol on forearm blood flow and presynaptic beta-adrenoceptor-mediated norepinephrine release were determined in eight healthy volunteers. Intra-arterial isoproterenol at 400 ng/min resulted in a significant increase in forearm blood flow in all eight subjects at all time points, with no evidence of tachyphylaxis. In fact, forearm blood flow after 4 hours of the isoproterenol infusion (22.8 +/- 3.3 mL/100 mL per minute) was significantly greater than after 7 minutes (14.6 +/- 2.8 mL/100 mL per minute), 15 minutes (15.4 +/- 2.4 mL/100 mL per minute), and 30 minutes (17.4 +/- 3.0 mL/100 mL per minute) of the infusion (P < .05). Similarly, presynaptic beta-adrenoceptor responses showed no evidence of tachyphylaxis, so forearm norepinephrine spillover values after 7 minutes (6.6 +/- 0.94 ng/min), 15 minutes (7.6 +/- 1.5 ng/min), and 4 hours (8.8 +/- 1.1 ng/min) of isoproterenol infusion were increased and similar. Minimal systemic effects were observed, and there was no evidence of tolerance, there being no difference in heart rate after 7 minutes (70.7 +/- 2.7 beats per minute) and 4 hours (72.2 +/- 3.6 beats per minute) of isoproterenol infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

  9. Student Accomplishments in the Rapid Response Radiotherapy Program: A 10-Year Review.

    Science.gov (United States)

    McDonald, Rachel; Lechner, Breanne; Pulenzas, Natalie; Bedard, Gillian; Wong, Erin; Holden, Lori; Tsao, May; Barnes, Elizabeth; Szumacher, Ewa; Fenton, Gonenc; Chow, Edward; Popovic, Marko; Danjoux, Cyril

    2015-12-01

    In 1996, the Toronto Sunnybrook Regional Cancer Centre developed the Rapid Response Radiotherapy Program (RRRP). The objective of this clinic is to consult, simulate, plan, and treat patients with palliative radiotherapy on the same day. In 2004, the RRRP initiated a program to provide clinical and research experience to undergraduate students interested in health sciences. The purpose of this study is to review the 10-year (2004-2013) experience of the RRRP and to examine whether the goals of the student program have been met. Students who worked in the RRRP from 2004 to 2013 were contacted to complete a short survey regarding their overall experience with the program and their current endeavors. Student accomplishments were collected from an internal database as well as PubMed. Descriptive statistics were used to analyze results. A total of 54 students from ten postsecondary institutions have worked in the RRRP; 29 were from the University of Waterloo undergraduate co-op program. In total, 214 articles with first authorship from students were published, 93 (43%) of which can be found on PubMed. Other accomplishments include 40 book chapters, 58 invited presentations, and 99 awards cumulatively. Qualitative data regarding student perspectives of their experience in the RRRP were also analyzed. Over the past 10 years, the RRRP has achieved its goal of providing quality medical and research experience to students interested in the health sciences. Using the responses of past and present students, we hope to continue to shape our program and provide unique opportunities to future students.

  10. FIRST RESULTS FROM THE RAPID-RESPONSE SPECTROPHOTOMETRIC CHARACTERIZATION OF NEAR-EARTH OBJECTS USING UKIRT

    Energy Technology Data Exchange (ETDEWEB)

    Mommert, M.; Trilling, D. E.; Petersen, E. [Department of Physics and Astronomy, Northern Arizona University, Flagstaff, AZ 86001 (United States); Borth, D. [Deutsches Forschungszentrum für Künstliche Intelligenz (DFKI), D-67663 Kaiserslautern (Germany); Jedicke, R. [Institute for Astronomy, University of Hawaii at Manoa, Honolulu, HI 96822 (United States); Butler, N. [School of Earth and Space Exploration, Arizona State University, Tempe, AZ 85287 (United States); Reyes-Ruiz, M. [Universidad Nacional Autónoma de México, Instituto de Astronomía, Ensenada, B.C. 22860, México (Mexico); Pichardo, B. [Instituto de Astronomía, Universidad Nacional Autónoma de México, Ciudad Universitaria, D.F. 04510, México (Mexico); Axelrod, T. [Steward Observatory, University of Arizona, Tucson, AZ 85721 (United States); Moskovitz, N., E-mail: michael.mommert@nau.edu [Lowell Observatory, Flagstaff, AZ 86001 (United States)

    2016-04-15

    Using the Wide Field Camera for the United Kingdom Infrared Telescope (UKIRT), we measure the near-infrared colors of near-Earth objects (NEOs) in order to put constraints on their taxonomic classifications. The rapid-response character of our observations allows us to observe NEOs when they are close to the Earth and bright. Here we present near-infrared color measurements of 86 NEOs, most of which were observed within a few days of their discovery, allowing us to characterize NEOs with diameters of only a few meters. Using machine-learning methods, we compare our measurements to existing asteroid spectral data and provide probabilistic taxonomic classifications for our targets. Our observations allow us to distinguish between S-complex, C/X-complex, D-type, and V-type asteroids. Our results suggest that the fraction of S-complex asteroids in the whole NEO population is lower than the fraction of ordinary chondrites in the meteorite fall statistics. Future data obtained with UKIRT will be used to investigate the significance of this discrepancy.

  11. Rapid and Quantitative Assessment of Cancer Treatment Response Using In Vivo Bioluminescence Imaging

    Directory of Open Access Journals (Sweden)

    Alnawaz Rehemtulla

    2000-01-01

    Full Text Available Current assessment of orthotopic tumor models in animals utilizes survival as the primary therapeutic end point. In vivo bioluminescence imaging (BLI is a sensitive imaging modality that is rapid and accessible, and may comprise an ideal tool for evaluating antineoplastic therapies [1 ]. Using human tumor cell lines constitutively expressing luciferase, the kinetics of tumor growth and response to therapy have been assessed in intraperitoneal [2], subcutaneous, and intravascular [3] cancer models. However, use of this approach for evaluating orthotopic tumor models has not been demonstrated. In this report, the ability of BLI to noninvasively quantitate the growth and therapeuticinduced cell kill of orthotopic rat brain tumors derived from 9L gliosarcoma cells genetically engineered to stably express firefly luciferase (9LLuc was investigated. Intracerebral tumor burden was monitored over time by quantitation of photon emission and tumor volume using a cryogenically cooled CCD camera and magnetic resonance imaging (MRI, respectively. There was excellent correlation (r=0.91 between detected photons and tumor volume. A quantitative comparison of tumor cell kill determined from serial MRI volume measurements and BLI photon counts following 1,3-bis(2-chloroethyl-1-nitrosourea (BCNU treatment revealed that both imaging modalities yielded statistically similar cell kill values (P=.951. These results provide direct validation of BLI imaging as a powerful and quantitative tool for the assessment of antineoplastic therapies in living animals.

  12. NOAA Atmospheric, Marine and Arctic Monitoring Using UASs (including Rapid Response)

    Science.gov (United States)

    Coffey, J. J.; Jacobs, T.

    2015-12-01

    Unmanned systems have the potential to efficiently, effectively, economically, and safely bridge critical observation requirements in an environmentally friendly manner. As the United States' Atmospheric, Marine and Arctic areas of interest expand and include hard-to-reach regions of the Earth (such as the Arctic and remote oceanic areas) optimizing unmanned capabilities will be needed to advance the United States' science, technology and security efforts. Through increased multi-mission and multi-agency operations using improved inter-operable and autonomous unmanned systems, the research and operations communities will better collect environmental intelligence and better protect our Country against hazardous weather, environmental, marine and polar hazards. This presentation will examine NOAA's Atmospheric, Marine and Arctic Monitoring Unmanned Aircraft System (UAS) strategies which includes developing a coordinated effort to maximize the efficiency and capabilities of unmanned systems across the federal government and research partners. Numerous intra- and inter-agency operational demonstrations and assessments have been made to verify and validated these strategies. This includes the introduction of the Targeted Autonomous Insitu Sensing and Rapid Response (TAISRR) with UAS concept of operations. The presentation will also discuss the requisite UAS capabilities and our experience in using them.

  13. Defining impact of a rapid response team: qualitative study with nurses, physicians and hospital administrators.

    Science.gov (United States)

    Benin, Andrea L; Borgstrom, Christopher P; Jenq, Grace Y; Roumanis, Sarah A; Horwitz, Leora I

    2012-05-01

    The objective of this study was to qualitatively describe the impact of a Rapid Response Team (RRT) at a 944-bed, university-affiliated hospital. We analysed 49 open-ended interviews with administrators, primary team attending physicians, trainees, RRT attending hospitalists, staff nurses, nurses and respiratory technicians. Themes elicited were categorised into the domains of (1) morale and teamwork, (2) education, (3) workload, (4) patient care, and (5) hospital administration. Positive implications beyond improved care for acutely ill patients were: increased morale and empowerment among nurses, real-time redistribution of workload for nurses (reducing neglect of non-acutely ill patients during emergencies), and immediate access to expert help. Negative implications were: increased tensions between nurses and physician teams, a burden on hospitalist RRT members, and reduced autonomy for trainees. The RRT provides advantages that extend well beyond a reduction in rates of transfers to intensive care units or codes but are balanced by certain disadvantages. The potential impact from these multiple sources should be evaluated to understand the utility of any RRT programme.

  14. Republished: Defining impact of a rapid response team: qualitative study with nurses, physicians and hospital administrators.

    Science.gov (United States)

    Benin, Andrea L; Borgstrom, Christopher P; Jenq, Grace Y; Roumanis, Sarah A; Horwitz, Leora I

    2012-10-01

    The objective of this study was to qualitatively describe the impact of a Rapid Response Team (RRT) at a 944-bed, university-affiliated hospital. We analysed 49 open-ended interviews with administrators, primary team attending physicians, trainees, RRT attending hospitalists, staff nurses, nurses and respiratory technicians. Themes elicited were categorised into the domains of (1) morale and teamwork, (2) education, (3) workload, (4) patient care, and (5) hospital administration. Positive implications beyond improved care for acutely ill patients were: increased morale and empowerment among nurses, real-time redistribution of workload for nurses (reducing neglect of non-acutely ill patients during emergencies), and immediate access to expert help. Negative implications were: increased tensions between nurses and physician teams, a burden on hospitalist RRT members, and reduced autonomy for trainees. The RRT provides advantages that extend well beyond a reduction in rates of transfers to intensive care units or codes but are balanced by certain disadvantages. The potential impact from these multiple sources should be evaluated to understand the utility of any RRT programme.

  15. Rapid identification of transience in streambed conductance by inversion of floodwave responses

    Science.gov (United States)

    Gianni, Guillaume; Richon, Julien; Perrochet, Pierre; Vogel, Alexandre; Brunner, Philip

    2016-04-01

    Streambed conductance controls the interaction between surface and groundwater. However, the streambed conductance is often subject to transience. Directly measuring hydraulic properties in a river yields only point values, is time-consuming and therefore not suited to detect transience of physical properties. Here, we present a method to continuously monitor transience in streambed conductance. Input data are time series of stream stage and near stream hydraulic head. The method is based on the inversion of floodwave responses. The analytical model consists of three parameters: x, the distance between streambank and an observation well, α, the aquifer diffusivity, and a the retardation coefficient that is inversely proportional to the streambed conductance. Estimation of a is carried out over successive time steps in order to identify transience in streambed conductance. The method is tested using synthetic data and is applied to field data from the Rhône River and its alluvial aquifer (Switzerland). The synthetic method demonstrated the robustness of the proposed methodology. Application of the method to the field data allowed identifying transience in streambed properties, following flood events in the Rhône. This method requires transience in the surface water, and the river should not change its width significantly with a rising water level. If these conditions are fulfilled, this method allows for a rapid and effective identification of transience in streambed conductance.

  16. Organizational Perspectives on Rapid Response Team Structure, Function, and Cost: A Qualitative Study.

    Science.gov (United States)

    Smith, Patricia L; McSweeney, Jean

    Understanding how an organization determines structure and function of a rapid response team (RRT), as well as cost evaluation and implications, can provide foundational knowledge to guide decisions about RRTs. The objectives were to (1) identify influencing factors in organizational development of RRT structure and function and (2) describe evaluation of RRT costs. Using a qualitative, ethnographic design, nurse executives and experts in 15 moderate-size hospitals were interviewed to explore their decision-making processes in determining RRT structure and function. Face-to-face interviews were audio recorded and transcribed verbatim and verified for accurateness. Using content analysis and constant comparison, interview data were analyzed. Demographic data were analyzed using descriptive statistics. The sample included 27 participants from 15 hospitals in 5 south-central states. They described a variety of RRT responders and functions, with the majority of hospitals having a critical care charge nurse attending all RRT calls for assistance. Others described a designated RRT nurse with primary RRT duties as responder to all RRT calls. Themes of RRT development from the data included influencers, decision processes, and thoughts about cost. It is important to understand how hospitals determine optimal structure and function to enhance support of quality nursing care. Determining the impact of an RRT on costs and benefits is vital in balancing patient safety and limited resources. Future research should focus on clarifying differences between team structure and function in outcomes as well as the most effective means to estimate costs and benefits.

  17. Acute Kidney Injury Risk Assessment and the Nephrology Rapid Response Team.

    Science.gov (United States)

    Rizo-Topete, Lilia Maria; Rosner, Mitchell H; Ronco, Claudio

    2017-01-01

    Acute kidney Injury (AKI) is a serious medical condition affecting more than 10 million people around the world annually and resulting in poor outcomes. It has been suggested that late recognition of the syndrome may lead to delayed interventions with increased morbidity and mortality. Early diagnosis and timely therapeutic strategies may be the cornerstone of future improvement in outcomes. The purpose of this article is to provide a practical model to identify patients at high risk for AKI in different environments, with the goal to prevent AKI. We describe the AKI Risk Assessment (ARA) as a proposed algorithm that systematically evaluates the patient in high-risk situations of AKI in a simple way no matter where the patient is located, and allows different medical specialists to approach patients as a team with a nephrologist to improve outcomes. The goal of the nephrology rapid response team (NRRT) is to prevent AKI or start treatment if AKI is already diagnosed as a consequence of progressive events that can lead to progressive deterioration of kidney tissues and eventual decline in renal function and to ensure appropriate follow-up of patients at risk for progressive chronic kidney disease after the episode of AKI. Prevention is the key to avoid mortality and morbidity associated with AKI. Integration of these assessment tools in a global methodology that includes a multi-disciplinary team (NRRT) is critical to success. Video Journal Club 'Cappuccino with Claudio Ronco' at http://www.karger.com/?doi=452402. © 2016 S. Karger AG, Basel.

  18. Utility and assessment of non-technical skills for rapid response systems and medical emergency teams.

    Science.gov (United States)

    Chalwin, R P; Flabouris, A

    2013-09-01

    Efforts are ongoing to improve outcomes from cardiac arrest and medical emergencies. A promising quality improvement modality is use of non-technical skills (NTS) that aim to address human factors through improvements in performance of leadership, communication, situational awareness and decision-making. Originating in the airline industry, NTS training has been successfully introduced into anaesthesia, surgery, emergency medicine and other acute medical specialities. Some aspects of NTS have already achieved acceptance for cardiac arrest teams. Leadership skills are emphasised in advanced life support training and have shown favourable results when employed in simulated and clinical resuscitation scenarios. The application of NTS in medical emergency teams as part of a rapid response system attending medical emergencies is less certain; however, observations of simulations have also shown promise. This review highlights the potential benefits of NTS competency for cardiac arrest teams and, more importantly, medical emergency teams because of the diversity of clinical scenarios encountered. Discussion covers methods to assess and refine NTS and NTS training to optimise performance in the clinical environment. Increasing attention should be applied to yielding meaningful patient and organisational outcomes from use of NTS. Similarly, implementation of any training course should receive appropriate scrutiny to refine team and institutional performance. © 2013 The Authors; Internal Medicine Journal © 2013 Royal Australasian College of Physicians.

  19. Rapid Response of Eastern Mediterranean Deep Sea Microbial Communities to Oil

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Jiang; Techtmann, Stephen M.; Woo, Hannah L.; Ning, Daliang; Fortney, Julian L.; Hazen, Terry C.

    2017-07-18

    Deep marine oil spills like the Deepwater Horizon (DWH) in the Gulf of Mexico have the potential to drastically impact marine systems. Crude oil contamination in marine systems remains a concern, especially for countries around the Mediterranean Sea with off shore oil production. The goal of this study was to investigate the response of indigenous microbial communities to crude oil in the deep Eastern Mediterranean Sea (E. Med.) water column and to minimize potential bias associated with storage and shifts in microbial community structure from sample storage. 16S rRNA amplicon sequencing was combined with GeoChip metagenomic analysis to monitor the microbial community changes to the crude oil and dispersant in on-ship microcosms set up immediately after water collection. After 3 days of incubation at 14 °C, the microbial communities from two different water depths: 824 m and 1210 m became dominated by well-known oil degrading bacteria. The archaeal population and the overall microbial community diversity drastically decreased. Similarly, GeoChip metagenomic analysis revealed a tremendous enrichment of genes related to oil biodegradation, which was consistent with the results from the DWH oil spill. These results highlight a rapid microbial adaption to oil contamination in the deep E. Med., and indicate strong oil biodegradation potentia

  20. Optical satellite data volcano monitoring: a multi-sensor rapid response system

    Science.gov (United States)

    Duda, Kenneth A.; Ramsey, Michael; Wessels, Rick L.; Dehn, Jonathan

    2009-01-01

    response program described in this chapter also improves the temporal resolution of the ASTER instrument. ASTER has been acquiring images of volcanic eruptions since soon after its launch in December 1999. An early example included the observations of the large pyroclastic flow deposit emplaced at Bezymianny volcano in Kamchatka, Russia. The first images in March 2000, just weeks after the eruption, revealed the extent, composition, and cooling history of this large deposit and of the active lava dome (Ramsey and Dehn, 2004). The initial results from these early datasets spurred interest in using ASTER data for expanded volcano monitoring in the north Pacific. It also gave rise to the multi-year NASA-funded programs of rapid response scheduling and imaging throughout the Aleutian, Kamchatka and Kurile arcs. Since the formal establishment of the programs, the data have provided detailed descriptions of the eruptions of Augustine, Bezymianny, Kliuchevskoi and Sheveluch volcanoes over the past nine years (Wessels et al., in press; Carter et al., 2007, 2008; Ramsey et al., 2008; Rose and Ramsey, 2009). The initial research focus of this rapid response program was specifically on automating the ASTER sensor’s ability for targeted observational scheduling using the expedited data system. This urgent request protocol is one of the unique characteristics of ASTER. It provides a limited number of emergency observations, typically at a much-improved temporal resolution and quicker turnaround with data processing in the United States rather than in Japan. This can speed the reception of the processed data by several days to a week. The ongoing multi-agency research and operational collaboration has been highly successful. AVO serves as the primary source for status information on volcanic activity, working closely with the National Weather Service (NWS), Federal Aviation Administration (FAA), military and other state and federal emergency services. Collaboration with the Russian

  1. Cobra venom cytotoxins; apoptotic or necrotic agents?

    Science.gov (United States)

    Ebrahim, Karim; Shirazi, Farshad H; Mirakabadi, Abbas Zare; Vatanpour, Hossein

    2015-12-15

    Organs homeostasis is controlled by a dynamic balance between cell proliferation and apoptosis. Failure to induction of apoptosis has been implicated in tumor development. Cytotoxin-I (CTX-I) and cytotoxin-II (CTX-II) are two physiologically active polypeptides found in Caspian cobra venom. Anticancer activity and mechanism of cell death induced by these toxins have been studied. The toxins were purified by different chromatographic steps and their cytotoxicity and pattern of cell death were determined by MTT, LDH release, acridine orange/ethidium bromide (AO/EtBr) double staining, flow cytometric analysis, caspase-3 activity and neutral red assays. The IC50 of CTX-II in MCF-7, HepG2, DU-145 and HL-60 was 4.1 ± 1.3, 21.2 ± 4.4, 9.4 ± 1.8 μg/mL and 16.3 ± 1.9 respectively while the IC50 of this toxin in normal MDCK cell line was 54.5 ± 3.9 μg/mL. LDH release suddenly increase after a specific toxins concentrations in all cell lines. AO/EtBr double staining, flow cytometric analysis and caspase-3 activity assay confirm dose and time-dependent induction of apoptosis by both toxins. CTX-I and CTX-II treated cells lost their lysosomal membrane integrity and couldn't uptake neutral red day. CTX-I and CTX-II showed significant anticancer activity with minimum effects on normal cells and better IC50 compared to current anticancer drug; cisplatin. They induce their apoptotic effect via lysosomal pathways and release of cathepsins to cytosol. These effects were seen in limited rage of toxins concentrations and pattern of cell death rapidly changes to necrosis by increase in toxin's concentration. In conclusion, significant apoptogenic effects of these toxins candidate them as a possible anticancer agent. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. The complexity of apoptotic cell death in mollusks: An update.

    Science.gov (United States)

    Romero, A; Novoa, B; Figueras, A

    2015-09-01

    Apoptosis is a type of programmed cell death that produces changes in cell morphology and in biochemical intracellular processes without inflammatory reactions. The components of the apoptotic pathways are conserved throughout evolution. Caspases are key molecules involved in the transduction of the death signal and are responsible for many of the biochemical and morphological changes associated with apoptosis. Nowadays, It is known that caspases are activated through two major apoptotic pathways (the extrinsic or death receptor pathway and the intrinsic or mitochondrial pathway), but there are also evidences of at least other alternative pathway (the perforin/granzyme pathway). Apoptosis in mollusks seems to be similar in complexity to apoptosis in vertebrates but also has unique features maybe related to their recurrent exposure to environmental changes, pollutants, pathogens and also related to the sedentary nature of some stages in the life cycle of mollusks bivalves and gastropods. As in other animals, apoptotic process is involved in the maintenance of tissue homeostasis and also constitutes an important immune response that can be triggered by a variety of stimuli, including cytokines, hormones, toxic insults, viruses, and protozoan parasites. The main goal of this work is to present the current knowledge of the molecular mechanisms of apoptosis in mollusks and to highlight those steps that need further study. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Macrophage Clearance of Apoptotic Cells: A Critical Assessment

    Directory of Open Access Journals (Sweden)

    Siamon Gordon

    2018-01-01

    Full Text Available As the body continues to grow and age, it becomes essential to maintain a balance between living and dying cells. Macrophages and dendritic cells play a central role in discriminating among viable, apoptotic, and necrotic cells, as selective and efficient phagocytes, without inducing inappropriate inflammation or immune responses. A great deal has been learnt concerning clearance receptors for modified and non-self-ligands on potential targets, mediating their eventual uptake, disposal, and replacement. In this essay, we assess current understanding of the phagocytic recognition of apoptotic cells within their tissue environment; we conclude that efferocytosis constitutes a more complex process than simply removal of corpses, with regulatory interactions between the target and effector cells, which determine the outcome of this homeostatic process.

  4. Communication and general concern criterion prior to activation of the rapid response team: a grounded theory.

    Science.gov (United States)

    Martland, Jarrad; Chamberlain, Diane; Hutton, Alison; Smigielski, Michael

    2016-11-01

    Objective Patients commonly show signs and symptoms of deterioration for hours or days before cardiorespiratory arrest. Rapid response teams (RRT) were created to improve recognition and response to patient deterioration in these situations. Activation criteria include vital signs or 'general concern' by a clinician or family member. The general concern criterion for RRT activation accounts for nearly one-third of all RRT activity, and although it is well established that communication deficits between staff can contribute to poorer outcomes for patients, there is little evidence pertaining to communication and its effects on the general concern RRT activation. Thus, the aim of the present study was to develop a substantive grounded theory related to the communication process between clinicians that preceded the activation of an RRT when general concern criterion was used. Methods Qualitative grounded theory involved collection of three types of data details namely personal notes from participants in focus groups with white board notes from discussions and audio recordings of the focus groups sessions. Focus groups were conducted with participants exploring issues associated with clinician communication and how it related to the activation of an RRT using the general concern criterion. Results The three main phases of coding (i.e. open, axial and selective coding) analysis identified 322 separate open codes. The strongest theme contributed to a theory of ineffective communication and decreased psychological safety, namely that 'In the absence of effective communication there is a subsequent increase in anxiety, fear or concern that can be directly attributed to the activation of an RRT using the 'general concern' criterion'. The RRT filled cultural and process deficiencies in the compliance with an escalation protocol. Issues such as 'not for resuscitation documentation' and 'inability to establish communication with and between medical or nursing personnel' rated

  5. Rapid disruption of axon-glial integrity in response to mild cerebral hypoperfusion

    Science.gov (United States)

    Reimer, Michell Mario; McQueen, Jamie; Searcy, Luke; Scullion, Gillian; Zonta, Barbara; Desmazieres, Anne; Holland, Philip Robert; Smith, Jessica; Gliddon, Catherine; Wood, Emma R; Herzyk, Pawel; Brophy, Peter; McCulloch, James; Horsburgh, Karen

    2015-01-01

    proliferation processes. Our results demonstrated that in response to hypoperfusion there is a rapid disruption of key proteins critical to the stability of the paranodes and axon-glial connection that is mediated by a diversity of molecular events. PMID:22159130

  6. Rapid response of the steatosis-sensing hepatokine LECT2 during diet-induced weight cycling in mice.

    Science.gov (United States)

    Chikamoto, Keita; Misu, Hirofumi; Takayama, Hiroaki; Kikuchi, Akihiro; Ishii, Kiyo-Aki; Lan, Fei; Takata, Noboru; Tajima-Shirasaki, Natsumi; Takeshita, Yumie; Tsugane, Hirohiko; Kaneko, Shuichi; Matsugo, Seiichi; Takamura, Toshinari

    2016-09-23

    Dieting often leads to body weight cycling involving repeated weight loss and regain. However, little information is available regarding rapid-response serum markers of overnutrition that predict body weight alterations during weight cycling. Here, we report the rapid response of serum leukocyte cell-derived chemotaxin 2 (LECT2), a hepatokine that induces insulin resistance in skeletal muscle, during diet-induced weight cycling in mice. A switch from a high-fat diet (HFD) to a regular diet (RD) in obese mice gradually decreased body weight but rapidly decreased serum LECT2 levels within 10 days. In contrast, a switch from a RD to a HFD rapidly elevated serum LECT2 levels. Serum LECT2 levels showed a positive correlation with liver triglyceride contents but not with adipose tissue weight. This study demonstrates the rapid response of LECT2 preceding body weight alterations during weight cycling in mice and suggests that measurement of serum LECT2 may be clinically useful in the management of obesity. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  7. Different changes in mitochondrial apoptotic pathway in lymphocytes and granulocytes in cirrhotic patients with sepsis.

    Science.gov (United States)

    Precone, Vincenza; Stornaiuolo, Gianfranca; Amato, Annamaria; Brancaccio, Giuseppina; Nardiello, Salvatore; Gaeta, Giovanni B

    2013-07-01

    Apoptosis regulates leucocyte response during bacterial infections. This study explored leucocyte apoptotic pathway in cirrhotic patients with or without infections or sepsis. In cirrhotic patients with bacterial infection or sepsis, the expression of Caspase 9, Bcl-2 family proteins, which comprises pro-apoptotic molecules, such as Bax, and anti-apoptotic molecules, such as Bcl-2 and Bcl-xL, were measured in peripheral lymphocytes and granulocytes. Regulatory microRNAs MIR-15 and MIR-16 were also measured. This study enrolled 80 patients with cirrhosis, of whom 28 had no evidence of infections, 32 had bacterial infections and 20 had sepsis; reference values were obtained from 10 age-matched healthy subjects. An over-expression of Caspase-9 and pro-apoptotic protein Bax was found in lymphocytes of cirrhotic patients with infection or sepsis as compared with non-infected cases (P = 0.05 and 0.0001, respectively), while anti-apoptotic proteins Bcl-2 and Bcl-xL were downregulated. In granulocytes, lowest expression of pro-apoptotic protein Bax occurred in septic patients, while in cirrhotics with infections anti-apoptotic Bcl-2 and Bcl-xL were upregulated. Eight patients died; the survivors had less derangements in Bax, Bcl-2 and BcL-xL expression than non-survivors. The pro-apoptotic miRNA, MIR-15 and MIR-16, were upregulated in cirrhotics with bacterial infections. Overall, the data show in lymphocytes, and not in granulocytes, an activation of the pro-apoptotic pathway in cirrhotic patients with bacterial infections, which correlates with the severity of the infection and the outcome. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. Fabrication and response of alpha-hydroxybutyrate sensors for rapid assessment of cardiometabolic disease risk.

    Science.gov (United States)

    Sarswat, Prashant K; Mishra, Yogendra Kumar; Free, Michael L

    2017-03-15

    Early diagnosis and treatment can prevent or delay progression of early-stage type 2 diabetes and prediabetes. Unfortunately, tests such as hemoglobin A1c (HbA1c)/fasting plasma glucose (FPG) alone fail to diagnose or miscategorize up to 40% of individuals with impaired glucose tolerance (IGT) or frank diabetes based on the rarely utilized oral glucose tolerance test (OGTT). The serum metabolite alpha-hydroxybutyrate (AHB) is increasingly recognized as a reliable IGT and diabetes predictor, and can be measured using liquid chromatography-tandem mass spectrometry. However, to address AHB adoption as a population screening tool, the reliable and low-cost measurement techniques are proposed. A periodate based oxidation was performed for an AHB-based buffer, and both nitroprusside and Raman tests confirmed the formation of a slow-oxidation product. Electrochemical tests of AHB-based buffers using electrodes such as Au-honeycomb, thiol self-assembled monolayers coated Au, 2D material (black-P) coated FTO, (3-aminophenyl) triethoxysilane modified TiO2, were performed. Many of these electrodes exhibited a systematic response when AHB concentration was varied from ~1.0-12.0µg/ml. A colorimetric assay containing a vicinal-diol recognition moiety, additives, and a photoinitiator, exhibited a different color for AHB based buffer. Benesi-Hildebrand analysis indicated the association behavior of boronic acid and AHB. These methods have a potential to be used for rapid point-of-care measurements of AHB that could enhance population-wide diabetes and prediabetes screening strategies. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Using a Novel Spatial Tool to Inform Invasive Species Early Detection and Rapid Response Efforts

    Science.gov (United States)

    Davidson, Alisha D.; Fusaro, Abigail J.; Kashian, Donna R.

    2015-07-01

    Management of invasive species has increasingly emphasized the importance of early detection and rapid response (EDRR) programs in limiting introductions, establishment, and impacts. These programs require an understanding of vector and species spatial dynamics to prioritize monitoring sites and efficiently allocate resources. Yet managers often lack the empirical data necessary to make these decisions. We developed an empirical mapping tool that can facilitate development of EDRR programs through identifying high-risk locations, particularly within the recreational boating vector. We demonstrated the utility of this tool in the Great Lakes watershed. We surveyed boaters to identify trips among water bodies and to quantify behaviors associated with high likelihood of species transfer (e.g., not removing organic materials from boat trailers) during that trip. We mapped water bodies with high-risk inbound and outbound boater movements using ArcGIS. We also tested for differences in high-risk behaviors based on demographic variables to understand risk differences among boater groups. Incorporation of boater behavior led to identification of additional high-risk water bodies compared to using the number of trips alone. Therefore, the number of trips itself may not fully reflect the likelihood of invasion. This tool can be broadly applied in other geographic contexts and with different taxa, and can be adjusted according to varying levels of information concerning the vector or species of interest. The methodology is straightforward and can be followed after a basic introduction to ArcGIS software. The visual nature of the mapping tool will facilitate site prioritization by managers and stakeholders from diverse backgrounds.

  10. Rapid phosphatidic acid accumulation in response to low temperature stress in Arabidopsis is generated through diacylglycerol kinase.

    NARCIS (Netherlands)

    Arisz, S.A.; van Wijk, R.; Roels, W.; Zhu, J.K.; Haring, M.A.; Munnik, T.

    2013-01-01

    Phosphatidic acid (PtdOH) is emerging as an important signaling lipid in abiotic stress responses in plants. The effect of cold stress was monitored using (32)P-labeled seedlings and leaf discs of Arabidopsis thaliana. Low, non-freezing temperatures were found to trigger a very rapid (32)P-PtdOH

  11. Incidence of cardiac arrests and unexpected deaths in surgical patients before and after implementation of a rapid response system.

    NARCIS (Netherlands)

    Simmes, F.; Schoonhoven, L.; Mintjes, J.; Fikkers, B.G.; Hoeven, J.G. van der

    2012-01-01

    ABSTRACT: BACKGROUND: Rapid response systems (RRSs) are considered an important tool for improving patient safety. We studied the effect of an RRS on the incidence of cardiac arrests and unexpected deaths. METHODS: Retrospective before- after study in a university medical centre. We included 1376

  12. 20 CFR 665.330 - Are the NAFTA-TAA program requirements for rapid response also required activities?

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Are the NAFTA-TAA program requirements for... WORKFORCE INVESTMENT ACT Rapid Response Activities § 665.330 Are the NAFTA-TAA program requirements for... WIA are made available to workers who, under the NAFTA Implementation Act (Public Law 103-182), are...

  13. Incidence of cardiac arrests and unexpected deaths in surgical patients before and after implementation of a rapid response system

    NARCIS (Netherlands)

    Joke Mintjes; Lisette Schoonhoven; Hans van der Hoeven; Friede Simmes; B.G. Fikkers

    2012-01-01

    Rapid response systems (RRSs) are considered an important tool for improving patient safety. We studied the effect of an RRS on the incidence of cardiac arrests and unexpected deaths. Retrospective before- after study in a university medical centre. We included 1376 surgical patients before

  14. Why is it so difficult to prove that rapid response systems improve patient outcome? : Directions for further research

    NARCIS (Netherlands)

    H.G. van der Hoeven; Joke Mintjes; Lisette Schoonhoven; Friede Simmes; B.G. Fikkers

    2012-01-01

    The implementation of rapid response systems (RRS) is based on the knowledge that deteriorating physiological processes are frequently present for hours or days before clear clinical deterioration is recognized [1,2]. It is assumed that this physiological deterioration is often treatable and that

  15. Mandibular response after rapid maxillary expansion in class II growing patients: a pilot randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Roberta Lione

    2017-11-01

    Full Text Available Abstract Background The aim of this pilot randomized controlled trial (RCT was to evaluate the sagittal mandibular response induced by rapid maxillary expansion (RME therapy in mixed dentition patients with class II malocclusion, comparing the effects of bonded RME and banded RME with a matched untreated class II control group. Methods This RCT was designed in parallel with an allocation ratio of 1:1:1. The sample consisted of 30 children with a mean age of 8.1 ± 0.6 years who were randomly assigned to three groups: group 1 treated with bonded RME, group 2 treated with banded RME, and group 3 the untreated control group. All patients met the following inclusion criteria: early mixed dentition, class II molar relationship, transverse discrepancy ≥ 4 mm, overjet ≥ 5 mm, and prepubertal skeletal maturity stage (CS1–CS2. The expansion screw was activated one quarter of a turn per day (0.25 mm until overcorrection was reached. For each subject, lateral cephalograms and plaster casts were obtained before treatment (T1 and after 1 year (T2. A randomization list was created for the group assignment, with an allocation ratio of 1:1:1. The observer who performed all the measurements was blinded to group assignment. The study was single-blinded in regard to statistical analysis. Results RME was effective in the correction of maxillary deficiency. Class II patients treated with both types of RME showed no significant improvement of the anteroposterior relationship of the maxilla and the mandible at both skeletal and occlusal levels. The acrylic splint RME had significant effects on reducing the skeletal vertical dimension and the gonial angle. Conclusions The orthopedic expansion did not affect the sagittal relationship of class II patients treated in the early mixed dentition when compared with the untreated control group. Additional studies with a larger sample are warranted to elucidate individual variations in dento-skeletal mandibular

  16. Mandibular response after rapid maxillary expansion in class II growing patients: a pilot randomized controlled trial.

    Science.gov (United States)

    Lione, Roberta; Brunelli, Valerio; Franchi, Lorenzo; Pavoni, Chiara; Quiroga Souki, Bernardo; Cozza, Paola

    2017-11-06

    The aim of this pilot randomized controlled trial (RCT) was to evaluate the sagittal mandibular response induced by rapid maxillary expansion (RME) therapy in mixed dentition patients with class II malocclusion, comparing the effects of bonded RME and banded RME with a matched untreated class II control group. This RCT was designed in parallel with an allocation ratio of 1:1:1. The sample consisted of 30 children with a mean age of 8.1 ± 0.6 years who were randomly assigned to three groups: group 1 treated with bonded RME, group 2 treated with banded RME, and group 3 the untreated control group. All patients met the following inclusion criteria: early mixed dentition, class II molar relationship, transverse discrepancy ≥ 4 mm, overjet ≥ 5 mm, and prepubertal skeletal maturity stage (CS1-CS2). The expansion screw was activated one quarter of a turn per day (0.25 mm) until overcorrection was reached. For each subject, lateral cephalograms and plaster casts were obtained before treatment (T1) and after 1 year (T2). A randomization list was created for the group assignment, with an allocation ratio of 1:1:1. The observer who performed all the measurements was blinded to group assignment. The study was single-blinded in regard to statistical analysis. RME was effective in the correction of maxillary deficiency. Class II patients treated with both types of RME showed no significant improvement of the anteroposterior relationship of the maxilla and the mandible at both skeletal and occlusal levels. The acrylic splint RME had significant effects on reducing the skeletal vertical dimension and the gonial angle. The orthopedic expansion did not affect the sagittal relationship of class II patients treated in the early mixed dentition when compared with the untreated control group. Additional studies with a larger sample are warranted to elucidate individual variations in dento-skeletal mandibular response to the maxillary expansion protocol in class

  17. Analysis of predictive factors for rapid virologic response in treating patients with chronic hepatitis C

    Directory of Open Access Journals (Sweden)

    ZHANG Dandan

    2014-12-01

    Full Text Available ObjectiveTo analyze the predictive factors for rapid virologic response (RVR in patients with chronic hepatitis C (CHC who received combination therapy with pegylated interferon (PEG-IFN and ribavirin. MethodsA total of 127 CHC patients who were admitted to our department from 2010 to 2012 and received PEG-IFN combined with ribavirin were enrolled in this retrospective cohort study. The patients were divided into RVR group and non-RVR (NRVR group according to their virologic responses after 4 weeks of antiviral therapy. Demographic characteristics and the clinical features prior to treatment were compared between the two groups, and the potential factors that contributed to the acquisition of RVR were analyzed. Comparison of categorical data between groups was made by chi-square test, predictive factors were analyzed by nonparametric test for two independent samples (Mann-Whitney U test, independent predictive factors were tested by univariate and multivariate logistic regression analyses, and the continuous variables of predictive factors were analyzed using receiver operating characteristic curves. ResultsOf the 127 CHC patients, 86 were males and 41 females. There were 11 confirmed cases of liver cirrhosis. There were 100 patients (78.74% who achieved an RVR, and 27 (21.26% with NRVR. Nonparametric analysis showed that eight factors, which were age, time of infection, level of pre-treatment alanine aminotransferase, level of pre-treatment hyaluronic acid, development of hypertension, type of interferon, pathway of infection, and hepatitis C virus (HCV genotype, were significantly different between the RVR and NRVR groups (P<0.05. The logistic regression analysis identified the following factors as independent predictive factors for RVR: non-genotype 1 (OR: 0.203, 95%CI: 0.051-0.802, P<0.05, time of infection (OR: 0.925, 95%CI: 0.868-0.987, P<0.05, and absence of hypertension (OR: 0.129, 95%CI: 0.032-0.521, P<0.05. Conclusion

  18. Non-apoptotic function of apoptotic proteins in the development of ...

    Indian Academy of Sciences (India)

    2011-07-08

    Jul 8, 2011 ... Non-apoptotic function of apoptotic proteins in the development of Malpighian tubules of Drosophila melanogaster ... Drosophila metamorphosis is characterized by the histolysis of larval structures by programmed cell death, which paves the way for the establishment of adult-specific structures under the ...

  19. PDT-treated apoptotic cells induce macrophage synthesis NO

    Science.gov (United States)

    Song, S.; Xing, D.; Zhou, F. F.; Chen, W. R.

    2009-11-01

    Nitric oxide (NO) is a biologically active molecule which has multi-functional in different species. As a second messenger and neurotransmitter, NO is not only an important regulatory factor between cells' information transmission, but also an important messenger in cell-mediated immunity and cytotoxicity. On the other side, NO is involving in some diseases' pathological process. In pathological conditions, the macrophages are activated to produce a large quantity of nitric oxide synthase (iNOS), which can use L-arginine to produce an excessive amount of NO, thereby killing bacteria, viruses, parasites, fungi, tumor cells, as well as in other series of the immune process. In this paper, photofrin-based photodynamic therapy (PDT) was used to treat EMT6 mammary tumors in vitro to induce apoptotic cells, and then co-incubation both apoptotic cells and macrophages, which could activate macrophage to induce a series of cytotoxic factors, especially NO. This, in turn, utilizes macrophages to activate a cytotoxic response towards neighboring tumor cells. These results provided a new idea for us to further study the immunological mechanism involved in damaging effects of PDT, also revealed the important function of the immune effect of apoptotic cells in PDT.

  20. Macrophage function in tissue repair and remodeling requires IL-4 or IL-13 with apoptotic cells

    Science.gov (United States)

    Bosurgi, Lidia; Cao, Y. Grace; Cabeza-Cabrerizo, Mar; Tucci, Andrea; Hughes, Lindsey D.; Kong, Yong; Weinstein, Jason S.; Licona-Limon, Paula; Schmid, Edward T.; Pelorosso, Facundo; Gagliani, Nicola; Craft, Joseph E.; Flavell, Richard A.; Ghosh, Sourav; Rothlin, Carla V.

    2017-01-01

    Tissue repair is a subset of a broad repertoire of interleukin-4 (IL-4)- and IL-13-dependent host responses during helminth infection. Here we show that IL-4 or IL-13 alone was not sufficient, but IL-4 or IL-13 together with apoptotic cells induced the tissue repair program in macrophages. Genetic ablation of sensors of apoptotic cells impaired the proliferation of tissue-resident macrophages and the induction of anti-inflammatory and tissue repair genes in the lungs after helminth infection or in the gut after induction of colitis. By contrast, the recognition of apoptotic cells was dispensable for cytokine-dependent induction of pattern recognition receptor, cell adhesion, or chemotaxis genes in macrophages. Detection of apoptotic cells can therefore spatially compartmentalize or prevent premature or ectopic activity of pleiotropic, soluble cytokines such as IL-4 or IL-13. PMID:28495875

  1. Rapid Response to Decision Making for Complex Issues - How Technologies of Cooperation Can Help

    National Research Council Canada - National Science Library

    Saveri, Andrea; Vian, Kathi; Rheingold, Howard

    2005-01-01

    .... A new capacity for rapid, ad hoc, and distributed decision making is emerging from the intersection of technologies of cooperation and new knowledge about the nature of cooperation and cooperative strategies...

  2. T-type Ca2+channels elicit pro-proliferative and anti-apoptotic responses through impaired PP2A/Akt1 signaling in PASMCs from patients with pulmonary arterial hypertension.

    Science.gov (United States)

    Sankhe, Safietou; Manousakidi, Sevasti; Antigny, Fabrice; Arthur Ataam, Jennifer; Bentebbal, Sana; Ruchon, Yann; Lecerf, Florence; Sabourin, Jessica; Price, Laura; Fadel, Elie; Dorfmüller, Peter; Eddahibi, Saadia; Humbert, Marc; Perros, Frédéric; Capuano, Véronique

    2017-10-01

    Idiopathic pulmonary arterial hypertension (iPAH) is characterized by obstructive hyperproliferation and apoptosis resistance of distal pulmonary artery smooth muscle cells (PASMCs). T-type Ca 2+ channel blockers have been shown to reduce experimental pulmonary hypertension, although the impact of T-type channel inhibition remains unexplored in PASMCs from iPAH patients. Here we show that T-type channels Cav3.1 and Cav3.2 are present in the lung and PASMCs from iPAH patients and control subjects. The blockade of T-type channels by the specific blocker, TTA-A2, prevents cell cycle progression and PASMCs growth. In iPAH cells, T-type channel signaling fails to activate phosphatase PP2A, leading to an increase in ERK1/2, P38 activation. Moreover, T-type channel signaling is redirected towards the activation of the kinase Akt1, leading to increased expression of the anti-apoptotic protein survivin, and a decrease in the pro-apoptotic mediator FoxO3A. Finally, in iPAH cells, Akt1 is no longer able to regulate caspase 9 activation, whereas T-type channel overexpression reverses PP2A defect in iPAH cells but reinforces the deleterious effects of Akt1 activation. Altogether, these data highlight T-type channel signaling as a strong trigger of the pathological phenotype of PASMCs from iPAH patients (hyper-proliferation/cells survival and apoptosis resistance), suggesting that both T-type channels and PP2A may be promising therapeutic targets for pulmonary hypertension. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. CE: Original research: hospital system barriers to rapid response team activation: a cognitive work analysis.

    Science.gov (United States)

    Braaten, Jane Saucedo

    2015-02-01

    The goal of rapid response team (RRT) activation in acute care facilities is to decrease mortality from preventable complications, but such efforts have been only moderately successful. Although recent research has shown decreased mortality when RRTs are activated more often, many hospitals have low activation rates. This has been linked to various hospital, team, and nursing factors. Yet there is a dearth of research examining how hospital systems shape nurses' behavior with regard to RRT activation. Making systemic constraints visible and modifying them may be the key to improving RRT activation rates and saving more lives. The purpose of this study was to use cognitive work analysis to describe factors within the hospital system that shape medical-surgical nurses' RRT activation behavior. Cognitive work analysis offers a framework for the study of complex sociotechnical systems. This framework was used as the organizing element of the study. Qualitative descriptive design was used to obtain data to fill the framework's five domains: resources, tasks, strategies, social systems, and worker competency. Data were obtained from interviews with 12 medical-surgical nurses and document review. Directed content analysis was used to place the obtained data into the framework's predefined domains. Many system factors affected participants' decisions to activate or not activate an RRT. Systemic constraints, especially in cases of subtle or gradual clinical changes, included a lack of adequate information, the availability of multiple strategies, the need to justify RRT activation, a scarcity of human resources, and informal hierarchical norms in the hospital culture. The most profound constraint was the need to justify the call. Justification was based on the objective or subjective nature of clinical changes, whether the nurse expected to be able to "handle" these changes, the presence or absence of a physician, and whether there was an expectation of support from the RRT

  4. UMTS rapid response real-time seismic networks: implementation and strategies at INGV

    Science.gov (United States)

    Govoni, A.; Margheriti, L.; Moretti, M.; Lauciani, V.; Sensale, G.; Bucci, A.; Criscuoli, F.

    2015-12-01

    Universal Mobile Telecommunications System (UMTS) and its evolutions are nowadays the most affordable and widespread data communication infrastructure available almost world wide. Moreover the always growing cellular phone market is pushing the development of new devices with higher performances and lower power consumption. All these characteristics make UMTS really useful for the implementation of an "easy to deploy" temporary real-time seismic station. Despite these remarkable features, there are many drawbacks that must be properly taken in account to effectively transmit the seismic data: Internet security, signal and service availability, power consumption. - Internet security: exposing seismological data services and seismic stations to the Internet is dangerous, attack prone and can lead to downtimes in the services, so we setup a dedicated Virtual Private Network (VPN) service to protect all the connected devices. - Signal and service availability: while for temporary experiment a carefull planning and an accurate site selection can minimize the problem, this is not always the case with rapid response networks. Moreover, as with any other leased line, the availability of the UMTS service during a seismic crisis is basically unpredictable. Nowadays in Italy during a major national emergency a Committee of the Italian Civil Defense ensures unified management and coordination of emergency activities. Inside it the telecom companies are committed to give support to the crisis management improving the standards in their communication networks. - Power consumption: it is at least of the order of that of the seismic station and, being related to data flow and signal quality is largely unpredictable. While the most secure option consists in adding a second independent solar power supply to the seismic station, this is not always a very convenient solution since it doubles the cost and doubles the equipment on site. We found that an acceptable trade-off is to add an

  5. Using Rapid Improvement Events for Disaster After-Action Reviews: Experience in a Hospital Information Technology Outage and Response.

    Science.gov (United States)

    Little, Charles M; McStay, Christopher; Oeth, Justin; Koehler, April; Bookman, Kelly

    2018-02-01

    The use of after-action reviews (AARs) following major emergency events, such as a disaster, is common and mandated for hospitals and similar organizations. There is a recurrent challenge of identified problems not being resolved and repeated in subsequent events. A process improvement technique called a rapid improvement event (RIE) was used to conduct an AAR following a complete information technology (IT) outage at a large urban hospital. Using RIE methodology to conduct the AAR allowed for the rapid development and implementation of major process improvements to prepare for future IT downtime events. Thus, process improvement methodology, particularly the RIE, is suited for conducting AARs following disasters and holds promise for improving outcomes in emergency management. Little CM , McStay C , Oeth J , Koehler A , Bookman K . Using rapid improvement events for disaster after-action reviews: experience in a hospital information technology outage and response. Prehosp Disaster Med. 2018;33(1):98-100.

  6. Priors engaged in long-latency responses to mechanical perturbations suggest a rapid update in state estimation.

    Directory of Open Access Journals (Sweden)

    Frédéric Crevecoeur

    Full Text Available In every motor task, our brain must handle external forces acting on the body. For example, riding a bike on cobblestones or skating on irregular surface requires us to appropriately respond to external perturbations. In these situations, motor predictions cannot help anticipate the motion of the body induced by external factors, and direct use of delayed sensory feedback will tend to generate instability. Here, we show that to solve this problem the motor system uses a rapid sensory prediction to correct the estimated state of the limb. We used a postural task with mechanical perturbations to address whether sensory predictions were engaged in upper-limb corrective movements. Subjects altered their initial motor response in ∼60 ms, depending on the expected perturbation profile, suggesting the use of an internal model, or prior, in this corrective process. Further, we found trial-to-trial changes in corrective responses indicating a rapid update of these perturbation priors. We used a computational model based on Kalman filtering to show that the response modulation was compatible with a rapid correction of the estimated state engaged in the feedback response. Such a process may allow us to handle external disturbances encountered in virtually every physical activity, which is likely an important feature of skilled motor behaviour.

  7. Acute pressure on the sciatic nerve results in rapid inhibition of the wide dynamic range neuronal response

    Directory of Open Access Journals (Sweden)

    Wang Wenxue

    2012-12-01

    Full Text Available Abstract Background Acute pressure on the sciatic nerve has recently been reported to provide rapid short-term relief of pain in patients with various pathologies. Wide dynamic range (WDR neurons transmit nociceptive information from the dorsal horn to higher brain centers. In the present study, we examined the effect of a 2-min application of sciatic nerve pressure on WDR neuronal activity in anesthetized male Sprague–Dawley rats. Results Experiments were carried out on 41 male Sprague–Dawley albino rats weighing 160–280 grams. Dorsal horn WDR neurons were identified on the basis of characteristic responses to mechanical stimuli applied to the cutaneous receptive field. Acute pressure was applied for 2 min to the sciatic nerve using a small vascular clip. The responses of WDR neurons to three mechanical stimuli applied to the cutaneous receptive field were recorded before, and 2, 5 and 20 min after cessation of the 2-min pressure application on the sciatic nerve. Two-min pressure applied to the sciatic nerve caused rapid attenuation of the WDR response to pinching, pressure and brushing stimuli applied to the cutaneous receptive field. Maximal attenuation of the WDR response to pinching and pressure was noted 5 min after release of the 2-min pressure on the sciatic nerve. The mean firing rate decreased from 31.7±1.7 Hz to 13±1.4 Hz upon pinching (p p p Conclusions Our results indicate that acute pressure applied to the sciatic nerve exerts a rapid inhibitory effect on the WDR response to both noxious and innocuous stimuli. Our results may partially explain the rapid analgesic effect of acute sciatic nerve pressure noted in clinical studies, and also suggest a new model for the study of pain.

  8. Comparative Antioxidant, Antiproliferative and Apoptotic Effects of ...

    African Journals Online (AJOL)

    Purpose: To determine and compare the antioxidant, antiproliferative and apoptotic effects of leaf infusions of Ilex laurina and Ilex paraguariensis in colon cancer cells. Methods: Antioxidant activity was determined by ORAC (Oxygen Radical Absorbance Capacity) and FRAP (Ferric Reducing Antioxidant Power). Cytotoxic ...

  9. Apoptotic Potential of Artemsia sieberia Besser (Asteraceae ...

    African Journals Online (AJOL)

    Purpose: To investigate the anti-proliferative and apoptotic activity of crude and dichloromethane fraction of A. sieberi against seven cancer cell lines (Colo20, HCT116, DLD, MCF7, Jurkat, HepG2 and L929). Methods: A. sieberi was extracted with methanol and further purification was carried out using liquidliquid extraction ...

  10. Rapid Response: To Scan or Not to Scan? The Utility of Noncontrast CT Head for Altered Mental Status.

    Science.gov (United States)

    Thacker, Purujit J; Sethi, Mansha; Sternlieb, Jonathan; Schneider, Doron; Naglak, Mary; Patel, Rajeshkumar R

    2018-01-17

    The aims of the study were the following: (1) to determine how often computed tomography (CT) scans of the head are obtained on rapid responses called for altered mental status (AMS), (2) to determine whether CT imaging of the head is required during all rapid responses called for AMS, (3) to determine which patients would benefit from CT scans of the head in this setting, (4) to note whether an adequate neurologic exam was documented, (5) to determine the cost of CT scans that did not change management, and (6) to examine the role of medications leading to AMS. The study was a retrospective chart review at Abington Jefferson Hospital. Data collected included the age, sex, time of rapid response, clinical condition of the patient, whether an arterial blood gas and blood glucose were done, and whether a neurological exam was documented in the resident's rapid response team note. The patient's medications were also reviewed. Computed tomography scan findings as well as changes made in a patient's care as a result of the scan were recorded. Any findings that did not lead to a change in management were considered a "negative" scan. Overall, 610 rapid responses were activated from January to August 2016. One hundred four (17.04%) of the total rapid responses were for AMS and 83 (79.8%) of these patients underwent noncontrast CT scan of the head. The mean (SD) age of the patients was 74.7 (13.6) years. A total of 56.6% were female. The most frequent clinical conditions documented at the time of rapid responses were noted as confused (33.7%, 28/83), either lethargic or unconscious (32.5%, 27/83), and concern for stroke (21.7%, 18/83). A total of 96.4% (80/83) of the CT scans done were negative for any acute changes. The three patients with positive scans (3/83) had a change in management as a result of the scans. If patients with symptoms concerning for stroke and unconscious patients are excluded, the total number of remaining patients is 56. Of these, zero patients had

  11. NIH Director's Award Recognizes Rapid Response to Avert Potential Health Crisis | FNLCR

    Science.gov (United States)

    In July 2012, members of a multidisciplinary research team of both SAIC-Frederick and NCI Center for Cancer Research scientists were recognized with the NIH Director’s Award for their outstanding work to rapidly evaluate a potential threat to the n

  12. Response to “Rapid tests for HIV type discrimination in West Africa may perform differently”

    National Research Council Canada - National Science Library

    Tchounga, Boris K; Ekouevi, Didier K; Eholie, Serge P

    2015-01-01

    ... of each test used for the initial discrimination of HIV‐positive patients. Our team previously conducted in 2004 a field evaluation of rapid HIV serologic tests in Côte d'Ivoire and highlighted the lower accuracy of Genie II for differentiating between HIV‐1, HIV‐2 and dually reactive patients [ 4 ]. In our most recent study, the initial HIV diag...

  13. Response to "Rapid tests for HIV type discrimination in West Africa may perform differently"

    National Research Council Canada - National Science Library

    Tchounga, Boris K; Ekouevi, Didier K; Eholie, Serge P

    2015-01-01

    ... test used for the initial discrimination of HIV-positive patients. Our team previously conducted in 2004 a field evaluation of rapid HIV serologic tests in Cote d'Ivoire and highlighted the lower accuracy of Genie II for differentiating between HIV-1, HIV-2 and dually reactive patients [4]. In our most recent study, the initial HIV diagnostic te...

  14. The rapid cold hardening response of Collembola is influenced by thermal variability of the habitat

    DEFF Research Database (Denmark)

    Bahrndorff, Simon; Loeschcke, Volker; Pertoldi, Cino

    2009-01-01

    exposure to a range of temperatures from 1 ° C to –12 ° C. Rapid cold-hardening (RCH) was induced by cooling individuals from 20 ° C to a temperature 7 ° C above the LT 50 during 80 min, followed by 1 h at the specific cold shock temperature, which was close to the LT 50 of the particular species. 5...

  15. NIAAA's Rapid Response to College Drinking Problems Initiative: Reinforcing the Use of Evidence-Based Approaches in College Alcohol Prevention*

    Science.gov (United States)

    DeJong, William; Larimer, Mary E.; Wood, Mark D.; Hartman, Roger

    2009-01-01

    Objective: The National Institute on Alcohol Abuse and Alcoholism (NIAAA) created the Rapid Response to College Drinking Problems initiative so that senior college administrators facing an alcohol-related crisis could get assistance from well-established alcohol researchers and NIAAA staff. Method: Based on a competitive grant process, NIAAA selected five teams of research scientists with expertise in college drinking research. NIAAA then invited college administrators to propose interventions to address a recently experienced alcohol-related problem. Between September 2004 and September 2005, NIAAA selected 15 sites and paired each recipient college with a scientific team. Together, each program development/evaluation team, working closely with NIAAA scientific staff, jointly designed, implemented, and evaluated a Rapid Response project. Results: This supplement reports the results of several Rapid Response projects, plus other findings of interest that emerged from that research. Eight articles present evaluation findings for prevention and treatment interventions, which can be grouped by the individual, group/interpersonal, institutional, and community levels of the social ecological framework. Additional studies provide further insights that can inform prevention and treatment programs designed to reduce alcohol-related problems among college students. This article provides an overview of these findings, placing them in the context of the college drinking intervention literature. Conclusions: College drinking remains a daunting problem on many campuses, but evidence-based strategies—such as those described in this supplement—provide hope that more effective solutions can be found. The Rapid Response initiative has helped solidify the necessary link between research and practice in college alcohol prevention and treatment. PMID:19538907

  16. ShakeMap implementation for Pyrenees in France-Spain border: regional adaptation and earthquake rapid response process.

    OpenAIRE

    Bertil, Didier; Roviró, Jordi; Antonio Jara, Jose; Susagna, Teresa; Nus, Eduard; Goula, Xavier; Colas, Bastien; Dumont, Guillaume; Cabañas, Luis; Anton, Resurección; Calvet, Marie

    2012-01-01

    International audience; The USGS-ShakeMap package is used with a regional adaptation to provide automatic shake maps in rapid response for Pyrenean earthquakes. The Near Real Time system relies on servers designed for data exchange between transborder organizations involved in the Sispyr project. First maps will be provide as soon as possible after the shock, and updated with observed macroseismic intensities on the following hours. Regional Predictive Equations Tapia (2006) and Goula et al. ...

  17. Stimulus and Response-Locked P3 Activity in a Dynamic Rapid Serial Visual Presentation (RSVP) Task

    Science.gov (United States)

    2013-01-01

    electroencephalogram EOG electrooculography ERP event - related potential P3 P300 RSVP rapid serial visual presentation RT reaction time NO. OF NO. OF...4 Figure 3. Left: stimulus-locked P3 event - related potentials at electrode Pz from nontargets and targets in each quartile. Right...average). .....6 Figure 5. Left: response-locked P3 event - related potentials at electrode Pz from targets in each quartile. Right: corresponding

  18. Increased Baseline Proinflammatory Cytokine Production in Chronic Hepatitis C Patients with Rapid Virological Response to Peginterferon Plus Ribavirin

    OpenAIRE

    Par, Gabriella; Szereday, Laszlo; Berki, Timea; et al.

    2013-01-01

    BACKGROUND: Chronic hepatitis C (CHC) patients achieving rapid virological response (RVR) on PEG-IFN/ribavirin (P/R) therapy have high chance of sustained virological response (SVR). To analyze host immunological factors associated with RVR, viral kinetics, phenotype distribution and Th1/Th2 cytokine production by peripheral blood mononuclear cells (PBMC) were studied prior to and during P/R therapy. METHODS: TNF-α, IFN-γ, IL-2, IL-6, IL-4 and IL-10 production by PBMC were measured after Toll...

  19. Transient Response to Rapid Cooling of a Stainless Steel Sodium Heat Pipe

    Science.gov (United States)

    Mireles, Omar R.; Houts, Michael G.

    2011-01-01

    Compact fission power systems are under consideration for use in long duration space exploration missions. Power demands on the order of 500 W, to 5 kW, will be required for up to 15 years of continuous service. One such small reactor design consists of a fast spectrum reactor cooled with an array of in-core alkali metal heat pipes coupled to thermoelectric or Stirling power conversion systems. Heat pipes advantageous attributes include a simplistic design, lack of moving parts, and well understood behavior. Concerns over reactor transients induced by heat pipe instability as a function of extreme thermal transients require experimental investigations. One particular concern is rapid cooling of the heat pipe condenser that would propagate to cool the evaporator. Rapid cooling of the reactor core beyond acceptable design limits could possibly induce unintended reactor control issues. This paper discusses a series of experimental demonstrations where a heat pipe operating at near prototypic conditions experienced rapid cooling of the condenser. The condenser section of a stainless steel sodium heat pipe was enclosed within a heat exchanger. The heat pipe - heat exchanger assembly was housed within a vacuum chamber held at a pressure of 50 Torr of helium. The heat pipe was brought to steady state operating conditions using graphite resistance heaters then cooled by a high flow of gaseous nitrogen through the heat exchanger. Subsequent thermal transient behavior was characterized by performing an energy balance using temperature, pressure and flow rate data obtained throughout the tests. Results indicate the degree of temperature change that results from a rapid cooling scenario will not significantly influence thermal stability of an operating heat pipe, even under extreme condenser cooling conditions.

  20. Operational response to malaria epidemics: are rapid diagnostic tests cost-effective?

    OpenAIRE

    Rolland, E; Checchi, F; Pinoges, L.; Balkan, S; Guthmann, J P; Guerin, P. J.

    2006-01-01

    OBJECTIVE: To compare the cost-effectiveness of malaria treatment based on presumptive diagnosis with that of malaria treatment based on rapid diagnostic tests (RDTs). METHODS: We calculated direct costs (based on experience from Ethiopia and southern Sudan) and effectiveness (in terms of reduced over-treatment) of a free, decentralised treatment programme using artesunate plus amodiaquine (AS + AQ) or artemether-lumefantrine (ART-LUM) in a Plasmodium falciparum epidemic. Our main cost-effect...

  1. A replicated climate change field experiment reveals rapid evolutionary response in an ecologically important soil invertebrate

    DEFF Research Database (Denmark)

    Bataillon, Thomas; Galtier, Nicolas; Bernard, Aurelien

    2016-01-01

    associated to changes in soil temperature and soil moisture. This shows an evolutionaryresponse to realistic climate change happening over short-time scale, and calls for incorporating evolution into modelspredicting future response of species to climate change. It also shows that designed climate change...... experiments coupled with genome sequencing offer great potential to test for the occurrence (or lack) of an evolutionary response.......Whether species can respond evolutionarily to current climate change is crucial for the persistence of many species. Yet, very few studies have examined genetic responses to climate change in manipulated experiments carried out innatural field conditions. We examined the evolutionary response...

  2. Patient characteristics, interventions and outcomes of 1151 rapid response team activations in a tertiary hospital: a prospective study.

    Science.gov (United States)

    White, K; Scott, I A; Bernard, A; McCulloch, K; Vaux, A; Joyce, C; Sullivan, C M

    2016-12-01

    The characteristics of mature contemporary rapid response systems are unclear. To determine the patient characteristics, processes and outcomes, both in-hospital and post-discharge, of a well-established rapid response system in a tertiary adult hospital. This is a prospective study of consecutive rapid response team (RRT) activations between 1 July and 25 November 2015. Variables included patient characteristics, timing, location and triggers of RRT activations, interventions undertaken, mortality and readmission status at 28 days post-discharge. A total of 1151 RRT activations was analysed (69.1 per 1000 admissions), involving 800 patients, of whom 81.5% were emergency admissions. A total of 351 (30.5%) activations comprised repeat activations for the same patient. Most activations (723; 62.8%) occurred out of hours, and 495 (43%) occurred within 48 h of admission. Hypotension, decreased level of consciousness and oxygen desaturation were the most common triggers. Advanced life support was undertaken in less than 7%; 198 (17.2%) responses led to transfer to higher-level care units. Acute resuscitation plans were noted for only 29.1% of RRT activations, with 80.3% stipulating supportive care only. A total of 103 (12.6%) patients died in hospital, equalling 14 deaths per 100 RRT activations. At 28 days, 150 (18.8%) patients had died, significantly more among those with multiple versus single RRT activations (24.9 vs 16.6%; odds ratio 1.66, 95% confidence interval 1.31-2.44; P = 0.013). Relatively few RRT activations are associated with acute resuscitation plans, and most interventions during RRT responses are low level. The high rate of post-RRT deaths and transfers to higher-level care units calls for the prospective identification of such patients in targeting appropriate care. © 2016 Royal Australasian College of Physicians.

  3. A rapid method of monitoring the acute phase response in a rat model

    African Journals Online (AJOL)

    collectively as the acute phase response (APR), take place. This response ... The blood samples (in Eppendorf tubes) were chilled on ice ... MG in the samples. The latter were then corrected for a sample volume of 200 JJI and the weights of MG in the two spiked samples recovered were calculated from their difference from ...

  4. Early Flood Detection for Rapid Humanitarian Response: Harnessing Near Real-Time Satellite and Twitter Signals

    NARCIS (Netherlands)

    Jongman, B.; Wagemaker, J.; Revilla Romero, B.; Coughlan de Perez, E.

    2015-01-01

    Humanitarian organizations have a crucial role in response and relief efforts after floods. The effectiveness of disaster response is contingent on accurate and timely information regarding the location, timing and impacts of the event. Here we show how two near-real-time data sources, satellite

  5. Oxidized low-density lipoprotein-induced apoptotic dendritic cells as a novel therapy for atherosclerosis.

    Science.gov (United States)

    Frodermann, Vanessa; van Puijvelde, Gijs H M; Wierts, Laura; Lagraauw, H Maxime; Foks, Amanda C; van Santbrink, Peter J; Bot, Ilze; Kuiper, Johan; de Jager, Saskia C A

    2015-03-01

    Modulation of immune responses may form a powerful approach to treat atherosclerosis. It was shown that clearance of apoptotic cells results in tolerance induction to cleared Ags by dendritic cells (DCs); however, this seems impaired in atherosclerosis because Ag-specific tolerance is lacking. This could result, in part, from decreased emigration of DCs from atherosclerotic lesions because of the high-cholesterol environment. Nonetheless, local induction of anti-inflammatory responses by apoptotic cell clearance seems to dampen atherosclerosis, because inhibition of apoptotic cell clearance worsens atherosclerosis. In this study, we assessed whether i.v. administration of oxLDL-induced apoptotic DCs (apop(ox)-DCs) and, as a control, unpulsed apoptotic DCs could modulate atherosclerosis by inducing tolerance. Adoptive transfer of apop(ox)-DCs into low-density lipoprotein receptor knockout mice either before or during feeding of a Western-type diet resulted in increased numbers of CD103(+) tolerogenic splenic DCs, with a concomitant increase in regulatory T cells. Interestingly, both types of apoptotic DCs induced an immediate 40% decrease in Ly-6C(hi) monocyte numbers and a 50% decrease in circulating CCL2 levels, but only apop(ox)-DC treatment resulted in long-term effects on monocytes and CCL2 levels. Although initial lesion development was reduced by 40% in both treatment groups, only apop(ox)-DC treatment prevented lesion progression by 28%. Moreover, progressed lesions of apop(ox)-DC-treated mice showed a robust 45% increase in collagen content, indicating an enhanced stability of lesions. Our findings clearly show that apoptotic DC treatment significantly decreases lesion development, but only apop(ox)-DCs can positively modulate lesion progression and stability. These findings may translate into a safe treatment for patients with established cardiovascular diseases using patient-derived apop(ox)-DCs. Copyright © 2015 by The American Association of

  6. The dynamic pressure response to rapid dilatation of the resting urethra in healthy women

    DEFF Research Database (Denmark)

    Bagi, P; Thind, P; Colstrup, H

    1993-01-01

    The urethral pressure response to a sudden forced dilatation was studied at the bladder neck, in the high-pressure zone and in the distal urethra in ten healthy female volunteers. The pressure response was fitted with a double exponential function of the form Pt = Pequ + P alpha e-t/tau alpha + P...... tissues were computed. The results showed significant differences along the urethra, with the high-pressure zone showing the highest maximum and equilibrium pressures, fastest pressure decay and highest elastic coefficient. The pressure response represents an integrated stress response from...... a detailed assessment of static and dynamic urethral responses to dilatation which can be applied as an experimental simulation of urine ingression, and is therefore presumed to be of value in the evaluation of normal and pathological urethral sphincter function....

  7. Intercellular communication in plants: evidence for two rapidly transmitted systemic signals generated in response to electromagnetic field stimulation in tomato.

    Science.gov (United States)

    Beaubois, Elisabeth; Girard, Sebastien; Lallechere, Sebastien; Davies, Eric; Paladian, Françoise; Bonnet, Pierre; Ledoigt, Gerard; Vian, Alain

    2007-07-01

    Exposing all of a wild-type tomato plant to electromagnetic radiation evoked rapid and substantial accumulation of basic leucine-zipper transcription factor (bZIP) mRNA in the terminal leaf (#4) with kinetics very similar to that seen in response to wounding, while in the abscisic acid (ABA) mutant (Sitiens), the response was more rapid, but transient. Submitting just the oldest leaf (#1) of a wild-type plant to irradiation evoked bZIP mRNA accumulation both locally in the exposed leaf and systemically in the unexposed (distant) leaf #4, although systemic accumulation was delayed somewhat. Accumulation of Pin2 mRNA was less than bZIP in both the exposed and distant leaves in wild type, but there was no delay in the systemic response. In Sitiens, bZIP mRNA accumulation was far less than in wild type in both local and distant leaves, while Pin2 mRNA accumulation was stronger in the exposed leaf, but totally prevented in the systemic leaf. In the jasmonic acid (JA) mutant (JL-5) and in wild-type plants treated with the ABA biosynthesis inhibitor, naproxen, responses were similar to those in the ABA mutant, while treatment of the exposed leaf with calcium antagonists totally abolished both local and systemic increases in bZIP transcript accumulation.

  8. Rapid response, monitoring, and mitigation of induced seismicity near Greeley, Colorado

    Science.gov (United States)

    Yeck, William; Sheehan, A.F; Benz, Harley M.; Weingarten, Matthew; Nakai, J

    2016-01-01

    On 1 June 2014 (03:35 UTC), an Mw 3.2 earthquake occurred in Weld County, Colorado, a historically aseismic area of the Denver–Julesburg basin. Weld County is a prominent area of oil and gas development, including many high‐rate class II wastewater injection wells. In the days following the earthquake, the University of Colorado, with support from the U.S. Geological Survey and Incorporated Research Institutions for Seismology–Portable Array Seismic Studies of the Continental Lithosphere, rapidly deployed six seismic stations to characterize the seismicity associated with the 1 June earthquake (the Greeley sequence) and to investigate its possible connection to wastewater disposal. The spatial and temporal proximity of earthquakes to a high‐rate wastewater disposal well strongly suggests these earthquakes were induced. Scientific communication between the university, state agencies, and the energy industry led to rapid mitigation strategies to reduce the occurrence of further earthquakes. Mitigation efforts included implementing a temporary moratorium on injection at the well, cementing the bottom portion of the disposal well to minimize hydrologic connectivity between the disposal formation and the underlying crystalline basement, and subsequently allowing injection to resume at lower rates. Following the resumption of wastewater disposal, microseismicity was closely monitored for both increases in earthquake rate and magnitude. Following mitigation efforts, between 13 August 2014 and 29 December 2015, no earthquakes larger than M 1.5 occurred near the Greeley sequence. This study demonstrates that a detailed and rapid characterization of a seismic sequence in space and time relative to disposal, combined with collaboration and communication between scientists, regulators, and industry, can lead to objective and actionable mitigation efforts that potentially reduced the rate of earthquakes and the possible generation of larger earthquakes.

  9. In vitro Anti-proliferative and Apoptotic Activities of Eurycoma ...

    African Journals Online (AJOL)

    HP

    Purpose: To investigate the anti-proliferative, apoptotic and differentiating activities of Eurycoma ... and differentiation activities of E. longifolia on the ... instructions. Flow cytometric analysis was performed within 1 h of staining. The number of early apoptotic and late apoptotic/necrotic cells were determined as the percentage ...

  10. A Response Function Approach for Rapid Far-Field Tsunami Forecasting

    Science.gov (United States)

    Tolkova, Elena; Nicolsky, Dmitry; Wang, Dailin

    2017-08-01

    Predicting tsunami impacts at remote coasts largely relies on tsunami en-route measurements in an open ocean. In this work, these measurements are used to generate instant tsunami predictions in deep water and near the coast. The predictions are generated as a response or a combination of responses to one or more tsunameters, with each response obtained as a convolution of real-time tsunameter measurements and a pre-computed pulse response function (PRF). Practical implementation of this method requires tables of PRFs in a 3D parameter space: earthquake location-tsunameter-forecasted site. Examples of hindcasting the 2010 Chilean and the 2011 Tohoku-Oki tsunamis along the US West Coast and beyond demonstrated high accuracy of the suggested technology in application to trans-Pacific seismically generated tsunamis.

  11. Data for Macrophyte Community Response to Nitrogen Loading and Thermal Stressors in Rapidly Flushed Mesocosm Systems

    Data.gov (United States)

    U.S. Environmental Protection Agency — Data represent response variables from a series of mesocosm experiments to assess how estuarine macrophyte communities respond to nitrogen loading under two...

  12. The Mannose Receptor Is Involved in the Phagocytosis of Mycobacteria-Induced Apoptotic Cells

    Directory of Open Access Journals (Sweden)

    Teresa Garcia-Aguilar

    2016-01-01

    Full Text Available Upon Mycobacterium tuberculosis infection, macrophages may undergo apoptosis, which has been considered an innate immune response. The pathways underlying the removal of dead cells in homeostatic apoptosis have been extensively studied, but little is known regarding how cells that undergo apoptotic death during mycobacterial infection are removed. This study shows that macrophages induced to undergo apoptosis with mycobacteria cell wall proteins are engulfed by J-774A.1 monocytic cells through the mannose receptor. This demonstration was achieved through assays in which phagocytosis was inhibited with a blocking anti-mannose receptor antibody and with mannose receptor competitor sugars. Moreover, elimination of the mannose receptor by a specific siRNA significantly diminished the expression of the mannose receptor and the phagocytosis of apoptotic cells. As shown by immunofluorescence, engulfed apoptotic bodies are initially located in Rab5-positive phagosomes, which mature to express the phagolysosome marker LAMP1. The phagocytosis of dead cells triggered an anti-inflammatory response with the production of TGF-β and IL-10 but not of the proinflammatory cytokines IL-12 and TNF-α. This study documents the previously unreported participation of the mannose receptor in the removal of apoptotic cells in the setting of tuberculosis (TB infection. The results challenge the idea that apoptotic cell phagocytosis in TB has an immunogenic effect.

  13. MFG-E8 released by apoptotic endothelial cells triggers anti-inflammatory macrophage reprogramming.

    Directory of Open Access Journals (Sweden)

    Marie-Joëlle Brissette

    Full Text Available Apoptotic endothelial cells are an important component of the "response to injury" process. Several atherosclerosis risk factors such as hyperglycemia and oxidized low-density lipoproteins, and immune injuries, such as antibodies and complement, induce endothelial cell apoptosis. While endothelial cell apoptosis is known to affect neighboring vascular wall cell biology, its consequences on macrophage reprogramming are ill defined. In this study, we report that apoptosis of human and mouse endothelial cells triggers the release of milk fat globule-epidermal growth factor 8 (MFG-E8 and reprograms macrophages into an anti-inflammatory cells. We demonstrated that MFG-E8 is released by apoptotic endothelial cells in a caspase-3-dependent manner. When macrophages were exposed to conditioned media from serum-starved apoptotic endothelial cells, they adopt a high anti-inflammatory, low pro-inflammatory cytokine/chemokine secreting phenotype that is lost if MFG-E8 is absent from the media. Macrophage treatment with recombinant MFG-E8 recapitulates the effect of conditioned media. Finally, we showed that MFG-E8-mediated reprogramming of macrophages occurs through increased phosphorylation of signal transducer and activator of transcription-3 (STAT-3. Taken together, our study suggests a key role of MFG-E8 release from apoptotic endothelial cells in macrophage reprogramming and demonstrates the importance of the apoptotic microenvironment in anti-inflammatory macrophage responses.

  14. Predicting Meaningful Outcomes to Medication and Self-Help Treatments for Binge Eating Disorder in Primary Care: The Significance of Early Rapid Response

    Science.gov (United States)

    Grilo, Carlos M.; White, Marney A.; Masheb, Robin M.; Gueorguieva, Ralitza

    2014-01-01

    Objective We examined rapid response among obese patients with binge-eating disorder (BED) in a randomized clinical trial testing anti-obesity medication and self-help cognitive-behavioral therapy (shCBT), alone and in combination, in primary-care settings. Method 104 obese patients with BED were randomly assigned to one of four treatments: sibutramine, placebo, shCBT+sibutramine, or shCBT+placebo. Treatments were delivered by generalist primary-care physicians and the medications were given double-blind. Independent assessments were performed by trained and monitored doctoral research-clinicians monthly throughout treatment, post-treatment (4 months), and at 6- and 12-month follow-ups (i.e., 16 months after randomization). Rapid response, defined as ≥65% reduction in binge-eating by the fourth treatment week, was used to predict outcomes. Results Rapid response characterized 47% of patients. Rapid response was unrelated to demographic and baseline clinical characteristics. Rapid response was significantly associated prospectively with remission from binge eating at post-treatment (51% versus 9% for non-rapid responders), 6-month (53% vs 23.6%), and 12-month (46.9% vs 23.6%) follow-ups. Mixed effects model analyses revealed rapid response was significantly associated with greater decreases in binge-eating, eating-disorder psychopathology, depression, and percent weight loss. Discussion Our findings, based on a diverse obese patient group receiving medication and self-help CBT treatments for BED in primary care settings, indicate that patients who have a rapid response achieve good clinical outcomes through 12-month follow-ups after ending treatments. Rapid response represents a strong prognostic indicator of clinically meaningful outcomes even in low intensity medication and self-help interventions. Rapid response has important clinical implications for stepped-care treatment models for BED. Clinical Trial Registration clinicaltrials.gov: NCT00537810 PMID

  15. Use of basic biological information for rapid prediction of the response of species to habitat loss.

    Science.gov (United States)

    Hockey, Philip A R; Curtis, Odette E

    2009-02-01

    Much research has focused on identifying traits that can act as useful indicators of how habitat loss affects the extinction risk of species, and the results are mixed. We developed 2 simple, rapid-assessment models of the susceptibility of species to habitat loss. We based both on an index of range size, but one also incorporated an index of body mass and the other an index combining habitat and dietary specialization. We applied the models to samples of birds (Accipitridae and Bucerotidae) and to the lemurs of Madagascar and compared the models' classifications of risk with the IUCN's global threat status of each species. The model derived from ecological attributes was much more robust than the one derived from body mass. Ecological attributes identified threatened birds and lemurs with an average of 80% accuracy and endangered and critically endangered species with 100% accuracy and identified some species not currently listed as threatened that almost certainly warrant conservation consideration. Appropriate analysis of even fairly crude biological information can help raise early-warning flags to the relative susceptibilities of species to habitat loss and thus provide a useful and rapid technique for highlighting potential species-level conservation issues. Advantages of this approach to classifying risk include flexibility in the specialization parameters used as well as its applicability at a range of spatial scales.

  16. Acute pressure on the sciatic nerve results in rapid inhibition of the wide dynamic range neuronal response.

    Science.gov (United States)

    Wang, Wenxue; Tan, Wei; Luo, Danping; Lin, Jianhua; Yu, Yaoqing; Wang, Qun; Zhao, Wangyeng; Wu, Buling; Chen, Jun; He, Jiman

    2012-12-04

    Acute pressure on the sciatic nerve has recently been reported to provide rapid short-term relief of pain in patients with various pathologies. Wide dynamic range (WDR) neurons transmit nociceptive information from the dorsal horn to higher brain centers. In the present study, we examined the effect of a 2-min application of sciatic nerve pressure on WDR neuronal activity in anesthetized male Sprague-Dawley rats. Experiments were carried out on 41 male Sprague-Dawley albino rats weighing 160-280 grams. Dorsal horn WDR neurons were identified on the basis of characteristic responses to mechanical stimuli applied to the cutaneous receptive field. Acute pressure was applied for 2 min to the sciatic nerve using a small vascular clip. The responses of WDR neurons to three mechanical stimuli applied to the cutaneous receptive field were recorded before, and 2, 5 and 20 min after cessation of the 2-min pressure application on the sciatic nerve. Two-min pressure applied to the sciatic nerve caused rapid attenuation of the WDR response to pinching, pressure and brushing stimuli applied to the cutaneous receptive field. Maximal attenuation of the WDR response to pinching and pressure was noted 5 min after release of the 2-min pressure on the sciatic nerve. The mean firing rate decreased from 31.7±1.7 Hz to 13±1.4 Hz upon pinching (p < 0.001), from 31.2±2.3 Hz to 10.9±1.4 Hz (p < 0.001) when pressure was applied, and from 18.9±1.2 Hz to 7.6±1.1 Hz (p < 0.001) upon brushing. Thereafter, the mean firing rates gradually recovered. Our results indicate that acute pressure applied to the sciatic nerve exerts a rapid inhibitory effect on the WDR response to both noxious and innocuous stimuli. Our results may partially explain the rapid analgesic effect of acute sciatic nerve pressure noted in clinical studies, and also suggest a new model for the study of pain.

  17. Low Cost Rapid Response Spacecraft, (LCRRS): A Research Project in Low Cost Spacecraft Design and Fabrication in a Rapid Prototyping Environment

    Science.gov (United States)

    Spremo, Stevan; Bregman, Jesse; Dallara, Christopher D.; Ghassemieh, Shakib M.; Hanratty, James; Jackson, Evan; Kitts, Christopher; Klupar, Pete; Lindsay, Michael; Ignacio, Mas; hide

    2009-01-01

    The Low Cost Rapid Response Spacecraft (LCRRS) is an ongoing research development project at NASA Ames Research Center (ARC), Moffett Field, California. The prototype spacecraft, called Cost Optimized Test for Spacecraft Avionics and Technologies (COTSAT) is the first of what could potentially be a series of rapidly produced low-cost satellites. COTSAT has a target launch date of March 2009 on a SpaceX Falcon 9 launch vehicle. The LCRRS research system design incorporates use of COTS (Commercial Off The Shelf), MOTS (Modified Off The Shelf), and GOTS (Government Off The Shelf) hardware for a remote sensing satellite. The design concept was baselined to support a 0.5 meter Ritchey-Chretien telescope payload. This telescope and camera system is expected to achieve 1.5 meter/pixel resolution. The COTSAT team is investigating the possibility of building a fully functional spacecraft for $500,000 parts and $2,000,000 labor. Cost is dramatically reduced by using a sealed container, housing the bus and payload subsystems. Some electrical and RF designs were improved/upgraded from GeneSat-1 heritage systems. The project began in January 2007 and has yielded two functional test platforms. It is expected that a flight-qualified unit will be finished in December 2008. Flight quality controls are in place on the parts and materials used in this development with the aim of using them to finish a proto-flight satellite. For LEO missions the team is targeting a mission class requiring a minimum of six months lifetime or more. The system architecture incorporates several design features required by high reliability missions. This allows for a true skunk works environment to rapidly progress toward a flight design. Engineering and fabrication is primarily done in-house at NASA Ames with flight certifications on materials. The team currently employs seven Full Time Equivalent employees. The success of COTSATs small team in this effort can be attributed to highly cross trained

  18. Logarithmic superposition of force response with rapid length changes in relaxed porcine airway smooth muscle.

    Science.gov (United States)

    Ijpma, G; Al-Jumaily, A M; Cairns, S P; Sieck, G C

    2010-12-01

    We present a systematic quantitative analysis of power-law force relaxation and investigate logarithmic superposition of force response in relaxed porcine airway smooth muscle (ASM) strips in vitro. The term logarithmic superposition describes linear superposition on a logarithmic scale, which is equivalent to multiplication on a linear scale. Additionally, we examine whether the dynamic response of contracted and relaxed muscles is dominated by cross-bridge cycling or passive dynamics. The study shows the following main findings. For relaxed ASM, the force response to length steps of varying amplitude (0.25-4% of reference length, both lengthening and shortening) are well-fitted with power-law functions over several decades of time (10⁻² to 10³ s), and the force response after consecutive length changes is more accurately fitted assuming logarithmic superposition rather than linear superposition. Furthermore, for sinusoidal length oscillations in contracted and relaxed muscles, increasing the oscillation amplitude induces greater hysteresivity and asymmetry of force-length relationships, whereas increasing the frequency dampens hysteresivity but increases asymmetry. We conclude that logarithmic superposition is an important feature of relaxed ASM, which may facilitate a more accurate prediction of force responses in the continuous dynamic environment of the respiratory system. In addition, the single power-function response to length changes shows that the dynamics of cross-bridge cycling can be ignored in relaxed muscle. The similarity in response between relaxed and contracted states implies that the investigated passive dynamics play an important role in both states and should be taken into account.

  19. Rapid effects of melatonin on hormonal and behavioral stressful responses in ewes.

    Science.gov (United States)

    Guesdon, Vanessa; Malpaux, Benoît; Delagrange, Philippe; Spedding, Michael; Cornilleau, Fabien; Chesneau, Didier; Haller, József; Chaillou, Elodie

    2013-08-01

    Sheep are gregarious mammals with complex social interactions. As such, they are very sensitive to social isolation and constitute a relevant animal model to study specifically the biological consequences of social stress. We examined previously the behavioral and endocrine responses in ewes isolated socially in the familiar conspecific withdrawal model (FCW) and showed that stressful responses increased and maintenance behaviors decreased, confirming that social isolation is a strong stressor in sheep. Melatonin synchronizes seasonal and circadian rhythms; and several studies reported its implication in cognitive processes as emotion. Here we investigated its role in the modulation of social stressful responses. Firstly, we studied ewes in the FCW model during the day (characterized by low melatonin levels) and the night (characterized by high melatonin levels). We found lower stressful responses (significant lower levels of cortisol plasma, number of foot pawings, of circling attempts) during the night as compared to the day. To investigate whether these effects were due to melatonin or to darkness, we submitted ewes to FCW during the night with lights on, a condition that suppresses melatonin secretion. Ewes infused with melatonin under these conditions showed decreased stressful responses (significant lower levels cortisol plasma, number of vocalizations, time spent with the head out of the cage) as compared to ewes infused with saline. These findings demonstrate that melatonin diminishes the endocrine and behavioral impact of social isolation in ewes and support the idea that melatonin has a calming effect in socially stressful situations. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. Evolution and behavioural responses to human-induced rapid environmental change

    Science.gov (United States)

    Sih, Andrew; Ferrari, Maud C O; Harris, David J

    2011-01-01

    Almost all organisms live in environments that have been altered, to some degree, by human activities. Because behaviour mediates interactions between an individual and its environment, the ability of organisms to behave appropriately under these new conditions is crucial for determining their immediate success or failure in these modified environments. While hundreds of species are suffering dramatically from these environmental changes, others, such as urbanized and pest species, are doing better than ever. Our goal is to provide insights into explaining such variation. We first summarize the responses of some species to novel situations, including novel risks and resources, habitat loss/fragmentation, pollutants and climate change. Using a sensory ecology approach, we present a mechanistic framework for predicting variation in behavioural responses to environmental change, drawing from models of decision-making processes and an understanding of the selective background against which they evolved. Where immediate behavioural responses are inadequate, learning or evolutionary adaptation may prove useful, although these mechanisms are also constrained by evolutionary history. Although predicting the responses of species to environmental change is difficult, we highlight the need for a better understanding of the role of evolutionary history in shaping individuals’ responses to their environment and provide suggestion for future work. PMID:25567979

  1. The emergence of pan-resistant Gram-negative pathogens merits a rapid global political response.

    Science.gov (United States)

    Walsh, Timothy R; Toleman, Mark A

    2012-01-01

    Recent media coverage of New Delhi metallo-β-lactamase (NDM-1) put antibiotic resistance back on the political map if only for the wrong reasons, mainly the reaction to the naming of NDM-1 and the incorrect assumption that medical tourism was being deliberately targeted. However, work on NDM-1 has most certainly highlighted the rapid dissemination of new antibiotic resistance mechanisms via economic globalization. The example of NDM-1 has also magnified the desperate need for a publicly funded global antibiotic surveillance system rather than just national or regional systems. Furthermore, there is a pressing need to establish a global task force to enforce international transparency and accountability on antibiotic stewardship and the implementation of measures to curb antibiotic resistance. An international antibiotic stewardship index should be established that is related to each country's gross domestic product (GDP) and assesses how much of their GDP is committed to publically funded health initiatives aimed at controlling antibiotic resistance.

  2. Polar bear and walrus response to the rapid decline in Arctic sea ice

    Science.gov (United States)

    Oakley, K.; Whalen, M.; Douglas, D.; Udevitz, M.; Atwood, T.; Jay, C.

    2012-01-01

    The Arctic is warming faster than other regions of the world due to positive climate feedbacks associated with loss of snow and ice. One highly visible consequence has been a rapid decline in Arctic sea ice over the past 3 decades - a decline projected to continue and result in ice-free summers likely as soon as 2030. The polar bear (Ursus maritimus) and the Pacific walrus (Odobenus rosmarus divergens) are dependent on sea ice over the continental shelves of the Arctic Ocean's marginal seas. The continental shelves are shallow regions with high biological productivity, supporting abundant marine life within the water column and on the sea floor. Polar bears use sea ice as a platform for hunting ice seals; walruses use sea ice as a resting platform between dives to forage for clams and other bottom-dwelling invertebrates. How have sea ice changes affected polar bears and walruses? How will anticipated changes affect them in the future?

  3. Rapid and durable response to intravenous immunoglobulin in delayed heparin-induced thrombocytopenia: a case report.

    Science.gov (United States)

    Lei, Brandon Z; Shatzel, Joseph J; Sendowski, Merav

    2017-04-01

    Heparin-induced thrombocytopenia (HIT) results in platelet consumption and a virulent thrombotic state, which generally responds to cessation of heparin and initiation of anticoagulation. Rarely, delayed HIT can occur and/or persist after heparin is discontinued. A 47-year-old male developed delayed HIT with severe thrombocytopenia and thrombosis after cardiac surgery. Thrombocytopenia developed and persisted after heparin cessation and did not improve despite sequential use of argatroban followed by bivalirudin. Treatment with intravenous immunoglobulin (IVIg) was well tolerated and resulted in rapid resolution of thrombocytopenia. There are few case reports on the management of delayed HIT with severe and prolonged thrombocytopenia. The risk for thrombosis and bleeding in the setting of an undefined time course increases uncertainty in management. This case, along with others accumulating in the literature, suggest that IVIg may be effective in treating delayed HIT with persistent thrombocytopenia. © 2016 AABB.

  4. Rapid curtailing of the stringent response by toxin-antitoxin module-encoded mRNases

    DEFF Research Database (Denmark)

    Tian, Chengzhe; Roghanian, Mohammed; Jørgensen, Mikkel Girke

    2016-01-01

    Escherichia coli regulates its metabolism to adapt to changes in the environment, in particular to stressful downshifts in nutrient quality. Such shifts elicit the so-called stringent response coordinated by the alarmone guanosine tetra- and pentaphosphate [(p)ppGpp]. At sudden amino-acid (aa......RNase-encoding TA modules present in the wt strain. This observation suggested that toxins are part of the negative feedback to control the (p)ppGpp level during early stringent response. We built a ribosome trafficking model to evaluate the fold of increase in the RelA activity just after the onset of aa...... %. IMPORTANCE: The early stringent response elicited by amino-acid starvation is controlled by a sharp increase of the cellular (p)ppGpp level. Toxin-antitoxin encoded mRNases are activated by (p)ppGpp through enhanced degradation of antitoxins. The present work shows that this activation happens at a very...

  5. The dynamic pressure response to rapid dilatation of the resting urethra in healthy women

    DEFF Research Database (Denmark)

    Bagi, P; Thind, P; Colstrup, H

    1993-01-01

    beta e-t/tau beta, where Pequ, P alpha and P beta are constants, and tau alpha and tau beta are time constants; this equation has previously been demonstrated to describe the pressure decay following dilatation. On the basis of a theoretical model the elastic and viscous constants for the urethral......The urethral pressure response to a sudden forced dilatation was studied at the bladder neck, in the high-pressure zone and in the distal urethra in ten healthy female volunteers. The pressure response was fitted with a double exponential function of the form Pt = Pequ + P alpha e-t/tau alpha + P...... a detailed assessment of static and dynamic urethral responses to dilatation which can be applied as an experimental simulation of urine ingression, and is therefore presumed to be of value in the evaluation of normal and pathological urethral sphincter function....

  6. Rapid and widely disseminated acute phase protein response after experimental bacterial infection of pigs

    DEFF Research Database (Denmark)

    Skovgaard, Kerstin; Mortensen, Shila; Boye, Mette

    2009-01-01

    The acute phase protein response is a well-described generalized early host response to tissue injury, inflammation and infection, observed as pronounced changes in the concentrations of a number of circulating serum proteins. The biological function of this response and its interplay with other...... infection in pigs. The lung infection was established with the pig specific respiratory pathogen Actinobacillus pleuropneumoniae. Quantitative real-time PCR based expression analysis were performed on samples from liver, tracheobronchial lymph node, tonsils, spleen and on blood leukocytes, supplemented...... with measurements of interleukin-6 and selected acute phase proteins in serum. C-reactive protein and serum amyloid A were clearly induced 14-18 h after infection. Extrahepatic expression of acute phase proteins was found to be dramatically altered as a result of the lung infection with an extrahepatic acute phase...

  7. Human annoyance, acceptability and concern as responses to vibration from the construction of Light Rapid Transit lines in residential environments

    Energy Technology Data Exchange (ETDEWEB)

    Wong-McSweeney, D., E-mail: D.B.C.WongMcSweeney@salford.ac.uk [Acoustics Research Centre, University of Salford, Salford M5 4TW (United Kingdom); Woodcock, J.S.; Peris, E.; Waddington, D.C.; Moorhouse, A.T. [Acoustics Research Centre, University of Salford, Salford M5 4TW (United Kingdom); Redel-Macías, M.D. [Dep. Rural Engineering Campus de Rabanales, University of Córdoba, Córdoba (Spain)

    2016-10-15

    The aim of this paper is to investigate the use of different self-reported measures for assessing the human response to environmental vibration from the construction of an urban LRT (Light Rapid Transit) system. The human response to environmental stressors such as vibration and noise is often expressed in terms of exposure–response relationships that describe annoyance as a function of the magnitude of the vibration. These relationships are often the basis of noise and vibration policy and the setting of limit values. This paper examines measures other than annoyance by expressing exposure–response relationships for vibration in terms of self-reported concern about property damage and acceptability. The exposure–response relationships for concern about property damage and for acceptability are then compared with those for annoyance. It is shown that concern about property damage occurs at vibration levels well below those where there is any risk of damage. Earlier research indicated that concern for damage is an important moderator of the annoyance induced. Acceptability, on the other hand, might be influenced by both annoyance and concern, as well as by other considerations. It is concluded that exposure–response relationships expressing acceptability as a function of vibration exposure could usefully complement existing relationships for annoyance in future policy decisions regarding environmental vibration. The results presented in this paper are derived from data collected through a socio-vibration survey (N = 321) conducted for the construction of an urban LRT in the United Kingdom. - Highlights: • The human response to construction vibration is assessed in residential environments. • Exposure–response relationships are generated based on survey and semi-empirical vibration estimation. • Annoyance, concern and acceptability are compared as response measures. • Concern and acceptability are viable measures complementing annoyance.

  8. Emergency Ebola response: a new approach to the rapid design and development of vaccines against emerging diseases.

    Science.gov (United States)

    Tully, Claire M; Lambe, Teresa; Gilbert, Sarah C; Hill, Adrian V S

    2015-03-01

    The epidemic of Ebola virus disease has spread at an alarming rate despite containment efforts. As a result, unprecedented large-scale international response efforts have been made in an attempt to gain control of the outbreak and reduce transmission. Several international consortia have been formed in a remarkable worldwide collaborative effort to expedite trials of two candidate Ebola virus vaccines: cAd3-EBOZ and rVSV-EBOV. In parallel, both vaccines are being manufactured in large amounts to enable future rapid deployment for management of the crisis. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Rapid responses of the cupula in the lateral line of ruffe (Gymnocephalus cernuus)

    NARCIS (Netherlands)

    Curcic-Blake, B; van Netten, SM

    Displacements of cupulae in the supraorbital lateral line canal in ruffe (Gymnocephalus cernuus) have been measured using laser interferometry and by applying transient as well as sinusoidal fluid stimuli in the lateral line canal. The cupular displacement in response to impulses of fluid velocity

  10. Footsteps from insect larvae damage leaf surfaces and initiate rapid responses

    NARCIS (Netherlands)

    Hall, D.E.; MacGregor, K.B.; Nijsse, J.; Bown, A.W.

    2004-01-01

    Plant resistance to insect herbivory involves gene expression in response to wounding and the detection of insect elicitors in oral secretions (Kessler and Baldwin, 2002, Ann. Rev. Plant/ Biol. 53: 299¿328). However, crawling insect larvae stimulate the synthesis of 4-aminobutyrate within minutes

  11. RAPID RESCUE: BREAKING THE MOLD OF ROUTINE CONTINGENCY RESPONSE FOR PERSONNEL RECOVERY

    Science.gov (United States)

    2016-10-23

    acc- commander-releases-new-command-strategy.aspx. 15 Ibid., 6. 16 Alan Vick , David Orletsky, Bruce Prinie, and Seth Jones, The Stryker Brigade... Vick , Alan, David Orletsky, Bruce Prinie, and Seth Jones. The Stryker Brigade Combat Team: Rethinking Strategic Responsiveness and Assessing

  12. Terra-Kleen Response Group, Inc. Solvent Extraction Technology Rapid Commercialization Initiative Report

    Science.gov (United States)

    Terra-Kleen Response Group Inc. (Terra-Kleen), has commercialized a solvent extraction technology that uses a proprietary extraction solvent to transfer organic constituents from soil to a liquid phase in a batch process at ambient temperatures. The proprietary solvent has a rel...

  13. Lumped Parameter Modeling for Rapid Vibration Response Prototyping and Test Correlation for Electronic Units

    Science.gov (United States)

    Van Dyke, Michael B.

    2013-01-01

    Present preliminary work using lumped parameter models to approximate dynamic response of electronic units to random vibration; Derive a general N-DOF model for application to electronic units; Illustrate parametric influence of model parameters; Implication of coupled dynamics for unit/board design; Demonstrate use of model to infer printed wiring board (PWB) dynamics from external chassis test measurement.

  14. The neural response properties and cortical organization of a rapidly adapting muscle sensory group response that overlaps with the frequencies that elicit the kinesthetic illusion.

    Science.gov (United States)

    Marasco, Paul D; Bourbeau, Dennis J; Shell, Courtney E; Granja-Vazquez, Rafael; Ina, Jason G

    2017-01-01

    Kinesthesia is the sense of limb movement. It is fundamental to efficient motor control, yet its neurophysiological components remain poorly understood. The contributions of primary muscle spindles and cutaneous afferents to the kinesthetic sense have been well studied; however, potential contributions from muscle sensory group responses that are different than the muscle spindles have not been ruled out. Electrophysiological recordings in peripheral nerves and brains of male Sprague Dawley rats with a degloved forelimb preparation provide evidence of a rapidly adapting muscle sensory group response that overlaps with vibratory inputs known to generate illusionary perceptions of limb movement in humans (kinesthetic illusion). This group was characteristically distinct from type Ia muscle spindle fibers, the receptor historically attributed to limb movement sensation, suggesting that type Ia muscle spindle fibers may not be the sole carrier of kinesthetic information. The sensory-neural structure of muscles is complex and there are a number of possible sources for this response group; with Golgi tendon organs being the most likely candidate. The rapidly adapting muscle sensory group response projected to proprioceptive brain regions, the rodent homolog of cortical area 3a and the second somatosensory area (S2), with similar adaption and frequency response profiles between the brain and peripheral nerves. Their representational organization was muscle-specific (myocentric) and magnified for proximal and multi-articulate limb joints. Projection to proprioceptive brain areas, myocentric representational magnification of muscles prone to movement error, overlap with illusionary vibrational input, and resonant frequencies of volitional motor unit contraction suggest that this group response may be involved with limb movement processing.

  15. Three dimensional evaluation of alveolar bone changes in response to different rapid palatal expansion activation rates

    Directory of Open Access Journals (Sweden)

    Brian LaBlonde

    Full Text Available ABSTRACT Introduction: The aim of this multi-center retrospective study was to quantify the changes in alveolar bone height and thickness after using two different rapid palatal expansion (RPE activation protocols, and to determine whether a more rapid rate of expansion is likely to cause more adverse effects, such as alveolar tipping, dental tipping, fenestration and dehiscence of anchorage teeth. Methods: The sample consisted of pre- and post-expansion records from 40 subjects (age 8-15 years who underwent RPE using a 4-banded Hyrax appliance as part of their orthodontic treatment to correct posterior buccal crossbites. Subjects were divided into two groups according to their RPE activation rates (0.5 mm/day and 0.8 mm/day; n = 20 each group. Three-dimensional images for all included subjects were evaluated using Dolphin Imaging Software 11.7 Premium. Maxillary base width, buccal and palatal cortical bone thickness, alveolar bone height, and root angulation and length were measured. Significance of the changes in the measurements was evaluated using Wilcoxon signed-rank test and comparisons between groups were done using ANOVA. Significance was defined at p ≤ 0.05. Results: RPE activation rates of 0.5 mm per day (Group 1 and 0.8 mm per day (Group 2 caused significant increase in arch width following treatment; however, Group 2 showed greater increases compared to Group 1 (p < 0.01. Buccal alveolar height and width decreased significantly in both groups. Both treatment protocols resulted in significant increases in buccal-lingual angulation of teeth; however, Group 2 showed greater increases compared to Group 1 (p < 0.01. Conclusion: Both activation rates are associated with significant increase in intra-arch widths. However, 0.8 mm/day resulted in greater increases. The 0.8 mm/day activation rate also resulted in more increased dental tipping and decreased buccal alveolar bone thickness over 0.5 mm/day.

  16. Marine Ecosystem Response to Rapid Climate Warming on the West Antarctic Peninsula (Invited)

    Science.gov (United States)

    Ducklow, H.; Baker, K. S.; Doney, S. C.; Fraser, B.; Martinson, D. G.; Meredith, M. P.; Montes-Hugo, M. A.; Sailley, S.; Schofield, O.; Sherrell, R. M.; Stammerjohn, S. E.; Steinberg, D. K.

    2010-12-01

    The Palmer, Antarctica LTER builds on meteorological, ocean color and seabird observations since the late 1970s. It occupies annually in summer a regional-scale grid extending 700 km northward from Charcot Island to Anvers Island, and 200 km cross-shelf from the coast to the shelfbreak. In addition to routine CTD profiles and zooplankton tows throughout the grid, the observing system also includes Slocum Glider surveys and thermistor moorings. Geophysical changes include +6C atmospheric warming in winter since 1950, a 20% increase in heat content over the continental shelf since 1990, a surface ocean warming of +1C since 1950, an 83-day reduction in sea ice duration (advance 48 days later, retreat 35 days earlier) over the greater southern Bellingshausen Sea region from 1979-2007, intensification of westerly winds and differential changes in cloudiness. In response to these large changes in the regional climate, the marine ecosystem of the western Peninsula is changing at all trophic levels from diatoms to penguins. Ocean color indicates differential changes in phytoplankton stocks in response to regional decreases in sea ice cover. Surface chlorophyll has declined 89% in the north and increased 67% in the south. Antarctic krill and salps have declined and increased in our study area, respectively. Penguin diet sampling suggests changes in populations or distributions of the Antarctic Silverfish in the Anvers Island vicinity, possibly in response to ocean warming. Adélie penguins have declined 75% from 15000 to <3000 pairs at since 1975 in response to changes in food availability and increased late spring snow accumulation. Changes in pygoscelid penguin breeding populations in the Anvers Island vicinity of the West Antarctic Peninsula

  17. Rapid Disruption of Axon–Glial Integrity in Response to Mild Cerebral Hypoperfusion

    OpenAIRE

    Reimer, Michell M.; McQueen, Jamie; Searcy, Luke; Scullion, Gillian; Zonta, Barbara; Desmazieres, Anne; Philip R Holland; Smith, Jessica; Gliddon, Catherine; Wood, Emma R.; Herzyk, Pawel; Brophy, Peter J.; Mcculloch, James; Horsburgh, Karen

    2011-01-01

    Myelinated axons have a distinct protein architecture which is essential for action potential propagation, neuronal communication and maintaining cognitive function. Damage to myelinated axons, associated with cerebral hypoperfusion, is suggested to contribute to age-related cognitive decline. We sought to determine whether there are selective and early alterations in the protein architecture of myelinated axons in response to cerebral hypoperfusion. Using a mouse model of hypoperfusion we as...

  18. Use of SMS-Based Surveys in the Rapid Response to the Ebola Outbreak in Liberia: Opening Community Dialogue.

    Science.gov (United States)

    Berman, Amanda; Figueroa, Maria Elena; Storey, J Douglas

    2017-01-01

    During an emerging health crisis like the 2014 Ebola outbreak in West Africa, communicating with communities to learn from them and to provide timely information can be a challenge. Insight into community thinking, however, is crucial for developing appropriate communication content and strategies and for monitoring the progress of the emergency response. In November 2014, the Health Communication Capacity Collaborative partnered with GeoPoll to implement a Short Message Service (SMS)-based survey that could create a link with affected communities and help guide the communication response to Ebola. The ideation metatheory of communication and behavior change guided the design of the survey questionnaire, which produced critical insights into trusted sources of information, knowledge of transmission modes, and perceived risks-all factors relevant to the design of an effective communication response that further catalyzed ongoing community actions. The use of GeoPoll's infrastructure for data collection proved a crucial source of almost-real-time data. It allowed for rapid data collection and processing under chaotic field conditions. Though not a replacement for standard survey methodologies, SMS surveys can provide quick answers within a larger research process to decide on immediate steps for communication strategies when the demand for speedy emergency response is high. They can also help frame additional research as the response evolves and overall monitor the pulse of the situation at any point in time.

  19. Rapid poleward range expansion of tropical reef corals in response to rising sea surface temperatures

    Science.gov (United States)

    Yamano, Hiroya; Sugihara, Kaoru; Nomura, Keiichi

    2011-02-01

    Rising temperatures caused by climatic warming may cause poleward range shifts and/or expansions in species distribution. Tropical reef corals (hereafter corals) are some of the world's most important species, being not only primary producers, but also habitat-forming species, and thus fundamental ecosystem modification is expected according to changes in their distribution. Although most studies of climate change effects on corals have focused on temperature-induced coral bleaching in tropical areas, poleward range shifts and/or expansions may also occur in temperate areas. We show the first large-scale evidence of the poleward range expansion of modern corals, based on 80 years of national records from the temperate areas of Japan, where century-long measurements of in situ sea-surface temperatures have shown statistically significant rises. Four major coral species categories, including two key species for reef formation in tropical areas, showed poleward range expansions since the 1930s, whereas no species demonstrated southward range shrinkage or local extinction. The speed of these expansions reached up to 14 km/year, which is far greater than that for other species. Our results, in combination with recent findings suggesting range expansions of tropical coral-reef associated organisms, strongly suggest that rapid, fundamental modifications of temperate coastal ecosystems could be in progress.

  20. Rapid warming in Tibet, China: public perception, response and coping resources in urban Lhasa.

    Science.gov (United States)

    Bai, Li; Cirendunzhu; Pengcuociren; Dawa; Woodward, Alistair; Liu, Xiaobo; Baimaciwang; Dazhen; Sang, Shaowei; Wan, Fangjun; Zhou, Lin; Xu, Junfang; Li, Xiaolu; Wu, Haixia; Yu, Baorong; Xiraoruodeng; Liu, Qiyong

    2013-08-27

    Tibet, average altitude more than 4,000 meters, is warming faster than anywhere else in China. The increase in temperatures may aggravate existing health problems and lead to the emergence of new risks. However, there are no actions being taken at present to protect population health due to limited understanding about the range and magnitude of health effects of climate change. The study was a cross-sectional survey of 619 respondents from urban Lhasa, Tibet in August 2012 with the aim to investigate public perceptions of risk, heat experiences, and coping resources. Respondents are aware of the warming that has occurred in Lhasa in recent years. Over 78% reported that rising temperature is either a "very" or "somewhat" serious threat to their own health, and nearly 40% reported they had experienced heat-related symptoms. Sex, age, education and income influenced perceived risks, health status, and heat experience. The vast majority of respondents reported that they had altered their behaviour on hot summer days. Bakuo, a sub-district at the city center, is considered especially vulnerable to heat because of sparse vegetation, high population density, poor dwelling conditions and a high proportion of low-income population. However, neighborhood social ties were stronger in Bakuo than other study locations. The study suggests that actions are needed now to minimize downside effects of rapid warming in Tibet, because of increasing human exposure to high temperatures and uneven distribution of the resources needed to cope.

  1. Evidence of Rapid Modulation by Social Information of Subjective, Physiological, and Neural Responses to Emotional Expressions

    Directory of Open Access Journals (Sweden)

    Martial Mermillod

    2018-01-01

    Full Text Available Recent research suggests that conceptual or emotional factors could influence the perceptual processing of stimuli. In this article, we aimed to evaluate the effect of social information (positive, negative, or no information related to the character of the target on subjective (perceived and felt valence and arousal, physiological (facial mimicry as well as on neural (P100 and N170 responses to dynamic emotional facial expressions (EFE that varied from neutral to one of the six basic emotions. Across three studies, the results showed reduced ratings of valence and arousal of EFE associated with incongruent social information (Study 1, increased electromyographical responses (Study 2, and significant modulation of P100 and N170 components (Study 3 when EFE were associated with social (positive and negative information (vs. no information. These studies revealed that positive or negative social information reduces subjective responses to incongruent EFE and produces a similar neural and physiological boost of the early perceptual processing of EFE irrespective of their congruency. In conclusion, the article suggests that the presence of positive or negative social context modulates early physiological and neural activity preceding subsequent behavior.

  2. Maternal and infant infections stimulate a rapid leukocyte response in breastmilk.

    Science.gov (United States)

    Hassiotou, Foteini; Hepworth, Anna R; Metzger, Philipp; Tat Lai, Ching; Trengove, Naomi; Hartmann, Peter E; Filgueira, Luis

    2013-04-01

    Breastmilk protects infants against infections; however, specific responses of breastmilk immune factors to different infections of either the mother or the infant are not well understood. Here, we examined the baseline range of breastmilk leukocytes and immunomodulatory biomolecules in healthy mother/infant dyads and how they are influenced by infections of the dyad. Consistent with a greater immunological need in the early postpartum period, colostrum contained considerable numbers of leukocytes (13-70% out of total cells) and high levels of immunoglobulins and lactoferrin. Within the first 1-2 weeks postpartum, leukocyte numbers decreased significantly to a low baseline level in mature breastmilk (0-2%) (P<0.001). This baseline level was maintained throughout lactation unless the mother and/or her infant became infected, when leukocyte numbers significantly increased up to 94% leukocytes out of total cells (P<0.001). Upon recovery from the infection, baseline values were restored. The strong leukocyte response to infection was accompanied by a more variable humoral immune response. Exclusive breastfeeding was associated with a greater baseline level of leukocytes in mature breastmilk. Collectively, our results suggest a strong association between the health status of the mother/infant dyad and breastmilk leukocyte levels. This could be used as a diagnostic tool for assessment of the health status of the lactating breast as well as the breastfeeding mother and infant.

  3. Apoptotic cells can induce non-autonomous apoptosis through the TNF pathway

    Science.gov (United States)

    Pérez-Garijo, Ainhoa; Fuchs, Yaron; Steller, Hermann

    2013-01-01

    Apoptotic cells can produce signals to instruct cells in their local environment, including ones that stimulate engulfment and proliferation. We identified a novel mode of communication by which apoptotic cells induce additional apoptosis in the same tissue. Strong induction of apoptosis in one compartment of the Drosophila wing disc causes apoptosis of cells in the other compartment, indicating that dying cells can release long-range death factors. We identified Eiger, the Drosophila tumor necrosis factor (TNF) homolog, as the signal responsible for apoptosis-induced apoptosis (AiA). Eiger is produced in apoptotic cells and, through activation of the c-Jun N-terminal kinase (JNK) pathway, is able to propagate the initial apoptotic stimulus. We also show that during coordinated cell death of hair follicle cells in mice, TNF-α is expressed in apoptotic cells and is required for normal cell death. AiA provides a mechanism to explain cohort behavior of dying cells that is seen both in normal development and under pathological conditions. DOI: http://dx.doi.org/10.7554/eLife.01004.001 PMID:24066226

  4. Uptake of apoptotic cells drives the growth of a pathogenic trypanosome in macrophages

    Science.gov (United States)

    Freire-de-Lima, Célio G.; Nascimento, Danielle O.; Soares, Milena B. P.; Bozza, Patricia T.; Castro-Faria-Neto, Hugo C.; de Mello, Fernando G.; Dosreis, George A.; Lopes, Marcela F.

    2000-01-01

    After apoptosis, phagocytes prevent inflammation and tissue damage by the uptake and removal of dead cells. In addition, apoptotic cells evoke an anti-inflammatory response through macrophages. We have previously shown that there is intense lymphocyte apoptosis in an experimental model of Chagas' disease, a debilitating cardiac illness caused by the protozoan Trypanosoma cruzi. Here we show that the interaction of apoptotic, but not necrotic T lymphocytes with macrophages infected with T. cruzi fuels parasite growth in a manner dependent on prostaglandins, transforming growth factor-β (TGF-β) and polyamine biosynthesis. We show that the vitronectin receptor is critical, in both apoptotic-cell cytoadherence and the induction of prostaglandin E2/TGF-β release and ornithine decarboxylase activity in macrophages. A single injection of apoptotic cells in infected mice increases parasitaemia, whereas treatment with cyclooxygenase inhibitors almost completely ablates it in vivo. These results suggest that continual lymphocyte apoptosis and phagocytosis of apoptotic cells by macrophages have a role in parasite persistence in the host, and that cyclooxygenase inhibitors have potential therapeutic application in the control of parasite replication and spread in Chagas' disease.

  5. Macrophage function in tissue repair and remodeling requires IL-4 or IL-13 with apoptotic cells

    OpenAIRE

    Bosurgi, Lidia; Cao, Y. Grace; Cabeza-Cabrerizo, Mar; Tucci,Andrea; Hughes, Lindsey D.; Kong, Yong; Weinstein, Jason S.; Licona-Limon, Paula; Schmid, Edward T.; Pelorosso, Facundo; Gagliani, Nicola; Craft, Joseph E.; Flavell, Richard A.; Ghosh, Sourav; Rothlin, Carla V.

    2017-01-01

    Tissue repair is a subset of a broad repertoire of interleukin-4 (IL-4)- and IL-13-dependent host responses during helminth infection. Here we show that IL-4 or IL-13 alone was not sufficient, but IL-4 or IL-13 together with apoptotic cells induced the tissue repair program in macrophages. Genetic ablation of sensors of apoptotic cells impaired the proliferation of tissue-resident macrophages and the induction of anti-inflammatory and tissue repair genes in the lungs after helminth infection ...

  6. Invasive species information networks: Collaboration at multiple scales for prevention, early detection, and rapid response to invasive alien species

    Science.gov (United States)

    Simpson, Annie; Jarnevich, Catherine S.; Madsen, John; Westbrooks, Randy G.; Fournier, Christine; Mehrhoff, Les; Browne, Michael; Graham, Jim; Sellers, Elizabeth A.

    2009-01-01

    Accurate analysis of present distributions and effective modeling of future distributions of invasive alien species (IAS) are both highly dependent on the availability and accessibility of occurrence data and natural history information about the species. Invasive alien species monitoring and detection networks (such as the Invasive Plant Atlas of New England and the Invasive Plant Atlas of the MidSouth) generate occurrence data at local and regional levels within the United States, which are shared through the US National Institute of Invasive Species Science. The Inter-American Biodiversity Information Network's Invasives Information Network (I3N), facilitates cooperation on sharing invasive species occurrence data throughout the Western Hemisphere. The I3N and other national and regional networks expose their data globally via the Global Invasive Species Information Network (GISIN). International and interdisciplinary cooperation on data sharing strengthens cooperation on strategies and responses to invasions. However, limitations to effective collaboration among invasive species networks leading to successful early detection and rapid response to invasive species include: lack of interoperability; data accessibility; funding; and technical expertise. This paper proposes various solutions to these obstacles at different geographic levels and briefly describes success stories from the invasive species information networks mentioned above. Using biological informatics to facilitate global information sharing is especially critical in invasive species science, as research has shown that one of the best indicators of the invasiveness of a species is whether it has been invasive elsewhere. Data must also be shared across disciplines because natural history information (e.g. diet, predators, habitat requirements, etc.) about a species in its native range is vital for effective prevention, detection, and rapid response to an invasion. Finally, it has been our

  7. Oxidized low-density lipoprotein-induced apoptotic dendritic cells as a novel therapy for atherosclerosis

    NARCIS (Netherlands)

    Frodermann, Vanessa; van Puijvelde, Gijs H M; Wierts, Laura; Lagraauw, H Maxime; Foks, Amanda C; van Santbrink, Peter J; Bot, Ilze; Kuiper, Johan; de Jager, Saskia C A

    2015-01-01

    Modulation of immune responses may form a powerful approach to treat atherosclerosis. It was shown that clearance of apoptotic cells results in tolerance induction to cleared Ags by dendritic cells (DCs); however, this seems impaired in atherosclerosis because Ag-specific tolerance is lacking. This

  8. Rapid selection of escape mutants by the first CD8 T cell responses in acute HIV-1 infection

    Energy Technology Data Exchange (ETDEWEB)

    Korber, Bette Tina Marie [Los Alamos National Laboratory

    2008-01-01

    The recent failure of a vaccine that primes T cell responses to control primary HIV-1 infection has raised doubts about the role of CD8+ T cells in early HIV-1 infection. We studied four patients who were identified shortly after HIV-1 infection and before seroconversion. In each patient there was very rapid selection of multiple HIV-1 escape mutants in the transmitted virus by CD8 T cells, including examples of complete fixation of non-synonymous substitutions within 2 weeks. Sequencing by single genome amplification suggested that the high rate of virus replication in acute infection gave a selective advantage to virus molecules that contained simultaneous and gained sequential T cell escape mutations. These observations show that whilst early HIV-1 specific CD8 T cells can act against virus, rapid escape means that these T cell responses are unlikely to benefit the patient and may in part explain why current HIV-1 T cell vaccines may not be protective.

  9. Transcriptome Signatures Reveal Rapid Induction of Immune-Responsive Genes in Human Memory CD8(+) T Cells.

    Science.gov (United States)

    Yang, Cheng; Khanniche, Asma; DiSpirito, Joanna R; Ji, Ping; Wang, Shujun; Wang, Ying; Shen, Hao

    2016-05-31

    Memory T cells (TM) play a prominent role in protection and auto-immunity due to their ability to mount a more effective response than naïve T cells (TN). However, the molecular mechanisms underlying enhanced functionality of TM are not well defined, particularly in human TM. We examined the global gene expression profiles of human CD8(+) TN and TM before and after stimulation. There were 1,284, 1,373 and 1,629 differentially expressed genes between TN and TM at 0 hr, 4 hr and 24 hr after stimulation, respectively, with more genes expressed to higher levels in TM. Genes rapidly up-regulated in TN cells were largely involved in nitrogen, nucleoside and amino acid metabolisms. In contrast, those in CD8(+) TM were significantly enriched for immune-response-associated processes, including cytokine production, lymphocyte activation and chemotaxis. Multiple cytokines were rapidly up-regulated in TM cells, including effector cytokines known to be produced by CD8(+) T cells and important for their functions, as well as regulatory cytokines, both pro- and anti-inflammatory, that are not typically produced by CD8(+) T cells. These results provide new insights into molecular mechanisms that contribute to the enhanced functionality of human CD8(+) TM and their prominent role in protection and auto-immunity.

  10. Sedimentary evidence for enhanced hydrological cycling in response to rapid carbon release during the early Toarcian oceanic anoxic event

    Science.gov (United States)

    Izumi, Kentaro; Kemp, David B.; Itamiya, Shoma; Inui, Mutsuko

    2018-01-01

    A pronounced excursion in the carbon-isotope composition of biospheric carbon and coeval seawater warming during the early Toarcian (∼183 Ma) has been linked to the large-scale transfer of 12C-enriched carbon to the oceans and atmosphere. A European bias in the distribution of available data means that the precise pattern, tempo and global expression of this carbon cycle perturbation, and the associated environmental responses, remain uncertain. Here, we present a new cm-scale terrestrial-dominated carbon-isotope record through an expanded lower Toarcian section from Japan that displays a negative excursion pattern similar to marine and terrestrial carbon-isotope records documented from Europe. These new data suggest that 12C-enriched carbon was added to the biosphere in at least one rapid, millennial-scale pulse. Sedimentological analysis indicates a close association between the carbon-isotope excursion and high-energy sediment transport and enhanced fluvial discharge. Together, these data support the hypothesis that a sudden strengthening of the global hydrological cycle occurred in direct and immediate response to rapid carbon release and atmospheric warming.

  11. Rapid ocean-atmosphere response to Southern Ocean freshening during the last glacial period

    Science.gov (United States)

    Turney, Christian; Jones, Richard; Phipps, Steven; Thomas, Zoë; Hogg, Alan; Kershaw, Peter; Fogwill, Christopher; Palmer, Jonathan; Bronk Ramsey, Christopher; Adolphi, Florian; Muscheler, Raimund; Hughen, Konrad; Staff, Richard; Grosvenor, Mark; Golledge, Nicholas; Rasmussen, Sune; Hutchinson, David; Haberle, Simon; Lorrey, Andrew; Boswijk, Gretel

    2017-04-01

    Contrasting Greenland and Antarctic temperature trends during the late last glacial period (60,000 to 11,703 years ago) are thought to be driven by imbalances in the rate of formation of North Atlantic and Antarctic Deep Water (the 'bipolar seesaw'), with cooling in the north leading the onset of warming in the south. Some events, however, appear to have occurred independently of changes in deep water formation but still have a southern expression, implying that an alternative mechanism may have driven some global climatic changes during the glacial. Testing these competing hypotheses is challenging given the relatively large uncertainties associated with correlating terrestrial, marine and ice core records of abrupt change. Here we exploit a bidecadally-resolved 14C calibration dataset obtained from New Zealand kauri (Agathis australis) to undertake high-precision alignment of key climate datasets spanning 28,400 to 30,400 years ago. We observe no divergence between terrestrial and marine 14C datasets implying limited impact of freshwater hosing on the Atlantic Meridional Overturning Circulation (AMOC). However, an ice-rafted debris event (SA2) in Southern Ocean waters appears to be associated with dramatic synchronous warming over the North Atlantic and contrasting precipitation patterns across the low latitudes. Using a fully coupled climate system model we undertook an ensemble of transient meltwater simulations and find that a southern salinity anomaly can trigger low-latitude temperature changes through barotropic and baroclinic oceanic waves that are atmospherically propagated globally via a Rossby wave train, consistent with contemporary modelling studies. Our results suggest the Antarctic ice sheets and Southern Ocean dynamics may have contributed to some global climatic changes through rapid ocean-atmospheric teleconnections, with implications for past (and future) change.

  12. Beta-Amyloid Oligomers Activate Apoptotic BAK Pore for Cytochrome c Release

    Science.gov (United States)

    Kim, Jaewook; Yang, Yoosoo; Song, Seung Soo; Na, Jung-Hyun; Oh, Kyoung Joon; Jeong, Cherlhyun; Yu, Yeon Gyu; Shin, Yeon-Kyun

    2014-01-01

    In Alzheimer’s disease, cytochrome c-dependent apoptosis is a crucial pathway in neuronal cell death. Although beta-amyloid (Aβ) oligomers are known to be the neurotoxins responsible for neuronal cell death, the underlying mechanisms remain largely elusive. Here, we report that the oligomeric form of synthetic Aβ of 42 amino acids elicits death of HT-22 cells. But, when expression of a bcl-2 family protein BAK is suppressed by siRNA, Aβ oligomer-induced cell death was reduced. Furthermore, significant reduction of cytochrome c release was observed with mitochondria isolated from BAK siRNA-treated HT-22 cells. Our in vitro experiments demonstrate that Aβ oligomers bind to BAK on the membrane and induce apoptotic BAK pores and cytochrome c release. Thus, the results suggest that Aβ oligomers function as apoptotic ligands and hijack the intrinsic apoptotic pathway to cause unintended neuronal cell death. PMID:25296312

  13. Anti-apoptotic signaling and failure of apoptosis in the ischemic rat hippocampus

    DEFF Research Database (Denmark)

    Müller, Georg Johannes; Lassmann, Hans; Johansen, Flemming Fryd

    2007-01-01

    colchicine injection severed as a reference for classical apoptosis. Heat shock protein 70 (Hsp70), neuronal apoptosis inhibitory protein (NAIP) and manganese superoxide dismutase (MnSOD) were upregulated in the majority of intact CA1 neurons paralleling the occurrence of CA1 neuronal death (days 3......-7) as well as in a proportion of apoptosis-(Colchicine did not provoke an anti-apoptotic response in DGC at all. In addition, more than 70% of apoptosis- and necrosis-like CA1 neurons had completely lost their RCC subunits suggesting bioenergetic failure......; by contrast, following colchicine injection, 88% of all apoptotic DGC presented RCC subunits. Thus, anti-apoptotic proteins may, in a subset of ischemic CA1 neurons, prevent cell death, while in others, affected by pronounced energy failure, they may cause secondary necrosis....

  14. Rapid evolution of coral proteins responsible for interaction with the environment.

    Science.gov (United States)

    Voolstra, Christian R; Sunagawa, Shinichi; Matz, Mikhail V; Bayer, Till; Aranda, Manuel; Buschiazzo, Emmanuel; Desalvo, Michael K; Lindquist, Erika; Szmant, Alina M; Coffroth, Mary Alice; Medina, Mónica

    2011-01-01

    Corals worldwide are in decline due to climate change effects (e.g., rising seawater temperatures), pollution, and exploitation. The ability of corals to cope with these stressors in the long run depends on the evolvability of the underlying genetic networks and proteins, which remain largely unknown. A genome-wide scan for positively selected genes between related coral species can help to narrow down the search space considerably. We screened a set of 2,604 putative orthologs from EST-based sequence datasets of the coral species Acropora millepora and Acropora palmata to determine the fraction and identity of proteins that may experience adaptive evolution. 7% of the orthologs show elevated rates of evolution. Taxonomically-restricted (i.e. lineage-specific) genes show a positive selection signature more frequently than genes that are found across many animal phyla. The class of proteins that displayed elevated evolutionary rates was significantly enriched for proteins involved in immunity and defense, reproduction, and sensory perception. We also found elevated rates of evolution in several other functional groups such as management of membrane vesicles, transmembrane transport of ions and organic molecules, cell adhesion, and oxidative stress response. Proteins in these processes might be related to the endosymbiotic relationship corals maintain with dinoflagellates in the genus Symbiodinium. This study provides a birds-eye view of the processes potentially underlying coral adaptation, which will serve as a foundation for future work to elucidate the rates, patterns, and mechanisms of corals' evolutionary response to global climate change.

  15. Operational response to malaria epidemics: are rapid diagnostic tests cost-effective?

    Science.gov (United States)

    Rolland, Estelle; Checchi, Francesco; Pinoges, Loretxu; Balkan, Suna; Guthmann, Jean-Paul; Guerin, Philippe J

    2006-04-01

    To compare the cost-effectiveness of malaria treatment based on presumptive diagnosis with that of malaria treatment based on rapid diagnostic tests (RDTs). We calculated direct costs (based on experience from Ethiopia and southern Sudan) and effectiveness (in terms of reduced over-treatment) of a free, decentralised treatment programme using artesunate plus amodiaquine (AS + AQ) or artemether-lumefantrine (ART-LUM) in a Plasmodium falciparum epidemic. Our main cost-effectiveness measure was the incremental cost per false positive treatment averted by RDTs. As malaria prevalence increases, the difference in cost between presumptive and RDT-based treatment rises. The threshold prevalence above which the RDT-based strategy becomes more expensive is 21% in the AS + AQ scenario and 55% in the ART-LUM scenario, but these thresholds increase to 58 and 70%, respectively, if the financing body tolerates an incremental cost of 1 euro per false positive averted. However, even at a high (90%) prevalence of malaria consistent with an epidemic peak, an RDT-based strategy would only cost moderately more than the presumptive strategy: +29.9% in the AS + AQ scenario and +19.4% in the ART-LUM scenario. The treatment comparison is insensitive to the age and pregnancy distribution of febrile cases, but is strongly affected by variation in non-biomedical costs. If their unit price were halved, RDTs would be more cost-effective at a malaria prevalence up to 45% in case of AS + AQ treatment and at a prevalence up to 68% in case of ART-LUM treatment. In most epidemic prevalence scenarios, RDTs would considerably reduce over-treatment for only a moderate increase in costs over presumptive diagnosis. A substantial decrease in RDT unit price would greatly increase their cost-effectiveness, and should thus be advocated. A tolerated incremental cost of 1 euro is probably justified given overall public health and financial benefits. The RDTs should be considered for malaria epidemics if

  16. Completion report for Early Detection Rapid Response Projects : Inventory and control of yellow toadflax (Linaria vulgaris) on Kulm Wetland Management District

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — Completion report for Early Detection Rapid Response Project (EDRR) "Inventory and control of yellow toadflax (Linaria vulgaris) on Kulm Wetland Management District"...

  17. Rapid Evolution of Coral Proteins Responsible for Interaction with the Environment

    Science.gov (United States)

    Matz, Mikhail V.; Bayer, Till; Aranda, Manuel; Buschiazzo, Emmanuel; DeSalvo, Michael K.; Lindquist, Erika; Szmant, Alina M.; Coffroth, Mary Alice; Medina, Mónica

    2011-01-01

    Background Corals worldwide are in decline due to climate change effects (e.g., rising seawater temperatures), pollution, and exploitation. The ability of corals to cope with these stressors in the long run depends on the evolvability of the underlying genetic networks and proteins, which remain largely unknown. A genome-wide scan for positively selected genes between related coral species can help to narrow down the search space considerably. Methodology/Principal Findings We screened a set of 2,604 putative orthologs from EST-based sequence datasets of the coral species Acropora millepora and Acropora palmata to determine the fraction and identity of proteins that may experience adaptive evolution. 7% of the orthologs show elevated rates of evolution. Taxonomically-restricted (i.e. lineage-specific) genes show a positive selection signature more frequently than genes that are found across many animal phyla. The class of proteins that displayed elevated evolutionary rates was significantly enriched for proteins involved in immunity and defense, reproduction, and sensory perception. We also found elevated rates of evolution in several other functional groups such as management of membrane vesicles, transmembrane transport of ions and organic molecules, cell adhesion, and oxidative stress response. Proteins in these processes might be related to the endosymbiotic relationship corals maintain with dinoflagellates in the genus Symbiodinium. Conclusion/Relevance This study provides a birds-eye view of the processes potentially underlying coral adaptation, which will serve as a foundation for future work to elucidate the rates, patterns, and mechanisms of corals' evolutionary response to global climate change. PMID:21633702

  18. Rapid Evolution of Coral Proteins Responsible for Interaction with the Environment

    Energy Technology Data Exchange (ETDEWEB)

    Voolstra, Christian R.; Sunagawa, Shinichi; Matz, Mikhail V.; Bayer, Till; Aranda, Manuel; Buschiazzo, Emmanuel; DeSalvo, Michael K.; Lindquist, Erika; Szmant, Alina M.; Coffroth, Mary Alice; Medina, Monica

    2011-01-31

    Background: Corals worldwide are in decline due to climate change effects (e.g., rising seawater temperatures), pollution, and exploitation. The ability of corals to cope with these stressors in the long run depends on the evolvability of the underlying genetic networks and proteins, which remain largely unknown. A genome-wide scan for positively selected genes between related coral species can help to narrow down the search space considerably. Methodology/Principal Findings: We screened a set of 2,604 putative orthologs from EST-based sequence datasets of the coral species Acropora millepora and Acropora palmata to determine the fraction and identity of proteins that may experience adaptive evolution. 7percent of the orthologs show elevated rates of evolution. Taxonomically-restricted (i.e. lineagespecific) genes show a positive selection signature more frequently than genes that are found across many animal phyla. The class of proteins that displayed elevated evolutionary rates was significantly enriched for proteins involved in immunity and defense, reproduction, and sensory perception. We also found elevated rates of evolution in several other functional groups such as management of membrane vesicles, transmembrane transport of ions and organic molecules, cell adhesion, and oxidative stress response. Proteins in these processes might be related to the endosymbiotic relationship corals maintain with dinoflagellates in the genus Symbiodinium. Conclusion/Relevance: This study provides a birds-eye view of the processes potentially underlying coral adaptation, which will serve as a foundation for future work to elucidate the rates, patterns, and mechanisms of corals? evolutionary response to global climate change.

  19. Rapid evolution of coral proteins responsible for interaction with the environment.

    Directory of Open Access Journals (Sweden)

    Christian R Voolstra

    Full Text Available BACKGROUND: Corals worldwide are in decline due to climate change effects (e.g., rising seawater temperatures, pollution, and exploitation. The ability of corals to cope with these stressors in the long run depends on the evolvability of the underlying genetic networks and proteins, which remain largely unknown. A genome-wide scan for positively selected genes between related coral species can help to narrow down the search space considerably. METHODOLOGY/PRINCIPAL FINDINGS: We screened a set of 2,604 putative orthologs from EST-based sequence datasets of the coral species Acropora millepora and Acropora palmata to determine the fraction and identity of proteins that may experience adaptive evolution. 7% of the orthologs show elevated rates of evolution. Taxonomically-restricted (i.e. lineage-specific genes show a positive selection signature more frequently than genes that are found across many animal phyla. The class of proteins that displayed elevated evolutionary rates was significantly enriched for proteins involved in immunity and defense, reproduction, and sensory perception. We also found elevated rates of evolution in several other functional groups such as management of membrane vesicles, transmembrane transport of ions and organic molecules, cell adhesion, and oxidative stress response. Proteins in these processes might be related to the endosymbiotic relationship corals maintain with dinoflagellates in the genus Symbiodinium. CONCLUSION/RELEVANCE: This study provides a birds-eye view of the processes potentially underlying coral adaptation, which will serve as a foundation for future work to elucidate the rates, patterns, and mechanisms of corals' evolutionary response to global climate change.

  20. Human adaptation responses to a rapidly changing Arctic: A research context for building system resilience

    Science.gov (United States)

    Chapin, T.; Brinkman, T. J.

    2016-12-01

    Although human behavior accounts for more uncertainty in future trajectories in climate change than do biophysical processes, most climate-change research fails to include human actions in research design and implementation. This is well-illustrated in the Arctic. At the global scale, arctic processes strongly influence the strength of biophysical feedbacks between global human emissions and the rate of climate warming. However, most human actions in the arctic have little effect on these feedbacks, so research can contribute most effectively to reduction in arctic warming through improved understanding of the strength of arctic-global biophysical feedbacks, as in NASA's ABoVE program, and its effective communication to policy makers and the public. In contrast, at the local to regional scale within the arctic, human actions may influence the ecological and societal consequences of arctic warming, so research benefits from active stakeholder engagement in research design and implementation. Human communities and other stakeholders (government and NGOs) respond heterogeneously to socioeconomic and environmental change, so research that documents the range of historical and current adaptive responses to change provides insights on the resilience (flexibility of future options) of social-ecological processes in the arctic. Alaskan communities have attempted a range of adaptive responses to coastal erosion (e.g., seasonal migration, protection in place, relocation), wildfire (fire suppression to use of fire to manage wildlife habitat or landscape heterogeneity), declining sea ice (e.g., new hunting technology, sea ice observations and predictions), and changes in wildlife and fish availability (e.g., switch to harvest of alternative species, harvest times, or harvest locations). Research that draws on both traditional and western knowledge facilitates adaptation and predictions of the likely societal consequences of climate change in the Arctic. Effective inclusion of

  1. Anti-apoptotic signaling as a cytoprotective mechanism in mammalian hibernation

    Directory of Open Access Journals (Sweden)

    Andrew N. Rouble

    2013-02-01

    Full Text Available In the context of normal cell turnover, apoptosis is a natural phenomenon involved in making essential life and death decisions. Apoptotic pathways balance signals which promote cell death (pro-apoptotic pathways or counteract these signals (anti-apoptotic pathways. We proposed that changes in anti-apoptotic proteins would occur during mammalian hibernation to aid cell preservation during prolonged torpor under cellular conditions that are highly injurious to most mammals (e.g. low body temperatures, ischemia. Immunoblotting was used to analyze the expression of proteins associated with pro-survival in six tissues of thirteen-lined ground squirrels, Ictidomys tridecemlineatus. The brain showed a concerted response to torpor with significant increases in the levels of all anti-apoptotic targets analyzed (Bcl-2, Bcl-xL, BI-1, Mcl-1, cIAP1/2, xIAP as well as enhanced phosphorylation of Bcl-2 at S70 and T56. Heart responded similarly with most anti-apoptotic proteins elevated significantly during torpor except for Bcl-xL and xIAP that decreased and Mcl-1 that was unaltered. In liver, BI-1 increased whereas cIAP1/2 decreased. In kidney, there was an increase in BI-1, cIAP and xIAP but decreases in Bcl-xL and p-Bcl-2(T56 content. In brown adipose tissue, protein levels of BI-1, cIAP1/2, and xIAP decreased significantly during torpor (compared with euthermia whereas Bcl-2, Bcl-xL, Mcl-1 were unaltered; however, Bcl-2 showed enhanced phosphorylation at Thr56 but not at Ser70. In skeletal muscle, only xIAP levels changed significantly during torpor (an increase. The data show that anti-apoptotic pathways have organ-specific responses in hibernators with a prominent potential role in heart and brain where coordinated enhancement of anti-apoptotic proteins occurred in response to torpor.

  2. A Mixed Stimuli-Responsive Magnetic and Gold Nanoparticle System for Rapid Purification, Enrichment, and Detection of Biomarkers

    Science.gov (United States)

    Nash, Michael A.; Yager, Paul; Hoffman, Allan S.; Stayton, Patrick S.

    2010-01-01

    A new diagnostic system for the enrichment and detection of protein biomarkers from human plasma is presented. Gold nanoparticles (AuNPs) were surface-modified with a diblock copolymer synthesized using reversible addition fragmentation chain transfer (RAFT) polymerization. The diblock copolymer contained a thermally-responsive poly(N-isopropylacrylamide) (pNIPAAm) block, a cationic amine-containing block, and a semi-telechelic PEG2-biotin end group. When a mixed suspension of 23 nm pNIPAAm-modified AuNPs was heated with pNIPAAm-coated 10 nm iron oxide magnetic nanoparticles (mNPs) in human plasma, the thermally-responsive pNIPAAm directed the formation of mixed AuNP/mNP aggregates that could be separated efficiently with a magnet. Model studies showed that this mixed nanoparticle system could efficiently purify and strongly enrich the model biomarker protein streptavidin in spiked human plasma. A 10 ng/mL streptavidin sample was mixed with the biotinylated and pNIPAAm modified AuNP and magnetically separated in the mixed nanoparticle system with pNIPAAm mNPs. The aggregates were concentrated into a 50-fold smaller fluid volume at room temperature where the gold nanoparticle reagent redissolved with the streptavidin target still bound. The concentrated gold-labeled streptavidin could be subsequently analyzed directly using lateral flow immunochromatography. This rapid capture and enrichment module thus utilizes the mixed stimuli-responsive nanoparticle system to achieve direct concentration of a gold-labeled biomarker that can be directly analyzed using lateral flow or other rapid diagnostic strategies. PMID:21070026

  3. Boom and bust: rapid feedback responses between insect outbreak dynamics and canopy leaf area impacted by rainfall and CO2.

    Science.gov (United States)

    Gherlenda, Andrew N; Esveld, Jessica L; Hall, Aidan A G; Duursma, Remko A; Riegler, Markus

    2016-11-01

    Frequency and severity of insect outbreaks in forest ecosystems are predicted to increase with climate change. How this will impact canopy leaf area in future climates is rarely tested. Here, we document function of insect outbreaks that fortuitously and rapidly occurred in an ecosystem under free-air CO2 enrichment. Over the first 2 years of CO2 fumigation of a naturally established mature Eucalyptus woodland, we continuously assessed population responses of three sap-feeding insect species of the psyllid genera Cardiaspina, Glycaspis and Spondyliaspis for up to ten consecutive generations. Concurrently, we quantified changes in the canopy leaf area index (LAI). Large and rapid shifts in psyllid community composition were recorded between species with either flush (Glycaspis) or senescence-inducing (Cardiaspina, Spondyliaspis) feeding strategies. Within the second year, two psyllid species experienced significant and rapid population build-up resulting in two consecutive outbreaks: first, rainfall stimulated Eucalyptus leaf production increasing LAI, which supported population growth of flush-feeding Glycaspis without impacting LAI. Glycaspis numbers then crashed and were followed by the outbreak of senescence-feeding Cardiaspina fiscella that led to significant defoliation and reduction in LAI. For all three psyllid species, the abundance of lerps, protective coverings excreted by the sessile nymphs, decreased at e[CO2 ]. Higher lerp weight at e[CO2 ] for Glycaspis but not the other psyllid species provided evidence for compensatory feeding by the flush feeder but not the two senescence feeders. Our study demonstrates that rainfall drives leaf phenology, facilitating the rapid boom-and-bust succession of psyllid species, eventually leading to significant defoliation due to the second but not the first outbreaking psyllid species. In contrast, e[CO2 ] may impact psyllid abundance and feeding behaviour, with psyllid species-specific outcomes for defoliation

  4. Automated Formosat Image Processing System for Rapid Response to International Disasters

    Science.gov (United States)

    Cheng, M. C.; Chou, S. C.; Chen, Y. C.; Chen, B.; Liu, C.; Yu, S. J.

    2016-06-01

    FORMOSAT-2, Taiwan's first remote sensing satellite, was successfully launched in May of 2004 into the Sun-synchronous orbit at 891 kilometers of altitude. With the daily revisit feature, the 2-m panchromatic, 8-m multi-spectral resolution images captured have been used for researches and operations in various societal benefit areas. This paper details the orchestration of various tasks conducted in different institutions in Taiwan in the efforts responding to international disasters. The institutes involved including its space agency-National Space Organization (NSPO), Center for Satellite Remote Sensing Research of National Central University, GIS Center of Feng-Chia University, and the National Center for High-performance Computing. Since each institution has its own mandate, the coordinated tasks ranged from receiving emergency observation requests, scheduling and tasking of satellite operation, downlink to ground stations, images processing including data injection, ortho-rectification, to delivery of image products. With the lessons learned from working with international partners, the FORMOSAT Image Processing System has been extensively automated and streamlined with a goal to shorten the time between request and delivery in an efficient manner. The integrated team has developed an Application Interface to its system platform that provides functions of search in archive catalogue, request of data services, mission planning, inquiry of services status, and image download. This automated system enables timely image acquisition and substantially increases the value of data product. Example outcome of these efforts in recent response to support Sentinel Asia in Nepal Earthquake is demonstrated herein.

  5. Inspection times, the change task, and the rapid-response selection task.

    Science.gov (United States)

    Roberts, M J; Newton, E J

    2001-11-01

    Three experiments are reported, which are based upon the Wason four-card selection task inspection time paradigm, in which subjects solve computer-presented trials while using a mouse to indicate the card currently under consideration. Evans (1996) had shown that selected cards were inspected for longer than non-selected cards, and this was taken as support for the existence of pre-conscious heuristic processes that direct attention towards relevant aspects of a problem. However, Roberts (1998b) suggested that this inspection time effect is artefactual, due to task format induced biases. Experiment 1 utilized a "change" task: Cards were presented either as selected or not selected, and subjects changed these where necessary. This demonstrated an association between card selection and inspection time independently of one between the act of response and inspection time. Experiment 2 utilized a standard selection task, but subjects either responded within 2 s of each card presentation, or made selections with no time pressure. The curtailment of thinking time increased matching behaviour--more cards matching the terms in the rules were selected--and was replicated in Experiment 3 using a within-subjects design. Overall, the data support Evans' heuristic-analytic framework albeit with some caveats.

  6. Laser Chemosensor with Rapid Responsivity and Inherent Memory Based on a Polymer of Intrinsic Microporosity

    Directory of Open Access Journals (Sweden)

    Graham A. Turnbull

    2011-02-01

    Full Text Available This work explores the use of a polymer of intrinsic microporosity (PIM-1 as the active layer within a laser sensor to detect nitroaromatic-based explosive vapors. We show successful detection of dinitrobenzene (DNB by monitoring the real-time photoluminescence. We also show that PIM-1 has an inherent memory, so that it accumulates the analyte during exposure. In addition, the optical gain and refractive index of the polymer were studied by amplified spontaneous emission and variable-angle ellipsometry, respectively. A second-order distributed feedback PIM-1 laser sensor was fabricated and found to show an increase in laser threshold of 2.5 times and a reduction of the laser slope efficiency by 4.4 times after a 5-min exposure to the DNB vapor. For pumping at 2 times threshold, the lasing action was stopped within 30 s indicating that PIM-1 has a very fast responsivity and as such has a potential sensing ability for ultra-low-concentration explosives.

  7. Laser chemosensor with rapid responsivity and inherent memory based on a polymer of intrinsic microporosity.

    Science.gov (United States)

    Wang, Yue; McKeown, Neil B; Msayib, Kadhum J; Turnbull, Graham A; Samuel, Ifor D W

    2011-01-01

    This work explores the use of a polymer of intrinsic microporosity (PIM-1) as the active layer within a laser sensor to detect nitroaromatic-based explosive vapors. We show successful detection of dinitrobenzene (DNB) by monitoring the real-time photoluminescence. We also show that PIM-1 has an inherent memory, so that it accumulates the analyte during exposure. In addition, the optical gain and refractive index of the polymer were studied by amplified spontaneous emission and variable-angle ellipsometry, respectively. A second-order distributed feedback PIM-1 laser sensor was fabricated and found to show an increase in laser threshold of 2.5 times and a reduction of the laser slope efficiency by 4.4 times after a 5-min exposure to the DNB vapor. For pumping at 2 times threshold, the lasing action was stopped within 30 s indicating that PIM-1 has a very fast responsivity and as such has a potential sensing ability for ultra-low-concentration explosives.

  8. pH-Responsive Poly(D,L-lactic-co-glycolic acid) Nanoparticles with Rapid Antigen Release Behavior Promote Immune Response.

    Science.gov (United States)

    Liu, Qi; Chen, Xiaoming; Jia, Jilei; Zhang, Weifeng; Yang, Tingyuan; Wang, Lianyan; Ma, Guanghui

    2015-05-26

    In the quest to treat intracellular infectious diseases and virus infection, nanoparticles (NPs) have been considered to be efficient tools for inducing potent immune responses, specifically cellular immunity. Antigen processing and presenting by antigen presenting cells (APCs) could influence immune response, especially the priming of T-cell-mediated cellular immunity. Here, we fabricated pH-responsive poly(D,L-lactic-co-glycolic acid) (PLGA) NPs with rapid antigen intracellular release behavior in APCs. The NPs, which had thin shells and large inner space, contain ammonium bicarbonate (NH4HCO3), which could regulate release in endosomes and lysosomes, acting as an antigen release promoter in dendritic cells (DCs), and were coencapsulated with antigen (ovalbumin, OVA). Hydrogen ions (H(+)) in DC endosomes and lysosomes (pH ∼5.0 and 6.5) could react with NH4HCO3 to generate NH3 and CO2, which broke NPs and released antigens. After uptake by DCs, antigens encapsulated in pH-responsive PLGA NPs could escape from lysosomes into the cytoplasm and be cross-presented. Moreover, the NPs induced up-regulation of co-stimulatory molecules and stimulated cytokine production. Mouse immunization with pH-responsive PLGA NPs induced greater lymphocyte activation, more antigen-specific CD8(+) T cells, stronger cytotoxic capacity (IFN-γ and granzyme B), enhanced antigen-specific IgG antibodies, and higher serum IgG2a/IgG1, indicating cellular immunity. The NPs also improved generation of memory T cells to protect against reinfection. Thus, pH-responsive PLGA NPs, which induced strong cellular immune responses and offered antibody protection, could be potentially useful as effective vaccine delivery and adjuvant systems for the therapy of intracellular infectious diseases and virus infection.

  9. Apoptotic Cell Clearance in Drosophila melanogaster

    Directory of Open Access Journals (Sweden)

    Qian Zheng

    2017-12-01

    Full Text Available The swift clearance of apoptotic cells (ACs (efferocytosis by phagocytes is a critical event during development of all multicellular organisms. It is achieved through phagocytosis by professional or amateur phagocytes. Failure in this process can lead to the development of inflammatory autoimmune or neurodegenerative diseases. AC clearance has been conserved throughout evolution, although many details in its mechanisms remain to be explored. It has been studied in the context of mammalian macrophages, and in the nematode Caenorhabditis elegans, which lacks “professional” phagocytes such as macrophages, but in which other cell types can engulf apoptotic corpses. In Drosophila melanogaster, ACs are engulfed by macrophages, glial, and epithelial cells. Drosophila macrophages perform similar functions to those of mammalian macrophages. They are professional phagocytes that participate in phagocytosis of ACs and pathogens. Study of AC clearance in Drosophila has identified some key elements, like the receptors Croquemort and Draper, promoting Drosophila as a suitable model to genetically dissect this process. In this review, we survey recent works of AC clearance pathways in Drosophila, and discuss the physiological outcomes and consequences of this process.

  10. Timing of palliative care team referrals for inpatients receiving rapid response services: A retrospective pilot study in a US hospital.

    Science.gov (United States)

    Williams, M; Cardona-Morrell, M; Stevens, P; Bey, J; Smith Glasgow, M E

    2017-10-01

    Research indicates up to one-third of rapid response team calls relate to end-of-life symptoms. The CriSTAL criteria were developed as a screening tool to identify high risk of death within three months. The primary purpose of this pilot study was to investigate the timing of palliative care referrals in patients receiving rapid response team services, and patients' CriSTAL criteria score on admission. The potential feasibility of using the CriSTAL tool to stimulate earlier Palliative Care Team (PCT) referral served as an underlying goal, and investigation of a relationship between specific CriSTAL criteria and the prediction of in-hospital death was a secondary objective. A retrospective chart review of rapid response calls made in 2015 was used to identify patient risk of death on admission based on the CriSTAL criteria. The presence and timing of PCT referral as well as patient survival status to hospital discharge were documented for comparison. A sample of 183 charts from 584 inpatients involved in over 600 RRT events recorded in 2015. The study was undertaken in a 676-bed teaching hospital in the Midwestern U.S. Ninety-one patients died during the hospital stay while 92 patients from the 493 individuals who survived were randomly selected for full analysis. Applying CriSTAL criteria to the 141 individuals aged 50 years or older indicated that frailty (OR=1.43, 95%CI 1.08-1.89, p=0.012), being a male (OR=3.14; 95%CI 1.40-7.05, p=0.006), and the presence of two or more comorbidities (OR=3.71, 95%CI 1.67-8.24, p=0.001) were the most significant predictors of in-hospital death after adjusting for age. A CriSTAL score of 6 was the optimal cut-off for high-risk of in-hospital death. Palliative care consultations within the high-risk population occurred for 45.2% of the deceased and 40.4% of the survivors. Consultation often occurred within two days of the RRT event and many patients (46.8%) died within one day of the consultation. A positive relationship was found

  11. Behavioral responses of deafened guinea pigs to intracochlear electrical stimulation: a new rapid psychophysical procedure.

    Science.gov (United States)

    Agterberg, Martijn J H; Versnel, Huib

    2014-07-01

    In auditory research the guinea pig is often preferred above rats and mice because of the easily accessible cochlea and because the frequency range of its hearing is more comparable to that of humans. Studies of the guinea-pig auditory system primarily apply histological and electrophysiological measures. Behavioral animal paradigms, in particular in combination with these histological and electrophysiological methods, are necessary in the development of new therapeutic interventions. However, the guinea pig is not considered an attractive animal for behavioral experiments. Therefore, the purpose of this study was to develop a behavioral task suitable for guinea pigs, that can be utilized in cochlear-implant related research. Guinea pigs were trained in a modified shuttle-box in which a stream of air was used as unconditioned stimulus (UCS). A stream of air was preferred over conventionally used methods as electric foot-shocks since it produces less stress, which is a confounding factor in behavioral experiments. Hearing guinea pigs were trained to respond to acoustic stimuli. They responded correctly within only five sessions of ten minutes. The animals maintained their performance four weeks after the right cochlea was implanted with an electrode array. After systemic deafening, the animals responded in the first session immediately to intracochlear electrical stimulation. These responses were not affected by daily chronic electrical stimulation (CES). In conclusion, the present study demonstrates that guinea pigs can be trained relatively fast to respond to acoustic stimuli, and that the training has a lasting effect, which generalizes to intracochlear electrical stimulation after deafening. Furthermore, it demonstrates that bilaterally deafened guinea pigs with substantial (∼50%) loss of spiral ganglion cells (SGCs), detect intracochlear electrical stimulation. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. Rapid response of a marine mammal species to holocene climate and habitat change.

    Directory of Open Access Journals (Sweden)

    Mark de Bruyn

    2009-07-01

    Full Text Available Environmental change drives demographic and evolutionary processes that determine diversity within and among species. Tracking these processes during periods of change reveals mechanisms for the establishment of populations and provides predictive data on response to potential future impacts, including those caused by anthropogenic climate change. Here we show how a highly mobile marine species responded to the gain and loss of new breeding habitat. Southern elephant seal, Mirounga leonina, remains were found along the Victoria Land Coast (VLC in the Ross Sea, Antarctica, 2,500 km from the nearest extant breeding site on Macquarie Island (MQ. This habitat was released after retreat of the grounded ice sheet in the Ross Sea Embayment 7,500-8,000 cal YBP, and is within the range of modern foraging excursions from the MQ colony. Using ancient mtDNA and coalescent models, we tracked the population dynamics of the now extinct VLC colony and the connectivity between this and extant breeding sites. We found a clear expansion signal in the VLC population approximately 8,000 YBP, followed by directional migration away from VLC and the loss of diversity at approximately 1,000 YBP, when sea ice is thought to have expanded. Our data suggest that VLC seals came initially from MQ and that some returned there once the VLC habitat was lost, approximately 7,000 years later. We track the founder-extinction dynamics of a population from inception to extinction in the context of Holocene climate change and present evidence that an unexpectedly diverse, differentiated breeding population was founded from a distant source population soon after habitat became available.

  13. AUTOMATED FORMOSAT IMAGE PROCESSING SYSTEM FOR RAPID RESPONSE TO INTERNATIONAL DISASTERS

    Directory of Open Access Journals (Sweden)

    M. C. Cheng

    2016-06-01

    Full Text Available FORMOSAT-2, Taiwan’s first remote sensing satellite, was successfully launched in May of 2004 into the Sun-synchronous orbit at 891 kilometers of altitude. With the daily revisit feature, the 2-m panchromatic, 8-m multi-spectral resolution images captured have been used for researches and operations in various societal benefit areas. This paper details the orchestration of various tasks conducted in different institutions in Taiwan in the efforts responding to international disasters. The institutes involved including its space agency-National Space Organization (NSPO, Center for Satellite Remote Sensing Research of National Central University, GIS Center of Feng-Chia University, and the National Center for High-performance Computing. Since each institution has its own mandate, the coordinated tasks ranged from receiving emergency observation requests, scheduling and tasking of satellite operation, downlink to ground stations, images processing including data injection, ortho-rectification, to delivery of image products. With the lessons learned from working with international partners, the FORMOSAT Image Processing System has been extensively automated and streamlined with a goal to shorten the time between request and delivery in an efficient manner. The integrated team has developed an Application Interface to its system platform that provides functions of search in archive catalogue, request of data services, mission planning, inquiry of services status, and image download. This automated system enables timely image acquisition and substantially increases the value of data product. Example outcome of these efforts in recent response to support Sentinel Asia in Nepal Earthquake is demonstrated herein.

  14. Fluvial response to the last Holocene rapid climate change in the Northwestern Mediterranean coastlands

    Science.gov (United States)

    Degeai, Jean-Philippe; Devillers, Benoît; Blanchemanche, Philippe; Dezileau, Laurent; Oueslati, Hamza; Tillier, Margaux; Bohbot, Hervé

    2017-05-01

    The variability of fluvial activity in the Northwestern Mediterranean coastal lowlands and its relationship with modes of climate change were analysed from the late 9th to the 18th centuries CE. Geochemical analyses were undertaken from a lagoonal sequence and surrounding sediments in order to track the fluvial inputs into the lagoon. An index based on the K/S and Rb/S ratios was used to evidence the main periods of fluvial activity. This index reveals that the Medieval Climate Anomaly (MCA) was a drier period characterized by a lower fluvial activity, while the Little Ice Age (LIA) was a wetter period with an increase of the river dynamics. Three periods of higher than average fluvial activity were evidenced at the end of the first millennium CE (ca. 900-950 cal yr CE), in the first half of the second millennium CE (ca. 1150-1550 cal yr CE), and during the 1600s-1700s CE (ca. 1650-1800 cal yr CE). The comparison of these fluvial periods with other records of riverine or lacustrine floods in Spain, Italy, and South of France seems to indicate a general increase in fluvial and flood patterns in the Northwestern Mediterranean in response to the climate change from the MCA to the LIA, although some episodes of flooding are not found in all records. Besides, the phases of higher than average fluvial dynamics are in good agreement with the North Atlantic cold events evidenced from records of ice-rafted debris. The evolution of fluvial activity in the Northwestern Mediterranean coastlands during the last millennium could have been driven by atmospheric and oceanic circulation patterns.

  15. A New Wine Tasting Approach Based on Emotional Responses to Rapidly Recognize Classic European Wine Styles

    Directory of Open Access Journals (Sweden)

    Virgílio Loureiro

    2016-03-01

    Full Text Available Conventional tasting sheets are widely used to evaluate wine quality in wine tasting competitions. However, the higher scores are mostly obtained by international commercial wines, resulting in lower scores being awarded to the classic European wines. We hypothesize that this is due to the tasting methodology that fails to recognize this wine style. Therefore, the purpose of this work was to show the implementation of a new wine tasting approach to overcome this drawback. The proposed training technique is based on the emotional responses of the taster after smelling two wines of clearly opposite styles. The first wine is characterized by high aromatic intensity but low in-mouth intensity, perceived as disappointing to the taster, here defined as an “easy” wine. The second wine is characterized as a wine with low aromatic intensity but that provides an unexpectedly positive in-mouth experience, here defined as a “difficult” wine. These emotions are explained by the wine sensorial characteristics. The “easy” wine has an intense, simple smell with short persistence while the “difficult” wine has a low intensity, complex aroma, and long persistence. The first style corresponds to the international commercial wines most prized in international wine challenges. The second, frequently rejected by untrained tasters, is consistent with the “so called” classic European wines, and is characterized by light red or yellow straw colors, weak smell intensity, and aggressive mouth-feel. After no more than four training sessions and using the OIV tasting sheet, inexperienced tasters were able to score “difficult” wines equally as “easy” wines and understand their different attributes. In conclusion, this new tasting approach may be used by wine professionals to explain the characteristics of high quality wines that are not easily recognized by untrained consumers.

  16. Wetland vegetation in Manzala lagoon, Nile Delta coast, Egypt: Rapid responses of pollen to altered nile hydrology and land use

    Science.gov (United States)

    Bernhardt, C.E.; Stanley, J.-D.; Horton, B.P.

    2011-01-01

    The pollen record in a sediment core from Manzala lagoon on the Nile delta coastal margin of Egypt, deposited from ca. AD 1860 to 1990, indicates rapid coastal wetland vegetation responses to two primary periods of human activity. These are associated with artificially altered Nile hydrologic regimes in proximal areas and distal sectors located to ???1200 km south of Manzala. Freshwater wetland plants that were dominant, such as Typha and Phragmites, decreased rapidly, whereas in the early 1900s, brackish water wetland species (e.g., Amaranthaceae) increased. This change occurred after closure of the Aswan Low Dam in 1902. The second major modification in the pollen record occurred in the early 1970s, after Aswan High Dam closure from 1965 to 1970, when Typha pollen abundance increased rapidly. Massive population growth occurred along the Nile during the 130 years represented by the core section. During this time, the total volume of lagoon water decreased because of conversion of wetland areas to agricultural land, and input of organic-rich sediment, sewage (municipal, agricultural, industrial), and fertilizer in Manzala lagoon increased markedly. Although the wetland plant community has continued to respond to increasingly intensified and varied human-induced pressures in proximal sectors, the two most marked changes in Manzala pollen best correlate with distal events (i.e., closure of the two dams at Aswan). The study also shows that the two major vegetation changes in Manzala lagoon each occurred less than 10 years after closure upriver of the Low and High dams that markedly altered the Nile regime from Upper Egypt to the coast. ?? 2011, the Coastal Education & Research Foundation (CERF).

  17. Liver Stiffness Decreases Rapidly in Response to Successful Hepatitis C Treatment and Then Plateaus.

    Directory of Open Access Journals (Sweden)

    Sweta Chekuri

    Full Text Available To investigate the impact of a sustained virological response (SVR to hepatitis C virus (HCV treatment on liver stiffness (LS.LS, measured by transient elastography (FibroScan, demographic and laboratory data of patients treated with interferon (IFN-containing or IFN-free regimens who had an SVR24 (undetectable HCV viral load 24 weeks after the end of treatment were analyzed using two-tailed paired t-tests, Mann-Whitney Wilcoxon Signed-rank tests and linear regression. Two time intervals were investigated: pre-treatment to SVR24 and SVR24 to the end of follow-up. LS scores ≥ 12.5 kPa indicated LS-defined cirrhosis. A p-value below 0.05 was considered statistically significant.The median age of the patients (n = 100 was 60 years [IQR (interquartile range 54-64; 72% were male; 60% were Caucasian; and 42% had cirrhosis pre-treatment according to the FibroScan measurement. The median LS score dropped from 10.40 kPa (IQR: 7.25-18.60 pre-treatment to 7.60 kPa (IQR: 5.60-12.38 at SVR24, p <0.01. Among the 42 patients with LS-defined cirrhosis pre-treatment, 25 (60% of patients still had LS scores ≥ 12.5 kPa at SVR24, indicating the persistence of cirrhosis. The median change in LS was similar in patients receiving IFN-containing and IFN-free regimens: -1.95 kPa (IQR: -5.75 --0.38 versus -2.40 kPa (IQR: -7.70 --0.23, p = 0.74. Among 56 patients with a post-SVR24 LS measurement, the LS score changed by an additional -0.90 kPa (IQR: -2.98-0.5 during a median follow-up time of 1.17 (IQR: 0.88-1.63 years, which was not a statistically significant decrease (p = 0.99.LS decreased from pre-treatment to SVR24, but did not decrease significantly during additional follow-up. Earlier treatment may be needed to reduce the burden of liver disease.

  18. Optimizing the Attitude Control of Small Satellite Constellations for Rapid Response Imaging

    Science.gov (United States)

    Nag, S.; Li, A.

    2016-12-01

    -off and minimum image distortion among the satellites, using Landsat's specifications. Attitude-specific constraints such as power consumption, response time, and stability were factored into the optimality computations. The algorithm can integrate cloud cover predictions, specific ground and air assets and angular constraints.

  19. Empirically defining rapid response to intensive treatment to maximize prognostic utility for bulimia nervosa and purging disorder.

    Science.gov (United States)

    MacDonald, Danielle E; Trottier, Kathryn; McFarlane, Traci; Olmsted, Marion P

    2015-05-01

    Rapid response (RR) to eating disorder treatment has been reliably identified as a predictor of post-treatment and sustained remission, but its definition has varied widely. Although signal detection methods have been used to empirically define RR thresholds in outpatient settings, RR to intensive treatment has not been investigated. This study investigated the optimal definition of RR to day hospital treatment for bulimia nervosa and purging disorder. Participants were 158 patients who completed ≥6 weeks of day hospital treatment. Receiver operating characteristic (ROC) analysis was used to create four definitions of RR that could differentiate between remission and nonremission at the end of treatment. Definitions were based on binge/vomit episode frequency or percent reduction from pre-treatment, during either the first four or first two weeks of treatment. All definitions were associated with higher remission rates in rapid compared to nonrapid responders. Only one definition (i.e., ≤3 episodes in the first four weeks of treatment) predicted sustained remission (versus relapse) at 6- and 12-month follow-up. These findings provide an empirically derived definition of RR to intensive eating disorder treatment, and provide further evidence that early change is an important prognostic indicator. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. The Technical Efficiency of Earthquake Medical Rapid Response Teams Following Disasters: The Case of the 2010 Yushu Earthquake in China.

    Science.gov (United States)

    Liu, Xu; Tang, Bihan; Yang, Hongyang; Liu, Yuan; Xue, Chen; Zhang, Lulu

    2015-12-04

    Performance assessments of earthquake medical rapid response teams (EMRRTs), particularly the first responders deployed to the hardest hit areas following major earthquakes, should consider efficient and effective use of resources. This study assesses the daily technical efficiency of EMRRTs in the emergency period immediately following the 2010 Yushu earthquake in China. Data on EMRRTs were obtained from official daily reports of the general headquarters for Yushu earthquake relief, the emergency office of the National Ministry of Health, and the Health Department of Qinghai Province, for a sample of data on 15 EMRRTs over 62 days. Data envelopment analysis was used to examine the technical efficiency in a constant returns to scale model, a variable returns to scale model, and the scale efficiency of EMRRTs. Tobit regression was applied to analyze the effects of corresponding influencing factors. The average technical efficiency scores under constant returns to scale, variable returns to scale, and the scale efficiency scores of the 62 units of analysis were 77.95%, 89.00%, and 87.47%, respectively. The staff-to-bed ratio was significantly related to global technical efficiency. The date of rescue was significantly related to pure technical efficiency. The type of institution to which an EMRRT belonged and the staff-to-bed ratio were significantly related to scale efficiency. This study provides evidence that supports improvements to EMRRT efficiency and serves as a reference for earthquake emergency medical rapid assistance leaders and teams.

  1. Adenovirus-vectored drug-vaccine duo as a rapid-response tool for conferring seamless protection against influenza.

    Directory of Open Access Journals (Sweden)

    Jianfeng Zhang

    Full Text Available Few other diseases exert such a huge toll of suffering as influenza. We report here that intranasal (i.n. administration of E1/E3-defective (ΔE1E3 adenovirus serotype 5 (Ad5 particles rapidly induced an anti-influenza state as a means of prophylactic therapy which persisted for several weeks in mice. By encoding an influenza virus (IFV hemagglutinin (HA HA1 domain, an Ad5-HA1 vector conferred rapid protection as a prophylactic drug followed by elicitation of sustained protective immunity as a vaccine for inducing seamless protection against influenza as a drug-vaccine duo (DVD in a single package. Since Ad5 particles induce a complex web of host responses, which could arrest influenza by activating a specific arm of innate immunity to impede IFV growth in the airway, it is conceivable that this multi-pronged influenza DVD may escape the fate of drug resistance that impairs the current influenza drugs.

  2. The Technical Efficiency of Earthquake Medical Rapid Response Teams Following Disasters: The Case of the 2010 Yushu Earthquake in China

    Directory of Open Access Journals (Sweden)

    Xu Liu

    2015-12-01

    Full Text Available Purpose: Performance assessments of earthquake medical rapid response teams (EMRRTs, particularly the first responders deployed to the hardest hit areas following major earthquakes, should consider efficient and effective use of resources. This study assesses the daily technical efficiency of EMRRTs in the emergency period immediately following the 2010 Yushu earthquake in China. Methods: Data on EMRRTs were obtained from official daily reports of the general headquarters for Yushu earthquake relief, the emergency office of the National Ministry of Health, and the Health Department of Qinghai Province, for a sample of data on 15 EMRRTs over 62 days. Data envelopment analysis was used to examine the technical efficiency in a constant returns to scale model, a variable returns to scale model, and the scale efficiency of EMRRTs. Tobit regression was applied to analyze the effects of corresponding influencing factors. Results: The average technical efficiency scores under constant returns to scale, variable returns to scale, and the scale efficiency scores of the 62 units of analysis were 77.95%, 89.00%, and 87.47%, respectively. The staff-to-bed ratio was significantly related to global technical efficiency. The date of rescue was significantly related to pure technical efficiency. The type of institution to which an EMRRT belonged and the staff-to-bed ratio were significantly related to scale efficiency. Conclusions: This study provides evidence that supports improvements to EMRRT efficiency and serves as a reference for earthquake emergency medical rapid assistance leaders and teams.

  3. PARP Inhibition Restores Extrinsic Apoptotic Sensitivity in Glioblastoma

    Science.gov (United States)

    Karpel-Massler, Georg; Pareja, Fresia; Aimé, Pascaline; Shu, Chang; Chau, Lily; Westhoff, Mike-Andrew; Halatsch, Marc-Eric; Crary, John F.; Canoll, Peter; Siegelin, Markus D.

    2014-01-01

    Background Resistance to apoptosis is a paramount issue in the treatment of Glioblastoma (GBM). We show that targeting PARP by the small molecule inhibitors, Olaparib (AZD-2281) or PJ34, reduces proliferation and lowers the apoptotic threshold of GBM cells in vitro and in vivo. Methods The sensitizing effects of PARP inhibition on TRAIL-mediated apoptosis and potential toxicity were analyzed using viability assays and flow cytometry in established GBM cell lines, low-passage neurospheres and astrocytes in vitro. Molecular analyses included western blots and gene silencing. In vivo, effects on tumor growth were examined in a murine subcutaneous xenograft model. Results The combination treatment of PARP inhibitors and TRAIL led to an increased cell death with activation of caspases and inhibition of formation of neurospheres when compared to single-agent treatment. Mechanistically, pharmacological PARP inhibition elicited a nuclear stress response with up-regulation of down-stream DNA-stress response proteins, e.g., CCAAT enhancer binding protein (C/EBP) homology protein (CHOP). Furthermore, Olaparib and PJ34 increased protein levels of DR5 in a concentration and time-dependent manner. In turn, siRNA-mediated suppression of DR5 mitigated the effects of TRAIL/PARP inhibitor-mediated apoptosis. In addition, suppression of PARP-1 levels enhanced TRAIL-mediated apoptosis in malignant glioma cells. Treatment of human astrocytes with the combination of TRAIL/PARP inhibitors did not cause toxicity. Finally, the combination treatment of TRAIL and PJ34 significantly reduced tumor growth in vivo when compared to treatment with each agent alone. Conclusions PARP inhibition represents a promising avenue to overcome apoptotic resistance in GBM. PMID:25531448

  4. Atrial Fibrillation with Rapid Ventricular Response following use of Dietary Supplement Containing 1,3 Dimethylamylamine and Caffeine.

    Science.gov (United States)

    Armstrong, Michael

    2012-01-01

    Our nation?s servicemembers commonly use dietary supplements to enhance their performance. Despite this prolific use, many of these products have detrimental side-effects that compromise servicemembers? health and could, by proxy, compromise a mission. This paper presents the case of a 32-year old Navy Special Operations Forces (SOF) Sailor who, prior to physical training, used a supplement containing 1,3 Dimethylamylamine (DMAA), and then developed atrial fibrillation with rapid ventricular response. He required intravenous calcium channel blocker administration, followed by beta blockers, for rate control. As military providers, we routinely ask our patients about their use of supplements and while the regulation of these products is beyond the scope of practice for most of us, it is our duty to become better educated about the risks and benefits of these supplements. We must educate our patients and our commands on the potential harm that these supplements may pose. 2012.

  5. Rapid response for invasive waterweeds at the arctic invasion front: Assessment of collateral impacts from herbicide treatments

    Science.gov (United States)

    Sethi, Suresh; Carey, Michael P.; Morton, John M.; Guerron-Orejuela, Edgar; Decino, Robert; Willette, Mark; Boersma, James; Jablonski, Jillian; Anderson, Cheryl

    2017-01-01

    The remoteness of subarctic and arctic ecosystems no longer protects against invasive species introductions. Rather, the mix of urban hubs surrounded by undeveloped expanses creates a ratchet process whereby anthropogenic activity is sufficient to introduce and spread invaders, but for which the costs of monitoring and managing remote ecosystems is prohibitive. Elodea spp. is the first aquatic invasive plant to become established in Alaska and has potential for widespread deleterious ecological and economic impacts. A rapid eradication response with herbicides has been identified as a priority invasion control strategy. We conducted a multi-lake monitoring effort to assess collateral impacts from herbicide treatment for Elodea in high latitude systems. Variability in data was driven by seasonal dynamics and natural lake-to-lake differences typical of high latitude waterbodies, indicating lack of evidence for systematic impacts to water quality or plankton communities associated with herbicide treatment of Elodea. Impacts on native macrophytes were benign with the exception of some evidence for earlier onset of leaf senescence for lily pads(Nuphar spp.) in treated lakes. We observed a substantial increase in detected native flora richness after Elodea was eradicated from the most heavily infested lake, indicating potential for retention of native macrophyte communities if infestations are addressed quickly. While avoiding introductions through prevention may be the most desirable outcome, these applications indicated low risks of non-target impacts associated with herbicide treatment as a rapid response option for Elodea in high latitude systems.

  6. Chemotherapy of colorectal liver metastases induces a rapid rise in intermediate blood monocytes which predicts treatment response

    Science.gov (United States)

    Schauer, Dominic; Starlinger, Patrick; Alidzanovic, Lejla; Zajc, Philipp; Maier, Thomas; Feldman, Alexandra; Padickakudy, Robin; Buchberger, Elisabeth; Elleder, Vanessa; Spittler, Andreas; Stift, Judith; Pop, Lorand; Gruenberger, Birgit; Gruenberger, Thomas; Brostjan, Christine

    2016-01-01

    ABSTRACT We have previously reported that intermediate monocytes (CD14++/CD16+) were increased in colorectal cancer (CRC) patients, while the subset of pro-angiogenic TIE2-expressing monocytes (TEMs) was not significantly elevated. This study was designed to evaluate changes in frequency and function of intermediate monocytes and TEMs during chemotherapy and anti-angiogenic cancer treatment and their relation to treatment response. Monocyte populations were determined by flow cytometry in 60 metastasized CRC (mCRC) patients who received neoadjuvant chemotherapy with or without bevacizumab. Blood samples were taken before treatment, after two therapy cycles, at the end of neoadjuvant therapy and immediately before surgical resection of liver metastases. Neoadjuvant treatment resulted in a significant increase in circulating intermediate monocytes which was most pronounced after two cycles and positively predicted tumor response (AUC = 0.875, p = 0.005). With a cut-off value set to 1% intermediate monocytes of leukocytes, this parameter showed a predictive sensitivity and specificity of 75% and 88%. Anti-angiogenic therapy with bevacizumab had no impact on monocyte populations including TEMs. In 15 patients and six healthy controls, the gene expression profile and the migratory behavior of monocyte subsets was evaluated. The profile of intermediate monocytes suggested functions in antigen presentation, inflammatory cytokine production, chemotaxis and was remarkably stable during chemotherapy. Intermediate monocytes showed a preferential migratory response to tumor-derived signals in vitro and correlated with the level of CD14+/CD16+ monocytic infiltrates in the resected tumor tissue. In conclusion, the rapid rise of intermediate monocytes during chemotherapy may offer a simple marker for response prediction and a timely change in regimen. PMID:27471631

  7. Rapid Induction of Multiple Terpenoid Groups by Ponderosa Pine in Response to Bark Beetle-Associated Fungi.

    Science.gov (United States)

    Keefover-Ring, Ken; Trowbridge, Amy; Mason, Charles J; Raffa, Kenneth F

    2016-01-01

    Ponderosa pine (Pinus ponderosa) is a major and widely distributed component of conifer biomes in western North America and provides substantial ecological and economic benefits. This tree is exposed to several tree-killing bark beetle-microbial complexes, including the mountain pine beetle (Dendroctonus ponderosae) and the phytopathogenic fungus Grosmannia clavigera that it vectors, which are among the most important. Induced responses play a crucial role in conifer defenses, yet these have not been reported in ponderosa pine. We compared concentrations of terpenes and a phenylpropanoid, two phytochemical classes with strong effects against bark beetles and their symbionts, in constitutive phloem tissue and in tissue following mechanical wounding or simulated D. ponderosae attack (mechanical wounding plus inoculation with G. clavigera). We also tested whether potential induced responses were localized or systemic. Ponderosa pines showed pronounced induced defenses to inoculation, increasing their total phloem concentrations of monoterpenes 22.3-fold, sesquiterpenes 56.7-fold, and diterpenes 34.8-fold within 17 days. In contrast, responses to mechanical wounding alone were only 5.2, 11.3, and 7.7-fold, respectively. Likewise, the phenylpropanoid estragole (4-allyanisole) rose to 19.1-fold constitutive levels after simulated attack but only 4.4-fold after mechanical wounding. Overall, we found no evidence of systemic induction after 17 days, which spans most of this herbivore's narrow peak attack period, as significant quantitative and compositional changes within and between terpenoid groups were localized to the wound site. Implications to the less frequent exploitation of ponderosa than lodgepole pine by D. ponderosae, and potential advantages of rapid localized over long-term systemic responses in this system, are discussed.

  8. Predicting meaningful outcomes to medication and self-help treatments for binge-eating disorder in primary care: The significance of early rapid response.

    Science.gov (United States)

    Grilo, Carlos M; White, Marney A; Masheb, Robin M; Gueorguieva, Ralitza

    2015-04-01

    We examined rapid response among obese patients with binge-eating disorder (BED) in a randomized clinical trial testing antiobesity medication and self-help cognitive-behavioral therapy (shCBT), alone and in combination, in primary-care settings. One hundred four obese patients with BED were randomly assigned to 1 of 4 treatments: sibutramine, placebo, shCBT + sibutramine, or shCBT + placebo. Treatments were delivered by generalist primary-care physicians and the medications were given double-blind. Independent assessments were performed by trained and monitored doctoral research clinicians monthly throughout treatment, posttreatment (4 months), and at 6- and 12-month follow-ups (i.e., 16 months after randomization). Rapid response, defined as ≥65% reduction in binge eating by the fourth treatment week, was used to predict outcomes. Rapid response characterized 47% of patients, was unrelated to demographic and baseline clinical characteristics, and was significantly associated, prospectively, with remission from binge eating at posttreatment (51% vs. 9% for nonrapid responders), 6-month (53% vs. 23.6%), and 12-month (46.9% vs. 23.6%) follow-ups. Mixed-effects model analyses revealed that rapid response was significantly associated with greater decreases in binge-eating or eating-disorder psychopathology, depression, and percent weight loss. Our findings, based on a diverse obese patient group receiving medication and shCBT for BED in primary-care settings, indicate that patients who have a rapid response achieve good clinical outcomes through 12-month follow-ups after ending treatment. Rapid response represents a strong prognostic indicator of clinically meaningful outcomes, even in low-intensity medication and self-help interventions. Rapid response has important clinical implications for stepped-care treatment models for BED. clinicaltrials.gov: NCT00537810 (PsycINFO Database Record (c) 2015 APA, all rights reserved).

  9. GeoNet's `Felt Rapid': Collecting What Is Needed, When You Need It, No More, No Less. Rapid, Volumous Data For Response Versus Detailed, Precise Data For Research

    Science.gov (United States)

    Little, C. L.; McBride, S.; Balfour, N.

    2016-12-01

    New Zealand's geohazard monitoring agency, GeoNet, recently implemented `Felt Rapid': earthquake felt reporting that is quick and simple. GeoNet locates 20,000 earthquakes each year with hundreds of those reported as being felt. Starting in the late 1800s, the New Zealand public has become adept at completing felt reports but feedback since the Canterbury Earthquake Sequence suggested that traditional felt reporting was not meeting researchers' or the public's needs. GeoNet required something rapid, adaptable and robust. The solution was Felt Rapid, a mobile app and website where respondents simply pick from 6 cartoon images - representing Modified Mercalli Intensity (MMI) 3-8 - that best aligned to what they felt. For the last decade, felt reporting has been conducted via the GeoNet website, with additional targeted surveys after damaging earthquakes. The vast majority of the submitted felt reports were for earthquakes too small to cause damage, as these are by far the most frequent. Reports from small events are of little interest to researchers who are only concerned with damaging, MMI6 and above. However, we found that when damaging earthquakes did occur, such as Christchurch's M6.3, they were only sparsely reported (3,776 reports). Understandably, sitting at a computer and completing a lengthy online form wasn't a priority for people after a devastating earthquake. With Felt Rapid, reporting has to be completed within an hour of an earthquake, the use of GeoNet's automatically compiled felt reporting maps had evolved; their main purpose is immediate assessment of an earthquake's impact on populations, and is used by Civil Defence agencies. Reports are immediately displayed on an interactive map via the website and mobile app. With over 250,000 users this provides rapid and robust information regarding the experienced shaking. When a damaging earthquake occurs and researchers want to collect important and rare damaging felt reports, a separate in-depth survey

  10. Genes of the mitochondrial apoptotic pathway in Mytilus galloprovincialis.

    Directory of Open Access Journals (Sweden)

    Noelia Estévez-Calvar

    Full Text Available Bivalves play vital roles in marine, brackish, freshwater and terrestrial habitats. In recent years, these ecosystems have become affected through anthropogenic activities. The ecological success of marine bivalves is based on the ability to modify their physiological functions in response to environmental changes. One of the most important mechanisms involved in adaptive responses to environmental and biological stresses is apoptosis, which has been scarcely studied in mollusks, although the final consequence of this process, DNA fragmentation, has been frequently used for pollution monitoring. Environmental stressors induce apoptosis in molluscan cells via an intrinsic pathway. Many of the proteins involved in vertebrate apoptosis have been recognized in model invertebrates; however, this process might not be universally conserved. Mytilus galloprovincialis is presented here as a new model to study the linkage between molecular mechanisms that mediate apoptosis and marine bivalve ecological adaptations. Therefore, it is strictly necessary to identify the key elements involved in bivalve apoptosis. In the present study, six mitochondrial apoptotic-related genes were characterized, and their gene expression profiles following UV irradiation were evaluated. This is the first step for the development of potential biomarkers to assess the biological responses of marine organisms to stress. The results confirmed that apoptosis and, more specifically, the expression of the genes involved in this process can be used to assess the biological responses of marine organisms to stress.

  11. Interagency partnering for weed prevention--progress on development of a National Early Detection and Rapid Response System for Invasive Plants in the United States

    Science.gov (United States)

    Westbrooks, R.; Westbrooks, R.

    2011-01-01

    Over the past 50 years, experience has shown that interagency groups provide an effective forum for addressing various invasive species issues and challenges on multiple land units. However, more importantly, they can also provide a coordinated framework for early detection, reporting, identification and vouchering, rapid assessment, and rapid response to new and emerging invasive plants in the United States. Interagency collaboration maximizes the use of available expertise, resources, and authority for promoting early detection and rapid response (EDRR) as the preferred management option for addressing new and emerging invasive plants. Currently, an interagency effort is underway to develop a National EDRR System for Invasive Plants in the United States. The proposed system will include structural and informational elements. Structural elements of the system include a network of interagency partner groups to facilitate early detection and rapid response to new invasive plants, including the Federal Interagency Committee for the Management of Noxious and Exotic Weeds (FICMNEW), State Invasive Species Councils, State Early Detection and Rapid Response Coordinating Committees, State Volunteer Detection and Reporting Networks, Invasive Plant Task Forces, and Cooperative Weed Management Areas. Informational elements and products being developed include Regional Invasive Plant Atlases, and EDRR Guidelines for EDRR Volunteer Network Training, Rapid Assessment and Rapid Response, and Criteria for Selection of EDRR Species. System science and technical support elements which are provided by cooperating state and federal scientists, include EDRR guidelines, training curriculum for EDRR volunteers and agency field personnel, plant identification and vouchering, rapid assessments, as well as predictive modeling and ecological range studies for invasive plant species.

  12. A small graphene oxide sheet/polyvinylidene fluoride bilayer actuator with large and rapid responses to multiple stimuli.

    Science.gov (United States)

    Xu, Guochuang; Zhang, Miao; Zhou, Qinqin; Chen, Hongwu; Gao, Tiantian; Li, Chun; Shi, Gaoquan

    2017-11-16

    A high-performance actuator should be able to deliver large-shape deformations, fast actuations and sensitive responses to multiple stimuli. Here, we report such an actuator constructed from one layer of polyvinylidene fluoride (PVDF) with a high coefficient of thermal expansion (CTE), and another layer of small sheets of graphene oxide (SGO) with a negative CTE. The opposite deformations of both actuation layers make the SGO/PVDF bilayer actuator highly sensitive to the temperature stimulus with a large bending sensitivity of 1.5 cm(-1) °C(-1). Upon irradiation with 60 mW cm(-2) infrared light, this SGO/PVDF bilayer actuator displayed an extremely rapid tip displacement rate of 140 mm s(-1). Furthermore, this actuator can also sensitively respond to moisture because of its SGO layer, showing a curvature change from -22 to 13 cm(-1) upon changing the relative humidity (RH) from 11% to 86%. This actuator can generate a contractile or relaxed stress 18 times that of mammalian skeletal muscle, under light irradiation or moisture with a response time as short as 1 s, being capable of lifting an object with a weight 80 times that of itself. Furthermore, it also showed excellent stability and repeatability.

  13. Rapid response of alpine timberline vegetation to the Younger Dryas climate oscillation in the Colorado Rocky Mountains, USA

    Energy Technology Data Exchange (ETDEWEB)

    Reasoner, M.A.; Jodry, M.A.

    2000-01-01

    Paleobotanical records from two high-altitude (>3,300 m) sites in Colorado show a clear and immediate response to the Younger Dryas climate oscillation. The Black Mountain Lake and Sky Pond records indicate that alpine timberline migrated upslope to near-modern elevations during the late Bolling-Allerod (13.6--12.9 ka). Subsequent declines in arboreal pollen percentages and accumulation rates during the Younger Dryas interval (12.9--11.7 ka) reflect a downslope displacement of the alpine timberline ecotone of 60--120 m in elevation. This change translates to a cooling of summer temperature by {approximately}0.4--0.9 C and is consistent with proposed Younger Dryas advances of alpine glaciers in the Rocky Mountains to positions close to Little Ice Age maxima. Alpine timberline readvanced upslope to elevations above both sites between 11.7 and 11.4 ka. The concomitant response of temperature-sensitive alpine timberline vegetation in Colorado and late-glacial changes in North Atlantic thermohaline circulating implicates a rapid, widespread atmospheric transmission of the Younger Dryas climate oscillation.

  14. Abnormal response of melanin-concentrating hormone deficient mice to fasting: hyperactivity and rapid eye movement sleep suppression.

    Science.gov (United States)

    Willie, J T; Sinton, C M; Maratos-Flier, E; Yanagisawa, M

    2008-10-28

    Melanin-concentrating hormone (MCH) is a hypothalamic neuropeptide that has been implicated in energy homeostasis. Pharmacological studies with MCH and its receptor antagonists have suggested additional behavioral roles for the neuropeptide in the control of mood and vigilance states. These suggestions have been supported by a report of modified sleep in the MCH-1 receptor knockout mouse. Here we found that MCH knockout (MCH(-)(/)(-)) mice slept less during both the light and dark phases under baseline conditions. In response to fasting, MCH(-)(/)(-) mice exhibited marked hyperactivity, accelerated weight loss and an exaggerated decrease in rapid eye movement (REM) sleep. Following a 6-h period of sleep deprivation, however, the sleep rebound in MCH(-)(/)(-) mice was normal. Thus MCH(-)(/)(-) mice adapt poorly to fasting, and their loss of bodyweight under this condition is associated with behavioral hyperactivity and abnormal expression of REM sleep. These results support a role for MCH in vigilance state regulation in response to changes in energy homeostasis and may relate to a recent report of initial clinical trials with a novel MCH-1 receptor antagonist. When combined with caloric restriction, the treatment of healthy, obese subjects with this compound resulted in some subjects experiencing vivid dreams and sleep disturbances.

  15. Increased baseline proinflammatory cytokine production in chronic hepatitis C patients with rapid virological response to peginterferon plus ribavirin.

    Science.gov (United States)

    Par, Gabriella; Szereday, Laszlo; Berki, Timea; Palinkas, Laszlo; Halasz, Melinda; Miseta, Attila; Hegedus, Geza; Szekeres-Bartho, Julia; Vincze, Aron; Hunyady, Bela; Par, Alajos

    2013-01-01

    Chronic hepatitis C (CHC) patients achieving rapid virological response (RVR) on PEG-IFN/ribavirin (P/R) therapy have high chance of sustained virological response (SVR). To analyze host immunological factors associated with RVR, viral kinetics, phenotype distribution and Th1/Th2 cytokine production by peripheral blood mononuclear cells (PBMC) were studied prior to and during P/R therapy. TNF-α, IFN-γ, IL-2, IL-6, IL-4 and IL-10 production by PBMC were measured after Toll-like receptor 4 (TLR-4) or phorbol myristate acetate/Ionomycin stimulation in 20 healthy controls and in 50 CHC patients before receiving and during P/R therapy. RVR was achieved by 14, complete early virological response (cEVR) by 19 patients and 17 patients were null-responders (NR). Patients with RVR showed an increased baseline TNF-α and IL-6 production by TLR-4 activated monocytes and increased IFN-γ, decreased IL-4 and IL-10 production by lymphocytes compared to non-RVR patients. SVR was also associated with increased baseline TNF-α production and decreased IL-10 levels compared to patients who did not achieve SVR. Baseline IL-2 production was higher in cEVR compared to NR patients. Antiviral treatment increased TNF-α, IL-6 production by monocytes and IFN-γ secretion by lymphocytes and decreased IL-4 and IL-10 production by lymphocytes in cEVR compared to NR patients. RVR was associated with increased baseline proinflammatory cytokine production by TLR-4 stimulated monocytes and by activated lymphocytes. In null-responders and in patients who did not achieve SVR both TLR-4 sensing function and proinflammatory cytokine production were impaired, suggesting that modulation of TLR activity and controlled induction of inflammatory cytokine production may provide further therapeutic strategy for CHC patients non-responding to P/R treatment.

  16. Increased baseline proinflammatory cytokine production in chronic hepatitis C patients with rapid virological response to peginterferon plus ribavirin.

    Directory of Open Access Journals (Sweden)

    Gabriella Par

    Full Text Available BACKGROUND: Chronic hepatitis C (CHC patients achieving rapid virological response (RVR on PEG-IFN/ribavirin (P/R therapy have high chance of sustained virological response (SVR. To analyze host immunological factors associated with RVR, viral kinetics, phenotype distribution and Th1/Th2 cytokine production by peripheral blood mononuclear cells (PBMC were studied prior to and during P/R therapy. METHODS: TNF-α, IFN-γ, IL-2, IL-6, IL-4 and IL-10 production by PBMC were measured after Toll-like receptor 4 (TLR-4 or phorbol myristate acetate/Ionomycin stimulation in 20 healthy controls and in 50 CHC patients before receiving and during P/R therapy. RVR was achieved by 14, complete early virological response (cEVR by 19 patients and 17 patients were null-responders (NR. RESULTS: Patients with RVR showed an increased baseline TNF-α and IL-6 production by TLR-4 activated monocytes and increased IFN-γ, decreased IL-4 and IL-10 production by lymphocytes compared to non-RVR patients. SVR was also associated with increased baseline TNF-α production and decreased IL-10 levels compared to patients who did not achieve SVR. Baseline IL-2 production was higher in cEVR compared to NR patients. Antiviral treatment increased TNF-α, IL-6 production by monocytes and IFN-γ secretion by lymphocytes and decreased IL-4 and IL-10 production by lymphocytes in cEVR compared to NR patients. CONCLUSION: RVR was associated with increased baseline proinflammatory cytokine production by TLR-4 stimulated monocytes and by activated lymphocytes. In null-responders and in patients who did not achieve SVR both TLR-4 sensing function and proinflammatory cytokine production were impaired, suggesting that modulation of TLR activity and controlled induction of inflammatory cytokine production may provide further therapeutic strategy for CHC patients non-responding to P/R treatment.

  17. Effect of dual tasking on postural responses to rapid lower limb movement while seated on an exercise ball.

    Science.gov (United States)

    Jones, P; Sorinola, I; Strutton, P H

    2014-06-01

    Postural adjustments are used by the central nervous system to pre-empt and correct perturbations in balance during voluntary body movements. Alteration in these responses is associated with a number of neuromuscular/musculoskeletal conditions. Attention has been identified as important in this system; performing a concurrent cognitive task has been suggested to reduce the efficacy of this postural control. The aim of this study was to examine the effect of concurrent cognitive tasking on anticipatory postural adjustments while sitting on an exercise ball with a view to help inform future rehabilitation programmes. Bilateral EMG activity was recorded from the external and internal obliques, rectus abdominis, erector spinae and the right rectus femoris of 20 healthy subjects (9 males) with mean (SD) age of 21.88 (0.86) years (range 21-24 years). A rapid hip flexion protocol was carried out under three conditions: no concurrent task, counting out loud up from one and completing a serial sevens task. The addition of the cognitive task delayed and reduced the EMG in the prime mover muscle but had little impact on the responses of the trunk muscles within the time frame of the anticipatory responses; suggestive of a decoupling of voluntary and postural control mechanisms. The results of this study suggest that perhaps the clinical effects of dual task may not be largely due to changes in anticipatory postural adjustments. However, it would be important to compare these results to those seen in older and functionally impaired individuals as this would be more representative of the typical population undertaking such rehabilitation programmes. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. Evaluating the Process and Extent of Institutionalization: A Case Study of a Rapid Response Unit for Health Policy in Burkina Faso.

    Science.gov (United States)

    Zida, Andre; Lavis, John N; Sewankambo, Nelson K; Kouyate, Bocar; Ouedraogo, Salimata

    2017-04-10

    Good decision-making requires gathering and using sufficient information. Several knowledge translation platforms have been introduced in Burkina Faso to support evidence-informed decision-making. One of these is the rapid response service for health. This platform aims to provide quick access for policy-makers in Burkina Faso to highquality research evidence about health systems. The purpose of this study is to describe the process and extent of the institutionalization of the rapid response service. A qualitative case study design was used, drawing on interviews with policy-makers, together with documentary analysis. Previously used institutionalization frameworks were combined to guide the analysis. Burkina Faso's rapid response service has largely reached the consolidation phase of the institutionalization process but not yet the final phase of maturity. The impetus for the project came from designated project leaders, who convinced policy-makers of the importance of the rapid response service, and obtained resources to run a pilot. During the expansion stage, additional policy-makers at national and sub-national levels began to use the service. Unit staff also tried to improve the way it was delivered, based on lessons learned during the pilot stage. The service has, however, stagnated at the consolidation stage, and not moved into the final phase of maturity. The institutionalization process for the rapid response service in Burkina Faso has been fluid rather than linear, with some areas developing faster than others. The service has reached the consolidation stage, but now requires additional efforts to reach maturity.

  19. Feasibility of a rapid response mechanism to meet policymakers' urgent needs for research evidence about health systems in a low income country: a case study.

    Science.gov (United States)

    Mijumbi, Rhona M; Oxman, Andrew D; Panisset, Ulysses; Sewankambo, Nelson K

    2014-09-10

    Despite the recognition of the importance of evidence-informed health policy and practice, there are still barriers to translating research findings into policy and practice. The present study aimed to establish the feasibility of a rapid response mechanism, a knowledge translation strategy designed to meet policymakers' urgent needs for evidence about health systems in a low income country, Uganda. Rapid response mechanisms aim to address the barriers of timeliness and relevance of evidence at the time it is needed. A rapid response mechanism (service) designed a priori was offered to policymakers in the health sector in Uganda. In the form of a case study, data were collected about the profile of users of the service, the kinds of requests for evidence, changes in answers, and courses of action influenced by the mechanism and their satisfaction with responses and the mechanism in general. We found that in the first 28 months, the service received 65 requests for evidence from 30 policymakers and stakeholders, the majority of whom were from the Ministry of Health. The most common requests for evidence were about governance and organization of health systems. It was noted that regular contact between the policymakers and the researchers at the response service was an important factor in response to, and uptake of the service. The service seemed to increase confidence for policymakers involved in the policymaking process. Rapid response mechanisms designed to meet policymakers' urgent needs for research evidence about health systems are feasible and acceptable to policymakers in low income countries.

  20. Integrin βν-mediated phagocytosis of apoptotic cells in Drosophila embryos.

    Science.gov (United States)

    Nagaosa, Kaz; Okada, Ryo; Nonaka, Saori; Takeuchi, Kazuki; Fujita, Yu; Miyasaka, Tomoyuki; Manaka, Junko; Ando, István; Nakanishi, Yoshinobu

    2011-07-22

    To identify molecules that play roles in the clearance of apoptotic cells by Drosophila phagocytes, we examined a series of monoclonal antibodies raised against larval hemocytes for effects on phagocytosis in vitro. One antibody that inhibited phagocytosis recognized terribly reduced optic lobes (Trol), a core protein of the perlecan-type proteoglycan, and the level of phagocytosis in embryos of a Trol-lacking fly line was lower than in a control line. The treatment of a hemocyte cell line with a recombinant Trol protein containing the amino acid sequence RGD augmented the phosphorylation of focal adhesion kinase, a hallmark of integrin activation. A loss of integrin βν, one of the two β subunits of Drosophila integrin, brought about a reduction in the level of apoptotic cell clearance in embryos. The presence of integrin βν at the surface of embryonic hemocytes was confirmed, and forced expression of integrin βν in hemocytes of an integrin βν-lacking fly line recovered the defective phenotype of phagocytosis. Finally, the level of phagocytosis in a fly line that lacks both integrin βν and Draper, another receptor required for the phagocytosis of apoptotic cells, was lower than that in a fly line lacking either protein. We suggest that integrin βν serves as a phagocytosis receptor responsible for the clearance of apoptotic cells in Drosophila, independent of Draper.

  1. Integrin βν-mediated Phagocytosis of Apoptotic Cells in Drosophila Embryos*

    Science.gov (United States)

    Nagaosa, Kaz; Okada, Ryo; Nonaka, Saori; Takeuchi, Kazuki; Fujita, Yu; Miyasaka, Tomoyuki; Manaka, Junko; Ando, István; Nakanishi, Yoshinobu

    2011-01-01

    To identify molecules that play roles in the clearance of apoptotic cells by Drosophila phagocytes, we examined a series of monoclonal antibodies raised against larval hemocytes for effects on phagocytosis in vitro. One antibody that inhibited phagocytosis recognized terribly reduced optic lobes (Trol), a core protein of the perlecan-type proteoglycan, and the level of phagocytosis in embryos of a Trol-lacking fly line was lower than in a control line. The treatment of a hemocyte cell line with a recombinant Trol protein containing the amino acid sequence RGD augmented the phosphorylation of focal adhesion kinase, a hallmark of integrin activation. A loss of integrin βν, one of the two β subunits of Drosophila integrin, brought about a reduction in the level of apoptotic cell clearance in embryos. The presence of integrin βν at the surface of embryonic hemocytes was confirmed, and forced expression of integrin βν in hemocytes of an integrin βν-lacking fly line recovered the defective phenotype of phagocytosis. Finally, the level of phagocytosis in a fly line that lacks both integrin βν and Draper, another receptor required for the phagocytosis of apoptotic cells, was lower than that in a fly line lacking either protein. We suggest that integrin βν serves as a phagocytosis receptor responsible for the clearance of apoptotic cells in Drosophila, independent of Draper. PMID:21592968

  2. Meat Feeding Restricts Rapid Cold Hardening Response and Increases Thermal Activity Thresholds of Adult Blow Flies, Calliphora vicina (Diptera: Calliphoridae.

    Directory of Open Access Journals (Sweden)

    Paul C Coleman

    Full Text Available Virtually all temperate insects survive the winter by entering a physiological state of reduced metabolic activity termed diapause. However, there is increasing evidence that climate change is disrupting the diapause response resulting in non-diapause life stages encountering periods of winter cold. This is a significant problem for adult life stages in particular, as they must remain mobile, periodically feed, and potentially initiate reproductive development at a time when resources should be diverted to enhance stress tolerance. Here we present the first evidence of protein/meat feeding restricting rapid cold hardening (RCH ability and increasing low temperature activity thresholds. No RCH response was noted in adult female blow flies (Calliphora vicina Robineau-Desvoidy fed a sugar, water and liver (SWL diet, while a strong RCH response was seen in females fed a diet of sugar and water (SW only. The RCH response in SW flies was induced at temperatures as high as 10°C, but was strongest following 3h at 0°C. The CTmin (loss of coordinated movement and chill coma (final appendage twitch temperature of SWL females (-0.3 ± 0.5°C and -4.9 ± 0.5°C, respectively was significantly higher than for SW females (-3.2 ± 0.8°C and -8.5 ± 0.6°C. We confirmed this was not directly the result of altered extracellular K+, as activity thresholds of alanine-fed adults were not significantly different from SW flies. Instead we suggest the loss of cold tolerance is more likely the result of diverting resource allocation to egg development. Between 2009 and 2013 winter air temperatures in Birmingham, UK, fell below the CTmin of SW and SWL flies on 63 and 195 days, respectively, suggesting differential exposure to chill injury depending on whether adults had access to meat or not. We conclude that disruption of diapause could significantly impact on winter survival through loss of synchrony in the timing of active feeding and reproductive development with

  3. Hepatitis E in a food handler--a rapid risk assessment to guide the public health response.

    Science.gov (United States)

    Appuhamy, Ranil; Moffatt, Cameron; Davis, Stephanie; Kelly, Paul; Kennedy, Karina

    2014-01-01

    The Australian Capital Territory Health Directorate was notified of a food handler with hepatitis E virus (HEV) infection. To guide the public health response, a rapid risk assessment was undertaken to determine the risk of transmission of HEV from the infected food handler to restaurant patrons. The literature on HEV was reviewed and expert advice sought from clinical and public health specialists. This was supplemented by results of a site investigation and a case interview. The risk rating was determined to be the product of the likelihood of transmission and the consequence of the infection. The food handler was likely to have been infectious at the time he was working at the restaurant. He had handled high-risk foods, and the site inspection revealed potential opportunities for transmission. HEV is not common in Australia and it was assumed that the population was non-immune and hence susceptible to the disease. Therefore, there was a low but possible likelihood of transmission of HEV. If infected, HEV has the potential for major consequences in vulnerable populations especially among women who are pregnant. The overall level of risk was considered to be very high. The general public and health practitioners were alerted to enable early identification of symptoms and prompt disease management. There were no secondary cases of HEV associated with this event. In the absence of published guidelines and limited evidence, a risk assessment framework was a useful tool to inform public health decision-making.

  4. Prompt Assessment of Global Earthquakes for Response (PAGER): A System for Rapidly Determining the Impact of Earthquakes Worldwide

    Science.gov (United States)

    Earle, Paul S.; Wald, David J.; Jaiswal, Kishor S.; Allen, Trevor I.; Hearne, Michael G.; Marano, Kristin D.; Hotovec, Alicia J.; Fee, Jeremy

    2009-01-01

    Within minutes of a significant earthquake anywhere on the globe, the U.S. Geological Survey (USGS) Prompt Assessment of Global Earthquakes for Response (PAGER) system assesses its potential societal impact. PAGER automatically estimates the number of people exposed to severe ground shaking and the shaking intensity at affected cities. Accompanying maps of the epicentral region show the population distribution and estimated ground-shaking intensity. A regionally specific comment describes the inferred vulnerability of the regional building inventory and, when available, lists recent nearby earthquakes and their effects. PAGER's results are posted on the USGS Earthquake Program Web site (http://earthquake.usgs.gov/), consolidated in a concise one-page report, and sent in near real-time to emergency responders, government agencies, and the media. Both rapid and accurate results are obtained through manual and automatic updates of PAGER's content in the hours following significant earthquakes. These updates incorporate the most recent estimates of earthquake location, magnitude, faulting geometry, and first-hand accounts of shaking. PAGER relies on a rich set of earthquake analysis and assessment tools operated by the USGS and contributing Advanced National Seismic System (ANSS) regional networks. A focused research effort is underway to extend PAGER's near real-time capabilities beyond population exposure to quantitative estimates of fatalities, injuries, and displaced population.

  5. Hepatitis E in a food handler – a rapid risk assessment to guide the public health response

    Directory of Open Access Journals (Sweden)

    Ranil Appuhamy

    2014-10-01

    Full Text Available Objective: The Australian Capital Territory Health Directorate was notified of a food handler with hepatitis E virus (HEV infection. To guide the public health response, a rapid risk assessment was undertaken to determine the risk of transmission of HEV from the infected food handler to restaurant patrons. Method: The literature on HEV was reviewed and expert advice sought from clinical and public health specialists. This was supplemented by results of a site investigation and a case interview. The risk rating was determined to be the product of the likelihood of transmission and the consequence of the infection. Results: The food handler was likely to have been infectious at the time he was working at the restaurant. He had handled high-risk foods, and the site inspection revealed potential opportunities for transmission. HEV is not common in Australia and it was assumed that the population was non-immune and hence susceptible to the disease. Therefore, there was a low but possible likelihood of transmission of HEV. If infected, HEV has the potential for major consequences in vulnerable populations especially among women who are pregnant. The overall level of risk was considered to be very high. Discussion: The general public and health practitioners were alerted to enable early identification of symptoms and prompt disease management. There were no secondary cases of HEV associated with this event. In the absence of published guidelines and limited evidence, a risk assessment framework was a useful tool to inform public health decision-making.

  6. Analysis of readmission rates to the intensive care unit after implementation of a rapid response team in a University Hospital.

    Science.gov (United States)

    Bergamasco E Paula, R; Tanita, M T; Festti, J; Queiroz Cardoso, L T; Carvalho Grion, C M

    2017-10-01

    To compare readmission rates to the intensive care unit (ICU) before and after the implementation of a rapid response team (RRT), and to identify risk factors for readmission. A quasi-experimental before-after study was carried out. A University Hospital. All patients discharged from the ICU from January to December 2008 (control group) and from January 2010 to December 2012 (intervention group). Implementation of an RRT. The data included demographic parameters, diagnoses upon admission, ICU readmission, APACHE II, SOFA, and TISS 28 scores, and routine daily assessment by an RRT of patients discharged from the ICU. During the study interval, 380 patients were analyzed in the period prior to the implementation of the RRT and 1361 after implementation. There was a tendency toward decreased readmission rates one year after RRT implementation. The APACHE II score and SOFA score at ICU discharge were independent factors associated to readmission, as well as clinical referral to the ICU. The RRT intervention resulted in a sustained decrease in readmission rates one year after implementation of this service. The use of a specialized team in health institutions can be recommended for ICU survivors. Copyright © 2016 Elsevier España, S.L.U. y SEMICYUC. All rights reserved.

  7. HIV-1 Tat activates neuronal ryanodine receptors with rapid induction of the unfolded protein response and mitochondrial hyperpolarization.

    Directory of Open Access Journals (Sweden)

    John P Norman

    Full Text Available Neurologic disease caused by human immunodeficiency virus type 1 (HIV-1 is ultimately refractory to highly active antiretroviral therapy (HAART because of failure of complete virus eradication in the central nervous system (CNS, and disruption of normal neural signaling events by virally induced chronic neuroinflammation. We have previously reported that HIV-1 Tat can induce mitochondrial hyperpolarization in cortical neurons, thus compromising the ability of the neuron to buffer calcium and sustain energy production for normal synaptic communication. In this report, we demonstrate that Tat induces rapid loss of ER calcium mediated by the ryanodine receptor (RyR, followed by the unfolded protein response (UPR and pathologic dilatation of the ER in cortical neurons in vitro. RyR antagonism attenuated both Tat-mediated mitochondrial hyperpolarization and UPR induction. Delivery of Tat to murine CNS in vivo also leads to long-lasting pathologic ER dilatation and mitochondrial morphologic abnormalities. Finally, we performed ultrastructural studies that demonstrated mitochondria with abnormal morphology and dilated endoplasmic reticulum (ER in brain tissue of patients with HIV-1 inflammation and neurodegeneration. Collectively, these data suggest that abnormal RyR signaling mediates the neuronal UPR with failure of mitochondrial energy metabolism, and is a critical locus for the neuropathogenesis of HIV-1 in the CNS.

  8. Rapid response of tattoo-associated cutaneous sarcoidosis to minocycline: case report and review of the literature.

    Science.gov (United States)

    Sheu, Johanna; Saavedra, Arturo P; Mostaghimi, Arash

    2014-08-17

    Cutaneous sarcoidosis can present in pre-existing tattoos. Previous reports suggest modest improvement with systemic or topical corticosteroids or other immunomodulating medications. Tetracyclines have anti-inflammatory properties and have been shown to be efficacious in non-tattoo associated cutaneous sarcoidosis. The pharmacology of minocycline suggests that its higher concentration in the skin may improve its efficacy in the treatment of cutaneous granulomas. We present a case of a 35-year-old man with a history of pulmonary sarcoidosis who developed raised plaques within tattoos present for over 10 years. Skin biopsy findings revealed non-caseating granulomas consistent with cutaneous sarcoidosis. The patient was started on minocycline 100mg twice daily and had resolution of pruritus in four days and improvement of sarcoidal plaques within one week. To our knowledge, this is the first report of cutaneous sarcoidosis in tattoos treated with minocycline. Our patient's rapid response to minocycline suggests that minocycline may be a quickly effective medication for cutaneous sarcoidosis and should be considered as a therapeutic option given its favorable side-effect profile.

  9. Two genes with similarity to bacterial response regulators are rapidly and specifically induced by cytokinin in Arabidopsis

    Science.gov (United States)

    Brandstatter, I.; Kieber, J. J.; Evans, M. L. (Principal Investigator)

    1998-01-01

    Cytokinins are central regulators of plant growth and development, but little is known about their mode of action. By using differential display, we identified a gene, IBC6 (for induced by cytokinin), from etiolated Arabidopsis seedlings, that is induced rapidly by cytokinin. The steady state level of IBC6 mRNA was elevated within 10 min by the exogenous application of cytokinin, and this induction did not require de novo protein synthesis. IBC6 was not induced by other plant hormones or by light. A second Arabidopsis gene with a sequence highly similar to IBC6 was identified. This IBC7 gene also was induced by cytokinin, although with somewhat slower kinetics and to a lesser extent. The pattern of expression of the two genes was similar, with higher expression in leaves, rachises, and flowers and lower transcript levels in roots and siliques. Sequence analysis revealed that IBC6 and IBC7 are similar to the receiver domain of bacterial two-component response regulators. This homology, coupled with previously published work on the CKI1 histidine kinase homolog, suggests that these proteins may play a role in early cytokinin signaling.

  10. Rapid virological response of telaprevir and boceprevir in a Brazilian cohort of HCV genotype 1 patients: a multicenter longitudinal study

    Directory of Open Access Journals (Sweden)

    Borba HHL

    2017-01-01

    Full Text Available Helena HL Borba,1 Astrid Wiens,1 Laiza M Steimbach,1 Fernanda S Tonin,1 Maria LA Pedroso,2 Cláudia AP Ivantes,3 Fernando Fernandez-Llimos,4 Roberto Pontarolo1 1Pharmaceutical Sciences Postgraduate Research Program, Department of Pharmacy, 2Gastroenterology Service, Hospital de Clínicas, Federal University of Paraná, 3Guidance and Counseling Center, Curitiba City Hall, Curitiba, Paraná, Brazil; 4Department of Social Pharmacy, Faculty of Pharmacy, Research Institute for Medicines, University of Lisboa, Lisbon, Portugal Background: Chronic hepatitis C is a major public health issue, but there is a gap in the literature regarding the effectiveness and safety of direct-acting antiviral agents in the Brazilian population. The main aim of this study was to describe the effectiveness of boceprevir and telaprevir in patients treated at public health care institutions in Brazil.Materials and methods: A prospective longitudinal and multicenter study was conducted in five centers in the State of Paraná between September 2014 and June 2016. Data regarding effectiveness and safety were collected from medical records of patients treated with boceprevir or telaprevir. The effectiveness outcome comprised the rapid virological response (RVR. Multivariate analysis was performed to verify the influence of independent variables (ie, age, gender, baseline viral load on RVR achievement.Results: Data were collected from 117 patients with chronic hepatitis C virus (HCV genotype 1 infection. Fifteen patients received treatment with boceprevir and 102 received telaprevir. The mean age was 51.6 years, 64.1% were male, 44.4% were infected with HCV subtype 1a, 62.4% had a high baseline viral load (≥800,000 IU/mL and 33% were cirrhotic. Furthermore, 79.5% of patients achieved RVR (26.7% in the boceprevir group and 87.3% in the telaprevir group. Multivariate analysis demonstrated that the type of protease inhibitor (boceprevir or telaprevir and the baseline viral load

  11. Anti-Apoptotic Machinery Protects the Necrotrophic Fungus Botrytis cinerea from Host-Induced Apoptotic-Like Cell Death during Plant Infection

    Science.gov (United States)

    Shlezinger, Neta; Minz, Anna; Gur, Yonatan; Hatam, Ido; Dagdas, Yasin F.; Talbot, Nicholas J.; Sharon, Amir

    2011-01-01

    Necrotrophic fungi are unable to occupy living plant cells. How such pathogens survive first contact with living host tissue and initiate infection is therefore unclear. Here, we show that the necrotrophic grey mold fungus Botrytis cinerea undergoes massive apoptotic-like programmed cell death (PCD) following germination on the host plant. Manipulation of an anti-apoptotic gene BcBIR1 modified fungal response to PCD-inducing conditions. As a consequence, strains with reduced sensitivity to PCD were hyper virulent, while strains in which PCD was over-stimulated showed reduced pathogenicity. Similarly, reduced levels of PCD in the fungus were recorded following infection of Arabidopsis mutants that show enhanced susceptibility to B. cinerea. When considered together, these results suggest that Botrytis PCD machinery is targeted by plant defense molecules, and that the fungal anti-apoptotic machinery is essential for overcoming this host-induced PCD and hence, for establishment of infection. As such, fungal PCD machinery represents a novel target for fungicides and antifungal drugs. PMID:21876671

  12. Anti-apoptotic machinery protects the necrotrophic fungus Botrytis cinerea from host-induced apoptotic-like cell death during plant infection.

    Directory of Open Access Journals (Sweden)

    Neta Shlezinger

    2011-08-01

    Full Text Available Necrotrophic fungi are unable to occupy living plant cells. How such pathogens survive first contact with living host tissue and initiate infection is therefore unclear. Here, we show that the necrotrophic grey mold fungus Botrytis cinerea undergoes massive apoptotic-like programmed cell death (PCD following germination on the host plant. Manipulation of an anti-apoptotic gene BcBIR1 modified fungal response to PCD-inducing conditions. As a consequence, strains with reduced sensitivity to PCD were hyper virulent, while strains in which PCD was over-stimulated showed reduced pathogenicity. Similarly, reduced levels of PCD in the fungus were recorded following infection of Arabidopsis mutants that show enhanced susceptibility to B. cinerea. When considered together, these results suggest that Botrytis PCD machinery is targeted by plant defense molecules, and that the fungal anti-apoptotic machinery is essential for overcoming this host-induced PCD and hence, for establishment of infection. As such, fungal PCD machinery represents a novel target for fungicides and antifungal drugs.

  13. Rapid response to intensive treatment for bulimia nervosa and purging disorder: A randomized controlled trial of a CBT intervention to facilitate early behavior change.

    Science.gov (United States)

    MacDonald, Danielle E; McFarlane, Traci L; Dionne, Michelle M; David, Lauren; Olmsted, Marion P

    2017-09-01

    Rapid response to cognitive behavior therapy (CBT) for eating disorders (i.e., rapid and substantial change to key eating disorder behaviors in the initial weeks of treatment) robustly predicts good outcome at end-of-treatment and in follow up. The objective of this study was to determine whether rapid response to day hospital (DH) eating disorder treatment could be facilitated using a brief adjunctive CBT intervention focused on early change. 44 women (average age 27.3 [8.4]; 75% White, 6.3% Black, 6.9% Asian) were randomly assigned to 1 of 2 4-session adjunctive interventions: CBT focused on early change, or motivational interviewing (MI). DH was administered as usual. Outcomes included binge/purge frequency, Eating Disorder Examination-Questionnaire and Difficulties in Emotion Regulation Scale. Intent-to-treat analyses were used. The CBT group had a higher rate of rapid response (95.7%) compared to MI (71.4%; p = .04, V = .33). Those who received CBT also had fewer binge/purge episodes (p = .02) in the first 4 weeks of DH. By end-of-DH, CBT participants made greater improvements on overvaluation of weight and shape (p = .008), and emotion regulation (ps .05). The results of this study demonstrate that rapid response can be clinically facilitated using a CBT intervention that explicitly encourages early change. This provides the foundation for future research investigating whether enhancing rates of rapid response using such an intervention results in improved longer term outcomes. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  14. Lipoxins and Annexin-1: Resolution of Inflammation and Regulation of Phagocytosis of Apoptotic Cells

    Directory of Open Access Journals (Sweden)

    Michael Scannell

    2006-01-01

    Full Text Available Phagocytosis of apoptotic cells plays a pivotal role in developmental processes and in the resolution of inflammation. Failed or delayed clearance of apoptotic cells can result in chronic inflammation. Furthermore, clearance of apoptotic cells leads to release of anti-inflammatory cytokines. Recent evidence has shown that endogenous mediators can regulate such processes. In this article, we will review the recognition and signaling mechanisms involved in the phagocytosis of apoptotic cells as well as the role of endogenous compounds that play a relevant role in the modulation of inflammation. The first of these endogenous local mediators to be described are lipoxins (LXs. LXs and aspirin-triggered LXs (ATLs are considered to act as “braking signals” in inflammation, limiting the entrance of leukocytes to the site of inflammation through inhibition of neutrophil and eosinophil trafficking. LXs are actively involved in resolution of inflammation, stimulating nonphlogistic phagocytosis of apoptotic cells by macrophages. LXA4 and ATLs elicit cellular responses by interacting with a G protein -coupled receptor (ALXR that is expressed in various cell types. ALXR, originally identified as a low-affinity N-formyl-methionyl-leucyl-phenylalanine receptor-like 1, can bind pleiotropic ligands, i.e., both lipid and peptides, including the glucocorticoid-inducible protein, annexin-1. Interestingly, a role for annexin-1 in phagocytosis has recently emerged. Understanding the role and mechanism of the powerful anti-inflammatory and proresolution actions of endogenous compounds can be a useful tool in the development of potential therapeutics in resolving inflammatory diseases.

  15. Different apoptotic responses to Plasmodium chabaudi malaria in ...

    African Journals Online (AJOL)

    hope&shola

    2010-11-08

    Nov 8, 2010 ... The few available anti-malaria drugs are becoming increasingly ineffective due to the increasing resistance of the parasites (Carlton et al., 2001). All efforts to develop an effective anti-malaria vaccine have failed to date (Hviid and Barfold, 2008). Basic research is therefore more than ever, urgently, required ...

  16. Kinetics of apoptotic markers in exogeneously induced apoptosis of EL4 cells.

    Science.gov (United States)

    Jessel, Robert; Haertel, Steffen; Socaciu, Carmen; Tykhonova, Svetlana; Diehl, Horst A

    2002-01-01

    We investigated the time-dependence of apoptotic events in EL4 cells by monitoring plasma membrane changes in correlation to DNA fragmentation and cell shrinkage. We applied three apoptosis inducers (staurosporine, tubericidine and X-rays) and we looked at various markers to follow the early-to-late apoptotic events: phospholipid translocation (identified through annexin V-fluorescein assay and propidium iodide), lipid package (via merocyanine assay), membrane fluidity and anisotropy (via fluorescent measurements), DNA fragmentation by the fluorescence-labeling test and cell size measurements. The different apoptotic inducers caused different reactions of the cells: staurosporine induced apoptosis most rapidly in a high number of cells, tubercidine triggered apoptosis only in the S phase cells, while X-rays caused a G2/M arrest and subsequently apoptosis. Loss of lipid asymmetry is promptly detectable after one hour of incubation time. The phosphatidylserine translocation, decrease of lipid package and anisotropy, and the increase of membrane fluidity appeared to be based on the same process of lipid asymmetry loss. Therefore, the DNA fragmentation and the cell shrinkage appear to be parallel and independent processes running on different time scales but which are kinetically inter-related. The results indicate different signal steps to apoptosis dependent on inducer characteristics but the kinetics of "early-to-late" apoptosis appears to be a fixed program.

  17. Evaluation of apoptotic and anti-apoptotic genes on efficacy of DNA vaccine encoding glycoprotein B of Herpes Simplex Virus type 1.

    Science.gov (United States)

    Parsania, Masoud; Bamdad, Taravat; Hassan, Zuhair Mohammad; Kheirandish, Maryam; Pouriayevali, Mohammad Hassan; Sari, Rohollah Dorostkar; Jamali, Abbas

    2010-02-16

    Many approaches have so far been tried to enhance the immunogenicity of DNA vaccine. These include the use of various factors that induce apoptosis or anti-apoptosis effects when co-delivered with DNA vaccine. In the present study, the effects of pro-apoptotic Bax encoding plasmid (pBax) and anti-apoptotic Bcl-X(L) encoding plasmid (pBcl-xl), intradermally co-injected with glycoprotein B (gB) of Herpes Simplex Virus (HSV)-1 encoding plasmid (pgB) into the C57BL/6 mice were evaluated. Immune responses of the mice to the antigen were assessed by antibody assay, lymphoproliferative responses as well as cytokine and cytotoxic T-lymphocyte (CTL) assay. Analysis of the humoral and cellular responses showed that the mice immunized with pBax and pgB induced higher levels of antibody and Interleukin-4 as well as stronger lymphocyte proliferative responses and cytotoxic activity compared to those mice received pgB alone. pBcl-xl when intradermally co-injected with pgB showed no significant enhancement in immune responses comparing to pgB. Copyright (c) 2009 Elsevier B.V. All rights reserved.

  18. A rapid diagnostic test and mobile "lab in a suitcase" platform for detecting Ceratocystis spp. responsible for Rapid ‘Ōhi‘a Death

    Science.gov (United States)

    Atkinson, Carter T.; Watcher-Weatherwax, William; Roy, Kylle; Heller, Wade P; Keith, Lisa

    2017-01-01

    We describe a field compatible molecular diagnostic test for two new species of Ceratocystis that infect `ōhi`a (Metrosideros polymorpha) and cause the disease commonly known as Rapid `Ōhi`a Death. The diagnostic is based on amplification of a DNA locus within the internal transcribed spacer region that separates fungal 5.8S ribosomal genes. The assay uses forward and reverse primers, recombinase polymerase, and a fluorescent probe that allows isothermal (40oC) amplification and simultaneous quantification of a 115 base pair product with a battery operated fluorometer. DNA extractions are field compatible and can be done by heating wood drill shavings to 100oC in Instagene® solution containing Chelex® resin to bind potential amplification inhibitors. The initial heat treatment is followed by a short bead beating step with steel ball bearings and zirconium beads to release DNA. DNA is subsequently purified with a magnetic bead based extraction method that does not require silica columns or centrifugation. The assay is designed around a portable “lab-in-a-suitcase” platform that includes a portable fluorometer, miniature centrifuge, and heat block that operate off either 120V AC power sources or a 12 volt battery with a portable inverter, a magnetic rack designed for 1.5 ml tubes and magnetic bead DNA purification, pipettes and consumable reagents and tubes. The entire assay from DNA extraction to results can be performed in less than 90 minutes on up to six independent samples plus a positive and negative control. Sensitivity based on suspensions of Ceratocystis endoconidia (spores) that were added to wood shavings and processed under field conditions by Instagene® magnetic bead DNA extraction was up to 163 spores/mg wood for Species A and 55 spores/mg wood for Species B in 95% of replicates as determined by probit analysis. Sensitivity increased 5–10 fold to 19 spores/mg wood for Species A and 9 spores/mg wood for Species B when extractions were

  19. The Rapid Response Radiation Survey (R3S) Mission Using the HiSat Conformal Satellite Architecture

    Science.gov (United States)

    Miller, Nathanael A.; Norman, Ryan B.; Soto, Hector L.; Stewart, Victor A.; Jones, Mark L.; Kowalski, Matthew C.; Ben Shabat, Adam; Gough, Kerry M.; Stavely, Rebecca L.; Shim, Alex C.; hide

    2015-01-01

    The Rapid Response Radiation Survey (R3S) experiment, designed as a quick turnaround mission to make radiation measurements in Low Earth Orbit (LEO), will fly as a hosted payload in partnership with NovaWurks using their Hyper-integrated Satlet (HISat) architecture. The need for the mission arises as the Nowcast of Atmospheric Ionization Radiation for Aviation Safety (NAIRAS) model moves from a research effort into an operational radiation assessment tool. Currently, airline professionals are the second largest demographic of radiation workers and to date their radiation exposure is undocumented in the USA. The NAIRAS model seeks to fill this information gap. The data collected by R3S, in addition to the complementary data from a NASA Langley Research Center (LaRC) atmospheric balloon mission entitled Radiation Dosimetry Experiment (RaD-X), will validate exposure prediction capabilities of NAIRAS. The R3S mission collects total dose and radiation spectrum measurements using a Teledyne µDosimeter and a Liulin-6SA2 LED spectrometer. These two radiation sensors provide a cross correlated radiometric measurement in combination with the Honeywell HMR2300 Smart Digital Magnetometer. The magnetometer assesses the Earth's magnetic field in the LEO environment and allows radiation dose to be mapped as a function of the Earth's magnetic shielding. R3S is also unique in that the radiation sensors will be exposed on the outer surface of the spacecraft, possibly making this the first measurements of the LEO radiation environment with bare sensors. Viability of R3S as an extremely fast turnaround mission is due, in part, to the nature of the robust, well-defined interfaces of the conformal satellite HiSat Architecture. The HiSat architecture, which was developed with the support of the Defense Advanced Research Projects Agency's (DARPA's) Phoenix Program, enabled the R3S system to advance from the first concept to delivery of preliminary design review (PDR) level documents in

  20. The habitus of 'rescue' and its significance for implementation of rapid response systems in acute health care.

    Science.gov (United States)

    Mackintosh, Nicola; Humphrey, Charlotte; Sandall, Jane

    2014-11-01

    The need to focus on patient safety and improve the quality and consistency of medical care in acute hospital settings has been highlighted in a number of UK and international reports. When patients on a hospital ward become acutely unwell there is often a window of opportunity for staff, patients and relatives to contribute to the 'rescue' process by intervening in the trajectory of clinical deterioration. This paper explores the social and institutional processes associated with the practice of rescue, and implications for the implementation and effectiveness of rapid response systems (RRSs) within acute health care. An ethnographic case study was conducted in 2009 in two UK hospitals (focussing on the medical directorates in each organisation). Data collection involved 180 h of observation, 35 staff interviews (doctors, nurses, health care assistants and managers) and documentary review. Analysis was informed by Bourdieu's logic of practice and his relational concept of the 'field' of the general medical ward. Three themes illustrated the nature of rescue work within the field and collective rules which guided associated occupational distinction practices: (1) the 'dirty work' of vital sign recording and its distinction from diagnostic (higher order) interpretive work; (2) the moral order of legitimacy claims for additional help; and (3) professional deference and the selective managerial control of rescue work. The discourse of rescue provided a means of exercising greater control over clinical uncertainty. The acquisition of 'rescue capital' enabled the social positioning of health care assistants, nurses and doctors, and shaped use of the RRS on the wards. Boundary work, professional legitimation and jurisdictional claims defined the social practice of rescue, as clinical staff had to balance safety, professional and organisational concerns within the field. This paper offers a nuanced understanding of patient safety on the front-line, challenging notions of

  1. Rapid Response to Evaluate the Presence of Amphibian Chytrid Fungus (Batrachochytrium dendrobatidis) and Ranavirus in Wild Amphibian Populations in Madagascar.

    Science.gov (United States)

    Kolby, Jonathan E; Smith, Kristine M; Ramirez, Sara D; Rabemananjara, Falitiana; Pessier, Allan P; Brunner, Jesse L; Goldberg, Caren S; Berger, Lee; Skerratt, Lee F

    2015-01-01

    We performed a rapid response investigation to evaluate the presence and distribution of amphibian pathogens in Madagascar following our identification of amphibian chytrid fungus (Batrachochytrium dendrobatidis, Bd) and ranavirus in commercially exported amphibians. This targeted risk-based field surveillance program was conducted from February to April 2014 encompassing 12 regions and 47 survey sites. We simultaneously collected amphibian and environmental samples to increase survey sensitivity and performed sampling both in wilderness areas and commercial amphibian trade facilities. Bd was not detected in any of 508 amphibian skin swabs or 68 water filter samples, suggesting pathogen prevalence was below 0.8%, with 95% confidence during our visit. Ranavirus was detected in 5 of 97 amphibians, including one adult Mantidactylus cowanii and three unidentified larvae from Ranomafana National Park, and one adult Mantidactylus mocquardi from Ankaratra. Ranavirus was also detected in water samples collected from two commercial amphibian export facilities. We also provide the first report of an amphibian mass-mortality event observed in wild amphibians in Madagascar. Although neither Bd nor ranavirus appeared widespread in Madagascar during this investigation, additional health surveys are required to disentangle potential seasonal variations in pathogen abundance and detectability from actual changes in pathogen distribution and rates of spread. Accordingly, our results should be conservatively interpreted until a comparable survey effort during winter months has been performed. It is imperative that biosecurity practices be immediately adopted to limit the unintentional increased spread of disease through the movement of contaminated equipment or direct disposal of contaminated material from wildlife trade facilities. The presence of potentially introduced strains of ranaviruses suggests that Madagascar's reptile species might also be threatened by disease

  2. Use of a cholera rapid diagnostic test during a mass vaccination campaign in response to an epidemic in Guinea, 2012.

    Directory of Open Access Journals (Sweden)

    Isabel Martinez-Pino

    Full Text Available BACKGROUND: During the 2012 cholera outbreak in the Republic of Guinea, the Ministry of Health, supported by Médecins Sans Frontières - Operational Center Geneva, used the oral cholera vaccine Shanchol as a part of the emergency response. The rapid diagnostic test (RDT Crystal VC, widely used during outbreaks, detects lipopolysaccharide antigens of Vibrio cholerae O1 and O139, both included in Shanchol. In the context of reactive use of a whole-cell cholera vaccine in a region where cholera cases have been reported, it is essential to know what proportion of vaccinated individuals would be reactive to the RDT and for how long after vaccination. METHODOLOGY/PRINCIPAL FINDINGS: A total of 108 vaccinated individuals, selected systematically among all persons older than one year, were included at vaccination sites and 106 were included in the analysis. Stools samples of this cohort of vaccinated participants were collected and tested with the RDT every day until the test was negative for two consecutive visits or for a maximum of 7 days. A total of 94.3% of cholera vaccine recipients had a positive test after vaccination; all except one of these positive results were reactive only with the O139 antigen. The mean time to become negative in those with an initial positive result after vaccination was 3.8 days, standard deviation 1.1 days. CONCLUSIONS/SIGNIFICANCE: The RDT Crystal VC becomes positive in persons recently vaccinated against cholera, although almost exclusively to the O139 antigen. This reactivity largely disappeared within five days after vaccination. These results suggest that the test can be used normally as soon as 24 hours after vaccination in a context of O1 epidemics, which represent the vast majority of cases, and after a period of five days in areas where V. cholerae O139 is present. The reason why only O139 test line became positive remains to be investigated.

  3. Frequency and significance of qSOFA criteria during adult rapid response team reviews: A prospective cohort study.

    Science.gov (United States)

    LeGuen, Maurice; Ballueer, Yvonne; McKay, Richard; Eastwood, Glenn; Bellomo, Rinaldo; Jones, Daryl

    2018-01-01

    A new definition of sepsis released by an international task-force has introduced the concept of quick Sequential (Sepsis-Related) Organ Failure Assessment (qSOFA). This study aimed to measure the proportion of patients who fulfilled qSOFA criteria during a Rapid Response Team (RRT) review and to assess their associated outcomes. We conducted a prospective study of adult RRT reviews over a one month period between 6th June and 10th July 2016 in a large tertiary hospital in Melbourne Australia RESULTS: Over a one-month period, there were 282 RRT reviews, 258 of which were included. One hundred out of 258 (38.8%) RRT review patients fulfilled qSOFA criteria. qSOFA positive patients were more likely to be admitted to the intensive care unit (29% vs 18%, P=0.04), to have repeat RRT reviews (27% vs 13%; p=0.007) and die in hospital (31% vs 10%, P<0.001). qSOFA positive patients with suspected infection were more likely to be admitted to the intensive care unit compared to patients with infection alone (37% vs 15%, P=0.002). Eleven of 42 patients (26%) who had infection and qSOFA died whilst in hospital, compared to 8/55 (15%) of patients with infection alone (P=0.2). Adult patients who are qSOFA positive at the time of their RRT review are at increased risk of in-hospital mortality. The assessment of qSOFA may be a useful triage tool during a RRT review. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

  4. Rapid Response to Evaluate the Presence of Amphibian Chytrid Fungus (Batrachochytrium dendrobatidis) and Ranavirus in Wild Amphibian Populations in Madagascar

    Science.gov (United States)

    Kolby, Jonathan E.; Smith, Kristine M.; Ramirez, Sara D.; Rabemananjara, Falitiana; Pessier, Allan P.; Brunner, Jesse L.; Goldberg, Caren S.; Berger, Lee; Skerratt, Lee F.

    2015-01-01

    We performed a rapid response investigation to evaluate the presence and distribution of amphibian pathogens in Madagascar following our identification of amphibian chytrid fungus (Batrachochytrium dendrobatidis, Bd) and ranavirus in commercially exported amphibians. This targeted risk-based field surveillance program was conducted from February to April 2014 encompassing 12 regions and 47 survey sites. We simultaneously collected amphibian and environmental samples to increase survey sensitivity and performed sampling both in wilderness areas and commercial amphibian trade facilities. Bd was not detected in any of 508 amphibian skin swabs or 68 water filter samples, suggesting pathogen prevalence was below 0.8%, with 95% confidence during our visit. Ranavirus was detected in 5 of 97 amphibians, including one adult Mantidactylus cowanii and three unidentified larvae from Ranomafana National Park, and one adult Mantidactylus mocquardi from Ankaratra. Ranavirus was also detected in water samples collected from two commercial amphibian export facilities. We also provide the first report of an amphibian mass-mortality event observed in wild amphibians in Madagascar. Although neither Bd nor ranavirus appeared widespread in Madagascar during this investigation, additional health surveys are required to disentangle potential seasonal variations in pathogen abundance and detectability from actual changes in pathogen distribution and rates of spread. Accordingly, our results should be conservatively interpreted until a comparable survey effort during winter months has been performed. It is imperative that biosecurity practices be immediately adopted to limit the unintentional increased spread of disease through the movement of contaminated equipment or direct disposal of contaminated material from wildlife trade facilities. The presence of potentially introduced strains of ranaviruses suggests that Madagascar's reptile species might also be threatened by disease

  5. A SIMPLE AND RAPID MATRIX-ASSISTED LASER DESORPTION/IONIZATION TIME OF FLIGHT MASS SPECTROMETRY METHOD TO SCREEN FISH PLASMA SAMPLES FOR ESTROGEN-RESPONSIVE BIOMARKERS

    Science.gov (United States)

    In this study, we describe and evaluate the performance of a simple and rapid mass spectral method for screening fish plasma for estrogen-responsive biomarkers using matrix assisted laster desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS) couopled with a short...

  6. Standardized measurement of the Modified Early Warning Score results in enhanced implementation of a Rapid Response System: a quasi-experimental study

    NARCIS (Netherlands)

    Ludikhuize, Jeroen; Borgert, Marjon; Binnekade, Jan; Subbe, Christian; Dongelmans, Dave; Goossens, Astrid

    2014-01-01

    To study the effect of protocolized measurement (three times daily) of the Modified Early Warning Score (MEWS) versus measurement on indication on the degree of implementation of the Rapid Response System (RRS). A quasi-experimental study was conducted in a University Hospital in Amsterdam between

  7. Capturing early signs of deterioration: the dutch-early-nurse-worry-indicator-score and its value in the Rapid Response System

    NARCIS (Netherlands)

    Douw, G.; Huisman-de Waal, G.J.; Zanten, A.R. van; Hoeven, J.G. van der; Schoonhoven, L.

    2017-01-01

    AIMS AND OBJECTIVES: To determine the predictive value of individual and combined dutch-early-nurse-worry-indicator-score indicators at various Early Warning Score levels, differentiating between Early Warning Scores reaching the trigger threshold to call a rapid response team and Early Warning

  8. Do thermal tolerances and rapid thermal responses contribute to the invasion potential of Bactrocera dorsalis (Diptera: Tephritidae)?

    Science.gov (United States)

    Pieterse, Welma; Terblanche, John S; Addison, Pia

    2017-04-01

    Bactrocera dorsalis (Hendel) (Diptera: Tephritidae) has shown remarkable range expansion over the past 10years and invaded several new continents including Africa. Here we report results of a detailed assessment of acute high and low temperature survival ability and the plasticity thereof, to test the hypothesis that traits of the thermal niche have contributed to the species' invasion ability. We also assess life-stage-related variation of thermal tolerances to determine potential stage-related environmental sensitivity. The temperatures at which c. 20% of the population survived of B. dorsalis were determined to be -6.5°C and 42.7°C, respectively, when using 2h exposures. Further, four life stages of B. dorsalis (egg, 3rd instar larvae, pupae and adults) were exposed to high and low discriminating temperatures to compare their thermal survival rates. The egg stage was found to be the most resistant life stage to both high and low temperatures, since 44±2.3% survived the low and 60±4.2% survived the high discriminating temperature treatments respectively. Finally, the potential for adult hardening responses to mediate tolerance of extremes was also considered using a diverse range of acute conditions (using 2h exposures to 15°C, 10°C and 5°C and 30°C, 35°C, 37°C and 39°C as hardening temperatures, and some treatments with and without recovery periods between hardening and discriminating temperature treatment). These showed that although some significant hardening responses could be detected in certain treatments (e.g. after exposure to 37°C and 39°C), the magnitude of this plasticity was generally low compared to two other wide-spread and more geographically-range-restricted con-familial species, Ceratitis capitata and C. rosa. In other words, Bactrocera dorsalis adults were unable to rapidly heat- or cold-harden to the same extent as the other Ceratitis species examined to date. These results suggest a narrower thermal niche in B. dorsalis compared

  9. MULTIVALENT DISPLAY OF PENDANT PRO-APOPTOTIC PEPTIDES INCREASES CYTOTOXIC ACTIVITY

    Science.gov (United States)

    Chu, David S.H.; Bocek, Michael J.; Shi, Julie; Ta, Anh; Ngambenjawong, Chayanon; Rostomily, Robert C.; Pun, Suzie H.

    2015-01-01

    Several cationic antimicrobial peptides have been investigated as potential anti-cancer drugs due to their demonstrated selective toxicity towards cancer cells relative to normal cells. For example, intracellular delivery of KLA, a pro-apoptotic peptide, results in toxicity against a variety of cancer cell lines; however, the relatively low activity and small size leads to rapid renal excretion when applied in vivo, limiting its therapeutic potential. In this work, apoptotic peptide-polymer hybrid materials were developed to increase apoptotic peptide activity via multivalent display. Multivalent peptide materials were prepared with comb-like structure by RAFT copolymerization of peptide macromonomers with N-(2-hydroxypropyl) methacrylamide (HPMA). Polymers displayed a GKRK peptide sequence for targeting p32, a protein often overexpressed on the surface of cancer cells, either fused with or as a comonomer to a KLA macromonomer. In three tested cancer cell lines, apoptotic polymers were significantly more cytotoxic than free peptides as evidenced by an order of magnitude decrease in IC50 values for the polymers compared to free peptide. The uptake efficiency and intracellular trafficking of one polymer construct was determined by radiolabeling and subcellular fractionation. Despite their more potent cytotoxic profile, polymeric KLA constructs have poor cellular uptake efficiency (<1%). A significant fraction (20%) of internalized constructs localize with intact mitochondrial fractions. In an effort to increase cellular uptake, polymer amines were converted to guanidines by reaction with O-methylisourea. Guanidinylated polymers disrupted function of isolated mitochondria more than their lysine-based analogs, but overall toxicity was decreased, likely due to inefficient mitochondrial trafficking. Thus, while multivalent KLA polymers are more potent than KLA peptides, these materials can be substantially improved by designing next generation materials with improved

  10. Antiproliferative and apoptotic effect of Astrodaucus orientalis (L ...

    African Journals Online (AJOL)

    Antiproliferative and apoptotic effect of Astrodaucus orientalis (L.) drude on T47D human breast cancer cell line: Potential mechanisms of action. M.H Abdolmohammadi, S Fouladdel, A Shafiee, G Amin, S Ghaffari, E Azizi ...

  11. Apoptotic-like Leishmania exploit the host´s autophagy machinery to reduce T-cell-mediated parasite elimination

    Science.gov (United States)

    Crauwels, Peter; Bohn, Rebecca; Thomas, Meike; Gottwalt, Stefan; Jäckel, Florian; Krämer, Susi; Bank, Elena; Tenzer, Stefan; Walther, Paul; Bastian, Max; van Zandbergen, Ger

    2015-01-01

    Apoptosis is a well-defined cellular process in which a cell dies, characterized by cell shrinkage and DNA fragmentation. In parasites like Leishmania, the process of apoptosis-like cell death has been described. Moreover upon infection, the apoptotic-like population is essential for disease development, in part by silencing host phagocytes. Nevertheless, the exact mechanism of how apoptosis in unicellular organisms may support infectivity remains unclear. Therefore we investigated the fate of apoptotic-like Leishmania parasites in human host macrophages. Our data showed—in contrast to viable parasites—that apoptotic-like parasites enter an LC3+, autophagy-like compartment. The compartment was found to consist of a single lipid bilayer, typical for LC3-associated phagocytosis (LAP). As LAP can provoke anti-inflammatory responses and autophagy modulates antigen presentation, we analyzed how the presence of apoptotic-like parasites affected the adaptive immune response. Macrophages infected with viable Leishmania induced proliferation of CD4+ T-cells, leading to a reduced intracellular parasite survival. Remarkably, the presence of apoptotic-like parasites in the inoculum significantly reduced T-cell proliferation. Chemical induction of autophagy in human monocyte-derived macrophage (hMDM), infected with viable parasites only, had an even stronger proliferation-reducing effect, indicating that host cell autophagy and not parasite viability limits the T-cell response and enhances parasite survival. Concluding, our data suggest that apoptotic-like Leishmania hijack the host cells´ autophagy machinery to reduce T-cell proliferation. Furthermore, the overall population survival is guaranteed, explaining the benefit of apoptosis-like cell death in a single-celled parasite and defining the host autophagy pathway as a potential therapeutic target in treating Leishmaniasis. PMID:25801301

  12. Apoptotic-like Leishmania exploit the host's autophagy machinery to reduce T-cell-mediated parasite elimination.

    Science.gov (United States)

    Crauwels, Peter; Bohn, Rebecca; Thomas, Meike; Gottwalt, Stefan; Jäckel, Florian; Krämer, Susi; Bank, Elena; Tenzer, Stefan; Walther, Paul; Bastian, Max; van Zandbergen, Ger

    2015-01-01

    Apoptosis is a well-defined cellular process in which a cell dies, characterized by cell shrinkage and DNA fragmentation. In parasites like Leishmania, the process of apoptosis-like cell death has been described. Moreover upon infection, the apoptotic-like population is essential for disease development, in part by silencing host phagocytes. Nevertheless, the exact mechanism of how apoptosis in unicellular organisms may support infectivity remains unclear. Therefore we investigated the fate of apoptotic-like Leishmania parasites in human host macrophages. Our data showed--in contrast to viable parasites--that apoptotic-like parasites enter an LC3(+), autophagy-like compartment. The compartment was found to consist of a single lipid bilayer, typical for LC3-associated phagocytosis (LAP). As LAP can provoke anti-inflammatory responses and autophagy modulates antigen presentation, we analyzed how the presence of apoptotic-like parasites affected the adaptive immune response. Macrophages infected with viable Leishmania induced proliferation of CD4(+) T-cells, leading to a reduced intracellular parasite survival. Remarkably, the presence of apoptotic-like parasites in the inoculum significantly reduced T-cell proliferation. Chemical induction of autophagy in human monocyte-derived macrophage (hMDM), infected with viable parasites only, had an even stronger proliferation-reducing effect, indicating that host cell autophagy and not parasite viability limits the T-cell response and enhances parasite survival. Concluding, our data suggest that apoptotic-like Leishmania hijack the host cells' autophagy machinery to reduce T-cell proliferation. Furthermore, the overall population survival is guaranteed, explaining the benefit of apoptosis-like cell death in a single-celled parasite and defining the host autophagy pathway as a potential therapeutic target in treating Leishmaniasis.

  13. Perceptions of interactions between staff members calling, and those responding to, rapid response team activations for patient deterioration.

    Science.gov (United States)

    Chalwin, Richard; Flabouris, Arthas; Kapitola, Karoline; Dewick, Leonie

    2016-09-01

    Objectives The aim of the present study was to investigate experiences of staff interactions and non-technical skills (NTS) at rapid response team (RRT) calls, and their association with repeat RRT calls. Methods Mixed-methods surveys were conducted of RRT members and staff who activate the RRT (RRT users) for their perceptions and attitudes regarding the use of NTS during RRT calls. Responses within the survey were recorded as Likert items, ranked data and free comments. The latter were coded into nodes relating to one of four NTS domains: leadership, communication, cooperation and planning. Results Two hundred and ninety-seven (32%) RRT users and 79 (73.8%) RRT members provided responses. Of the RRT user respondents, 76.5% had activated the RRT at some point. Deficits in NTS at RRT calls were revealed, with 36.9% of users not feeling involved during RRT calls and 24.7% of members perceiving that users were disinterested. Unresolved user clinical concerns, or persistence of RRT calling criteria, were reasons cited by 37.6% and 23%, respectively, of RRT users for reactivating an RRT to the same patient. Despite recollections of conflict at previous RRT calls, 92% of users would still reactivate the RRT. The most common theme in the free comments related to deficiencies in cooperation (52.9%), communication (28.6%) and leadership (14.3%). Conclusions This survey of RRT users and members revealed problems with RRT users' and members' interactions at the time of an RRT call. Both users and members considered NTS to be important, but lacking. These findings support NTS training for RRT members and users. What is known about the topic? Previous surveying has related experiences of criticism and conflict between clinical staff at RRT activations. This leads to reluctance to call the RRT when indicated, with risks to patient safety, especially if subsequent RRT activation is necessary. Training in NTS has improved clinician interactions in simulated emergencies, but the

  14. Genotoxic and apoptotic effects of Goeckerman therapy for psoriasis

    Energy Technology Data Exchange (ETDEWEB)

    Borska, L.; Andrys, C.; Krejsek, J.; Hamakova, K.; Kremlacek, J.; Palicka, V.; Ranna, D.; Fiala, Z. [Charles University Prague, Prague (Czech Republic). Faculty of Medicine

    2010-03-15

    Goeckerman therapy (GT) for psoriasis is based on cutaneous application of crude coal tar (polycyclic aromatic hydrocarbons (PAH)) and exposure to ultraviolet radiation (UVR). PAH and UVR are mutagenic, carcinogenic and immunotoxic agents that promote apoptosis. We evaluated dermal absorption of PAH as well as the genotoxic and apoptotic effects of GT in 20 patients with psoriasis, by determining numbers of chromosomal abnormalities in peripheral lymphocytes, and levels of 1-hydroxypyrene (1-OHP), p53 protein and soluble FasL (sFasL) in urine and/or blood, before and after GT. Psoriasis Area and Severity Index (PASI) score was used to evaluate clinical efficacy of GT. Compared with pre-treatment levels, there was a significant increase in urine 1-OHP, indicating a high degree of dermal absorption of PAH (P <0.01). We also found a significant increase in the number of chromosomal abnormalities in peripheral blood lymphocytes (P <0.001), suggesting that GT is genotoxic; significantly increased p53 protein in plasma (P <0.05), an indicator of cell response to DNA damage; and significantly increased sFasL in serum (P <0.01), an indicator of apoptosis. The PASI score was significantly decreased after GT (P <0.001), confirming clinical benefit of this treatment. Our results demonstrate high dermal absorption of PAH during GT and provide evidence that GT promotes genotoxicity and apoptosis.

  15. Galleria mellonella lysozyme induces apoptotic changes in Candida albicans cells.

    Science.gov (United States)

    Sowa-Jasiłek, Aneta; Zdybicka-Barabas, Agnieszka; Stączek, Sylwia; Wydrych, Jerzy; Skrzypiec, Krzysztof; Mak, Paweł; Deryło, Kamil; Tchórzewski, Marek; Cytryńska, Małgorzata

    2016-12-01

    The greater wax moth Galleria mellonella has been increasingly used as a model host to determine Candida albicans virulence and efficacy of antifungal treatment. The G. mellonella lysozyme, similarly to its human counterpart, is a member of the c-type family of lysozymes that exhibits antibacterial and antifungal activity. However, in contrast to the relatively well explained bactericidal action, the mechanism of fungistatic and/or fungicidal activity of lysozymes is still not clear. In the present study we provide the direct evidences that the G. mellonella lysozyme binds to the protoplasts as well as to the intact C. albicans cells and decreases the survival rate of both these forms in a time-dependent manner. No enzymatic activity of the lysozyme towards typical chitinase and β-glucanase substrates was detected, indicating that hydrolysis of main fungal cell wall components is not responsible for anti-Candida activity of the lysozyme. On the other hand, pre-treatment of cells with tetraethylammonium, a potassium channel blocker, prevented them from the lysozyme action, suggesting that lysozyme acts by induction of programmed cell death. In fact, the C. albicans cells treated with the lysozyme exhibited typical apoptotic features, i.e. loss of mitochondrial membrane potential, phosphatidylserine exposure in the outer leaflet of the cell membrane, as well as chromatin condensation and DNA fragmentation. Copyright © 2016 Elsevier GmbH. All rights reserved.

  16. Signaling pathway for phagocyte priming upon encounter with apoptotic cells.

    Science.gov (United States)

    Nonaka, Saori; Ando, Yuki; Kanetani, Takuto; Hoshi, Chiharu; Nakai, Yuji; Nainu, Firzan; Nagaosa, Kaz; Shiratsuchi, Akiko; Nakanishi, Yoshinobu

    2017-05-12

    The phagocytic elimination of cells undergoing apoptosis is an evolutionarily conserved innate immune mechanism for eliminating unnecessary cells. Previous studies showed an increase in the level of engulfment receptors in phagocytes after the phagocytosis of apoptotic cells, which leads to the enhancement of their phagocytic activity. However, precise mechanisms underlying this phenomenon require further clarification. We found that the pre-incubation of a Drosophila phagocyte cell line with the fragments of apoptotic cells enhanced the subsequent phagocytosis of apoptotic cells, accompanied by an augmented expression of the engulfment receptors Draper and integrin αPS3. The DNA-binding activity of the transcription repressor Tailless was transiently raised in those phagocytes, depending on two partially overlapping signal-transduction pathways for the induction of phagocytosis as well as the occurrence of engulfment. The RNAi knockdown of tailless in phagocytes abrogated the enhancement of both phagocytosis and engulfment receptor expression. Furthermore, the hemocyte-specific RNAi of tailless reduced apoptotic cell clearance in Drosophila embryos. Taken together, we propose the following mechanism for the activation of Drosophila phagocytes after an encounter with apoptotic cells: two partially overlapping signal-transduction pathways for phagocytosis are initiated; transcription repressor Tailless is activated; expression of engulfment receptors is stimulated; and phagocytic activity is enhanced. This phenomenon most likely ensures the phagocytic elimination of apoptotic cells by stimulated phagocytes and is thus considered as a mechanism to prime phagocytes in innate immunity. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  17. Rapid and Sensitive Detection of Bacteria Response to Antibiotics Using Nanoporous Membrane and Graphene Quantum Dot (GQDs-Based Electrochemical Biosensors

    Directory of Open Access Journals (Sweden)

    Weiwei Ye

    2017-05-01

    Full Text Available The wide abuse of antibiotics has accelerated bacterial multiresistance, which means there is a need to develop tools for rapid detection and characterization of bacterial response to antibiotics in the management of infections. In the study, an electrochemical biosensor based on nanoporous alumina membrane and graphene quantum dots (GQDs was developed for bacterial response to antibiotics detection. Anti-Salmonella antibody was conjugated with amino-modified GQDs by glutaraldehyde and immobilized on silanized nanoporous alumina membranes for Salmonella bacteria capture. The impedance signals across nanoporous membranes could monitor the capture of bacteria on nanoporous membranes as well as bacterial response to antibiotics. This nanoporous membrane and GQD-based electrochemical biosensor achieved rapid detection of bacterial response to antibiotics within 30 min, and the detection limit could reach the pM level. It was capable of investigating the response of bacteria exposed to antibiotics much more rapidly and conveniently than traditional tools. The capability of studying the dynamic effects of antibiotics on bacteria has potential applications in the field of monitoring disease therapy, detecting comprehensive food safety hazards and even life in hostile environment.

  18. Extracellular Vesicles Arising from Apoptotic Cells in Tumors: Roles in Cancer Pathogenesis and Potential Clinical Applications

    Directory of Open Access Journals (Sweden)

    Catherine Lynch

    2017-09-01

    Full Text Available It is known that apoptotic cells can have diverse effects on the tumor microenvironment. Emerging evidence indicates that, despite its renowned role in tumor suppression, apoptosis may also promote oncogenic evolution or posttherapeutic relapse through multiple mechanisms. These include immunomodulatory, anti-inflammatory, and trophic environmental responses to apoptosis, which drive tumor progression. Our group has introduced the term “onco-regenerative niche (ORN” to describe a conceptual network of conserved cell death-driven tissue repair and regeneration mechanisms that are hijacked in cancer. We propose that, among the key elements of the ORN are extracellular vesicles (EVs, notably those derived from apoptotic tumor cells. EVs are membrane-delimited subcellular particles, which contain multiple classes of bioactive molecules including markers of the cell from which they are derived. EVs are implicated in an increasing number of physiological and pathological contexts as mediators of local and systemic intercellular communication and detection of specific EVs may be useful in monitoring disease progression. Here, we discuss the mechanisms by which EVs produced by apoptotic tumor cells—both constitutively and as a consequence of therapy—may mediate host responsiveness to cell death in cancer. We also consider how the monitoring of such EVs and their cargoes may in the future help to improve cancer diagnosis, staging, and therapeutic efficacy.

  19. The anti-apoptotic members of the Bcl-2 family are attractive tumor-associated antigens

    DEFF Research Database (Denmark)

    Straten, Per thor; Andersen, Mads Hald; Andersen, Mads Hald

    2010-01-01

    Anti-apoptotic members of the Bcl-2 family (Bcl-2, Bcl-X(L) and Mcl-2) are pivotal regulators of apoptotic cell death. They are all highly overexpressed in cancers of different origin in which they enhance the survival of the cancer cells. Consequently, they represent prime candidates for anti......-cancer therapy and specific antisense oligonucleotides or small molecule inhibitors have shown broad anti-cancer activities in pre-clinical models and are currently tested in clinical trials. In addition, immune-mediated tumor destruction is emerging as an interesting modality to treat cancer patients. Notably......, spontaneous cellular immune responses against the Bcl-2 family proteins have been identified as frequent features in cancer patients underscoring that these proteins are natural targets for the immune system. Thus, Bcl-2 family may serve as an important and widely applicable target for anti...

  20. Improvement of DC vaccine with ALA-PDT induced immunogenic apoptotic cells for skin squamous cell carcinoma.

    Science.gov (United States)

    Ji, Jie; Fan, Zhixia; Zhou, Feifan; Wang, Xiaojie; Shi, Lei; Zhang, Haiyan; Wang, Peiru; Yang, Degang; Zhang, Linglin; Chen, Wei R; Wang, Xiuli

    2015-07-10

    Dendritic cell (DC) based vaccines have emerged as a promising immunotherapy for cancers. However, most DC vaccines so far have achieved only limited success in cancer treatment. Photodynamic therapy (PDT), an established cancer treatment strategy, can cause immunogenic apoptosis to induce an effective antitumor immune response. In this study, we developed a DC-based cancer vaccine using immunogenic apoptotic tumor cells induced by 5-aminolevulinic acid (ALA) mediated PDT. The maturation of DCs induced by PDT-treated apoptotic cells was evaluated using electron microscopy, FACS, and ELISA. The anti-tumor immunity of ALA-PDT-DC vaccine was tested with a mouse model. We observed the maturations of DCs potentiated by ALA-PDT treated tumor cells, including morphology maturation (enlargement of dendrites and increase of lysosomes), phenotypic maturation (upregulation of surface expression of MHC-II, DC80, and CD86), and functional maturation (enhanced capability to secrete IFN-γ and IL-12, and to induce T cell proliferation). Most interestingly, PDT-induced apoptotic tumor cells are more capable of potentiating maturation of DCs than PDT-treated or freeze/thaw treated necrotic tumor cells. ALA-PDT-DC vaccine mediated by apoptotic cells provided protection against tumors in mice, far stronger than that of DC vaccine obtained from freeze/thaw treated tumor cells. Our results indicate that immunogenic apoptotic tumor cells can be more effective in enhancing a DC-based cancer vaccine, which could improve the clinical application of PDT-DC vaccines.

  1. Targeting multiple pro-apoptotic signaling pathways with curcumin in prostate cancer cells.

    Directory of Open Access Journals (Sweden)

    Mariela Rivera

    Full Text Available Curcumin, an extract from the turmeric rhizome (Curcuma longa, is known to exhibit anti-inflammatory, antioxidant, chemopreventive and antitumoral activities against aggressive and recurrent cancers. Accumulative data indicate that curcumin may induce cancer cell death. However, the detailed mechanism underlying its pro-apoptotic and anti-cancer effects remains to be elucidated. In the present study, we examined the signaling pathways triggered by curcumin, specifically, the exact molecular mechanisms of curcumin-induced apoptosis in highly metastatic human prostate cancer cells. The effect of curcumin was evaluated using for the first time in prostate cancer, a gel-free shotgun quantitative proteomic analysis coupled with Tandem Mass Tag isobaric labeling-based-signaling networks. Results were confirmed at the gene expression level by qRT-PCR and at the protein expression level by western blot and flow cytometry. Our findings revealed that curcumin induced an Endoplasmic Reticulum stress-mediated apoptosis in PC3. The mechanisms by which curcumin promoted cell death in these cells were associated with cell cycle arrest, increased reactive oxygen species, autophagy and the Unfolded Protein Response. Furthermore, the upregulation of ER stress was measured using key indicators of ER stress: Glucose-Regulated Protein 78, Inositol-Requiring Enzyme 1 alpha, Protein Disulfide isomerase and Calreticulin. Chronic ER stress induction was concomitant with the upregulation of pro-apoptotic markers (caspases 3,9,12 and Poly (ADP-ribose polymerase. The downregulated proteins include anti-apoptotic and anti-tumor markers, supporting their curcumin-induced pro-apoptotic role in prostate cancer cells. Taken together, these data suggest that curcumin may serve as a promising anticancer agent by inducing a chronic ER stress mediated cell death and activation of cell cycle arrest, UPR, autophagy and oxidative stress responses.

  2. A Small Molecule That Protects the Integrity of the Electron Transfer Chain Blocks the Mitochondrial Apoptotic Pathway.

    Science.gov (United States)

    Jiang, Xian; Li, Li; Ying, Zhengxin; Pan, Chenjie; Huang, Shaoqiang; Li, Lin; Dai, Miaomiao; Yan, Bo; Li, Ming; Jiang, Hui; Chen, She; Zhang, Zhiyuan; Wang, Xiaodong

    2016-07-21

    In response to apoptotic stimuli, mitochondria in mammalian cells release cytochrome c and other apoptogenic proteins, leading to the subsequent activation of caspases and apoptotic cell death. This process is promoted by the pro-apoptotic members of the Bcl-2 family of proteins, such as Bim and Bax, which, respectively, initiate and execute cytochrome c release from the mitochondria. Here we report the discovery of a small molecule that efficiently blocks Bim-induced apoptosis after Bax is activated on the mitochondria. The cellular target of this small molecule was identified to be the succinate dehydrogenase subunit B (SDHB) protein of complex II of the mitochondrial electron transfer chain (ETC). The molecule protects the integrity of the ETC and allows treated cells to continue to proliferate after apoptosis induction. Moreover, this molecule blocked dopaminergic neuron death and reversed Parkinson-like behavior in a rat model of Parkinson's disease. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. CD40 stimulation of B-cell chronic lymphocytic leukaemia cells enhances the anti-apoptotic profile, but also Bid expression and cells remain susceptible to autologous cytotoxic T-lymphocyte attack

    NARCIS (Netherlands)

    Kater, Arnon P.; Evers, Ludo M.; Remmerswaal, Ester B. M.; Jaspers, Annelieke; Oosterwijk, Michiel F.; van Lier, René A. W.; van Oers, Marinus H. J.; Eldering, Eric

    2004-01-01

    To enhance the poor antigen-presenting capacity of B-cell chronic lymphocytic leukaemia (B-CLL), CD40 triggering has been considered as an active immunotherapy. However, CD40 stimulation also has an anti-apoptotic effect and may further impair the dysregulated response of B-CLL to apoptotic stimuli.

  4. A phase I clinical study of vaccination of melanoma patients with dendritic cells loaded with allogeneic apoptotic/necrotic melanoma cells. Analysis of toxicity and immune response to the vaccine and of IL-10 -1082 promoter genotype as predictor of disease progression

    Directory of Open Access Journals (Sweden)

    von Euw Erika M

    2008-01-01

    Full Text Available Abstract Background Sixteen melanoma patients (1 stage IIC, 8 stage III, and 7 stage IV were treated in a Phase I study with a vaccine (DC/Apo-Nec composed of autologous dendritic cells (DCs loaded with a mixture of apoptotic/necrotic allogeneic melanoma cell lines (Apo-Nec, to evaluate toxicity and immune responses. Also, IL-10 1082 genotype was analyzed in an effort to predict disease progression. Methods PBMC were obtained after leukapheresis and DCs were generated from monocytes cultured in the presence of GM-CSF and IL-4 in serum-free medium. Immature DCs were loaded with gamma-irradiated Apo-Nec cells and injected id without adjuvant. Cohorts of four patients were given four vaccines each with 5, 10, 15, or 20 × 106 DC/Apo-Nec cell per vaccine, two weeks apart. Immune responses were measured by ELISpot and tetramer analysis. Il-10 genotype was measured by PCR and corroborated by IL-10 production by stimulated PBMC. Results Immature DCs efficiently phagocytosed melanoma Apo-Nec cells and matured after phagocytosis as evidenced by increased expression of CD83, CD80, CD86, HLA class I and II, and 75.2 ± 16% reduction in Dextran-FITC endocytosis. CCR7 was also up-regulated upon Apo-Nec uptake in DCs from all patients, and accordingly DC/Apo-Nec cells were able to migrate in vitro toward MIP-3 beta. The vaccine was well tolerated in all patients. The DTH score increased significantly in all patients after the first vaccination (Mann-Whitney Test, p +T lymphocytes specific to gp100 and Melan A/MART-1 Ags was determined by ELISpot and tetramer analysis in five HLA-A*0201 patients before and after vaccination; one patient had stable elevated levels before and after vaccination; two increased their CD8 + levels, one had stable moderate and one had negligible levels. The analysis of IL-10 promoter -1082 polymorphism in the sixteen patients showed a positive correlation between AA genotype, accompanied by lower in vitro IL-10 production by

  5. Molecular analysis of neutrophil spontaneous apoptosis reveals a strong role for the pro-apoptotic BH3-only protein Noxa

    OpenAIRE

    Kirschnek, Susanne; Vier, Juliane; Gautam, Sanjivan; Frankenberg, Tobias; Rangelova, Svetla; Eitz Ferrer, Pedro; Grespi, Francesca; Ottina, Eleonora; Villunger, Andreas; Haecker, Hans; Hacker, Georg

    2011-01-01

    Abstract Neutrophils enter the peripheral blood from the bone marrow and die after a short time. Molecular analysis of spontaneous neutrophil apoptosis is difficult as these cells die rapidly and cannot be easily manipulated. We use conditional Hoxb8-expression to generate mouse neutrophils and test the regulation of apoptosis by extensive manipulation of Bcl-2 family proteins. Spontaneous apoptosis was preceded by down-regulation of anti-apoptotic Bcl-2 proteins. Loss of the pro-a...

  6. Rapid responses of mesophyll conductance to changes of CO2 concentration, temperature and irradiance are affected by N supplements in rice.

    Science.gov (United States)

    Xiong, Dongliang; Liu, Xi; Liu, Limin; Douthe, Cyril; Li, Yong; Peng, Shaobing; Huang, Jianliang

    2015-12-01

    Photosynthesis in C3 plants is significantly limited by mesophyll conductance (gm ), which can vary with leaf anatomical traits and nitrogen (N) supplements. Several studies have investigated the response of gm to N supplements; however, none examined the implications of N supplements on the response of gm to rapid environmental changes. Here we investigated the effect of N supplement on gm and the response of gm to change of CO2 , temperature and irradiance in rice. High N supplement (HN) increased mesophyll cell wall surface area and chloroplast surface area exposed to intercellular airspace per leaf area, and reduced cell wall thickness. These changes resulted in increased gm . The gm of leaves with HN was more sensitive to changes in CO2 concentration, temperature and irradiance. The difference in leaf structural features between low N supplement and HN indicates that a rapid change in gm is related to the regulation of diffusion through biological membranes rather than leaf structural features. These results will contribute to an understanding of the determinants of gm response to rapid changes in environmental factors. © 2015 John Wiley & Sons Ltd.

  7. Differential regulation of caspase-9 by ionizing radiation- and UV-induced apoptotic pathways in thymic cells

    Energy Technology Data Exchange (ETDEWEB)

    Okamoto, Mayumi; Koga, Satomi [Department of Life Sciences, Faculty of Life and Environmental Sciences, Prefectural University of Hiroshima, Hiroshima 727-0023 (Japan); Tatsuka, Masaaki, E-mail: tatsuka@pu-hiroshima.ac.jp [Department of Life Sciences, Faculty of Life and Environmental Sciences, Prefectural University of Hiroshima, Hiroshima 727-0023 (Japan)

    2010-06-01

    In mouse thymic lymphoma 3SB cells bearing wild type p53, ionizing radiation (IR) and UV light are potent triggers of caspase-3-dependent apoptosis. Although cytochrome c was released from mitochondria as expected, caspase-9 activation was not observed in UV-exposed cells. Laser scanning confocal microscopy analysis showed that caspase-9 is localized in an unusual punctuated pattern in UV-induced apoptotic cells. In agreement with differences in the status of caspase-9 activation between IR and UV, subcellular protein fractionation experiments showed that pro-apoptotic apoptosis protease-activating factor 1 (Apaf-1), normally a part of the apoptosome assembled in response to the release of cytochrome c from mitochondria, and B-cell lymphoma extra long (Bcl-xL), an inhibitor of the change in mitochondrial membrane permeability, were redistributed by the IR-exposure but not by the UV-exposure. Instead of the sequestration of the capase-9/apoptosome activation in UV-induced apoptotic cells, the extrinsic apoptotic signaling generated by caspase-8 activation and consequent activation of B-cell lymphoma extra long (Bid) to release cytochrome c from mitochondria was observed. Thus, the post-mitochondrial apoptotic pathway downstream of cytochrome c release cannot operate the apoptosome function in UV-induced apoptosis in thymic 3SB cells. The intracellular redistribution and sequestration of apoptosis-related proteins upon mitochondrion-based apoptotic signaling was identified as a novel cellular mechanism to respond to DNA damage in an agent type-specific manner. This finding suggests that the kind of the critical ultimate apoptosis-inducing DNA lesion complex form resulting from the agent-specific DNA damage responses is important to determine which of apoptosis signals would be activated.

  8. Mechanical response of local rapid cooling by spray water on constrained steel frame structure at high temperature in fire

    Directory of Open Access Journals (Sweden)

    Xia Yunchun

    2015-01-01

    Full Text Available Locally rapid cooling of spray water had strong impact on high temperature steel structure. When temperature of beam reached 600°C and cooling rate was more than 20°C/s, the maximum axial tension could reach more than 5 times of the originally compressive force. The compressive bending moment at joint of beam-to-column changed to tensile bending moment, and the maximum bending moment could reach above 4 times as that when heated. After rapid cooling by spray water, deflection at mid-span increased slightly.

  9. SLCO1B1 and SLC19A1 gene variants and irinotecan-induced rapid response and survival: a prospective multicenter pharmacogenetics study of metastatic colorectal cancer.

    Directory of Open Access Journals (Sweden)

    Liu Huang

    Full Text Available Rapid response to chemotherapy in metastatic colorectal cancer (mCRC patients (response within 12 weeks of chemotherapy may increase the chance of complete resection and improved survival. Few molecular markers predict irinotecan-induced rapid response and survival. Single-nucleotide polymorphisms (SNPs in solute carrier genes are reported to correlate with the variable pharmacokinetics of irinotecan and folate in cancer patients. This study aims to evaluate the predictive role of 3 SNPs in mCRC patients treated with irinotecan and fluoropyrimidine-containing regimens.Three SNPs were selected and genotyped in 137 mCRC patients from a Chinese prospective multicenter trial (NCT01282658. The chi-squared test, univariate and multivariable logistic regression model, and receiver operating characteristic analysis were used to evaluate correlations between the genotypes and rapid response. Kaplan-Meier survival analysis and Cox proportional hazard models were used to evaluate the associations between genotypes and survival outcomes. Benjamini and Hochberg False Discovery Rate correction was used in multiple testing.Genotype GA/AA of SNP rs2306283 of the gene SLCO1B1 and genotype GG of SNP rs1051266 of the gene SLC19A1 were associated with a higher rapid response rate (odds ratio [OR] =3.583 and 3.521, 95%CI =1.301-9.871 and 1.271-9.804, p=0.011 and p=0.013, respectively. The response rate was 70% in patients with both genotypes, compared with only 19.7% in the remaining patients (OR = 9.489, 95%CI = 2.191-41.093, Fisher's exact test p=0.002. Their significances were all maintained even after multiple testing (all p c < 0.05. The rs2306283 GA/AA genotype was also an independent prognostic factor of longer progression-free survival (PFS (hazard ratio = 0.402, 95%CI = 0.171-0.945, p=0.037. None of the SNPs predicted overall survival.Polymorphisms of solute carriers' may be useful to predict rapid response to irinotecan plus fluoropyrimidine and PFS in m

  10. Comparison of two dengue NS1 rapid tests for sensitivity, specificity and relationship to viraemia and antibody responses

    Directory of Open Access Journals (Sweden)

    Farrar Jeremy

    2010-05-01

    Full Text Available Abstract Background Dengue is a major public health problem in tropical and subtropical countries. Rapid and easy diagnosis of dengue can assist patient triage and care-management. The detection of DENV NS1 on rapid lateral flow tests offers a fast route to a presumptive dengue diagnosis but careful evaluations are urgently needed as more and more people use them. Methods The sensitivity and specificity of the Bio-Rad NS1 Ag Strip and SD Dengue Duo (NS1/IgM/IgG lateral flow rapid tests were evaluated in a panel of plasma samples from 245 Vietnamese patients with RT-PCR confirmed dengue and 47 with other febrile illnesses. Results The NS1 rapid tests had similar diagnostic sensitivities (respectively 61.6% and 62.4% in confirmed dengue cases but were 100% specific. When IgM/IgG results from the SD Dengue Duo were included in the test interpretation, the sensitivity improved significantly from 62.4% with NS1 alone to 75.5% when NS1 and/or IgM was positive and 83.7% when NS1 and/or IgM and/or IgG was positive. Both NS1 assays were significantly more sensitive for primary than secondary dengue. NS1 positivity was associated with the underlying viraemia as NS1-positive samples had a significantly higher viraemia than NS1-negative samples. Conclusions These data suggest that the NS1 test component of these assays are highly specific and have similar levels of sensitivity. The IgM parameter in the SD Duo test improved overall test sensitivity without compromising specificity. The SD Dengue Duo lateral flow rapid test deserves further prospective evaluation in dengue endemic settings.

  11. Plasmapheresis Responsive Rapid Onset Dementia with Predominantly Frontal Dysfunction in the Context of Hashimoto’s Encephalopathy

    Directory of Open Access Journals (Sweden)

    Dominique Endres

    2017-10-01

    Full Text Available BackgroundHashimoto’s encephalopathy (HE is a rare immunological neuropsychiatric disorder characterized by increased antithyroid antibodies and mixed neurological and psychiatric symptoms. HE has been previously discussed as a differential diagnosis for rapid progressive dementia. However, most of these patients suffered from additional neurological symptoms, like ataxia or seizures.Case presentationHere, we present the case of a 59-year-old female patient suffering rapid onset dementia with salient frontal executive dysfunction. She developed rapid onset symptoms, including apathy, verbal depletion up to a stuporous state, severe working memory deficits, evidence of primitive reflexes, disturbed Luria’s three-step test, and micturition disorder. Analysis of her cerebrospinal fluid was normal. The serum analyses showed increased antithyroid (antithyroid peroxidase and antithyroglobulin antibodies. In the cerebral magnetic resonance imaging, supratentorial deep and peripheral white matter lesions were found; the electroencephalography showed intermittent slowing, and the [18F]fluorodeoxyglucose positron emission tomography (FDG-PET depicted medial and superior dorsolateral frontal hypometabolism. Several different psychopharmacological therapeutic approaches with various neuroleptics, antidepressants, and high doses of lorazepam were unsuccessful. Due to the organic alterations, including increased antithyroid antibodies, HE was suspected. Against expectations, treatment with high-dose corticosteroids proved to be ineffective and was associated with worsening symptoms. However, escalated treatment with plasmapheresis over 5 days led to significant improvement in all reported symptoms and in psychometric testing. The neuropsychological improvement was stable over a 6-month follow-up period, and the FDG-PET normalized.ConclusionThis case report reveals that (1 HE can mimic rapid onset dementia with predominantly frontal dysfunction; (2 this

  12. Phagocytosis Assay for Apoptotic Cells in Drosophila Embryos.

    Science.gov (United States)

    Nonaka, Saori; Hori, Aki; Nakanishi, Yoshinobu; Kuraishi, Takayuki

    2017-08-03

    The molecular mechanisms underlying the phagocytosis of apoptotic cells need to be elucidated in more detail because of its role in immune and inflammatory intractable diseases. We herein developed an experimental method to investigate phagocytosis quantitatively using the fruit fly Drosophila, in which the gene network controlling engulfment reactions is evolutionally conserved from mammals. In order to accurately detect and count engulfing and un-engulfing phagocytes using whole animals, Drosophila embryos were homogenized to obtain dispersed cells including phagocytes and apoptotic cells. The use of dispersed embryonic cells enables us to measure in vivo phagocytosis levels as if we performed an in vitro phagocytosis assay in which it is possible to observe all phagocytes and apoptotic cells in whole embryos and precisely quantify the level of phagocytosis. We confirmed that this method reproduces those of previous studies that identified the genes required for the phagocytosis of apoptotic cells. This method allows the engulfment of dead cells to be analyzed, and when combined with the powerful genetics of Drosophila, will reveal the complex phagocytic reactions comprised of the migration, recognition, engulfment, and degradation of apoptotic cells by phagocytes.

  13. Non-apoptotic cell death in animal development.

    Science.gov (United States)

    Kutscher, Lena M; Shaham, Shai

    2017-08-01

    Programmed cell death (PCD) is an important process in the development of multicellular organisms. Apoptosis, a form of PCD characterized morphologically by chromatin condensation, membrane blebbing, and cytoplasm compaction, and molecularly by the activation of caspase proteases, has been extensively investigated. Studies in Caenorhabditis elegans, Drosophila, mice, and the developing chick have revealed, however, that developmental PCD also occurs through other mechanisms, morphologically and molecularly distinct from apoptosis. Some non-apoptotic PCD pathways, including those regulating germ cell death in Drosophila, still appear to employ caspases. However, another prominent cell death program, linker cell-type death (LCD), is morphologically conserved, and independent of the key genes that drive apoptosis, functioning, at least in part, through the ubiquitin proteasome system. These non-apoptotic processes may serve as backup programs when caspases are inactivated or unavailable, or, more likely, as freestanding cell culling programs. Non-apoptotic PCD has been documented extensively in the developing nervous system, and during the formation of germline and somatic gonadal structures, suggesting that preservation of these mechanisms is likely under strong selective pressure. Here, we discuss our current understanding of non-apoptotic PCD in animal development, and explore possible roles for LCD and other non-apoptotic developmental pathways in vertebrates. We raise the possibility that during vertebrate development, apoptosis may not be the major PCD mechanism.

  14. Rapid metabolic profiling of Nicotiana tabacum defence responses against Phytophthora nicotianae using direct infrared laser desorption ionization mass spectrometry and principal component analysis.

    Science.gov (United States)

    Ibáñez, Alfredo J; Scharte, Judith; Bones, Philipp; Pirkl, Alexander; Meldau, Stefan; Baldwin, Ian T; Hillenkamp, Franz; Weis, Engelbert; Dreisewerd, Klaus

    2010-06-09

    Successful defence of tobacco plants against attack from the oomycete Phytophthora nicotianae includes a type of local programmed cell death called the hypersensitive response. Complex and not completely understood signaling processes are required to mediate the development of this defence in the infected tissue. Here, we demonstrate that different families of metabolites can be monitored in small pieces of infected, mechanically-stressed, and healthy tobacco leaves using direct infrared laser desorption ionization orthogonal time-of-flight mass spectrometry. The defence response was monitored for 1 - 9 hours post infection. Infrared laser desorption ionization orthogonal time-of-flight mass spectrometry allows rapid and simultaneous detection in both negative and positive ion mode of a wide range of naturally occurring primary and secondary metabolites. An unsupervised principal component analysis was employed to identify correlations between changes in metabolite expression (obtained at different times and sample treatment conditions) and the overall defence response.A one-dimensional projection of the principal components 1 and 2 obtained from positive ion mode spectra was used to generate a Biological Response Index (BRI). The BRI obtained for each sample treatment was compared with the number of dead cells found in the respective tissue. The high correlation between these two values suggested that the BRI provides a rapid assessment of the plant response against the pathogen infection. Evaluation of the loading plots of the principal components (1 and 2) reveals a correlation among three metabolic cascades and the defence response generated in infected leaves. Analysis of selected phytohormones by liquid chromatography electrospray ionization mass spectrometry verified our findings. The described methodology allows for rapid assessment of infection-specific changes in the plant metabolism, in particular of phenolics, alkaloids, oxylipins, and carbohydrates

  15. Rapid metabolic profiling of Nicotiana tabacum defence responses against Phytophthora nicotianae using direct infrared laser desorption ionization mass spectrometry and principal component analysis

    Directory of Open Access Journals (Sweden)

    Weis Engelbert

    2010-06-01

    Full Text Available Abstract Background Successful defence of tobacco plants against attack from the oomycete Phytophthora nicotianae includes a type of local programmed cell death called the hypersensitive response. Complex and not completely understood signaling processes are required to mediate the development of this defence in the infected tissue. Here, we demonstrate that different families of metabolites can be monitored in small pieces of infected, mechanically-stressed, and healthy tobacco leaves using direct infrared laser desorption ionization orthogonal time-of-flight mass spectrometry. The defence response was monitored for 1 - 9 hours post infection. Results Infrared laser desorption ionization orthogonal time-of-flight mass spectrometry allows rapid and simultaneous detection in both negative and positive ion mode of a wide range of naturally occurring primary and secondary metabolites. An unsupervised principal component analysis was employed to identify correlations between changes in metabolite expression (obtained at different times and sample treatment conditions and the overall defence response. A one-dimensional projection of the principal components 1 and 2 obtained from positive ion mode spectra was used to generate a Biological Response Index (BRI. The BRI obtained for each sample treatment was compared with the number of dead cells found in the respective tissue. The high correlation between these two values suggested that the BRI provides a rapid assessment of the plant response against the pathogen infection. Evaluation of the loading plots of the principal components (1 and 2 reveals a correlation among three metabolic cascades and the defence response generated in infected leaves. Analysis of selected phytohormones by liquid chromatography electrospray ionization mass spectrometry verified our findings. Conclusion The described methodology allows for rapid assessment of infection-specific changes in the plant metabolism, in particular

  16. Oncogenic properties of apoptotic tumor cells in aggressive B cell lymphoma.

    Science.gov (United States)

    Ford, Catriona A; Petrova, Sofia; Pound, John D; Voss, Jorine J L P; Melville, Lynsey; Paterson, Margaret; Farnworth, Sarah L; Gallimore, Awen M; Cuff, Simone; Wheadon, Helen; Dobbin, Edwina; Ogden, Carol Anne; Dumitriu, Ingrid E; Dunbar, Donald R; Murray, Paul G; Ruckerl, Dominik; Allen, Judith E; Hume, David A; van Rooijen, Nico; Goodlad, John R; Freeman, Tom C; Gregory, Christopher D

    2015-03-02

    Cells undergoing apoptosis are known to modulate their tissue microenvironments. By acting on phagocytes, notably macrophages, apoptotic cells inhibit immunological and inflammatory responses and promote trophic signaling pathways. Paradoxically, because of their potential to cause death of tumor cells and thereby militate against malignant disease progression, both apoptosis and tumor-associated macrophages (TAMs) are often associated with poor prognosis in cancer. We hypothesized that, in progression of malignant disease, constitutive loss of a fraction of the tumor cell population through apoptosis could yield tumor-promoting effects. Here, we demonstrate that apoptotic tumor cells promote coordinated tumor growth, angiogenesis, and accumulation of TAMs in aggressive B cell lymphomas. Through unbiased "in situ transcriptomics" analysis-gene expression profiling of laser-captured TAMs to establish their activation signature in situ-we show that these cells are activated to signal via multiple tumor-promoting reparatory, trophic, angiogenic, tissue remodeling, and anti-inflammatory pathways. Our results also suggest that apoptotic lymphoma cells help drive this signature. Furthermore, we demonstrate that, upon induction of apoptosis, lymphoma cells not only activate expression of the tumor-promoting matrix metalloproteinases MMP2 and MMP12 in macrophages but also express and process these MMPs directly. Finally, using a model of malignant melanoma, we show that the oncogenic potential of apoptotic tumor cells extends beyond lymphoma. In addition to its profound tumor-suppressive role, apoptosis can potentiate cancer progression. These results have important implications for understanding the fundamental biology of cell death, its roles in malignant disease, and the broader consequences of apoptosis-inducing anti-cancer therapy. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  17. The MODIS Land Rapid Response Project: A Comprehensive Suite of Products to Support U.S.D.A. Forest Service Fire Management

    Science.gov (United States)

    Descloitres, J.; Giglio, L.; Sohlberg, R.; Owens, J.; Justice, C.; Townshend, J.; Seaton, J.; Crisologo, M.; Carroll, M.; Finco, M.

    2001-12-01

    The Moderate-resolution Imaging Spectroradiometer (MODIS) instrument on board the Terra satellite offers exceptional capabilities of observation for terrestrial surfaces. MODIS is viewing almost the entire Earth's surface every day, with a spatial resolution ranging from 1km to 250m, and covering a wide spectral range of observation, from visible to thermal infrared. The unprecedented combination of daily spatial coverage, 250m spatial resolution, and spectral characteristics makes MODIS ideal to observe a variety of rapid events: fires, floods, smoke transport, dust storms, severe storms, volcanic eruptions. A new processing system has been developed at NASA's Goddard Space Flight Center to provide a rapid response to those events, with initial emphasis on active fire detection and quasi-true-color 250m-resolution imagery. MODIS data of most of the Earth's land surface is processed within a few hours of data acquisition. A basic atmospheric correction is performed operationally to provide true-color imagery. An operational detection process retrieves the location of active fires. The perimeter of the fires are overlaid on true-color imagery and posted on a web site. A collaboration between NASA, the University of Maryland and the USDA Forest Service has been developed to provide fire information derived from MODIS to the fire managers. Active fire locations detected by MODIS in the conterminous United States are communicated to the USDA Forest Service within a few minutes of production. These active fire locations are used to generate cumulative fire maps, updated daily and made available to the fire managers. Active fire locations are also distributed through a web interface integrating MODIS active fire locations and Geographic Information System (GIS) datasets using GIS technology, as a contribution to the Global Observation of Forest Cover (GOFC) project. Burn severity maps derived from MODIS data are also being developed and will be made available within a

  18. Comparing different methods for fast screening of microbiological quality of beach sand aimed at rapid-response remediation.

    Science.gov (United States)

    Testolin, Renan C; Almeida, Tito C M; Polette, Marcus; Branco, Joaquim O; Fischer, Larissa L; Niero, Guilherme; Poyer-Radetski, Gabriel; Silva, Valéria C; Somensi, Cleder A; Corrêa, Albertina X R; Corrêa, Rogério; Rörig, Leonardo R; Itokazu, Ana Gabriela; Férard, Jean-François; Cotelle, Sylvie; Radetski, Claudemir M

    2017-05-15

    There is scientific evidence that beach sands are a significant contributor to the pathogen load to which visitors are exposed. To develop beach quality guidelines all beach zones must be included in microbiological evaluations, but monitoring methods for beach sand quality are relatively longstanding, expensive, laborious and require moderate laboratory infrastructure. This paper aimed to evaluate the microorganism activity in different beach zones applying and comparing a classical method of membrane filtration (MF) with two colorimetric screening methods based on fluorescein (FDA) and tetrazolium (TTC) salt biotransformation to evaluate a new rapid and low-cost method for beach sand microbiological contamination assessments. The colorimetric results can help beach managers to evaluate rapidly and at low cost the microbiological quality of different beach zones in order to decide whether remedial actions need to be adopted to prevent exposure of the public to microbes due to beach sand and/or water contamination. Copyright © 2017. Published by Elsevier Ltd.

  19. Rapid response of leaf photosynthesis in two fern species Pteridium aquilinum and Thelypteris dentata to changes in CO2 measured by tunable diode laser absorption spectroscopy.

    Science.gov (United States)

    Nishida, Keisuke; Kodama, Naomi; Yonemura, Seiichiro; Hanba, Yuko T

    2015-09-01

    We investigated stomatal conductance (g(s)) and mesophyll conductance (g(m)) in response to atmospheric CO2 concentration [CO2] in two primitive land plants, the fern species Pteridium aquilinum and Thelypteris dentata, using the concurrent measurement of leaf gas exchange and carbon isotope discrimination. [CO2] was initially decreased from 400 to 200 μmol mol(-1), and then increased from 200 to 700 μmol mol(-1), and finally decreased from 700 to 400 μmol mol(-1). Analysis by tunable diode laser absorption spectroscopy (TDLAS) revealed a rapid and continuous response in g m within a few minutes. In most cases, both ferns showed rapid and significant responses of g m to changes in [CO2]. The largest changes (quote % decrease) were obtained when [CO2] was decreased from 400 to 200 μmol mol(-1). This is in contrast to angiosperms where an increase in g(m) is commonly observed at low [CO2]. Similarly, fern species observed little or no response of g(s) to changes in [CO2] whereas, a concomitant decline of g(m) and g(s) with [CO2] is often reported in angiosperms. Together, these results suggest that regulation of g(m) to [CO2] may differ between angiosperms and ferns.

  20. ATF3 Repression of BCL-XL Determines Apoptotic Sensitivity to HDAC Inhibitors across Tumor Types.

    Science.gov (United States)

    Chüeh, Anderly C; Tse, Janson W T; Dickinson, Michael; Ioannidis, Paul; Jenkins, Laura; Togel, Lars; Tan, BeeShin; Luk, Ian; Davalos-Salas, Mercedes; Nightingale, Rebecca; Thompson, Matthew R; Williams, Bryan R G; Lessene, Guillaume; Lee, Erinna F; Fairlie, Walter D; Dhillon, Amardeep S; Mariadason, John M

    2017-09-15

    Purpose: Histone deacetylase inhibitors (HDACi) are epigenome-targeting small molecules approved for the treatment of cutaneous T-cell lymphoma and multiple myeloma. They have also demonstrated clinical activity in acute myelogenous leukemia, non-small cell lung cancer, and estrogen receptor-positive breast cancer, and trials are underway assessing their activity in combination regimens including immunotherapy. However, there is currently no clear strategy to reliably predict HDACi sensitivity. In colon cancer cells, apoptotic sensitivity to HDACi is associated with transcriptional induction of multiple immediate-early (IE) genes. Here, we examined whether this transcriptional response predicts HDACi sensitivity across tumor type and investigated the mechanism by which it triggers apoptosis.Experimental Design: Fifty cancer cell lines from diverse tumor types were screened to establish the correlation between apoptotic sensitivity, induction of IE genes, and components of the intrinsic apoptotic pathway.Results: We show that sensitivity to HDACi across tumor types is predicted by induction of the IE genes FOS, JUN, and ATF3, but that only ATF3 is required for HDACi-induced apoptosis. We further demonstrate that the proapoptotic function of ATF3 is mediated through direct transcriptional repression of the prosurvival factor BCL-XL (BCL2L1) These findings provided the rationale for dual inhibition of HDAC and BCL-XL, which we show strongly cooperate to overcome inherent resistance to HDACi across diverse tumor cell types.Conclusions: These findings explain the heterogeneous responses of tumor cells to HDACi-induced apoptosis and suggest a framework for predicting response and expanding their therapeutic use in multiple cancer types. Clin Cancer Res; 23(18); 5573-84. ©2017 AACR. ©2017 American Association for Cancer Research.

  1. Nisqually - Early Detection Rapid Response, Monitoring and Mapping of High Priority Invasives with Refuge Weed Warriors 2006

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This project plan was to initiate a program for early detection and response, monitoring and mapping of invasive species on Grays Harbor NWR and continued current...

  2. A Flow Cytometry Method for Rapidly Assessing Mycobacterium tuberculosis Responses to Antibiotics with Different Modes of Action.

    Science.gov (United States)

    Hendon-Dunn, Charlotte Louise; Doris, Kathryn Sarah; Thomas, Stephen Richard; Allnutt, Jonathan Charles; Marriott, Alice Ann Neville; Hatch, Kim Alexandra; Watson, Robert James; Bottley, Graham; Marsh, Philip David; Taylor, Stephen Charles; Bacon, Joanna

    2016-07-01

    Current methods for assessing the drug susceptibility of Mycobacterium tuberculosis are lengthy and do not capture information about viable organisms that are not immediately culturable under standard laboratory conditions as a result of antibiotic exposure. We have developed a rapid dual-fluorescence flow cytometry method using markers for cell viability and death. We show that the fluorescent marker calcein violet with an acetoxy-methyl ester group (CV-AM) can differentiate between populations of M. tuberculosis growing at different rates, while Sytox green (SG) can differentiate between live and dead mycobacteria. M. tuberculosis was exposed to isoniazid or rifampin at different concentrations over time and either dual stained with CV-AM and SG and analyzed by flow cytometry or plated to determine the viability of the cells. Although similar trends in the loss of viability were observed when the results of flow cytometry and the plate counting methods were compared, there was a lack of correlation between these two approaches, as the flow cytometry analysis potentially captured information about cell populations that were unable to grow under standard conditions. The flow cytometry approach had an additional advantage in that it could provide insights into the mode of action of the drug: antibiotics targeting the cell wall gave a flow cytometry profile distinct from those inhibiting intracellular processes. This rapid drug susceptibility testing method could identify more effective antimycobacterials, provide information about their potential mode of action, and accelerate their progress to the clinic. Copyright © 2016 Hendon-Dunn et al.

  3. Rapid Genome-wide Recruitment of RNA Polymerase II Drives Transcription, Splicing, and Translation Events during T Cell Responses

    Directory of Open Access Journals (Sweden)

    Kathrin Davari

    2017-04-01

    Full Text Available Activation of immune cells results in rapid functional changes, but how such fast changes are accomplished remains enigmatic. By combining time courses of 4sU-seq, RNA-seq, ribosome profiling (RP, and RNA polymerase II (RNA Pol II ChIP-seq during T cell activation, we illustrate genome-wide temporal dynamics for ∼10,000 genes. This approach reveals not only immediate-early and posttranscriptionally regulated genes but also coupled changes in transcription and translation for >90% of genes. Recruitment, rather than release of paused RNA Pol II, primarily mediates transcriptional changes. This coincides with a genome-wide temporary slowdown in cotranscriptional splicing, even for polyadenylated mRNAs that are localized at the chromatin. Subsequent splicing optimization correlates with increasing Ser-2 phosphorylation of the RNA Pol II carboxy-terminal domain (CTD and activation of the positive transcription elongation factor (pTEFb. Thus, rapid de novo recruitment of RNA Pol II dictates the course of events during T cell activation, particularly transcription, splicing, and consequently translation.

  4. Rapid drawdown of Antarctica's Wordie Ice Shelf glaciers in response to ENSO/Southern Annular Mode-driven warming in the Southern Ocean

    Science.gov (United States)

    Walker, C. C.; Gardner, A. S.

    2017-10-01

    Here we investigate the largest acceleration in ice flow across all of Antarctica between ∼2008 InSAR and 2014 Landsat velocity mappings. This occurred in glaciers that used to feed into the Wordie Ice Shelf on the west Antarctic Peninsula, which rapidly disintegrated in ∼1989. Between 2008 and 2014, these glaciers experienced at least a threefold increase in surface elevation drawdown relative to the 2002-2008 time period. After ∼20 yrs of relative stability, it is unlikely that the ice shelf collapse played a role in the large response. Instead, we find that the rapid acceleration and surface drawdown is linked to enhanced melting at the ice-ocean boundary, attributable to changes in winds driven by global atmospheric circulation patterns, namely the El Niño-Southern Oscillation (ENSO) and Southern Annular Mode (SAM), linking changes in grounded ice to atmospheric-driven ocean warming.

  5. Cytotoxicity and Apoptotic Activity of Ficus pseudopalma Blanco ...

    African Journals Online (AJOL)

    Purpose: To investigate the cytotoxic and apoptotic activities of Ficus pseudopalma (FP) Blanco leaf extracts against normal human FSE cells and human prostate PRST2 cancer cell line. Methods: FP leaves were extracted with 95 % ethanol, and partitioned with chloroform, ethylacetate, and water. The presence of ...

  6. In vitro Anti-proliferative and Apoptotic Activities of Eurycoma ...

    African Journals Online (AJOL)

    Purpose: To investigate the anti-proliferative, apoptotic and differentiating activities of Eurycoma longifolia root extracts on HL-60 leukemic cells. Methods: HL-60 cells were treated with different partially purified sub-fractions (F1 – F3) derived from the resin chromatography of the crude methanol root extract of E. longifolia ...

  7. Apoptotic gene analysis in idiopathic talipes equinovarus (clubfoot).

    Science.gov (United States)

    Ester, Audrey R; Tyerman, Gayle; Wise, Carol A; Blanton, Susan H; Hecht, Jacqueline T

    2007-09-01

    Idiopathic talipes equinovarus, also known as clubfoot, is a common birth defect occurring in one of 1000 live births. It is a complex disorder in which multiple genes and environmental factors may play an etiologic role. Several chromosomal deletion regions, including 2q31-33, are associated with talipes equinovarus and may harbor genes that contribute to the idiopathic talipes equinovarus phenotype. Previously, two STRs in the 2q31-33, GATA149B10 and D2S1371, showed linkage with association to idiopathic talipes equinovarus. Single nucleotide polymorphisms (SNPs) in three apoptotic genes (Casp8, Casp10, and CFLAR) near GATA149B10 were genotyped in idiopathic talipes equinovarus families. rs3731714 in Casp10 showed linkage with association, suggesting variation in the apoptotic gene pathway, which is important in limb morphogenesis, and may play a role in the development of idiopathic talipes equinovarus. We genotyped SNPs spanning seven apoptotic genes-Casp3, Casp8, Casp9, Casp10, Bid, Bcl-2 and Apaf1-in 210 simplex trios and 139 multiplex families and tested for link-age and association to idiopathic talipes equinovarus. One SNP in each of the genes provided suggestive evidence of association with idiopathic talipes equinovarus. Several haplotypes constructed from these SNPs displayed altered transmission. These data suggest genetic variation in apoptotic genes may play a role in development of idiopathic talipes equinovarus.

  8. Role of airway epithelium in engulfing apoptotic eosinophils | Alenzi ...

    African Journals Online (AJOL)

    Role of airway epithelium in engulfing apoptotic eosinophils. FQ Alenzi. Abstract. No Abstract. Full Text: EMAIL FULL TEXT EMAIL FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT · http://dx.doi.org/10.4314/njm.v18i2.45054 · AJOL African Journals Online. HOW TO USE AJOL... for Researchers · for ...

  9. Growth inhibitory, apoptotic and anti-inflammatory activities ...

    Indian Academy of Sciences (India)

    apoptotic activity on many types of cancer cell lines. For instance, CDDO induces apoptosis of acute myelogenous leukaemia (Konopleva et al. 2004), osteosarcoma (Ito et al. 2001) and skin cancer (Hail et al. 2004). The methyl ester of CDDO, CDDO-Me, triggers apoptosis in lung carcinoma. (Kim et al. 2002) and prostate ...

  10. Apoptotic cells as sources for biologically active oxidized phospholipids.

    Science.gov (United States)

    Kadl, Alexandra; Bochkov, Valery N; Huber, Joakim; Leitinger, Norbert

    2004-04-01

    Acute inflammation is characterized by an accumulation of polymorphonuclear cells (PMNs), generation of reactive oxygen species, subsequent apoptosis of PMNs, and finally phagocytosis of apoptotic cells by macrophages. Recently, it has been demonstrated that during apoptosis oxidation of membrane phospholipids, especially phosphatidylserine, occurs. Moreover, we have shown that membrane vesicles released from apoptotic cells contain biologically active oxidized phospholipids. The involvement of oxidized phospholipids in the development of atherosclerosis, which is described as a chronic inflammatory disease, is increasingly recognized. These oxidized phospholipids were shown to induce several proinflammatory genes, such as monocyte chemoattractant protein 1 or interleukin-8, and it is hypothesized that lipid oxidation products also play a role in other chronic inflammatory disorders. On the other hand, oxidized phospholipids were shown to exert antiendotoxin effects by inhibiting lipopolysaccharide-induced signaling, representing a possible feedback loop during gram-negative infection. Additionally, it has been described that oxidized phospholipids are capable of inducing genes such as heme oxygenase-1 that are important for the resolution of acute inflammation. Moreover, oxidized phospholipids serve as recognition signals on apoptotic cells facilitating phagocytosis. In this review, we discuss the hypothesis that oxidized phospholipids generated in apoptotic cells (a) propagate chronic inflammation and (b) contribute to the resolution of acute inflammation.

  11. Detection of apoptotic cells using propidium iodide staining

    NARCIS (Netherlands)

    Newbold, Andrea; Martin, Ben P.; Cullinane, Carleen; Bots, Michael

    2014-01-01

    Flow cytometry assays are often used to detect apoptotic cells in in vitro cultures. Depending on the experimental model, these assays can also be useful in evaluating apoptosis in vivo. In this protocol, we describe a propidium iodide (PI) flow cytometry assay to evaluate B-cell lymphomas that have

  12. Elimination of apoptotic boar spermatozoa using magnetic activated cell sorting

    Directory of Open Access Journals (Sweden)

    Janko Mrkun

    2014-01-01

    Full Text Available One of the features of apoptosis is the externalization of phosphatidylserine which could be used to remove apoptotic cells from semen preparations. Magnetic-activated cell sorting using annexin V-conjugated microbeads which bind to phosphatidylserine could be used to enhance semen quality. Twelve boar semen samples after 3 days of liquid storage at 16­­–17 °C were subjected to magnetic-activated cell sorting. Bound and unbound fractions and control samples were subjected to flow cytometry following the staining of spermatozoa with Annexin V conjugated with Alexa Fluor 488 and propidium iodide. Four subpopulations were obtained: live, early apoptotic live, late apoptotic, early necrotic dead and late necrotic dead. The frequency of early apoptotic and late necrotic spermatozoa was significantly higher (P P P P < 0.05 lower proportion of morphologically normal spermatozoa was observed in both fractions compared to control (67.2 ± 17.0%. Boar spermatozoa were separated by the above method for the first time, however, the results showed this method to be inappropriate for boar semen separation under the tested conditions.

  13. Apoptotic index for prediction of postmolar gestational trophoblastic neoplasia.

    Science.gov (United States)

    Braga, Antonio; Maestá, Izildinha; Rocha Soares, Renan; Elias, Kevin M; Custódio Domingues, Maria Aparecida; Barbisan, Luis Fernando; Berkowitz, Ross S

    2016-09-01

    Although 85% of patients with a complete hydatidiform mole achieve spontaneous remission after a few months, 15% of them will experience gestational trophoblastic neoplasia, which requires chemotherapy. To date, there is no biomarker to predict post-molar gestational trophoblastic neoplasia before the initiation of human chorionic gonadotropin surveillance. The purpose of this study was to assess the relationship between the expression of apoptosis markers in the molar villous trophoblasts and the subsequent development of gestational trophoblastic neoplasia after the evacuation of a complete hydatidiform mole. This was a retrospective cohort study of patients with complete hydatidiform mole who were diagnosed, treated, and followed at the Center of Trophoblastic Diseases (Botucatu/São Paulo State and Rio de Janeiro/Rio de Janeiro State, Brazil) from 1995-2014. Patients were divided temporally into derivation (1995-2004) and validation (2005-2014) cohorts. Immunohistochemistry was used to examine tissue expression of the apoptosis inhibitor survivin or the pro-apoptotic enzyme caspase-3. Survivin stains for cytoplasmic and nuclear expression were evaluated independently. Caspase-3 expression was measured as an apoptotic index of positive staining cells over negative staining cells multiplied by 100. Receiver operating characteristic curves were then constructed, and the area under the curve was calculated to test the performance characteristics of the staining to predict the subsequent development of gestational trophoblastic neoplasia. The final study population comprised 780 patients, with 390 patients in each temporal cohort: 590 patients entered spontaneous remission, and 190 patients experienced post-molar gestational trophoblastic neoplasia. Neither nuclear nor cytoplasmic survivin expression performed well as a predictor of subsequent gestational trophoblastic neoplasia. The caspase-3 apoptotic index was a strong risk factor for subsequent gestational

  14. Potent, transient inhibition of BCR-ABL with dasatinib 100 mg daily achieves rapid and durable cytogenetic responses and high transformation-free survival rates in chronic phase chronic myeloid leukemia patients with resistance, suboptimal response or intolerance to imatinib

    Science.gov (United States)

    Shah, Neil P.; Kim, Dong-Wook; Kantarjian, Hagop; Rousselot, Philippe; Llacer, Pedro Enrique Dorlhiac; Enrico, Alicia; Vela-Ojeda, Jorge; Silver, Richard T.; Khoury, Hanna Jean; Müller, Martin C.; Lambert, Alexandre; Matloub, Yousif; Hochhaus, Andreas

    2010-01-01

    Background Dasatinib 100 mg once daily achieves intermittent BCR-ABL kinase inhibition and is approved for chronic-phase chronic myeloid leukemia patients resistant or intolerant to imatinib. To better assess durability of response to and tolerability of dasatinib, data from a 2-year minimum follow-up for a dose-optimization study in chronic-phase chronic myeloid leukemia are reported here. Design and Methods In a phase 3 study, 670 chronic-phase chronic myeloid leukemia patients with resistance, intolerance, or suboptimal response to imatinib were randomized to dasatinib 100 mg once-daily, 50 mg twice-daily, 140 mg once-daily, or 70 mg twice-daily. Results Data from a 2-year minimum follow-up demonstrate that dasatinib 100 mg once daily achieves major cytogenetic response and complete cytogenetic response rates comparable to those in the other treatment arms, and reduces the frequency of key side effects. Comparable 2-year progression-free survival and overall survival rates were observed (80% and 91%, respectively, for 100 mg once daily, and 75%–76% and 88%–94%, respectively, in other arms). Complete cytogenetic responses were achieved rapidly, typically by 6 months. In patients treated with dasatinib 100 mg once daily for 6 months without complete cytogenetic response, the likelihood of achieving such a response by 2 years was 50% for patients who had achieved a partial cytogenetic response, and only 8% or less for patients with minor, minimal, or no cytogenetic response. Less than 3% of patients suffered disease transformation to accelerated or blast phase. Conclusions Intermittent kinase inhibition can achieve rapid and durable responses, indistinguishable from those achieved with more continuous inhibition. PMID:20139391

  15. Fatty acid amide hydrolase inhibitors produce rapid anti-anxiety responses through amygdala long-term depression in male rodents.

    Science.gov (United States)

    Duan, Tingting; Gu, Ning; Wang, Ying; Wang, Feng; Zhu, Jie; Fang, Yiru; Shen, Yuan; Han, Jing; Zhang, Xia

    2017-06-01

    Pathological anxiety is the most common type of psychiatric disorder. The current first-line anti-anxiety treatment, selective serotonin/noradrenaline reuptake inhibitors, produces a delayed onset of action with modest therapeutic and substantial adverse effects, and long-term use of the fast-acting anti-anxiety benzodiazepines causes severe adverse effects. Inhibition of the fatty acid amide hydrolase (FAAH), the endocannabinoid N-arachidonoylethanolamine (AEA) degradative enzyme, produces anti-anxiety effects without substantial "unwanted effects" of cannabinoids, but its anti-anxiety mechanism is unclear. We used behavioural, electrophysiological, morphological and mutagenesis strategies to assess the anti-anxiety mechanism of the FAAH inhibitors PF3845 and URB597. PF3845 exerts rapid and long-lasting anti-anxiety effects in mice exposed acutely to stress or chronically to the stress hormone corticosterone. PF3845-induced anti-anxiety effects and in vivo long-term depression (LTD) of synaptic strength at the prefrontal cortical input onto the basolateral amygdala neurons are abolished in mutant mice without CB1 cannabinoid receptors (CB1R) in brain astroglial cells, but are conserved in mice without CB1R in glutamatergic neurons. Blockade of glutamate N-methyl-D-aspartate receptors and of synaptic trafficking of glutamate AMPA receptors also abolishes PF3845-induced anti-anxiety effects in mice and LTD production in rats. URB597 produces similar anti-anxiety effects, which are abolished by blockade of LTD induction in mice. The determination of FAAH in which types of brain cells contribute to AEA degradation for the maintenance of amygdala interstitial AEA has yet to be determined. We propose that the rapid anti-anxiety effects of FAAH inhibition are due to AEA activation of astroglial CB1R and subsequent basolateral amygdala LTD in vivo.

  16. Response of canopy nitrogen uptake to a rapid decrease in bulk nitrate deposition in two eastern Canadian boreal forests.

    Science.gov (United States)

    Houle, D; Marty, C; Duchesne, L

    2015-01-01

    A few studies have reported a recent and rapid decline in NO3(-) deposition in eastern North America. Whether this trend can be observed at remote boreal sites with low rates of N deposition and how it could impact canopy uptake (CU) of N remain unknown. Here we report trends between 1997/1999 and 2012 for precipitation, throughfall N deposition as well as inorganic N CU for two boreal forest sites of Quebec, Canada, with contrasted N deposition rates and tree species composition. NO3(-) bulk deposition declined by approximately 50% at both sites over the studied period while no change was observed for NH4(+). As a result, the contribution of NH4(+) to inorganic N deposition changed from ~33% to more than 50% during the study period. On average, 52-59% of N deposition was intercepted by the canopy, the retention being higher for NH4(+) (60-67%) than for NO3(-) (45-54%). The decrease in NO3(-) bulk deposition and the increase in the NH4(+):NO3(-) ratio had important impacts on N-canopy interactions. The contribution of NH4(+) CU to that of total inorganic N CU increased at both sites but the trend was significant only at Tirasse (lowest N deposition). At this site, absolute NO3(-) CU significantly decreased (as did total N CU) during the study period, a consequence of the strong relationship (r(2) = 0.88) between NO3(-) bulk deposition and NO3(-) CU. Our data suggest that N interactions with forest canopies may change rapidly with changes in N deposition as well as with tree species composition.

  17. When falsified medicines enter the supply chain: description of an incident in Kenya and lessons learned for rapid response.

    Science.gov (United States)

    Cohn, Jennifer; von Schoen-Angerer, Tido; Jambert, Elodie; Arreghini, Guido; Childs, Michelle

    2013-01-01

    Falsified and substandard medicines present serious concerns for public health. We describe an event that occurred in late 2011 involving falsified antiretroviral medicines found in the supplies of Médecins Sans Frontières (MSF) projects in Kenya. We discuss factors contributing to these falsified medicines entering the supply chain as well as the response by MSF and others. We make recommendations to help defend against future episodes of entry of falsified medicines into the supply chain as well as comments on appropriate responses in cases of falsified medicines.

  18. Postconditioning with metformin attenuates apoptotic events in cardiomyoblasts associated with ischemic reperfusion injury.

    Science.gov (United States)

    Ramachandran, Rajesh; Saraswathi, Mini

    2017-12-01

    Ischemic postconditioning is considered as a potent method to combat ischemic reperfusion injury than preconditioning and rapid initiation of reperfusion with potent antioxidant compounds can be one of the most effective treatments to reduce the infarct size and behavioral deficits as a result of ischemic insult. The present study aims to determine the postconditioning effects of metformin in experimental ischemia. H9C2 cells were subjected to experimental ischemia and reperfused with metformin. Viability, oxidative stress and apoptotic events were determined. Postconditioning with Metformin effectively maintained cell viability and membrane stability of H9C2 cardiomyoblast cells from ischemic injury at a concentration of 2.5 µg/mL. Decrease in cell death was established viz fluorescent staining and Annexin V-FITC flow cytometric analysis. In metformin treated ischemic cells the DNA fragmentation and comet length were significantly reduced (p=.0001) affirming antiapoptotic activity of metformin. There was an increase in protein carbonyl content and decrease in nitrate levels after ischemic injuries which were alleviated with metformin treatment. Wound closure was enhanced by metformin treatment. Metformin synchronized the apoptotic proteins such as FasL and antiapoptotic proteins such as Bcl2, Bcl-xL and p21 which can be attributed as the major mechanism of cardioprotection. The results envisage therapeutic potential of metformin at lower concentrations as an effective postischemic conditioning agent. © 2017 John Wiley & Sons Ltd.

  19. Tight Sequestration of BH3 Proteins by BCL-xL at Subcellular Membranes Contributes to Apoptotic Resistance

    Directory of Open Access Journals (Sweden)

    Jessie Pécot

    2016-12-01

    Full Text Available Anti-apoptotic BCL-2 family members bind to BH3-only proteins and multidomain BAX/BAK to preserve mitochondrial integrity and maintain survival. Whereas inhibition of these interactions is the biological basis of BH3-mimetic anti-cancer therapy, the actual response of membrane-bound protein complexes to these compounds is currently ill-defined. Here, we find that treatment with BH3 mimetics targeting BCL-xL spares subsets of cells with the highest levels of this protein. In intact cells, sequestration of some pro-apoptotic activators (including PUMA and BIM by full-length BCL-xL is much more resistant to derepression than previously described in cell-free systems. Alterations in the BCL-xL C-terminal anchor that impacts subcellular membrane-targeting and localization dynamics restore sensitivity. Thus, the membrane localization of BCL-xL enforces its control over cell survival and, importantly, limits the pro-apoptotic effects of BH3 mimetics by selectively influencing BCL-xL binding to key pro-apoptotic effectors.

  20. Apoptotic inducers activate the release of D-aspartate through a hypotonic stimulus-triggered mechanism in PC12 cells.

    Science.gov (United States)

    Furuchi, Takemitsu; Suzuki, Toshiyuki; Sekine, Masae; Katane, Masumi; Homma, Hiroshi

    2009-10-15

    We have characterized release of D-aspartate (D-Asp), a regulator of hormone synthesis and secretion, via a volume-sensitive organic anion channel (VSOC) in PC12 cells by studying its response to apoptotic stimuli. PC12 cells have been demonstrated to endogenously synthesize D-Asp. Apoptotic inducers, including staurosporin (STS), tumor necrosis factor (TNF)-alpha, H(2)O(2), and C2-ceramide, activate the release of D-Asp through a hypotonic stimulus-triggered mechanism. Putative blockers of the anion channel, 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB) and 4,4'-diisothiocyanostilbene-2,2'-sulphonic acid (DIDS), significantly inhibited stress-induced D-Asp release under hypotonic conditions following the application of apoptotic inducers. Hypotonic conditions are essential for activation by apoptotic inducers. Phorbol 12-mirystate 13-acetate and the Ca(2+) ionophore A23187 increased D-Asp efflux via the VSOC, implying the involvement of intracellular Ca(2+) in the activation of the D-Asp efflux. However, hypotonic stress and STS had no effect on the concentration of intracellular Ca(2+) in PC12 cells. Furthermore, an unknown EGTA-sensitive factor(s), other than Ca(2+), and peroxynitrite may play pivotal roles in STS-enhanced D-Asp release.

  1. Economic and clinical effects of evaluating rapid viral response to peginterferon alfa-2b plus ribavirin for the initial treatment of chronic hepatitis C.

    Science.gov (United States)

    Wong, John B; Davis, Gary L; McHutchison, John G; Manns, Michael P; Albrecht, Janice K

    2003-11-01

    Evaluation of 12-wk viral response to initial antiviral therapy for chronic hepatitis C has been recommended to minimize antiviral-associated morbidity and costs. The aim of this study was to examine the economic and clinical effects of evaluating rapid viral response during antiviral therapy for treatment naive chronic hepatitis C patients. We applied viral response and drug dosage from an international randomized clinical trial of ribavirin plus peginterferon alfa-2b or ribavirin plus interferon alfa-2b to a previously published computer cohort simulation to project lifelong clinical and economic outcomes. Natural history and economic estimates were based on published literature, expert panel estimates, and actual variable and reimbursement cost data. The assessment of 12-wk rapid viral response reduced antiviral treatment duration by 40-44% and antiviral costs by 44-45% (savings of $15,116-16,268 for peginterferon plus ribavirin and $8300 for interferon plus ribavirin) compared to full 48-wk dosing. With the 12-wk evaluation, the marginal cost-effectiveness of peginterferon plus ribavirin versus interferon plus ribavirin was $13,600-22,800 compared with $14,600-25,000 per discounted quality adjusted life-year gained with the 24-wk evaluation. For genotype 1, hepatitis C infected patients, 12-wk testing for peginterferon plus ribavirin remaining preferred and cost-effective compared with interferon plus ribavirin. For genotype 2 or 3, hepatitis C infected patients, 12-wk testing yielded similar results to those of 24-wk treatment. Assessment of 12-wk viral response in genotype 1, hepatitis C infected patients should reduce peginterferon plus ribavirin morbidity and costs and improve its cost-effectiveness; however, for genotype 2 and 3, hepatitis C infected patients, 12-wk testing and 24-wk treatment have similar outcomes. Decisions regarding continuation of antiviral treatment should also consider the variability in the accuracy of quantitative viral assays as

  2. Synthetic Toll-like receptor 4 (TLR4) and TLR7 ligands as influenza virus vaccine adjuvants induce rapid, sustained, and broadly protective responses.

    Science.gov (United States)

    Goff, Peter H; Hayashi, Tomoko; Martínez-Gil, Luis; Corr, Maripat; Crain, Brian; Yao, Shiyin; Cottam, Howard B; Chan, Michael; Ramos, Irene; Eggink, Dirk; Heshmati, Mitra; Krammer, Florian; Messer, Karen; Pu, Minya; Fernandez-Sesma, Ana; Palese, Peter; Carson, Dennis A

    2015-03-01

    Current vaccines against influenza virus infection rely on the induction of neutralizing antibodies targeting the globular head of the viral hemagglutinin (HA). Protection against seasonal antigenic drift or sporadic pandemic outbreaks requires further vaccine development to induce cross-protective humoral responses, potentially to the more conserved HA stalk region. Here, we present a novel viral vaccine adjuvant comprised of two synthetic ligands for Toll-like receptor 4 (TLR4) and TLR7. 1Z105 is a substituted pyrimido[5,4-b]indole specific for the TLR4-MD2 complex, and 1V270 is a phospholipid-conjugated TLR7 agonist. Separately, 1Z105 induces rapid Th2-associated IgG1 responses, and 1V270 potently generates Th1 cellular immunity. 1Z105 and 1V270 in combination with recombinant HA from the A/Puerto Rico/8/1934 strain (rPR/8 HA) effectively induces rapid and sustained humoral immunity that is protective against lethal challenge with a homologous virus. More importantly, immunization with the combined adjuvant and rPR/8 HA, a commercially available split vaccine, or chimeric rHA antigens significantly improves protection against both heterologous and heterosubtypic challenge viruses. Heterosubtypic protection is associated with broadly reactive antibodies to HA stalk epitopes. Histological examination and cytokine profiling reveal that intramuscular (i.m.) administration of 1Z105 and 1V270 is less reactogenic than a squalene-based adjuvant, AddaVax. In summary, the combination of 1Z105 and 1V270 with a recombinant HA induces rapid, long-lasting, and balanced Th1- and Th2-type immunity; demonstrates efficacy in a variety of murine influenza virus vaccine