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Sample records for hypertonically challenged imcd3

  1. Urea-inducible Egr-1 transcription in renal inner medullary collecting duct (mIMCD3) cells is mediated by extracellular signal-regulated kinase activation.

    PubMed Central

    Cohen, D M

    1996-01-01

    Urea (200-400 milliosmolar) activates transcription, translation of, and trans-activation by the immediate-early gene transcription factor Egr-1 in a renal epithelial cell-specific fashion. The effect at the transcriptional level has been attributed to multiple serum response elements and their adjacent Ets motifs located within the Egr-1 promoter. Elk-1, a principal ternary complex factor and Ets domain-containing protein, is a substrate of the extracellular signal-regulated kinase (ERK) mitogen-activated protein kinases. In the renal medullary mIMCD3 cell line, urea (200-400 milliosmolar) activated both ERK1 and ERK2 as determined by in-gel kinase assay and immune-complex kinase assay of epitope-tagged] ERK1 and ERK2. Importantly, urea did not affect abundance of either ERK. Urea-inducible Egr-1 transcription was a consequence of ERK activation because the ERK-specific inhibitor, PD98059, abrogated transcription from the murine Egr-1 promoter in a luciferase reported gene assay. In addition, activators of protein kinase A, including forskolin and 8-Br-cAMP, which are known to inhibit ERK-mediated events, also inhibited urea-inducible Egr-1 transcription. Furthermore, urea-inducible activation of the physiological ERK substrate and transcription factor, Elk-1, was demonstrated through transient cotransfection of a chimeric Elk-1/GAL4 expression plasmid and a GAL4-driven luciferase reporter plasmid. Taken together, these data indicate that, in mIMCD3 cells, urea activates ERKs and the ERK substrate, Elk-1, and that ERK inhibition abrogates urea-inducible Egr-1 transcription. These data are consistent with a model of urea-inducible renal medullary gene expression wherein sequential activation of ERKs and Elk-1 results in increased transcription of Egr-1 through serum response element/Ets motifs. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 PMID:8855340

  2. Hypertonic saline.

    PubMed

    Constable, P D

    1999-11-01

    A key feature in the successful resuscitation of dehydrated or endotoxemic ruminants is the total amount of sodium administered. Administration of small volumes of HS and HSD offer major advantages over large volumes of isotonic saline because HS and HSD do not require intravenous catheterization or periodic monitoring, and are therefore suitable for use in the field. Hypertonic saline and HSD exert their beneficial effect by rapidly increasing preload and transiently decreasing afterload. Contrary to early reports, HS and HSD decrease cardiac contractility and do not activate a pulmonary reflex. The osmolality of HS and HSD should be 2400 mOsm/L (7.2% NaCl solution, 8 times normal plasma osmolality). Use of HS and HSD solutions of different osmolality to 2400 mOsm/L should be avoided at all costs, as too low a tonicity removes the main advantages of HS (low cost, decreased infusion time), whereas too high a tonicity may cause rapid vasodilation and decreased cardiac contractility, resulting in death. Rapid administration (> 1 mL/kg-1/min-1) of HS (2400 mOsm/L) should be avoided, as the induced hypotension may be fatal when coupled with a transient decrease in cardiac contractility. For treating dehydrated adult ruminants, HS (2400 mOsm/L, 4-5 mL/kg i.v. over 4-5 minutes) should be administered through the jugular vein and the cow allowed to drink water. This means that 2 L of HS should be administered to adult cattle. HSD should be administered in conjunction with isotonic oral electrolyte solutions to all calves 8% or more dehydrated (eyes recessed > or = 4 mm into the orbit, cervical skin tent duration > 6 seconds) or calves with reduced cardiac output (fetlock temperature < 29 degrees C when housed at 10-24 degrees C). For treating dehydrated calves, HSD (2400 mOsm/L NaCl in 6% dextran-70, 4-5 mL/kg i.v. over 4-5 minutes) should be administered through the jugular vein and the calf allowed to suckle an isotonic oral electrolyte solution. This means that 120

  3. Tolerability of hypertonic injectables.

    PubMed

    Wang, Wei

    2015-07-25

    Injectable drug products are ideally developed as isotonic solutions. Often, hypertonic injectables may have to be marketed for a variety of reasons such as product solubilization and stabilization. A key concern during product formulation development is the local and systemic tolerability of hypertonic products upon injection. This report reviews and discusses the tolerability in terms of local discomfort, irritation, sensation of heat and pain, along with other observed side effects of hypertonicity in both in-vitro systems and in-vivo animal and human models. These side effects clearly depend on the degree of hypertonicity. The sensation of pain among different injection routes seems to follow this order: intramuscular>subcutaneous>intravenous or intravascular. It is recommended that the upper osmolality limit should be generally controlled under 600 mOsm/kg for drug products intended for intramuscular or subcutaneous injection. For drug products intended for intravenous or intravascular injection, the recommended upper limit should be generally controlled under 1,000 mOsm/kg for small-volume injections (≤ 100 mL) and 500 mOsm/kg for large-volume injections (>100mL). Several options are available for minimization of hypertonicity-induced pain upon product administration. PMID:26027488

  4. Effect of Atractylodes macrocephala on Hypertonic Stress-Induced Water Channel Protein Expression in Renal Collecting Duct Cells.

    PubMed

    Lee, Yong Pyo; Lee, Yun Jung; Lee, So Min; Yoon, Jung Joo; Kim, Hye Yoom; Kang, Dae Gill; Lee, Ho Sub

    2012-01-01

    Edema is a symptom that results from the abnormal accumulation of fluid in the body. The cause of edema is related to the level of aquaporin (AQP)2 protein expression, which regulates the reabsorption of water in the kidney. Edema is caused by overexpression of the AQP2 protein when the concentration of Na(+) in the blood increases. The rhizome of Atractylodes macrocephala has been used in traditional oriental medicine as a diuretic drug; however, the mechanism responsible for the diuretic effect of the aqueous extract from A. macrocephala rhizomes (AAMs) has not yet been identified. We examined the effect of the AAM on the regulation of water channels in the mouse inner medullary collecting duct (mIMCD)-3 cells under hypertonic stress. Pretreatment of AAM attenuates a hypertonicity-induced increase in AQP2 expression as well as the trafficking of AQP2 to the apical plasma membrane. Tonicity-responsive enhancer binding protein (TonEBP) is a transcription factor known to play a central role in cellular homeostasis by regulating the expression of some proteins, including AQP2. Western immunoblot analysis demonstrated that the protein and mRNA expression levels of TonEBP also decrease after AAM treatment. These results suggest that the AAM has a diuretic effect by suppressing water reabsorption via the downregulation of the TonEBP-AQP2 signaling pathway. PMID:23258995

  5. Role of nuclear factor of activated T-cells 5 in regulating hypertonic-mediated secretin receptor expression in kidney collecting duct cells.

    PubMed

    Chua, Oscar W H; Wong, Kenneth K L; Ko, Ben C; Chung, Sookja K; Chow, Billy K C; Lee, Leo T O

    2016-07-01

    A growing body of evidence suggests that secretin (SCT) is an important element in the osmoregulatory pathway. It is interesting to note that both SCT and its receptor (SCTR) gene are activated upon hyperosmolality in the kidney. However, the precise molecular mechanisms underlying the induction of the SCTR gene expression in response to changes in osmolality have yet to be clarified. Detailed DNA sequence analysis of the promoter regions of the SCTR gene reveals the presence of multiple osmotic response elements (ORE). The ORE is the binding site of a key osmosensitive transactivator, namely, the nuclear factor of activated T-cells 5 (NFAT5). SCTR and NFAT5 are co-expressed in the kidney cortex and medulla collecting duct cells. We therefore hypothesize that NFAT5 is responsible for modulating SCTR expression in hypertonic environments. In this study, we found hypertonicity stimulates the promoter activities and endogenous gene expression of SCTR in mouse kidney cortex collecting duct cells (M1) and inner medulla collecting duct cells (mIMCD3). The overexpression and silencing of NFAT5 further confirmed it to be responsible for the up-regulation of the SCTR gene under hypertonic conditions. A significant increase in the interaction between NFAT5 and the SCTR promoter was also observed following chromatin immunoprecipitation assay. In vivo, osmotic stress up-regulates the SCTR gene in the kidney cortex and medulla of wild-type mice, but does not do so in NFAT5(+/-) animals. Hence, this study provides comprehensive information on how NFAT5 regulates SCTR expression in different osmotic environments. PMID:27080132

  6. Hypertonicity: Pathophysiologic Concept and Experimental Studies.

    PubMed

    Argyropoulos, Christos; Rondon-Berrios, Helbert; Raj, Dominic S; Malhotra, Deepak; Agaba, Emmanuel I; Rohrscheib, Mark; Khitan, Zeid; Murata, Glen H; Shapiro, Joseph I; Tzamaloukas, Antonios H

    2016-01-01

    Disturbances in tonicity (effective osmolarity) are the major clinical disorders affecting cell volume. Cell shrinking secondary to hypertonicity causes severe clinical manifestations and even death. Quantitative management of hypertonic disorders is based on formulas computing the volume of hypotonic fluids required to correct a given level of hypertonicity. These formulas have limitations. The major limitation of the predictive formulas is that they represent closed system calculations and have been tested in anuric animals. Consequently, the formulas do not account for ongoing fluid losses during development or treatment of the hypertonic disorders. In addition, early comparisons of serum osmolality changes predicted by these formulas and observed in animals infused with hypertonic solutions clearly demonstrated that hypertonicity creates new intracellular solutes causing rises in serum osmolality higher than those predicted by the formulas. The mechanisms and types of intracellular solutes generated by hypertonicity and the effects of the solutes have been studied extensively in recent times. The solutes accumulated intracellularly in hypertonic states have potentially major adverse effects on the outcomes of treatment of these states. When hypertonicity was produced by the infusion of hypertonic sodium chloride solutions, the predicted and observed changes in serum sodium concentration were equal. This finding justifies the use of the predictive formulas in the management of hypernatremic states. PMID:27382523

  7. Hypertonicity: Pathophysiologic Concept and Experimental Studies

    PubMed Central

    Argyropoulos, Christos; Rondon-Berrios, Helbert; Raj, Dominic S; Malhotra, Deepak; Agaba, Emmanuel I; Rohrscheib, Mark; Khitan, Zeid; Murata, Glen H; Shapiro, Joseph I.

    2016-01-01

    Disturbances in tonicity (effective osmolarity) are the major clinical disorders affecting cell volume. Cell shrinking secondary to hypertonicity causes severe clinical manifestations and even death. Quantitative management of hypertonic disorders is based on formulas computing the volume of hypotonic fluids required to correct a given level of hypertonicity. These formulas have limitations. The major limitation of the predictive formulas is that they represent closed system calculations and have been tested in anuric animals. Consequently, the formulas do not account for ongoing fluid losses during development or treatment of the hypertonic disorders. In addition, early comparisons of serum osmolality changes predicted by these formulas and observed in animals infused with hypertonic solutions clearly demonstrated that hypertonicity creates new intracellular solutes causing rises in serum osmolality higher than those predicted by the formulas. The mechanisms and types of intracellular solutes generated by hypertonicity and the effects of the solutes have been studied extensively in recent times. The solutes accumulated intracellularly in hypertonic states have potentially major adverse effects on the outcomes of treatment of these states. When hypertonicity was produced by the infusion of hypertonic sodium chloride solutions, the predicted and observed changes in serum sodium concentration were equal. This finding justifies the use of the predictive formulas in the management of hypernatremic states. PMID:27382523

  8. Controlled aquaporin-2 expression in the hypertonic environment.

    PubMed

    Hasler, Udo

    2009-04-01

    The corticomedullary osmolality gradient is the driving force for water reabsorption occurring in the kidney. In the collecting duct, this gradient allows luminal water to move across aquaporin (AQP) water channels, thereby increasing urine concentration. However, this same gradient exposes renal cells to great osmotic challenges. These cells must constantly adapt to fluctuations of environmental osmolality that challenge cell volume and incite functional change. This implies profound alterations of cell phenotype regarding water permeability. AQP2 is an essential component of the urine concentration mechanism whose controlled expression dictates apical water permeability of collecting duct principal cells. This review focuses on changes of AQP2 abundance and trafficking in hypertonicity-challenged cells. Intracellular mechanisms governing these events are discussed and the biological relevance of altered AQP2 expression by hypertonicity is outlined. PMID:19211910

  9. Effects of hypertonic buffer composition on lymph node uptake and bioavailability of rituximab, after subcutaneous administration

    PubMed Central

    Fathallah, Anas M.; Turner, Michael R.; Balu-Iyer, Sathy V.

    2015-01-01

    Subcutaneous administration of biologics is highly desirable; however, incomplete bioavailability after sc administration remains a major challenge. In this work we investigated the effects of excipient dependent hyper-osmolarity on lymphatic uptake and plasma exposure of rituximab as a model protein. Using Swiss Webster (SW) mice as our animal model, we compared the effects of NaCl, mannitol and, O-Phospho-L-Serine (OPLS) on plasma concentration of rituximab over 5 days after sc administration. We observed an increase in plasma concentrations in animals administered rituximab in hypertonic buffer solutions, as compared to isotonic buffer. Bioavailability, as estimated by our pharmacokinetic model, increased from 29% in isotonic buffer to 54% in hypertonic buffer containing NaCl, to almost complete bioavailability in hypertonic buffers containing high dose OPLS or mannitol. This improvement in plasma exposure is due to improved lymphatic trafficking as evident from the increase in the fraction of dose trafficked through the lymph node in the presence of hypertonic buffers. The fraction of the dose trafficked through the lymphatic, as estimated by the model, increased from 0.05 % in isotonic buffer to 13% in hyper-tonic buffer containing NaCl to about 30% for hypertonic buffers containing high dose OPLS and mannitol. Our data suggests that hypertonic solutions may be a viable option to improve sc bioavailability. PMID:25377184

  10. Acute Hypertonicity Alters Aquaporin-2 Trafficking and Induces a MAPK-dependent Accumulation at the Plasma Membrane of Renal Epithelial Cells*

    PubMed Central

    Hasler, Udo; Nunes, Paula; Bouley, Richard; Lu, Hua A. J.; Matsuzaki, Toshiyuki; Brown, Dennis

    2008-01-01

    The unique phenotype of renal medullary cells allows them to survive and functionally adapt to changes of interstitial osmolality/tonicity. We investigated the effects of acute hypertonic challenge on AQP2 (aquaporin-2) water channel trafficking. In the absence of vasopressin, hypertonicity alone induced rapid (<10 min) plasma membrane accumulation of AQP2 in rat kidney collecting duct principal cells in situ, and in several kidney epithelial lines. Confocal microscopy revealed that AQP2 also accumulated in the trans-Golgi network (TGN) following hypertonic challenge. AQP2 mutants that mimic the Ser256-phosphorylated and -nonphosphorylated state accumulated at the cell surface and TGN, respectively. Hypertonicity did not induce a change in cytosolic cAMP concentration, but inhibition of either calmodulin or cAMP-dependent protein kinase A activity blunted the hypertonicity-induced increase of AQP2 cell surface expression. Hypertonicity increased p38, ERK1/2, and JNK MAPK activity. Inhibiting MAPK activity abolished hypertonicity-induced accumulation of AQP2 at the cell surface but did not affect either vasopressin-dependent AQP2 trafficking or hypertonicity-induced AQP2 accumulation in the TGN. Finally, increased AQP2 cell surface expression induced by hypertonicity largely resulted from a reduction in endocytosis but not from an increase in exocytosis. These data indicate that acute hypertonicity profoundly alters AQP2 trafficking and that hypertonicity-induced AQP2 accumulation at the cell surface depends on MAP kinase activity. This may have important implications on adaptational processes governing transcellular water flux and/or cell survival under extreme conditions of hypertonicity. PMID:18664568

  11. Diagnosis of hypertonic Oddi's sphincter dyskinesia

    SciTech Connect

    Varro, V.; Doebroente, Z.; Hajnal, F.; Csernay, L.; Nemessanyi, Z.; Lang, J.; Narai, G.; Szabo, E.

    1983-11-01

    The diagnostic possibility of hypertonic Oddi's sphincter dysfunction was evaluated in 100 cholecystectomized and 28 noncholecystectomized patients. An organic lesion interfering with free bile flow was ruled out in every case. The existence of the syndrome, i.e., the dysfunction of the Oddi's musculature, was verified using the morphine-choleretic test combined with either dynamic hepatobiliary scintigraphy or (in selected cases) percutaneous transhepatic cholangiography. Hypertonic Oddi's sphincter dyskinesia can be regarded as an independent clinical syndrome.

  12. Environmental Hypertonicity Causes Induction of Gluconeogenesis in the Air-Breathing Singhi Catfish, Heteropneustes fossilis

    PubMed Central

    Das, Manas; Banerjee, Bodhisattwa; Choudhury, Mahua G.; Saha, Nirmalendu

    2013-01-01

    The air-breathing singhi catfish (Heteropneustes fossilis) is frequently being challenged by different environmental insults such as hyper-ammonia, dehydration and osmotic stresses in their natural habitats throughout the year. The present study investigated the effect of hyperosmotic stress, due to exposure to hypertonic environment (300 mM mannitol) for 14 days, on gluconeogenesis in this catfish. In situ exposure to hypertonic environment led to significant stimulation of gluconeogenic fluxes from the perfused liver after 7 days of exposure, followed by further increase after 14 days in presence of three different potential gluconeogenic substrates (lactate, pyruvate and glutamate). Environmental hypertonicity also caused a significant increase of activities of key gluconeogenic enzymes, namely phosphoenolpyruvate carboxykinase, fructose 1, 6-bisphosphatase and glucose 6-phosphatase by about 2-6 fold in liver, and 3-6 fold in kidney tissues. This was accompanied by more abundance of enzyme proteins by about 1.8–3.7 fold and mRNAs by about 2.2–5.2 fold in both the tissues with a maximum increase after 14 days of exposure. Hence, the increase in activities of key gluconeogenic enzymes under hypertonic stress appeared to be as a result of transcriptional regulation of genes. Immunocytochemical analysis further confirmed the tissue specific localized expression of these enzymes in both the tissues with the possibility of expressing more in the same localized places. The induction of gluconeogenesis during exposure to environmental hypertonicity possibly occurs as a consequence of changes in hydration status/cell volume of different cell types. Thus, these adaptational strategies related to gluconeogenesis that are observed in this catfish under hypertonic stress probably help in maintaining glucose homeostasis and also for a proper energy supply to support metabolic demands mainly for ion transport and other altered metabolic processes under various

  13. 5'-Untranslated region of heat shock protein 70 mRNA drives translation under hypertonic conditions.

    PubMed

    Rocchi, Laura; Alfieri, Roberta R; Petronini, Pier Giorgio; Montanaro, Lorenzo; Brigotti, Maurizio

    2013-02-01

    In mammalian cells, adaptation to hypertonic conditions leads to the activation of an array of early (cell shrinkage, regulatory volume increase) and late (accumulation of compatible osmolytes) responses and increased level of HSPs (heat shock proteins). Protein synthesis is strongly inhibited few minutes after the hypertonic challenge as demonstrated in whole cells and as reproduced under controlled conditions in cell-free systems. Different mechanisms known to mediate the accumulation of HSP70, such as mRNA transcription and stabilization, require fully active protein synthesis. We show that the 5'-untranslated region of HSP70 messenger drives a hypertonicity-resistant translation (up to 0.425 osmol/kg of water), whereas cap-dependent protein synthesis is almost totally blocked under the same conditions. The results, obtained in cell-free systems and in whole cells, might help to explain why HSP70 is accumulated in cells when total protein synthesis is impaired. We also observed that translation initiated by viral IRES (from Cricket paralysis virus) is highly efficient in cells exposed to hyperosmolarity, suggesting that the resistance to hypertonic conditions is a more general feature of cap-independent translation. The described mechanism may also play a role in the control of translation of other messengers encoding for proteins involved in the adaptation to hypertonicity. PMID:23291172

  14. Pelvic floor hypertonic disorders: identification and management.

    PubMed

    Butrick, Charles W

    2009-09-01

    Patients with hypertonic pelvic floor disorders can present with pelvic pain or dysfunction. Each of the various syndromes will be discussed including elimination disorders, bladder pain syndrome/interstitial cystitis (BPS/IC), vulvodynia, vaginismus, and chronic pelvic pain. The symptoms and objective findings on physical examination and various diagnostic studies will be reviewed. Therapeutic options including physical therapy, pharmacologic management, and trigger point injections, as well as botulinum toxin injections will be reviewed in detail. PMID:19932423

  15. Monitoring the intracellular calcium response to a dynamic hypertonic environment

    NASA Astrophysics Data System (ADS)

    Huang, Xiaowen; Yue, Wanqing; Liu, Dandan; Yue, Jianbo; Li, Jiaqian; Sun, Dong; Yang, Mengsu; Wang, Zuankai

    2016-03-01

    The profiling of physiological response of cells to external stimuli at the single cell level is of importance. Traditional approaches to study cell responses are often limited by ensemble measurement, which is challenging to reveal the complex single cell behaviors under a dynamic environment. Here we report the development of a simple microfluidic device to investigate intracellular calcium response to dynamic hypertonic conditions at the single cell level in real-time. Interestingly, a dramatic elevation in the intracellular calcium signaling is found in both suspension cells (human leukemic cell line, HL-60) and adherent cells (lung cancer cell line, A549), which is ascribed to the exposure of cells to the hydrodynamic stress. We also demonstrate that the calcium response exhibits distinct single cell heterogeneity as well as cell-type-dependent responses to the same stimuli. Our study opens up a new tool for tracking cellular activity at the single cell level in real time for high throughput drug screening.

  16. Ionic imbalance, in addition to molecular crowding, abates cytoskeletal dynamics and vesicle motility during hypertonic stress

    PubMed Central

    Nunes, Paula; Roth, Isabelle; Meda, Paolo; Féraille, Eric; Brown, Dennis; Hasler, Udo

    2015-01-01

    Cell volume homeostasis is vital for the maintenance of optimal protein density and cellular function. Numerous mammalian cell types are routinely exposed to acute hypertonic challenge and shrink. Molecular crowding modifies biochemical reaction rates and decreases macromolecule diffusion. Cell volume is restored rapidly by ion influx but at the expense of elevated intracellular sodium and chloride levels that persist long after challenge. Although recent studies have highlighted the role of molecular crowding on the effects of hypertonicity, the effects of ionic imbalance on cellular trafficking dynamics in living cells are largely unexplored. By tracking distinct fluorescently labeled endosome/vesicle populations by live-cell imaging, we show that vesicle motility is reduced dramatically in a variety of cell types at the onset of hypertonic challenge. Live-cell imaging of actin and tubulin revealed similar arrested microfilament motility upon challenge. Vesicle motility recovered long after cell volume, a process that required functional regulatory volume increase and was accelerated by a return of extracellular osmolality to isosmotic levels. This delay suggests that, although volume-induced molecular crowding contributes to trafficking defects, it alone cannot explain the observed effects. Using fluorescent indicators and FRET-based probes, we found that intracellular ATP abundance and mitochondrial potential were reduced by hypertonicity and recovered after longer periods of time. Similar to the effects of osmotic challenge, isovolumetric elevation of intracellular chloride concentration by ionophores transiently decreased ATP production by mitochondria and abated microfilament and vesicle motility. These data illustrate how perturbed ionic balance, in addition to molecular crowding, affects membrane trafficking. PMID:26045497

  17. 21 CFR 349.16 - Ophthalmic hypertonicity agent.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Ophthalmic hypertonicity agent. 349.16 Section 349.16 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... Ophthalmic hypertonicity agent. The active ingredient and its concentration in the product is as...

  18. 21 CFR 349.16 - Ophthalmic hypertonicity agent.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Ophthalmic hypertonicity agent. 349.16 Section 349.16 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE OPHTHALMIC DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 349.16 Ophthalmic hypertonicity agent. The...

  19. Mannitol versus hypertonic saline: Safety and efficacy of mannitol and hypertonic saline in sputum induction and bronchial hyperreactivity assessment.

    PubMed

    Alvarez-Puebla, M J; Olaguibel, J M; Almudevar, E; Echegoyen, A A; Vela, C; de Esteban, B

    2015-08-01

    Eosinophilic asthma phenotype predicts good response to corticosteroids and associates to asthmatic exacerbations. Sputum induction by hypertonic saline (HS) inhalation is technically demanding. Bronchial hyperresponsiveness (BHR) to osmotic agents indirectly mirrors active airway inflammation. We compared the safety and ability of HS and mannitol to induce sputum and measure BHR. We evaluated the stability of inflammatory phenotypes. We studied 35 non-smoking asthmatics randomized to undergo HS and mannitol challenges on 2 days 1 week apart. Sputum was sampled for cell analysis and phenotyped as eosinophilic (≥3% eosinophils) and non-eosinophilic (<3%) asthma. Nineteen subjects had BHR to mannitol and nine of them also had BHR to HS. Drops in forced expiratory volume in 1 s were higher from HS challenge than from mannitol challenge. Adequate sputum samples were obtained from 80% subjects (68% mannitol and 71% HS). Eosinophils and macrophages from both challenges correlated. Neutrophils were higher in sputum from HS. Ninety percent samples were equally phenotyped with HS and mannitol. Fractional exhaled nitric oxide, sputum eosinophils and BHR correlated in both challenges. HS and mannitol showed similar capacity to produce valuable sputum samples. BHR to both osmotic stimuli partially resembled airway eosinophilic inflammation but mannitol was more sensitive than HS to assess BHR. Eosinophilic phenotype remained stable in most patients with both stimuli. PMID:25761367

  20. Therapeutic effects of compound hypertonic saline on rats with sepsis.

    PubMed

    Dong, Fang; Chen, Wei; Xu, Liang; Wang, Huabing; Lu, Huizhi

    2014-01-01

    Sepsis is one of the major causes of death and is the biggest obstacle preventing improvement of the success rate in curing critical illnesses. Currently, isotonic solutions are used in fluid resuscitation technique. Several studies have shown that hypertonic saline applied in hemorrhagic shock can rapidly increase the plasma osmotic pressure, facilitate the rapid return of interstitial fluid into the blood vessels, and restore the effective circulating blood volume. Here, we established a rat model of sepsis by using the cecal ligation and puncture approach. We found that intravenous injection of hypertonic saline dextran (7.5% NaCl/6% dextran) after cecal ligation and puncture can improve circulatory failure at the onset of sepsis. We found that the levels of tumor necrosis factor-α, interleukin-1β, interleukin-6 and intracellular adhesion molecule 1 levels in the lung tissue of cecal ligation and puncture rats treated with hypertonic saline dextran were significantly lower than the corresponding levels in the control group. We inferred that hypertonic saline dextran has a positive immunoregulatory effect and inhibits the overexpression of the inflammatory response in the treatment of sepsis. The percentage of neutrophils, lung myeloperoxidase activity, wet to dry weight ratio of lung tissues, histopathological changes in lung tissues, and indicators of arterial blood gas analysis was significantly better in the hypertonic saline dextran-treated group than in the other groups in this study. Hypertonic saline dextran-treated rats had significantly improved survival rates at 9 and 18 h compared to the control group. Our results suggest that hypertonic saline dextran plays a protective role in acute lung injury caused after cecal ligation and puncture. In conclusion, hypertonic/hyperoncotic solutions have beneficial therapeutic effects in the treatment of an animal model of sepsis. PMID:24983672

  1. Monitoring the intracellular calcium response to a dynamic hypertonic environment

    PubMed Central

    Huang, Xiaowen; Yue, Wanqing; Liu, Dandan; Yue, Jianbo; Li, Jiaqian; Sun, Dong; Yang, Mengsu; Wang, Zuankai

    2016-01-01

    The profiling of physiological response of cells to external stimuli at the single cell level is of importance. Traditional approaches to study cell responses are often limited by ensemble measurement, which is challenging to reveal the complex single cell behaviors under a dynamic environment. Here we report the development of a simple microfluidic device to investigate intracellular calcium response to dynamic hypertonic conditions at the single cell level in real-time. Interestingly, a dramatic elevation in the intracellular calcium signaling is found in both suspension cells (human leukemic cell line, HL-60) and adherent cells (lung cancer cell line, A549), which is ascribed to the exposure of cells to the hydrodynamic stress. We also demonstrate that the calcium response exhibits distinct single cell heterogeneity as well as cell-type-dependent responses to the same stimuli. Our study opens up a new tool for tracking cellular activity at the single cell level in real time for high throughput drug screening. PMID:27004604

  2. Hypertonicity augments bullfrog taste nerve responses to inorganic salts.

    PubMed

    Beppu, Namie; Higure, Yoko; Mashiyama, Kazunori; Ohtubo, Yoshitaka; Kumazawa, Takashi; Yoshii, Kiyonori

    2012-06-01

    The tonicity of taste stimulating solutions has been usually ignored, though taste substances themselves yielded the tonicity. We investigated the effect of hypertonicity on bullfrog taste nerve responses to inorganic salts by adding nonelectrolytes such as urea and sucrose that elicited no taste nerve responses. Here, we show that hypertonicity alters bullfrog taste nerve-response magnitude and firing pattern. The addition of urea or sucrose enhances the taste nerve-response magnitude to NaCl and shifts the concentration-response curve to the left. The effect of hypertonicity on responses to CaCl(2) is bimodal; hypertonicity suppresses CaCl(2) responses at concentrations less than ~30 mM and enhances them at concentrations greater than ~30 mM. The hypertonicity also enhances response magnitude to other monovalent salts. The extent of the enhancing effects depends on the difference between the mobility of the cation and anion in the salt. We quantitatively suggest that both the enhancing and suppressing effects result from the magnitude and direction of local circuit currents generated by diffusion potentials across tight junctions surrounding taste receptor cells. PMID:22422087

  3. Rat supraoptic neurones: the effects of locally applied hypertonic saline.

    PubMed

    Leng, G

    1980-07-01

    1. Extracellular action potentials were recorded from supraoptic neurones in lactating, urethane-anaesthetized rats. A microtap was used to apply a very small volume (about 10(-7) ml.) of hypertonic saline (1-4 M-NaCl) to the immediate neighbourhood of these units over about 1 min.2. Twenty-five of twenty-seven supraoptic neurones were excited by this local osmotic stimulus. The response of individual units was reversible and repeatable. Microtap applications of isotonic saline to supraoptic neurones were without observed effect.3. Continuously firing supraoptic neurones responded to hypertonic saline with a smooth acceleration in firing rate. Phasic neurones showed an increase in the over-all level of activity, and in particular, a prolongation of the active phases. Slow, irregularly firing cells responded either with a smooth acceleration in firing rate, or with phasic behaviour.4. The response to local hypertonic saline appears to be reasonably specific to the supraoptic nucleus. Of thirty-five neurones recorded close to the supraoptic nucleus but which were not antidromically activated from stimulation of the neural stalk, only nine responded to the local application of hypertonic saline.5. Similarities between the manner of response of supraoptic neurones to local application of hypertonic saline and the manner of their response to systemic increases in the osmotic pressure of blood plasma support the hypothesis that supraoptic neurones are osmosensitive. PMID:7441542

  4. Hypertonic saline dextran resuscitation of thermal injury.

    PubMed Central

    Horton, J W; White, D J; Baxter, C R

    1990-01-01

    Burn treatment requires large volumes of crystalloid, which may exacerbate burn-induced cardiopulmonary dysfunction. Small-volume hypertonic saline dextran (HSD) resuscitation has been used for effective treatment of several types of shock. In this study isolated coronary perfused guinea pig hearts were used to determine if HSD improved left ventricular contractile response to burn injuries. Parameters measured included left ventricular pressure (LVP) and maximal rate of LVP rise (+dP/dt max) and fall (-dP/dt max) at a constant preload. Third-degree scald burns comprising 45% of total body surface area (burn groups, N = 75), or 0% for controls (group 1, N = 25) were produced using a template device. In group 2, 25 burned guinea pigs were not fluid resuscitated and served as untreated burns; 20 burns were resuscitated with 4 mL lactated Ringer's (LR) solution/kg/% burn for 24 hours (group 3); additional burn groups were treated with an initial bolus of HSD (4 mL/kg, 2400 mOsm, sodium chloride, 6% dextran 70) followed by either 1, 2, or 4 mL LR/kg/% burn over 24 hours (groups 4, 5, and 6, respectively). Untreated burn injury significantly impaired cardiac function, as indicated by a fall in LVP (from 88 +/- 3 to 68 +/- 4 mmHg; p = 0.01) and +/- dP/dt max (from 1352 +/- 50 to 1261 +/- 90 and from 1150 +/- 35 to 993 +/- 59; p = 0.01, respectively) and a downward shift of LV function curves from those obtained from control hearts. Compared to untreated burns, hearts from burned animals treated with LR alone showed no significant improvement in cardiac function. However hearts from burned animals treated with HSD + 1 mL LR/kg/% burn had significantly higher LVP (79 +/- 4 vs. 68 +/- 4 mmHg, p = 0.01) and +/- dP/dt max (+dP/dt: 1387 +/- 60 vs. 1261 +/- 90 mmHg/sc, p = 0.01; -dP/dt: 1079 +/- 50 vs. 993 +/- 59 mmHg/sc, p = 0.01) than hearts from untreated burned animals and generated left ventricular function curves comparable to those calculated for hearts from control

  5. Hypertonicity compromises renal mineralocorticoid receptor signaling through Tis11b-mediated post-transcriptional control.

    PubMed

    Viengchareun, Say; Lema, Ingrid; Lamribet, Khadija; Keo, Vixra; Blanchard, Anne; Cherradi, Nadia; Lombès, Marc

    2014-10-01

    The mineralocorticoid receptor (MR) mediates the Na(+)-retaining action of aldosterone. MR is highly expressed in the distal nephron, which is submitted to intense variations in extracellular fluid tonicity generated by the corticopapillary gradient. We previously showed that post-transcriptional events control renal MR abundance. Here, we report that hypertonicity increases expression of the mRNA-destabilizing protein Tis11b, a member of the tristetraprolin/ZFP36 family, and thereby, decreases MR expression in renal KC3AC1 cells. The 3'-untranslated regions (3'-UTRs) of human and mouse MR mRNA, containing several highly conserved adenylate/uridylate-rich elements (AREs), were cloned downstream of a reporter gene. Luciferase activities of full-length or truncated MR Luc-3'-UTR mutants decreased drastically when cotransfected with Tis11b plasmid, correlating with an approximately 50% shorter half-life of ARE-containing transcripts. Using site-directed mutagenesis and RNA immunoprecipitation, we identified a crucial ARE motif within the MR 3'-UTR, to which Tis11b must bind for destabilizing activity. Coimmunoprecipitation experiments suggested that endogenous Tis11b physically interacts with MR mRNA in KC3AC1 cells, and Tis11b knockdown prevented hypertonicity-elicited repression of MR. Moreover, hypertonicity blunted aldosterone-stimulated expression of glucocorticoid-induced leucine-zipper protein and the α-subunit of the epithelial Na(+) channel, supporting impaired MR signaling. Challenging the renal osmotic gradient by submitting mice to water deprivation, diuretic administration, or high-Na(+) diet increased renal Tis11b and decreased MR expression, particularly in the cortex, thus establishing a mechanistic pathway for osmotic regulation of MR expression in vivo. Altogether, we uncovered a mechanism by which renal MR expression is regulated through mRNA turnover, a post-transcriptional control that seems physiologically relevant. PMID:24700863

  6. Hypertonicity Compromises Renal Mineralocorticoid Receptor Signaling through Tis11b-Mediated Post-Transcriptional Control

    PubMed Central

    Viengchareun, Say; Lema, Ingrid; Lamribet, Khadija; Keo, Vixra; Blanchard, Anne

    2014-01-01

    The mineralocorticoid receptor (MR) mediates the Na+-retaining action of aldosterone. MR is highly expressed in the distal nephron, which is submitted to intense variations in extracellular fluid tonicity generated by the corticopapillary gradient. We previously showed that post-transcriptional events control renal MR abundance. Here, we report that hypertonicity increases expression of the mRNA-destabilizing protein Tis11b, a member of the tristetraprolin/ZFP36 family, and thereby, decreases MR expression in renal KC3AC1 cells. The 3′-untranslated regions (3′-UTRs) of human and mouse MR mRNA, containing several highly conserved adenylate/uridylate-rich elements (AREs), were cloned downstream of a reporter gene. Luciferase activities of full-length or truncated MR Luc-3′-UTR mutants decreased drastically when cotransfected with Tis11b plasmid, correlating with an approximately 50% shorter half-life of ARE-containing transcripts. Using site-directed mutagenesis and RNA immunoprecipitation, we identified a crucial ARE motif within the MR 3′-UTR, to which Tis11b must bind for destabilizing activity. Coimmunoprecipitation experiments suggested that endogenous Tis11b physically interacts with MR mRNA in KC3AC1 cells, and Tis11b knockdown prevented hypertonicity-elicited repression of MR. Moreover, hypertonicity blunted aldosterone-stimulated expression of glucocorticoid-induced leucine-zipper protein and the α-subunit of the epithelial Na+ channel, supporting impaired MR signaling. Challenging the renal osmotic gradient by submitting mice to water deprivation, diuretic administration, or high-Na+ diet increased renal Tis11b and decreased MR expression, particularly in the cortex, thus establishing a mechanistic pathway for osmotic regulation of MR expression in vivo. Altogether, we uncovered a mechanism by which renal MR expression is regulated through mRNA turnover, a post-transcriptional control that seems physiologically relevant. PMID:24700863

  7. Phosphoinositolphosphate (PIP) cascade induction by hypertonic stress of plant tissue

    SciTech Connect

    Srivastava, A.; Jacoby, B. )

    1989-04-01

    Inositol 1,4,5-trisphosphate (IP{sub 3}) was determined by competition with ({sup 3}H)-IP{sub 3} for binding to an IP{sub 3} specific protein. A hypertonic mannitol, sorbitol or lactose shock induced an increase in the rate of K{sup +} uptake and raised the IP{sub 3} content of Beta vulgaris slices, excised Vigna mungo and Sorghum bicolor roots, as well as attached V. mungo roots. Increased K{sup +} uptake could also be induced by compounds that artificially induce the PIP cascade, or mimic it's products. A hypertonic shock, administered to intact B. vulgaris slices, further enhanced the phosphorylation of a 20 kD protein in the plasmalemma. Maximal IP{sub 3} content was found 10 min after hypertonic induction and maximal K{sup +} uptake was obtained 10 min later. The effect of a continuous hypertonic treatment on IP{sub 3} content, but not on K{sup +} uptake, was transient. Li{sup +} decreased the rate of IP{sub 3} metabolism.

  8. Oral hypertonic saline causes transient fall of vasopressin in humans

    SciTech Connect

    Seckl, J.R.; Williams, D.M.; Lightman, S.L.

    1986-08-01

    After dehydration, oral rehydration causes a fall in plasma arginine vasopressin (AVP) that precedes changes in plasma osmolality. To investigate further the stimulus for this effect, its specificity, and association with thirst, six volunteers were deprived of water for 24 h and given a salt load on two separate occasions. On each study day they then drank rapidly 10 ml/kg of either tap water or hypertonic saline (360 mosmol/kg). There was a significant fall in plasma AVP from 2.0 +/- 0.3 to 1.2 +/- 0.4 pmol/l 5 min after drinking water and from 1.8 +/- 0.3 to 0.9 +/- 0.2 pmol/l after hypertonic saline. Plasma osmolality fell 30-60 min after water and was unchanged after saline. Plasma renin activity, oxytocin, and total protein all remained unchanged. All subjects reported diminished thirst after hypertonic saline. Gargling with water reduced thirst but did not affect plasma AVP. There appears to be a drinking-mediated neuroendocrine reflex that decreases plasma AVP irrespective of the osmolality of the liquid consumed. The sensation of thirst did not correlate with plasma osmolality and was not always related to plasma AVP concentration. AVP was measured by radioimmunoassay.

  9. Out-of-hospital Hypertonic Resuscitation After Traumatic Hypovolemic Shock

    PubMed Central

    Bulger, Eileen M.; May, Susanne; Kerby, Jeffery D.; Emerson, Scott; Stiell, Ian G.; Schreiber, Martin A.; Brasel, Karen J.; Tisherman, Samuel A.; Coimbra, Raul; Rizoli, Sandro; Minei, Joseph P.; Hata, J. Steven; Sopko, George; Evans, David C.; Hoyt, David B.

    2011-01-01

    Objective To determine whether out-of-hospital administration of hypertonic fluids would improve survival after severe injury with hemorrhagic shock. Background Hypertonic fluids have potential benefit in the resuscitation of severely injured patients because of rapid restoration of tissue perfusion, with a smaller volume, and modulation of the inflammatory response, to reduce subsequent organ injury. Methods Multicenter, randomized, blinded clinical trial, May 2006 to August 2008, 114 emergency medical services agencies in North America within the Resuscitation Outcomes Consortium. Inclusion criteria: injured patients, age ≥ 15 years with hypovolemic shock (systolic blood pressure ≤ 70 mm Hg or systolic blood pressure 71–90 mm Hg with heart rate ≥ 108 beats per minute). Initial resuscitation fluid, 250 mL of either 7.5% saline per 6% dextran 70 (hypertonic saline/dextran, HSD), 7.5% saline (hypertonic saline, HS), or 0.9% saline (normal saline, NS) administered by out-of-hospital providers. Primary outcome was 28-day survival. On the recommendation of the data and safety monitoring board, the study was stopped early (23% of proposed sample size) for futility and potential safety concern. Results A total of 853 treated patients were enrolled, among whom 62% were with blunt trauma, 38% with penetrating. There was no difference in 28-day survival—HSD: 74.5% (0.1; 95% confidence interval [CI], −7.5 to 7.8); HS: 73.0% (−1.4; 95% CI, −8.7–6.0); and NS: 74.4%, P = 0.91. There was a higher mortality for the postrandomization subgroup of patients who did not receive blood transfusions in the first 24 hours, who received hypertonic fluids compared to NS [28-day mortality—HSD: 10% (5.2; 95% CI, 0.4–10.1); HS: 12.2% (7.4; 95% CI, 2.5–12.2); and NS: 4.8%, P < 0.01]. Conclusion Among injured patients with hypovolemic shock, initial resuscitation fluid treatment with either HS or HSD compared with NS, did not result in superior 28-day survival. However

  10. Epinephrine Improves the Efficacy of Nebulized Hypertonic Saline in Moderate Bronchiolitis: A Randomised Clinical Trial

    PubMed Central

    Comino-Vazquez, Paloma; Palma-Zambrano, Encarnación; Bulo-Concellón, Rocio; Santos-Sánchez, Vanessa

    2015-01-01

    Background and Aims There is no evidence that the epinephrine-3% hypertonic saline combination is more effective than 3% hypertonic saline alone for treating infants hospitalized with acute bronchiolitis. We evaluated the efficacy of nebulized epinephrine in 3% hypertonic saline. Patients and Methods We performed a randomized, double-blind, placebo-controlled clinical trial in 208 infants hospitalized with acute moderate bronchiolitis. Infants were randomly assigned to receive nebulized 3% hypertonic saline with either 3 mL of epinephrine or 3 mL of placebo, administered every four hours. The primary outcome measure was the length of hospital stay. Results A total of 185 infants were analyzed: 94 in the epinephrine plus 3% hypertonic saline group and 91 in the placebo plus 3% hypertonic saline group. Baseline demographic and clinical characteristics were similar in both groups. Length of hospital stay was significantly reduced in the epinephrine group as compared with the placebo group (3.94 ±1.88 days vs. 4.82 ±2.30 days, P = 0.011). Disease severity also decreased significantly earlier in the epinephrine group (P = 0.029 and P = 0.036 on days 3 and 5, respectively). Conclusions In our setting, nebulized epinephrine in 3% hypertonic saline significantly shortens hospital stay in hospitalized infants with acute moderate bronchiolitis compared to 3% hypertonic saline alone, and improves the clinical scores of severity from the third day of treatment, but not before. Trial Registration EudraCT 2009-016042-57 PMID:26575036

  11. Hypertonic stress induces rapid and widespread protein damage in C. elegans.

    PubMed

    Burkewitz, Kris; Choe, Keith; Strange, Kevin

    2011-09-01

    Proteostasis is defined as the homeostatic mechanisms that maintain the function of all cytoplasmic proteins. We recently demonstrated that the capacity of the proteostasis network is a critical factor that defines the limits of cellular and organismal survival in hypertonic environments. The current studies were performed to determine the extent of protein damage induced by cellular water loss. Using worm strains expressing fluorescently tagged foreign and endogenous proteins and proteins with temperature-sensitive point mutations, we demonstrate that hypertonic stress causes aggregation and misfolding of diverse proteins in multiple cell types. Protein damage is rapid. Aggregation of a polyglutamine yellow fluorescent protein reporter is observable with <1 h of hypertonic stress, and aggregate volume doubles approximately every 10 min. Aggregate formation is irreversible and occurs after as little as 10 min of exposure to hypertonic conditions. To determine whether endogenous proteins are aggregated by hypertonic stress, we quantified the relative amount of total cellular protein present in detergent-insoluble extracts. Exposure for 4 h to 400 mM or 500 mM NaCl induced a 55-120% increase in endogenous protein aggregation. Inhibition of insulin signaling or acclimation to mild hypertonic stress increased survival under extreme hypertonic conditions and prevented aggregation of endogenous proteins. Our results demonstrate that hypertonic stress causes widespread and dramatic protein damage and that cells have a significant capacity to remodel the network of proteins that function to maintain proteostasis. These findings have important implications for understanding how cells cope with hypertonic stress and other protein-damaging stressors. PMID:21613604

  12. Pleuropulmonary hydatid disease treated with thoracoscopic instillation of hypertonic saline.

    PubMed

    Lakshmanan P, Hari; Musthafa A, Monhammed; Suraj, Kp; Ravidran, C

    2008-01-01

    Hydatid disease is caused by the larval stage of the cestode, Echinococcus granulosus. Man is the intermediate host in its life cycle. The most common organ involved is liver followed by lung. Although surgery remains the definitive treatment for symptomatic lesions, it is associated with considerable morbidity. Other less invasive treatment strategies as an adjunct to medical treatment that have been tried in various case series include percutaneous aspiration, instillation and reaspiration of scolicidal agents (PAIR), and thoracoscopic removal of cysts located subpleurally. Here we report the case of a 58 year old gentleman with hepatic and pleuropulmonary hydatid disease who was subjected to medical thoracoscopy and instillation of hypertonic saline (3%), followed by medical management with albendazole with which complete resolution of the pulmonary cysts was achieved. PMID:20390071

  13. Hypertonic Dextrose Injection for The Treatment of a Baker’s Cyst

    PubMed Central

    Kibar, Sibel; Balaban, Birol

    2016-01-01

    We present extremely rare and interesting case of a Baker’s cyst treated with hypertonic dextrose injection. A 54-year-old female patient had a Baker’s cyst which was diagnosed by an ultrasonography. After the failure of the two-weekly conservative treatment, we injected hypertonic dextrose (25%) into her right knee joint for the treatment of a Baker’s cyst. Two weeks after the injection, the patient reported improvement in posterior knee pain, and an US showed a resolution of the posterior knee cyst. Certainly hypertonic dextrose injection for the treatment of a Baker’s cyst appears to be a reasonable treatment option. Further studies are needed in order to elucidate the efficacy of hypertonic dextrose injection in the treatment of Baker’s cysts. PMID:27042572

  14. Comparison of Normal Saline, Hypertonic Saline Albumin and Terlipressin plus Hypertonic Saline Albumin in an Infant Animal Model of Hypovolemic Shock

    PubMed Central

    2015-01-01

    Introduction In series of cases and animal models suffering hemorrhagic shock, the use of vasopressors has shown potential benefits regarding hemodynamics and tissue perfusion. Terlipressin is an analogue of vasopressin with a longer half-life that can be administered by bolus injection. We have previously observed that hypertonic albumin improves resuscitation following controlled hemorrhage in piglets. The aim of the present study was to analyze whether the treatment with the combination of terlipressin and hypertonic albumin can produce better hemodynamic and tissular perfusion parameters than normal saline or hypertonic albumin alone at early stages of hemorrhagic shock in an infant animal model. Methods Experimental, randomized animal study including 39 2-to-3-month-old piglets. Thirty minutes after controlled 30 ml/kg bleed, pigs were randomized to receive either normal saline (NS) 30 ml/kg (n = 13), 5% albumin plus 3% hypertonic saline (AHS) 15 ml/kg (n = 13) or single bolus of terlipressin 15 μg/kg i.v. plus 5% albumin plus 3% hypertonic saline 15 ml/kg (TAHS) (n = 13) over 30 minutes. Global hemodynamic and tissular perfusion parameters were compared. Results After controlled bleed a significant decrease of blood pressure, cardiac index, central venous saturation, carotid and peripheral blood flow, brain saturation and an increase of heart rate, gastric PCO2 and lactate was observed. After treatment no significant differences in most hemodynamic (cardiac index, mean arterial pressure) and perfusion parameters (lactate, gastric PCO2, brain saturation, cutaneous blood flow) were observed between the three therapeutic groups. AHS and TAHS produced higher increase in stroke volume index and carotid blood flow than NS. Conclusions In this pediatric animal model of hypovolemic shock, albumin plus hypertonic saline with or without terlipressin achieved similar hemodynamics and perfusion parameters than twice the volume of NS. Addition of terlipressin did not

  15. Midtrimester abortion by hypertonic saline instillation experience in Ramathibodi Hospital.

    PubMed

    Suthutvoravut, S; Supacharapongkul, V; Bhiromswasdi, S

    1983-03-01

    A retrospective study of midtrimester abortions using the intraamniotic instillation of hypertonic saline solution was conducted. All 62 cases admitted to the Ramathibodi Hospital in Bangkok, Thailand for midtrimester abortion in 1980 were terminated by intraamniotic hypertonic saline instillation. The pregnancies were unwanted in 32 (51.6%) of the cases because of family problems, poor socioeconomic status, and deteriorated psychological health. 15 cases (24.2%) were preganancy from rape; 9 (14.5%) had rubella infection during the 1st trimester; and 3 cases (4.8%) were mentally retarded. There was 1 case of renal staghorn calculi post nephrostomy, 1 of multiparity with history of hemophilia in the family, and 1 of failed IUD contraception. The women were between 16-25 years of age in 39 cases, aged 15 or under in 4 cases (6.5%), and over age 35 in 4 cases. In 49 cases (79%) abortion was performed during 16-20 weeks gestation, in 12 cases (19.1%) at 21-24 weeks, and in 1 case at 25 weeks of gestation. The time interval from hypertonic saline instillation to abortion was analyzed in order to evaluate the effect of parity, amount of amniotic fluid withdrawn, and oxytocin augmentation. The mean instillation to abortion time (I-A) was 30.19 +or- 11.25 hours. There were 3 cases which did not receive oxytocin and who spontaneously aborted within 24 hours. Among cases which received oxytocin augmentation, there were 9 who received oxytocin immediately after instillation and 50 who received it 18-24 hours later. The I-A time was 31.22 +or- 11.63 hours in the group that received oxytocin immediately and 31.09 +or- 10.68 in the group receiving it later. There was no statistical difference between the 2 groups. Among the 50 cases which received oxytocin augmentation 18-24 hours later, there was no statistical difference between groups of nulliparity and multiparity. There were 46 cases in which the amount of amniotic fluid withdrawn was noted. In the group in which more than

  16. Airway responsiveness to hypertonic saline: dose-response slope or PD15?

    PubMed

    de Meer, G; Marks, G B; de Jongste, J C; Brunekreef, B

    2005-01-01

    The result of airway challenge test with hypertonic saline (HS) is expressed as the dose causing a 15% fall in forced expiratory volume in one second (FEV1; PD15). A noncensored measure, such as the dose-response slope (DRS), allows the evaluation of the risk of asthma for subjects with a fall in FEV1 <15%. The aim of this study was to assess the relationship between airway responsiveness to HS by PD15 or DRS, asthma symptoms and markers of eosinophilic inflammation. Data on current wheeze and airway responsiveness were obtained for 1,107 children (aged 8-13 yrs). Blood eosinophils and serum eosinophil cationic protein (ECP) were assessed in subsets (n = 683 and 485). PD15 was assessed if FEV1 fell > or =15%, and the DRS was calculated for all tests. Graphs were constructed to visualise relationships with current wheeze, blood eosinophils and serum ECP. Odds ratios and Spearman's correlation coefficients were calculated to quantify these relationships. Children with features of asthma had lower PD15 and higher DRS, and separation was most pronounced for DRS. Prevalence of current wheeze increased continuously over the entire range of DRS values. Blood eosinophils were significantly higher only for the highest values of DRS. In conclusion, the continuous relationship between airway responsiveness and asthma symptoms is in favour of a noncensored measure of airway responsiveness, such as the dose-response slope. PMID:15640337

  17. Out-of-Hospital Hypertonic Resuscitation Following Severe Traumatic Brain Injury: A Randomized Controlled Trial

    PubMed Central

    Bulger, Eileen M.; May, Susanne; Brasel, Karen J.; Schreiber, Martin; Kerby, Jeffrey D.; Tisherman, Samuel A.; Newgard, Craig; Slutsky, Arthur; Coimbra, Raul; Emerson, Scott; Minei, Joseph P.; Bardarson, Berit; Kudenchuk, Peter; Baker, Andrew; Christenson, Jim; Idris, Ahamed; Davis, Daniel; Fabian, Timothy C.; Aufderheide, Tom P.; Callaway, Clifton; Williams, Carolyn; Banek, Jane; Vaillancourt, Christian; van Heest, Rardi; Sopko, George; Hata, J. Steven; Hoyt, David B.

    2010-01-01

    Context Hypertonic fluids restore cerebral perfusion with reduced cerebral edema and modulate inflammatory response to reduce subsequent neuronal injury and thus have potential benefit in resuscitation of patients with traumatic brain injury (TBI). Objective To determine whether out-of-hospital administration of hypertonic fluids improves neurologic outcome following severe TBI. Design, Setting, and Participants Multicenter, double-blind, randomized, placebo-controlled clinical trial involving 114 North American emergency medical services agencies within the Resuscitation Outcomes Consortium, conducted between May 2006 and May 2009 among patients 15 years or older with blunt trauma and a prehospital Glasgow Coma Scale score of 8 or less who did not meet criteria for hypovolemic shock. Planned enrollment was 2122 patients. Intervention A single 250-mL bolus of 7.5% saline/6% dextran 70 (hypertonic saline/dextran), 7.5% saline (hypertonic saline), or 0.9% saline (normal saline) initiated in the out-of-hospital setting. Main Outcome Measure Six-month neurologic outcome based on the Extended Glasgow Outcome Scale (GOSE) (dichotomized as >4 or ≤4). Results The study was terminated by the data and safety monitoring board after randomization of 1331 patients, having met prespecified futility criteria. Among the 1282 patients enrolled, 6-month outcomes data were available for 1087 (85%). Baseline characteristics of the groups were equivalent. There was no difference in 6-month neurologic outcome among groups with regard to proportions of patients with severe TBI (GOSE ≤4) (hypertonic saline/dextran vs normal saline: 53.7% vs 51.5%; difference, 2.2% [95% CI, −4.5% to 9.0%]; hypertonic saline vs normal saline: 54.3% vs 51.5%; difference, 2.9% [95% CI, −4.0% to 9.7%]; P=.67). There were no statistically significant differences in distribution of GOSE category or Disability Rating Score by treatment group. Survival at 28 days was 74.3% with hypertonic saline

  18. Immunomodulatory effect of hypertonic saline in hemorrhagic shock.

    PubMed

    Motaharinia, Javad; Etezadi, Farhad; Moghaddas, Azadeh; Mojtahedzadeh, Mojtaba

    2015-01-01

    Multiple organ dysfunction syndrome (MODS) and nosocomial infection following trauma-hemorrhage are among the most important causes of mortality in hemorrhagic shock patients. Dysregulation of the immune system plays a central role in MODS and a fluid having an immunomodulatory effect could be advantageous in hemorrhagic shock resuscitation. Hypertonic saline (HS) is widely used as a resuscitation fluid in trauma-hemorrhagic patients. Besides having beneficial effects on the hemodynamic parameters, HS has modulatory effects on various functions of immune cells such as degranulation, adhesion molecules and cytokines expression, as well as reactive oxygen species production. This article reviews clinical evidence for decreased organ failure and mortality in hemorrhagic shock patients resuscitated with HS. Despite promising results in animal models, results from pre-hospital and emergency department administration in human studies did not show improvement in survival, organ failure, or a reduction in nosocomial infection by HS resuscitation. Further post hoc analysis showed some benefit from HS resuscitation for severely-injured patients, those who received more than ten units of blood by transfusion, patients who underwent surgery, and victims of traumatic brain injury. Several reasons are suggested to explain the differences between clinical and animal models. PMID:26437974

  19. Biofilm formation by Escherichia coli in hypertonic sucrose media.

    PubMed

    Kawarai, Taketo; Furukawa, Soichi; Narisawa, Naoki; Hagiwara, Chisato; Ogihara, Hirokazu; Yamasaki, Makari

    2009-06-01

    High osmotic environments produced by NaCl or sucrose have been used as reliable and traditional methods of food preservation. We tested, Escherichia coli as an indicator of food-contaminating bacterium, to determine if it can form biofilm in a hyperosmotic environment. E. coli K-12 IAM1264 did not form biofilm in LB broth that contained 1 M NaCl. However, the bacterium formed biofilm in LB broth that contained 1 M sucrose, although the planktonic growth was greatly suppressed. The biofilm, formed on solid surfaces, such as titer-plate well walls and glass slides, solely around the air-liquid interface. Both biofilm forming cells and planktonic cells in the hypertonic medium adopted a characteristic, fat and filamentous morphology with no FtsZ rings, which are a prerequisite for septum formation. Biofilm forming cells were found to be alive based on propidium iodide staining. The presence of 1 M sucrose in the food environment is not sufficient to prevent biofilm formation by E. coli. PMID:19447340

  20. Biphasic modulation of synaptic transmission by hypertonicity at the embryonic Drosophila neuromuscular junction

    PubMed Central

    Suzuki, Kazuhiro; Okamoto, Tomonori; Kidokoro, Yoshiaki

    2002-01-01

    Puff-application of hypertonic saline (sucrose added to external saline) causes a transient increase in the frequency of spontaneous miniature synaptic currents (mSCs) at the neuromuscular junctions of Drosophila embryos. The frequency gradually returns to pre-application levels. External Ca2+ is not needed for this response, but it may modify it. At 50 mm added sucrose, for example, enhanced spontaneous release was observed only in the presence of external Ca2+, suggesting that Ca2+ augments the response. In a high-K+ solution, in which the basal mSC frequency was elevated, higher sucrose concentrations produced an increase in mSC frequency that was followed (during and after the hypertonic exposure) by depression, with the magnitude of both effects increasing with hypertonicity between 100 and 500 mm. Evoked release by nerve stimulation showed only depression in response to hypertonicity. We do not believe that the depression of spontaneous or evoked release can be explained by the depletion of releasable quanta, however, since the frequency of quantal release did not reach levels compatible with this explanation and the enhancement and depression could be obtained independent of one another. In a mutant lacking neuronal synaptobrevin, only the depression of mSC frequency was induced by hypertonicity. Conversely, only the enhancing effect was observed in wild-type embryos when the mSC frequency was elevated with forskolin in Ca2+-free saline. In cultured embryonic Drosophila neurons, Ca2+ signals that were induced by high K+ and detected by Fura-2, were reduced by hypertonicity, suggesting that the depressing response is due to a direct effect of hypertonicity on Ca2+ influx. PMID:12433954

  1. Correlation of growth of aerobic blood cultures in hypertonic broth with antibiotic therapy.

    PubMed Central

    Eng, J; Maeland, A

    1982-01-01

    The aim of this study was to elucidate the mechanisms by which sucrose improves growth in a hypertonic medium for isolating aerobes from blood. Clinical blood cultures were made routinely in duplicate in plain broth consisting of brain heart infusion broth with sodium polyanetholesulfonate, gelatin, and penicillinase and the same broth with 20% sucrose added. The growth patterns of Staphylococcus aureus and Enterobacteriaceae from plain and from hypertonic broth were correlated with the presence or absence of antimicrobial therapy in patients when the blood cultures were collected. In S. aureus bacteremias, 58.7% of the positive cultures collected during treatment of patients with beta-lactam antibiotics showed earlier growth or growth only in hypertonic broth, compared with 16.7% of the cultures taken during treatment with other antimicrobial agents (P less than 0.05) and 17.6% of the cultures made in antibiotic-free intervals (P less than 0.01). In the group of cultures yielding growth of Enterobacteriaceae, growth occurred earlier or solely in hypertonic broth in 28.9% of the cultures taken during treatment with beta-lactam antibiotics, compared with 15.7% of the cultures taken during treatment with other antimicrobial agents and 21.6% of the cultures collected in antibiotic-free intervals (differences not statistically significant). It is concluded that treatment with beta-lactam antibiotics is an important reason for the improved growth of S. aureus from hypertonic broth, but other factors are also involved. PMID:7153339

  2. Modulation of TonEBP activity by SUMO modification in response to hypertonicity

    PubMed Central

    Kim, Jeong-Ah; Kwon, Mi Jin; Lee-Kwon, Whaseon; Choi, Soo Youn; Sanada, Satoru; Kwon, Hyug Moo

    2014-01-01

    TonEBP is a DNA binding transcriptional enhancer that enables cellular adaptation to hypertonic stress by promoting expression of specific genes. TonEBP expression is very high in the renal medulla because local hypertonicity stimulates its expression. Given the high level of expression, it is not well understood how TonEBP activity is modulated. Here we report that TonEBP is post-translationally modified by SUMO, i.e., sumoylated, in the renal medulla but not in other isotonic organs. The sumoylation is reproduced in cultured cells when switched to hypertonicity. Analyses of site-directed TonEBP mutants reveal that K556 and K603 are independently sumoylated in response to hypertonicity. DNA binding is required for the sumoylation. Functional analyses of non-sumoylated mutants and SUMO-conjugated constructs show that sumoylation inhibits TonEBP in a dose-dependent manner but independent of the site of SUMO conjugation. Sumoylation inhibits transactivation without affecting nuclear translocation or DNA binding. These data suggest that sumoylation modulates the activity of TonEBP in the hypertonic renal medulla to prevent excessive action of TonEBP. PMID:24994984

  3. Hypertonic upregulation of amino acid transport system A in vascular smooth muscle cells.

    PubMed

    Chen, J G; Klus, L R; Steenbergen, D K; Kempson, S A

    1994-08-01

    The A10 line of vascular smooth muscle cells has Na+ dependent transport systems for alanine, proline, and Pi, whereas uptake of leucine, myo-inositol and D-glucose is Na+ independent. When A10 cells were incubated for 4 h in medium made hypertonic by addition of sucrose, there was a marked increase in Na(+)-dependent transport of alanine and proline but no change in Na(+)-dependent Pi uptake or Na(+)-independent uptake of leucine and inositol. Intracellular alanine content was increased 61% by the hypertonic treatment. Other nonpenetrating solutes, such as cellobiose and mannitol, reproduced the effect of sucrose, but urea, a penetrating solute, did not. Studies with 2-(methylamino)-isobutyric acid revealed that the upregulation by hypertonicity involved only system A. Increases in alanine and proline uptake also occurred after incubating the cells in isotonic medium containing 0.1 mM ouabain, suggesting that an increase in intracellular Na+ may be part of the intracellular signal for upregulation of system A. Hypertonic upregulation of Na(+)-dependent alanine transport occurred also in primary cultures of vascular smooth muscle cells. The response was blocked by actinomycin D and cycloheximide, indicating that gene transcription and protein synthesis play important roles in the mechanism leading to increased alanine uptake. We conclude that vascular smooth muscle cells, during prolonged hypertonic stress, activate system A and accumulate specific neutral amino acids which may act as organic osmolytes to help maintain normal cell volume. PMID:8074188

  4. Common toads (Bufo arenarum) learn to anticipate and avoid hypertonic saline solutions.

    PubMed

    Daneri, M Florencia; Papini, Mauricio R; Muzio, Rubén N

    2007-11-01

    Toads (Bufo arenarum) were exposed to pairings between immersion in a neutral saline solution (i.e., one that caused no significant variation in fluid balance), followed by immersion in a highly hypertonic saline solution (i.e., one that caused water loss). In Experiment 1, solutions were presented in a Pavlovian conditioning arrangement. A group receiving a single neutral-highly hypertonic pairing per day exhibited a greater conditioned increase in heart rate than groups receiving either the same solutions in an explicitly unpaired fashion, or just the neutral solution. Paired toads also showed a greater ability to compensate for water loss across trials than that of the explicitly unpaired group. Using the same reinforcers and a similar apparatus, Experiment 2 demonstrated that toads learn a one-way avoidance response motivated by immersion in the highly hypertonic solution. Cardiac and avoidance conditioning are elements of an adaptive system for confronting aversive situations involving loss of water balance. PMID:18085926

  5. Hypertonicity-induced p38MAPK activation elicits recovery of corneal epithelial cell volume and layer integrity.

    PubMed

    Bildin, V N; Wang, Z; Iserovich, P; Reinach, P S

    2003-05-01

    In hypertonicity-stressed (i.e., 600 mOsm) SV40-immortalized rabbit and human corneal epithelial cell layers (RCEC and HCEC, respectively), we characterized the relationship between time-dependent changes in translayer resistance, relative cell volume and modulation of MAPK superfamily activities. Sulforhodamine B permeability initially increased by 1.4- and 2-fold in RCEC and HCEC, respectively. Subsequently, recovery to its isotonic level only occurred in RCEC. Light scattering revealed that in RCEC 1) regulatory volume increase (RVI) extent was 20% greater; 2) RVI half-time was 2.5-fold shorter. However, inhibition of Na-K-2Cl cotransporter and Na/K-ATPase activity suppressed the RVI response more in HCEC. MAPK activity changes were as follows: 1) p38 was wave-like and faster as well as larger in RCEC than in HCEC (90- and 18-fold, respectively); 2) increases in SAPK/JNK activity were negligible in comparison to those of p38; 3) Erk1/2 activity declined to 30-40% of their basal values. SB203580, a specific p38 inhibitor, dose dependently suppressed the RVI responses in both cell lines. However, neither U0126, which inhibits MEK, the kinase upstream of Erk, nor SP600125, inhibitor of SAPK/JNK, had any effect on this response. Taken together, sufficient activation of the p38 limb of the MAPK superfamily during a hypertonic challenge is essential for maintaining epithelial cell volume and translayer resistance. On the other hand, Erk1/2 activity restoration seems to be dependent on cell volume recovery. PMID:12879161

  6. Hypertonic Saline Dextran Ameliorates Organ Damage in Beagle Hemorrhagic Shock

    PubMed Central

    You, Guo-xing; Wang, Ying; Chen, Gan; Wang, Quan; Zhang, Xi-gang; Zhao, Lian; Zhou, Hong; He, Yue-zhong

    2015-01-01

    Objective The goal of this study was to investigate the effect of hypertonic saline with 6% Dextran-70 (HSD) resuscitation on organ damage and the resuscitation efficiency of the combination of HSD and lactated ringers (LR) in a model of hemorrhage shock in dogs. Methods Beagles were bled to hold their mean arterial pressure (MAP) at 50±5 mmHg for 1 h. After hemorrhage, beagles were divided into three groups (n = 7) to receive pre-hospital resuscitation for 1 h (R1): HSD (4 ml/kg), LR (40 ml/kg), and HSD+LR (a combination of 4 ml/kg HSD and 40 ml/kg LR). Next, LR was transfused into all groups as in-hospital resuscitation (R2). After two hours of observation (R3), autologous blood was transfused. Hemodynamic responses and systemic oxygenation were measured at predetermined phases. Three days after resuscitation, the animals were sacrificed and tissues including kidney, lung, liver and intestinal were obtained for pathological analysis. Results Although the initial resuscitation with HSD was shown to be faster than LR with regard to an ascending MAP, the HSD group showed a similar hemodynamic performance compared to the LR group throughout the experiment. Compared with the LR group, the systemic oxygenation performance in the HSD group was similar but showed a lower venous-to-arterial CO2 gradient (Pv-aCO2) at R3 (p < 0.05). Additionally, the histology score of the kidneys, lungs and liver were significantly lower in the HSD group than in the LR group (p < 0.05). The HSD+LR group showed a superior hemodynamic response but higher extravascular lung water (EVLW) and lower arterial oxygen tension (PaO2) than the other groups (p < 0.05). The HSD+LR group showed a marginally improved systemic oxygenation performance and lower histology score than other groups. Conclusions Resuscitation after hemorrhagic shock with a bolus of HSD showed a similar hemodynamic response compared with LR at ten times the volume of HSD, but HSD showed superior efficacy in organ protection

  7. Effect of hypertonicity on augmentation and potentiation and on corresponding quantal parameters of transmitter release.

    PubMed

    Cheng, H; Miyamoto, M D

    1999-03-01

    Augmentation and (posttetanic) potentiation are two of the four components comprising the enhanced release of transmitter following repetitive nerve stimulation. To examine the quantal basis of these components under isotonic and hypertonic conditions, we recorded miniature endplate potentials (MEPPs) from isolated frog (Rana pipiens) cutaneous pectoris muscles, before and after repetitive nerve stimulation (40 s at 80 Hz). Continuous recordings were made in low Ca2+ high Mg2+ isotonic Ringer solution, in Ringer that was made hypertonic with 100 mM sucrose, and in wash solution. Estimates were obtained of m (no. of quanta released), n (no. of functional release sites), p (mean probability of release), and vars p (spatial variance in p), using a method that employed MEPP counts. Hypertonicity abolished augmentation without affecting potentiation. There were prolonged poststimulation increases in m, n, and p and a marked but transient increase in vars p in the hypertonic solution. All effects were completely reversed with wash. The time constants of decay for potentiation and for vars p were virtually identical. The results are consistent with the notion that augmentation is caused by Ca2+ influx through voltage-gated calcium channels and that potentiation is due to Na+-induced Ca2+ release from mitochondria. The results also demonstrate the utility of this approach for analyzing the dynamics of quantal transmitter release. PMID:10085369

  8. Rejoining and misrejoining of radiation-induced chromatin breaks. III. Hypertonic treatment

    NASA Technical Reports Server (NTRS)

    Durante, M.; George, K.; Wu, H. L.; Yang, T. C.

    1998-01-01

    It has been shown that treatment in anisotonic medium modifies rejoining of radiation-induced breaks in interphase chromosomes. In previous work, we have demonstrated that formation of exchanges in human lymphocytes has a slow component (half-time of 1-2 h), but a fraction of exchanges are also observed in samples assayed soon after exposure. In this paper we studied the effect of hypertonic treatment on rejoining and misrejoining of radiation-induced breaks using fluorescence in situ hybridization of prematurely condensed chromosomes in human lymphocytes. Isolated lymphocytes were irradiated with 7 Gy gamma rays, fused to mitotic hamster cells and incubated in hypertonic solution (0.5 M NaCl) for the period normally allowed for interphase chromosome condensation to occur. The data from hypertonic treatment experiments indicate the presence of a class of interphase chromosome breaks that rejoin and misrejoin very quickly (half-time of 5-6 min). The fast misrejoining of these lesions is considered to be responsible for the initial level of exchanges which we reported previously. No significant effect of hypertonic treatment on the yield of chromosome aberrations scored at the first postirradiation mitosis was detected.

  9. In vitro increase of mean corpuscular volume difference (dMCV) as a marker for serum hypertonicity in dogs.

    PubMed

    Reinhart, Jennifer M; Yancey, Misty R; Pohlman, Lisa M; Schermerhorn, Thomas

    2014-06-01

    Spurious increase in erythrocyte mean corpuscular volume (MCV) on automated cell analyzers is a well-characterized lab error in hypertonic patients. A difference between automated and manual MCV (dMCV) greater than 2 fl has been shown to predict hypertonicity in humans. The purpose of this study was to investigate dMCV as a marker for serum hypertonicity in dogs and to examine the relationship between dMCV and three methods of estimating serum tonicity: measured (OsMM), calculated (OsMC), and calculated effective (OsMCE) osmolalities. OsMC, OsMCE, and dMCV were calculated from routine blood values and OsMM was directly measured in 121 dogs. The dMCV of hypertonic dogs was significantly larger than that of normotonic dogs for all three osmolality methods. dMCV predicted hypertonicity as estimated by OsMM better than it predicted hypertonicity as estimated by OsMC and OsMCE. A cutoff of 2.96 fl yielded the best sensitivity (76%) and specificity (71%) for hypertonicity estimated by OsMM. PMID:24656345

  10. Abnormal Osmotic Avoidance Behavior in C. elegans Is Associated with Increased Hypertonic Stress Resistance and Improved Proteostasis

    PubMed Central

    Lee, Elaine C.; Kim, Heejung; Ditano, Jennifer; Manion, Dacie; King, Benjamin L.; Strange, Kevin

    2016-01-01

    Protein function is controlled by the cellular proteostasis network. Proteostasis is energetically costly and those costs must be balanced with the energy needs of other physiological functions. Hypertonic stress causes widespread protein damage in C. elegans. Suppression and management of protein damage is essential for optimal survival under hypertonic conditions. ASH chemosensory neurons allow C. elegans to detect and avoid strongly hypertonic environments. We demonstrate that mutations in osm-9 and osm-12 that disrupt ASH mediated hypertonic avoidance behavior or genetic ablation of ASH neurons are associated with enhanced survival during hypertonic stress. Improved survival is not due to altered systemic volume homeostasis or organic osmolyte accumulation. Instead, we find that osm-9(ok1677) mutant and osm-9(RNAi) worms exhibit reductions in hypertonicity induced protein damage in non-neuronal cells suggesting that enhanced proteostasis capacity may account for improved hypertonic stress resistance in worms with defects in osmotic avoidance behavior. RNA-seq analysis revealed that genes that play roles in managing protein damage are upregulated in osm-9(ok1677) worms. Our findings are consistent with a growing body of work demonstrating that intercellular communication between neuronal and non-neuronal cells plays a critical role in integrating cellular stress resistance with other organismal physiological demands and associated energy costs. PMID:27111894

  11. Inhibition of Neutrophils by Hypertonic Saline Involves Pannexin-1, CD39, CD73, and Other Ectonucleotidases.

    PubMed

    Chen, Yu; Bao, Yi; Zhang, Jingping; Woehrle, Tobias; Sumi, Yuka; Ledderose, Stephan; Li, Xiaoou; Ledderose, Carola; Junger, Wolfgang G

    2015-09-01

    Hypertonic saline (HS) resuscitation has been studied as a possible strategy to reduce polymorphonuclear neutrophil (PMN) activation and tissue damage in trauma patients. Hypertonic saline blocks PMNs by adenosine triphosphate (ATP) release and stimulation of A2a adenosine receptors. Here, we studied the underlying mechanisms in search of possible reasons for the inconsistent results of recent clinical trials with HS resuscitation. Purified human PMNs or PMNs in whole blood were treated with HS to simulate hypertonicity levels found after HS resuscitation (40 mmol/L beyond isotonic levels). Adenosine triphosphate release was measured with a luciferase assay. Polymorphonuclear neutrophil activation was assessed by measuring oxidative burst. The pannexin-1 (panx1) inhibitor panx1 and the gap junction inhibitor carbenoxolone (CBX) blocked ATP release from PMNs in purified and whole blood preparations, indicating that HS releases ATP via panx1 and gap junction channels. Hypertonic saline blocked N-formyl-Met-Leu-Phe-induced PMN activation by 40% in purified PMN preparations and by 60% in whole blood. These inhibitory effects were abolished by panx1 but only partially reduced by CBX, which indicates that panx1 has a central role in the immunomodulatory effects of HS. Inhibition of the ectonucleotidases CD39 and CD73 abolished the suppressive effect of HS on purified PMN cultures but only partially reduced the effect of HS in whole blood. These findings suggest redundant mechanisms in whole blood that may strengthen the immunomodulatory effect of HS in vivo. We conclude that HS resuscitation exerts anti-inflammatory effects that involve panx1, CD39, CD73, and other ectonucleotidases, which produce the adenosine that blocks PMNs by stimulating their A2a receptors. Our findings shed new light on the immunomodulatory mechanisms of HS and suggest possible new strategies to improve the clinical efficacy of hypertonic resuscitation. PMID:26009814

  12. Hypertonic fluid administration in patients with septic shock: a prospective randomized controlled pilot study.

    PubMed

    van Haren, Frank M P; Sleigh, James; Boerma, E Christiaan; La Pine, Mary; Bahr, Mohamed; Pickkers, Peter; van der Hoeven, Johannes G

    2012-03-01

    We assessed the short-term effects of hypertonic fluid versus isotonic fluid administration in patients with septic shock. This was a double-blind, prospective randomized controlled trial in a 15-bed intensive care unit. Twenty-four patients with septic shock were randomized to receive 250 mL 7.2% NaCl/6% hydroxyethyl starch (HT group) or 500 mL 6% hydroxyethyl starch (IT group). Hemodynamic measurements included mean arterial blood pressure (MAP), central venous pressure, stroke volume index, stroke volume variation, intrathoracic blood volume index, gastric tonometry, and sublingual microcirculatory flow as assessed by sidestream dark field imaging. Systolic tissue Doppler imaging velocities of the medial mitral annulus were measured using echocardiography to assess left ventricular contractility. Log transformation of the ratio MAP divided by the norepinephrine infusion rate (log MAP/NE) quantified the combined effect on both parameters. Compared with the IT group, hypertonic solution treatment resulted in an improvement in log MAP/NE (P = 0.008), as well as an increase in systolic tissue Doppler imaging velocities (P = 0.03) and stroke volume index (P = 0.017). No differences between the groups were found for preload parameters (central venous pressure, stroke volume variation, intrathoracic blood volume index) or for afterload parameters (systemic vascular resistance index, MAP). Hypertonic solution treatment decreased the need for ongoing fluid resuscitation (P = 0.046). No differences between groups were observed regarding tonometry or the sublingual microvascular variables. In patients with septic shock, hypertonic fluid administration did not promote gastrointestinal mucosal perfusion or sublingual microcirculatory blood flow in comparison to isotonic fluid. Independent of changes in preload or afterload, hypertonic fluid administration improved the cardiac contractility and vascular tone compared with isotonic fluid. The need for ongoing fluid

  13. ROC trials update on prehospital hypertonic saline resuscitation in the aftermath of the US-Canadian trials

    PubMed Central

    Dubick, Michael A; Shek, Pang; Wade, Charles E

    2013-01-01

    The objectives of this review are to assess the current state of hypertonic saline as a prehospital resuscitation fluid in hypotensive trauma patients, particularly after the 3 major Resuscitation Outcomes Consortium trauma trials in the US and Canada were halted due to futility. Hemorrhage and traumatic brain injury are the leading causes of death in both military and civilian populations. Prehospital fluid resuscitation remains controversial in civilian trauma, but small-volume resuscitation with hypertonic fluids is of utility in military scenarios with prolonged or delayed evacuation times. A large body of pre-clinical and clinical literature has accumulated over the past 30 years on the hemodynamic and, most recently, the anti-inflammatory properties of hypertonic saline, alone or with dextran-70. This review assesses the current state of hypertonic fluid resuscitation in the aftermath of the failed Resuscitation Outcomes Consortium trials. PMID:23778489

  14. Challenger

    ERIC Educational Resources Information Center

    Allday, Jonathan

    2002-01-01

    The events that led to the spectacular destruction of the Space Shuttle "Challenger" in 1986 are detailed here. They show how NASA should have heeded engineers' worries over materials problems resulting from a launch in cold weather. Suggestions are made of how pupils could also learn from this tragedy. (Contains 4 figures and 2 footnotes.)

  15. Challenger

    NASA Astrophysics Data System (ADS)

    Allday, Jonathan

    2002-09-01

    The events that led to the spectacular destruction of the Space Shuttle Challenger in 1986 are detailed here. They show how NASA should have heeded engineers' worries over materials problems resulting from a launch in cold weather. Suggestions are made of how pupils could also learn from this tragedy.

  16. Challenges

    ERIC Educational Resources Information Center

    Moore, Thomas R.

    1975-01-01

    Domestic and international challenges facing the National Society for the Prevention of Blindness are discussed; and U.S. and Russian programs in testing and correcting children's vision, developing eye safety programs in agriculture and industry, and disseminating information concerning the detection and treatment of cataracts are compared. (SB)

  17. Effect of hypertonic saline treatment on the inflammatory response after hydrochloric acid-induced lung injury in pigs

    PubMed Central

    Holms, Carla Augusto; Otsuki, Denise Aya; Kahvegian, Marcia; Massoco, Cristina Oliveira; Fantoni, Denise Tabacchi; Gutierrez, Paulo Sampaio; Junior, Jose Otavio Costa Auler

    2015-01-01

    OBJECTIVES: Hypertonic saline has been proposed to modulate the inflammatory cascade in certain experimental conditions, including pulmonary inflammation caused by inhaled gastric contents. The present study aimed to assess the potential anti-inflammatory effects of administering a single intravenous dose of 7.5% hypertonic saline in an experimental model of acute lung injury induced by hydrochloric acid. METHODS: Thirty-two pigs were anesthetized and randomly allocated into the following four groups: Sham, which received anesthesia and were observed; HS, which received intravenous 7.5% hypertonic saline solution (4 ml/kg); acute lung injury, which were subjected to acute lung injury with intratracheal hydrochloric acid; and acute lung injury + hypertonic saline, which were subjected to acute lung injury with hydrochloric acid and treated with hypertonic saline. Hemodynamic and ventilatory parameters were recorded over four hours. Subsequently, bronchoalveolar lavage samples were collected at the end of the observation period to measure cytokine levels using an oxidative burst analysis, and lung tissue was collected for a histological analysis. RESULTS: Hydrochloric acid instillation caused marked changes in respiratory mechanics as well as blood gas and lung parenchyma parameters. Despite the absence of a significant difference between the acute lung injury and acute lung injury + hypertonic saline groups, the acute lung injury animals presented higher neutrophil and tumor necrosis factor alpha (TNF-α), interleukin (IL)-6 and IL-8 levels in the bronchoalveolar lavage analysis. The histopathological analysis revealed pulmonary edema, congestion and alveolar collapse in both groups; however, the differences between groups were not significant. Despite the lower cytokine and neutrophil levels observed in the acute lung injury + hypertonic saline group, significant differences were not observed among the treated and non-treated groups. CONCLUSIONS: Hypertonic saline

  18. Time-dependent expression of hypertonic effects on bullfrog taste nerve responses to salts and bitter substances.

    PubMed

    Mashiyama, Kazunori; Nozawa, Yuhei; Ohtubo, Yoshitaka; Kumazawa, Takashi; Yoshii, Kiyonori

    2014-03-27

    We previously showed that the hypertonicity of taste stimulating solutions modified tonic responses, the quasi-steady state component following the transient (phasic) component of each integrated taste nerve response. Here we show that the hypertonicity opens tight junctions surrounding taste receptor cells in a time-dependent manner and modifies whole taste nerve responses in bullfrogs. We increased the tonicity of stimulating solutions with non-taste substances such as urea or ethylene glycol. The hypertonicity enhanced phasic responses to NaCl>0.2M, and suppressed those to NaCl<0.1M, 1mM CaCl2, and 1mM bitter substances (quinine, denatonium and strychnine). The hypertonicity also enhanced the phasic responses to a variety of 0.5M salts such as LiCl and KCl. The enhancing effect was increased by increasing the difference between the ionic mobilities of the cations and anions in the salt. A preincubation time >20s in the presence of 1M non-taste substances was needed to elicit both the enhancing and suppressing effects. Lucifer Yellow CH, a paracellular marker dye, diffused into bullfrog taste receptor organs in 30s in the presence of hypertonicity. These results agreed with our proposed mechanism of hypertonic effects that considered the diffusion potential across open tight junctions. PMID:24513402

  19. Roles of TauT and system A in cytoprotection of rat syncytiotrophoblast cell line exposed to hypertonic stress.

    PubMed

    Nishimura, T; Sai, Y; Fujii, J; Muta, M; Iizasa, H; Tomi, M; Deureh, M; Kose, N; Nakashima, E

    2010-11-01

    The purpose of this study was to clarify the cytoprotective mechanism(s) induced in a conditionally immortalized syncytiotrophoblast cell line (TR-TBT 18d-1) exposed to hypertonic conditions. Hypertonicity-induced apoptosis of TR-TBT 18d-1 cells, but this was blocked by addition of 1 mM taurine to the culture medium. TauT-knockdown using siRNA revealed that TauT is a major contributor to taurine uptake by TR-TBT 18d-1 cells, at least under normal conditions. Cellular uptake of [(3)H]taurine and [(14)C]betaine by TR-TBT 18d-1 cells cultured under hypertonic conditions was increased compared to that under normal conditions. TauT, BGT-1, ATA2 and HSP70 mRNAs were upregulated by hypertonicity, while OCTN2, ENT1 and CNT1 mRNAs were downregulated. [(3)H]Taurine uptake was strongly inhibited by TauT inhibitors such as hypotaurine and β-alanine. MeAIB, a system A specific substrate, inhibited hypertonic stress-induced [(14)C]betaine uptake. These results suggest that TauT and system A play cytoprotective roles in syncytiotrophoblasts exposed to hypertonic stress. PMID:20801504

  20. Hypertonic Saline for the Treatment of Bronchiolitis in Infants and Young Children: A Critical Review of the Literature

    PubMed Central

    Baron, Jeffrey

    2016-01-01

    Bronchiolitis, an infection of the lower respiratory tract, is the leading cause of infant and child hospitalization in the United States. Therapeutic options for management of bronchiolitis are limited. Hypertonic saline inhalation therapy has been studied in numerous clinical trials with mixed results. In 2014, the American Academy of Pediatrics (AAP) published updated guidelines on the diagnosis and management of bronchiolitis, which include new recommendations on the use of hypertonic saline. We reviewed all published clinical trials mentioned in the 2014 AAP guidelines, as well as additional trials published since the guidelines, and critically evaluated each trial to determine efficacy, safety, and expectations of hypertonic saline inhalation therapy. A total of 2682 infants were studied over the course of 22 clinical trials. Nine trials were carried out in the outpatient/clinic/emergency department and 13 in the inpatient setting. We agree with the AAP guidelines regarding the recommendation to use nebulized hypertonic saline for infants hospitalized with bronchiolitis, with the expectation of reducing bronchiolitis scores and length of stay when it is expected to last more than 72 hours. However, we also believe there might be an advantage for hypertonic saline in reducing admission rates from the emergency department, based on close examination of the results of recent trials. This review also highlights important gaps in the available literature that need to be addressed in order to define the role of inhaled hypertonic saline therapy. PMID:26997926

  1. Prehospital Resuscitation of Traumatic Hemorrhagic Shock with Hypertonic Solutions Worsens Hypocoagulation and Hyperfibrinolysis.

    PubMed

    Delano, Matthew J; Rizoli, Sandro B; Rhind, Shawn G; Cuschieri, Joseph; Junger, Wolfgang; Baker, Andrew J; Dubick, Michael A; Hoyt, David B; Bulger, Eileen M

    2015-07-01

    Impaired hemostasis frequently occurs after traumatic shock and resuscitation. The prehospital fluid administered can exacerbate subsequent bleeding and coagulopathy. Hypertonic solutions are recommended as first-line treatment of traumatic shock; however, their effects on coagulation are unclear. This study explores the impact of resuscitation with various hypertonic solutions on early coagulopathy after trauma. We conducted a prospective observational subgroup analysis of large clinical trial on out-of-hospital single-bolus (250 mL) hypertonic fluid resuscitation of hemorrhagic shock trauma patients (systolic blood pressure, ≤70 mmHg). Patients received 7.5% NaCl (HS), 7.5% NaCl/6% Dextran 70 (HSD), or 0.9% NaCl (normal saline [NS]) in the prehospital setting. Thirty-four patients were included: 9 HS, 8 HSD, 17 NS. Treatment with HS/HSD led to higher admission systolic blood pressure, sodium, chloride, and osmolarity, whereas lactate, base deficit, fluid requirement, and hemoglobin levels were similar in all groups. The HSD-resuscitated patients had higher admission international normalized ratio values and more hypocoagulable patients, 62% (vs. 55% HS, 47% NS; P < 0.05). Prothrombotic tissue factor was elevated in shock treated with NS but depressed in both HS and HSD groups. Fibrinolytic tissue plasminogen activator and anti-fibrinolytic plasminogen activator inhibitor type 1 were increased by shock but not thrombin-activatable fibrinolysis inhibitor. The HSD patients had the worst imbalance between procoagulation/anticoagulation and profibrinolysis/antifibrinolysis, resulting in more hypocoagulability and hyperfibrinolysis. We concluded that resuscitation with hypertonic solutions, particularly HSD, worsens hypocoagulability and hyperfibrinolysis after hemorrhagic shock in trauma through imbalances in both procoagulants and anticoagulants and both profibrinolytic and antifibrinolytic activities. PMID:25784523

  2. Hypertonic saline monotherapy in children with perennial allergic rhinitis: a pilot study.

    PubMed

    Barberi, S; D'Auria, E; Bernardo, L; Ferrara, F; Pietra, B; Pinto, F; Ferrero, F; Ciprandi, G

    2016-01-01

    Perennial allergic rhinitis (PAR) is very common in children and has a relevant impact on their families. House dust mites (HDM) are the most relevant cause of PAR. The present pilot study aimed to evaluate whether hypertonic saline (3%) nasal spray as monotherapy is able to improve: nasal symptom severity and parental perception of rhinitis control, sleep, and school performance in HDM-mono-sensitized children with PAR. Globally, 25 children (13 males and 12 females; mean age 9.5±3.1 years) were treated for 3 weeks. They were visited at baseline, at the end of treatment, and after a 2-week follow-up. Hypertonic saline significantly reduced total symptom score, and improved the perception, according to their parents, of rhinitis control, sleep, and school performance. In conclusion, the present pilot study provided the first evidence that 3% hypertonic saline monotherapy was able to relieve nasal symptoms and parental perception of PAR impact as well as being safe and well tolerated. PMID:27049102

  3. Sphingomyelin metabolism is involved in the differentiation of MDCK cells induced by environmental hypertonicity

    PubMed Central

    Favale, Nicolás Octavio; Santacreu, Bruno Jaime; Pescio, Lucila Gisele; Marquez, Maria Gabriela; Sterin-Speziale, Norma Beatriz

    2015-01-01

    Sphingolipids (SLs) are relevant lipid components of eukaryotic cells. Besides regulating various cellular processes, SLs provide the structural framework for plasma membrane organization. Particularly, SM is associated with detergent-resistant microdomains. We have previously shown that the adherens junction (AJ) complex, the relevant cell-cell adhesion structure involved in cell differentiation and tissue organization, is located in an SM-rich membrane lipid domain. We have also demonstrated that under hypertonic conditions, Madin-Darby canine kidney (MDCK) cells acquire a differentiated phenotype with changes in SL metabolism. For these reasons, we decided to evaluate whether SM metabolism is involved in the acquisition of the differentiated phenotype of MDCK cells. We found that SM synthesis mediated by SM synthase 1 is involved in hypertonicity-induced formation of mature AJs, necessary for correct epithelial cell differentiation. Inhibition of SM synthesis impaired the acquisition of mature AJs, evoking a disintegration-like process reflected by the dissipation of E-cadherin and β- and α-catenins from the AJ complex. As a consequence, MDCK cells did not develop the hypertonicity-induced differentiated epithelial cell phenotype. PMID:25670801

  4. Biochemical and histochemical features of human cultured cells (EUE) adapted to hypertonic medium.

    PubMed

    Bolognani, L; Fantin, A M; Conti, A M; Gervaso, M V; Salè, M F

    1978-01-01

    EUE cells from a human heteroploid line cultured in hypertonic medium (0.274 M NaCl) modify their lipid pattern: sulfolipid concentration reaches 86 to 90 microgram/mg protein whilst it ranges between 19 to 32 microgram/mg in cells cultured in isotonic medium. Ganglioside concentration reaches 2.6 nmoles of sialic acid/mg protein (after 75 days) and 13 (after 85 days) in hypertonic saline medium. Whilst it is 0.5 in isotonic medium. Phospholipid concentration does not show any similar change. Cytoenzymatic analysis reveals that dehydrogenases (lactate, G-6-P dehydrogenases, tetrahydrofolate reductase and NADH diaphorase) appear strongly enhanced in cells grown on hypertonic medium. On the contrary higher acid phosphatase and ATPase activity was demonstrable in cells grown on isotonic medium. These results are similar (except for ATPase activity) to those observed in salt secreting glands involved in strong osmotic work. The results are discussed in relation to the problem of energy supply in cells performing osmotic work. PMID:151474

  5. Pre-Exercise Ingestion of Pickle Juice, Hypertonic Saline, or Water and Aerobic Performance and Thermoregulation

    PubMed Central

    Peikert, Jarett; Miller, Kevin C.; Albrecht, Jay; Tucker, Jared; Deal, James

    2014-01-01

    Context: Ingesting high-sodium drinks pre-exercise can improve thermoregulation and performance. Athletic trainers (19%) give athletes pickle juice (PJ) prophylactically for cramping. No data exist on whether this practice affects aerobic performance or thermoregulation. Objective: To determine if drinking 2 mL/kg body mass of PJ, hypertonic saline, or deionized water (DIW) pre-exercise affects aerobic performance or thermoregulation. Design: Crossover study. Setting: Controlled laboratory study. Patients or Other Participants: Nine euhydrated men (age = 22 ± 3 years, height = 184.0 ± 8.2 cm, mass = 82.6 ± 16.0 kg) completed testing. Intervention(s): Participants rested for 65 minutes. During this period, they ingested 2 mL/kg of PJ, hypertonic saline, or DIW. Next, they drank 5 mL/kg of DIW. Blood was collected before and after ingestion of all fluids. Participants were weighed and ran in the heat (temperature = 38.3°C ± 1°C, relative humidity = 21.1% ± 4.7%) at increasing increments of maximal heart rate (50%, 60%, 70%, 80%, 90%, 95%) until exhaustion or until rectal temperature exceeded 39.5°C. Participants were weighed postexercise so we could calculate sweat volume. Main Outcome Measure(s): Time to exhaustion, rectal temperature, changes in plasma volume, and sweat volume. Results: Time to exhaustion did not differ among drinks (PJ = 77.4 ± 5.9 minutes, hypertonic saline = 77.4 ± 4.0 minutes, DIW = 75.7 ± 3.2 minutes; F2,16 = 1.1, P = .40). Core temperature of participants was similar among drinks (PJ = 38.7°C ± 0.3°C, hypertonic saline = 38.7°C ± 0.4°C, DIW = 38.8°C ± 0.4°C; P = .74) but increased from pre-exercise (36.7°C ± 0.2°C) to postexercise (38.7°C ± 0.4°C) (P < .05). No differences were observed for changes in plasma volume or sweat volume among drinks (P > .05). Conclusions: Ingesting small amounts of PJ or hypertonic saline with water did not affect performance or select thermoregulatory measures. Drinking larger volumes of

  6. Hypertonicity increases NO production to modulate the firing rate of magnocellular neurons of the supraoptic nucleus of rats.

    PubMed

    da Silva, M P; Ventura, R R; Varanda, W A

    2013-10-10

    Increases in plasma osmolality enhance nitric oxide (NO) levels in magnocellular neurosecretory cells (MNCs) of the supraoptic nucleus (SON) and modulate the secretion of both vasopressin (VP) and oxytocin (OT). In this paper, we describe the effects of hypertonicity on the electrical properties of MNCs by focusing on the nitrergic modulation of their activity in this condition. Membrane potentials were measured using the patch clamp technique, in the presence of both glutamatergic and GABAergic neurotransmission blockers, in coronal brain slices of male Wistar rats. The recordings were first made under a control condition (295 mosm/kg H2O), then in the presence of a hypertonic stimulus (330 mosm/kg H2O) and, finally, with a hypertonic stimulus plus 500 μM L-Arginine or 100 μM N-nitro-L-Arginine methyl ester hydrochloride (L-NAME). Hypertonicity per se increased the firing frequency of the neurons. L-Arginine prevented the increase in fire frequency induced by hypertonic stimulus, and L-NAME (inhibitor of nitric oxide synthase) induced an additional increase in frequency when applied together with the hypertonic solution. Moreover, L-Arginine hyperpolarizes the resting potential and decreases the peak value of the after-hyperpolarization; both effects were blocked by L-NAME and hypertonicity and/or L-NAME reduced the time constant of the rising phase of the after-depolarization. These results demonstrate that an intrinsic nitrergic system is part of the mechanisms controlling the excitability of MNCs of the SON when the internal fluid homeostasis is disturbed. PMID:23850590

  7. Inhibition of neutrophils by hypertonic saline involves pannexin-1, CD39, CD73, and other ectonucleotidases

    PubMed Central

    Chen, Yu; Bao, Yi; Zhang, Jingping; Woehrle, Tobias; Sumi, Yuka; Ledderose, Stephan; Li, Xiaoou; Ledderose, Carola; Junger, Wolfgang G.

    2015-01-01

    Hypertonic saline (HS) resuscitation has been studied as a possible strategy to reduce PMN activation and tissue damage in trauma patients. HS blocks PMNs by ATP release and stimulation of A2a adenosine receptors. Here we studied the underlying mechanisms in search of possible reasons for the inconsistent results of recent clinical trials with HS resuscitation. Purified human PMNs or PMNs in whole blood were treated with HS to simulate hypertonicity levels found after HS resuscitation (40 mM beyond isotonic levels). ATP release was measured with a luciferase assay. PMN activation was assessed by measuring oxidative burst. The pannexin-1 (panx1) inhibitor 10panx1 and the gap junction inhibitor carbenoxolone (CBX) blocked ATP release from PMNs in purified and whole blood preparations, indicating that HS releases ATP via panx1 and gap junction channels. HS blocked fMLP-induced PMN activation by 40% in purified PMN preparations and by 60% in whole blood. These inhibitory effects were abolished by 10panx1 but only partially reduced by CBX, which indicates that panx1 has a central role in the immunomodulatory effects of HS. Inhibition of the ectonucleotidases CD39 and CD73 abolished the suppressive effect of HS on purified PMN cultures but only partially reduced the effect of HS in whole blood. These findings suggest redundant mechanisms in whole blood that may strengthen the immunomodulatory effect of HS in vivo. We conclude that HS resuscitation exerts anti-inflammatory effects that involve panx1, CD39, CD73, and other ectonucleotidases, which produce the adenosine that blocks PMNs by stimulating their A2a receptors. Our findings shed new light on the immunomodulatory mechanisms of HS and suggest possible new strategies to improve the clinical efficacy of hypertonic resuscitation. PMID:26009814

  8. Fluid deprivation increases isotonic NaCl intake, but not hypertonic salt intake, under normal and heated conditions in obese Zucker rats.

    PubMed

    Omouessi, S T; Lemamy, G J; Kiki-Mvouaka, S; Fernette, B; Falconetti, C; Ndeboko, B; Mouecoucou, J; Thornton, S N

    2016-02-01

    In the course of exposure to fluid deprivation and heated environment, mammals regulate their hydromineral balance and body temperature by a number of mechanisms including sweating, water and salt intakes. Here we challenged obese Zucker rats, known to have a predisposition to hypertension, with 0.9%NaCl alone or with 2%NaCl solution + water to drink under fluid deprivation and heated conditions. Food and fluid intakes, body weight, diuresis and natriuresis were measured daily throughout. Serum aldosterone levels and Na(+) concentration were also analyzed. Data showed that obese and lean rats presented similar baseline measurements of food, 0.9%NaCl and fluid intakes, diuresis and fluid balance; whereas hypertonic 2%NaCl consumption was almost absent. Before and during fluid deprivation animals increased isotonic but not hypertonic NaCl intake; the obese showed significant increases in diuresis and Na(+) excretion, whereas, total fluid intake was similar between groups. Heat increased isotonic NaCl intake and doubled natriuresis in obese which were wet on their fur and displayed a paradoxical increase of fluid gain. Fluid deprivation plus heat produced similar negative fluid balance in all groups. Body weight losses, food intake and diuresis reductions were amplified under the combined conditions. Animals exposed to 2%NaCl showed higher circulating levels of aldosterone and obese were lower than leans. In animals which drank 0.9%NaCl, obese showed higher serum levels of Na(+) than leans. We conclude that in spite of their higher sensitivity to high salt and heat obese Zucker rats can control hydromineral balance in response to fluid deprivation and heat by adjusting isotonic NaCl preference with sodium balance and circulating levels of aldosterone. This suggests a key hormonal role in the mechanisms underlying thermoregulation, body fluid homeostasis and sodium intake. PMID:26621332

  9. Serotonin, glutamate and glycerol are released after the injection of hypertonic saline into human masseter muscles – a microdialysis study

    PubMed Central

    2014-01-01

    Background Chronic myalgia is associated with higher muscle levels of certain algesic biomarkers. The aim of this study was to investigate if hypertonic saline-induced jaw myalgia also leads to release of such biomarkers and if there were any sex differences in this respect. Methods Healthy participants, 15 men and 15 aged-matched women (25.7 ± 4.3 years) participated. Intramuscular microdialysis into masseter muscles was performed to sample serotonin (5-HT), glutamate, lactate, pyruvate, glucose and glycerol. After 2 hours 0.2 mL hypertonic saline (58.5 mg/mL) was injected into the masseter on one side and 0.2 mL isotonic saline (9 mg/mL) into the contralateral masseter close to the microdialysis catheter. Microdialysis continued for 1 hour after the injections. Pressure pain thresholds (PPT) and pain were assessed before and after injections. Results The median (IQR) peak pain intensity (0–100 visual analogue scale) after hypertonic saline was 52.5 (38.0) and after isotonic saline 7.5 (24.0) (p < 0.05). 5-HT, glutamate and glycerol increased after hypertonic saline injection (p < 0.05). Lactate, pyruvate and glucose showed no change. PPT after microdialysis was reduced on both sides (p < 0.05) but without side differences. Pain after hypertonic saline injection correlated positively to 5-HT (p < 0.05) and negatively to glycerol (p < 0.05). Conclusions 5-HT, glutamate and glycerol increased after a painful hypertonic saline injection into the masseter muscle, but without sex differences. Since increased levels of 5-HT and glutamate have been reported in chronic myalgia, this strengthens the validity of the pain model. Glycerol warrants further investigations. PMID:25519464

  10. Can empirical hypertonic saline or sodium bicarbonate treatment prevent the development of cardiotoxicity during serious amitriptyline poisoning? Experimental research

    PubMed Central

    Sukru Paksu, Muhammet; Zengin, Halit; Uzun, Adem; Ilkaya, Fatih; Guzel, Hasan; Paksu, Sule; Ucar, Durmus; Alacam, Hasan; Duran, Latif; Murat, Naci; Guzel, Ahmet

    2015-01-01

    Summary Objective The aim of this experimental study was to investigate whether hypertonic saline or sodium bicarbonate administration prevented the development of cardiotoxicity in rats that received toxic doses of amitriptyline. Method Thirty-six Sprague Dawley rats were used in the study. The animals were divided into six groups. Group 1 received toxic doses of i.p. amitriptyline. Groups 2 and 3 toxic doses of i.p. amitriptyline, plus i.v. sodium bicarbonate and i.v. hypertonic saline, respectively. Group 4 received only i.v. sodium bicarbonate, group 5 received only i.v. hypertonic saline, and group 6 was the control. Electrocardiography was recorded in all rats for a maximum of 60 minutes. Blood samples were obtained to measure the serum levels of sodium and ionised calcium. Results The survival time was shorter in group 1. In this group, the animals’ heart rates also decreased over time, and their QRS and QTc intervals were significantly prolonged. Groups 2 and 3 showed less severe changes in their ECGs and the rats survived for a longer period. The effects of sodium bicarbonate or hypertonic saline treatments on reducing the development of cardiotoxicity were similar. The serum sodium levels decreased in all the amitriptyline-applied groups. Reduction of serum sodium level was most pronounced in group 1. Conclusion Empirical treatment with sodium bicarbonate or hypertonic saline can reduce the development of cardiotoxicity during amitriptyline intoxication. As hypertonic saline has no adverse effects on drug elimination, it should be considered as an alternative to sodium bicarbonate therapy. PMID:25939777

  11. Hypertonic conditions trigger transient plasmolysis, growth arrest and blockage of transporter endocytosis in Aspergillus nidulans and Saccharomyces cerevisiae.

    PubMed

    Bitsikas, Vassilis; Karachaliou, Mayia; Gournas, Christos; Diallinas, George

    2011-01-01

    By using Aspergillus nidulans strains expressing functional GFP-tagged transporters under hypertonic conditions, we noticed the rapid appearance of cortical, relatively static, fluorescent patches (0.5-2.3 μm). These patches do not correspond to transporter microdomains as they co-localize with other plasma membrane-associated molecules, such as the pleckstrin homology (PH) domain and the SsoA t-Snare, or the lipophilic markers FM4-64 and filipin. In addition, they do not show characteristics of lipid rafts, MCCs or other membrane microdomains. Deconvoluted microscopic images showed that fluorescent patches correspond to plasma membrane invaginations. Transporters remain fully active during this phenomenon of localized plasmolysis. Plasmolysis was however associated with reduced growth rate and a dramatic blockage in transporter and FM4-64 endocytosis. These phenomena are transient and rapidly reversible upon wash-out of hypertonic media. Based on the observation that block in endocytosis by hypertonic treatment altered dramatically the cellular localization of tropomyosin (GFP-TpmA), although it did not affect the cortical appearance of upstream (SlaB-GFP) or downstream (AbpA-mRFP) endocytic components, we conclude that hypertonicity modifies actin dynamics and thus acts indirectly on endocytosis. This was further supported by the effect of latrunculin B, an actin depolymerization agent, on endocytosis. We show that the phenomena observed in A. nidulans also occur in Saccharomyces cerevisiae, suggesting that they constitute basic homeostatic responses of ascomycetes to hypertonic shock. Finally, our work shows that hypertonic treatments can be used as physiological tools to study the endocytic down-regulation of transporters in A. nidulans, as non-conditional genetic blocks affecting endocytic internalization are lethal or severely debilitating. PMID:20919858

  12. INHALED HYPERTONIC SALINE IN INFANTS AND CHILDREN LESS THAN SIX YEARS OF AGE WITH CYSTIC FIBROSIS: THE ISIS RANDOMIZED TRIAL

    PubMed Central

    Rosenfeld, Margaret; Ratjen, Felix; Brumback, Lyndia; Daniel, Stephen; Rowbotham, Ron; McNamara, Sharon; Johnson, Robin; Kronmal, Richard; Davis, Stephanie D

    2013-01-01

    Context Inhaled hypertonic saline is recommended as therapy for cystic fibrosis (CF) patients 6 years of age and older, but its efficacy has never been evaluated in CF patients <6 years of age. Objective To determine if hypertonic saline reduces the rate of protocol-defined pulmonary exacerbations in CF patients <6 years of age. Design and Setting A multicenter, randomized, double-blind placebo-controlled trial was conducted from April 2009 to October 2011 at 30 CF care centers in the United States and Canada. Participants Participants had an established diagnosis of CF and were 4 to 60 months of age. A total of 344 patients were assessed for eligibility; 321 participants were randomized; 29 (9%) withdrew prematurely. Intervention The active group (n=158) received 7% hypertonic saline and the control group (n=163) received 0.9% isotonic saline nebulized twice daily for 48 weeks. Both groups received albuterol or levalbuterol prior to each study drug dose. Main Outcome Measures the rate of protocol-defined pulmonary exacerbations during the 48 week treatment period treated with oral, inhaled or intravenous antibiotics. Results The mean pulmonary exacerbation rate (events/person-year) was 2.3 (95% CI, 2.0, 2.5) in the hypertonic saline group and 2.3 (95% CI, 2.1, 2.6) in the isotonic saline group; the rate ratio was 0.98 (95% CI, 0.84, 1.14)). Among participants with pulmonary exacerbations, the mean number of total antibiotic treatment days for a pulmonary exacerbation was 60 (95% CI 49, 70) in the hypertonic saline group and 52 (95% CI 43, 61) in the isotonic saline group. There was no significant difference in secondary endpoints including height, weight, respiratory rate, oxygen saturation, cough or respiratory symptom scores. Infant pulmonary function testing performed as an exploratory outcome in a subgroup (N=73, with acceptable measurements at 2 visits in 45) did not demonstrate significant differences between groups except for the mean change in forced

  13. Endocytic response of type I alveolar epithelial cells to hypertonic stress

    PubMed Central

    Wang, Shaohua; Singh, Raman Deep; Godin, Lindsay; Pagano, Richard E.

    2011-01-01

    We present plasma membrane (PM) internalization responses of type I alveolar epithelial cells to a 50 mosmol/l increase in tonicity. Our research is motivated by interest in ATI repair, for which endocytic retrieval of PM appears to be critical. We validated pharmacological and molecular tools to dissect the endocytic machinery of these cells and used these tools to test the hypothesis that osmotic stress triggers a pathway-specific internalization of PM domains. Validation experiments confirmed the fluorescent analogs of lactosyl-ceramide, transferrin, and dextran as pathway-specific cargo of caveolar, clathrin, and fluid-phase uptake, respectively. Pulse-chase experiments indicate that hypertonic exposure causes a downregulation of clathrin and fluid-phase endocytosis while stimulating caveolar endocytosis. The tonicity-mediated increase in caveolar endocytosis was associated with the translocation of caveolin-1 from the PM and was absent in cells that had been transfected with dominant-negative dynamin constructs. In separate experiments we show that hypertonic exposure increases the probability of PM wound repair following micropuncture from 82 ± 4 to 94 ± 2% (P < 0.01) and that this effect depends on Src pathway activation-mediated caveolar endocytosis. The therapeutic and biological implications of our findings are discussed. PMID:21257731

  14. [Bioregulating therapy and life quality in aged patients with hypertonic angioretinopathy].

    PubMed

    Trofimova, S V; Atakhanova, L E; Akhmedova, E P

    2008-01-01

    The researches data of influence of vascular impair of a retina in aged patients with arterial hypertension (AH) on their life quality (LQ) are given in the article. The questionnaires "The Scale of an estimation of life quality", SF-36 and VF-16 in authors updating were used. Ultrasonic dopplerography of retina vessels in patients with hypertonic angioretinopathy showed the authentic decrease of maximal systolic speeds of a blood-groove of an orbital artery, increase in its index of resistance and decrease of ophthalmic-retinal factor in comparison with normal parameters in the given age group. The studying of the comparative analysis of change of LQ and visual functions of aged patients with hypertonic angioretinopathy under adding to complex hypotensive therapies the Cortexin (the basic group, 28 people) and Actovegin (control group, 30 people) was held. As a result of treatment disappearance or reduction of visual discomfort and improvement of the emotional condition of 61% of patients of the basic group and 36% of patients of control group were marked. Improvement of LQ and subjective quality of eyesight correlated with improvement of visual functions. Thus, the researches enable to include people of elderly and senile age with AH into group of risk with probable decrease in visual functions; inclusion the neuro-protector cortexin in complex treatment of elderly and senile patients with AH and changes in eye-bottom considerably raises and stabilizes LQ and quality of eyesight of these patients. PMID:19432215

  15. Symptomatic Abdominal Simple Cysts: Is Percutaneous Sclerotherapy with Hypertonic Saline and Bleomycin a Treatment Option?

    PubMed Central

    Souftas, V. D.; Kosmidou, M.; Karanikas, M.; Souftas, D.; Menexes, G.; Prassopoulos, P.

    2015-01-01

    Aim. To evaluate the feasibility of percutaneous sclerotherapy of symptomatic simple abdominal cysts, using hypertonic saline and bleomycin, as an alternative to surgery. Materials and Methods. This study involved fourteen consecutive patients (ten women, four men, mean age: 59.2 y) with nineteen symptomatic simple cysts (liver n = 14, kidney n = 3, and adrenal n = 2) treated percutaneously using a modified method. Initially CT-guided drainage was performed; the next day the integrity of the cyst/exclusion of extravasation or communications was evaluated under fluoroscopy, followed by two injections/reabsorptions of the same quantity of hypertonic NaCl 15% solution and three-time repetition of the same procedure with the addition of bleomycin. The catheter was then removed; the patients were hospitalized for 12 hours and underwent follow-ups on 1st, 3rd, 6th, and 12th months. Cyst's volumes and the reduction rate (%) were calculated in each evaluation. Results. No pain or complications were noted. A significant cyst's volume reduction was documented over time (P < 0.001). On the 12th month 17 cysts disappeared and two displayed a 98.7% and 68.9% reduction, respectively. Conclusion. This percutaneous approach constitutes a very promising nonsurgical alternative for patients with symptomatic simple cyst, without complications under proper precautions, leading to eliminating the majority of cysts. PMID:25878660

  16. Neurohypophyseal response to fluid resuscitation with hypertonic saline during septic shock in rats.

    PubMed

    Santiago, Michael Brian; Vieira, Alexandre Antonio; Elias, Lucila L K; Rodrigues, José Antunes; Giusti-Paiva, Alexandre

    2013-02-01

    Septic shock is a serious condition with a consequent drop in blood pressure and inadequate tissue perfusion. Small-volume resuscitation with hypertonic saline (HS) has been proposed to restore physiological haemodynamics during haemorrhagic and endotoxic shock. In the present study, we sought to determine the effects produced by an HS infusion in rats subjected to caecal ligation and perforation (CLP). Male Wistar rats were randomly grouped and submitted to either CLP or sham surgery. Either HS (7.5% NaCl, 4 ml kg(-1) i.v.) or isotonic saline (IS; 0.9% NaCl, 4 ml kg(-1) i.v.) was administered 6 h after CLP. Recordings of mean arterial pressure and heart rate were made during this protocol. Moreover, measurements of electrolyte, vasopressin and oxytocin secretion were analysed after either the HS or the IS treatment. Six hours after CLP, we observed a characteristic decrease in mean arterial pressure that occurs after CLP. The HS infusion in these rats produced a transient elevation of the plasma sodium concentration and osmolality and increased plasma vasopressin and oxytocin levels. Moreover, the HS infusion could restore the mean arterial pressure after CLP, which was completely blunted by the previous injection of the vasopressin but not the oxytocin antagonist. The present study demonstrated that rats subjected to CLP and an infusion of hypertonic saline respond with secretion of neurohypophyseal hormones and a transient increase in blood pressure mediated by the V(1) receptor. PMID:22903979

  17. Hypertonicity sensing in organum vasculosum lamina terminalis neurons: a mechanical process involving TRPV1 but not TRPV4.

    PubMed

    Ciura, Sorana; Liedtke, Wolfgang; Bourque, Charles W

    2011-10-12

    Primary osmosensory neurons in the mouse organum vasculosum lamina terminalis (OVLT) transduce hypertonicity via the activation of nonselective cation channels that cause membrane depolarization and increased action potential discharge, and this effect is absent in mice lacking expression of the transient receptor potential vanilloid 1 (Trpv1) gene (Ciura and Bourque, 2006). However other experiments have indicated that channels encoded by Trpv4 also contribute to central osmosensation in mice (Liedtke and Friedman, 2003; Mizuno et al., 2003). At present, the mechanism by which hypertonicity modulates cation channels in OVLT neurons is unknown, and it remains unclear whether Trpv1 and Trpv4 both contribute to this process. Here, we show that physical shrinking is necessary and sufficient to mediate hypertonicity sensing in OVLT neurons isolated from adult mice. Steps coupling progressive decreases in cell volume to increased neuronal activity were quantitatively equivalent whether shrinking was evoked by osmotic pressure or mechanical aspiration. Finally, modulation of OVLT neurons by tonicity or mechanical stimulation was unaffected by deletion of trpv4 but was abolished in cells lacking Trpv1 or wild-type neurons treated with the TRPV1 antagonist SB366791. Thus, hypertonicity sensing is a mechanical process requiring Trpv1, but not Trpv4. PMID:21994383

  18. AMPK potentiates hypertonicity-induced apoptosis by suppressing NFκB/COX-2 in medullary interstitial cells.

    PubMed

    Han, Qifei; Zhang, Xiaoyan; Xue, Rui; Yang, Hang; Zhou, Yunfeng; Kong, Xiaomu; Zhao, Pan; Li, Jing; Yang, Jichun; Zhu, Yi; Guan, Youfei

    2011-10-01

    Cells residing in the hypertonic, hypoxic renal medulla depend on dynamic adaptation mechanisms to respond to changes in energy supply and demand. The serine/threonine kinase 5'-AMP protein kinase (AMPK) is a sensor of cellular energy status, but whether it contributes to the survival of cells in the renal medulla is unknown. Here, hypertonic conditions induced a decrease in AMPK phosphorylation within 12 hours in renal medullary interstitial cells (RMIC), followed by a gradual return to baseline levels. Activation of AMPK markedly increased hypertonicity-induced apoptosis of RMICs and suppressed both hypertonicity-induced NFκB nuclear translocation and cyclooxygenase-2 (COX-2) activation; overexpression of COX-2 significantly attenuated these effects. AMPK activation also markedly reduced generation of reactive oxygen species and nuclear expression of tonicity-responsive enhancer-binding protein, which prevented upregulation of osmoprotective genes. In vivo, pharmacologic activation of AMPK led to massive apoptosis of RMICs and renal dysfunction in the setting of water deprivation in mice. Taken together, these results identify a critical role for AMPK in the maintenance of RMIC viability and suggest that AMPK modulates the NFκB-COX-2 survival pathway in the renal medulla. Furthermore, this study raises safety concerns for the development of AMPK activators as anti-diabetic drugs, especially for patients prone to dehydration. PMID:21903993

  19. Hypertonic enhancement of transmitter release from frog motor nerve terminals: Ca2+ independence and role of integrins

    NASA Technical Reports Server (NTRS)

    Kashani, A. H.; Chen, B. M.; Grinnell, A. D.

    2001-01-01

    Hyperosmotic solutions cause markedly enhanced spontaneous quantal release of neurotransmitter from many nerve terminals. The mechanism of this enhancement is unknown. We have investigated this phenomenon at the frog neuromuscular junction with the aim of determining the degree to which it resembles the modulation of release by stretch, which has been shown to be mediated by mechanical tension on integrins.The hypertonicity enhancement, like the stretch effect, does not require Ca2+ influx or release from internal stores, although internal release may contribute to the effect. The hypertonicity effect is sharply reduced (but not eliminated) by peptides containing the RGD sequence, which compete with native ligands for integrin bonds.There is co-variance in the magnitude of the stretch and osmotic effects; that is, individual terminals exhibiting a large stretch effect also show strong enhancement by hypertonicity, and vice versa. The stretch and osmotic enhancements also can partially occlude each other.There remain some clear-cut differences between osmotic and stretch forms of modulation: the larger range of enhancement by hypertonic solutions, the relative lack of effect of osmolarity on evoked release, and the reported higher temperature sensitivity of osmotic enhancement. Nevertheless, our data strongly implicate integrins in a significant fraction of the osmotic enhancement, possibly acting via the same mechanism as stretch modulation.

  20. The membrane properties of the smooth muscle of the guinea-pig portal vein in isotonic and hypertonic solutions.

    PubMed

    Kuriyama, H; Oshima, K; Sakamoto, Y

    1971-08-01

    The membrane properties of the longitudinal smooth muscle of the guinea-pig portal vein were investigated under various experimental conditions.1. In isotonic Krebs solution, the membrane potential (-48.7 mV), the maximum rates of rise and fall of the spike (4.6 and 2.3 V/sec respectively), the space constant (0.61 mm), the conduction velocity of excitation (0.97 cm/sec) and the time constant of the foot of the propagated spike (18.4 msec) were measured.2. The various parameters of the muscle membrane in the isotonic solution were compared with those in the hypertonic solution prepared by the addition of solid sucrose (twice the normal tonicity).3. When the muscles were perfused with hypertonic solution, marked depolarization of the membrane and increased membrane resistance occurred. These were probably due to reduction of the K permeability, increased internal resistance of the muscle and shrinkage of the muscle fibre.4. The membrane potential in isotonic and hypertonic solutions was analysed into two components, i.e. the metabolic (electrogenic Na-pump) and the ionic (electrical diffusion potential) component in the various environmental conditions.(a) In isotonic and hypertonic solutions, the membrane was depolarized by lowering the temperature or by removal of K ion from the solutions. When the tissues were rewarmed or on readdition of K ion, the membrane was markedly hyperpolarized. These hyperpolarizations of the membrane were suppressed by treatment with ouabain (10(-5) g/ml.), by warming to only 20 degrees C and by K-free solution.(b) The relationships between the membrane potential and the [K](o) in isotonic Krebs, in the hypertonic (sucrose) Krebs, in the Na-free (Tris) Krebs and in the Cl-deficient (C(6)H(5)SO(3)) Krebs were observed. The maximum slopes of the membrane depolarization against tenfold changes of [K](o) were much lower than that expected if it behaved like a K electrode.(c) In Na-free (Tris) solution, the membrane was not depolarized in

  1. Intracellular hypertonicity is responsible for water flux associated with Na+/glucose cotransport.

    PubMed

    Charron, François M; Blanchard, Maxime G; Lapointe, Jean-Yves

    2006-05-15

    Detection of a significant transmembrane water flux immediately after cotransporter stimulation is the experimental basis for the controversial hypothesis of secondary active water transport involving a proposed stoichiometry for the human Na(+)/glucose cotransporter (SGLT1) of two Na(+), one glucose, and 264 water molecules. Volumetric measurements of Xenopus laevis oocytes coexpressing human SGLT1 and aquaporin can be used to detect osmotic gradients with high sensitivity. Adding 2 mM of the substrate alpha-methyl-glucose (alphaMG) created mild extracellular hypertonicity and generated a large cotransport current with minimal cell volume changes. After 20, 40, and 60 s of cotransport, the return to sugar-free, isotonic conditions was accompanied by measurable cell swelling averaging 0.051, 0.061, and 0.077 nl/s, respectively. These water fluxes are consistent with internal hypertonicities of 1.5, 1.7, and 2.2 mOsm for these cotransport periods. In the absence of aquaporin, the measured hypertonicites were 4.6, 5.0, and 5.3 mOsm for the same cotransport periods Cotransport-dependent water fluxes, previously assumed to be water cotransport, could be largely explained by hypertonicities of such amplitudes. Using intracellular Na(+) injection and Na(+)-selective electrode, the intracellular diffusion coefficient for Na(+) was estimated at 0.29 +/- 0.03 x 10(-5) cm(2) s(-1). Using the effect of intracellular alphaMG injection on the SGLT1-mediated outward current, the intracellular diffusion coefficient of alphaMG was estimated at 0.15 +/- 0.01 x 10(-5) cm(2) s(-1). Although these intracellular diffusion coefficients are much lower than in free aqueous solution, a diffusion model for a single solute in an oocyte would require a diffusion coefficient three times lower than estimated to explain the local osmolyte accumulation that was experimentally detected. This suggests that either the diffusion coefficients were overestimated, possibly due to the presence of

  2. Hypertonic glucose pleurodesis and surgical diaphragmatic repair for tension hydrothorax complicating continuous ambulatory peritoneal dialysis.

    PubMed

    Wei, Gui-Na; Mao, Jian-Hua

    2016-05-01

    We herein describe a case of tension hydrothorax that occurred on continuous ambulatory peritoneal dialysis (CAPD), highlighting the problems of diagnosis and a novel management. A 38-year-old male with end-stage renal disease (ESRD) due to diabetes mellitus developed dyspnea and poor drainage after 13 months of CAPD. Chest X-ray revealed massive right-sided hydrothorax and mediastinal shift. He underwent emergency thoracentesis and pleural fluid showed a high level of glucose. Pleuroperitoneal communication was strongly suspected, although the methylene blue test was negative. We temporarily performed hemodialysis. Two weeks later, PD was resumed but failed with recurrent right-side hydrothorax in 4 months. The pleuroperitoneal leakage was definitively confirmed by video-assisted thoracoscopic surgery (VATS). Diaphragmatic repair and pleurodesis with hypertonic glucose were performed. There was no recurrence of hydrothorax after treatment. PMID:26784913

  3. Ultramicroscopic and biochemical changes in ram spermatozoa cryopreserved with trehalose-based hypertonic extenders.

    PubMed

    Aisen, E; Quintana, M; Medina, V; Morello, H; Venturino, A

    2005-06-01

    The ability of a range of extenders to cryopreserve ram spermatozoa was tested. The extenders were modified by the inclusion of citrate, Tris buffer, trehalose, and EDTA. Ejaculates from three Pampinta rams were evaluated and pooled at 30 degrees C. The semen was diluted to contain 1 x 10(9) cells/mL, cooled to 5 degrees C, loaded into 0.25-mL straws, frozen and stored in liquid nitrogen. Evaluation was based on the hypoosmotic swelling test (HOS test), electron microscopy, and biochemical parameters such as lipid peroxidation and reduced and total glutathione levels, all measured after thawing. The HOS test indicated that the percentage of intact plasma membranes after freezing and thawing was significantly higher for the hypertonic extender containing trehalose (T), compared with an extender containing trehalose+EDTA (TE) or an isotonic Tris extender (B) (p < 0.05). Membrane evaluation by ultramicroscopy also indicated better sperm cryopreservation in extender T compared with the others, and there was a significant reduction in the number of damaged membranes (27%, p < 0.0002). The level of reduced glutathione was significantly higher after sperm cryopreservation in either hypertonic diluent (T and TE) with respect to the isotonic extender B, immediately after thawing (12%) and after a 3-h post-thawing thermotolerance test at 37 degrees C (17%, p = 0.007). Total glutathione levels did not show statistical differences among the extenders. After 3h post-thawing incubation at 37 degrees C, lipid peroxide levels in spermatozoa were statistically lower for T than TE (35%) or isotonic extender B (44%) (p = 0.002). Taken together these results indicate a reduction in the oxidative stress provoked by freezing and thawing when semen is cryopreserved in extender T. The antioxidant properties of extender T may be related to its effectiveness in membrane cryopreservation. PMID:15925576

  4. Hypertonic conditions enhance cartilage formation in scaffold-free primary chondrocyte cultures.

    PubMed

    Ylärinne, Janne H; Qu, Chengjuan; Lammi, Mikko J

    2014-11-01

    The potential of hypertonic conditions at in vivo levels to promote cartilage extracellular matrix accumulation in scaffold-free primary chondrocyte cultures was investigated. Six million bovine primary chondrocytes were cultured in transwell inserts in low glucose (LG), high glucose (HG), or hypertonic high glucose (HHG) DMEM supplemented with fetal bovine serum, antibiotics, and ascorbate under 5 % or 20 % O2 tension with and without transforming growth factor (TGF)-β3 for 6 weeks. Samples were collected for histological staining of proteoglycans (PGs) and type II collagen, analysis by quantitative reverse transcription plus the polymerase chain reaction (RT-PCR) of mRNA expression of aggrecan and procollagen α1 (II) and of Sox9 and procollagen α2 (I), and quantitation of PGs and PG separation in agarose gels. Cartilage tissues produced at 20 % O2 tension were larger than those formed at 5 % O2 tension. Compared with LG, the tissues grew to larger sizes in HG or HHG medium. Histological staining showed the strongest PG and type II collagen staining in cartilage generated in HG or HHG medium at 20 % O2 tension. Quantitative RT-PCR results indicated significantly higher expression of procollagen α1 (II) mRNA in cartilage generated in HHG medium at 20 % O2 tension compared with that in the other samples. TGF-β3 supplements in the culture medium provided no advantage for cartilage formation. Thus, HHG medium used at 20 % O2 tension is the most beneficial combination of the tested culture conditions for scaffold-free cartilage production in vitro and should improve cell culture for research into cartilage repair or tissue engineering. PMID:25107609

  5. The transport systems of Ventricaria ventricosa: hypotonic and hypertonic turgor regulation.

    PubMed

    Bisson, M A; Beilby, M J

    2002-11-01

    The time course of hypertonic and hypotonic turgor regulation was studied in Ventricaria (Valonia) using pressure probe and I/V(current-voltage) analysis. Of 11 cells, 9 exhibited hypertonic turgor regulation, ranging from 100% regulation in 150 min to 14% regulation (14% recovery of the decrease in turgor) in 314 min. Some cells began regulating immediately, others took up to 90 min to begin. The resting PD (potential difference) became more positive in most cells. The I/V characteristics became more nonlinear with high resistance between -150 and -20 mV and negative conductance region near -70 mV. Prolonged (16 sec) voltage clamps to negative levels (-100 to -150 mV) showed progressively more rapid current turn-off, but subsequent I/V characteristics were not affected. Clamping to +150 mV, however, abolished the high conductance between -50 and +100 mV to yield a uniform high resistance I/V characteristic, similar to that in high [K+]o. Decreasing illumination from 2.02 micromol sec(-1) m(-2) to 0.5 micromol sec(-1)1 m(-2) had a similar effect. Two out of a total of three cells exhibited hypotonic turgor regulation. Both cells started regulating within minutes and achieved near 50% regulation within 50 min. The PD became more negative. The I/V curves exhibited high resistance between +50 and +150 mV. The characteristics were similar to those in cells exposed to low [K+]o. Prolonged voltage clamps to both negative and positive levels showed slow current increase. Decreased illumination increased the membrane resistance. PMID:12422271

  6. The sensitivity of apical Na+ permeability in frog skin to hypertonic stress.

    PubMed

    Zeiske, W; Van Driessche, W

    1984-02-01

    Na+ transport across abdominal skins of the frog species Rana esculenta and Rana pipiens was analyzed by recording short-circuit current (Isc), transepithelial conductance (Gt), and the current noise generated by the random blockage of apical Na+ channels by the diuretic, amiloride. Specific Na+ current (INa) and conductance (GNa), as reflected by the amiloride-sensitive part of Isc and Gt, respectively, were markedly depressed after addition of some osmotically active substances, like sugars or alcohols to the mucosal Na+-Ringer solution. These hypertonicity-induced reactions were fast and fully reversible, even at mucosal osmolarities of 1 Osmol. With mucosal solutions of moderate hyperosmolarity a recovery of INa and GNa was observed in presence of the osmotic gradient. This "regulatory" current showed to be carried by Na+ through the Na+-specific apical channels. Contrary to the fast current drop during the initial phase of hyperosmotic shocks, the "osmoregulation" was considerably slower. The recovery of INa was only complete at smaller osmotic gradients but became more and more suppressed at higher osmolarities. Steady-state analysis of the kinetics of the Na+-specific current revealed that the current depression by osmotic shocks obeys Michaelis-Menten kinetics. This current depression at high osmolarities, as well as during the initial phase before "osmoregulation" with small osmotic gradients, can be described in terms of a non-competitive inhibition. This was also suggested by Na+-concentration jump experiments indicating a reduction of the maximal, apical Na+ permeability as mechanism of the hypertonicity-induced drop in INa. The INa kinetics after complete "osmoregulation" were, however, indistinguishable from the isotonic control condition.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:6326045

  7. [The influence of an isotonic solution containing benzalkonium chloride and a hypertonic seawater solution on the function of ciliary epithelium from the nasal cavity in vitro].

    PubMed

    Laberko, E L; Bogomil'sky, M R; Soldatsky, Yu L; Pogosova, I E

    2016-01-01

    The objective of the present study was to evaluate the influence of an isotonic saline solution containing benzalconium chloride and of a hypertonic seawater solution on the function of ciliary epithelium in the nasal cavity in vitro. To this effect, we investigated the cytological material obtained from 35 children presenting with adenoid tissue hypertrophy. The tissue samples were taken from the nasal cavity by the standard method. A cellular biopsy obtained from each patient was distributed between three tubes that contained isotonic saline solution supplemented by benzalconium chloride (0.1 mg/ml), a hypertonic seawater solution, and a standard physiological saline solution. It was shown that the number of the viable cells in both isotonic solutions was statistically comparable and significantly higher than in the hypertonic solution (p<0.05). The ciliary beat frequency of the cells embedded in the two isotonic solutions was not significantly different but considerably exceeded that in the hypertonic seawater solution (p<0.05). Thus, the present study has demonstrated the absence of the ciliotoxic influence of isotonic saline solution containing benzalconium chloride at a concentration of 0.1 mg/ml and the strong ciliotoxic effect of the hypertonic seawater solution. This finding gives reason to recommend isotonic solutions for the regular application whereas hypertonic solutions can be prescribed only during infectious and/or inflammatory ENT diseases. PMID:27213656

  8. Hypertonic-induced lamin A/C synthesis and distribution to nucleoplasmic speckles is mediated by TonEBP/NFAT5 transcriptional activator

    SciTech Connect

    Favale, Nicolas O.; Sterin Speziale, Norma B.; Fernandez Tome, Maria C.

    2007-12-21

    Lamin A/C is the most studied nucleoskeletal constituent. Lamin A/C expression indicates cell differentiation and is also a structural component of nuclear speckles, which are involved in gene expression regulation. Hypertonicity has been reported to induce renal epithelial cell differentiation and expression of TonEBP (NFAT5), a transcriptional activator of hypertonicity-induced gene transcription. In this paper, we investigate the effect of hypertonicity on lamin A/C expression in MDCK cells and the involvement of TonEBP. Hypertonicity increased lamin A/C expression and its distribution to nucleoplasm with speckled pattern. Microscopy showed codistribution of TonEBP and lamin A/C in nucleoplasmic speckles, and immunoprecipitation demonstrated their interaction. TonEBP silencing caused lamin A/C redistribution from nucleoplasmic speckles to the nuclear rim, followed by lamin decrease, thus showing that hypertonicity induces lamin A/C speckles through a TonEBP-dependent mechanism. We suggest that lamin A/C speckles could serve TonEBP as scaffold thus favoring its role in hypertonicity.

  9. Hypertonic saline solutions do not influence the solubility of sputum from secretor and non-secretor cystic fibrosis patients

    PubMed Central

    Barboza, Marcelo A.I.; Brandão de Mattos, Cinara C.; Ferreira, Ana Iara C.; Barja, Paulo R.; Santos de Faria Junior, Newton; de Oliveira, Luís Vicente F.; de Mattos, Luiz C.

    2011-01-01

    Introduction Functional alterations of the cystic fibrosis transmembrane conductance regulator gene (CFTR) increase the viscoelasticity of pulmonary secretions of cystic fibrosis (CF) patients and require the use of therapeutic aerosols. The biochemical properties of exocrine secretions are influenced by the expression of the FUT2 gene which determine the secretor and non-secretor phenotypes of the ABH glycoconjugates. The aim of this study was to determine the influence of secretor and non-secretor phenotypes by means of photoacoustic analysis, both the typical interaction time (t 0) and the solubilization interval (Δt) of the sputum of secretor and non-secretor CF patients nebulized by hypertonic saline solutions at different concentrations. Material and methods Sputum samples were obtained by spontaneous expectoration from 6 secretor and 4 non-secretor patients with CF. Each sample was nebulized with 3%, 6%, and 7% hypertonic saline solutions in a photoacoustic cell. The values of t 0 and Δt were determined using the Origin 7.5® computer program (Microcal Software Inc.). The t-test was employed using the GraphPad Instat 3.0® computer program to calculate the mean and standard deviation for each parameter. Results For all hypertonic saline solutions tested, the mean values of t 0 and Δt do not show statistically significant differences between secretor and non-secretor patients. Conclusions The secretor and non-secretor phenotypes do not influence the in vitro solubilization of the sputum nebulized by hypertonic saline solutions at different concentrations when analysed by photoacoustic technique. PMID:22291775

  10. Osmotic injury of PC-3 cells by hypertonic NaCl solutions at temperatures above 0 degrees C.

    PubMed

    Zawlodzka, Sylwia; Takamatsu, Hiroshi

    2005-02-01

    Cell injury due to osmotic dehydration, which is regarded as a major cause of injury during freeze-thaw processes, was examined closely using a perfusion microscope. Human prostatic adenocarcinoma cells (PC-3), which were put in a chamber, were subjected to hyperosmotic stresses by perfusing NaCl solutions of varying concentrations into the chamber. Cells were exposed to 2.5 and 4.5M NaCl solutions for 1-60 min by changing the concentrations at 0.2, 1, and 10 M/min. Decrease in cell viability was biphasic: the viability decreased first after the increase in NaCl concentration due to dehydration and then after return to isotonic conditions due to rehydration. Rehydration was substantially more responsible for cell injury than dehydration, which was marked at lower NaCl concentrations and lower temperatures. Injury resulting from contraction was negligible at the 2.5 M NaCl solution. While the hypertonic cell survival, which was determined without a return to isotonic conditions, was almost independent of time of exposure to hyperosmotic concentrations, the post-hypertonic survival after returning to isotonic conditions decreased with increasing exposure time, suggesting that the rehydration-induced injury was a consequence of time-dependent alteration of the plasma membrane. The post-hypertonic survival was lower for higher NaCl concentrations and higher temperatures, which was qualitatively consistent with previous studies. Effects of the rate of concentration change on the post-hypertonic cell survival were observed at 4.5 M; the highest rate of survival was obtained by slower increase and faster decrease in the NaCl concentration. However, the effect was negligible at 2.5 M. PMID:15710370

  11. Acute inhalation of hypertonic saline does not improve mucociliary clearance in all children with cystic fibrosis

    PubMed Central

    2011-01-01

    Background Little is known of how mucociliary clearance (MCC) in children with cystic fibrosis (CF) and normal pulmonary function compares with healthy adults, or how an acute inhalation of 7% hypertonic saline (HS) aerosol affects MCC in these same children. Methods We compared MCC in 12 children with CF and normal pulmonary function after an acute inhalation of 0.12% saline (placebo), or HS, admixed with the radioisotope 99 mtechnetium sulfur colloid in a double-blind, randomized, cross-over study. Mucociliary clearance on the placebo day in the children was also compared to MCC in 10 healthy, non-CF adults. Mucociliary clearance was quantified over a 90 min period, using gamma scintigraphy, and is reported as MCC at 60 min (MCC60) and 90 min (MCC90). Results Median [interquartile range] MCC60 and MCC90 in the children on the placebo visit were 15.4 [12.4-24.5]% and 19.3 [17.3-27.8%]%, respectively, which were similar to the adults with 17.8 [6.4-28.7]% and 29.6 [16.1-43.5]%, respectively. There was no significant improvement in MCC60 (2.2 [-6.2-11.8]%) or MCC90 (2.3 [-1.2-10.5]%) with HS, compared to placebo. In addition, 5/12 and 4/12 of the children showed a decrease in MCC60 and MCC90, respectively, after inhalation of HS. A post hoc subgroup analysis of the change in MCC90 after HS showed a significantly greater improvement in MCC in children with lower placebo MCC90 compared to those with higher placebo MCC90 (p = 0.045). Conclusions These data suggest that percent MCC varies significantly between children with CF lung disease and normal pulmonary functions, with some children demonstrating MCC values within the normal range and others showing MCC values that are below normal values. In addition, although MCC did not improve in all children after inhalation of HS, improvement did occur in children with relatively low MCC values after placebo. This finding suggests that acute inhalation of hypertonic saline may benefit a subset of children with low MCC

  12. Opposite effects of oxytocin on water intake induced by hypertonic NaCl or polyethylene glycol administration.

    PubMed

    Bernal, Antonio; Mahía, Javier; Mediavilla, Cristina; Puerto, Amadeo

    2015-03-15

    Oxytocin (OT), a neurohormone, has been related to natriuretic and diuretic effects and also to water intake and sodium appetite. The objective of the present study was to determine the effect of subcutaneous OT administration on water intake and urine-related measures induced by the administration of hypertonic NaCl (experiment 1) or polyethylene glycol (PEG) (experiment 2). Experiment 1 showed that OT administration increases the urine volume, urinary sodium concentration, and natriuresis and reduces the water intake, water and sodium balances, and estimated plasma sodium concentration induced by hypertonic NaCl administration. Conversely, experiment 2 showed that OT administration increases the water intake and the antidiuretic response induced by PEG administration. These results show that the opposite effects of OT on the water intake induced by hypertonic NaCl or PEG administration are accompanied by differential regulatory effects, enhancing a natriuretic response in the first experiment and generating an antidiuretic reaction in the second experiment. This study suggests a differential regulatory effect of OT during states of intra- and extracellular thirst. PMID:25617595

  13. Hypertonic NaCl enhances adenosine release and hormonal cAMP production in mouse thick ascending limb.

    PubMed

    Baudouin-Legros, M; Badou, A; Paulais, M; Hammet, M; Teulon, J

    1995-07-01

    Adenosine 3',5'-cyclic monophosphate (cAMP), accumulated in the presence of adenosine, was measured in medullary portions of mouse thick ascending limbs of Henle's loop, suspended either in classic extracellular buffer or in the presence of added NaCl. Under control conditions (140 mmol/l NaCl), adenosine (< 10(-5) mol/l) and N6-cyclohexyladenosine, an A1 adenosine receptor agonist, inhibit the cAMP accumulation induced by arginine vasopressin (AVP). On the other hand, high concentrations of adenosine and CGS-21680, an A2 adenosine receptor agonist, stimulate cAMP formation. Addition of NaCl (+300 mmol/l) to extracellular buffer stimulates the release of endogenous adenosine. It also enhances A2 receptor-induced cAMP accumulation but suppresses A1 receptor-mediated inhibition of adenylyl cyclase. This hypertonic NaCl medium also potentiates the stimulatory action of AVP on adenylyl cyclase. The modifications of tubular responses to both AVP and A1 and A2 agonists, brought about by hypertonic NaCl, were all inhibited by adenosine deaminase, thereby demonstrating the involvement of endogenous adenosine. Adenosine, the release and the effects of which are modulated by hypertonic NaCl, thus appears to act as an endogenous physiological modulator of kidney medulla function. PMID:7631823

  14. NFAT5 in cellular adaptation to hypertonic stress - regulations and functional significance.

    PubMed

    Cheung, Chris Yk; Ko, Ben Cb

    2013-01-01

    The Nuclear Factor of Activated T Cells-5 (NFAT5), also known as OREBP or TonEBP, is a member of the nuclear factors of the activated T cells family of transcription factors. It is also the only known tonicity-regulated transcription factor in mammals. NFAT5 was initially known for its role in the hypertonic kidney inner medulla for orchestrating a genetic program to restore the cellular homeostasis. Emerging evidence, however, suggests that NFAT5 might play a more diverse functional role, including a pivotal role in blood pressure regulation and the development of autoimmune diseases. Despite the growing significance of NFAT5 in physiology and diseases, our understanding of how its activity is regulated remains very limited. Furthermore, how changes in tonicities are converted into functional outputs via NFAT5 remains elusive. Therefore, this review aims to summarize our current knowledge on the functional roles of NFAT5 in osmotic stress adaptation and the signaling pathways that regulate its activity. PMID:23618372

  15. Mannitol or hypertonic saline in the setting of traumatic brain injury: What have we learned?

    PubMed Central

    Boone, Myles Dustin; Oren-Grinberg, Achikam; Robinson, Timothy Matthew; Chen, Clark C.; Kasper, Ekkehard M.

    2015-01-01

    Background: Intracranial hypertension, defined as an intracranial pressure (ICP) >20 mmHg for a period of more than 5 min, worsens neurologic outcome in traumatic brain injury (TBI). While several mechanisms contribute to poor outcome, impaired cerebral perfusion appears to be a highly significant common denominator. Management guidelines from the Brain Trauma Foundation recommend measuring ICP to guide therapy. In particular, hyperosmolar therapy, which includes mannitol or hypertonic saline (HTS), is frequently administered to reduce ICP. Currently, mannitol (20%) is considered the gold standard hyperosmolar agent. However, HTS is increasingly used in this setting. This review sought to compare the efficacy of mannitol to HTS in severe TBI. Methods: The PubMed database was used to systematically search for articles comparing mannitol to HTS in severe TBI. The following medical subject headings were used: HTS, sodium lactate, mannitol, ICP, intracranial hypertension, and TBI. We included both prospective and retrospective randomized controlled studies of adult patients with intracranial hypertension as a result of severe TBI who received hyperosmolar therapy. Results: Out of 45 articles, seven articles were included in our review: 5 were prospective, randomized trials; one was a prospective, nonrandomized trial; and one was a retrospective, cohort study. Conclusions: While all seven studies found that both mannitol and HTS were effective in reducing ICP, there was heterogeneity with regard to which agent was most efficacious. PMID:26673517

  16. Hypertonic saline infusion in traumatic brain injury increases the incidence of pulmonary infection.

    PubMed

    Coritsidis, George; Diamond, Nechama; Rahman, Aleef; Solodnik, Paul; Lawrence, Kayode; Rhazouani, Salwa; Phalakornkul, Suganda

    2015-08-01

    We aimed to investigate the incidence of electrolyte abnormalities, acute kidney injury (AKI), deep venous thrombosis (DVT) and infections in patients with traumatic brain injury (TBI) treated with hypertonic saline (HTS) as osmolar therapy. We retrospectively studied 205 TBI patients, 96 with HTS and 109 without, admitted to the surgical/trauma intensive care unit between 2006 and 2012. Hemodynamics, electrolytes, length of stay (LOS), acute physiological assessment and chronic health evaluation II (APACHE II), injury severity scores (ISS) and mortality were tabulated. Infection, mechanical ventilation, DVT and AKI incidence were reviewed. HTS was associated with increased LOS and all infections (p=0.0001). After correction for the Glasgow coma scale (GCS) and ventilator need, pulmonary infections (p=0.001) and LOS remained higher with HTS (p=0.0048). HTS did not result in increased blood pressure, DVT, AKI or neurological benefits. HTS significantly increased the odds for all infections, most specifically pulmonary infections, in patients with GCS<8. Due to these findings, HTS in TBI should be administered with caution regardless of acuity. PMID:26055957

  17. Hypertonic saline activation of p38 MAPK primes the PMN respiratory burst.

    PubMed

    Ciesla, D J; Moore, E E; Biffl, W L; Gonzalez, R J; Moore, H B; Silliman, C C

    2001-10-01

    Investigation of hypertonic saline (HTS) modulation of neutrophils (PMN) cytotoxic responses has generated seemingly contradictory results. Clinically relevant levels of HTS attenuate receptor-mediated p38 MAPK signaling, whereas higher levels activate p38 MAPK. Concurrently, HTS exerts a dose-dependent attenuation of the PMN respiratory burst, most notably at concentrations where p38 MAPK is activated. We hypothesized that HTS-mediated p38 MAPK activation augments the PMN respiratory burst on return to normotonicity. We found that although clinically relevant levels of HTS (Na+ > or = 200 mM) did not activate p38 MAPK, higher concentrations (Na+ > or = 300 mM) resulted in activation comparable with that after PAF stimulation. Transient stimulation with high levels of HTS primed the PMN respiratory burst in response to fMLP and PMA. This effect was attenuated by pretreatment with SB 203580, a p38 MAPK specific inhibitor. We conclude that severe osmotic shock primes the respiratory burst via p38 MAPK signaling, further supporting the role of this signaling cascade in PMN priming. PMID:11580111

  18. Two isoforms of aquaporin 2 responsive to hypertonic stress in the bottlenose dolphin.

    PubMed

    Suzuki, Miwa; Wakui, Hitomi; Itou, Takuya; Segawa, Takao; Inoshima, Yasuo; Maeda, Ken; Kikuchi, Kiyoshi

    2016-04-15

    This study investigated the expression of aquaporin 2 (AQP2) and its newly found alternatively spliced isoform (alternative AQP2) and the functions of these AQP2 isoforms in the cellular hyperosmotic tolerance in the bottlenose dolphin, ITALIC! Tursiops truncatus mRNA sequencing revealed that alternative AQP2 lacks the fourth exon and instead has a longer third exon that includes a part of the original third intron. The portion of the third intron, now part of the coding region of alternative AQP2, is highly conserved among many species of the order Cetacea but not among terrestrial mammals. Semi-quantitative PCR revealed that AQP2 was expressed only in the kidney, similar to terrestrial mammals. In contrast, alternative AQP2 was expressed in all organs examined, with strong expression in the kidney. In cultured renal cells, expression of both AQP2 isoforms was upregulated by the addition to the medium of NaCl but not by the addition of mannitol, indicating that the expression of both isoforms is induced by hypersalinity. Treatment with small interfering RNA for both isoforms resulted in a decrease in cell viability in hypertonic medium (500 mOsm kg(-1)) when compared with controls. These findings indicate that the expression of alternatively spliced AQP2 is ubiquitous in cetacean species, and it may be one of the molecules important for cellular osmotic tolerance throughout the body. PMID:26944501

  19. Micropuncture study of hypertonic mannitol diuresis in the proximal and distal tubule of the dog kidney

    PubMed Central

    Seely, John F.; Dirks, John H.

    1969-01-01

    Fractional reabsorption of water, sodium, and potassium at proximal and distal tubular sites within the nephron was studied by recollection-micropuncture experiments on dogs undergoing hypertonic mannitol diuresis. After an initial control hydropenic phase, 16% mannitol in modified Ringer's solution was administered intravenously, resulting in marked increases in fractional excretion of water (28.7%), sodium (12.6%), and potassium (63.9%). Inulin clearance decreased significantly from 35.1 to 25.2 ml/min. Analysis of paired micropuncture data revealed a significant decrease in tubule fluid to plasma (TF:P) inulin ratios in both the proximal tubule (1.63-1.45) and distal tubule (5.38-1.94). There was also a significant decrease in proximal TF:P sodium ratios (0.99-0.93) and potassium ratios (1.05-0.98). Distal TF:P sodium ratios, in contrast, rose significantly (0.38-0.59), while TF:P potassium ratios tended towards unity whether initially greater or less than one. Fractional reabsorption of sodium and water decreased by 5% and 10% respectively in the proximal tubule, but to a lesser extent than the resulting increases in fractional urinary excretion. The nonreabsorbed fraction, however, had increased sharply at the point of distal puncture for water (32%), sodium (26%), and potassium (26%), indicating a large inhibitory effect within the loop of Henle in addition to the smaller proximal effects. PMID:5355344

  20. Influence of environmental hypertonicity on the induction of ureogenesis and amino acid metabolism in air-breathing walking catfish (Clarias batrachus, Bloch).

    PubMed

    Banerjee, Bodhisattwa; Bhuyan, Gitalee; Saha, Nirmalendu

    2014-07-01

    Effect of environmental hypertonicity, due to exposure to 300 mM mannitol solution for 7 days, on the induction of ureogenesis and also on amino acid metabolism was studied in the air-breathing walking catfish, C. batrachus, which is already known to have the capacity to face the problem of osmolarity stress in addition to other environmental stresses in its natural habitats. Exposure to hypertonic mannitol solution led to reduction of ammonia excretion rate by about 2-fold with a concomitant increase of urea-N excretion rate by about 2-fold. This was accompanied by significant increase in the levels of both ammonia and urea in different tissues and also in plasma. Further, the environmental hypertonicity also led to significant accumulation of different non-essential free amino acids (FAAs) and to some extent the essential FAAs, thereby causing a total increase of non-essential FAA pool by 2-3-fold and essential FAA pool by 1.5-2.0-fold in most of the tissues studied including the plasma. The activities of three ornithine-urea cycle (OUC) enzymes such as carbamoyl phosphate synthetase, argininosuccinate synthetase and argininosuccinate lyase in liver and kidney tissues, and four key amino acid metabolism-related enzymes such as glutamine synthetase, glutamate dehydrogenase (reductive amination), alanine aminotransaminase and aspartate aminotransaminase were also significantly up-regulated in different tissues of the fish while exposing to hypertonic environment. Thus, more accumulation and excretion of urea-N observed during hypertonic exposure were probably associated with the induction of ureogenesis through the induced OUC, and the increase of amino acid pool was probably mainly associated with the up-regulation of amino acid synthesizing machineries in this catfish in hypertonic environment. These might have helped the walking catfish in defending the osmotic stress and to acclimatize better under hypertonic environment, which is very much uncommon among

  1. Renal Blood Flow Response to Angiotensin 1-7 versus Hypertonic Sodium Chloride 7.5% Administration after Acute Hemorrhagic Shock in Rats

    PubMed Central

    Maleki, Maryam; Nematbakhsh, Mehdi

    2016-01-01

    Background. Angiotensin 1-7 (Ang1-7) plays an important role in renal circulation. Hemorrhagic shock (HS) may cause kidney circulation disturbance, and this study was designed to investigate the renal blood flow (RBF) response to Ang1-7 after HS. Methods. 27 male Wistar rats were subjected to blood withdrawal to reduce mean arterial pressure (MAP) to 45 mmHg for 45 min. The animals were treated with saline (group 1), Ang1-7 (300 ng·kg−1 min−1), Ang1-7 in hypertonic sodium chloride 7.5% (group 3), and hypertonic solution alone (group 4). Results. MAP was increased in a time-related fashion (Ptime < 0.0001) in all groups; however, there was a tendency for the increase in MAP in response to hypertonic solution (P = 0.09). Ang1-7, hypertonic solution, or combination of both increased RBF in groups 2-4, and these were significantly different from saline group (P = 0.05); that is, Ang1-7 leads to a significant increase in RBF to 1.35 ± 0.25 mL/min compared with 0.55 ± 0.12 mL/min in saline group (P < 0.05). Conclusion. Although Ang1-7 administration unlike hypertonic solution could not elevate MAP after HS, it potentially could increase RBF similar to hypertonic solution. This suggested that Ang1-7 recovers RBF after HS when therapeutic opportunities of hypertonic solution are limited. PMID:27073699

  2. Hypertonicity-induced transmitter release at Drosophila neuromuscular junctions is partly mediated by integrins and cAMP/protein kinase A

    NASA Technical Reports Server (NTRS)

    Suzuki, Kazuhiro; Grinnell, Alan D.; Kidokoro, Yoshiaki

    2002-01-01

    The frequency of quantal transmitter release increases upon application of hypertonic solutions. This effect bypasses the Ca(2+) triggering step, but requires the presence of key molecules involved in vesicle fusion, and hence could be a useful tool for dissecting the molecular process of vesicle fusion. We have examined the hypertonicity response at neuromuscular junctions of Drosophila embryos in Ca(2+)-free saline. Relative to wild-type, the response induced by puff application of hypertonic solution was enhanced in a mutant, dunce, in which the cAMP level is elevated, or in wild-type embryos treated with forskolin, an activator of adenylyl cyclase, while protein kinase A (PKA) inhibitors decreased it. The response was also smaller in a mutant, DC0, which lacks the major subunit of PKA. Thus the cAMP/PKA cascade is involved in the hypertonicity response. Peptides containing the sequence Arg-Gly-Asp (RGD), which inhibit binding of integrins to natural ligands, reduced the response, whereas a peptide containing the non-binding sequence Arg-Gly-Glu (RGE) did not. A reduced response persisted in a mutant, myospheroid, which expresses no integrins, and the response in DC0 was unaffected by RGD peptides. These data indicate that there are at lease two components in the hypertonicity response: one that is integrin mediated and involves the cAMP/PKA cascade, and another that is not integrin mediated and does not involve the cAMP/PKA cascade.

  3. Salt appetite is reduced by a single experience of drinking hypertonic saline in the adult rat.

    PubMed

    Greenwood, Michael P; Greenwood, Mingkwan; Paton, Julian F R; Murphy, David

    2014-01-01

    Salt appetite, the primordial instinct to favorably ingest salty substances, represents a vital evolutionary important drive to successfully maintain body fluid and electrolyte homeostasis. This innate instinct was shown here in Sprague-Dawley rats by increased ingestion of isotonic saline (IS) over water in fluid intake tests. However, this appetitive stimulus was fundamentally transformed into a powerfully aversive one by increasing the salt content of drinking fluid from IS to hypertonic saline (2% w/v NaCl, HS) in intake tests. Rats ingested HS similar to IS when given no choice in one-bottle tests and previous studies have indicated that this may modify salt appetite. We thus investigated if a single 24 h experience of ingesting IS or HS, dehydration (DH) or 4% high salt food (HSD) altered salt preference. Here we show that 24 h of ingesting IS and HS solutions, but not DH or HSD, robustly transformed salt appetite in rats when tested 7 days and 35 days later. Using two-bottle tests rats previously exposed to IS preferred neither IS or water, whereas rats exposed to HS showed aversion to IS. Responses to sweet solutions (1% sucrose) were not different in two-bottle tests with water, suggesting that salt was the primary aversive taste pathway recruited in this model. Inducing thirst by subcutaneous administration of angiotensin II did not overcome this salt aversion. We hypothesised that this behavior results from altered gene expression in brain structures important in thirst and salt appetite. Thus we also report here lasting changes in mRNAs for markers of neuronal activity, peptide hormones and neuronal plasticity in supraoptic and paraventricular nuclei of the hypothalamus following rehydration after both DH and HS. These results indicate that a single experience of drinking HS is a memorable one, with long-term changes in gene expression accompanying this aversion to salty solutions. PMID:25111786

  4. Osmotic hypertonicity of the renal medulla during changes in renal perfusion pressure in the rat

    PubMed Central

    Dobrowolski, Leszek; Ba̧dzyńska, Bożena; Walkowska, Agnieszka; Sadowski, Janusz

    1998-01-01

    The relationship between renal perfusion pressure (RPP) and ion concentration in renal medulla was studied in anaesthetized rats. RPP was changed in steps within the pressure range 130–80 mmHg, while tissue electrical admittance (Y, index of interstitial ion concentration) and medullary and cortical blood flow (MBF and CBF; laser Doppler flowmetry) were measured, along with glomerular filtration rate (Cin) and renal excretion. With a RPP reduction from 130 to 120 mmHg, tissue Y remained stable; at 100 and 80 mmHg, Y was 5 and 17 % lower, respectively, than at 120 mmHg. CBF fell less than RPP (partial autoregulation) in the range 130–100 mmHg only. MBF was autoregulated within 120–100 mmHg, but not above or below this range. Each step of RPP reduction was followed by a decrease in sodium and water excretion (UNaV and V). The osmolality of excised inner medulla fragments was similar at 120 and 105 mmHg (586 ± 45 and 618 ± 35 mosmol (kg H2O)−1, respectively) but lower at 80 mmHg (434 ± 31 mosmol (kg H2O)−1, P < 0.01); the ion concentration changed in parallel. The data show that medullary hypertonicity was well preserved during RPP fluctuations within 130–100 mmHg, but not below this range. RPP-dependent changes of UNaV and V were not clearly associated with changes in solute concentration in medullary tissue. PMID:9518743

  5. K(+) channels of squid giant axons open by an osmotic stress in hypertonic solutions containing nonelectrolytes.

    PubMed

    Kukita, Fumio

    2011-08-01

    In hypertonic solutions made by adding nonelectrolytes, K(+) channels of squid giant axons opened at usual asymmetrical K(+) concentrations in two different time courses; an initial instantaneous activation (I (IN)) and a sigmoidal activation typical of a delayed rectifier K(+) channel (I (D)). The current-voltage relation curve for I (IN) was fitted well with Goldman equation described with a periaxonal K(+) concentration at the membrane potential above -10 mV. Using the activation-voltage curve obtained from tail currents, K(+) channels for I (IN) are confirmed to activate at the membrane potential that is lower by 50 mV than those for I (D). Both I (IN) and I (D) closed similarly at the holding potential below -100 mV. The logarithm of I (IN)/I (D) was linearly related with the osmolarity for various nonelectrolytes. Solute inaccessible volumes obtained from the slope increased with the nonelectrolyte size from 15 to 85 water molecules. K(+) channels representing I (D) were blocked by open channel blocker tetra-butyl ammonium (TBA) more efficiently than in the absence of I (IN), which was explained by the mechanism that K(+) channels for I (D) were first converted to those for I (IN) by the osmotic pressure and then blocked. So K(+) channels for I (IN) were suggested to be derived from the delayed rectifier K(+) channels. Therefore, the osmotic pressure is suggested to exert delayed-rectifier K(+) channels to open in shrinking rather hydrophilic flexible parts outside the pore than the pore itself, which is compatible with the recent structure of open K(+) channel pore. PMID:21773888

  6. Median Preoptic Nucleus Mediates the Cardiovascular Recovery Induced by Hypertonic Saline in Hemorrhagic Shock

    PubMed Central

    Amaral, Nathalia Oda; Naves, Lara Marques; Ferreira-Neto, Marcos Luiz; Freiria-Oliveira, André Henrique; Colombari, Eduardo; Reis, Angela Adamski da Silva; Xavier, Carlos Henrique; Pedrino, Gustavo Rodrigues

    2014-01-01

    Changes in plasma osmolarity, through central and peripheral osmoreceptors, activate the median preoptic nucleus (MnPO) that modulates autonomic and neuroendocrine adjustments. The present study sought to determine the participation of MnPO in the cardiovascular recovery induced by hypertonic saline infusion (HSI) in rats submitted to hemorrhagic shock. The recordings of mean arterial pressure (MAP) and renal vascular conductance (RVC) were carried out on male Wistar rats (250–300 g). Hemorrhagic shock was induced by blood withdrawal over 20 min until the MAP values of approximately 60 mmHg were attained. The nanoinjection (100 nL) of GABAA agonist (Muscimol 4 mM; experimental group (EXP)) or isotonic saline (NaCl 150 mM; control (CONT)) into MnPO was performed 2 min prior to intravenous overload of sodium through HSI (3 M NaCl, 1.8 mL/kg, b.wt.). Hemorrhagic shock reduced the MAP in control (62 ± 1.1 mmHg) and EXP (61 ± 0.4 mmHg) equipotently. The inhibition of MnPO impaired MAP (CONT: 104 ± 4.2 versus EXP: 60 ± 6.2 mmHg) and RVC (CONT: 6.4 ± 11.4 versus EXP: -53.5 ± 10.0) recovery 10 min after HSI. The overall results in this study demonstrated, for the first time, that the MnPO plays an essential role in the HSI induced resuscitation during hypovolemic hemorrhagic shock. PMID:25485300

  7. Release of uremic retention solutes from protein binding by hypertonic predilution hemodiafiltration.

    PubMed

    Böhringer, Falko; Jankowski, Vera; Gajjala, Prathibha R; Zidek, Walter; Jankowski, Joachim

    2015-01-01

    Protein-bound uremic retention solutes accumulate in patients suffering from chronic kidney disease, and the removal of these solutes by hemodialysis is hampered. Therefore, we developed a dialysis technique where the protein-bound uremic retention solutes are removed more efficiently under high ionic strength. Protein-bound uremic solutes such as phenylacetic acid, indoxyl sulfate, and p-cresyl sulfate were combined with plasma in the presence of increased ionic strength. The protein integrity of proteins and enzymatic activities were analyzed. In vitro dialysis of albumin solution was performed to investigate the clearance of the bound uremic retention solutes. In vitro hemodiafiltrations of human blood were performed to investigate the influence of increased ionic strength on blood cell survival. The protein-bound fraction of phenylacetic acid, indoxyl sulfate, and p-cresyl sulfate was significantly decreased from 59.4% ± 3.4%, 95.7% ± 0.6%, 96.9% ± 1.5% to 36.4% ± 3.7%, 87.8% ± 0.6%, and 90.8% ± 1.3%, respectively. The percentage of phenylacetic acid, indoxyl sulfate, and p-cresyl sulfate released from protein was 23.0% ± 5.7%, 7.9% ± 1.1%, and 6.1% ± 0.2%, respectively. The clearance during in vitro dialysis was increased by 13.1% ± 3.6%, 68.8% ± 15.1%, and 53.6% ± 10.2%, respectively. There was no difference in NaCl concentrations at the outlet of the dialyzer using isotonic and hypertonic solutions. In conclusion, this study forms the basis for establishing a novel therapeutic approach to remove protein-bound retention solutes. PMID:25419832

  8. Inhaled hypertonic saline in adults hospitalised for exacerbation of cystic fibrosis lung disease: a retrospective study

    PubMed Central

    Stoltz, David A; Hornick, Douglas B; Durairaj, Lakshmi

    2012-01-01

    Background Inhaled hypertonic saline (HTS) improves quality of life and reduces pulmonary exacerbations when given long term in patients with cystic fibrosis (CF). While increasingly being offered for acute pulmonary exacerbations, little is known about the efficacy in this setting. Objectives The authors examined the tolerability and efficacy of HTS use among adult subjects hospitalised with a CF pulmonary exacerbation and hypothesised that use of HTS would improve pulmonary function during the admission. Design Pilot retrospective non-randomised study. Setting Single tertiary care centre. Participants 45 subjects admitted to the inpatient service for acute CF pulmonary exacerbation in 2006–2007. A subset of 18 subjects who were also admitted in 2005 when HTS was not available was included in the comparative study. Primary outcome Change in forced expiratory volume in one second from admission to discharge. Secondary outcomes Change in weight from admission to discharge and time to next exacerbation. Results Mean age was 32.5 years, and mean length of stay was 11.5 days. HTS was offered to 33 subjects and was well tolerated for a total use of 336 days out of 364 days of hospital stay. Baseline demographics, lung function and sputum culture results were comparable in first and second visits. Use of HTS was not associated with an improvement in forced expiratory volume in one second (p=0.1), weight gain (p=0.24) or in the time to next admission (p=0.08). Conclusions These pilot data suggest that HTS is well tolerated during CF pulmonary exacerbation but offers no clear outcome benefits. It is possible that HTS may not have much advantage above and beyond intensive rehabilitation and intravenous antibiotics and may add to hospital costs and treatment burden. PMID:22517980

  9. Baclofen into the lateral parabrachial nucleus induces hypertonic sodium chloride intake during cell dehydration

    PubMed Central

    2013-01-01

    Background Activation of GABAB receptors with baclofen into the lateral parabrachial nucleus (LPBN) induces ingestion of water and 0.3 M NaCl in fluid replete rats. However, up to now, no study has investigated the effects of baclofen injected alone or combined with GABAB receptor antagonist into the LPBN on water and 0.3 M NaCl intake in rats with increased plasma osmolarity (rats treated with an intragastric load of 2 M NaCl). Male Wistar rats with stainless steel cannulas implanted bilaterally into the LPBN were used. Results In fluid replete rats, baclofen (0.5 nmol/0.2 μl), bilaterally injected into the LPBN, induced ingestion of 0.3 M NaCl (14.3 ± 4.1 vs. saline: 0.2 ± 0.2 ml/210 min) and water (7.1 ± 2.9 vs. saline: 0.6 ± 0.5 ml/210 min). In cell-dehydrated rats, bilateral injections of baclofen (0.5 and 1.0 nmol/0.2 μl) into the LPBN induced an increase of 0.3 M NaCl intake (15.6 ± 5.7 and 21.5 ± 3.5 ml/210 min, respectively, vs. saline: 1.7 ± 0.8 ml/210 min) and an early inhibition of water intake (3.5 ± 1.4 and 6.7 ± 2.1 ml/150 min, respectively, vs. saline: 9.2 ± 1.4 ml/150 min). The pretreatment of the LPBN with 2-hydroxysaclofen (GABAB antagonist, 5 nmol/0.2 μl) potentiated the effect of baclofen on 0.3 M NaCl intake in the first 90 min of test and did not modify the inhibition of water intake induced by baclofen in cell-dehydrated rats. Baclofen injected into the LPBN did not affect blood pressure and heart rate. Conclusions Thus, injection of baclofen into the LPBN in cell-dehydrated rats induced ingestion of 0.3 M NaCl and inhibition of water intake, suggesting that even in a hyperosmotic situation, the blockade of LPBN inhibitory mechanisms with baclofen is enough to drive rats to drink hypertonic NaCl, an effect independent of changes in blood pressure. PMID:23642235

  10. Ad Libitum Fluid Intake and Plasma Responses After Pickle Juice, Hypertonic Saline, or Deionized Water Ingestion

    PubMed Central

    Allen, Scott; Miller, Kevin C.; Albrecht, Jay; Garden-Robinson, Julie; Blodgett-Salafia, Elizabeth

    2013-01-01

    Context: Adding sodium (Na+) to drinks improves rehydration and ad libitum fluid consumption. Clinicians (∼25%) use pickle juice (PJ) to treat cramping. Scientists warn against PJ ingestion, fearing it will cause rapid plasma volume restoration and thereby decrease thirst and delay rehydration. Advice about drinking PJ has been developed but never tested. Objective: To determine if drinking small volumes of PJ, hypertonic saline (HS), or deionized water (DIW) affects ad libitum DIW ingestion, plasma variables, or perceptual indicators. Design: Crossover study. Setting: Laboratory. Patients or Other Participants: Fifteen, euhydrated (urine specific gravity ≤ 1.01) men (age = 22 ± 2 years, height = 178 ± 6 cm, mass = 82.9 ± 8.4 kg). Intervention(s): Participants completed 3 testing days (≥72 hours between days). After a 30-minute rest, a blood sample was collected. Participants completed 60 minutes of hard exercise (temperature = 36 ± 2°C, relative humidity = 16 ± 1%). Postexercise, they rested for 30 minutes; had a blood sample collected; rated thirst, fullness, and nausea; and ingested 83 ± 8 mL of PJ, HS, or DIW. They rated drink palatability (100-mm visual analog scale) and were allowed to drink DIW ad libitum for 60 minutes. Blood samples and thirst, fullness, and nausea ratings (100-mm visual analog scales) were collected at 15, 30, 45, and 60 minutes posttreatment drink ingestion. Main Outcome Measure(s): Ad libitum DIW volume, percentage change in plasma volume, plasma osmolality (OSMp,) plasma sodium concentration ([Na+]p), and thirst, fullness, nausea, and palatability ratings. Results: Participants consumed more DIW ad libitum after HS (708.03 ± 371.03 mL) than after DIW (532.99 ± 337.14 mL, P < .05). Ad libitum DIW ingested after PJ (700.35 ± 366.15 mL) was similar to that after HS and DIW (P > .05). Plasma sodium concentration, OSMp, percentage change in plasma volume, thirst, fullness, and nausea did not differ among treatment drinks

  11. Detailed Description of all Deaths in Both the Shock and Traumatic Brain Injury Hypertonic Saline Trials of the Resuscitation Outcomes Consortium

    PubMed Central

    Tisherman, Samuel A; Schmicker, Robert H.; Brasel, Karen J; Bulger, Eileen M; Kerby, Jeffrey D; Minei, Joseph P; Powell, Judy L; Reiff, Donald A; Rizoli, Sandro B; Schreiber, Martin A

    2014-01-01

    Objective To identify causes and timing of mortality in trauma patients to determine targets for future studies. Summary Background Data In trials conducted by the Resuscitation Outcomes Consortium (ROC) in patients with traumatic hypovolemic shock (shock) or traumatic brain injury (TBI), hypertonic saline failed to improve survival. Selecting appropriate candidates is challenging. Methods Retrospective review of patients enrolled in multicenter, randomized, trials performed 2006–2009. Inclusion criteria were: injured patients, age ≥ 15 years with hypovolemic shock (systolic blood pressure (SBP) ≤ 70 mm Hg or SBP 71–90 mm Hg with heart rate ≥ 108) or severe TBI [Glasgow Coma Score (GCS) ≤8]. Initial fluid administered was 250 mL of either 7.5% saline with 6% dextran 70, 7.5% saline or 0.9% saline. Results 2061 subjects were enrolled (809 shock, 1252 TBI) and 571 (27.7%) died. Survivors were younger than non-survivors [30(IQR 23) vs 42(34)] and had a higher GCS, though similar hemodynamics. Most deaths occurred despite ongoing resuscitation. Forty six percent of deaths in the TBI cohort were within 24 hours, compared with 82% in the shock cohort and 72% in the cohort with both shock and TBI. Median time to death was 29 hours in the TBI cohort, 2 hours in the shock cohort, and 4 hours in patients with both. Sepsis and multiple organ dysfunction accounted for 2% of deaths. Conclusions Most deaths from trauma with shock or TBI occur within 24 hours of from hypovolemic shock or TBI. Novel resuscitation strategies should focus on early deaths, though prevention may have a greater impact. PMID:25072443

  12. Comparative study of midtrimester termination of pregnancy using hypertonic saline, ethacridine lactate, prostaglandin analogue and iodine-saline.

    PubMed

    Allahbadia, G

    1992-09-01

    The study consisted of terminations of 200 cases of second trimester pregnancies ranging from 14 weeks to 20 weeks. Out of these 200 cases, in 50 cases intra-amniotic instillation of 20% hypertonic saline (200 ml) was done after withdrawing 35-200 ml of amniotic fluid. Ethacridine lactate was instilled in 50 cases extra-amniotically. Prostaglandin F2 alpha was injected intramuscularly at regular intervals in 50 cases. Fifty cases of pregnancies were terminated with extra-amniotic instillation of 5% povidone-iodine solution mixed with normal saline. Comparison was made among all the methods regarding instillation-abortion interval, completeness of abortion, failure of the procedure and postoperative complications. Solution of 5% povidone-iodine in normal saline was found to be comparable in all aspects to other methods and above all a much cheaper alternative for poor patients. Success rate was highest with iodine-saline solution (100%) followed by ethacridine lactate (98%), hypertonic saline (96%) and lowest with prostaglandin F2 alpha (90%). PMID:1460314

  13. Randomised clinical study comparing the effectiveness and physiological effects of hypertonic and isotonic polyethylene glycol solutions for bowel cleansing

    PubMed Central

    Yamano, Hiro-o; Matsushita, Hiro-o; Yoshikawa, Kenjiro; Takagi, Ryo; Harada, Eiji; Tanaka, Yoshihito; Nakaoka, Michiko; Himori, Ryogo; Yoshida, Yuko; Satou, Kentarou; Imai, Yasushi

    2016-01-01

    Objectives Bowel cleansing is necessary before colonoscopy, but is a burden to patients because of the long cleansing time and large dose volume. A low-volume (2 L) hypertonic polyethylene glycol-ascorbic acid solution (PEG-Asc) has been introduced, but its possible dehydration effects have not been quantitatively studied. We compared the efficacy and safety including the dehydration risk between hypertonic PEG-Asc and isotonic PEG regimens. Design This was an observer-blinded randomised study. Participants (n=310) were allocated to receive 1 of 3 regimens on the day of colonoscopy: PEG-Asc (1.5 L) and water (0.75 L) dosed with 1 split (PEG-Asc-S) or 4 splits (PEG-Asc-M), or PEG-electrolyte solution (PEG-ES; 2.25 L) dosed with no split. Dehydration was analysed by measuring haematocrit (Ht). Results The cleansing time using the hypertonic PEG-Asc-S (3.33±0.48 hours) was significantly longer than that with isotonic PEG-ES (3.05±0.56 hours; p<0.001). PEG-Asc-M (3.00±0.53 hours) did not have this same disadvantage. Successful cleansing was achieved in more than 94% of participants using each of the 3 regimens. The percentage changes in Ht from baseline (before dosing) to the end of dosing with PEG-Asc-S (3.53±3.32%) and PEG-Asc-M (4.11±3.07%) were significantly greater than that with PEG-ES (1.31±3.01%). Conclusions These 3 lower volume regimens were efficacious and had no serious adverse effects. Even patients cleansed with isotonic PEG-ES showed significant physiological dehydration at the end of dosing. The four-split PEG-Asc-M regimen is recommended because of its shorter cleansing time without causing serious nausea. Trial registration number UMIN000013103; Results. PMID:27547443

  14. Capability of hypertonic saline cough provocation test to predict the response to inhaled corticosteroids in chronic cough: a prospective, open-label study

    PubMed Central

    2013-01-01

    Background Many patients with chronic cough respond to treatment with inhaled corticosteroids but it is difficult to predict which patients are likely to respond. The primary aim of the present study was to define the capability of hypertonic saline cough provocation test to predict the responsiveness to inhaled corticosteroids in chronic cough. The secondary aim was to assess the ability of the saline test to monitor the healing of cough during corticosteroid treatment. Methods Forty-three patients with chronic cough were recruited. Before therapy, spirometry, ambulatory peak flow monitoring, nitric oxide measurement, histamine airway challenge, and saline test were performed. Those responding to the first saline test repeated it and the nitric oxide measurement during the subsequent visits. The patients used inhaled budesonide, 400 ug twice daily, for twelve weeks. The treatment response was assessed by Leicester Cough Questionnaire at baseline, and at one, four, and twelve weeks. Results Seventy-seven % of the patients demonstrated the minimal important difference in the Leicester Cough Questionnaire indicating a symptomatic response. Neither the response magnitude nor the speed was predicted by the saline test. Histamine challenge showed the strongest predictive ability: The maximal improvement in Leicester Cough Questionnaire total score was 5.08 (3.76 – 6.40) points in the histamine positive and 2.78 (1.55 – 4.01) points in the histamine negative subjects (p = 0.006). Baseline nitric oxide level also associated with the improvement in Leicester Cough Questionnaire total score (p = 0.02). During the treatment, the cough sensitivity to saline gradually decreased among the budesonide responders but not in the non-responders. Nitric oxide levels decreased very rapidly among the responders. Conclusions Saline test cannot predict the responsiveness to inhaled corticosteroids in chronic cough but it may be utilized to monitor the effect of this

  15. Long-term improvement of lung clearance index in patients with mild cystic fibrosis lung disease: Does hypertonic saline play a role?

    PubMed

    Ellemunter, Helmut; Eder, Johannes; Fuchs, Susanne; Gappa, Monika; Steinkamp, Gratiana

    2016-01-01

    To assess whether long-term inhalation with hypertonic saline is able to halt the progression of mild CF lung disease, we analysed longitudinal data of lung clearance index (LCI) and spirometry. A total of 34 patients with mild lung disease (FEV1 ≥ 70% of predicted) had at least one LCI result before and ≥2 LCI measurements after start of hypertonic saline (HS) therapy. After a mean follow-up of 39.7 (SD 7.4) months after starting HS, LCI improved significantly from 7.89 (SD 1.35) at baseline to 6.96 (SD 1.03), and 19/34 patients had a normal LCI value at the last measurement. No decrease in mean FEV1 was observed. Thus, ventilation inhomogeneity can improve in patients with mild lung disease. PMID:26190829

  16. Substance P-like peptides and vasopressin release from posterior pituitary lobe incubated in situ after intracarotid injections of hypertonic solution in rats.

    PubMed

    Traczyk, W Z; Strumillo-Dyba, E

    1977-01-01

    The experiments were performed on male rats, drinking 2% NaCl solution ad libitum for 12 days instead of tap water. The pituitary gland was exposed by the transpharyngeal approach under urethane-chloralose anaesthesia. The posterior lobe remained in neural and partial vascular connection with the hypothalamus, whereas the anterior lobe was entirely removed. Samples of the outflow medium from the incubated in situ rat posterior pituitary lobe were collected during 30 min intervals. Substance P-like peptides and vasopressin activities were assayed by the biological tests. Injections of hypertonic solution into the internal carotid artery did not change vasopressin release, but induced an increase in Substance P release from the posterior pituitary lobe into the incubation medium. Under conditions of unexcitability of the osmosensitive cells, triggering vasopressin release, the injection of hypertonic solution into the internal carotid artery stimulated the Substance P-like peptides release from the posterior pituitary lobe. PMID:22985

  17. Body water handling in response to hypertonic-saline induced diuresis in fasting northern elephant seal pups (Mirounga angustirostris)

    NASA Technical Reports Server (NTRS)

    Ortiz, Rudy M.; Wade, Charles E.; Ortiz, C. Leo

    2003-01-01

    During natural fasting conditions in postweaned northern elephant seal (NES) (Mirounga angustirostris) pups, urinary water loss is minimized and percent total body water (TBW) is maintained constant. However, following infusion of hypertonic saline, glomerular filtration rate (GFR) and urine output increased in fasting pups. Therefore, we quantified the magnitude of the hypernatremia-induced diuresis relative to the animal's total body water (TBW) pool and the percentage of filtered water reabsorbed. Following a 24 h control period, naturally fasting NES pups (n=7) were infused (4 ml min(-1)) with hypertonic saline (16.7%) at a dose of 3 mmol NaCl kg(-1) body mass. Total body water was estimated prior to infusion by tritium dilution, GFR was estimated by standard creatinine clearance, and urine output (V) was measured for 24 h during the control and post infusion periods. Percentage of filtered water reabsorbed was calculated as (1-(V/GFR))x100. Twenty-four hours following the infusion, GFR (control: 69+/-12 ml min(-1) and post-infusion: 118+/-19 ml min(-1); mean+/-S.E.) increased 77+/-28% above control and the percentage of filtered water reabsorbed was decreased 0.4+/-0.1%. The increase in urine output (control: 218+/-47 ml d(-1) and post-infusion: 883+/-92 ml d(-1)) accounted for 1.7+/-0.2% of the pups' TBW. The hypernatremia-induced diuresis was accompanied by the loss of body water indicating the lack of water retention. Although the 77% increase in GFR was only associated with a 0.4% decrease in the percentage of filtered water reabsorbed, this decrease was significant enough to result in a 4-fold increase in urine output. Despite the observed diuresis, fasting NES pups appear to possess an efficient water recycling mechanism requiring only a small percentage of body water to excrete an excess salt load. This water recycling mechanism may allow pups to avoid negative perturbations in body water as they initiate feeding in a marine environment following the

  18. Selective response of human airway epithelia to luminal but not serosal solution hypertonicity. Possible role for proximal airway epithelia as an osmolality transducer.

    PubMed Central

    Willumsen, N J; Davis, C W; Boucher, R C

    1994-01-01

    The response of cultured human nasal epithelia to hypertonic bathing solutions was tested using ion-selective microelectrode and quantitative microscopy. Raised luminal, but not serosal, osmolality (+/- 150 mM mannitol) decreased Na+ absorption but did not induce Cl- secretion. Raised luminal osmolality increased cell Cl- activity, Na+ activity, and transepithelial resistance and decreased both apical and basolateral membrane potentials and the fractional resistance of the apical membrane; equivalent circuit analysis revealed increases in apical, basolateral, and shunt resistances. Prolonged exposure (10 min) to 430 mosM luminal solution elicited no regulation of any parameter. Optical measurements revealed a reduction in the thickness of preparations only in response to luminal hypertonic solutions. We conclude that (a) airway epithelial cells exhibit asymmetric water transport properties, with the apical membrane water permeability exceeding that of the basolateral membrane; (b) the cellular response to volume loss is a deactivation of the basolateral membrane K+ conductance and the apical membrane Cl- conductance; (c) luminal hypertonicity slows the rate of Na+ absorption but does not induce Cl- secretion; and (d) cell volume loss increases the resistance of the paracellular path. We speculate that these properties configure human nasal epithelium to behave as an osmotic sensor, transducing information about luminal solutions to the airway wall. Images PMID:8040333

  19. Hypertonic dextrose injections (prolotherapy) in the treatment of symptomatic knee osteoarthritis: A systematic review and meta-analysis.

    PubMed

    Sit, Regina Ws; Chung, Vincent Ch; Reeves, Kenneth D; Rabago, David; Chan, Keith Kw; Chan, Dicken Cc; Wu, Xinyin; Ho, Robin St; Wong, Samuel Ys

    2016-01-01

    Hypertonic dextrose injections (prolotherapy) is an emerging treatment for symptomatic knee osteoarthritis (OA) but its efficacy is uncertain. We conducted a systematic review with meta-analysis to synthesize clinical evidence on the effect of prolotherapy for knee OA. Fifteen electronic databases were searched from their inception to September 2015. The primary outcome of interest was score change on the Western Ontario and McMaster Universities Arthritis Index (WOMAC). Three randomized controlled trials (RCTs) of moderate risk of bias and one quasi-randomized trial were included, with data from a total of 258 patients. In the meta-analysis of two eligible studies, prolotherapy is superior to exercise alone by a standardized mean difference (SMD) of 0.81 (95% CI: 0.18 to 1.45, p = 0.012), 0.78 (95% CI: 0.25 to 1.30, p = 0.001) and 0.62 (95% CI: 0.04 to 1.20, p = 0.035) on the WOMAC composite scale; and WOMAC function and pain subscale scores respectively. Moderate heterogeneity exists in all cases. Overall, prolotherapy conferred a positive and significant beneficial effect in the treatment of knee OA. Adequately powered, longer-term trials with uniform end points are needed to better elucidate the efficacy of prolotherapy. PMID:27146849

  20. G-CSF Administration after the Intraosseous Infusion of Hypertonic Hydroxyethyl Starches Accelerating Wound Healing Combined with Hemorrhagic Shock

    PubMed Central

    Huang, Hong; Liu, Jiejie; Hao, Haojie; Tong, Chuan; Ti, Dongdong; Liu, Huiling; Song, Haijing; Jiang, Chaoguang; Fu, Xiaobing; Han, Weidong

    2016-01-01

    Objective. To evaluate the therapeutic effects of G-CSF administration after intraosseous (IO) resuscitation in hemorrhagic shock (HS) combined with cutaneous injury rats. Methods. The rats were randomly divided into four groups: (1) HS with resuscitation (blank), (2) HS with resuscitation + G-CSF (G-CSF, 200 μg/kg body weight, subcutaneous injection), (3) HS with resuscitation + normal saline solution injection (normal saline), and (4) HS + G-CSF injection without resuscitation (Unres/G-CSF). To estimate the treatment effects, the vital signs of alteration were first evaluated, and then wound closure rates and homing of MSCs and EPCs to the wound skins and vasculogenesis were measured. Besides, inflammation and vasculogenesis related mRNA expressions were also examined. Results. IO infusion hypertonic hydroxyethyl starch (HHES) exhibited beneficial volume expansion roles and G-CSF administration accelerated wound healing 3 days ahead of other groups under hemorrhagic shock. Circulating and the homing of MSCs and EPCs at wound skins were significantly elevated at 6 h after G-CSF treatment. Inflammation was declined since 3 d while angiogenesis was more obvious in G-CSF treated group on day 9. Conclusions. These results suggested that the synergistical application of HHES and G-CSF has life-saving effects and is beneficial for improving wound healing in HS combined with cutaneous injury rats. PMID:26989687

  1. Ejaculatio praecox, erectio praecox, and detumescentia praecox as symptoms of a hypertonic state in lifelong premature ejaculation: a new hypothesis.

    PubMed

    Waldinger, Marcel D

    2014-06-01

    In the last two decades, in vivo animal research and human neurobiological, genetic and pharmacological research of lifelong premature ejaculation (PE) have much contributed to a better understanding of the role of the central and peripheral nervous systems in mediating ejaculation. Research of genetic polymorphisms in men with lifelong PE and clinical research of the validity of the classification into four PE subtypes have provided a better insight into lifelong PE and its distinction from the three other PE subtypes. Nevertheless, a number of symptoms of lifelong PE and its treatment by SSRIs are still not well understood. In the current article, it will be argued that lifelong PE is characterized not only by early ejaculations (ejaculatio praecox), a diminished control over ejaculation, and negative personal consequences, but also by early erections (erectio praecox) and an immediately occurring detumescence of the penis after ejaculation (detumescentia praecox) as symptoms of an (sub)acute hypertonic or hypererotic physical state when making love. Based on animal research it is postulated that the facilitated erection, facilitated ejaculation and facilitated penile detumescence are associated with centrally and peripherally increased oxytocin release. In addition, it is postulated that mechano- and thermosensory activity of transient receptor potential (TRP) ion channels, located in skin receptors of the glans penis, are associated with lifelong PE. Research into the three characteristics of the (sub)acute hypererotic state will presumably contribute to a better phenomenological description of and better neurobiological understanding of lifelong PE and its delineation to the three other PE subtypes. PMID:24333546

  2. Effects of hypertonic stimuli and arginine vasotocin (AVT) on water absorption response in Japanese treefrog, Hyla japonica.

    PubMed

    Maejima, Sho; Yamada, Toshiki; Hamada, Takayuki; Matsuda, Kouhei; Uchiyama, Minoru

    2008-06-01

    Anuran amphibians do not drink orally but absorb water osmotically through the highly permeable ventral skin. In this cutaneous water absorption, roles of the putative cerebral osmoreceptors and functions of arginine vasotocin (AVT) were examined in the central nervous system of the Japanese treefrog, Hyla japonica. Intracerebroventricular (ICV) or intralymphatic sac (ILS) administration of various hypertonic solutions (NaCl, mannitol and urea) significantly extended the residence time in water in a dose-dependent manner, suggesting facilitation of water absorption in frogs. ICV injection of AVT also increased significantly the residence time in a dose-dependent manner. The water absorption effect of AVT was significantly inhibited by pretreatment of ICV OPC-21268, a vasopressin V(1) receptor antagonist. But pre-ICV injection of OPC-31260, a vasopressin V(2) receptor antagonist, did not block the water absorption effect of AVT. Extension of the residence time induced by hyperosmotic NaCl (1000 mOsm) ICV injection was significantly inhibited by pretreatment of ICV OPC-21268. The present results showed that increases of osmotic pressure in plasma and/or cerebrospinal fluid stimulate water absorption response, suggesting that osmoreceptors are certainly present in the central nervous system and AVT may directly stimulate water absorption in the treefrog. It is also suggested that AVT activates cellular mechanisms via V(1)-like but not V(2)-like receptors in the central nervous system and facilitates water absorption response in the treefrog. PMID:18555070

  3. Hypertonic dextrose injections (prolotherapy) in the treatment of symptomatic knee osteoarthritis: A systematic review and meta-analysis

    PubMed Central

    Sit, Regina WS; Chung, Vincent CH; Reeves, Kenneth D.; Rabago, David; Chan, Keith KW; Chan, Dicken CC; Wu, Xinyin; Ho, Robin ST; Wong, Samuel YS

    2016-01-01

    Hypertonic dextrose injections (prolotherapy) is an emerging treatment for symptomatic knee osteoarthritis (OA) but its efficacy is uncertain. We conducted a systematic review with meta-analysis to synthesize clinical evidence on the effect of prolotherapy for knee OA. Fifteen electronic databases were searched from their inception to September 2015. The primary outcome of interest was score change on the Western Ontario and McMaster Universities Arthritis Index (WOMAC). Three randomized controlled trials (RCTs) of moderate risk of bias and one quasi–randomized trial were included, with data from a total of 258 patients. In the meta-analysis of two eligible studies, prolotherapy is superior to exercise alone by a standardized mean difference (SMD) of 0.81 (95% CI: 0.18 to 1.45, p = 0.012), 0.78 (95% CI: 0.25 to 1.30, p = 0.001) and 0.62 (95% CI: 0.04 to 1.20, p = 0.035) on the WOMAC composite scale; and WOMAC function and pain subscale scores respectively. Moderate heterogeneity exists in all cases. Overall, prolotherapy conferred a positive and significant beneficial effect in the treatment of knee OA. Adequately powered, longer-term trials with uniform end points are needed to better elucidate the efficacy of prolotherapy. PMID:27146849

  4. Inhaled hypertonic saline for cystic fibrosis: Reviewing the potential evidence for modulation of neutrophil signalling and function

    PubMed Central

    Reeves, Emer P; McCarthy, Cormac; McElvaney, Oliver J; Vijayan, Maya Sakthi N; White, Michelle M; Dunlea, Danielle M; Pohl, Kerstin; Lacey, Noreen; McElvaney, Noel G

    2015-01-01

    Cystic fibrosis (CF) is a multisystem disorder with significantly shortened life expectancy. The major cause of mortality and morbidity is lung disease with increasing pulmonary exacerbations and decline in lung function predicting significantly poorer outcomes. The pathogenesis of lung disease in CF is characterised in part by decreased airway surface liquid volume and subsequent failure of normal mucociliary clearance. This leads to accumulation of viscous mucus in the CF airway, providing an ideal environment for bacterial pathogens to grow and colonise, propagating airway inflammation in CF. The use of nebulised hypertonic saline (HTS) treatments has been shown to improve mucus clearance in CF and impact positively upon exacerbations, quality of life, and lung function. Several mechanisms of HTS likely improve outcome, resulting in clinically relevant enhancement in disease parameters related to increase in mucociliary clearance. There is increasing evidence to suggest that HTS is also beneficial through its anti-inflammatory properties and its ability to reduce bacterial activity and biofilm formation. This review will first describe the use of HTS in treatment of CF focusing on its efficacy and tolerability. The emphasis will then change to the potential benefits of aerosolized HTS for the attenuation of receptor mediated neutrophil functions, including down-regulation of oxidative burst activity, adhesion molecule expression, and the suppression of neutrophil degranulation of proteolytic enzymes. PMID:26261770

  5. Inhaled hypertonic saline for cystic fibrosis: Reviewing the potential evidence for modulation of neutrophil signalling and function.

    PubMed

    Reeves, Emer P; McCarthy, Cormac; McElvaney, Oliver J; Vijayan, Maya Sakthi N; White, Michelle M; Dunlea, Danielle M; Pohl, Kerstin; Lacey, Noreen; McElvaney, Noel G

    2015-08-01

    Cystic fibrosis (CF) is a multisystem disorder with significantly shortened life expectancy. The major cause of mortality and morbidity is lung disease with increasing pulmonary exacerbations and decline in lung function predicting significantly poorer outcomes. The pathogenesis of lung disease in CF is characterised in part by decreased airway surface liquid volume and subsequent failure of normal mucociliary clearance. This leads to accumulation of viscous mucus in the CF airway, providing an ideal environment for bacterial pathogens to grow and colonise, propagating airway inflammation in CF. The use of nebulised hypertonic saline (HTS) treatments has been shown to improve mucus clearance in CF and impact positively upon exacerbations, quality of life, and lung function. Several mechanisms of HTS likely improve outcome, resulting in clinically relevant enhancement in disease parameters related to increase in mucociliary clearance. There is increasing evidence to suggest that HTS is also beneficial through its anti-inflammatory properties and its ability to reduce bacterial activity and biofilm formation. This review will first describe the use of HTS in treatment of CF focusing on its efficacy and tolerability. The emphasis will then change to the potential benefits of aerosolized HTS for the attenuation of receptor mediated neutrophil functions, including down-regulation of oxidative burst activity, adhesion molecule expression, and the suppression of neutrophil degranulation of proteolytic enzymes. PMID:26261770

  6. Comparison of Melatonin, Hypertonic Saline, and Hydroxyethyl Starch for Resuscitation of Secondary Intra-Abdominal Hypertension in an Animal Model.

    PubMed

    Chang, Mingtao; Tang, Hao; Liu, Dong; Li, Yang; Zhang, Lianyang

    2016-01-01

    A variety of agents may have a beneficial effect in reducing injury-induced intestinal edema of fluid, but studies confirming the efficacy and mechanisms of these agents in secondary intra-abdominal hypertension (IAH) are lacking. This study was to compare the effectiveness of melatonin, 7.5% hypertonic saline (HS), and hydroxyethyl starch 130/0.4 (HES) on the resuscitation of secondary IAH in a rat model. Female SD rats were divided into: sham group, shock group, lactated Ringer solution (LR) group, melatonin group, HS group, and HES group. Except for the sham group, all rats underwent a combination of inducing portal hypertension, hemorrhaging to a MAP of 40 mmHg for 2 hr, and using an abdominal restraint device. The collected blood was reinfused and the rats were treated with LR (30ml/h), melatonin (50 mg/kg) + LR, HS (6 ml/kg) + LR, and HES (30 ml/kg) + LR, respectively. The shock group received no fluids. LR was continuously infused for 6hr. The intestinal permeability, immunofluorescence of tight junction proteins, transmission electron microscopy, level of inflammatory mediators (TNF-a, IL-1β, IL-6) and of biochemical markers of oxidative stress (malondialdehyde, myeloperoxidase activity, and glutathione peroxidase) were assessed. Expressions of the protein kinase B (Akt) and of tight junction proteins were detected by Western blot. Compared with LR, HS, and HES, melatonin was associated with less inflammatory and oxidative injury, less intestinal permeability and injury, and lower incidence of secondary IAH in this model. The salutary effect of melatonin in this model was associated with the upregulation of intestinal Akt phosphorylation. PMID:27560478

  7. Focal adhesion kinase regulates the activity of the osmosensitive transcription factor TonEBP/NFAT5 under hypertonic conditions

    PubMed Central

    Neuhofer, Wolfgang; Küper, Christoph; Lichtnekert, Julia; Holzapfel, Konstantin; Rupanagudi, Khader V.; Fraek, Maria-Luisa; Bartels, Helmut; Beck, Franz-Xaver

    2014-01-01

    TonEBP/NFAT5 is a major regulator of the urinary concentrating process and is essential for the osmoadaptation of renal medullary cells. Focal adhesion kinase (FAK) is a mechanosensitive non-receptor protein tyrosine kinase expressed abundantly in the renal medulla. Since osmotic stress causes cell shrinkage, the present study investigated the contribution of FAK on TonEBP/NFAT5 activation. Osmotic stress induced time-dependent activation of FAK as evidenced by phosphorylation at Tyr-397, and furosemide reduces FAK Tyr-397 phosphorylation in the rat renal medulla. Both pharmacological inhibition of FAK and siRNA-mediated knockdown of FAK drastically reduced TonEBP/NFAT5 transcriptional activity and target gene expression in HEK293 cells. This effect was not mediated by impaired nuclear translocation or by reduced transactivating activity of TonEBP/NFAT5. However, TonEBP/NFAT5 abundance under hypertonic conditions was diminished by 50% by FAK inhibition or siRNA knockdown of FAK. FAK inhibition only marginally reduced transcription of the TonEBP/NFAT5 gene. Rather, TonEBP/NFAT5 mRNA stability was diminished significantly by FAK inhibition, which correlated with reduced reporter activity of the TonEBP/NFAT5 mRNA 3′ untranslated region (3′-UTR). In conclusion, FAK is a major regulator of TonEBP/NFAT5 activity by increasing its abundance via stabilization of the mRNA. This in turn, depends on the presence of the TonEBP/NFAT5 3′-UTR. PMID:24772088

  8. Comparison of Melatonin, Hypertonic Saline, and Hydroxyethyl Starch for Resuscitation of Secondary Intra-Abdominal Hypertension in an Animal Model

    PubMed Central

    Liu, Dong; Li, Yang; Zhang, Lianyang

    2016-01-01

    A variety of agents may have a beneficial effect in reducing injury-induced intestinal edema of fluid, but studies confirming the efficacy and mechanisms of these agents in secondary intra-abdominal hypertension (IAH) are lacking. This study was to compare the effectiveness of melatonin, 7.5% hypertonic saline (HS), and hydroxyethyl starch 130/0.4 (HES) on the resuscitation of secondary IAH in a rat model. Female SD rats were divided into: sham group, shock group, lactated Ringer solution (LR) group, melatonin group, HS group, and HES group. Except for the sham group, all rats underwent a combination of inducing portal hypertension, hemorrhaging to a MAP of 40 mmHg for 2 hr, and using an abdominal restraint device. The collected blood was reinfused and the rats were treated with LR (30ml/h), melatonin (50 mg/kg) + LR, HS (6 ml/kg) + LR, and HES (30 ml/kg) + LR, respectively. The shock group received no fluids. LR was continuously infused for 6hr. The intestinal permeability, immunofluorescence of tight junction proteins, transmission electron microscopy, level of inflammatory mediators (TNF-a, IL-1β, IL-6) and of biochemical markers of oxidative stress (malondialdehyde, myeloperoxidase activity, and glutathione peroxidase) were assessed. Expressions of the protein kinase B (Akt) and of tight junction proteins were detected by Western blot. Compared with LR, HS, and HES, melatonin was associated with less inflammatory and oxidative injury, less intestinal permeability and injury, and lower incidence of secondary IAH in this model. The salutary effect of melatonin in this model was associated with the upregulation of intestinal Akt phosphorylation. PMID:27560478

  9. Increased long-latency reflex activity as a sufficient explanation for childhood hypertonic dystonia: a neuromorphic emulation study

    PubMed Central

    Sohn, Won J.; Niu, Chuanxin M.; Sanger, Terence D.

    2015-01-01

    Objective Childhood dystonia is a movement disorder that interferes with daily movements and can have a devastating effect on quality of life for children and their families. Although injury to basal ganglia is associated with dystonia, the neurophysiological mechanisms leading to the clinical manifestations of dystonia are not understood. Previous work suggested that long-latency stretch reflex (LLSR) is hyperactive in children with hypertonia due to secondary dystonia. We hypothesize that abnormal activity in motor cortices may cause an increase in the long-latency stretch reflex leading to hypertonia. Approach We modelled two possibilities of hyperactive LLSR by either creating a tonic involuntary drive to cortex, or increasing the synaptic gain in cortical neurons. Both models are emulated using programmable Very-Large-Scale-Integrated-circuit (VLSI) hardware to test their sufficiency for producing dystonic symptoms. The emulation includes a joint with two Hill-type muscles, realistic muscle spindles, and 2,304 Izhikevich-type spiking neurons. The muscles are regulated by a monosynaptic spinal pathway with 32ms delay and a long-latency pathway with 64ms loop-delay representing transcortical/supra-spinal connections. Main results When the limb is passively stretched, both models produce involuntary resistance with increased antagonist EMG responses similar to human data; also the muscle relaxation is delayed similar to human data. Both models predict reduced range of motion in voluntary movements. Significance Although our model is a highly simplified and limited representation of reflex pathways, it shows that increased activity of the long-latency stretch reflex is by itself sufficient to cause many of the features of hypertonic dystonia. PMID:25946372

  10. N-butyl-2-cyanoacrylate, iso-amyl-2-cyanoacrylate and hypertonic glucose with 72% chromated glycerin in gastric varices

    PubMed Central

    Elwakil, Reda; Montasser, Mohamed Fawzy; Abdelhakam, Sara M; Ibrahim, Wesam A

    2015-01-01

    AIM: To compare n-butyl-2-cyanoacrylate, iso-amyl-2-cyanoacrylate and a mixture of 72% chromated glycerin with hypertonic glucose solution in management of gastric varices. METHODS: Ninety patients with gastric varices presented to Endoscopy Unit of Ain Shams University Hospital were included. They were randomly allocated into three groups; each group included 30 patients treated with intravariceal sclerosant injections in biweekly sessions till complete obturation of gastric varices; Group I (n-butyl-2-cyanoacrylate; Histoacryl®), Group II (iso-amyl-2-cyanoacrylate; Amcrylate®) and Group III (mixture of 72% chromated glycerin; Scleremo® with glucose solution 25%). All the procedures were performed electively without active bleeding. Recruited patients were followed up for 3 mo. RESULTS: 26% of Scleremo group had bleeding during puncture vs 3.3% in each of the other two groups with significant difference, (P < 0.05). None of Scleremo group had needle obstruction vs 13.3% in each of the other two groups with no significant difference, (P > 0.05). Rebleeding occurred in 13.3% of Histoacryl and Amcrylate groups vs 0% in Scleremo group with no significant difference. The in hospital mortality was 6.6% in both Histoacryl and Amcrylate groups, while it was 0% in Scleremo group with no significant difference. In the first and second sessions, the amount of Scleremo needed for obturation was significantly high, while the amount of Histoacryl was significantly low. Scleremo was the less costly of the two treatments. CONCLUSION: All used sclerosant substances showed efficacy and success in management of gastric varices with no significant differences except in total amount, cost and bleeding during puncture. PMID:25901221

  11. Increased long-latency reflex activity as a sufficient explanation for childhood hypertonic dystonia: a neuromorphic emulation study

    NASA Astrophysics Data System (ADS)

    Sohn, Won J.; Niu, Chuanxin M.; Sanger, Terence D.

    2015-06-01

    Objective. Childhood dystonia is a movement disorder that interferes with daily movements and can have a devastating effect on quality of life for children and their families. Although injury to basal ganglia is associated with dystonia, the neurophysiological mechanisms leading to the clinical manifestations of dystonia are not understood. Previous work suggested that long-latency stretch reflex (LLSR) is hyperactive in children with hypertonia due to secondary dystonia. We hypothesize that abnormal activity in motor cortices may cause an increase in the LLSR leading to hypertonia. Approach. We modeled two possibilities of hyperactive LLSR by either creating a tonic involuntary drive to cortex, or increasing the synaptic gain in cortical neurons. Both models are emulated using programmable very-large-scale-integrated-circuit hardware to test their sufficiency for producing dystonic symptoms. The emulation includes a joint with two Hill-type muscles, realistic muscle spindles, and 2,304 Izhikevich-type spiking neurons. The muscles are regulated by a monosynaptic spinal pathway with 32 ms delay and a long-latency pathway with 64 ms loop-delay representing transcortical/supra-spinal connections. Main results. When the limb is passively stretched, both models produce involuntary resistance with increased antagonist EMG responses similar to human data; also the muscle relaxation is delayed similar to human data. Both models predict reduced range of motion in voluntary movements. Significance. Although our model is a highly simplified and limited representation of reflex pathways, it shows that increased activity of the LLSR is by itself sufficient to cause many of the features of hypertonic dystonia.

  12. Mutation of a single threonine in the cytoplasmic NH2 terminus disrupts trafficking of renal betaine-GABA transporter 1 during hypertonic stress.

    PubMed

    Schweikhard, Eva S; Kempson, Stephen A; Ziegler, Christine; Burckhardt, Birgitta C

    2014-07-01

    Betaine is an important osmolyte and is, compared with other organs, much more abundant in the kidneys, where it enters cells in the medulla by betaine-GABA transporter 1 (BGT1) to balance osmoregulation in the countercurrent system. In wild-type (wt-)BGT1-expressing oocytes, GABA-mediated currents were diminished by preincubation of oocytes with 100 nM PMA or 5 μM dioctanoyl-sn-glycerol, activators of PKC, whereas the application of staurosporine before the application of dioctanoyl-sn-glycerol restored the response to GABA. Four potential phosphorylation sites on BGT1 were mutated to alanine by site-directed mutagenesis. Three mutants (T235A, S428A, and S564A) evoked GABA currents comparable in magnitude to currents observed in wt-BGT1-expressing oocytes, whereas GABA currents in T40A were barely detectable. Uptake of [(3)H]GABA was also determined in human embryonic kidney-293 cells expressing enhanced green fluorescent protein (EGFP)-tagged BGT1 with the same mutations. T235A, S428A, and S564A showed upregulation of GABA uptake after hypertonic stress and downregulation by PMA similar to EGFP-wt-BGT1. In contrast, T40A did not respond to either hypertonicity or PMA. Confocal microscopy of the EGFP-BGT1 mutants expressed in Madin-Darby canine kidney cells revealed that T40A was present in the cytoplasm after 24 h of hypertonic stress. whereas the other mutants and EGFP-wt-BGT1 were in the plasma membrane. All mutants, including T40A, comigrated with wt-BGT1 on Western blots, suggesting that they are full-length proteins. T40A, however, cannot be phosphorylated, as revealed using a specific anti-phosphoantibody, and, therefore, T40 may be important for the trafficking and insertion of BGT1 in the plasma membrane. PMID:24829506

  13. ‘Indirect’ challenges from science to clinical practice

    PubMed Central

    Anderson, Sandra D.

    2016-01-01

    Indirect challenges act to provoke bronchoconstriction by causing the release of endogenous mediators and are used to identify airway hyper-responsiveness. This paper reviews the historical development of challenges, with exercise, eucapnic voluntary hyperpnoea (EVH) of dry air, wet hypertonic saline, and with dry powder mannitol, that preceded their use in clinical practice. The first challenge developed for clinical use was exercise. Physicians were keen for a standardized test to identify exercise-induced asthma (EIA) and to assess the effect of drugs such as disodium cromoglycate. EVH with dry air became a surrogate for exercise to increase ventilation to very high levels. A simple test was developed with EVH and used to identify EIA in defence force recruits and later in elite athletes. The research findings with different conditions of inspired air led to the conclusion that loss of water by evaporation from the airway surface was the stimulus to EIA. The proposal that water loss caused a transient increase in osmolarity led to the development of the hypertonic saline challenge. The wet aerosol challenge with 4.5% saline, provided a known osmotic stimulus, to which most asthmatics were sensitive. To simplify the osmotic challenge, a dry powder of mannitol was specially prepared and encapsulated. The test pack with different doses and an inhaler provided a common operating procedure that could be used at the point of care. All these challenge tests have a high specificity to identify currently active asthma. All have been used to assess the benefit of treatment with inhaled corticosteroids. Over the 50 years, the methods for testing became safer, less complex, and less expensive and all used forced expiratory volume in 1 sec to measure the response. Thus, they became practical to use routinely and were recommended in guidelines for use in clinical practice. PMID:26908255

  14. Hypertonic saline resuscitation enhances blood pressure recovery and decreases organ injury following hemorrhage in acute alcohol intoxicated rodents

    PubMed Central

    Sulzer, Jesse K.; Whitaker, Annie M.; Molina, Patricia E.

    2012-01-01

    Background Acute alcohol intoxication (AAI) impairs the hemodynamic and arginine vasopressin (AVP) counter-regulation to hemorrhagic shock (HS) and lactated Ringer’s (LR) fluid resuscitation (FR). The mechanism of AAI-induced suppression of AVP release in response to HS involves accentuated nitric oxide (NO) inhibitory tone. In contrast, AAI does not prevent AVP response to increased osmolarity produced by hypertonic saline (HTS) infusion. We hypothesized that FR with HTS during AAI would enhance AVP release by decreasing PVN NO inhibitory tone subsequently improving mean arterial blood pressure (MABP) and organ perfusion. Methods Male Sprague Dawley rats received a 15h alcohol infusion (2.5g/kg + 0.3 g/kg/h) or dextrose (DEX) prior to HS (40mmHg × 60 min) and FR with HTS (7.5%; 4ml/kg) or LR (2.4 × blood volume removed). Organ blood flow was determined and brains collected for NO content at 2h post-FR. Results HTS improved MABP recovery in AAI (109 vs 80mmHg) and DEX (114 vs 83mmHg) animals compared to LR. This was associated with higher (>60%) circulating AVP levels at 2h post-FR than those detected in LR animals in both groups. Neither AAI alone nor HS in DEX animals resuscitated with LR altered organ blood flow. In AAI animals, HS and FR with LR reduced blood flow to liver (72%), small intestine (65%), and large intestine (67%) compared to shams. FR with HTS improved liver (3-fold) and small intestine (2-fold) blood flow compared to LR in AAI-HS animals. The enhanced MABP response to HTS was prevented by pretreatment with a systemic AVP V1a receptor antagonist. HTS decreased PVN NO content in both groups 2h post-FR. Conclusions These results suggest that FR with HTS in AAI results in removal of central NO inhibition of AVP, restoring AVP levels and improving MABP and organ perfusion in AAI-HS. PMID:23147176

  15. A Physiologically-Motivated Compartment-Based Model of the Effect of Inhaled Hypertonic Saline on Mucociliary Clearance and Liquid Transport in Cystic Fibrosis

    PubMed Central

    Markovetz, Matthew R.; Corcoran, Timothy E.; Locke, Landon W.; Myerburg, Michael M.; Pilewski, Joseph M.; Parker, Robert S.

    2014-01-01

    Background Cystic Fibrosis (CF) lung disease is characterized by liquid hyperabsorption, airway surface dehydration, and impaired mucociliary clearance (MCC). Herein, we present a compartment-based mathematical model of the airway that extends the resolution of functional imaging data. Methods Using functional imaging data to inform our model, we developed a system of mechanism-motivated ordinary differential equations to describe the mucociliary clearance and absorption of aerosolized radiolabeled particle and small molecules probes from human subjects with and without CF. We also utilized a novel imaging metric in vitro to gauge the fraction of airway epithelial cells that have functional ciliary activity. Results This model, and its incorporated kinetic rate parameters, captures the MCC and liquid dynamics of the hyperabsorptive state in CF airways and the mitigation of that state by hypertonic saline treatment. Conclusions We postulate, based on the model structure and its ability to capture clinical patient data, that patients with CF have regions of airway with diminished MCC function that can be recruited with hypertonic saline treatment. In so doing, this model structure not only makes a case for durable osmotic agents used in lung-region specific treatments, but also may provide a possible clinical endpoint, the fraction of functional ciliated airway. PMID:25383714

  16. Thermal skin injury: I. Acute hemodynamic effects of fluid resuscitation with lactated Ringer's, plasma, and hypertonic saline (2,400 mosmol/l) in the rat.

    PubMed

    Onarheim, H; Lund, T; Reed, R

    1989-01-01

    Heart rate (HR), central venous pressure (CVP), mean arterial pressure (MAP), and cardiac index (CI) were measured in anesthetized rats subjected to a 40% body surface area full-thickness scald burn. Postburn intravenous fluid therapy with lactated Ringer's (5 ml/hr), plasma (2.5 ml/hr), or very hypertonic saline (2,400 mosmol/l) (0.75 ml/hr) was compared to unburned or burned, untreated controls. HR and CVP were not influenced significantly by thermal injury. MAP decreased steadily in the untreated group from 110 mmHg to 80 mmHg at 3 hr postburn. In the fluid-treated groups MAP did not change significantly. During the first 15 min postburn, CI was reduced to 58-71% of control values (P less than 0.01). CI increased during Ringer's and plasma infusion to 74-80% of control values (P less than 0.02 vs. unburned). Despite infusion therapy, hematocrit increased from 48 to 52%, clearly less than in the unresuscitated group (increase from 48 to 58%). Theoretically, the 2,400 mosmol/l saline would expand extracellular volume by five to six times the infused volume. Still, CI was reduced by 55% at 3 hr postburn in the hypertonic saline as well as in the burned, untreated group (P less than 0.001 vs. unburned). The low CI was mainly due to a reduced stroke volume. PMID:2917370

  17. Up-regulation of hypertonicity-activated myo-inositol transporter SMIT1 by the cell volume-sensitive protein kinase SGK1.

    PubMed

    Klaus, F; Palmada, M; Lindner, R; Laufer, J; Jeyaraj, S; Lang, F; Boehmer, C

    2008-03-15

    Mechanisms of regulatory cell volume increase following cell shrinkage include accumulation of organic osmolytes such as betaine, taurine, sorbitol, glycerophosphorylcholine (GPC) and myo-inositol. Myo-inositol is taken up by the sodium-myo-inositol-transporter SMIT1 (SLC5A3) expressed in a wide variety of cell types. Hypertonicity induces the transcription of the SMIT1 gene upon binding of the transcription factor tonicity enhancer binding protein (TonEBP) to tonicity responsive enhancers (TonE) in the SMIT1 promoter region. However, little is known about post-translational regulation of the carrier protein. In this study we show that SMIT1 is modulated by the serum- and glucocorticoid-inducible kinase SGK1, a protein genomically up-regulated by hypertonicity. As demonstrated by two-electrode voltage-clamp in the Xenopus oocyte expression system, SMIT1-mediated myo-inositol-induced currents are up-regulated by coexpression of wild type SGK1 and constitutively active (S422D)SGK1 but not by inactive (K127N)SGK1. The increase in SMIT1 activity is due to an elevated cell surface expression of the carrier while its kinetic properties remain unaffected. According to the decay of SMIT1 activity in the presence of brefeldin A, SGK1 stabilizes the SMIT1 protein in the plasma membrane. The SGK isoforms SGK2, SGK3 and the closely related protein kinase B (PKB) are similarly capable of activating SMIT1 activity. SMIT1-mediated currents are decreased by coexpression of the ubiquitin-ligase Nedd4-2, an effect counteracted by additional coexpression of SGK1. In conclusion, the present observations disclose SGK isoforms and protein kinase B as novel regulators of SMIT1 activity. PMID:18202099

  18. Regional suppression by lesions in the anterior third ventricle of c-fos expression induced by either angiotensin II or hypertonic saline.

    PubMed

    Xu, Z; Herbert, J

    1995-07-01

    Angiotensin II (250 pmol) infused into the cerebral ventricles of male rats induces the expression of c-fos in the subfornical organ, supraoptic and paraventricular nuclei of the hypothalamus, as well as in the lateral parabrachial nucleus, locus coeruleus and the nucleus of the solitary tract in the brainstem. Electrolytic lesions of the anteroventral third ventricle, principally the subcommissural (ventral) median preoptic nucleus, inhibited the dipsogenic response to i.c.v. angiotensin II and also suppressed c-fos expression in supraoptic nucleus, paraventricular nucleus, lateral parabrachial nucleus, locus coeruleus and nucleus of the solitary tract but not in the subfornical organ or dorsal median preoptic nucleus. The stimulating effect of i.c.v. angiotensin II on corticosterone was also reduced. Median preoptic nucleus lesions also suppressed the expression of c-fos following i.v. infusions of 6 micrograms angiotensin II in supraoptic nucleus and paraventricular nucleus but not in subfornical organ, dorsal median preoptic nucleus, lateral parabrachial nucleus, locus coeruleus and nucleus of the solitary tract. Median preoptic nucleus lesions reduced the dipsogenic effects of an intragastric infusion of hypertonic (1.5 M) saline and suppressed c-fos expression in supraoptic nucleus and paraventricular nucleus compared to sham-lesioned rats. However, c-fos expression was unaltered in subfornical organ, dorsal median preoptic nucleus lesions had no effect on the increased corticosterone induced by hypertonic saline. Subfornical organ lesions did not alter dipsogenic responses to i.c.v. angiotensin II, nor was the i.c.v. angiotensin II-induced expression of c-fos suppressed in the basal forebrain. These experiments show that the ventral median preoptic nucleus (but not the subfornical organ), part of the anteroventral third ventricle, is critical for the expression of c-fos in more caudal areas of the brain following i.c.v. angiotensin II. c-fos expression in

  19. SGEM Hot Off the Press: hypertonic saline in severe traumatic brain injury: a systematic review and meta-analysis of randomized controlled trials.

    PubMed

    Purdy, Eve; Thoma, Brent; Milne, Ken; Bond, Chris

    2016-09-01

    As part of the Canadian Journal of Emergency Medicine's (CJEM) developing social media strategy, 1 we are collaborating with the Skeptics' Guide to Emergency Medicine (SGEM) to summarize and critically appraise the current emergency medicine (EM) literature using evidence-based medicine principles. In the "Hot Off the Press" series, we select original research manuscripts published in CJEM to be featured on the SGEM website/podcast and discussed by the study authors and the online EM community. A similar collaboration is under way between the SGEM and Academic Emergency Medicine. What follows is a summary of the selected article, the immediate post-publication synthesis from the SGEM podcast, commentary by the first author, and the subsequent discussion from the SGEM blog and other social media. Through this series, we hope to enhance the value, accessibility, and application of important, clinically relevant EM research. In this, the second SGEM HOP hosted collaboratively with CJEM, we discuss a systematic review evaluating the use of hypertonic saline in the treatment of severe traumatic brain injury. 2. PMID:27618977

  20. Inhibition of natriuresis in median eminence polydipsia: effects after intake of diets with different osmolalities and after hypertonic NaCl administration.

    PubMed

    Mahía, Javier; Bernal, Antonio; Puerto, Amadeo

    2013-01-01

    Lesions in the hypothalamic median eminence (ME) induce polydipsia and polyuria in male rats. A first experiment was designed to examine the effect of salt consumption (standard 0.25 percent Na+ vs. low-salt 0.04 percent Na+ diet) on the fluid-electrolytic balance (plasma sodium, urinary sodium excretion, urine osmolality) and water intake of ME polydipsic animals. In the first 6 h post-surgery, the natriuretic response was higher in ME-lesioned animals than in control groups. At 24 h post-surgery, however, less sodium was excreted by ME rats fed with a standard salt diet (ME/SS), despite showing no decrease in salt intake, and they evidenced an increase in plasma sodium concentration and water intake. Urine osmolality was significantly higher in control animals than in either ME-lesioned group. In experiment 2, hypertonic NaCl administration (2 ml/2M) increased the polydipsic behavior of ME-lesioned but not control rats (day 2). Animals deprived of food/salt showed a significant reduction (on day 2) in the initial (day 1) polydipsia, which increased on day 3 when the animals had access to a standard-salt diet. These results suggest that the reduced natriuretic response and the consequent sodium retention observed in ME animals may exacerbate the hydromineral imbalance of this polydipsic syndrome. PMID:24129482

  1. Regulation of expression of the stress response gene, Osp94: identification of the tonicity response element and intracellular signalling pathways.

    PubMed Central

    Kojima, Ryoji; Randall, Jeffrey D; Ito, Eri; Manshio, Hiroyuki; Suzuki, Yoshio; Gullans, Steven R

    2004-01-01

    Osp94 (osmotic stress protein of 94 kDa) is known to be up-regulated by hypertonic and heat-shock stresses in mouse renal inner medullary collecting duct (mIMCD3) cells. To investigate the molecular mechanism of transcriptional regulation of the Osp94 gene under these stresses, we cloned and characterized the 5'-flanking region of the gene. Sequence analysis of the proximal 4 kb 5'-flanking region revealed a TATA-less G/C-rich promoter region containing a cluster of Sp1 sites. We also identified upstream sequence motifs similar to the consensus TonE/ORE (tonicity-response element/osmotic response element) as well as the consensus HSE (heat-shock element). Luciferase activities in cells transfected with reporter constructs containing a TonE/ORE-like element (Osp94-TonE; 5'-TGGAAAGGACCAG-3') and HSE enhanced reporter gene expression under hypertonic stress and heat-shock stress respectively. Electrophoretic gel mobility-shift assay showed a slowly migrating band binding to the Osp94-TonE probe, probably representing binding of TonEBP (TonE binding protein) to this enhancer element. Furthermore, treatment of mIMCD3 cells with MAPK (mitogen-activated protein kinase) inhibitors (SB203580, PD98059, U0126 and SP600125) and a proteasome inhibitor (MG132) suppressed the increase in Osp94 gene expression caused by hypertonic NaCl. These results indicate that the 5'-flanking region of Osp94 gene contains a hypertonicity sensitive cis -acting element, Osp94-TonE, which is distinct from a functional HSE. Furthermore, the MAPK and proteasome systems appear to be, at least in part, involved in hypertonic-stressmediated regulation of Osp94 through Osp94-TonE. PMID:15018608

  2. An equiosmolar study on early intracranial physiology and long term outcome in severe traumatic brain injury comparing mannitol and hypertonic saline.

    PubMed

    Jagannatha, Aniruddha Tekkatte; Sriganesh, Kamath; Devi, Bhagavatula Indira; Rao, Ganne Sesha Umamaheswara

    2016-05-01

    The impact of hypertonic saline (HTS) on long term control of intracranial hypertension (ICH) is yet to be established. The current prospective randomized controlled study was carried out in 38 patients with severe traumatic brain injury (TBI). Over 450 episodes of refractory ICH were treated with equiosmolar boluses of 20% mannitol in 20 patients and 3.0% HTS in 18 subjects. Intracranial pressure (ICP) was monitored for 6days. ICP and cerebral perfusion pressure (CPP) were comparable between the groups. The mannitol group had a progressive increase in the ICP over the study period (p=0.01). A similar increase was not seen in the HTS group (p=0.1). The percentage time for which the ICP remained below a threshold of 20 mmHg on day6 was higher in the HTS group (63% versus 49%; p=0.3). The duration of inotrope requirement in the HTS group was less compared to the mannitol group (p=0.06). The slope of fall in ICP in response to a bolus dose at a given baseline value of ICP was higher with HTS compared to mannitol (p=0.0001). In-hospital mortality tended to be lower in the HTS group (3 versus 10; p=0.07) while mortality at 6 months was not different between the groups (6 versus 10; p=0.41). Dichotomized Glasgow Outcome Scale scores at 6months were comparable between the groups (p=0.21). To conclude, immediate physiological advantages seen with HTS over mannitol did not translate into long term benefit on ICP/CPP control or mortality of patients with TBI. PMID:26924183

  3. Improvement of Neuroenergetics by Hypertonic Lactate Therapy in Patients with Traumatic Brain Injury Is Dependent on Baseline Cerebral Lactate/Pyruvate Ratio

    PubMed Central

    Quintard, Hervé; Patet, Camille; Zerlauth, Jean-Baptiste; Suys, Tamarah; Bouzat, Pierre; Pellerin, Luc; Meuli, Reto; Magistretti, Pierre J.

    2016-01-01

    Abstract Energy dysfunction is associated with worse prognosis after traumatic brain injury (TBI). Recent data suggest that hypertonic sodium lactate infusion (HL) improves energy metabolism after TBI. Here, we specifically examined whether the efficacy of HL (3h infusion, 30–40 μmol/kg/min) in improving brain energetics (using cerebral microdialysis [CMD] glucose as a main therapeutic end-point) was dependent on baseline cerebral metabolic state (assessed by CMD lactate/pyruvate ratio [LPR]) and cerebral blood flow (CBF, measured with perfusion computed tomography [PCT]). Using a prospective cohort of 24 severe TBI patients, we found CMD glucose increase during HL was significant only in the subgroup of patients with elevated CMD LPR >25 (n = 13; +0.13 [95% confidence interval (CI) 0.08–0.19] mmol/L, p < 0.001; vs. +0.04 [–0.05–0.13] in those with normal LPR, p = 0.33, mixed-effects model). In contrast, CMD glucose increase was independent from baseline CBF (coefficient +0.13 [0.04–0.21] mmol/L when global CBF was <32.5 mL/100 g/min vs. +0.09 [0.04–0.14] mmol/L at normal CBF, both p < 0.005) and systemic glucose. Our data suggest that improvement of brain energetics upon HL seems predominantly dependent on baseline cerebral metabolic state and support the concept that CMD LPR – rather than CBF – could be used as a diagnostic indication for systemic lactate supplementation following TBI. PMID:26421521

  4. Temporal profile of arginine vasopressin release from the neurohypophysis in response to hypertonic saline and hypotension measured using a fluorescent fusion protein.

    PubMed

    Yao, Song T; Antunes, Vagner R; Bradley, Peter M J; Kasparov, Sergey; Ueta, Yoichi; Paton, Julian F R; Murphy, David

    2011-09-30

    Methods currently employed to study the release of hormones such as arginine vasopressin (AVP), while sensitive, suffer from a low temporal resolution such that the monitoring of AVP release on a moment-to-moment basis is not possible. Here, we describe a new approach to indirectly monitor the temporal profile of AVP release from the neurohypophysis of transgenic rats expressing an AVP-eGFP fusion gene. Using fibre-optic probes (termed 'optrodes') we were able to indirectly monitor AVP release via a reporter moiety in real-time. This method is a major advance over current methods used to monitor AVP release. Intravenous administration of hypertonic saline (3M NaCl) induced a rapid (latency of 2-3s) increase in fluorescence detected in the neurohypophysis that lasted on average for 60s - a response that was highly reproducible. Infusion of sodium nitroprusside induced a rapid fall in blood pressure accompanied by a rapid, stimulus-locked increase in fluorescent signal that returned to baseline with the recovery of blood pressure to pre-stimulus levels - again this response was highly reproducible. Withdrawal of blood (to simulate haemorrhage) also resulted in a stimulus-locked increase in fluorescence that return to baseline after the withdrawn blood was returned to the animal. In conclusion, we developed a highly sensitive approach that allows the indirect measurement of AVP release via the monitoring of a reporter gene in real-time. This technology can be adapted to permit the study of a whole array of neurohormones/chemicals in transgenic animals expressing a fluorescent reporter construct. PMID:21855574

  5. Clinical challenge.

    PubMed

    2016-09-01

    Questions for this month's clinical challenge are based on articles in this issue. The clinical challenge is endorsed by the RACGP Quality Improvement and Continuing Professional Development (QI&CPD) program and has been allocated four Category 2 points (Activity ID:59922). Answers to this clinical challenge are available immediately following successful completion online at http://gplearning.racgp.org.au. Clinical challenge quizzes may be completed at any time throughout the 2014-16 triennium; therefore, the previous months' answers are not published. Each of the questions or incomplete statements below is followed by four suggested answers or completions. Select the most appropriate statement as your answer. PMID:27606376

  6. Featherweight Challenge

    ERIC Educational Resources Information Center

    Love, Tyler S.; Ryan, Larry

    2012-01-01

    As science, technology education, and engineering programs suffer budget cuts, educators continue to seek cost-effective activities that engage students and reinforce standards. The featherweight challenge is a hands-on activity that challenges students to continually refine their design while not breaking the budget. This activity uses one of the…

  7. Variation of pain and vasomotor responses evoked by intramuscular infusion of hypertonic saline in human subjects: influence of gender and its potential neural mechanisms.

    PubMed

    Lei, Jing; You, Hao-Jun

    2012-04-10

    The aim of current study was to explore role of gender in pain and cutaneous vasomotor responses during the condition of intramuscular (i.m.) hypertonic (HT, 5.8%) saline induced muscle pain. In 20 healthy human subjects (10 females), 2-4.8ml of either HT or isotonic (IT, 0.9%) saline was infused into the left tibialis anterior muscle to elicit muscle pain, during which the intensity and distribution of pain together with skin vasomotor responses were investigated. Cutaneous blood flow was assessed using laser-Doppler flowmetry in 4 different skin areas: ipsilateral infusion area (5cm×5cm), ipsilateral referred pain area (5cm×10cm), contralateral area to the infusion site (5cm×5cm), and contralateral area to the referred pain site (5cm×10cm). Among the different i.m. infusions, 4.8ml HT saline evoked the highest pain intensity, the longest pain duration, and the largest pain distribution area in different subjects (P<0.001). Gender-related differences in pain and skin vasomotor responses were observed following the i.m. HT, but not IT, saline infusion while women exhibited stronger pain intensity and duration (P<0.001), and more expressed vasomotor responses (P<0.05) at the infusion area and contralateral mirror site. Intramuscularly pre-treating the infusion area with 1ml of 2% lidocaine markedly reduced the muscle pain and blocked the increased skin blood flow in both men and women (P<0.05). However, post-treatment with lidocaine significantly reduced the pain intensity and the increased skin blood flow only in men, but not women. The data demonstrate that gender-associated difference exists in HT saline intramuscularly induced local muscle pain and vasomotor responses. Neural mechanisms underlying gender-related differences in vasomotor responses is significantly different, suggesting that local pre-treatment, but not post-treatment, with anesthetic may provide superior analgesia to block sex-associated difference in pain and vasomotor responses. PMID

  8. Role of permissive hypotension, hypertonic resuscitation and the global increased permeability syndrome in patients with severe hemorrhage: adjuncts to damage control resuscitation to prevent intra-abdominal hypertension.

    PubMed

    Duchesne, Juan C; Kaplan, Lewis J; Balogh, Zsolt J; Malbrain, Manu L N G

    2015-01-01

    Secondary intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) are closely related to fluid resuscitation. IAH causes major deterioration of the cardiac function by affecting preload, contractility and afterload. The aim of this review is to discuss the different interactions between IAH, ACS and resuscitation, and to explore a new hypothesis with regard to damage control resuscitation, permissive hypotension and global increased permeability syndrome. Review of the relevant literature via PubMed search. The recognition of the association between the development of ACS and resuscitation urged the need for new approach in traumatic shock management. Over a decade after wide spread application of damage control surgery damage control resuscitation was developed. DCR differs from previous resuscitation approaches by attempting an earlier and more aggressive correction of coagulopathy, as well as metabolic derangements like acidosis and hypothermia, often referred to as the 'deadly triad' or the 'bloody vicious cycle'. Permissive hypotension involves keeping the blood pressure low enough to avoid exacerbating uncontrolled haemorrhage while maintaining perfusion to vital end organs. The potential detrimental mechanisms of early, aggressive crystalloid resuscitation have been described. Limitation of fluid intake by using colloids, hypertonic saline (HTS) or hyperoncotic albumin solutions have been associated with favourable effects. HTS allows not only for rapid restoration of circulating intravascular volume with less administered fluid, but also attenuates post-injury oedema at the microcirculatory level and may improve microvascular perfusion. Capillary leak represents the maladaptive, often excessive, and undesirable loss of fluid and electrolytes with or without protein into the interstitium that generates oedema. The global increased permeability syndrome (GIPS) has been articulated in patients with persistent systemic inflammation failing

  9. Chloride/bicarbonate exchanger SLC26A7 is localized in endosomes in medullary collecting duct cells and is targeted to the basolateral membrane in hypertonicity and potassium depletion.

    PubMed

    Xu, Jie; Worrell, Roger T; Li, Hong C; Barone, Sharon L; Petrovic, Snezana; Amlal, Hassane; Soleimani, Manoocher

    2006-04-01

    SLC26A7 is a Cl(-)/HCO(3)(-) exchanger that is expressed on the basolateral membrane and in the cytoplasm of two distinct acid-secreting epithelial cells: The A-intercalated cells in the kidney outer medullary collecting duct and the gastric parietal cells. The intracellular localization of SLC26A7 suggests the possibility of trafficking between cell membrane and intracellular compartments. For testing this hypothesis, full-length human SLC26A7 cDNA was fused with green fluorescence protein and transiently expressed in MDCK epithelial cells. In monolayer cells in isotonic medium, SLC26A7 showed punctate distribution throughout the cytoplasm. However, in medium that was made hypertonic for 16 h, SLC26A7 was detected predominantly in the plasma membrane. The presence of mitogen-activated protein kinase inhibitors blocked the trafficking of SLC26A7 to the plasma membrane. Double-labeling studies demonstrated the localization of SLC26A7 to the transferrin receptor-positive endosomes. A chimera that was composed of the amino terminal fragment of SLC26A7 and the carboxyl terminal fragment of SLC26A1, and a C-terminal-truncated SLC26A7 were retained in the cytoplasm in hypertonicity. In separate studies, SLC26A7 showed predominant localization in plasma membrane in potassium-depleted isotonic medium (0.5 or 2 mEq/L KCl) versus cytoplasmic distribution in normal potassium isotonic medium (4 mEq/L). It is concluded that SLC26A7 is present in endosomes, and its targeting to the basolateral membrane is increased in hypertonicity and potassium depletion. The trafficking to the cell surface suggests novel functional upregulation of SLC26A7 in states that are associated with hypokalemia or increased medullary tonicity. Additional studies are needed to ascertain the role of SLC26A7 in enhanced bicarbonate absorption in outer medullary collecting duct in hypokalemia and in acid-base regulation in conditions that are associated with increased medullary tonicity. PMID:16524946

  10. Ethical Challenges

    ERIC Educational Resources Information Center

    Morris, Michael

    2004-01-01

    All evaluators face the challenge of striving to adhere to the highest possible standards of ethical conduct. Translating the AEA's Guiding Principles and the Joint Committee's Program Evaluation Standards into everyday practice, however, can be a complex, uncertain, and frustrating endeavor. Moreover, acting in an ethical fashion can require…

  11. Quill Challenge

    ERIC Educational Resources Information Center

    Stevens, Lori

    2006-01-01

    Teaching high school students the "grammar" of art--the principles and elements of art and design--while also teaching them about creativity and concept can be difficult. This author has found that combining beginning lessons in line, shape, value, texture, form, and color with projects requiring innovation and inspiration, though challenging, is…

  12. Environmental challenge

    SciTech Connect

    Conable, B.; Warford, J.; Partow, Z.; Lutz, E.; Munasinghe, M.

    1991-09-01

    The contents include the following: Development and the Environment: A Global Balance; Evolution of the World Bank's Environmental Policy; Accounting for the Environment; Public Policy and the Environment; Managing Drylands; Environmental Action Plans in Africa; Agroforestry in Sub-Saharan Africa; Irrigation and the Environmental Challenge; Curbing Pollution in Developing Countries; Global Warming and the Developing World; and The Global Environment Facility.

  13. The ΔC splice-variant of TRPM2 is the hypertonicity-induced cation channel in HeLa cells, and the ecto-enzyme CD38 mediates its activation

    PubMed Central

    Numata, Tomohiro; Sato, Kaori; Christmann, Jens; Marx, Romy; Mori, Yasuo; Okada, Yasunobu; Wehner, Frank

    2012-01-01

    Hypertonicity-induced cation channels (HICCs) are key-players in proliferation and apoptosis but their molecular correlate remains obscure. Furthermore, the activation profile of HICCs is not well defined yet. We report here that, in HeLa cells, intracellular adenosine diphosphate ribose (ADPr) and cyclic ADPr (cADPr), as supposed activators of TRPM2, elicited cation currents that were virtually identical to the osmotic activation of HICCs. Silencing of the expression of TRPM2 and of the ecto-enzyme CD38 (as a likely source of ADPr and cADPr) inhibited HICC as well as nucleotide-induced currents and, in parallel, the hypertonic volume response of cells (the regulatory volume increase, RVI) was attenuated. Quantification of intracellular cADPr levels and the systematic application of extra- vs. intracellular nucleotides indicate that the outwardly directed gradient rather than the cellular activity of ADPr and cADPr triggers TRPM2 activation, probably along with a simultaneous biotransformation of nucleotides. Cloning of TRPM2 identified the ΔC-splice variant as the molecular correlate of the HICC, which could be strongly supported by a direct comparison of the respective Ca2+ selectivity. Finally, immunoprecipitation and high-resolution FRET/FLIM imaging revealed the interaction of TRPM2 and CD38 in the native as well as in a heterologous (HEK293T) expression system. We propose transport-related nucleotide export via CD38 as a novel mechanism of TRPM2/HICC activation. With the biotransformation of nucleotides running in parallel, continuous zero trans-conditions are achieved which will render the system infinitely sensitive. PMID:22219339

  14. The challenge

    NASA Astrophysics Data System (ADS)

    Freeman, Roger L.

    1988-01-01

    Radio systems in space are on the brink of achieving throughout data rates in the hundred of megabits. At present, radio systems operate below 60 GHz and are the traditional workhorses of satellite communications. Legal constraints and the laws of physics limit data rates on the systems. It is maintained that the challenge to provide high technology tools to develop viable high-data-rate space transmission systems can be met before the next century if three optical system and technology issues are overcome. In declining order of importance, the issues are: precise optical pointing, acquisition, and tracking; efficient laser diode optical sources producing sufficient output power; and advanced optical detector technology.

  15. Abnormal urinary excretion of NKCC2 and AQP2 in response to hypertonic saline in chronic kidney disease: an intervention study in patients with chronic kidney disease and healthy controls

    PubMed Central

    2014-01-01

    Background Renal handling of sodium and water is abnormal in chronic kidney disease (CKD). The aim of this study was to test the hypothesis that abnormal activity of the aquaporin-2 water channels (AQP2), the sodium-potassium-2chloride transporter (NKCC2) and/or the epithelial sodium channels (ENaC) contribute to this phenomenon. Methods 23 patients with CKD and 24 healthy controls at baseline and after 3% saline infusion were compared. The following measurements were performed: urinary concentrations of AQP2 (u-AQP2), NKCC2 (u-NKCC2), ENaC (u-ENaCγ), glomerular filtration rate (GFR) estimated by 51Cr-EDTA clearance, free water clearance (CH2O), urinary output (UO), fractional excretion of sodium (FENa), plasma concentrations of AVP, renin (PRC), Angiotensin II (ANG II), Aldosterone (Aldo) and body fluid volumes. Results At baseline, GFR was 34 ml/min in CKD patients and 89 ml/ml in controls. There were no significant differences in u-AQP2, u-NKCC2 or u-ENaCγ, but FENa, p-Aldo and p-AVP were higher in CKD patients than controls. In response to hypertonic saline, patients with CKD had an attenuated decrease in CH2O and UO. A greater increase in U-AQP2 was observed in CKD patients compared to controls. Furthermore, u-NKCC2 increased in CKD patients, whereas u-NKCC2 decreased in controls. Body fluid volumes did not significantly differ. Conclusions In response to hypertonic saline, u-NKCC2 increased, suggesting an increased sodium reabsorption via NKCC2 in patients with CKD. U-AQP2 increased more in CKD patients, despite an attenuated decrease in CH2O. Thus, though high levels of p-AVP and p-Aldo, the kidneys can only partly compensate and counteract acute volume expansion due to a defective tubular response. Trial registration Clinical trial no: NCT01623661. Date of trial registration: 18.06.2012. PMID:24970686

  16. Daunting challenges.

    PubMed

    Wirth, T E

    1994-09-01

    Excerpts of a speech on behalf of the United States at the Third Preparatory Meeting of the International Conference on Population and Development on April 5, 1994 are presented. The Draft Program of Action defines an international agenda for the Cairo Conference and for sustained, priority action in the remainder of this century and on into the 21st. 1) Quality voluntary family planning and reproductive health services must be universally available early in the 21st century by broadening the contraceptive choice as well as expanding and improving reproductive health services without coercion. As President Clinton has said, abortion should be safe, legal, and rare. 2) Educating females is a priority because it raises the status of women as well as lowers infant and maternal mortality and poverty. 3) The extent must be assessed of the national unmet need for antenatal care, childbirth care, immunization, and the monitoring of growth and development. 4) Emphasizing to adolescents the responsibilities of sexuality will reinforce health, education, and economic objectives. 5) As women are empowered, so must men be empowered to be responsible in relation to fertility as well as sexual and reproductive health. 6) Responsible mutually respectful sexual behavior must be encouraged among both men and women and the importance of such behavior must be taught to both boys and girls. 7) Any discussion of responsibility must also include emphasis on the family, which is challenged globally as never before. 8) The Cairo conference provides the opportunity to discuss the current unprecedented migrations of human populations around the world; the link between environmental degradation and migration; and the potential effect of development programs on population movements. 9) North-South partnerships must be nurtured, recognizing the mutually reinforcing roles and responsibilities of all countries for sustainable development. PMID:12288264

  17. Thermal skin injury: II. Effects on edema formation and albumin extravasation of fluid resuscitation with lactated Ringer's, plasma, and hypertonic saline (2,400 mosmol/l) in the rat.

    PubMed

    Onarheim, H; Lund, T; Reed, R

    1989-01-01

    Pentobarbital anesthetized rats were subjected to a 40% body surface area full-thickness scald burn. Intravenous fluid therapy was given as lactated Ringer's (5 ml/hr), plasma (2.5 ml/hr), or very hypertonic saline (2,400 mosmol/l) (0.75 ml/hr) and compared to unburned or burned, untreated controls. At 3 hr postburn, skin water and albumin content and extravasation of radiolabelled albumin were determined. Water content in injured skin increased by 35-78% (least in the untreated group, most in the plasma group) compared to unburned controls (P less than 0.05). After lactated Ringer's therapy water content increased even in unburned skin and in muscle (P less than 0.05). Tissue albumin mass increased generally slightly more than the increase in water content, from 37% (lactated Ringer's group) to 126% (plasma group) in burned areas. Extravasation rate of radiolabelled albumin increased 5-80 times in burned areas, most following plasma treatment (equivalent to 0.6-1.0 ml plasma/g dry weight/180 min). A major part of the estimated total fluid loss following therapy by lactated Ringer's took place in noninjured tissue. Plasma therapy gave less fluid accumulation in unburned tissues but more edema in the injured areas than lactated Ringer's. PMID:2917371

  18. Developing a Watershed Challenge

    ERIC Educational Resources Information Center

    Roman, Harry T.

    2010-01-01

    This article presents a watershed challenge that gives students an opportunity to investigate the challenge of using a watershed area as a site for development, examining the many aspects of this multifaceted problem. This design challenge could work well in a team-based format, with students taking on specific aspects of the challenges and…

  19. 78 FR 49296 - Centennial Challenges 2014 Sample Return Robot Challenge

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-13

    ... SPACE ADMINISTRATION Centennial Challenges 2014 Sample Return Robot Challenge AGENCY: National Aeronautics and Space Administration (NASA). ACTION: Notice of Centennial Challenges 2014 Sample Return Robot... Robot Challenge is scheduled and teams that wish to compete may register. Centennial Challenges is...

  20. Minority Innovation Challenges Institute

    NASA Video Gallery

    Do you want to learn more about how to compete in NASA’s technical challenges for both prestige and significant cash prizes? NASA’s Minority Innovation Challenges Institute trains and mentors mino...

  1. Green Flight Challenge

    NASA Video Gallery

    The CAFE Green Flight Challenge sponsored by Google will be held at the CAFE Foundation Flight Test Center at Charles M. Schulz Sonoma County Airport in Santa Rosa, Calif. The Green Flight Challeng...

  2. The Backpack Design Challenge

    ERIC Educational Resources Information Center

    Roman, Harry T.

    2010-01-01

    Something as simple as carrying books to school can be an interesting design challenge for students. It's an old problem that gets reinvented from time to time. In this article, the author discusses a backpack design challenge in which teachers work with students to design another way to carry books to school. The challenge started by trying to…

  3. NASA Centennial Challenges: After the Challenge

    NASA Video Gallery

    What's it like to participate in a NASA Centennial Challenge? In their own words: "We really had no idea what to expect when we got here. Being able to take all of this...now we have an idea for ne...

  4. Challenging Behaviour: A Challenge To Change.

    ERIC Educational Resources Information Center

    van Berckelaer-Onnes, I. A.; van Loon, J.; Peelen, A.

    2002-01-01

    This article discusses the role in the Netherlands of independent regional advisory teams made up of professionals who have experience with individuals who exhibit challenging behaviors. One team's methods are illustrated by describing the case of a completely isolated 24-year-old man who, after a 7-year intervention, was able to fulfill a long…

  5. Efficiency of 7.2% hypertonic saline hydroxyethyl starch 200/0.5 versus mannitol 15% in the treatment of increased intracranial pressure in neurosurgical patients – a randomized clinical trial [ISRCTN62699180

    PubMed Central

    Harutjunyan, Lilit; Holz, Carsten; Rieger, Andreas; Menzel, Matthias; Grond, Stefan; Soukup, Jens

    2005-01-01

    Introduction This prospective randomized clinical study investigated the efficacy and safety of 7.2% hypertonic saline hydroxyethyl starch 200/0.5 (7.2% NaCl/HES 200/0.5) in comparison with 15% mannitol in the treatment of increased intracranial pressure (ICP). Methods Forty neurosurgical patients at risk of increased ICP were randomized to receive either 7.2% NaCl/HES 200/0.5 or 15% mannitol at a defined infusion rate, which was stopped when ICP was < 15 mmHg. Results Of the 40 patients, 17 patients received 7.2% NaCl/HES 200/0.5 and 15 received mannitol 15%. In eight patients, ICP did not exceed 20 mmHg so treatment was not necessary. Both drugs decreased ICP below 15 mmHg (p < 0.0001); 7.2% NaCl/HES 200/0.5 within 6.0 (1.2–15.0) min (all results are presented as median (minimum-maximum range)) and mannitol within 8.7 (4.2–19.9) min (p < 0.0002). 7.2% NaCl/HES 200/0.5 caused a greater decrease in ICP than mannitol (57% vs 48%; p < 0.01). The cerebral perfusion pressure was increased from 60 (39–78) mmHg to 72 (54–85) mmHg by infusion with 7.2% NaCl/HES 200/0.5 (p < 0.0001) and from 61 (47–71) mmHg to 70 (50–79) mmHg with mannitol (p < 0.0001). The mean arterial pressure was increased by 3.7% during the infusion of 7.2% NaCl/HES 200/0.5 but was not altered by mannitol. There were no clinically relevant effects on electrolyte concentrations and osmolarity in the blood. The mean effective dose to achieve an ICP below 15 mmHg was 1.4 (0.3–3.1) ml/kg for 7.2% NaCl/HES 200/0.5 and 1.8 (0.45–6.5) ml/kg for mannitol (p < 0.05). Conclusion 7.2% NaCl/HES 200/0.5 is more effective than mannitol 15% in the treatment of increased ICP. A dose of 1.4 ml/kg of 7.2% NaCl/HES 200/0.5 can be recommended as effective and safe. The advantage of 7.2% NaCl/HES 200/0.5 might be explained by local osmotic effects, because there were no clinically relevant differences in hemodynamic clinical chemistry parameters. PMID:16277715

  6. Bacterial challenges in food

    PubMed Central

    Collee, J. G.

    1974-01-01

    Qualitative and quantitative aspects of bacterial challenges that might be encountered in food are discussed with reference to recognized and relatively unrecognized hazards. Mechanisms of pathogenicity are reviewed and the populations at risk are noted. The bacterial content of food as it is served at table merits more study. The challenge of prevention by education is discussed. Indirect bacterial challenges in our food are considered. The real challenge of diagnosis depends upon an awareness of a complex range of conditions; the importance of effective communication with efficient laboratory and epidemiological services is stressed. There is an increasing need for care in the preparation and distribution of food. PMID:4467860

  7. NASA Exploration Design Challenge

    NASA Video Gallery

    From the International Space Station, astronaut Sunita Williams welcomes participants to the NASA Exploration Design Challenge and explains the uncertainties about the effects of space radiation on...

  8. The Multimedia Challenge.

    ERIC Educational Resources Information Center

    Penuel, William R.; Means, Barbara; Simkins, Michael

    2000-01-01

    Teachers implementing a local history project in Belmont, California, had help from a federally funded technology innovation challenge grant: the Challenge 2000 Multimedia Project. Sponsored by a Silicon Valley school-business partnership, the initiative illustrates how technology can transform classroom learning while supporting instructional…

  9. A Call to Challenge

    ERIC Educational Resources Information Center

    Colleary, Shawn

    2004-01-01

    This article features the Challenge School, a magnet school in the CherryCreek School District in Colorado that focuses on academically advanced, motivated, and gifted students. The school was developed as an alternative to best meet the needs of these students. The Challenge School focuses on high student achievement and commensurate academic…

  10. Virtual Bridge Design Challenge

    ERIC Educational Resources Information Center

    Mitts, Charles R.

    2013-01-01

    This design/problem-solving activity challenges students to design a replacement bridge for one that has been designated as either structurally deficient or functionally obsolete. The Aycock MS Technology/STEM Magnet Program Virtual Bridge Design Challenge is an authentic introduction to the engineering design process. It is a socially relevant…

  11. The Intersection Challenge

    ERIC Educational Resources Information Center

    Roman, Harry T.

    2011-01-01

    Street intersections are a source of accidents--for both automobiles and pedestrians. This article presents an intersection challenge that allows students to explore some possible ways to change the traditional intersection. In this challenge, teachers open up the boundaries and allow students to redesign their world. The first step is to help…

  12. Challenges Facing Special Education.

    ERIC Educational Resources Information Center

    Meyen, Edward L., Ed.; And Others

    This book presents 17 selected papers from recent issues of the journal, "Focus on Exceptional Children," concerning current and emerging challenges facing the field of special education. The book is organized in two parts. Part 1, "Contemporary Challenges," includes the following articles: "Transitions in Early Childhood Special Education: Issues…

  13. Challenges and Roadblocks

    ERIC Educational Resources Information Center

    Hargrove, Kathy

    2011-01-01

    Gifted education has many challenges, and gifted programs sometimes throw up significant roadblocks. But passionate teachers can still make a difference in developing the gifts of the children. In this article, the author summarizes the challenges teachers face in serving gifted students and the roadblocks preventing a strong, supportive gifted…

  14. Science Challenge Day

    ERIC Educational Resources Information Center

    Siegel, Deborah

    2013-01-01

    Science fairs can be good motivators, but as extracurricular activities, they leave some students behind. However, by staging a Science Challenge Day at school, educators can involve all students in doing everything from choosing activities to judging projects. This article presents a model for running a successful Science Challenge Day. The…

  15. First Aid Challenge

    ERIC Educational Resources Information Center

    Roman, Harry T.

    2011-01-01

    This article describes a challenge wherein students will be asked to design a portable first aid kit that is normally carried in a recreational vehicle (RV), but can also be hand-carried or backpacked off road for distances of approximately 1-2 miles. This can be a very practical challenge for the students because it touches everyone. Everybody…

  16. Challenge and Change

    ERIC Educational Resources Information Center

    Mehaffy, George L.

    2012-01-01

    In the past twenty years, various industries have been forever altered by technology: newspapers, book publishing, the photography business, and many more. Higher education too faces unprecedented challenges primarily driven by rapid changes in technology. To meet these challenges and adapt to these changes, new models are needed. Six challenges…

  17. Dewey's Challenge to Teachers

    ERIC Educational Resources Information Center

    Fishman, Stephen M.; McCarthy, Lucille

    2010-01-01

    Given the serious social problems confronting Americans and others worldwide, the authors propose that Dewey's 1932 challenge to teachers is worthy of reconsideration by educators at all levels. In times similar to our own, Dewey challenged teachers to cultivate students' capacities to identify their happiness with what they can do to improve the…

  18. The Jet Travel Challenge

    ERIC Educational Resources Information Center

    Roman, Harry T.

    2007-01-01

    Airplane travelers are dismayed by the long lines and seemingly chaotic activities that precede boarding a full airplane. Surely, the one who can solve this problem is going to make many travelers happy. This article describes the Jet Travel Challenge, an activity that challenges students to create some alternatives to this now frustrating…

  19. Challenge College, Bradford

    ERIC Educational Resources Information Center

    Flecknoe, Mervyn

    2004-01-01

    What can you expect from a school in an area of high crime where 50 percent of the pupils take free school meals and which operates on a site that cannot be accessed from its main catchment area? In this article, the author shares his experience when he visited Challenge College. A low wall separates Challenge College from the area where most of…

  20. ELN implementation challenges.

    PubMed

    Drake, David J

    2007-08-01

    Electronic Laboratory Notebooks are becoming foundation platforms within many pharmaceutical companies because of the benefits that they offer to both the business and the scientists alike. Implementing an ELN within an established organisation presents challenges for the project team, both in terms of managing the impact on the scientists and the technical requirements for integration and data management. Implementation of a commercial ELN is not exempt from such challenges, and working with a third party supplier offers both advantages and additional challenges. PMID:17706546

  1. Challenging behaviour: a challenge to change.

    PubMed

    van Berckelaer-Onnes, I A; van Loon, J; Peelen, A

    2002-09-01

    People with intellectual disability often exhibit severe behavioural problems. Treatment of these problems is frequently very difficult. In The Netherlands, parents, institutes, schools and others can request the services of an independent advisory team with a pool of professionals who have experience with individuals who exhibit challenging behaviour. In this article the methods of the team will be described using a 24-year-old man as an example. The process took almost 7 years. Finally, this man, who had been living full time in one room in total isolation from the rest of the world, fulfilled his heart's desire--visiting the UK by Hovercraft. PMID:12212917

  2. Green Flight Challenge Highlights

    NASA Video Gallery

    On Monday, October 3, 2011, NASA's Centennial Challenges program awarded the largest prize in aviation history, created to inspire the development of more fuel-efficient aircraft and spark the star...

  3. Overcoming Breastfeeding Challenges

    MedlinePlus Videos and Cool Tools

    ... and Human Services Office on Women's Health Skip Navigation Skip top navigation Home A-Z Health Topics ePublications News About Us Contact Us Text size | Print | Skip left navigation It's Only Natural Planning ahead Overcoming challenges Overcoming ...

  4. Mars Balance Challenge

    NASA Video Gallery

    The Challenge is to develop ideas for how NASA can turn available entry, descent, and landing balance mass on a future Mars mission into a scientific or technological payload. Proposed concepts sho...

  5. International Space Apps Challenge

    NASA Video Gallery

    During the 2013 Space Apps Challenge, space enthusiasts with diverse backgrounds gathered April 20-21 for a collaborative, global problem-solving effort. Held at Kennedy Space Center Visitor Comple...

  6. Better Buildings Challenge Overview

    SciTech Connect

    2011-06-01

    The Better Buildings Challenge is a national leadership initiative calling on corporate chief executive officers, university presidents, and state and local leaders to make a significant commitment to building energy efficiency.

  7. The 2061 Challenge.

    ERIC Educational Resources Information Center

    Hundt, Lin

    1999-01-01

    Presents an interview with George Nelson, former astronaut and director of Project 2061 at the American Association for the Advancement of Science (AAAS). Nelson discusses his interest in science and math education, and future challenges for educators. (WRM)

  8. The Electric Car Challenge.

    ERIC Educational Resources Information Center

    Diehl, Brian E.

    1997-01-01

    Describes the Electric Car Challenge during which students applied methods of construction to build lightweight, strong vehicles that were powered by electricity. The activity required problem solving, sheet metal work, electricity, design, and construction skills. (JOW)

  9. Solving Aviation Challenges

    NASA Video Gallery

    This video highlights the challenges NASA aeronautics researchers are tackling to reduce aircraft noise, emissions, fuel consumption, and the innovative ways they're helping to debut NextGen, a rev...

  10. 2002 Controls Design Challenge

    NASA Technical Reports Server (NTRS)

    Hess, Ronald A.; Vetter, T. K.; Wells, S. R.

    2002-01-01

    This document is intended to provide the specifications and requirements for a flight control system design challenge. The response to the challenge will involve documenting whether the particular design has met the stated requirements through analysis and computer simulation. The response should be written in the general format of a technical publication with corresponding length limits, e.g., an approximate maximum length of 45 units, with each full-size figure and double-spaced typewritten page constituting one unit.

  11. The new productivity challenge.

    PubMed

    Drucker, P F

    1991-01-01

    "The single greatest challenge facing managers in the developed countries of the world is to raise the productivity of knowledge and service workers," writes Peter F. Drucker in "The New Productivity Challenge." Productivity, says Drucker, ultimately defeated Karl Marx; it gave common laborers the chance to earn the wages of skilled workers. Now five distinct steps will raise the productivity of knowledge and service workers--and not only stimulate new economic growth but also defuse rising social tensions. PMID:10114929

  12. Challenges in obesity research.

    PubMed

    Palou, Andreu; Bonet, M Luisa

    2013-09-01

    Obesity is the main nutritional problem and one of the most important health problems in developed societies. Central to the challenge of obesity prevention and management is a thoroughly understanding of its determinants. Multiple socio-cultural, socio-economic, behavioural and biological factors--often interrelated and many of them still unknown or poorly understood--can contribute to the establishment and perpetuation of obese phenotypes. Here, we address current research challenges regarding basic aspects of obesity and emerging science for its control, including brown adipose tissue thermogenesis and browning of white fat as possible therapeutic targets for obesity, the influence of the microbioma, and genetics, epigenetics, nutrigenomics and nutrigenetics of obesity. We also highlight hot topics in relation to food and lifestyle as determinants of obesity, including the brain mechanisms underlying environmental motivation to eat, the biological control of spontaneous physical activity, the possible role of concrete foods and food components, and the importance of early life nutrition and environment. Challenges regarding the connections of obesity with other alterations and pathologies are also briefly addressed, as well as social and economical challenges in relation to healthy food production and lifestyle for the prevention of obesity, and technological challenges in obesity research and management. The objective is to give a panoramic of advances accomplished and still ahead relevant to the different stakeholders engaged in understanding and combating obesity. PMID:24010755

  13. Banff Challenge 2

    SciTech Connect

    Junk, Thomas R.; /Fermilab

    2011-08-01

    Experimental particle physics collaborations constantly seek newer and better ideas for improving the sensitivity of their searches for new particles and phenomena. Statistical techniques are the last step in interpreting the results of an experiment; they are used to make discoveries (hypothesis testing), and to measure parameters (point estimation). They are also used in the first step - experiment and analysis design. Banff Challenge 2 asks participants to test their methods of discovering hidden signals in simulated datasets and of measuring the properties of these signals. The Challenge problems are described, and the performances of the submitted entries is summarized, for datasets with and without simulated signals present.

  14. Challenges facing production grids

    SciTech Connect

    Pordes, Ruth; /Fermilab

    2007-06-01

    Today's global communities of users expect quality of service from distributed Grid systems equivalent to that their local data centers. This must be coupled to ubiquitous access to the ensemble of processing and storage resources across multiple Grid infrastructures. We are still facing significant challenges in meeting these expectations, especially in the underlying security, a sustainable and successful economic model, and smoothing the boundaries between administrative and technical domains. Using the Open Science Grid as an example, I examine the status and challenges of Grids operating in production today.

  15. HELIOS Technology Challenge, Part 2

    NASA Video Gallery

    The HELIOS Technology Challenge seeks to combine open source innovation, collaboration and partnership with makerspace and input from the general public to help NASA solve major technology challeng...

  16. HELIOS Technology Challenge, Part 5

    NASA Video Gallery

    The HELIOS Technology Challenge seeks to combine open source innovation, collaboration and partnership with makerspace and input from the general public to help NASA solve major technology challeng...

  17. HELIOS Technology Challenge, Part 3

    NASA Video Gallery

    The HELIOS Technology Challenge seeks to combine open source innovation, collaboration and partnership with makerspace and input from the general public to help NASA solve major technology challeng...

  18. HELIOS Technology Challenge, Part 1

    NASA Video Gallery

    The HELIOS Technology Challenge seeks to combine open source innovation, collaboration and partnership with makerspace and input from the general public to help NASA solve major technology challeng...

  19. HELIOS Technology Challenge, Part 4

    NASA Video Gallery

    The HELIOS Technology Challenge seeks to combine open source innovation, collaboration and partnership with makerspace and input from the general public to help NASA solve major technology challeng...

  20. 76 FR 56819 - Centennial Challenges 2012 Sample Return Robot Challenge

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-14

    ... SPACE ADMINISTRATION Centennial Challenges 2012 Sample Return Robot Challenge AGENCY: National... 42 U.S.C. 2451(314)(d). The 2012 Sample Return Robot Challenge is scheduled and teams that wish to... technologies of interest and value to NASA and the nation. The 2012 Sample Return Robot Challenge is a...

  1. 77 FR 70835 - Centennial Challenges 2013 Sample Return Robot Challenge

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-27

    ... SPACE ADMINISTRATION Centennial Challenges 2013 Sample Return Robot Challenge AGENCY: National... in accordance with 51 U.S.C. 20144(c). The 2013 Sample Return Robot Challenge is scheduled and teams... Robot Challenge is a prize competition designed to encourage development of new technologies...

  2. Toward Green Challenge Courses.

    ERIC Educational Resources Information Center

    Johnson, Karl E.

    1999-01-01

    Designing environmentally friendly challenge courses involves considering factors such as clearing, trees versus poles, soil erosion and compaction, toilet design, waste disposal, and carrying capacity. Strategies used in "green development" such as systems thinking, solution multipliers, and brainstorming with stakeholders could promote challenge…

  3. Elementary Design Challenges

    ERIC Educational Resources Information Center

    Gerlach, Jonathan W.

    2010-01-01

    How many of our students come to the classroom with little background knowledge about the world around them and how things work? To help students develop conceptual understanding and explore the design process, the author brought the NASA "Engineering Design Challenges" program to his school district, redeveloped for elementary students. In this…

  4. Challenges to LRS Materials.

    ERIC Educational Resources Information Center

    Austin Community Coll., TX.

    The Learning Resource Services (LRS) department at Austin Community College, in Texas, has developed a procedure for dealing with situations when a library user objects to items in a collection or display or protests that an item is not in the collection. First, three resources have been created to handle challenges. The LRS Materials Selection…

  5. The Wall Coverings Challenge

    ERIC Educational Resources Information Center

    Roman, Harry T.

    2012-01-01

    Students love nothing better than personalizing their space--desk, bedroom, or even their cars. This article describes a classroom challenge that gives students a chance to let their spirits soar with the invention of a new form of wall treatment. A trip to a big box store might prove to be most helpful for students to visualize their new product…

  6. Rooftop Garden Design Challenge

    ERIC Educational Resources Information Center

    Roman, Harry T.

    2010-01-01

    A small commercial building in a nearby industrial park has decided to install a rooftop garden for its employees to enjoy. The garden will be about 100 feet long and 75 feet wide. This article presents a design challenge for technology and engineering students wherein they will assist in the initial conceptual design of the rooftop garden. The…

  7. Curriculum Challenges in California.

    ERIC Educational Resources Information Center

    Adler, Louise

    1993-01-01

    This paper presents findings from a longitudinal study that examined the extent and types of challenges to curriculum in California school districts. A survey of school districts conducted in 1990 yielded 421 usable responses. The second survey, sent in 1991, elicited 379 responses, a 37.5 percent response rate. Findings indicate that the number…

  8. The Better Boat Challenge

    ERIC Educational Resources Information Center

    Schomburg, Aaron

    2008-01-01

    "On your mark, get set, go!" Elementary students love to hear these words as they participate in the annual Third Grade Better Boat Challenge. This highly motivational project started a few years ago as the author was developing the third-grade science curriculum to include a study that revolved around models, design, and problem solving. It has…

  9. Kayak Design Challenge

    ERIC Educational Resources Information Center

    Wood, Anson

    2011-01-01

    Living in the Adirondack Park and being an avid outdoorsman has often resulted in the author's love of the outdoors working its way into class projects. In 2010, the author gave a group of 25 students in grades 9-12 a challenge that required them to design and construct a prototype inexpensive, lightweight kayak for backpackers and fisherman. In…

  10. Meeting the Challenge

    ERIC Educational Resources Information Center

    Mathews, Jay

    2005-01-01

    The Challenge Index ranks high schools according to how many students take AP and IB exams, not on how well they do or how many pass. This index is published in Newsweek and the magazine calls it "America's Best High Schools." In this article, the author, also the creator of this index, answers some frequently asked questions about the index and…

  11. Symposium on Contemporary Challenges

    ERIC Educational Resources Information Center

    Berry, David A.; Graff, Gerald; Nelson, Cary

    2010-01-01

    In this article, the authors discuss contemporary challenges. David Berry offers advice on teaching the humanities at a community college; Gerald Graff examines how the traditional organization of universities undermines student learning; and Cary Nelson considers the effects on the humanities of the increasing reliance on contingent faculty.

  12. Challenge Beginning Teacher Beliefs

    ERIC Educational Resources Information Center

    Lannin, John K.; Chval, Kathryn B.

    2013-01-01

    As beginning teachers start to recognize the complexity of teaching mathematics in elementary school classrooms and how their new vision for teaching mathematics creates new challenges, they experience discomfort--a healthy awareness that much is to be learned. Brousseau (1997) notes that changes in the roles that are implicitly assigned to the…

  13. Challenges of the Presidency.

    ERIC Educational Resources Information Center

    McLean, Sandi, Ed.

    "Challenges of the Presidency" explores the circumstances and forces that affect the college president's leadership in identifying and accomplishing the educational mission of the institution. These four papers examine the external forces of government and population trends as well as the internal pressures from faculty and students, and offer…

  14. Leadership in Challenging Times

    ERIC Educational Resources Information Center

    City, Elizabeth A.

    2013-01-01

    In spite of tough financial times, resourceful school leaders devise ways to overcome challenges and improve education. To do this, they make strategic use of the resources they have. And they also cultivate learning communities. In this article, Elizabeth A. City describes how school leaders can make more strategic use of three essential…

  15. A Cool Challenge

    ERIC Educational Resources Information Center

    Roman, Harry T.

    2012-01-01

    The world of man-made design is all around, in everyday objects and appliances people use without a second thought. In this exercise, students have an opportunity to challenge the common refrigerator's design--and improve it. This approach can be used with many other appliances.

  16. Challenges for Visual Analytics

    SciTech Connect

    Thomas, James J.; Kielman, Joseph

    2009-09-23

    Visual analytics has seen unprecedented growth in its first five years of mainstream existence. Great progress has been made in a short time, yet great challenges must be met in the next decade to provide new technologies that will be widely accepted by societies throughout the world. This paper sets the stage for some of those challenges in an effort to provide the stimulus for the research, both basic and applied, to address and exceed the envisioned potential for visual analytics technologies. We start with a brief summary of the initial challenges, followed by a discussion of the initial driving domains and applications, as well as additional applications and domains that have been a part of recent rapid expansion of visual analytics usage. We look at the common characteristics of several tools illustrating emerging visual analytics technologies, and conclude with the top ten challenges for the field of study. We encourage feedback and collaborative participation by members of the research community, the wide array of user communities, and private industry.

  17. Challenges of Retrenchment.

    ERIC Educational Resources Information Center

    Mingle, James R.; And Others

    The retrenchment experiences of a variety of institutions--large and small, public and private--are described and evaluated using an extensive spectrum of case studies sponsored by the Southern Regional Education Board. Part One discusses challenges of retrenchment (James R. Mingle) and strategies for the 1980s (David W. Breneman). Part Two,…

  18. The Store Challenge

    ERIC Educational Resources Information Center

    Roman, Harry T.

    2014-01-01

    Biomedical and robotic technologies are merging to present a wonderful opportunity to develop artificial limbs and prosthetic devices for humans injured on the job, in the military, or due to disease. In this challenge, students will have the opportunity to design a store or online service that specifically dedicates itself to amputees. Described…

  19. Challenging Entropic Gravity

    NASA Astrophysics Data System (ADS)

    Roveto, Jonathan

    2011-11-01

    A recent proposal by Erik Verlinde claims that gravity should be viewed not as a fundamental force, but an emergent thermodynamic phenomenon due to some yet undetermined microscopic theory. We present a challenge to this reformulation of gravity. Our claim is that a detailed derivation using Verlinde's proposed theory fails to correctly give Newton's laws or Einstein gravity.

  20. The Challenge of Leadership.

    ERIC Educational Resources Information Center

    Young, Andrew

    1979-01-01

    The challenge is still before Black people to give the kind of moral leadership that would help this nation to see what it is that the poor are struggling with. Black people who become successful must not forget the sufferings of those who made it possible for them to get where they are today. (Author/WI)

  1. The Urban Challenge.

    ERIC Educational Resources Information Center

    Agron, Joe, Ed.

    1998-01-01

    Discusses the myriad of challenges facing urban schools and the problems their districts must struggle through in finding solutions. The severity of these problems, such as additional facility demand, school deterioration, increasing rates of school takeovers, and tight budgets are described. (GR)

  2. The Clay Challenge Continues...

    ERIC Educational Resources Information Center

    Coy, Mary

    2007-01-01

    It was time for yet another challenge. Bright colored glazes were on hiatus; earth tones and mixed media took center stage. Inspiration was provided this time by the myriad Native American potters from the desert Southwest. The project: create a coil pot that demonstrates interesting form and good artistry and reflects, through symbolism or mixed…

  3. MALL: The Pedagogical Challenges

    ERIC Educational Resources Information Center

    Burston, Jack

    2014-01-01

    In this paper the development of mobile-assisted language learning (MALL) over the past 20 years is reviewed with a particular focus on the pedagogical challenges facing its exploitation. Following a consideration of the definition of mobile learning, the paper describes the dominant mobile technologies upon which MALL applications have been…

  4. Electric Vehicle Battery Challenge

    ERIC Educational Resources Information Center

    Roman, Harry T.

    2014-01-01

    A serious drawback to electric vehicles [batteries only] is the idle time needed to recharge their batteries. In this challenge, students can develop ideas and concepts for battery change-out at automotive service stations. Such a capability would extend the range of electric vehicles.

  5. The Moon Challenge

    ERIC Educational Resources Information Center

    Fitzsimmons, Pat; Leddy, Diana; Johnson, Lindy; Biggam, Sue; Locke, Suzan

    2013-01-01

    This article describes a first-grade research project that incorporates trade books and challenges misconceptions. Educators see the power of their students' wonder at work in their classrooms on a daily basis. This wonder must be nourished by students' own experiences--observing the moon on a crystal clear night--as well as by having…

  6. Educational Challenges in Toxicology.

    ERIC Educational Resources Information Center

    Dixon, Robert L.

    1984-01-01

    Issues and topics related to educational challenges in toxicology at all levels are discussed. They include public awareness and understanding, general approach to toxicology, quality structure-activity relationships, epidemiological studies, quantification of risk, and the types of toxicants studied. (JN)

  7. Matriculation Project: Prerequisite Challenges.

    ERIC Educational Resources Information Center

    Demerjian, Marlene

    A study was undertaken at California's College of the Canyons to determine outcomes for students who challenged course prerequisites and enrolled in courses requiring placement levels higher than recommended between spring 1993 and fall 1994. Data were gathered from analyses of 529 placement/prerequisite waiver forms and transcripts from 445…

  8. The Dirty Water Challenge

    ERIC Educational Resources Information Center

    Walker, Mark; Kremer, Angelika; Schluter, Kirsten

    2007-01-01

    "The Dirty Water Challenge" is a fun activity that teaches children about their environment in an engaging and practical way. Inquiry is embedded within the practical--students have to design, plan, and then build their own design of water filter. Students are exposed to important concepts from a variety of scientific disciplines, including how…

  9. A Challenge to Watson

    ERIC Educational Resources Information Center

    Detterman, Douglas K.

    2011-01-01

    Watson's Jeopardy victory raises the question of the similarity of artificial intelligence and human intelligence. Those of us who study human intelligence issue a challenge to the artificial intelligence community. We will construct a unique battery of tests for any computer that would provide an actual IQ score for the computer. This is the same…

  10. Seven challenges for neuroscience.

    PubMed

    Markram, Henry

    2013-01-01

    Although twenty-first century neuroscience is a major scientific enterprise, advances in basic research have not yet translated into benefits for society. In this paper, I outline seven fundamental challenges that need to be overcome. First, neuroscience has to become "big science" - we need big teams with the resources and competences to tackle the big problems. Second, we need to create interlinked sets of data providing a complete picture of single areas of the brain at their different levels of organization with "rungs" linking the descriptions for humans and other species. Such "data ladders" will help us to meet the third challenge - the development of efficient predictive tools, enabling us to drastically increase the information we can extract from expensive experiments. The fourth challenge goes one step further: we have to develop novel hardware and software sufficiently powerful to simulate the brain. In the future, supercomputer-based brain simulation will enable us to make in silico manipulations and recordings, which are currently completely impossible in the lab. The fifth and sixth challenges are translational. On the one hand we need to develop new ways of classifying and simulating brain disease, leading to better diagnosis and more effective drug discovery. On the other, we have to exploit our knowledge to build new brain-inspired technologies, with potentially huge benefits for industry and for society. This leads to the seventh challenge. Neuroscience can indeed deliver huge benefits but we have to be aware of widespread social concern about our work. We need to recognize the fears that exist, lay them to rest, and actively build public support for neuroscience research. We have to set goals for ourselves that the public can recognize and share. And then we have to deliver on our promises. Only in this way, will we receive the support and funding we need. PMID:24139651

  11. Educational Challenges for Children with Cochlear Implants.

    ERIC Educational Resources Information Center

    Chute, Patricia M.; Nevins, Mary Ellen

    2003-01-01

    This article addresses educational challenges for children with severe to profound hearing loss who receive cochlear implants. Despite the implants, these children face acoustic challenges, academic challenges, attention challenges, associative challenges, and adjustment challenges. (Contains references.) (Author/DB)

  12. NASA Microclimate Cooling Challenges

    NASA Technical Reports Server (NTRS)

    Trevino, Luis A.

    2004-01-01

    The purpose of this outline form presentation is to present NASA's challenges in microclimate cooling as related to the spacesuit. An overview of spacesuit flight-rated personal cooling systems is presented, which includes a brief history of cooling systems from Gemini through Space Station missions. The roles of the liquid cooling garment, thermal environment extremes, the sublimator, multi-layer insulation, and helmet visor UV and solar coatings are reviewed. A second section is presented on advanced personal cooling systems studies, which include heat acquisition studies on cooling garments, heat rejection studies on water boiler & radiators, thermal storage studies, and insulation studies. Past and present research and development and challenges are summarized for the advanced studies.

  13. Challenges in sexual medicine.

    PubMed

    Cellek, Selim; Giraldi, Annamaria

    2012-09-01

    The sexual medicine field has been in mode of revolution until recently. Like all other fields of biomedical research, the economic situation around the world has had a negative impact on the field's momentum-research funding bodies, regulatory bodies and pharmaceutical companies seem to have placed sexual medicine in their low-priority list. But this is not the only challenge the field is facing. The successful development of phosphodiesterase type 5 (PDE5) inhibitors for treatment of erectile dysfunction (ED) means that research in this area seems to have slowed. However, there remain several unmet medical needs within sexual medicine such as premature ejaculation, severe ED and hypoactive sexual desire disorder, which await novel therapeutic approaches. Despite these challenges, research into finding and developing such therapies is likely to continue in the sexual medicine field, in an effort to improve the lives of our patients, who wait for effective therapies. PMID:22777290

  14. The Chinese healthcare challenge

    PubMed Central

    Fabre, Guilhem

    2015-01-01

    Investments in the extension of health insurance coverage, the strengthening of public health services, as well as primary care and better hospitals, highlights the emerging role of healthcare as part of China’s new growth regime, based on an expansion of services, and redistributive policies. Such investments, apart from their central role in terms of relief for low-income people, serve to rebalance the Chinese economy away from export-led growth toward the domestic market, particularly in megacity-regions as Shanghai and the Pearl River Delta, which confront the challenge of integrating migrant workers. Based on the paper by Gusmano and colleagues, one would expect improvements in population health for permanent residents of China’s cities. The challenge ahead, however, is how to address the growth of inequalities in income, wealth and the social wage. PMID:25774379

  15. Flying qualities research challenges

    NASA Technical Reports Server (NTRS)

    Sliwa, Steven M.; George, Frank L.

    1987-01-01

    Traditional flying qualities requirements for airplane dynamics are based on airplane modal response characteristics derived from linear small-perturbation analysis. These requirements are supported by a large experimental data base. The challenge to the flying qualities community is to demonstrate how flying qualities, the control system and aircraft configuration are still closely linked. This is evident in the definition of flying qualities and, as far as pilots are concerned, that flying qualities are still the measure of overall design success.

  16. Terabit Wireless Communication Challenges

    NASA Technical Reports Server (NTRS)

    Hwu, Shian U.

    2012-01-01

    This presentation briefly discusses a research effort on Terabit Wireless communication systems for possible space applications. Recently, terahertz (THz) technology (300-3000 GHz frequency) has attracted a great deal of interest from academia and industry. This is due to a number of interesting features of THz waves, including the nearly unlimited bandwidths available, and the non-ionizing radiation nature which does not damage human tissues and DNA with minimum health threat. Also, as millimeter-wave communication systems mature, the focus of research is, naturally, moving to the THz range. Many scientists regard THz as the last great frontier of the electromagnetic spectrum, but finding new applications outside the traditional niches of radio astronomy, Earth and planetary remote sensing, and molecular spectroscopy particularly in biomedical imaging and wireless communications has been relatively slow. Radiologists find this area of study so attractive because t-rays are non-ionizing, which suggests no harm is done to tissue or DNA. They also offer the possibility of performing spectroscopic measurements over a very wide frequency range, and can even capture signatures from liquids and solids. According to Shannon theory, the broad bandwidth of the THz frequency bands can be used for terabit-per-second (Tb/s) wireless communication systems. This enables several new applications, such as cell phones with 360 degrees autostereoscopic displays, optic-fiber replacement, and wireless Tb/s file transferring. Although THz technology could satisfy the demand for an extremely high data rate, a number of technical challenges need to be overcome before its development. This presentation provides an overview the state-of-the- art in THz wireless communication and the technical challenges for an emerging application in Terabit wireless systems. The main issue for THz wave propagation is the high atmospheric attenuation, which is dominated by water vapor absorption in the THz

  17. Nuclear Proliferation Challenges

    SciTech Connect

    Professor William Potter

    2005-11-28

    William C. Potter, Director of the Center for Non Proliferation Studies and the Center for Russian and Eurasian Studies at the Monterey Institute of International Studies, will present nuclear proliferation challenges following the 2005 Nuclear Non-Proliferation Treaty (NPT) Review Conference. In addition to elucidating reasons for, and implications of, the conference’s failure, Dr. Potter will discuss common ground between nuclear proliferation and terrorism issues and whether corrective action can be taken.

  18. Challenges for space medicine.

    PubMed

    Sri Kantha, S

    1994-03-01

    Since April 1961, when Yuri Gagarin first orbited the earth about 270 astronauts (predominantly males) have lived in space. More than 90 percent of these astronauts were natives of the USA and the ex-USSR. In this commentary, the challenges confronting the discipline of space medicine are reviewed. These include, (1) space sickness, (2) wasting of the musculoskeletal system and (3) developing a longterm life support system. PMID:7910785

  19. Challenges in Replicating Interventions

    PubMed Central

    Bell, Stephanie G; Newcomer, Susan F; Bachrach, Christine; Borawski, Elaine; Jemmott, John L; Morrison, Diane; Stanton, Bonita; Tortolero, Susan; Zimmerman, Richard

    2007-01-01

    Purpose This paper describes and reflects on an effort to document, through a set of six interventions, the process of adapting effective youth risk behavior interventions for new settings. It provides insights into how this might best be accomplished. It discusses six studies funded by NIH starting in 1999. The studies were funded in response to a Request for Applications [RFA] to replicate HIV prevention interventions for youth. Researchers were to select an HIV risk reduction intervention program shown to be effective in one adolescent population and to replicate it in a new community or different adolescent population. This was to be done while systematically documenting those processes and aspects of the intervention hypothesized to be critical to the development of community-based, culturally sensitive programs. The replication was to assess the variations necessary to gain cooperation, implement a locally feasible and meaningful intervention, and evaluate the outcomes in the new setting. Methods This paper lays out the rationale for this initiative and describes the goals and the approaches to adaptation of the funded researchers. Results The paper discusses issues relevant to all interventions, those unique to replication and to these replications in particular. It then reflects on the processes and the consequences of the adaptations. It does not address the further challenges in taking a successful intervention “to scale.” Conclusions Replications of effective interventions face all of the challenges of implementation design plus additional challenges of balancing fidelity to the original intervention and sensitivity to the needs of new populations. PMID:17531757

  20. Nanotechnology: Opportunities and Challenges

    NASA Technical Reports Server (NTRS)

    Meyyappan, Meyya

    2003-01-01

    Nanotechnology seeks to exploit novel physical, chemical, biological, mechanical, electrical, and other properties, which arise primarily due to the nanoscale nature of certain materials. A key example is carbon nanotubes (CNTs) which exhibit unique electrical and extraordinary mechanical properties and offer remarkable potential for revolutionary applications in electronics devices, computing, and data storage technology, sensors, composites, nanoelectromechanical systems (NEMS), and as tip in scanning probe microscopy (SPM) for imaging and nanolithography. Thus the CNT synthesis, characterization, and applications touch upon all disciplines of science and engineering. This presentation will provide an overview and progress report on this and other major research candidates in Nanotechnology and address opportunities and challenges ahead.

  1. The Global Energy Challenge

    ScienceCinema

    Crabtree, George

    2010-01-08

    The expected doubling of global energy demand by 2050 challenges our traditional patterns of energy production, distribution and use.   The continued use of fossil fuels raises concerns about supply, security, environment and climate.  New routes are needed for the efficient conversion of energy from chemical fuel, sunlight, and heat to electricity or hydrogen as an energy carrier and finally to end uses like transportation, lighting, and heating. Opportunities for efficient new energy conversion routes based on nanoscale materials will be presented, with emphasis on the sustainable energy technologies they enable.

  2. The Global Energy Challenge

    SciTech Connect

    Crabtree, George

    2007-09-12

    The expected doubling of global energy demand by 2050 challenges our traditional patterns of energy production, distribution and use.   The continued use of fossil fuels raises concerns about supply, security, environment and climate.  New routes are needed for the efficient conversion of energy from chemical fuel, sunlight, and heat to electricity or hydrogen as an energy carrier and finally to end uses like transportation, lighting, and heating. Opportunities for efficient new energy conversion routes based on nanoscale materials will be presented, with emphasis on the sustainable energy technologies they enable.

  3. Challenges of Physiome Projects

    NASA Astrophysics Data System (ADS)

    Nomura, Taishin

    The integration of knowledge from many disciplines and vast amount of biological data in the post-genome era together with mathematical and information sciences is moving the world towards a new generation of life science where physiological and pathological information from the living human body can be quantitatively described in silico across multiple scales of time and size and through diverse hierarchies of organization. The Physiome Project represents such emerging sciences. The challenge is to understand and quantitatively integrate not only structure and function of biological entities such as ion channel proteins and enzymes on a single spatio-temporal scale, but also functional relationships between entities across multiple scales. This integrative approach is in stark contrast to the linear approach of reductionist life science, and it will allow us to understand the mechanisms underlying biological functions that will emerge through the dynamics of each element and large aggregations of the elements. This article discusses several points of the challenge that are expected to be resolved through the Physiome Project.

  4. Challenge of biomechanics.

    PubMed

    Volokh, K Y

    2013-06-01

    The application of mechanics to biology--biomechanics--bears great challenges due to the intricacy of living things. Their dynamism, along with the complexity of their mechanical response (which in itself involves complex chemical, electrical, and thermal phenomena) makes it very difficult to correlate empirical data with theoretical models. This difficulty elevates the importance of useful biomechanical theories compared to other fields of engineering. Despite inherent imperfections of all theories, a well formulated theory is crucial in any field of science because it is the basis for interpreting observations. This is all-the-more vital, for instance, when diagnosing symptoms, or planning treatment to a disease. The notion of interpreting empirical data without theory is unscientific and unsound. This paper attempts to fortify the importance of biomechanics and invigorate research efforts for those engineers and mechanicians who are not yet involved in the field. It is not aimed here, however, to give an overview of biomechanics. Instead, three unsolved problems are formulated to challenge the readers. At the micro-scale, the problem of the structural organization and integrity of the living cell is presented. At the meso-scale, the enigma of fingerprint formation is discussed. At the macro-scale, the problem of predicting aneurysm ruptures is reviewed. It is aimed here to attract the attention of engineers and mechanicians to problems in biomechanics which, in the author's opinion, will dominate the development of engineering and mechanics in forthcoming years. PMID:24015479

  5. Aerodynamic challenges of ALT

    NASA Technical Reports Server (NTRS)

    Hooks, I.; Homan, D.; Romere, P. O.

    1985-01-01

    The approach and landing test (ALT) of the Space Shuttle Orbiter presented a number of unique challenges in the area of aerodynamics. The purpose of the ALT program was both to confirm the use of the Boeing 747 as a transport vehicle for ferrying the Orbiter across the country and to demonstrate the flight characteristics of the Orbiter in its approach and landing phase. Concerns for structural fatigue and performance dictated a tailcone be attached to the Orbiter for ferry and for the initial landing tests. The Orbiter with a tailcone attached presented additional challenges to the normal aft sting concept of wind tunnel testing. The landing tests required that the Orbiter be separated from the 747 at approximately 20,000 feet using aerodynamic forces to fly the vehicles apart. The concept required a complex test program to determine the relative effects of the two vehicles on each other. Also of concern, and tested, was the vortex wake created by the 747 and the means for the Orbiter to avoid it following separation.

  6. Continuing challenges in influenza

    PubMed Central

    Webster, Robert G.; Govorkova, Elena A.

    2014-01-01

    Influenza is an acute respiratory disease in mammals and domestic poultry that emerges from zoonotic reservoirs in aquatic birds and bats. Although influenza viruses are among the most intensively studied pathogens, existing control options require further improvement. Influenza vaccines must be regularly updated because of continuous antigenic drift and sporadic antigenic shifts in the viral surface glycoproteins. Currently, influenza therapeutics are limited to neuraminidase inhibitors; novel drugs and vaccine approaches are therefore urgently needed. Advances in vaccinology and structural analysis have revealed common antigenic epitopes on hemagglutinins across all influenza viruses and suggest that a universal influenza vaccine is possible. In addition, various immunomodulatory agents and signaling pathway inhibitors are undergoing preclinical development. Continuing challenges in influenza include the emergence of pandemic H1N1 influenza in 2009, human infections with avian H7N9 influenza in 2013, and sporadic human cases of highly pathogenic avian H5N1 influenza. Here, we review the challenges facing influenza scientists and veterinary and human public health officials; we also discuss the exciting possibility of achieving the ultimate goal of controlling influenza’s ability to change its antigenicity. PMID:24891213

  7. CTF Challenge: Result Summary

    PubMed Central

    Marabini, Roberto; Carragher, Bridget; Chen, Shaoxia; Chen, James; Cheng, Anchi; Downing, Kenneth H.; Frank, Joachim; Grassucci, Robert A.; Heymann, J. Bernard; Jiang, Wen; Jonic, Slavica; Liao, Hstau Y.; Ludtke, Steven J.; Patwari, Shail; Piotrowski, Angela L.; Quintana, Adrian; Sorzano, Carlos O.S.; Stahlberg, Henning; Vargas, Javier; Voss, Neil R.; Chiu, Wah; Carazo, Jose M.

    2015-01-01

    Image formation in bright field electron microscopy can be described with the help of the contrast transfer function (CTF). In this work the authors describe the “CTF Estimation Challenge”, called by the Madrid Instruct Image Processing Center (I2PC) in collaboration with the National Center for Macromolecular Imaging (NCMI) at Houston. Correcting for the effects of the CTF requires accurate knowledge of the CTF parameters, but these have often been difficult to determine. In this challenge, researchers have had the opportunity to test their ability in estimating some of the key parameters of the electron microscope CTF on a large micrograph data set produced by well-known laboratories on a wide set of experimental conditions. This work presents the first analysis of the results of the CTF Estimation Challenge, including an assessment of the performance of the different software packages under different conditions, so as to identify those areas of research where further developments would be desirable in order to achieve high-resolution structural information. PMID:25913484

  8. Managing the Fukushima Challenge

    PubMed Central

    Suzuki, Atsuyuki

    2014-01-01

    The Fukushima Daiichi accident raises a fundamental question: Can science and technology prevent the inevitability of serious accidents, especially those with low probabilities and high consequences? This question reminds us of a longstanding challenge with the trans-sciences, originally addressed by Alvin Weinberg well before the Three Mile Island and Chernobyl accidents. This article, revisiting Weinberg's issue, aims at gaining insights from the accident with a special emphasis on the sociotechnical or human behavioral aspects lying behind the accident's causes. In particular, an innovative method for managing the challenge is explored referring to behavioral science approaches to a decision-making process on risk management; such as managing human behavioral risks with information asymmetry, seeking a rational consensus with communicative action, and pursuing procedural rationality through interactions with the outer environment. In short, this article describes the emerging need for Japan to transform its national safety management institutions so that these might be based on interactive communication with parties inside and outside Japan. PMID:24954604

  9. Managing the Fukushima challenge.

    PubMed

    Suzuki, Atsuyuki

    2014-07-01

    The Fukushima Daiichi accident raises a fundamental question: Can science and technology prevent the inevitability of serious accidents, especially those with low probabilities and high consequences? This question reminds us of a longstanding challenge with the trans-sciences, originally addressed by Alvin Weinberg well before the Three Mile Island and Chernobyl accidents. This article, revisiting Weinberg's issue, aims at gaining insights from the accident with a special emphasis on the sociotechnical or human behavioral aspects lying behind the accident's causes. In particular, an innovative method for managing the challenge is explored referring to behavioral science approaches to a decision-making process on risk management; such as managing human behavioral risks with information asymmetry, seeking a rational consensus with communicative action, and pursuing procedural rationality through interactions with the outer environment. In short, this article describes the emerging need for Japan to transform its national safety management institutions so that these might be based on interactive communication with parties inside and outside Japan. PMID:24954604

  10. Pharmacogenomics: Challenges and Opportunities

    PubMed Central

    Roden, Dan M.; Altman, Russ B.; Benowitz, Neal L.; Flockhart, David A.; Giacomini, Kathleen M.; Johnson, Julie A.; Krauss, Ronald M.; McLeod, Howard L.; Ratain, Mark J.; Relling, Mary V.; Ring, Huijun Z.; Shuldiner, Alan R.; Weinshilboum, Richard M.; Weiss, Scott T.

    2016-01-01

    The outcome of drug therapy is often unpredictable, ranging from beneficial effects to lack of efficacy to serious adverse effects. Variations in single genes are 1 well-recognized cause of such unpredictability, defining the field of pharmacogenetics (see Glossary). Such variations may involve genes controlling drug metabolism, drug transport, disease susceptibility, or drug targets. The sequencing of the human genome and the cataloguing of variants across human genomes are the enabling resources for the nascent field of pharmacogenomics (see Glossary), which tests the idea that genomic variability underlies variability in drug responses. However, there are many challenges that must be overcome to apply rapidly accumulating genomic information to understand variable drug responses, including defining candidate genes and pathways; relating disease genes to drug response genes; precisely defining drug response phenotypes; and addressing analytic, ethical, and technological issues involved in generation and management of large drug response data sets. Overcoming these challenges holds the promise of improving new drug development and ultimately individualizing the selection of appropriate drugs and dosages for individual patients. PMID:17116919

  11. Challenges of Virtual School Leadership

    ERIC Educational Resources Information Center

    Richardson, Jayson W.; LaFrance, Jason; Beck, Dennis

    2015-01-01

    The purpose of this case study was to examine challenges faced by virtual school leaders in the United States. Through semistructured interviews, the researchers explored challenges faced by eighteen leaders of fully online or blended online programs. Analysis revealed six main challenges: funding, staff, accountability, time, parents, and…

  12. NASA Space Rocket Logistics Challenges

    NASA Technical Reports Server (NTRS)

    Bramon, Chris; Neeley, James R.; Jones, James V.; Watson, Michael D.; Inman, Sharon K.; Tuttle, Loraine

    2014-01-01

    The Space Launch System (SLS) is the new NASA heavy lift launch vehicle in development and is scheduled for its first mission in 2017. SLS has many of the same logistics challenges as any other large scale program. However, SLS also faces unique challenges. This presentation will address the SLS challenges, along with the analysis and decisions to mitigate the threats posed by each.

  13. The challenge of definition.

    PubMed

    Koop, C Everett

    1989-01-01

    Koop, Surgeon General of the United States, argues that the term "euthanasia," meaning "happy death," challenges the life-centered values of Western culture and heritage which hold each individual personally responsible for being a life-centered member of the human community. To reverse these values within the arena of medicine is to unleash the terror of a "euthanasian ethic" reminiscent of the state-sponsored euthanasia of Nazi Germany, which labeled millions of people "devoid of value." The terms "quality of life" and "withholding nutrition and fluids" are discussed within the context of the Baby Doe case of 1982, and the hypothetical case of "Granny Doe" is proposed as an illustration of the need to provide whatever medical treatment is indicated and to effectively manage pain during the remaining hours of life rather than hasten death with the overdose of a powerful painkiller. PMID:11650122

  14. LSST EPO Plans & Challenges

    NASA Astrophysics Data System (ADS)

    Jacoby, Suzanne

    2006-12-01

    Scheduled to see "first light" in 2013, the 8.4-meter LSST will be able to survey the entire visible sky every three nights with its three-billion pixel digital camera, probing the mysteries of Dark Matter and Dark Energy. LSST will open a movie-like window on objects that change or move on rapid timescales: exploding supernovae, potentially hazardous near-Earth asteroids as small as 100 meters, and distant Kuiper Belt Objects. The potential for education and outreach with the LSST is as far reaching as the telescope itself. All data are public and offered through an EPO program that actively engages the public in the universe. In this talk, we give a brief overview of the EPO Operations Plan for LSST, describe challenges known to the EPO team, and invite discussion.

  15. Challenges of Antibacterial Discovery

    PubMed Central

    Silver, Lynn L.

    2011-01-01

    Summary: The discovery of novel small-molecule antibacterial drugs has been stalled for many years. The purpose of this review is to underscore and illustrate those scientific problems unique to the discovery and optimization of novel antibacterial agents that have adversely affected the output of the effort. The major challenges fall into two areas: (i) proper target selection, particularly the necessity of pursuing molecular targets that are not prone to rapid resistance development, and (ii) improvement of chemical libraries to overcome limitations of diversity, especially that which is necessary to overcome barriers to bacterial entry and proclivity to be effluxed, especially in Gram-negative organisms. Failure to address these problems has led to a great deal of misdirected effort. PMID:21233508

  16. The Sustainable Energy Challenge

    NASA Astrophysics Data System (ADS)

    Crabtree, George

    2010-02-01

    The dependence on oil and fossil fuels for over 80% of our energy and the continued emission of carbon dioxide threatening stable climate are captured in a single term: sustainability. Although we generally agree that sustainability is valuable, there is less agreement on how much sustainability is necessary or desirable. In this talk, three criteria describing increasingly strict features of sustainability will be presented and applied to evaluate the alternatives to oil and carbon dioxide emission, such as tapping unused energy flows in sunlight and wind, producing electricity without carbon emissions from clean coal and high efficiency nuclear power plants, and replacing oil with biofuels or electricity. Implementing these more sustainable alternatives requires new materials of increasing complexity and functionality that control the transformation of energy between light, electrons and chemical bonds at the nanoscale. Challenges and opportunities for developing the complex materials and controlling the chemical changes that enable greater sustainability will be presented. )

  17. Multicore Programming Challenges

    NASA Astrophysics Data System (ADS)

    Perrone, Michael

    The computer industry is facing fundamental challenges that are driving a major change in the design of computer processors. Due to restrictions imposed by quantum physics, one historical path to higher computer processor performance - by increased clock frequency - has come to an end. Increasing clock frequency now leads to power consumption costs that are too high to justify. As a result, we have seen in recent years that the processor frequencies have peaked and are receding from their high point. At the same time, competitive market conditions are giving business advantage to those companies that can field new streaming applications, handle larger data sets, and update their models to market conditions faster. The desire for newer, faster and larger is driving continued demand for higher computer performance.

  18. CHALLENGE MEASUREMENTS FOR AUTHENTICATION

    SciTech Connect

    Pitts, W. Karl

    2009-10-07

    Authentication of systems with an information barrier that protects sensitive information is difficult; in particular, the information barrier can allow a hidden switch to be implemented by the system fabricator and operator. The hidden switch is the operator’s ability to subvert the measurement system and force it to produce a desired and false result. It is usually discussed in the context of an attribute measurement in which a faked item is presented in place of a real item regulated by an agreement, with the driving motivation being the ability to preserve a stock of valuable items. In simple terms, the hidden switch enables a shell game with assets, and the information barrier protects the switch. This presentation outlines challenge measurements that could be used to detect the implementation of a hidden switch and assist the authentication process.

  19. Challenges to academic psychiatry.

    PubMed

    Pardes, H; Pincus, H A

    1983-09-01

    Economic constraints, effects of retrenchments in federal health policy, and increased competition for resources are challenging all sectors of academic medicine. Departments of psychiatry are at particular risk during this era for reasons including the lack of a sound research and research training base in many psychiatry departments; the small number of students entering the field and implications therein for the availability of residency slots in psychiatry; and patterns of allocating resources within academic medical centers which, combined with biases in reimbursement policy toward cognitively based specialties, threaten the economic strength of psychiatric departments. A conceptual model based on marketing principles is proposed to aid in identifying and capitalizing on the unique strengths of the field. PMID:6412571

  20. Polyhydroxyalkanoates, challenges and opportunities.

    PubMed

    Wang, Ying; Yin, Jin; Chen, Guo-Qiang

    2014-12-01

    Microbial polyhydroxyalkanoates (PHA) have been developed as biodegradable plastics for the past many years. However, PHA still have only a very limited market. Because of the availability of large amount of shale gas, petroleum will not raise dramatically in price, this situation makes PHA less competitive compared with low cost petroleum based plastics. Therefore, two strategies have been adopted to meet this challenge: first, the development of a super PHA production strain combined with advanced fermentation processes to produce PHA at a low cost; second, the construction of functional PHA production strains with technology to control the precise structures of PHA molecules, this will allow the resulting PHA with high value added applications. The recent systems and synthetic biology approaches allow the above two strategies to be implemented. In the not so distant future, the new technology will allow PHA to be produced with a competitive price compared with petroleum-based plastics. PMID:24976377

  1. A specific nanomanufacturing challenge.

    PubMed

    Kelly, M J; Dean, M C

    2016-03-18

    For a science to become a technology, a certain level of control has to have been established over the way items are fabricated for manufacture and use. Here we first consider the challenge of making and using a LEGO(®) brick scaled down by a factor of 10(n) for n = 0-6 in each spatial dimension, i.e. from millimetres to nanometres. We consider both the manufacture and the subsequent properties of the nanobricks that pertain to their use in constructing and dismantling structures. As n increases, the ability to use fails first, to manufacture fails second and to fabricate fails last. Applied to the vast literature in nanoscience, this process emphasises the unmanufacturability of most nanoscale artefacts. PMID:26871372

  2. A specific nanomanufacturing challenge

    NASA Astrophysics Data System (ADS)

    Kelly, M. J.; Dean, M. C.

    2016-03-01

    For a science to become a technology, a certain level of control has to have been established over the way items are fabricated for manufacture and use. Here we first consider the challenge of making and using a LEGO® brick scaled down by a factor of 10 n for n = 0-6 in each spatial dimension, i.e. from millimetres to nanometres. We consider both the manufacture and the subsequent properties of the nanobricks that pertain to their use in constructing and dismantling structures. As n increases, the ability to use fails first, to manufacture fails second and to fabricate fails last. Applied to the vast literature in nanoscience, this process emphasises the unmanufacturability of most nanoscale artefacts.

  3. The EOSDIS software challenge

    NASA Astrophysics Data System (ADS)

    Jaworski, Allan

    1993-08-01

    The Earth Observing System (EOS) Data and Information System (EOSDIS) will serve as a major resource for the earth science community, supporting both command and control of complex instruments onboard the EOS spacecraft and the archiving, distribution, and analysis of data. The scale of EOSDIS and the volume of multidisciplinary research to be conducted using EOSDIS resources will produce unparalleled needs for technology transparency, data integration, and system interoperability. The scale of this effort far outscopes any previous scientific data system in its breadth or operational and performance needs. Modern hardware technology can meet the EOSDIS technical challenge. Multiprocessing speeds of many giga-flops are being realized by modern computers. Online storage disk, optical disk, and videocassette libraries with storage capacities of many terabytes are now commercially available. Radio frequency and fiber optics communications networks with gigabit rates are demonstrable today. It remains, of course, to perform the system engineering to establish the requirements, architectures, and designs that will implement the EOSDIS systems. Software technology, however, has not enjoyed the price/performance advances of hardware. Although we have learned to engineer hardware systems which have several orders of magnitude greater complexity and performance than those built in the 1960's, we have not made comparable progress in dramatically reducing the cost of software development. This lack of progress may significantly reduce our capabilities to achieve economically the types of highly interoperable, responsive, integraded, and productive environments which are needed by the earth science community. This paper describes some of the EOSDIS software requirements and current activities in the software community which are applicable to meeting the EOSDIS challenge. Some of these areas include intelligent user interfaces, software reuse libraries, and domain engineering

  4. 76 FR 41526 - Centennial Challenges 2011 Strong Tether Challenge

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-14

    ...This notice is issued in accordance with 42 U.S.C. 2451 (314)(d). The 2011 Strong Tether Challenge is scheduled and teams that wish to compete may register. Centennial Challenges is a program of prize competitions to stimulate innovation in technologies of interest and value to NASA and the nation. The 2011 Strong Tether Challenge is a prize competition designed to encourage development of......

  5. IAC Library: Some Challenges

    NASA Astrophysics Data System (ADS)

    Gomez, M.

    2010-10-01

    Since its beginnings in 1985, the IAC Library has evolved from a traditional library where the physical place and collections were essential, to a hybrid library where users can often get what they need without going to the library. In this paper, we present how the various changes due to information technology advances that occurred in the 1990s, followed by a series of works carried out from 2004 to 2008 at IAC, as well as several internal and external events or decisions, have led the IAC Library to face three new challenges. First, as the library building has been enlarged and new spaces are now available for users and for shelving, we have to decide what we should we do with the new spaces. How we can make them attractive for users at a time when users often don't need to visit the library to access the information they need? Second, as IAC will implement a new integrated information system, we have an opportunity to define how the library system will participate within the IAC global information system, bringing to this great project our knowledge of information management, essential to improve the actual processes. Third, as the Ministry has created a working group on access to electronic resources, with participation by seven affiliated research institutions, we have, as a member of this group, to define how to deal with the Ministry and the other centres to set a library policy that will benefit the IAC Library.

  6. Physician Challenges in 2015.

    PubMed

    Cascardo, Debra

    2015-01-01

    While the influx of new patients resulting from the ACA will increase the number of people receiving healthcare, the regulations associated with it will add to physicians' administrative duties, as will government regulations associated with HIPAA and Meaningful Use. Further stress will come from the demands of both payers and patients, requiring doctors to walk a fine line to protect themselves from litigation. Technology also will play an increasing role. The continuing move toward EHRs and the new ICD-10 coding standard will require investments in software, testing, and training staff, and may also require an investment in new computer hardware. Physicians and staff will have to teach patients how to use EHR portals and how to follow the record-keeping requirements of their insurance providers. The regulatory changes and increased costs of time and money associated with them may drive many physicians out of private practice and into hospital system-based team practices, which will face a greater challenge in recruiting and retaining top talent. Other physicians, in contrast, may continue to seek the independence of private practice; some of them may decide to stop accepting insurance because of their need for autonomy in their practices. Regardless of what decisions doctors choose to make within the changing nature of healthcare, it is important to keep abreast of the changes and develop a plan for dealing with them, in 2015 and beyond. PMID:26182706

  7. Challenges in organ transplantation.

    PubMed

    Beyar, Rafael

    2011-04-01

    Organ transplantation has progressed tremendously with improvements in surgical methods, organ preservation, and pharmaco-immunologic therapies and has become a critical pathway in the management of severe organ failure worldwide. The major sources of organs are deceased donors after brain death; however, a substantial number of organs come from live donations, and a significant number can also be obtained from non-heart-beating donors. Yet, despite progress in medical, pharmacologic, and surgical techniques, the shortage of organs is a worldwide problem that needs to be addressed internationally at the highest possible levels. This particular field involves medical ethics, religion, and society behavior and beliefs. Some of the critical ethical issues that require aggressive interference are organ trafficking, payments for organs, and the delicate balance in live donations between the benefit to the recipient and the possible harm to the donor and others. A major issue in organ transplantation is the definition of death and particularly brain death. Another major critical factor is the internal tendency of a specific society to donate organs. In the review below, we will discuss the various challenges that face organ donation worldwide, and particularly in Israel, and some proposed mechanisms to overcome this difficulty. PMID:23908807

  8. Challenges in Piaget's legacy.

    PubMed

    Bibace, Roger

    2013-03-01

    The publication of After Piaget (Martí and Rodríguez 2012) hopefully triggers a new effort to understand the richness of the efforts of that major psychologist of the 20th century. Piaget was consistently concerned with part/whole relationships throughout his life. He addressed this issue philosophically, epistemologically, and psychologically. Conceptually Piaget struggled with the issue of continuity/discontinuity in development and changed his mind about how to reconcile the discontinuities of stages with his concept of development. I also attribute his variability to the implications of his important work on perception, and to his willingness to get involved in widespread concrete applications of his approach to education including the education of children with special needs; his center for genetic epistemology, and his interest in psychoanalysis. Benefiting from all the authors of After Piaget, I want to point out that Piaget has identified many major issues that will continue to constitute challenges to psychology in this century. These include specifying terms such as 'development;' methodological issues such as sampling both quantitatively in one culture and across cultures; comprehensive inclusion of the psychological processes covered by introductory textbooks in psychology; and conceptual issues such as the relationships among all these parts within a whole. I make a distinction between an 'issue' and a 'problem'--problems have solutions; while issues refer to controversies in science generally as well as in psychology that have persisted for centuries. PMID:22733313

  9. Challenges in Astronomy Education

    NASA Astrophysics Data System (ADS)

    De Greve, Jean-Pierre

    2010-11-01

    Astronomy is an attractive subject for education. It deals with fascination of the unknown and the unreachable, yet is uses tools, concepts and insights from various fundamental sciences such as mathematics, physics, chemistry, biology. Because of this it can be well used for introducing sciences to young people and to raise their interest in further studies in that direction. It is also an interesting subject for teaching as its different aspects (observation techniques, theory, data sampling and analysis, modelling,?) offer various didactical approaches towards different levels of pupils, students and different backgrounds. And it gives great opportunities to teach and demonstrate the essence of scientific research, through tutorials and projects. In this paper we discuss some of the challenges education in general, and astronomy in particular, faces in the coming decades, given the major geophysical and technological changes that can be deducted from our present knowledge. This defines a general, but very important background in terms of educational needs at various levels, and in geographical distribution of future efforts of the astronomical community. Special emphasis will be given to creative approaches to teaching, to strategies that are successful (such as the use of tutorials with element from computer games), and to initiatives complementary to the regular educational system. The programs developed by the IAU will be briefly highlighted.

  10. [Geriatrics - an interdisciplinary challenge].

    PubMed

    Nau, Roland; Djukic, Marija; Wappler, Manfred

    2016-06-01

    The care of elderly patients will continue to challenge the healthcare system over the next decades. As a rule geriatric patients suffer from multimorbidities with complex disease patterns, and the ability to cope with everyday life is severely reduced. Treatment is provided by a multiprofessional geriatric team, and the primary goal is improvement of functional status, quality of life in the social environment and autonomy by employing a holistic approach. In Germany geriatric care is provided by physicians from various medical specialties (e.g. general practitioners, internists, neurologists and psychiatrists). In the training for the subspecialty clinical geriatrics, these specialties enjoy equal rights. Recent efforts to establish a qualification as physician for internal medicine and geriatrics have initiated a discussion to make the suitability for qualification as a geriatrician dependent on the medical specialty. Geriatric patients benefit from multidisciplinary cooperation. Neurologists possess great expertise in the treatment of patients with dementia, depression, delirium, consequences of degenerative spinal cord diseases and vertebral bone fractures, stroke, Parkinson's syndrome, epileptic seizures, vertigo and dizziness, neuropathies, lesions of peripheral nerves and in the multimodal therapy of pain. To function in a position of responsibility in a geriatric department, neurologists need skills in general internal medicine. These are acquired either on a geriatric ward or during specialization as a neurologist by full time secondment to large neurological or interdisciplinary intensive care units. PMID:27167886

  11. Orion: challenges and benefits

    NASA Astrophysics Data System (ADS)

    Phipps, Claude R.

    1998-09-01

    ORION is a practical proposal for removing the 150,000 pieces of manmade space debris in the 1- to 10-cm size range now orbiting the Earth below 1500 km altitude which threaten large space systems in low Earth orbit. It is based on using the thrust produced by pulsed laser ablation of a thin layer on the debris surface to drop its perigee sufficiently for reentry and burnup. Applied when the object is rising between about 45 and 15-degree zenith angle, the necessary (Delta) v is of order 100 m/s. A laser of 30 kW average power at 10-ns pulsewidth and a 6-m mirror with adaptive optics can clear near-Earth space of these debris in 2 years of operation. Technical challenges faced by such a system include: heavy demands on detection, tracking and adaptive optics arising from the tiny optical cross section of the smallest debris and the required pointing accuracy and steering rate, stimulated Raman conversion and nonlinear refraction of the laser beam in the atmosphere, uncertainty of momentum coupling coefficients (Cm) for some materials, and high-average-power laser development. It is crucial that the system we propose be developed under international aegis, to insure that its installation does not increase international tensions. It should be viewed as a single-pay lifetime insurance policy for the World's space assets whose premium is less than 1% of the protected asset value, an excellent rate for such contracts.

  12. Offshore production challenged

    SciTech Connect

    Franco, A.

    1983-10-01

    The capability to produce oil fields from under 20,000 ft of water or below the thick and treacherous Arctic icepack are 2 of the breakthroughs that have been brought about by a quietly emerging technology. A scan of announcements by designers, contractors, operators, and manufacturers reveals that substantial research and development efforts are being undertaken to ease the task of bringing to market the energy resources trapped under presently inaccessible locations. As a result, entirely new breeds of permanent or temporary drilling/production systems are evolving, some of which could be scaled down to face still another challenge: the economic exploitation of marginal offshore fields, whose meager reserves do not justify development by conventional means. New offshore systems described include the mobile Arctic drilling system, the mobile concrete island drilling system, the base and independent deck platform, the buoyant tower, the semiflex floating station, the tension leg platform, the big buoy floating cylinder, and the Sea Plex retrievable drilling/production system.

  13. Challenges in publication ethics.

    PubMed

    Barbour, V; Astaneh, B; Irfan, M

    2016-04-01

    skill. Finally, the editor needs to deal with the journal's ethical policy when examples of plagiarism, author disputes or other forms of misconduct are evident. Breaches of publication ethics are forms of scientific misconduct that can undermine science and challenge editors, many of whom have little formal training in this field. In this respect, the Committee on Publication Ethics (COPE), founded in 1997 as a voluntary body, has become a central player. COPE provides a discussion forum and advice as well as guidelines for scientific editors with the aim of finding practical ways to deal with forms of misconduct. The Annals is a member of COPE and follows its code of conduct for journal editors. (2) It is a privilege that the current chair of COPE, Dr Barbour, and her colleagues have written this final article in the medical publishing series about challenges in publication ethics. I hope you have found this series useful and enjoyed reading the range of articles we have published from many experts in their fields. JYOTI SHAH Commissioning Editor References 1. Sanders SA , Reinisch JM . Would you say you 'had sex' if…? JAMA 1999 ; 281 : 275 - 277 . 2. Committee on Publication Ethics . Code of Conduct and Best Practice Guidelines for Journal Editors . Harleston, UK : COPE ; 2011 . PMID:26985812

  14. The Repack Challenge

    NASA Astrophysics Data System (ADS)

    Kruse, Daniele Francesco

    2014-06-01

    Physics data stored in CERN tapes is quickly reaching the 100 PB milestone. Tape is an ever-changing technology that is still following Moore's law in terms of capacity. This means we can store every year more and more data in the same amount of tapes. However this doesn't come for free: the first obvious cost is the new higher capacity media. The second less known cost is related to moving the data from the old tapes to the new ones. This activity is what we call repack. Repack is vital for any large tape user: without it, one would have to buy more tape libraries and more floor space and, eventually, data on old non supported tapes would become unreadable and be lost forever. In this paper we describe the challenge of repacking 115 PB before LHC data taking starts in the beginning of 2015. This process will have to run concurrently with the existing experiment tape activities, and therefore needs to be as transparent as possible for users. Making sure that this works out seamlessly implies careful planning of the resources and the various policies for sharing them fairly and conveniently. To tackle this problem we need to fully exploit the speed and throughput of our modern tape drives. This involves proper dimensioning and configuration of the disk arrays and all the links between them and the tape servers, i.e the machines responsible for managing the tape drives. It is also equally important to provide tools to improve the efficiency with which we use our tape libraries. The new repack setup we deployed has on average increased tape drive throughput by 80%, allowing them to perform closer to their design specifications. This improvement in turn means a 48% decrease in the number of drives needed to achieve the required throughput to complete the full repack on time.

  15. Echidna: the engineering challenges

    NASA Astrophysics Data System (ADS)

    Brzeski, Jurek K.; Gillingham, Peter; Correll, David; Dawson, John; Moore, Anna M.; Muller, Rolf; Smedley, Scott; Smith, Greg A.

    2004-09-01

    The Anglo-Australian Observatory's (AAO's) FMOS-Echidna project is for the Fiber Multi-Object Spectroscopy system for the Subaru Telescope. It includes three parts: the 400-fiber positioning system, the focal plane imager (FPI) and the prime focus corrector. The Echidna positioner concept and the role of the AAO in the FMOS project have been described in previous SPIE proceedings. The many components for the system are now being manufactured, after prototype tests have demonstrated that the required performance will be achieved. In this paper, the techniques developed to overcome key mechanical and electronic engineering challenges for the positioner and the FPI are described. The major performance requirement is that all 400 science fiber cores and up to 14 guide fiber bundles are to be re-positioned to an accuracy of 10μm within 10 minutes. With the fast prime focus focal ratio, a close tolerance on the axial position of the fiber tips must also be held so efficiency does not suffer from de-focus. Positioning accuracy is controlled with the help of the FPI, which measures the positions of the fiber tips to an accuracy of a few μm and allows iterative positioning. Maintaining fiber tips sufficiently co-planar requires accurate control in the assembly of the several components that contribute to such errors. Assembly jigs have been developed and proven adequate for this purpose. Attaining high reliability in an assembly with many small components of disparate materials bonded together, including piezo ceramics, carbon fiber reinforced plastic, hardened steel, and electrical circuit boards, has entailed careful selection and application of cements and tightly controlled soldering for electrical connections.

  16. HEPEX - achievements and challenges!

    NASA Astrophysics Data System (ADS)

    Pappenberger, Florian; Ramos, Maria-Helena; Thielen, Jutta; Wood, Andy; Wang, Qj; Duan, Qingyun; Collischonn, Walter; Verkade, Jan; Voisin, Nathalie; Wetterhall, Fredrik; Vuillaume, Jean-Francois Emmanuel; Lucatero Villasenor, Diana; Cloke, Hannah L.; Schaake, John; van Andel, Schalk-Jan

    2014-05-01

    HEPEX is an international initiative bringing together hydrologists, meteorologists, researchers and end-users to develop advanced probabilistic hydrological forecast techniques for improved flood, drought and water management. HEPEX was launched in 2004 as an independent, cooperative international scientific activity. During the first meeting, the overarching goal was defined as: "to develop and test procedures to produce reliable hydrological ensemble forecasts, and to demonstrate their utility in decision making related to the water, environmental and emergency management sectors." The applications of hydrological ensemble predictions span across large spatio-temporal scales, ranging from short-term and localized predictions to global climate change and regional modeling. Within the HEPEX community, information is shared through its blog (www.hepex.org), meetings, testbeds and intercompaison experiments, as well as project reportings. Key questions of HEPEX are: * What adaptations are required for meteorological ensemble systems to be coupled with hydrological ensemble systems? * How should the existing hydrological ensemble prediction systems be modified to account for all sources of uncertainty within a forecast? * What is the best way for the user community to take advantage of ensemble forecasts and to make better decisions based on them? This year HEPEX celebrates its 10th year anniversary and this poster will present a review of the main operational and research achievements and challenges prepared by Hepex contributors on data assimilation, post-processing of hydrologic predictions, forecast verification, communication and use of probabilistic forecasts in decision-making. Additionally, we will present the most recent activities implemented by Hepex and illustrate how everyone can join the community and participate to the development of new approaches in hydrologic ensemble prediction.

  17. Challenges When Introducing Electronic Exam

    ERIC Educational Resources Information Center

    Kuikka, Matti; Kitola, Markus; Laakso, Mikko-Jussi

    2014-01-01

    Time pressures often necessitate the use of more efficient exam tools, such as electronic exams (e-exams), instead of traditional paper exams. However, teachers may face challenges when introducing e-exams in a higher education context. This paper describes what kinds of challenges teachers may face when introducing e-exams, based on experiences…

  18. Statistics Poster Challenge for Schools

    ERIC Educational Resources Information Center

    Payne, Brad; Freeman, Jenny; Stillman, Eleanor

    2013-01-01

    The analysis and interpretation of data are important life skills. A poster challenge for schoolchildren provides an innovative outlet for these skills and demonstrates their relevance to daily life. We discuss our Statistics Poster Challenge and the lessons we have learned.

  19. IT Challenges for Space Medicine

    NASA Technical Reports Server (NTRS)

    Johnson-Throop, Kathy

    2010-01-01

    This viewgraph presentation reviews the various Information Technology challenges for aerospace medicine. The contents include: 1) Space Medicine Activities; 2) Private Medical Information; 3) Lifetime Surveillance of Astronaut Health; 4) Mission Medical Support; 5) Data Repositories for Research; 6) Data Input and Output; 7) Finding Data/Information; 8) Summary of Challenges; and 9) Solutions and questions.

  20. A Window-Washing Challenge

    ERIC Educational Resources Information Center

    Roman, Harry T.

    2010-01-01

    Skyscrapers sure do have a lot of windows, and these windows are cleaned and checked regularly. All this takes time, money, and puts workers at potential risk. Might there be a better way to do it? In this article, the author discusses a window-washing challenge and describes how students can tackle this task, pick up the challenge, and creatively…

  1. Influenza Vaccines: Challenges and Solutions

    PubMed Central

    Houser, Katherine; Subbarao, Kanta

    2015-01-01

    Vaccination is the best method for the prevention and control of influenza. Vaccination can reduce illness and lessen severity of infection. This review focuses on how currently licensed influenza vaccines are generated in the U.S., why the biology of influenza poses vaccine challenges, and vaccine approaches on the horizon that address these challenges. PMID:25766291

  2. Changes & Challenges for Rural Schools.

    ERIC Educational Resources Information Center

    Blair, Leslie Asher, Ed.

    2001-01-01

    This theme issue of the newsletter SEDLetter contains articles about the challenges facing rural youth, communities, and schools, and the ways that rural schools are meeting those challenges. "When Rural Traditions Really Count" (Ullik Rouk) outlines the rural situation with regard to adolescent substance abuse, youth gangs, teen pregnancy,…

  3. Challenging High-Ability Students

    ERIC Educational Resources Information Center

    Scager, Karin; Akkerman, Sanne F.; Pilot, Albert; Wubbels, Theo

    2014-01-01

    The existing literature on indicators of an optimal learning environment for high-ability students frequently discusses the concept of challenge. It is, however, not clear what, precisely, constitutes appropriate challenge for these students. In this study, the authors examined an undergraduate honours course, Advanced Cell Biology, which has…

  4. Challenges Facing Group Work Online

    ERIC Educational Resources Information Center

    Chang, Bo; Kang, Haijun

    2016-01-01

    Online group work can be complicated because of its asynchronous characteristics and lack of physical presence, and its requirements for skills in handling technology, human relationships, and content-related tasks. This study focuses on the administrative, logistical and relationship-related challenges in online group work. Challenges in areas…

  5. Five Biggest Challenges for 2002.

    ERIC Educational Resources Information Center

    Ishizuka, Kathy; Minkel, Walter; St. Lifer, Evan

    2002-01-01

    Addresses five themes that represent school librarians' overriding challenges for the year 2002: gaining the respect of school administrators; making information literacy a higher priority; recruiting new librarians to meet the growing demand; dealing with fiscal uncertainty in a recession; and the challenge of accessing information in a filtered…

  6. Interior Design: Challenges and Solutions.

    ERIC Educational Resources Information Center

    School Planning and Management, 1999

    1999-01-01

    Presents solutions to architectural challenges in school interior design; these solutions made the indoor environments more conducive and attractive for learning. Addresses four challenges: making a long corridor look less like a tunnel; maintaining tradition and minimizing cost in a new athletic facility; designing a kindergarten that is secure…

  7. Comparative Education: Challenge and Response.

    ERIC Educational Resources Information Center

    Kelly, Gail P.; Altbach, Philip G.

    1986-01-01

    Examines research reported in major books and journals of comparative education since 1977, focusing on challenges to established research traditions and the field's responses. Highlights work directing attention to new subjects of inquiry and challenging the nation-state as the exclusive research framework, input-output models and dominant…

  8. Organizational leadership: meeting the challenge.

    PubMed

    Hart, A L

    1994-06-01

    Leadership can be learned. Knowledge of leadership theories can serve as basis for developing skills and techniques. Style, trait, and transformational leadership can be applied in both health care institutions and professional associations. Organizational leadership is challenging, but those challenges can help individual nurses grow in the leadership skills that will continue to be demanded in the ever changing healthcare arena. PMID:8075165

  9. Lifelong Learning in Challenging Times

    ERIC Educational Resources Information Center

    Thomson, Alastair

    2010-01-01

    In the wake of the general election, the new government--and the United Kingdom--face a range of pressing challenges. In this article, the author sets out what he believes to be the principal challenges and calls for action to create a learning society. The agenda set out would, if followed by the new government, pave the way to a genuine learning…

  10. Higher Education Marketing: A Challenge.

    ERIC Educational Resources Information Center

    Canterbury, Richard

    1999-01-01

    States that similarities between education and other services may not be sufficient to conclude that services marketing methods can be easily transferred to all markets in higher education. Article identifies and discusses why higher education marketing is a particular challenge. Suggests that understanding these challenges can help in making…

  11. Adaptive challenges in medical practices.

    PubMed

    Daiker, Barbara L

    2013-01-01

    The purpose of this qualitative grounded theory study was to describe the theoretical structures of the strategies used by medical practices to navigate adaptive challenges. The process of responding to adaptive challenges in five medical practices was studied using a grounded theory approach, collecting data from interviews with the organizations' leaders and managers. The leadership of these medical practices had successfully navigated adaptive challenges within two years of the study. The analysis revealed a model that describes the key elements in finding solutions to adaptive challenges. The model was named the Adaptation Solution Dynamic, which explains the elements of Rational Tools, Relationship Commitment, and Achievement Drive. The findings from the results of this study provide a theoretical basis for studying how leaders support identifying solutions to adaptive challenges. PMID:23866647

  12. Eight challenges in phylodynamic inference

    PubMed Central

    Frost, Simon D.W.; Pybus, Oliver G.; Gog, Julia R.; Viboud, Cecile; Bonhoeffer, Sebastian; Bedford, Trevor

    2015-01-01

    The field of phylodynamics, which attempts to enhance our understanding of infectious disease dynamics using pathogen phylogenies, has made great strides in the past decade. Basic epidemiological and evolutionary models are now well characterized with inferential frameworks in place. However, significant challenges remain in extending phylodynamic inference to more complex systems. These challenges include accounting for evolutionary complexities such as changing mutation rates, selection, reassortment, and recombination, as well as epidemiological complexities such as stochastic population dynamics, host population structure, and different patterns at the within-host and between-host scales. An additional challenge exists in making efficient inferences from an ever increasing corpus of sequence data. PMID:25843391

  13. Challenges in aerospace medicine education.

    PubMed

    Grenon, S Marlene; Saary, Joan

    2011-11-01

    Aerospace medicine training and research represents a dream for many and a challenge for most. In Canada, although some opportunities exist for the pursuit of education and research in the aerospace medicine field, they are limited despite the importance of this field for enabling safe human space exploration. In this commentary, we aim to identify some of the challenges facing individuals wishing to get involved in the field as well as the causal factors for these challenges. We also explore strategies to mitigate against these. PMID:22097645

  14. Nuclear Proliferation and Grand Challenges

    ScienceCinema

    McCarthy, Kathy

    2013-05-28

    Nuclear engineer Dr. Kathy McCarthy leads systems analysis. She talks about proliferation and the grand challenges of nuclear R&D. For more information about INL energy research, visit http://www.facebook.com/idahonationallaboratory.

  15. Challenge of COPD: Getting Tested

    MedlinePlus

    ... please turn JavaScript on. Feature: The Challenge of COPD Getting Tested Past Issues / Fall 2014 Table of Contents Getting Tested Everyone at risk for COPD who has cough, sputum production, or shortness of ...

  16. Nuclear Proliferation and Grand Challenges

    SciTech Connect

    McCarthy, Kathy

    2009-01-01

    Nuclear engineer Dr. Kathy McCarthy leads systems analysis. She talks about proliferation and the grand challenges of nuclear R&D. For more information about INL energy research, visit http://www.facebook.com/idahonationallaboratory.

  17. The Humpty-Dumpty Challenge.

    ERIC Educational Resources Information Center

    Chock, Jan S.

    1995-01-01

    Describes a twist on the egg-drop challenge activity for an 8th grade physical science unit. Students engage in active inquiry and explore the laws of physics, develop critical thinking skills, and practice problem-solving tasks. (NB)

  18. The Challenge of Clean Air

    ERIC Educational Resources Information Center

    Turner, John M.

    1974-01-01

    The country's first two-year education program in Air Pollution Technology trains students to work for industry or government. Although two to three jobs are available for each graduate, attracting interested students remains a challenge. (AJ)

  19. Reasons to Do Food Challenges

    MedlinePlus

    ... allergic reactions to tree nuts may outgrow their sensitivity. A carefully performed food challenge can safely document ... is drastically reduced. 4. Discover the degree of sensitivity. Discovering the degree of sensitivity is another reason ...

  20. International Collaboration: Promises and Challenges

    PubMed Central

    Widmer, R. Jay; Widmer, Jocelyn M.; Lerman, Amir

    2015-01-01

    We currently face a myriad of grand global challenges in fields such as poverty, the environment, education, science, and medicine. However, our current means of dealing with such challenges has fallen short, and ingenious solutions are required to overcome the inherent resistance to progress toward ameliorating such difficulties. Here, we highlight the promises and challenges of international collaboration in achieving success toward these trials. We note prior successes in fields such as education, medicine, science, and environmental issues made to date, yet at the same time we do note deficiencies and shortcomings in these efforts. Hence, the notion of international collaboration should be strengthened and encouraged by governments, non-profit organizations, and others moving forward using creative means to bring talented teams together to tackle these challenges across the globe. PMID:25973264

  1. Aircraft Emergencies: Challenge and Response

    NASA Technical Reports Server (NTRS)

    Burian, Barbara K.

    2010-01-01

    Emergency and abnormal situations in aviation present flight crews with a number of challenges. Checklists are essential tools that have been developed to assist them to meet these challenges. However, in order for checklists to be most effective in these situations they must be designed with the operational and situational demands of emergencies and abnormal conditions in mind as well as human performance capabilities and limitations under high stress and workload.

  2. Systems Challenges for Hypersonic Vehicles

    NASA Technical Reports Server (NTRS)

    Hunt, James L.; Laruelle, Gerard; Wagner, Alain

    1997-01-01

    This paper examines the system challenges posed by fully reusable hypersonic cruise airplanes and access to space vehicles. Hydrocarbon and hydrogen fueled airplanes are considered with cruise speeds of Mach 5 and 10, respectively. The access to space matrix is examined. Airbreathing and rocket powered, single- and two-stage vehicles are considered. Reference vehicle architectures are presented. Major systems/subsystems challenges are described. Advanced, enhancing systems concepts as well as common system technologies are discussed.

  3. Life Support Systems Microbial Challenges

    NASA Technical Reports Server (NTRS)

    Roman, Monserrate C.

    2009-01-01

    This viewgraph presentation reviews the current microbial challenges of environmental control and life support systems. The contents include: 1) Environmental Control and Life Support Systems (ECLSS) What is it?; 2) A Look Inside the International Space Station (ISS); 3) The Complexity of a Water Recycling System; 4) ISS Microbiology Acceptability Limits; 5) Overview of Current Microbial Challenges; 6) In a Perfect World What we Would like to Have; and 7) The Future.

  4. The Mock LISA Data Challenges: from Challenge 1B to Challenge 3

    NASA Astrophysics Data System (ADS)

    Babak, Stanislav; Baker, John G.; Benacquista, Matthew J.; Cornish, Neil J.; Crowder, Jeff; Larson, Shane L.; Plagnol, Eric; Porter, Edward K.; Vallisneri, Michele; Vecchio, Alberto; Data Challenge Task Force, The Mock LISA; Arnaud, Keith; Barack, Leor; Błaut, Arkadiusz; Cutler, Curt; Fairhurst, Stephen; Gair, Jonathan; Gong, Xuefei; Harry, Ian; Khurana, Deepak; Królak, Andrzej; Mandel, Ilya; Prix, Reinhard; Sathyaprakash, B. S.; Savov, Pavlin; Shang, Yu; Trias, Miquel; Veitch, John; Wang, Yan; Wen, Linqing; Whelan, John T.; Challenge-1B participants, the

    2008-09-01

    The Mock LISA Data Challenges are a programme to demonstrate and encourage the development of LISA data-analysis capabilities, tools and techniques. At the time of this workshop, three rounds of challenges had been completed, and the next was about to start. In this paper we provide a critical analysis of the entries to the latest completed round, Challenge 1B. The entries confirm the consolidation of a range of data-analysis techniques for galactic and massive-black-hole binaries, and they include the first convincing examples of detection and parameter estimation of extreme-mass-ratio inspiral sources. In this paper we also introduce the next round, Challenge 3. Its data sets feature more realistic waveform models (e.g., galactic binaries may now chirp, and massive-black-hole binaries may precess due to spin interactions), as well as new source classes (bursts from cosmic strings, isotropic stochastic backgrounds) and more complicated nonsymmetric instrument noise.

  5. 33 CFR 125.41 - Challenges.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... requested a hearing shall have two peremptory challenges, one challenge for the management member and one challenge for the labor member of the Hearing Board. Should the management member be so challenged, the person who made the challenge may elect to have the management member replaced by another...

  6. 33 CFR 125.41 - Challenges.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... requested a hearing shall have two peremptory challenges, one challenge for the management member and one challenge for the labor member of the Hearing Board. Should the management member be so challenged, the person who made the challenge may elect to have the management member replaced by another...

  7. 33 CFR 125.41 - Challenges.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... requested a hearing shall have two peremptory challenges, one challenge for the management member and one challenge for the labor member of the Hearing Board. Should the management member be so challenged, the person who made the challenge may elect to have the management member replaced by another...

  8. 33 CFR 125.41 - Challenges.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... requested a hearing shall have two peremptory challenges, one challenge for the management member and one challenge for the labor member of the Hearing Board. Should the management member be so challenged, the person who made the challenge may elect to have the management member replaced by another...

  9. 33 CFR 125.41 - Challenges.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... requested a hearing shall have two peremptory challenges, one challenge for the management member and one challenge for the labor member of the Hearing Board. Should the management member be so challenged, the person who made the challenge may elect to have the management member replaced by another...

  10. Stable isotope views on ecosystem function: challenging or challenged?

    PubMed Central

    Resco, Víctor; Querejeta, José I.; Ogle, Kiona; Voltas, Jordi; Sebastià, Maria-Teresa; Serrano-Ortiz, Penélope; Linares, Juan C.; Moreno-Gutiérrez, Cristina; Herrero, Asier; Carreira, José A.; Torres-Cañabate, Patricia; Valladares, Fernando

    2010-01-01

    Stable isotopes and their potential for detecting various and complex ecosystem processes are attracting an increasing number of scientists. Progress is challenging, particularly under global change scenarios, but some established views have been challenged. The IX meeting of the Spanish Association of Terrestrial Ecology (AAET, Úbeda, 18–22 October 2009) hosted a symposium on the ecology of stable isotopes where the linear mixing model approach of partitioning sinks and sources of carbon and water fluxes within an ecosystem was challenged, and new applications of stable isotopes for the study of plant interactions were evaluated. Discussion was also centred on the need for networks that monitor ecological processes using stable isotopes and key ideas for fostering future research with isotopes. PMID:20015858

  11. Dealing with the Biological Challenge

    NASA Astrophysics Data System (ADS)

    Schultz, Emeric

    1996-05-01

    The bio-technological revolution presents a real challenge to the chemical education community. This challenge is two-fold: 1) the necessity of teaching students the underlying chemical principles and other skills necessary for sucess in the expanding biotechnological workplace and 2) ensuring and enhancing respect from the biological community for the first two years of the chemistry curriculum. In the opinion of the author, we are not doing a particularly good job of meeting this challenge, although progress is being made. As the "doing" of chemistry becomes easier for biologists, there is the real danger that the knowledge of a significant portion of the underlying chemistry will increasingly be viewed as less valuable, and perhaps even superfluous. The three "Trojan Horses" are: synthetic, analytical, and "process" kits; instrumentation coupled with computer "interpretation"; and molecular modeling. The author believes that in order to address the biological challenge head on, we should give serious consideration to the following: 1) reversing the "learning arrow"; 2) embedding molecular and other modeling; 3) incorporating instrumental analysis and chemistry-by-kit. Reversing the learning arrow approaches the chemistry curriculum by starting with large biomolecules first and working toward smaller fundamental units. The author believes that this approach and a more proactive stance on establishing what is in the domain of chemistry is the means by which the biological challenge, spawned by the bio-technological revolution, can most forcefully be addressed.

  12. Ecological Challenges for Closed Systems

    NASA Astrophysics Data System (ADS)

    Nelson, Mark; Dempster, William; Allen, John P.

    2012-07-01

    Closed ecological systems are desirable for a number of purposes. In space life support systems, material closure allows precious life-supporting resources to be kept inside and recycled. Closure in small biospheric systems facilitates detailed measurement of global ecological processes and biogeochemical cycles. Closed testbeds facilitate research topics which require isolation from the outside (e.g. genetically modified organisms; radioisotopes) so their ecological interactions and fluxes can be studied separate from interactions with the outside environment. But to achieve and maintain closure entails solving complex ecological challenges. These challenges include being able to handle faster cycling rates and accentuated daily and seasonal fluxes of critical life elements such as carbon dioxide, oxygen, water, macro- and mico-nutrients. The problems of achieving sustainability in closed systems for life support include how to handle atmospheric dynamics including trace gases, producing a complete human diet and recycling nutrients and maintaining soil fertility, the sustaining of healthy air and water and preventing the loss of crucial elements from active circulation. In biospheric facilities the challenge is also to produce analogues to natural biomes and ecosystems, studying processes of self-organization and adaptation in systems that allow specification or determination of state variables and cycles which may be followed through all interactions from atmosphere to soils. Other challenges include the dynamics and genetics of small populations, the psychological challenges for small isolated human groups and measures and options which may be necessary to ensure long-term operation of closed ecological systems.

  13. 77 FR 72337 - Apps for Vehicles Challenge

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-05

    ... of Energy Efficiency and Renewable Energy Apps for Vehicles Challenge AGENCY: Office of Energy... Vehicles: improving safety and fuel efficiency through technology innovation''. DATES: See, 1. Key Challenge Dates & Deadlines in SUPPLEMENTARY INFORMATION. ADDRESSES: The Apps for Vehicles Challenge...

  14. Pediatric Sedation: A Global Challenge

    PubMed Central

    Gozal, David; Mason, Keira P.

    2010-01-01

    Pediatric sedation is a challenge which spans all continents and has grown to encompass specialties outside of anesthesia, radiology and emergency medicine. All sedatives are not universally available and local and national regulations often limit the sedation practice to specific agents and those with specific credentials. Some specialties have established certification and credentials for sedation delivery whereas most have not. Some of the relevant sedation guidelines and recommendations of specialty organizations worldwide will be explored. The challenge facing sedation care providers moving forward in the 21st century will be to determine how to apply the local, regional and national guidelines to the individual sedation practices. A greater challenge, perhaps impossible, will be to determine whether the sedation community can come together worldwide to develop standards, guidelines and recommendations for safe sedation practice. PMID:20981309

  15. Challenge problems for artificial intelligence

    SciTech Connect

    Selman, B.; Brooks, R.A.; Dean, T.

    1996-12-31

    AI textbooks and papers of ten discuss the big questions, such as {open_quotes}how to reason with uncertainty{close_quotes}, {open_quotes}how to reason efficiently{close_quotes}, or {open_quotes}how to improve performance through learning.{close_quotes} It is more difficult, however, to find descriptions of concrete problems or challenges that are still ambitious and interesting, yet not so open-ended. The goal of this panel is to formulate a set of such challenge problems for the field. Each panelist was asked to formulate one or more challenges. The emphasis is on problems for which there is a good chance that they will be resolved within the next five to ten years.

  16. Success of Breast Cancer Startup Challenge Inspires Second Challenge | Poster

    Cancer.gov

    By Thomas Stackhouse, Joseph Conrad, and Michele Newton, Contributing Writers, and Rosemarie Truman, Guest Writer Sixty-one teams have been accepted into, and are now competing in, the Neuro Startup Challenge, a new collaboration established by the National Institutes of Health (NIH) with The Center for Advancing Innovation (CAI) and Heritage Provider Network, Inc.

  17. Campus Challenge - Part 2: Benefits and Challenges of BACnet

    DOE PAGESBeta

    Masica, Ken

    2016-01-15

    Additional challenges of implementing a BACnet network in a large campus environment are explored in this article: providing BACnet campus connectivity, protecting BACnet network traffic, and controlling the resulting broadcast traffic. An example of BACnet implementation is also presented, unifying concepts presented in this and Part One of the article.

  18. The Challenge of Prejudice: Counsellors' Talk about Challenging Clients' Prejudices

    ERIC Educational Resources Information Center

    Spong, Sheila J.

    2012-01-01

    This paper considers the implications for training and practice of counsellors' responses to the notion of challenging clients' prejudices. It explores tensions in counselling discourse between social responsibility, responsibility to the client and responsibility for one's self as counsellor. Three focus groups of counsellors were asked whether a…

  19. Challenged

    ERIC Educational Resources Information Center

    Manzo, Kathleen Kennedy

    2006-01-01

    The work of librarians can be a lifeline to youths dealing with difficult personal issues, such as family strife, growing up, and sexuality. This paper presents an issue where school library books at Fayetteville High School are questioned because their books are too sexually explicit or mature for teenagers. In the midst of intense media coverage…

  20. The challenges of big data

    PubMed Central

    2016-01-01

    ABSTRACT The largely untapped potential of big data analytics is a feeding frenzy that has been fueled by the production of many next-generation-sequencing-based data sets that are seeking to answer long-held questions about the biology of human diseases. Although these approaches are likely to be a powerful means of revealing new biological insights, there are a number of substantial challenges that currently hamper efforts to harness the power of big data. This Editorial outlines several such challenges as a means of illustrating that the path to big data revelations is paved with perils that the scientific community must overcome to pursue this important quest. PMID:27147249

  1. New Challenges in Model Checking

    NASA Technical Reports Server (NTRS)

    Holzmann, Gerard J.; Joshi, Rajeev; Groce, Alex

    2006-01-01

    In the last 25 years, the notion of performing software verification with logic model checking techniques has evolved from intellectual curiosity to accepted technology with significant potential for broad practical application. In this paper we look back at the main steps in this evolution and illustrate how the challenges have changed over the years, as we sharpened our theories and tools. Next we discuss a typical challenge in software verification that we face today - and that perhaps we can look back on in another 25 years as having inspired the next logical step towards a broader integration of model checking into the software development process.

  2. Grand Challenges of Enterprise Integration

    SciTech Connect

    Brosey, W.D; Neal, R.E.; Marks, D.

    2001-04-01

    Enterprise Integration connects and combines people, processes, systems, and technologies to ensure that the right people and the right processes have the right information and the right resources at the right time. A consensus roadmap for Technologies for Enterprise Integration was created as part of an industry/government/academia partnership in the Integrated Manufacturing Technology Initiative (IMTI). Two of the grand challenges identified by the roadmapping effort will be addressed here--Customer Responsive Enterprises and Totally Connected Enterprises. Each of these challenges is briefly discussed as to the current state of industry and the future vision as developed in the roadmap.

  3. Challenger as seen from SPAS

    NASA Technical Reports Server (NTRS)

    1983-01-01

    Full view of Space Shuttle Orbiter Challenger in space, taken by the Space Pallet Satellite (SPAS). A heavily cloud-covered portion of the earth forms the backdrop for this scene of Challenger. Visible in the payload bay are the protective cradles for the Palapa-B and Telesat F communications satellites, the pallet for the NASA Office of Space and Terrestrial Applications (OSTA-2), the Remote Manipulator System (RMS) robot arm in the shape of the numeral seven and the KU- band antenna. A number of GetAway Special (GAS) canisters are also visible along the port side.

  4. The challenges of big data.

    PubMed

    Mardis, Elaine R

    2016-05-01

    The largely untapped potential of big data analytics is a feeding frenzy that has been fueled by the production of many next-generation-sequencing-based data sets that are seeking to answer long-held questions about the biology of human diseases. Although these approaches are likely to be a powerful means of revealing new biological insights, there are a number of substantial challenges that currently hamper efforts to harness the power of big data. This Editorial outlines several such challenges as a means of illustrating that the path to big data revelations is paved with perils that the scientific community must overcome to pursue this important quest. PMID:27147249

  5. Prospects and Challenges for Helioseismology

    NASA Astrophysics Data System (ADS)

    Toomre, J.; Thompson, M. J.

    2015-12-01

    Helioseismology has advanced considerably our knowledge of the interior of the Sun over the past three decades. Our understanding of the Sun's internal structure, its dynamics, rotation, convection and magnetism, have all been advanced. Yet there are challenges, areas where the results from helioseismology are tantalizing but inconclusive, and aspects where the interpretation of the data has still to be put on a firm footing. In this paper we shall focus on a number of those challenges and give our assessment of where progress needs to be made in the next decade.

  6. Facing Violence - A Global Challenge.

    PubMed

    Wenzel, Thomas; Kienzler, Hanna; Wollmann, Andreas

    2015-09-01

    Violence has been shown to be a global challenge resulting in long-lasting social, medical, and mental health sequelae. In this article, we focus on massive social violence, such as war and civil war. Social suffering and mental health problems related to violence as a global public health problem can be tackled only with a holistic approach that addresses the specific region, culture and group and the limited resources available in most countries. Research that can give a reliable assessment of complex long-term outcomes is still largely missing, and can be seen as a major and complex challenge for future study. PMID:26300037

  7. Inspection challenges -- pigs versus pipes

    SciTech Connect

    Holden, E.M.; Grimes, K.

    1996-12-31

    As the size of the international pipeline network grows, and systems age (by the year 2000, over 50% of US gas transmission pipelines will be over 40 years old), and as environmental pressures increase, the demand for inspection is ever more apparent. Pipeline operations` experience has revealed many new defects and new inspection problems, many of which have challenged in-line inspection technology and stimulated further developments. This paper describes what pipeline inspection needs to find, the available technology and some examples of the inspection challenges.

  8. Conclusion: challenges for the future

    PubMed Central

    North, D. Warner

    1993-01-01

    The title “Challenges for the Future” implies the challenge to summarize a very complex meeting. Of necessity, I will present a personal impression. My interest is in risk assessment, which I define as a process for summarizing science in support of decision making. Risk assessment is sometimes regarded as arcane numerology, a rigid process of computing risk numbers in which much available science is unused. I am a strong advocate for the broader definition of risk assessment. It is encouraging to learn how much science is becoming available for use in risk assessment for gasoline, its components, and alternative fuels. PMID:17539103

  9. Conclusion: challenges for the future.

    PubMed

    North, D W

    1993-12-01

    The title "Challenges for the Future" implies the challenge to summarize a very complex meeting. Of necessity, I will present a personal impression. My interest is in risk assessment, which I define as a process for summarizing science in support of decision making. Risk assessment is sometimes regarded as arcane numerology, a rigid process of computing risk numbers in which much available science is unused. I am a strong advocate for the broader definition of risk assessment. It is encouraging to learn how much science is becoming available for use in risk assessment for gasoline, its components, and alternative fuels. PMID:17539103

  10. The Mock LISA Data Challenges: from challenge 3 to challenge 4

    NASA Astrophysics Data System (ADS)

    Babak, Stanislav; Baker, John G.; Benacquista, Matthew J.; Cornish, Neil J.; Larson, Shane L.; Mandel, Ilya; McWilliams, Sean T.; Petiteau, Antoine; Porter, Edward K.; Robinson, Emma L.; Vallisneri, Michele; Vecchio, Alberto; Data Challenge Task Force, the Mock LISA; Adams, Matt; Arnaud, Keith A.; Błaut, Arkadiusz; Bridges, Michael; Cohen, Michael; Cutler, Curt; Feroz, Farhan; Gair, Jonathan R.; Graff, Philip; Hobson, Mike; Shapiro Key, Joey; Królak, Andrzej; Lasenby, Anthony; Prix, Reinhard; Shang, Yu; Trias, Miquel; Veitch, John; Whelan, John T.; participants, the Challenge 3

    2010-04-01

    The Mock LISA Data Challenges are a program to demonstrate LISA data-analysis capabilities and to encourage their development. Each round of challenges consists of one or more datasets containing simulated instrument noise and gravitational waves from sources of undisclosed parameters. Participants analyze the datasets and report best-fit solutions for the source parameters. Here we present the results of the third challenge, issued in April 2008, which demonstrated the positive recovery of signals from chirping galactic binaries, from spinning supermassive-black-hole binaries (with optimal SNRs between ~10 and 2000), from simultaneous extreme-mass-ratio inspirals (SNRs of 10-50), from cosmic-string-cusp bursts (SNRs of 10-100), and from a relatively loud isotropic background with Ωgw(f) ~ 10-11, slightly below the LISA instrument noise.

  11. Hypertonic saline in the treatment of corneal jellyfish stings.

    PubMed

    Yu Yao, Hsin; Cho, Ta Hsiung; Lu, Ching Hsiang; Lin, Feng Chi; Horng, Chi Ting

    2016-02-01

    A 20-year-old male soldier was hit by the jellyfish. The ophthalmic examination revealed that epithelial keratitis and corneal oedema in the right eye. We prescribed 3% NaCl eyedrops and 0.3% Norfloxacin eyedrops in the treatment of the corneal jellyfish stings. Two weeks later, the cornea in the right eye healed. In this case report, 3% NaCl eyedrops was effective in the treatment of acute phase of jellyfish stings of the cornea. PMID:26883926

  12. Laminar flow: Challenge and potential

    NASA Technical Reports Server (NTRS)

    Kirchner, Mark E.

    1987-01-01

    Commercial air transportation has experienced revolutionary technology advances since WWII. These technology advances have resulted in an explosive growth in passenger traffic. Today, however, many technologies have matured, and maintaining a similar growth rate will be a challenge. A brief history of laminar flow technology and its application to subsonic and supersonic air transportation is presented.

  13. The Electric Power Exhibit Challenge

    ERIC Educational Resources Information Center

    Roman, Harry T.

    2012-01-01

    A design challenge is all about planning first and understanding the problem before diving in and looking frantically for a solution. Any experienced engineer or designer will tell one to think first and plan the steps before acting. An experienced carpenter friend of the author always said to "take many measurements and cut once." There is great…

  14. President's Challenge. Spotlight: Physical Development.

    ERIC Educational Resources Information Center

    Montessori Life, 2000

    2000-01-01

    Describes the President's Challenge, a program of fitness testing for 6- to 17-year-olds from the President's Council on Physical Fitness and Sports. Identifies requirements for the Presidential Physical Fitness Award for exercises and running, by age level and sex. Includes information on the validity of the award standards. (KB)

  15. Vocational Psychology and New Challenges

    ERIC Educational Resources Information Center

    Metz, A. J.; Guichard, Jean

    2009-01-01

    A discussion group composed of vocational psychologists, guidance professionals, and career development specialists from around the world identified and discussed new challenges in understanding work and providing relevant career services. Four major themes emerged: What revisions are necessary in the profession's theory and practice to address…

  16. A Water-Service Challenge

    ERIC Educational Resources Information Center

    Roman, Harry T.

    2011-01-01

    It is important to let students see the value of mathematics in design--and how mathematics lends perspective to problem solving. In this article, the author describes a water-service challenge which enables students to design a water utility system that uses surface runoff into an open reservoir as the potable water source. This challenge…

  17. The Real Challenge of ESD

    ERIC Educational Resources Information Center

    Jackson, M. G.

    2011-01-01

    Between the Inter-governmental Conference on Environmental Education at Tbilisi in 1977 and the Fourth International Conference on Environmental Education at Ahmedabad in 2007, our conception of the challenge posed by the global crises of climate change, environmental destruction, social disintegration, poverty, natural resources exhaustion and…

  18. The Challenge of New Science

    ERIC Educational Resources Information Center

    Rowland, Gordon

    2007-01-01

    A wide range of developments in science in recent years has altered our views of our world and ourselves in significant ways. These views challenge the direction of applied science and technology in many fields, including those associated with learning and performance in organizations. At the same time, they open up opportunities and…

  19. Training Information Consumers: Today's Challenge.

    ERIC Educational Resources Information Center

    Gordon, Dena W.

    The revolution in the information environment caused by new technology is making the training of information consumers a major challenge for publishers of business-targeted databases and vendors of online systems. Research conducted by Data Courier in 1981 and 1982 suggests that online searching by information consumers will continue to increase.…

  20. eHealth Recruitment Challenges

    ERIC Educational Resources Information Center

    Thompson, Debbe; Canada, Ashanti; Bhatt, Riddhi; Davis, Jennifer; Plesko, Lisa; Baranowski, Tom; Cullen, Karen; Zakeri, Issa

    2006-01-01

    Little is known about effective eHealth recruitment methods. This paper presents recruitment challenges associated with enrolling African-American girls aged 8-10 years in an eHealth obesity prevention program, their effect on the recruitment plan, and potential implications for eHealth research. Although the initial recruitment strategy was…

  1. New challenges in computational biochemistry

    SciTech Connect

    Honig, B.

    1996-12-31

    The new challenges in computational biochemistry to which the title refers include the prediction of the relative binding free energy of different substrates to the same protein, conformational sampling, and other examples of theoretical predictions matching known protein structure and behavior.

  2. The Challenge of Urban Policy

    ERIC Educational Resources Information Center

    Glaeser, Edward L.

    2012-01-01

    Urbanization almost invariably accompanies development, and the cities of India and China are experiencing spectacular increases in population. The concentration of millions of people in a small mass creates challenges for public policy, especially in the areas of basic infrastructure, public health, traffic congestion, and often law enforcement…

  3. The Challenges of Digital Leadership

    ERIC Educational Resources Information Center

    McLeod, Scott

    2015-01-01

    Because digital devices and online environments can simultaneously be transformatively empowering and maddeningly disruptive, the work of integrating digital learning tools into schools is usually difficult and complex. Common challenges arise, however, and can be thoughtfully addressed by proactive leadership. In the end, technology change in…

  4. Kids Camping Takes the Challenge.

    ERIC Educational Resources Information Center

    James, Vickie L.; Hohnbaum, Claudia

    2002-01-01

    A Wisconsin Girl Scout camp integrated The Healthy Kids Challenge into its program. The camp evaluated policies related to meals, snacks, physical activities, team building, and self-esteem. Staff inservice training resulted in healthier meals on the same budget and developed ownership of the program. Campers and families had opportunities to…

  5. Engineering Encounters: The Tightrope Challenge

    ERIC Educational Resources Information Center

    Burton, Bill

    2014-01-01

    In order to prepare students to become the next innovators, teachers need to provide real-world challenges that allow children to exercise their innovation muscles. Innovation starts with a problem and innovators work to solve a problem by planning, creating, and testing. The real-world innovation process does not happen on a worksheet, and it…

  6. Beyond the Family Geography Challenge.

    ERIC Educational Resources Information Center

    Keeler, Christy

    1997-01-01

    Describes a school-community program based on and extending the efforts of the Michigan Model Family Geography Challenge. The program includes inviting community members to participate in hands-on activities, as well as, shared activities between parents and students followed by dinner and socializing. Discusses materials, assessment, and…

  7. Challenging Sexual Harassment on Campus

    ERIC Educational Resources Information Center

    Baker, Nancy V.

    2010-01-01

    More than thirty years ago, an administrative assistant at Cornell University first challenged her university's indifference to her boss's sexually predatory behavior. While she did not prevail, her case sparked a movement. Litigation, news stories, and government guidelines defining sexual harassment followed. And universities responded: policies…

  8. The Speeding Car Design Challenge

    ERIC Educational Resources Information Center

    Roman, Harry T.

    2009-01-01

    All too often, one reads about high-speed police chases in pursuit of stolen cars that result in death and injury to people and innocent bystanders. Isn't there another way to accomplish the apprehension of the thieves that does not put people at such great risk? This article presents a classroom challenge to use technology to remotely shutdown…

  9. Digital Libraries: The Grand Challenges.

    ERIC Educational Resources Information Center

    Garrett, John R.

    1993-01-01

    Describes the technical, economic, social, and cultural challenges to building a national digital library system. Selecting and filtering information, building and scaling distributed digital library networks, invoicing, payment, authorizing access, the locus of planning leadership, and the information poor are discussed. (Contains three…

  10. Teaching OOA: Issues and Challenges.

    ERIC Educational Resources Information Center

    Sim, Edward

    This paper presents the argument that object oriented analysis (OOA) is rapidly becoming an important systems analysis methodology and that current systems analysis and design courses should present OOA. However, because of the embryonic nature and rapidly changing content of OOA, instructors are faced with special challenges when designing OOA…

  11. Challenging Behaviours: Prevalence and Topographies

    ERIC Educational Resources Information Center

    Lowe, K.; Allen, D.; Jones, E.; Brophy, S.; Moore, K.; James, W.

    2007-01-01

    Background: Variations in reported prevalence of challenging behaviour indicate the need for further epidemiological research to support accurate planning of future service provision. Methods: All services providing for people with learning disabilities across seven unitary authorities, with a total population of 1.2 million, were screened to…

  12. Schools that Like a Challenge

    ERIC Educational Resources Information Center

    Hamilton, Joan; Johnston, Sheryl; Marshall, Jane; Shields, Carolyn

    2006-01-01

    Four dissimilar schools each respond to a learning challenge by questioning set-in-stone thinking and taking risks. A K-8 school in Toronto bypasses the traditional--and problematic--long summer vacation to follow a balanced calendar model. Students attend school year-round with two-week breaks scattered throughout the year; both remedial and…

  13. eHealth recruitment challenges

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Little is known about effective eHealth recruitment methods. This paper presents recruitment challenges associated with enrolling African-American girls aged 8-10 years in an eHealth obesity prevention program, their effect on the recruitment plan, and potential implications for eHealth research. Al...

  14. Meeting the Challenges of Inclusion

    ERIC Educational Resources Information Center

    Hills, Joanne

    2011-01-01

    Managing practical science activities effectively is demanding for any teacher and especially so for inexperienced practitioners. Add the problems posed by integrating children with learning and behavioural difficulties and one has the sort of challenge that makes working in education rewarding--but not easy! As a newly qualified teacher, the…

  15. ARPA-E LITECAR Challenge

    SciTech Connect

    Liu, Ping; Salvi, Ashwin

    2015-04-20

    With more than 250 conceptual designs submitted, we are pleased to highlight the winners of the LIghtweighting Technologies Enabling Comprehensive Automotive Redesign (LITECAR) Challenge. These innovative conceptual designs seek to lightweight a vehicle while maintaining or exceeding current U.S. automotive safety standards.

  16. Monitoring challenges and innovative ideas

    SciTech Connect

    O'Neill, R.V.; Hunsaker, C.T.; Levine, D.A.

    1990-01-01

    Monitoring programs are difficult to design even when they focus on specific problems. Ecosystems are complex, and it is often impossible to predetermine what aspects of system structure or dynamics will respond to a specific insult. It is equally difficult to interpret whether a response is a stabilizing compensatory mechanism or a real loss of capacity to maintain the ecosystem. The problems are compounded in a broad monitoring program designed to assess ecosystem health'' at regional and continental scales. It is challenging in the extreme to monitor ecosystem response, at any scale, to past insults as well as an unknown future array of impacts. The present paper will examine some of the fundamental issues and challenges raised by large-scale monitoring efforts. The challenges will serve as a framework and as an excuse to discuss several important topics in more detail. Following the discussion of challenges, we suggest some basic innovations that could be important across a range of monitoring programs. The innovations include integrative measures, innovative methodology, and creative interpretation. 59 refs., 1 tab.

  17. THE CHALLENGE OF CURRICULAR CHANGE.

    ERIC Educational Resources Information Center

    SCHWILCK, GENE L.; AND OTHERS

    THIS DOCUMENT IS A COLLECTION OF FIFTEEN PAPERS PRESENTED AT THE COLLOQUIUM ON THE CHALLENGE OF CURRICULAR CHANGE. BROADER TOPICS DISCUSSED INCLUDE--(1) THE EXTENT AND CHARACTERISTICS OF CURRICULAR CHANGE IN SECONDARY SCHOOLS, (2) THE RESPONSES OF COLLEGES TO THESE CHANGES, THE BARRIERS TO CHANGE IN THE COLLEGES, AND SOME CURRENT EXPERIMENTS WHICH…

  18. The Professional Challenges for Counselors.

    ERIC Educational Resources Information Center

    Garfield, Nancy J.; And Others

    This document consists of the fourth section of a book written to educate and inform those in the helping professions on how to deal with Acquired Immune Deficiency Syndrome (AIDS). The three chapters in section 4 are devoted to special issues for counselors, issues that directly affect the caregiver. They examine professional challenges to…

  19. Fostering Reflection through Challenging Practica

    ERIC Educational Resources Information Center

    Nickel, Jodi; Sutherby, Linda; Garrow-Oliver, Susan

    2010-01-01

    This article describes challenging practicum situations that provided three early childhood education students with leadership opportunities to promote best practices in child care centers. Using excerpts from student journals and meetings, the article documents students' initial discouragement at practices observed, inspiration through…

  20. Sustaining Leadership in Challenging Times

    ERIC Educational Resources Information Center

    Middlehurst, Robin

    2010-01-01

    Some governments hit by recession have chosen to invest in higher education as part of long-term economic and social development and international competitiveness agendas; others have opted for a route of cuts, financial stringency and contraction of their higher education systems. This article explores challenges to leadership in the latter…

  1. Climate Change: Meeting the Challenge

    ERIC Educational Resources Information Center

    Chance, Paul; Heward, William L.

    2010-01-01

    In "Climate Change: Meeting the Challenge," we conclude the special section by assuming that you have been persuaded by Thompson's paper or other evidence that global warming is real and poses a threat that must be dealt with, and that for now the only way to deal with it is by changing behavior. Then we ask what you, as behavior analysts, can do…

  2. The Concrete and Pavement Challenge

    ERIC Educational Resources Information Center

    Roman, Harry T.

    2012-01-01

    The modern world is characterized by the extensive use of concrete and asphalt pavement. Periodically, these materials are replaced and the old materials disposed of. In this challenge, students will be asked to develop ways to reuse the old materials. It is important for students to understand how concrete and asphalt are made and applied, as…

  3. The Challenge of Institutionalizing Technology.

    ERIC Educational Resources Information Center

    Anandam, Kamala

    In order to meet the challenge of institutionalizing technology, community college educators must first define their needs; second, delineate the physical, social, and cultural conditions that affect the environment; and third, examine the knowledge made available through the computer and its paraphernalia. Institutionalizing technology requires:…

  4. Novice Teachers: Meeting the Challenge

    ERIC Educational Resources Information Center

    Martin, Patricia

    2008-01-01

    Seasoned principals know that when veteran teachers are replaced by large numbers of teachers new to the profession, student achievement levels are threatened. The influx of new teachers, coupled with consistently high rate of teacher attrition, creates challenges for principals who have the responsibility of bringing new teachers up the…

  5. Kinesiology: Challenges of Multiple Agendas

    ERIC Educational Resources Information Center

    Newell, Karl M.

    2007-01-01

    This paper addresses the challenge of how the field of kinesiology can exploit the advantages of multiple agendas while minimizing the disadvantages. Agendas here are the scholarly themes that help organize the field of study explicitly or implicitly and that give emphases to it with respect to its content and impact in society. The issue of…

  6. Space tubes: A major challenge

    NASA Technical Reports Server (NTRS)

    Kosmahl, H.

    1982-01-01

    The application of the TWT - the backbone of all civilian and military space communication programs - to past, present and future satellites is discussed. Performance characteristics and the trends and challenges in the future are reviewed. Finally, a comparison with Solid States devices, as derived from fundamental laws, is made and limitations discussed.

  7. NASA Space Rocket Logistics Challenges

    NASA Technical Reports Server (NTRS)

    Neeley, James R.; Jones, James V.; Watson, Michael D.; Bramon, Christopher J.; Inman, Sharon K.; Tuttle, Loraine

    2014-01-01

    The Space Launch System (SLS) is the new NASA heavy lift launch vehicle and is scheduled for its first mission in 2017. The goal of the first mission, which will be uncrewed, is to demonstrate the integrated system performance of the SLS rocket and spacecraft before a crewed flight in 2021. SLS has many of the same logistics challenges as any other large scale program. Common logistics concerns for SLS include integration of discreet programs geographically separated, multiple prime contractors with distinct and different goals, schedule pressures and funding constraints. However, SLS also faces unique challenges. The new program is a confluence of new hardware and heritage, with heritage hardware constituting seventy-five percent of the program. This unique approach to design makes logistics concerns such as commonality especially problematic. Additionally, a very low manifest rate of one flight every four years makes logistics comparatively expensive. That, along with the SLS architecture being developed using a block upgrade evolutionary approach, exacerbates long-range planning for supportability considerations. These common and unique logistics challenges must be clearly identified and tackled to allow SLS to have a successful program. This paper will address the common and unique challenges facing the SLS programs, along with the analysis and decisions the NASA Logistics engineers are making to mitigate the threats posed by each.

  8. DAPcentrism: Challenging Developmentally Appropriate Practice.

    ERIC Educational Resources Information Center

    Fleer, Marilyn, Ed.

    This book examines the implications of existing learning theories for early childhood education, with a special emphasis on Developmentally Appropriate Practice (DAP). Chapter 1, "Challenging Developmentally Appropriate Practice: An Introduction (Marilyn Fleer), presents the debate and summarizes the remaining chapters. Chapter 2, "Does Cognition…

  9. Academic Challenge Program: Evaluation Report.

    ERIC Educational Resources Information Center

    Harty, Harold; And Others

    The evaluation report by Bartholomew Consolidated School Corporation (Columbus, Indiana) describes findings concerning what works and what does not work in the Academic Challenge Program, a gifted and talented education program at the elementary and middle school levels. A corollary purpose of the report is to share the evaluation plan itself,…

  10. Challenges for cancer vaccine development.

    PubMed

    Tabi, Z; Man, S

    2006-10-01

    The first generation of human cancer vaccines has been tested in phase III clinical trials, but only a few of these have demonstrated sufficient efficacy to be licensed for clinical use. This article reviews some of the mechanisms that could contribute to these limited clinical responses, and highlights the challenges faced for development of future vaccines. PMID:16979786

  11. Developmental Audits with Challenging Youth

    ERIC Educational Resources Information Center

    Brendtro, Larry K.; du Toit, Lesley; Bath, Howard; Van Bockern, Steve

    2006-01-01

    The Developmental Audit[R] is a new strength-based assessment model for youth who are in conflict in home, school, or community. Developmental Audits involve collaboration with young persons who are seen as experts on themselves. Discussing challenging life events provides a window to the young person's private logic and goals. The audit scans…

  12. Information Technology: Opportunities and Challenges.

    ERIC Educational Resources Information Center

    Wang, Chih

    This article begins with an introduction to recent developments in information technology, including investment activities related to the technology in Europe, Japan, and the United States. It then deals with the challenging issues of access to electronic information of the U.S. government, fee or free for electronic information in publicly…

  13. Human Challenges in Exploration Missions

    NASA Technical Reports Server (NTRS)

    Lloyd, Charles W.

    2007-01-01

    This viewgraph presents an overview using pictures some of the history of human exploration of the new frontiers of Earth and then examines some of the challenges to human exploration of space. Particular attention is given to the environmental factors and to the social and human factors that effect humans in space environments.

  14. The Health and Fitness Challenge.

    ERIC Educational Resources Information Center

    Snelling, Anastasia M.

    1999-01-01

    "Health and Fitness Challenge" program was implemented using the "social marketing model" to raise awareness of health education and related services to students. Collaboration between faculty, student affairs professionals, and students occurred from design through evaluation. The primary goal of bringing students, faculty and staff together was…

  15. Success of Breast Cancer Startup Challenge Inspires Second Challenge | Poster

    Cancer.gov

    By Thomas Stackhouse, Joseph Conrad, and Michele Newton, Contributing Writers, and Rosemarie Truman, Guest Writer Sixty-one teams have been accepted into, and are now competing in, the Neuro Startup Challenge, a new collaboration established by the National Institutes of Health (NIH) with The Center for Advancing Innovation (CAI) and Heritage Provider Network, Inc.

  16. An All-School Library Challenge

    ERIC Educational Resources Information Center

    Quirk, Connie

    2005-01-01

    The library media center is hosting an all-school team challenge, designed to celebrate reading and library skills. Students could choose from the contest categories like "Lord of the Rings", "Harry Potter", Author Facts Challenge and Opening Lines Challenge for the competition and those students who read more challenging books show their…

  17. Terahertz applications: trends and challenges

    NASA Astrophysics Data System (ADS)

    Robin, Thierry; Bouye, Clementine; Cochard, Jacques

    2014-03-01

    The objective of our work [1] was to determine the opportunities and challenges for Terahertz application development for the next years with a focus on systems: for homeland security and for Non Destructive Testing (NDT). Terahertz radiation has unique abilities and has been the subject of extensive research for many years. Proven concepts have emerged for numerous applications including Industrial NDT, Security, Health, Telecommunications, etc. Nevertheless, there has been no widely deployed application and Businesses based on THz technologies are still in their infancy. Some technological, market and industrial barriers are still to be broken. We summarize the final analysis and data: study of the technology trends and major bottlenecks per application segment, main challenges to be addressed in the next years, key opportunities for THz technologies based on market needs and requirements.

  18. Addressing Global Data Sharing Challenges.

    PubMed

    Alter, George C; Vardigan, Mary

    2015-07-01

    This issue of the Journal of Empirical Research on Human Research Ethics highlights the ethical issues that arise when researchers conducting projects in low- and middle-income countries seek to share the data they produce. Although sharing data is considered a best practice, the barriers to doing so are considerable and there is a need for guidance and examples. To that end, the authors of this article reviewed the articles in this special issue to identify challenges common to the five countries and to offer some practical advice to assist researchers in navigating this "uncharted territory," as some termed it. Concerns around informed consent, data management, data dissemination, and validation of research contributions were cited frequently as particularly challenging areas, so the authors focused on these four topics with the goal of providing specific resources to consult as well as examples of successful projects attempting to solve many of the problems raised. PMID:26297753

  19. Challenges for Success in Startups

    NASA Astrophysics Data System (ADS)

    Spitzer, Richard

    2000-03-01

    The basic challenges to a startup company such as IME have stemmed from the need to balance the business world's goal of fast entry into the market place with the necessity for a solid foundation in technology. Our technology base is broad - indeed it has the makings of a new industry - and the lure of quick commercial success in a specific application could easily make IME vulnerable to the R&D might of giant international companies. The essential challenges for success play out in business/technology decision tradeoffs: (i) preserving equity and viability while keeping R&D momentum and establishing intellectual property, (ii) attracting investors while maintaining focus on long-range goals, and (iii) developing a complete team while protecting capital resources. This balancing act keeps the company agile and resilient, qualities that large corporations could emulate with profit.

  20. Grand challenges for biological engineering

    PubMed Central

    Yoon, Jeong-Yeol; Riley, Mark R

    2009-01-01

    Biological engineering will play a significant role in solving many of the world's problems in medicine, agriculture, and the environment. Recently the U.S. National Academy of Engineering (NAE) released a document "Grand Challenges in Engineering," covering broad realms of human concern from sustainability, health, vulnerability and the joy of living. Biological engineers, having tools and techniques at the interface between living and non-living entities, will play a prominent role in forging a better future. The 2010 Institute of Biological Engineering (IBE) conference in Cambridge, MA, USA will address, in part, the roles of biological engineering in solving the challenges presented by the NAE. This letter presents a brief outline of how biological engineers are working to solve these large scale and integrated problems of our society. PMID:19772647

  1. Smart textiles: Challenges and opportunities

    NASA Astrophysics Data System (ADS)

    Cherenack, Kunigunde; van Pieterson, Liesbeth

    2012-11-01

    Smart textiles research represents a new model for generating creative and novel solutions for integrating electronics into unusual environments and will result in new discoveries that push the boundaries of science forward. A key driver for smart textiles research is the fact that both textile and electronics fabrication processes are capable of functionalizing large-area surfaces at very high speeds. In this article we review the history of smart textiles development, introducing the main trends and technological challenges faced in this field. Then, we identify key challenges that are the focus of ongoing research. We then proceed to discuss fundamentals of smart textiles: textile fabrication methods and textile interconnect lines, textile sensor, and output device components and integration of commercial components into textile architectures. Next we discuss representative smart textile systems and finally provide our outlook over the field and a prediction for the future.

  2. The Higgs Machine Learning Challenge

    NASA Astrophysics Data System (ADS)

    Adam-Bourdarios, C.; Cowan, G.; Germain-Renaud, C.; Guyon, I.; Kégl, B.; Rousseau, D.

    2015-12-01

    The Higgs Machine Learning Challenge was an open data analysis competition that took place between May and September 2014. Samples of simulated data from the ATLAS Experiment at the LHC corresponding to signal events with Higgs bosons decaying to τ+τ- together with background events were made available to the public through the website of the data science organization Kaggle (kaggle.com). Participants attempted to identify the search region in a space of 30 kinematic variables that would maximize the expected discovery significance of the signal process. One of the primary goals of the Challenge was to promote communication of new ideas between the Machine Learning (ML) and HEP communities. In this regard it was a resounding success, with almost 2,000 participants from HEP, ML and other areas. The process of understanding and integrating the new ideas, particularly from ML into HEP, is currently underway.

  3. Challenges of Space Mission Interoperability

    NASA Technical Reports Server (NTRS)

    Martin, Warren L.; Hooke, Adrian J.

    2007-01-01

    This viewgraph presentation reviews some of the international challenges to space mission interoperability. Interoperability is the technical capability of two or more systems or components to exchange information and to use the information that has been exchanged. One of the challenges that is addressed is the problem of spectrum bandwidth, and interference. The key to interoperability is the standardization of space communications services and protocols. Various levels of international cross support are reviewed: harmony, cooperation cross support and confederation cross support. The various international bodies charged with implementing cross support are reviewed. The goal of the Interagency Operations Advisory Group (IOAG) is to achieve plug-and-play operations where all that is required is for each of the systems to use an agreed communications medium, after which the systems configure each other for the purpose of exchanging information and subsequently effect such exchange automatically.

  4. Addressing Global Data Sharing Challenges

    PubMed Central

    Alter, George C.

    2015-01-01

    This issue of the Journal of Empirical Research on Human Research Ethics highlights the ethical issues that arise when researchers conducting projects in low- and middle-income countries seek to share the data they produce. Although sharing data is considered a best practice, the barriers to doing so are considerable and there is a need for guidance and examples. To that end, the authors of this article reviewed the articles in this special issue to identify challenges common to the five countries and to offer some practical advice to assist researchers in navigating this “uncharted territory,” as some termed it. Concerns around informed consent, data management, data dissemination, and validation of research contributions were cited frequently as particularly challenging areas, so the authors focused on these four topics with the goal of providing specific resources to consult as well as examples of successful projects attempting to solve many of the problems raised. PMID:26297753

  5. Chip Scale Package Implementation Challenges

    NASA Technical Reports Server (NTRS)

    Ghaffarian, Reza

    1998-01-01

    The JPL-led MicrotypeBGA Consortium of enterprises representing government agencies and private companies have jointed together to pool in-kind resources for developing the quality and reliability of chip scale packages (CSPs) for a variety of projects. In the process of building the Consortium CSP test vehicles, many challenges were identified regarding various aspects of technology implementation. This paper will present our experience in the areas of technology implementation challenges, including design and building both standard and microvia boards, and assembly of two types of test vehicles. We also discuss the most current package isothermal aging to 2,000 hours at 100 C and 125 C and thermal cycling test results to 1,700 cycles in the range of -30 to 100 C.

  6. Heparin Characterization: Challenges and Solutions

    NASA Astrophysics Data System (ADS)

    Jones, Christopher J.; Beni, Szabolcs; Limtiaco, John F. K.; Langeslay, Derek J.; Larive, Cynthia K.

    2011-07-01

    Although heparin is an important and widely prescribed pharmaceutical anticoagulant, its high degree of sequence microheterogeneity and size polydispersity make molecular-level characterization challenging. Unlike nucleic acids and proteins that are biosynthesized through template-driven assembly processes, heparin and the related glycosaminoglycan heparan sulfate are actively remodeled during biosynthesis through a series of enzymatic reactions that lead to variable levels of O- and N-sulfonation and uronic acid epimers. As summarized in this review, heparin sequence information is determined through a bottom-up approach that relies on depolymerization reactions, size- and charge-based separations, and sensitive mass spectrometric and nuclear magnetic resonance experiments to determine the structural identity of component oligosaccharides. The structure-elucidation process, along with its challenges and opportunities for future analytical improvements, is reviewed and illustrated for a heparin-derived hexasaccharide.

  7. Overcoming challenges in improvement work.

    PubMed

    Crisp, Helen

    2013-09-01

    The Health Foundation is an independent charity working to improve healthcare in the UK, so that we have a system of the highest possible quality-safe, effective, person-centred, timely, efficient and equitable. We believe that in order to achieve this, health services need to continually improve the way they work. The Foundation conducts research and evaluation, puts ideas into practice through improvement programmes, develops leaders and shares evidence to drive wider change. The work is a focused around two priority areas: patient safety and person-centred care. The Foundation has supported work to improve services for patients with kidney disease and, in common with other quality improvement projects, there have been challenges to overcome. Awareness of these common challenges can help others to be more prepared when planning service improvements. PMID:23941702

  8. Challenges of Human Space Flight

    NASA Technical Reports Server (NTRS)

    Davis, Jeffrey R.; Charles, John B.

    2006-01-01

    The presentations will be given during the X-Prize symposium, exploring the multi-faceted dimensions of spaceflight ranging from the technical developments necessary to achieve safe routine flight to and from and through space to the new personal business opportunities and economic benefits that will open in space and here on Earth. The symposium will delve into the technical, regulatory, market and financial needs and challenges that must be met in charting and executing the incremental developments leading to Personal Spaceflight and the opening of a Place Called Space. The presentation covers facets of human space flight including descriptions of life in space, the challenges of delivering medical care in space, and the preparations needed for safe and productive human travel to the moon and Mars.

  9. The challenge of unconventional superconductivity.

    SciTech Connect

    Norman, M. R.

    2011-04-08

    During the past few decades, several new classes of superconductors have been discovered that do not appear to be related to traditional superconductors. The source of the superconductivity of these materials is likely different from the electron-ion interactions that are at the heart of conventional superconductivity. Developing a rigorous theory for any of these classes of materials has proven to be a difficult challenge and will remain one of the major problems in physics in the decades to come.

  10. Challenges to sustainable risk management

    SciTech Connect

    Pinto, Ariel C., Aurora, Ashish, Hall, Dennis E.,

    2004-08-09

    This paper summarizes the intermediate lessons learned from the analyses of the risk management problems in three technological endeavors. These problems are: the absence of a structure for rewarding successful project risk management; the need for an ever-more accurate economic measure of risk; and the difficulty of transferring risks to contract-bound independent outsourcing entity. This paper also describes recent advancement towards providing answers to these challenges and future research endeavors in this field.

  11. New vaccines: challenges of discovery.

    PubMed

    Mahmoud, Adel

    2016-09-01

    Vaccines have been a major component of preventing and controlling infectious diseases. The basis for discovery of what protects is reviewed as well as new attempts in utilizing Reverse Vaccinology, RNA-RNA methods and proteome analysis are adding significantly to our knowledge. The challenge of how to define protective and defined components of microbes is still hampering efforts to discover new vaccines. Recent excitement about immunotherapy of cancer opens the way to develop vaccines against multiple malignancies. PMID:27534704

  12. Challenges of Big Data Analysis.

    PubMed

    Fan, Jianqing; Han, Fang; Liu, Han

    2014-06-01

    Big Data bring new opportunities to modern society and challenges to data scientists. On one hand, Big Data hold great promises for discovering subtle population patterns and heterogeneities that are not possible with small-scale data. On the other hand, the massive sample size and high dimensionality of Big Data introduce unique computational and statistical challenges, including scalability and storage bottleneck, noise accumulation, spurious correlation, incidental endogeneity, and measurement errors. These challenges are distinguished and require new computational and statistical paradigm. This article gives overviews on the salient features of Big Data and how these features impact on paradigm change on statistical and computational methods as well as computing architectures. We also provide various new perspectives on the Big Data analysis and computation. In particular, we emphasize on the viability of the sparsest solution in high-confidence set and point out that exogeneous assumptions in most statistical methods for Big Data can not be validated due to incidental endogeneity. They can lead to wrong statistical inferences and consequently wrong scientific conclusions. PMID:25419469

  13. Challenges of Big Data Analysis

    PubMed Central

    Fan, Jianqing; Han, Fang; Liu, Han

    2014-01-01

    Big Data bring new opportunities to modern society and challenges to data scientists. On one hand, Big Data hold great promises for discovering subtle population patterns and heterogeneities that are not possible with small-scale data. On the other hand, the massive sample size and high dimensionality of Big Data introduce unique computational and statistical challenges, including scalability and storage bottleneck, noise accumulation, spurious correlation, incidental endogeneity, and measurement errors. These challenges are distinguished and require new computational and statistical paradigm. This article gives overviews on the salient features of Big Data and how these features impact on paradigm change on statistical and computational methods as well as computing architectures. We also provide various new perspectives on the Big Data analysis and computation. In particular, we emphasize on the viability of the sparsest solution in high-confidence set and point out that exogeneous assumptions in most statistical methods for Big Data can not be validated due to incidental endogeneity. They can lead to wrong statistical inferences and consequently wrong scientific conclusions. PMID:25419469

  14. Edrophonium Challenge Test for Blepharospasm

    PubMed Central

    Matsumoto, Shinichi; Murakami, Nagahisa; Koizumi, Hidetaka; Takahashi, Masatoshi; Izumi, Yuishin; Kaji, Ryuji

    2016-01-01

    Background: Blepharospasm is typically diagnosed by excluding any secondary diseases and neuropsychiatric disorders, as specific tests for blepharospasm are currently unavailable. Since anticholinergic agents are used to improve the symptoms of dystonia, we hypothesized that edrophonium chloride, an acetylcholinesterase inhibitor, may make the symptoms of dystonia more apparent. Therefore, we examined whether an edrophonium challenge test would be useful for diagnosing blepharospasm. Methods: We studied 10 patients with blepharospasm and 10 with hemifacial spasms (as disease controls). We administered edrophonium and saline in this double-blind study. Before and after the injection, we recorded the clinical signs using a video camera to assess the objective symptoms every 2 min. Ten minutes after the isotonic sodium chloride and edrophonium injections, the patients evaluated their subjective signs using a visual analog scale (VAS). The objective signs on the video recordings were scored by specialists who were blind to the treatment. Results: The subjective and objective signs of the patients with blepharospasm were amplified by edrophonium. In contrast, the signs in patients with hemifacial spasms were not changed by the edrophonium challenge test. Conclusions: The edrophonium challenge test may be used to diagnose blepharospasm. The study was registered with a ICMJE recognized registry, the UMIN-CTR, with the number UMIN000022557. PMID:27375406

  15. Challenges in complex systems science

    NASA Astrophysics Data System (ADS)

    San Miguel, M.; Johnson, J. H.; Kertesz, J.; Kaski, K.; Díaz-Guilera, A.; MacKay, R. S.; Loreto, V.; Érdi, P.; Helbing, D.

    2012-11-01

    FuturICT foundations are social science, complex systems science, and ICT. The main concerns and challenges in the science of complex systems in the context of FuturICT are laid out in this paper with special emphasis on the Complex Systems route to Social Sciences. This include complex systems having: many heterogeneous interacting parts; multiple scales; complicated transition laws; unexpected or unpredicted emergence; sensitive dependence on initial conditions; path-dependent dynamics; networked hierarchical connectivities; interaction of autonomous agents; self-organisation; non-equilibrium dynamics; combinatorial explosion; adaptivity to changing environments; co-evolving subsystems; ill-defined boundaries; and multilevel dynamics. In this context, science is seen as the process of abstracting the dynamics of systems from data. This presents many challenges including: data gathering by large-scale experiment, participatory sensing and social computation, managing huge distributed dynamic and heterogeneous databases; moving from data to dynamical models, going beyond correlations to cause-effect relationships, understanding the relationship between simple and comprehensive models with appropriate choices of variables, ensemble modeling and data assimilation, modeling systems of systems of systems with many levels between micro and macro; and formulating new approaches to prediction, forecasting, and risk, especially in systems that can reflect on and change their behaviour in response to predictions, and systems whose apparently predictable behaviour is disrupted by apparently unpredictable rare or extreme events. These challenges are part of the FuturICT agenda.

  16. Pyoderma gangrenosum: challenges and solutions

    PubMed Central

    Gameiro, Ana; Pereira, Neide; Cardoso, José Carlos; Gonçalo, Margarida

    2015-01-01

    Pyoderma gangrenosum (PG) is a rare disease, but commonly related to important morbidity. PG was first assumed to be infectious, but is now considered an inflammatory neutrophilic disease, often associated with autoimmunity, and with chronic inflammatory and neoplastic diseases. Currently, many aspects of the underlying pathophysiology are not well understood, and etiology still remains unknown. PG presents as painful, single or multiple lesions, with several clinical variants, in different locations, with a non specific histology, which makes the diagnosis challenging and often delayed. In the classic ulcerative variant, characterized by ulcers with inflammatory undermined borders, a broad differential diagnosis of malignancy, infection, and vasculitis needs to be considered, making PG a diagnosis of exclusion. Moreover, there are no definitively accepted diagnostic criteria. Treatment is also challenging since, due to its rarity, clinical trials are difficult to perform, and consequently, there is no “gold standard” therapy. Patients frequently require aggressive immunosuppression, often in multidrug regimens that are not standardized. We reviewed the clinical challenges of PG in order to find helpful clues to improve diagnostic accuracy and the treatment options, namely topical care, systemic drugs, and the new emerging therapies that may reduce morbidity. PMID:26060412

  17. VAST 2010 Challenge: Arms Dealings and Pandemics

    SciTech Connect

    Grinstein, Georges; Konecni, Shawn; Plaisant, Catherine; Scholtz, Jean; Whiting, Mark A.

    2010-10-23

    The 5th VAST Challenge consisted of three mini-challenges that involved both intelligence analysis and bioinformatics. Teams could solve one, two or all three mini-challenges and assess the overall situation to enter the Grand Challenge. Mini-challenge one involved text reports about people and events giving information about arms dealers, situations in various countries and linkages between different countries. Mini-challenge two involved hospital admission and death records from various countries providing information about the spread of a world wide pandemic. Mini-challenge three involved genetic data to be used to identify the origin of the pandemic and the most dangerous viral mutations. The Grand Challenge was to determine how these various mini-challenges were connected. As always the goal was to analyze the data and provide novel interactive visualizations useful in the analytic process. We received 58 submissions in total and gave 15 awards.

  18. 75 FR 21044 - Notice of Centennial Challenges 2011 CAFE Green Flight Challenge

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-22

    ... SPACE ADMINISTRATION Notice of Centennial Challenges 2011 CAFE Green Flight Challenge AGENCY: National Aeronautics and Space Administration (NASA). ACTION: Notice of Centennial Challenges 2011 CAFE Green Flight... Flight Challenge is scheduled and teams that wish to compete may register. Centennial Challenges is...

  19. Challenges of NDE Simulation Tool Challenges of NDE Simulation Tool

    NASA Technical Reports Server (NTRS)

    Leckey, Cara A. C.; Juarez, Peter D.; Seebo, Jeffrey P.; Frank, Ashley L.

    2015-01-01

    Realistic nondestructive evaluation (NDE) simulation tools enable inspection optimization and predictions of inspectability for new aerospace materials and designs. NDE simulation tools may someday aid in the design and certification of advanced aerospace components; potentially shortening the time from material development to implementation by industry and government. Furthermore, modeling and simulation are expected to play a significant future role in validating the capabilities and limitations of guided wave based structural health monitoring (SHM) systems. The current state-of-the-art in ultrasonic NDE/SHM simulation cannot rapidly simulate damage detection techniques for large scale, complex geometry composite components/vehicles with realistic damage types. This paper discusses some of the challenges of model development and validation for composites, such as the level of realism and scale of simulation needed for NASA' applications. Ongoing model development work is described along with examples of model validation studies. The paper will also discuss examples of the use of simulation tools at NASA to develop new damage characterization methods, and associated challenges of validating those methods.

  20. VAST 2009 Challenge: An Insider Threat

    SciTech Connect

    Grinstein, Georges; Scholtz, Jean; Whiting, Mark A.; Plaisant, Catherine

    2009-10-01

    The 4th year of the VAST Challenge offered participating teams the opportunity to analyze three mini challenges and to combine the data and analyses and enter the Grand challenge. In this paper we provide a description of the data collections used, the overall scenario and the specific questions asked in the mini challenges. We also discuss the infrastructure developed to evaluate accuracy measures in this year’s social network mini challenge. We provide a few examples of visualizations that merited awards. As in previous year, The VAST 2009 Challenge was held in conjunction with the 2009 IEEE VAST Symposium.

  1. Fossil Energy: Drivers and Challenges.

    NASA Astrophysics Data System (ADS)

    Friedmann, Julio

    2007-04-01

    Concerns about rapid economic growth, energy security, and global climate change have created a new landscape for fossil energy exploration, production, and utilization. Since 85% of primary energy supply comes from fossil fuels, and 85% of greenhouse gas emissions come from fossil fuel consumption, new and difficult technical and political challenges confront commercial, governmental, and public stakeholders. As such, concerns over climate change are explicitly weighed against security of international and domestic energy supplies, with economic premiums paid for either or both. Efficiency improvements, fuel conservation, and deployment of nuclear and renewable supplies will help both concerns, but are unlikely to offset growth in the coming decades. As such, new technologies and undertakings must both provide high quality fossil energy with minimal environmental impacts. The largest and most difficult of these undertakings is carbon management, wherein CO2 emissions are sequestered indefinitely at substantial incremental cost. Geological formations provide both high confidence and high capacity for CO2 storage, but present scientific and technical challenges. Oil and gas supply can be partially sustained and replaced through exploitation of unconventional fossil fuels such as tar-sands, methane hydrates, coal-to-liquids, and oil shales. These fuels provide enormous reserves that can be exploited at current costs, but generally require substantial energy to process. In most cases, the energy return on investment (EROI) is dropping, and unconventional fuels are generally more carbon intensive than conventional, presenting additional carbon management challenges. Ultimately, a large and sustained science and technology program akin to the Apollo project will be needed to address these concerns. Unfortunately, real funding in energy research has dropped dramatically (75%) in the past three decades, and novel designs in fission and fusion are not likely to provide any

  2. Silicon photonics: some remaining challenges

    NASA Astrophysics Data System (ADS)

    Reed, G. T.; Topley, R.; Khokhar, A. Z.; Thompson, D. J.; Stanković, S.; Reynolds, S.; Chen, X.; Soper, N.; Mitchell, C. J.; Hu, Y.; Shen, L.; Martinez-Jimenez, G.; Healy, N.; Mailis, S.; Peacock, A. C.; Nedeljkovic, M.; Gardes, F. Y.; Soler Penades, J.; Alonso-Ramos, C.; Ortega-Monux, A.; Wanguemert-Perez, G.; Molina-Fernandez, I.; Cheben, P.; Mashanovich, G. Z.

    2016-03-01

    This paper discusses some of the remaining challenges for silicon photonics, and how we at Southampton University have approached some of them. Despite phenomenal advances in the field of Silicon Photonics, there are a number of areas that still require development. For short to medium reach applications, there is a need to improve the power consumption of photonic circuits such that inter-chip, and perhaps intra-chip applications are viable. This means that yet smaller devices are required as well as thermally stable devices, and multiple wavelength channels. In turn this demands smaller, more efficient modulators, athermal circuits, and improved wavelength division multiplexers. The debate continues as to whether on-chip lasers are necessary for all applications, but an efficient low cost laser would benefit many applications. Multi-layer photonics offers the possibility of increasing the complexity and effectiveness of a given area of chip real estate, but it is a demanding challenge. Low cost packaging (in particular, passive alignment of fibre to waveguide), and effective wafer scale testing strategies, are also essential for mass market applications. Whilst solutions to these challenges would enhance most applications, a derivative technology is emerging, that of Mid Infra-Red (MIR) silicon photonics. This field will build on existing developments, but will require key enhancements to facilitate functionality at longer wavelengths. In common with mainstream silicon photonics, significant developments have been made, but there is still much left to do. Here we summarise some of our recent work towards wafer scale testing, passive alignment, multiplexing, and MIR silicon photonics technology.

  3. Materials Challenges in Nuclear Energy

    SciTech Connect

    Zinkle, Steven J; Was, Gary

    2013-01-01

    Nuclear power currently provides about 13% of the worldwide electrical power, and has emerged as a reliable baseload source of electricity. A number of materials challenges must be successfully resolved for nuclear energy to continue to make further improvements in reliability, safety and economics. The operating environment for materials in current and proposed future nuclear energy systems is summarized, along with a description of materials used for the main operating components. Materials challenges associated with power uprates and extensions of the operating lifetimes of reactors are described. The three major materials challenges for the current and next generation of water-cooled fission reactors are centered on two structural materials aging degradation issues (corrosion and stress corrosion cracking of structural materials and neutron-induced embrittlement of reactor pressure vessels), along with improved fuel system reliability and accident tolerance issues. The major corrosion and stress corrosion cracking degradation mechanisms for light water reactors are reviewed. The materials degradation issues for the Zr alloy clad UO2 fuel system currently utilized in the majority of commercial nuclear power plants is discussed for normal and off-normal operating conditions. Looking to proposed future (Generation IV) fission and fusion energy systems, there are 5 key bulk radiation degradation effects (low temperature radiation hardening and embrittlement, radiation-induced and modified solute segregation and phase stability, irradiation creep, void swelling, and high temperature helium embrittlement) and a multitude of corrosion and stress corrosion cracking effects (including irradiation-assisted phenomena) that can have a major impact on the performance of structural materials.

  4. International migration: a global challenge.

    PubMed

    Martin, P; Widgren, J

    1996-04-01

    Trends in international migration are presented in this multiregional analysis. Seven of the world's wealthiest countries have about 33% of the world's migrant population, but under 16% of the total world population. Population growth in these countries is substantially affected by the migrant population. The migration challenge is external and internal. The external challenge is to balance the need for foreign labor and the commitment to human rights for those migrants seeking economic opportunity and political freedom. The internal challenge is to assure the social adjustment of immigrants and their children and to integrate them into society as citizens and future leaders. Why people cross national borders and how migration flows are likely to evolve over the next decades are explained. This report also presents some ways that countries can manage migration or reduce the pressures which force people to migrate. It is recommended that receiving nations control immigration by accelerating global economic growth and reducing wars and human rights violations. This report examines the impact of immigration on international trade, aid, and direct intervention policies. Although migration is one of the most important international economic issues, it is not coordinated by an international group. The European experience indicates that it is not easy to secure international cooperation on issues that affect national sovereignty. It is suggested that countries desiring control of their borders should remember that most people never cross national borders to live or work in another country, that 50% of the world's migrants move among developing countries, and that countries can shift from being emigration to immigration countries. The author suggests that sustained reductions in migration pressure are a better alternative than the "quick fixes" that may invite the very much feared mass and unpredictable movements. PMID:12320315

  5. Challenges in plasma membrane phosphoproteomics

    PubMed Central

    Orsburn, Benjamin C; Stockwin, Luke H; Newton, Dianne L

    2011-01-01

    The response to extracellular stimuli often alters the phosphorylation state of plasma membrane-associated proteins. In this regard, generation of a comprehensive membrane phosphoproteome can significantly enhance signal transduction and drug mechanism studies. However, analysis of this subproteome is regarded as technically challenging, given the low abundance and insolubility of integral membrane proteins, combined with difficulties in isolating, ionizing and fragmenting phosphopeptides. In this article, we highlight recent advances in membrane and phosphoprotein enrichment techniques resulting in improved identification of these elusive peptides. We also describe the use of alternative fragmentation techniques, and assess their current and future value to the field of membrane phosphoproteomics. PMID:21819303

  6. Engineering Innovations for Exploration Challenges

    NASA Technical Reports Server (NTRS)

    Dumbacher, Daniel L.

    2010-01-01

    This slide presentation reviews some of the engineering innovations requirements for the challenges of space exploration which NASA has and will be involved in. It reviews some significant successes in space transportation, exploration and science accomplished during 2009, and it reviews some of the places that are available for exploration in the near term and the specific missions that NASA has assigned to Marshall. It also reviews the project lifecycle management model, that is designed to reduce undefined, but known, risks. It also demonstrates the sustainable long-term program of block upgrades that contribute to long-term success of programs.

  7. Facing Tomorrow's Challenges - An Overview

    USGS Publications Warehouse

    U.S. Geological Survey

    2008-01-01

    In 2007, the U.S. Geological Survey (USGS) developed a science strategy outlining the major natural-science issues facing the Nation in the next decade. The science strategy consists of six science directions of critical importance, focusing on areas where natural science can make a substantial contribution to the well-being of the Nation and the world. This fact sheet is an overview of the science strategy and describes how USGS research can strengthen the Nation with information needed to meet the challenges of the 21st century.

  8. The Challenges of Community Engagement.

    PubMed

    Cormick, Craig

    2010-12-01

    Lyons and Whelan provide a useful list of recommendations as to how community engagement on nanotechnology could be improved, which very few people working in community engagement could disagree with. However, as the conclusions of any study are dependent on the data obtained, if more data had been obtained and analysed then different conclusions might have been reached. Addressing the key issues in the paper and providing more data, also allows an opportunity to expand on current issues relating to community engagement on nanotechnology and the challenges it provides for practitioners. PMID:21258427

  9. Addressing the workforce pipeline challenge

    SciTech Connect

    Leonard Bond; Kevin Kostelnik; Richard Holman

    2006-11-01

    A secure and affordable energy supply is essential for achieving U.S. national security, in continuing U.S. prosperity and in laying the foundations to enable future economic growth. To meet this goal the next generation energy workforce in the U.S., in particular those needed to support instrumentation, controls and advanced operations and maintenance, is a critical element. The workforce is aging and a new workforce pipeline, to support both current generation and new build has yet to be established. The paper reviews the challenges and some actions being taken to address this need.

  10. Airport Noise Tech Challenge Overview

    NASA Technical Reports Server (NTRS)

    Bridges, James

    2011-01-01

    The Supersonics Project, operating under NASA Aeronautics Mission Directorate#s Fundamental Aero Program, has been organized around the Technical Challenges that have historically precluded commercial supersonic flight. One of these Challenges is making aircraft that are capable of such high aerodynamic performance quiet enough around airports that they will not be objectionable. It is recognized that a successful civilian supersonic aircraft will be a system where many new technologies will come together, and for this to happen not only will new low noise propulsion concepts be required, but new engineering tools that predict the noise of the aircraft as these technologies are combined and compromised with the rest of the aircraft design. These are the two main objectives of the Airport Noise Tech Challenge. " ! As a Project in the Fundamental Aero Program, we work at a relatively low level of technology readiness. However, we have high level milestones which force us to integrate our efforts to impact systems-level activities. To keep the low-level work tied to delivering engineering tools and low-noise concepts, we have structured our milestones around development of the concepts and organized our activities around developing and applying our engineering tools to these concepts. The final deliverables in these milestones are noise prediction modules validated against the best embodiment of each concept. These will then be used in cross-disciplinary exercises to demonstrate the viability of aircraft designs to meet all the Technical Challenges. Some of the concepts being developed are shown: Fan Flow Diverters, Multi-jet Shielding, High-Aspect Ratio Embedded Nozzles, Plasma Actuated Instability Manipulation, Highly Variable Cycle Mixer- Ejectors, and Inverted Velocity Profiles. These concepts are being developed for reduced jet noise along with the design tools which describe how they perform when used in various aircraft configurations. Several key upcoming

  11. International radioactive material recycling challenges

    SciTech Connect

    Greeves, John T.; Lieberman, James

    2007-07-01

    The paper explores current examples of successful International radioactive recycling programs and also explores operational regulatory and political challenges that need to be considered for expanding international recycling world-wide. Most countries regulations are fully consistent with the International Atomic Agency (IAEA) Code of Practice on the International Transboundary Movement of Radioactive Material and the IAEA Code of Conduct on the Safety and Security of Radioactive Sources. IAEA member States reported on the status of their efforts to control transboundary movement of radioactive material recently during the Joint Convention on the Safety of Spent Fuel management and on the Safety of Radioactive Waste Management meeting in May 2006. (authors)

  12. Earth Science Missions Engineering Challenges

    NASA Technical Reports Server (NTRS)

    Marius, Julio L.

    2009-01-01

    This presentation gives a general overlook of the engineering efforts that are necessary to meet science mission requirement especially for Earth Science missions. It provides brief overlook of NASA's current missions and future Earth Science missions and the engineering challenges to meet some of the specific science objectives. It also provides, if time permits, a brief summary of two significant weather and climate phenomena in the Southern Hemisphere: El Nino and La Nina, as well as the Ozone depletion over Antarctica that will be of interest to IEEE intercom 2009 conference audience.

  13. Sonic Boom Modeling Technical Challenge

    NASA Technical Reports Server (NTRS)

    Sullivan, Brenda M.

    2007-01-01

    This viewgraph presentation reviews the technical challenges in modeling sonic booms. The goal of this program is to develop knowledge, capabilities and technologies to enable overland supersonic flight. The specific objectives of the modeling are: (1) Develop and validate sonic boom propagation model through realistic atmospheres, including effects of turbulence (2) Develop methods enabling prediction of response of and acoustic transmission into structures impacted by sonic booms (3) Develop and validate psychoacoustic model of human response to sonic booms under both indoor and outdoor listening conditions, using simulators.

  14. Developmental psychopathology: concepts and challenges.

    PubMed

    Rutter, M; Sroufe, L A

    2000-01-01

    The defining features of developmental psychopathology concepts include attention to the understanding of causal processes, appreciation of the role of developmental mechanisms, and consideration of continuities and discontinuities between normality and psychopathology. Accomplishments with respect to these issues are reviewed in relation to attachment disorders, antisocial behavior, autism, depressive disorder, schizophrenia, and intellectual development. Major research challenges remain in relation to measurement issues, comorbidity, gender differences, cognitive processing, nature-nurture interplay, heterotypic continuity, continuities between normal variations and disorders, developmental programming, and therapeutic mechanisms in effective treatments. PMID:11014739

  15. A Challenge to Entropic Gravity

    NASA Astrophysics Data System (ADS)

    Roveto, Jonathan; Munoz, Gerardo

    2012-03-01

    In a recent publication, Erik Verlinde attempts to show that gravity should be viewed not as a fundamental force, but rather as an emergent thermodynamic phenomenon arising from an unspecified microscopic theory via equipartition and holography. We present a challenge to his reformulation of gravity. A detailed examination of Verlinde's derivation leads to a number of questions that severely weaken the claim that such a theory correctly reproduces Newton's laws or Einstein gravity. In particular, we find that neither Newtonian gravity nor the Einstein equations are uniquely determined using Verlinde's postulates.

  16. The challenges of technology transfer

    NASA Technical Reports Server (NTRS)

    Hazelwood, J. N.

    1974-01-01

    Observations of challenges of technology transfer are presented with emphasis placed on the position of industry seeking technology through the media of technology searches. Factors considered are: (1) not-invented-here syndrome; (2) penetration of technological literature; (3) gap between origin and industry use; (4) large aerospace manufacturer vs. the small manufacturer; (5) link between the technology disseminator and the potential user; (6) feasibility of substitutions in terms of production costs; and (7) role of patents. It is shown that industry, government agencies, and others having technology to disseminate or use, must mutually understand the technology tools and translate to one another's capabilities, in order to profit from this national resource.

  17. Aircraft gas turbine emissions challenge

    SciTech Connect

    Koff, B.L. )

    1994-07-01

    The new generation of jet powered aircraft faces a significant challenge to reduce pollutant emissions while increasing fuel efficiency. Carbon monoxide (CO) and unburned hydrocarbon (HC) emissions are already very low and continued control of these pollutants is expected as engine temperatures and pressure ratios are increased. In contrast, significant system design improvements are needed to reduce oxides of nitrogen (NO[sub x]) emissions because of their harmful effect on the earth's ozone layer. This paper discusses the prospects and technical approaches for significant NO[sub x] reductions in current and future subsonic and supersonic aircraft.

  18. X-15 Hardware Design Challenges

    NASA Technical Reports Server (NTRS)

    Storms, Harrison A., Jr.

    1991-01-01

    Historical events in the development of the X-15 hardware design are presented. Some of the topics covered include: (1) drivers that led to the development of the X-15; (2) X-15 space research objectives; (3) original performance targets; (4) the X-15 typical mission; (5) X-15 dimensions and weight; (5) the propulsion system; (6) X-15 development milestones; (7) engineering and manufacturing challenges; (8) the X-15 structure; (9) ballistic flight control; (10) landing gear; (11) nose gear; and (12) an X-15 program recap.

  19. Heminasal agenesis: a reconstructive challenge.

    PubMed

    Fisher, Mark; Zelken, Jonathan; Redett, Richard J

    2014-05-01

    Heminasal agenesis is a rare congenital malformation often associated with deformities of the eyes and lacrimal system, midface, and proboscis lateralis. Reconstruction is especially challenging because of missing lining, cartilage, and skin. We present a case of heminasal agenesis in a 5-year-old girl with concomitant hypertelorism, coloboma of the eyelids, and maxillary hypoplasia. The patient underwent facial bipartition for hypertelorism correction and cantilever bone graft. A forehead flap was designed using an anaplastic model from the patient's twin sister. Cartilage harvested from the conchal bowl and rib provided alar and dorsal support. Reconstructive goals, timing, and options are discussed. PMID:24777004

  20. Verification Challenges at Low Numbers

    SciTech Connect

    Benz, Jacob M.; Booker, Paul M.; McDonald, Benjamin S.

    2013-07-16

    This paper will explore the difficulties of deep reductions by examining the technical verification challenges. At each step on the road to low numbers, the verification required to ensure compliance of all parties will increase significantly. Looking post New START, the next step will likely include warhead limits in the neighborhood of 1000 (Pifer 2010). Further reductions will include stepping stones at 100’s of warheads, and then 10’s of warheads before final elimination could be considered of the last few remaining warheads and weapons. This paper will focus on these three threshold reduction levels, 1000, 100’s, 10’s. For each, the issues and challenges will be discussed, potential solutions will be identified, and the verification technologies and chain of custody measures that address these solutions will be surveyed. It is important to note that many of the issues that need to be addressed have no current solution. In these cases, the paper will explore new or novel technologies that could be applied. These technologies will draw from the research and development that is ongoing throughout the national lab complex, and will look at technologies utilized in other areas of industry for their application to arms control verification.

  1. The challenge to balloon science

    NASA Astrophysics Data System (ADS)

    Jones, W. Vernon

    A thorough review of the NASA balloon program in 1995 confirmed both the inherent importance of balloon science investigations and their value for developing technology for future space missions. A follow-on study in 1996 looked into restructuring the entire suborbital program, in order to find more efficient and effective ways of doing business. These studies were mandated by the adverse impact of NASA's declining budgets and work force constraints on all aspects of space research. The challenge is to accomplish more with less. The balloon program began stepping up to this challenge several years ago with the advent of 10 - 20 day long-duration flights in Antarctica. We must now push ahead with enhanced flight capabilities and with new science instrument technologies, as we forge alliances with other modes of low-cost access to space. Specifically, the development of sealed superpressure balloons could extend flight duration by another order of magnitude, to about 100 days, making ballooning even more competitive with space missions.

  2. Applied aerodynamics: Challenges and expectations

    NASA Technical Reports Server (NTRS)

    Peterson, Victor L.; Smith, Charles A.

    1993-01-01

    Aerospace is the leading positive contributor to this country's balance of trade, derived largely from the sale of U.S. commercial aircraft around the world. This powerfully favorable economic situation is being threatened in two ways: (1) the U.S. portion of the commercial transport market is decreasing, even though the worldwide market is projected to increase substantially; and (2) expenditures are decreasing for military aircraft, which often serve as proving grounds for advanced aircraft technology. To retain a major share of the world market for commercial aircraft and continue to provide military aircraft with unsurpassed performance, the U.S. aerospace industry faces many technological challenges. The field of applied aerodynamics is necessarily a major contributor to efforts aimed at meeting these technological challenges. A number of emerging research results that will provide new opportunities for applied aerodynamicists are discussed. Some of these have great potential for maintaining the high value of contributions from applied aerodynamics in the relatively near future. Over time, however, the value of these contributions will diminish greatly unless substantial investments continue to be made in basic and applied research efforts. The focus: to increase understanding of fluid dynamic phenomena, identify new aerodynamic concepts, and provide validated advanced technology for future aircraft.

  3. Gulf War Illness: Challenges Persist

    PubMed Central

    Nettleman, Mary

    2015-01-01

    It has been more than 20 years since the United States and coalition forces entered Kuwait and Iraq. Actual combat was of remarkably short duration: less than 1 week of sustained ground activity and 6 weeks of air missions. Thus, it was surprising when approximately 200,000 returning US veterans were affected by a chronic multi-symptom illness that came to be known as Gulf War Illness (GWI). There were many challenges in investigating GWI, not least of which was that it took several years before the condition was officially taken seriously. There were multiple exposures to potentially causal agents on and off the battlefield, but these exposures were documented incompletely if at all, leaving epidemiologists to rely on self-report for information. In the past 2 years, significant controversy has arisen over the future directions of the field. Despite these challenges, several studies have implicated exposure to acetylcholinesterase inhibitors such as pyridostigmine bromide in the genesis of the condition. The story of GWI can inform research into other conditions and guide future work on veterans' health. PMID:26330683

  4. Obturator hernia: A diagnostic challenge

    PubMed Central

    Tokushima, Midori; Aihara, Hidetoshi; Tago, Masaki; Tomonaga, Motosuke; Sakanishi, Yuta; Yoshioka, Tsuneaki; Hyakutake, Masaki; Kyoraku, Itaru; Sugioka, Takashi; Yamashita, Shu-ichi

    2014-01-01

    Patient: Female, 90 Final Diagnosis: Obturator hernia Symptoms: Epigastric pain • vomiting Medication: — Clinical Procedure: — Specialty: Gastroenterology and Hepatology Objective: Challenging differential diagnosis Background: Obturator hernia (OH) can be difficult to diagnose because it shows only nonspecific signs and symptoms. Although pain in a lower limb caused by compression of the obturator nerve by the hernia in the obturator canal (Howship-Romberg sign) is a characteristic sign, its presence is rather rare. Case Report: We herein describe the case of a 90-year-old woman with an OH that was difficult to diagnose because of her slight abdominal signs and symptoms on admission and subtle abdominal computed tomography (CT) findings. Although the CT images revealed the presence of an OH, this finding was overlooked because it contained only a part of the small intestine wall, which is called the Richter type. Fortunately, her condition improved dramatically with only conservative treatment. Conclusions: Although early diagnosis is essential to reduce morbidity and mortality, OH can be a diagnostic challenge even with abdominal CT. PMID:25006359

  5. Managing neurocysticercosis: challenges and solutions

    PubMed Central

    Fogang, Yannick Fogoum; Savadogo, Abdoul Aziz; Camara, Massaman; Toffa, Dènahin Hinnoutondji; Basse, Anna; Sow, Adjaratou Djeynabou; Ndiaye, Mouhamadou Mansour

    2015-01-01

    Taenia solium neurocysticercosis (NCC) is a major cause of neurological morbidity in the world. Variability in the neuropathology and clinical presentation of NCC often make it difficult to diagnose and manage. Diagnosis of NCC can be challenging especially in endemic and resource-limited countries where laboratory and imaging techniques are often lacking. NCC management can also be challenging as current treatment options are limited and involve symptomatic agents, antiparasitic agents, or surgery. Although antiparasitic treatment probably reduces the number of active lesions and long-term seizure frequency, its efficacy is limited and strategies to improve treatment regimens are warranted. Treatment decisions should be individualized in relation to the type of NCC. Initial measures should focus on symptomatic management, with antiparasitic therapy only to be considered later on, when appropriate. Symptomatic treatment remains the cornerstone in NCC management which should not only focuses on epilepsy, but also on other manifestations that cause considerable burden (recurrent headaches, cognitive decline). Accurate patients’ categorization, better antiparasitic regimens, and definition of new clinical outcomes for trials on NCC could improve management quality and prognosis of NCC. Prevention strategies targeting tapeworm carriers and infected pigs are yielding good results in local models. If local elimination of transmission is confirmed and replicated, this will open the door to cysticercosis eradication efforts worldwide. PMID:26527895

  6. Managing neurocysticercosis: challenges and solutions.

    PubMed

    Fogang, Yannick Fogoum; Savadogo, Abdoul Aziz; Camara, Massaman; Toffa, Dènahin Hinnoutondji; Basse, Anna; Sow, Adjaratou Djeynabou; Ndiaye, Mouhamadou Mansour

    2015-01-01

    Taenia solium neurocysticercosis (NCC) is a major cause of neurological morbidity in the world. Variability in the neuropathology and clinical presentation of NCC often make it difficult to diagnose and manage. Diagnosis of NCC can be challenging especially in endemic and resource-limited countries where laboratory and imaging techniques are often lacking. NCC management can also be challenging as current treatment options are limited and involve symptomatic agents, antiparasitic agents, or surgery. Although antiparasitic treatment probably reduces the number of active lesions and long-term seizure frequency, its efficacy is limited and strategies to improve treatment regimens are warranted. Treatment decisions should be individualized in relation to the type of NCC. Initial measures should focus on symptomatic management, with antiparasitic therapy only to be considered later on, when appropriate. Symptomatic treatment remains the cornerstone in NCC management which should not only focuses on epilepsy, but also on other manifestations that cause considerable burden (recurrent headaches, cognitive decline). Accurate patients' categorization, better antiparasitic regimens, and definition of new clinical outcomes for trials on NCC could improve management quality and prognosis of NCC. Prevention strategies targeting tapeworm carriers and infected pigs are yielding good results in local models. If local elimination of transmission is confirmed and replicated, this will open the door to cysticercosis eradication efforts worldwide. PMID:26527895

  7. Organismal Responses to Hypoxemic Challenges.

    PubMed

    Fitzgerald, Robert S; Dehghani, Gholam A; Kiihl, Samara

    2015-01-01

    As a counterpoint to the volumes of beautiful work exploring how the carotid bodies (CBs) sense and transduce stimuli into neural traffic, this study explored one organismal reflex response to such stimulation. We challenged the anesthetized, paralyzed, artificially ventilated cat with two forms of acute hypoxemia: 10 % O(2)/balance N(2) (hypoxic hypoxia [HH] and carbon monoxide hypoxia [COH]). HH stimulates both CBs and aortic bodies (ABs), whereas COH stimulates only the ABs. Our design was to stimulate both with HH (HHint), then to stimulate only the ABs with COH (COHint); then, after aortic depressor nerve transaction, only the CBs with HH (HHabr), and finally neither with COH (COHabr). We recorded whole animal responses from Group 1 cats (e.g., cardiac output, arterial blood pressure, pulmonary arterial pressure/and vascular resistance) before and after sectioning the aortic depressor nerves. From Group 2 cats (intact) and Group 3 cats (aortic body resected) we recorded the vascular resistance in several organs (e.g., brain, heart, spleen, stomach, pancreas, adrenal glands, eyes). The HHint challenge was the most effective at keeping perfusion pressures adequate to maintain homeostasis in the face of a systemic wide hypoxemia with locally mediated vasodilation. The spleen and pancreas, however, showed a vasoconstrictive response. The adrenals and eyes showed a CB-mediated vasodilation. The ABs appeared to have a significant impact on the pulmonary vasculature as well as the stomach. Chemoreceptors via the sympathetic nervous system play the major role in this organism's response to hypoxemia. PMID:26303472

  8. Medical humanities’ challenge to medicine

    PubMed Central

    Macnaughton, Jane

    2015-01-01

    Medicine is predicated on a view of human nature that is highly positivist and atomistic. This is apparent in the way in which its students are taught, clinical consultations are structured and medical evidence is generated. The field of medical humanities originally emerged as a challenge to this overly narrow view, but it has rarely progressed beyond tinkering around the edges of medical education. This is partly because its practitioners have largely been working from within a pervasive medical culture from which it is difficult to break free, and partly because the field has been insufficiently armed with scholarly thinking from the humanities. This is beginning to change and there is a sign that research in medical humanities has the potential to mount a persuasive challenge to medicine’s ways of teaching, working and finding out. This article problematizes medicine’s narrow viewpoint, grounding its critique in philosophical ideas from phenomenology and pragmatism. I will reflect upon the historical context within which medical humanities has emerged and briefly examine specific examples of how its interdisciplinary approach, involving humanities scholars with clinicians and medical scientists, may develop new research directions in medicine. PMID:21851510

  9. Multiphysics simulations: challenges and opportunities.

    SciTech Connect

    Keyes, D.; McInnes, L. C.; Woodward, C.; Gropp, W.; Myra, E.; Pernice, M.

    2012-11-29

    This report is an outcome of the workshop Multiphysics Simulations: Challenges and Opportunities, sponsored by the Institute of Computing in Science (ICiS). Additional information about the workshop, including relevant reading and presentations on multiphysics issues in applications, algorithms, and software, is available via https://sites.google.com/site/icismultiphysics2011/. We consider multiphysics applications from algorithmic and architectural perspectives, where 'algorithmic' includes both mathematical analysis and computational complexity and 'architectural' includes both software and hardware environments. Many diverse multiphysics applications can be reduced, en route to their computational simulation, to a common algebraic coupling paradigm. Mathematical analysis of multiphysics coupling in this form is not always practical for realistic applications, but model problems representative of applications discussed herein can provide insight. A variety of software frameworks for multiphysics applications have been constructed and refined within disciplinary communities and executed on leading-edge computer systems. We examine several of these, expose some commonalities among them, and attempt to extrapolate best practices to future systems. From our study, we summarize challenges and forecast opportunities. We also initiate a modest suite of test problems encompassing features present in many applications.

  10. Challenges for the 80's

    SciTech Connect

    Lesch, J.R.

    1980-09-01

    Finding and developing the necessary petroleum reserves in the 1980's will require drilling deeper wells in more hostile environments, drilling in increasing water depths, drilling in hostile Arctic areas and in waters where icebergs must be dealt with, and exploring deeper onshore horizons in more difficult topographical areas. These conditions impose severe demands on drilling and production equipment. The deeper wells will challenge drilling and production capabilities because of higher down-hole temperatures, greater capacity requirements on surface equipment, and more critical demands on the associated down-hole equipment. Drilling fluids, tools, and elastomers will need to withstand higher temperatures and greater stresses. Drilling in deeper waters will require the development and refinement of better and more economical drilling and production platforms. Increased drilling from platforms will necessitate improved drilling fluids to minimize torque, drill string, and casing wear in highly deviated holes. Another technological challenge is rig automation to minimize the physical work and injury factors associated with tripping and to reduce personnel requirements on the drilling rig.

  11. Gulf War Illness: Challenges Persist.

    PubMed

    Nettleman, Mary

    2015-01-01

    It has been more than 20 years since the United States and coalition forces entered Kuwait and Iraq. Actual combat was of remarkably short duration: less than 1 week of sustained ground activity and 6 weeks of air missions. Thus, it was surprising when approximately 200,000 returning US veterans were affected by a chronic multi-symptom illness that came to be known as Gulf War Illness (GWI). There were many challenges in investigating GWI, not least of which was that it took several years before the condition was officially taken seriously. There were multiple exposures to potentially causal agents on and off the battlefield, but these exposures were documented incompletely if at all, leaving epidemiologists to rely on self-report for information. In the past 2 years, significant controversy has arisen over the future directions of the field. Despite these challenges, several studies have implicated exposure to acetylcholinesterase inhibitors such as pyridostigmine bromide in the genesis of the condition. The story of GWI can inform research into other conditions and guide future work on veterans' health. PMID:26330683

  12. Space Shuttle Star Tracker Challenges

    NASA Technical Reports Server (NTRS)

    Herrera, Linda M.

    2010-01-01

    The space shuttle fleet of avionics was originally designed in the 1970's. Many of the subsystems have been upgraded and replaced, however some original hardware continues to fly. Not only fly, but has proven to be the best design available to perform its designated task. The shuttle star tracker system is currently flying as a mixture of old and new designs, each with a unique purpose to fill for the mission. Orbiter missions have tackled many varied missions in space over the years. As the orbiters began flying to the International Space Station (ISS), new challenges were discovered and overcome as new trusses and modules were added. For the star tracker subsystem, the growing ISS posed an unusual problem, bright light. With two star trackers on board, the 1970's vintage image dissector tube (IDT) star trackers track the ISS, while the new solid state design is used for dim star tracking. This presentation focuses on the challenges and solutions used to ensure star trackers can complete the shuttle missions successfully. Topics include KSC team and industry partner methods used to correct pressurized case failures and track system performance.

  13. HSR Aerodynamic Performance Status and Challenges

    NASA Technical Reports Server (NTRS)

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

    1999-01-01

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

  14. VAST Challenge 2014: The Kronos Incident

    SciTech Connect

    Whiting, Mark A.; Cook, Kristin A.; Grinstein, Georges; Liggett, Kristen; Cooper, Michael J.; Fallon, John; Morin, Marc P.

    2014-10-31

    The 2014 IEEE Visual Analytics Science and Technology (VAST) Challenge presented researchers with a single fictitious scenario: the disappearance of staff members of the GASTech oil and gas company on location on the island of Kronos. A group named the Protectors of Kronos (POK) was the prime suspect in the disappearance. Three mini-challenges and a grand challenge were offered. Mini-challenge 1 included multiple types of text data for participants to provide a timeline of key events and characterize the POK, mini-challenge 2 focused on individuals’ movement and financial data for participants to provide patterns of daily life, and mini-challenge 3 featured real-time streaming social media and emergency service data for participants to provide hostage and kidnapper information. The grand challenge asked the participants to integrate results and generate a synopsis of events. The VAST Challenge received 73 submissions from 13 countries

  15. Managing Challenges in a Multi Contractor Project

    NASA Technical Reports Server (NTRS)

    King, Ron

    2011-01-01

    The presentation provides a project description, describes the integrated product team, and review project challenges. The challenges include programmatic, technical, basic drop tests, heavy drop tests, C-17 envelope expansion, and Ares I-X.

  16. Global Climate Change and the Mitigation Challenge

    EPA Science Inventory

    Book edited by Frank Princiotta titled Global Climate Change--The Technology Challenge Transparent modeling tools and the most recent literature are used, to quantify the challenge posed by climate change and potential technological remedies. The chapter examines forces driving ...

  17. Current challenges in interventional mitral valve treatment

    PubMed Central

    Candreva, Alessandro; Pozzoli, Alberto; Guidotti, Andrea; Gaemperli, Oliver; Nietlispach, Fabian; Barthelmes, Jens; Emmert, Maximilian Y.; Weber, Alberto; Benussi, Stefano; Alfieri, Ottavio; Maisano, Francesco

    2015-01-01

    Transcatheter mitral valve therapies have emerged as an alternative option in high surgical risk or inoperable patients with severe and symptomatic mitral regurgitation (MR). As multiple technologies and different approaches will become available in the field of mitral valve interventions, different challenges are emerging, both patient- (clinical challenges) and procedure-related (technical challenges). This review will briefly explore the current open challenges in the evolving fields of interventional mitral valve treatment. PMID:26543599

  18. Builders Challenge Quality Criteria Support Document

    SciTech Connect

    2009-06-01

    This document provides guidance to U.S. home builders participating in Builders Challenge. To qualify for the Builders Challenge, a home must score 70 or less on the EnergySmart Home Scale (E-Scale). Homes also must meet the Builders Challenge Quality Cri

  19. Reflections of a Faraday Challenge Day Leader

    ERIC Educational Resources Information Center

    Sewell, Keira

    2014-01-01

    Keira Sewell has just finished her second year as a Challenge Leader for the Faraday Challenge, a STEM-based scheme run by the Institution of Engineering and Technology. Aimed at 12-13 year-old students, its purpose is to engage students in future careers in engineering. Each year, a new challenge is held in over sixty schools and universities…

  20. Educational Leadership: Key Challenges and Ethical Tensions

    ERIC Educational Resources Information Center

    Duignan, Patrick

    2007-01-01

    "Educational Leadership" is a major research book on contemporary leadership challenges for educational leaders. In this groundbreaking new work, educational leaders in schools, including teachers, are provided with ways of analysing and resolving common but complex leadership challenges. Ethical tensions inherent in these challenges are…

  1. 28 CFR 17.30 - Classification challenges.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Classification challenges. 17.30 Section... ACCESS TO CLASSIFIED INFORMATION Classified Information § 17.30 Classification challenges. (a) Authorized... is improperly classified or unclassified are encouraged and expected to challenge the...

  2. iSTEM: The Aerospace Engineering Challenge

    ERIC Educational Resources Information Center

    English, Lyn D.; King, Donna T.; Hudson, Peter; Dawes, Les

    2014-01-01

    The authors developed The Paper Plane Challenge as one of a three-part response to The Aerospace Engineering Challenge. The Aerospace Engineering Challenge was the second of three multi-part activities that they had developed with the teachers during the year. Their aim was to introduce students to the exciting world of engineering, where they…

  3. Project Challenge: A Therapeutic Child Care Program.

    ERIC Educational Resources Information Center

    Adger, Susan

    Project Challenge is a unit of Project Playpen, Inc., in Pinellas County, Florida, which serves children from birth to age 5 who attend child care programs and display mild to moderate degrees of emotional challenge. This program guide describes the activities, structures, and design of Project Challenge to meet the needs of child care for working…

  4. 22 CFR 9.8 - Classification challenges.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... Foreign Relations DEPARTMENT OF STATE GENERAL SECURITY INFORMATION REGULATIONS § 9.8 Classification challenges. (a) Challenges. Holders of information pertaining to the Department of State who believe that its... information. Holders of information making challenges to the classification status of information shall not...

  5. 22 CFR 9.8 - Classification challenges.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... Foreign Relations DEPARTMENT OF STATE GENERAL SECURITY INFORMATION REGULATIONS § 9.8 Classification challenges. (a) Challenges. Holders of information pertaining to the Department of State who believe that its... information. Holders of information making challenges to the classification status of information shall not...

  6. 22 CFR 9.8 - Classification challenges.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Foreign Relations DEPARTMENT OF STATE GENERAL SECURITY INFORMATION REGULATIONS § 9.8 Classification challenges. (a) Challenges. Holders of information pertaining to the Department of State who believe that its... information. Holders of information making challenges to the classification status of information shall not...

  7. 22 CFR 9.8 - Classification challenges.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... Foreign Relations DEPARTMENT OF STATE GENERAL SECURITY INFORMATION REGULATIONS § 9.8 Classification challenges. (a) Challenges. Holders of information pertaining to the Department of State who believe that its... information. Holders of information making challenges to the classification status of information shall not...

  8. 22 CFR 9.8 - Classification challenges.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... Foreign Relations DEPARTMENT OF STATE GENERAL SECURITY INFORMATION REGULATIONS § 9.8 Classification challenges. (a) Challenges. Holders of information pertaining to the Department of State who believe that its... information. Holders of information making challenges to the classification status of information shall not...

  9. Challenges in Developing Clinical Workstation

    SciTech Connect

    Narayanan, Venkatesh; Vedula, Venumadhav

    2008-09-26

    Over the years, medical imaging has become very common and data intensive. New technology is needed to help visualize and analyze these large, complex data sets, especially in an acute care situation where time is of the essence. Also it is very important to present the data in an efficient and simple manner to aid the clinical decision making processes. There is a need for a clinical workstation that handles data from different modalities and performs the necessary post- processing operations on the data in order to enhance the image quality and improve the reliability of diagnosis. This paper briefly explains clinical workstation, emphasizing the requirements and challenges in design and architecture for the development of such systems.

  10. Teaching of leprosy: current challenges*

    PubMed Central

    Alves, Cynthia Rossetti Portela; Ribeiro, Maria Mônica Freitas; Melo, Elza Machado; Araújo, Marcelo Grossi

    2014-01-01

    In the context of declining leprosy endemicity worldwide, keeping the interest in knowledge and expertise in leprosy alive has been a matter of concern. Approaching the problem only in primary care, without the proper integration with other levels of care in the health system fails to account for the complexity of the disease. Training professionals to work at different levels of health care is a current challenge. The objective of this review was to look for experiences related to the teaching of leprosy both in undergraduate courses in the field of health sciences and in training programs for professionals who work in patient care. We highlight the role of the dermatologist in the management of control programs, diagnosis and treatment of the disease, as well as in the continuous education of other health professionals. PMID:24937820

  11. Materials for Space: It's Challenging!

    NASA Technical Reports Server (NTRS)

    Johnson, Sylvia M.

    2016-01-01

    Space environments place tremendous demands on materials that must perform with exceptional reliability to realize the goals of human or robotic space exploration missions. Materials are subjected to extremes of temperature, pressure, radiation and mechanical loads during all phases of use, including takeoff and ascent, exposure to space or entry into an atmosphere, and operation in a planetary atmosphere. Space materials must be robust and enable the formation of lightweight structures or components that perform the required functions; materials that perform multiple functions are of particular interest. This talk will review the unique challenges for materials in space and some of the specific material capabilities that will be needed for future exploration missions. A description of needs and trends in thermal protection materials and systems will complete the talk.

  12. Eosinophilic ascites: a diagnostic challenge.

    PubMed

    Khalil, Hesham; Joseph, Moby

    2016-01-01

    Eosinophilic ascites is a rare feature of eosinophilic gastroenteritis. We would like to highlight this increasingly recognised diagnosis in a case of unexplained ascites. We present a challenging case of a woman aged 25 years who presented with nausea, vomiting, diarrhoea, generalised abdominal pain and swelling 8-week following delivery of her first baby. Her symptoms were primarily aggravated by eating, and she had also noticed postprandial itching and self-limiting generalised rash. She had a strong history of atopy. Physical examination revealed abdominal tenderness and distension with shifting dullness. Urticarial skin rash was noted on the face, neck, chest and abdomen. Routine biochemistry was normal apart from peripheral eosinophilia. Imaging confirmed moderate ascites. Diagnostic paracentesis showed exudative ascites with numerous eosinophils. Histology of the upper and lower gastrointestinal tract showed infiltration of the oesophageogastroduodenal and rectosigmoid mucosa with eosinophils. The patient significantly improved following a course of steroids and six-food elimination diet. PMID:27600059

  13. eHealth recruitment challenges.

    PubMed

    Thompson, Debbe; Canada, Ashanti; Bhatt, Riddhi; Davis, Jennifer; Plesko, Lisa; Baranowski, Tom; Cullen, Karen; Zakeri, Issa

    2006-11-01

    Little is known about effective eHealth recruitment methods. This paper presents recruitment challenges associated with enrolling African-American girls aged 8-10 years in an eHealth obesity prevention program, their effect on the recruitment plan, and potential implications for eHealth research. Although the initial recruitment strategy was literature-informed, it failed to enroll the desired number of girls within a reasonable time period. Therefore, the recruitment strategy was reformulated to incorporate principles of social marketing and traditional marketing techniques. The resulting plan included both targeted, highly specific strategies (e.g., selected churches), and more broad-based approaches (e.g., media exposure, mass mailings, radio advertisements). The revised plan enabled recruitment goals to be attained. Media appeared to be particularly effective at reaching the intended audience. Future research should identify the most effective recruitment strategies for reaching potential eHealth audiences. PMID:17950873

  14. THE CONTINUING CHALLENGE OF ESBLS

    PubMed Central

    Perez, Federico; Endimiani, Andrea; Hujer, Kristine M.; Bonomo, Robert A.

    2007-01-01

    Summary of recent advances Since their first description more than twenty years ago, Escherichia coli and Klebsiella pneumoniae possessing extended-spectrum class A beta-lactamases (ESBLs) continue to thwart our best clinical efforts. In the “early years” the most common beta-lactamases were of the TEM and SHV varieties. Now, CTX-M enzymes are being discovered though out the world and are becoming the most prevalent beta-lactamases found in clinical isolates. The Klebsiella pneumoniae carbapenemases (KPC) (ESBL type enzymes that confer resistance to extended spectrum cephalosporins and carbapenems) present the most significant challenge to date. Structural studies of ESBLs indicate that active site expansion and remodeling are responsible for this extended hydrolytic activity. Continuing questions still exist regarding the optimal detection method for ESBLs. Most relevant are the increasing concerns regarding the status of carbapenems as “best therapy” for ESBL producing bacteria in light of the emergence of carbapenemases. PMID:17875405

  15. Challenges of the Innovation Project

    NASA Astrophysics Data System (ADS)

    Hayrapetyan, Ruben

    2010-04-01

    In order to be successful in the modern world a professional needs to be creative, open to innovation, and able to take responsibilities. Innovation and creativity are not skills a person is born with, they have to be taught. However, the course syllabus has almost no room for teaching anything except of standard course topics and even more standard applications. Course project may be a solution to this problem. But being a strong tool for teaching an innovation, such a project is a challenge for both students and instructors. In this talk I will discuss some outputs (both positive and negative) of the innovation project ``Trip to Mars'' given in my ``Differential Equations'' class.

  16. The RHIC project -- Physical challenges

    SciTech Connect

    Wei, J.

    1997-11-01

    The design and construction status of the Relativistic Heavy Ion Collider, RHIC, is discussed. Those novel features of a heavy ion Collider that are distinct from conventional hadron Colliders in general are noted. These features are derived from the experimental requirements of operation with a variety of ion species over a wide energy range including collisions between ions of unequal energies. The project is in the fifth year of a seven-year construction cycle. A review of the superconducting magnet program is given together with progress to date on the machine construction and commissioning. Emphasis is made on challenging issues including intrabeam scattering, interaction-region error compensation, magnet alignments, and matched transition-energy jump.

  17. Clinical challenges in mechanical ventilation.

    PubMed

    Goligher, Ewan C; Ferguson, Niall D; Brochard, Laurent J

    2016-04-30

    Mechanical ventilation supports gas exchange and alleviates the work of breathing when the respiratory muscles are overwhelmed by an acute pulmonary or systemic insult. Although mechanical ventilation is not generally considered a treatment for acute respiratory failure per se, ventilator management warrants close attention because inappropriate ventilation can result in injury to the lungs or respiratory muscles and worsen morbidity and mortality. Key clinical challenges include averting intubation in patients with respiratory failure with non-invasive techniques for respiratory support; delivering lung-protective ventilation to prevent ventilator-induced lung injury; maintaining adequate gas exchange in severely hypoxaemic patients; avoiding the development of ventilator-induced diaphragm dysfunction; and diagnosing and treating the many pathophysiological mechanisms that impair liberation from mechanical ventilation. Personalisation of mechanical ventilation based on individual physiological characteristics and responses to therapy can further improve outcomes. PMID:27203509

  18. The Challenge of Orbital Debris

    NASA Technical Reports Server (NTRS)

    Matney, Mark

    2012-01-01

    Since the dawn of the Space Age more than 50 years ago, humans have been launching objects into the space environment faster than they have been removed by active means or natural decay. This has led to a proliferation of debris -- derelict satellites, discarded rocket upper stages, and pieces from satellite breakups -- in Earth orbit, especially in well-used orbital regimes. This talk will summarize the current knowledge of the debris environment and describe plans to address the challenges orbital debris raises for the future usability of near-Earth space. The talk will be structured around 4 categories: Measurements, Modeling, Shielding, and Mitigation. This will include discussions of the long-term prognosis of debris growth (i.e., the "Kessler Syndrome") as well as plans for active debris removal.

  19. The personal challenge of advocacy.

    PubMed

    Rocklage, M R

    1992-04-01

    Advocacy is the embracing of a cause or issue, a conversion to a mission that makes a very real claim on the advocate. It is the activity of altering structures, of changing the status quo. Like prophetic ministry, the task of advocacy is to nurture, nourish, and evoke consciousness of different ways of considering and doing things, to champion new models of organization. Effective advocacy entails three distinct steps: envisioning an alternative, challenging the status quo, and energizing persons and communities. It is characterized by the emergence of an alternative community concerned with different issues and different ways of doing things. It also involves the integration of advocacy into our daily lives and a penetration of the numbness of life. How will we know when we are truly serving as advocates of the Church's healing ministry? We will have an inkling that we are on the right track when we move from charity to justice. PMID:10116739

  20. Epidemics Modelings: Some New Challenges

    NASA Astrophysics Data System (ADS)

    Boatto, Stefanella; Khouri, Renata Stella; Solerman, Lucas; Codeço, Claudia; Bonnet, Catherine

    2010-09-01

    Epidemics modeling has been particularly growing in the past years. In epidemics studies, mathematical modeling is used in particular to reach a better understanding of some neglected diseases (dengue, malaria, …) and of new emerging ones (SARS, influenza A,….) of big agglomerates. Such studies offer new challenges both from the modeling point of view (searching for simple models which capture the main characteristics of the disease spreading), data analysis and mathematical complexity. We are facing often with complex networks especially when modeling the city dynamics. Such networks can be static (in first approximation) and homogeneous, static and not homogeneous and/or not static (when taking into account the city structure, micro-climates, people circulation, etc.). The objective being studying epidemics dynamics and being able to predict its spreading.

  1. Challenges for Better thesis supervision

    PubMed Central

    Ghadirian, Laleh; Sayarifard, Azadeh; Majdzadeh, Reza; Rajabi, Fatemeh; Yunesian, Masoud

    2014-01-01

    Background: Conduction of thesis by the students is one of their major academic activities. Thesis quality and acquired experiences are highly dependent on the supervision. Our study is aimed at identifing the challenges in thesis supervision from both students and faculty members point of view. Methods: This study was conducted using individual in-depth interviews and Focus Group Discussions (FGD). The participants were 43 students and faculty members selected by purposive sampling. It was carried out in Tehran University of Medical Sciences in 2012. Data analysis was done concurrently with data gathering using content analysis method. Results: Our data analysis resulted in 162 codes, 17 subcategories and 4 major categories, "supervisory knowledge and skills", "atmosphere", "bylaws and regulations relating to supervision" and "monitoring and evaluation". Conclusion: This study showed that more attention and planning in needed for modifying related rules and regulations, qualitative and quantitative improvement in mentorship training, research atmosphere improvement and effective monitoring and evaluation in supervisory area. PMID:25250273

  2. Unmet Challenges of Structural Genomics

    PubMed Central

    Chruszcz, Maksymilian; Domagalski, Marcin; Osinski, Tomasz; Wlodawer, Alexander; Minor, Wladek

    2010-01-01

    Summary Structural genomics (SG) programs have developed during the last decade many novel methodologies for faster and more accurate structure determination. These new tools and approaches led to determination of thousands of protein structures. The generation of enormous amounts of experimental data resulted in significant improvements in the understanding of many biological processes at molecular levels. However, the amount of data collected so far is so large that traditional analysis methods are limiting the rate of extraction of biological and biochemical information from 3-D models. This situation has prompted us to review the challenges that remain unmet by structural genomics, as well as the areas in which the potential impact of SG could exceed what has been achieved so far. PMID:20810277

  3. Future challenges in renal transplantation.

    PubMed

    Whalen, H; Clancy, M; Jardine, A

    2012-02-01

    There is a worldwide increase in the incidence of end-stage renal disease. Renal transplantation has been shown to be cost effective, prolong survival and provide a better quality of life in comparison to dialysis. Consequently, there has been a steady increase in demand for organs leading to a shortage of available kidneys, and an increase in transplant waiting lists. Renal transplantation is therefore an expanding field with a number of unique future challenges to address. This article outlines strategies that may be employed to expand organ supply in order to meet increased demand. The ethical issues surrounding this are also summarized. Furthermore, we highlight techniques with the potential to minimize peri-transplant injury to the kidney on its journey from donor to recipient. Current and potential future management strategies to optimize graft and patient survival are also discussed. PMID:22361673

  4. Adolescent pregnancy: an intervention challenge.

    PubMed

    Trad, P V

    1993-01-01

    Even in the best of circumstances, pregnancy is a time of emotional upheaval. This is especially true for pregnant adolescents who are also attempting to adjust to pubertal status and to establish an identity independent from their family. Although research has focused on the etiology of teenage pregnancy, relatively few interventions consider the developmental obstacles encountered when treating pregnant teenagers. In particular, adolescents are cognitively unprepared to predict long-term outcomes, a skill essential for confronting the challenges of pregnancy. One new intervention, known as previewing, seeks to overcome this deficit. Previewing encourages expectant teenage mothers to represent future scenarios with the infant as a means of predicting and rehearsing adaptive outcomes. PMID:8287695

  5. Challenges in pediatric renal transplantation

    PubMed Central

    Peruzzi, Licia; Amore, Alessandro; Coppo, Rosanna

    2014-01-01

    Transplantation in children is the best option to treat renal failure. Over the last 25 years the improvements in therapy have dramatically reduced the risk of early acute rejection and graft loss, however the long term results in terms of graft survival and morbidity still require search for new immunosuppressive regimens. Tolerance of the graft and minimization of side effects are the challenges for improving the outcome of children with a grafted kidney. Notwithstanding the difficulties in settling in children large multicenter trials to derive statistically useful data, many important contributions in the last years brought important modifications in the immunosuppressive therapy, including minimization protocols of steroids and calcineurin inhibitors and new induction drugs. New methods for diagnosis of anti HLA antibodies and some new protocols to improve both chance and outcome of transplantation in immunized subjects represent area of ongoing research of extreme interest for children. PMID:25540732

  6. Integrated Modular Avionics: The Challenges

    NASA Astrophysics Data System (ADS)

    Charrier, O.

    2009-05-01

    The need to reduce Space, Weight, and Power (SWaP) across the embedded market leads many Systems Suppliers to run multiple applications on the same processor. The concept seems deceptively simple. However, a lack of experience using this approach, may lead to many mistakes, resulting in unacceptable system performance and unacceptable costs. The objective of this paper is to review the challenges of controlling the execution of multiple applications on the same processor in a Safety or Mission Critical context and, based on return of experiences, point out some of the common mistakes and the limit of what an operating system can control. As no-one has an unlimited budget, the ability to develop and verify such system at reasonable cost, reduced risk, and re-use of the expended effort will be emphasized.

  7. Multiphysics Simulations: Challenges and Opportunities

    SciTech Connect

    Keyes, David; McInnes, Lois C.; Woodward, Carol; Gropp, William; Myra, Eric; Pernice, Michael; Bell, John; Brown, Jed; Clo, Alain; Connors, Jeffrey; Constantinescu, Emil; Estep, Don; Evans, Kate; Farhat, Charbel; Hakim, Ammar; Hammond, Glenn E.; Hansen, Glen; Hill, Judith; Isaac, Tobin; Jiao, Xiangmin; Jordan, Kirk; Kaushik, Dinesh; Kaxiras, Efthimios; Koniges, Alice; Lee, Ki Hwan; Lott, Aaron; Lu, Qiming; Magerlein, John; Maxwell, Reed M.; McCourt, Michael; Mehl, Miriam; Pawlowski, Roger; Randles, Amanda; Reynolds, Daniel; Riviere, Beatrice; Rude, Ulrich; Scheibe, Timothy D.; Shadid, John; Sheehan, Brendan; Shephard, Mark; Siegel, Andrew; Smith, Barry; Tang, Xianzhu; Wilson, Cian; Wohlmuth, Barbara

    2013-02-12

    We consider multiphysics applications from algorithmic and architectural perspectives, where ‘‘algorithmic’’ includes both mathematical analysis and computational complexity, and ‘‘architectural’’ includes both software and hardware environments. Many diverse multiphysics applications can be reduced, en route to their computational simulation, to a common algebraic coupling paradigm. Mathematical analysis of multiphysics coupling in this form is not always practical for realistic applications, but model problems representative of applications discussed herein can provide insight. A variety of software frameworks for multiphysics applications have been constructed and refined within disciplinary communities and executed on leading-edge computer systems. We examine several of these, expose some commonalities among them, and attempt to extrapolate best practices to future systems. From our study, we summarize challenges and forecast opportunities.

  8. Emerging infections: a perpetual challenge

    PubMed Central

    Morens, David M; Folkers, Gregory K; Fauci, Anthony S

    2008-01-01

    Emerging and re-emerging infectious diseases, and their determinants, have recently attracted substantial scientific and popular attention. HIV/AIDS, severe acute respiratory syndrome, H5N1 avian influenza, and many other emerging diseases have either proved fatal or caused international alarm. Common and interactive co-determinants of disease emergence, including population growth, travel, and environmental disruption, have been increasingly documented and studied. Are emerging infections a new phenomenon related to modern life, or do more basic determinants, transcending time, place, and human progress, govern disease generation? By examining a number of historically notable epidemics, we suggest that emerging diseases, similar in their novelty, impact, and elicitation of control responses, have occurred throughout recorded history. Fundamental determinants, typically acting in concert, seem to underlie their emergence, and infections such as these are likely to continue to remain challenges to human survival. PMID:18992407

  9. Adversarial reasoning: challenges and approaches

    NASA Astrophysics Data System (ADS)

    Kott, Alexander; Ownby, Michael

    2005-05-01

    This paper defines adversarial reasoning as computational approaches to inferring and anticipating an enemy's perceptions, intents and actions. It argues that adversarial reasoning transcends the boundaries of game theory and must also leverage such disciplines as cognitive modeling, control theory, AI planning and others. To illustrate the challenges of applying adversarial reasoning to real-world problems, the paper explores the lessons learned in the CADET -- a battle planning system that focuses on brigade-level ground operations and involves adversarial reasoning. From this example of current capabilities, the paper proceeds to describe RAID -- a DARPA program that aims to build capabilities in adversarial reasoning, and how such capabilities would address practical requirements in Defense and other application areas.

  10. Image Processing: Some Challenging Problems

    NASA Astrophysics Data System (ADS)

    Huang, T. S.; Aizawa, K.

    1993-11-01

    Image processing can be broadly defined as the manipulation of signals which are inherently multidimensional. The most common such signals are photographs and video sequences. The goals of processing or manipulation can be (i) compression for storage or transmission; (ii) enhancement or restoration; (iii) analysis, recognition, and understanding; or (iv) visualization for human observers. The use of image processing techniques has become almost ubiquitous; they find applications in such diverse areas as astronomy, archaeology, medicine, video communication, and electronic games. Nonetheless, many important problems in image processing remain unsolved. It is the goal of this paper to discuss some of these challenging problems. In Section I, we mention a number of outstanding problems. Then, in the remainder of this paper, we concentrate on one of them: very-low-bit-rate video compression. This is chosen because it involves almost all aspects of image processing.

  11. Reading Challenging Barcodes with Cameras

    PubMed Central

    Gallo, Orazio; Manduchi, Roberto

    2010-01-01

    Current camera-based barcode readers do not work well when the image has low resolution, is out of focus, or is motion-blurred. One main reason is that virtually all existing algorithms perform some sort of binarization, either by gray scale thresholding or by finding the bar edges. We propose a new approach to barcode reading that never needs to binarize the image. Instead, we use deformable barcode digit models in a maximum likelihood setting. We show that the particular nature of these models enables efficient integration over the space of deformations. Global optimization over all digits is then performed using dynamic programming. Experiments with challenging UPC-A barcode images show substantial improvement over other state-of-the-art algorithms. PMID:20617113

  12. Multiphysics Simulations: Challenges and Opportunities

    SciTech Connect

    Keyes, David E; McInnes, Lois; Woodward, Carol; Evans, Katherine J; Hill, Judith C

    2013-01-01

    We consider multiphysics applications from algorithmic and architectural perspectives, where algorithmic in- cludes both mathematical analysis and computational complexity and architectural includes both software and hard- ware environments. Many diverse multiphysics applications can be reduced, en route to their computational simu- lation, to a common algebraic coupling paradigm. Mathematical analysis of multiphysics coupling in this form is not always practical for realistic applications, but model problems representative of applications discussed herein can provide insight. A variety of software frameworks for multiphysics applications have been constructed and refined within disciplinary communities and executed on leading-edge computer systems. We examine several of these, ex- pose some commonalities among them, and attempt to extrapolate best practices to future systems. From our study, we summarize challenges and forecast opportunities. We also initiate a modest suite of test problems encompassing features present in many applications.

  13. Cardiovascular response to thermoregulatory challenges.

    PubMed

    Liu, Cuiqing; Yavar, Zubin; Sun, Qinghua

    2015-12-01

    A growing number of extreme climate events are occurring in the setting of ongoing climate change, with an increase in both the intensity and frequency. It has been shown that ambient temperature challenges have a direct and highly varied impact on cardiovascular health. With a rapidly growing amount of literature on this issue, we aim to review the recent publications regarding the impact of cold and heat on human populations with regard to cardiovascular disease (CVD) mortality/morbidity while also examining lag effects, vulnerable subgroups, and relevant mechanisms. Although the relative risk of morbidity/mortality associated with extreme temperature varied greatly across different studies, both cold and hot temperatures were associated with a positive mean excess of cardiovascular deaths or hospital admissions. Cause-specific study of CVD morbidity/mortality indicated that the sensitivity to temperature was disease-specific, with different patterns for acute and chronic ischemic heart disease. Vulnerability to temperature-related mortality was associated with some characteristics of the populations, including sex, age, location, socioeconomic condition, and comorbidities such as cardiac diseases, kidney diseases, diabetes, and hypertension. Temperature-induced damage is thought to be related to enhanced sympathetic reactivity followed by activation of the sympathetic nervous system, renin-angiotensin system, as well as dehydration and a systemic inflammatory response. Future research should focus on multidisciplinary adaptation strategies that incorporate epidemiology, climatology, indoor/building environments, energy usage, labor legislative perfection, and human thermal comfort models. Studies on the underlying mechanism by which temperature challenge induces pathophysiological response and CVD await profound and lasting investigation. PMID:26432837

  14. Partnership challenges fund in India.

    PubMed

    1994-03-01

    The Family Planning Association of India (FPAI) Small Family by Choice project is the first large program to be funded by the International Planned Parenthood Federation (IPPF) Partnership Challenges Fund. This project endorses FPAI's integrated approach to family planning to address the family planning and reproductive health needs of the population in Northern India. The project will accelerate family planning acceptance in 3 districts in Madhya Pradesh State covering a population of some 3.6 million people. These strategies will include community participation, women's empowerment, literacy programs, male involvement, and youth mobilization. The project is the core of FPAI's Strategic Plan for 1992-2000, which strives to reach areas of greatest need, improve quality of care in family planning services, promote appropriate contraceptive choice, and provide supplies. Women will be helped through literacy, education, skills development and income generation. Particular emphasis will be placed on involving men in family planning and reproductive health choices within the family. The Small Families project will concentrate on the individual needs of people within the local community. The project will accelerate family planning acceptance through people's participation while improving their health and socioeconomic conditions. Service will be delivered through local NGOs and women's groups. Initially, this project will be carried out as operations research to identify the most effective combination of interventions. The project may be expanded to other states, incorporating findings from the initial project. The Partnership Challenges Fund has been established to support innovative projects that satisfy the expectations of the IPPF Vision 2000 Strategic Plan, and address priority reproductive health issues within FPAs strategic planning. The Fund intends to support projects that address the reproductive health needs of people within the community, and affect changes

  15. Challenges for Large Scale Simulations

    NASA Astrophysics Data System (ADS)

    Troyer, Matthias

    2010-03-01

    With computational approaches becoming ubiquitous the growing impact of large scale computing on research influences both theoretical and experimental work. I will review a few examples in condensed matter physics and quantum optics, including the impact of computer simulations in the search for supersolidity, thermometry in ultracold quantum gases, and the challenging search for novel phases in strongly correlated electron systems. While only a decade ago such simulations needed the fastest supercomputers, many simulations can now be performed on small workstation clusters or even a laptop: what was previously restricted to a few experts can now potentially be used by many. Only part of the gain in computational capabilities is due to Moore's law and improvement in hardware. Equally impressive is the performance gain due to new algorithms - as I will illustrate using some recently developed algorithms. At the same time modern peta-scale supercomputers offer unprecedented computational power and allow us to tackle new problems and address questions that were impossible to solve numerically only a few years ago. While there is a roadmap for future hardware developments to exascale and beyond, the main challenges are on the algorithmic and software infrastructure side. Among the problems that face the computational physicist are: the development of new algorithms that scale to thousands of cores and beyond, a software infrastructure that lifts code development to a higher level and speeds up the development of new simulation programs for large scale computing machines, tools to analyze the large volume of data obtained from such simulations, and as an emerging field provenance-aware software that aims for reproducibility of the complete computational workflow from model parameters to the final figures. Interdisciplinary collaborations and collective efforts will be required, in contrast to the cottage-industry culture currently present in many areas of computational

  16. Safe prescribing: a titanic challenge

    PubMed Central

    Routledge, Philip A

    2012-01-01

    The challenge to achieve safe prescribing merits the adjective ‘titanic’. The organisational and human errors leading to poor prescribing (e.g. underprescribing, overprescribing, misprescribing or medication errors) have parallels in the organisational and human errors that led to the loss of the Titanic 100 years ago this year. Prescribing can be adversely affected by communication failures, critical conditions, complacency, corner cutting, callowness and a lack of courage of conviction, all of which were also factors leading to the Titanic tragedy. These issues need to be addressed by a commitment to excellence, the final component of the ‘Seven C's’. Optimal prescribing is dependent upon close communication and collaborative working between highly trained health professionals, whose role is to ensure maximum clinical effectiveness, whilst also protecting their patients from avoidable harm. Since humans are prone to error, and the environments in which they work are imperfect, it is not surprising that medication errors are common, occurring more often during the prescribing stage than during dispensing or administration. A commitment to excellence in prescribing includes a continued focus on lifelong learning (including interprofessional learning) in pharmacology and therapeutics. This should be accompanied by improvements in the clinical working environment of prescribers, and the encouragement of a strong safety culture (including reporting of adverse incidents as well as suspected adverse drug reactions whenever appropriate). Finally, members of the clinical team must be prepared to challenge each other, when necessary, to ensure that prescribing combines the highest likelihood of benefit with the lowest potential for harm. PMID:22738396

  17. Technical solutions to nonproliferation challenges

    SciTech Connect

    Satkowiak, Lawrence

    2014-05-09

    The threat of nuclear terrorism is real and poses a significant challenge to both U.S. and global security. For terrorists, the challenge is not so much the actual design of an improvised nuclear device (IND) but more the acquisition of the special nuclear material (SNM), either highly enriched uranium (HEU) or plutonium, to make the fission weapon. This paper provides two examples of technical solutions that were developed in support of the nonproliferation objective of reducing the opportunity for acquisition of HEU. The first example reviews technologies used to monitor centrifuge enrichment plants to determine if there is any diversion of uranium materials or misuse of facilities to produce undeclared product. The discussion begins with a brief overview of the basics of uranium processing and enrichment. The role of the International Atomic Energy Agency (IAEA), its safeguard objectives and how the technology evolved to meet those objectives will be described. The second example focuses on technologies developed and deployed to monitor the blend down of 500 metric tons of HEU from Russia's dismantled nuclear weapons to reactor fuel or low enriched uranium (LEU) under the U.S.-Russia HEU Purchase Agreement. This reactor fuel was then purchased by U.S. fuel fabricators and provided about half the fuel for the domestic power reactors. The Department of Energy established the HEU Transparency Program to provide confidence that weapons usable HEU was being blended down and thus removed from any potential theft scenario. Two measurement technologies, an enrichment meter and a flow monitor, were combined into an automated blend down monitoring system (BDMS) and were deployed to four sites in Russia to provide 24/7 monitoring of the blend down. Data was downloaded and analyzed periodically by inspectors to provide the assurances required.

  18. Technical solutions to nonproliferation challenges

    NASA Astrophysics Data System (ADS)

    Satkowiak, Lawrence

    2014-05-01

    The threat of nuclear terrorism is real and poses a significant challenge to both U.S. and global security. For terrorists, the challenge is not so much the actual design of an improvised nuclear device (IND) but more the acquisition of the special nuclear material (SNM), either highly enriched uranium (HEU) or plutonium, to make the fission weapon. This paper provides two examples of technical solutions that were developed in support of the nonproliferation objective of reducing the opportunity for acquisition of HEU. The first example reviews technologies used to monitor centrifuge enrichment plants to determine if there is any diversion of uranium materials or misuse of facilities to produce undeclared product. The discussion begins with a brief overview of the basics of uranium processing and enrichment. The role of the International Atomic Energy Agency (IAEA), its safeguard objectives and how the technology evolved to meet those objectives will be described. The second example focuses on technologies developed and deployed to monitor the blend down of 500 metric tons of HEU from Russia's dismantled nuclear weapons to reactor fuel or low enriched uranium (LEU) under the U.S.-Russia HEU Purchase Agreement. This reactor fuel was then purchased by U.S. fuel fabricators and provided about half the fuel for the domestic power reactors. The Department of Energy established the HEU Transparency Program to provide confidence that weapons usable HEU was being blended down and thus removed from any potential theft scenario. Two measurement technologies, an enrichment meter and a flow monitor, were combined into an automated blend down monitoring system (BDMS) and were deployed to four sites in Russia to provide 24/7 monitoring of the blend down. Data was downloaded and analyzed periodically by inspectors to provide the assurances required.

  19. Challenges of CPAS Flight Testing

    NASA Technical Reports Server (NTRS)

    Ray, Eric S.; Morris, Aaron L.

    2011-01-01

    The Crew Exploration Vehicle Parachute Assembly System (CPAS) is being designed to land the Orion Crew Module (CM) at a safe rate of descent at splashdown via a series of Drogue, Pilot, and Main parachutes. Because Orion is considerably larger and heavier than Apollo, many of the flight test techniques developed during the Apollo program must be modified. The Apollo program had a dedicated C-133 aircraft, which was modified to allow a simple airdrop of "boilerplate" flight test vehicles. However, the CPAS program must use either commercial or military assets with minimal modifications to airframes or procedures. Conceptual envelopes from 2-Degree Of Freedom trajectories are presented for several existing and novel architectures. Ideally, the technique would deliver a representative capsule shape to the desired altitude and dynamic pressure at test initiation. However, compromises must be made on the characteristics of trajectories or the fidelity of test articles to production hardware. Most of the tests to date have used traditional pallet and weight tub or missile-shaped test vehicles. New test vehicles are being designed to better incorporate Orion structural components and deploy parachutes in a more representative fashion. The first attempt to test a capsule-shaped vehicle failed due to unexpected events while setting up the test condition through a series of complex procedures. In order to avoid the loss of another expensive test article which will delay the program, simpler deployment methods are being examined and more positive control of the vehicle will be maintained. Existing challenges include interfacing with parent aircraft, separating test vehicles, achieving test conditions, and landing within limited test ranges. All these challenges must be met within cost and schedule limits.

  20. Quantum Information: Opportunities and Challenges

    SciTech Connect

    Bennink, Ryan S

    2008-01-01

    Modern society is shaped by the ability to transmit, manipulate, and store large amounts of information. Although we tend to think of information as abstract, information is physical, and computing is a physical process. How then should we understand information in a quantum world, in which physical systems may exist in multiple states at once and are altered by the very act of observation? This question has evolved into an exciting new field of research called Quantum Information (QI). QI challenges many accepted rules and practices in computer science. For example, a quantum computer would turn certain hard problems into soft problems, and would render common computationally-secure encryption methods (such as RSA) insecure. At the same time, quantum communication would provide an unprecedented kind of intrinsic information security at the level of the smallest physical objects used to store or transmit the information. This talk provides a general introduction to the subject of quantum information and its relevance to cyber security. In the first part, two of the stranger aspects of quantum physics namely, superposition and uncertainty are explained, along with their relation to the concept of information. These ideas are illustrated with a few examples: quantum ID cards, quantum key distribution, and Grover s quantum search algorithm. The state-of-the-art in quantum computing and communication hardware is then discussed, along with the daunting technological challenges that must be overcome. Relevant experimental and theoretical efforts at ORNL are highlighted. The talk concludes with speculations on the short- and long-term impact of quantum information on cyber security.

  1. Time Domain Challenges for Exoplanets

    NASA Astrophysics Data System (ADS)

    Dawson, Rebekah Ilene

    2016-01-01

    Over the past couple decades, thousands of extra-solar planets have been discovered orbiting other stars. Most have been detected and characterized using transit and/or radial velocity time series, and these techniques have undergone huge improvements in instrumental precision. However, the improvements in precision have brought to light new statistical challenges in detecting and characterizing exoplanets in the presence of correlated noise caused by stellar activity (transits and radial velocities) and gaps in the time sampling (radial velocities). These challenges have afflicted many of the most interesting exoplanets, from Earth-like planets to planetary systems whose orbital dynamics place important constraints on how planetary systems form and evolve. In the first part of the talk, I will focus on the problem of correlated noise for characterizing transiting exoplanets using transit timing variations. I will present a comparison of several techniques using wavelets, Gaussian processes, and polynomial splines to account for correlated noise in the likelihood function when inferring planetary parameters. I will also present results on the characteristics of correlated noise that cause planets to be missed by the Kepler and homegrown pipelines despite high nominal signal-to-noise. In the second part of the talk, I will focus on the problem of aliasing caused by gaps in the radial-velocity time series on yearly, daily, and monthly timescales. I will present results on identifying aliases in the Fourier domain by taking advantage of aliasing on multiple timescales and discuss the interplay between aliasing and stellar activity for several habitable-zone "planets" that have recently been called into question as possible spurious signals caused by activity. As we push toward detecting and characterizing lower mass planets, it is essential that astrostatistical advances keep pace with advances in instrumentation.

  2. Challenge in learning and teaching science

    NASA Astrophysics Data System (ADS)

    Baird, John R.; Penna, Chris

    1996-09-01

    Taking as a basis a conceptualisation of personal challenge having both cognitive/metacognitive (thinking) and affective (feeling) components, the nature and extent of perceived challenge in learning and teaching science were explored for seven teachers and thirty-seven students in five secondary schools over a period of five months. Findings suggest that many secondary students are not challenged by the science they learn in school. Similary, many secondary science teachers are insufficiently challenged by the task of teaching. There are indications, however, that science teaching and learning attitudes and practices can be improved if teachers work to diagnose and change key classroom factors that influence level of perceived challenge in learning.

  3. Small Space Launch: Origins & Challenges

    NASA Astrophysics Data System (ADS)

    Freeman, T.; Delarosa, J.

    2010-09-01

    The United States Space Situational Awareness capability continues to be a key element in obtaining and maintaining the high ground in space. Space Situational Awareness satellites are critical enablers for integrated air, ground and sea operations, and play an essential role in fighting and winning conflicts. The United States leads the world space community in spacecraft payload systems from the component level into spacecraft, and in the development of constellations of spacecraft. In the area of launch systems that support Space Situational Awareness, despite the recent development of small launch vehicles, the United States launch capability is dominated by an old, unresponsive and relatively expensive set of launchers in the Expandable, Expendable Launch Vehicles (EELV) platforms; Delta IV and Atlas V. The United States directed Air Force Space Command to develop the capability for operationally responsive access to space and use of space to support national security, including the ability to provide critical space capabilities in the event of a failure of launch or on-orbit capabilities. On 1 Aug 06, Air Force Space Command activated the Space Development & Test Wing (SDTW) to perform development, test and evaluation of Air Force space systems and to execute advanced space deployment and demonstration projects to exploit new concepts and technologies, and rapidly migrate capabilities to the warfighter. The SDTW charged the Launch Test Squadron (LTS) with the mission to develop the capability of small space launch, supporting government research and development space launches and missile defense target missions, with operationally responsive spacelift for Low-Earth-Orbit Space Situational Awareness assets as a future mission. This new mission created new challenges for LTS. The LTS mission tenets of developing space launches and missile defense target vehicles were an evolution from the squadrons previous mission of providing sounding rockets under the Rocket

  4. Ulysses mission design after Challenger

    NASA Technical Reports Server (NTRS)

    Luthey, Joe L.; Peralta, Fernando; Pojman, Joan L.

    1990-01-01

    The delay of the Ulysses launch from May 1986 to October 1990, because of the Challenger disaster, has altered both the constraints under which the mission must be designed and the timing of several mission critical events. Safety and launch reliability concerns from the Shuttle have increased the effective launch window to durations greater than one hour. Fortuitously high declinations of the launch asymptote (DLA), of the order of the launch site latitude, ameliorate the impact of the new constraints on the launch window. Target overlays in the first hour of the launch window provide higher departure energies that improve mission performance and avoid a science schedule conflict at second opposition near the time of closest Jupiter approach. The mission design starts with the maximum earth departure energy that the upper stage can deliver within the launch constraints. The Jupiter arrival asymptotes are chosen from the optimal point of mission performance in the mission space defined in the Jupiter B-plane by contours mapped by the science and spacecraft constraints. More than half the orbital energy of the earth-to-Jupiter transfer orbit is lost in the Jupiter flyby, and the Jupiter gravitational assist rotates the orbit plane out of the ecliptic to an inclination of about 80 degrees.

  5. Tuberculosis diagnostics: Challenges and opportunities.

    PubMed

    Nema, Vijay

    2012-07-01

    Tuberculosis (TB) has been a disease affecting almost all parts of the world since ages. Lot many efforts came in the past for improving diagnosis and treatment. Also, an effective vaccine has been sought after for long. With the emergence of resistant strains of Mycobacterium tuberculosis, the causal organisms of tuberculosis, and complexities emerging due to other associated infections and disease conditions, there is a desperate need for further research input in the field. Be it the better medication and care or better resistance management, proper diagnostics holds the key to success. It has been observed that a high burden of the disease was accompanied by resource limitations and poor research set-up. The scenario remained like this for several decades. With the refreshed vision of resourceful countries and funding agencies, funding is being provided in many areas of research in tuberculosis diagnosis and treatment. This review has been written with an aim to bring forth the limitations of available methods in the field of diagnostics and making researchers aware about the changing scenario with better funding opportunities and support. The author visualizes an enthusiasm from all over the world for the development of better modalities and urges scientists to join the struggle at this very perfect time to take the challenge and come forward with innovations in this field. PMID:22919166

  6. The challenge of managing fusariosis.

    PubMed

    Muhammed, Maged; Coleman, Jeffrey J; Carneiro, Herman A; Mylonakis, Eleftherios

    2011-01-01

    Fusarium is the second most frequent mold involved in fungal infections and is particularly important among immunocompromised patients. Culture methods and microscopy are still routinely used in clinical laboratories to identify Fusarium spp, and more sophisticated, timely, and effective methods for detecting Fusarium spp. in laboratory samples could improve the outcome of the patient. These investigational diagnostic approaches include serological assays and specific nested PCR assays that can yield positive and negative predictive values of over 90%. Other assays in development, such as mass spectroscopy techniques, can provide accurate and consistent results. The treatment of fusariosis in immunocompromised patients remains a challenge and the prognosis of systemic fusariosis in this population remains poor. Successful treatment is highly dependent on the particular Fusarium species involved in the infection. High dose intravenous amphotericin B formulation is recommended as the first line of therapy in management of fusariosis in patients. Voriconazole is also effective in treating fusariosis. Intolerance, contraindication, or failure of the amphotericin B formulation warrants the use of voriconazole as an alternative agent, and posaconazole is licensed as salvage therapy against invasive fusariosis. Adjunctive therapies such as surgical debridement of infected tissue, granulocyte colony stimulating factor (G-CSF) or granulocyte-macrophage colony stimulating factor (GM-CSF) infusions, or granulocyte transfusions are also tools for managing fusariosis. In conclusion, Fusarium infection is considered an emerging problem and should be suspected in immunocompromised patients experiencing systemic infection and should be treated accordingly. PMID:21304267

  7. Pair Programming: Issues and Challenges

    NASA Astrophysics Data System (ADS)

    Lui, Kim Man; Barnes, Kyle Atikus; Chan, Keith C. C.

    Pair programming, two programmers collaborating on design, coding and testing, has been a controversial focus of interest as Agile Software Development continues to grow in popularity both among academics and practitioners. As a result of the many investigations into the effectiveness of pair programming in the last decade, many have come to realize that there are many hard-to-control factors in pair programming in particular and in empirical software engineering in general. Because of these factors, the results of many pair programming experiments are not easy to replicate and the relative productivity of pair and solo programming are still not fully understood. So far, it has been concluded by previous studies that pair programming productivity can vary, but few have shown how and why this is the case. In this chapter, we discuss a number of challenging factors in the adoption of pair programming and present an approach to deal with them. We discuss how different factors may affect our experimental outcomes and improve experiment design to reveal how and why pair programming can be made productive, at least, in controlled situations.

  8. Rotavirus vaccines: successes and challenges.

    PubMed

    Glass, Roger I; Parashar, Umesh; Patel, Manish; Gentsch, Jon; Jiang, Baoming

    2014-01-01

    Since 2006, the availability of two new rotavirus vaccines has raised enthusiasm to consider the eventual control and elimination of severe rotavirus diarrhea through the global use of vaccines. Rotavirus remains the most severe cause of acute diarrhea in children worldwide responsible for several hundred thousands of deaths in low income countries and up to half of hospital admissions for diarrhea around the world. The new vaccines have been recommended by WHO for all infants and in more than 47 countries, their introduction into routine childhood immunization programs has led to a remarkable decline in hospital admissions and even deaths within 3 years of introduction. Challenges remain with issues of vaccine finance globally and the problem that these live oral vaccines perform less well in low income settings where they are needed most. Ongoing research that will accompany vaccine introduction might help address these issues of efficacy and new vaccines and novel financing schemes may both help make these vaccines universally available and affordable in the decade. PMID:24156947

  9. Peptide Vaccine: Progress and Challenges

    PubMed Central

    Li, Weidang; Joshi, Medha D.; Singhania, Smita; Ramsey, Kyle H.; Murthy, Ashlesh K.

    2014-01-01

    Conventional vaccine strategies have been highly efficacious for several decades in reducing mortality and morbidity due to infectious diseases. The bane of conventional vaccines, such as those that include whole organisms or large proteins, appear to be the inclusion of unnecessary antigenic load that, not only contributes little to the protective immune response, but complicates the situation by inducing allergenic and/or reactogenic responses. Peptide vaccines are an attractive alternative strategy that relies on usage of short peptide fragments to engineer the induction of highly targeted immune responses, consequently avoiding allergenic and/or reactogenic sequences. Conversely, peptide vaccines used in isolation are often weakly immunogenic and require particulate carriers for delivery and adjuvanting. In this article, we discuss the specific advantages and considerations in targeted induction of immune responses by peptide vaccines and progresses in the development of such vaccines against various diseases. Additionally, we also discuss the development of particulate carrier strategies and the inherent challenges with regard to safety when combining such technologies with peptide vaccines. PMID:26344743

  10. Verification Challenges at Low Numbers

    SciTech Connect

    Benz, Jacob M.; Booker, Paul M.; McDonald, Benjamin S.

    2013-06-01

    Many papers have dealt with the political difficulties and ramifications of deep nuclear arms reductions, and the issues of “Going to Zero”. Political issues include extended deterrence, conventional weapons, ballistic missile defense, and regional and geo-political security issues. At each step on the road to low numbers, the verification required to ensure compliance of all parties will increase significantly. Looking post New START, the next step will likely include warhead limits in the neighborhood of 1000 . Further reductions will include stepping stones at1000 warheads, 100’s of warheads, and then 10’s of warheads before final elimination could be considered of the last few remaining warheads and weapons. This paper will focus on these three threshold reduction levels, 1000, 100’s, 10’s. For each, the issues and challenges will be discussed, potential solutions will be identified, and the verification technologies and chain of custody measures that address these solutions will be surveyed. It is important to note that many of the issues that need to be addressed have no current solution. In these cases, the paper will explore new or novel technologies that could be applied. These technologies will draw from the research and development that is ongoing throughout the national laboratory complex, and will look at technologies utilized in other areas of industry for their application to arms control verification.

  11. Environmental epidemiology: challenges and opportunities.

    PubMed Central

    Pekkanen, J; Pearce, N

    2001-01-01

    Epidemiology is struggling increasingly with problems with correlated exposures and small relative risks. As a consequence, some scholars have strongly emphasized molecular epidemiology, whereas others have argued for the importance of the population context and the reintegration of epidemiology into public health. Environmental epidemiology has several unique features that make these debates especially pertinent to it. The very large number of environmental exposures require prioritization, and the relative risks are usually very low. Furthermore, many environmental exposures can be addressed only by comparing populations rather than individuals, and the disruption of both local and global ecosystems requires us to develop new methods of study design. The population context is also very important to consider in risk management decisions because of the involuntary nature of most environmental exposures and the diversity of possible outcomes, both health- and nonhealth-related. Studies at the individual or molecular level tend to focus the research hypotheses and subsequent interventions at that level, even when research and interventions at other levels may be more appropriate. Thus, only by starting from the population and ecosystem levels can we ensure that these are given appropriate consideration. Although better research is needed at all levels, it is crucially important to choose the most appropriate level, or levels, of research for a particular problem. Only by conducting research at all these levels and by developing further methods to combine evidence from these different levels can we hope to address the challenges facing environmental epidemiology today. PMID:11171517

  12. Using Ada: The deeper challenges

    NASA Technical Reports Server (NTRS)

    Feinberg, David A.

    1986-01-01

    The Ada programming language and the associated Ada Programming Support Environment (APSE) and Ada Run Time Environment (ARTE) provide the potential for significant life-cycle cost reductions in computer software development and maintenance activities. The Ada programming language itself is standardized, trademarked, and controlled via formal validation procedures. Though compilers are not yet production-ready as most would desire, the technology for constructing them is sufficiently well known and understood that time and money should suffice to correct current deficiencies. The APSE and ARTE are, on the other hand, significantly newer issues within most software development and maintenance efforts. Currently, APSE and ARTE are highly dependent on differing implementer concepts, strategies, and market objectives. Complex and sophisticated mission-critical computing systems require the use of a complete Ada-based capability, not just the programming language itself; yet the range of APSE and ARTE features which must actually be utilized can vary significantly from one system to another. As a consequence, the need to understand, objectively evaluate, and select differing APSE and ARTE capabilities and features is critical to the effective use of Ada and the life-cycle efficiencies it is intended to promote. It is the selection, collection, and understanding of APSE and ARTE which provide the deeper challenges of using Ada for real-life mission-critical computing systems. Some of the current issues which must be clarified, often on a case-by-case basis, in order to successfully realize the full capabilities of Ada are discussed.

  13. Challenges in product definition management

    SciTech Connect

    Trost, S.R.

    1988-04-14

    Lawrence Livermore National Laboratory (LLNL), together with other DOE agencies, is participating in a multi-year program to provide full CIM capability across four design laboratories and seven manufacturing plants. We have gained substantial experience in computer aided design, secure electronic transmission using the IGES standard, and transferring designs to our manufacturing partners. Two major shortcomings exist in current implementations: 1) IGES is insufficient to meet our needs and 2) database management and archival technologies require much more effort. We are addressing the first concern by active participation in development of the Product Definition Exchange Standard (PDES). We are also actively pursuing solutions to the second problem; we have learned that the ultimate development and application of PDES will affect data base management and archival. New challenges emerge in an electronic environment. Among these are the merging of corporate and engineering databases, lack of industry standards, many new archival technologies including optical and magnetic media, and different data formats (raster, IGES, native CAD, pilot). We must learn to manage 3 dimensional geometric data in addition to flat drawings. Producing new standards to help promote these technologies is vital. We are approaching system design and implementation by application of a multi-layer model of the drafting and records environment. This logical model lets us break down requirements into easily understood and managed entities. Included are views of the drafter, drafting room, project, and entire laboratory. This paper discusses this model and implications for other organizations. 5 refs., 4 figs.

  14. Challenges to Scaling CIGS Photovoltaics

    NASA Astrophysics Data System (ADS)

    Stanbery, B. J.

    2011-03-01

    The challenges of scaling any photovoltaic technology to terawatts of global capacity are arguably more economic than technological or resource constraints. All commercial thin-film PV technologies are based on direct bandgap semiconductors whose absorption coefficient and bandgap alignment with the solar spectrum enable micron-thick coatings in lieu to hundreds of microns required using indirect-bandgap c-Si. Although thin-film PV reduces semiconductor materials cost, its manufacture is more capital intensive than c-Si production, and proportional to deposition rate. Only when combined with sufficient efficiency and cost of capital does this tradeoff yield lower manufacturing cost. CIGS has the potential to become the first thin film technology to achieve the terawatt benchmark because of its superior conversion efficiency, making it the only commercial thin film technology which demonstrably delivers performance comparable to the dominant incumbent, c-Si. Since module performance leverages total systems cost, this competitive advantage bears directly on CIGS' potential to displace c-Si and attract the requisite capital to finance the tens of gigawatts of annual production capacity needed to manufacture terawatts of PV modules apace with global demand growth.

  15. Virtual physiological human: training challenges.

    PubMed

    Lawford, Patricia V; Narracott, Andrew V; McCormack, Keith; Bisbal, Jesus; Martin, Carlos; Bijnens, Bart; Brook, Bindi; Zachariou, Margarita; Freixa, Jordi Villà I; Kohl, Peter; Fletcher, Katherine; Diaz-Zuccarini, Vanessa

    2010-06-28

    The virtual physiological human (VPH) initiative encompasses a wide range of activities, including structural and functional imaging, data mining, knowledge discovery tool and database development, biomedical modelling, simulation and visualization. The VPH community is developing from a multitude of relatively focused, but disparate, research endeavours into an integrated effort to bring together, develop and translate emerging technologies for application, from academia to industry and medicine. This process initially builds on the evolution of multi-disciplinary interactions and abilities, but addressing the challenges associated with the implementation of the VPH will require, in the very near future, a translation of quantitative changes into a new quality of highly trained multi-disciplinary personnel. Current strategies for undergraduate and on-the-job training may soon prove insufficient for this. The European Commission seventh framework VPH network of excellence is exploring this emerging need, and is developing a framework of novel training initiatives to address the predicted shortfall in suitably skilled VPH-aware professionals. This paper reports first steps in the implementation of a coherent VPH training portfolio. PMID:20478909

  16. Clinical Bioinformatics: challenges and opportunities

    PubMed Central

    2012-01-01

    Background Network Tools and Applications in Biology (NETTAB) Workshops are a series of meetings focused on the most promising and innovative ICT tools and to their usefulness in Bioinformatics. The NETTAB 2011 workshop, held in Pavia, Italy, in October 2011 was aimed at presenting some of the most relevant methods, tools and infrastructures that are nowadays available for Clinical Bioinformatics (CBI), the research field that deals with clinical applications of bioinformatics. Methods In this editorial, the viewpoints and opinions of three world CBI leaders, who have been invited to participate in a panel discussion of the NETTAB workshop on the next challenges and future opportunities of this field, are reported. These include the development of data warehouses and ICT infrastructures for data sharing, the definition of standards for sharing phenotypic data and the implementation of novel tools to implement efficient search computing solutions. Results Some of the most important design features of a CBI-ICT infrastructure are presented, including data warehousing, modularity and flexibility, open-source development, semantic interoperability, integrated search and retrieval of -omics information. Conclusions Clinical Bioinformatics goals are ambitious. Many factors, including the availability of high-throughput "-omics" technologies and equipment, the widespread availability of clinical data warehouses and the noteworthy increase in data storage and computational power of the most recent ICT systems, justify research and efforts in this domain, which promises to be a crucial leveraging factor for biomedical research. PMID:23095472

  17. Materials Challenges in Space Exploration

    NASA Technical Reports Server (NTRS)

    Bhat, Biliyar N.

    2005-01-01

    United States civil space program administered by National Aeronautics and Space Administration has a new strategic direction to explore the solar system. This new 'vision for space exploration' encompasses a broad range of human and robotic missions, including the Moon. Mars and destinations beyond. These missions require advanced systems and capabilities that will accelerate the development of many critical technologies, including advanced materials and structural concepts. Specifically, it is planned to develop high-performance materials for vehicle structures, propulsion systems, and space suits; structural concepts for modular assembly for space infrastructure: lightweight deployable and inflatable structures for large space systems and crew habitats; and highly integrated structural systems and advanced thermal management systems for reducing launch mass and volume. This paper will present several materials challenges in advanced space systems-high performance structural and thermal materials, space durable materials, radiation protection materials, and nano-structural materials. Finally, the paper will take a look at the possibility of utilizing materials in situ, i.e., processing materials on the surface of the Moon and Mars.

  18. Challenges in Commercializing Biomimetic Membranes.

    PubMed

    Perry, Mark; Madsen, Steen Ulrik; Jørgensen, Tine; Braekevelt, Sylvie; Lauritzen, Karsten; Hélix-Nielsen, Claus

    2015-01-01

    The discovery of selective water channel proteins-aquaporins-has prompted growing interest in using these proteins, as the building blocks for designing new types of membranes. However, as with any other new and potentially disruptive technology, barriers for successful market entry exist. One category includes customer-related barriers, which can be influenced to some extent. Another category includes market-technical-related barriers, which can be very difficult to overcome by an organization/company aiming at successfully introducing their innovation on the market-in particular if both the organization and the technology are at early stages. Often, one faces barriers from both these categories at the same time, which makes it necessary to gain insight of the particular market when introducing a new innovative product. In this review we present the basic concepts and discuss some of these barriers and challenges associated with introducing biomimetic aquaporin membranes. These include technical issues in membrane production and product testing. Then we discuss possible business models for introducing new technologies in general, followed by a presentation of beach-head market segments relevant for biomimetic aquaporin membranes. PMID:26556379

  19. Catalytic nanomotors: challenges and opportunities

    NASA Astrophysics Data System (ADS)

    Gibbs, John; Zhao, Yiping

    2011-06-01

    The fabrication of integrated nanomachinary systems can enable break-through applications in nanoelectronics, photonics, bioengineering, and drug delivery or disease treatment. Naturally occurring nanomotors are biological motor proteins powered by catalytic reactions, which convert the chemical energy from the environment into mechanical energy directly. It has been demonstrated recently that using a simple catalytic reaction and an asymmetric bimetallic nanorod, one can produce catalytic nanomotors that mimic the autonomous motions of bionanomotors. Yet the construction of artificial nanomachines remains a major contemporary challenge due to the lack of a flexible fabrication technique that can design the desired dynamic components. We use a design technique called dynamic shadowing growth that allows for the fabrication of a wide range of various geometries and the asymmetric placement of the catalyst is easily accomplished as well which is necessary for directed propulsion. Programming nanomotor behavior is possible through geometrically-focused design and by incorporating different materials into the nanomotor structure is a simple process as well. A propulsion mechanism based upon bubble ejection from the catalyst surface is introduced to explain the driving force, and the comparison of this driving mechanism with the self-electrophoresis mechanism is also studied. We have also successfully incorporated multiple parts to form complex nanomotor assemblies which exhibit motions not observed from individual parts by using magnetic interactions.

  20. Challenges for Cryogenics at Iter

    NASA Astrophysics Data System (ADS)

    Serio, L.

    2010-04-01

    Nuclear fusion of light nuclei is a promising option to provide clean, safe and cost competitive energy in the future. The ITER experimental reactor being designed by seven partners representing more than half of the world population will be assembled at Cadarache, South of France in the next decade. It is a thermonuclear fusion Tokamak that requires high magnetic fields to confine and stabilize the plasma. Cryogenic technology is extensively employed to achieve low-temperature conditions for the magnet and vacuum pumping systems. Efficient and reliable continuous operation shall be achieved despite unprecedented dynamic heat loads due to magnetic field variations and neutron production from the fusion reaction. Constraints and requirements of the largest superconducting Tokamak machine have been analyzed. Safety and technical risks have been initially assessed and proposals to mitigate the consequences analyzed. Industrial standards and components are being investigated to anticipate the requirements of reliable and efficient large scale energy production. After describing the basic features of ITER and its cryogenic system, we shall present the key design requirements, improvements, optimizations and challenges.