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Sample records for hypertonically challenged imcd3

  1. Hypertonic saline challenge in an adult epidemiological survey.

    PubMed

    Rabone, S J; Phoon, W O; Anderson, S D; Wan, K C; Seneviratne, M; Gutierrez, L; Brannan, J

    1996-06-01

    Bronchial provocation tests using pharmacological agents such as methacholine or histamine are used in epidemiological studies to identify asthma despite recognition of limitations in specificity, positive predictive value and availability of reagents. Hypertonic saline (4.5%) bronchial challenge (HSBC), although less sensitive than pharmacological challenges, is reportedly highly specific in diagnosing current asthma. Added advantages are that reagents are cheap, stable and recognized by participants. Thus, HSBC may offer benefits over pharmacological tests in epidemiological surveys. This paper reports on the second field survey using the test, a study of 99 adults from the timber industry in Western Australia. The test is described and critically appraised as a practical epidemiological tool for assessing asthma prevalence. At a cutoff point of 20% FEV, fall, HSBC was positive in 8% of subjects, appeared specific for asthma, was safe, well-accepted and easy to use in the field.

  2. The voltage-dependent Cl− channel ClC-5 and plasma membrane Cl− conductances of mouse renal collecting duct cells (mIMCD-3)

    PubMed Central

    Sayer, J A; Stewart, G S; Boese, S H; Gray, M A; Pearce, S H S; Goodship, T H J; Simmons, N L

    2001-01-01

    We have tested the hypothesis that the voltage-dependent Cl− channel, ClC-5 functions as a plasma membrane Cl− conductance in renal inner medullary collecting duct cells. Full-length mouse kidney ClC-5 (mClC-5) was cloned and transiently expressed in CHO-K1 cells. Fast whole-cell patch-clamp recordings confirmed that mClC-5 expression produces a voltage-dependent, strongly outwardly rectifying Cl− conductance that was unaffected by external DIDS. Slow whole-cell recordings, using nystatin-perforated patches from transfected CHO-K1 cells, also produced voltage-dependent Cl− currents consistent with ClC-5 expression. However, under this recording configuration an endogenous DIDS-sensitive Ca2+-activated Cl− conductance was also evident, which appeared to be activated by green fluorescent protein (GFP) transfection. A mClC-5-GFP fusion protein was transiently expressed in CHO-K1 cells; confocal laser scanning microscopy (CLSM) showed localization at the plasma membrane, consistent with patch-clamp experiments. Endogenous expression of mClC-5 was demonstrated in mouse renal collecting duct cells (mIMCD-3) by RT-PCR and by immunocytochemistry. Using slow whole-cell current recordings, mIMCD-3 cells displayed three biophysically distinct Cl−-selective currents, which were all inhibited by DIDS. However, no cells exhibited whole-cell currents that had mClC-5 characteristics. Transient transfection of mIMCD-3 cells with antisense mClC-5 had no effect on the endogenous Cl− conductances. Transient transfection with sense mClC-5 failed to induce the Cl− conductance seen in CHO-K1 cells but stimulated levels of the endogenous Ca2+-activated Cl− conductance 24 h post-transfection. Confocal laser scanning microscopy of mIMCD-3 cells transfected with mClC-5-GFP showed that the protein was absent from the plasma membrane and was instead localized to acidic endosomal compartments. These data discount a major role for ClC-5 as a plasma membrane Cl− conductance in

  3. Altered plasma and pituitary arginine vasotocin and hypothalamic provasotocin expression in flounder (Platichthys flesus) following hypertonic challenge and distribution of vasotocin receptors within the kidney.

    PubMed

    Warne, J M; Bond, H; Weybourne, E; Sahajpal, V; Lu, W; Balment, R J

    2005-12-01

    Plasma AVT concentration, pituitary AVT content, hypothalamic provasotocin mRNA expression and other osmoregulatory parameters were measured in euryhaline flounder 4, 8, and 24 h after the hypertonic challenge of transfer from fresh water (FW) to seawater (SW). Osmolality and the concentration of major plasma ions, sodium and chloride, were significantly higher in fish transferred to SW by comparison with time matched controls, an effect evident within 4 h. By comparison with time matched controls, pituitary store of AVT was lower while plasma AVT concentration was higher 8 and 24 h after transfer to SW. Higher provasotocin mRNA expression in the hypothalamus was also seen at 4 and 8 h in flounder transferred from FW to SW compared with time matched controls. The lower pituitary store and higher circulating levels imply substantial AVT secretion occurs in the early phase response to this hypertonic challenge. Changes in the regulation of AVT synthesis and secretion appeared quickly following movement to SW, consistent with the rapid osmoregulatory response, including reduced urine production that fish require to accommodate the dehydrative water losses and salt loading on exposure to the new hyperosmotic environment. qPCR measures of whole kidney vasotocin receptor mRNA expression indicated similar levels in SW and FW. Immunohistochemistry for the vasotocin receptor in flounder kidney showed localisation on the afferent and efferent arterioles of the glomerulus and on the capillary bed that extends from the efferent arteriole to the smooth muscle surrounding the collecting duct. Localisation of the vasotocin receptor was comparable in SW and FW fish.

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

    PubMed Central

    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. 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

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

    PubMed

    Fathallah, Anas M; Turner, Michael R; Mager, Donald E; Balu-Iyer, Sathy V

    2015-03-01

    The subcutaneous administration of biologics is highly desirable; however, incomplete bioavailability after s.c. administration remains a major challenge. In this work we investigated the effects of excipient dependent hyperosmolarity on lymphatic uptake and plasma exposure of rituximab as a model protein. Using Swiss Webster (SW) mice as the animal model, we compared the effects of NaCl, mannitol and O-phospho-L-serine (OPLS) on the plasma concentration of rituximab over 5 days after s.c. administration. An increase was observed in plasma concentrations in animals administered rituximab in hypertonic buffer solutions, compared with 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 the improved lymphatic trafficking as evident from the increase in the fraction of dose trafficked through the lymph nodes in the presence of hypertonic buffers. The fraction of the dose trafficked through the lymphatics, as estimated by the model, increased from 0.05% in isotonic buffer to 13% in hypertonic buffer containing NaCl to about 30% for hypertonic buffers containing high dose OPLS and mannitol. The data suggest that hypertonic solutions may be a viable option for improving s.c. bioavailability.

  7. 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

  8. 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.

  9. Hypertonicity: Clinical entities, manifestations and treatment

    PubMed Central

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

    2017-01-01

    Hypertonicity causes severe clinical manifestations and is associated with mortality and severe short-term and long-term neurological sequelae. The main clinical syndromes of hypertonicity are hypernatremia and hyperglycemia. Hypernatremia results from relative excess of body sodium over body water. Loss of water in excess of intake, gain of sodium salts in excess of losses or a combination of the two are the main mechanisms of hypernatremia. Hypernatremia can be hypervolemic, euvolemic or hypovolemic. The management of hypernatremia addresses both a quantitative replacement of water and, if present, sodium deficit, and correction of the underlying pathophysiologic process that led to hypernatremia. Hypertonicity in hyperglycemia has two components, solute gain secondary to glucose accumulation in the extracellular compartment and water loss through hyperglycemic osmotic diuresis in excess of the losses of sodium and potassium. Differentiating between these two components of hypertonicity has major therapeutic implications because the first component will be reversed simply by normalization of serum glucose concentration while the second component will require hypotonic fluid replacement. An estimate of the magnitude of the relative water deficit secondary to osmotic diuresis is obtained by the corrected sodium concentration, which represents a calculated value of the serum sodium concentration that would result from reduction of the serum glucose concentration to a normal level. PMID:28101446

  10. Early Response of Protein Quality Control in Gills Is Associated with Survival of Hypertonic Shock in Mozambique tilapia

    PubMed Central

    Tang, Cheng-Hao; Lee, Tsung-Han

    2013-01-01

    The protein quality control (PQC) mechanism is essential for cell function and viability. PQC with proper biological function depends on molecular chaperones and proteases. The hypertonicity-induced protein damage and responses of PQC mechanism in aquatic organisms, however, are poorly understood. In this study, we examine the short-term effects of different hypertonic shocks on the levels of heat shock proteins (HSPs, e.g., HSP70 and HSP90), ubiquitin-conjugated proteins and protein aggregation in gills of the Mozambique tilapia (Oreochromis mossambicus). Following transfer from fresh water (FW) to 20‰ hypertonicity, all examined individuals survived to the end of experiment. Moreover, the levels of branchial HSPs and ubiquitin-conjugated proteins significantly increased at 3 and 24 h post-transfer, respectively. Up-regulation of HSPs and ubiquitin-conjugated proteins was sufficient to prevent the accumulation of aggregated proteins. However, the survival rate of tilapia dramatically declined at 5 h and all fish died within 7 h after direct transfer to 30‰ hypertonicity. We presumed that this result was due to the failed activation of gill PQC system, which resulted in elevating the levels of aggregated proteins at 3 and 4 h. Furthermore, in aggregated protein fractions, the amounts of gill Na+/K+-ATPase (NKA) remained relatively low when fish were transferred to 20‰ hypertonicity, whereas abundant NKA was found at 4 h post-transfer to 30‰ hypertonicity. This study demonstrated that the response of PQC in gills is earlier than observable changes in localization of ion-secreting transport proteins upon hypertonic challenge. To our knowledge, this is the first study to investigate the regulation of PQC mechanism in fish and characterize its important role in euryhaline teleost survival in response to hypertonic stress. PMID:23690986

  11. 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.

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

    PubMed

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

    2015-06-16

    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.

  13. [Stiff baby syndrome is a rare cause of neonatal hypertonicity].

    PubMed

    Rønne, Maria Sode; Nielsen, Preben Berg; Mogensen, Christian Backer

    2014-02-24

    Stiff baby syndrome (hyperekplexia) is a rare genetic disorder. The condition can easily be misdiagnosed as epilepsy or severe sepsis because of hypertonicity and seizure-like episodes and has an increased risk of severe apnoea and sudden infant death. Tapping of the nasal bridge inducing a startle response is the clinical hallmark. We report cases of two sisters born with stiff baby syndrome with hypertonicity, exaggerated startle reaction and cyanosis. The syndrome has a good prognosis if treated with clonazepam and both cases were developmental normal after one year.

  14. 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

  15. 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.

  16. Efflux of red cell water into buffered hypertonic solutions.

    PubMed

    OLMSTEAD, E G

    1960-03-01

    Buffered NaCl solutions hypertonic to rabbit serum were prepared and freezing point depressions of each determined after dilution with measured amounts of water. Freezing point depression of these dilutions was a linear function of the amount of water added. One ml. of rabbit red cells was added to each 4 ml. of the hypertonic solutions and after incubation at 38 degrees C. for 30 minutes the mixture was centrifuged and a freezing point depression determined on the supernatant fluid. The amount of water added to the hypertonic solutions by the red cells was calcuated from this freezing point depression. For each decrease in the freezing point of -0.093 degrees C. of the surrounding solution red cells gave up approximately 5 ml. of water per 100 ml. of red cells in the range of -0.560 to -0.930 degrees C. Beyond -0.930 degrees C. the amount of water given up by 100 ml. of red cells fits best a parabolic equation. The maximum of this equation occurred at a freezing point of the hypertonic solution of -2.001 degrees C. at which time the maximum amount of water leaving the red cells would be 39.9 ml. per 100 ml. of red cells. The data suggest that only about 43 per cent of the red cell water is available for exchange into solutions of increasing tonicity.

  17. Hypertonic saline inhibits luminal sodium channels in respiratory epithelium.

    PubMed

    Hebestreit, Alexandra; Kersting, Ulrich; Hebestreit, Helge

    2007-05-01

    Physical exercise with increased ventilation leads to a considerable rise in water loss from the airways. The mechanisms underlying the regulation of transepithelial fluid transport necessary to compensate for these losses are unknown but may include changes in luminal ion channel conductance. The present study was designed to examine the effects of an increase in luminal chloride and sodium concentrations which may locally occur during hyperventilation on luminal ion conductance in the respiratory epithelium of healthy controls and patients diagnosed with cystic fibrosis (CF). Changes in luminal chloride and sodium conductance were inferred by recording nasal potential difference in eight healthy subjects and 10 patients with CF, using superfusing solutions based on isotonic saline (150 mM) on one occasion and solutions based on hypertonic saline (300 mM) on the other. Switching from isotonic to hypertonic saline superfusion decreased potential difference in controls and CF patients significantly. Amiloride induced a decrease of potential difference which was larger with isotonic than with hypertonic saline (controls 9.5 +/- 6.1 vs. 3.7 +/- 4.6 mV; CF 17.2 +/- 7.2 vs. 9.8 +/- 7.6 mV). Chloride conductance stimulated with solutions low in chloride and containing isoproterenol was not significantly changed by hypertonic saline solutions compared with isotonic solutions in both groups. The findings indicate a significant inhibition of luminal sodium conductance by high luminal sodium concentrations. This mechanism may be involved in the regulation of fluid transport across the respiratory epithelium during exercise and in the improvement of mucociliary clearance and lung functions with inhalation of hypertonic saline in CF.

  18. Release of ATP induced by hypertonic solutions in Xenopus oocytes

    PubMed Central

    Aleu, Jordi; Martín-Satué, Mireia; Navarro, Piedad; de Lara, Ivanna Pérez; Bahima, Laia; Marsal, Jordi; Solsona, Carles

    2003-01-01

    ATP mediates intercellular communication. Mechanical stress and changes in cell volume induce ATP release from various cell types, both secretory and non-secretory. In the present study, we stressed Xenopus oocytes with a hypertonic solution enriched in mannitol (300 mm). We measured simultaneously ATP release and ionic currents from a single oocyte. A decrease in cell volume, the activation of an inward current and ATP release were coincident. We found two components of ATP release: the first was associated with granule or vesicle exocytosis, because it was inhibited by tetanus neurotoxin, and the second was related to the inward current. A single exponential described the correlation between ATP release and the hypertonic-activated current. Gadolinium ions, which block mechanically activated ionic channels, inhibited the ATP release and the inward current but did not affect the decrease in volume. Oocytes expressing CFTR (cystic fibrosis transmembrane regulator) released ATP under hypertonic shock, but ATP release was significantly inhibited in the first component: that related to granule exocytosis. Since the ATP measured is the balance between ATP release and ATP degradation by ecto-enzymes, we measured the nucleoside triphosphate diphosphohydrolase (NTPDase) activity of the oocyte surface during osmotic stress, as the calcium-dependent hydrolysis of ATP, which was inhibited by more than 50 % in hypertonic conditions. The best-characterized membrane protein showing NTPDase activity is CD39. Oocytes injected with an antisense oligonucleotide complementary to CD39 mRNA released less ATP and showed a lower amplitude in the inward current than those oocytes injected with water. PMID:12562935

  19. 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.

  20. Treatment of hypertonicity in muscles of lip retraction.

    PubMed

    Hand, C R; Burns, M O; Ireland, E

    1979-06-01

    An EMG biofeedback program was developed for a 56-year-old Parkinsonism patient who exhibited pathological lip hypertonia and retraction. The program was designed to achieve the following goals: (1) to demonstrate a reduction in postural lip hypertonicity and (2) to demonstrate a reduction in lip hypertonicity during a series of increasingly complex speech activities. To achieve the first goal, contrastive tasks of full contraction and relaxation were utilized. Each posture was sustained while voltage measurements were made at specific intervals. Procedures to modify lip retraction during speech included five tasks in which the patient was to monitor the audio feedback signal. The tasks involved: prolongation of a neutral vowel, consonant-vowel combinations, monosyllabic words, sentences, and a paragraph-reading task. Data collected over six biofeedback sessions are presented. Trend analyses showed consistent muscular reduction within each task. The following explanations for the decrease in the patient's hypertonicity were discussed: (1) reduction of anisometric contraction, (2) reduction of isometric contraction, (3) relearning of agonistic-antagonistic muscle balance.

  1. 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

  2. Cap-independent protein synthesis is enhanced by betaine under hypertonic conditions.

    PubMed

    Carnicelli, Domenica; Arfilli, Valentina; Onofrillo, Carmine; Alfieri, Roberta R; Petronini, Pier Giorgio; Montanaro, Lorenzo; Brigotti, Maurizio

    2017-02-12

    Protein synthesis is one of the main cellular functions inhibited during hypertonic challenge. The subsequent accumulation of the compatible osmolyte betaine during the later adaptive response allows not only recovery of translation but also its stimulation. In this paper, we show that betaine modulates translation by enhancing the formation of cap-independent 48 S pre-initiation complexes, leaving cap-dependent 48 S pre-initiation complexes basically unchanged. In the presence of betaine, CrPV IRES- and sodium-dependent neutral amino acid transporter-2 (SNAT2) 5'-UTR-driven translation is 2- and 1.5-fold stimulated in MCF7 cells, respectively. Thus, betaine could provide an advantage in translation of messengers coding for proteins implicated in the response of cells to different stressors, which are often recognized by ribosomal 40 S subunit through simplified cap-independent mechanisms.

  3. Membrane potential stabilization in amphibian skeletal muscle fibres in hypertonic solutions

    PubMed Central

    Ferenczi, Emily A; Fraser, James A; Chawla, Sangeeta; Skepper, Jeremy N; Schwiening, Christof J; Huang, Christopher L-H

    2004-01-01

    This study investigated membrane transport mechanisms influencing relative changes in cell volume (V) and resting membrane potential (Em) following osmotic challenge in amphibian skeletal muscle fibres. It demonstrated a stabilization of Em despite cell shrinkage, which was attributable to elevation of intracellular [Cl−] above electrochemical equilibrium through Na+–Cl− and Na+−K+−2Cl− cotransporter action following exposures to extracellular hypertonicity. Fibre volumes (V) determined by confocal microscope xz-scanning of cutaneous pectoris muscle fibres varied linearly with [1/extracellular osmolarity], showing insignificant volume corrections, in fibres studied in Cl−-free, normal and Na+-free Ringer solutions and in the presence of bumetanide, chlorothiazide and ouabain. The observed volume changes following increases in extracellular tonicity were compared with microelectrode measurements of steady-state resting potentials (Em). Fibres in isotonic Cl−-free, normal and Na+-free Ringer solutions showed similar Em values consistent with previously reported permeability ratios PNa/PK(0.03–0.05) and PCl/PK (∼2.0) and intracellular [Na+], [K+] and [Cl−]. Increased extracellular osmolarities produced hyperpolarizing shifts in Em in fibres studied in Cl−-free Ringer solution consistent with the Goldman-Hodgkin-Katz (GHK) equation. In contrast, fibres exposed to hypertonic Ringer solutions of normal ionic composition showed no such Em shifts, suggesting a Cl−-dependent stabilization of membrane potential. This stabilization of Em was abolished by withdrawing extracellular Na+ or by the combined presence of the Na+–Cl− cotransporter (NCC) inhibitor chlorothiazide (10 μm) and the Na+−K+−2Cl− cotransporter (NKCC) inhibitor bumetanide (10 μm), or the Na+−K+-ATPase inhibitor ouabain (1 or 10 μm) during alterations in extracellular osmolarity. Application of such agents after such increases in tonicity only produced a

  4. Vasopressin responses to corticotropin-releasing factor and hypertonicity after truncal vagotomy in dogs.

    PubMed

    Raff, H; Papanek, P E; Cowles, V E

    1996-01-01

    Infusion of corticotropin-releasing factor (CRF) augments the plasma vasopressin response to infusion of hypertonic saline in conscious dogs. Furthermore, afferent vagal nerve input from the abdomen is involved in the control of vasopressin release and may be altered by CRF. The purpose of the present study was to characterize the effect of CRF on the vasopressin response to hypertonic saline and to determine if it is mediated by afferent input carried from the abdominal vagus. Conscious male dogs (n = 5) underwent infusion of isotonic saline (vehicle), CRF (10 or 20 ng.kg-1.min-1), hypertonic saline (0.2 mmol.kg-1.min-1), or the combination of CRF and hypertonic saline. Hypertonic saline increased plasma sodium from 147 +/- 1 to 153 +/- 1 meq/1 and plasma vasopressin from 2.5 +/- 0.1 to 5.8 +/- 0.4 pg/ml. CRF infusion alone had no effect on plasma vasopressin. The addition of 10 or 20 ng.kg-1.min-1 CRF augmented the vasopressin response to hypertonic saline to 7.7 +/- 1.7 and 6.9 +/- 0.3 pg/ml, respectively. Truncal vagotomy did not attenuate the vasopressin response to hypertonic saline with or without CRF infusion. We conclude that CRF augments the vasopressin response to hypertonic saline and that this effect is not mediated via afferents from the abdominal vagus.

  5. 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

  6. Protein kinase Cmu plays an essential role in hypertonicity-induced heat shock protein 70 expression.

    PubMed

    Lim, Yun Sook; Lee, Jae Seon; Huang, Tai Qin; Seo, Jeong Sun

    2008-12-31

    Heat shock protein 70 (HSP70), which evidences important functions as a molecular chaperone and anti-apoptotic molecule, is substantially induced in cells exposed to a variety of stresses, including hypertonic stress, heavy metals, heat shock, and oxidative stress, and prevents cellular damage under these conditions. However, the molecular mechanism underlying the induction of HSP70 in response to hypertonicity has been characterized to a far lesser extent. In this study, we have investigated the cellular signaling pathway of HSP70 induction under hypertonic conditions. Initially, we applied a variety of kinase inhibitors to NIH3T3 cells that had been exposed to hypertonicity. The induction of HSP70 was suppressed specifically by treatment with protein kinase C (PKC) inhibitors (Gö6976 and GF109203X). As hypertonicity dramatically increased the phosphorylation of PKCmu, we then evaluated the role of PKCmu in hypertonicity-induced HSP70 expression and cell viability. The depletion of PKCmu with siRNA or the inhibition of PKCmu activity with inhibitors resulted in a reduction in HSP70 induction and cell viability. Tonicity-responsive enhancer binding protein (TonEBP), a transcription factor for hypertonicity-induced HSP70 expression, was translocated rapidly into the nucleus and was modified gradually in the nucleus under hypertonic conditions. When we administered treatment with PKC inhibitors, the mobility shift of TonEBP was affected in the nucleus. However, PKCmu evidenced no subcellular co-localization with TonEBP during hypertonic exposure. From our results, we have concluded that PKCmu performs a critical function in hypertonicity-induced HSP70 induction, and finally cellular protection, via the indirect regulation of TonEBP modification.

  7. Rationale for hypertonic saline therapy for cystic fibrosis lung disease.

    PubMed

    Tarran, Robert; Donaldson, Scott; Boucher, Richard C

    2007-06-01

    Cystic fibrosis (CF) is caused by alterations in the CF transmembrane conductance regulator ( CFTCR) gene. More than 1400 mutations in the CFTCR gene have been described, but the most common mutation (noted in 70% of CF chromosomes) is DeltaF508. Alterations in the CFTCR gene result in deranged sodium and chloride ion transport channels. This leads to failure of airway epithelia to hydrate their surfaces normally, particularly in response to infectious or toxic insults. Additional effects include mucus adhesion to airway surface, chronic inflammation, and infections. The concept that airway surface dehydration can cause CF-like lung disease is supported by in vitro data and in vivo animal models. Rehydrating airway surfaces may reduce or prevent lung injury and damage. Short- and longer term studies have shown that inhalation of hypertonic saline is well tolerated and improves lung function, reduces exacerbations, and improves quality of life in CF patients. This review discusses the importance of airway epithelial sodium and chloride channels in the pathogenesis of CF, and strategies (particularly the use of inhaled hypertonic saline) to reverse or minimize lung inflammation and injury in this disease.

  8. Intradermal microdialysis of hypertonic saline attenuates cutaneous vasodilatation in response to local heating.

    PubMed

    DuPont, Jennifer J; Farquhar, William B; Edwards, David G

    2011-07-01

    We tested the hypothesis that microdialysis of hypertonic saline would attenuate the skin blood flow response to local heating. Seventeen healthy subjects (23 ± 1 years old) were studied. In one group (n = 9), four microdialysis fibres were placed in the forearm skin and infused with the following: (1) Ringer solution; (2) normal saline (0.9% NaCl); (3) hypertonic saline (3% NaCl); and (4) 10 mm l-NAME. A second group (n = 8) was infused with the following: (1) normal saline; (2) hypertonic saline; (3) normal saline + l-NAME; and (4) hypertonic saline + l-NAME. Red blood cell flux was measured via laser Doppler flowmetry during local heating to 42°C. Site-specific maximal vasodilatation was determined by infusing 28 mm sodium nitroprusside while the skin was heated to 43°C. Data were expressed as the percentage of maximal cutaneous vascular conductance (%CVC(max)). The local heating response at the Ringer solution and normal saline sites did not differ (n = 9; initial peak Ringer solution, 69 ± 6 versus normal saline, 66 ± 2%CVC(max); plateau Ringer solution, 89 ± 4 versus normal saline, 89 ± 5%CVC(max)). Hypertonic saline reduced the initial peak (n = 9; normal saline, 66 ± 2 versus hypertonic saline, 54 ± 4%CVC(max); P < 0.05) and plateau (normal saline, 89 ± 5 versus hypertonic saline, 78 ± 2%CVC(max); P < 0.05) compared with normal saline. Plateau %CVC(max) was attenuated to a similar value at the normal saline + l-NAME and hypertonic saline + l-NAME sites (n = 8; normal saline + l-NAME, 39 ± 6 and hypertonic saline + l-NAME, 39 ± 5%CVC(max)). The nitric oxide contribution (plateau %CVC(max) - l-NAME plateau %CVC(max)) was lower at the hypertonic saline site (normal saline, 55 ± 6 versus hypertonic saline, 35 ± 4; P < 0.01). These data suggest an effect of salt on the cutaneous response to local heating, which may be mediated through a decreased production and/or availability of nitric oxide.

  9. What are the effects of hypertonic saline plus furosemide in acute heart failure?

    PubMed

    Zepeda, Patricio; Rain, Carmen; Sepúlveda, Paola

    2015-08-27

    In search of new therapies to solve diuretic resistance in acute heart failure, the addition of hypertonic saline has been proposed. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified two systematic reviews including nine pertinent randomized controlled trials. We combined the evidence and generated a summary of findings following the GRADE approach. We concluded hypertonic saline associated with furosemide probably decrease mortality, length of hospital stay and hospital readmission in patients with acute decompensated heart failure.

  10. Dose Response Effects of Hypertonic Saline and Dextran on Cardiovascular Responses in Sheep

    DTIC Science & Technology

    1995-02-01

    137-144, 1995 DOSE RESPONSE EFFECTS OF HYPERTONIC SALINE AND DEXTRAN ON CARDIOVASCULAR RESPONSES AND PLASMA VOLUME EXPANSION IN SHEEP Michael A...addressed the dose - response effects of HS or D-70 solutions or their possible synergistic combinations to evaluate optimal concentrations of the HS and D...205-217, 1989. 13. Halvorsen L, Günther RA, Dubick MA, Holcroft JW: Dose response characteristics of hypertonic saline dextran solution. J Trauma

  11. 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

  12. Hypertonicity enhances GABA uptake by cultured rat retinal capillary endothelial cells.

    PubMed

    Yahara, Tohru; Tachikawa, Masanori; Akanuma, Shin-ichi; Hosoya, Ken-ichi

    2010-01-01

    We have reported previously that taurine transporter (TauT) mediates γ-aminobutyric acid (GABA) as a substrate in a conditionally immortalized rat retinal capillary endothelial cell line (TR-iBRB2 cells). This study investigates how TauT-mediated GABA transport is regulated in TR-iBRB2 cells under hypertonic conditions. [³H]GABA uptake by TR-iBRB2 cells exposed to 12 h- to 24 h-hypertonic culture medium was significantly greater than that of isotonic culture medium. [³H]GABA uptake by TR-iBRB2 cells was Na(+)-, Cl(-)-, and concentration-dependent with a Michaelis-Menten (K(m)) constant of 3.5 mM under isotonic conditions and K(m) of 0.324 and 5.48 mM under hypertonic conditions. Under hypertonic conditions, [³H]GABA uptake by TR-iBRB2 cells was more potently inhibited by substrates of TauT, such as taurine and β-alanine, than those of GABA transporters such as GABA, nipecotic acid, and betaine. These results suggest that an unknown high-affinity GABA transport process and TauT-mediated GABA transport are enhanced under hypertonic conditions. In conclusion, hypertonicity enhances GABA uptake by cultured rat retinal capillary endothelial cells.

  13. Effects of hypertonic perfusion on the ultrastructure of frog cardiac muscle.

    PubMed

    Hatae, J; Kawata, H

    1978-11-01

    The ultrastructural changes induced by hypertonic perfusion were investigated using the ventricular muscle of the bullfrog. It was demonstrated that the fixative tonicity critically affects the ultrastructure. Effects of sucrose-, NaCl- and urea-hypertonicities were investigated and compared. In both sucrose- and NaCl-hypertonic media, although the cardiac muscle strongly shrank and the extracellular spaces markedly increased according to increasing tonicity the width of the intercalated disc cleft remained unchanged and the cleft was never separated even in 3 times hypertonicity. The sucrose-hypertonicity made the feature of the fine structure extremely obscure and the electron densities in both the Z-line and the intercalated disc region markedly decreased. When both the perfusate and fixative were made hypertonic by urea, which is known to easily penetrate the cell membrane, a shrinkage of the myocardial cells was observed but to a lesser extent as compared with sucrose or NaCl. The striation pattern was disordered in this condition though the intercalated discs were never affected.

  14. Creatine as a compatible osmolyte in muscle cells exposed to hypertonic stress

    PubMed Central

    Alfieri, Roberta R; Bonelli, Mara A; Cavazzoni, Andrea; Brigotti, Maurizio; Fumarola, Claudia; Sestili, Piero; Mozzoni, Paola; De Palma, Giuseppe; Mutti, Antonio; Carnicelli, Domenica; Vacondio, Federica; Silva, Claudia; Borghetti, Angelo F; Wheeler, Kenneth P; Petronini, Pier Giorgio

    2006-01-01

    Exposure of C2C12 muscle cells to hypertonic stress induced an increase in cell content of creatine transporter mRNA and of creatine transport activity, which peaked after about 24 h incubation at 0.45 osmol (kg H2O)−1. This induction of transport activity was prevented by addition of either cycloheximide, to inhibit protein synthesis, or of actinomycin D, to inhibit RNA synthesis. Creatine uptake by these cells is largely Na+ dependent and kinetic analysis revealed that its increase under hypertonic conditions resulted from an increase in Vmax of the Na+-dependent component, with no significant change in the Km value of about 75 μmol l−1. Quantitative real-time PCR revealed a more than threefold increase in the expression of creatine transporter mRNA in cells exposed to hypertonicity. Creatine supplementation significantly enhanced survival of C2C12 cells incubated under hypertonic conditions and its effect was similar to that obtained with the well known compatible osmolytes, betaine, taurine and myo-inositol. This effect seemed not to be linked to the energy status of the C2C12 cells because hypertonic incubation caused a decrease in their ATP content, with or without the addition of creatine at 20 mmol l−1 to the medium. This induction of creatine transport activity by hypertonicity is not confined to muscle cells: a similar induction was shown in porcine endothelial cells. PMID:16873409

  15. Hypertonic saline up-regulates A3 adenosine receptors expression of activated neutrophils and increases acute lung injury after sepsis

    PubMed Central

    Inoue, Yoshiaki; Chen, Yu; Pauzenberger, Reinhard; Mark, Hirsh I.; Junger, Wolfgang G.

    2008-01-01

    Objective Hypertonic saline resuscitation reduces tissue damage by inhibiting polymorphonuclear neutrophils. Hypertonic saline triggers polymorphonuclear neutrophils to release adenosine triphosphate that is converted to adenosine, inhibiting polymorphonuclear neutrophils through A2a adenosine receptors. polymorphonuclear neutrophils also express A3 adenosine receptors that enhance polymorphonuclear neutrophils functions. Here we investigated whether A3 receptors may diminish the efficacy of hypertonic saline in a mouse model of acute lung injury. Design Randomized animal study and laboratory investigation. Setting University research laboratory. Interventions The effect of A3 receptors on the efficacy of hypertonic saline resuscitation was assessed in A3 receptor knockout and wild-type mice. Animals were treated with hypertonic saline (7.5% NaCl, 4 mL/kg) before or after cecal ligation and puncture, and acute lung injury and mortality were determined. The effect of timing of hypertonic saline exposure on A3 receptor expression and degranulation was studied in vitro with isolated human polymorphonuclear neutrophils. Measurements and main results Treatment of human polymorphonuclear neutrophils with hypertonic saline before stimulation with formyl methionyl-leucyl-phenylalanine inhibited A3 receptor expression and degranulation, whereas hypertonic saline-treatment after formyl methionyl-leucyl-phenylalanine-stimulation augmented A3 receptor expression and degranulation. Acute lung injury in wild-type mice treated with hypertonic saline after cecal ligation and puncture was significantly greater than in wild-type mice pretreated with hypertonic saline. This aggravating effect of delayed hypertonic saline-treatment was absent in A3 receptor knockout mice. Similarly, mortality in wild-type mice with delayed hypertonic saline-treatment was significantly higher (88%) than in animals treated with hypertonic saline before cecal ligation and puncture (50%). Mortality in A3

  16. 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

  17. Abstracts of the International Conference on Hypertonic Resuscitation (5th) Held in Galveston, Texas on 3-5 June 1992

    DTIC Science & Technology

    1992-08-01

    Intracranial Hypertension: Mannitol us. Hypertonlc/Hyperoncotic Saline/ Dextran R. Harti (Munich, Germany): Hypertonic/Hyperoncotic Solutions in Traumatic...Hyperoncotic Saline Oextran (HHS: 7.2% NaCI/18% Dextran 66) Instantaneously Restores Gut Mucosal Blood Flow (BF). K. Kesel (Munich, Germany): Hypertonic...Hyperoncotic Resuscitation from Hemorrhagic Shock Effectively Improves Intramucosal Acidosis. C. Com (Galveston, U.S.A.): Hypertonic Saline- Dextran Does

  18. Immunomodulatory effect of hypertonic saline in hemorrhagic shock.

    PubMed

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

    2015-10-05

    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.

  19. 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)

  20. 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.)

  1. 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

  2. Hypertonic Saline Resuscitation Restores Inflammatory Cytokine Balance in Post-Traumatic Hemorrhagic Shock Patients

    DTIC Science & Technology

    2004-08-01

    immunocompetant cells experience bidirectional communication with hormones and cytokines [35,40]. Thus, despite compelling experimental findings, HSD has not...hypertonic saline with 6% dextran-70 (HSD) has been shown in experimental studies to reduce shock/resuscitation-induced inflammatory reactions and...alterations have been described in clinical and experimental investigations of post-traumatic hemorrhagic shock [13]. The initial immunological

  3. Hypertonic Saline Resuscitation Restores Inflammatory Cytokine Balance in Post-Traumatic Hemorrhagic Shock Patients

    DTIC Science & Technology

    2004-09-01

    hypertonic saline with 6% dextran-70 (HSD) has been shown in experimental studies to reduce shock/resuscitation-induced inflammatory reactions and...hemodynamics and reestablishing inflammatory equilibrium [12]. Various immunoinflammatory alterations have been described in clinical and experimental ...ultimately causing greater morbidity and mortality [4]. Moreover, convincing experimental evidence indicates that conventional large-volume fluid

  4. Cerebral regulation of renal sodium excretion in sheep infused intravenously with hypertonic NaCl.

    PubMed Central

    Chodobski, A; McKinley, M J

    1989-01-01

    1. The natriuretic response to intravenous infusion of 2 M-NaCl was investigated in six conscious sheep. This hypertonic NaCl load resulted in relatively small, physiological (2-3 mmol l-1) increases in plasma Na+ concentration and was followed by a natriuresis with a maximum mean urinary sodium excretion 5 times higher than pre-infusion values. 2. Intravenous infusion of isotonic NaCl, delivering the same Na+ load as hypertonic NaCl infusion, did not induce natriuresis. This suggested, therefore, that with the hypertonic sodium load administered in the present study, the rise in plasma Na+ and/or tonicity rather than increase in blood volume is important in evoking the natriuretic response. 3. Intracerebroventricular infusion of low-Na+ artificial cerebrospinal fluid (CSF) reduced CSF Na+ concentration, decreased plasma vasopressin (AVP) levels and caused a copious water diuresis. This was associated with excessive loss of water and large increases in plasma Na+ concentration and osmolality. 4. The natriuresis induced by intravenous hypertonic NaCl load could be blocked by lowering CSF Na+ concentration in situations where water diuresis was either prevented or reduced by intravenous infusion of AVP or by delayed intracerebroventricular infusion of low-Na+ CSF, respectively. 5. The results of the present study provide further evidence that renal sodium excretion can be controlled by the central nervous system. PMID:2621619

  5. Dose Effect of HSD (Hypertonic Saline/Dextran) Survival Following Hemorrhage

    DTIC Science & Technology

    1989-06-01

    injured patients. Ann Surg 1987;206:279-288. 6. Kramer GC, Perron PR, Lindsey C , et al. Small-volume resuscitation with hypertonic saline dextran...No.3:297-298. 12. Greenfield RH, Bessen HA, Henneman PL. Effect of crystalloid infusion on hematocrit and intravascular volume in healthy, nonbleeding

  6. The hypertonic environment differentially regulates wild-type CFTR and TNR-CFTR chloride channels.

    PubMed

    Lassance-Soares, Roberta M; Cheng, Jie; Krasnov, Kristina; Cebotaru, Liudmila; Cutting, Garry R; Souza-Menezes, Jackson; Morales, Marcelo M; Guggino, William B

    2010-01-01

    This study tested the hypotheses that the hypertonic environment of the renal medulla regulates the expression of cystic fibrosis transmembrane conductance regulator protein (CFTR) and its natural splice variant, TNR-CFTR. To accomplish this, Madin-Darby canine kidney (MDCK) stable cell lines expressing TNR-CFTR or CFTR were used. The cells were treated with hypertonic medium made with either NaCl or urea or sucrose (480 mOsm/kg or 560 mOsm/kg) to mimic the tonicity of the renal medulla environment. Western blot data showed that CFTR and TNR-CFTR total cell protein is increased by hypertonic medium, but using the surface biotinylation technique, only CFTR was found to be increased in cell plasma membrane. Confocal microscopy showed TNR-CFTR localization primarily at the endoplasmic reticulum and plasma membrane. In conclusion, CFTR and TNR-CFTR have different patterns of distribution in MDCK cells and they are modulated by a hypertonic environment, suggesting their physiological importance in renal medulla.

  7. Hypertonic saline attenuates TNF-alpha-induced NF-kappaB activation in pulmonary epithelial cells.

    PubMed

    Nydam, Trevor L; Moore, Ernest E; McIntyre, Robert C; Wright, Franklin L; Gamboni-Robertson, Fabia; Eckels, Phillip C; Banerjee, Anirban

    2009-05-01

    Resuscitation with hypertonic saline (HTS) attenuates acute lung injury (ALI) and modulates postinjury hyperinflammation. TNF-alpha-stimulated pulmonary epithelium is a major contributor to hemorrhage-induced ALI. We hypothesized that HTS would inhibit TNF-alpha-induced nuclear factor (NF)-kappaB proinflammatory signaling in pulmonary epithelial cells. Therefore, we pretreated human pulmonary epithelial cells (A549) with hypertonic medium (180 mM NaCl) for 30 min, followed by TNF-alpha stimulation (10 ng/mL). Key regulatory steps and protein concentrations in this pathway were assessed for significant alterations. Hypertonic saline significantly reduced TNF-alpha-induced intercellular adhesion molecule 1 levels and NF-kappaB nuclear localization. The mechanism is attenuated phosphorylation and delayed degradation of IkappaB alpha. Hypertonic saline did not alter TNF-alpha-induced p38 mitogen-activated protein kinase phosphorylation or constitutive vascular endothelial growth factor expression, suggesting that the observed inhibition is not a generalized suppression of protein phosphorylation or cellular function. These results show that HTS inhibits TNF-alpha-induced NF-kappaB activation in the pulmonary epithelium and, further, our understanding of its beneficial effects in hemorrhage-induced ALI.

  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. 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

  10. [Peritoneal equilibrium test with hypertonic exchange: practical application in a peritoneal dialysis program].

    PubMed

    Ortiz, A; Marrón, B; Berlanga, J R; Reyero, A; Gazapo, R

    2001-01-01

    Peritoneal equilibration test (PET) employing a 2.27%/2.5% glucose exchange is the most widely used method of to evaluating peritoneal function and small solute transport. Hypertonic (3.86%/4.25% glucose) PET has been recently recommended for the evaluation of ultrafiltration and to study certain causes of ultrafiltration failure, such as aquaporin dysfunction, through the analysis of dialysate sodium. However, there is not enough information on the optimal way to express the changes in dialysate sodium concentration, the normal range of values for this parameter, and possible adverse effects of hypertonic PET in the general population of peritoneal dialysis patients. A hypertonic PET was performed in 22 patients. Ultrafiltration failure (ultrafiltration < 0.4 L) was present in seven patients. Patients with ultrafiltration failure had higher small solute peritoneal transport and dialysate sodium concentration and had been treated with peritoneal dialysis for longer periods of time. Dialysate sodium concentration at 60 and 240 minutes was directly correlated with small solute peritoneal transport calculated as D/PCr240 (r = 0.74, p = 0.0008 y r = 0.84, p < 0.0001) and inversely correlated with ultrafiltration (r = 0.64, p = 0.0016 y r = 0.72, p = 0.0002). An absence of a dip in dialysis sodium, suggestive of aquaporin dysfunction, was only observed in one patient with a high-average small solute peritoneal transport. Dialysate sodium concentration at 60 minutes is a better discriminator between ultrafiltration failure patients than parameters such as D/PNa or the absolute dip in dialysate sodium with respect to time zero. We observed the following adverse effects: symptomatic hypotension in 2 patients with preserved ultrafiltration. In conclusion, hypertonic PET allows to confirm the diagnosis of ultrafiltration failure, but monitoring dialysate sodium concentration offers additional information only in patients with severe aquaporin dysfunction. Hypertonic PET may

  11. The cardioprotective effect of hypertonic saline is associated with inhibitory effect on macrophage migration inhibitory factor in sepsis.

    PubMed

    Wang, Yi-Li; Lam, Kwok-Keung; Cheng, Pao-Yun; Kung, Ching-Wen; Chen, Shu-Ying; Chao, Chun-Chih; Hwang, Hwong-Ru; Chung, Ming-Ting; Lee, Yen-Mei

    2013-01-01

    Sepsis can cause myocardial dysfunction, which contributes to the high mortality of sepsis. Hypertonic saline (HS) has been reported to increase myocardial contractility in sepsis. In the present study, mechanisms of action of HS resuscitation (4 mL of 7.5% NaCl per kilogram) on cardiac function have been evaluated in septic rats. HS was administered 1 h after LPS (10 mg/kg, i.v.) challenge. The mean arterial blood pressure significantly decreased 4 h after LPS challenge, and septic shock was observed at the end of experiment (6 h). Posttreatment with HS prevented hypotension caused by LPS and significantly improved cardiac function, evidenced by increases in left ventricular developed pressure, mean +dP/dt and -dP/dt. The amplitude of electrical-stimulated intracellular Ca(2+) transient in isolated single cardiomyocytes was significantly reduced after 6 h LPS insult, which was recovered by HS. In addition, LPS resulted in significant increases in neutrophil myeloperoxidase activity, macrophage migration inhibitory factor (MIF), and NF-κB phospho-p65 protein levels in myocardium at 6 h, which were significantly attenuated by HS. In conclusion, HS improved myocardial contractility and prevented circulatory failure induced by endotoxemia, which may attribute to improvement of intracellular calcium handling process and inhibitory effects on neutrophil infiltration and MIF production in hearts.

  12. Superiority of Hypertonic Saline/Dextran Over Hypertonic Saline during the First 30 Minutes of Resuscitation Following Hemorrhagic Hypotension in Conscious Swine

    DTIC Science & Technology

    1989-06-01

    Comole:ion. :mediately after nerorrhage, zne swine were aarnin stereo nyoer:cn c sal ine/dextran or hyper~onc saline at 4 mi/kg, and 4finCtiona; variac as... C , Ho HS, Gunther RA, Boyle WA, Holcroft JW. Small-volume resuscitation with hypertonic saline dextran solution. Surg 1986;100(No. 2):239-246. 2...concept. J Trauma 1985;25:65-70. 11. Border JR, Lewis FR, Aprahamian C , Haller JA, Jacobs LM, Luterman A. Prehospital trauma care--stabilize or scoop and

  13. Cysteinyl Leukotriene Antagonism Inhibits Bronchoconstriction in Respose to Hypertonic Saline Inhalation in Asthma

    PubMed Central

    Kazani, Shamsah; Sadeh, Jonathan; Bunga, Sreedhar; Wechsler, Michael E; Israel, Elliot

    2010-01-01

    Background In asthma, cysteinyl leukotrienes (CysLTs) play varying roles in the bronchomotor response to multiple provocative stimuli. The contribution of CysLTs on the airway's response to hypertonic saline (HS) inhalation in asthma is unknown. Whether polymorphisms in the leukotriene biosynthetic pathway affect the contribution of CysLTs to this response is also unknown. Methods In a prospective, randomized, double blind, placebo-controlled cross-over study, mild and moderate asymptomatic asthmatics underwent inhaled 3% HS challenge by doubling the duration of nebulization (0.5, 1, 2, 4, and 8 min) two hours after one dose of montelukast (a CysLT receptor 1 [CysLTR1] antagonist) or placebo, and after three week courses. We examined the effect of the leukotriene C4 synthase (LTC4S) polymorphism (A-444C) on the efficacy of montelukast against HS inhalation in an exploratory manner. Results In 37 subjects, two hours after administration of montelukast, the mean provocative dose of HS required to cause a 20% drop in FEV1 (HS-PD20) increased by 59% (9.17 after placebo vs. 14.55 ml after montelukast, p = 0.0154). Three weeks of cysLTR1 antagonism increased the HS-PD20 by 84% (10.97 vs. 20.21 ml, p = 0.0002). Three weeks of CysLTR1 antagonism appeared to produce greater effects on blocking bronchial hyper responsiveness (two hour vs. three week HS-PD20 values 14.55 vs. 20.21 ml respectively, p = 0.0898). We did not observe an effect of the LTC4S polymorphism on the response to CysLTR1 antagonism in this cohort. Conclusions A significant proportion of HS-induced bronchoconstriction is mediated by release of leukotrienes as evidenced by substantial acute inhibition with a CysLTR1 antagonist. There was a trend toward greater inhibition of bronchial responsiveness with three weeks of therapy as opposed to acute CysLTR1 antagonism. PMID:21169002

  14. 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

  15. 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

  16. Hypertonic sabouraud broth as a simple and powerful test for Candida dubliniensis screening.

    PubMed

    Alves, Sydney Hartz; Milan, Eveline Pipolo; de Laet Sant'Ana, Priscilla; Oliveira, Loiva O; Santurio, Janio M; Colombo, Arnaldo Lopes

    2002-05-01

    We developed a new screening test for C. dubliniensis based on its inability to grow on Sabouraud dextrose broth with 6.5% NaCl. A total of 266 clinical yeast isolates and 3 reference strains were tested, including 250 C. albicans and 19 C. dubliniensis strains. All C. albicans isolates tested exhibited significant growth on hypertonic Sabouraud broth up to 96 h, while, all C. dubliniensis isolates did not exhibit any visually detectable growth during the same period.

  17. Emergency anesthesia for evacuating a traumatic acute subdural hemorrhage in a child overdosed with hypertonic saline

    PubMed Central

    Goonasekera, Chulananda; Bedford, James; Harpreet, Sodhi; Giombini, Mariangela; Sheikh, Asme

    2016-01-01

    A previously healthy 1-year-old child with a traumatic acute subdural hemorrhage received 10 times higher dose of hypertonic saline inadvertently immediately before surgery. This case report describes deviations in fluid management needed to alleviate salt toxicity and its adverse effects during surgery under anesthesia perioperatively. The child made an uneventful recovery with no evident residual damage at follow-up. PMID:28217157

  18. Combination of Hot-Hypertonic Saline and Pressure Dressing in the Management of Parotid Fistula.

    PubMed

    Aisha; Fatima, Saira; Memon, Aijaz Ahmed

    2015-12-01

    Parotid fistula is a rare complication of surgical or non-surgical trauma on or in the vicinity of parotid gland. Many pharmacological agents and surgical methods are used to treat it with their own merits, demerits and patient preferences. Injection of hypertonic hot saline along with compression dressing is an economical, patient-preferred and almost complication-free method to deal parotid fistula with promising results.

  19. Effects of hypertonic saline infusion and water drinking on atrial peptide.

    PubMed

    Salazar, F J; Granger, J P; Joyce, M L; Burnett, J C; Bove, A A; Romero, J C

    1986-12-01

    This study was undertaken to define the changes in plasma levels of atrial natriuretic peptide (ANP) induced by hypertonic saline infusion followed by spontaneous water drinking and to determine whether these changes in ANP are correlated with changes in right atrial pressure (RAP) and plasma levels of vasopressin (AVP). Conscious dogs (n = 5) were infused with hypertonic saline (6%) at a rate of 1.4 ml/min for 4 h. Water was withheld for the first 2 h and administered ad libitum for the final 2 h. Hypertonic saline infusion induced increases (P less than 0.05) in plasma osmolality (posM), pAVP, mean arterial pressure (MAP), and RAP (1.9 +/- 0.6 to 3.1 +/- 0.7 mmHg). These changes were accompanied by an increase of pANP (68 +/- 14 to 120 +/- 33 pg/ml, P less than 0.05). Spontaneous water drinking (1,410 +/- 127 ml) returned posM and pAVP to control levels and produced a further and significant increment in RAP (150%) and pANP (100%). During the water-drinking phase MAP was not further altered, and hematocrit decreased by 11.1% (P less than 0.05). A positive linear correlation (P less than 0.001) was found between increases in RAP and pANP. The administration of an AVP vasopressor antagonist in a similar protocol, and before hypertonic saline infusion, inhibited the increase of MAP, but it did not alter the changes of posM, hematocrit, RAP, nor pANP. These results suggest that changes in the release of ANP during increases in posM and after spontaneous water drinking are predominantly controlled by changes in RAP.(ABSTRACT TRUNCATED AT 250 WORDS)

  20. Early Implementation of THAM for ICP Control: Therapeutic Hypothermia Avoidance and Reduction in Hypertonics/Hyperosmotics.

    PubMed

    Zeiler, F A; Gillman, L M; Teitelbaum, J; West, M

    2014-01-01

    Background. Tromethamine (THAM) has been demonstrated to reduce intracranial pressure (ICP). Early consideration for THAM may reduce the need for other measures for ICP control. Objective. To describe 4 cases of early THAM therapy for ICP control and highlight the potential to avoid TH and paralytics and achieve reduction in sedation and hypertonic/hyperosmotic agent requirements. Methods. We reviewed the charts of 4 patients treated with early THAM for ICP control. Results. We identified 2 patients with aneurysmal subarachnoid hemorrhage (SAH) and 2 with traumatic brain injury (TBI) receiving early THAM for ICP control. The mean time to initiation of THAM therapy was 1.8 days, with a mean duration of 5.3 days. In all patients, after 6 to 12 hours of THAM administration, ICP stability was achieved, with reduction in requirements for hypertonic saline and hyperosmotic agents. There was a relative reduction in mean hourly hypertonic saline requirements of 89.1%, 96.1%, 82.4%, and 97.0% for cases 1, 2, 3, and 4, respectively, comparing pre- to post-THAM administration. Mannitol, therapeutic hypothermia, and paralytics were avoided in all patients. Conclusions. Early administration of THAM for ICP control could potentially lead to the avoidance of other ICP directed therapies. Prospective studies of early THAM administration are warranted.

  1. [Septic shock. Update of treatment using hypertonic saline and antidiuretic hormone-vasopressin].

    PubMed

    Pascual-Ramírez, J; Aguirre Sánchez-Covisa, M; Araujo, F; Gil Trujillo, S; Collar, L G; Bocharán, S

    2012-01-01

    Safety in the use of small volumes of hypertonic saline solution for hypovolaemic shock and in the treatment of intracranial hypertension has been demonstrated in studies in the field of resuscitation. There is little experience of this for septic shock in humans. Beneficial immunomodulatory effects have been detected in pre-clinical studies. Interactions with the pituitary-adrenal axis and with the secretion of anti-diuretic hormone are varied and suggestive, but are not sufficiently understood. On the other hand, vasopressin has cardiovascular, osmoregulatory, and coagulation effects, and also acts on the hypothalamic-pituitary-adrenal axis. There is a relative deficit of vasopressin in septic shock. Its use in these patients does not seem to have any advantages as regards mortality, but may be beneficial in patients at risk from acute renal failure, or those who receive corticosteroids. Terlipressin is a vasopressin analogue that has also been studied. The synergy between vasopressin and hypertonic saline is a hypothesis that is mainly supported in pre-clinical studies. The use of hypertonic saline solution in septic shock, although promising, is still experimental, and must be restricted to the field of controlled clinical trials.

  2. 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

  3. The effect of cooling and hypertonic exposure on murine oocyte function, fertilization, and development.

    PubMed

    Hunter, J E; Fuller, B J; Bernard, A; Shaw, R W

    1995-08-01

    Several individual but related steps are involved in the cryopreservation process, including the addition of cryoprotectants at various temperatures, cooling to subzero temperatures, and long-term storage. The process is completed by rewarming and removal of cryoprotectants prior to a return to physiological conditions. In this series of experiments we have attempted to distinguish the effects of some of these procedures. Control, untreated ovulated mouse oocytes showed 95% in vitro fertilization (190/200) and 92% subsequent development to hatching blastocyst (184/200). Exposure of oocytes to either isotonic or hypertonic media at 37 degrees C did not significantly change the rate of fertilization (90%, 108/120; and 89%, 154/174, respectively) or subsequent embryonic development (85%, 102/120; and 82%, 143/174, respectively). Slow cooling in isotonic medium (-3 degrees C/min) to 0 degree C had no effect on the rate of fertilization (83%, 103/124), but rapid cooling (> 1000 degrees C/min) to 0 degree C resulted in a significant reduction in fertilization rate to 75% (151/202). When oocytes suspended in a hypertonic solution were cooled using slow or rapid rates, there were marked decreases in fertilization to 26% (61/231) and 56% (156/278), respectively. Subsequent embryonic growth was reduced to 15% (34/231) after slow cooling and 26% (72/278) after rapid cooling. Exposure of oocytes to glycerol at 37 degrees C and dimethyl sulfoxide at 0 degree C reduced the fertilization rate to 57% (67/118) and 73% (103/145), respectively, with a corresponding reduction in embryonic growth to 52% (61/118) and 65% (94/145), but there were no additional effects of cooling or hypertonic exposure after addition of cryoprotectants.

  4. SABRE: a multicentre randomised control trial of nebulised hypertonic saline in infants hospitalised with acute bronchiolitis

    PubMed Central

    Everard, Mark L; Hind, Daniel; Ugonna, Kelechi; Freeman, Jennifer; Bradburn, Mike; Cooper, Cindy L; Cross, Elizabeth; Maguire, Chin; Cantrill, Hannah; Alexander, John; McNamara, Paul S

    2014-01-01

    Aim Acute bronchiolitis is the commonest cause for hospitalisation in infancy. Supportive care remains the cornerstone of current management and no other therapy has been shown to influence the course of the disease. It has been suggested that adding nebulised hypertonic saline to usual care may shorten the duration of hospitalisation. To determine whether hypertonic saline does have beneficial effects we undertook an open, multi-centre parallel-group, pragmatic RCT in ten UK hospitals. Methods Infants admitted to hospital with a clinical diagnosis of acute bronchiolitis and requiring oxygen therapy were randomised to receive usual care alone or nebulised 3% hypertonic saline (HS) administered 6-hourly. Randomisation was within 4 h of admission. The primary outcome was time to being assessed as ‘fit’ for discharge with secondary outcomes including time to discharge, incidence of adverse events together with follow up to 28 days assessing patient centred health related outcomes. Results A total of 317 infants were recruited to the study. 158 infants were randomised to HS (141 analysed) and 159 to standard care (149 analysed). There was no difference between the two arms in time to being declared fit for discharge (hazard ratio: 0−95, 95% CI: 0.75−1.20) nor to actual discharge (hazard ratio: 0.97, 95% CI: 0.76−1.23). There was no difference in adverse events. One infant in the HS group developed bradycardia with desaturation. Conclusion This study does not support the use of nebulised HS in the treatment of acute bronchiolitis over usual care with minimal handlings. ClinicalTrials.gov registration number NCT01469845. PMID:25389139

  5. Hypertonic/Hyperoncotic Resuscitation from Shock: Reduced Volume Requirement and Lower Intracranial Pressure

    DTIC Science & Technology

    1989-10-01

    volume re- gs reference organs for measurement 3f organ blood suscitation with hypertonic saline dextran flow, using radioactive microspheres. All...oastllto Amaintained throyighout the 30 minute shoth Interval Blood was At ot; sir -o,;tnrn M,’.t was rvdured Iron 1111 tmean+SC r-ov~ed to reduce...a volume much smaller than the original shed blood volume (4-12). The addition of colloid, usually 6.0% low-molecular weight dextran , has been used

  6. Evaluation of the Maintained Effect of 3% Hypertonic Saline Solution in an Animal Model of Intracranial Hypertension

    PubMed Central

    Sousa, Leonardo M.; de Andrade, Almir F.; Belon, Alessandro R.; Soares, Matheus S.; Amorim, Robson Luis; Otochi, Jose Pinhata; Teixeira, Manoel J.; Paiva, Wellingson S.

    2016-01-01

    Background Current clinical treatment methods for refractory intracranial hypertension include elevation of the decubitus, ventilation adjustment, and use of hypertonic solutions such as hypertonic saline and mannitol solutions. Previous studies have shown that hypertonic solutions are particularly effective. Although several concentrations of saline solution have been proposed, a 3% solution is the most widely used. The aim of this study was to evaluate the maintained efficacy of a 3% hypertonic saline solution in an experimental model of intracranial hypertension. Material/Methods A porcine model of reversible intracranial hypertension was created by inserting a balloon catheter into the brain parenchyma, which was inflated and deflated to simulate intracranial hypertension and its surgical correction. The experiment included 3 groups of animals (A, B, and C) with different balloon inflation volumes. In group B, balloons were inflated 2 times to simulate reexpansion. A 20 mL/kg bolus of 3% saline solution was infused using a pump 90 minutes after the start of balloon inflation, and the effects of intracranial pressure were evaluated 60 minutes after infusion. Results No increases outside of the normal range were observed in mean serum sodium concentrations (p=0.09). In addition, we identified no differences within each group in serum sodium levels measured during hypertonic saline infusion (p=0.21). No significant reductions in intracranial pressure were observed in any of the 3 groups. Conclusions Bolus infusion of 3% hypertonic saline solution with the aid of a pump does not significantly reduce intracranial pressure in an animal model of intracranial hypertension. PMID:27777397

  7. Resuscitation of traumatic hemorrhagic shock patients with hypertonic saline-without dextran-inhibits neutrophil and endothelial cell activation.

    PubMed

    Junger, Wolfgang G; Rhind, Shawn G; Rizoli, Sandro B; Cuschieri, Joseph; Shiu, Maria Y; Baker, Andrew J; Li, Linglin; Shek, Pang N; Hoyt, David B; Bulger, Eileen M

    2012-10-01

    Posttraumatic inflammation and excessive neutrophil activation cause multiple organ dysfunction syndrome (MODS), a major cause of death among hemorrhagic shock patients. Traditional resuscitation strategies may exacerbate inflammation; thus, novel fluid treatments are needed to reduce such posttraumatic complications. Hypertonic resuscitation fluids inhibit inflammation and reduce MODS in animal models. Here we studied the anti-inflammatory efficacy of hypertonic fluids in a controlled clinical trial. Trauma patients in hypovolemic shock were resuscitated in a prehospital setting with 250 mL of either 7.5% hypertonic saline (HS; n = 9), 7.5% hypertonic saline + 6% dextran 70 (HSD; n = 8), or 0.9% normal saline (NS; n = 17). Blood samples were collected on hospital admission and 12 and 24 h after resuscitation. Multicolor flow cytometry was used to quantify neutrophil expression of cell-surface activation/adhesion (CD11b, CD62L, CD64) and degranulation (CD63, CD66b, CD35) markers as well as oxidative burst activity. Circulating concentrations of soluble intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVACM-1), P- and E-selectins, myeloperoxidase (MPO), and matrix metalloproteinase 9 (MMP-9) were assessed by immunoassay. Multiple organ dysfunction syndrome, leukocytosis, and mortality were lower in the HS and HSD groups than in the NS group. However, these differences were not statistically significant. Hypertonic saline prevented priming and activation and neutrophil oxidative burst and CD11b and CD66b expression. Hypertonic saline also reduced circulating markers of neutrophil degranulation (MPO and MMP-9) and endothelial cell activation (sICAM-1, sVCAM-1, soluble E-selectin, and soluble P-selectin). Hypertonic saline + 6% dextran 70 was less capable than HS of suppressing the upregulation of most of these activation markers. This study demonstrates that initial resuscitation with HS, but neither NS nor HSD, can attenuate

  8. The effect of hypertonic saline dextran solutions on hypoxic pulmonary vasoconstriction in anaesthetised piglets.

    PubMed

    Bellezza, M; Kerbaul, F; Roussel, L; Imbert, M; Guidon, C

    2002-10-01

    Hypoxic pulmonary vasoconstriction (HPV) is a regulatory mechanism by which blood is diverted from poorly ventilated to better ventilated areas of the lung. The aim of the present study was to assess the extent to which hypertonic saline dextran and dextran solutions modify the magnitude of HPV during isovolumic haemodilution in intact acutely instrumented piglets. Eighteen large white piglets were anesthetised and assigned to two groups. Mean pulmonary arterial pressure (PAP) and cardiac output (Q), systemic arterial pressure and left arterial pressure (LAP) were measured. A decrease in Q was obtained by reducing venous return. This enabled measurement of transpulmonary pressures (mean PAP minus LAP) at four levels of Q in hyperoxia (inspiratory oxygen fraction (FiO2)=0.4) then in hypoxia (Fi,O2=0.1) in the two groups before blood soustraction (10 mL x kg(-1)) and after loading with sodium chloride (NaCl) 7.5% and dextran 6% or with dextran 6% alone. Dextran alone led to a decrease in mean PAP-LAP/Q values, and NaCl with dextran was associated with a significant shift of mean PAP-LAP/Q plots to higher pressures in hypoxia. Hypertonic saline dextran solution, as replacement fluid in isovolaemic haemodilution increased the magnitude of hypoxic pulmonary vasoconstriction, whereas dextran solution reduced it.

  9. Desiccation and hypertonicity of the airway surface fluid and thermally induced asthma.

    PubMed

    Kotaru, Chakradhar; Hejal, Rana B; Finigan, J H; Coreno, Albert J; Skowronski, Mary E; Brianas, Lori; McFadden, E R

    2003-01-01

    To determine whether drying and hypertonicity of the airway surface fluid (ASF) are involved in thermally induced asthma, nine subjects performed isocapnic hyperventilation (HV) (minute ventilation 62.2 +/- 8.3 l/min) of frigid air (-8.9 +/- 3.3 degrees C) while periciliary fluid was collected endoscopically from the trachea. Osmolality was measured by freezing-point depression. The baseline 1-s forced expiratory volume was 73 +/- 4% of predicted and fell 26.4% 10 min postchallenge (P > 0.0001). The volume of ASF collected was 11.0 +/- 2.2 microl at rest and remained constant during and after HV as the airways narrowed (HV 10.6 +/- 1.9, recovery 6.5 +/- 1.7 microl; P = 0.18). The osmolality also remained stable throughout (rest 336 +/- 16, HV 339 +/- 16, and recovery 352 +/- 19 mosmol/kgH(2)O, P = 0.76). These data demonstrate that airway desiccation and hypertonicity of the ASF do not develop during hyperpnea in asthma; therefore, other mechanisms must cause exercise- and hyperventilation-induced airflow limitation.

  10. Resuscitation with a Bolus of Hypertonic Saline/Dextran Improves Renal Function Following Hemorrhage in Conscious Swine

    DTIC Science & Technology

    1989-11-28

    is well-known that infusions of hypertonic salt solutions induce a diuresis and a natriuresis - this occurred in both the control as well as the...pressure), neither pigs (18) nor humans (19-21) responded with an excessive diuresis which would exacerbate hypovolemia. Sondeen et al -- 9 Although it

  11. Comparison of intranasal hypertonic dead sea saline spray and intranasal aqueous triamcinolone spray in seasonal allergic rhinitis.

    PubMed

    Cordray, Scott; Harjo, Jim B; Miner, Linda

    2005-07-01

    Intranasal corticosteroids are well known to be efficacious in the treatment of allergic rhinitis. Nasal irrigation with saline, including hypertonic saline, has long been recommended for the treatment of sinonasal disease, and it has been shown to have a positive effect on the physiology of the nasal mucosa. Until now, no study of the clinical efficacy of intranasal hypertonic Dead Sea saline as a monotherapy for seasonal allergic rhinitis has been reported. We conducted a prospective, randomized, single-blind, placebo-controlled comparison of intranasal hypertonic Dead Sea saline spray and intranasal aqueous triamcinolone spray in 15 patients with seasonal allergic rhinitis. Results were based on a 7-day regimen. Based on Rhinoconjunctivitis Quality of Life Questionnaire scores, clinically and statistically significant (p < 0.0001) improvements were seen in both active-treatment groups; as expected, the corticosteroid spray was the more effective of the two treatments. No significant improvement occurred in the control group. Our preliminary results not only confirm the efficacy of intranasal corticosteroid therapy in moderate-to-severe allergic rhinitis, they also suggest that the Dead Sea saline solution can be an effective alternative in mild-to-moderate allergic rhinitis, particularly with respect to nasal and eye symptoms. The hypertonicity of the Dead Sea solution may have a positive effect on the physiology of the nasal mucosa by improving mucociliary clearance. In addition, the dominant cation in the Dead Sea solution--magnesium--probably exerts anti-inflammatory effects on the nasal mucosa and on the systemic immune response.

  12. Analysis of central opioid receptor subtype antagonism of hypotonic and hypertonic saline intake in water-deprived rats.

    PubMed

    Bodnar, R J; Glass, M J; Koch, J E

    1995-01-01

    Intake of either hypotonic or hypertonic saline solutions is modulated in part by the endogenous opioid system. Morphine and selective mu and delta opioid agonists increase saline intake, while general opioid antagonists reduce saline intake in rats. The present study evaluated whether intracerebroventricular administration of general (naltrexone) and selective mu (beta-funaltrexamine, 5-20 micrograms), mu, (naloxonazine, 50 micrograms), kappa (nor-binaltorphamine, 5-20 micrograms), delta (naltrindole, 20 micrograms), or delta 1 (DALCE, 40 micrograms) opioid receptor subtype antagonists altered water intake and either hypotonic (0.6%) or hypertonic (1.7%) saline intake in water-deprived (24 h) rats over a 3-h time course in a two-bottle choice test. Whereas peripheral naltrexone (0.5-2.5 mg/kg) significantly reduced water intake and hypertonic saline intake, central naltrexone (1-50 micrograms) significantly reduced water intake and hypotonic saline intake. Water intake was significantly reduced following mu and kappa receptor antagonism, but not following mu 1, delta, or delta 1 receptor antagonism. In contrast, neither hypotonic nor hypertonic saline intake was significantly altered by any selective antagonist. These data are discussed in terms of opioid receptor subtype control over saline intake relative to the animal's hydrational state and the roles of palatability and/or salt appetite.

  13. 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.

  14. Elemental distribution in striated muscle and the effects of hypertonicity: Electron probe analysis of cryo sections

    PubMed Central

    Somlyo, AV; Shuman, H; Somlyo, AP

    1977-01-01

    A method of rapid freezing in supercooled Freon 22 (monochlorodifluoromethane) followed by cryoultramicrotomy is described and shown to yield ultrathin sections in which both the cellular ultrastructure and the distribution of diffusible ions across the cell membrane are preserved and intracellular compartmentalization of diffusabler ions can be quantitated. Quantitative electron probe analysis (Shuman, H., A.V. Somlyo, and A.P. Somlyo. 1976. Ultramicros. 1:317-339.) of freeze-dried ultrathin cryto sections was found to provide a valid measure of the composition of cells and cellular organelles and was used to determine the ionic composition of the in situ terminal cisternae of the sarcoplasmic reticulum (SR), the distribution of CI in skeletal muscle, and the effects of hypertonic solutions on the subcellular composition if striated muscle. There was no evidence of sequestered CI in the terminal cisternae of resting muscles, although calcium (66mmol/kg dry wt +/- 4.6 SE) was detected. The values of [C1](i) determined with small (50-100 nm) diameter probes over cytoplasm excluding organelles over nuclei or terminal cisternae were not significantly different. Mitochondria partially excluded C1, with a cytoplasmic/ mitochondrial Ci ratio of 2.4 +/- 0.88 SD. The elemental concentrations (mmol/kg dry wt +/- SD) of muscle fibers measured with 0.5-9-μm diameter electron probes in normal frog striated muscle were: P, 302 +/- 4.3; S, 189 +/- 2.9;C1, 24 +/- 1.1;K, 404 +/- 4.3, and Mg, 39 +/- 2.1. It is concluded that: (a) in normal muscle the "excess CI" measured with previous bulk chemical analyses and flux studies is not compartmentalized in the SR or in other cellular organelles, and (b) the cytoplasmic C1 in low [K](0) solutions exceeds that predicted by a passive electrochemical distribution. Hypertonic 2.2 X NaCl, 2.5 X sucrose, or 2.2 X Na isethionate produced: (a) swollen vacuoles, frequently paired, adjacent to the Z lines and containing significantly higher than

  15. Osmolyte and Na+ transport balances of rat hepatocytes as a function of hypertonic stress.

    PubMed

    Wehner, F; Tinel, H

    2000-11-01

    The initial event in the regulatory volume increase (RVI) of rat hepatocytes is an influx of Na+ that is then exchanged for K+ via stimulation of Na+/K+-adenosine triphosphatase (ATPase). In this study, we analysed the activation pattern of the Na+ transporters underlying RVI as a function of the degree of hypertonic stress. In confluent primary cultures, four hypertonic conditions were tested (changes from 300 to 327, 360, 400 or 450 mosmol/l) and the activities of Na+ conductance, Na+/H+ antiport, Na+-K+-2Cl- symport and Na+/K+-ATPase were quantified using intracellular microelectrodes, microfluorometry and time-dependent, furosemide- or ouabain-sensitive 86Rb+ uptake, respectively. Neither Na+ conductance nor Na+-K+-2Cl- symport responded to 327 mosmol/A. At 360, 400 and 450 mosmol/l, uptake via these transporters would lead to increases of cell Na+ by 33.0, 49.0 and 49.0 and by 4.5, 10.4 and 9.2 mmol/l per 10 min, respectively. In contrast, Na+/H+ antiport exhibited 65% of its maximal activation already at 327 mosmol/l. At the four osmolarities tested, this transporter would augment cell Na+ by 6.9, 8.9, 9.8 and 10.6 mmol/l per 10 min. The sums of Na+ import were consistent with the amounts of Na+ exported via Na+/K+-ATPase plus the actual increases of cell Na+ (21.2, 58.5, 63.6 and 68.3 mmol/l per 10 min and 2.2, 4.0, 6.3 and 8.2 mmol/l, respectively). In addition, these elevations of cell Na+ plus the increases of cell K+ (via Na+/K+-ATPase) that amounted to 5.0, 6.5, 17.5 and 18.4 mmol/l were consistent with the increases of intracellular osmotic (cationic) activity of 2.5, 11.5, 21.0 and 28.5 mmol/l, respectively, computed from RVI data. It is concluded that the principle of rat hepatocyte RVI, i.e. an initial uptake of Na+ that is then exchanged for K+ via Na+/K+-ATPase, is realized over the entire range of 9-50% hypertonicity tested. The set-point for the activation of RVI clearly lies below 327 mosmol/l. Na+/H+ antiport is the most sensitive Na+ importer

  16. Hypertonic stress induces VEGF production in human colon cancer cell line Caco-2: inhibitory role of autocrine PGE₂.

    PubMed

    Gentile, Luciana B; Piva, Bruno; Diaz, Bruno L

    2011-01-01

    Vascular Endothelial Growth Factor (VEGF) is a major regulator of angiogenesis. VEGF expression is up regulated in response to micro-environmental cues related to poor blood supply such as hypoxia. However, regulation of VEGF expression in cancer cells is not limited to the stress response due to increased volume of the tumor mass. Lipid mediators in particular arachidonic acid-derived prostaglandin (PG)E₂ are regulators of VEGF expression and angiogenesis in colon cancer. In addition, increased osmolarity that is generated during colonic water absorption and feces consolidation seems to activate colon cancer cells and promote PGE₂ generation. Such physiological stimulation may provide signaling for cancer promotion. Here we investigated the effect of exposure to a hypertonic medium, to emulate colonic environment, on VEGF production by colon cancer cells. The role of concomitant PGE₂ generation and MAPK activation was addressed by specific pharmacological inhibition. Human colon cancer cell line Caco-2 exposed to a hypertonic environment responded with marked VEGF and PGE₂ production. VEGF production was inhibited by selective inhibitors of ERK 1/2 and p38 MAPK pathways. To address the regulatory role of PGE₂ on VEGF production, Caco-2 cells were treated with cPLA₂ (ATK) and COX-2 (NS-398) inhibitors, that completely block PGE₂ generation. The Caco-2 cells were also treated with a non selective PGE₂ receptor antagonist. Each treatment significantly increased the hypertonic stress-induced VEGF production. Moreover, addition of PGE₂ or selective EP₂ receptor agonist to activated Caco-2 cells inhibited VEGF production. The autocrine inhibitory role for PGE₂ appears to be selective to hypertonic environment since VEGF production induced by exposure to CoCl₂ was decreased by inhibition of concomitant PGE₂ generation. Our results indicated that hypertonicity stimulates VEGF production in colon cancer cell lines. Also PGE₂ plays an inhibitory

  17. Isotonic and hypertonic saline droplet deposition in a human upper airway model.

    PubMed

    Zhang, Zhe; Kleinstreuer, Clement; Kim, Chong S

    2006-01-01

    The evaporative and hygroscopic effects and deposition of isotonic and hypertonic saline droplets have been simulated from the mouth to the first four generations of the tracheobronchial tree under laminar-transitional-turbulent inspiratory flow conditions. Specifically, the local water vapor transport, droplet evaporation rate, and deposition fractions are analyzed. The effects of inhalation flow rates, thermodynamic air properties and NaCl-droplet concentrations of interest are discussed as well. The validated computer simulation results indicate that the increase of NaCl-solute concentration, increase of inlet relative humidity, or decrease of inlet air temperature may reduce water evaporation and increase water condensation at saline droplet surfaces, resulting in higher droplet depositions due to the increasing particle diameter and density. However, solute concentrations below 10% may not have a very pronounced effect on droplet deposition in the human upper airways.

  18. 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.

  19. Centrally administered vasopressin cross-sensitizes rats to amphetamine and drinking hypertonic NaCl.

    PubMed

    McBride, Shawna M; Flynn, Francis W

    2007-09-01

    Prior sodium restriction cross-sensitizes rats to the psychomotor effects of amphetamines and vice versa. Repeated central injections of vasopressin (VP) induce a psychomotor sensitization similar to amphetamine sensitization and repeated sodium deficiency. Thus brain VP signaling may be a common mechanism involved in mediating these two motivational systems. In experiment 1, we tested the hypothesis that rats previously sensitized to central VP would show enhanced psychomotor responses to amphetamine. Rats were administered saline, VP (50 ng), or amphetamine (1 mg/kg or 3 mg/kg) on days 1 and 2, and given saline or amphetamine on day 3. Amphetamine produced psychomotor arousal in all groups. However, amphetamine on day 3 elicited a significantly greater psychomotor response in rats that had prior injections of amphetamine or VP than in rats previously treated with saline. In experiment 2, the hypothesis that prior experience with central VP would cross-sensitize rats to drinking hypertonic sodium (NaCl) solutions was tested. Rats were administered VP (50 ng) or saline for 3 days. On the fourth day, nondeprived rats were given access to 0.3 M NaCl and water for 1 h. Control and saline-treated rats only drank 1 ml of 0.3 M NaCl, but rats previously exposed to central VP drank significantly more hypertonic saline (4 ml). These results show that prior experience with central VP cross-sensitizes rats to the psychomotor stimulant effects of amphetamine and the ingestion of concentrated NaCl solutions. This pattern of cross-sensitization links central VP signaling, amphetamine, and sodium deficiency, and therefore it may play a role in the cross-sensitization between sodium appetite and amphetamines.

  20. Axial hypertonicity in Parkinson's disease: direct measurements of trunk and hip torque.

    PubMed

    Wright, W G; Gurfinkel, V S; Nutt, J; Horak, F B; Cordo, P J

    2007-11-01

    A cardinal feature of Parkinson's disease (PD) is muscle hypertonicity, i.e. rigidity. Little is known about the axial tone in PD or the relation of hypertonia to functional impairment. We quantified axial rigidity to assess its relation to motor symptoms as measured by UPDRS and determine whether rigidity is affected by levodopa treatment. Axial rigidity was measured in 12 PD and 14 age-matched controls by directly measuring torsional resistance of the longitudinal axis to twisting (+/-10 degrees ). Feet were rotated relative to fixed hips (Hip Tone) or feet and hips were rotated relative to fixed shoulders (Trunk Tone). To assess tonic activity only, low constant velocity rotation (1 degrees /s) and low acceleration (<12 degrees /s(2)) were used to avoid eliciting phasic sensorimotor responses. Subjects stood during testing without changing body orientation relative to gravity. Body parts fixed against rotation could translate laterally within the boundaries of normal postural sway, but could not rotate. PD OFF-medication had higher axial rigidity (p<0.05) in hips (5.07 N m) and trunk (5.30 N m) than controls (3.51 N m and 4.46 N m, respectively), which did not change with levodopa (p>0.10). Hip-to-trunk torque ratio was greater in PD than controls (p<0.05) and unchanged by levodopa (p=0.28). UPDRS scores were significantly correlated with hip rigidity for PD OFF-medication (r values=0.73, p<0.05). Torsional resistance to clockwise versus counter-clockwise axial rotation was more asymmetrical in PD than controls (p<0.05), however, there was no correspondence between direction of axial asymmetry and side of disease onset. In conclusion, these findings concerning hypertonicity may underlie functional impairments of posture and locomotion in PD. The absence of a levodopa effect on axial tone suggests that axial and appendicular tones are controlled by separate neural circuits.

  1. [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.

  2. Sensory findings after stimulation of the thoracolumbar fascia with hypertonic saline suggest its contribution to low back pain.

    PubMed

    Schilder, Andreas; Hoheisel, Ulrich; Magerl, Walter; Benrath, Justus; Klein, Thomas; Treede, Rolf-Detlef

    2014-02-01

    Injection of hypertonic saline into deep tissues of the back (subcutis, muscle, or the surrounding fascia) can induce acute low back pain (LBP). So far, no study has analyzed differences in temporal, qualitative, and spatial pain characteristics originating from these tissues. The current study aimed to investigate the role of the thoracolumbar fascia as a potential source of LBP. In separate sessions, 12 healthy subjects received ultrasound-guided bolus injections of isotonic saline (0.9%) or hypertonic saline (5.8%) into the erector spinae muscle, the thoracolumbar fascia (posterior layer), and the overlying subcutis. Subjects were asked to rate pain intensity, duration, quality, and spatial extent. Pressure pain thresholds were determined pre and post injection. Injections of hypertonic saline into the fascia resulted in significantly larger area under the curve of pain intensity over time than injections into subcutis (P<0.01) or muscle (P<0.001), primarily based on longer pain durations and, to a lesser extent, on higher peak pain ratings. Pressure hyperalgesia was only induced by injection of hypertonic saline into muscle, but not fascia or subcutis. Pain radiation and pain affect evoked by fascia injection exceeded those of the muscle (P<0.01) and the subcutis significantly (P<0.05). Pain descriptors after fascia injection (burning, throbbing, and stinging) suggested innervation by both A- and C-fiber nociceptors. These findings show that the thoracolumbar fascia is the deep tissue of the back that is most sensitive to chemical stimulation, making it a prime candidate to contribute to nonspecific LBP but not to localized pressure hyperalgesia.

  3. 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

  4. Generating chimeric mice from embryonic stem cells via vial coculturing or hypertonic microinjection.

    PubMed

    Lee, Kun-Hsiung

    2014-01-01

    The generation of a fertile embryonic stem cell (ESC)-derived or F0 (100 % coat color chimerism) mice is the final criterion in proving that the ESC is truly pluripotent. Many methods have been developed to produce chimeric mice. To date, the most popular methods for generating chimeric embryos is well sandwich aggregation between zona pellucida (ZP) removed (denuded) 2.5-day post-coitum (dpc) embryos and ESC clumps, or direct microinjection of ESCs into the cavity (blastocoel) of 3.5-dpc blastocysts. However, due to systemic limitations and the disadvantages of conventional microinjection, aggregation, and coculturing, two novel methods (vial coculturing and hypertonic microinjection) were developed in recent years at my laboratory.Coculturing 2.5-dpc denuded embryos with ESCs in 1.7-mL vials for ~3 h generates chimeras that have significantly high levels of chimerism (including 100 % coat color chimerism) and germline transmission. This method has significantly fewer instrumental and technological limitations than existing methods, and is an efficient, simple, inexpensive, and reproducible method for "mass production" of chimeric embryos. For laboratories without a microinjection system, this is the method of choice for generating chimeric embryos. Microinjecting ESCs into a subzonal space of 2.5-dpc embryos can generate germline-transmitted chimeras including 100 % coat color chimerism. However, this method is adopted rarely due to the very small and tight space between ZP and blastomeres. Using a laser pulse or Piezo-driven instrument/device to help introduce ESCs into the subzonal space of 2.5-dpc embryos demonstrates the superior efficiency in generating ESC-derived (F0) chimeras. Unfortunately, due to the need for an expensive instrument/device and extra fine skill, not many studies have used either method. Recently, ESCs injected into the large subzonal space of 2.5-dpc embryos in an injection medium containing 0.2-0.3 M sucrose very efficiently generated

  5. Hypertonic Glucose Combined with Negative Pressure Wound Therapy to Prepare Wounds with Pseudomonas aeruginosa Infection for Skin Grafting: A Report of 3 Cases.

    PubMed

    Zhao, Jing-Chun; Xian, Chun-Jing; Yu, Jia-Ao; Shi, Kai; Hong, Lei

    2015-06-01

    Soft tissue losses from acute or chronic trauma are a challenge for surgeons. To explore a method to expedite granulation tissue formation in preparation for a split-thickness skin graft (STSG), the medical records of 3 patients - 2 adult men with wounds related to trauma injury and 1 infant with necrotizing fasciitis, all infected with Pseudomonas aeruginosa - were reviewed. All wounds were surgically debrided and managed by applying gauze soaked in 50% glucose followed by continuous negative pressure wound therapy (NPWT) before definitive skin grafting. NPWT pressure was applied at -80 mm Hg for the 2 adult males (ages 39 and 25 years) and -50 mm Hg for the 7-month-old male infant. The dressings were changed every 2 to 3 days. No adverse events occurred, and wounds were successfully closed with a STSG after an average of 7 days. In 1 case, NPWT was able to help affix dressings in a difficult-to-dress area (genital region). The combination of hypertonic glucose and hand-made, gauze-based NPWT was found to be safe, well-tolerated, and effective in preparing the wound bed for grafting. Prospective, randomized, controlled clinical studies are needed to compare the safety, effectiveness, and efficacy of this method to other treatment approaches for P. aeruginosa-infected wounds.

  6. TRPV4 mediates pain-related behavior induced by mild hypertonic stimuli in the presence of inflammatory mediator.

    PubMed

    Alessandri-Haber, Nicole; Joseph, Elizabeth; Dina, Olayinka A; Liedtke, Wolfgang; Levine, Jon D

    2005-11-01

    The ligand-gated ion channel, TRPV4, functions as a transducer of hypotonic stimuli in primary afferent nociceptive neurons and contributes to inflammatory and neuropathic pain. Hypertonic saline also stimulates primary afferent nociceptors and the injection of mild hypertonic saline (2-5%) is widely used as an experimental model of pain in humans. Therefore, we tested whether TRPV4 participates in the transduction of hypertonic stimuli. Intradermal injection of 2% (607 mOsm) or 10% (3,250 mOsm) saline solution in the hind paw of rats induced a concentration-dependent pain-related behavior, flinching. Sensitization with prostaglandin E(2) (PGE(2)) caused a 7-fold increase in the number of flinches induced by 2% saline but failed to increase those caused by 10% saline. Spinal administration of antisense oligodeoxynucleotides to TRPV4 caused a 46% decrease in the number of flinches induced by 2% saline, but there was no change in flinching induced by 10% saline. Similarly, only the nociceptive behavior caused by 2% saline was reduced in TRPV4(-/-) knockout mice. The TRPV4-mediated nociceptive behaviors induced by hyper- and hypotonic stimuli were dependent on Src tyrosine kinase. We suggest TRPV4 is a transducer in primary afferents that mediates nociceptive behavior induced by small increases or decreases in osmolarity. Such changes in osmolarity might contribute to pain in inflammatory and neuropathic states.

  7. [Effect of sodium cromoglycate on airway vascular leakage caused by hypertonic saline in the rat trachea].

    PubMed

    Yamawaki, I; Tamaoki, J; Takeda, Y; Konno, K

    1996-09-01

    The action of the anti-asthmatic drug sodium cromoglycate (SCG) on airway inflammation remains uncertain. Using Evans blue dye as a maker of plasma leakage, we studied the effect of SCG on neurogenic vascular extravasation evoked by hypertonic saline (HTS) in the rat trachea. Inhalation of HTS (5-15%) caused a concentration-dependent increase in plasma leakage, but inhaled 0.9% NaCl had no effect. Inhalation of SCG did not affect the baseline level of vascular permeability, but it inhibited the effect of HTS in a dose-dependent manner: plasma extravasation induced by 10% NaCl was significantly reduced by 2 minutes of inhalation of SCG at concentrations of 10 and 50 mg/ml (p < 0.05 and p < 0.01, respectively). SCG (10 mg/ml), also inhibited the changes in microvascular permeability caused by aerosols of substance P (10(-4) M), whereas it did not affect the responses to aerosols of platelet-activating factor (3 x 10(-4) M). A similar dose of SCG did not significantly alter microvascular leakage caused by 5% NaCl. However, phosphoramidon, a selective inhibitor of neutral endopeptidase, potentiated the response to 5% NaCl, an effect that was inhibited by SCG (p < 0.05). These results suggest that SCG inhibits HTS-induced airway vascular permeability, presumably through a tachykinin-antagonist-like property, and that this inhibition is exaggerated when the activity of endogenous neutral endopeptidase is low.

  8. Some Effects of Hypertonic Solutions on Contraction and Excitation-Contraction Coupling in Frog Skeletal Muscles

    PubMed Central

    Gordon, A. M.; Godt, R. E.

    1970-01-01

    In frog fast skeletal muscle, we find a decline of twitch, tetanus, and maximum K and caffeine contracture tensions as tonicity of the bathing solution is increased. The decline of tension independent of the method of producing contraction indicates that the major effect of hypertonicity is directly on contractile tension probably because of the increased internal ionic strength. However, there is some apparent disruption of excitation-contraction (E-C) coupling in solutions made three times the normal tonicity (3T solutions) since: (a) in 3T solutions tetanic and K contracture tensions decline to zero from a value near the average maximum caffeine contracture tension at this tonicity (10% of 1T tetanic tension). At this time, caffeine contractures of 10% of 1T tetanic tension can be elicited; (b) once the K contracture tension has declined, elevated [Ca++]o, 19.8 mM, restores K contracture tension to 13% of 1T tetanic tension. This probable disruption is not caused by changes in mechanical threshold since in 2T solutions the mechanical threshold is shifted by 12 mv in the hyperpolarizing direction. This is consistent with neutralization of fixed negative charges on the inside of the membrane. The repriming curve is also shifted in the hyperpolarizing direction in 2T solutions. Shifts of the repriming curve coupled with membrane depolarizations in 3T solutions (about 20 mv) may produce loss of repriming ability at the resting potential and disruption of E-C coupling. PMID:5415044

  9. Cardiovascular effects of hypertonic sodium chloride solutions when injected into the liquor space of anaesthetized cats.

    PubMed

    Feldberg, W; Wei, E

    1979-05-01

    1 In cats anaesthetized with chloralose, hyper- and hypotonic solutions were injected into the cisterna magna (in 0.5 ml) or into a lateral cerebral ventricle (in 0.2 to 0.3 ml), with aqueduct cannulated to prevent the injected solution from entering the subarachnoid space, and the effects on blood pressure and heart rate were examined. 2 Cisternal injections of hyper- and hypotonic solutions of NaCl (0.51 M and 0.05 M), glucose (1.03 M and 0.10 M), or sucrose (1.02 M and 0.10 M), as well as distilled water produced a rise in arterial blood pressure with tachycardias. Isotonic solutions of NaCl, glucose or sucrose were ineffective. 3 Ventricular injections of the hypertonic NaCl solution, also produced a pressor response with tachycardia effects when injected in this way. 4 The pressor responses and the tachycardias occurred after bilateral vagotomy and resulted from a sympathetic discharge which, on cisternal injection, originated from structures reached from the subarachnoid space, and on ventricular injection, from structures in the ventricular walls, probably in the hypothalamus. 5 The stimuli responsible for the discharge, were, on cisternal injection, the changes in osmolarity and on ventricular injection, the sodium ions.

  10. Osmoregulation in water-deprived rats drinking hypertonic saline: effect of area postrema lesions.

    PubMed

    Stricker, E M; Craver, C F; Curtis, K S; Peacock-Kinzig, K A; Sved, A F; Smith, J C

    2001-03-01

    Rats drank rapidly when 0.3 M NaCl was the only drinking fluid available after overnight water deprivation, consuming approximately 200 ml/24 h. Although such large intakes of this hypertonic solution initially elevated plasma osmolality, excretion of comparable volumes of urine more concentrated than 300 meq Na(+)/l ultimately appears to restore plasma osmolality to normal levels. Rats drank approximately 100 ml of 0.5 M NaCl after overnight water deprivation, but urine Na(+) concentration (U(Na)) did not increase sufficiently to achieve osmoregulation. When an injected salt load exacerbated the initial dehydration caused by water deprivation, rats increased U(Na) to void the injected load and did not significantly alter 24-h intake of 0.3 or 0.5 M NaCl. Rats with lesions of area postrema had much higher saline intakes and lower U(Na) than did intact control rats; nonetheless, they appeared to osmoregulate well while drinking 0.3 M NaCl but not while drinking 0.5 M NaCl. Detailed analyses of drinking behavior by intact rats suggest that individual bouts were terminated by some rapid postabsorptive consequence of the ingested NaCl load that inhibited further NaCl intake, not by a fixed intake volume or number of licks that temporarily satiated thirst.

  11. Repeated Dosing of 23.4% Hypertonic Saline for Refractory Intracranial Hypertension. A Case Report

    PubMed Central

    Valentino, Alden K; Nau, Karen M; Miller, David A; Hanel, Ricardo A; Freeman, WD

    2008-01-01

    Background: Hypertonic saline (HTS) at a concentration of 23.4% is an emerging therapy for intracranial hypertension. Compared to mannitol which can be given as a single bolus or as repeated bolus dosing, little data exists regarding safety or efficacy of repeated dosing of 23.4% HTS. We report the first case of 16 doses of 23.4% HTS over a 5 day period in a patient with refractory intracranial hypertension. Case Report: A 43-year-old woman with Fisher 3 subarachnoid hemorrhage and hydrocephalus requiring an external ventricular drain developed global cerebral edema on computed tomography. Medically refractory intracranial hypertension ensued which required repeated dosing of 23.4% HTS. Reductions in intracranial pressure (ICP) occurred after each dose of 23.4% HTS. No central nervous system complications occurred. Anasarca was the only observed complication, which responded to furosemide diuresis. Conclusion: Repeated dosing of 23.4% HTS was effective in reducing ICP in a case of medically refractory intracranial hypertension without major systemic complications. Prospective studies should address the safety and efficacy of repeat dose 23.4% HTS on serum sodium, intracranial pressure, and complications. PMID:22518235

  12. A3 adenosine receptor inhibition improves the efficacy of hypertonic saline resuscitation

    PubMed Central

    Inoue, Yoshiaki; Tanaka, Hiroshi; Sumi, Yuka; Woehrle, Tobias; Chen, Yu; Hirsh, Mark I.; Junger, Wolfgang G.

    2011-01-01

    We reported previously that hypertonic saline (HS) treatment can prevent or upregulate the function of polymorphonuclear neutrophils (PMN) via A2a adenosine receptors (A2aR) or A3 adenosine receptors (A3R), respectively. A3R translocate to the cell surface upon PMN stimulation and thus HS promotes PMN responses under conditions of delayed HS treatment. Here we investigated if inhibition of A3R improves the protective effects of HS resuscitation in a mouse sepsis model. We found that HS nearly triples extracellular adenosine concentrations in whole blood and that inhibition of A3R with the selective antagonist MRS-1191 dose-dependently improves the inhibitory effect of HS. MRS-1191 at a concentration of 1 nM enhanced the inhibitory effect of HS and reduced stimulatory effects of delayed HS treatment. Using a mouse model of cecal ligation and puncture (CLP)-induced sepsis, we found that MRS-1191 reduces acute lung injury and PMN accumulation in lung tissue. While delayed HS treatment (4 ml/kg of 7.5 % NaCl) of mice 1 h after CLP aggravated PMN accumulation, lung tissue damage, and mortality 24 h after CLP, infusion of MRS-1191 (2 ng/kg body weight) combined with HS reduced these detrimental effects of delayed HS treatment. Our data thus show that A3 receptor antagonists can strengthen the beneficial effects of HS resuscitation by avoiding stimulatory side effects that result from delayed HS administration. PMID:20661181

  13. Muscular hypertonicity: a suspected contributor to rheumatological manifestations observed in ambulatory practice

    PubMed Central

    Masi, Alfonse T.; Kamat, Sona; Gajdosik, Richard; Ahmad, Naila; Aldag, Jean C.

    2015-01-01

    Objective The objective of this retrospective study of non-inflammatory rheumatic disease patients was to investigate if the individuals clinically identified with muscular hypertonicity (MHT) had increased clinical manifestations compared with those of age- and gender-matched patients with the same disorders. Material and Methods The MHT status was clinically identified in the rheumatologist’s myofascial protocol examination as relatively increased passive resistance of relaxed muscle on a slow gentle stretch. Clinical and laboratory data were abstracted on a pre-coded form, including symptom and physical examination features, serum assays, and medications. Results The 19 MHT cases complained of greater subjective stiffness (p=0.010) and tiredness (p=0.018) at initial encounters and increased aching pain (p=0.049) and were prescribed more (p=0.003) mild narcotic analgesics than the 19 comparison patients. The cases had higher (p=0.027) serum creatine kinase levels, and patients with diffuse MHT had greater frequency of heavy (30+pack-years) cigarette smoking (p=0.002) than comparison subjects. Narcotic usage was also greater in cases with diffuse involvement. Conclusion Non-inflammatory rheumatic disease patients with MHT had an overall similar profile as that of comparison patients but had greater musculoskeletal complaints, and those with diffuse involvement had greater narcotic usage. Further research, including quantitative measurements of muscle stiffness, are required to determine whether MHT is a documented entity associated with increased rheumatological manifestations. PMID:27708929

  14. 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

  15. 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.

  16. Effect of hypertonic NaCl-starch-solution on oedema of different pathogenesis.

    PubMed

    Koch, T; Neuhof, H; Kohler, P; Duncker, H P; Buse, A; van Ackern, K

    1994-02-01

    Small volumes of hypertonic NaCl-solutions have been proven to restore haemodynamics in hypovolemic shock patients. Topic of this study was to investigate whether bolus application of 7.5% NaCl-6.5% starch-solution (HSS) apart from its relevance in shock might be an effective therapy in oedema. Considering differential therapeutic aspects, the volume effects of 7.2 ml HSS were tested in three types of oedema: hydrostatic oedema induced by venous congestion (n = 6), oedema caused by bradykinin injection (n = 6), and proteinase-induced oedema (n = 6). The arterial, venous pressure and weight changes indicating volume shifts between intra- and extravascular space were continuously monitored in 36 isolated perfused rabbit hindlimbs. Oedema formation was induced corresponding to a weight gain of 18-20 g. Subsequently 7.2 ml HSS were injected into the extracorporeal circulation system containing 200 ml cell free, isoosmotic perfusate. Six experiments of each oedema group without HSS-application served as controls. 75-100% of oedema formation could be remobilised via bolus application of HSS within 5 min in all types of oedema. A persisting weight reduction was detectable in the hydrostatic and bradykinin oedema, whereas in the elastase oedema the initial weight loss was followed by a regain of weight up to 180% of initial oedema formation at 120 min after HSS-application. The results show that, due to the osmotic gradient induced by bolus application of HSS, the hydrostatic and bradykinin oedema can be permanently remobilised, whereas the therapeutic effect during proteinase oedema is only short-lasting due to an irreversible damage of barrier function.

  17. Median preoptic nucleus mediates the cardiovascular recovery induced by hypertonic saline in hemorrhagic shock.

    PubMed

    Amaral, Nathalia Oda; Naves, Lara Marques; Ferreira-Neto, Marcos Luiz; Freiria-Oliveira, André Henrique; Colombari, Eduardo; Rosa, Daniel Alves; Reis, Angela Adamski da Silva; Ianzer, Danielle; 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.

  18. Chronic physiological increases in cortisol inhibit the vasopressin response to hypertonicity in conscious dogs.

    PubMed

    Papanek, P E; Raff, H

    1994-11-01

    Chronic increases in cortisol inhibit basal plasma arginine vasopressin (AVP). Acute pretreatment with cortisol inhibits the large increase in AVP during hypotension or hypoxia but does not inhibit the modest increase in AVP in response to hypertonic saline (HS). We evaluated the effect of a chronic increase in cortisol (physiological range) on the acute AVP response to HS. Five male dogs received a continuous infusion of either vehicle or cortisol (65 mg/day) for 7 days. The AVP response to HS (0.2 mmol.kg-1.min-1 for 30 min) was tested before infusion, on days 1, 4, and 7 of chronic infusion, and 2 days after the infusion was discontinued. Plasma cortisol increased significantly from 1.0 +/- 0.2 micrograms/dl to an average over the 7 days of infusion of 5.0 +/- 0.2 micrograms/dl, and basal plasma AVP was significantly decreased during cortisol infusion. The increase in plasma Na and osmolality during HS was unaffected by chronic infusion. HS resulted in an increase in AVP from 3.5 +/- 0.2 to 7.1 +/- 0.7 pg/ml before cortisol infusion. After 7 days of cortisol, the AVP response to HS (from 2.6 +/- 0.1 to 3.9 +/- 0.7 pg/ml) was significantly attenuated. Sustained, physiological increases in cortisol significantly inhibited osmotically stimulated AVP release. The decrease in AVP during hypercortisolism and the syndrome of inappropriate antidiuretic hormone in patients with adrenal insufficiency appear to be due to an inhibitory effect of cortisol on the osmotic sensitivity of the AVP control system.

  19. Comparison of 3% and 7.5% Hypertonic Saline in Resuscitation After Traumatic Hypovolemic Shock.

    PubMed

    Han, Juan; Ren, Hui-Qin; Zhao, Qing-Bo; Wu, You-Liang; Qiao, Zhuo-Yi

    2015-03-01

    Hypertonic saline solutions (HSSs) (7.5%) are useful in the resuscitation of patients with hypovolemic shock because they provide immediate intravascular volume expansion via the delivery of a small volume of fluid, improving cardiac function. However, the effects of using 3% HSS in hypovolemic shock resuscitation are not well known. This study was designed to compare the effects of and complications associated with 3% HSS, 7.5% HSS, and standard fluid in resuscitation. In total, 294 severe trauma patients were enrolled from December 2008 to February 2012 and subjected to a double-blind randomized clinical trial. Individual patients were treated with 3% HSS (250 mL), 7.5% HSS (250 mL), or lactated Ringer's solution (LRS) (250 mL). Mean arterial pressure, blood pressure, and heart rate were monitored and recorded before fluid infusion and at 10, 30, 45, and 60 min after infusion, and the incidence of complications and survival rate were analyzed. The results indicate that 3% and 7.5% HSSs rapidly restored mean arterial pressure and led to the requirement of an approximately 50% lower total fluid volume compared with the LRS group (P < 0.001). However, a single bolus of 7.5% HSS resulted in an increase in heart rate (mean of 127 beats/min) at 10 min after the start of resuscitation. Higher rates of arrhythmia and hypernatremia were noted in the 7.5% HSS group, whereas higher risks of renal failure (P< 0.001), coagulopathy (P < 0.001), and pulmonary edema (P < 0.001) were observed in the LRS group. Neither severe electrolyte disturbance nor anaphylaxis was observed in the HSS groups. It is notable that 3% HSS had similar effects on resuscitation because both the 7.5% HSS and LRS groups but resulted in a lower occurrence of complications. This study demonstrates the efficacy and safety of 3% HSS in the resuscitation of patients with hypovolemic shock.

  20. Predictors of Acute Kidney Injury in Neurocritical Care Patients Receiving Continuous Hypertonic Saline

    PubMed Central

    Riha, Heidi; Bode, Lauren; Chang, Jason J.; Jones, G. Morgan

    2016-01-01

    Background and Purpose: Continuous intravenous 3% hypertonic saline (HTS) infusions are commonly used for the management of cerebral edema following severe neurologic injuries. Despite widespread use, data regarding the incidence and predictors of nephrotoxicity are lacking. The purpose of this study was to describe the incidence and identify predictors of acute kidney injury (AKI) in neurocritical care patients administered continuous infusion HTS. Methods: This was an institutional review board–approved, multicenter, retrospective cohort study of patients receiving HTS infusions at 2 academic medical centers. A univariate analysis and multivariable logistic regression were used to identify predictors of AKI. Data regarding AKI were evaluated during treatment with HTS and up to 24 hours after discontinuation. Results: A total of 329 patients were included in our analysis, with 54 (16%) developing AKI. Those who developed AKI experienced significantly longer stays in the intensive care unit (14.8 vs 11.5 days; P = .006) and higher mortality (48.1% vs 21.9%; P < .001). We identified past medical history of chronic kidney disease (odds ratio [OR]: 9.7, 95% confidence interval [CI]: 1.9-50.6; P = .007), serum sodium greater than 155 mmol/L (OR: 4.1, 95% CI: 2.1-8.0; P < .001), concomitant administration of piperacillin/tazobactam (OR: 3.9, 95% CI: 1.7-9.3; P = .002), male gender (OR: 3.2, 95% CI: 1.5-6.6; P = .002), and African American race (OR: 2.6, 95% CI: 1.3-5.2; P = .007) as independent predictors of AKI. Conclusion: Acute kidney injury is relatively common in patients receiving continuous HTS and may significantly impact clinical outcomes. PMID:28042364

  1. Duration of action of hypertonic saline on mucociliary clearance in the normal lung

    PubMed Central

    Wu, J.; Fuller, F.; Balcazar, J. R.; Zeman, K. L.; Duckworth, H.; Donn, K. H.; O'Riordan, T. G.; Boucher, R. C.; Donaldson, S. H.

    2015-01-01

    Inhalation of hypertonic saline (HS) acutely enhances mucociliary clearance (MC) in both health and disease. In patients with cystic fibrosis (CF), repeated use of HS causes a sustained improvement in MC as well as clinical benefit. The pharmacodynamic duration of activity on MC may be an important determinant of its therapeutic potential in other airways diseases. Before moving toward testing the clinical benefits of HS for non-CF indications, we sought to assess the duration of pharmacodynamic effects of HS in healthy subjects by performing radiotracer clearance studies at baseline, 30-min post-HS administration, and 4-h post-HS administration. Indeed, acceleration of MC was observed when measured 30 min after HS inhalation. This acceleration was most pronounced in the first 30 min after inhaling the radiotracer in the central lung region (mean Ave30Clr = 15.5 vs. 8.6% for 30-min post-HS treatment vs. mean baseline, respectively, P < 0.005), suggesting that acute HS effects were greatest in the larger bronchial airways. In contrast, when MC was measured 4 h after HS administration, all indices of central lung region MC were slower than at baseline: Ave30Clr = 5.9% vs. 8.6% (P = 0.10); Ave90Clr = 12.4% vs. 16.8% (P < 0.05); clearance through 3 h = 29.4 vs. 43.7% (P < 0.002); and clearance through 6 h = 39.4 vs. 50.2% (P < 0.02). This apparent slowing of MC in healthy subjects 4-h post-HS administration may reflect depletion of airway mucus following acute HS administration. PMID:25911685

  2. CNS sites activated by renal pelvic epithelial sodium channels (ENaCs) in response to hypertonic saline in awake rats.

    PubMed

    Goodwill, Vanessa S; Terrill, Christopher; Hopewood, Ian; Loewy, Arthur D; Knuepfer, Mark M

    2017-05-01

    In some patients, renal nerve denervation has been reported to be an effective treatment for essential hypertension. Considerable evidence suggests that afferent renal nerves (ARN) and sodium balance play important roles in the development and maintenance of high blood pressure. ARN are sensitive to sodium concentrations in the renal pelvis. To better understand the role of ARN, we infused isotonic or hypertonic NaCl (308 or 500mOsm) into the left renal pelvis of conscious rats for two 2hours while recording arterial pressure and heart rate. Subsequently, brain tissue was analyzed for immunohistochemical detection of the protein Fos, a marker for neuronal activation. Fos-immunoreactive neurons were identified in numerous sites in the forebrain and brainstem. These areas included the nucleus tractus solitarius (NTS), the lateral parabrachial nucleus, the paraventricular nucleus of the hypothalamus (PVH) and the supraoptic nucleus (SON). The most effective stimulus was 500mOsm NaCl. Activation of these sites was attenuated or prevented by administration of benzamil (1μM) or amiloride (10μM) into the renal pelvis concomitantly with hypertonic saline. In anesthetized rats, infusion of hypertonic saline but not isotonic saline into the renal pelvis elevated ARN activity and this increase was attenuated by simultaneous infusion of benzamil or amiloride. We propose that renal pelvic epithelial sodium channels (ENaCs) play a role in activation of ARN and, via central visceral afferent circuits, this system modulates fluid volume and peripheral blood pressure. These pathways may contribute to the development of hypertension.

  3. Induction of the high-affinity Na(+)-dependent glutamate transport system XAG- by hypertonic stress in the renal epithelial cell line NBL-1.

    PubMed Central

    Ferrer-Martinez, A; Felipe, A; Nicholson, B; Casado, J; Pastor-Anglada, M; McGivan, J

    1995-01-01

    The high-affinity Na(+)-dependent glutamate transport system XAG- is induced (threefold increase in Vmax. with no change in Km) by hypertonicity in the renal epithelial cell line NBL-1. This effect is dependent on protein synthesis and glycosylation and is accompanied by an increase in EAAC1 mRNA levels. Other Na(+)-dependent transport systems in this cell line do not respond to hypertonic stress. In contrast to recent findings [Ruiz-Montasell, Gomez-Angelats, Casado, Felipe, McGivan and Pastor-Anglada (1994) Proc. Natl. Acad. Sci. U.S.A. 91, 9569-9573] showing that increased system A activity after hyperosmotic shock results from induction of a regulatory protein, this is the first demonstration that hypertonicity may increase the expression of the gene for an amino acid transport protein itself. Images Figure 4 PMID:7654212

  4. Impact of hypertonic saline on postoperative complications for patients undergoing upper gastrointestinal surgery

    PubMed Central

    Hong, Siqi; Shang, Qingjuan; Geng, Qiankun; Yang, Yang; Wang, Yan; Guo, Chunbao

    2017-01-01

    Abstract The aim of this study was to explore the impact of 3% hypertonic saline (HS) intragastric administration for patients who underwent upper gastrointestinal surgery. During the postoperative period, 3% HS has been suggested as a means to improve the intestinal edema and reduce gastrointestinal complications. The medical records of 111 patients with HS intragastric administration following upper gastrointestinal surgery and 268 patients, served as control, were reviewed retrospectively. Propensity score matching was performed to adjust for selected baseline variables. Clinical outcomes, including early gastrointestinal function recovery, postoperative complications, and length of hospital stay, were compared according to the HS intragastric administration or not. HS intragastric administration was associated with prompt postoperative gastrointestinal function recovery, including first flatus (risk ratio [RR], 1.32; 95% confidence interval [CI], 0.89–1.65; P = 0.048) and feeding within 3 postoperative days (RR (95% CI), 0.57 (0.49–0.77); P = 0.036). Early ileus occurred in 25 of 108 patients with HS treatment versus 36 of 108 patients without HS treatment (RR (95% CI), 1.43 (0.63–2.15); P = 0.065). The patients with HS experienced a lower overall postoperative complication (odds ratio [OD] 0.57; 95% CI, 0.33–1.09; P = 0.063), including trend toward a decrease for infectious complications (15[13.9] vs 23[21.3]; P = 0.11; OD, 0.59; 95% CI, 0.29–1.22). There was a decreased incidence of anastomotic leakage (1[0.9] vs 7[6.5]; P = 0.033) and postoperative ileuas (5[4.6%] vs 11[10.2%]; P = 0.096) in the HS administration patients. Our study demonstrated beneficial postoperative clinical effects of HS intragastric administration in patients who had undergone upper gastrointestinal surgery, such as prompt postoperative gastrointestinal function recovery and reduced overall postoperative complications, which may be attributed to a

  5. Escherichia coli and Salmonella enterica are protected against acetic acid, but not hydrochloric acid, by hypertonicity.

    PubMed

    Chapman, B; Ross, T

    2009-06-01

    Chapman et al. (B. Chapman, N. Jensen, T Ross, and M. B. Cole, Appl. Environ. Microbiol. 72:5165-5172, 2006) demonstrated that an increased NaCl concentration prolongs survival of Escherichia coli O157 SERL 2 in a broth model simulating the aqueous phase of a food dressing or sauce containing acetic acid. We examined the responses of five other E. coli strains and four Salmonella enterica strains to increasing concentrations of NaCl under conditions of lethal acidity and observed that the average "lag" time prior to inactivation decreases in the presence of hydrochloric acid but not in the presence of acetic acid. For E. coli in the presence of acetic acid, the lag time increased with increasing NaCl concentrations up to 2 to 4% at pH 4.0, up to 4 to 6% at pH 3.8, and up to 4 to 7% (wt/wt of water) NaCl at pH 3.6. Salmonella was inactivated more rapidly by combined acetic acid and NaCl stresses than E. coli, but increasing NaCl concentrations still decreased the lag time prior to inactivation in the presence of acetic acid; at pH 4.0 up to 1 to 4% NaCl was protective, and at pH 3.8 up to 1 to 2% NaCl delayed the onset of inactivation. Sublethal injury kinetics suggest that this complex response is a balance between the lethal effects of acetic acid, against which NaCl is apparently protective, and the lethal effects of the NaCl itself. Compared against 3% NaCl, 10% (wt/wt of water) sucrose with 0.5% NaCl (which has similar osmotic potential) was found to be equally protective against adverse acetic acid conditions. We propose that hypertonicity may directly affect the rate of diffusion of acetic acid into cells and hence cell survival.

  6. 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

  7. Potassium depletion and hypertonic medium reduce "non-coated" and clathrin-coated pit formation, as well as endocytosis through these two gates.

    PubMed

    Carpentier, J L; Sawano, F; Geiger, D; Gorden, P; Perrelet, A; Orci, L

    1989-03-01

    Intracellular potassium depletion inhibits receptor-mediated endocytotic processes occurring through clathrin-coated pits. Besides the clathrin-coated pit route, flask-shaped invaginations that do not bear a typical clathrin coat have been recently implicated in receptor-mediated endocytosis of cholera toxin. These invaginations are called "non-coated" to distinguish them from the typical clathrin-coated pits. In the present study, we have investigated whether "non-coated" invaginations are sensitive, as are clathrin-coated pits, to potassium depletion and whether hypertonic medium, which inhibits receptor-mediated endocytosis, also affects "non-coated" invaginations. We found that 1) both potassium depletion and hypertonic medium reduce "non-coated" invaginations on the cell surface; 2) similar to potassium depletion, hypertonic medium markedly decreases the number of clathrin-coated pits; 3) these changes are accompanied by an inhibition of the internalization (measured morphologically) of cholera toxin-gold through "non-coated" invaginations, as well as of alpha 2-macroglobulin-gold taken up by clathrin-coated pits; and 4) in addition, both the hypertonic medium and potassium depletion inhibit the uptake of horseradish peroxidase, a marker of fluid-phase endocytosis.

  8. 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

  9. Antinociception by neutrophil-derived opioid peptides in noninflamed tissue--role of hypertonicity and the perineurium.

    PubMed

    Rittner, H L; Hackel, D; Yamdeu, R-S; Mousa, S A; Stein, C; Schäfer, M; Brack, A

    2009-05-01

    Inflammatory pain can be controlled by intraplantar opioid injection or by secretion of endogenous opioid peptides from leukocytes in inflamed rat paws. Antinociception requires binding of opioid peptides to opioid receptors on peripheral sensory nerve terminals. In the absence of inflammation, hydrophilic opioid peptides do not penetrate the perineurial barrier and, thus, do not elicit antinociception. This study was designed to examine the conditions under which endogenous, neutrophil-derived hydrophilic opioid peptides (i.e. Met-Enkephalin and beta-endorphin) can raise nociceptive thresholds in noninflamed tissue in rats. Intraplantar injection of the chemokine CXCL2/3 (macrophage inflammatory protein-2) induced selective neutrophil recruitment without overt signs of inflammation or changes in mechanical nociceptive thresholds (paw pressure threshold). Following intraplantar injection of hypertonic saline, the perineurial barrier was permeable for hours and intraplantar injection of opioid peptides increased mechanical nociceptive thresholds. While formyl-Met-Leu-Phe (fMLP) triggered opioid peptide release from neutrophils in vitro, nociceptive thresholds were unchanged in vivo. In vitro, hypertonicity interfered with fMLP-induced p38 mitogen activated kinase (MAPK) phosphorylation and opioid peptide release from neutrophils. These inhibitory effects were fully reversible by washout. In vivo, return to normotonicity occurred within 30min while the perineurium remained permeable for hours. Under these conditions, fMLP triggered MAPK phosphorylation and induced opioid peptide-mediated increases in nociceptive thresholds in the noninflamed paw. Taken together, antinociception mediated by endogenous opioids in noninflamed tissue has two important requirements: (i) opening of the perineurial barrier for opioid peptide access and (ii) opioid peptide release from neutrophils involving p38 MAPK.

  10. Treatment of transtentorial herniation unresponsive to hyperventilation using hypertonic saline in dogs: effect on cerebral blood flow and metabolism.

    PubMed

    Qureshi, Adnan I; Wilson, David A; Traystman, Richard J

    2002-01-01

    We tested the hypothesis that transtentorial herniation (TTH) represents a state of cerebral ischemia that can be reversed by hypertonic saline. Because of the high mortality associated with TTH, new therapeutic strategies need to be developed for rapid and effective reversal of this process. We produced TTH (defined by acute dilatation of one or both pupils) by creating supratentorial intracerebral hemorrhage with autologous blood injection in seven mongrel dogs anesthetized using intravenous pentobarbital and fentanyl. We measured serial rCBF (regional cerebral blood flow) using radiolabeled microspheres in regions around and distant to the hematoma. Cerebral oxygen extraction and oxygen consumption (CMRO2) were measured by serial sampling of cerebral venous blood from the sagittal sinus. Mean arterial pressure (MAP) and intracranial pressure (ICP) were continuously monitored. TTH was successfully reversed over a mean period of 25.7 +/- 4.9 minutes after intravenous administration of 23.4% sodium chloride (1.4 mL/kg) in all animals. All measurements were recorded 15, 30, 60, and 90 minutes after administration of 23.4% sodium chloride. Compared to prehematoma ICP (14.1 +/- 1.7 mm Hg, mean +/- SE), elevation in ICP was observed during TTH (36.2 +/- 7.2 mm Hg) with no change in cerebral perfusion pressure (CPP) (80.4 +/- 4.7 vs. 76.7 +/- 10.1 mm Hg) because of concomitant elevation in mean arterial pressure. Compared to baseline values, there was a reduction in rCBF (mL/100 gm/min +/- SE) in brainstem (12.1 +/- 2.0 vs. 21.4 +/- 1.4), gray matter (18.2 +/- 2.1 vs. 31.4 +/- 1.8), and white matter (8.6 +/- 1.7 vs.18.7 +/- 0.9) in the hemisphere contralateral to the hematoma; and gray matter (12.9 +/- 2.9 vs. 27.9 +/- 2.2) and white matter (8.3 +/- 2.0 vs.19.9 +/- 1.0) in the ipsilateral hemisphere distant from the hematoma. Administration of 23.4% sodium chloride resulted in reduced ICP at 15 minutes (12.7 +/- 1.4) and 30 minutes (15.6 +/- 3.1) after administration

  11. NKCC2A and NFAT5 regulate renal TNF production induced by hypertonic NaCl intake.

    PubMed

    Hao, Shoujin; Bellner, Lars; Ferreri, Nicholas R

    2013-03-01

    Pathways that contribute to TNF production by the kidney are not well defined. Mice given 1% NaCl in the drinking water for 3 days exhibited a 2.5-fold increase in urinary, but not plasma, TNF levels compared with mice given tap water. Since furosemide attenuated the increase in TNF levels, we hypothesized that hypertonic NaCl intake increases renal TNF production by a pathway involving the Na(+)-K(+)-2Cl(-) cotransporter (NKCC2). A 2.5-fold increase in NKCC2A mRNA accumulation was observed in medullary thick ascending limb (mTAL) tubules from mice given 1% NaCl; a concomitant 2-fold increase in nuclear factor of activated T cells 5 (NFAT5) mRNA and protein expression was observed in the outer medulla. Urinary TNF levels were reduced in mice given 1% NaCl after an intrarenal injection of a lentivirus construct designed to specifically knockdown NKCC2A (EGFP-N2A-ex4); plasma levels of TNF did not change after injection of EGFP-N2A-ex4. Intrarenal injection of EGFP-N2A-ex4 also inhibited the increase of NFAT5 mRNA abundance in the outer medulla of mice given 1% NaCl. TNF production by primary cultures of mTAL cells increased approximately sixfold in response to an increase in osmolality to 400 mosmol/kgH2O produced with NaCl and was inhibited in cells transiently transfected with a dnNFAT5 construct. Transduction of cells with EGFP-N2A-ex4 also prevented increases in TNF mRNA and protein production in response to high NaCl concentration and reduced transcriptional activity of a NFAT5 promoter construct. Since NKCC2A expression is restricted to the TAL, NKCC2A-dependent activation of NFAT5 is part of a pathway by which the TAL produces TNF in response to hypertonic NaCl intake.

  12. 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

  13. Requirement for the eIF4E binding proteins for the synergistic down-regulation of protein synthesis by hypertonic conditions and mTOR inhibition.

    PubMed

    Clemens, Michael J; Elia, Androulla; Morley, Simon J

    2013-01-01

    The protein kinase mammalian target of rapamycin (mTOR) regulates the phosphorylation and activity of several proteins that have the potential to control translation, including p70S6 kinase and the eIF4E binding proteins 4E-BP1 and 4E-BP2. In spite of this, in exponentially growing cells overall protein synthesis is often resistant to mTOR inhibitors. We report here that sensitivity of wild-type mouse embryonic fibroblasts (MEFs) to mTOR inhibitors can be greatly increased when the cells are subjected to the physiological stress imposed by hypertonic conditions. In contrast, protein synthesis in MEFs with a double knockout of 4E-BP1 and 4E-BP2 remains resistant to mTOR inhibitors under these conditions. Phosphorylation of p70S6 kinase and protein kinase B (Akt) is blocked by the mTOR inhibitor Ku0063794 equally well in both wild-type and 4E-BP knockout cells, under both normal and hypertonic conditions. The response of protein synthesis to hypertonic stress itself does not require the 4E-BPs. These data suggest that under certain stress conditions: (i) translation has a greater requirement for mTOR activity and (ii) there is an absolute requirement for the 4E-BPs for regulation by mTOR. Importantly, dephosphorylation of p70S6 kinase and Akt is not sufficient to affect protein synthesis acutely.

  14. Regulation of the hypertonic stress response and other cellular functions by the Rel-like transcription factor NFAT5.

    PubMed

    Aramburu, José; Drews-Elger, Katherine; Estrada-Gelonch, Anaïs; Minguillón, Jordi; Morancho, Beatriz; Santiago, Verónica; López-Rodríguez, Cristina

    2006-11-30

    Stress, be it from environmental factors or intrinsic to the cell as result of growth and metabolism, can be harmful to cells. Mammalian cells have developed numerous mechanisms to respond to diverse forms of stress. These mechanisms combine signaling cascades and activation of gene expression programs to orchestrate an adaptive response that will allow the cell to survive and resume its normal functioning. In this review we will focus on the transcription factor NFAT5, a fundamental regulator of the response to osmotic stress in mammalian cells. Identified in 1999, NFAT5 is the latest addition to the Rel family, which comprises the NF-kappaB and NFATc proteins. Though in some of its structural and functional features NFAT5 is a hybrid between these two major groups of Rel proteins, it has unique characteristics that make it stand on its own as a third type of Rel transcription factor. Since its discovery, NFAT5 has been studied mostly in the context of the hypertonicity stress response. The advent of mouse models deficient in NFAT5 and other recent advances have confirmed a fundamental osmoprotective role for this factor in mammals, but also revealed features that suggest it may have a wider range of functions.

  15. 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

  16. Impact of fluid resuscitation with hypertonic-hydroxyethyl starch versus lactated ringer on hemorheology and microcirculation in hemorrhagic shock.

    PubMed

    Guerci, Philippe; Tran, Nguyen; Menu, Patrick; Losser, Marie-Reine; Meistelman, Claude; Longrois, Dan

    2014-01-01

    The choice of volume expander for fluid resuscitation in hemorrhagic shock is still debated. Changes in plasma viscosity (PV) are barely investigated while PV modulates functional capillary density, microcirculation and organ function. The present study evaluated the impact of 2 strategies of fluid resuscitation in hemorrhagic shock in pigs. Ten pigs were subjected to hemorrhagic shock and randomly assigned to a low viscosity fluid regimen (Lactated Ringer's, LR) group or a high viscosity regimen (hypertonic-hydroxyethyl starch, HES) for volume resuscitation. Sublingual microcirculatory flow and tissue oxygen tension were assessed together with macro- and microcirculatory, biochemical and rheological variables at baseline, 30 minutes after hemorrhagic shock, immediately after reaching resuscitation endpoints (R-0), and 60 minutes after resuscitation (R-60). PV decreased similarly in both groups following resuscitation (from 1.36 [1.32-1.38] to 1.21 [1.21-1.23] for LR, and from 1.32 [1.31-1.32] to 1.20 [1.17-1.21] mPa.s for HES). No differences were found between the groups for other rheological variables, microcirculatory flow or tissue oxygen tension at R-0 and R-60. Despite a 6-fold difference in the volumes required to achieve blood flow endpoints, commercially available volume expanders had similar effects on rheological and microcirculatory variables, irrespective of their viscosity. Our findings are consistent with the absence of clinically relevant differences between crystalloid and colloid resuscitation of hemorrhagic shock.

  17. ‘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

  18. 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

  19. 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.

  20. Reduction of Tendon Adhesions following Administration of Adaprev, a Hypertonic Solution of Mannose-6-Phosphate: Mechanism of Action Studies

    PubMed Central

    Wong, Jason K. F.; Metcalfe, Anthony D.; Wong, Richard; Bush, Jim; Platt, Chris; Garcon, Arnaud; Goldspink, Nick; McGrouther, Duncan A.; Ferguson, Mark W. J.

    2014-01-01

    Repaired tendons may be complicated by progressive fibrosis, causing adhesion formation or tendon softening leading to tendon rupture and subsequent reduced range of motion. There are few therapies available which improve the gliding of damaged tendons in the hand. We investigate the role of Mannose 6-phosphate (M6P) in a 600 mM hypertonic solution (Adaprev) on tendon adhesion formation in vivo using a mouse model of severed tendon in conjunction with analysis of collagen synthesis, cellular proliferation and receptors involved in TGF beta signalling. Cytotoxicity was assessed by measuring tissue residency, mechanical strength and cell viability of tendons after treatment with Adaprev. To elicit potential modes of action, in vitro and ex vivo studies were performed investigating phosphorylation of p38, cell migration and proliferation. Adaprev treatment significantly (p<0.05) reduced the development of adhesions and improved collagen organisation without reducing overall collagen synthesis following tendon injury in vivo. The bioavailability of Adaprev saw a 40% reduction at the site of administration over 45 minutes and tendon fibroblasts tolerated up to 120 minutes of exposure without significant loss of cell viability or tensile strength. These favourable effects were independent of CI-MPR and TGF-β signalling and possibly highlight a novel mechanism of action related to cellular stress demonstrated by phosphorylation of p38. The effect of treatment reduced tendon fibroblast migration and transiently halted tendon fibroblast proliferation in vitro and ex vivo. Our studies demonstrate that the primary mode of action for Adaprev is potentially via a physical, non-chemical, hyperosmotic effect. PMID:25383548

  1. LL-37 complexation with glycosaminoglycans in cystic fibrosis lungs inhibits antimicrobial activity, which can be restored by hypertonic saline.

    PubMed

    Bergsson, Gudmundur; Reeves, Emer P; McNally, Paul; Chotirmall, Sanjay H; Greene, Catherine M; Greally, Peter; Murphy, Philip; O'Neill, Shane J; McElvaney, Noel G

    2009-07-01

    There is an abundance of antimicrobial peptides in cystic fibrosis (CF) lungs. Despite this, individuals with CF are susceptible to microbial colonization and infection. In this study, we investigated the antimicrobial response within the CF lung, focusing on the human cathelicidin LL-37. We demonstrate the presence of the LL-37 precursor, human cathelicidin precursor protein designated 18-kDa cationic antimicrobial protein, in the CF lung along with evidence that it is processed to active LL-37 by proteinase-3. We demonstrate that despite supranormal levels of LL-37, the lung fluid from CF patients exhibits no demonstrable antimicrobial activity. Furthermore Pseudomonas killing by physiological concentrations of exogenous LL-37 is inhibited by CF bronchoalveolar lavage (BAL) fluid due to proteolytic degradation of LL-37 by neutrophil elastase and cathepsin D. The endogenous LL-37 in CF BAL fluid is protected from this proteolysis by interactions with glycosaminoglycans, but while this protects LL-37 from proteolysis it results in inactivation of LL-37 antimicrobial activity. By digesting glycosaminoglycans in CF BAL fluid, endogenous LL-37 is liberated and the antimicrobial properties of CF BAL fluid restored. High sodium concentrations also liberate LL-37 in CF BAL fluid in vitro. This is also seen in vivo in CF sputum where LL-37 is complexed to glycosaminoglycans but is liberated following nebulized hypertonic saline resulting in increased antimicrobial effect. These data suggest glycosaminoglycan-LL-37 complexes to be potential therapeutic targets. Factors that disrupt glycosaminoglycan-LL-37 aggregates promote the antimicrobial effects of LL-37 with the caveat that concomitant administration of antiproteases may be needed to protect the now liberated LL-37 from proteolytic cleavage.

  2. 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

  3. Unilateral fluid absorption and effects on peak power after ingestion of commercially available hypotonic, isotonic, and hypertonic sports drinks.

    PubMed

    Rowlands, David S; Bonetti, Darrell L; Hopkins, Will G

    2011-12-01

    Isotonic sports drinks are often consumed to offset the effects of dehydration and improve endurance performance, but hypotonic drinks may be more advantageous. The purpose of the study was to compare absorption and effects on performance of a commercially available hypotonic sports drink (Mizone Rapid: 3.9% carbohydrate [CHO], 218 mOsmol/kg) with those of an isotonic drink (PowerAde: 7.6% CHO, 281 mOsmol/ kg), a hypertonic drink (Gatorade: 6% CHO, 327 mOsmol/kg), and a noncaloric placebo (8 mOsmol/kg). In a crossover, 11 cyclists consumed each drink on separate days at 250 ml/15 min during a 2-hr preload ride at 55% peak power followed by an incremental test to exhaustion. Small to moderate increases in deuterium oxide enrichment in the preload were observed with Mizone Rapid relative to PowerAde, Gatorade, and placebo (differences of 88, 45, and 42 parts per million, respectively; 90% confidence limits ±28). Serum osmolality was moderately lower with Mizone Rapid than with PowerAde and Gatorade (-1.9, -2.4; mOsmol/L; ±1.2 mOsmol/L) but not clearly different vs. placebo. Plasma volume reduction was small to moderate with Mizone Rapid, PowerAde, and Gatorade relative to placebo (-1.9%, -2.5%, -2.9%; ± 2.5%). Gut comfort was highest with Mizone Rapid but clearly different (8.4% ± 4.8%) only vs PowerAde. Peak power was highest with Mizone Rapid (380 W) vs. placebo and other drinks (1.2-3.0%; 99% confidence limits ±4.7%), but differences were inconclusive with reference to the smallest important effect (~1.2%). The outcomes are consistent with fastest fluid absorption with the hypotonic sports drink. Further research should determine whether the effect has a meaningful impact on performance.

  4. Lower dose of hypertonic saline dextran reduces the risk of lethal rebleeding in uncontrolled hemorrhage.

    PubMed

    Riddez, Louis; Drobin, Dan; Sjöstrand, Fredrik; Svensén, Christer; Hahn, Robert G

    2002-05-01

    To challenge whether the recommended dose of 4 mL/kg of 7.5% sodium chloride in 6% Dextran (HSD) is optimal for fluid resuscitation in uncontrolled hemorrhage, 30 anesthetized pigs were randomized to receive a 5-min intravenous infusion of either 1, 2, or 4 mL/kg of HSD beginning 10 min after inducing a 5-mm laceration in the infrarenal aorta. In addition to conventional hemodynamic monitoring, the blood loss was calculated as the difference in blood flow rates between flow probes placed proximal and distal to the injury. The results show that the bleeding stopped between 3 and 4 min after the injury and amounted to 338+/-92 mL (mean +/- SEM), which corresponds to 28.5%+/-6.6% of the estimated blood volume. After treatment with HSD was started, six rebleeding events occurred in the 1-mL group, 11 in the 2-mL group, and 16 in the 4-mL group. The amount of blood lost due to rebleeding increased significantly with the dose of HSD and was also associated with a fatal outcome. The total blood loss was 408 mL in the survivors and 630 mL in the nonsurvivors (median, P < 0.007). The mortality in the three groups was 20%, 50%, and 50%, respectively. In conclusion, infusing 4 mL/kg of HSD after uncontrolled aortic hemorrhage promoted rebleeding and increased the mortality, while a dose of 1 mL/kg appeared to be more suitable.

  5. Early free access to hypertonic NaCl solution induces a long-term effect on drinking, brain cell activity and gene expression of adult rat offspring.

    PubMed

    Macchione, A F; Beas, C; Dadam, F M; Caeiro, X E; Godino, A; Ponce, L F; Amigone, J L; Vivas, L

    2015-07-09

    Exposure to an altered osmotic environment during a pre/postnatal period can differentially program the fluid intake and excretion pattern profile in a way that persists until adulthood. However, knowledge about the programming effects on the underlying brain neurochemical circuits of thirst and hydroelectrolyte balance, and its relation with behavioral outputs, is limited. We evaluated whether early voluntary intake of hypertonic NaCl solution may program adult offspring fluid balance, plasma vasopressin, neural activity, and brain vasopressin and angiotensinergic receptor type 1a (AT1a)-receptor gene expression. The manipulation (M) period covered dams from 1 week before conception until offspring turned 1-month-old. The experimental groups were (i) Free access to hypertonic NaCl solution (0.45 M NaCl), food (0.18% NaCl) and water [M-Na]; and (ii) Free access to food and water only [M-Ctrol]. Male offspring (2-month-old) were subjected to iv infusion (0.15 ml/min) of hypertonic (1.5M NaCl), isotonic (0.15M NaCl) or sham infusion during 20 min. Cumulative water intake (140 min) and drinking latency to the first lick were recorded from the start of the infusion. Our results indicate that, after systemic sodium overload, the M-Na group had increased water intake, and diminished neuronal activity (Fos-immunoreactivity) in the subfornical organ (SFO) and nucleus of the solitary tract. They also showed reduced relative vasopressin (AVP)-mRNA and AT1a-mRNA expression at the supraoptic nucleus and SFO, respectively. The data indicate that the availability of a rich source of sodium during the pre/postnatal period induces a long-term effect on drinking, neural activity, and brain gene expression implicated in the control of hydroelectrolyte balance.

  6. Infusion of hypertonic saline into the lung parenchyma during radiofrequency ablation of the lungs with multitined expandable electrodes: results using a porcine model.

    PubMed

    Iishi, Tatsuhiko; Hiraki, Takao; Mimura, Hidefumi; Gobara, Hideo; Kurose, Taichi; Fujiwara, Hiroyasu; Sakurai, Jun; Yanai, Hiroyuki; Yoshino, Tadashi; Kanazawa, Susumu

    2009-06-01

    The present study was performed to clarify the effect of hypertonic saline infusion into the lung parenchyma on radiofrequency ablation (RFA) of the lungs. A total of 20 ablation zones were created in 3 pigs. The ablation zones were divided into 3 groups. Group 1 (n=6) consisted of ablation zones created by applying smaller radiofrequency (RF) power without saline infusion; group 2 (n=5) zones were created by applying greater RF power without saline infusion;and group 3 (n=9) zones were created by applying greater RF power with saline infusion. The techniques of saline infusion included administration of hypertonic saline 1 ml before RFA, followed by continuous administration at a rate of 1 ml/min during the first 2 min after the initiation of RFA. The ablation parameters and coagulation necrosis volumes were compared among the groups. Group 3 had a tendency toward smaller mean impedance than group 1 (p=0.059) and group 2 (p=0.053). Group 3 showed significantly longer RF application time than group 2 (p=0.004) and significantly greater maximum RF power than group 1 (p=0.001) and group 2 (p=0.004). Group 3 showed significantly larger coagulation necrosis volume (mean, 1,421mm3) than group 2 (mean, 858 mm3, p=0.039) and had a tendency toward larger necrosis volume than group 1 (mean, 878 mm3, p=0.077). Although this small study had limited statistical power, hypertonic saline infusion during RFA appeared to enlarge coagulation necrosis of the lung parenchyma.

  7. Complications associated with insertion of intrauterine pressure catheters: an unusual case of uterine hypertonicity and uterine perforation resulting in fetal distress after insertion of an intrauterine pressure catheter.

    PubMed

    Rood, Kara M

    2012-01-01

    Insertion of intrauterine pressure catheters is a routine procedure performed in labor and delivery departments, with few associated complications. There are several reports of maternal and neonatal morbidity associated with the use of intrauterine pressure catheters and their rare adverse outcomes. We report an unusual case of uterine hypertonicity resulting in fetal distress, immediately after the placement of an intrauterine pressure catheter. An emergent Cesarean section was performed for fetal distress and revealed a 5 cm vertical rent in the posterior lower uterine segment. The uterine perforation was repaired intraoperatively. Mother and infant did well and were discharged home on postoperative day four.

  8. Continuous controlled-infusion of hypertonic saline solution in traumatic brain-injured patients: a 9-year retrospective study

    PubMed Central

    2011-01-01

    Introduction Description of a continuous hypertonic saline solution (HSS) infusion using a dose-adaptation of natremia in traumatic brain injured (TBI) patients with refractory intracranial hypertension (ICH). Methods We performed a single-center retrospective study in a surgical intensive care unit of a tertiary hospital. Fifty consecutive TBI patients with refractory ICH treated with continuous HSS infusion adapted to a target of natremia. In brief, a physician set a target of natremia adapted to the evolution of intracranial pressure (ICP). Flow of NaCl 20% was a priori calculated according to natriuresis, and the current and target natremia that were assessed every 4 hours. Results The HSS infusion was initiated for a duration of 7 (5 to 10) (8 ± 4) days. ICP decreased from 29 (26 to 34) (31 ± 9) mm Hg at H0 to 20 (15 to 26) (21 ± 8) mm Hg at H1 (P < 0.05). Cerebral perfusion pressure increased from 61 (50 to 70) (61 ± 13) mm Hg at H0 up to 67 (60 to 79) (69 ± 12) mm Hg at H1 (P < 0.05). No rebound of ICH was reported after stopping continuous HSS infusion. Natremia increased from 140 (138 to 143) (140 ± 4) at H0 up to 144 (141 to 148) (144 ± 4) mmol/L at H4 (P < 0.05). Plasma osmolarity increased from 275 (268 to 281) (279 ± 17) mmol/L at H0 up to 290 (284 to 307) (297 ± 17) mmol/L at H24 (P < 0.05). The main side effect observed was an increase in chloremia from 111 (107 to 119) (113 ± 8) mmol/L at H0 up to 121 (117 to 124) (121 ± 6) mmol/L at H24 (P < 0.05). Neither acute kidney injury nor pontine myelinolysis was recorded. Conclusions Continuous HSS infusion adapted to close biologic monitoring enables long-lasting control of natremia in TBI patients along with a decreased ICP without any rebound on infusion discontinuation. PMID:22035596

  9. Hypertonicity regulates the function of human neutrophils by modulating chemoattractant receptor signaling and activating mitogen-activated protein kinase p38.

    PubMed Central

    Junger, W G; Hoyt, D B; Davis, R E; Herdon-Remelius, C; Namiki, S; Junger, H; Loomis, W; Altman, A

    1998-01-01

    Excessive neutrophil activation causes posttraumatic complications, which may be reduced with hypertonic saline (HS) resuscitation. We tested if this is because of modulated neutrophil function by HS. Clinically relevant hypertonicity (10-25 mM) suppressed degranulation and superoxide formation in response to fMLP and blocked the activation of the mitogen activated protein kinases (MAPK) ERK1/2 and p38, but did not affect Ca2+ mobilization. HS did not suppress oxidative burst in response to phorbol myristate acetate (PMA). This indicates that HS suppresses neutrophil function by intercepting signal pathways upstream of or apart from PKC. HS activated p38 by itself and enhanced degranulation in response to PKC activation. This enhancement was reduced by inhibition of p38 with SB203580, suggesting that p38 up-regulation participates in HS-induced enhancements of degranulation. HS had similar effects on the degranulation of cells that were previously stimulated with fMLP, but had no effect on its own, suggesting that HS enhancement of degranulation requires another signal. We conclude that depending on other stimuli, HS can suppress neutrophil activation by intercepting multiple receptor signals or augment degranulation by enhancing p38 signaling. In patients HS resuscitation may reduce posttraumatic complications by preventing neutrophil activation via chemotactic factors released during reperfusion. PMID:9637711

  10. 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

  11. Efficacy and Safety of Continuous Micro-Pump Infusion of 3% Hypertonic Saline combined with Furosemide to Control Elevated Intracranial Pressure

    PubMed Central

    Li, Yuqian; Li, Zhihong; Li, Min; Yang, Yanlong; Wang, Bao; Gao, Li; Zhang, Xingye; Cheng, Hongyu; Fang, Wei; Zhao, Bo; Wang, Boliang; Gao, Guodong; Li, Lihong

    2015-01-01

    Background Elevated intracranial pressure is one of the most common problems in patients with diverse intracranial disorders, leading to increased morbidity and mortality. Effective management for increased intracranial pressure is based mainly on surgical and medical techniques with hyperosmolar therapy as one of the core medical treatments. The study aimed to explore the effects of continuous micro-pump infusions of 3% hypertonic saline combined with furosemide on intracranial pressure control. Material/Methods We analyzed data on 56 eligible participants with intracranial pressure >20 mmHg from March 2013 to July 2014. The target was to increase and maintain plasma sodium to a level between 145 and 155 mmol/L and osmolarity to a level of 310 to 320 mOsmol/kg. Results Plasma sodium levels significantly increased from 138±5 mmol/L at admission to 151±3 mmol/L at 24 h (P<0.01). Osmolarity increased from 282±11 mOsmol/kg at baseline to 311±8 mOsmol/kg at 24 h (P<0.01). Intracranial pressure significantly decreased from 32±7 mmHg to 15±6 mmHg at 24 h (P<0.01). There was a significant improvement in CPP (P<0.01). Moreover, central venous pressure, mean arterial pressure, and Glasgow Coma Scale slightly increased. However, these changes were not statistically significant. Conclusions Continuous infusion of 3% hypertonic saline + furosemide is effective and safe for intracranial pressure control. PMID:26082293

  12. Efficacy of conivaptan and hypertonic (3%) saline in treating hyponatremia due to syndrome of inappropriate antidiuretic hormone in a tertiary Intensive Care Unit

    PubMed Central

    Reddy, Sridhar Nagepalli Venkatarami; Rangappa, Pradeep; Jacob, Ipe; Janakiraman, Rajeswari; Rao, Karthik

    2016-01-01

    Background: Hyponatremia is one of the most common electrolyte abnormalities encountered in clinical practice and has a significant impact on morbidity and mortality in hospitalized patients. The optimal management of hyponatremia is still evolving. Over the last decade, vaptans have been increasingly used in clinical practice with promising results. Materials and Methods: The study included eighty patients with symptomatic hyponatremia due to syndrome of inappropriate antidiuretic hormone (SIADH) admitted and treated in Intensive Care Unit (ICU) with either conivaptan or hypertonic (3%) saline. They were compared for time taken to achieve normal serum sodium, length of ICU and hospital stay, and adverse effects. Results: The demographic data and serum sodium levels at admission were comparable between the two groups. After initiating correction, sodium levels at 6, 12, and 24 h were similar between the two groups. However, at 48 h, patients in the conivaptan group (Group C) had higher sodium levels (133.0 ± 3.8 mEq/L) as compared to hypertonic saline group (Group HS) (128.9 ± 2.6 mEq/L), which was statistically significant (P < 0.001). The length of ICU stay was less in the Group C (3.35 ± 0.89 days) when compared with the Group HS (4.61 ± 0.91 days) (P < 0.001). There was no significant difference in mortality between the two groups. Conclusion: In patients with symptomatic hyponatremia due to SIADH, conivaptan with its aquaresis property can achieve a significantly better sodium correction, resulting in reduced ICU and hospital stay with no significant adverse effects. PMID:28149029

  13. In rat hepatocytes, the hypertonic activation of Na(+) conductance and Na(+)-K(+)-2Cl(-) symport--but not Na(+)-H(+) antiport--is mediated by protein kinase C.

    PubMed

    Heinzinger, H; van den Boom, F; Tinel, H; Wehner, F

    2001-11-01

    1. The initial event in the regulatory volume increase (RVI) of rat hepatocytes is an import of extracellular Na(+) via Na(+) conductance, Na(+)-K(+)-2Cl(-) symport, and Na(+)-H(+) antiport. 2. Here, the protein kinase inhibitors staurosporine (100 nmol l(-1)) and bis-indolyl-maleimide I (400 nmol l(-1)) were used to test for a possible contribution of protein kinase C (PKC) to the hypertonic activation of these transporters in confluent primary cultures. 3. Stimulation of Na(+) conductance was monitored: (i) by use of a differential approach based on Na(+) fluxes, (ii) by means of cable analysis, and (iii) in experiments with low Na(+) pulses. All three experimental protocols in concert demonstrated a block of the activation of Na(+) conductance by staurosporine and bis-indolyl-maleimide I. 4. In addition, both compounds significantly reduced the hypertonic activation of Na(+)-K(+)-2Cl(-) symport (quantified on the basis of furosemide-sensitive (86)Rb(+) uptake) to approximately 30 %. 5. In contrast, neither staurosporine nor bis-indolyl-maleimide I had any detectable effect on the hypertonicity-induced alkalinization of cell pH via Na(+)-H(+) antiport (determined fluorometrically). 6. Staurosporine and bis-indolyl-maleimide I completely blocked the RVI of rat hepatocytes (quantified by means of confocal laser-scanning microscopy). The high efficiency of the block suggests an additional inhibitory effect of both compounds on the activity of Na(+)/K(+)-ATPase (determined as ouabain-sensitive (86)Rb(+) uptake). 7. It is concluded that the hypertonic activation of rat hepatocyte Na(+) conductance and Na(+)-K(+)-2Cl(-) symport--but not Na(+)-H(+) antiport--is probably mediated by PKC.

  14. Comparison of the protoscolocidal effectiveness of hypertonic saline, povidone-iodine and albendazole solutions in an experimental lung hydatid cyst model.

    PubMed

    Durgun Yetim, T; Basoglu, A; Taslak Sengul, A; Yetim, I; Serdar Bekdemir, O; Hokelek, M

    2011-01-01

    Secondary hydatidosis is an important problem encountered during the surgical treatment of hydatid cysts. This study describes an experimental model of secondary hydatidosis by cyst inoculation, used to explore whether simultaneous inoculation of protoscolocidal agents could prevent secondary hydatidosis. Fertile cyst fluid was injected into the pleural space of rabbits alone (group 1, n = 8), and in combination with 2% albendazole solution (group 2, n = 8), 20% hypertonic saline (group 3, n = 8) or 10% povidone-iodine (group 4, n = 8). Computed tomography imaging of the thorax, indirect haemagglutination (IHA) titres and eosinophil counts were used to determine cyst development. After 16 months, three control rabbits had pneumothorax, seven had cysts and four had parenchymal nodules. Histopathological investigation of nodules revealed 87.5% cyst formation. Pleural thickening was observed in rabbits from all groups. Cyst formation rates, IHA titres and eosinophilia counts were higher in group 1 than in groups 2-4. This study demonstrated the experimental formation of secondary hydatidosis and found that topical protoscolocidal agents were beneficial in preventing cyst recurrence.

  15. Comparison of effects of equiosmolar doses of mannitol and hypertonic saline on cerebral blood flow and metabolism in traumatic brain injury.

    PubMed

    Cottenceau, Vincent; Masson, Francoise; Mahamid, Eugenia; Petit, Laurent; Shik, Venyamin; Sztark, Francois; Zaaroor, Menashe; Soustiel, Jean Francois

    2011-10-01

    The potential superiority of hypertonic saline (HTS) over mannitol (MTL) for control of intracranial pressure (ICP) following traumatic brain injury (TBI) is still debated. Forty-seven severe TBI patients with increased ICP were prospectively recruited in two university hospitals and randomly treated with equiosmolar infusions of either MTL 20% (4 mL/kg; n=25 patients) or HTS 7.5% (2 mL/kg; n=22 patients). Serum sodium, hematocrit, ICP, arterial blood pressure, cerebral perfusion pressure (CPP), shear rate, global indices of cerebral blood flow (CBF) and metabolism were measured before, and 30 and 120 min following each infusion during the course of illness. Outcome was assessed at 6 months. Both HTS and MTL effectively and equally reduced ICP levels with subsequent elevation of CPP and CBF, although this effect was significantly stronger and of longer duration after HTS and correlated with improved rheological blood properties induced by HTS. Further, effect of HTS on ICP appeared to be more robust in patients with diffuse brain injury. In contrast, oxygen and glucose metabolic rates were left equally unaffected by both solutions. Accordingly, there was no significant difference in neurological outcome between the two groups. In conclusion, MTL was as effective as HTS in decreasing ICP in TBI patients although both solutions failed to improved cerebral metabolism. HTS showed an additional and stronger effect on cerebral perfusion of potential benefit in the presence of cerebral ischemia. Treatment selection should therefore be individually based on sodium level and cerebral hemodynamics.

  16. [Effect of incubation in sodium chloride hypertonic solutions on human blood lymphocyte DNA damage formation by long-wave UV-radiation].

    PubMed

    Smetanina, N M; Pustovalova, M V; Osipov, A N

    2013-01-01

    Effect of incubation in NaCl hypertonic solutions (0.2, 0.35 and 0.5 mol/L for 1 h at 4 degrees C) on the DNA single-strand breaks (SSB) and alkaline-labile site (ALS) yields induced by long-wave UV-radiation (365 +/- 10 nm) in human blood peripheral lymphocytes in vitro was investigated. It was shown that compared to the cells incubated in NaCl isotonic solution (0.14 mol/L) statistically significant increases in the yields of both spontaneous (-1.5-1.9 times) and UV-A radiation induced (-1.6-1.7 times) DNA damage was observed only at the NaCl concentration of 0.5 mol/L. It is assumed that at this concentration of NaCl, dissociation of the linker histone H1 occurs, the structure of chromatin is disrupted and the free radical-induced DNA damage output dramatically increases.

  17. Short-term hypertonic exposure enhances in vitro follicle growth and meiotic competence of enclosed oocytes while modestly affecting mRNA expression of aquaporin and steroidogenic genes in the domestic cat model.

    PubMed

    Songsasen, N; Thongkittidilok, C; Yamamizu, K; Wildt, D E; Comizzoli, P

    2017-03-01

    Using the domestic cat as a non-rodent, larger animal model, the objective was to determine the impact of a brief incubation in a hypertonic microenvironment on (1) ovarian follicle and oocyte growth in vitro, (2) developmental capacity of the resident oocyte, and (3) expression of aquaporin (AQP) genes in parallel with genes involved in regulation of folliculogenesis. In Study 1: Secondary or early antral follicles encapsulated in 0.5% alginate were allocated to one of three treatment groups: 1) culture in standard medium at 290 mOsm for 15 d (Control); 2) incubation in 350 mOsm medium for 1 h followed by culture in standard medium for 15 d (Hypertonic-1h); or 3) incubation in 350 mOsm medium for 24 h followed by incubation in standard medium for additional 14 d (Hypertonic-24h). After measuring follicle and oocyte diameters on Day 15, in vitro-grown oocytes were incubated for 24 h before assessing nuclear status. In Study 2: secondary or early antral follicles were subjected to one of the three treatments: 1) culture in standard medium at 290 mOsm for 48 h; 2) incubation in 350 mOsm medium for 1 h followed by culture in standard medium for additional 47 h; or 3) incubation in 350 mOsm medium for 24 h followed by culture in standard medium for additional 24 h. At the end of the culture period, all follicles were assessed for mRNA level of Cyp17a1, Cyp19a1, Star, Aqp1, 3, 5, 7 and 8 as well as Fshr using qPCR. Freshly collected follicles also were subjected to gene expression analysis and served as the 'Non-cultured control'. Hypertonic-24h follicles grew larger (P < 0.05) than the control, whereas those in Hypertonic-1h group exhibited intermediate growth, especially when the culture started at the early antral stage. Oocytes in the Hypertonic-24h group were larger and resumed meiosis at a higher rate than in the other treatments. In vitro culture affected (P < 0.05) mRNA expression of Cyp19a1, Star, Aqp1, and Aqp7 in both the secondary and early

  18. 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…

  19. In Situ Fluorescence Measurement of Tear Film [Na+], [K+], [Cl−], and pH in Mice Shows Marked Hypertonicity in Aquaporin-5 Deficiency

    PubMed Central

    Ruiz-Ederra, Javier; Levin, Marc H.; Verkman, A. S.

    2009-01-01

    Purpose Tear film composition depends on water and ion transport across ocular surface epithelia and on fluid secretion by lacrimal glands. The purpose of this study was to establish in situ fluorescence methods to measure tear film ionic concentrations and pH in mice and to determine whether tear film composition is sensitive to deficiency of the major ocular surface aquaporin water channels. Methods Tear film ionic concentrations and pH were measured in anesthetized mice by ratio imaging fluorescence microscopy after topical application of ion/pH-sensing, dual-wavelength fluorescent indicators. [Na+], [K+], and [Cl−] were measured with membrane-impermeant indicators developed by our laboratory, and pH was measured with bis(carboxyethyl)-carboxyfluorescein fluorescence-conjugated dextran. Measurements were performed on wild-type mice and on knockout mice lacking aquaporins AQP1, AQP3, and AQP5. Results In wild-type mice, tear film [Na+] was 139 ± 8 mM, [K+] was 48 ± 1 mM, [Cl−] was 127 ± 4 mM, and pH was 7.59 ± 0.2 (SE; n = 5–8). pH did not differ significantly in the AQP knockout mice. [Na+] was increased by approximately twofold in AQP5 null mice (230 ± 20 mM) and was greatly reduced after exposure of the ocular surface to a humidified atmosphere. [K+] was mildly reduced in AQP1 null mice. Conclusions These results establish an in situ optical methodology to measure tear film [Na+], [K+], [Cl−], and pH in living mice, without the need for fluid sampling. Tear film hypertonicity in AQP5 deficiency is likely caused by reduced transcorneal water secretion in response to evaporative water loss. PMID:19136711

  20. The influence of hypertonic mannitol on regional myocardial blood flow during acute and chronic myocardial ischemia in anesthetized and awake intact dogs.

    PubMed Central

    Willerson, J T; Watson, J T; Hutton, I; Fixler, D E; Curry, G C; Templeton, G H

    1975-01-01

    The influence of hypertonic mannitol on regional myocardial blood flow and ventricular performance was studied during acute myocardial ischemia in awake, unsedated and in anesthesized dogs and after myocardial infarction in awake unsedated dogs. Regional myocardial blood flow was measured with radioactive microspheres. Generalized increases in regional myocardial blood flow occurred after mannitol in all of the different animal models studied. The increases in coronary blood flow after mannitol were just as impressive in the nonischemic regions as in the ischemic portion of the left ventricle in all of the different models that were examined in this study. Improvement in regional myocardial blood flow to the ischemic area of the left ventricle after mannitol was associated with a reduction in ST segment elevation during acute myocardial ischemia in anesthetized dogs. The increases in regional myocardial flow after mannitol were also associated with increases in contractility, but the increases in flow appeared to be more impressive than the changes in contractility. The data obtained demonstrate that mannitol increases regional coronary blood flow to both ischemic and nonischemic myocardium in both anesthetized and awake, unsedated, intact dogs with acute and chronic myocardial ischemia and that mannitol reduces ST segment elevation during acute myocardial ischemia in anesthetized dogs. Thus the results suggest that under these circumstances the increases in regional myocardial blood flow after mannitol are of physiological importance in reducing the extent of myocardial injury. Since coronary blood flow increased to nonischemic regions the increases in regional myocardial flow demonstrated in this study after mannitol cannot be entirely explained by the mechanism of reduction in ischemic cell swelling. PMID:1123427

  1. Timing of hypertonic saline and airway clearance techniques in adults with cystic fibrosis during pulmonary exacerbation: pilot data from a randomised crossover study

    PubMed Central

    O'Neill, Katherine; Moran, Fidelma; Tunney, Michael M; Elborn, J Stuart; Bradbury, Ian; Downey, Damian G; Rendall, Jackie; Bradley, Judy M

    2017-01-01

    Background Streamlining the timing of treatments in cystic fibrosis (CF) is important to optimise adherence while ensuring efficacy. The optimal timing of treatment with hypertonic saline (HTS) and airway clearance techniques (ACT) is unknown. Objectives This study hypothesised that HTS before ACT would be more effective than HTS during ACT as measured by Lung Clearance Index (LCI). Methods Adults with CF providing written informed consent were randomised to a crossover trial of HTS before ACT or HTS during ACT on consecutive days. ACT treatment consisted of Acapella Duet. Patients completed LCI and spirometry at baseline and 90 min post treatment. Mean difference (MD) and 95% CIs were reported. Results 13 subjects completed the study (mean (SD) age 33 (12) years, forced expiratory volume in 1second % (FEV1%) predicted 51% (22), LCI (no. turnovers) 14 (4)). Comparing the two treatments (HTS before ACT vs HTS during ACT), the change from baseline to 90 min post treatment in LCI (MD (95% CI) −0.02 (−0.63 to 0.59)) and FEV1% predicted (MD (95% CI) −0.25 (−2.50 to 1.99)) was not significant. There was no difference in sputum weight (MD (95% CI) −3.0 (−14.9 to 8.9)), patient perceived ease of clearance (MD (95% CI) 0.4 (−0.6 to 1.3) or satisfaction (MD (95% CI) 0.4 (−0.6 to 1.5)). The time taken for HTS during ACT was significantly shorter (MD (95% CI) 14.7 (9.8 to 19.6)). Conclusions In this pilot study, HTS before ACT was no more effective than HTS during ACT as measured by LCI. Trial registration number NCT01753869; Pre-results. PMID:28123751

  2. Immune-Inflammatory and Metabolic Effects of High Dose Furosemide plus Hypertonic Saline Solution (HSS) Treatment in Cirrhotic Subjects with Refractory Ascites

    PubMed Central

    Bellia, Chiara; Clemente, Giuseppe; Pecoraro, Rosaria; Maida, Carlo; Simonetta, Irene; Vassallo, Valerio; Di Bona, Danilo; Gulotta, Eliana; Ciaccio, Marcello; Pinto, Antonio

    2016-01-01

    Introduction Patients with chronic liver diseases are usually thin as a result of hypermetabolism and malnutrition expressed by reduced levels of leptin and impairment of other adyponectins such as visfatin. Aims We evaluated the metabolic and inflammatory effects of intravenous high-dose furosemide plus hypertonic saline solutions (HSS) compared with repeated paracentesis and a standard oral diuretic schedule, in patients with cirrhosis and refractory ascites. Methods 59 consecutive cirrhotic patients with refractory ascites unresponsive to outpatient treatment. Enrolled subjects were randomized to treatment with intravenous infusion of furosemide (125–250mg⁄bid) plus small volumes of HSS from the first day after admission until 3 days before discharge (Group A, n:38), or repeated paracentesis from the first day after admission until 3 days before discharge (Group B, n: 21). Plasma levels of ANP, BNP, Leptin, visfatin, IL-1β, TNF-a, IL-6 were measured before and after the two type of treatment. Results Subjects in group A were observed to have a significant reduction of serum levels of TNF-α, IL-1β, IL-6, ANP, BNP, and visfatin, thus regarding primary efficacy endpoints, in Group A vs. Group B we observed higher Δ-TNF-α, Δ-IL-1β, Δ-IL-6, Δ-ANP, Δ-BNP, Δ-visfatin, Δ-Leptin at discharge. Discussion Our findings underline the possible inflammatory and metabolic effect of saline overload correction in treatment of cirrhosis complications such as refractory ascites, suggesting a possible role of inflammatory and metabolic-nutritional variables as severity markers in these patients. PMID:27941973

  3. Hypertonic saline protects brain endothelial cells against hypoxia correlated to the levels of estimated glomerular filtration rate and interleukin-1β

    PubMed Central

    Chen, Sheng-Long; Deng, Yi-Yu; Wang, Qiao-Sheng; Han, Yong-Li; Jiang, Wen-Qiang; Fang, Ming; Hu, Bei; Wu, Zhi-Xin; Huang, Lin-Qiang; Zeng, Hong-Ke

    2017-01-01

    Abstract Objective: The aim of this study was to verify the protective effect of hypertonic saline (HS) on brain endothelial cells under hypoxic conditions and the relevant underlying mechanism. Methods: bEnd.3 cells were treated with oxygen-glucose deprivation (OGD)-induced injury. To measure HS performance, cell viability was determined using the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium salt assay, and cell apoptosis was assessed by flow cytometry and Terminal deoxynucleotidyl transferase UTP nick-end labeling staining. RNA-seq was performed to assess the expression profiles and screen the candidate genes that participated in OGD-induced injury and the HS protective effect. Quantitative real-time polymerase chain reaction (qPCR) and western blot analysis were used to confirm the expression of candidate genes, and enzyme-linked immunosorbent assay was used to measure the level of interleukin (IL)-1β. Overexpression analyses were performed to confirm the functions of the differentially expressed genes. Results: HS with a concentration of 40 mmol/L NaCl had an obvious protective effect on bEnd.3 cells after OGD-induced injury, resulting in increased cell viability and a smaller percentage of apoptotic cells. According to the RNA-seq results, epidermal growth factor receptor (EGFR) was chosen as the differentially expressed gene target in this study. The qPCR and western blot analyses further confirmed that the levels of EGFR/phosphorylated epidermal growth factor receptor and IL-1β were enhanced after OGD-induced injury, but attenuated after treatment with 40 mmol/L of NaCl HS. Overexpressed EGFR reversed the protective effect of HS that caused low viability and high rates of apoptosis in cells. Conclusion: HS can protect endothelial cells against OGD-induced injury, but is affected by the expression of EGFR/p-EGFR and IL-1β. PMID:28072729

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

    PubMed

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

    2016-04-01

    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.

  5. 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.

  6. 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.

  7. Challenging Behavior.

    ERIC Educational Resources Information Center

    Reichle, Joe, Ed.; DePaepe, Paris, Ed.

    1991-01-01

    The articles in this feature or theme issue describe successful approaches to positive, community-based management of severe challenging behavior. Programs include: a train-the-trainer strategy for inservice training used across the country; the use of student volunteers as community integration facilitators; a school-based intervention project…

  8. 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…

  9. National Drug IQ Challenge

    MedlinePlus

    ... National Drug IQ Challenge 2016 National Drug & Alcohol IQ Challenge Print Get Started! Correct/Total Questions: Score: ... accessible version of the 2016 National Drug & Alcohol IQ Challenge , [PDF, 637KB]. Download an accessible version of ...

  10. 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…

  11. 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...

  12. Challenges of Parenting Multiples

    MedlinePlus

    ... the American Society for Reproductive Medicine Challenges of Parenting Multiples There are many psychological, social, and economic ... the unique challenges and rewards that come from parenting multiples. For more information on the medical aspects ...

  13. 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...

  14. 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...

  15. 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…

  16. Correlation of measured and calculated serum osmolality during mannitol or hypertonic saline infusion in patients after craniotomy: a study protocol and statistical analysis plan for a randomised controlled trial

    PubMed Central

    Li, Qian; Xu, Ming; Zhou, Jian-Xin

    2014-01-01

    Introduction Brain oedema is a major complication after craniotomy. Hyperosmolar agents have been used as the medical treatment for this condition. Measurement and estimation of serum osmolality during hyperosmolar agent infusion is of clinical importance to evaluate clinical efficacy, adjust dosage and avoid side effects. However, several studies have shown that calculated serum osmolality may lead to a systematic bias compared with direct measurement. In the present study, mannitol or hypertonic saline (HS) will be used in patients after elective craniotomy. We aim to determine the accuracy of serum osmolality estimation during the application of hyperosmolar agent. Methods and analysis The study is a prospective, randomised, double-blinded, controlled, parallel-group design. Adult patients requiring the use of hyperosmolar agents for the prevention or treatment of postoperative brain oedema are enrolled and assigned randomly to one of the two treatment study groups, labelled as ‘M group’ and ‘HS group’. Patients in the M and HS groups receive intravenous infusion of 125 mL of either 20% mannitol or 3.1% sodium chloride solution, respectively. Data will be collected immediately before the infusion of study agents, 15, 30, 60, 120, 240 and 360 min after the start of infusion of experimental agents, which includes serum osmolality, concentration of serum sodium, potassium, urea and glucose. Serum osmolality will be measured by means of freezing point depression. Estimated serum osmolality will also be calculated by using four formulas published previously. Osmole gap is calculated as the difference between the measured and the estimated values. The primary endpoint is the correlation of measured and estimated serum osmolality during hyperosmolar agent infusion. Ethics and dissemination The study was approved by the International Review Board (IRB) of Beijing Tiantan Hospital, Capital Medical University. Study findings will be disseminated through peer

  17. 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...

  18. 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.

  19. College and University Challenge

    EPA Pesticide Factsheets

    This EPA's Green Power Partnership Challenge tracks and recognizes U.S. colleges and universities recognizes the largest single green power users within each participating collegiate athletic conferences.

  20. 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...

  1. 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…

  2. 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…

  3. 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…

  4. 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…

  5. 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…

  6. 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…

  7. 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…

  8. Challenges to Financing Education.

    ERIC Educational Resources Information Center

    Wood, R. Craig; Ruch, Robert W.

    1986-01-01

    Reviews court decisions involving challenges to state systems of financing education. The challenges have been based on Fourteenth Amendment rights to equal protection. To date 24 states have been involved with litigation. Systems that promote local control have been generally held to be constitutional. (42 references) (MD)

  9. 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…

  10. 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…

  11. 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…

  12. 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…

  13. Effect of a single dose of salmeterol on the increase in airway eosinophils induced by allergen challenge in asthmatic subjects

    PubMed Central

    Dente, F.; Bancalari, L.; Bacci, E.; Bartoli, M.; Carnevali, S.; Cianchetti, S.; Di, F; Giannini, D.; Vagaggini, B.; Testi, R.; Paggiaro, P.

    1999-01-01

    BACKGROUND—The long acting β2 agonist salmeterol is very effective in preventing asthmatic responses to specific stimuli, and this effect could theoretically be due to some anti-inflammatory property in addition to bronchodilator property.
METHODS—The protective effect of a single dose of salmeterol (50 µg) on allergen induced early and late responses and on the associated airway inflammation was investigated in a double blind, placebo controlled, crossover study in 11 atopic asthmatic subjects. Eosinophil percentages and concentrations of eosinophil cationic protein (ECP) in peripheral blood and in hypertonic saline induced sputum were measured 24 hours after allergen inhalation.
RESULTS—Salmeterol effectively inhibited both early and late asthmatic responses in comparison with placebo. Salmeterol also inhibited the increase in the percentage of eosinophils in the sputum 24hours after allergen inhalation (median (range) baseline 6% (1-36), after placebo 31% (5-75), after salmeterol 12% (1-63)). However, the increase in both sputum and serum ECP concentrations 24 hours after allergen challenge was not affected by pretreatment with salmeterol.
CONCLUSIONS—A single dose of salmeterol inhibits the allergen induced airway responses and the increase in sputum eosinophils after allergen challenge.

 PMID:10377209

  14. 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...

  15. 2017 TRI University Challenge

    EPA Pesticide Factsheets

    Details about the 2017 TRI University Challenge, in which EPA is looking to academic institutions to help build a diverse portfolio of practical and replicable projects that benefit communities, the environment, academic institutions, and the TRI Program.

  16. 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...

  17. 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)

  18. Another challenge for scientists

    PubMed Central

    Christian, Laura M; Naqvi, Hassan R; Schmidt, Christian; Covarrubias, David; Mathur, Shawn

    2008-01-01

    By nature, scientists contribute to our understanding of nature and ourselves. As communities undergo significant changes, new challenges are presented. Here, we offer alternative views on recent changes in society. PMID:18637170

  19. 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...

  20. 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)

  1. 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...

  2. 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.

  3. 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.

  4. 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.

  5. The LSST Data Challenges

    NASA Astrophysics Data System (ADS)

    Axelrod, Tim S.; Becla, J.; Connolly, A.; Dossa, D.; Jagatheesan, A.; Kantor, J.; Levine, D.; Lupton, R.; Plante, R.; Smith, C.; Thakar, A.; Tyson, J. A.; LSST Data Management Team

    2007-12-01

    The development of the LSST Data Management System (DMS) includes a series of four Data Challenges that take place during the Design and Development phase of the project. The Data Challenges are partial prototypes of the full DMS, each validating different aspects of the system. DC1, which was executed in 2006, emphasized scalability of the overall processing and data flows. DC2, which was executed in 2007, prototyped the nightly processing pipelines and the middleware that supports them. DC3, planned for execution in 2008, will prototype the data release pipelines. DC4, the final Data Challenge before construction begins, will focus on data access by the astronomical community and the data processing that supports scientific use of the LSST data.

  6. The challenge of sustainability

    SciTech Connect

    Orr, D.W.

    1993-01-01

    This paper discusses sustainability in a world that has changed rapidly. The author suggests that ecological assumptions embedded in communism and capitalism are badly flawed, but the flaws were not apparent when there were fewer than a billion people on earth living at low technology levels. Sustaining the earth's vital signs is a challenge to our perception of time, and the numbers - population, environmental damage, oil consumption, waste disposal - are too large to comprehend easily. There is a global debate about what sustainability means. In fact the challenge of sustainability is 6 different challenges: overcoming the tendency to deny inconvenient realities; establishing accurate indicators of human and ecological health; questions about the kinds of technology necessary to make the transition to sustainability; education; the need for an emotional bond between man and nature; rebuilding the existing democratic institutions. 16 refs.

  7. 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.

  8. Mars - Destination and challenge

    NASA Astrophysics Data System (ADS)

    Aldrich, Arnold D.

    A general evaluation is conducted of the challenges associated with prospective Mars exploration efforts. The technical challenge posed stems from the unforgiving physical environment of space travel, and such peculiarities of Mars as its great orbital eccentricity and 15-year cyclic variation in transfer energy. Additional considerations arise from the 'architecture' of NASA's Space Exploration Initiative, encompassing the determination of a Mars exploration effort's purpose, scope, and schedule. Finally, numerous unresolved issues arise from the definition of detailed scientific experimentation that is to be done for the sake of the greatest long-term benefit to an understanding of Mars, and the rallying of political support behind a major new exploration initiative.

  9. Mars - Destination and challenge

    NASA Technical Reports Server (NTRS)

    Aldrich, Arnold D.

    1992-01-01

    A general evaluation is conducted of the challenges associated with prospective Mars exploration efforts. The technical challenge posed stems from the unforgiving physical environment of space travel, and such peculiarities of Mars as its great orbital eccentricity and 15-year cyclic variation in transfer energy. Additional considerations arise from the 'architecture' of NASA's Space Exploration Initiative, encompassing the determination of a Mars exploration effort's purpose, scope, and schedule. Finally, numerous unresolved issues arise from the definition of detailed scientific experimentation that is to be done for the sake of the greatest long-term benefit to an understanding of Mars, and the rallying of political support behind a major new exploration initiative.

  10. 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.

  11. 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...

  12. 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...

  13. 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...

  14. 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...

  15. 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...

  16. 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…

  17. 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.

  18. 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…

  19. India's Higher Education Challenges

    ERIC Educational Resources Information Center

    Altbach, Philip G.

    2014-01-01

    India, with the world's second largest higher education system and a rapidly growing economy as one of the BRIC nations, faces significant challenges in building both capacity and excellence in higher education. India's higher education system is characterized by "islands of excellence in a sea of mediocrity." The mainstream universities…

  20. "Conversations": Challenge and Change.

    ERIC Educational Resources Information Center

    American Research Association - Slater School & College Services, Philadelphia, PA.

    The academic community is recovering from recent shock waves of frequently violent student protest that challenged the traditional authority and even the basic purposes and structure of colleges and universities. The students were demanding reform in curriculum matters as well as in matters of educational administration. In this document a…

  1. 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…

  2. Managing "Challenging" Teachers

    ERIC Educational Resources Information Center

    Yariv, Eliezer; Coleman, Marianne

    2005-01-01

    Purpose: The purpose of this paper is to investigate the ways in which elementary school principals in Israel deal with teachers who are "challenging" in their behaviour, that is those who are perceived as under-performing. This is an important and under-researched area of educational management. Design/methodology/approach: Interviews…

  3. 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…

  4. 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…

  5. 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.

  6. 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,…

  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 challenge of denitrification

    NASA Astrophysics Data System (ADS)

    Groffman, P. M.

    2015-12-01

    Understanding the nitrogen cycle at ecosystem, landscape, regional and global scales is a great current challenge in environmental science. Large amounts of "missing nitrogen" dominate nitrogen balances at all scales and have complicated efforts to address the effects of excess reactive nitrogen pollution on tropospheric ozone levels, coastal eutrophication and drinking water quality, and to determine "critical loads" for atmospheric nitrogen deposition. Uncertainty about nitrogen balances has led to increased interest in nitrogen gas fluxes as a fate of excess nitrogen. Denitrification, the conversion of reactive nitrogen oxides such as nitrate and nitrite into nitrogen gases, is a challenging process to study in terrestrial ecosystems. This process is difficult to quantify because of problematic measurement techniques, high spatial and temporal variability, and a lack of methods for scaling point measurements to larger areas. A particular challenge is that small areas (hotspots) and brief periods (hot moments) account for a high percentage of nitrogen gas flux activity. However, recent advances have yielded new methods capable of producing well constrained estimates of denitrification at the ecosystem scale, new ideas about the occurrence of hotspots and hot moments at ecosystem and landscape scales, and powerful new tools for extrapolation and validation. Progress on the challenges of denitrification suggest that we are poised for advances more generally across the genomes-to-ecosystems cascade.

  9. 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…

  10. 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…

  11. 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…

  12. The Best of Challenge.

    ERIC Educational Resources Information Center

    American Association for Health, Physical Education, and Recreation, Washington, DC.

    The articles on physical education and recreation for the mentally retarded have been compiled from the first five volumes of Challenge, a bi-monthly newsletter dealing with physical education, recreation, camping, outdoor education, and related activities for the retarded. Also included are a few entries from Outlook, a newsletter dealing with…

  13. US Cyber Challenge Research

    DTIC Science & Technology

    2012-02-01

    0 2 2 Maryland Cyber Challenge & Conference 0 1 0 0 0 1 Miami Electronic Crimes Task Force 0 0 1 0 0 1 MITRE STEM CTF 0 0 2 0 0 2 Moraine Valley...Security and Information Assurance (CSSIA) has a CTF technical environment hosted at Moraine Valley Community College outside of Chicago, IL. This

  14. 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.

  15. 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…

  16. 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…

  17. 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…

  18. 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…

  19. Challenges for PISA

    ERIC Educational Resources Information Center

    Schleicher, Andreas

    2016-01-01

    The OECD Programme for International Student Assessment (PISA) provides a framework in which over 80 countries collaborate to build advanced global metrics to assess the knowledge, skills and character attributes of the students. The design of assessments poses major conceptual and technical challenges, as successful learning. Beyond a sound…

  20. Challenge Your Top Students

    ERIC Educational Resources Information Center

    Smutny, Joan Franklin

    2011-01-01

    Fast learners frequently get left behind. There's no question that time is a major obstacle for teachers who are contending with a wide range of learning needs in their classrooms--but there are ways to ratchet up the challenges. Over the years that the author has been teaching gifted children and mentoring teachers, she has found that there are…

  1. 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…

  2. 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...

  3. 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...

  4. 81 FR 54853 - Notice of Centennial Challenges Space Robotics Challenge

    Federal Register 2010, 2011, 2012, 2013, 2014

    2016-08-17

    ... Space Robotics Challenge AGENCY: National Aeronautics and Space Administration (NASA). NOTICE: (16-056). ACTION: Notice of Centennial Challenges Space Robotics Challenge. SUMMARY: This notice is issued in accordance with 51 U.S.C. 20144(c). The Space Robotics Challenge is open and teams that wish to compete...

  5. 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.

  6. 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

  7. The connectomics challenge

    PubMed Central

    Silvestri, Ludovico; Sacconi, Leonardo; Pavone, Francesco Saverio

    Summary One of the most fascinating challenges in neuroscience is the reconstruction of the connectivity map of the brain. Recent years have seen a rapid expansion in the field of connectomics, whose aim is to trace this map and understand its relationship with neural computation. Many different approaches, ranging from electron and optical microscopy to magnetic resonance imaging, have been proposed to address the connectomics challenge on various spatial scales and in different species. Here, we review the main technological advances in the microscopy techniques applied to connectomics, highlighting the potential and limitations of the different methods. Finally, we briefly discuss the role of connectomics in the Human Brain Project, the Future and Emerging Technologies (FET) Flagship recently approved by the European Commission. PMID:24139653

  8. 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)

  9. 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

  10. Bioinformatics Challenge Days

    DTIC Science & Technology

    2013-12-30

    from a subject that suffered from periodontal disease . The rationale for including these two samples was to identify the differences and similarities...differentials between datasets derived from healthy and diseased samples, in particular the different read depths observed for bacteria. 5 Figure 1...presentations are summarized below. Team Disease Easy: 7 people, Metagenomic Visual Challenge Focused their visual output on Swann plots (a type of

  11. 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.

  12. 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.

  13. Hybrid Warfare and Challenges

    DTIC Science & Technology

    2009-01-01

    against financial targets. Hybrid challenges are not limited to non - state actors. States can shift their conventional units to irregular formations and... non -state actors, using both simple and sophisticated technolo- gies in innovative ways.”23 Tomorrow’s conflicts will not be easily categorized into...between “regular” and “irregu- lar” warfare are blurring. Even non -state groups are increasingly gaining access to the kinds of weapons that were once

  14. DARPA 7-Day Challenge

    DTIC Science & Technology

    2014-03-17

    live fire challenge. ....................................... 54 Figure 62: Schedule for Live Fire Test with B. pseudomallei strain 1028...currently being investigated in clinical trials for the treatment of AIDS, hepatitis C and cancer 3 . However, antigen delivery problems have...from Ac-DEX are pH- sensitive and degrade quicker in lysosomal pH (~ 5) compared to physiological pH (7.4). Beyond its performance in vaccine

  15. Challenges in childhood tuberculosis.

    PubMed

    Swaminathan, S; Ramachandran, G

    2015-09-01

    While tuberculosis (TB) typically causes respiratory disease in adults, the spectrum of disease is different in children, ranging from paucibacillary lymphadenitis or limited intrathoracic disease to severe disseminated disease. Diagnosing pediatric TB and monitoring treatment response is challenging, as collecting respiratory specimens is difficult in children and disease may be extrapulmonary. While basic principles of treatment are similar to adults, developmental differences in pharmacokinetics and pharmacodynamics require that drug dosages in children be adjusted for body weight and age.

  16. Differential effects of osmotic and SSR149415 challenges in maternally separated and control rats: the role of vasopressin on spatial learning.

    PubMed

    Hernandez, Vito S; Ruíz-Velazco, Silvia; Zhang, Limei

    2012-10-24

    Maternal separation (MS) has been demonstrated to up-regulate the hypothalamic vasopressin (VP) system. Intracerebrally released VP has been demonstrated to affect several types of animal behaviour, such as active/passive avoidance, social recognition, and learning and memory. However, the role of VP in spatial learning remains unclear. In the present study, we investigated the effects of an osmotic challenge and a V1b receptor-specific (V1bR) antagonist, SSR149415, on spatial learning of maternally separated and animal facility reared (AFR) adult male Wistar rats. The osmotic challenge was applied by injecting a hypertonic saline solution, 1h before the Morris water maze test (MWM). V1bR antagonist SSR149415 (5mg/kg) was injected i.p. twice (1h and 30 min) previous to the MWM. A combined treatment with both osmotic challenge and the SSR149415 was applied to the third group whereas rats for basal condition were injected with isotonic saline. Under basal condition no differences between AFR and MS groups were observed. MS rats showed severe impairment during the MWM after the osmotic challenge, but not after the administration of SSR149415. For AFR rats, the opposite phenomenon was observed. The joint application of SSR149415 and osmotic challenge restored the spatial learning ability for both groups. The differential impairment produced by osmotic stress-induced up-regulation and SSR149415 induced V1bR blockage in MS and control rats suggested that VP involvement in spatial learning depends on the individual intrinsic ligand-receptor functional state.

  17. 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.

  18. Challenging times ahead.

    PubMed

    While, Alison

    2008-07-01

    The global economic challenges will not only affect the banks but also healthcare staff and their patients. Indeed, no-one will be unaffected. At this moment community nurses are not being properly reimbursed for the cost of using their cars to deliver care in the home as the price of petrol rises ever higher and older people are counting the cost of ever rising energy and food costs. Additionally there will be less extra money available to fund public services as the government attempts to balance its expenditure against tax receipts without further increasing government debt.

  19. Electronic materials pose challenges

    SciTech Connect

    Frezzo, D.C.

    1986-04-01

    To prove that the Strategic Defense Initiative (SDI) is technically feasible, several demanding scientific and engineering criteria must be met. Electronic materials processing and electronics reliability are the challenging areas where it is necessary to demonstrate that SDI would be effective, survivable, and cost-effective. The rad-hardened ICs which enable sensors to see and which are critical to the surveillance satellites demonstrate the complexity of the problem. A long-term interest in SDI research will drive much of the world's technical development for decades, and indirectly affect the professional roles of scientists and engineers, who have both a social and technical responsibility to contribute to the debate.

  20. The Global Energy Challenge

    ScienceCinema

    Crabtree, George

    2016-07-12

    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.

  1. Therapeutic challenges of urosepsis.

    PubMed

    Wagenlehner, F M E; Pilatz, A; Naber, K G; Weidner, W

    2008-10-01

    Urosepsis accounts for approximately 25% of all sepsis cases and may develop from a community or nosocomial acquired urinary tract infection (UTI). The underlying UTI is almost exclusively a complicated one with involvement of parenchymatous urogenital organs (e.g. kidneys, prostate). In urosepsis, as in other types of sepsis, the severity of sepsis depends mostly upon the host response. The treatment of urosepsis comprises four major aspects: Early goal directed therapy, early optimal pharmacodynamic exposure to antimicrobials, early control of the complicating factor in the urinary tract and specific sepsis therapy. Following these prerequisites there appear two major challenges that need to be addressed: Firstly, time from admission to therapy is critical; the shorter the time to effective treatment, the higher the success rate. This aspect has to become incorporated into the organisational process. Secondly, adequate initial antibiotic therapy has to be insured. This goal implies however, a wide array of measures to ensure rational antibiotic policy. Both challenges are best targeted if an interdisciplinary approach at any level of the process is established, encompassing urologists, intensive care specialists, radiologists, microbiologists and clinical pharmacologists working tightly together at any time.

  2. 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.

  3. Safeguards by Design Challenge

    SciTech Connect

    Alwin, Jennifer Louise

    2016-09-13

    The International Atomic Energy Agency (IAEA) defines Safeguards as a system of inspection and verification of the peaceful uses of nuclear materials as part of the Nuclear Nonproliferation Treaty. IAEA oversees safeguards worldwide. Safeguards by Design (SBD) involves incorporation of safeguards technologies, techniques, and instrumentation during the design phase of a facility, rather that after the fact. Design challenge goals are the following: Design a system of safeguards technologies, techniques, and instrumentation for inspection and verification of the peaceful uses of nuclear materials. Cost should be minimized to work with the IAEA’s limited budget. Dose to workers should always be as low are reasonably achievable (ALARA). Time is of the essence in operating facilities and flow of material should not be interrupted significantly. Proprietary process information in facilities may need to be protected, thus the amount of information obtained by inspectors should be the minimum required to achieve the measurement goal. Then three different design challenges are detailed: Plutonium Waste Item Measurement System, Marine-based Modular Reactor, and Floating Nuclear Power Plant (FNPP).

  4. 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

  5. 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.

  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. 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.

  8. 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

  9. 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.

  10. 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…

  11. 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

  12. 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.

  13. Bioanalytical challenges of biosimilars.

    PubMed

    Islam, Rafiq

    2014-02-01

    Biologics such as monoclonal antibodies and recombinant proteins represent a significant portion of the pharmaceutical market. With many of the first generation biologics' patents expiring, an increasing number of biosimilars will be submitted for approval in the near future. The successful development of a biosimilar requires the demonstration of biosimilarity in terms of efficacy, safety and purity to an innovator-approved product. While regulatory frameworks have been established for the approval of biosimilars in several countries, there is not an established guidance for bioanalytical testing of biosimilars. Although there are regulatory guidances and White Papers on testing requirements for biologics in general, there is a need to address the bioanalytical challenges and solutions that apply specifically to the analysis of biosimilars in biological samples. This paper will focus on components of the PK and immunogenicity assays that are critical to biosimilar drug development.

  14. Ayurveda research: Ontological challenges

    PubMed Central

    Nayak, Jayakrishna

    2012-01-01

    Collaborative research involving Ayurveda and the current sciences is undoubtedly an imperative and is emerging as an exciting horizon, particularly in basic sciences. Some work in this direction is already going on and outcomes are awaited with bated breath. For instance the ‘ASIIA (A Science Initiative In Ayurveda)’ projects of Dept of Science and Technology, Govt of India, which include studies such as Ayurvedic Prakriti and Genetics. Further intense and sustained collaborative research needs to overcome a subtle and fundamental challenge-the ontologic divide between Ayurveda and all the current sciences. Ontology, fundamentally, means existence; elaborated, ontology is a particular perspective of an object of existence and the vocabulary developed to share that perspective. The same object of existence is susceptible to several ontologies. Ayurveda and modern biomedical as well as other sciences belong to different ontologies, and as such, collaborative research cannot be carried out at required levels until a mutually acceptable vocabulary is developed. PMID:22529675

  15. Gonorrhea: new challenges.

    PubMed

    Skerlev, Mihael; Čulav-Košćak, Ivana

    2014-01-01

    As "a paradigm of the classical Venereology" for many decades, gonorrhea appears to be the second most common sexually transmitted infection of bacterial origin today. In spite of its mostly uncomplicated clinical course, gonorrhea may sometimes result with serious complications such as pelvic inflammatory disease, ectopic pregnancy, infertility, epididymitis, gonococcemia, and disseminated gonococcal infection. Perhaps the most important challenge today is the emergence of multidrug-resistant gonorrhea, which is currently the main reason for public concern. Eventually, Neisseria gonorrhoeae turned out to be one of the most "evolutionarily successful" pathogens. Effective treatment of gonorrhea providing that N gonorrhoeae might also facilitate the transmission of HIV is a complex task and almost an imperative in the "sexually transmitted infection world" today.

  16. 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.

  17. 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

  18. The Challenge for computational science

    SciTech Connect

    Post, D. E. ,

    2004-01-01

    The High Performance Computer and Computational Science communities face three major challenges: The Performance Challenge, making the next generation of high performance computers, The Programming Challenge, writing codes that can run on the next generation of very complicated computers, and The Prediction Challenge, writing very complex codes that can give accurate answers that can be relied upon for the important decisions that determine the future of society. The first challenge is being met. The second challenge needs work and focus, but is being addressed. The Computational Science community is, however, falling short of meeting the third challenge. It needs to focus on reaching the same level of credibility and maturity as the accepted methodologies of theory, experiment and engineering design.

  19. Challenges of climate change

    PubMed Central

    Husaini, Amjad M

    2014-01-01

    Kashmir valley is a major saffron (Crocus sativus Kashmirianus) growing area of the world, second only to Iran in terms of production. In Kashmir, saffron is grown on uplands (termed in the local language as “Karewas”), which are lacustrine deposits located at an altitude of 1585 to 1677 m above mean sea level (amsl), under temperate climatic conditions. Kashmir, despite being one of the oldest historical saffron-producing areas faces a rapid decline of saffron industry. Among many other factors responsible for decline of saffron industry the preponderance of erratic rainfalls and drought-like situation have become major challenges imposed by climate change. Saffron has a limited coverage area as it is grown as a ‘niche crop’ and is a recognized “geographical indication,” growing under a narrow microclimatic condition. As such it has become a victim of climate change effects, which has the potential of jeopardizing the livelihood of thousands of farmers and traders associated with it. The paper discusses the potential and actual impact of climate change process on saffron cultivation in Kashmir; and the biotechnological measures to address these issues. PMID:25072266

  20. 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.

  1. 'Endurance': A Daunting Challenge

    NASA Technical Reports Server (NTRS)

    2004-01-01

    This image shows the approximate size of the Mars Exploration Rover Opportunity in comparison to the impressive impact crater dubbed 'Endurance,' which is roughly 130 meters (430 feet) across. A model of Opportunity has been superimposed on top of an approximate true-color image taken by the rover's panoramic camera. Scientists are eager to explore Endurance for clues to the red planet's history. The crater's exposed walls provide a window to what lies beneath the surface of Mars and thus what geologic processes occurred there in the past. While recent studies of the smaller crater nicknamed 'Eagle' revealed an evaporating body of salty water, that crater was not deep enough to indicate what came before the water. Endurance may be able to help answer this question, but the challenge is getting to the scientific targets: most of the crater's rocks are embedded in vertical cliffs. Rover planners are developing strategies to overcome this obstacle.

    This image is a portion of a larger mosaic taken with the panoramic camera's 480-, 530- and 750-nanometer filters on sols 97 and 98.

  2. Hermes: the engineering challenges

    NASA Astrophysics Data System (ADS)

    Brzeski, Jurek; Gers, Luke; Smith, Greg; Staszak, Nicholas

    2012-09-01

    The Australian Astronomical Observatory is building a 4-channel VPH-grating High Efficiency and Resolution Multi Element Spectrograph (HERMES) for the 3.9 meter Anglo-Australian Telescope (AAT). HERMES will provide a nominal spectral resolving power of 28,000 for Galactic Archaeology with an optional high-resolution mode of 45,000 with the use of a slit mask. HERMES is fed by a fibre positioning robot called 2dF at the telescope prime focus. There are a total of 784 science fibres, which interface with the spectrograph via two separate slit body assemblies, each comprising of 392 science fibers. The slit defines the spectral lines of 392 fibres on the detector. The width of the detector determines the spectral bandwidth and the detector height determines the fibre to fibre spacing or cross talk. Tolerances that follow from this are all in the 10 micrometer range. The slit relay optics must contribute negligibly to the overall image quality budget and uniformly illuminate the spectrograph exit pupil. The latter requirement effectively requires that the relay optics provide a telecentric input at the collimator entrance slit. As a result it is critical to align the optical components to extreme precision required by the optical design. This paper discusses the engineering challenges of designing, optimising, tolerancing and manufacturing of very precise mechanical components for housing optics and the design of low cost of jigs and fixtures for alignment and assembly of the optics.

  3. Face transplantation: Anesthetic challenges

    PubMed Central

    Dalal, Aparna

    2016-01-01

    Face transplantation is a complex vascular composite allotransplantation (VCA) surgery. It involves multiple types of tissue, such as bone, muscles, blood vessels, nerves to be transferred from the donor to the recipient as one unit. VCAs were added to the definition of organs covered by the Organ Procurement and Transplantation Network Final Rule and National Organ Transplant Act. Prior to harvest of the face from the donor, a tracheostomy is usually performed. The osteotomies and dissection of the midface bony skeleton may involve severe hemorrhagic blood loss often requiring transfusion of blood products. A silicon face mask created from the facial impression is used to reconstruct the face and preserve the donor’s dignity. The recipient airway management most commonly used is primary intubation of an existing tracheostoma with a flexometallic endotracheal tube. The recipient surgery usually averages to 19-20 h. Since the face is a very vascular organ, there is usually massive bleeding, both in the dissection phase as well as in the reperfusion phase. Prior to reperfusion, often, after one sided anastomosis of the graft, the contralateral side is allowed to bleed to get rid of the preservation solution and other additives. Intraoperative product replacement should be guided by laboratory values and point of care testing for coagulation and hemostasis. In face transplantation, bolus doses of pressors or pressor infusions have been used intraoperatively in several patients to manage hypotension. This article reviews the anesthetic considerations for management for face transplantation, and some of the perioperative challenges faced. PMID:28058213

  4. 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.

  5. Challenges in publication ethics

    PubMed Central

    Astaneh, B; Irfan, M

    2016-01-01

    is a vital 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. SandersSA, ReinischJM Would you say you ‘had sex’ if…? JAMA 1999; : 275–277.9918484 2. Committee on Publication Ethics Code of Conduct and Best Practice Guidelines for Journal Editors. Harleston, UK: COPE; 2011. PMID:26985812

  6. 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.

  7. 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.

  8. 78 FR 19742 - Centennial Challenges: 2014 Night Rover Challenge

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-02

    ... Night Rover Challenge is a prize competition designed to encourage development of new energy storage... environments. Competitors will need to demonstrate high energy density storage systems (>330w-hr/kg) that would... Challenge will be conducted in an ambient Earth environment in a NASA test chamber. The Phase I...

  9. 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.

  10. 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…

  11. Emerging Challenges Facing School Principals

    ERIC Educational Resources Information Center

    Wise, Donald

    2015-01-01

    This article provides insights into the challenges facing US public school principals. A survey was sent to a random sample of over 10,000 principals throughout the US. Written responses from a representative sample were analyzed for content and themes. Results indicate that principals are facing emerging challenges never before seen in education,…

  12. 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,…

  13. 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

  14. 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…

  15. The Challenge of the Deanship.

    ERIC Educational Resources Information Center

    Montez, Joni; Wolverton, Mimi

    This paper addresses the evolution of the kinds of challenges that deans have met over time and examines perceptions of today's deans concerning their ability to deal effectively with current challenges. A sample of deans (n=695) in the colleges of education, business, liberal arts, and nursing at 360 public and private institutions was surveyed…

  16. 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…

  17. Defining and treating challenging behaviour.

    PubMed

    Tarbuck, P; Thompson, T

    Behavioural disorders present extreme problems for clients and careers. In this article, the authors discuss a definition of challenging behaviour. Types of behaviour classified as 'challenging' and possible responses to them, are also considered. Some of the points are illustrated with short case studies.

  18. Layered Manufacturing: Challenges and Opportunities

    DTIC Science & Technology

    2003-04-01

    UNCLASSIFIED Defense Technical Information Center Compilation Part Notice ADP014215 TITLE: Layered Manufacturing : Challenges and Opportunities ...Research Society LL1.4 Layered Manufacturing : Challenges and Opportunities Khershed P. Cooper Materials Science and Technology Division, Naval Research...Laboratory Washington, DC 20375-5343, U.S.A. ABSTRACT Layered Manufacturing (LM) refers to computer-aided manufacturing processes in which parts are made

  19. 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…

  20. Sustainable Materials Management Challenge Data

    EPA Pesticide Factsheets

    Sustainable Materials Management (SMM) is a systemic approach to using and reusing materials more productively over their entire lifecycles. It represents a change in how our society thinks about the use of natural resources and environmental protection. By looking at a product's entire lifecycle we can find new opportunities to reduce environmental impacts, conserve resources, and reduce costs. There are multiple challenge programs available as part of the SMM program, including the Food Recovery Challenge, the Electronics Challenge, the Federal Green Challenge, and the WasteWise program. As part of EPA's Food Recovery Challenge, organizations pledge to improve their sustainable food management practices and report their results. The SMM Electronics Challenge encourages electronics manufacturers, brand owners and retailers to strive to send 100 percent of the used electronics they collect from the public, businesses and within their own organizations to third-party certified electronics refurbishers and recyclers. The Federal Green Challenge, a national effort under the EPA??s Sustainable Materials Management Program, challenges EPA and other federal agencies throughout the country to lead by example in reducing the federal government's environmental impact. EPA??s WasteWise encourages organizations and businesses to achieve sustainability in their practices and reduce select industrial wastes. WasteWise is part of EPA??s sustaina

  1. 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…

  2. 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…

  3. 76 FR 41526 - Centennial Challenges 2011 Strong Tether Challenge

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-14

    ... register. Centennial Challenges is a program of prize competitions to stimulate innovation in technologies...,000 (two million U.S. dollars). Incremental prizes will be offered for entries that meet...

  4. 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.

  5. Nuclear Proliferation and Grand Challenges

    ScienceCinema

    McCarthy, Kathy

    2016-07-12

    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.

  6. 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)

  7. 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 ...

  8. CSB's Key Management Challenges - 2014

    EPA Pesticide Factsheets

    The Office of Inspector General is beginning work to update the fiscal year 2014 list of areas we consider to be the key management challenges confronting the U.S. Chemical Safety and Hazard Investigation Board.

  9. Japanese Management: An American Challenge.

    ERIC Educational Resources Information Center

    Rehder, Robert R.

    1979-01-01

    In contrast to the American system of management, Japanese management motivates its employees by challenging them with high goals and by providing inhouse training and development opportunities to meet their self-fulfillment needs. (Author/LD)

  10. Wildland Fire Sensors Challenge Webinar

    EPA Pesticide Factsheets

    This challenge seeks a field-ready prototype system capable of measuring constituents of smoke, including particulates, carbon monoxide, ozone, and carbon dioxide, over the wide range of levels expected during wildland fires.

  11. EPA's Key Management Challenges - 2016

    EPA Pesticide Factsheets

    Report #16-N-0206, June 16, 2016. Attention to agency management challenges could result in stronger results and protection for the public and increased confidence in management integrity and accountability.

  12. 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.

  13. EPA's Key Management Challenges - 2015

    EPA Pesticide Factsheets

    Report #15-N-0164, May 28, 2015. Attention to agency management challenges could result in stronger results and protection for the public, and increased confidence in management integrity and accountability.

  14. 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

  15. 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.

  16. 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.

  17. 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.

  18. Cybersecurity Challenges for Program Managers

    DTIC Science & Technology

    2014-10-01

    41 Defense AT&L: September–October 2014 Cybersecurity Challenges for Program Managers Steve Mills n Rob Goldsmith Mills is a former program...University. Goldsmith is a systems engineer and currently the Aviation and Missile Research, Development and Engineering Center Cybersecurity Lead at...Redstone Arsenal, Ala. Cybersecurity threats to Department of De-fense (DoD) acquisi-tion programs are both challenging and com- plex. Program managers (PMs

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

    PubMed

    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

    2010-06-23

    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, Ubeda, 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.

  20. 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

  1. 33 CFR 125.41 - Challenges.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... hearing. In the event the Chairman is challenged, he shall forthwith notify the Commandant, furnishing the... 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,...

  2. 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.

  3. 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.

  4. 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…

  5. What's the Cube Quest Challenge?

    NASA Technical Reports Server (NTRS)

    Cockrell, Jim

    2016-01-01

    Cube Quest Challenge, sponsored by Space Technology Mission Directorates Centennial Challenges program, is NASAs first in-space prize competition. Cube Quest is open to any U.S.-based, non-government CubeSat developer. Entrants will compete for one of three available 6U CubeSat dispenser slots on the EM-1 mission the first un-crewed lunar flyby of the Orion spacecraft launched by the Space Launch System in early 2018. The Cube Quest Challenge will award up to $5M in prizes. The advanced CubeSat technologies demonstrated by Cube Quest winners will enable NASA, universities, and industry to more quickly and affordably accomplish science and exploration objectives. This paper describes the teams, their novel CubeSat designs, and the emerging technologies for CubeSat operations in deep space environment.

  6. 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

  7. Zebrafish Behavior: Opportunities and Challenges.

    PubMed

    Orger, Michael B; de Polavieja, Gonzalo G

    2017-04-03

    A great challenge in neuroscience is understanding how activity in the brain gives rise to behavior. The zebrafish is an ideal vertebrate model to address this challenge, thanks to the capacity, at the larval stage, for precise behavioral measurements, genetic manipulations, and recording and manipulation of neural activity noninvasively and at single-neuron resolution throughout the whole brain. These techniques are being further developed for application in freely moving animals and juvenile stages to study more complex behaviors including learning, decision making, and social interactions. We review some of the approaches that have been used to study the behavior of zebrafish and point to opportunities and challenges that lie ahead. Expected final online publication date for the Annual Review of Neuroscience Volume 40 is July 8, 2017. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

  8. 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.

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

    DOE PAGES

    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.

  10. 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…

  11. 75 FR 47316 - Centennial Challenges 2010 Strong Tether Challenge

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-05

    .... 2451 (314)(d). The 2010 Strong Tether Challenge is scheduled and teams that wish to compete may... designed to encourage development of very strong, lightweight material for use in a multitude of structural... prize competitors must (1) register and comply with all requirements in the rules and team agreement;...

  12. 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.

  13. ITER safety challenges and opportunities

    SciTech Connect

    Piet, S.J.

    1991-01-01

    Results of the Conceptual Design Activity (CDA) for the International Thermonuclear Experimental Reactor (ITER) suggest challenges and opportunities. ITER is capable of meeting anticipated regulatory dose limits,'' but proof is difficult because of large radioactive inventories needing stringent radioactivity confinement. We need much research and development (R D) and design analysis to establish that ITER meets regulatory requirements. We have a further opportunity to do more to prove more of fusion's potential safety and environmental advantages and maximize the amount of ITER technology on the path toward fusion power plants. To fulfill these tasks, we need to overcome three programmatic challenges and three technical challenges. The first programmatic challenge is to fund a comprehensive safety and environmental ITER R D plan. Second is to strengthen safety and environment work and personnel in the international team. Third is to establish an external consultant group to advise the ITER Joint Team on designing ITER to meet safety requirements for siting by any of the Parties. The first of the three key technical challenges is plasma engineering -- burn control, plasma shutdown, disruptions, tritium burn fraction, and steady state operation. The second is the divertor, including tritium inventory, activation hazards, chemical reactions, and coolant disturbances. The third technical challenge is optimization of design requirements considering safety risk, technical risk, and cost. Some design requirements are now too strict; some are too lax. Fuel cycle design requirements are presently too strict, mandating inappropriate T separation from H and D. Heat sink requirements are presently too lax; they should be strengthened to ensure that maximum loss of coolant accident temperatures drop.

  14. 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.

  15. 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.

  16. 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.

  17. 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

  18. Novel strategies: challenge loop diuretics and sodium management in heart failure--part II.

    PubMed

    Di Pasquale, Pietro; Sarullo, Filippo M; Paterna, Salvatorew

    2007-01-01

    The conflicting results of diuretic treatments in heart failure (HF) and the importance of Na management in the context of the cardiorenal syndrome and neurohormonal activation in HF have suggested novel and counterintuitive strategies, focused primarily on the use of vasopressin antagonists and hypertonic saline solution with high doses of loop diuretics and their neurohormonal interference. The emerging novel therapies involving direct inhibition of vasopressin receptors appear to show promising results. The use of hypertonic saline solution mixed with a high dose of loop diuretics produces, probably by indirect mechanisms, a reduction or inhibition of the activated neurohormonal systems in HF patients. This treatment opens a new window on the role of sodium management in these patients and on the relation between sodium and the kidney's role and function in heart failure. The authors review the current evidence for these therapies and suggest hypothetical bases for their efficacy.

  19. 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…

  20. 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…

  1. 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,…

  2. Tomorrow's Leisure: Meeting the Challenges.

    ERIC Educational Resources Information Center

    Kraus, Richard

    1994-01-01

    Given the realities of contemporary American life, there are six challenges that will face leisure service providers in the year 2000 and beyond: impact of multiculturalism, environmental concerns, leisure education and values-oriented play, conflict in leisure service goals and strategies, agency coordination and professional development, and…

  3. The Leaking-Toilet Challenge

    ERIC Educational Resources Information Center

    Roman, Harry T.

    2008-01-01

    Leaking toilets can cost homeowners big dollars--often before it is even realized. Homeowners do not necessarily hear it leaking. It just does, and when the water bill comes due, it can be a most unpleasant surprise. This article presents a classroom challenge to try to develop leak-detection ideas that would be inexpensive and easily added to…

  4. 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…

  5. Challenges in Measuring Teachers' Knowledge

    ERIC Educational Resources Information Center

    Fauskanger, Janne

    2015-01-01

    Mathematical knowledge for teaching (MKT) measures have been widely adopted by researchers. Critics have debated the value of such measures and questioned the type of knowledge that these access. This article reports on a study where the challenges in measuring teachers' knowledge were illuminated through investigating relationships between the…

  6. ACES's Challenges: Past Presidents Comment.

    ERIC Educational Resources Information Center

    Sheeley, Vernon Lee

    1990-01-01

    Recognizes the golden anniversary of the Association for Counselor Education and Supervision (ACES) and presents the statements of 15 past presidents of the association. Presidential leaders briefly review the association's past and suggest opportunities to help create a promising future for ACES. Outlines nine challenges which confront members of…

  7. 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.

  8. 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…

  9. 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…

  10. 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…

  11. 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.

  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. 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. Legal Challenges to Christian Colleges.

    ERIC Educational Resources Information Center

    Stephens, W. Richard

    Legal challenges faced by Christian liberal arts colleges affiliated with the Christian College Coalition were studied in 1983. Fifty-one of the 70 college presidents that were contacted returned questionnaires. The following areas were assessed: direct legal involvements during the past 5 years, threatened legal involvements, expected types of…

  15. 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…

  16. 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…

  17. 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.

  18. 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…

  19. 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.

  20. ARPA-E LITECAR Challenge

    ScienceCinema

    Liu, Ping; Salvi, Ashwin

    2016-07-12

    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.

  1. 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.

  2. The Challenges Facing American Education.

    ERIC Educational Resources Information Center

    Mondale, Walter F.

    1982-01-01

    Three challenges of adaptation face education: great demographic change, the technological revolution, and change in social and cultural attitudes. The first task is to improve elementary and secondary education, but then it is to renew support of higher and graduate education as an essential investment in people. (Author/MSE)

  3. 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…

  4. 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…

  5. 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…

  6. 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…

  7. Marital therapy: issues and challenges.

    PubMed Central

    Johnson, S M

    1991-01-01

    This paper outlines the advances made in the field of marital therapy in the last decade. The present status of clinical intervention, empirical research and theoretical conceptualization is reviewed. In addition, the challenges the field now faces are outlined, and proposals made for future directions, which would enable marital intervention to become a more comprehensive and systematic endeavor. PMID:1958653

  8. 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…

  9. 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…

  10. 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…

  11. 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…

  12. 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.

  13. Grand challenges for biological engineering.

    PubMed

    Yoon, Jeong-Yeol; Riley, Mark R

    2009-09-22

    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.

  14. 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.

  15. 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.

  16. Antibiotic resistance: An ethical challenge.

    PubMed

    Littmann, Jasper; Buyx, Alena; Cars, Otto

    2015-10-01

    In this paper, we argue that antibiotic resistance (ABR) raises a number of ethical problems that have not yet been sufficiently addressed. We outline four areas in which ethical issues that arise in relation to ABR are particularly pressing. First, the emergence of multidrug-resistant and extensively drug-resistant infections exacerbates traditional ethical challenges of infectious disease control, such as the restriction of individual liberty for the protection of the public's health. Second, ABR raises issues of global distributive justice, both with regard to the overuse and lack of access to antibiotics. Third, the use of antibiotics in veterinary medicine raises serious concerns for animal welfare and sustainable farming practices. Finally, the diminishing effectiveness of antibiotics leads to questions about intergenerational justice and our responsibility for the wellbeing of future generations. We suggest that current policy discussions should take ethical conflicts into account and engage openly with the challenges that we outline in this paper.

  17. Challenging/interesting lignin times

    DOE PAGES

    Ragauskas, Arthur J.

    2016-08-31

    Anyone who is working in the fuels industry knows that we are living in challenging times. On a personal note, I recall that ~5 years ago, some of my children's friends headed out into the petroleum industry to start their careers and several have now returned because of the retrenching work force. Despite these challenging times, the cellulosic ethanol industry continues to develop commercial operations, but with today's cost structure, biofuels production facilities have certainly slowed their pace of development and roll-out. Furthermore, the biological technology platform for biorefining plant polysaccharides to biofuels has been reported to have an intrinsicmore » advantage, if it can convert its waste lignin stream to value-added components.[1]« less

  18. 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.

  19. Challenges in evaluating surgical innovation

    PubMed Central

    Ergina, Patrick L; Cook, Jonathan A; Blazeby, Jane M; Boutron, Isabelle; Clavien, Pierre-Alain; Reeves, Barnaby C; Seiler, Christoph M

    2010-01-01

    Research on surgical interventions is associated with several methodological and practical challenges of which few, if any, apply only to surgery. However, surgical evaluation is especially demanding because many of these challenges coincide. In this report, the second of three on surgical innovation and evaluation, we discuss obstacles related to the study design of randomised controlled trials and non-randomised studies assessing surgical interventions. We also describe the issues related to the nature of surgical procedures—for example, their complexity, surgeon-related factors, and the range of outcomes. Although difficult, surgical evaluation is achievable and necessary. Solutions tailored to surgical research and a framework for generating evidence on which to base surgical practice are essential. PMID:19782875

  20. Technical challenges for dismantlement verification

    SciTech Connect

    Olinger, C.T.; Stanbro, W.D.; Johnston, R.G.; Nakhleh, C.W.; Dreicer, J.S.

    1997-11-01

    In preparation for future nuclear arms reduction treaties, including any potential successor treaties to START I and II, the authors have been examining possible methods for bilateral warhead dismantlement verification. Warhead dismantlement verification raises significant challenges in the political, legal, and technical arenas. This discussion will focus on the technical issues raised by warhead arms controls. Technical complications arise from several sources. These will be discussed under the headings of warhead authentication, chain-of-custody, dismantlement verification, non-nuclear component tracking, component monitoring, and irreversibility. The authors will discuss possible technical options to address these challenges as applied to a generic dismantlement and disposition process, in the process identifying limitations and vulnerabilities. They expect that these considerations will play a large role in any future arms reduction effort and, therefore, should be addressed in a timely fashion.

  1. 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.

  2. Present challenges in hadrontherapy techniques

    NASA Astrophysics Data System (ADS)

    Amaldi, U.; Braccini, S.

    2011-07-01

    Hadrontherapy is a high-precision technique in cancer radiation therapy, which allows obtaining a superior conformal treatment with respect to photons used in conventional radiation therapy. To reach this ambitious goal without reducing the patient throughput needed in a hospital-based environment, the physical and radiobiological properties of charged hadrons, protons and carbon ions in particular, have to be exploited at best, making use of the most modern technologies issued from research in nuclear and particle physics. In the present days, we are assisting to a continuous technological challenge, leading to the conception and to the development of innovative methods and instruments. In this paper, the most relevant challenges in dose delivery systems, gantries, imaging, quality assurance and particle accelerators are reviewed.

  3. Challenging/interesting lignin times

    SciTech Connect

    Ragauskas, Arthur J.

    2016-08-31

    Anyone who is working in the fuels industry knows that we are living in challenging times. On a personal note, I recall that ~5 years ago, some of my children's friends headed out into the petroleum industry to start their careers and several have now returned because of the retrenching work force. Despite these challenging times, the cellulosic ethanol industry continues to develop commercial operations, but with today's cost structure, biofuels production facilities have certainly slowed their pace of development and roll-out. Furthermore, the biological technology platform for biorefining plant polysaccharides to biofuels has been reported to have an intrinsic advantage, if it can convert its waste lignin stream to value-added components.[1

  4. 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.

  5. 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.

  6. Challenges of evaluating multilevel interventions.

    PubMed

    Nastasi, Bonnie K; Hitchcock, John

    2009-06-01

    This article uses the Comprehensive Mixed-Methods Participatory Evaluation (CMMPE; Nastasi and Hitchcock Transforming school mental health services: Population-based approaches to promoting the competency and wellness of children, Thousand Oaks, CA: Corwin Press with National Association of School Psychologists 2008; Nastasi et al. School-based mental health services: creating comprehensive and culturally specific programs. Washington, DC: American Psychological Association 2004) model as a framework for addressing the multiplicity of evaluation decisions and complex nature of questions related to program success in multilevel interventions. CMMPE defines program success in terms of acceptability, integrity, social or cultural validity, outcomes (impact), sustainability and institutionalization, thus broadening the traditional notions of program outcomes. The authors use CMMPE and an example of a community-based multilevel sexual risk prevention program with multiple outcomes to discuss challenges of evaluating multilevel interventions. The sexual risk program exemplifies what Schensul and Trickett (this issue) characterize as multilevel intervention-multilevel evaluation (M-M), with both intervention and evaluation at community, health practitioner, and patient levels. The illustration provides the context for considering several challenges related to M-M designs: feasibility of randomized controlled trials within community-based multilevel intervention; acceptability and social or cultural validity of evaluation procedures; implementer, recipient, and contextual variations in program success; interactions among levels of the intervention; unanticipated changes or conditions; multiple indicators of program success; engaging multiple stakeholders in a participatory process; and evaluating sustainability and institutionalization. The complexity of multilevel intervention and evaluation designs challenges traditional notions of evaluation research and experimental

  7. 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.

  8. Teaching Strategy: Challenge and Response

    DTIC Science & Technology

    2010-03-01

    dropped. And five out of six regions in the developing world have seen a net decrease in core human rights abuses.2 Nevertheless, today’s world and...replaced by “economic calculations, the endless solving of technical problems, environmental concern, 11 and the satisfaction of consumer demands.”3 The...moral values and violates our sense of what the post-Cold War order should represent. Environmental degradation challenges the health of our citizens

  9. 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.

  10. 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.

  11. 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

  12. Obturator hernia: A diagnostic challenge

    PubMed Central

    Kulkarni, Sanjeev R.; Punamiya, Aditya R.; Naniwadekar, Ramchandra G.; Janugade, Hemant B.; Chotai, Tejas D.; Vimal Singh, T.; Natchair, Arafath

    2013-01-01

    INTRODUCTION Obturator hernia is an extremely rare type of hernia with relatively high mortality and morbidity. Its early diagnosis is challenging since the signs and symptoms are non specific. PRESENTATION OF CASE Here in we present a case of 70 years old women who presented with complaints of intermittent colicky abdominal pain and vomiting. Plain radiograph of abdomen showed acute dilatation of stomach. Ultrasonography showed small bowel obstruction at the mid ileal level with evidence of coiled loops of ileum in pelvis. On exploration, Right Obstructed Obturator hernia was found. The obstructed Intestine was reduced and resected and the obturator foramen was closed with simple sutures. Postoperative period was uneventful. DISCUSSION Obturator hernia is a rare pelvic hernia and poses a diagnostic challenge. Obturator hernia occurs when there is protrusion of intra-abdominal contents through the obturator foramen in the pelvis. The signs and symptoms are non specific and generally the diagnosis is made during exploration for the intestinal obstruction, one of the four cardinal features. Others are pain on the medial aspect of thigh called as Howship Rombergs sign, repeated attacks of Intestinal Obstruction and palpable mass on the medial aspect of thigh. CONCLUSION Obturator hernia is a rare but significant cause of intestinal obstruction especially in emaciated elderly woman and a diagnostic challenge for the Doctors. CT scan is valuable to establish preoperative diagnosis. Surgery either open or laproscopic, is the only treatment. The need for the awareness is stressed and CT scan can be helpful. PMID:23708307

  13. 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.

  14. 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

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. Challenges in describing ribosome dynamics

    NASA Astrophysics Data System (ADS)

    Nguyen, Kien; Whitford, Paul Charles

    2017-04-01

    For decades, protein folding and functional dynamics have been described in terms of diffusive motion across an underlying energy landscape. With continued advances in structural biology and high-performance computing, the field is positioned to extend these approaches to large biomolecular assemblies. Through the application of energy landscape techniques to the ribosome, one may work towards establishing a comprehensive description of the dynamics, which will bridge theoretical concepts and experimental observations. In this perspective, we discuss a few of the challenges that will need to be addressed as we extend the application of landscape principles to the ribosome.

  1. 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.

  2. 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.

  3. Intelligent Transformer: Possibilities and Challenges

    NASA Astrophysics Data System (ADS)

    Viktor, Beldjajev; Indrek, Roasto; Tõnu, Lehtla

    2011-01-01

    This paper covers the concept of an intelligent transformer that is a good candidate to replace a conventional low frequency transformer in the microgrids. As the power production and consumption can vary in a wide range, the new substations have to meet many requirements to guarantee reliable energy management in the autonomous networks. Different topologies of intelligent transformers can be used to meet these requirements. Therefore the advantages and disadvantages of the existing topologies were analyzed. The future trends and challenges are also discussed.

  4. 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)

  5. LHC Status and Upgrade Challenges

    NASA Astrophysics Data System (ADS)

    Smith, Jeffrey

    2009-11-01

    The Large Hadron Collider has had a trying start-up and a challenging operational future lays ahead. Critical to the machine's performance is controlling a beam of particles whose stored energy is equivalent to 80 kg of TNT. Unavoidable beam losses result in energy deposition throughout the machine and without adequate protection this power would result in quenching of the superconducting magnets. A brief overview of the machine layout and principles of operation will be reviewed including a summary of the September 2008 accident. The current status of the LHC, startup schedule and upgrade options to achieve the target luminosity will be presented.

  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. 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.

  8. 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

  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. Computational Challenges of Personal Genomics

    PubMed Central

    Bolouri, Hamid

    2008-01-01

    It is widely predicted that cost and efficiency gains in sequencing will usher in an era of personal genomics and personalized, predictive, preventive, and participatory medicine within a decade. I review the computational challenges ahead and propose general and specific directions for research and development. There is an urgent need to develop semantic ontologies that span genomics, molecular systems biology, and medical data. Although the development of such ontologies would be costly and difficult, the benefits will far outweigh the costs. I argue that availability of such ontologies would allow a revolution in web-services for personal genomics and medicine. PMID:19440448

  11. 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.

  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. The sleepy teenager - diagnostic challenges.

    PubMed

    Landtblom, Anne-Marie; Engström, Maria

    2014-01-01

    The sleepy teenager puts the doctor in a, often tricky, situation where it must be decided if we deal with normal physiology or if we should suspect pathological conditions. What medical investigations are proper to consider? What differential diagnoses should be considered in the first place? And what tools do we actually have? The symptoms and problems that usually are presented at the clinical visit can be both of medical and psychosocial character - and actually they are often a mixture of both. Subsequently, the challenge to investigate the sleepy teenager often includes the examination of a complex behavioral pattern. It is important to train and develop diagnostic skills and to realize that the physiological or pathological conditions that can cause the symptoms may have different explanations. Research in sleep disorders has shown different pathological mechanisms congruent with the variations in the clinical picture. There are probably also different patterns of involved neuronal circuits although common pathways may exist. The whole picture remains to be drawn in this interesting and challenging area.

  14. Challenges in contemporary academic neurosurgery.

    PubMed

    Black, Peter M

    2006-03-01

    Traditionally, the ideal academic neurosurgeon has been a "quadruple threat," with excellence in clinical work, teaching, research, and administration. This tradition was best exemplified in Harvey Cushing, who developed the field of neurosurgery 90 years ago. This paradigm will probably have to change as academic neurosurgeons face major challenges. In patient care, these include increasing regulatory control, increasing malpractice costs, consolidation of expensive care in academic centers, and decreasing reimbursement; in resident teaching, work hour limitations and a changing resident culture; in research, the increasing dominance of basic scientists in governmental funding decisions and decreased involvement of neurosurgeons in scientific review committees; and in administration, problems of relationships in the workplace, patient safety, and employment compliance in an increasingly bureaucratic system. To meet these challenges, the new academic neurosurgeon will probably not be a quadruple threat personally but will be part of a quadruple threat in a department and institution. Neurosurgeons in such a setting will have to work with hospital, medical school, and national and international groups to address malpractice, reimbursement, subspecialization, and training problems; find supplemental sources of income through grants, development funds, and hospital support; lead in the development of multidisciplinary centers for neuroscience, brain tumor, spine, and other initiatives; and focus on training leaders for hospital, regional, and national groups to reconfigure neurosurgery. Collaboration, flexibility, and leadership will be characteristic of the academic neurosurgeon in this new era.

  15. Safe prescribing: a titanic challenge.

    PubMed

    Routledge, Philip A

    2012-10-01

    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.

  16. 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.

  17. 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

  18. 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

  19. 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.

  20. 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.

  1. The challenges of amblyopia treatment.

    PubMed

    Maconachie, Gail D E; Gottlob, Irene

    2015-12-01

    The treatment of amblyopia, particularly anisometropic (difference in refractive correction) and/or strabismic (turn of one eye) amblyopia has long been a challenge for many clinicians. Achieving optimum outcomes, where the amblyopic eye reaches a visual acuity similar to the fellow eye, is often impossible in many patients. Part of this challenge has resulted from a previous lack of scientific evidence for amblyopia treatment that was highlight by a systematic review by Snowdon et al. in 1998. Since this review, a number of publications have revealed new findings in the treatment of amblyopia. This includes the finding that less intensive occlusion treatments can be successful in treating amblyopia. A relationship between adherence to treatment and visual acuity has also been established and has been shown to be influenced by the use of intervention material. In addition, there is growing evidence of that a period of glasses wearing only can significantly improve visual acuity alone without any other modes of treatment. This review article reports findings since the Snowdon's report.

  2. 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.

  3. 75 FR 21044 - Notice of Centennial Challenges 2011 CAFE Green Flight Challenge

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-22

    .... It is being administered for NASA by the Comparative Aircraft Flight Efficiency (CAFE) Foundation... 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...

  4. HSR Aerodynamic Performance Status and Challenges

    NASA Technical Reports Server (NTRS)

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

    1999-01-01

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

  5. 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.

  6. 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 ...

  7. 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

  8. Analysis of the IJCNN 2011 UTL Challenge

    DTIC Science & Technology

    2012-01-13

    Laboratory Abstract We organized a challenge in “ Unsupervised and Transfer Learning”: the UTL challenge (http: //clopinet.com/ul). We made available...supervised learning “target tasks” unknown to the participants. The first phase of the challenge was dedicated to “ unsupervised transfer learning” (the...machine learning, transfer learning, unsupervised learning, metric learning, kernel learning, unlabeled data, challenge, competition 1. Introduction

  9. Analysis Of The IJCNN 2011 UTL Challenge

    DTIC Science & Technology

    2012-01-13

    Laboratory Abstract We organized a challenge in “ Unsupervised and Transfer Learning”: the UTL challenge (http: //clopinet.com/ul). We made available...supervised learning “target tasks” unknown to the participants. The first phase of the challenge was dedicated to “ unsupervised transfer learning” (the...machine learning, transfer learning, unsupervised learning, metric learning, kernel learning, unlabeled data, challenge, competition 1. Introduction

  10. Challenges of Web-Based Assessment.

    ERIC Educational Resources Information Center

    Luecht, Richard M.

    This paper discusses six challenges relevant to Web-based testing. Some of these challenges are not specific to Web-based testing, but generalize to all computer-based testing. The challenges are: (1) security and using test centers for Web-based testing; (2) measuring complex skills and problem-solving tasks on the Web; (3) integrating modern…

  11. 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

  12. 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…

  13. 32 CFR 2001.14 - Classification challenges.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 32 National Defense 6 2011-07-01 2011-07-01 false Classification challenges. 2001.14 Section 2001.14 National Defense Other Regulations Relating to National Defense INFORMATION SECURITY OVERSIGHT... Classification § 2001.14 Classification challenges. (a) Challenging classification. Authorized holders,...

  14. 32 CFR 2001.14 - Classification challenges.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 32 National Defense 6 2012-07-01 2012-07-01 false Classification challenges. 2001.14 Section 2001.14 National Defense Other Regulations Relating to National Defense INFORMATION SECURITY OVERSIGHT... Classification § 2001.14 Classification challenges. (a) Challenging classification. Authorized holders,...

  15. 32 CFR 2001.14 - Classification challenges.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 6 2010-07-01 2010-07-01 false Classification challenges. 2001.14 Section 2001.14 National Defense Other Regulations Relating to National Defense INFORMATION SECURITY OVERSIGHT... Classification § 2001.14 Classification challenges. (a) Challenging classification. Authorized holders,...

  16. 32 CFR 2001.14 - Classification challenges.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 32 National Defense 6 2013-07-01 2013-07-01 false Classification challenges. 2001.14 Section 2001.14 National Defense Other Regulations Relating to National Defense INFORMATION SECURITY OVERSIGHT... Classification § 2001.14 Classification challenges. (a) Challenging classification. Authorized holders,...

  17. 32 CFR 2001.14 - Classification challenges.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 32 National Defense 6 2014-07-01 2014-07-01 false Classification challenges. 2001.14 Section 2001.14 National Defense Other Regulations Relating to National Defense INFORMATION SECURITY OVERSIGHT... Classification § 2001.14 Classification challenges. (a) Challenging classification. Authorized holders,...

  18. 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…

  19. 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…

  20. A Clinical Approach to Antioxidant Therapy: Hypertonic Fluid Resuscitation Trial

    DTIC Science & Technology

    2003-06-01

    5 2. Experimental Section...limited forward surgical care and delayed evacuation.[9] 1.1.1 Current Fluid Resuscitation Standard of Care By virtue of clinical experience , low cost...bleeding, thereby potentially increasing mortality. Indeed, evidence from experimental animal studies suggests that small-volume hypotensive

  1. 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.

  2. Neuroendocrine Responses to Hypertonic Saline/Dextran Resuscitation

    DTIC Science & Technology

    1990-04-01

    serum of plasma norepinephrine by reverse-phase liquid chromatography. Anal Chen 1981;53:156-159. Wade et al.--13 16. Netter J, Wasserman W. Applied...Cardiovascular Physiology , edited by A.C. Guyton and J.E. Hall. Baltimore, MD: University Park, 1982, vol. IV, p. 189-242. 22. Reid IA, Ganong WF. Control of... physiological thresholds of metabolic and hemodynamic actions in man. J Clin Invest 1980;66:94-101. 25. Nahas GG, Ligou JC, Mehlman B. Effects of pH changes on 02

  3. Image processing: some challenging problems.

    PubMed Central

    Huang, T S; Aizawa, K

    1993-01-01

    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. PMID:8234312

  4. Tuberculosis 2004: Challenges and Opportunities

    PubMed Central

    Glassroth, Jeffrey

    2005-01-01

    Tuberculosis (TB) continues as a major public health challenge worldwide. HIV-TB coinfection is especially concerning as it accelerates progression of infection to active disease and amplifies spread of TB including drug resistant disease. Application of molecular biology and insights from classic microbiology to TB control have resulted in important innovations in diagnosis and treatment. Radiometric assay and, particularly, PCR, with nucleic acid probing, have reduced the time to diagnosis. Moreover, the sensitivity of these techniques is potentially log orders of magnitude more sensitive. Molecular techniques can be adapted to drug susceptibility testing. The differential activity and post-antibiotic effect of various drugs against TB have led to highly effective briefer regimens and to directly observed therapy. Insights into basic host defense against TB and description of the M. tuberculosis genome have created optimism for developing new treatments and effective vaccines in the years to come. PMID:16555622

  5. 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.

  6. X-IFU technical challenge

    NASA Astrophysics Data System (ADS)

    Lam Trong, Thien

    2016-07-01

    The X-ray Integral Field Unit (X-IFU) on board the Advanced Telescope for High Energy Astrophysics (Athena), will provide high spectral resolution (2.5 eV up to 7 keV) over a 5 arc minute (equivalent diameter) field of view. The X-IFU is currently in the middle of its Phase A study phase. In this paper, we review the technical challenges (system level issues, TES array, readout, cooling, …) as identified during the first year of the study. This instrument is developed by a large international consortium under a French leadership. The Netherlands and Italy, as Co-PIs, with ESA member state from Belgium, Finland, Germany, Poland, Spain, Switzerland, are the European contributors, with additional contributions from the United States and Japan.

  7. Space health requirements: the challenges.

    PubMed

    Czerwinski, B S; Booher, C R

    1998-01-01

    This article explores the application of theoretical knowledge to clinical situations based on general systems theory and space health requirements to familiarize health care providers with requirements for the space environment. Preparation for extended periods of humans living in the space environment requires carefully planned delivery system that will promote and maintain health. Past, present, and future efforts for the establishment of'space health delivery systems are discussed. The National Aeronautics and Space Administration (NASA), Man-systems integration standards, NASA-STD-3000 Volume 1-MSIS, Revision B (1995, July), Houston, TX, National Aeronautics and Space Administration documents will be reviewed. Health care services will be supported by the available crew health care and emergency services systems. Providing health care in the extreme space environment with limited resources in which to carry out health practices offers challenges to health care providers.

  8. Multiphysics Simulations: Challenges and Opportunities

    SciTech Connect

    Michael Pernice

    2013-02-01

    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.

  9. 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.

  10. Clinical Genomics: Challenges and Opportunities.

    PubMed

    Vijay, Priyanka; McIntyre, Alexa B R; Mason, Christopher E; Greenfield, Jeffrey P; Li, Sheng

    2016-01-01

    Next-generation sequencing (NGS) approaches are highly applicable to clinical studies. We review recent advances in sequencing technologies, as well as their benefits and tradeoffs, to provide an overview of clinical genomics from study design to computational analysis. Sequencing technologies enable genomic, transcriptomic, and epigenomic evaluations. Studies that use a combination of whole genome, exome, mRNA, and bisulfite sequencing are now feasible due to decreasing sequencing costs. Single-molecule sequencing increases read length, with the MinIONTM nanopore sequencer, which offers a uniquely portable option at a lower cost. Many of the published comparisons we review here address the challenges associated with different sequencing methods. Overall, NGS techniques, coupled with continually improving analysis algorithms, are useful for clinical studies in many realms, including cancer, chronic illness, and neurobiology. We, and others in the field, anticipate the clinical use of NGS approaches will continue to grow, especially as we shift into an era of precision medicine.

  11. 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

  12. Inhalation challenge in humidifier fever.

    PubMed

    Edwards, J H; Cockcroft, A

    1981-05-01

    When exposed to an amount of contaminated humidifier water roughly equivalent to that inhaled over an 8-hour period at their work place, four out of six subjects developed symptoms of humidifier fever. Two non-exposed subjects failed to react to the same challenge. Characteristic lung function, temperature and leucocyte changes were recorded; however, a fall in gas transfer previously reported was not seen. That the reaction was immunologically mediated and not due to endotoxin activity was shown by a negative pyrogen response in rabbits inoculated intravenously with concentrated humidifier water. The nature of the immune response has not as yet been evaluated but it does not reside with the ability of humidifier fever antigens to activate complement. Skin testing produced an immediate weal and flare in the four subjects with precipitins and may reflect the presence of short-term anaphylactic IgG antibody.

  13. Carbon nanotubes: opportunities and challenges

    NASA Astrophysics Data System (ADS)

    Dai, Hongjie

    2002-03-01

    Carbon nanotubes are graphene sheets rolled-up into cylinders with diameters as small as one nanometer. Extensive work carried out worldwide in recent years has revealed the intriguing electrical and mechanical properties of these novel molecular scale wires. It is now well established that carbon nanotubes are ideal model systems for studying the physics in one-dimensional solids and have significant potential as building blocks for various practical nanoscale devices. Nanotubes have been shown to be useful for miniaturized electronic, mechanical, electromechanical, chemical and scanning probe devices and materials for macroscopic composites. Progress in nanotube growth has facilitated the fundamental study and applications of nanotubes. Gaining control over challenging nanotube growth issues is critical to the future advancement of nanotube science and technology, and is being actively pursued by researchers.

  14. New transmission lines: The challenge

    SciTech Connect

    Pierobon, J.R. |

    1995-03-15

    Increasing competition in the electric power industry is likely to entail a little-recognized major complication---difficulty in siting of transmission lines. The stakes will often be greater, the competition could be stronger, and both put a premium on finding a process that can win public acceptance cost-effectively. There are at least three major reasons why siting new lines will become more difficult: (1) More communities in the paths of the new lines will not be served by them and will see no benefit to offset the nuisance, (2) In addition to the perceived health threats of electric and magnetic fields, opposition will arise based on claims about siting of lines in low-income or minority neighborhoods, and (3) Electric power companies that stand to lose market share if the lines are completed may align themselves with the opposition. This article is a review of the challenges that utilities may face in their efforts.

  15. 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.

  16. The Shigella human challenge model.

    PubMed

    Porter, C K; Thura, N; Ranallo, R T; Riddle, M S

    2013-02-01

    Shigella is an important bacterial cause of infectious diarrhoea globally. The Shigella human challenge model has been used since 1946 for a variety of objectives including understanding disease pathogenesis, human immune responses and allowing for an early assessment of vaccine efficacy. A systematic review of the literature regarding experimental shigellosis in human subjects was conducted. Summative estimates were calculated by strain and dose. While a total of 19 studies evaluating nine strains at doses ranging from 10 to 1 × 1010 colony-forming units were identified, most studies utilized the S. sonnei strain 53G and the S. flexneri strain 2457T. Inoculum solution and pre-inoculation buffering has varied over time although diarrhoea attack rates do not appear to increase above 75-80%, and dysentery rates remain fairly constant, highlighting the need for additional dose-ranging studies. Expansion of the model to include additional strains from different serotypes will elucidate serotype and strain-specific outcome variability.

  17. 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.

  18. 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.

  19. 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.

  20. 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

  1. Emerging infections: a perpetual challenge.

    PubMed

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

    2008-11-01

    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.

  2. EUV Lithography: New Metrology Challenges

    SciTech Connect

    Wood, Obert

    2007-09-26

    Extreme ultraviolet lithography is one of the most promising printing techniques for high volume semiconductor manufacturing at the 22 nm half-pitch device node and beyond. Because its imaging wavelength is approximately twenty times shorter than those currently in use (13.5 nm versus 193-248 nm) and because EUV optics and masks must be provided with highly-precise reflective multilayer coatings, EUV lithography presents a number of new and difficult metrology challenges. In this paper, the current status of the metrology tools being used to characterize the figure and finish of EUV mirror surfaces, the defectivity and flatness of EUV mask blanks and the outgassing rates of EUV resist materials are discussed.

  3. DSM-5: Challenging diagnostic testimony.

    PubMed

    Hagan, Leigh D; Guilmette, Thomas J

    2015-01-01

    The Diagnostic and Statistical Manual of Mental Disorders' (DSM) 60-year evolution has not been particularly linear nor cumulative with respect to the process of its construction, its stated purpose, its framework, and inclusion of specific disorders. We consider DSM-5's stated purpose in light of the manual's explicit cautions and other complications encountered when presenting diagnoses in the course of psychological expert testimony under the applicable rules of evidence. This review considers the extent to which DSM-5 bears up under numerous criticisms when employed for forensic purposes and points out challenges that the expert should anticipate when offering diagnostic opinions underpinned by DSM-5 generally and by neurocognitive disorders in particular.

  4. 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

  5. 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.

  6. 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.

  7. The DEMO wall load challenge

    NASA Astrophysics Data System (ADS)

    Wenninger, R.; Albanese, R.; Ambrosino, R.; Arbeiter, F.; Aubert, J.; Bachmann, C.; Barbato, L.; Barrett, T.; Beckers, M.; Biel, W.; Boccaccini, L.; Carralero, D.; Coster, D.; Eich, T.; Fasoli, A.; Federici, G.; Firdaouss, M.; Graves, J.; Horacek, J.; Kovari, M.; Lanthaler, S.; Loschiavo, V.; Lowry, C.; Lux, H.; Maddaluno, G.; Maviglia, F.; Mitteau, R.; Neu, R.; Pfefferle, D.; Schmid, K.; Siccinio, M.; Sieglin, B.; Silva, C.; Snicker, A.; Subba, F.; Varje, J.; Zohm, H.

    2017-04-01

    For several reasons the challenge to keep the loads to the first wall within engineering limits is substantially higher in DEMO compared to ITER. Therefore the pre-conceptual design development for DEMO that is currently ongoing in Europe needs to be based on load estimates that are derived employing the most recent plasma edge physics knowledge. An initial assessment of the static wall heat load limit in DEMO infers that the steady state peak heat flux limit on the majority of the DEMO first wall should not be assumed to be higher than 1.0 MW m‑2. This compares to an average wall heat load of 0.29 MW m‑2 for the design {\\tt {EU}}{\\tt {~}}{\\tt {DEMO1}}{\\tt {~2015}} assuming a perfect homogeneous distribution. The main part of this publication concentrates on the development of first DEMO estimates for charged particle, radiation, fast particle (all static) and disruption heat loads. Employing an initial engineering wall design with clear optimization potential in combination with parameters for the flat-top phase (x-point configuration), loads up to 7 MW m‑2 (penalty factor for tolerances etc not applied) have been calculated. Assuming a fraction of power radiated from the x-point region between 1/5 and 1/3, peaks of the total power flux density due to radiation of 0.6–0.8 MW m‑2 are found in the outer baffle region. This first review of wall loads, and the associated limits in DEMO clearly underlines a significant challenge that necessitates substantial engineering efforts as well as a considerable consolidation of the associated physics basis.

  8. 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.

  9. Childhood vaccination: achievements and challenges.

    PubMed

    Ndumbe, P

    1996-09-01

    As the goal of eradicating smallpox was being met, the World Health Organization created its Expanded Programme on Immunisation (EPI) in 1974 and reached its initial goal of achieving full vaccination of 80% of the world's children by 1990. This effort was aided by the creation of "cold chain" delivery systems and resulted in the annual saving of 3.5 million children in less-developed countries. Current EPI vaccination goals include 1) eradication of poliomyelitis by the year 2000, 2) elimination of neonatal tetanus by the year 1995, 3) control of measles and hepatitis B, and 4) immunization of 90% of the world's children 1 year or younger by the year 2000. Goals of the Children's Vaccine Initiative (formed in 1991) include 1) provision of an adequate supply of affordable, safe, and effective vaccines; 2) production of improved and new vaccines; and 3) simplification of the logistics of vaccine delivery. Future challenges are to sustain high vaccination coverage, reach the unreached, achieve proper storage of vaccines and reduce waste, integrate new vaccines into national programs, and achieve vaccine self-sufficiency. The fact that these challenges will be difficult to achieve is illustrated by the situation in Africa where the high immunization levels achieved in 1990 have dropped dramatically. Those who must act to implement immunization programs are health personnel, families, governments, and development partners. In order to achieve equity in health, every child must be reached, governments must be made accountable for programs, health workers must convince families of the importance of vaccination, delivery systems must be in place to take advantage of the new vaccines being delivered, and a multisectoral approach must be taken to assure sustainability.

  10. 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

  11. Cardiovascular response to thermoregulatory challenges

    PubMed Central

    Liu, Cuiqing; Yavar, Zubin

    2015-01-01

    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

  12. Legal challenges in neurological practice

    PubMed Central

    Jayalakshmi, Sita; Vooturi, Sudhindra

    2016-01-01

    Clinical neuroscience has made tremendous advances over the last century. Neurology as a discipline is still considered challenging and at times risky due to the natural history and progressive course of few of the neurological diseases. Encouragingly, the patient and their caregivers are now increasingly willing to be actively involved in making decisions. The patients’ relationship with the doctor is a reflection of the society. A society that is orienting itself toward “rating” and “feedback” has made this doctor–patient relationship, a consumer–service provider relationship. This perhaps is due to commercialization of health that usually accompanies globalization. Moreover, a rapid influx of information from potential erroneous sources such as the Internet has also made patient and caregivers not being hesitant to taking legal course in the case of adverse events during treatment or simply because of dissatisfaction. The purpose of the legal process initiated by patients with neurological ailments is more often to compensate for the income lost, physical and psychological anguish that accompanies disease and its treatment, and to fund treatment or rehabilitation requirements. However, it is not clearly established if monetary benefits acquired lead to better opportunities for recovery of the patient. The consumer protection act and commercialization of medical services may well have an adverse effect on the doctor and patient relationship. Hence, there is a great need for all medical professionals to mutually complement and update each other. This review examines legal (litigation) processes with special interest on medicolegal system in patients with neurological ailments and the challenges faced by the neurologist during day-to-day clinical practice. PMID:27891018

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. [Sex and gender: five challenges for epidemiologists].

    PubMed

    Doyal, L

    2004-03-01

    This paper explores the challenges posed by sex and gender for epidemiologists as they try to integrate sex and gender concerns into their work in more appropriate and effective ways. The first challenge is one of conceptual clarification with considerable confusion still surrounding the use of the terms sex and gender themselves. The second challenge is to develop a broader understanding of the links between biological sex and health. The third challenge is to create a more comprehensive understanding of the ways in which social gender shapes the health of both women and men. The fourth challenge is to ensure that all research designs are both sex and gender sensitive. And the final challenge is to find a strategy for integrating findings on both sex and gender into wider equality agendas. This paper will examine each of these challenges in turn.

  18. 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

  19. Challenges in Commercializing Biomimetic Membranes

    PubMed Central

    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

  20. 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.

  1. Design challenges for space bioreactors

    NASA Technical Reports Server (NTRS)

    Seshan, P. K.; Petersen, G. R.

    1989-01-01

    The design of bioreactors for operation under conditions of microgravity presents problems and challenges. Absence of a significant body force such as gravity can have profound consequences for interfacial phenomena. Marangoni convection can no longer be overlooked. Many speculations on the advantages and benefits of microgravity can be found in the literature. Initial bioreactor research considerations for space applications had little regard for the suitability of the designs for conditions of microgravity. Bioreactors can be classified in terms of their function and type of operation. The complex interaction of parameters leading to optimal design and operation of a bioreactor is illustrated by the JSC mammalian cell culture system. The design of a bioreactor is strongly dependent upon its intended use as a production unit for cell mass and/or biologicals or as a research reactor for the study of cell growth and function. Therefore a variety of bioreactor configurations are presented in rapid summary. Following this, a rationale is presented for not attempting to derive key design parameters such as the oxygen transfer coefficient from ground-based data. A set of themes/objectives for flight experiments to develop the expertise for design of space bioreactors is then proposed for discussion. These experiments, carried out systematically, will provide a database from which engineering tools for space bioreactor design will be derived.

  2. 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 (NASA) 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-peformance 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. The paper will also address smart materials and structures and examine space environmental effects on materials and methods of mitigating them. Finally, the paper will take a look at the possibility of utilizing materials in situ, i.e., processing and using desired materials on the surface of the Moon and Mars.

  3. Current challenges in pediatric nutrition.

    PubMed

    Krawinkel, Michael B

    2011-10-01

    In pediatric nutrition the most important overall theme is breastfeeding. While there is no alternative in most mammals--and offspring would die if the mother had no milk or could not feed the newborn--human mothers were offered alternative ways of infant feeding. Today restoring breastfeeding is a major goal for pediatricians, midwifes, and lactation advisers. Feeding the premature baby and adding long chain fatty acids and prebiotics to formula is an area of growing interest. Undernutrition is a special challenge for nutritional care because even in recent years severely undernourished children die of inadequate management with too much volume and too much protein in the initial phase. Much knowledge has been gained about parenteral nutrition for children with gut failure. Even children with very short bowel length at birth have a good prognosis and can often achieve enteral adaptation. New solutions for parenteral nutrition, new materials, and new care concepts have been identified. Problems considered inherent to parenteral nutrition are widely preventable.

  4. Organ printing: promises and challenges.

    PubMed

    Mironov, Vladimir; Kasyanov, Vladimir; Drake, Christopher; Markwald, Roger R

    2008-01-01

    Organ printing or biomedical application of rapid prototyping, also defined as additive layer-by-layer biomanufacturing, is an emerging transforming technology that has potential for surpassing traditional solid scaffold-based tissue engineering. Organ printing has certain advantages: it is an automated approach that offers a pathway for scalable reproducible mass production of tissue engineered products; it allows a precised simultaneous 3D positioning of several cell types; it enables creation tissue with a high level of cell density; it can solve the problem of vascularization in thick tissue constructs; finally, organ printing can be done in situ. The ultimate goal of organ-printing technology is to fabricate 3D vascularized functional living human organs suitable for clinical implantation. The main practical outcomes of organ-printing technology are industrial scalable robotic biofabrication of complex human tissues and organs, automated tissue-based in vitro assays for clinical diagnostics, drug discovery and drug toxicity, and complex in vitro models of human diseases. This article describes conceptual framework and recent developments in organ-printing technology, outlines main technological barriers and challenges, and presents potential future practical applications.

  5. Antiphospholipid syndrome: A diagnostic challenge.

    PubMed

    Mallhi, R S; Kushwaha, Neerja; Chatterjee, T; Philip, J

    2016-12-01

    The antiphospholipid syndrome (APS) is an acquired autoimmune thrombophilic disorder that is characterized by thrombosis (venous, arterial and microvascular) and obstetric morbidity due to a diverse family of antibodies against phospholipid-binding proteins present in plasma. The term antiphospholipid antibody is actually a misnomer as the antibodies are not against the phospholipid per se, but target the plasma protein co-factors, which bind to anionic PLs. The exact etiology has not been elucidated and is multifactorial. The initial guidelines for the diagnosis of APS were laid down in Sapporo, 1999, which were subsequently revised as the Sydney Consensus Conference criteria in 2006. Major changes were the inclusion of β2GPI as independent laboratory criteria, addition of ischemic stroke and transient cerebral ischemia as established clinical criteria and the requirement of repeating the test after 12 weeks. The laboratory tests recommended are coagulation assays, which study the effect of lupus anticoagulant on the clotting time and immunological assays, mostly ELISAs to detect IgG and IgM antibodies against cardiolipin and/or β2 glycoprotein I. For the diagnosis of APS, at least one clinical criterion and one laboratory criterion should be present. Limitations pertaining to the standardization, reproducibility and robustness of the currently recommended diagnostic tests still remain. Despite elaborate guidelines and syndrome defining criteria, the diagnosis of APS still remains a challenge. A greater interaction between the clinicians and the laboratory professionals is necessary for arriving at the correct diagnosis as a misdiagnosis of APS can have grave consequences.

  6. The Airframe Noise Reduction Challenge

    NASA Technical Reports Server (NTRS)

    Lockhard, David P.; Lilley, Geoffrey M.

    2004-01-01

    The NASA goal of reducing external aircraft noise by 10 dB in the near-term presents the acoustics community with an enormous challenge. This report identifies technologies with the greatest potential to reduce airframe noise. Acoustic and aerodynamic effects will be discussed, along with the likelihood of industry accepting and implementing the different technologies. We investigate the lower bound, defined as noise generated by an aircraft modified with a virtual retrofit capable of eliminating all noise associated with the high lift system and landing gear. However, the airframe noise of an aircraft in this 'clean' configuration would only be about 8 dB quieter on approach than current civil transports. To achieve the NASA goal of 10 dB noise reduction will require that additional noise sources be addressed. Research shows that energy in the turbulent boundary layer of a wing is scattered as it crosses trailing edge. Noise generated by scattering is the dominant noise mechanism on an aircraft flying in the clean configuration. Eliminating scattering would require changes to much of the aircraft, and practical reduction devices have yet to receive serious attention. Evidence suggests that to meet NASA goals in civil aviation noise reduction, we need to employ emerging technologies and improve landing procedures; modified landing patterns and zoning restrictions could help alleviate aircraft noise in communities close to airports.

  7. Challenging Return to Play Decisions

    PubMed Central

    Asplund, Chad A.; O’Connor, Francis G.

    2015-01-01

    Context: Sports medicine providers frequently return athletes to play after sports-related injuries and conditions. Many of these conditions have guidelines or medical evidence to guide the decision-making process. Occasionally, however, sports medicine providers are challenged with complex medical conditions for which there is little evidence-based guidance and physicians are instructed to individualize treatment; included in this group of conditions are exertional heat stroke (EHS), exertional rhabdomyolysis (ER), and exertional collapse associated with sickle cell trait (ECAST). Evidence Acquisition: The MEDLINE (2000-2015) database was searched using the following search terms: exertional heat stroke, exertional rhabdomyolysis, and exertional collapse associated with sickle cell trait. References from consensus statements, review articles, and book chapters were also utilized. Study Design: Clinical review. Level of Evidence: Level 4. Results: These entities are unique in that they may cause organ system damage capable of leading to short- or long-term detriments to physical activity and may not lend to complete recovery, potentially putting the athlete at risk with premature return to play. Conclusion: With a better understanding of the pathophysiology of EHS, ER, and ECAST and the factors associated with recovery, better decisions regarding return to play may be made. PMID:26896216

  8. Computational Aeroelasticity: Success, Progress, Challenge

    NASA Technical Reports Server (NTRS)

    Schuster, David M.; Liu, Danny D.; Huttsell, Lawrence J.

    2003-01-01

    The formal term Computational Aeroelasticity (CAE) has only been recently adopted to describe aeroelastic analysis methods coupling high-level computational fluid dynamics codes with structural dynamics techniques. However, the general field of aeroelastic computations has enjoyed a rich history of development and application since the first hand-calculations performed in the mid 1930 s. This paper portrays a much broader definition of Computational Aeroelasticity; one that encompasses all levels of aeroelastic computation from the simplest linear aerodynamic modeling to the highest levels of viscous unsteady aerodynamics, from the most basic linear beam structural models to state-of-the-art Finite Element Model (FEM) structural analysis. This paper is not written as a comprehensive history of CAE, but rather serves to review the development and application of aeroelastic analysis methods. It describes techniques and example applications that are viewed as relatively mature and accepted, the "successes" of CAE. Cases where CAE has been successfully applied to unique or emerging problems, but the resulting techniques have proven to be one-of-a-kind analyses or areas where the techniques have yet to evolve into a routinely applied methodology are covered as "progress" in CAE. Finally the true value of this paper is rooted in the description of problems where CAE falls short in its ability to provide relevant tools for industry, the so-called "challenges" to CAE.

  9. The challenge of patient adherence

    PubMed Central

    Martin, Leslie R; Williams, Summer L; Haskard, Kelly B; DiMatteo, M Robin

    2005-01-01

    Quality healthcare outcomes depend upon patients' adherence to recommended treatment regimens. Patient nonadherence can be a pervasive threat to health and wellbeing and carry an appreciable economic burden as well. In some disease conditions, more than 40% of patients sustain significant risks by misunderstanding, forgetting, or ignoring healthcare advice. While no single intervention strategy can improve the adherence of all patients, decades of research studies agree that successful attempts to improve patient adherence depend upon a set of key factors. These include realistic assessment of patients' knowledge and understanding of the regimen, clear and effective communication between health professionals and their patients, and the nurturance of trust in the therapeutic relationship. Patients must be given the opportunity to tell the story of their unique illness experiences. Knowing the patient as a person allows the health professional to understand elements that are crucial to the patient's adherence: beliefs, attitudes, subjective norms, cultural context, social supports, and emotional health challenges, particularly depression. Physician–patient partnerships are essential when choosing amongst various therapeutic options to maximize adherence. Mutual collaboration fosters greater patient satisfaction, reduces the risks of nonadherence, and improves patients' healthcare outcomes. PMID:18360559

  10. GEOSS: Addressing Big Data Challenges

    NASA Astrophysics Data System (ADS)

    Nativi, S.; Craglia, M.; Ochiai, O.

    2014-12-01

    In the sector of Earth Observation, the explosion of data is due to many factors including: new satellite constellations, the increased capabilities of sensor technologies, social media, crowdsourcing, and the need for multidisciplinary and collaborative research to face Global Changes. In this area, there are many expectations and concerns about Big Data. Vendors have attempted to use this term for their commercial purposes. It is necessary to understand whether Big Data is a radical shift or an incremental change for the existing digital infrastructures. This presentation tries to explore and discuss the impact of Big Data challenges and new capabilities on the Global Earth Observation System of Systems (GEOSS) and particularly on its common digital infrastructure called GCI. GEOSS is a global and flexible network of content providers allowing decision makers to access an extraordinary range of data and information at their desk. The impact of the Big Data dimensionalities (commonly known as 'V' axes: volume, variety, velocity, veracity, visualization) on GEOSS is discussed. The main solutions and experimentation developed by GEOSS along these axes are introduced and analyzed. GEOSS is a pioneering framework for global and multidisciplinary data sharing in the Earth Observation realm; its experience on Big Data is valuable for the many lessons learned.

  11. Silicon spintronics: Progress and challenges

    NASA Astrophysics Data System (ADS)

    Sverdlov, Viktor; Selberherr, Siegfried

    2015-07-01

    Electron spin attracts much attention as an alternative to the electron charge degree of freedom for low-power reprogrammable logic and non-volatile memory applications. Silicon appears to be the perfect material for spin-driven applications. Recent progress and challenges regarding spin-based devices are reviewed. An order of magnitude enhancement of the electron spin lifetime in silicon thin films by shear strain is predicted and its impact on spin transport in SpinFETs is discussed. A relatively weak coupling between spin and effective electric field in silicon allows magnetoresistance modulation at room temperature, however, for long channel lengths. Due to tunneling magnetoresistance and spin transfer torque effects, a much stronger coupling between the spin (magnetization) orientation and charge current is achieved in magnetic tunnel junctions. Magnetic random access memory (MRAM) built on magnetic tunnel junctions is CMOS compatible and possesses all properties needed for future universal memory. Designs of spin-based non-volatile MRAM cells are presented. By means of micromagnetic simulations it is demonstrated that a substantial reduction of the switching time can be achieved. Finally, it is shown that any two arbitrary memory cells from an MRAM array can be used to perform a logic operation. Thus, an intrinsic non-volatile logic-in-memory architecture can be realized.

  12. Challenges and Solutions in Proteomics

    PubMed Central

    Hongzhan, Huang; Shukla, Hem D; Cathy, Wu; Satya, Saxena

    2007-01-01

    The accelerated growth of proteomics data presents both opportunities and challenges. Large-scale proteomic profiling of biological samples such as cells, organelles or biological fluids has led to discovery of numerous key and novel proteins involved in many biological/disease processes including cancers, as well as to the identification of novel disease biomarkers and potential therapeutic targets. While proteomic data analysis has been greatly assisted by the many bioinformatics tools developed in recent years, a careful analysis of the major steps and flow of data in a typical highthroughput analysis reveals a few gaps that still need to be filled to fully realize the value of the data. To facilitate functional and pathway discovery for large-scale proteomic data, we have developed an integrated proteomic expression analysis system, iProXpress, which facilitates protein identification using a comprehensive sequence library and functional interpretation using integrated data. With its modular design, iProXpress complements and can be integrated with other software in a proteomic data analysis pipeline. This novel approach to complex biological questions involves the interrogation of multiple data sources, thereby facilitating hypothesis generation and knowledge discovery from the genomic-scale studies and fostering disease diagnosis and drug development. PMID:18645629

  13. Historical challenge of large lenses

    NASA Astrophysics Data System (ADS)

    Johnson, Kevin L.

    2002-02-01

    To present a full account of the developments in the manufacture of large lenses one needs to address wider issues rather than just provide a catalogue of technological progress. The advances in glass manufacture and improvement in optical techniques have to be considered in relation to the cultural, social and economic factors that have determined where, how and why large lens manufacture developed in specific countries. The challenge facing historians trying to tackle this technological theme, is that it is often poorly documented and little is preserved in the historical records. Until relatively recent times, opticians have concealed their methods, trade secrecy being an important economic strategy. To provide an example, it should be noted that although William Herschel produced the best optics and telescopes of the day, he published practically nothing about his methods. What has been gleaned of his techniques has only been uncovered by careful study of surviving manuscript sources and measurement of his surviving optics. Such was William's personal knowledge, that his son John had to take instruction from his father to refurbish William Herschel's 20-foot telescope. This training gave John tacit knowledge of William's methods and allowed him to successfully undertake his cape observations in the Southern Hemisphere. In spite of the shortcomings of the historical record, historians can give a measured account of the developments of lens optics by studying surviving telescopes and their optics.

  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. The Continuing Challenges of Leprosy

    PubMed Central

    Scollard, D. M.; Adams, L. B.; Gillis, T. P.; Krahenbuhl, J. L.; Truman, R. W.; Williams, D. L.

    2006-01-01

    Leprosy is best understood as two conjoined diseases. The first is a chronic mycobacterial infection that elicits an extraordinary range of cellular immune responses in humans. The second is a peripheral neuropathy that is initiated by the infection and the accompanying immunological events. The infection is curable but not preventable, and leprosy remains a major global health problem, especially in the developing world, publicity to the contrary notwithstanding. Mycobacterium leprae remains noncultivable, and for over a century leprosy has presented major challenges in the fields of microbiology, pathology, immunology, and genetics; it continues to do so today. This review focuses on recent advances in our understanding of M. leprae and the host response to it, especially concerning molecular identification of M. leprae, knowledge of its genome, transcriptome, and proteome, its mechanisms of microbial resistance, and recognition of strains by variable-number tandem repeat analysis. Advances in experimental models include studies in gene knockout mice and the development of molecular techniques to explore the armadillo model. In clinical studies, notable progress has been made concerning the immunology and immunopathology of leprosy, the genetics of human resistance, mechanisms of nerve injury, and chemotherapy. In nearly all of these areas, however, leprosy remains poorly understood compared to other major bacterial diseases. PMID:16614253

  16. 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.

  17. Neuromodulation: Selected approaches and challenges

    PubMed Central

    Parpura, Vladimir; Silva, Gabriel A.; Tass, Peter A.; Bennet, Kevin E.; Meyyappan, Meyya; Koehne, Jessica; Lee, Kendall H.; Andrews, Russell J.

    2012-01-01

    The brain operates through complex interactions in the flow of information and signal processing within neural networks. The “wiring” of such networks, being neuronal or glial, can physically and/or functionally go rogue in various pathological states. Neuromodulation, as a multidisciplinary venture, attempts to correct such faulty nets. In this review, selected approaches and challenges in neuromoduation are discussed. The use of water-dispersible carbon nanotubes have proven effective in modulation of neurite outgrowth in culture as well as in aiding regeneration after spinal cord injury in vivo. Studying neural circuits using computational biology and analytical engineering approaches brings to light geometrical mapping of dynamics within neural networks, much needed information for stimulation interventions in medical practice. Indeed, sophisticated desynchronization approaches used for brain stimulation have been successful in coaxing “misfiring” neuronal circuits to resume productive firing patterns in various human disorders. Devices have been developed for the real time measurement of various neurotransmitters as well as electrical activity in the human brain during electrical deep brain stimulation. Such devices can establish the dynamics of electrochemical changes in the brain during stimulation. With increasing application of nanomaterials in devices for electrical and chemical recording and stimulating in the brain, the era of cellular, and even intracellular, precision neuromodulation will soon be upon us. PMID:23190025

  18. Gastroparesis: Concepts, Controversies, and Challenges

    PubMed Central

    Bielefeldt, Klaus

    2012-01-01

    Patients with gastroparesis often present a challenge to the treating physician. Postprandial symptoms with nausea and vomiting may not only lead to nutritional and metabolic consequences, but also cause significant disruptions to social activities that often center around food. While the definition of gastroparesis focuses on impaired gastric emptying, treatment options that affect gastric function are limited and often disappointing. The female predominance, the mostly idiopathic nature of the illness with a common history of abuse, and coexisting anxiety or depression show parallels with other functional disorders of the gastrointestinal tract. These parallels provided the rationale for some initial studies investigating alternative therapies that target the brain rather than the stomach. This emerging shift in medical therapy comes at a time when clinical studies suggest that gastric electrical stimulation may exert its effects by modulating visceral sensory processing rather than altering gastric motility. Physiologic and detailed anatomic investigations also support a more complex picture with different disease mechanisms, ranging from impaired accommodation to apparent visceral hypersensitivity or decreased interstitial cells of Cajal to inflammatory infiltration of myenteric ganglia. Delayed gastric emptying remains the endophenotype defining gastroparesis. However, our treatment options go beyond prokinetics and may allow us to improve the quality of life of affected individuals. PMID:24278691

  19. 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.

  20. 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

  1. 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.

  2. 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

  3. 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.

  4. Drugging Topoisomerases: Lessons and Challenges

    PubMed Central

    Pommier, Yves

    2013-01-01

    Topoisomerases are ubiquitous enzymes that control DNA supercoiling and entanglements. They are essential during transcription and replication and topoisomerase inhibitors are among the most effective and most commonly used anticancer and antibacterial drugs. This review consists in two parts. In the first part (“Lessons”), it gives background information on the catalytic mechanisms of the different enzyme families (6 different genes in humans and 4 in most bacteria), describes the “interfacial inhibition” by which topoisomerase-targeted drugs act as topoisomerase poisons and describes clinically relevant topoisomerase inhibitors. It generalizes the interfacial inhibition principle, which was discovered from the mechanism of action of topoisomerase inhibitors, and discusses how topoisomerase inhibitors kill cells by trapping topoisomerases on DNA rather than by classical enzymatic inhibition. Trapping protein-DNA complexes extends to a novel mechanism of action of PARP inhibitors and could be applied to the targeting of transcription factors. The second part of the review focuses on the challenges for discovery and precise use of topoisomerase inhibitors, including targeting topoisomerase inhibitors using chemical coupling and encapsulation for selective tumor delivery, use of pharmacodynamic biomarkers to follow drug activity, complexity of the response determinants for anticancer activity and patient selection, prospects of rational combinations with DNA repair inhibitors targeting tyrosyl-DNA-phosphodiesterases 1 and 2 (TDP1 and TDP2) and PARP, and the unmeet need to develop inhibitors for type IA enzymes. PMID:23259582

  5. Astronomy Education Challenges in Egypt

    NASA Astrophysics Data System (ADS)

    El Fady Beshara Morcos, Abd

    2015-08-01

    One of the major challenges in Egypt is the quality of education. Egypt has made significant progress towards achieving the Education for All and the Millennium Development Goals (MDGs). Many associations and committees as education reform program and education support programs did high efforts in supporting scientific thinking through the scientific clubs. The current state of astronomical education in Egypt has been developed. Astronomy became a part in both science and geography courses of primary, preparatory and secondary stages. Nowadays the Egyptian National Committee for Astronomy, put on its shoulders the responsibility of revising of astronomy parts in the education courses, beside preparation of some training programs for teachers of different stages of educations, in collaboration with ministry of education. General lectures program has been prepared and started in public places , schools and universities. Many TV and Radio programs aiming to spread astronomical culture were presented. In the university stage new astronomy departments are established and astrophysics courses are imbedded in physics courses even in some private universities.

  6. Two Sea-Level Challenges

    NASA Astrophysics Data System (ADS)

    Galvin, C.

    2008-12-01

    "No place on the sandy ocean shores of the world has been shown to be eroding because of sea level rise." This statement appeared nearly 19 years ago in bold print at the top of the page in a brief article published in Shore and Beach (Galvin,1990). The term "sea level rise" was defined in 1990 as follows: "In this statement, "sea level rise" has the meaning that the average person on the street usually attaches to that term. That is, sea level is rising; not, as in some places like the Mississippi River delta, land level is sinking." While still a subject of controversy, it is now (2008) increasingly plausible (Tornqvist et al,2008) that damage from Hurricane Katrina was significantly worse on the Mississippi River delta because floodwaters exploited wetlands and levees whose elevations had been lowered by decades of compaction in the underlying soil. (1) "Sea level" commonly appears in the literature as "relative sea level rise", occurring that way in 711 publications between 1980 and 2009 (GeoRef database on 8 Sep 08). "Relative sea level rise" does not appear in the 2005 AGI Glossary. The nearest Glossary term is "relative change in sea level", but that term occurs in only 12 publications between 1980 and 2009. The Glossary defines this term in a sequence stratigraphy sense, which infers that "relative sea level rise" is the sum of bottom subsidence and eustatic sea level rise. In plain English, "relative sea level rise" means "water depth increase". For present day coastal environments, "relative sea level rise" is commonly used where eustatic sea level rise is less than subsidence, that is, where the magnitude of actual sea level rise is smaller than the magnitude of subsidence. In that situation, "relative sea level rise" misleads both the average person and the scientist who is not a coastal geologist. Thus, the first challenge is to abandon "relative sea level rise" in favor of "water depth increase", in order that the words accurately descibe what happens

  7. Challenges in Essential Tremor Genetics

    PubMed Central

    Clark, Lorraine N.; Louis, Elan D.

    2015-01-01

    The field of essential tremor (ET) genetics remains extremely challenging. The relative lack of progress in understanding the genetic etiology of ET; however, does not reflect the lack of a genetic contribution, but rather, the presence of substantial phenotypic and genotypic heterogeneity. A meticulous approach to phenotyping is important for genetic research in ET. The only tool for phenotyping is the clinical history and examination. There is currently no ET-specific serum or imaging biomarker or defining neuropathological feature (e.g., a protein aggregate specific to ET) that can be used for phenotyping, and there is considerable clinical overlap with other disorders such as Parkinson’s disease (PD) and dystonia. These issues greatly complicate phenotyping; thus, in some studies, as many as 30 – 50% of cases labeled as “ET” have later been found to carry other diagnoses (e.g., dystonia, PD) rather than ET. A cursory approach to phenotyping (e.g., merely defining ET as an “action tremor”) is likely a major issue in some family studies of ET, and this as well as lack of standardized phenotyping across studies and patient centers is likely to be a major contributor to the relative lack of success of genome wide association studies (GWAS). To dissect the genetic architecture of ET, whole genome sequencing (WGS) in carefully characterized and well-phenotyped discovery and replication datasets of large case-control and familial cohorts will likely be of value. This will allow specific hypotheses about the mode of inheritance and genetic architecture to be tested. There are a number of approaches that still remain unexplored in ET genetics, including the contribution of copy number variants (CNVs), ‘uncommon’ moderate effect alleles, ‘rare’ variant large effect alleles (including Mendelian and complex/polygenic modes of inheritance), de novo and gonadal mosaicism, epigenetic changes and non-coding variation. Using these approaches is likely to

  8. Telepsychiatry: Promise, potential, and challenges.

    PubMed

    Malhotra, Savita; Chakrabarti, Subho; Shah, Ruchita

    2013-01-01

    Despite the high prevalence and potentially disabling consequences of mental disorders, specialized mental health services are extremely deficient, leading to the so-called 'Mental Health Gap'. Moreover, the services are concentrated in the urban areas, further worsening the rural-urban and tertiary primary care divide. Strengthening of and expanding the existing human resources and infrastructure, and integrating mental health into primary care appear to be the two major solutions. However, both the strategies are riddled with logistic difficulties and have a long gestation period. In such a scenario, telepsychiatry or e-mental health, defined as the use of information and communication technology to provide or support psychiatric services across distances, appears to be a promising answer. Due to its enormous potential, a review of the existing literature becomes imperative. An extensive search of literature was carried out and has been presented to delineate the modes of communication, acceptability and satisfaction, reliability, outcomes, cost-effectiveness, and legal and ethical challenges related to telepsychiatry. Telepsychiatry has been applied for direct patient care (diagnosis and management), consultation, and training, education, and research purposes. Both real-time, live interaction (synchronous) and store-forward (asynchronous) types of technologies have been used for these purposes. A growing amount of literature shows that training, supervision, and consultation by specialists to primary care physicians through telepsychiatry has several advantages. In this background, we have further focused on the models of telepsychiatry best suited for India, considering that mental health care can be integrated into primary care and taken to the doorstep of patients in the community.

  9. JWST ISIM Distortion Analysis Challenge

    NASA Technical Reports Server (NTRS)

    Cifie, Emmanuel; Matzinger, Liz; Kuhn, Jonathan; Fan, Terry

    2004-01-01

    Very tight distortion requirements are imposed on the JWST's ISM structure due to the sensitivity of the telescope's mirror segment and science instrument positioning. The ISIM structure is a three dimensional truss with asymmetric gusseting and metal fittings. One of the primary challenges for ISIM's analysis team is predicting the thermal distortion of the structure both from the bulk cooldown from ambient to cryo, and the smaller temperature changes within the cryogenic operating environment. As a first cut to estimate thermal distortions, a finite element model of bar elements was created. Elements representing joint areas and metal fittings use effective properties that match the behavior of the stack-up of the composite tube, gusset and adhesive under mechanical and thermal loads. These properties were derived by matching tip deflections of a solid model simplified T-joint. Because of the structure s asymmetric gusseting, this effective property model is a first attempt at predicting rotations that cannot be captured with a smeared CTE approach. In addition to the finite element analysis, several first order calculations have been performed to gauge the feasibility of the material design. Because of the stringent thermal distortion requirements at cryogenic temperatures, a composite tube material with near zero or negative CTE is required. A preliminary hand analysis of the contribution of the various components along the distortion path between FGS and the other instruments, neglecting second order effects were examined. A plot of bounding tube longitudinal and transverse CTEs for thermal stability requirements was generated to help determine the feasibility of meeting these requirements. This analysis is a work in progress en route to a large degree of freedom hi-fidelity FEA model for distortion analysis. Methods of model reduction, such as superelements, are currently being investigated.

  10. Bear reintroduction: Lessons and challenges

    USGS Publications Warehouse

    Clark, Joseph D.; Huber, Djuro; Servheen, Christopher

    2002-01-01

    Reintroduction is defined as an attempt to establish a species in an area that was once part of its historical range, but from which it has been extirpated or become extinct. Historically, one of the most successful programs was the reintroduction of 254 American black bears (Ursus americanus) from Minnesota to the Interior Highlands of Arkansas in the 1960s; that population has grown to >2,500 today. More recent efforts have involved fewer but better monitored animals and have sometimes employed techniques to improve site fidelity and survival. In Pennsylvania, for example, pregnant female American black bears were successfully translocated from winter dens, the premise being that the adult females would be less likely to return because of the presence of young cubs. That winter-release technique was compared to summer trapping and release in Tennessee; winter releases resulted in greater survival and reduced post-release movements. Homing has not been a problem for small numbers of brown bears (Ursus arctos) reintroduced to the Cabinet-Yaak ecosystem in Montana and Idaho and to the mountains of Austria and France. Reintroduction success appears to be correlated with translocation distance and is greater for subadults and females. As with any small population, reintroduced bear populations are susceptible to environmental variation and stochastic demographic and genetic processes. Although managers have focused on these biological barriers, sociopolitical impediments to bear reintroduction are more difficult to overcome. Poor public acceptance and understanding of bears are the main reasons some reintroduction programs have been derailed. Consequently, the public should be involved in the reintroduction process from the outset; overcoming negative public perceptions about bear reintroduction will be our greatest challenge.

  11. Phenylketonuria: nutritional advances and challenges

    PubMed Central

    2012-01-01

    Despite the appearance of new treatment, dietary approach remains the mainstay of PKU therapy. The nutritional management has become complex to optimize PKU patients' growth, development and diet compliance. This paper review critically new advances and challenges that have recently focused attention on potential relevant of LCPUFA supplementation, progress in protein substitutes and new protein sources, large neutral amino acids and sapropterin. Given the functional effects, DHA is conditionally essential substrates that should be supplied with PKU diet in infancy but even beyond. An European Commission Programme is going on to establish quantitative DHA requirements in this population. Improvements in the palatability, presentation, convenience and nutritional composition of protein substitutes have helped to improve long-term compliance with PKU diet, although it can be expected for further improvement in this area. Glycomacropeptide, a new protein source, may help to support dietary compliance of PKU subject but further studies are needed to evaluate this metabolic and nutritional issues. The PKU diet is difficult to maintain in adolescence and adult life. Treatment with large neutral amino acids or sapropterin in selected cases can be helpful. However, more studies are necessary to investigate the potential role, dose, and composition of large neutral amino acids in PKU treatment and to show long-term efficacy and tolerance. Ideally treatment with sapropterin would lead to acceptable blood Phe control without dietary treatment but this is uncommon and sapropterin will usually be given in combination with dietary treatment, but clinical protocol evaluating adjustment of PKU diet and sapropterin dosage are needed. In conclusion PKU diet and the new existing treatments, that need to be optimized, may be a complete and combined strategy possibly positive impacting on the psychological, social, and neurocognitive life of PKU patients. PMID:22305125

  12. Homeland Security. Management Challenges Facing Federal Leadership

    DTIC Science & Technology

    2002-12-01

    Security Management Challenges Facing Federal Leadership 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT... challenged in meeting dual or unrelated missions while maintaining and strengthening homeland security operations. Government organizational changes...including attention to management practices and key success factors. HOMELAND SECURITY Management Challenges Facing Federal Leadership www.gao.gov/cgi

  13. NASA Space Flight Vehicle Fault Isolation Challenges

    NASA Technical Reports Server (NTRS)

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

    2016-01-01

    The Space Launch System (SLS) is the new NASA heavy lift launch vehicle in development and is scheduled for its first mission in 2018. SLS has many of the same logistics challenges as any other large scale program. However, SLS also faces unique challenges related to testability. This presentation will address the SLS challenges for diagnostics and fault isolation, along with the analyses and decisions to mitigate risk.

  14. NASA Space Flight Vehicle Fault Isolation Challenges

    NASA Technical Reports Server (NTRS)

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

    2016-01-01

    The Space Launch System (SLS) is the new NASA heavy lift launch vehicle in development and is scheduled for its first mission in 2018.SLS has many of the same logistics challenges as any other large scale program. However, SLS also faces unique challenges related to testability. This presentation will address the SLS challenges for diagnostics and fault isolation, along with the analyses and decisions to mitigate risk..

  15. Australian Defence Force Demographic Data and Challenges

    DTIC Science & Technology

    2001-10-01

    AUSTRALIAN DEFENCE FORCE DEMOGRAPHIC DATA AND CHALLENGES Directorate of Strategic Personnel Planning and Research DSPPR Technical Note 10/2001...DATE 00 OCT 2001 2. REPORT TYPE N/A 3. DATES COVERED - 4. TITLE AND SUBTITLE Australian Defence Force Demographic Data and Challenges 5a...Prescribed by ANSI Std Z39-18 AUSTRALIAN DEFENCE FORCE DEMOGRAPHIC DATA AND CHALLENGES The findings and views expressed in this report are the results

  16. Climate challenges, vulnerabilities, and food security.

    PubMed

    Nelson, Margaret C; Ingram, Scott E; Dugmore, Andrew J; Streeter, Richard; Peeples, Matthew A; McGovern, Thomas H; Hegmon, Michelle; Arneborg, Jette; Kintigh, Keith W; Brewington, Seth; Spielmann, Katherine A; Simpson, Ian A; Strawhacker, Colleen; Comeau, Laura E L; Torvinen, Andrea; Madsen, Christian K; Hambrecht, George; Smiarowski, Konrad

    2016-01-12

    This paper identifies rare climate challenges in the long-term history of seven areas, three in the subpolar North Atlantic Islands and four in the arid-to-semiarid deserts of the US Southwest. For each case, the vulnerability to food shortage before the climate challenge is quantified based on eight variables encompassing both environmental and social domains. These data are used to evaluate the relationship between the "weight" of vulnerability before a climate challenge and the nature of social change and food security following a challenge. The outcome of this work is directly applicable to debates about disaster management policy.

  17. Climate challenges, vulnerabilities, and food security

    PubMed Central

    Nelson, Margaret C.; Ingram, Scott E.; Dugmore, Andrew J.; Streeter, Richard; Peeples, Matthew A.; McGovern, Thomas H.; Hegmon, Michelle; Arneborg, Jette; Brewington, Seth; Spielmann, Katherine A.; Simpson, Ian A.; Strawhacker, Colleen; Comeau, Laura E. L.; Torvinen, Andrea; Madsen, Christian K.; Hambrecht, George; Smiarowski, Konrad

    2016-01-01

    This paper identifies rare climate challenges in the long-term history of seven areas, three in the subpolar North Atlantic Islands and four in the arid-to-semiarid deserts of the US Southwest. For each case, the vulnerability to food shortage before the climate challenge is quantified based on eight variables encompassing both environmental and social domains. These data are used to evaluate the relationship between the “weight” of vulnerability before a climate challenge and the nature of social change and food security following a challenge. The outcome of this work is directly applicable to debates about disaster management policy. PMID:26712017

  18. Infant learning: Historical, conceptual, and methodological challenges

    PubMed Central

    Aslin, Richard N.

    2015-01-01

    Acquiring knowledge about the underlying structures of the environment presents a number of challenges for a naive learner. These challenges include the absence of reinforcement to guide learning, the presence of numerous information sources from which only a select few are relevant, and the uncertainty about when an underlying structure may have undergone a change. A crucial implication of these challenges is that the naive learner must make implicit decisions about when to generalize to novel inputs and when to restrict generalization because there are multiple underlying structures. An historical perspective on these challenges is presented and some potential solutions are proposed. PMID:26568702

  19. Presidential Green Chemistry Challenge: 2009 Academic Award

    EPA Pesticide Factsheets

    Presidential Green Chemistry Challenge 2009 award winner, Professor Krzysztof Matyjaszewski, developed Atom Transfer Radical Polymerization to make polymers with copper catalysts and environmentally friendly reducing agents.

  20. Power-Efficient Design Challenges

    NASA Astrophysics Data System (ADS)

    Pangrle, Barry

    significant gains can be realized and why power-efficiency requirements will continue to challenge designers into the future. Despite new process technologies, the future will continue to rely on innovative design approaches.