Overwhelming tPA Release, not PAI-1 Degradation, is Responsible for Hyperfibrinolysis in Severely Injured Trauma Patients

PubMed Central

Chapman, Michael P.; Moore, Ernest E.; Moore, Hunter B.; Gonzalez, Eduardo; Gamboni, Fabia; Chandler, James G.; Mitra, Sanchayita; Ghasabyan, Arsen; Chin, Theresa L.; Sauaia, Angela; Banerjee, Anirban; Silliman, Christopher C.

2015-01-01

Background Trauma induced coagulopathy (TIC) is associated with a four-fold increased risk of mortality. Hyperfibrinolysis is a component of TIC, but its mechanism is poorly understood. PAI-1 degradation by activated protein C has been proposed as mechanism for deregulation of the plasmin system in hemorrhagic shock, but in other settings of ischemia, tPA has been shown to be elevated. We hypothesized that the hyperfibrinolysis in TIC is not the result of PAI-1 degradation, but is driven by an increase in tPA, with resultant loss of PAI-1 activity through complexation with tPA. Methods 86 consecutive trauma activation patients had blood collected at the earliest time after injury, and were screened for hyperfibrinolysis using thrombelastography (TEG). Twenty-five hyperfibrinolytic patients were compared to 14 healthy controls using ELISAs for active tPA, active PAI-1 and PAI-1/tPA complex. Blood was also subjected to TEG with exogenous tPA-challenge as a functional assay for PAI-1 reserve. Results Total levels of PAI-1 (the sum of the active PAI-1 species and its covalent complex with tPA) are not significantly different between hyperfibrinolytic trauma patients and healthy controls: median 104 pM (IQR 48—201 pM) versus 115 pM (IQR 54—202 pM). The ratio of active to complexed PAI-1, however, was two orders of magnitude lower in hyperfibrinolysis than controls. Conversely, total tPA levels (active plus complex) were significantly higher in hyperfibrinolysis than controls: 139 pM (IQR 68—237 pM) versus 32 pM (IQR 16—37 pM). Hyperfibrinolytic trauma patients displayed increased sensitivity to exogenous challenge with tPA: median LY30 of 66.8% compared to 9.6% for controls. Conclusions Depletion of PAI-1 in TIC is driven by an increase in tPA, not PAI-1 degradation. The tPA-challenged TEG, based on this principle, is a functional test for PAI-1 reserves. Exploration of the mechanism of upregulation of tPA is critical to an understanding of hyperfibrinolysis in

Remote supervision of IV-tPA for acute ischemic stroke by telemedicine or telephone before transfer to a regional stroke center is feasible and safe.

PubMed

Pervez, Muhammad A; Silva, Gisele; Masrur, Shihab; Betensky, Rebecca A; Furie, Karen L; Hidalgo, Renzo; Lima, Fabricio; Rosenthal, Eric S; Rost, Natalia; Viswanathan, Anand; Schwamm, Lee H

2010-01-01

Because of a shortage of stroke specialists, many outlying or "spoke" hospitals initiate intravenous (IV) thrombolysis using telemedicine or telephone consultation before transferring patients to a regional stroke center (RSC) hub. We analyzed complications and outcomes of patients treated with IV tissue plasminogen activator (tPA) using the "drip and ship" approach compared to those treated directly at the RSC. A retrospective review of our Get With the Guidelines Stroke (GWTG-Stroke) database from 01/2003 to 03/2008 identified 296 patients who received IV tPA within 3 hours of symptom onset without catheter-based reperfusion. GWTG-Stroke definitions for symptomatic intracranial (sICH), systemic hemorrhage, discharge functional status, and destination were applied. Follow-up modified Rankin Score was recorded when available. Of 296 patients, 181 (61.1%) had tPA infusion started at an outside spoke hospital (OSH) and 115 (38.9%) at the RSC hub. OSH patients were younger with fewer severe strokes than RSC patients. Patients treated based on telestroke were more frequently octogenarians than patients treated based on a telephone consult. Mortality, sICH, and functional outcomes were not different between OSH versus RSC and telephone versus telestroke patients. Among survivors, mean length of stay was shorter for OSH patients but discharge status was similar and 75% of patients walked independently at discharge. Outcomes in OSH "drip and ship" patients treated in a hub-and-spoke network were comparable to those treated directly at an RSC. These data suggest that "drip and ship" is a safe and effective method to shorten time to treatment with IV tPA.

33 CFR 100.T05-0443 - Safety Zone; Fireworks Display, Delaware River, New Hope, PA.

Code of Federal Regulations, 2010 CFR

2010-07-01

..., Delaware River, New Hope, PA. 100.T05-0443 Section 100.T05-0443 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY REGATTAS AND MARINE PARADES SAFETY OF LIFE ON NAVIGABLE WATERS § 100.T05-0443 Safety Zone; Fireworks Display, Delaware River, New Hope, PA. (a) Location. The safety zone will restrict...

[Disseminated intravascular coagulation induced by endotoxin in rabbits: effect of treatment with t-PA and urokinase].

PubMed

Paloma, M J; Páramo, J A; Rifón, J; Rocha, E

1992-12-01

To assess the therapeutic efficacy of agents capable of stimulating the fibrinolytic system, such as tissue plasminogen activator (t-PA) and urokinase (UK) on endotoxin-induced disseminated intravascular coagulation (DIC) in the rabbit. DIC was induced by intravenous administration of endotoxin, 20 micrograms/kg/hr during 6 hr. Four different groups were established: a) control group, receiving only saline solution; b) t-PA group receiving 0.2 mg/kg; c) t-PA group receiving 0.7 mg/kg, and d) UK group, which was given 3,000 IU/kg/hr for 6 hr. Blood samples were drawn before and after 2 hr and 6 hr of endotoxin administration. Platelet count, and fibrinogen, factor XII and antithrombin III concentrations, were assessed in each sample. Mean, standard deviation and percentage of increase or decrease with respect to the basal value, this considered 100%, were used to evaluate the findings. For comparison of values, Student's t and Mann Whitney's U were used; the Fisher test was used for mortality studies. No statistical differences appeared for any of the values in the rabbits under basal conditions. The rabbits in the control group developed DIC. No doses of t-PA modified the changes appearing in blood coagulation. UK reduced the fibrinogen and factor XII consumption induced by endotoxin. The mortality rate in the control group reached 70%. High-dose t-PA decreased such figure to 50%, while low-dose t-PA or UK failed to reduce mortality. High-dose t-PA has beneficial effects on endotoxin-induced DIC in rabbits. UK failed to achieve such effect at the doses given in this experimental DIC model.

Mucosal priming of newborn mice with S. Typhi Ty21a expressing anthrax protective antigen (PA) followed by parenteral PA-boost induces B and T cell-mediated immunity that protects against infection bypassing maternal antibodies

PubMed Central

Ramirez, Karina; Ditamo, Yanina; Galen, James E.; Baillie, Les W. J.; Pasetti, Marcela F.

2010-01-01

The currently licensed anthrax vaccine has several limitations and its efficacy has been proven only in adults. Effective immunization of newborns and infants requires adequate stimulation of their immune system, which is competent but not fully activated. We explored the use of the licensed live attenuated S. Typhi vaccine strain Ty21a expressing Bacillus anthracis protective antigen [Ty21a(PA)] followed PA-alum as a strategy for immunizing the pediatric population. Newborn mice primed with a single dose of Ty21a(PA) exhibited high frequencies of mucosal IgA-secreting B cells and IFN-γ-secreting T cells during the neonatal period, none of which was detected in newborns immunized with a single dose of PA-alum. Priming with Ty21a(PA) followed by PA-boost resulted in high levels of PA-specific IgG, toxin-neutralizing and opsonophagocytic antibodies and increased frequency of bone marrow IgG plasma cells and memory B cells compared with repeated immunization with PA-alum alone. Robust B and T cell responses developed even in the presence of maternal antibodies. The prime-boost protected against systemic and respiratory infection. Mucosal priming with a safe and effective S. Typhi-based anthrax vaccine followed by PA-boost could serve as a practical and effective prophylactic approach to prevent anthrax early in life. PMID:20619377

The serum protein levels of the tPA-BDNF pathway are implicated in depression and antidepressant treatment.

PubMed

Jiang, H; Chen, S; Li, C; Lu, N; Yue, Y; Yin, Y; Zhang, Y; Zhi, X; Zhang, D; Yuan, Y

2017-04-04

Evidence demonstrates that brain-derived neurotrophic factor (BDNF) has a pivotal role in the pathogenesis of major depressive disorder (MDD). Precursor-BDNF (proBDNF) and mature BDNF (mBDNF) have opposing biological effects in neuroplasticity, and the tissue-type plasminogen activator (tPA)/plasmin system is crucial in the cleavage processing of proBDNF to mBDNF. However, very little is known about the role of the tPA-BDNF pathway in MDD. We examined serum protein concentrations in the tPA-BDNF pathway, including tPA, BDNF, tropomyosin receptor kinase B (TrkB), proBDNF and p75NTR, obtained from 35 drug-free depressed patients before and after 8 weeks of escitalopram (mean 12.5 mg per day) or duloxetine (mean 64 mg per day) treatment and 35 healthy controls using sandwich ELISA (enzyme-linked immunosorbent assay) methods. Serum tPA and BDNF and the ratio of BDNF/proBDNF were significantly lower in the MDD patients than in controls, whereas TrkB, proBDNF and its receptor p75NTR were higher. After 8 weeks of treatment, tPA, BDNF and proBDNF and the BDNF/proBDNF ratio were reversed, but p75NTR was higher than baseline, and TrkB was not significantly changed. tPA, BDNF, TrkB, proBDNF and p75NTR all yielded fairly good or excellent diagnostic performance (area under the receiver operating characteristic curve (AUC) >0.8 or 0.9). Combination of these five proteins demonstrated much better diagnostic effectiveness (AUC: 0.977) and adequate sensitivity and specificity of 88.1% and 92.7%, respectively. Our results suggest that the tPA-BDNF lysis pathway may be implicated in the pathogenesis of MDD and the mechanisms underlying antidepressant therapeutic action. The combination of tPA, BDNF, TrkB, proBDNF and p75NTR may provide a diagnostic biomarker panel for MDD.

Inhibition of PAI-1 Antiproteolytic Activity Against tPA by RNA Aptamers

PubMed Central

Damare, Jared; Brandal, Stephanie

2014-01-01

Plasminogen activator inhibitor-1 (PAI-1; SERPINE1) inhibits the plasminogen activators: tissue-type plasminogen activator (tPA) and urokinase-type plasminogen activator (uPA). Elevated levels of PAI-1 have been correlated with an increased risk for cardiovascular disease. Pharmacologically suppressing PAI-1 might prevent, or successfully treat PAI-1 related vascular diseases. This can potentially be accomplished by using small RNA molecules (aptamers). This study's goal is to develop RNA aptamers to a region of PAI-1 that will prevent the ability of PAI-1 to interact with the plasminogen activators. The aptamers were generated through a systematic evolution of ligands via exponential enrichment approach that ensures the creation of RNA molecules that bind to our target protein, PAI-1. In vitro assays were used to determine the effect of these aptamers on PAI-1's inhibitory activity. Three aptamers that bind to PAI-1 with affinities in the nanomolar range were isolated. The aptamer clones R10-4 and R10-2 inhibited PAI-1's antiproteolytic activity against tPA and disrupted PAI-1's ability to form a stable covalent complex with tPA. Increasing aptamer concentrations correlated positively with an increase in cleaved PAI-1. To the best of our knowledge, this is the first report of RNA molecules that inhibit the antiproteolytic activity of PAI-1. PMID:24922319

Catheter-directed Thrombolysis with Argatroban and tPA for Massive Iliac and Femoropopliteal Vein Thrombosis

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

Sharifi, Mohsen, E-mail: seyedmohsensharifi@yahoo.com; Bay, Curt; Nowroozi, Sasan

2013-12-15

Purpose: Catheter-directed thrombolysis (CDT) is a highly effective approach in the treatment of deep venous thrombosis (DVT). There are no data on the primary use of CDT with argatroban and tissue plasminogen activator (tPA) in patients without heparin-induced thrombocytopenia (HIT). The aim of this study was to evaluate the efficacy and safety of the combined administration of argatroban and tPA during CDT for massive DVT in patients without HIT. Methods: Thirty-three patients with massive symptomatic iliac and femoropopliteal DVT underwent CDT with tPA and argatroban within 28 {+-} 6 h of presentation. The dose of tPA was 0.75-1 mg/h throughmore » the infusion port and that of argatroban at 0.3-1 {mu}g/kg/min through the side port of the sheath. The patients were evaluated for the efficacy and safety of CDT and recurrent symptomatic venous thromboembolism (VTE) at a mean follow-up of 22 months. Results: There was no bleeding or iatrogenic pulmonary embolism with the CDT regimen we used. Grade III lysis (complete resolution of thrombus on venography) was achieved in 30 patients (91 %). In 3 patients with additional inferior vena cava filter thrombosis, further thrombectomy of the filter was required. No patient developed recurrent VTE. Conclusion: Concomitant administration of argatroban and tPA is a highly safe and effective regimen for CDT for massive DVT.« less

14-Day thawed plasma retains clot enhancing properties and inhibits tPA-induced fibrinolysis.

PubMed

Huebner, Benjamin R; Moore, Ernest E; Moore, Hunter B; Shepherd-Singh, Raymond; Sauaia, Angela; Stettler, Gregory R; Nunns, Geoffrey R; Silliman, Christopher C

2017-11-01

Plasma-first resuscitation attenuates trauma-induced coagulopathy (TIC); however, the logistics of plasma-first resuscitation require thawed plasma (TP) be readily available due to the obligatory thawing time of fresh frozen plasma (FFP). The current standard is storage of TP for up to 5 days at 4°C, based on factor levels at outdate, for use in patients at risk for TIC, but there remains a 2.2% outdated wastage rate. However, the multitude of plasma proteins in attenuating TIC remains unknown. We hypothesize that TP retains the ability to enhance clotting and reduce tPA-induced fibrinolysis at 14-day storage. FFP was thawed and stored at 4°C at the following intervals: 14, 10, 7, 5, 3, and 1-day prior to the experiment. Healthy volunteers underwent blood draws followed by 50% dilution with TP stored at previously mentioned intervals as well as FFP, normal saline (NS), albumin, and whole blood (WB) control. Samples underwent tPA-modified (75 ng/mL) thrombelastography (TEG) with analysis of R-time, angle, maximum amplitude (MA), and LY30. TEG properties did not change significantly over the thawed storage. 14-day TP retained the ability to inhibit tPA-induced hyperfibrinolysis (median LY30% 9.6%) similar to FFP (5.6%), WB (14.6%), and superior to albumin (59.3%) and NS (58.1%). 14-day TP also retained faster clot formation (median angle, 66.2°) and superior clot strength (MA, 61.5 mm) to albumin (34.8°, 21.6 mm) and NS (41.6°, 32.2 mm). TP plasma stored for 14 days retains clot-enhancing ability and resistance to clot degradation similar to FFP. A clinical trial is needed to validate these in vitro results. Copyright © 2017 Elsevier Inc. All rights reserved.

Body temperature and major neurological improvement in tPA-treated stroke patients.

PubMed

Kvistad, C E; Thomassen, L; Waje-Andreassen, U; Logallo, N; Naess, H

2014-05-01

Major neurological improvement (MNI) at 24 hours represents a marker of early recanalization in ischaemic stroke. Although low body temperature is considered neuroprotective in cerebral ischaemia, some studies have suggested that higher body temperature may promote clot lysis in the acute phase of ischaemic stroke. We hypothesized that higher body temperature was associated with MNI in severe stroke patients treated with tPA, suggesting a beneficial effect of higher body temperature on clot lysis and recanalization. Patients with ischaemic stroke or transient ischaemic attack (TIA) treated with tPA between February 2006 and August 2012 were prospectively included and retrospectively analysed. Body temperature was measured upon admission. MNI was defined by a ≥8 point improvement in NIHSS score at 24 hours as compared to NIHSS score on admission. No significant improvement (no-MNI) was defined by either an increase in NIHSS score or a decrease of ≤2 points at 24 hours in patients with an admission NIHSS score of ≥8. Of the 2351 patients admitted with ischaemic stroke or TIA, 347 patients (14.8%) were treated with tPA. A total of 32 patients (9.2%) had MNI and 56 patients (16.1%) had no-MNI. Patients with MNI had higher body temperatures compared with patients with no-MNI (36.7°C vs 36.3°C, P = 0.004). Higher body temperature was independently associated with MNI when adjusted for confounders (OR 5.16, P = 0.003). Higher body temperature was independently associated with MNI in severe ischaemic stroke patients treated with tPA. This may suggest a beneficial effect of higher body temperature on clot lysis and recanalization. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

35% Good Outcome Rate in IV-tPA treated Patients with CTA Confirmed Severe Anterior Circulation Occlusive Stroke

PubMed Central

González, R. Gilberto; Furie, Karen L.; Goldmacher, Gregory V.; Smith, Wade S.; Kamalian, Shervin; Payabvash, Seyedmehdi; Harris, Gordon J.; Halpern, Elkan F.; Koroshetz, Walter J.; Camargo, Erica C. S.; Dillon, William P.; Lev, Michael H.

2015-01-01

BACKGROUND AND PURPOSE To determine the effect of IV-tPA on outcomes in patients with severe major anterior circulation ischemic stroke. METHODS Prospectively, 649 acute stroke patients had admission NIH stroke scale scores (NIHSS), non-contrast CT, CT angiography (CTA), and 6-month outcome assessed using modified Rankin scale (mRS). IV-tPA treatment decisions were made prior to CTA, at the time of non-contrast CT scanning, as per routine clinical protocol. Severe symptoms were defined as NIHSS>10. Poor outcome was defined as mRS>2. Major occlusions were identified on CTA. Univariate and multivariate stepwise-forward logistic regression analyses of the full cohort were performed. RESULTS Of 649 patients, 188 (29%) presented with NIHSS>10, and 64/188 (34%) of these received IV-tPA. Admission NIHSS, large artery occlusion, and IV-tPA all independently predicted good outcomes, however a significant interaction existed between IV-tPA and occlusion (p<0.001). Of NIHSS>10 patients with anterior circulation occlusion, twice the percentage had good outcomes if they received IV-tPA (17/49, 35%), than if they did not (13/77, 17%; p=0.031). The “number needed to treat” was 7 (95% CI = 3–60). CONCLUSIONS IV-tPA treatment resulted in significantly more good outcomes in severely symptomatic stroke patients with major anterior circulation occlusions. The 35% good outcome rate was similar to rates found in endovascular therapy trials. Vascular imaging may help in patient selection and stratification for trials of IV-thrombolytic and endovascular therapies. PMID:24003051

THR-18, a 18-mer peptide derived from PAI-1, is neuroprotective and improves thrombolysis by tPA in rat stroke models.

PubMed

Krakovsky, M; Polianski, V; Nimrod, A; Higazi, A; Leker, R R; Lamensdorf, I

2011-11-01

The thrombolytic treatment of stroke is limited by a narrow therapeutic time window and is associated with significant adverse side effects. To improve this situation, the modulation of tissue-type plasminogen activator (tPA) activity by a synthetic plasminogen activator inhibitor-1-derived 18-mer peptide (THR-18) was examined in two models of stroke in rats. In the first model (thromboembolic), stroke was induced by intra-carotid injection of micro-clots to rats, and tPA (6 mg/kg) was intravenously infused for 30 minutes with or without THR-18 (1 mg/kg) at 4 hours post-induction. In the second model [transient middle cerebral artery occlusion (tMCAO)], stroke was induced for 2 hours by a transient mechanical occlusion. tPA and/or THR-18 (0.02, 0.1, and 1 mg/kg) were intravenously infused for 60 minutes at the time of reperfusion. In the thromboembolic model, cerebral blood flow, measured before and up to 5.5 hours post-induction, revealed that tPA administration caused reperfusion of flow at 30 minutes post-infusion. Later on, an additional increase in reperfusion was seen in the tPA+THR-18 group, and not with tPA alone. In both models, the frequency of intracranial hemorrhage in the tPA-treated group was found to be significantly higher than the control, and this tPA effect was attenuated by THR-18. In the thromboembolic study, infarct size and brain edema were similar in the control and tPA-treated rats. However, the combination of tPA and THR-18 caused a statistically significant reduction in both parameters (infarct size 17.8 versus 25.0%, brain edema 5 versus 8%, tPA+THR-18 versus control, respectively). In the tMCAO mechanical model, infarct size and brain edema were both increased by tPA treatment as compared to the control group, and this increase was markedly diminished by THR-18 co-administration. Neurobehavioral assessment of the tMCAO animals performed at 72 hours post-stroke induction revealed significant improvements (P<0.05-0.01) in neuroscores in

Prognostic value of tissue-type plasminogen activator (tPA) and its complex with the type-1 inhibitor (PAI-1) in breast cancer

PubMed Central

Witte, J H de; Sweep, C G J; Klijn, J G M; Grebenschikov, N; Peters, H A; Look, M P; Tienoven, ThH van; Heuvel, J J T M; Vries, J Bolt-De; Benraad, ThJ; Foekens, J A

1999-01-01

The prognostic value of tissue-type plasminogen activator (tPA) measured in samples derived from 865 patients with primary breast cancer using a recently developed enzyme-linked immunosorbent assay (ELISA) was evaluated. Since the assay could easily be adapted to the assessment of the complex of tPA with its type-1 inhibitor (PAI-1), it was investigated whether the tPA:PAI-1 complex also provides prognostic information. To this end, cytosolic extracts and corresponding detergent extracts of 100 000 g pellets obtained after ultracentrifugation when preparing the cytosolic fractions for routine steroid hormone receptor determination were assayed. Statistically significant correlations were found between the cytosolic levels and those determined in the pellet extracts (Spearman correlation coefficient rs = 0.75, P < 0.001 for tPA and r = 0.50, P < 0.001 for tPA:PAI-1 complex). In both Cox univariate and multivariate analysis elevated levels of (total) tPA determined in the pellet extracts, but not in cytosols, were associated with prolonged relapse-free (RFS) and overall survival (OS). In contrast, high levels of the tPA:PAI-1 complex measured in cytosols, but not in the pellet extracts, were associated with a poor RFS and OS. The prognostic information provided by the cytosolic tPA:PAI-1 complex was comparable to that provided by cytosolic (total) PAI-1. Furthermore, the estimated levels of free, uncomplexed tPA and PAI-1, in cytosols and in pellet extracts, were related to patient prognosis in a similar way as the (total) levels of tPA and PAI-1 respectively. Determination of specific forms of components of the plasminogen activation system, i.e. tPA:PAI-1 complex and free, uncomplexed tPA and/or PAI-1, may be considered a useful adjunct to the analyses of the separate components (tPA and/or PAI-1) and provide valuable additional prognostic information with respect to survival of breast cancer patients. © 1999 Cancer Research Campaign PMID:10390010

Management of acute ischemic stroke. What is the role of tPA and antithrombotic agents?

PubMed

Meschia, J F

2000-05-15

Every patient with acute stroke who presents to a medical center that has appropriate resources should undergo evaluation for intravenous tPA therapy. Such therapy should not be given unless the patient meets strict eligibility criteria based on clinical, radiographic, and laboratory data. Intra-arterial thrombolysis may be a promising alternative to intravenous tPA therapy, but it should still be regarded as experimental. Daily aspirin therapy should be initiated immediately in most patients who do not receive intravenous tPA therapy and after 24 hours in most patients who receive this treatment. Measures should be taken to prevent medical complications, such as aspiration pneumonia, deep vein thrombosis, contractures, and pressure sores. Early initiation of rehabilitation can maximize stroke recovery. Whenever feasible, institutions should have stroke teams or units to streamline care and provide expertise for patients with acute stroke.

Current status of intravenous thrombolysis for acute ischemic stroke in Asia.

PubMed

Sharma, Vijay K; Ng, Kay W P; Venketasubramanian, Narayanaswamy; Saqqur, Maher; Teoh, Hock L; Kaul, Subash; Srivastava, Padma M V; Sergentanis, Theodoris; Suwanwela, Nijasri; Nguyen, Thang H; Lawrence Wong, K S; Chan, Bernard P L

2011-12-01

Data regarding thrombolysis for acute ischemic stroke in Asia are scarce and only a small percentage of patients are thrombolysed. The dose of intravenous tissue plasminogen activator (IV-tPA) in Asia remains controversial. Case-controlled observation studies in Asia included only Japanese patients and suggested the clinical efficacy and safety of low-dose IV-tPA (0.6 mg/kg body weight; max 60 mg) comparable to standard dose (0.9 mg/kg body weight; max. 90 mg). Reduced treatment cost, lower symptomatic intracerebral hemorrhage risk and comparable efficacy encouraged many Asian centers to adopt low-dose or even variable-dose IV-tPA regimens. We evaluated various Asian thrombolysis studies and compared with SITS-MOST registry and NINDS trial. We included the published studies on acute ischemic stroke thrombolysis in Asia. Unadjusted relative risks and 95% Confidence intervals were calculated for each study. Pooled estimates from random effects models were used because the tests for heterogeneity were significant. We found only 18 publications regarding acute ischemic stroke thrombolysis in Asia that included total of 9300 patients. Owing to ethnic differences, stroke severity, small number of cases in individual reports, outcome measures and tPA dose regimes, it is difficult to compare these studies. Functional outcomes were almost similar (to Japanese studies) when lower-dose IV-tPA was used in non-Japanese populations across Asia. Interestingly, with standard dose IV-tPA, considerably better functional outcomes were observed, without increasing symptomatic intracerebral hemorrhage rates. Variable dose regimens of IV-tPA are used across Asia without any reliable or established evidence. Establishing a uniform IV-tPA regimen is essential since the rapid improvements in health-care facilities and public awareness are expected to increase the rates of thrombolysis in Asia. © 2011 The Authors. International Journal of Stroke © 2011 World Stroke Organization.

Very Mild Hypothermia (35°C) Postischemia Reduces Infarct Volume and Blood/Brain Barrier Breakdown Following tPA Treatment in the Mouse.

PubMed

Cechmanek, Brian K; Tuor, Ursula I; Rushforth, David; Barber, Philip A

2015-12-01

Reperfusion therapies for stroke diminish in effectiveness and safety as time to treatment increases. Hypothermia neuroprotection for stroke is established, but its clinical translation has been hampered by uncertainties regarding optimal temperature and complications associated with moderate hypothermia. Also, hypothermia targeting temperatures of 32-33°C is associated with clinical and logistical problems related to induction and adverse side effects. We hypothesized that ischemic damage and tPA-exacerbated blood/brain barrier (BBB) breakdown produced following 30 minutes of middle cerebral artery occlusion and either 1 hour of saline or tPA infusion would be reduced by treatment with very mild cooling of 1.5°C for 48 hours followed by 24 hours of gradual rewarming. Infarct volume was reduced by 29.6% (p<0.001) and 41.9% (p<0.001) in hypothermic-tPA (Hypo_tPA)-treated and hypothermic-saline (Hypo_Sal)-treated animals compared to normothermic-tPA (Norm_tPA) and saline (Norm_Sal)-treated animals, respectively. Hypothermia also reduced IgG extravasation in tPA-treated, but not saline-treated groups compared to their normothermic controls (p<0.001). The ipsilateral-contralateral changes in optical density for IgG extravasation were 18.4% greater in the Norm_tPA than Norm_Sal (p<0.001) group. The ipsilateral-contralateral changes in optical density for IgG extravasation were reduced by 17.8% (p<0.001) in the Hypo_tPA compared to Norm_tPA group. No significant mean difference in IgG extravasation was seen between Hypo_tPA and Hypo_Sal groups (p>0.05). Very modest hypothermia to reduce the BBB breakdown could improve the availability and safety of reperfusion treatments for stroke.

An in vitro study of the effects of t-PA and tranexamic acid on whole blood coagulation and fibrinolysis.

PubMed

Godier, Anne; Parmar, Kiran; Manandhar, Karuna; Hunt, Beverley J

2017-02-01

Acute traumatic coagulopathy is characterised by fibrinolysis and low fibrinogen. It is unclear how much fibrinogenolysis contributes to reduce fibrinogen levels. The study aim was to: investigate in vitro the effects of tissue-plasminogen activator (t-PA) and tranexamic acid (TXA) on coagulation and fibrinolysis. Whole blood was spiked with varying t-PA concentrations. Clauss fibrinogen levels and thrombelastography (TEG, Haemonetics) were performed, including functional fibrinogen level (FLEV). TXA effects were assessed using four TXA concentrations. Recorded parameters from kaolin activated TEG included maximal amplitude (MA), clot strength (G), percentage lysis (LY). Plasmin-antiplasmin complex (PAP), endogenous thrombin potential (ETP), prothrombin fragment 1+2 (PF1+2), factor V and factor VIII levels were all measured. t-PA induced fibrinolysis: it increased PAP and LY, but decreased MA and G. t-PA induced fibrinogenolysis, with a concentration-dependant decrease in fibrinogen from 2.7 (2.6-3.1) to 0.8 (0.8-0.9) g/L with 60 nM t-PA. FLEV and fibrinogen levels were well correlated. High t-PA doses increased PF1+2, decreased ETP of 19% and FVIII of 63% but not FV. TXA had no effect on plasmin generation as evidenced by no change in PAP. It corrected LY, MA and G and partly protected fibrinogen against fibrinogenolysis: 0.03 mg/mL TXA reduced the fibrinogen fall induced by t-PA 20 nM from 43% to 14%. TXA halved the FVIII fall and increased ETP. t-PA induced plasminogen activation and fibrinogenolysis in a concentration-dependant manner. TXA did not affect plasmin activation but reduced fibrinogenolysis. These results suggest that TXA given early in bleeding patients may prevent fibrinogenolysis. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Genome-Wide Association Study for Circulating Tissue Plasminogen Activator (tPA) Levels and Functional Follow-up Implicates Endothelial STXBP5 and STX2

PubMed Central

Huang, Jie; Huffman, Jennifer E.; Yamkauchi, Munekazu; Trompet, Stella; Asselbergs, Folkert W.; Sabater-Lleal, Maria; Trégouët, David-Alexandre; Chen, Wei-Min; Smith, Nicholas L.; Kleber, Marcus E.; Shin, So-Youn; Becker, Diane M.; Tang, Weihong; Dehghan, Abbas; Johnson, Andrew D.; Truong, Vinh; Folkersen, Lasse; Yang, Qiong; Oudot-Mellakh, Tiphaine; Buckley, Brendan M.; Moore, Jason H.; Williams, Frances M.K.; Campbell, Harry; Silbernagel, Günther; Vitart, Veronique; Rudan, Igor; Tofler, Geoffrey H.; Navis, Gerjan J.; DeStefano, Anita; Wright, Alan F.; Chen, Ming-Huei; de Craen, Anton J.M.; Worrall, Bradford B.; Rudnicka, Alicja R.; Rumley, Ann; Bookman, Ebony B.; Psaty, Bruce M.; Chen, Fang; Keene, Keith L.; Franco, Oscar H.; Böhm, Bernhard O.; Uitterlinden, Andre G.; Carter, Angela M.; Jukema, J. Wouter; Sattar, Naveed; Bis, Joshua C.; Ikram, Mohammad A.; Sale, Michèle M.; McKnight, Barbara; Fornage, Myriam; Ford, Ian; Taylor, Kent; Slagboom, P. Eline; McArdle, Wendy L.; Hsu, Fang-Chi; Franco-Cereceda, Anders; Goodall, Alison H.; Yanek, Lisa R.; Furie, Karen L.; Cushman, Mary; Hofman, Albert; Witteman, Jacqueline CM.; Folsom, Aaron R.; Basu, Saonli; Matijevic, Nena; van Gilst, Wiek H.; Wilson, James F.; Westendorp, Rudi G.J.; Kathiresan, Sekar; Reilly, Muredach P.; Tracy, Russell P.; Polasek, Ozren; Winkelmann, Bernhard R.; Grant, Peter J.; Hillege, Hans L.; Cambien, Francois; Stott, David J.; Lowe, Gordon D.; Spector, Timothy D.; Meigs, James B.; Marz, Winfried; Eriksson, Per; Becker, Lewis C.; Morange, Pierre-Emmanuel; Soranzo, Nicole; Williams, Scott M.; Hayward, Caroline; van der Harst, Pim; Hamsten, Anders; Lowenstein, Charles J.; Strachan, David P.; O'Donnell, Christopher J.

2014-01-01

Objective Tissue plasminogen activator (tPA), a serine protease, catalyzes the conversion of plasminogen to plasmin, the major enzyme responsible for endogenous fibrinolysis. In some populations, elevated plasma levels of tPA have been associated with myocardial infarction and other cardiovascular diseases (CVD). We conducted a meta-analysis of genome-wide association studies (GWAS) to identify novel correlates of circulating levels of tPA. Approach and Results Fourteen cohort studies with tPA measures (N=26,929) contributed to the meta-analysis. Three loci were significantly associated with circulating tPA levels (P <5.0×10−8). The first locus is on 6q24.3, with the lead SNP (rs9399599, P=2.9×10−14) within STXBP5. The second locus is on 8p11.21. The lead SNP (rs3136739, P=1.3×10−9) is intronic to POLB and less than 200kb away from the tPA encoding gene PLAT. We identified a non-synonymous SNP (rs2020921) in modest LD with rs3136739 (r2 = 0.50) within exon 5 of PLAT (P=2.0×10−8). The third locus is on 12q24.33, with the lead SNP (rs7301826, P=1.0×10−9) within intron 7 of STX2. We further found evidence for association of lead SNPs in STXBP5 and STX2 with expression levels of the respective transcripts. In in vitro cell studies, silencing STXBP5 decreased release of tPA from vascular endothelial cells, while silencing of STX2 increased tPA release. Through an in-silico lookup, we found no associations of the three lead SNPs with coronary artery disease or stroke. Conclusions We identified three loci associated with circulating tPA levels, the PLAT region, STXBP5 and STX2. Our functional studies implicate a novel role for STXBP5 and STX2 in regulating tPA release. PMID:24578379

76 FR 29176 - Airworthiness Directives; Piper Aircraft, Inc. PA-23, PA-31, and PA-42 Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-20

...-0218; Directorate Identifier 2009-CE-006-AD] RIN 2120-AA64 Airworthiness Directives; Piper Aircraft... (AD) that applies to Piper Aircraft, Inc. PA-23, PA-31, and PA-42 airplanes. The existing AD currently... Federal holidays. For service information identified in this AD, contact Piper Aircraft, Inc., 2926 Piper...

Good outcome rate of 35% in IV-tPA-treated patients with computed tomography angiography confirmed severe anterior circulation occlusive stroke.

PubMed

González, R Gilberto; Furie, Karen L; Goldmacher, Gregory V; Smith, Wade S; Kamalian, Shervin; Payabvash, Seyedmehdi; Harris, Gordon J; Halpern, Elkan F; Koroshetz, Walter J; Camargo, Erica C S; Dillon, William P; Lev, Michael H

2013-11-01

To determine the effect of intravenous tissue plasminogen activator (IV-tPA) on outcomes in patients with severe major anterior circulation ischemic stroke. Prospectively, 649 patients with acute stroke had admission National Institutes of Health stroke scale (NIHSS) scores, noncontrast computed tomography (CT), CT angiography (CTA), and 6-month outcome assessed using modified Rankin scale. IV-tPA treatment decisions were made before CTA, at the time of noncontrast CT scanning, as per routine clinical protocol. Severe symptoms were defined as NIHSS>10. Poor outcome was defined as modified Rankin scale >2. Major occlusions were identified on CTA. Univariate and multivariate stepwise-forward logistic regression analyses of the full cohort were performed. Of 649 patients, 188 (29%) patients presented with NIHSS>10, and 64 out of 188 (34%) patients received IV-tPA. Admission NIHSS, large artery occlusion, and IV-tPA all independently predicted good outcomes; however, a significant interaction existed between IV-tPA and occlusion (P<0.001). Of the patients who presented with NIHSS>10 with anterior circulation occlusion, twice the percentage had good outcomes if they received IV-tPA (17 out of 49 patients, 35%) than if they did not (13 out of 77 patients, 17%; P=0.031). The number needed to treat was 7 (95% confidence interval, 3-60). IV-tPA treatment resulted in significantly better outcomes in patients with severely symptomatic stroke with major anterior circulation occlusions. The 35% good outcome rate was similar to rates found in endovascular therapy trials. Vascular imaging may help in patient selection and stratification for trials of IV-thrombolytic and endovascular therapies.

In vitro investigations into enhancement of tPA bioavailability in whole blood clots using pulsed-high intensity focused ultrasound exposures.

PubMed

Jones, Guy; Hunter, Finnie; Hancock, Hilary A; Kapoor, Ankur; Stone, Michael J; Wood, Bradford J; Xie, Jianwu; Dreher, Matthew R; Frenkel, Victor

2010-01-01

Investigations were carried out on the manner by which pulsed-high intensity focused ultrasound (HIFU) enhances the effectiveness of tissue plasminogen activator (tPA) in whole blood clots, in vitro. Scanning electronic microscope (SEM) of the surface of the clots showed that the exposures increased exposed fibrin, as well as the number of openings to more interior regions. These findings were supported by fluorescent antibody labeling of tPA in frozen sections of clots treated post-HIFU. Here, improved accumulation at the surface and penetration of the tPA into the clots were observed in those treated with HIFU. Fluorescence recovery after photobleaching was also performed, indicating that the diffusion coefficient increased 6.3-fold for fluorescently labeled dextrans, comparable in size to tPA, in the HIFU-treated clots. Improved understanding of the manner by which pulsed--HIFU exposures can improve the effectiveness of thrombolytics will help optimize the exposures for this application and potentially facilitate translation to the clinic.

In Vitro Investigations Into Enhancement of tPA Bioavailability in Whole Blood Clots Using Pulsed–High Intensity Focused Ultrasound Exposures

PubMed Central

Jones, Guy; Hunter, Finnie; Hancock, Hilary A.; Kapoor, Ankur; Stone, Michael J.; Wood, Bradford J.; Xie, Jianwu; Dreher, Matthew R.

2012-01-01

Investigations were carried out on the manner by which pulsed–high intensity focused ultrasound (HIFU) enhances the effectiveness of tissue plasminogen activator (tPA) in whole blood clots, in vitro. Scanning electronic microscope (SEM) of the surface of the clots showed that the exposures increased exposed fibrin, as well as the number of openings to more interior regions. These findings were supported by fluorescent antibody labeling of tPA in frozen sections of clots treated post-HIFU. Here, improved accumulation at the surface and penetration of the tPA into the clots were observed in those treated with HIFU. Fluorescence recovery after photobleaching was also performed, indicating that the diffusion coefficient increased 6.3-fold for fluorescently labeled dextrans, comparable in size to tPA, in the HIFU-treated clots. Improved understanding of the manner by which pulsed–HIFU exposures can improve the effectiveness of thrombolytics will help optimize the exposures for this application and potentially facilitate translation to the clinic. PMID:20064753

Pretreatment Blood Brain Barrier Damage and Post Treatment Intracranial Hemorrhage in Patients Receiving IV tPA

PubMed Central

Leigh, Richard; Jen, Shyian S.; Hillis, Argye E.; Krakauer, John W.; Barker, Peter B.

2014-01-01

Background and Purpose Early blood brain barrier (BBB) damage after acute ischemic stroke (AIS) has previously been qualitatively linked to subsequent intracranial hemorrhage (ICH). In this quantitative study, it was investigated whether the amount of BBB damage evident on pre-tPA MRI scans was related to the degree of post-tPA ICH in patients with AIS. Methods Analysis was performed on a database of patients with AIS provided by the STIR and VISTA Imaging Investigators. Patients with perfusion-weighted imaging (PWI) lesions >10mL and negative gradient-recalled echo (GRE) imaging prior to IV tPA were included. Post processing of the PWI source images was performed to estimate changes in BBB permeability within the perfusion deficit relative to the unaffected hemisphere. Follow-up GRE images were reviewed for evidence of ICH and divided into three groups according to ECASS criteria: no hemorrhage (NH), hemorrhagic infarction (HI), and parenchymal hematoma (PH). Results 75 patients from the database met the inclusion criteria, 28 of whom experienced ICH, of which 19 were classified as HI, and nine were classified as PH. The mean permeability (±standard deviations), expressed as an index of contrast leakage, was 17.0%±8.8 in the NH group, 19.4%±4.0 in the HI group, and 24.6%±4.5 in the PH group. Permeability was significantly correlated with ICH grade in univariate (p=0.007) and multivariate (p=0.008) linear regression modeling. Conclusions A PWI-derived index of BBB damage measured prior to IV tPA is associated with the severity of ICH after treatment in patients with AIS. PMID:24876245

77 FR 47671 - TA-W-81,520, T-Mobile USA, Inc., Call Center, Allentown, PA; TA-W-81,520G, T-Mobile USA, Inc...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-09

... DEPARTMENT OF LABOR Employment and Training Administration TA-W-81,520, T-Mobile USA, Inc., Call Center, Allentown, PA; TA- W-81,520G, T-Mobile USA, Inc., Headquarters Office, Bellevue, WA; Amended... of T-Mobile USA, Inc., Call Center, Allentown, Pennsylvania (TA-W-81,520), Fort Lauderdale, Florida...

33 CFR 165.T05-0495 - Safety Zone, Sugar House Casino Fireworks Display, Delaware River; Philadelphia, PA.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 33 Navigation and Navigable Waters 2 2014-07-01 2014-07-01 false Safety Zone, Sugar House Casino Fireworks Display, Delaware River; Philadelphia, PA. 165.T05-0495 Section 165.T05-0495 Navigation and... Areas Fifth Coast Guard District § 165.T05-0495 Safety Zone, Sugar House Casino Fireworks Display...

Double Dose: The cumulative effect of TV viewing at home and in preschool on children’s activity patterns and weight status

PubMed Central

Ross, Sharon Taverno; Dowda, Marsha; Saunders, Ruth P.; Pate, Russell R.

2015-01-01

Little is known about how screen-based sedentary behavior at home and in preschool influences children’s health and activity patterns. The current study examined the individual and cumulative influence of TV viewing at home and in preschool on children’s physical activity (PA) and weight status. Children (n=339) attending 16 preschools in South Carolina were grouped into high and low TV groups based on parent report of children’s TV viewing at home and director report of TV use/rules in preschool. T-tests and mixed model ANOVAs examined differences in weight status and PA (min/hr) by high and low TV groups. Results revealed that children who were classified as High TV both at home and in preschool had significantly lower levels of moderate-to-vigorous PA compared with their Low TV counterparts. These findings demonstrate the importance of total environmental TV exposure on preschooler’s PA. Longitudinal and observational research to assess preschoolers’ cumulative screen-based sedentary behavior and its relationship with PA and weight status is needed. PMID:23502043

Anti-hypertensive treatment prolongs tPA door-to-treatment time: Secondary analysis of the INSTINCT trial.

PubMed Central

Skolarus, Lesli E.; Scott, Phillip A.; Burke, James F.; Adelman, Eric E.; Frederiksen, Shirley M.; Kade, Allison M.; Kalbfleisch, Jack D.; Ford, Andria L.; Meurer, William J.

2012-01-01

Background/Purpose Identifying modifiable tPA treatment delays may improve stroke outcomes. We hypothesized that pre-thrombolytic anti-hypertensive treatment (AHT) may prolong door-to-treatment time (DTT). Methods Analysis of consecutive tPA-treated patients at 24 randomly selected community hospitals in the INSTINCT trial between 2007-2010. DTTs among stroke patients who received pre-thrombolytic AHT were compared to those that did not receive pre-thrombolytic AHT. We then calculated a propensity score for the probability of receiving pre-thrombolytic AHT using logistic regression with demographics, stroke risk factors, home medications, stroke severity (NIHSS), onset-to-door time, admission glucose, pretreatment blood pressure, EMS transport and location at time of stroke as independent variables. A paired t-test was performed to compare the DTTs between the propensity matched groups. Results Of 534 tPA treated stroke patients analyzed, 95 received pre-thrombolytic AHT. In the unmatched cohort, patients who received pre-thrombolytic AHT had a longer DTT (mean increase 9 minutes; 95% confidence interval (CI) 2-16 minutes) than patients who did not. After propensity matching, patients who received pre-thrombolytic AHT had a longer DTT (mean increase 10.4 minutes, 95% CI 1.9 - 18.8) than patients who did not receive pre-thrombolytic AHT. Conclusion Pre-thrombolytic AHT is associated with modest delays in DTT. This represents a potential target for quality improvement initiatives. Further research evaluating optimum pre-thrombolytic hypertension management is warranted. PMID:23033348

Low current performance of the Bern medical cyclotron down to the pA range

NASA Astrophysics Data System (ADS)

Auger, M.; Braccini, S.; Ereditato, A.; Nesteruk, K. P.; Scampoli, P.

2015-09-01

A medical cyclotron accelerating H- ions to 18 MeV is in operation at the Bern University Hospital (Inselspital). It is the commercial IBA 18/18 cyclotron equipped with a specifically conceived 6 m long external beam line ending in a separate bunker. This feature is unique for a hospital-based facility and makes it possible to conduct routine radioisotope production for PET diagnostics in parallel with multidisciplinary research activities, among which are novel particle detectors, radiation biophysics, radioprotection, radiochemistry and radiopharmacy developments. Several of these activities, such as radiobiology experiments for example, require low current beams down to the pA range, while medical cyclotrons are designed for high current operation above 10 μA. In this paper, we present the first results on the low current performance of a PET medical cyclotron obtained by ion source, radio-frequency and main coil tuning. With this method, stable beam currents down to (1.5+/- 0.5 ) pA were obtained and measured with a high-sensitivity Faraday cup located at the end of the beam transport line.

Release of Matrix Metalloproteinases-2 and 9 by S-Nitrosylated Caveolin-1 Contributes to Degradation of Extracellular Matrix in tPA-Treated Hypoxic Endothelial Cells

PubMed Central

Bi, Gang; Zhu, Yihui; Jun, Wei; Ma, Wenlin; Wu, Huimin

2016-01-01

Intracranial hemorrhage remains the most feared complication in tissue plasminogen activator (tPA) thrombolysis for ischemic stroke. However, the underlying molecular mechanisms are still poorly elucidated. In this study, we reported an important role of caveolin-1 (Cav-1) s-nitrosylation in matrix metalloproteinase (MMP)-2 and 9 secretion from tPA-treated ischemic endothelial cells. Brain vascular endothelial cells (bEND3) were exposed to oxygen-glucose deprivation (OGD) for 2 h before adding recombinant human tPA for 6 h. This treatment induced a significant increase of MMP2 and 9 in the media of bEND3 cells and a simultaneous degradation of fibronectin and laminin β-1, the two main components of extracellular matrix (ECM). Inhibition of MMP2 and 9 with SB-3CT completely blocked the degradation of fibronectin and laminin β-1. ODG+tPA treatment led to Cav-1 shedding from bEND3 cells into the media. Notably, OGD triggered nitric oxide (NO) production and S-nitrosylationof Cav-1 (SNCav-1). Meanwhile tPA induced activation of ERK signal pathway and stimulates the secretion of SNCav-1. Pretreatment of bEND3 cells with C-PTIO (a NO scavenger) or U0126 (a specific ERK inhibitor) significantly reduced OGD-induced S-nitrosylation of Cav-1 in cells and blocked the secretion of Cav-1 and MMP2 and 9 into the media as well as the degradation of fibronectin and laminin β-1 in OGD and tPA-treated cells. These data indicate that OGD-triggered Cav-1 S-nitrosylation interacts with tPA-induced ERK activation to augment MMP2 and 9 secretion and subsequent ECM degradation, which may account for the exacerbation of ischemic blood brain barrier damage following tPA thrombolysis for ischemic stroke. PMID:26881424

Release of Matrix Metalloproteinases-2 and 9 by S-Nitrosylated Caveolin-1 Contributes to Degradation of Extracellular Matrix in tPA-Treated Hypoxic Endothelial Cells.

PubMed

Song, Haoming; Cheng, Youjun; Bi, Gang; Zhu, Yihui; Jun, Wei; Ma, Wenlin; Wu, Huimin

2016-01-01

Intracranial hemorrhage remains the most feared complication in tissue plasminogen activator (tPA) thrombolysis for ischemic stroke. However, the underlying molecular mechanisms are still poorly elucidated. In this study, we reported an important role of caveolin-1 (Cav-1) s-nitrosylation in matrix metalloproteinase (MMP)-2 and 9 secretion from tPA-treated ischemic endothelial cells. Brain vascular endothelial cells (bEND3) were exposed to oxygen-glucose deprivation (OGD) for 2 h before adding recombinant human tPA for 6 h. This treatment induced a significant increase of MMP2 and 9 in the media of bEND3 cells and a simultaneous degradation of fibronectin and laminin β-1, the two main components of extracellular matrix (ECM). Inhibition of MMP2 and 9 with SB-3CT completely blocked the degradation of fibronectin and laminin β-1. ODG+tPA treatment led to Cav-1 shedding from bEND3 cells into the media. Notably, OGD triggered nitric oxide (NO) production and S-nitrosylationof Cav-1 (SNCav-1). Meanwhile tPA induced activation of ERK signal pathway and stimulates the secretion of SNCav-1. Pretreatment of bEND3 cells with C-PTIO (a NO scavenger) or U0126 (a specific ERK inhibitor) significantly reduced OGD-induced S-nitrosylation of Cav-1 in cells and blocked the secretion of Cav-1 and MMP2 and 9 into the media as well as the degradation of fibronectin and laminin β-1 in OGD and tPA-treated cells. These data indicate that OGD-triggered Cav-1 S-nitrosylation interacts with tPA-induced ERK activation to augment MMP2 and 9 secretion and subsequent ECM degradation, which may account for the exacerbation of ischemic blood brain barrier damage following tPA thrombolysis for ischemic stroke.

t-PA power-pulse spray with rheolytic mechanical thrombectomy using cross-sectional image-guided portal vein access for single setting treatment of subacute superior mesenteric vein thrombosis.

PubMed

Syed, Mubin I; Gallagher, Ryan M; Ahmed, Rukan S; Shaikh, Azim; Roberto, Edward; Patel, Sumeet

2018-01-01

Isolated superior mesenteric vein (SMV) thrombosis is a rare but potentially fatal condition if untreated. Current treatments include transjugular or transhepatic approaches for rheolytic mechanical thrombectomy and subsequent infusions of thrombolytics. Tissue plasminogen activator (t-PA) power-pulse spray can provide benefit in a single setting without thrombolytic infusions. Computed tomography (CT) guidance for portal vein access is underutilized in this setting. Case 1 discusses acute SMV thrombosis treated with rheolytic mechanical thrombectomy alone using ultrasound guidance for portal vein access. Case 2 discusses subacute SMV thrombosis treated with the addition of t-PA power-pulse spray to the rheolytic mechanical thrombectomy, using CT guidance for portal vein access. With rheolytic mechanical thrombectomy alone, the patient in Case 1 had significant improvement in abdominal pain. Follow-up CT demonstrated no residual SMV thrombosis and the patient continued to do well in long-term follow-up. With the addition of t-PA power-pulse spray to rheolytic mechanical thrombectomy, the patient in Case 2 with subacute SMV thrombosis dramatically improved postprocedure with resolution of abdominal pain. Follow-up imaging demonstrated patency to the SMV and partial resolution of thrombus. The patient continued to do well at 2-year follow-up. Adding t-PA power-pulse spray to rheolytic mechanical thrombectomy can provide benefit in a single setting versus mechanical thrombectomy alone and prevent the need for subsequent infusions of thrombolytic therapy. CT guidance is a useful alternative of localization for portal vein access via the transhepatic route that is nonoperator-dependent and helpful in the case of obese patients.

75 FR 11937 - J.I.T. Tool and Die, Inc., Brockport, PA; Notice of Termination of Investigation

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-12

... DEPARTMENT OF LABOR Employment and Training Administration [TA-W-73,086] J.I.T. Tool and Die, Inc., Brockport, PA; Notice of Termination of Investigation Pursuant to Section 223 of the Trade Act of 1974, as... official on behalf of workers of J.I.T. Tool and Die, Inc., Brockport, Pennsylvania. The petitioner has...

Prediction of habitual physical activity level and weight status from fundamental movement skill level.

PubMed

Bryant, Elizabeth Sarah; James, Rob S; Birch, Samantha Louise; Duncan, Mike

2014-01-01

Fundamental movement skills (FMS) have been assessed in children in order to investigate the issues of the low proportion of children who meet physical activity (PA) guidelines and rising levels of obesity. The aim of this research was to identify whether previous or current FMS level is a better predictor of PA levels and weight status in children. In January 2012 (year 1), 281 children were recruited from one primary school in the West Midlands, UK. Children performed eight FMS three times, which were videoed and assessed using a subjective checklist. Sprint speed and jump height were measured objectively. Height and mass were measured to calculate the body mass index to determine the weight status. Skinfold calliper readings were used to calculate body fat percentage. One year later, in January 2013, all these tests were repeated on the same children, with the additional collection of PA data via the use of pedometers. Following multiple linear regression, it was identified that prior mastery in FMS was a better predictor of current PA, whereas current FMS was a better predictor of current weight status. Overall, FMS mastery is needed in childhood to be able to participate in PA and maintain a healthy weight status.

Current MBDA R&T Effort on Ram/Scramjet and Detonation Wave Engine

DTIC Science & Technology

2006-05-01

13] to[18]), • WRR program (MBDA France and MAI) ([19] to[23]), • PROMETHEE program (ONERA and MBDA France) ([24] to [27]), Current MBDA R&T...significant step passed for technology and combustion processes mastering - AIAA-2003-7004. [24] F. FALEMPIN, L. SERRE The French PROMETHEE Program...status in 2000 - AIAA – 2000 – 3341 [25] L.SERRE, F. FALEMPIN The French PROMETHEE Program on hydrocarbon fueled dual-mode ramjet–status in 2001

Combination treatment of r-tPA and an optimized human apyrase reduces mortality rate and hemorrhagic transformation 6h after ischemic stroke in aged female rats.

PubMed

Tan, Zhenjun; Li, Xinlan; Turner, Ryan C; Logsdon, Aric F; Lucke-Wold, Brandon; DiPasquale, Kenneth; Jeong, Soon Soeg; Chen, Ridong; Huber, Jason D; Rosen, Charles L

2014-09-05

Recombinant tissue plasminogen activator (r-tPA) is the only FDA-approved drug treatment for ischemic stroke and must be used within 4.5h. Thrombolytic treatment with r-tPA has deleterious effects on the neurovascular unit that substantially increases the risk of intracerebral hemorrhage if administered too late. These therapeutic shortcomings necessitate additional investigation into agents that can extend the therapeutic window for safe use of thrombolytics. In this study, combination of r-tPA and APT102, a novel form of human apyrase/ADPase, was investigated in a clinically-relevant aged-female rat embolic ischemic stroke model. We propose that successfully extending the therapeutic window of r-tPA administration would represent a significant advance in the treatment of ischemic stroke due to a significant increase in the number of patients eligible for treatment. Results of our study showed significantly reduced mortality from 47% with r-tPA alone to 16% with co-administration of APT102 and r-tPA. Co-administration decreased cortical (47 ± 5% vs. 29 ± 5%), striatal (50 ± 2%, vs. 40 ± 3%) and total (48 ± 3%vs. 33 ± 4%) hemispheric infarct volume compared to r-tPA alone. APT102 improved neurological outcome (8.9±0.6, vs. 6.8 ± 0.8) and decreased hemoglobin extravasation in cortical tissue (1.9 ± 0.1mg/dl vs. 1.4 ± 0.1mg/dl) striatal tissue (2.1 ± 0.3mg/dl vs. 1.4 ± 0.1mg/dl) and whole brain tissue (2.0 ± 0.2mg/dl vs. 1.4 ± 0.1mg/dl). These data suggest that APT102 can safely extend the therapeutic window for r-tPA mediated reperfusion to 6h following experimental stroke without increased hemorrhagic transformation. APT102 offers to be a viable adjunct therapeutic option to increase the number of clinical patients eligible for thrombolytic treatment after ischemic stroke. Copyright © 2014 Elsevier B.V. All rights reserved.

Live immunization against East Coast fever--current status.

PubMed

Di Giulio, Giuseppe; Lynen, Godelieve; Morzaria, Subhash; Oura, Chris; Bishop, Richard

2009-02-01

The infection-and-treatment method (ITM) for immunization of cattle against East Coast fever has historically been used only on a limited scale because of logistical and policy constraints. Recent large-scale deployment among pastoralists in Tanzania has stimulated demand. Concurrently, a suite of molecular tools, developed from the Theileria parva genome, has enabled improved quality control of the immunizing stabilate and post-immunization monitoring of the efficacy and biological impact of ITM in the field. This article outlines the current status of ITM immunization in the field, with associated developments in the molecular epidemiology of T. parva.

Noninvasive transcranial direct current stimulation (tDCS) for the treatment of orofacial pain.

PubMed

Fricova, Jitka; Englerova, Katerina; Rokyta, Richard

2016-10-01

tDCS is a promising method for the treatment of chronic pain. Electrode placement locations must be chosen in accordance with the density and the time course of the current in order to prevent pathological changes in the underlying tissue. In order to reduce current spatial variability, more electrodes of the same polarity are placed in a circle around the second electrode of the opposite polarity. The applied current produced the greatest changes directly beneath the electrodes: the cathode reduces the excitability of cortical neurons, while the anode has the opposite effect. Based on inclusion criteria, 10 patients with chronic orofacial pain, secondary trigeminal neuralgia after oral surgery, were enrolled and underwent both anode and cathode stimulation. Before the first session we measured pain intensity on a numeric pain rating scale and tactile and thermal stimulation were used to assess somatosensory status. tDCS was applied for five consecutive days. At the end of tDCS application, somatosensory status was assessed again. From our results we can conclude that the application of tDCS improves the perception of some types of pain. When we increase our sample size, we would expect confirmation not only on our positive results, but also some additional findings for explaining the pathophysiology of orofacial pain. These pathophysiological findings and explanations are very important for the application of tDCS in the treatment of orofacial pain and also for other types of neuropathic pain.

Barriers to administering intravenous tissue plasminogen activator (tPA) for acute ischemic stroke in the emergency department: A cross-sectional survey of stroke centers.

PubMed

Hargis, Mitch; Shah, Jharna N; Mazabob, Janine; Rao, Chethan Venkatasubba; Suarez, Jose I; Bershad, Eric M

2015-08-01

The logistics involved in administration of IV tPA for acute ischemic stroke patients are complex, and may contribute to variability in door-to-needle times between different hospitals. We sought to identify practice patterns in stroke centers related to IV tPA use. We hypothesized that there would be significant variability in logistics related to ancillary staff (i.e. nursing, pharmacists) processes in the emergency room setting. A 21 question survey was distributed to attendees of the AHA/ASA Southwest Affiliate Stroke Coordinators Conference to evaluate potential barriers and delays with regards to thrombolysis for acute strokes patients in the Emergency Department setting. Answers were anonymous and aggregated to examine trends in responses. Responses were obtained from 37 of 67 (55%) stroke centers, which were located mainly in the Southwest United States. Logistical processes differed between facilities. Nursing and pharmacy carried stroke pagers in only 19% of the centers, and pharmacy responded to stroke alerts only one-third of centers. Insertion of Foley catheters and nasogastric tubes prior to tPA was routine in some of the sites. Other barriers to IV tPA administration included physician reluctance and inadequate communication between health care providers. Practices regarding logistics for giving IV tPA may be variable amongst different stroke centers. Given this potential variability, prospective evaluation to confirm these preliminary findings is warranted. Copyright © 2015 Elsevier B.V. All rights reserved.

Pawedness Trait Test (PaTRaT)—A New Paradigm to Evaluate Paw Preference and Dexterity in Rats

PubMed Central

Cunha, Ana M.; Esteves, Madalena; das Neves, Sofia P.; Borges, Sónia; Guimarães, Marco R.; Sousa, Nuno; Almeida, Armando; Leite-Almeida, Hugo

2017-01-01

In rodents, dexterity is commonly analyzed in preference paradigms in which animals are given the chance to use either the left or the right front paws to manipulate food. However, paw preference and dexterity at population and individual levels are controversial as results are incongruent across paradigms. We have therefore developed a semi-quantitative method—the pawdeness trait test (PaTRaT)—to evaluate paw preference degree in rats. The PaTRaT consists in a classification system, ranging from +4 to −4 where increasingly positive and negative values reflect the bias for left or right paw use, respectively. Sprague-Dawley male rats were confined into a metal rectangular mesh cylinder, from which they can see, smell and reach sugared rewards with their paws. Due to its size, the reward could only cross the mesh if aligned with its diagonal, imposing additional coordination. Animals were allowed to retrieve 10 rewards per session in a total of four sessions while their behavior was recorded. PaTRaT was repeated 4 and 8 weeks after the first evaluation. To exclude potential bias, rats were also tested for paw fine movement and general locomotion in other behavioral paradigms as well as impulsivity (variable delay-to-signal, VDS), memory and cognitive flexibility (water maze). At the population level 54% of the animals presented a rightward bias. Individually, all animals presented marked side-preferences, >2 and <−2 for left- and right-sided bias, respectively, and this preference was stable across the three evaluations. Inter-rater consistency was very high between two experienced raters and substantial when two additional inexperienced raters were included. Left- and right-biased animals presented no differences in the ability to perform fine movements with any of the forelimbs (staircase) and general locomotor performance. Additionally, these groups performed similarly in executive function and memory tasks. In conclusion, PaTRaT is able to reliably

Differential control of MMP and t-PA/PAI-1 expressions by sympathetic and renin-angiotensin systems in rat left ventricle.

PubMed

Dab, Houcine; Hachani, Rafik; Hodroj, Wassim; Sakly, Mohsen; Bricca, Giampiero; Kacem, Kamel

2009-10-05

In the present study, we tested the hypothesis that angiotensin II (Ang II) has both direct (via AT1 receptors) and indirect (via sympathostimulator pathway) actions on the synthesis and activity of the enzymes involved in the extracellular matrix degradation in vivo. For this purpose, sympathectomy and blockade of the Ang II receptor AT1 were performed alone or in combination in normotensive rats. The mRNA of the plasminogen activator (t-PA) and its inhibitor (PAI-1), the mRNA, protein and activity of the matrix metalloproteinases MMP-2 and MMP-9 were examined by Q-RT-PCR, immunoblotting and zymographic methods in the left ventricle. t-PA and PAI-1 mRNA were decreased after sympathectomy and remained unchanged after AT1 receptors blockade. mRNA was increased for t-PA and decreased by similar degree for PAI-1 after double treatment. MMPs mRNA and protein levels were decreased either after sympathectomy or AT1 receptors blockade and an additive effect was acquired after double treatment. MMPs activity was decreased by similar degree in the three treated groups. Deducted interpretations from our experimental approach suggest that Ang II inhibits directly (via AT1 receptors) and indirectly (via sympathostimulator pathway) t-PA mRNA synthesis. It seems unable to influence directly PAI-1 mRNA, but stimulates indirectly PAI-1 mRNA synthesis. Ang II stimulates directly (via AT1 receptors) and indirectly (via sympathostimulator pathway) MMPs synthesis at both transcriptional and protein levels. The enzymatic activity of MMPs does not seem to be influenced directly by Ang II but it could be stimulated indirectly (via sympathostimulator pathway).

Transcranial Direct Current Stimulation (tDCS): A Promising Treatment for Major Depressive Disorder?

PubMed Central

Bennabi, Djamila; Haffen, Emmanuel

2018-01-01

Background: Transcranial direct current stimulation (tDCS) opens new perspectives in the treatment of major depressive disorder (MDD), because of its ability to modulate cortical excitability and induce long-lasting effects. The aim of this review is to summarize the current status of knowledge regarding tDCS application in MDD. Methods: In this review, we searched for articles published in PubMed/MEDLINE from the earliest available date to February 2018 that explored clinical and cognitive effects of tDCS in MDD. Results: Despite differences in design and stimulation parameters, the examined studies indicated beneficial effects of tDCS for MDD. These preliminary results, the non-invasiveness of tDCS, and its good tolerability support the need for further research on this technique. Conclusions: tDCS constitutes a promising therapeutic alternative for patients with MDD, but its place in the therapeutic armamentarium remains to be determined. PMID:29734768

A Balanced Risk-Benefit Analysis to Determine Human Risks Associated with Pyrrolizidine Alkaloids (PA)-The Case of Tea and Herbal Infusions.

PubMed

Habs, Michael; Binder, Karin; Krauss, Stefan; Müller, Karolina; Ernst, Brigitte; Valentini, Luzia; Koller, Michael

2017-07-07

Humans are exposed to pyrrolizidine alkaloids (PA) through different sources, mainly from contaminated foodstuff. Teas and herbal infusions (T&HI) can be contaminated by PA producing weed. PA can possess toxic, mutagenic, genotoxic, and carcinogenic properties. Thus, possible health risks for the general population are under debate. There is a strong safety record for T&HI and additionally epidemiological evidence for the preventive effects of regular tea consumption on cardiovascular events and certain types of cancer. There is no epidemiological evidence, however, for human risks of regular low dose PA exposure. Recommended regulatory PA-threshold values are based on experimental data only, accepting big uncertainties. If a general risk exists through PA contaminated T&HI, it must be small compared to other frequently accepted risks of daily living and the proven health effects of T&HI. Decision making should be based on a balanced riskbenefit analysis. Based on analyses of the scientific data currently available, it is concluded that the benefits of drinking T&HI clearly outweigh the negligible health risk of possible PA contamination. At the same time, manufacturers must continue their efforts to secure good product quality and to be transparent on their measures of quality control and risk communication.

tPA-MMP-9 Axis Plays a Pivotal Role in Mobilization of Endothelial Progenitor Cells from Bone Marrow to Circulation and Ischemic Region for Angiogenesis

PubMed Central

Day, Yuan-Ji

2016-01-01

We examined the role of tissue plasminogen activator- (tPA-) matrix metalloproteinase- (MMP-) 9 in mobilizing endothelial progenitor cells (EPCs) from bone marrow to circulation and critical limb ischemia (CLI) region. Male C57BL/6J mice having been irradiated were categorized into wild-type mice (WT) receiving WT bone marrow cell (BMC) transfusion (group 1), WT mice receiving MMP-9 knockout (MMP-9−/−) BMC (group 2), MMP-9−/− receiving MMP-9−/− BMC (group 3), and MMP-9−/− receiving WT BMC (group 4), each of which was subdivided into sham control (SC), CLI, SC-tPA, and CLI-tPA. In groups 1 and 4, by post-CLI 18 h and day 14, circulating EPC (C-kit+/CD31+, Sca-1+/KDR+) levels were highest in CLI-tPA subgroup. In groups 2 and 3, EPC levels did not differ among all subgroups. The EPC levels in bone marrow were higher in groups 2 and 3 than those in groups 1 and 4. By day 14, in animals with CLI, expression levels of proangiogenic factors (CXCR4, SDF-1α, and VEGF) showed similar trends as circulating EPC levels. Moreover, the number of infiltrated neutrophils and macrophages in quadriceps was higher in groups 1 and 4 than groups in 2 and 3. In conclusion, tPA-MMP-9 axis plays a crucial role in EPC mobilization and angiogenesis in experimental CLI. PMID:27610138

Functional Characterization of Phalaenopsis aphrodite Flowering Genes PaFT1 and PaFD

PubMed Central

Jang, Seonghoe; Choi, Sang-Chul; Li, Hsing-Yi; An, Gynheung; Schmelzer, Elmon

2015-01-01

We show that the key flowering regulators encoded by Phalaenopsis aphrodite FLOWERING LOCUS T1 (PaFT1) and PaFD share high sequence homologies to these from long-day flowering Arabidopsis and short-day flowering rice. Interestingly, PaFT1 is specifically up-regulated during flowering inductive cooling treatment but is not subjected to control by photoperiod in P. aphrodite. Phloem or shoot apex-specific expression of PaFT1 restores the late flowering of Arabidopsis ft mutants. Moreover, PaFT1 can suppress the delayed flowering caused by SHORT VEGATATIVE PHASE (SVP) overexpression as well as an active FRIGIDA (FRI) allele, indicating the functional conservation of flowering regulatory circuit in different plant species. PaFT1 promoter:GUS in Arabidopsis showed similar staining pattern to that of Arabidopsis FT in the leaves and guard cells but different in the shoot apex. A genomic clone or heat shock-inducible expression of PaFT1 is sufficient to the partial complementation of the ft mutants. Remarkably, ectopic PaFT1 expression also triggers precocious heading in rice. To further demonstrate the functional conservation of the flowering regulators, we show that PaFD, a bZIP transcription factor involved in flowering promotion, interacts with PaFT1, and PaFD partially complemented Arabidopsis fd mutants. Transgenic rice expressing PaFD also flowered early with increased expression of rice homologues of APETALA1 (AP1). Consistently, PaFT1 knock-down Phalaenopsis plants generated by virus-induced gene silencing exhibit delayed spiking. These studies suggest functional conservation of FT and FD genes, which may have evolved and integrated into distinct regulatory circuits in monopodial orchids, Arabidopsis and rice that promote flowering under their own inductive conditions. PMID:26317412

Predictive Toxicology: Current Status and Future Outlook (EBI ...

EPA Pesticide Factsheets

Slide presentation at the EBI-EMBL Industry Programme Workshop on Predictive Toxicology and the currently status of Computational Toxicology activities at the US EPA. Slide presentation at the EBI-EMBL Industry Programme Workshop on Predictive Toxicology and the currently status of Computational Toxicology activities at the US EPA.

Intraarterial Thrombolysis with r-tPA for Treatment of Anterior Circulation Acute Ischemic Stroke

PubMed Central

Baltacioğlu, F.; Afşar, N.; Ekinci, G.; Tuncer-Elmaci, N.; Çagatay Çimşit, N; Aktan, S.; Erzen, C.

2003-01-01

Summary To investigate factors effecting the safety and recanalization efficacy of local intraarterial (IA) recombinant tissue plasminogen activator (r-tPA) delivery in patients with acute ischemic stroke. Eleven patients with anterior circulation acute ischemic stroke were treated. The neurological status of the patients were graded with the Glasgow Coma Scale (GCS) and National Institute of Health Stroke Scale (NIHSS). All patients underwent a computed tomography (CT) examination at admission. In addition four patients had diffusion-weighted and one patient had a perfusion magnetic resonance (MR) examinations. Patients were treated within six hours from stroke onset. Immediate, six hours, and 24 hours follow-up CT examinations were performed in order to evaluate the haemorrhagic complications and the extent of the ischemic area. The Rankin Scale (RS) was used as an outcome measure. Two of the 11 patients had carotid “T” occlusion (CTO), nine had middle cerebral artery (MCA) main trunk occlusion. Four patients had symptomatic haemorrhage with a large haematoma rupturing into the ventricles and subarachnoid space. Of these, three patients died within 24 hours. The remaining seven patients had asymptomatic haematomas that were smaller compared to symptomatic ones, and showed regression in size and density on follow-up CTs. At third month five patients had a good outcome and three patients had a poor outcome. In acute ischemic stroke, local IA thrombolysis is a feasible treatment when you select the right patient. Haemorrhage rate does not seem to exceed that occuring in the natural history of the disease and in other treatment modalities. PMID:20591253

Unreviewed Disposal Question Evaluation: Impact of New Information since 2008 PA on Current Low-Level Solid Waste Operations

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

Flach, G.; Smith, F.; Hamm, L.

2014-10-06

Solid low-level waste disposal operations are controlled in part by an E-Area Low-Level Waste Facility (ELLWF) Performance Assessment (PA) that was completed by the Savannah River National Laboratory (SRNL) in 2008 (WSRC 2008). Since this baseline analysis, new information pertinent to disposal operations has been identified as a natural outcome of ongoing PA maintenance activities and continuous improvement in model simulation techniques (Flach 2013). An Unreviewed Disposal Question (UDQ) Screening (Attachment 1) has been initiated regarding the continued ability of the ELLWF to meet Department of Energy (DOE) Order 435.1 performance objectives in light of new PA items and datamore » identified since completion of the original UDQ Evaluation (UDQE). The present UDQE assesses the ability of Solid Waste (SW) to meet performance objectives by estimating the influence of new information items on a recent sum-of-fractions (SOF) snapshot for each currently active E-Area low-level waste disposal unit. A final SOF, as impacted by this new information, is projected based on the assumptions that the current disposal limits, Waste Information Tracking System (WITS) administrative controls, and waste stream composition remain unchanged through disposal unit operational closure (Year 2025). Revision 1 of this UDQE addresses the following new PA items and data identified since completion of the original UDQE report in 2013: New K d values for iodine, radium and uranium; Elimination of cellulose degradation product (CDP) factors; Updated radionuclide data; Changes in transport behavior of mobile radionuclides; Potential delay in interim closure beyond 2025; and Component-in-grout (CIG) plume interaction correction. Consideration of new information relative to the 2008 PA baseline generally indicates greater confidence that PA performance objectives will be met than indicated by current SOF metrics. For SLIT9, the previous prohibition of non-crushable containers in revision 0

Meeting Recommended Levels of Physical Activity in Relation to Preventive Health Behavior and Health Status Among Adults.

PubMed

Hart, Peter D; Benavidez, Gabriel; Erickson, James

2017-01-01

The purpose of this study was to examine the relationship of meeting the recommended levels of physical activity (PA) with health status and preventive health behavior in adults. A total of 5630 adults 18 years of age or older were included in this study. PA was assessed using a series of questions that categorized activities based on their metabolic equivalent values and then categorized individuals based on the reported frequency and duration of such activities. Participants reporting 150 minutes or more of moderate-intensity PA per week were considered to have met the PA guidelines. Multiple logistic regression was used to model the relationships between meeting PA guidelines and health status and preventive health behavior, while controlling for confounding variables. Overall, 53.9% (95% confidence interval [CI], 51.9 to 55.9%) of adults reported meeting the recommended levels of PA. Among adults with good general health, 56.9% (95% CI, 54.7 to 59.1%) reported meeting the recommended levels of PA versus 43.1% (95% CI, 40.9 to 45.3%) who did not. Adults who met the PA guidelines were significantly more likely not to report high cholesterol, diabetes, chronic obstructive pulmonary disease, arthritis, asthma, depression, or overweight. Furthermore, adults meeting the PA guidelines were significantly more likely to report having health insurance, consuming fruits daily, consuming vegetables daily, and not being a current cigarette smoker. In this study, we found meeting the current guidelines for PA to have a protective relationship with both health status and health behavior in adults. Health promotion programs should focus on strategies that help individuals meet the current guidelines of at least 150 minutes per week of moderate-intensity PA.

Evidence for a role of the rare p.A152T variant in MAPT in increasing the risk for FTD-spectrum and Alzheimer's diseases

PubMed Central

Coppola, Giovanni; Chinnathambi, Subashchandrabose; Lee, Jason JiYong; Dombroski, Beth A.; Baker, Matt C.; Soto-Ortolaza, Alexandra I.; Lee, Suzee E.; Klein, Eric; Huang, Alden Y.; Sears, Renee; Lane, Jessica R.; Karydas, Anna M.; Kenet, Robert O.; Biernat, Jacek; Wang, Li-San; Cotman, Carl W.; DeCarli, Charles S.; Levey, Allan I.; Ringman, John M.; Mendez, Mario F.; Chui, Helena C.; Le Ber, Isabelle; Brice, Alexis; Lupton, Michelle K.; Preza, Elisavet; Lovestone, Simon; Powell, John; Graff-Radford, Neill; Petersen, Ronald C.; Boeve, Bradley F.; Lippa, Carol F.; Bigio, Eileen H.; Mackenzie, Ian; Finger, Elizabeth; Kertesz, Andrew; Caselli, Richard J.; Gearing, Marla; Juncos, Jorge L.; Ghetti, Bernardino; Spina, Salvatore; Bordelon, Yvette M.; Tourtellotte, Wallace W.; Frosch, Matthew P.; Vonsattel, Jean Paul G.; Zarow, Chris; Beach, Thomas G.; Albin, Roger L.; Lieberman, Andrew P.; Lee, Virginia M.; Trojanowski, John Q.; Van Deerlin, Vivianna M.; Bird, Thomas D.; Galasko, Douglas R.; Masliah, Eliezer; White, Charles L.; Troncoso, Juan C.; Hannequin, Didier; Boxer, Adam L.; Geschwind, Michael D.; Kumar, Satish; Mandelkow, Eva-Maria; Wszolek, Zbigniew K.; Uitti, Ryan J.; Dickson, Dennis W.; Haines, Jonathan L.; Mayeux, Richard; Pericak-Vance, Margaret A.; Farrer, Lindsay A.; Ross, Owen A.; Rademakers, Rosa; Schellenberg, Gerard D.; Miller, Bruce L.; Mandelkow, Eckhard; Geschwind, Daniel H.

2012-01-01

Rare mutations in the gene encoding for tau (MAPT, microtubule-associated protein tau) cause frontotemporal dementia-spectrum (FTD-s) disorders, including FTD, progressive supranuclear palsy (PSP) and corticobasal syndrome, and a common extended haplotype spanning across the MAPT locus is associated with increased risk of PSP and Parkinson's disease. We identified a rare tau variant (p.A152T) in a patient with a clinical diagnosis of PSP and assessed its frequency in multiple independent series of patients with neurodegenerative conditions and controls, in a total of 15 369 subjects. Tau p.A152T significantly increases the risk for both FTD-s (n = 2139, OR = 3.0, CI: 1.6–5.6, P = 0.0005) and Alzheimer's disease (AD) (n = 3345, OR = 2.3, CI: 1.3–4.2, P = 0.004) compared with 9047 controls. Functionally, p.A152T (i) decreases the binding of tau to microtubules and therefore promotes microtubule assembly less efficiently; and (ii) reduces the tendency to form abnormal fibers. However, there is a pronounced increase in the formation of tau oligomers. Importantly, these findings suggest that other regions of the tau protein may be crucial in regulating normal function, as the p.A152 residue is distal to the domains considered responsible for microtubule interactions or aggregation. These data provide both the first genetic evidence and functional studies supporting the role of MAPT p.A152T as a rare risk factor for both FTD-s and AD and the concept that rare variants can increase the risk for relatively common, complex neurodegenerative diseases, but since no clear significance threshold for rare genetic variation has been established, some caution is warranted until the findings are further replicated. PMID:22556362

Current Status of the Nitrogen Oxygen Recharge System

NASA Technical Reports Server (NTRS)

Dick, Brandon

2011-01-01

This paper presents an overview of the Nitrogen Oxygen Recharge System (NORS) to date and the current development status of the system. NORS is an element of the International Space Station (ISS) Environmental Control and Life Support Systems (ECLSS) used to resupply the ISS with Nitrogen and Oxygen following the impending retirement of the Space Shuttle. The paper will discuss why NASA is developing NORS, including a summary of other concepts considered, and other related concepts currently being developed by NASA. The current system architecture will be described, along with a summary of the current design of the NORS. The overall programmatic schedule of the NORS in the context of the upcoming shuttle retirement and future launch vehicle development will also be presented. Finally, the paper will examine the significant technical challenges encountered during the requirements and preliminary design phase of NORS development. A key challenge to the development of NORS is the international shipment - and associated regulations - of pressurized Oxygen, which is necessary due to the use of launch vehicles based in Japan and French Guiana to send NORS gasses to the ISS. The storage and use of relatively large quantities of high pressure (41,000 kPa) Oxygen and Nitrogen within the ISS, which is unprecedented both on the ISS and other space vehicles, has had a significant impact on the design and architecture of the system. The high pressure of the system also poses unique thermal considerations, which has led to the development of a heater system for thermal conditioning of high pressure gas to avoid thermal impacts on downstream hardware. The on-orbit envelope allocated to the NORS has changed (gotten smaller) and has impacted both the design and architecture of the system. Finally, the balance of safety considerations associated with these high pressure gasses, particularly high pressure Oxygen, with the functionality of the system has profoundly impacted the form

PA28γ is a novel corepressor of HTLV-1 replication and controls viral latency

PubMed Central

Ko, Nga Ling; Taylor, John M.; Bellon, Marcia; Bai, Xue Tao; Shevtsov, Sergey P.; Dundr, Miroslav

2013-01-01

The establishment of a latent reservoir by human tumor viruses is a vital step in initiating cellular transformation and represents a major shortcoming to current therapeutic strategies and the ability to eradicate virus-infected cells. Human T-cell leukemia virus type 1 (HTLV-1) establishes a lifelong infection and is linked to adult T-cell leukemia lymphoma (ATLL). Here, we demonstrate that HTLV-1 p30 recruits the cellular proteasome activator PA28γ onto the viral tax/rex mRNA to prevent its nuclear export and suppress virus replication. Interaction of p30 with a PA28γ retaining fully functional proteasome activity is required for p30's ability to repress HTLV-1. Consistently, HTLV-1 molecular clones replicate better and produce more virus particles in PA28γ-deficient cells. These results define a unique and novel role for the cellular factor PA28γ in the control of nuclear RNA trafficking and HTLV-1–induced latency. Importantly, knockdown of PA28γ expression in ATLL cells latently infected with HTLV-1 reactivates expression of viral tax/rex RNA and the Tax protein. Because Tax is the most immunogenic viral antigen and triggers strong CTL responses, our results suggest that PA28γ-targeted therapy may reactivate virus expression from latently infected cells and allow their eradication from the host. PMID:23104922

PA-6 inhibits inward rectifier currents carried by V93I and D172N gain-of-function KIR2.1 channels, but increases channel protein expression.

PubMed

Ji, Yuan; Veldhuis, Marlieke G; Zandvoort, Jantien; Romunde, Fee L; Houtman, Marien J C; Duran, Karen; van Haaften, Gijs; Zangerl-Plessl, Eva-Maria; Takanari, Hiroki; Stary-Weinzinger, Anna; van der Heyden, Marcel A G

2017-07-15

The inward rectifier potassium current I K1 contributes to a stable resting membrane potential and phase 3 repolarization of the cardiac action potential. KCNJ2 gain-of-function mutations V93I and D172N associate with increased I K1 , short QT syndrome type 3 and congenital atrial fibrillation. Pentamidine-Analogue 6 (PA-6) is an efficient (IC 50  = 14 nM with inside-out patch clamp methodology) and specific I K1 inhibitor that interacts with the cytoplasmic pore region of the K IR 2.1 ion channel, encoded by KCNJ2. At 10 μM, PA-6 increases wild-type (WT) K IR 2.1 expression in HEK293T cells upon chronic treatment. We hypothesized that PA-6 will interact with and inhibit V93I and D172N K IR 2.1 channels, whereas impact on channel expression at the plasma membrane requires higher concentrations. Molecular modelling was performed with the human K IR 2.1 closed state homology model using FlexX. WT and mutant K IR 2.1 channels were expressed in HEK293 cells. Patch-clamp single cell electrophysiology measurements were performed in the whole cell and inside-out mode of the patch clamp method. K IR 2.1 expression level and localization were determined by western blot analysis and immunofluorescence microscopy, respectively. PA-6 docking in the V93I/D172N double mutant homology model of K IR 2.1 demonstrated that mutations and drug-binding site are >30 Å apart. PA-6 inhibited WT and V93I outward currents with similar potency (IC 50  = 35.5 and 43.6 nM at +50 mV for WT and V93I), whereas D172N currents were less sensitive (IC 50  = 128.9 nM at +50 mV) using inside-out patch-clamp electrophysiology. In whole cell mode, 1 μM of PA-6 inhibited outward I K1 at -50 mV by 28 ± 36%, 18 ± 20% and 10 ± 6%, for WT, V93I and D172N channels respectively. Western blot analysis demonstrated that PA-6 (5 μM, 24 h) increased K IR 2.1 expression levels of WT (6.3 ± 1.5 fold), and V93I (3.9 ± 0.9) and D172N (4.8 ± 2.0) mutants. Immunofluorescent

Current Status of Infrared Technology

NASA Astrophysics Data System (ADS)

Tsunawaki, Yoshiaki; Hangyo, Masanori; Hiromoto, Norihisa; Horinaka, Hiromichi

Infrared sience and technology has been contributing to the four important national priority researches which are nano-, bio-, information- and environmental technologies. In this manuscript we discuss the current status of the infrared science and technology as well as its crucial role in the four technologies.

Current Status and Problems of T790M Detection, a Molecular Biomarker of Acquired Resistance to EGFR Tyrosine Kinase Inhibitors, with Liquid Biopsy and Re-biopsy.

PubMed

Komiya, Kazutoshi; Nakashima, Chiho; Nakamura, Tomomi; Hirakawa, Haruki; Abe, Tomonori; Ogusu, Shinsuke; Takahashi, Koichiro; Takeda, Yuji; Egashira, Yoshiaki; Kimura, Shinya; Sueoka-Aragane, Naoko

2018-06-01

The purpose of this study was to consider appropriate application of liquid and re-biopsy through analysis of current status in practice. We performed a retrospective analysis of 22 patients with epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer who exhibited 1st/2nd generation EGFR-tyrosine kinase inhibitors resistance. The cobas® method was used to detect T790M with re-biopsy and the mutation-biased PCR and quenched probe method was used with liquid biopsy. T790M detection rate was 52% with re-biopsy and 58% with liquid biopsy. The concordance between tissue and plasma was 58%. One patient who was T790M-positive with liquid biopsy showed heterogeneity among metastatic lesions in terms of osimertinib efficacy, as revealed by T790M detection with re-biopsy. Liquid biopsy reflects the whole body, whereas re-biopsy is useful for spatial diagnosis. Considering these characteristics, a combination of liquid and re-biopsy contribute to enhanced treatment. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Proarrhythmia liability assessment and the comprehensive in vitro Proarrhythmia Assay (CiPA): An industry survey on current practice.

PubMed

Authier, Simon; Pugsley, Michael K; Koerner, John E; Fermini, Bernard; Redfern, William S; Valentin, Jean-Pierre; Vargas, Hugo M; Leishman, Derek J; Correll, Krystle; Curtis, Michael J

2017-07-01

The Safety Pharmacology Society (SPS) has conducted a survey of its membership to identify industry practices related to testing considered in the Comprehensive In vitro Proarrhythmia Assay (CiPA). Survey topics included nonclinical approaches to address proarrhythmia issues, conduct of in silico studies, in vitro ion channel testing methods used, drugs used as positive controls during the conduct of cardiac ion channel studies, types of arrhythmias observed in non-clinical studies and use of the anticipated CiPA ion channel assay. In silico studies were used to evaluate effects on ventricular action potentials by only 15% of responders. In vitro assays were used mostly to assess QT prolongation (95%), cardiac Ca 2+ and Na + channel blockade (82%) and QT shortening or QRS prolongation (53%). For de-risking of candidate drugs for proarrhythmia, those assays most relevant to CiPA including cell lines stably expressing ion channels used to determine potency of drug block were most frequently used (89%) and human stem cell-derived or induced pluripotent stem cell cardiomyocytes (46%). Those in vivo assays related to general proarrhythmia derisking include ECG recording using implanted telemetry technology (88%), jacketed external telemetry (62%) and anesthetized animal models (53%). While the CiPA initiative was supported by 92% of responders, there may be some disconnect between current practice and future expectations, as explained. Proarrhythmia liability assessment in drug development presently includes study types consistent with CiPA. It is anticipated that CiPA will develop into a workable solution to the concern that proarrhythmia liability testing remains suboptimal. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Histone deacetylase inhibitors: current status and overview of recent clinical trials.

PubMed

Ma, Xujun; Ezzeldin, Hany H; Diasio, Robert B

2009-10-01

Histone deacetylase (HDAC) inhibitors are a new group of anticancer agents that have a potential role in the regulation of gene expression, induction of cell death, apoptosis and cell cycle arrest of cancer cells by altering the acetylation status of chromatin and other non-histone proteins. In clinical trials, HDAC inhibitors have demonstrated promising antitumour activity as monotherapy in cutaneous T-cell lymphoma and other haematological malignancies. In solid tumours, several HDAC inhibitors have been shown to be efficacious as single agents; however, results of most clinical trials were in favour of using HDAC inhibitors either prior to the initiation of chemotherapy or in combination with other treatments. Currently, the molecular basis of response to HDAC inhibitors in patients is not fully understood. In this review, we summarize the current status of HDAC inhibitors, as single agents or in combination with other agents in different phases of clinical trials. In most of the clinical trials, HDAC inhibitors were tolerable and exerted biological or antitumor activity. HDAC inhibitors have been studied in phase I, II and III clinical trials with variable efficacy. The combination of HDAC inhibitors with other anticancer agents including epigenetic or chemotherapeutic agents demonstrated favourable clinical outcome.

Meridional circulation across the Antarctic Circumpolar Current serves as a double 231Pa and 230Th trap

NASA Astrophysics Data System (ADS)

Rutgers van der Loeff, Michiel; Venchiarutti, Celia; Stimac, Ingrid; van Ooijen, Jan; Huhn, Oliver; Rohardt, Gerd; Strass, Volker

2016-12-01

Upwelling of Circumpolar Deep Water in the Weddell Gyre and low scavenging rates south of the Antarctic Circumpolar Current (ACC) cause an accumulation of particle reactive nuclides in the Weddell Gyre. A ventilation/reversible scavenging model that successfully described the accumulation of 230Th in this area was tested with other particle reactive nuclides and failed to adequately describe the depth-distributions of 231Pa and 210Pb. We present here a modified model that includes a nutrient-like accumulation south of the Antarctic Polar Front in an upper meridional circulation cell, as well as transport to a deep circulation cell in the Weddell Gyre by scavenging and subsequent release at depth. The model also explains depletion of 231Pa and 230Th in Weddell Sea Bottom Water (WSBW) by ventilation of newly formed deep water on a timescale of 10 years, but this water mass is too dense to leave the Weddell Gyre. In order to quantify the processes responsible for the 231Pa- and 230Th-composition of newly formed Antarctic Bottom Water (AABW) we present a mass balance of 231Pa and 230Th in the Atlantic sector of the Southern Ocean based on new data from the GEOTRACES program. The ACC receives 6.0 ± 1.5 ×106 dpms-1 of 230Th from the Weddell Sea, similar in magnitude to the net input of 4.2 ± 3.0 ×106 dpms-1 from the north. For 231Pa, the relative contribution from the Weddell Sea is much smaller, only 0.3 ± 0.1 ×106, compared to 2.7 ± 1.4 ×106 dpms-1 from the north. Weddell Sea Deep Water (WSDW) leaving the Weddell Gyre northward to form AABW is exposed in the ACC to resuspended opal-rich sediments that act as efficient scavengers with a Th/Pa fractionation factor F ≤ 1. Hydrothermal inputs may provide additional removal with low F. Scavenging in the full meridional circulation across the opal-rich ACC thus acts as a double 231Pa and 230Th trap that preconditions newly formed AABW.

Reduction of intracerebral hemorrhage by rivaroxaban after tPA thrombolysis is associated with downregulation of PAR-1 and PAR-2.

PubMed

Morihara, Ryuta; Yamashita, Toru; Kono, Syoichiro; Shang, Jingwei; Nakano, Yumiko; Sato, Kota; Hishikawa, Nozomi; Ohta, Yasuyuki; Heitmeier, Stefan; Perzborn, Elisabeth; Abe, Koji

2017-09-01

This study aimed to assess the risk of intracerebral hemorrhage (ICH) after tissue-type plasminogen activator (tPA) treatment in rivaroxaban compared with warfarin-pretreated male Wistar rat brain after ischemia in relation to activation profiles of protease-activated receptor-1, -2, -3, and -4 (PAR-1, -2, -3, and -4). After pretreatment with warfarin (0.2 mg/kg/day), low-dose rivaroxaban (60 mg/kg/day), high-dose rivaroxaban (120 mg/kg/day), or vehicle for 14 days, transient middle cerebral artery occlusion was induced for 90 min, followed by reperfusion with tPA (10 mg/kg/10 ml). Infarct volume, hemorrhagic volume, immunoglobulin G leakage, and blood parameters were examined. Twenty-four hours after reperfusion, immunohistochemistry for PARs was performed in brain sections. ICH volume was increased in the warfarin-pretreated group compared with the rivaroxaban-treated group. PAR-1, -2, -3, and -4 were widely expressed in the normal brain, and their levels were increased in the ischemic brain, especially in the peri-ischemic lesion. Warfarin pretreatment enhanced the expression of PAR-1 and PAR-2 in the peri-ischemic lesion, whereas rivaroxaban pretreatment did not. The present study shows a lower risk of brain hemorrhage in rivaroxaban-pretreated compared with warfarin-pretreated rats following tPA administration to the ischemic brain. It is suggested that the relative downregulation of PAR-1 and PAR-2 by rivaroxaban compared with warfarin pretreatment might be partly involved in the mechanism of reduced hemorrhagic complications in patients receiving rivaroxaban in clinical trials. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

32 CFR 701.113 - PA exemptions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... DOCUMENTS AFFECTING THE PUBLIC DON Privacy Program § 701.113 PA exemptions. (a) Exempt systems of records. 5... records that is filed in a non-exempt system of records retains its exempt status. (e) Types of exemptions.... They are: (i) “(k)(1)”: Information which is properly classified under E.O. in the interest of national...

[Nutritional status in children victims of physical and sexual abuse].

PubMed

Martín-Martín, Verónica; Loredo-Abdalá, Arturo

2010-01-01

To assess and relate the nutritional status by type of abuse in a pediatric population diagnosed with physical abuse (PA) and sexual abuse (SA). It's a retrospective, cross-sectional, descriptive study of 178 clinical records of children aged less than 12 years, attended at the Clinic for the Integral Care of the Abused Child of the Instituto Nacional de Pediatría and the Universidad Nacional Autónoma de México (CAINM-INP-UNAM), during the period 1994 to 2005. The relationship of nutritional status with the type of abuse was analyzed in two age ranges (3 months to less than five years, and five to 11 years) and gender with Student t and chi-square tests. We identified that, in girls PA was associated with stunting (PA: 48% vs. SA: 12%, p < 0.005 and PA: 21% vs. SA: 0%, p < 0.002) and wasting (PA: 21% vs. SA: 0%, p < 0.01 and PA: 21% vs. SA: 0%, p < 0.002). Whereas in girls SA was associated with overweight and obesity in age range five to 11 years (PA: 0% vs. SA: 31%; p < 0.01). This study identified acute and chronic under nutrition in girls with PA, and overweight and obesity in girls with SA. These findings enrich the knowledge for the suspicion of maltreatment child syndrome during the search of the aetiology of the clinical expression studied.

Galactosidase Alpha p.A143T Variant Fabry Disease May Result in a Phenotype With Multifocal Microvascular Cerebral Involvement at a Young Age.

PubMed

Hauth, Lothar; Kerstens, Jeroen; Yperzeele, Laetitia; Eyskens, François; Parizel, Paul M; Willekens, Barbara

2018-01-01

A 16-year-old male presented with episodic headaches and a brain magnetic resonance imaging (MRI) that showed multifocal punctate to patchy white matter lesions. The diagnosis of Fabry disease (FD) was suggested upon the finding of significantly reduced plasma alpha-galactosidase A activity (0.62 µmol/L or 13% of normal; normal range ≥ 1.65 μmol/L) and genetic investigation confirmed the presence of a hemizygous missense variant in the galactosidase alpha (GLA) gene (p.A143T). Baseline assessment of other systemic involvement showed only a discrete proteinuria. FD is a rare lysosomal storage disorder. Genetic screening studies have revealed over 600 variants in the GLA gene. The p.A143T variant is a genetic variant of unknown significance, with its associated phenotype ranging from classical FD to healthy unaffected patients. Some authors, however, deem this variant non-pathogenic. We describe the case of a 16-year-old male with multifocal white matter lesions on brain MRI, who was diagnosed with FD and carried this genetic variant. The causative p.A143T mutation can be associated with a more severe subclinical phenotype than has been reported to date. Furthermore, a diagnosis of FD should be considered when finding asymptomatic cerebral white matter lesions in a young patient.

21 CFR 210.1 - Status of current good manufacturing practice regulations.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 4 2010-04-01 2010-04-01 false Status of current good manufacturing practice... SERVICES (CONTINUED) DRUGS: GENERAL CURRENT GOOD MANUFACTURING PRACTICE IN MANUFACTURING, PROCESSING, PACKING, OR HOLDING OF DRUGS; GENERAL § 210.1 Status of current good manufacturing practice regulations...

Identification of the I38T PA Substitution as a Resistance Marker for Next-Generation Influenza Virus Endonuclease Inhibitors

DOE PAGES

Jones, Jeremy C.; Kumar, Gyanendra; Barman, Subrata; ...

2018-04-24

ABSTRACT The clinical severity and annual occurrence of influenza virus epidemics, combined with the availability of just a single class of antivirals to treat infections, underscores the urgent need to develop new anti-influenza drugs. The endonuclease activity within the viral acidic polymerase (PA) protein is an attractive target for drug discovery due to the critical role it plays in viral gene transcription. RO-7 is a next-generation PA endonuclease inhibitor of influenza A and B viruses, but its drug resistance potential is unknown. Through serial passage of influenza A(H1N1) viruses in MDCK cells under selective pressure of RO-7, we identified anmore » I38T substitution within the PA endonuclease domain that conferred in vitro resistance to RO-7 (up to a 287-fold change in 50% effective concentration [EC 50 ]). I38T emerged between 5 and 10 passages, and when introduced into recombinant influenza A(H1N1) viruses, alone conferred RO-7 resistance (up to an 81-fold change in EC 50 ). Cocrystal structures of mutant and wild-type endonuclease domains with RO-7 provided the structural basis of resistance, where a key hydrophobic interaction between RO-7 and the Ile38 side chain is compromised when mutated to the polar threonine. While Ile38 does not have a crucial role in coordinating the endonuclease active site, the switch to threonine does affect the polymerase activity of some viruses and influences RO-7 affinity for the PA N target (i.e., the ≈200-residue N-terminal domain of PA). However, the change does not lead to a complete loss of replication activity in vitro . Our results predict that RO-7-resistant influenza viruses carrying the I38T substitution may emerge under treatment. This should be taken into consideration for clinical surveillance and in refinement of these drugs. IMPORTANCE The effectiveness of antiviral drugs can be severely compromised by the emergence of resistant viruses. Therefore, determination of the mechanisms by which viruses

Identification of the I38T PA Substitution as a Resistance Marker for Next-Generation Influenza Virus Endonuclease Inhibitors

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

Jones, Jeremy C.; Kumar, Gyanendra; Barman, Subrata

ABSTRACT The clinical severity and annual occurrence of influenza virus epidemics, combined with the availability of just a single class of antivirals to treat infections, underscores the urgent need to develop new anti-influenza drugs. The endonuclease activity within the viral acidic polymerase (PA) protein is an attractive target for drug discovery due to the critical role it plays in viral gene transcription. RO-7 is a next-generation PA endonuclease inhibitor of influenza A and B viruses, but its drug resistance potential is unknown. Through serial passage of influenza A(H1N1) viruses in MDCK cells under selective pressure of RO-7, we identified anmore » I38T substitution within the PA endonuclease domain that conferred in vitro resistance to RO-7 (up to a 287-fold change in 50% effective concentration [EC 50 ]). I38T emerged between 5 and 10 passages, and when introduced into recombinant influenza A(H1N1) viruses, alone conferred RO-7 resistance (up to an 81-fold change in EC 50 ). Cocrystal structures of mutant and wild-type endonuclease domains with RO-7 provided the structural basis of resistance, where a key hydrophobic interaction between RO-7 and the Ile38 side chain is compromised when mutated to the polar threonine. While Ile38 does not have a crucial role in coordinating the endonuclease active site, the switch to threonine does affect the polymerase activity of some viruses and influences RO-7 affinity for the PA N target (i.e., the ≈200-residue N-terminal domain of PA). However, the change does not lead to a complete loss of replication activity in vitro . Our results predict that RO-7-resistant influenza viruses carrying the I38T substitution may emerge under treatment. This should be taken into consideration for clinical surveillance and in refinement of these drugs. IMPORTANCE The effectiveness of antiviral drugs can be severely compromised by the emergence of resistant viruses. Therefore, determination of the mechanisms by which viruses

Adaptive threshold hunting for the effects of transcranial direct current stimulation on primary motor cortex inhibition.

PubMed

Mooney, Ronan A; Cirillo, John; Byblow, Winston D

2018-06-01

Primary motor cortex excitability can be modulated by anodal and cathodal transcranial direct current stimulation (tDCS). These neuromodulatory effects may, in part, be dependent on modulation within gamma-aminobutyric acid (GABA)-mediated inhibitory networks. GABAergic function can be quantified non-invasively using adaptive threshold hunting paired-pulse transcranial magnetic stimulation (TMS). The previous studies have used TMS with posterior-anterior (PA) induced current to assess tDCS effects on inhibition. However, TMS with anterior-posterior (AP) induced current in the brain provides a more robust measure of GABA-mediated inhibition. The aim of the present study was to assess the modulation of corticomotor excitability and inhibition after anodal and cathodal tDCS using TMS with PA- and AP-induced current. In 16 young adults (26 ± 1 years), we investigated the response to anodal, cathodal, and sham tDCS in a repeated-measures double-blinded crossover design. Adaptive threshold hunting paired-pulse TMS with PA- and AP-induced current was used to examine separate interneuronal populations within M1 and their influence on corticomotor excitability and short- and long-interval inhibition (SICI and LICI) for up to 60 min after tDCS. Unexpectedly, cathodal tDCS increased corticomotor excitability assessed with AP (P = 0.047) but not PA stimulation (P = 0.74). SICI AP was reduced after anodal tDCS compared with sham (P = 0.040). Pearson's correlations indicated that SICI AP and LICI AP modulation was associated with corticomotor excitability after anodal (P = 0.027) and cathodal tDCS (P = 0.042). The after-effects of tDCS on corticomotor excitability may depend on the direction of the TMS-induced current used to make assessments, and on modulation within GABA-mediated inhibitory circuits.

TAC Proton Accelerator Facility: The Status and Road Map

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

Algin, E.; Akkus, B.; Caliskan, A.

2011-06-28

Proton Accelerator (PA) Project is at a stage of development, working towards a Technical Design Report under the roof of a larger-scale Turkish Accelerator Center (TAC) Project. The project is supported by the Turkish State Planning Organization. The PA facility will be constructed in a series of stages including a 3 MeV test stand, a 55 MeV linac which can be extended to 100+ MeV, and then a full 1-3 GeV proton synchrotron or superconducting linac. In this article, science applications, overview, and current status of the PA Project will be given.

Optometry Basic Science Curricula: Current Status.

ERIC Educational Resources Information Center

Berman, Morris S.

1991-01-01

A national survey of optometry schools (n=10) concerning the status of basic biological science instruction provides insight into manpower, curriculum, learning resources, and budgetary support currently available. Results indicate that major changes must occur and that a national effort will be needed to support them. (Author/MSE)

PA700, the regulatory complex of the 26S proteasome, interferes with alpha-synuclein assembly.

PubMed

Ghee, Medeva; Melki, Ronald; Michot, Nadine; Mallet, Jacques

2005-08-01

Parkinson's disease is characterized by the loss of dopaminergic neurons in the nigrostriatal pathway accompanied by the presence of intracellular cytoplasmic inclusions, termed Lewy bodies. Fibrillized alpha-synuclein forms the major component of Lewy bodies. We reported a specific interaction between rat alpha-synuclein and tat binding protein 1, a subunit of PA700, the regulatory complex of the 26S proteasome. It has been demonstrated that PA700 prevents the aggregation of misfolded, nonubiquinated substrates. In this study, we examine the effect of PA700 on the aggregation of wild-type and A53T mutant alpha-synuclein. PA700 inhibits both wild-type and A53T alpha-synuclein fibril formation as measured by Thioflavin T fluorescence. Using size exclusion chromatography, we present evidence for a stable PA700-alpha-synuclein complex. Sedimentation analyses reveal that PA700 sequesters alpha-synuclein in an assembly incompetent form. Analysis of the morphology of wild-type and A53T alpha-synuclein aggregates during the course of fibrillization by electron microscopy demonstrate the formation of amyloid-like fibrils. Secondary structure analyses of wild-type and A53T alpha-synuclein assembled in the presence of PA700 revealed a decrease in the overall amount of assembled alpha-synuclein with no significant change in protein conformation. Thus, PA700 acts on alpha-synuclein assembly and not on the structure of fibrils. We hypothesize that PA700 sequesters alpha-synuclein oligomeric species that are the precursors of the fibrillar form of the protein, thus preventing its assembly into fibrils.

PANIC: current status

NASA Astrophysics Data System (ADS)

Cárdenas, M. C.; Rodríguez Gómez, J.

2011-11-01

PANIC, the PAnoramic Near Infrared Camera, is a new instrument for Calar Alto Observatory (CAHA) is a wide-field infraredimager for the CAHA 2.2 m and 3.5 m telescopes. The optics is a folded single optical train, pure lens optics, with a pixel scale of 0.45 arcsec/pixel (18 microns) at the 2.2 m telescope and 0.23 arcsec/pixel at the 3.5 m. A mosaic of four Hawaii-2RG detectorsprovides a field of view (FOV) of 0.5x0.5 degrees and 0.25x0.25 degrees, respectively. It will cover the photometric bandsfrom Z to K_s (0.8 to 2.5 microns) with a low thermal background due to cold stops. Here we present the current status of the project.

Current Status of On-Site Wastewater Management

ERIC Educational Resources Information Center

Senn, Charles L.

1978-01-01

Wastewater management is becoming an important environmental issue nationally. This article reports the history and current status of wastewater management. Regulatory programs are discussed with specific state examples. Needs assessment is also included. (MA)

PaR-PaR Laboratory Automation Platform

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

Linshiz, G; Stawski, N; Poust, S

2013-05-01

Labor-intensive multistep biological tasks, such as the construction and cloning of DNA molecules, are prime candidates for laboratory automation. Flexible and biology-friendly operation of robotic equipment is key to its successful integration in biological laboratories, and the efforts required to operate a robot must be much smaller than the alternative manual lab work. To achieve these goals, a simple high-level biology-friendly robot programming language is needed. We have developed and experimentally validated such a language: Programming a Robot (PaR-PaR). The syntax and compiler for the language are based on computer science principles and a deep understanding of biological workflows. PaR-PaRmore » allows researchers to use liquid-handling robots effectively, enabling experiments that would not have been considered previously. After minimal training, a biologist can independently write complicated protocols for a robot within an hour. Adoption of PaR-PaR as a standard cross-platform language would enable hand-written or software-generated robotic protocols to be shared across laboratories.« less

PaR-PaR laboratory automation platform.

PubMed

Linshiz, Gregory; Stawski, Nina; Poust, Sean; Bi, Changhao; Keasling, Jay D; Hillson, Nathan J

2013-05-17

Labor-intensive multistep biological tasks, such as the construction and cloning of DNA molecules, are prime candidates for laboratory automation. Flexible and biology-friendly operation of robotic equipment is key to its successful integration in biological laboratories, and the efforts required to operate a robot must be much smaller than the alternative manual lab work. To achieve these goals, a simple high-level biology-friendly robot programming language is needed. We have developed and experimentally validated such a language: Programming a Robot (PaR-PaR). The syntax and compiler for the language are based on computer science principles and a deep understanding of biological workflows. PaR-PaR allows researchers to use liquid-handling robots effectively, enabling experiments that would not have been considered previously. After minimal training, a biologist can independently write complicated protocols for a robot within an hour. Adoption of PaR-PaR as a standard cross-platform language would enable hand-written or software-generated robotic protocols to be shared across laboratories.

Characterization of biocenoses in the storage reservoirs of liquid radioactive wastes of Mayak PA. Initial descriptive report.

PubMed

Pryakhin, E A; Mokrov, Yu G; Tryapitsina, G A; Ivanov, I A; Osipov, D I; Atamanyuk, N I; Deryabina, L V; Shaposhnikova, I A; Shishkina, E A; Obvintseva, N A; Egoreichenkov, E A; Styazhkina, E V; Osipova, O F; Mogilnikova, N I; Andreev, S S; Tarasov, O V; Geras'kin, S A; Trapeznikov, A V; Akleyev, A V

2016-01-01

As a result of operation of the Mayak Production Association (Mayak PA), Chelyabinsk Oblast, Russia, an enterprise for production and separation of weapon-grade plutonium in the Soviet Union, ecosystems of a number of water bodies have been radioactively contaminated. The article presents information about the current state of ecosystems of 6 special industrial storage reservoirs of liquid radioactive waste from Mayak PA: reservoirs R-3, R-4, R-9, R-10, R-11 and R-17. At present the excess of the radionuclide content in the water of the studied reservoirs and comparison reservoirs (Shershnyovskoye and Beloyarskoye reservoirs) is 9 orders of magnitude for (90)Sr and (137)Cs, and 6 orders of magnitude for alpha-emitting radionuclides. According to the level of radioactive contamination, the reservoirs of the Mayak PA could be arranged in the ascending order as follows: R-11, R-10, R-4, R-3, R-17 and R-9. In 2007-2012 research of the status of the biocenoses of these reservoirs in terms of phytoplankton, zooplankton, bacterioplankton, zoobenthos, aquatic plants, ichthyofauna, avifauna parameters was performed. The conducted studies revealed decrease in species diversity in reservoirs with the highest levels of radioactive and chemical contamination. This article is an initial descriptive report on the status of the biocenoses of radioactively contaminated reservoirs of the Mayak PA, and is the first article in a series of publications devoted to the studies of the reaction of biocenoses of the fresh-water reservoirs of the Mayak PA to a combination of natural and man-made factors, including chronic radiation exposure. Copyright © 2015 Elsevier Ltd. All rights reserved.

[Expressions of EMMPRIN and its ligand CyPA in gingival crevicular fluid of chronic periodontitis patients].

PubMed

He, Yan-ping; Xie, Ming; Jiao, Ting

2016-02-01

To detect the expressions of EMMPRIN and its ligand CyPA in gingival crevicular fluid (GCF) of chronic periodontitis (CP) patients and explore their possible relation to the status of periodontal inflammation. GCF of CP patients (group CP) and periodontitis-free patients with intact dentition (the control group) were collected and assayed for EMMPRIN and CyPA expressions by ELISA. The clinical periodontal status of these patients were examined. Statistical analysis was performed by use of SPSS 17.0 software package. Spearman's correlation analysis was utilized to determine the relationships between the expressions of EMMPRIN and CyPA in GCF and the clinical parameters. In addition, analysis of variance (ANOVA) was used for comparing the difference between group CP and the control group. In group CP, GCF volume was positively correlated with EMMPRIN total amount, CyPA total amount and some clinical periodontal indexes (GI,SBI,AL). EMMPRIN total amount was positively correlated with GCF volume, CyPA total amount and some of clinical periodontal indexes (GI,SBI,AL), but it was negatively correlated with smoking status (P<0.05). Moreover, CyPA total amount was positively correlated with GCF volume, EMMPRIN total amount and some of clinical periodontal indexes (GI,SBI,AL). In the control group,there were significant positive correlations among GCF volume, EMMPRIN total amount and CyPA total amount. The difference of GCF, EMMPRIN and CyPA between the 2 groups were statistically significant (P<0.05). EMMPRIN and its ligand CyPA in GCF of periodontitis-free patients with intact dentition and CP patients were all detected. As the progress of periodontal inflammation, GCF secretion increases, as well as the expressions of EMMPRIN and CyPA in GCF.

Marginal regression approach for additive hazards models with clustered current status data.

PubMed

Su, Pei-Fang; Chi, Yunchan

2014-01-15

Current status data arise naturally from tumorigenicity experiments, epidemiology studies, biomedicine, econometrics and demographic and sociology studies. Moreover, clustered current status data may occur with animals from the same litter in tumorigenicity experiments or with subjects from the same family in epidemiology studies. Because the only information extracted from current status data is whether the survival times are before or after the monitoring or censoring times, the nonparametric maximum likelihood estimator of survival function converges at a rate of n(1/3) to a complicated limiting distribution. Hence, semiparametric regression models such as the additive hazards model have been extended for independent current status data to derive the test statistics, whose distributions converge at a rate of n(1/2) , for testing the regression parameters. However, a straightforward application of these statistical methods to clustered current status data is not appropriate because intracluster correlation needs to be taken into account. Therefore, this paper proposes two estimating functions for estimating the parameters in the additive hazards model for clustered current status data. The comparative results from simulation studies are presented, and the application of the proposed estimating functions to one real data set is illustrated. Copyright © 2013 John Wiley & Sons, Ltd.

[Effect of Sijunzi Decoction and enteral nutrition on T-cell subsets and nutritional status in patients with gastric cancer after operation: a randomized controlled trial].

PubMed

Cai, Jun; Wang, Hua; Zhou, Sheng; Wu, Bin; Song, Hua-Rong; Xuan, Zheng-Rong

2008-01-01

To observe the effect of perioperative application of Sijunzi Decoction and enteral nutrition on T-cell subsets and nutritional status in patients with gastric cancer after operation. In this prospective, single-blinded, controlled clinical trial, fifty-nine patients with gastric cancer were randomly divided into three groups: control group (n=20) and two study groups (group A, n=21; group B, n=18). Sjunzi Decoction (100 ml) was administered via nasogastric tube to the patients in the study group B from the second postoperation day to the 9th postoperation day. Patients in the two study groups were given an isocaloric and isonitrogonous enteral diet, which was started on the second day after operation, and continued for eight days. Patients in the control group were given an isocaloric and isonitrogonous parenteral diet for 9 days. All variables of nutritional status such as serum albumin (ALB), prealbumin (PA), transferrin (TRF) and T-cell subsets were measured one day before operation, and one day and 10 days after operation. All the nutritional variables and the levels of CD3(+), CD4(+), CD4(+)/CD8(+) were decreased significantly after operation. Ten days after operation, T-cell subsets and nutritional variables in the two study groups were increased as compare with the control group. The levels of ALB, TRF and T-cell subsets in the study group B were increased significantly as compared with the study group A (P<0.05). Enteral nutrition assisted with Sijunzi Decoction can positively improve and optimize cellular immune function and nutritional status in the patients with gastric cancer after operation.

Evaluation of ID-PaGIA syphilis antibody test.

PubMed

Naaber, Paul; Makoid, Ene; Aus, Anneli; Loivukene, Krista; Poder, Airi

2009-01-01

Laboratory diagnosis of syphilis is usually accomplished by serology. There are currently a large number of different commercial treponemal tests available that vary in format, sensitivity and specificity. To evaluate the ID-PaGIA Syphilis Antibody Test as an alternative to other specific treponemal tests for primary screening or confirmation of diagnosis. Serum samples from healthy adults (n = 100) were used for detection of specificity of ID-PaGIA. To evaluate sensitivity of ID-PaGIA serum samples (n = 101) from patients with confirmed or suspected syphilis were tested for syphilis antibodies with FTA-Abs IgM, ID-PaGIA, ELISA IgM and TPHA tests. No false-positive results were found with ID-PaGIA. Sensitivity of various treponemal tests was the following: FTA-Abs IgM: 95.5%, ID-PaGIA and ELISA IgM: 94%, and TPHA 75%. The positive and negative predictive values of ID-PaGIA were 100 and 89.5%, respectively. Compared with other treponemal tests ID-PaGIA has excellent sensitivity and specificity.

GSK-3β inhibitor TWS119 attenuates rtPA-induced hemorrhagic transformation and activates the Wnt/β-catenin signaling pathway after acute ischemic stroke in rats.

PubMed

Wang, Wei; Li, Mingchang; Wang, Yuefei; Li, Qian; Deng, Gang; Wan, Jieru; Yang, Qingwu; Chen, Qianxue; Wang, Jian

2016-12-01

Hemorrhagic transformation (HT) is a devastating complication for patients with acute ischemic stroke who are treated with tissue plasminogen activator (tPA). It is associated with high morbidity and mortality, but no effective treatments are currently available to reduce HT risk. Therefore, methods to prevent HT are urgently needed. In this study, we used TWS119, an inhibitor of glycogen synthase kinase 3β (GSK-3β), to evaluate the role of the Wnt/β-catenin signaling pathway in recombinant tPA (rtPA)-induced HT. Sprague-Dawley rats were subjected to a middle cerebral artery occlusion (MCAO) model of ischemic stroke and then were administered rtPA, rtPA combined with TWS119, or vehicle at 4 h. The animals were sacrificed 24 h after infarct induction. Rats treated with rtPA showed evident HT, had more severe neurologic deficit, brain edema, and blood-brain barrier breakdown, and had larger infarction volume than did the vehicle group. Rats treated with TWS119 had significantly improved outcomes compared with those of rats treated with rtPA alone. In addition, Western blot analysis showed that TWS119 increased the protein expression of β-catenin, claudin-3, and ZO-1 while suppressing the expression of GSK-3β. These results suggest that TWS119 reduces rtPA-induced HT and attenuates blood-brain barrier disruption, possibly through activation of the Wnt/β-catenin signaling pathway. This study provides a potential therapeutic strategy to prevent tPA-induced HT after acute ischemic stroke.

Expression profiling of FLOWERING LOCUS T-like gene in alternate bearing 'Hass' avocado trees suggests a role for PaFT in avocado flower induction.

PubMed

Ziv, Dafna; Zviran, Tali; Zezak, Oshrat; Samach, Alon; Irihimovitch, Vered

2014-01-01

In many perennials, heavy fruit load on a shoot decreases the ability of the plant to undergo floral induction in the following spring, resulting in a pattern of crop production known as alternate bearing. Here, we studied the effects of fruit load on floral determination in 'Hass' avocado (Persea americana). De-fruiting experiments initially confirmed the negative effects of fruit load on return to flowering. Next, we isolated a FLOWERING LOCUS T-like gene, PaFT, hypothesized to act as a phloem-mobile florigen signal and examined its expression profile in shoot tissues of on (fully loaded) and off (fruit-lacking) trees. Expression analyses revealed a strong peak in PaFT transcript levels in leaves of off trees from the end of October through November, followed by a return to starting levels. Moreover and concomitant with inflorescence development, only off buds displayed up-regulation of the floral identity transcripts PaAP1 and PaLFY, with significant variation being detected from October and November, respectively. Furthermore, a parallel microscopic study of off apical buds revealed the presence of secondary inflorescence axis structures that only appeared towards the end of November. Finally, ectopic expression of PaFT in Arabidopsis resulted in early flowering transition. Together, our data suggests a link between increased PaFT expression observed during late autumn and avocado flower induction. Furthermore, our results also imply that, as in the case of other crop trees, fruit-load might affect flowering by repressing the expression of PaFT in the leaves. Possible mechanism(s) by which fruit crop might repress PaFT expression, are discussed.

Current status of the HIBMC and results of representative diseases

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

Murakami, Masao; Demizu, Yusuke; Niwa, Yasue

2009-07-25

The proton radiotherapy (PRT) has been spreading, since 1990 when 250 MeV proton beams with rotation gantry was developed for medical use. On the other hand, carbon-ion radiotherapy (CRT) that has both physical and biological features is available at 4 facilities in the world. HIBMC is the only facility to be able to use both particles. From Apr 2001 to Dec 2008, 2486 patients were treated with PRT in 2030 patients or with CRT in 456. Treatment to the Head and Neck (H and N: in 405 patients), the lung (245), the liver (371), and the prostatic carcinoma (1059) wasmore » a major subject. The 2-year local control rates is 72% in H and N (n = 163, T1:9, T2:18, T3:36, T4:79, malignant melanoma 48, adenoid cystic carcinoma 35, squamous cell carcinoma (SCC) 32, adenocarcinoma 14, others 34), 88% in lung (n = 116, T1:59, T2:42, T3:4, T4:6, SCC 30, adenocarcinoma 59, others 27), and 89% in liver cancer (n = 153, Proton: 130, carbon: 23). Biochemical disease free 3-year survival of 291 prostate cancer is 100% in 9 patients with initial prostate-specific antigen (PSA) level < = 4 ng/ml, 99% in 140 with PSA 4.1-10 ng/ml, 90% in 71 with PSA 10.1-20 ng/ml, and 79% in 71 with PSA>20 ng/ml. These results are excellent comparable or superior to those of surgery. Thus, particle therapy is sophisticated radiotherapy, however the only problem to prohibit the progress is high costs for construction and maintenance. Facilities at which both proton and carbon ion beams can be used, including the HIBMC, have to investigate the differential use. We started clinical randomized trial to compare both ion beams, and started biological examinations in a project aiming at the development of a laser driven proton radiotherapy. We stated about the current status of the HIBMC and the results of representative diseases.« less

Current status of the HIBMC and results of representative diseases

NASA Astrophysics Data System (ADS)

Murakami, Masao; Demizu, Yusuke; Niwa, Yasue; Miyawaki, Daisuke; Terashima, Kazuki; Arimura, Takeshi; Mima, Masayuki; Nagayama, Shinichi; Maeda, Takuya; Baba, Masashi; Akagi, Takashi; Hishikawa, Yoshio; Abe, Mitsuyuki

2009-07-01

The proton radiotherapy (PRT) has been spreading, since 1990 when 250 MeV proton beams with rotation gantry was developed for medical use. On the other hand, carbon-ion radiotherapy (CRT) that has both physical and biological features is available at 4 facilities in the world. HIBMC is the only facility to be able to use both particles. From Apr 2001 to Dec 2008, 2486 patients were treated with PRT in 2030 patients or with CRT in 456. Treatment to the Head and Neck (H&N: in 405 patients), the lung (245), the liver (371), and the prostatic carcinoma (1059) was a major subject. The 2-year local control rates is 72% in H&N (n = 163, T1:9, T2:18, T3:36, T4:79, malignant melanoma 48, adenoid cystic carcinoma 35, squamous cell carcinoma (SCC) 32, adenocarcinoma 14, others 34), 88% in lung (n = 116, T1:59, T2:42, T3:4, T4:6, SCC 30, adenocarcinoma 59, others 27), and 89% in liver cancer (n = 153, Proton: 130, carbon: 23). Biochemical disease free 3-year survival of 291 prostate cancer is 100% in 9 patients with initial prostate-specific antigen (PSA) level < = 4 ng/ml, 99% in 140 with PSA 4.1-10 ng/ml, 90% in 71 with PSA 10.1-20 ng/ml, and 79% in 71 with PSA>20 ng/ml. These results are excellent comparable or superior to those of surgery. Thus, particle therapy is sophisticated radiotherapy, however the only problem to prohibit the progress is high costs for construction and maintenance. Facilities at which both proton and carbon ion beams can be used, including the HIBMC, have to investigate the differential use. We started clinical randomized trial to compare both ion beams, and started biological examinations in a project aiming at the development of a laser driven proton radiotherapy. We stated about the current status of the HIBMC and the results of representative diseases.

Next Generation Access Network Deployment in Croatia: Optical Access Networks and Current IoT/5G Status

NASA Astrophysics Data System (ADS)

Breskovic, Damir; Sikirica, Mladen; Begusic, Dinko

2018-05-01

This paper gives an overview and background of optical access network deployment in Croatia. Optical access network development in Croatia has been put into a global as well as in the European Union context. All the challenges and the driving factors for optical access networks deployment are considered. Optical access network architectures that have been deployed by most of the investors in Croatian telecommunication market are presented, as well as the architectures that are in early phase of deployment. Finally, an overview on current status of mobile networks of the fifth generation and Internet of Things is given.

Bullied Status and Physical Activity in Texas Adolescents.

PubMed

Case, Kathleen R; Pérez, Adriana; Saxton, Debra L; Hoelscher, Deanna M; Springer, Andrew E

2016-06-01

This study examined the association between having been bullied at school during the past 6 months ("bullied status") and not meeting physical activity (PA) recommendations of 60 minutes of daily PA during the past week among 8th- and 11th-grade Texas adolescents. Multiple logistic regression analysis was conducted to examine this association, adjusted for weight status, grade, race/ethnicity, and stratified by gender; furthermore, a significant interaction was found between bullied status and weight status. Results are presented by interaction status. Results indicated that overweight girls who reported never being bullied, as well as those who reported being bullied more than twice, had higher odds of not meeting PA recommendations than normal weight girls who were never bullied (adjusted odds ratio [AOR] = 2.12, 95% confidence interval [CI: 1.12, 3.99]; AOR = 9.18, 95% CI [2.26, 37.27], respectively). Obese girls who were bullied once or twice had higher odds of not meeting PA recommendations than normal weight girls who were never bullied (AOR = 2.89, 95% CI [1.06, 7.89]). Overweight boys who reported never being bullied had lower odds of not meeting PA recommendations than normal weight boys who were never bullied (AOR = 0.62, 95% CI [0.39, 0.97]). Conversely, obese boys who were bullied once or twice reported higher odds of not meeting PA recommendations than normal weight boys who were never bullied (AOR = 3.61, 95% CI [1.22, 10.67]). Findings from this study indicate that the association between bullied status and meeting PA recommendations is complex and may differ by gender and the interaction between bullied status and weight status. © 2015 Society for Public Health Education.

The MAJORANA DEMONSTRATOR for 0νββ: Current Status and Future Plans

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

Green, M. P.; Abgrall, N.; Aguayo, Estanislao

2015-03-24

The Majorana Demonstrator will search for neutrinoless-double-beta decay in 76Ge, while establishing the feasibility of a future tonne-scale germanium-based neutrinoless-double-beta decay experiment, and performing searches for new physics beyond the Standard Model. The experiment, currently under construction at the Sanford Underground Research Facility in Lead, SD, will consist of a pair of modular high-purity germanium detector arrays housed inside of a compact copper, lead, and polyethylene shield. Through a combination of strict materials qualifications and assay, low-background design, and powerful background rejection techniques, the Demonstrator aims to achieve a background rate in the neutrinoless-double-beta decay region of interest (ROI) ofmore » no more than 3cnts/(ROI-t-y). The current status of the Demonstrator is discussed, as are plans for its completion.« less

The Majorana Demonstrator for 0νββ: Current Status and Future Plans

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

Green, Matthew P.; Avignone, F. T.; Bertrand, Jr, Fred E

2015-01-01

The Majorana Demonstrator will search for neutrinoless-double-beta decay (0νββ) in 76Ge, while establishing the feasibility of a future tonne-scale germanium-based 0νββ experiment, and performing searches for new physics beyond the Standard Model. The experiment, currently under construction at the Sanford Underground Research Facility in Lead, SD, will consist of a pair of modular high-purity germanium detector arrays housed inside of a compact copper, lead, and polyethylene shield. Through a combination of strict materials qualifications and assay, low-background design, and powerful background rejection techniques, the Demonstrator aims to achieve a background rate in the 0νββ region of interest (ROI) of nomore » more than 3cnts/(ROI-t-y). The current status of the Demonstrator is discussed, as are plans for its completion.« less

Free Fatty Acid Effects on the Atrial Myocardium: Membrane Ionic Currents Are Remodeled by the Disruption of T-Tubular Architecture.

PubMed

O'Connell, Ryan P; Musa, Hassan; Gomez, Mario San Martin; Avula, Uma Mahesh; Herron, Todd J; Kalifa, Jerome; Anumonwo, Justus M B

2015-01-01

Epicardial adiposity and plasma levels of free fatty acids (FFAs) are elevated in atrial fibrillation, heart failure and obesity, with potentially detrimental effects on myocardial function. As major components of epicardial fat, FFAs may be abnormally regulated, with a potential to detrimentally modulate electro-mechanical function. The cellular mechanisms underlying such effects of FFAs are unknown. To determine the mechanisms underlying electrophysiological effects of palmitic (PA), stearic (SA) and oleic (OA) FFAs on sheep atrial myocytes. We used electrophysiological techniques, numerical simulations, biochemistry and optical imaging to examine the effects of acutely (≤ 15 min), short-term (4-6 hour) or 24-hour application of individual FFAs (10 μM) on isolated ovine left atrial myocytes (LAMs). Acute and short-term incubation in FFAs resulted in no differences in passive or active properties of isolated left atrial myocytes (LAMs). 24-hour application had differential effects depending on the FFA. PA did not affect cellular passive properties but shortened (p<0.05) action potential duration at 30% repolarization (APD30). APD50 and APD80 were unchanged. SA had no effect on resting membrane potential but reduced membrane capacitance by 15% (p<0.05), and abbreviated APD at all values measured (p≤0.001). OA did not significantly affect passive or active properties of LAMs. Measurement of the major voltage-gated ion channels in SA treated LAMs showed a ~60% reduction (p<0.01) of the L-type calcium current (ICa-L) and ~30% reduction (p<0.05) in the transient outward potassium current (ITO). A human atrial cell model recapitulated SA effects on APD. Optical imaging showed that SA incubated for 24 hours altered t-tubular structure in isolated cells (p<0.0001). SA disrupts t-tubular architecture and remodels properties of membrane ionic currents in sheep atrial myocytes, with potential implications in arrhythmogenesis.

Current status of accreditation for drug testing in hair.

PubMed

Cooper, Gail; Moeller, Manfred; Kronstrand, Robert

2008-03-21

At the annual meeting of the Society of Hair Testing in Vadstena, Sweden in 2006, a committee was appointed to address the issue of guidelines for hair testing and to assess the current status of accreditation amongst laboratories offering drug testing in hair. A short questionnaire was circulated amongst the membership and interested parties. Fifty-two responses were received from hair testing laboratories providing details on the amount and type of hair tests they offered and the status of accreditation within their facilities. Although the vast majority of laboratories follow current guidelines (83%), only nine laboratories were accredited to ISO/IEC 17025 for hair testing. A significant number of laboratories reporting that they were in the process of developing quality systems with a view to accrediting their methods within 2-3 years. This study provides an insight into the status of accreditation in hair testing laboratories and supports the need for guidelines to encourage best practice.

Quantile Regression Models for Current Status Data

PubMed Central

Ou, Fang-Shu; Zeng, Donglin; Cai, Jianwen

2016-01-01

Current status data arise frequently in demography, epidemiology, and econometrics where the exact failure time cannot be determined but is only known to have occurred before or after a known observation time. We propose a quantile regression model to analyze current status data, because it does not require distributional assumptions and the coefficients can be interpreted as direct regression effects on the distribution of failure time in the original time scale. Our model assumes that the conditional quantile of failure time is a linear function of covariates. We assume conditional independence between the failure time and observation time. An M-estimator is developed for parameter estimation which is computed using the concave-convex procedure and its confidence intervals are constructed using a subsampling method. Asymptotic properties for the estimator are derived and proven using modern empirical process theory. The small sample performance of the proposed method is demonstrated via simulation studies. Finally, we apply the proposed method to analyze data from the Mayo Clinic Study of Aging. PMID:27994307

Expression Profiling of FLOWERING LOCUS T-Like Gene in Alternate Bearing ‘Hass' Avocado Trees Suggests a Role for PaFT in Avocado Flower Induction

PubMed Central

Ziv, Dafna; Zviran, Tali; Zezak, Oshrat; Samach, Alon; Irihimovitch, Vered

2014-01-01

In many perennials, heavy fruit load on a shoot decreases the ability of the plant to undergo floral induction in the following spring, resulting in a pattern of crop production known as alternate bearing. Here, we studied the effects of fruit load on floral determination in ‘Hass' avocado (Persea americana). De-fruiting experiments initially confirmed the negative effects of fruit load on return to flowering. Next, we isolated a FLOWERING LOCUS T-like gene, PaFT, hypothesized to act as a phloem-mobile florigen signal and examined its expression profile in shoot tissues of on (fully loaded) and off (fruit-lacking) trees. Expression analyses revealed a strong peak in PaFT transcript levels in leaves of off trees from the end of October through November, followed by a return to starting levels. Moreover and concomitant with inflorescence development, only off buds displayed up-regulation of the floral identity transcripts PaAP1 and PaLFY, with significant variation being detected from October and November, respectively. Furthermore, a parallel microscopic study of off apical buds revealed the presence of secondary inflorescence axis structures that only appeared towards the end of November. Finally, ectopic expression of PaFT in Arabidopsis resulted in early flowering transition. Together, our data suggests a link between increased PaFT expression observed during late autumn and avocado flower induction. Furthermore, our results also imply that, as in the case of other crop trees, fruit-load might affect flowering by repressing the expression of PaFT in the leaves. Possible mechanism(s) by which fruit crop might repress PaFT expression, are discussed. PMID:25330324

Transcranial direct current stimulation (tDCS) and language

PubMed Central

Monti, Alessia; Ferrucci, Roberta; Fumagalli, Manuela; Mameli, Francesca; Cogiamanian, Filippo; Ardolino, Gianluca; Priori, Alberto

2013-01-01

Transcranial direct current stimulation (tDCS), a non-invasive neuromodulation technique inducing prolonged brain excitability changes and promoting cerebral plasticity, is a promising option for neurorehabilitation. Here, we review progress in research on tDCS and language functions and on the potential role of tDCS in the treatment of post-stroke aphasia. Currently available data suggest that tDCS over language-related brain areas can modulate linguistic abilities in healthy individuals and can improve language performance in patients with aphasia. Whether the results obtained in experimental conditions are functionally important for the quality of life of patients and their caregivers remains unclear. Despite the fact that important variables are yet to be determined, tDCS combined with rehabilitation techniques seems a promising therapeutic option for aphasia. PMID:23138766

The Current Status on the Overseas Development of Magnetic Suspension Railroads,

DTIC Science & Technology

1986-02-04

country appears to make all possible efforts to gain new technologies. Technologies obtained during the development stages are being applied to other...lQ63-A - 224 & FOREIGN TECHNOLOGY DIVISION IV-. THE CURRENT STATUS ON THE OVERSEAS DEVELOPMENT OF MAGNETIC SUSPENSION RAILROADS by Yoshiyasu 1Kyani...86 MICOFIHE R:FTD-86-C-001454 IV. THE CURRENT STATUS ON THE OVERSEAS DEVELOPMENT OF MAGNETIC SUSPENSION RAILROADS By: Yoshiyasu Kyotani English pages

Physiological regulation of MMPs and tPA/PAI in the arterial wall of rats by noradrenergic tone and angiotensin II.

PubMed

Dab, Houcine; Hachani, Rafik; Dhaouadi, Nedra; Hodroj, Wassim; Sakly, Mohsen; Randon, Jacques; Bricca, Giampiero; Kacem, Kamel

2012-03-01

The interactions between the sympathetic nervous system (SNS) and angiotensin II (ANG II), and their direct effects in vitro on the enzymes involved in vascular extracellular matrix (ECM) degradation, were examined. Rats were treated with guanethidine, losartan or the combined treatments. mRNA, protein and activity of matrix metalloproteinase (MMP)-2 and MMP-9 and mRNA of tissue plasminogen activator (t-PA) and plasminogen activator inhibitor 1 (PAI-1) were quantified in abdominal aorta (AA) and femoral artery (FA). Norepinephrine (NE) or ANG II with adrenergic (β, α1 and α2) or losartan antagonists was tested for MMP mRNA response in cultured vascular smooth muscle cells (VSMCs). Combined treatment enhances the inhibition of MMP-2 mRNA and protein level induced by simple treatment in AA. However MMP-9 in AA and MMP mRNA in FA were reduced in the same order by treatments. MMP activities were not affected by treatments. The t-PA/PAI-1 ratio, which reflects the fibrinolytic balance, remained higher after treatments. In cultured VSMCs, NE induced stimulation of MMP mRNA via α2 and β adrenergic receptors and MMP-2 activity via β adrenergic receptors, while ANG II-induced stimulation was abrogated by losartan. Overall, there is a synergic inhibition of both systems on the level of MMP-2 in AA.

Biological variation in tPA-induced plasma clot lysis time.

PubMed

Talens, Simone; Malfliet, Joyce J M C; Rudež, Goran; Spronk, Henri M H; Janssen, Nicole A H; Meijer, Piet; Kluft, Cornelis; de Maat, Moniek P M; Rijken, Dingeman C

2012-10-01

Hypofibrinolysis is a risk factor for venous and arterial thrombosis, and can be assessed by using a turbidimetric tPA-induced clot lysis time (CLT) assay. Biological variation in clot lysis time may affect the interpretation and usefulness of CLT as a risk factor for thrombosis. Sufficient information about assay variation and biological variation in CLT is not yet available. Thus, this study aimed to determine the analytical, within-subject and between-subject variation in CLT. We collected blood samples from 40 healthy individuals throughout a period of one year (average 11.8 visits) and determined the CLT of each plasma sample in duplicate. The mean (± SD) CLT was 83.8 (± 11.1) minutes. The coefficients of variation for total variation, analytical variation, within-subject variation and between-subject variation were 13.4%, 2.6%, 8.2% and 10.2%, respectively. One measurement can estimate the CLT that does not deviate more than 20% from its true value. The contribution of analytical variation to the within-subject variation was 5.0%, the index of individuality was 0.84 and the reference change value was 23.8%. The CLT was longer in the morning compared to the afternoon and was slightly longer in older individuals (> 40 years) compared to younger (≤40 years) individuals. There was no seasonal variation in CLT and no association with air pollution. CLT correlated weakly with fibrinogen, C-reactive protein, prothrombin time and thrombin generation. This study provides insight into the biological variation of CLT, which can be used in future studies testing CLT as a potential risk factor for thrombosis.

Detection of anthrax protective antigen (PA) using europium labeled anti-PA monoclonal antibody and time-resolved fluorescence ◊

PubMed Central

Stoddard, Robyn A.; Quinn, Conrad P.; Schiffer, Jarad M.; Boyer, Anne E.; Goldstein, Jason; Bagarozzi, Dennis A.; Soroka, Stephen D.; Dauphin, Leslie A.; Hoffmaster, Alex R.

2015-01-01

Inhalation anthrax is a rare but acute infectious disease following adsorption of Bacillus anthracis spores through the lungs. The disease has a high fatality rate if untreated, but early and correct diagnosis has a significant impact on case patient recovery. The early symptoms of inhalation anthrax are, however, non-specific and current anthrax diagnostics are primarily dependent upon culture and confirmatory real-time PCR. Consequently, there may be a significant delay in diagnosis and targeted treatment. Rapid, culture-independent diagnostic tests are therefore needed, particularly in the context of a large scale emergency response. The aim of this study was to evaluate the ability of monoclonal antibodies to detect anthrax toxin proteins that are secreted early in the course of B. anthracis infection using a time-resolved fluorescence (TRF) immunoassay. We selected monoclonal antibodies that could detect protective antigen (PA), as PA83 and also PA63 and LF in the lethal toxin complex. The assay reliable detection limit (RDL) was 6.63 × 10−6 μM (0.551 ng/ml) for PA83 and 2.51 × 10−5 μM (1.58 ng/ml) for PA63. Despite variable precision and accuracy of the assay, PA was detected in 9 out of 10 sera samples from anthrax confirmed case patients with cutaneous (n=7), inhalation (n=2), and gastrointestinal (n=1) disease. Anthrax Immune Globulin (AIG), which has been used in treatment of clinical anthrax, interfered with detection of PA. This study demonstrates a culture-independent method of diagnosing anthrax through use of monoclonal antibodies to detect PA and LF in the lethal toxin complex. PMID:24857756

Chemical Reaction Engineering: Current Status and Future Directions.

ERIC Educational Resources Information Center

Dudukovic, M. P.

1987-01-01

Describes Chemical Reaction Engineering (CRE) as the discipline that quantifies the interplay of transport phenomena and kinetics in relating reactor performance to operating conditions and input variables. Addresses the current status of CRE in both academic and industrial settings and outlines future trends. (TW)

The c.1364C>A (p.A455E) Mutation in the CFTR Pseudogene Results in an Incorrectly Assigned Carrier Status by a Commonly Used Screening Platform.

PubMed

Deeb, Kristin K; Metcalf, James D; Sesock, Kaitlin M; Shen, Junqing; Wensel, Christine A; Rippel, Larisa I; Smith, Michelle; Chapman, Mark S; Zhang, Shulin

2015-07-01

Cystic fibrosis (CF) is one of the most common recessive conditions among whites, with an estimated carrier frequency of 1 in 25 in the United States. Population-based CF carrier screening was implemented in the United States in 2001. The number of mutations screened by each laboratory may vary; however, the 23 most common CF mutations recommended for screening by the American College of Medical Genetics and American College of Obstetricians and Gynecologists are included in all platforms. The c.1364C>A (p.A455E) mutation located in exon 10 of the CFTR gene is one of the 23 mutations. Because CFTR exon 10 and its flanking intronic regions are duplicated and transposed onto several other chromosomes of the human genome during evolution and function as unprocessed pseudogenes, variations in the CFTR pseudogenes may confound CF screening results for mutations located in exon 10 of the CFTR gene. We report an incorrectly identified carrier status for the c.1364C>A (p.A455E) mutation in a healthy individual using the Hologic InPlex CF assay. Further analysis revealed that the mutation resides in one of the CFTR pseudogenes. Because most commercial kits and laboratory-developed tests for CF carrier screening involve a short amplicon encompassing this mutation, this finding suggests that individuals with the c.1364C>A (p.A455E) mutation may require further investigation to avoid a false assignment of CF carrier status. Copyright © 2015 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

Drugs in development for toxoplasmosis: advances, challenges, and current status.

PubMed

Alday, P Holland; Doggett, Joseph Stone

2017-01-01

Toxoplasma gondii causes fatal and debilitating brain and eye diseases. Medicines that are currently used to treat toxoplasmosis commonly have toxic side effects and require prolonged courses that range from weeks to more than a year. The need for long treatment durations and the risk of relapsing disease are in part due to the lack of efficacy against T. gondii tissue cysts. The challenges for developing a more effective treatment for toxoplasmosis include decreasing toxicity, achieving therapeutic concentrations in the brain and eye, shortening duration, eliminating tissue cysts from the host, safety in pregnancy, and creating a formulation that is inexpensive and practical for use in resource-poor areas of the world. Over the last decade, significant progress has been made in identifying and developing new compounds for the treatment of toxoplasmosis. Unlike clinically used medicines that were repurposed for toxoplasmosis, these compounds have been optimized for efficacy against toxoplasmosis during preclinical development. Medicines with enhanced efficacy as well as features that address the unique aspects of toxoplasmosis have the potential to greatly improve toxoplasmosis therapy. This review discusses the facets of toxoplasmosis that are pertinent to drug design and the advances, challenges, and current status of preclinical drug research for toxoplasmosis.

Drugs in development for toxoplasmosis: advances, challenges, and current status

PubMed Central

Alday, P Holland; Doggett, Joseph Stone

2017-01-01

Toxoplasma gondii causes fatal and debilitating brain and eye diseases. Medicines that are currently used to treat toxoplasmosis commonly have toxic side effects and require prolonged courses that range from weeks to more than a year. The need for long treatment durations and the risk of relapsing disease are in part due to the lack of efficacy against T. gondii tissue cysts. The challenges for developing a more effective treatment for toxoplasmosis include decreasing toxicity, achieving therapeutic concentrations in the brain and eye, shortening duration, eliminating tissue cysts from the host, safety in pregnancy, and creating a formulation that is inexpensive and practical for use in resource-poor areas of the world. Over the last decade, significant progress has been made in identifying and developing new compounds for the treatment of toxoplasmosis. Unlike clinically used medicines that were repurposed for toxoplasmosis, these compounds have been optimized for efficacy against toxoplasmosis during preclinical development. Medicines with enhanced efficacy as well as features that address the unique aspects of toxoplasmosis have the potential to greatly improve toxoplasmosis therapy. This review discusses the facets of toxoplasmosis that are pertinent to drug design and the advances, challenges, and current status of preclinical drug research for toxoplasmosis. PMID:28182168

Zinc induces long-term upregulation of T-type calcium current in hippocampal neurons in vivo.

PubMed

Ekstein, Dana; Benninger, Felix; Daninos, Moshe; Pitsch, Julika; van Loo, Karen M J; Becker, Albert J; Yaari, Yoel

2012-11-15

Extracellular zinc can induce numerous acute and persistent physiological and toxic effects in neurons by acting at their plasma membrane or intracellularly following permeation or uptake into them. Zinc acutely and reversibly blocks T-type voltage-gated calcium current (I(CaT)), but the long-term effect of zinc on this current has not been studied. Because chemically induced status epilepticus (SE) results in the release of zinc into the extracellular space, as well as in a long-lasting increase in I(CaT) in CA1 pyramidal cells, we hypothesized that zinc may play a causative role in I(CaT) upregulation. We tested this hypothesis by monitoring for 18 days the effects of zinc and ibotenic acid (a neurotoxic agent serving as control for zinc), injected into the right lateral ventricle, on I(CaT) in rat CA1 pyramidal cells. Both zinc and ibotenic acid caused marked hippocampal lesions on the side of injection, but only minor damage to contralateral hippocampi. Zinc, but not ibotenic acid, caused upregulation of a nickel-sensitive I(CaT) in a subset of contralateral CA1 pyramidal cells, appearing 2 days after injection and lasting for about 2 weeks thereafter. In contrast, acute application of zinc to CA1 pyramidal cells promptly blocked I(CaT). These data indicate that extracellular zinc has a dual effect on I(CaT), blocking it acutely while causing its long-term upregulation. Through the latter effect, zinc may regulate the intrinsic excitability of principal neurons, particularly in pathological conditions associated with enhanced release of zinc, such as SE.

Quantitative proteomics in A30P*A53T α-synuclein transgenic mice reveals upregulation of Sel1l.

PubMed

Yan, Jianguo; Zhang, Pei; Jiao, Fengjuan; Wang, Qingzhi; He, Feng; Zhang, Qian; Zhang, Zheng; Lv, Zexi; Peng, Xiang; Cai, Hongwei; Tian, Bo

2017-01-01

α-Synuclein is an abundantly expressed neuronal protein that is at the center of focus in understanding a group of neurodegenerative disorders called synucleinopathies, which are characterized by the intracellular presence of aggregated α-synuclein. However, the mechanism of α-synuclein biology in synucleinopathies pathogenesis is not fully understood. In this study, mice overexpressing human A30P*A53T α-synuclein were evaluated by a motor behavior test and count of TH-positive neurons, and then two-dimensional liquid chromatography-tandem mass spectrometry coupled with tandem mass tags (TMTs) labeling was employed to quantitatively identify the differentially expressed proteins of substantia nigra pars compacta (SNpc) tissue samples that were obtained from the α-synuclein transgenic mice and wild type controls. The number of SNpc dopaminergic neurons and the motor behavior were unchanged in A30P*A53T transgenic mice at the age of 6 months. Of the 4,715 proteins identified by proteomic techniques, 271 were differentially expressed, including 249 upregulated and 22 downregulated proteins. These alterations were primarily associated with mitochondrial dysfunction, oxidative stress, ubiquitin-proteasome system impairment, and endoplasmic reticulum (ER) stress. Some obviously changed proteins, which were validated by western blotting and immunofluorescence staining, including Sel1l and Sdhc, may be involved in the α-synuclein pathologies of synucleinopathies. A biological pathway analysis of common related proteins showed that the proteins were linked to a total of 31 KEGG pathways. Our findings suggest that these identified proteins may serve as novel therapeutic targets for synucleinopathies.

Cognitive function in older adults according to current socioeconomic status.

PubMed

Zhang, Michael; Gale, Shawn D; Erickson, Lance D; Brown, Bruce L; Woody, Parker; Hedges, Dawson W

2015-01-01

Cognitive function may be influenced by education, socioeconomic status, sex, and health status. Furthermore, aging interacts with these factors to influence cognition and dementia risk in late life. Factors that may increase or decrease successful cognitive aging are of critical importance, particularly if they are modifiable. The purpose of this study was to determine if economic status in late life is associated with cognition independent of socioeconomic status in early life. Cross-sectional demographic, socioeconomic, and cognitive function data were obtained in 2592 older adults (average age 71.6 years) from the Center for Disease Control's National Health and Nutrition Examination Survey (NHANES) and analyzed with linear regression modeling. Cognitive function, as measured with a test of processing speed, was significantly associated with poverty index scores after adjusting for educational attainment as an estimate of childhood socioeconomic status, ethnic background, age, health status, and sex (P < 0.001). Our findings suggest that current economic status is independently associated with cognitive function in adults over age 60 years.

Current Status of Gene Engineering Cell Therapeutics

PubMed Central

Saudemont, Aurore; Jespers, Laurent; Clay, Timothy

2018-01-01

Ex vivo manipulations of autologous patient’s cells or gene-engineered cell therapeutics have allowed the development of cell and gene therapy approaches to treat otherwise incurable diseases. These modalities of personalized medicine have already shown great promises including product commercialization for some rare diseases. The transfer of a chimeric antigen receptor or T cell receptor genes into autologous T cells has led to very promising outcomes for some cancers, and particularly for hematological malignancies. In addition, gene-engineered cell therapeutics are also being explored to induce tolerance and regulate inflammation. Here, we review the latest gene-engineered cell therapeutic approaches being currently explored to induce an efficient immune response against cancer cells or viruses by engineering T cells, natural killer cells, gamma delta T cells, or cytokine-induced killer cells and to modulate inflammation using regulatory T cells. PMID:29459866

Regression analysis of current-status data: an application to breast-feeding.

PubMed

Grummer-strawn, L M

1993-09-01

"Although techniques for calculating mean survival time from current-status data are well known, their use in multiple regression models is somewhat troublesome. Using data on current breast-feeding behavior, this article considers a number of techniques that have been suggested in the literature, including parametric, nonparametric, and semiparametric models as well as the application of standard schedules. Models are tested in both proportional-odds and proportional-hazards frameworks....I fit [the] models to current status data on breast-feeding from the Demographic and Health Survey (DHS) in six countries: two African (Mali and Ondo State, Nigeria), two Asian (Indonesia and Sri Lanka), and two Latin American (Colombia and Peru)." excerpt

The MAJORANA DEMONSTRATOR for 0νββ: Current Status and Future Plans

NASA Astrophysics Data System (ADS)

Green, M. P.; Abgrall, N.; Aguayo, E.; Avignone, F. T.; Barabash, A. S.; Bertrand, F. E.; Boswell, M.; Brudanin, V.; Busch, M.; Byram, D.; Caldwell, A. S.; Chan, Y.-D.; Christofferson, C. D.; Combs, D. C.; Cuesta, C.; Detwiler, J. A.; Doe, P. J.; Efremenko, Yu.; Egorov, V.; Ejiri, H.; Elliott, S. R.; Fast, J. E.; Finnerty, P.; Fraenkle, F. M.; Galindo-Uribarri, A.; Giovanetti, G. K.; Goett, J.; Gruszko, J.; Guiseppe, V. E.; Gusev, K.; Hallin, A. L.; Hazama, R.; Hegai, A.; Henning, R.; Hoppe, E. W.; Howard, S.; Howe, M. A.; Keeter, K. J.; Kidd, M. F.; Kochetov, O.; Konovalov, S. I.; Kouzes, R. T.; LaFerriere, B. D.; Leon, J.; Leviner, L. E.; Loach, J. C.; MacMullin, J.; MacMullin, S.; Martin, R. D.; Meijer, S.; Mertens, S.; Nomachi, M.; Orrell, J. L.; O'Shaughnessy, C.; Overman, N. R.; Phillips, D. G.; Poon, A. W. P.; Pushkin, K.; Radford, D. C.; Rager, J.; Rielage, K.; Robertson, R. G. H.; Romero-Romero, E.; Ronquest, M. C.; Schubert, A. G.; Shanks, B.; Shima, T.; Shirchenko, M.; Snavely, K. J.; Snyder, N.; Suriano, A. M.; Thompson, J.; Timkin, V.; Tornow, W.; Trimble, J. E.; Varner, R. L.; Vasilyev, S.; Vetter, K.; Vorren, K.; White, B. R.; Wilkerson, J. F.; Wiseman, C.; Xu, W.; Yakushev, E.; Young, A. R.; Yu, C.-H.; Yumatov, V.

The MAJORANA DEMONSTRATOR will search for neutrinoless-double-beta decay (0νββ) in 76Ge, while establishing the feasibility of a future tonne-scale germanium-based 0νββ experiment, and performing searches for new physics beyond the Standard Model. The experiment, currently under construction at the Sanford Underground Research Facility in Lead, SD, will consist of a pair of modular high-purity germanium detector arrays housed inside of a compact copper, lead, and polyethylene shield. Through a combination of strict materials qualifications and assay, low-background design, and powerful background rejection techniques, the Demonstrator aims to achieve a background rate in the 0νββ region of interest (ROI) of no more than 3 counts in the 0νββ-decay ROI per tonne of target isotope per year (cnts/(ROI-t-y)). The current status of the Demonstrator is discussed, as are plans for its completion.

The MAJORANA DEMONSTRATOR for 0νββ: Current status and future plans

DOE PAGES

Green, M. P.; Abgrall, N.; Aguayo, E.; ...

2015-01-01

The Majorana Demonstrator will search for neutrinoless-double-beta decay (0νββ) in 76Ge, while establishing the feasibility of a future tonne-scale germanium-based 0νββ experiment, and performing searches for new physics beyond the Standard Model. The experiment, currently under construction at the Sanford Underground Research Facility in Lead, SD, will consist of a pair of modular high-purity germanium detector arrays housed inside of a compact copper, lead, and polyethylene shield. Through a combination of strict materials qualifications and assay, low-background design, and powerful background rejection techniques, the Demonstrator aims to achieve a background rate in the 0νββ region of interest (ROI) of nomore » more than 3 counts in the 0νββ-decay ROI per tonne of target isotope per year (cnts/(ROI-t-y)). The current status of the Demonstrator is discussed, as are plans for its completion.« less

Current status of the CALET mission

NASA Astrophysics Data System (ADS)

Mori, Masaki

2017-01-01

The CALorimeteric Electron Telescope (CALET) is a Japanese-led international mission being developed as part of the utilization plan for the International Space Station (ISS). CALET was launched by an H-II B rocket utilizing the Japanese developed HTV (H-II Transfer Vehicle) in August 2015, and has been measuring high-energy electrons, cosmic rays as well as gamma rays above 10 GeV to about 10 TeV with high accuracy. In this paper we describe the current status of the CALET mission focused on gamma-ray observations.

Transcranial Alternating Current Stimulation (tACS) Mechanisms and Protocols

PubMed Central

Tavakoli, Amir V.; Yun, Kyongsik

2017-01-01

Perception, cognition and consciousness can be modulated as a function of oscillating neural activity, while ongoing neuronal dynamics are influenced by synaptic activity and membrane potential. Consequently, transcranial alternating current stimulation (tACS) may be used for neurological intervention. The advantageous features of tACS include the biphasic and sinusoidal tACS currents, the ability to entrain large neuronal populations, and subtle control over somatic effects. Through neuromodulation of phasic, neural activity, tACS is a powerful tool to investigate the neural correlates of cognition. The rapid development in this area requires clarity about best practices. Here we briefly introduce tACS and review the most compelling findings in the literature to provide a starting point for using tACS. We suggest that tACS protocols be based on functional brain mechanisms and appropriate control experiments, including active sham and condition blinding. PMID:28928634

Assigning Cytomegalovirus (CMV) Status in Children Awaiting Organ Transplant: Viral Shedding, CMV-Specific T-cells and CD27-CD28-CD4+ T-cells.

PubMed

Burton, Catherine E; Sester, Martina; Robinson, Joan L; Eurich, Dean T; Preiksaitis, Jutta K; Urschel, Simon

2018-05-24

Passive antibodies, maternal or transfusion-acquired, make serologic determination of pre-transplant cytomegalovirus (CMV) status unreliable. We evaluated 3 assays un-affected by passive antibodies, in assignment of CMV infection status in children awaiting solid organ transplant and in controls: i) CMV Nucleic Acid Amplification Testing (NAAT), quantification of ii) CMV-specific CD4+T-cells, and iii) CD27-CD28-CD4+T-cells. Our results highlight that CMV NAAT, from urine and oropharynx, is useful in confirming positive CMV status. Detection of CMV-specific CD4+T-cells was sensitive and specific in children >18 months but was less sensitive in children <12 months. CD27-CD28- CD4+T-cells are not likely useful in CMV risk-stratification in children.

A high-efficiency low-voltage class-E PA for IoT applications in sub-1 GHz frequency range

NASA Astrophysics Data System (ADS)

Zhou, Chenyi; Lu, Zhenghao; Gu, Jiangmin; Yu, Xiaopeng

2017-10-01

We present and propose a complete and iterative integrated-circuit and electro-magnetic (EM) co-design methodology and procedure for a low-voltage sub-1 GHz class-E PA. The presented class-E PA consists of the on-chip power transistor, the on-chip gate driving circuits, the off-chip tunable LC load network and the off-chip LC ladder low pass filter. The design methodology includes an explicit design equation based circuit components values' analysis and numerical derivation, output power targeted transistor size and low pass filter design, and power efficiency oriented design optimization. The proposed design procedure includes the power efficiency oriented LC network tuning, the detailed circuit/EM co-simulation plan on integrated circuit level, package level and PCB level to ensure an accurate simulation to measurement match and first pass design success. The proposed PA is targeted to achieve more than 15 dBm output power delivery and 40% power efficiency at 433 MHz frequency band with 1.5 V low voltage supply. The LC load network is designed to be off-chip for the purpose of easy tuning and optimization. The same circuit can be extended to all sub-1 GHz applications with the same tuning and optimization on the load network at different frequencies. The amplifier is implemented in 0.13 μm CMOS technology with a core area occupation of 400 μm by 300 μm. Measurement results showed that it provided power delivery of 16.42 dBm at antenna with efficiency of 40.6%. A harmonics suppression of 44 dBc is achieved, making it suitable for massive deployment of IoT devices. Project supported by the National Natural Science Foundation of China (No. 61574125) and the Industry Innovation Project of Suzhou City of China (No. SYG201641).

Special Education History, Current Status and Future: India

ERIC Educational Resources Information Center

Antony, Pavan John

2013-01-01

Education of all children in public schools, including those with disabilities, continues to be an unresolved issue in many countries around the globe. While education of all children is mandated by law and considered a basic human right in many countries, the current status of implementation varies. India, for example, is an ancient country that…

Reduced Current Spread by Concentric Electrodes in Transcranial Electrical Stimulation (tES).

PubMed

Bortoletto, M; Rodella, C; Salvador, R; Miranda, P C; Miniussi, C

2016-01-01

We propose the use of a new montage for transcranial direct current stimulation (tDCS), called concentric electrodes tDCS (CE-tDCS), involving two concentric round electrodes that may improve stimulation focality. To test efficacy and focality of CE-tDCS, we modelled the current distribution and tested physiological effects on cortical excitability. Motor evoked potentials (MEPs) from first dorsal interosseous (FDI) and abductor digiti minimi (ADM) were recorded before and after the delivery of anodal, cathodal and sham stimulation on the FDI hotspot for 10 minutes. MEP amplitude of FDI increased after anodal-tDCS and decreased after cathodal-tDCS, supporting the efficacy of CE-tDCS in modulating cortical excitability. Moreover, modelled current distribution and no significant effects of stimulation on MEP amplitude of ADM suggest high focality of CE-tDCS. CE-tDCS may allow a better control of current distribution and may represent a novel tool for applying tDCS and other transcranial current stimulation approaches. Copyright © 2016 Elsevier Inc. All rights reserved.

Current status and future challenges in T-cell receptor/peptide/MHC molecular dynamics simulations.

PubMed

Knapp, Bernhard; Demharter, Samuel; Esmaielbeiki, Reyhaneh; Deane, Charlotte M

2015-11-01

The interaction between T-cell receptors (TCRs) and major histocompatibility complex (MHC)-bound epitopes is one of the most important processes in the adaptive human immune response. Several hypotheses on TCR triggering have been proposed. Many of them involve structural and dynamical adjustments in the TCR/peptide/MHC interface. Molecular Dynamics (MD) simulations are a computational technique that is used to investigate structural dynamics at atomic resolution. Such simulations are used to improve understanding of signalling on a structural level. Here we review how MD simulations of the TCR/peptide/MHC complex have given insight into immune system reactions not achievable with current experimental methods. Firstly, we summarize methods of TCR/peptide/MHC complex modelling and TCR/peptide/MHC MD trajectory analysis methods. Then we classify recently published simulations into categories and give an overview of approaches and results. We show that current studies do not come to the same conclusions about TCR/peptide/MHC interactions. This discrepancy might be caused by too small sample sizes or intrinsic differences between each interaction process. As computational power increases future studies will be able to and should have larger sample sizes, longer runtimes and additional parts of the immunological synapse included. © The Author 2015. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

Current status of superficial pharyngeal squamous cell carcinoma in Japan.

PubMed

Rikitake, Ryoko; Ando, Mizuo; Saito, Yuki; Yoshimoto, Seiichi; Yamasoba, Tatsuya; Higashi, Takahiro

2017-10-01

To investigate the status and treatment of superficial pharyngeal squamous cell carcinoma in Japan. We analyzed all cases diagnosed between 2011 and 2013, as recorded in the national database of hospital-based cancer registries. We extracted data on patient sex, age, tumor locations, histology, presentation routes, initial treatments, and TNM stages. Additionally, we compared the characteristics of pharyngeal carcinoma to those of esophageal cancer. A total of 16,521 oropharyngeal and hypopharyngeal cancers from 409 institutions were included. Diagnosis of Tis tumors was infrequent, and both cancers were likely to be diagnosed at an advanced stage (n = 866, 5.3%). Tis diseases were the most commonly detected during follow-up examinations for other diseases (n = 608, 70%). While more oropharyngeal Tis patients were men compared to T1-4 patients (88 vs 82%, respectively), hypopharyngeal cancer patients comprised an equally high proportion of men (94 vs 92%, respectively). The most common location of oropharyngeal Tis tumors was the posterior wall (32%), whereas T1-4 tumors were most commonly found on the lateral wall (36%). In hypopharyngeal cancer, both Tis and T1-4 were most commonly located in the pyriform sinus (62%). The proportion of Tis tumors diagnosed at individual institutions showed a positive correlation with the number of endoscopic treatments (r = 0.32, P < 0.001) and the number of esophageal cancer cases (r = 0.37, P < 0.001). Our national database study elucidated the current characteristics of superficial pharyngeal squamous cell carcinoma patients in Japan. Further improvements in early diagnosis and standardized treatments are warranted.

Free Fatty Acid Effects on the Atrial Myocardium: Membrane Ionic Currents Are Remodeled by the Disruption of T-Tubular Architecture

PubMed Central

O’Connell, Ryan P.; Musa, Hassan; Gomez, Mario San Martin; Avula, Uma Mahesh; Herron, Todd J.; Kalifa, Jerome; Anumonwo, Justus M. B.

2015-01-01

Background Epicardial adiposity and plasma levels of free fatty acids (FFAs) are elevated in atrial fibrillation, heart failure and obesity, with potentially detrimental effects on myocardial function. As major components of epicardial fat, FFAs may be abnormally regulated, with a potential to detrimentally modulate electro-mechanical function. The cellular mechanisms underlying such effects of FFAs are unknown. Objective To determine the mechanisms underlying electrophysiological effects of palmitic (PA), stearic (SA) and oleic (OA) FFAs on sheep atrial myocytes. Methods We used electrophysiological techniques, numerical simulations, biochemistry and optical imaging to examine the effects of acutely (≤ 15 min), short-term (4–6 hour) or 24-hour application of individual FFAs (10 μM) on isolated ovine left atrial myocytes (LAMs). Results Acute and short-term incubation in FFAs resulted in no differences in passive or active properties of isolated left atrial myocytes (LAMs). 24-hour application had differential effects depending on the FFA. PA did not affect cellular passive properties but shortened (p<0.05) action potential duration at 30% repolarization (APD30). APD50 and APD80 were unchanged. SA had no effect on resting membrane potential but reduced membrane capacitance by 15% (p<0.05), and abbreviated APD at all values measured (p≤0.001). OA did not significantly affect passive or active properties of LAMs. Measurement of the major voltage-gated ion channels in SA treated LAMs showed a ~60% reduction (p<0.01) of the L-type calcium current (ICa-L) and ~30% reduction (p<0.05) in the transient outward potassium current (ITO). A human atrial cell model recapitulated SA effects on APD. Optical imaging showed that SA incubated for 24 hours altered t-tubular structure in isolated cells (p<0.0001). Conclusions SA disrupts t-tubular architecture and remodels properties of membrane ionic currents in sheep atrial myocytes, with potential implications in

[Effects of resolving phlegm method on fibrinolytic status in non-alcoholic steatohepatitis patients of phlegm and blood-stasis syndrome].

PubMed

Chen, Li; Jiang, Yang-Kun; Cai, Yan-Bo

2006-12-01

To observe the effect of resolving phlegm method (RPM) on fibrinolytic status in non-alcoholic steatohepatitis (NASH) patients of phlegm blood-stasis (PBS) syndrome type. Sixty-two patients were randomly assigned to 2 groups, namely the treated group (n = 34) treated with Chinese herbs for resolving phlegm and dampness, smoothing liver and gallbladder, promoting blood circulation and removing blood stasis (composition: Indigo Naturalis 10 g, Alumen 3 g, Semen Cassiae 15 g, Fructus Crataegi 15 g, vinegar prepared Radix Bupleuri 10 g, Radix Curcumae 10 g, Radix Salviae Miltiorrhizae 12 g, Herba Lycopi 12 g, talc 12 g and Radix Glycyrrhizae 2 g), one dose twice per day orally, and the control group (n = 28) with ursodeoxycholic acid tablet (UAT) 150 mg three times per day. The treatment course for both groups was 12 weeks. Liver function (ALT, AST, ALP), insulin resistance (IR) index represented by homeostasis model-IR (HOMA-IR) and insulin (Ins), levels of tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1), as well as main symptoms and physical signs were assessed before and after treatment. (1) Compared with those before treatment, levels of ALT, AST, HOMA-IR, t-PA, PAl-1 and main symptoms were all improved in the treated group (P < 0.05 or P < 0.01); (2) There was significant difference in ALP, HOMA-IR, t-PA and PAI-1 between the treated group and the control group (P < 0.05 or P < 0.01); (3) The improvement in liver function related indexes in the control group was mainly the level of ALT, t-PA (P < 0.01), and also shown on HOMA-IR, Ins and PAI-1. RPM could effectively improve liver function and fibrinolytic status. Its effect was better than that of UAT.

The relationship between adolescents' physical activity, fundamental movement skills and weight status.

PubMed

O' Brien, Wesley; Belton, Sarahjane; Issartel, Johann

2016-01-01

The aim of this study was to determine if a potential relationship among physical activity (PA), fundamental movement skills and weight status exists amongst early adolescent youth. Participants were a sample of 85 students; 54 boys (mean age = 12.94 ± 0.33 years) and 31 girls (mean age = 12.75 ± 0.43 years). Data gathered during physical education class included PA (accelerometry), fundamental movement skills and anthropometric measurements. Standard multiple regression revealed that PA and total fundamental movement skill proficiency scores explained 16.5% (P < 0.001) of the variance in the prediction of body mass index. Chi-square tests for independence further indicated that compared with overweight or obese adolescents, a significantly higher proportion of adolescents classified as normal weight achieved mastery/near-mastery in fundamental movement skills. Results from the current investigation indicate that weight status is an important correlate of fundamental movement skill proficiency during adolescence. Aligned with most recent research, school- and community-based programmes that include developmentally structured learning experiences delivered by specialists can significantly improve fundamental movement skill proficiency in youth.

Current status and perspectives of chimeric antigen receptor modified T cells for cancer treatment.

PubMed

Wang, Zhenguang; Guo, Yelei; Han, Weidong

2017-12-01

Chimeric antigen receptor (CAR) is a recombinant immunoreceptor combining an antibody-derived targeting fragment with signaling domains capable of activating cells, which endows T cells with the ability to recognize tumor-associated surface antigens independent of the expression of major histocompatibility complex (MHC) molecules. Recent early-phase clinical trials of CAR-modified T (CAR-T) cells for relapsed or refractory B cell malignancies have demonstrated promising results (that is, anti-CD19 CAR-T in B cell acute lymphoblastic leukemia (B-ALL)). Given this success, broadening the clinical experience of CAR-T cell therapy beyond hematological malignancies has been actively investigated. Here we discuss the basic design of CAR and review the clinical results from the studies of CAR-T cells in B cell leukemia and lymphoma, and several solid tumors. We additionally discuss the major challenges in the further development and strategies for increasing anti-tumor activity and safety, as well as for successful commercial translation.

Esophageal ultrasound (EUS) assessment of T4 status in NSCLC patients.

PubMed

Kuijvenhoven, Jolanda C; Crombag, Laurence; Breen, David P; van den Berk, Inge; Versteegh, Michel I M; Braun, Jerry; Winkelman, Toon A; van Boven, Wimjan; Bonta, Peter I; Rabe, Klaus F; Annema, Jouke T

2017-12-01

Mediastinal and central large vessels (T4) invasion by lung cancer is often difficult to assess preoperatively due to the limited accuracy of computed tomography (CT) scan of the chest. Esophageal ultrasound (EUS) can visualize the relationship of para-esophageally located lung tumors to surrounding mediastinal structures. To assess the value of EUS for detecting mediastinal invasion (T4) of centrally located lung tumors. Patients who underwent EUS for the diagnosis and staging of lung cancer and in whom the primary tumor was detected by EUS and who subsequently underwent surgical- pathological staging (2000-2016) were retrospectively selected from two university hospitals in The Netherlands. T status of the lung tumor was reviewed based on EUS, CT and thoracotomy findings. Surgical- pathological staging was the reference standard. In 426 patients, a lung malignancy was detected by EUS of which 74 subjects subsequently underwent surgical- pathological staging. 19 patients (26%) were diagnosed with stage T4 based on vascular (n=8, 42%) or mediastinal (n=8, 42%) invasion or both (n=2, 11%), one patient (5%) had vertebral involvement. Sensitivity, specificity, PPV and NPV for assessing T4 status were: for EUS (n=74); 42%, 95%, 73%, 83%, for chest CT (n=66); 76%, 61%, 41%, 88% and the combination of EUS and chest CT (both positive or negative for T4, (n=34); 83%, 100%, 100% 97%. EUS has a high specificity and NPV for the T4 assessment of lung tumors located para-esophageally and offers further value to chest CT scan. Copyright © 2017 Elsevier B.V. All rights reserved.

Regression analysis of informative current status data with the additive hazards model.

PubMed

Zhao, Shishun; Hu, Tao; Ma, Ling; Wang, Peijie; Sun, Jianguo

2015-04-01

This paper discusses regression analysis of current status failure time data arising from the additive hazards model in the presence of informative censoring. Many methods have been developed for regression analysis of current status data under various regression models if the censoring is noninformative, and also there exists a large literature on parametric analysis of informative current status data in the context of tumorgenicity experiments. In this paper, a semiparametric maximum likelihood estimation procedure is presented and in the method, the copula model is employed to describe the relationship between the failure time of interest and the censoring time. Furthermore, I-splines are used to approximate the nonparametric functions involved and the asymptotic consistency and normality of the proposed estimators are established. A simulation study is conducted and indicates that the proposed approach works well for practical situations. An illustrative example is also provided.

Helicopter Rotor Noise Prediction: Background, Current Status, and Future Direction

NASA Technical Reports Server (NTRS)

Brentner, Kenneth S.

1997-01-01

Helicopter noise prediction is increasingly important. The purpose of this viewgraph presentation is to: 1) Put into perspective the recent progress; 2) Outline current prediction capabilities; 3) Forecast direction of future prediction research; 4) Identify rotorcraft noise prediction needs. The presentation includes an historical perspective, a description of governing equations, and the current status of source noise prediction.

RIVERBANK AND MEADOW, LOOKING SOUTHEAST. PA148 AND PA149 CAN BE ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

RIVERBANK AND MEADOW, LOOKING SOUTHEAST. PA-1-48 AND PA-1-49 CAN BE PAIRED TO FORM A PANORAMA SHOWING THE RELATIONSHIP BETWEEN THE RIVERBANK AND THE MEADOW - John Bartram House & Garden, 54th Street & Lindbergh Boulevard, Philadelphia, Philadelphia County, PA

Fuel Cell Buses in U.S. Transit Fleets: Current Status 2011

DOT National Transportation Integrated Search

2011-11-11

his report is the fifth in a series of annual status reports that summarize the progress resulting from fuel cell transit bus demonstrations in the United States and provide a discussion of the achievements and challenges of fuel cell propulsion in t...

Current knowledge of US metal and nonmetal miner health: Current and potential data sources for analysis of miner health status

PubMed Central

Yeoman, K. M.; Halldin, C. N.; Wood, J.; Storey, E.; Johns, D.; Laney, A. S.

2016-01-01

ABSTRACT Little is known about the current health status of US metal and nonmetal (MNM) miners, in part because no health surveillance systems exist for this population. The National Institute for Occupational Safety and Health (NIOSH) is developing a program to characterize burden of disease among MNM miners. This report discusses current knowledge and potential data sources of MNM miner health. Recent national surveys were analyzed, and literature specific to MNM miner health status was reviewed. No robust estimates of disease prevalence were identified, and national surveys did not provide information specific to MNM miners. Because substantial gaps exist in the understanding of MNM miners' current health status, NIOSH plans to develop a health surveillance program for this population to guide intervention efforts to reduce occupational and personal risks for chronic illness. PMID:25658684

[Current status and prospects of gene doping detection].

PubMed

Wang, Wenjun; Zhang, Sichun; Xu, Jingjuan; Xia, Xinghua; Tian, Yaping; Zhang, Xinrong; Chen, Hong-Yuan

2008-07-01

The fast development of biotechnology promotes the development of doping. From recombinant protein to gene doping, there is a great challenge to their detection. The improvement of gene therapy and potential to enhance athletic performance open the door for gene doping. After a brief introduction of the concept of gene doping, the current status and prospects of gene doping detection are reviewed.

Charged-current multiple pion production using νμ in the PøD in the T2K experiment

NASA Astrophysics Data System (ADS)

Davis, Scott

2013-04-01

The T2K experiment is a long-baseline, off-axis neutrino oscillation experiment designed to search for the appearance of νe in a νμ beam. The Pi-Zero Detector (PøD) of the T2K off-axis near detector (ND280) is used to measure properties of the neutrino beam and measure cross sections relevant to the beam's energy. As the PøD contains a variety of nuclei, we can measure the cross section of various production modes on several targets. At the beam energies of T2K, the production of multiple pions, of any type, from neutrinos is not well understood. I will present the status of an analysis method to measure the production of multiple (2 or greater) pions from a charged-current interaction with νμ.

Distal protection in cardiovascular medicine: current status.

PubMed

Ali, Onn Akbar; Bhindi, Ravinay; McMahon, Aisling C; Brieger, David; Kritharides, Leonard; Lowe, Harry C

2006-08-01

Iatrogenic and spontaneous downstream microembolization of atheromatous material is increasingly recognized as a source of cardiovascular morbidity and mortality. Devising ways of reducing this distal embolization using a variety of mechanical means--distal protection--is currently under intense and diverse investigation. This review therefore summarizes the present status of distal protection. It examines the problem of distal embolization, describes the available distal protection devices, reviews those areas of cardiovascular medicine where distal protection devices are being investigated, and discusses potential future developments.

Inter- and Intra-individual Variability in Response to Transcranial Direct Current Stimulation (tDCS) at Varying Current Intensities.

PubMed

Chew, Taariq; Ho, Kerrie-Anne; Loo, Colleen K

2015-01-01

Translation of transcranial direct current stimulation (tDCS) from research to clinical practice is hindered by a lack of consensus on optimal stimulation parameters, significant inter-individual variability in response, and in sufficient intra-individual reliability data. Inter-individual differences in response to anodal tDCS at a range of current intensities were explored. Intra-individual reliability in response to anodal tDCS across two identical sessions was also investigated. Twenty-nine subjects participated in a crossover study. Anodal-tDCS using four different current intensities (0.2, 0.5, 1 and 2 mA), with an anode size of 16 cm2, was tested. The 0.5 mA condition was repeated to assess intra-individual variability. TMS was used to elicit 40 motor-evoked potentials (MEPs) before 10 min of tDCS, and 20 MEPs at four time-points over 30 min following tDCS. ANOVA revealed no main effect of TIME for all conditions except the first 0.5 mA condition, and no differences in response between the four current intensities. Cluster analysis identified two clusters for the 0.2 and 2 mA conditions only. Frequency distributions based on individual subject responses (excitatory, inhibitory or no response) to each condition indicate possible differential responses between individuals to different current intensities. Test-retest reliability was negligible (ICC(2,1) = -0.50). Significant inter-individual variability in response to tDCS across a range of current intensities was found. 2 mA and 0.2 mA tDCS were most effective at inducing a distinct response. Significant intra-individual variability in response to tDCS was also found. This has implications for interpreting results of single-session tDCS experiments. Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.

Technical Insights for Saltstone PA Maintenance

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

Flach, G.; Sarkar, S.; Mahadevan, S.

2011-07-20

The Cementitious Barriers Partnership (CBP) is a collaborative program sponsored by the US DOE Office of Waste Processing. The objective of the CBP is to develop a set of computational tools to improve understanding and prediction of the long-term structural, hydraulic, and chemical performance of cementitious barriers and waste forms used in nuclear applications. CBP tools are expected to better characterize and reduce the uncertainties of current methodologies for assessing cementitious barrier performance and increase the consistency and transparency of the assessment process, as the five-year program progresses. In September 2009, entering its second year of funded effort, the CBPmore » sought opportunities to provide near-term tangible support to DOE Performance Assessments (PAs). The Savannah River Saltstone Disposal Facility (SDF) was selected for the initial PA support effort because (1) cementitious waste forms and barriers play a prominent role in the performance of the facility, (2) certain important long-term behaviors of cementitious materials composing the facility are uncertain, (3) review of the SDF PA by external stakeholders is ongoing, and (4) the DOE contractor responsible for the SDF PA is open to receiving technical assistance from the CBP. A review of the current (SRR Closure & Waste Disposal Authority 2009) and prior Saltstone PAs (e.g., Cook et al. 2005) suggested five potential opportunities for improving predictions. The candidate topics considered were (1) concrete degradation from external sulfate attack, (2) impact of atmospheric exposure to concrete and grout before closure, such as accelerated slag and Tc-99 oxidation, (3) mechanistic prediction of geochemical conditions, (4) concrete degradation from rebar corrosion due to carbonation, and (5) early age cracking from drying and/or thermal shrinkage. The candidate topics were down-selected considering the feasibility of addressing each issue within approximately six months, and

Can differences in physical activity by socio-economic status in European adolescents be explained by differences in psychosocial correlates? A mediation analysis within the HELENA (Healthy Lifestyle in Europe by Nutrition in Adolescence) study.

PubMed

De Cocker, Katrien; Artero, Enrique G; De Henauw, Stefaan; Dietrich, Sabine; Gottrand, Frédéric; Béghin, Laurent; Hagströmer, Maria; Sjöström, Michael; Plada, Maria; Manios, Yannis; Mauro, Beatrice; Molnár, Dénes; Moreno, Luis A; Ottevaere, Charlene; Valtueña, Jara; Maes, Lea; De Bourdeaudhuij, Ilse

2012-11-01

Socio-economic status (SES) has been positively associated with physical activity (PA) levels in adolescents. In order to tackle these social inequalities, information is needed about the underlying mechanisms of this association. The present study aimed to investigate the potential mediating role of psychosocial correlates of PA on the relationship between SES and PA in European adolescents. Cross-sectional study testing the mediating role of psychosocial correlates in the SES-PA association using the product-of-coefficients test of MacKinnon. Ten European cities in nine different countries, the HELENA (Healthy Lifestyle in Europe by Nutrition in Adolescence) Study. Adolescents (n 2780) aged 12·5-17·49 years self-reported on PA (moderate-to-vigorous intensity PA and total PA), SES indicators (education of the mother and Family Affluence Scale) and psychosocial correlates of PA (stage of change, attitudes, awareness, modelling, social support, self-efficacy, benefits, barriers and environmental correlates). SES (Family Affluence Scale) was significantly associated with moderate-to-vigorous intensity PA. According to single-mediator models, this association was significantly mediated by stage of change (t = 3·6, P ≤ 0·001), awareness (t = 2·7, 0·001 < P ≤ 0·01), modelling (t = 4·8, P ≤ 0·001), self-efficacy (t = 2·5, 0·01

t = 2·7, 0·001 < P ≤ 0·01) and environmental (t = 3·0, 0·001 < P ≤ 0·01) correlates of PA. The multiple-mediators model showed that the mediating role of the combination of these psychosocial correlates was also significant (t = 6·2, P ≤ 0·001). Adolescents with low family wealth scored lower on stage of change, awareness, modelling, self-efficacy and environmental correlates of PA, and higher on PA barriers, which in turn resulted in lower levels of moderate-to-vigorous PA. Future interventions should target these individual and environmental constructs in order to tackle and intervene on

Current status of Japanese detectors

NASA Astrophysics Data System (ADS)

Tatsumi, Daisuke; Takahashi, Ryutaro; Arai, Koji; Nakagawa, Noriyasu; Agatsuma, Kazuhiro; Yamazaki, Toshitaka; Fukushima, Mitsuhiro; Fujimoto, Masa-Katsu; Takamori, Akiteru; Bertolini, Alessandro; Sannibale, Virginio; DeSalvo, Riccardo; Márka, Szabolcs; Ando, Masaki; Tsubono, Kimio; Akutsu, Tomomi; Yamamoto, Kazuhiro; Ishitsuka, Hideki; Uchiyama, Takashi; Miyoki, Shinji; Ohashi, Masatake; Kuroda, Kazuaki; Awaya, Norichika; Kanda, Nobuyuki; Araya, Akito; Telada, Souichi; Tomaru, Takayuki; Haruyama, Tomiyoshi; Yamamoto, Akira; Sato, Nobuaki; Suzuki, Toshitaka; Shintomi, Takakazu

2007-10-01

The current status of the TAMA and CLIO detectors in Japan is reported in this paper. These two interferometric gravitational wave detectors are being developed for the large cryogenic gravitational wave telescope (LCGT) which is a future plan for detecting gravitational wave signals at least once per year. TAMA300 is being upgraded to improve the sensitivity in a low-frequency region after the last observational experiment in 2004. To reduce the seismic noises, we are installing a new seismic isolation system, called the TAMA seismic attenuation system, for the four test masses. We confirmed stable mass locks of a cavity and improvements of length and angular fluctuations by using two SASs. We are currently optimizing the performance of the third and fourth SASs. We continue TAMA300 operation and R&D studies for the LCGT. The next data taking is planned for the summer of 2007. CLIO is a 100 m baseline length prototype detector for LCGT to investigate interferometer performance in cryogenic condition. The key features of CLIO are that it locates the Kamioka underground site for a low-seismic noise level, and adopts cryogenic Sapphire mirrors for low-thermal noise level. The first operation of the cryogenic interferometer was successfully demonstrated in February 2006. Current sensitivity at room temperature is close to the target sensitivity within a factor of 4. Several observational experiments at room temperature have been done. Once the displacement noise reaches the thermal noise level of room temperature, its improvement by cooling test mass mirrors should be demonstrated.

IVS: Current Status and Future Plans

NASA Astrophysics Data System (ADS)

Behrend, D.; Nothnagel, A.; Petrachenko, W. T.; Tuccari, G.

2016-12-01

The International VLBI Service for Geodesy and Astrometry (IVS) is a globally operating service that coordinates and performs Very Long Baseline Interferometry (VLBI) activities through its constituent components. The VLBI activities are associated with the creation, provision, dissemination, and archiving of relevant VLBI data and products. The products mostly pertain to the determination of the celestial and terrestrial reference frames, the Earth orientation parameters (EOP), atmospheric parameters as well as other ancillary parameters. The IVS observational network currently consists of about 40 radio telescopes worldwide. Subsets of these telescopes (8-12 stations) participate in 24-hour observing sessions that are run several times per week and in 1-hour intensive sessions for UT1 determination every day. The current VLBI network was developed mainly in the 1970s and 1980s. A number of factors, including aging infrastructure and demanding new scientific requirements, started to challenge its future sustainability and relevance. In response, the IVS and other groups developed and started implementing the next generation VLBI system, called VGOS (VLBI Global Observing System), at existing and new sites. The VGOS network is expected to reach maturity in the early 2020s. We describe the current status, progress, and anticipated prospects of geodetic/astrometric VLBI and the IVS.

ACRF Instrumentation Status: New, Current, and Future - January 2008

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

AS Koontz; S Choudhury; BD Ermold

2008-01-31

The purpose of this report is to provide status of the ingest software used to process instrument data for the Atmospheric Radiation Measurement Program Climate Research Facility (ACRF). The report is divided into 4 sections: (1) for news about ingests currently under development, (2) for current production ingests, (3) for future ingest development plans, and (4) for information on retired ingests. Please note that datastreams beginning in “xxx” indicate cases where ingests run at multiple ACRF sites, which results in a datastream(s) for each location.

PSMA Theranostics: Current Status and Future Directions

PubMed Central

Afshar-Oromieh, Ali; Jadvar, Hossein; Ahmadzadehfar, Hojjat

2018-01-01

Prostate-specific membrane antigen (PSMA) is a promising target for imaging diagnostics and targeted radionuclide therapy (theranostics) of prostate cancer and its metastases. There is increasing evidence of encouraging response rates and a low toxicity profile of radioligand therapy (RLT) of metastatic castration-resistant prostate cancer using 177Lu-labeled PSMA ligands. In this article, we review the current status of diagnostics and therapy using radiolabeled PSMA ligands. We also suggest protocols for patient selection criteria and conduct of PSMA-based RLT. Challenges and opportunities of PSMA theranostics are discussed. PMID:29873291

Colletotrichum – current status and future directions

PubMed Central

Cannon, P.F.; Damm, U.; Johnston, P.R.; Weir, B.S.

2012-01-01

A review is provided of the current state of understanding of Colletotrichum systematics, focusing on species-level data and the major clades. The taxonomic placement of the genus is discussed, and the evolution of our approach to species concepts and anamorph-teleomorph relationships is described. The application of multilocus technologies to phylogenetic analysis of Colletotrichum is reviewed, and selection of potential genes/loci for barcoding purposes is discussed. Host specificity and its relation to speciation and taxonomy is briefly addressed. A short review is presented of the current status of classification of the species clusters that are currently without comprehensive multilocus analyses, emphasising the orbiculare and destructivum aggregates. The future for Colletotrichum biology will be reliant on consensus classification and robust identification tools. In support of these goals, a Subcommission on Colletotrichum has been formed under the auspices of the International Commission on Taxonomy of Fungi, which will administer a carefully curated barcode database for sequence-based identification of species within the BioloMICS web environment. PMID:23136460

Death education within health education: current status, future directions.

PubMed

Crase, D

1981-12-01

A national survey was conducted among 205 university level divisions/departments of health education to determine the current status of death education courses within the health education field. Forty-nine college and university health educators currently teaching the course returned usable instruments. Death education receives the same credit, utilizes similar grading systems and is generally managed much like other academic courses. Since the discipline is in its infancy and many teachers are relatively unprepared, respondents called for greater quality control and improved professional preparation. Several concerns accompanying the growth of death education were identified.

Hardwood lumber supply chain: current status and market opportunities

Treesearch

Urs Buehlmann; Matthew Bumgardner; Al Schuler; Mark Barford

2007-01-01

The membership of the Appalachian Hardwood Manufacturers Association was surveyed in 2005 to determine the current status of large Appalachian sawmills. The primary focus was to assess the impacts of globalization on primary manufacturing, but attention was also paid to general issues affecting the hardwood lumber supply chain-from concerns over forest health and log...

Augmenting Visual Search Performance with Transcranial Direct Current Stimulation (tDCS)

DTIC Science & Technology

2015-03-01

AFRL-RH-WP-TR-2015-0013 Augmenting Visual Search Performance with transcranial Direct Current Stimulation ( tDCS ) Justin Nelson...Stimulation ( tDCS ) 5a. CONTRACT NUMBER In-House 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Justin Nelson‡, Dr. R. Andy McKinley...evaluate a form of non-invasive brain stimulation known as transcranial direct current stimulation ( tDCS ) over the left frontal eye field (LFEF) region

Cysticercosis/taeniasis endemicity in Southeast Asia: Current status and control measures.

PubMed

Wu, Hai-Wei; Ito, Akira; Ai, Lin; Zhou, Xiao-Nong; Acosta, Luz P; Lee Willingham, Arve

2017-01-01

The parasitic zoonoses cysticercosis/taeniasis is among the 17 major Neglected Tropical Diseases (NTDs) identified by the WHO as a focus for research and control. It is caused by a larval stage (cysticercus) infection of Taenia solium tapeworm in both humans and pigs. Cysticercosis occurs in many resource-poor countries, especially those with warm and mild climates in the regions of Latin America (LA), Asia and Sub-Saharan Africa (SSA). The prevalence of human cysticercosis is marked in those areas where individuals are traditionally keen to consume raw or insufficiently cooked pork and/or where the husbandry of pigs is improper. The worldwide burden of cysticercosis is unclear and notably, large-scale control initiatives are lacking in all regions. This review focuses on the current endemic status of cysticercosis caused by T. solium infection in both humans and pigs living in 13 Southeast Asian countries. We will also emphasize epidemiological data as well as prevention and control of human neurocysticercosis. Copyright © 2016 Elsevier B.V. All rights reserved.

Smart wearable systems: current status and future challenges.

PubMed

Chan, Marie; Estève, Daniel; Fourniols, Jean-Yves; Escriba, Christophe; Campo, Eric

2012-11-01

Extensive efforts have been made in both academia and industry in the research and development of smart wearable systems (SWS) for health monitoring (HM). Primarily influenced by skyrocketing healthcare costs and supported by recent technological advances in micro- and nanotechnologies, miniaturisation of sensors, and smart fabrics, the continuous advances in SWS will progressively change the landscape of healthcare by allowing individual management and continuous monitoring of a patient's health status. Consisting of various components and devices, ranging from sensors and actuators to multimedia devices, these systems support complex healthcare applications and enable low-cost wearable, non-invasive alternatives for continuous 24-h monitoring of health, activity, mobility, and mental status, both indoors and outdoors. Our objective has been to examine the current research in wearable to serve as references for researchers and provide perspectives for future research. Herein, we review the current research and development of and the challenges facing SWS for HM, focusing on multi-parameter physiological sensor systems and activity and mobility measurement system designs that reliably measure mobility or vital signs and integrate real-time decision support processing for disease prevention, symptom detection, and diagnosis. For this literature review, we have chosen specific selection criteria to include papers in which wearable systems or devices are covered. We describe the state of the art in SWS and provide a survey of recent implementations of wearable health-care systems. We describe current issues, challenges, and prospects of SWS. We conclude by identifying the future challenges facing SWS for HM. Copyright © 2012 Elsevier B.V. All rights reserved.

Current Status and Challenges of Atmospheric Data Assimilation

NASA Astrophysics Data System (ADS)

Atlas, R. M.; Gelaro, R.

2016-12-01

The issues of modern atmospheric data assimilation are fairly simple to comprehend but difficult to address, involving the combination of literally billions of model variables and tens of millions of observations daily. In addition to traditional meteorological variables such as wind, temperature pressure and humidity, model state vectors are being expanded to include explicit representation of precipitation, clouds, aerosols and atmospheric trace gases. At the same time, model resolutions are approaching single-kilometer scales globally and new observation types have error characteristics that are increasingly non-Gaussian. This talk describes the current status and challenges of atmospheric data assimilation, including an overview of current methodologies, the difficulty of estimating error statistics, and progress toward coupled earth system analyses.

Visualizing Transcranial Direct Current Stimulation (tDCS) in vivo using Magnetic Resonance Imaging

NASA Astrophysics Data System (ADS)

Jog, Mayank Anant

Transcranial Direct Current Stimulation (tDCS) is a low-cost, non-invasive neuromodulation technique that has been shown to treat clinical symptoms as well as improve cognition. However, no techniques exist at the time of research to visualize tDCS currents in vivo. This dissertation presents the theoretical framework and experimental implementations of a novel MRI technique that enables non-invasive visualization of the tDCS electric current using magnetic field mapping. The first chapter establishes the feasibility of measuring magnetic fields induced by tDCS currents. The following chapter discusses the state of the art implementation that can measure magnetic field changes in individual subjects undergoing concurrent tDCS/MRI. The final chapter discusses how the developed technique was integrated with BOLD fMRI-an established MRI technique for measuring brain function. By enabling a concurrent measurement of the tDCS current induced magnetic field as well as the brain's hemodynamic response to tDCS, our technique opens a new avenue to investigate tDCS mechanisms and improve targeting.

Chronic Pancreatitis: Current Status and Challenges for Prevention and Treatment

PubMed Central

Lew, Daniel; Afghani, Elham

2017-01-01

This paper reviews the current status of our understanding of the epidemiology, diagnosis, and management of the continuum of pancreatic diseases from acute and recurrent acute pancreatitis to chronic pancreatitis and the diseases that are often linked with pancreatitis including diabetes mellitus and pancreatic cancer. In addition to reviewing the current state of the field, we identify gaps in knowledge that are necessary to address to improve patient outcomes in these conditions. PMID:28501969

Chronic Pancreatitis: Current Status and Challenges for Prevention and Treatment.

PubMed

Lew, Daniel; Afghani, Elham; Pandol, Stephen

2017-07-01

This paper reviews the current status of our understanding of the epidemiology, diagnosis, and management of the continuum of pancreatic diseases from acute and recurrent acute pancreatitis to chronic pancreatitis and the diseases that are often linked with pancreatitis including diabetes mellitus and pancreatic cancer. In addition to reviewing the current state of the field, we identify gaps in knowledge that are necessary to address to improve patient outcomes in these conditions.

Counseling in Malaysia: History, Current Status, and Future Trends

ERIC Educational Resources Information Center

See, Ching Mey; Ng, Kok-Mun

2010-01-01

This article presents an overview of the history of counseling in Malaysia, provides an update of its current status, and discusses some anticipated future trends for the profession in light of recent developments in the country. Counseling in Malaysia began with school guidance in the 1960s and has now achieved recognition as a profession in…

A class of semiparametric cure models with current status data.

PubMed

Diao, Guoqing; Yuan, Ao

2018-02-08

Current status data occur in many biomedical studies where we only know whether the event of interest occurs before or after a particular time point. In practice, some subjects may never experience the event of interest, i.e., a certain fraction of the population is cured or is not susceptible to the event of interest. We consider a class of semiparametric transformation cure models for current status data with a survival fraction. This class includes both the proportional hazards and the proportional odds cure models as two special cases. We develop efficient likelihood-based estimation and inference procedures. We show that the maximum likelihood estimators for the regression coefficients are consistent, asymptotically normal, and asymptotically efficient. Simulation studies demonstrate that the proposed methods perform well in finite samples. For illustration, we provide an application of the models to a study on the calcification of the hydrogel intraocular lenses.

Structure and activity of the Pseudomonas aeruginosa hotdog-fold thioesterases PA5202 and PA2801.

PubMed

Gonzalez, Claudio F; Tchigvintsev, Anatoli; Brown, Greg; Flick, Robert; Evdokimova, Elena; Xu, Xiaohui; Osipiuk, Jerzy; Cuff, Marianne E; Lynch, Susan; Joachimiak, Andrzej; Savchenko, Alexei; Yakunin, Alexander F

2012-06-15

The hotdog fold is one of the basic protein folds widely present in bacteria, archaea and eukaryotes. Many of these proteins exhibit thioesterase activity against fatty acyl-CoAs and play important roles in lipid metabolism, cellular signalling and degradation of xenobiotics. The genome of the opportunistic pathogen Pseudomonas aeruginosa contains over 20 genes encoding predicted hotdog-fold proteins, none of which have been experimentally characterized. We have found that two P. aeruginosa hotdog proteins display high thioesterase activity against 3-hydroxy-3-methylglutaryl-CoA and glutaryl-CoA (PA5202), and octanoyl-CoA (PA2801). Crystal structures of these proteins were solved (at 1.70 and 1.75 Å for PA5202 and PA2801 respectively) and revealed a hotdog fold with a potential catalytic carboxylate residue located on the long α-helix (Asp(57) in PA5202 and Glu(35) in PA2801). Alanine residue replacement mutagenesis of PA5202 identified four residues (Asn(42), Arg(43), Asp(57) and Thr(76)) that are critical for its activity and are located in the active site. A P. aeruginosa PA5202 deletion strain showed an increased secretion of the antimicrobial pigment pyocyanine and an increased expression of genes involved in pyocyanin biosynthesis, suggesting a functional link between PA5202 activity and pyocyanin production. Thus the P. aeruginosa hotdog thioesterases PA5202 and PA2801 have similar structures, but exhibit different substrate preferences and functions.

The Current Experimental Status of the High Tc Problem

NASA Astrophysics Data System (ADS)

Greene, Richard

Over 50,000 experimental papers have been published since 1987 on the copper oxide (cuprate) high Tc superconductors. In this talk, I will attempt to summarize the experimental properties that we presently understand and those that we don't yet understand. I will not speculate on the ``unknown unknowns'', although some examples of these have appeared during the past 30 years of research. I may also present a few slides about the status of iron-based superconductors, the other major class of unconventional high Tc materials.

Instantaneous Project Controls: Current Status, State of the Art, Benefits, and Strategies

ERIC Educational Resources Information Center

Abbaszadegan, Amin

2016-01-01

Despite advancements in construction and construction-related technology, capital project performance deviations, typically overruns, remain endemic within the capital projects industry. Currently, management is generally unaware of the current status of their projects, and thus monitoring and control of projects are not achieved effectively. In…

Phase diagrams for the system water/butyric acid/propylene carbonate at T = 293.2-313.2 K and p = 101.3 kPa

NASA Astrophysics Data System (ADS)

Shekarsaraee, Sina; Nahzomi, Hossein Taherpour; Nasiri-Touli, Elham

2017-11-01

Phase diagrams for the system water/butyric acid/propylene carbonate were plotted at T = 293.2, 303.2, 313.2 K and p = 101.3 kPa. Acidimetric titration and refractive index methods were used to determine tie-line data. Solubility data revealed that the studied system exhibits type-1 behavior of liquid-liquid equilibrium. The experimental data were regressed and acceptably correlated using the UNIQUAC and NRTL models. As a result, propylene carbonate is a suitable separating agent for aqueous mixture of butyric acid.

Complete mitogenome sequencing and phylogenetic analysis of PaLi yak (Bos grunniens).

PubMed

Bao, Pengjia; Guo, Xian; Pei, Jie; Liang, Chunnian; Ding, Xuezhi; Min, Chu; Wang, Hongbo; Wu, Xiaoyun; Yan, Ping

2016-11-01

PaLi yak is a very important local breed in China; as a year-round grazing animal, it plays a very important role for the economic and native herdsmen. The PaLi yak complete mitochondrial DNA is sequenced in this study, the total length is 16,324 bp, containing 13 protein-coding genes, 22 tRNA genes, 2 rRNA genes and a non-coding control region (D-loop region). The order and composition are similar to most of the other vertebrates. The base contents are: 33.72% A, 25.80% C, 13.21% G and 27.27% T; A + T (60.99%) was higher than G + C (39.01%). The phylogenetic relationships were analyzed using the complete mitogenome sequence, results showed that the genetic relationship between yak and cattle is distinct. These information provides useful data for further study on protection of genetic resources and the taxonomy of Bovinae.

[Clinical MR at 3 Tesla: current status].

PubMed

Baudendistel, K T; Heverhagen, J T; Knopp, M V

2004-01-01

Clinical MRI is mostly performed at field strengths up to 1.5 Tesla (T). Recently, approved clinical whole-body MR-systems with a field strength of 3 T became available. Its installation base is more rapidly growing than anticipated. While site requirements and operation of these systems do not differ substantially from systems with lower field strength, there are differences in practical applications. Imaging applications can use the gain in signal-to-noise for increased spatial resolution or gain in speed. This comes at a trade off in increased sensitivity to field inhomogeneities and changes in relaxation times, which lead to changes in image contrast. The benefit of high field for spectroscopy consists in increased signal-to-noise-ratio and improvement in frequency resolution. The increase in energy deposition necessitates the use of special strategies to reduce the specific absorption rate (SAR). This paper summarizes the current state of MR at 3 T.

Socio-economic effects on meeting PA guidelines: comparisons among 32 countries

PubMed Central

Borraccino, A; Lemma, P; Iannotti, R; Zambon, A; Dalmasso, P; Lazzeri, G; Giacchi, M; Cavallo, F

2008-01-01

Purpose This study examined the relationship between age and gender with physical activity (PA) and how meeting of PA guidelines (PAGL) is related to socio-economic-status. Methods Data were collected from 11-, 13-, and 15-y.o. students in 32 countries participating in the Health Behaviour in School-aged Children (HBSC) survey 2001/2002. A self-completed questionnaire assessed moderate-to-vigorous physical activity (MVPA) for the past seven days and MVPA for a typical week. Socio-economic status (SES) was assessed using the Family Affluence Scale (FAS). Results None of the countries averaged enough MVPA to meet PAGL. The pattern of MVPA across gender and age was consistent among all countries. In all countries girls were significantly less active than boys (mean hours/week of MVPA 3.52 ±1.88 vs 4.13 ±1.95) and were more likely to not meet the PAGL; older children were less active when compared to the youngest. SES was significantly associated with the amount of reported MVPA. SES and PAGL were significantly related in seven countries and a significant decrease in the influence of age was observed in these countries compared to other countries. Conclusions Levels of MVPA during adolescence showed consistent patterns across countries in relation to age, gender and social-class. The limited effect of age on PA in countries where the influence of social class was less strong, suggesting the possibility of a moderating effect of context in the development of habits acquired in childhood PMID:19276860

Current Status of Islet Cell Transplantation

PubMed Central

Ichii, Hirohito; Ricordi, Camillo

2013-01-01

Despite substantial advances in islet isolation methods and immunosuppressive protocol, pancreatic islet cell transplantation remains an experimental procedure currently limited to the most severe cases of type 1 diabetes mellitus (T1DM). The objectives of this treatment are to prevent severe hypoglycemic episodes in patients with hypoglycemia unawareness, and to achieve a more physiological metabolic control. Insulin independence and long term-graft function with improvement of quality of life have been obtained in several international islet transplant centers. However, experimental trials of islet transplantation clearly highlighted several obstacles that remain to be overcome before the procedure could be proposed to a much larger patient population. This review provides a brief historical perspective of islet transplantation, islet isolation techniques, the transplant procedure, immunosuppressive therapy, and outlines current challenges and future directions in clinical islet transplantation. PMID:19110649

The ALMA Science Pipeline: Current Status

NASA Astrophysics Data System (ADS)

Humphreys, Elizabeth; Miura, Rie; Brogan, Crystal L.; Hibbard, John; Hunter, Todd R.; Indebetouw, Remy

2016-09-01

The ALMA Science Pipeline is being developed for the automated calibration and imaging of ALMA interferometric and single-dish data. The calibration Pipeline for interferometric data was accepted for use by ALMA Science Operations in 2014, and for single-dish data end-to-end processing in 2015. However, work is ongoing to expand the use cases for which the Pipeline can be used e.g. for higher frequency and lower signal-to-noise datasets, and for new observing modes. A current focus includes the commissioning of science target imaging for interferometric data. For the Single Dish Pipeline, the line finding algorithm used in baseline subtraction and baseline flagging heuristics have been greately improved since the prototype used for data from the previous cycle. These algorithms, unique to the Pipeline, produce better results than standard manual processing in many cases. In this poster, we report on the current status of the Pipeline capabilities, present initial results from the Imaging Pipeline, and the smart line finding and flagging algorithm used in the Single Dish Pipeline. The Pipeline is released as part of CASA (the Common Astronomy Software Applications package).

Current status of Paragonimus and paragonimiasis in Ecuador

PubMed Central

Calvopiña, Manuel; Romero, Daniel; Castañeda, Byron; Hashiguchi, Yoshihisa; Sugiyama, Hiromu

2014-01-01

A review of national and international publications on paragonimiasis in Ecuador, epidemiological records from the Ministry of Public Health and unpublished research data was conducted to summarise the current status of the parasite/disease. The purpose of the review is to educate physicians, policy-makers and health providers on the status of the disease and to stimulate scientific investigators to conduct further research. Paragonimiasis was first diagnosed in Ecuador 94 years ago and it is endemic to both tropical and subtropical regions in 19 of 24 provinces in the Pacific Coast and Amazon regions. Paragonimus mexicanus is the only known species in the country, with the mollusc Aroapyrgus colombiensis and the crabs Moreirocarcinus emarginatus, Hypolobocera chilensis and Hypolobocera aequatorialis being the primary and secondary intermediate hosts, respectively. Recent studies found P. mexicanus metacercariae in Trichodactylus faxoni crabs of the northern Amazon. Chronic pulmonary paragonimiasis is commonly misdiagnosed and treated as tuberculosis and although studies have demonstrated the efficacy of praziquantel and triclabendazole for the treatment of human infections, neither drug is available in Ecuador. Official data recorded from 1978-2007 indicate an annual incidence of 85.5 cases throughout the 19 provinces, with an estimated 17.2% of the population at risk of infection. There are no current data on the incidence/prevalence of infection, nor is there a national control programme. PMID:25410987

Safety of tPA in stroke mimics and neuroimaging-negative cerebral ischemia(Podcast)(e–Pub ahead of print)(CME)

PubMed Central

Chernyshev, O.Y.; Martin-Schild, S.; Albright, K.C.; Barreto, A.; Misra, V.; Acosta, I.; Grotta, J.C.; Savitz, S.I.

2010-01-01

Background: Patients with acute neurologic symptoms may have other causes simulating ischemic stroke, called stroke mimics (SM), but they may also have averted strokes that do not appear as infarcts on neuroimaging, which we call neuroimaging-negative cerebral ischemia (NNCI). We determined the safety and outcome of IV thrombolysis within 3 hours of symptom onset in patients with SM and NNCI. Methods: Patients treated with IV tissue plasminogen activator (tPA) within 3 hours of symptom onset were identified from our stroke registry from June 2004 to October 2008. We collected admission NIH Stroke Scale (NIHSS) score, modified Rankin score (mRS), length of stay (LOS), symptomatic intracerebral hemorrhage (sICH), and discharge diagnosis. Results: Among 512 treated patients, 21% were found not to have an infarct on follow-up imaging. In the SM group (14%), average age was 55 years, median admission NIHSS was 7, median discharge NIHSS was 0, median LOS was 3 days, and there were no instances of sICH. The most common etiologies were seizure, complicated migraine, and conversion disorder. In the NNCI group (7%), average age was 61 years, median admission NIHSS was 7, median discharge NIHSS was 0, median LOS was 3 days, and there were no instances of sICH. Nearly all SM (87%) and NNCI (91%) patients were functionally independent on discharge (mRS 0–1). Conclusions: Our data support the safety of administering IV tissue plasminogen activator to patients with suspected acute cerebral ischemia within 3 hours of symptom onset, even when the diagnosis ultimately is found not to be stroke or imaging does not show an infarct. GLOSSARY AIS = acute ischemic stroke; CI = confidence interval; DWI = diffusion-weighted imaging; ED = emergency department; LOS = length of stay; mRS = modified Rankin score; NIHSS = NIH Stroke Scale; NNCI = neuroimaging-negative cerebral ischemia; OR = odds ratio; sICH = symptomatic intracerebral hemorrhage; SM = stroke mimics; tPA = tissue plasminogen

High-level expression of a novel recombinant human plasminogen activator (rhPA) in the milk of transgenic rabbits and its thrombolytic bioactivity in vitro.

PubMed

Song, Shaozheng; Ge, Xin; Cheng, Yaobin; Lu, Rui; Zhang, Ting; Yu, Baoli; Ji, Xueqiao; Qi, Zhengqiang; Rong, Yao; Yuan, Yuguo; Cheng, Yong

2016-08-01

The human tissue-type plasminogen activator (tPA) is a key kinase of fibrinolysis that plays an important role in dissolving fibrin clots to promote thrombolysis. The recombinant human plasminogen activator (rhPA) has more thrombolytic advantages than the wild type tPA. To increase the half-life and thrombolytic activity of tPA, a mutant containing only the essential K2 fibrin-binding and P activating plasminogen domains of the wild type tPA was cloned. This fragment was then inserted into goat β-casein regulatory sequences. Then, a mammary gland-specific expression vector, PCL25/rhPA, was constructed, and the transgenic rabbits were generated. In this study, 18 live transgenic founders (12♀, 6♂) were generated using pronuclear microinjection. Six transgenic rabbits were obtained, and the expression levels of rhPA in the milk had a range of 15.2-630 µg/ml. A fibrin agarose plate assay of rhPA showed that it had strong thrombolytic bioactivity in vitro, and the highest specific activity was >360 (360 times more than that of alteplase). The results indicated that the rhPA containing only the K2 and P domains is efficiently expressed with higher thrombolytic bioactivity in the milk of transgenic rabbits. Our study also demonstrated a new method for the large-scale production of clinically relevant recombinant pharmaceutical proteins in the mammary glands of transgenic rabbits.

Current status, crisis and trends in Chinese dental technicians.

PubMed

Chaoyi, Ma; Liwei, Zheng; Li, Yue; Min, Zhou; Haiyang, Yu

2012-04-01

Chinese dental technicians play a significant role in the globalised market of dental prosthesis fabrication, but this subject has not been investigated in detail. The demand for dental prostheses increases as individuals pay increasing attention to their oral health. Therefore, it is important to investigate the status of Chinese dental technicians. To evaluate the current status of Chinese dental technicians. Dental technicians' resumés, which reveal information regarding dental technician manpower, degrees, working age and salary, etc., were analysed and compared with those abroad. We also estimated the future demands of dental technician manpower, and discussed some potential solutions. There are fewer dental technicians in China than in other developed countries; they are also of a lower standard. Male technicians outnumber females. The education level of technicians is insufficient, and the education programme is still in its exploratory stage. The development of dental technician teams in China represents both an opportunity and a challenge. It is important to move forward from the current situation to yield long-term development. This article provides information on the Chinese dental technology industry, identifies the problems and offers solutions for its development. © 2012 FDI World Dental Federation.

Current status of the UCSF second-generation PACS

NASA Astrophysics Data System (ADS)

Huang, H. K.; Arenson, Ronald L.; Wong, Albert W. K.; Bazzill, Todd M.; Lou, Shyhliang A.; Andriole, Katherine P.; Wang, Jun; Zhang, Jianguo; Wong, Stephen T. C.

1996-05-01

This paper describes the current status of the second generation PACS at UCSF commenced in October 1992. The UCSF PACS is designed in-house as a hospital-integrated PACS based on an open architecture concept using industrial standards including UNIX operating system, C programming language, X-Window user interface, TCP/IP communication protocol, DICOM 3.0 image standard and HL7 health data format. Other manufacturer's PACS components which conform with these standards can be easily integrated into the system. Relevant data from HIS and RIS is automatically incorporated into the PACS using HL7 data format and TCP/IP communication protocol. The UCSF system also takes advantage of state-of-the-art communication, storage, and software technologies in ATM, multiple storage media, automatic programming, multilevel processes for a better cost-performance system. The primary PACS network is the 155 Mbits/sec OC3 ATM with the Ethernet as the back-up. The UCSF PACS also connects Mt. Zion Hospital and San Francisco VA Medical Center in the San Francisco Bay area via an ATM wide area network with a T1 line as the back-up. Currently, five MR and five CT scanners from multiple sites, two computed radiography systems, two film digitizers, one US PACS module, the hospital HIS and the department RIS have been connected to the PACS network. The image data is managed by a mirrored database (Sybase). The PACS controller, with its 1.3 terabyte optical disk library, acquires 2.5 gigabytes digital data daily. Four 2K, five, 1,600-line multiple monitor display workstations are on line in neuroradiology, pediatric radiology and intensive care units for clinical use. In addition, the PACS supports over 100 Macintosh users in the department and selected hospital sites for both images and textual retrieval through a client/server mechanism. We are also developing a computation and visualization node in the PACS network for advancing radiology research.

Current status of quantitative rotational spectroscopy for atmospheric research

NASA Technical Reports Server (NTRS)

Drouin, Brian J.; Wlodarczak, Georges; Colmont, Jean-Marcel; Rohart, Francois

2004-01-01

Remote sensing of rotational transitions in the Earth's atmosphere has become an important method for the retrieval of geophysical temperatures, pressures and chemical composition profiles that requires accurate spectral information. This paper highlights the current status of rotational data that are useful for atmospheric measurements, with a discussion of the types the rotational lineshape measurements that are not generally available in either online repository.

Structure and activity of the Pseudomonas aeruginosa hotdog-fold thioesterases PA5202 and PA2801

PubMed Central

Gonzalez, Claudio F.; Tchigvintsev, Anatoli; Brown, Greg; Flick, Robert; Evdokimova, Elena; Xu, Xiaohui; Osipiuk, Jerzy; Cuff, Marianne E.; Lynch, Susan; Joachimiak, Andrzej; Savchenko, Alexei; Yakunin, Alexander F.

2013-01-01

The hotdog fold is one of the basic protein folds widely present in bacteria, archaea, and eukaryotes. Many of these proteins exhibit thioesterase activity against fatty acyl-CoAs and play important roles in lipid metabolism, cellular signaling, and degradation of xenobiotics. The genome of the opportunistic pathogen Pseudomonas aeruginosa contains over 20 genes encoding predicted hotdog-fold proteins, none of which have been experimentally characterized. We have found that two P. aeruginosa hotdog proteins display high thioesterase activity against 3-hydroxy-3-methylglutaryl-CoA and glutaryl-CoA (PA5202), and octanoyl-CoA (PA2801). Crystal structures of these proteins were solved (1.70 and 1.75 Å) and revealed a hotdog fold with a potential catalytic carboxylate residue located on the long alpha helix (Asp57 in PA5202 and Glu35 in PA2801). Alanine replacement mutagenesis of PA5202 identified four residues (Asn42, Arg43, Asp57, and Thr76), which are critical for activity and are located in the active site. A P. aeruginosa PA5202 deletion strain showed an increased secretion of the antimicrobial pigment pyocyanine and an increased expression of genes involved in pyocyanin biosynthesis suggesting a functional link between the PA5202 activity and pyocyanin production. Thus, the P. aeruginosa hotdog thioesterases PA5202 and PA2801 have similar structures, but exhibit different substrate preferences and functions. PMID:22439787

The current status of evidence-based practice in juvenile justice.

PubMed

McKee, Esther Chao; Rapp, Lisa

2014-01-01

The advent of evidence-based practice (EBP) has significantly changed the juvenile justice system while producing intense controversy. The intent of this article is to provide an update on the current status of EBP in the juvenile justice system. Specifically, this article will describe the evolution of juvenile justice philosophy as it has informed current juvenile justice policies and programs, discuss the scope of current juvenile justice research regarding EBP, identify barriers to implementing EBP, expound on the development of EBP in juvenile justice, discern the characteristics of evidence-based interventions in the juvenile justice system, and finally describe how to select and assess evidence-based practices and interventions.

Observed Near-Surface Currents Under High Wind Speeds

DTIC Science & Technology

2012-11-28

16 MHz radar in the coastal water [Shay et al., 2007 ], 2.1% with a 30 MHz radar in the southern hemisphere [Mao and Heron, 2008]; and the surface...formulas from Jarosz et al. [ 2007 ], Powell et al. [2003], and Black et al. [ 2007 ] are used in this study to represent such depen- dence of Cd on W...7 Pa;Cd from Jarosz et al: 2007 ½ ð Þ; ð4Þ U ¼ 0:336t þ 0:128; 0:9 Pa < t < 4:7 Pa;Cd from Powell et al: 2003½ ð Þ; ð5Þ U ¼ 0:394t þ 0:131; 0:8 Pa

ACRF Ingest Software Status: New, Current, and Future - April 2008

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

AS Koontz; S Choudhury; BD Ermold

2008-04-01

The purpose of this report is to provide status of the ingest software used to process instrument data for the Atmospheric Radiation Measurement Program Climate Research Facility (ACRF). The report is divided into 4 sections: (1) for news about ingests currently under development, (2) for current production ingests, (3) for future ingest development plans, and (4) for information on retired ingests. Please note that datastreams beginning in “xxx” indicate cases where ingests run at multiple ACRF sites, which results in a datastream(s) for each location.

ACRF Ingest Software Status: New, Current, and Future (September 2007)

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

Koontz, AS; Choudhury, S; Ermold, BD

2007-04-01

The purpose of this report is to provide status of the ingest software used to process instrument data for the Atmospheric Radiation Measurement Program Climate Research Facility (ACRF). The report is divided into 4 sections: (1) for news about ingests currently under development, (2) for current production ingests, (3) for future ingest development plans, and (4) for information on retired ingests. Please note that datastreams beginning in “xxx” indicate cases where ingests run at multiple ACRF sites, which results in a datastream(s) for each location.

ACRF Ingest Software Status: New, Current, and Future - May 2008

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

AS Koontz; S Choudhury; BD Ermold

2008-05-01

The purpose of this report is to provide status of the ingest software used to process instrument data for the Atmospheric Radiation Measurement Program Climate Research Facility (ACRF). The report is divided into 4 sections: (1) for news about ingests currently under development, (2) for current production ingests, (3) for future ingest development plans, and (4) for information on retired ingests. Please note that datastreams beginning in “xxx” indicate cases where ingests run at multiple ACRF sites, which results in a datastream(s) for each location.

The Current Status of Sport Sociology within American and Canadian Colleges and Universities.

ERIC Educational Resources Information Center

Brooks, Dana D.

The purpose of this study was to investigate the current status of sport sociology within American and Canadian Colleges and Universities. The study investigated: (1) the number of graduate and undergraduate courses offered in sport sociology; (2) current research area(s) of interest within sport sociology; (3) current text used as reference and…

Current status of the Taiwan Photon Source project

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

Chang, Shih-Lin

2014-03-05

The progress of establishment of a high brightness and low emittance mid-energy storage ring is reported. The status of the 3 GeV Taiwan Photon Source (TPS) currently under construction will be presented. The progress on the civil construction, manufacturing of machine components, as well as the opportunity of using low emittace synchrotron source and phase I beamlines at TPS will be mentioned. The future planning of phase II beamlines and related research will be sketched. Future developments will be also briefly outlined.

Current status of nuclear cardiology: a limited review

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

Botvinick, E.H.; Dae, M.; Hattner, R.S.

1985-11-01

To summarize the current status of nuclear cardiology, the authors will focus on areas that the emphasize the specific advantages of nuclear cardiology methods: (a) their benign, noninvasive nature, (b) their pathophysiologic nature, and (c) the ease of their computer manipulation and analysis, permitting quantitative evaluation. The areas covered include: (a) blood pool scintigraphy and parametric imaging, (b) pharmacologic intervention for the diagnosis of ischemic heart disease, (c) scintigraphic studies for the diagnosis and prognosis of coronary artery disease, and (d) considerations of cost effectiveness.

Current Status of Immunomodulatory and Cellular Therapies in Preclinical and Clinical Islet Transplantation

PubMed Central

Chhabra, Preeti; Brayman, Kenneth L.

2011-01-01

Clinical islet transplantation is a β-cell replacement strategy that represents a possible definitive intervention for patients with type 1 diabetes, offering substantial benefits in terms of lowering daily insulin requirements and reducing incidences of debilitating hypoglycemic episodes and unawareness. Despite impressive advances in this field, a limiting supply of islets, inadequate means for preventing islet rejection, and the deleterious diabetogenic and nephrotoxic side effects associated with chronic immunosuppressive therapy preclude its wide-spread applicability. Islet transplantation however allows a window of opportunity for attempting various therapeutic manipulations of islets prior to transplantation aimed at achieving superior transplant outcomes. In this paper, we will focus on the current status of various immunosuppressive and cellular therapies that promote graft function and survival in preclinical and clinical islet transplantation with special emphasis on the tolerance-inducing capacity of regulatory T cells as well as the β-cells regenerative capacity of stem cells. PMID:22046502

Current Backpack Weight Status for Primary Schoolchildren in Colima, Mexico

ERIC Educational Resources Information Center

Olmedo-Buenrostro, Bertha Alicia; Delgado-Enciso, Iván; Sánchez-Ramírez, Carmen Alicia; Cruz, Sergio Adrián Montero; Vásquez, Clemente; Mora-Brambila, Ana Bertha; Rodríguez-Sánchez, Iram P.; Martínez-Fierro, Margarita L.

2016-01-01

The purpose of the study was to identify the current status of backpack weight in primary schoolchildren in Colima, Mexico, in relation to gender, school grade level, and body mass index. A cross-sectional study was conducted on 240 randomly selected children from 20 primary schools. The participating children's parents signed statements of…

Corporate Blended Learning in Portugal: Current Status and Future Directions

ERIC Educational Resources Information Center

Marcal, Julia; Caetano, Antonio

2010-01-01

The aim of this study is to characterize the current status of blended learning in Portugal, given that b-learning has grown exponentially in the Portuguese market over recent years. 38 organizations (representing 68% of all institutions certified to provide distance training by the Government Labour Office--DGERT-) participated in this study. The…

Adoptive immunotherapy for hematological malignancies: Current status and new insights in chimeric antigen receptor T cells.

PubMed

Allegra, Alessandro; Innao, Vanessa; Gerace, Demetrio; Vaddinelli, Doriana; Musolino, Caterina

2016-11-01

Hematological malignancies frequently express cancer-associated antigens that are shared with normal cells. Such tumor cells elude the host immune system because several T cells targeted against self-antigens are removed during thymic development, and those that persist are eliminated by a regulatory population of T cells. Chimeric antigen receptor-modified T cells (CAR-Ts) have emerged as a novel modality for tumor immunotherapy due to their powerful efficacy against tumor cells. These cells are created by transducing genes-coding fusion proteins of tumor antigen-recognition single-chain Fv connected to the intracellular signaling domains of T cell receptors, and are classed as first-, second- and third-generation, differing on the intracellular signaling domain number of T cell receptors. CAR-T treatment has emerged as a promising approach for patients with hematological malignancies, and there are several works reporting clinical trials of the use of CAR-modified T-cells in acute lymphoblastic leukemia, chronic lymphoblastic leukemia, multiple myeloma, lymphoma, and in acute myeloid leukemia by targeting different antigens. This review reports the history of adoptive immunotherapy using CAR-Ts, the CAR-T manufacturing process, and T cell therapies in development for hematological malignancies. Copyright © 2016 Elsevier Inc. All rights reserved.

ACE Objectives, Current Status and the 2017 Decadal Survey

NASA Technical Reports Server (NTRS)

Da Silva, Arlindo

2018-01-01

In this talk we present an overview of the Aerosol-Cloud-Ecosystems (ACE) preformulation studies, a tier-2 satellite mission recommended by the 2007 Decadal Survey. We discuss the current status of ACE measurement concepts and associated retrieval algorithms. We conclude with a brief discussion of the recommendations by the 2017 Decadal Survey and how ACE accomplishments can inform the future Aerosol and Cloud, Convection & Precipitation Designated Observables.

The evolution of recombinant thrombolytics: Current status and future directions

PubMed Central

Adivitiya; Khasa, Yogender Pal

2017-01-01

ABSTRACT Cardiovascular disorders are on the rise worldwide due to alcohol abuse, obesity, hypertension, raised blood lipids, diabetes and age-related risks. The use of classical antiplatelet and anticoagulant therapies combined with surgical intervention helped to clear blood clots during the inceptive years. However, the discovery of streptokinase and urokinase ushered the way of using these enzymes as thrombolytic agents to degrade the fibrin network with an issue of systemic hemorrhage. The development of second generation plasminogen activators like anistreplase and tissue plasminogen activator partially controlled this problem. The third generation molecules, majorly t-PA variants, showed desirable properties of improved stability, safety and efficacy with enhanced fibrin specificity. Plasmin variants are produced as direct fibrinolytic agents as a futuristic approach with targeted delivery of these drugs using liposome technlogy. The novel molecules from microbial, plant and animal origin present the future of direct thrombolytics due to their safety and ease of administration. PMID:27696935

Current status of percutaneous coronary intervention of chronic total occlusion

PubMed Central

Ge, Jun-bo

2012-01-01

This paper describes the current status of percutaneous coronary intervention (PCI) for totally occluded coronary arteries. Chronic total occlusion is associated with 10%–20% of all PCI procedures. Results show that opening an occluded vessel, especially one supplying a considerable area of myocardium, may be beneficial for a patient’s angina relief and heart function. We describe the devices used currently in re-canalization such as new wires, microcatheters (including Tonus and Cosair) and intravascular ultrasound guidance. Different techniques to improve the success rate and reduce complications are discussed in detail. PMID:22843178

Testing Viable f(T) Models with Current Observations

NASA Astrophysics Data System (ADS)

Xu, Bing; Yu, Hongwei; Wu, Puxun

2018-03-01

We perform observational tests on the f(T) gravity with the BAO data (including the BOSS DR 12 galaxy sample, the DR12 Lyα-Forests measurement, the new eBOSS DR14 quasar sample, the 6dFGS, and the SDSS), the CMB distance priors from the Planck 2015, the SNIa data from the joint light-curve analysis, the latest H(z) data, and the local value of the Hubble constant. Six different f(T) models are investigated. Furthermore, the ΛCDM is also considered. All models are compared by using the Akaike information criteria (AIC) and the Bayesian information criteria (BIC). Our results show that the ΛCDM remains to be the most favored model by current observations. However, there are also the Hubble constant tension between the Planck measurements and the local Universe observations and the tension between the CMB data and the H(z) data in the ΛCDM. For f(T) models considered in this paper, half, which can reduce to the ΛCDM, have values of {{χ }2}\\min smaller than that of the ΛCDM and can relieve the tensions existing in the ΛCDM. However, they are punished slightly by the BIC due to one extra parameter. Two of six f(T) models, in which the crossing of the phantom divide line can be realized for the equation of state of the effective dark energy and this crossing is shown in this paper to be favored by current observations, are punished by the information criteria. In addition, we find that the logarithmic f(T) model is excluded by cosmological observations.

Project Plan 7930 Cell G PaR Remote Handling System Replacement

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

Kinney, Kathryn A

2009-10-01

For over 40 years the US Department of Energy (DOE) and its predecessors have made Californium-252 ({sup 252}Cf) available for a wide range of industries including medical, nuclear fuels, mining, military and national security. The Radiochemical Engineering Development Center (REDC) located within the Oak Ridge National Laboratory (ORNL) processes irradiated production targets from the High Flux Isotope Reactor (HFIR). Operations in Building 7930, Cell G provide over 70% of the world's demand for {sup 252}Cf. Building 7930 was constructed and equipped in the mid-1960s. Current operations for {sup 252}Cf processing in Building 7930, Cell G require use of through-the-wall manipulatorsmore » and the PaR Remote Handling System. Maintenance and repairs for the manipulators is readily accomplished by removal of the manipulator and relocation to a repair shop where hands-on work can be performed in glove boxes. Contamination inside cell G does not currently allow manned entry and no provisions were created for a maintenance area inside the cell. There has been no maintenance of the PaR system or upgrades, leaving operations vulnerable should the system have a catastrophic failure. The Cell G PaR system is currently being operated in a run to failure mode. As the manipulator is now 40+ years old there is significant risk in this method of operation. In 2006 an assessment was completed that resulted in recommendations for replacing the manipulator operator control and power centers which are used to control and power the PaR manipulator in Cell G. In mid-2008 the chain for the bridge drive failed and subsequent examinations indicated several damaged links (see Figure 1). To continue operations the PaR manipulator arm is being used to push and pull the bridge as a workaround. A retrieval tool was fabricated, tested and staged inside Cell G that will allow positioning of the bridge and manipulator arm for removal from the cell should the PaR system completely fail. A fully

Treatment of solid tumors with chimeric antigen receptor-engineered T cells: current status and future prospects.

PubMed

Di, Shengmeng; Li, Zonghai

2016-04-01

Chimeric antigen receptors (CARs) are artificial recombinant receptors that generally combine the antigen-recognition domain of a monoclonal antibody with T cell activation domains. Recent years have seen great success in clinical trials employing CD19-specific CAR-T cell therapy for B cell leukemia. Nevertheless, solid tumors remain a major challenge for CAR-T cell therapy. This review summarizes the preclinical and clinical studies on the treatment of solid tumors with CAR-T cells. The major hurdles for the success of CAR-T and the novel strategies to address these hurdles have also been described and discussed.

Pharmacodynamic evaluation of clopidogrel plus PA32540: the Spaced PA32540 With Clopidogrel Interaction Gauging (SPACING) study.

PubMed

Gurbel, P A; Bliden, K P; Fort, J; Zhang, Y; Plachetka, J R; Antonino, M; Gesheff, M; Tantry, U S

2011-12-01

PA32540 combines 325 mg enteric-coated (EC) aspirin (ASA) with 40 mg immediate-release omeprazole; its influence on the antiplatelet effect of clopidogrel (C) is unknown. In this randomized, open-label study, subjects (n = 30) were treated with (i) 300 mg C + 325 mg ECASA followed by 75 mg C + 325 mg ECASA on days 2-7, (ii) 300 mg C + PA32540 followed by 75 mg C + PA32540 on days 2-7, or (iii) PA32540 in the morning + 300 mg C 10 h later on day 1 and PA32540 in the morning + 75 mg C 10 h later on days 2-7. We analyzed the noninferiority of PA32540 relative to ECASA, as defined by the upper bound of the 95% confidence interval ≤10% for the difference in least-square means of platelet inhibition between the treatments. As compared to ECASA+C, synchronous treatment of PA32540+C was not noninferior, whereas the spacing strategy of PA32540+C was noninferior. Spacing the administration of PA32540 and clopidogrel lessens the interaction observed with synchronous administration; PA32540 administration with clopidogrel may be associated with a different antiplatelet profile.

Longitudinal Relationships of Fitness, Physical Activity, and Weight Status With Academic Achievement in Adolescents.

PubMed

Suchert, Vivien; Hanewinkel, Reiner; Isensee, Barbara

2016-10-01

To examine associations of cardiorespiratory fitness, physical activity (PA) and weight status with academic achievement 1 year later. In addition, the mediating role of psychological variables was tested. Longitudinal analyses included 1011 German students (M = 14.1 years, SD = 0.6 years). Cardiorespiratory fitness was determined with the 20 m shuttle run test. Compliance with PA guidelines was assessed through questionnaire. Weight status was based on body mass index percentiles. As proxy of academic achievement students' self-reported grades in Mathematics and German in their midterm report were averaged. Mediation analyses were conducted at follow-up testing general self-efficacy, depressed affect, and attention/hyperactivity problems. High levels of cardiorespiratory fitness predicted higher educational attainment (p = .007), while we found no longitudinal association for PA and weight status (p > .253). However, students being insufficiently physically active at baseline but meet PA guidelines at follow-up showed a significant improvement in educational attainment. The cross-sectional association between PA and academic achievement was mediated by students' general self-efficacy. High fitness in adolescence is associated with higher subsequent academic achievement. The promotion of PA might benefit school performance because of enhanced fitness levels in the long-term and positive influences of PA in the shortterm. The association between weight status and educational attainment remains controversial. © 2016, American School Health Association.

The Current Status of Classroom Inclusion Activities of Secondary Agriculture Teachers

ERIC Educational Resources Information Center

Hoerst, Caryn M.; Whittington, M. Susie

2009-01-01

The current status of classroom inclusion activities among agriculture teachers in comprehensive secondary agricultural education programs in Ohio is reported. The researchers describe secondary agriculture teachers' needs related to teaching learners with special needs in inclusion classes, given legislative mandates. Specifically, the…

Nano-JASMINE: current status and data output

NASA Astrophysics Data System (ADS)

Kobayashi, Yukiyasu; Yano, Taihei; Gouda, Naoteru; Niwa, Yoshito; Murooka, Jyunpei; Yamada, Yoshiyuki; Sako, Nobutada; Nakasuka, Shin'ichi

2010-07-01

The current status of the Nano-JASMINE project is reported. Nano-JASMINE is a very small-sized (50 cm cubic form) satellite that is expected to carry out astrometric observations of nearby bright stars. The satellite will determine distances of more than 8000 stars by performing annual parallax measurements, which is the only direct method to measure the distance of an astronomical object. The mission is required to continue for more than two years to obtain reliable annual parallax measurements. In addition, Nano-JASMINE will serve as a preliminary to the main JASMINE mission. We expect that Nano-JASMINE will be launched in August 2011 from the Alcantara Space Center in Brazil using the Cyclone-4 rocket.

History of co-occurring disorders and current mental health status among homeless veterans.

PubMed

Ding, Kele; Slate, Matthew; Yang, Jingzhen

2018-06-18

Homeless veterans are at high risk for co-occurring disorders (COD), defined as mental illnesses that include at least one alcohol or other drug use disorder and at least one non-drug related mental disorder. However, epidemiological studies examining the prevalence of COD and associated mental health status in this population are limited. The objectives of the study were: (1) to describe a history of diagnosed mental disorders among homeless veterans admitted to a transitional housing program, and (2) to examine the associations of the prior diagnosed COD and other mental disorders with current mental health status. Study participants were male homeless veterans admitted to a transitional housing program from July 2015 to September 2017 in a large municipal area in Northeast Ohio, the United States. Cross-sectional, self-reported data from the admission assessment were included and analyzed. History of mental disorder diagnoses were aggregated into five categories for the purpose of this study: no mental disorders, only alcohol or other drug use disorder(s), one non-drug related mental disorder, two or more non-drug related mental disorders, and COD. Current mental status were measured as empowerment, mental component summary score (MCS) and physical component summary score (PCS) of health related quality of life (VR-12), and perceived overall well-being. Sample distribution of the five categories and their associations with current mental status were examined using Generalized Linear Model test. Of all participants, 76.7% had at least one prior diagnosed mental disorder, including 47.4% with any drug-related disorders. Over one-third (37.2%) reported having COD. Compared to those with no mental disorder history, those with COD scored significantly lower on MCS and empowerment scores; those with any prior diagnosed non-drug related mental disorders also scored significantly lower on MCS. No significant differences, however, were found in current mental health

Feminist identity as a predictor of eating disorder diagnostic status.

PubMed

Green, Melinda A; Scott, Norman A; Riopel, Cori M; Skaggs, Anna K

2008-06-01

Passive Acceptance (PA) and Active Commitment (AC) subscales of the Feminist Identity Development Scale (FIDS) were examined as predictors of eating disorder diagnostic status as assessed by the Questionnaire for Eating Disorder Diagnoses (Q-EDD). Results of a hierarchical regression analysis revealed PA and AC scores were not statistically significant predictors of ED diagnostic status after controlling for diagnostic subtype. Results of a multiple regression analysis revealed FIDS as a statistically significant predictor of ED diagnostic status when failing to control for ED diagnostic subtype. Discrepancies suggest ED diagnostic subtype may serve as a moderator variable in the relationship between ED diagnostic status and FIDS. (c) 2008 Wiley Periodicals, Inc.

Current Status of Protein Force Fields for Molecular Dynamics

PubMed Central

Lopes, Pedro E.M.; Guvench, Olgun

2015-01-01

Summary The current status of classical force fields for proteins is reviewed. These include additive force fields as well as the latest developments in the Drude and AMOEBA polarizable force fields. Parametrization strategies developed specifically for the Drude force field are described and compared with the additive CHARMM36 force field. Results from molecular simulations of proteins and small peptides are summarized to illustrate the performance of the Drude and AMOEBA force fields. PMID:25330958

Regulatory T cells ameliorate tissue plasminogen activator-induced brain haemorrhage after stroke.

PubMed

Mao, Leilei; Li, Peiying; Zhu, Wen; Cai, Wei; Liu, Zongjian; Wang, Yanling; Luo, Wenli; Stetler, Ruth A; Leak, Rehana K; Yu, Weifeng; Gao, Yanqin; Chen, Jun; Chen, Gang; Hu, Xiaoming

2017-07-01

Delayed thrombolytic treatment with recombinant tissue plasminogen activator (tPA) may exacerbate blood-brain barrier breakdown after ischaemic stroke and lead to lethal haemorrhagic transformation. The immune system is a dynamic modulator of stroke response, and excessive immune cell accumulation in the cerebral vasculature is associated with compromised integrity of the blood-brain barrier. We previously reported that regulatory T cells, which function to suppress excessive immune responses, ameliorated blood-brain barrier damage after cerebral ischaemia. This study assessed the impact of regulatory T cells in the context of tPA-induced brain haemorrhage and investigated the underlying mechanisms of action. The number of circulating regulatory T cells in stroke patients was dramatically reduced soon after stroke onset (84 acute ischaemic stroke patients with or without intravenous tPA treatment, compared to 115 age and gender-matched healthy controls). Although stroke patients without tPA treatment gradually repopulated the numbers of circulating regulatory T cells within the first 7 days after stroke, post-ischaemic tPA treatment led to sustained suppression of regulatory T cells in the blood. We then used the murine suture and embolic middle cerebral artery occlusion models of stroke to investigate the therapeutic potential of adoptive regulatory T cell transfer against tPA-induced haemorrhagic transformation. Delayed administration of tPA (10 mg/kg) resulted in haemorrhagic transformation in the ischaemic territory 1 day after ischaemia. When regulatory T cells (2 × 106/mouse) were intravenously administered immediately after delayed tPA treatment in ischaemic mice, haemorrhagic transformation was significantly decreased, and this was associated with improved sensorimotor functions. Blood-brain barrier disruption and tight junction damages were observed in the presence of delayed tPA after stroke, but were mitigated by regulatory T cell transfer. Mechanistic

Curriculum leadership in the postgraduate: Gap between current and optimal status.

PubMed

Avizhgan, Maryam; Jafari, Ebrahim Mirshah; Nasr, Ahmad Reza; Changiz, Tahereh

2015-04-01

Identifying the strengths and weakness points is one of the effective methods to analyze current status, and prioritizing actions based on the gap between current and optimal status is necessary for short-term and long-term planning in departments and colleges. The aim of this study was to determine the gap between current and optimal status of curriculum leadership in the postgraduate courses in two Iranian universities. In this cross-sectional study, a sample of 212 faculty members from the two Iranian universities (one medical and one nonmedical) was randomly selected through stratified random sampling method. Data were collected by using a researcher-made questionnaire, with 55 items categorized in four areas of main dimensions in curriculum leadership. The validity of the questionnaire was determined by curriculum studies scholars, and the reliability was confirmed as the Cronbach's alpha calculated 0.969. Data were analyzed using descriptive and inferential statistics according to the variables. There was a gap in all dimensions and roles. The maximum gap (-1.70) with the highest frequency (98%) were related to "improving the educational atmosphere" dimension. As for items, the maximum gap (-2.41) was related to "society needs and expectations and the labor market" in "curriculum development and revision" dimension. The negative gap between all dimensions of curriculum leadership implies faculty members' dissatisfaction. Curriculum leadership at universities, colleges and departments of the study in all aspects need to be improved. Hence, it is necessary for managers to make use of the viewpoints of the faculty members to decrease the gap.

Overexpression of PaFT gene in the wild orchid Phalaenopsis amabilis (L.) Blume

NASA Astrophysics Data System (ADS)

Semiarti, Endang; Mercuriani, Ixora S.; Rizal, Rinaldi; Slamet, Agus; Utami, Bekti S.; Bestari, Ida A.; Aziz-Purwantoro, Moeljopawiro, S.; Jang, Soenghoe; Machida, Y.; Machida, C.

2015-09-01

To shorten vegetative stage and induce transition from vegetative to reproductive stage in orchids, we overexpressed Phalaenopsis amabilis Flowering LocusT (PaFT) gene under the control of Ubiquitin promoter into protocorm of Indonesian Wild Orchid Phalaenopsis amabilis (L.) Blume. The dynamic expression of vegetative gene Phalaenopsis Homeobox1 (POH1) and flowering time gene PaFT has been analyzed. Accumulation of mRNA was detected in shoot and leaves of both transgenic and non transgenic plants by using Reverse transcriptase-PCR (RT-PCR) with specific gene primers for POH1 and PaFT in 24 months old plants. To analyze the POH1 and PaFT genes, three pairs of degenerate primers PaFT degF1R1, F2R2 and F3R3 that amplified 531 bp PaFT cDNA were used. We detected 700 bp PaFTcDNA from leaves and shoots of transgenic plants, but not in NT plants. POH1 mRNA was detected in plants. PaFT protein consists of Phospatidyl Ethanolamine-Binding Protein (PEBP) in interval base 73-483 and CETS family protein at base 7-519, which are important motif for transmembrane protein. We inserted Ubipro::PaFT/pGAS101 into P. amabilis protocorm using Agrobacterium. Analysis of transgenic plants showed that PaFTmRNA was accumulated in leaves of 12 months after sowing, although it is not detected in non transgeic plants. Compare to the wild type (NT plants), ectopic expression of PaFT shows alter phenotype as follows: 31% normal, 19% with short-wavy leaves, 5% form rosette leaves and 45% produced multishoots. Analysis of protein profiles of trasgenic plants showed that a putative PaFT protein (MW 19,7 kDa) was produced in 1eaves and shoots.This means that at 12 months, POH1 gene expression gradually decreased/negatively regulated, the expression of PaFT gene was activated, although there is no flower initiation yet. Some environmental factors might play a role to induce inflorescens. This experiment is in progress.

In vitro resistance to the human immunodeficiency virus type 1 maturation inhibitor PA-457 (Bevirimat).

PubMed

Adamson, Catherine S; Ablan, Sherimay D; Boeras, Ioana; Goila-Gaur, Ritu; Soheilian, Ferri; Nagashima, Kunio; Li, Feng; Salzwedel, Karl; Sakalian, Michael; Wild, Carl T; Freed, Eric O

2006-11-01

3-O-(3',3'-dimethylsuccinyl)betulinic acid (PA-457 or bevirimat) potently inhibits human immunodeficiency virus type 1 (HIV-1) maturation by blocking a late step in the Gag processing pathway, specifically the cleavage of SP1 from the C terminus of capsid (CA). To gain insights into the mechanism(s) by which HIV-1 could evolve resistance to PA-457 and to evaluate the likelihood of such resistance arising in PA-457-treated patients, we sought to identify and characterize a broad spectrum of HIV-1 variants capable of conferring resistance to this compound. Numerous independent rounds of selection repeatedly identified six single-amino-acid substitutions that independently confer PA-457 resistance: three at or near the C terminus of CA (CA-H226Y, -L231F, and -L231M) and three at the first and third residues of SP1 (SP1-A1V, -A3T, and -A3V). We determined that mutations CA-H226Y, CA-L231F, CA-L231M, and SP1-A1V do not impose a significant replication defect on HIV-1 in culture. In contrast, mutations SP1-A3V and -A3T severely impaired virus replication and inhibited virion core condensation. The replication defect imposed by SP1-A3V was reversed by a second-site compensatory mutation in CA (CA-G225S). Intriguingly, high concentrations of PA-457 enhanced the maturation of SP1 residue 3 mutants. The different phenotypes associated with mutations that confer PA-457 resistance suggest the existence of multiple mechanisms by which HIV-1 can evolve resistance to this maturation inhibitor. These findings have implications for the ongoing development of PA-457 to treat HIV-1 infection in vivo.

Hunger Doesn't Take a Vacation: Summer Nutrition Status Report.

ERIC Educational Resources Information Center

Food Research and Action Center, Washington, DC.

This report describes the current status of the Summer Food Service Program (SFSP) and the National School Lunch Program (NSLP) (referred to in combination as the Summer Nutrition Programs), federal entitlement programs providing support for state and local efforts to offer low-income children nutritious summer meals and snacks during supervised…

Prognostics and Health Management of Wind Turbines: Current Status and Future Opportunities

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

Sheng, Shuangwen

This presentation was given at the 2016 Annual Conference of the Prognostics and Health Management Society. It covers the current status and challenges and opportunities of prognostics and health management of wind turbines.

Measuring stigma in children receiving mental health treatment: Validation of the Paediatric Self-Stigmatization Scale (PaedS).

PubMed

Kaushik, A; Papachristou, E; Dima, D; Fewings, S; Kostaki, E; Ploubidis, G B; Kyriakopoulos, M

2017-06-01

Research on the impact of stigma associated with mental illness in children is scarce. Considering the known negative effects of stigma associated with mental illness in adults, it is crucial to explore the stigma experienced by children who access mental health treatment. However, no scale measuring self-stigmatization in younger children is available to date. This study aimed to develop and validate such a scale, the Paediatric Self-Stigmatization Scale (PaedS). A total of 156 children (119 receiving outpatient and 37 receiving inpatient treatment), aged 8-12 years, completed the PaedS, the Self-Perception Profile for Children and the Pediatric Quality of Life Inventory (PedsQL - Child Report, ages 8-12). In addition, parents completed the PedsQL (Parent Report for Children, ages 8-12), the Strengths and Difficulties Questionnaire (SDQ) and a modified subscale of the PaedS measuring the children's rejection by others due to their mental health difficulties. A confirmatory factor analysis showed that a four-factor structure, comprising Societal Devaluation, Personal Rejection, Self-Stigma and Secrecy scales, had excellent fit to the data (CFI=0.95; TLI=0.95; RMSEA=0.05). Child-reported PaedS scores were positively correlated with parental-reported PaedS scores and negatively with PedsQL, the SDQ, and 5 out of 6 subscales of the Self-Perception Profile for Children, suggesting adequate convergent validity (all P-values<0.05). The PaedS is a valid instrument, which is hoped to advance the understanding of self-stigmatization in children with mental health difficulties and contribute to its prevention. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Current status and future prospects of research and development operations in traditional and complementary and alternative medicine manufacturing small- and medium-sized enterprises: a 2014 company-based survey.

PubMed

Ahn, Miyoung; Park, Eun-Ji; Woo, Jong-Min

2017-12-01

Small- and medium-sized enterprises (SMEs) have played key roles in the economic growth and technical innovation of traditional and complementary and alternative medicine (T&CM). Research and development (R&D) are critical activities for industrial progress. This study aimed to characterize the current status of SME R&D activities and to explore manufacturers' perceptions of R&D expansion. Records of the distribution of T&CM SMEs and R&D resources detailed in the 2014 Statistics of Korea T&CM Industries survey, a previously conducted survey on the industrial status of the T&CM field, were reviewed. Data on the perceptions of R&D activities were investigated through a company-based survey covering 285 T&CM-manufacturing SMEs. Greater than 99% of the 13,636 T&CM manufacturers at the time of the study were SMEs employing less than 50 workers. Natural cosmetics manufacturing SMEs (NC SMEs) had the highest R&D expenditures. NC SMEs rely heavily on internal R&D operations, which may contribute to their strong need for R&D collaboration with public research institutions and expanded T&CM-promoted R&D programs. "Digestive system disorders" are the main target diseases for current herbal and dietary supplement manufacturing SMEs and herbal medicine manufacturing SMEs. These SMEs tend to view their own product-related business as a priority for future R&D investment. This study represents the first attempt to assess SME perceptions of R&D activities. The findings herein can inform the design of sustainable programs that support R&D by reducing the gaps between the perspectives of T&CM product makers and policymakers.

Current status and perspectives of cysticercosis and taeniasis in Japan.

PubMed

Yamasaki, Hiroshi

2013-02-01

This mini-review describes recent epidemiological trends in cysticercosis and taeniasis in Japan. Some of the topics discussed herein were presented at the first symposium on "Current perspectives of Taenia asiatica researches", that was held in Osong in Chungbuk Province, South Korea, in October 2011 and organized by Prof. K. S. Eom, Chungbuk National University School of Medicine. To better understand the trends in the occurrence of cysticercosis and taeniasis in Japan, clinical cases reported in 2005 have been updated. In addition, the current status of Taenia asiatica infections successively occurring in Japan since 2010 is also discussed.

Current Status and Perspectives of Cysticercosis and Taeniasis in Japan

PubMed Central

2013-01-01

This mini-review describes recent epidemiological trends in cysticercosis and taeniasis in Japan. Some of the topics discussed herein were presented at the first symposium on "Current perspectives of Taenia asiatica researches", that was held in Osong in Chungbuk Province, South Korea, in October 2011 and organized by Prof. K. S. Eom, Chungbuk National University School of Medicine. To better understand the trends in the occurrence of cysticercosis and taeniasis in Japan, clinical cases reported in 2005 have been updated. In addition, the current status of Taenia asiatica infections successively occurring in Japan since 2010 is also discussed. PMID:23467264

Current status and challenges in developing Ni phytomining: An agronomic perspective

USDA-ARS?s Scientific Manuscript database

This review examines the current status, progress and challenges in Ni phytomining agronomy undertaken since the first field trial two decades ago. To date, over 400 Ni hyperaccumulators have been documented (of which >30% are in Cuba) including approximately 50 species with potential for use in Ni ...

Immunopotentiator from Pantoea agglomerans 1 (IP-PA1) Promotes Murine Hair Growth and Human Dermal Papilla Cell Gene Expression.

PubMed

Wakame, Koji; Okawa, Hiroshi; Komatsu, Ken-Ich; Nakata, Akifumi; Sato, Keisuke; Ingawa, Hiroyuki; Kohchi, Chie; Nishizawa, Takashi; Soma, Gen-Ichiro

2016-07-01

The lipopolysaccharide (LPS)-like compound derived from Pantoea agglomerans (immunopotentiator from Pantoea agglomerans 1 (IP-PA1)) has been used not only as dietary supplement or cosmetic for humans, but also by Japanese veterinarians as an anti-tumor, anti-allergy, "keep a fine coat of fur" and hair growth-promoting functional food for dogs and cats. In the present study, we focused on the hair growth-promoting effects of IP-PA1 on a hair-shaved animal model and its mechanism of action. We also investigated its potential on gene expression after stimulating human dermal papilla cells with IP-PA1. The hair on the back of a C3H/HeN mouse was shaved and IP-PA1 was orally administered or applied to the skin. The status of hair growth was observed and recorded for 14 days. Skin was collected and histological tissue examination was performed with respect to hair growth status using hematoxylin and eosin staining. After IP-PA1 administration (2 and 10 μg/ml) to human dermal papilla cell culture system for 24 h, fibroblast growth factor-7 (FGF-7) and vascular endothelial growth factor (VEGF) mRNA expression were measured using real-time polymerase chain reaction (PCR) analysis. IP-PA1, when given orally, showed a tendency to promote hair growth in mice. In addition, skin application also significantly promoted hair growth, while histopathological examinations further demonstrated hair elongation from dermal papilla cells. In the human dermal papilla cell culture system, significant FGF-7 and VEGF mRNA expressions were observed (p<0.05). An underlying mechanism of gene expression by which IP-PA1 promotes hair growth was suggested to be different from that of medicine and traditional hair tonics, such as minoxidil and adenosine. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Polycystic ovary syndrome: current status and future perspective

PubMed Central

Barthelmess, Erin K.; Naz, Rajesh K.

2015-01-01

Polycystic ovary syndrome (PCOS) is a widespread reproductive disorder that encompasses many associated health conditions and has an impact on various metabolic processes. PCOS is depicted by hyperandrogenism, polycystic ovaries, and anovulation. It increases the risk of insulin resistance (IR), type 2 diabetes, obesity, and cardiovascular disease. The etiology of the disease remains unclear, and the subjective phenotype makes a united diagnosis difficult among physicians. It seems to be a familial genetic syndrome caused by a combination of environmental and genetic factors. It can be linked with metabolic disorders in first-degree family members. PCOS is the cause of up to 30% of infertility in couples seeking treatment. Currently, there is no cure for PCOS. Despite the growing incidence of this syndrome, limited research has been done that encompasses the entirety of PCOS spectrum. In this review, the current status and possible future perspective will be discussed. PMID:24389146

Review: Current clinical applications of chimeric antigen receptor (CAR) modified T cells.

PubMed

Geyer, Mark B; Brentjens, Renier J

2016-11-01

The past several years have been marked by extraordinary advances in clinical applications of immunotherapy. In particular, adoptive cellular therapy utilizing chimeric antigen receptor (CAR)-modified T cells targeted to CD19 has demonstrated substantial clinical efficacy in children and adults with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL) and durable clinical benefit in a smaller subset of patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or B-cell non-Hodgkin lymphoma (B-NHL). Early-phase clinical trials are currently assessing CAR T-cell safety and efficacy in additional malignancies. Here, we discuss clinical results from the largest series to date investigating CD19-targeted CAR T cells in B-ALL, CLL, and B-NHL, including discussion of differences in CAR T-cell design and production and treatment approach, as well as clinical efficacy, nature of severe cytokine release syndrome and neurologic toxicities, and CAR T-cell expansion and persistence. We additionally review the current and forthcoming use of CAR T cells in multiple myeloma and several solid tumors and highlight challenges and opportunities afforded by the current state of CAR T-cell therapies, including strategies to overcome inhibitory aspects of the tumor microenvironment and enhance antitumor efficacy. Published by Elsevier Inc.

Current status of endoscopic simulation in gastroenterology fellowship training programs.

PubMed

Jirapinyo, Pichamol; Thompson, Christopher C

2015-07-01

Recent guidelines have encouraged gastroenterology and surgical training programs to integrate simulation into their core endoscopic curricula. However, the role that simulation currently has within training programs is unknown. This study aims to assess the current status of simulation among gastroenterology fellowship programs. This questionnaire study consisted of 38 fields divided into two sections. The first section queried program directors' experience on simulation and assessed the current status of simulation at their institution. The second portion surveyed their opinion on the potential role of simulation on the training curriculum. The study was conducted at the 2013 American Gastroenterological Association Training Directors' Workshop in Phoenix, Arizona. The participants were program directors from Accreditation Council for Graduate Medical Education accredited gastroenterology training programs, who attended the workshop. The questionnaire was returned by 69 of 97 program directors (response rate of 71%). 42% of programs had an endoscopic simulator. Computerized simulators (61.5%) were the most common, followed by mechanical (30.8%) and animal tissue (7.7%) simulators, respectively. Eleven programs (15%) required fellows to use simulation prior to clinical cases. Only one program has a minimum number of hours fellows have to participate in simulation training. Current simulators are deemed as easy to use (76%) and good educational tools (65%). Problems are cost (72%) and accessibility (69%). The majority of program directors believe that there is a need for endoscopic simulator training, with only 8% disagreeing. Additionally, a majority believe there is a role for simulation prior to initiation of clinical cases with 15% disagreeing. Gastroenterology fellowship program directors widely recognize the importance of simulation. Nevertheless, simulation is used by only 42% of programs and only 15% of programs require that trainees use simulation prior to

Association of Marital Status With T Stage at Presentation and Management of Early-Stage Melanoma.

PubMed

Sharon, Cimarron E; Sinnamon, Andrew J; Ming, Michael E; Chu, Emily Y; Fraker, Douglas L; Karakousis, Giorgos C

2018-05-01

Early detection of melanoma is associated with improved patient outcomes. Data suggest that spouses or partners may facilitate detection of melanoma before the onset of regional and distant metastases. Less well known is the influence of marital status on the detection of early clinically localized melanoma. To evaluate the association between marital status and T stage at the time of presentation with early-stage melanoma and the decision for sentinel lymph node biopsy (SLNB) in appropriate patients. This retrospective, population-based study used the Surveillance, Epidemiology, and End Results database of 18 population-based registered cancer institutes. Patients with cutaneous melanoma who were at least 18 years of age and without evidence of regional or distant metastases and presented from January 1, 2010, through December 31, 2014, were identified for the study. Data were analyzed from September 27 to December 5, 2017. Marital status, categorized as married, never married, divorced, or widowed. Clinical T stage at presentation and performance of SLNB for lesions with Breslow thickness greater than 1 mm. A total of 52 063 patients were identified (58.8% men and 41.2% women; median age, 64 years; interquartile range, 52-75 years). Among married patients, 16 603 (45.7%) presented with T1a disease, compared with 3253 never married patients (43.0%), 1422 divorced patients (39.0%), and 1461 widowed patients (32.2%) (P < .001). Conversely, 428 widowed patients (9.4%) presented with T4b disease compared with 1188 married patients (3.3%) (P < .001). The association between marital status and higher T stage at presentation remained significant among never married (odds ratio [OR], 1.32; 95% CI, 1.26-1.39; P < .001), divorced (OR, 1.38; 95% CI, 1.30-1.47; P < .001), and widowed (OR, 1.70; 95% CI, 1.60-1.81; P < .001) patients after adjustment for various socioeconomic and patient factors. Independent of T stage and other patient factors, married

[Nutritional status of adults with cystic fibrosis - current methods of assessment].

PubMed

Szabla, Anna; Skorupa, Wojciech; Milewska, Magdalena; Weker, Halina

2015-11-01

Cystic fibrosis (CF) is one of the most frequent monogenic disease in the Caucasian population, inherited in an autosomal recessive pattern. This is a multiple organ disease and its main manifestations include pulmonary and gastrointestinal dysfunction. The exocrine pancreatic deficiency results in impaired digestion and absorption what may lead to malnutrition and vitamins and minerals deficiencies. The life expectancy of cystic fibrosis patients has been increasing over the past years, so there is a need to verify usefulness of existing or create new methods of nutritional status assessment. The aim of this paper was presentation current data on the methods of assessment and monitoring of nutritional status. Particular attention has been paid to appropriate nutritional support in prevention and treatment of malnutrition patients with cystic fibrosis. On the basis of recent literature we can conclude that the advanced nutritional status assessment is recommended in patient with CF by using anthropometrical methods, body composition analysis and biochemical data. Good nutritional status is connected with pulmonary functions, quality and life length. © 2015 MEDPRESS.

Curriculum leadership in the postgraduate: Gap between current and optimal status

PubMed Central

Avizhgan, Maryam; Jafari, Ebrahim Mirshah; Nasr, Ahmad Reza; Changiz, Tahereh

2015-01-01

Background: Identifying the strengths and weakness points is one of the effective methods to analyze current status, and prioritizing actions based on the gap between current and optimal status is necessary for short-term and long-term planning in departments and colleges. The aim of this study was to determine the gap between current and optimal status of curriculum leadership in the postgraduate courses in two Iranian universities. Materials and Methods: In this cross-sectional study, a sample of 212 faculty members from the two Iranian universities (one medical and one nonmedical) was randomly selected through stratified random sampling method. Data were collected by using a researcher-made questionnaire, with 55 items categorized in four areas of main dimensions in curriculum leadership. The validity of the questionnaire was determined by curriculum studies scholars, and the reliability was confirmed as the Cronbach's alpha calculated 0.969. Data were analyzed using descriptive and inferential statistics according to the variables. Results: There was a gap in all dimensions and roles. The maximum gap (−1.70) with the highest frequency (98%) were related to “improving the educational atmosphere” dimension. As for items, the maximum gap (−2.41) was related to “society needs and expectations and the labor market” in “curriculum development and revision” dimension. Conclusion: The negative gap between all dimensions of curriculum leadership implies faculty members’ dissatisfaction. Curriculum leadership at universities, colleges and departments of the study in all aspects need to be improved. Hence, it is necessary for managers to make use of the viewpoints of the faculty members to decrease the gap. PMID:26109996

Does weight status influence associations between children's fundamental movement skills and physical activity?

PubMed

Hume, Clare; Okely, Anthony; Bagley, Sarah; Telford, Amanda; Booth, Michael; Crawford, David; Salmon, Jo

2008-06-01

This study sought to determine whether weight status influences the association among children's fundamental movement skills (FMS) and physical activity (PA). Two hundred forty-eight children ages 9-12 years participated. Proficiency in three object-control skills and two locomotor skills was examined. Accelerometers objectively assessed physical activity. Body mass index was calculated to determine weight status. Correlations between physical activity and FMS proficiency were evident among boys and girls. No significant interaction was apparent when examining FMS proficiency scores, PA variables, and weight status. Future studies should examine a broader range of skills and types of activities to better characterize this relationship and to inform the promotion of movement skill proficiency and PA.

Current status of syphilis in pregnant women in Japan.

PubMed

Suzuki, Shunji; Sekizawa, Akihiko; Tanaka, Masanobu; Okai, Takashi; Kinoshita, Katsuyuki; Kitamura, Tadaichi

2017-12-01

We examined the current status of syphilis-infected pregnant Japanese women, according to the results of syphilis screening and confirmation tests of women who gave birth in Japan between October, 2015 and March, 2016. We requested 2458 obstetrical facilities to provide information of syphilis screening tests and 78.1% of them responded. Considering the response rate and the rate of implementation of confirmation tests, the number of syphilis-infected pregnant Japanese women was estimated to be 250 (1/4022) per year.

The current status of 3D imaging in dental practice.

PubMed

McNamara, Clare; House, Kate; Davies, Rebecca; Barker, Chris S; Chawla, Ourvinder; Sandy, Jonathan R; Ireland, Anthony J

2011-12-01

This article aims to describe the current status of 3-dimensional (3D) imaging in dental practice. Advances in this field have made 3D imaging far more accessible in all dental fields. This paper describes methods of imaging dental hard and soft tissues and their clinical uses. In addition, the potential advantages and disadvantages of various systems are discussed, as well as expected future developments.

77 FR 22333 - Agency Information Collection Activities: USCIS Case Status Online, Extension of a Currently...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-13

... Collection Activities: USCIS Case Status Online, Extension of a Currently Approved Information Collection; Comment Request ACTION: 30-Day notice of information collection under review: USCIS case status online... the following information collection request to the Office of Management and Budget (OMB) for review...

Enzyme-linked immunosorbent assay using a recombinant baculovirus-expressed Bacillus anthracis protective antigen (PA): measurement of human anti-PA antibodies.

PubMed Central

Iacono-Connors, L C; Novak, J; Rossi, C; Mangiafico, J; Ksiazek, T

1994-01-01

We developed an antigen capture enzyme-linked immunosorbent assay (ELISA) which does not require purified protective antigen (PA) for detection of human antibodies to Bacillus anthracis PA. Lysates of Spodoptera frugiperda (Sf-9) cells infected with recombinant baculovirus containing the PA gene were used as the source of PA to develop the ELISA. Recombinant PA from crude Sf-9 cell lysates or PA purified from B. anthracis Sterne strain was captured by an anti-PA monoclonal antibody coated onto microtiter plates. We demonstrated that human serum antibody titers to PA were identical in the ELISA whether we used crude Sf-9 cell lysates containing recombinant baculovirus-expressed PA or purified Sterne PA. Finally, false-positive results observed in a direct ELISA were eliminated with this antigen capture ELISA. Thus, the antigen capture ELISA with crude preparations of baculovirus-expressed PA is reliable, safe, and inexpensive for determining anti-PA antibody levels in human sera. PMID:7496927

Folate intake and the MTHFR C677T genotype influence choline status in young Mexican American women☆

PubMed Central

Abratte, Christian M.; Wang, Wei; Li, Rui; Moriarty, David J.; Caudill, Marie A.

2009-01-01

Numerous studies have reported a relationship between folate status, the methylenetetrahydrofolate reductase (MTHFR) 677C→T variant and disease risk. Although folate and choline metabolism are inter-related, only limited data are available on the relationship between choline and folate status in humans. This study sought to examine the influences of folate intake and the MTHFR 677C→T variant on choline status. Mexican-American women (n =43; 14 CC, 12 CT and 17 TT) consumed 135 μg/day as dietary folate equivalents (DFE) for 7 weeks followed by randomization to 400 or 800 μg DFE/day for 7 weeks. Throughout the study, total choline intake remained unchanged at ∼350 mg/day. Plasma concentrations of betaine, choline, glycerophosphocholine, phosphatidylcholine and sphingomyelin were measured via LC-MS/MS for Weeks 0, 7 and 14. Phosphatidylcholine and sphingomyelin declined ( P=.001, P=.009, respectively) in response to folate restriction and increased ( P=.08, P=.029, respectively) in response to folate treatment. The increase in phosphatidylcholine occurred in response to 800 ( P=.03) not 400 ( P=.85) μg DFE/day (week×folate interaction, P=.017). The response of phosphatidylcholine to folate intake appeared to be influenced by MTHFR C677T genotype. The decline in phosphatidylcholine during folate restriction occurred primarily in women with the CC or CT genotype and not in the TT genotype (week×genotype interaction, P=.089). Moreover, when examined independent of folate status, phosphatidylcholine was higher ( P <.05) in the TT genotype relative to the CT genotype. These data suggest that folate intake and the MTHFR C677T genotype influence choline status in humans. PMID:17588738

A chronicle of PA journals.

PubMed

Hooker, Roderick S

2017-02-01

At its semicentennial mark, the PA profession appears to be flourishing. Over the past 50 years, a number of journals have emerged to highlight the development of the profession and offer observations on it. The Physician Associate Journal, launched in 1970, was the first foray into PA reporting. Following this small effort, a dozen journals or newspapers came into print, lasted for a while, and then were replaced or died. Of journals that survived to the present, four are in English and one in Dutch. Three of the five journals are association-based, and four produce clinical articles; publication is monthly, quarterly, or semiannually. Two journals produce original health services research or studies on the PA education process and have citable track records. Readership of all journals is growing, and collectively these periodicals produce a body of scholarly work that clarifies the PA as a healthcare professional growing on a world stage. This article describes the journalistic history of one aspect of PA development.

Proinflammatory T Cell Status Associated with Early Life Adversity.

PubMed

Elwenspoek, Martha M C; Hengesch, Xenia; Leenen, Fleur A D; Schritz, Anna; Sias, Krystel; Schaan, Violetta K; Mériaux, Sophie B; Schmitz, Stephanie; Bonnemberger, Fanny; Schächinger, Hartmut; Vögele, Claus; Turner, Jonathan D; Muller, Claude P

2017-12-15

Early life adversity (ELA) has been associated with an increased risk for diseases in which the immune system plays a critical role. The ELA immune phenotype is characterized by inflammation, impaired cellular immunity, and immunosenescence. However, data on cell-specific immune effects are largely absent. Additionally, stress systems and health behaviors are altered in ELA, which may contribute to the generation of the ELA immune phenotype. The present investigation tested cell-specific immune differences in relationship to the ELA immune phenotype, altered stress parameters, and health behaviors in individuals with ELA ( n = 42) and those without a history of ELA (control, n = 73). Relative number and activation status (CD25, CD69, HLA-DR, CD11a, CD11b) of monocytes, NK cells, B cells, T cells, and their main subsets were assessed by flow cytometry. ELA was associated with significantly reduced numbers of CD69 + CD8 + T cells ( p = 0.022), increased numbers of HLA-DR + CD4 and HLA-DR + CD8 T cells ( p < 0.001), as well as increased numbers of CD25 + CD8 + T cells ( p = 0.036). ELA also showed a trend toward higher numbers of CCR4 + CXCR3 - CCR6 + CD4 T cells. Taken together, our data suggest an elevated state of immune activation in ELA, in which particularly T cells are affected. Although several aspects of the ELA immune phenotype were related to increased activation markers, neither stress nor health-risk behaviors explained the observed group differences. Thus, the state of immune activation in ELA does not seem to be secondary to alterations in the stress system or health-risk behaviors, but rather a primary effect of early life programming on immune cells. Copyright © 2017 by The American Association of Immunologists, Inc.

The Current Status of Unsteady CFD Approaches for Aerodynamic Flow Control

NASA Technical Reports Server (NTRS)

Carpenter, Mark H.; Singer, Bart A.; Yamaleev, Nail; Vatsa, Veer N.; Viken, Sally A.; Atkins, Harold L.

2002-01-01

An overview of the current status of time dependent algorithms is presented. Special attention is given to algorithms used to predict fluid actuator flows, as well as other active and passive flow control devices. Capabilities for the next decade are predicted, and principal impediments to the progress of time-dependent algorithms are identified.

Bullied Status and Physical Activity in Texas Adolescents

ERIC Educational Resources Information Center

Case, Kathleen R.; Pérez, Adriana; Saxton, Debra L.; Hoelscher, Deanna M.; Springer, Andrew E.

2016-01-01

This study examined the association between having been bullied at school during the past 6 months ("bullied status") and not meeting physical activity (PA) recommendations of 60 minutes of daily PA during the past week among 8th- and 11th-grade Texas adolescents. Multiple logistic regression analysis was conducted to examine this…

Ureteroscopy and stones: Current status and future expectations

PubMed Central

Wright, Anna E; Rukin, Nicholas J; Somani, Bhaskar K

2014-01-01

Urolithaisis is becoming an ever increasing urological, nephrological and primary care problem. With a lifetime prevalence approaching 10% and increasing morbidity due to stone disease, the role of ureteroscopy and stone removal is becoming more important. We discuss the current status of stone disease and review the ever increasing role that ureteroscopy has to play in its management. We discuss technological advances that have been made in stone management and give you an overview of when, how and why ureteroscopy is the most common treatment option for stone management. We touch on the role of robotic ureteroscopy and the future of ureteroscopy in the next 10 years. PMID:25374818

Novel model of direct and indirect cost-benefit analysis of mechanical embolectomy over IV tPA for large vessel occlusions: a real-world dollar analysis based on improvements in mRS.

PubMed

Mangla, Sundeep; O'Connell, Keara; Kumari, Divya; Shahrzad, Maryam

2016-01-20

Ischemic strokes result in significant healthcare expenditures (direct costs) and loss of quality-adjusted life years (QALYs) (indirect costs). Interventional therapy has demonstrated improved functional outcomes in patients with large vessel occlusions (LVOs), which are likely to reduce the economic burden of strokes. To develop a novel real-world dollar model to assess the direct and indirect cost-benefit of mechanical embolectomy compared with medical treatment with intravenous tissue plasminogen activator (IV tPA) based on shifts in modified Rankin scores (mRS). A cost model was developed including multiple parameters to account for both direct and indirect stroke costs. These were adjusted based upon functional outcome (mRS). The model compared IV tPA with mechanical embolectomy to assess the costs and benefits of both therapies. Direct stroke-related costs included hospitalization, inpatient and outpatient rehabilitation, home care, skilled nursing facilities, and long-term care facility costs. Indirect costs included years of life expectancy lost and lost QALYs. Values for the model cost parameters were derived from numerous resources and functional outcomes were derived from the MR CLEAN study as a reflective sample of LVOs. Direct and indirect costs and benefits for the two treatments were assessed using Microsoft Excel 2013. This cost-benefit model found a cost-benefit of mechanical embolectomy over IV tPA of $163 624.27 per patient and the cost benefit for 50 000 patients on an annual basis is $8 181 213 653.77. If applied widely within the USA, mechanical embolectomy will significantly reduce the direct and indirect financial burden of stroke ($8 billion/50 000 patients). Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

History, Current Status, and Future Prospects of Counseling in South Korea

ERIC Educational Resources Information Center

Lee, Sang Min; Suh, Suhyun; Yang, Eunjoo; Jang, Yoo Jin

2012-01-01

Although the counseling profession was introduced to South Korea in the 1950s by American delegates of education, counseling has been only lately recognized as a specialized field that requires distinctive knowledge and skills. In this article, the authors describe the history and the current status of counseling in South Korea and then discuss…

Inhibition of motor cortex excitability with 15Hz transcranial alternating current stimulation (tACS).

PubMed

Zaghi, Soroush; de Freitas Rezende, Larissa; de Oliveira, Laís Machado; El-Nazer, Rasheda; Menning, Sanne; Tadini, Laura; Fregni, Felipe

2010-08-02

There remains a lack of solid evidence showing whether transcranial stimulation with weak alternating current (transcranial alternating current stimulation, tACS) can in fact induce significant neurophysiological effects. Previously, a study in which tACS was applied for 2 and 5min with current density=0.16-0.25A/m(2) was unable to show robust effects on cortical excitability. Here we applied tACS at a significantly higher current density (0.80A/m(2)) for a considerably longer duration (20min) and were indeed able to demonstrate measurable changes to cortical excitability. Our results show that active 15Hz tACS of the motor cortex (electrodes placed at C3 and C4) significantly diminished the amplitude of motor evoked potentials and decreased intracortical facilitation (ICF) as compared to baseline and sham stimulation. In addition, we show that our method of sham tACS is a reliable control condition. These results support the notion that AC stimulation with weak currents can induce significant changes in brain excitability; in this case, 15Hz tACS led to a pattern of inhibition of cortical excitability. We propose that tACS may have a dampening effect on cortical networks and perhaps interfere with the temporal and spatial summation of weak subthreshold electric potentials. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

Modelling the effect of electrode displacement on transcranial direct current stimulation (tDCS)

NASA Astrophysics Data System (ADS)

Ramaraju, Sriharsha; Roula, Mohammed A.; McCarthy, Peter W.

2018-02-01

Objective. Transcranial direct current stimulation (tDCS) is a neuromodulatory technique that delivers a low-intensity, direct current to cortical areas with the purpose of modulating underlying brain activity. Recent studies have reported inconsistencies in tDCS outcomes. The underlying assumption of many tDCS studies has been that replication of electrode montage equates to replicating stimulation conditions. It is possible however that anatomical difference between subjects, as well as inherent inaccuracies in montage placement, could affect current flow to targeted areas. The hypothesis that stimulation of a defined brain region will be stable under small displacements was tested. Approach. Initially, we compared the total simulated current flowing through ten specific brain areas for four commonly used tDCS montages: F3-Fp2, C3-Fp2, Fp1-F4, and P3-P4 using the software tool COMETS. The effect of a slight (~1 cm in each of four directions) anode displacement on the simulated regional current density for each of the four tDCS montages was then determined. Current flow was calculated and compared through ten segmented brain areas to determine the effect of montage type and displacement. The regional currents, as well as the localised current densities, were compared with the original electrode location, for each of these new positions. Main results. Recommendations for montages that maximise stimulation current for the ten brain regions are considered. We noted that the extent to which stimulation is affected by electrode displacement varies depending on both area and montage type. The F3-Fp2 montage was found to be the least stable with up to 38% change in average current density in the left frontal lobe while the Fp1-F4 montage was found to the most stable exhibiting only 1% change when electrodes were displaced. Significance. These results indicate that even relatively small changes in stimulation electrode placement appear to result in surprisingly large

Parallel cascade selection molecular dynamics (PaCS-MD) to generate conformational transition pathway

NASA Astrophysics Data System (ADS)

Harada, Ryuhei; Kitao, Akio

2013-07-01

Parallel Cascade Selection Molecular Dynamics (PaCS-MD) is proposed as a molecular simulation method to generate conformational transition pathway under the condition that a set of "reactant" and "product" structures is known a priori. In PaCS-MD, the cycle of short multiple independent molecular dynamics simulations and selection of the structures close to the product structure for the next cycle are repeated until the simulated structures move sufficiently close to the product. Folding of 10-residue mini-protein chignolin from the extended to native structures and open-close conformational transition of T4 lysozyme were investigated by PaCS-MD. In both cases, tens of cycles of 100-ps MD were sufficient to reach the product structures, indicating the efficient generation of conformational transition pathway in PaCS-MD with a series of conventional MD without additional external biases. Using the snapshots along the pathway as the initial coordinates, free energy landscapes were calculated by the combination with multiple independent umbrella samplings to statistically elucidate the conformational transition pathways.

Identification of novel amino acid residues of influenza virus PA-X that are important for PA-X shutoff activity by using yeast.

PubMed

Oishi, Kohei; Yamayoshi, Seiya; Kawaoka, Yoshihiro

2018-03-01

The influenza A virus protein PA-X comprises an N-terminal PA region and a C-terminal PA-X-specific region. PA-X suppresses host gene expression, termed shutoff, via mRNA cleavage. Although the endonuclease active site in the N-terminal PA region of PA-X and basic amino acids in the C-terminal PA-X-specific region are known to be important for PA-X shutoff activity, other amino acids may also play a role. Here, we used yeast to identify novel amino acids of PA-X that are important for PA-X shutoff activity. Unlike wild-type PA-X, most PA-X mutants predominantly localized in the cytoplasm, indicating that these mutations decreased the shutoff activity of PA-X by affecting PA-X translocation to the nucleus. Mapping of the identified amino acids onto the N-terminal structure of PA revealed that some of them likely contribute to the formation of the endonuclease active site of PA. Copyright © 2018. Published by Elsevier Inc.

Regulatory Considerations for the Clinical and Research Use of Transcranial Direct Current Stimulation (tDCS): review and recommendations from an expert panel

PubMed Central

Fregni, F; Nitsche, MA; Loo, C.K.; Brunoni, AR; Marangolo, P; Leite, J; Carvalho, S; Bolognini, N; Caumo, W; Paik, NJ; Simis, M; Ueda, K; Ekhitari, H; Luu, P; Tucker, DM; Tyler, WJ; Brunelin, J; Datta, A; Juan, CH; Venkatasubramanian, G; Boggio, PS; Bikson, M

2014-01-01

The field of transcranial electrical stimulation (tES) has experienced significant growth in the past 15 years. One of the tES techniques leading this increased interest is transcranial direct current stimulation (tDCS). Significant research efforts have been devoted to determining the clinical potential of tDCS in humans. Despite the promising results obtained with tDCS in basic and clinical neuroscience, further progress has been impeded by a lack of clarity on international regulatory pathways. We therefore convened a group of research and clinician experts on tDCS to review the research and clinical use of tDCS. In this report, we review the regulatory status of tDCS, and we summarize the results according to research, off-label and compassionate use of tDCS in the following countries: Australia, Brazil, France, Germany, India, Iran, Italy, Portugal, South Korea, Taiwan and United States. Research use, off label treatment and compassionate use of tDCS are employed in most of the countries reviewed in this study. It is critical that a global or local effort is organized to pursue definite evidence to either approve and regulate or restrict the use of tDCS in clinical practice on the basis of adequate randomized controlled treatment trials. PMID:25983531

Augmenting Visual Search Performance with Transcranial Direct Current Stimulation (tDCS)

DTIC Science & Technology

2015-09-28

Augmenting Visual Search Performance with Transcranial Direct Current Stimulation ( tDCS ) 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 62202F...stimulation ( tDCS ) over the left frontal eye field (LFEF) region of the scalp to improve cognitive performance. The participants received anodal and...blinking frequency in relation to stimulation condition. Our data suggest that tDCS over the LFEF would be a beneficial countermeasure to mitigate the

Comparison of anamnestic responses to rabies vaccination in dogs and cats with current and out-of-date vaccination status.

PubMed

Moore, Michael C; Davis, Rolan D; Kang, Qing; Vahl, Christopher I; Wallace, Ryan M; Hanlon, Cathleen A; Mosier, Derek A

2015-01-15

To compare anamnestic antibody responses of dogs and cats with current versus out-of-date vaccination status. Cross-sectional study. 74 dogs and 33 cats. Serum samples were obtained from dogs and cats that had been exposed to rabies and brought to a veterinarian for proactive serologic monitoring or that had been brought to a veterinarian for booster rabies vaccination. Blood samples were collected on the day of initial evaluation (day 0) and then again 5 to 15 days later. On day 0, a rabies vaccine was administered according to label recommendations. Paired serum samples were analyzed for antirabies antibodies by means of a rapid fluorescent focus inhibition test. All animals had an antirabies antibody titer ≥ 0.5 IU/mL 5 to 15 days after booster vaccination. Dogs with an out-of-date vaccination status had a higher median increase in titer, higher median fold increase in titer, and higher median titer following booster vaccination, compared with dogs with current vaccination status. Most (26/33) cats, regardless of rabies vaccination status, had a titer ≥ 12 IU/mL 5 to 15 days after booster vaccination. Results indicated that dogs with out-of-date vaccination status were not inferior in their antibody response following booster rabies vaccination, compared with dogs with current vaccination status. Findings supported immediate booster vaccination followed by observation for 45 days of dogs and cats with an out-of-date vaccination status that are exposed to rabies, as is the current practice for dogs and cats with current vaccination status.

Generic Medicine Pricing Policies in Europe: Current Status and Impact

PubMed Central

Dylst, Pieter; Simoens, Steven

2010-01-01

Generic medicine pricing is an area of national responsibility of European Union countries. This article aims to present the current status and impact of generic medicine pricing policies in ambulatory care in Europe. The study conducts a literature review of policies relating to free-pricing systems, price-regulated systems, price differentiation, price competition and discounts, and tendering procedures; and a survey of European generic medicine pricing policies. Competition from Indian generic medicine manufacturers, European variation in generic medicine prices and competition between generic medicine manufacturers by discount suggest that the potential savings to health care payers and patients from generic medicines are not fully realized in Europe. One way of attaining these savings may be to move away from competition by discount to competition by price. Free-pricing systems may drive medicine prices downwards under specific conditions. In price-regulated systems, regulation may lower prices of originator and generic medicines, but may also remove incentives for additional price reductions beyond those imposed by regulation. To date, little is known about the current status and impact of tendering procedures for medicines in ambulatory care. In conclusion, the European experience suggests that there is not a single approach towards developing generic medicine pricing policies in Europe. PMID:27713264

Magnetic resonance angiography: current status and future directions

PubMed Central

2011-01-01

With recent improvement in hardware and software techniques, magnetic resonance angiography (MRA) has undergone significant changes in technique and approach. The advent of 3.0 T magnets has allowed reduction in exogenous contrast dose without compromising overall image quality. The use of novel intravascular contrast agents substantially increases the image windows and decreases contrast dose. Additionally, the lower risk and cost in non-contrast enhanced (NCE) MRA has sparked renewed interest in these methods. This article discusses the current state of both contrast-enhanced (CE) and NCE-MRA. New CE-MRA methods take advantage of dose reduction at 3.0 T, novel contrast agents, and parallel imaging methods. The risks of gadolinium-based contrast media, and the NCE-MRA methods of time-of-flight, steady-state free precession, and phase contrast are discussed. PMID:21388544

Augmentation of Fear Extinction by Transcranial Direct Current Stimulation (tDCS)

PubMed Central

Dittert, Natalie; Hüttner, Sandrina; Polak, Thomas; Herrmann, Martin J.

2018-01-01

Although posttraumatic stress disorder (PTSD; DSM-V 309.82) and anxiety disorders (DSM-V 300.xx) are widely spread mental disorders, the effectiveness of their therapy is still unsatisfying. Non-invasive brain-stimulation techniques like transcranial direct current stimulation (tDCS) might be an option to improve extinction learning, which is a main functional factor of exposure-based therapy for anxiety disorders. To examine this hypothesis, we used a fear conditioning paradigm with female faces as conditioned stimuli (CS) and a 95-dB female scream as unconditioned stimulus (UCS). We aimed to perform a tDCS of the ventromedial prefrontal cortex (vmPFC), which is mainly involved in the control of extinction-processes. Therefore, we applied two 4 × 4 cm electrodes approximately at the EEG-positions F7 and F8 and used a direct current of 1.5 mA. The 20-min stimulation was started during a 10-min break between acquisition and extinction and went on overall extinction-trials. The healthy participants were randomly assigned in two double-blinded process into two sham stimulation and two verum stimulation groups with opposite current flow directions. To measure the fear reactions, we used skin conductance responses (SCR) and subjective ratings. We performed a generalized estimating equations model for the SCR to assess the impact of tDCS and current flow direction on extinction processes for all subjects that showed a successful conditioning (N = 84). The results indicate that tDCS accelerates early extinction processes with a significantly faster loss of CS+/CS– discrimination. The discrimination loss was driven by a significant decrease in reaction toward the CS+ as well as an increase in reaction toward the CS– in the tDCS verum groups, whereas the sham groups showed no significant reaction changes during this period. Therefore, we assume that tDCS of the vmPFC can be used to enhance early extinction processes successfully. But before it should be tested in a

Surface EEG-Transcranial Direct Current Stimulation (tDCS) Closed-Loop System.

PubMed

Leite, Jorge; Morales-Quezada, Leon; Carvalho, Sandra; Thibaut, Aurore; Doruk, Deniz; Chen, Chiun-Fan; Schachter, Steven C; Rotenberg, Alexander; Fregni, Felipe

2017-09-01

Conventional transcranial direct current stimulation (tDCS) protocols rely on applying electrical current at a fixed intensity and duration without using surrogate markers to direct the interventions. This has led to some mixed results; especially because tDCS induced effects may vary depending on the ongoing level of brain activity. Therefore, the objective of this preliminary study was to assess the feasibility of an EEG-triggered tDCS system based on EEG online analysis of its frequency bands. Six healthy volunteers were randomized to participate in a double-blind sham-controlled crossover design to receive a single session of 10[Formula: see text]min 2[Formula: see text]mA cathodal and sham tDCS. tDCS trigger controller was based upon an algorithm designed to detect an increase in the relative beta power of more than 200%, accompanied by a decrease of 50% or more in the relative alpha power, based on baseline EEG recordings. EEG-tDCS closed-loop-system was able to detect the predefined EEG magnitude deviation and successfully triggered the stimulation in all participants. This preliminary study represents a proof-of-concept for the development of an EEG-tDCS closed-loop system in humans. We discuss and review here different methods of closed loop system that can be considered and potential clinical applications of such system.

Australian shellfish ecosystems: Past distribution, current status and future direction.

PubMed

Gillies, Chris L; McLeod, Ian M; Alleway, Heidi K; Cook, Peter; Crawford, Christine; Creighton, Colin; Diggles, Ben; Ford, John; Hamer, Paul; Heller-Wagner, Gideon; Lebrault, Emma; Le Port, Agnès; Russell, Kylie; Sheaves, Marcus; Warnock, Bryn

2018-01-01

We review the status of marine shellfish ecosystems formed primarily by bivalves in Australia, including: identifying ecosystem-forming species, assessing their historical and current extent, causes for decline and past and present management. Fourteen species of bivalves were identified as developing complex, three-dimensional reef or bed ecosystems in intertidal and subtidal areas across tropical, subtropical and temperate Australia. A dramatic decline in the extent and condition of Australia's two most common shellfish ecosystems, developed by Saccostrea glomerata and Ostrea angasi oysters, occurred during the mid-1800s to early 1900s in concurrence with extensive harvesting for food and lime production, ecosystem modification, disease outbreaks and a decline in water quality. Out of 118 historical locations containing O. angasi-developed ecosystems, only one location still contains the ecosystem whilst only six locations are known to still contain S. glomerata-developed ecosystems out of 60 historical locations. Ecosystems developed by the introduced oyster Crasostrea gigas are likely to be increasing in extent, whilst data on the remaining 11 ecosystem-forming species are limited, preventing a detailed assessment of their current ecosystem-forming status. Our analysis identifies that current knowledge on extent, physical characteristics, biodiversity and ecosystem services of Australian shellfish ecosystems is extremely limited. Despite the limited information on shellfish ecosystems, a number of restoration projects have recently been initiated across Australia and we propose a number of existing government policies and conservation mechanisms, if enacted, would readily serve to support the future conservation and recovery of Australia's shellfish ecosystems.

Australian shellfish ecosystems: Past distribution, current status and future direction

PubMed Central

Gillies, Chris L.; McLeod, Ian M.; Alleway, Heidi K.; Cook, Peter; Crawford, Christine; Creighton, Colin; Diggles, Ben; Ford, John; Hamer, Paul; Heller-Wagner, Gideon; Lebrault, Emma; Le Port, Agnès; Russell, Kylie; Sheaves, Marcus; Warnock, Bryn

2018-01-01

We review the status of marine shellfish ecosystems formed primarily by bivalves in Australia, including: identifying ecosystem-forming species, assessing their historical and current extent, causes for decline and past and present management. Fourteen species of bivalves were identified as developing complex, three-dimensional reef or bed ecosystems in intertidal and subtidal areas across tropical, subtropical and temperate Australia. A dramatic decline in the extent and condition of Australia’s two most common shellfish ecosystems, developed by Saccostrea glomerata and Ostrea angasi oysters, occurred during the mid-1800s to early 1900s in concurrence with extensive harvesting for food and lime production, ecosystem modification, disease outbreaks and a decline in water quality. Out of 118 historical locations containing O. angasi-developed ecosystems, only one location still contains the ecosystem whilst only six locations are known to still contain S. glomerata-developed ecosystems out of 60 historical locations. Ecosystems developed by the introduced oyster Crasostrea gigas are likely to be increasing in extent, whilst data on the remaining 11 ecosystem-forming species are limited, preventing a detailed assessment of their current ecosystem-forming status. Our analysis identifies that current knowledge on extent, physical characteristics, biodiversity and ecosystem services of Australian shellfish ecosystems is extremely limited. Despite the limited information on shellfish ecosystems, a number of restoration projects have recently been initiated across Australia and we propose a number of existing government policies and conservation mechanisms, if enacted, would readily serve to support the future conservation and recovery of Australia’s shellfish ecosystems. PMID:29444143

Adoptive T-cell Therapy Using Autologous Tumor-infiltrating Lymphocytes for Metastatic Melanoma: Current Status and Future Outlook

PubMed Central

Wu, Richard; Forget, Marie-Andree; Chacon, Jessica; Bernatchez, Chantale; Haymaker, Cara; Chen, Jie Qing; Hwu, Patrick; Radvanyi, Laszlo

2012-01-01

Immunotherapy using autologous T-cells has emerged to be a powerful treatment option for patients with metastatic melanoma. These include the adoptive transfer of autologous tumor-infiltrating lymphocytes (TIL), T-cells transduced with high-affinity T-cell receptors (TCR) against major melanosomal tumor antigens, and T cells transduced with chimeric antigen receptors (CAR) composed of hybrid immunoglobulin light chains with endo-domains of T-cell signaling molecules. Among these and other options for T-cell therapy, TIL together with high-dose IL-2 has had the longest clinical history with multiple clinical trials in centers across the world consistently demonstrating durable clinical response rates near 50% or more. A distinct advantage of TIL therapy making it still the T-cell therapy of choice is the broad nature of the T-cell recognition against both defined as well as un-defined tumors antigens against all possible MHC, rather than the single specificity and limited MHC coverage of the newer TCR and CAR transduction technologies. In the past decade, significant inroads have been made in defining the phenotypes of T cells in TIL mediating tumor regression. CD8+ T cells are emerging to be critical, although the exact subset of CD8+ T cells exhibiting the highest clinical activity in terms of memory and effector markers is still controversial. We present a model in which both effector-memory and more differentiated effector T cells ultimately may need to cooperate to mediate long-term tumor control in responding patients. Although TIL therapy has shown great potential to treat metastatic melanoma, a number of issues have emerged that need to be addressed to bring it more into the mainstream of melanoma care. First, we have a reached the point where a pivotal phase II or phase III trials are needed in an attempt to gain regulatory approval of TIL as standard-of-care. Second, improvements in how we expand TIL for therapy are needed, that minimize the time the T

Income Inequality and Health Status in the United States: Evidence from the Current Population Survey.

ERIC Educational Resources Information Center

Mellor, Jennifer M.; Milyo, Jeffrey

2002-01-01

Current Population Survey data on self-reported health status and income for the general population and those in poverty were analyzed. No consistent association was found between income inequality and individual health status. Previous findings of such an association were attributed to ecological fallacy or failure to control for individual…

País de gordos/país de muertos: Obesity, death and nation in biomedical and forensic genetics in Mexico.

PubMed

García-Deister, Vivette; López-Beltrán, Carlos

2015-12-01

This article provides a comparison between genomic medicine and forensic genetics in Mexico, in light of recent depictions of the nation as a 'país de gordos' (country of the fat) and a 'país de muertos' (country of the dead). We examine the continuities and ruptures in the public image of genetics in these two areas of attention, health and security, focusing especially on how the relevant publics of genetic science are assembled in each case. Publics of biomedical and forensic genetics are assembled through processes of recruitment and interpellation, in ways that modulate current theorizations of co-production. The comparison also provides a vista onto discussions regarding the involvement of genetics in regimes of governance and citizenship and about the relationship between the state and biopower in a context of perceived health crisis and war-like violence.

Spaceborne GPS: Current Status and Future Visions

NASA Technical Reports Server (NTRS)

Bauer, Frank H.; Hartman, Kate; Lightsey, E. Glenn

1998-01-01

The Global Positioning System (GPS), developed by the Department of Defense is quickly revolutionizing the architecture of future spacecraft and spacecraft systems. Significant savings in spacecraft life cycle cost, in power, and in mass can be realized by exploiting GPS technology in spaceborne vehicles. These savings are realized because GPS is a systems sensor--it combines the ability to sense space vehicle trajectory, attitude, time, and relative ranging between vehicles into one package. As a result, a reduced spacecraft sensor complement can be employed and significant reductions in space vehicle operations cost can be realized through enhanced on-board autonomy. This paper provides an overview of the current status of spaceborne GPS, a description of spaceborne GPS receivers available now and in the near future, a description of the 1997-2000 GPS flight experiments, and the spaceborne GPS team's vision for the future.

PaPrBaG: A machine learning approach for the detection of novel pathogens from NGS data

NASA Astrophysics Data System (ADS)

Deneke, Carlus; Rentzsch, Robert; Renard, Bernhard Y.

2017-01-01

The reliable detection of novel bacterial pathogens from next-generation sequencing data is a key challenge for microbial diagnostics. Current computational tools usually rely on sequence similarity and often fail to detect novel species when closely related genomes are unavailable or missing from the reference database. Here we present the machine learning based approach PaPrBaG (Pathogenicity Prediction for Bacterial Genomes). PaPrBaG overcomes genetic divergence by training on a wide range of species with known pathogenicity phenotype. To that end we compiled a comprehensive list of pathogenic and non-pathogenic bacteria with human host, using various genome metadata in conjunction with a rule-based protocol. A detailed comparative study reveals that PaPrBaG has several advantages over sequence similarity approaches. Most importantly, it always provides a prediction whereas other approaches discard a large number of sequencing reads with low similarity to currently known reference genomes. Furthermore, PaPrBaG remains reliable even at very low genomic coverages. CombiningPaPrBaG with existing approaches further improves prediction results.

Cn(n=2-4): current status

NASA Astrophysics Data System (ADS)

Varandas, A. J. C.; Rocha, C. M. R.

2018-03-01

The major aspects of the C2, C3 and C4 elemental carbon clusters are surveyed. For C2, a brief analysis of its current status is presented. Regarding C3, the most recent results obtained in our group are reviewed with emphasis on modelling its potential energy surface which is particularly complicated due to the presence of multiple conical intersections. As for C4, the most stable isomeric forms of both triplet and singlet spin states and their possible interconversion pathways are examined afresh by means of accurate ab initio calculations. The main strategies for modelling the ground triplet C4 potential are also discussed. Starting from a truncated cluster expansion and a previously reported DMBE form for C3, an approximate four-body term is calibrated from the ab initio energies. The final six-dimensional global DMBE form so obtained reproduces all known topographical aspects while providing an accurate description of the C4 linear-rhombic isomerization pathway. It is therefore commended for both spectroscopic and reaction dynamics studies. This article is part of the theme issue `Modern theoretical chemistry'.

Selective retension of active cells employing low centrifugal force at the medium change during suspension culture of Chinese hamster ovary cells producing tPA.

PubMed

Takagi, M; Ilias, M; Yoshida, T

2000-01-01

The effect of centrifugal force applied for cell separation at the medium change on the growth, metabolism and tissue plasminogen activator (tPA) productivity of Chinese hamster ovary (CHO) cells suspension culture was investigated. The viability of the precipitated cells increased exponentially as the centrifugal force decreased. However, the cell recovery was lower than 91% when centrifugal forces applied for 5 min was less than 67 x g. In cultures incubated for 474 h with 7 medium changes employing centrifugal forces ranging from 67 to 364 x g, a centrifugal force lower than 119 x g resulted in higher specific rates of growth, glucose consumption, and lactate and tPA production during the whole culture period. On the other hand, daily centrifugation at 67 to 537 x g without discarding the supernatant had no effect on the specific rates. The cultures inoculated with cells precipitated at a centrifugal force of 67 x g showed apparently higher specific rates of metabolism compared to those inoculated with cells in the supernatant. The cells in the supernatant and the precipitate obtained following centrifugation at 67 x g have average diameters of 15.5 and 17.4 microm, respectively. The intracellular contents of amino acids, especially nonessential amino acids, of the precipitated cells were markedly higher than those of the cells in the supernatant. These results indicate that large cells with high amino acid content and metabolic activity were selectively retained in the culture by means of centrifugation at low forces such as 67 x g. Consequently, application of a low centrifugal force is recommended for medium change in order to maintain higher specific productivity of suspended mammalian cells in perfusion culture.

Effects of metamizole, MAA, and paracetamol on proliferation, apoptosis, and necrosis in the pancreatic cancer cell lines PaTu 8988 t and Panc-1.

PubMed

Malsy, Manuela; Graf, Bernhard; Bundscherer, Anika

2017-12-06

Adenocarcinoma of the pancreas is one of the most aggressive cancer diseases affecting the human body. Recent research has shown the importance of the perioperative phase in disease progression. Particularly during this vulnerable phase, substances such as metamizole and paracetamol are given as general anesthetics and postoperative analgesics. Therefore, the effects of metamizole and paracetamol on tumor progression should be investigated in more detail because the extent to which these substances influence the carcinogenesis of pancreatic carcinoma is still unclear. This study analyzed the influence of metamizole and its active metabolites MAA (4-N-methyl-aminoantipyrine) and paracetamol on the proliferation, apoptosis, and necrosis of the pancreatic cancer cell lines PaTu 8988t and Panc-1 in vitro. Cell proliferation was measured by means of the ELISA BrdU assay and the rate of apoptosis by flow cytometry using the Annexin V assay. Metamizole and paracetamol significantly inhibited cell proliferation in pancreatic cancer cells. After the addition of metamizole to PaTu 8988t cells, the rate of apoptosis was reduced after 3 h of incubation but significantly increased after 9 h of incubation. The oncogenic potential of pancreatic adenocarcinoma is mainly characterized by its extreme growth rate. Non-opioid analgesics such as metamizole and paracetamol are given as general anesthetics and postoperative analgesics. The combination of metamizole or paracetamol with cytotoxic therapeutic approaches may achieve synergistic effects. Further studies are necessary to identify the underlying mechanisms so that new therapeutic options may be developed for the treatment of this aggressive tumor.

Current Status of HbA1c Biosensors

PubMed Central

Lin, Hua; Yi, Jun

2017-01-01

Glycated hemoglobin (HbA1c) is formed via non-enzymatic glycosylation reactions at the α–amino group of βVal1 residues in the tetrameric Hb, and it can reflect the ambient glycemic level over the past two to three months. A variety of HbA1c detection methods, including chromatography, immunoassay, enzymatic measurement, electrochemical sensor and capillary electrophoresis have been developed and used in research laboratories and in clinics as well. In this review, we summarize the current status of HbA1c biosensors based on the recognition of the sugar moiety on the protein and also their applications in the whole blood sample measurements. PMID:28777351

DNA Methylation in Osteoarthritis: Current Status and Therapeutic Implications

PubMed Central

Miranda-Duarte, Antonio

2018-01-01

Background: Primary Osteoarthritis (OA) is a multifactorial disease in which genetic factors are strongly associated with its development; however, recently it has been observed that epigenetic modifications are also involved in the pathogenesis of OA. DNA methylation is related to gene silencing, and several studies have investigated its role in the loci of different pathways or molecules associated to OA. Objective: This review is focused on the current status of DNA methylation studies related to OA pathogenesis. Method: A review of the literature was conducted on searching in PUBMED for original papers on DNA methylation in OA. Conclusion: The DNA methylation research of loci related to OA pathogenesis has shown a correlation between methylation and gene repression; however, there are some exceptions to this rule. Recently, the development of genome-wide methylation and genome-wide hydroxymethylation profiles has demonstrated that several genes previously associated with OA can have changes in their methylation status, favoring the development of the disease, and these have even shown the role of other epigenetic markers. PMID:29682093

Comprehensive in vitro Proarrhythmia Assay (CiPA): Pending issues for successful validation and implementation.

PubMed

Cavero, Icilio; Guillon, Jean-Michel; Ballet, Veronique; Clements, Mike; Gerbeau, Jean-Frédéric; Holzgrefe, Henry

2016-01-01

The Comprehensive in vitro Proarrhythmia Assay (CiPA) is a nonclinical Safety Pharmacology paradigm for discovering electrophysiological mechanisms that are likely to confer proarrhythmic liability to drug candidates intended for human use. Key talks delivered at the 'CiPA on my mind' session, held during the 2015 Annual Meeting of the Safety Pharmacology Society (SPS), are summarized. Issues and potential solutions relating to crucial constituents [e.g., biological materials (ion channels and pluripotent stem cell-derived cardiomyocytes), study platforms, drug solutions, and data analysis] of CiPA core assays are critically examined. In order to advance the CiPA paradigm from the current testing and validation stages to a research and regulatory drug development strategy, systematic guidance by CiPA stakeholders is necessary to expedite solutions to pending and newly arising issues. Once a study protocol is proved to yield robust and reproducible results within and across laboratories, it can be implemented as qualified regulatory procedure. Copyright © 2016 Elsevier Inc. All rights reserved.

The California spotted owl: a technical assessment of its current status

Treesearch

Jared Verner; Kevin S. McKelvey; Barry R. Noon; R. J. Gutierrez; Gordon I. Jr. Gould; Thomas W. Beck

1992-01-01

This report is based an the Final Repart submitted on May 8, 1992 by the Technical Assessment Team to the interagency Steering Committee for the California Spotted Owl Assessment. The 13 chapters cover the assessment of the current status of the California spotted owl, its biology and habitat use, and forests where the subspecies occurs in the Sierra Nevada and...

Sliding friction study of the oscillating translational motion for steel on PA66 and PA46 type materials

NASA Astrophysics Data System (ADS)

Lates, M. T.; Velicu, R. G.; Papuc, R.

2016-08-01

The paper presents the study of the friction, by using tests, in the sliding translational oscillating motion of the steel on PA46 relative to the steel on PA66 type materials by considering as variables the testing parameters as: the load, the velocity and the operating temperature. The paper starts with a study of the literature and, according to that, presents the main conclusions regarding the sliding friction of the steel on PA66 and PA46 type materials and identifies the lacks of the results. The tests are performed on an oscillating motion type tribometer module. First, it is made a running-in program, for each of the materials, at 25 and 90°C, a load of 5 N and a frequency of 1 Hz for one hour; after that, there are performed tests at 90°C and 120°C, at loads of 3 N, 5 N, 7 N and at frequencies at 0.25 Hz, 5 Hz and 1 Hz. The results are presented for the PA46 type material relative to the PA66 material. The conclusions indicate in which conditions and with which advantages are used the PA66 and PA46 polyamides in the case of oscillating translational motions.

[ASSOCIATION BETWEEN HEALTH RELATED QUALITY OF LIFE, BODYWEIGHT STATUS (BMI) AND PHYSICAL ACTIVITY AND FITNESS LEVELS IN CHILEAN ADOLESCENTS].

PubMed

García-Rubio, Javier; Olivares, Pedro R; Lopez-Legarrea, Patricia; Gómez-Campos, Rossana; Cossio-Bolaños, Marco A; Merellano-Navarro, Eugenio

2015-10-01

the objective of this study was to analyze the potential relationships between Health Related Quality of Life (HRQoL) with weight status, physical activity (PA) and fitness in Chilean adolescents in both, independent and combined analysis. a sample of 767 participants (47.5% females) and aged between 12 and 18 (mean age 15.5) was employed. All measurements were carried out using selfreported instruments and Kidscreen-10, iPAQ and IFIS were used to assess HRQoL, PA and Fitness respectively. One factor ANOVA and linear regression models were applied to analyze associations between HRQoL, weight status, PA and fitness using age and sex as confounders. body mass index, level of PA and fitness were independently associated with HRQoL in Chilean adolescents. However, the combined and adjusted by sex and age analysis of these associations showed that only the fitness was significantly related with HRQoL. general fitness is associated with HRQoL independently of sex, age, bodyweight status and level of PA. The relationship between nutritional status and weekly PA with HRQoL are mediated by sex, age and general fitness. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

Current status and challenge of Human Parasitology teaching in China

PubMed Central

Peng, Hong-Juan; Zhang, Chao; Wang, Chun-Mei; Chen, Xiao-Guang

2012-01-01

Parasitic infection profile in China has been changed greatly with the rapid economic development in China since the 1980s, such as the tremendous decreased infection rate of the soil-borne helminthiasis, the elimination of filariasis, the control of malaria, and the initiation to eradicate malaria in 2020. Some food-borne parasitic infections have increased such as Clonorchiasis, Cysticercosis, and Echinococcosis, probably because of the increased chances of eating out. This trend directly affected the status of Human Parasitology teaching in medical universities, such as the shorten length of this course, re-adjusted contents structure and teaching manners, even the change of the name of this course. In this paper, we analyzed the current status and challenges of Human Parasitology teaching in medical universities, and discussed the requisite contents and manners in course delivery and measures to improve the quality of Human Parasitology teaching in China. PMID:23265609

Forensic psychiatry in India current status and future development.

PubMed

Shah, L P

1999-07-01

Forensic psychiatry is a developing superspeciality in India and other SAARC countries. After a brief historical review, the paper describes the current status of forensic psychiatry in India and compares it with the development in this field in Europe and America. It takes the stock of current scenario in three different areas viz., i) legal and clinical ii) teaching and training and Hi) research. It deliberates on need for teaching this subject at the undergraduate and the postgraduate medical and legal courses and necessity of full time consultants devoted to the practice of forensic psychiatry. It focuses on the recent developments in the field of forensic psychiatry like enactment of Narcotic and Psychotropic Substance Act (1985), Mental Health Act (1987), Juvenile Justice Act (1989), Act for the Disabled (1994) and the Consumer Protection Act (1986). The paper also recommends some strategies for teaching, training, research and future developments in this field.

The current status of medical marijuana in the United States.

PubMed

McKenna, Gerald J

2014-04-01

Medical marijuana is currently a controversial issue in medicine. There are strong pro and con opinions but relatively little scientific data on which to base medical decisions. The unfortunate scheduling of marijuana in class I has limited research and only serves to fuel the controversy. This article will review the history of laws to regulate drugs in the United States in the 20th century to provide context for the current status of medical marijuana. It will include the rationale for opposing medical marijuana laws and the problem of the Schedule I inclusion of marijuana as well as other drugs. It will examine the problems associated with smoking raw marijuana and review other routes of administration. Finally, it examines the inadvisability of medicine's promotion of smoked marijuana.

Current and past menstrual status is an important determinant of femoral neck geometry in exercising women.

PubMed

Mallinson, Rebecca J; Williams, Nancy I; Gibbs, Jenna C; Koehler, Karsten; Allaway, Heather C M; Southmayd, Emily; De Souza, Mary Jane

2016-07-01

Menstrual status, both past and current, has been established as an important determinant of bone mineral density (BMD) in young exercising women. However, little is known regarding the association between the cumulative effect of menstrual status and indices of bone health beyond BMD, such as bone geometry and estimated bone strength. This study explores the association between cumulative menstrual status and indices of bone health assessed using dual-energy x-ray absorptiometry (DXA), including femoral neck geometry and strength and areal BMD (aBMD), in exercising women. 101 exercising women (22.0±0.4years, BMI 21.0±0.2kg/m(2), 520±40min/week of self-reported exercise) participated in this cross-sectional study. Women were divided into three groups as follows based on their self-reported current and past menstrual status: 1) current and past regular menstrual cycles (C+P-R) (n=23), 2) current and past irregular menstrual cycles (C+P-IR) (n=56), 3) and current or past irregular cycles (C/P-RIR) (n=22). Current menstrual status was confirmed using daily urinary metabolites of reproductive hormones. DXA was used to assess estimates of femoral neck geometry and strength from hip strength analysis (HSA), aBMD, and body composition. Cross-sectional moment of inertia (CSMI), cross-sectional area (CSA), strength index (SI), diameter, and section modulus (Z) were calculated at the femoral neck. Low CSMI, CSA, SI, diameter, and Z were operationally defined as values below the median. Areal BMD (g/cm(2)) and Z-scores were determined at the lumbar spine, femoral neck, and total hip. Low BMD was defined as a Z-score<-1.0. Chi-square tests and multivariable logistic regression were performed to compare the prevalence and determine the odds, respectively, of low bone geometry, strength, and aBMD among groups. Cumulative menstrual status was identified as a significant predictor of low femoral neck CSMI (p=0.005), CSA (p≤0.024), and diameter (p=0.042) after controlling for

[Molecular imaging; current status and future prospects in USA].

PubMed

Kobayashi, Hisataka

2007-02-01

The goal of this review is to introduce the definition, current status, and future prospects of the molecular imaging, which has recently been a hot topic in medicine and the biological science in USA. In vivo imaging methods to visualize the molecular events and functions in organs or animals/humans are overviewed and discussed especially in combinations of imaging modalities (machines) and contrast agents(chemicals) used in the molecular imaging. Next, the close relationship between the molecular imaging and the nanotechnology, an important part of nanomedicine, is stressed from the aspect of united multidisciplinary sciences such as physics, chemistry, biology, and medicine.

Magnetic nanoparticles based cancer therapy: current status and applications.

PubMed

Zhang, Huan; Liu, Xiao Li; Zhang, Yi Fan; Gao, Fei; Li, Ga Long; He, Yuan; Peng, Ming Li; Fan, Hai Ming

2018-04-01

Nanotechnology holds a promising potential for developing biomedical nanoplatforms in cancer therapy. The magnetic nanoparticles, which integrate uniquely appealing features of magnetic manipulation, nanoscale heat generator, localized magnetic field and enzyme-mimics, prompt the development and application of magnetic nanoparticles-based cancer medicine. Considerable success has been achieved in improving the magnetic resonance imaging (MRI) sensitivity, and the therapeutic function of the magnetic nanoparticles should be given adequate attention. This work reviews the current status and applications of magnetic nanoparticles based cancer therapy. The advantages of magnetic nanoparticles that may contribute to improved therapeutics efficacy of clinic cancer treatment are highlighted here.

Current Status of Concentrator Photovoltaic (CPV) Technology

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

Philipps, Simon P.; Bett, Andreas W.; Horowitz, Kelsey

2015-12-01

This report summarizes the status of the concentrator photovoltaic (CPV) market and industry as well as current trends in research and technology. This report is intended to guide research agendas for Fraunhofer ISE, the National Renewable Energy Laboratory (NREL), and other R&D organizations. Version 1.1 of this report includes recent progress in CPV. The recent record module efficiency of 38.9% at Concentrator Standard Test Conditions (CSTC) is an impressive result, demonstrating the continuing opportunity for CPV technology to improve. 38.9% at Concentrator Standard Test Conditions (CSTC) is an impressive result, demonstrating the continuing opportunity for CPV technology to improve. 38.9%more » at Concentrator Standard Test Conditions (CSTC) is an impressive result, demonstrating the continuing opportunity for CPV technology to improve. 38.9% at Concentrator Standard Test Conditions (CSTC) is an impressive result, demonstrating the continuing opportunity for CPV technology to improve.« less

Spaceborne GPS Current Status and Future Visions

NASA Technical Reports Server (NTRS)

Bauer, Frank H.; Hartman, Kate; Lightsey, E. Glenn

1998-01-01

The Global Positioning System (GPS), developed by the Department of Defense, is quickly revolutionizing the architecture of future spacecraft and spacecraft systems. Significant savings in spacecraft life cycle cost, in power, and in mass can be realized by exploiting Global Positioning System (GPS) technology in spaceborne vehicles. These savings are realized because GPS is a systems sensor-it combines the ability to sense space vehicle trajectory, attitude, time, and relative ranging between vehicles into one package. As a result, a reduced spacecraft sensor complement can be employed on spacecraft and significant reductions in space vehicle operations cost can be realized through enhanced on- board autonomy. This paper provides an overview of the current status of spaceborne GPS, a description of spaceborne GPS receivers available now and in the near future, a description of the 1997-1999 GPS flight experiments and the spaceborne GPS team's vision for the future.

Nutritional status and physical inactivity in moderated asthmatics: A pilot study.

PubMed

Bruno, Andreina; Uasuf, Carina Gabriela; Insalaco, Giuseppe; Barazzoni, Rocco; Ballacchino, Antonella; Gjomarkaj, Mark; Pace, Elisabetta

2016-08-01

Preservation of nutritional status and of fat-free mass (FFM) and/or preventing of fat mass (FM) accumulation have a positive impact on well-being and prognosis in asthma patients. Physical inactivity is identified by World Health Organization as the fourth leading risk factor for global mortality. Physical activity (PA) may contribute to limit FM accumulation, but little information is available on the interactions between habitual PA and body composition and their association with disease severity in asthma severity.Associations between habitual PA, FM, FFM, and pulmonary function were investigated in 42 subjects (24 patients with mild-moderate asthma and 18 matched control subjects). Sensewear Armband was used to measure PA and metabolic equivalent of tasks (METs) continuously over 4 days, while body composition was measured by bioelectrical impedance analysis. Respiratory functions were also assessed in all study participants.FM and FFM were comparable in mild-moderate asthmatics and controls, but PA was lower in asthmatics and it was negatively correlated with FM and positively with the FFM marker body cell mass in all study subjects (P < 0.05). Among asthmatics, treated moderate asthmatics (ICS, n = 12) had higher FM and lower PA, METs, steps number/die, and forced expiratory volume in the 1st second (FEV1)/forced vital capacity (FVC) than in untreated intermittent asthmatics (UA, n = 12).This pilot study assesses that in mild-moderate asthma patients, lower PA is associated with higher FM and higher disease severity. The current results support enhancement of habitual PA as a potential tool to limit FM accumulation and potentially contribute to preserve pulmonary function in moderate asthma, considering the physical inactivity a strong risk factor for asthma worsening.

País de gordos/país de muertos: Obesity, death and nation in biomedical and forensic genetics in Mexico

PubMed Central

García-Deister, Vivette; López-Beltrán, Carlos

2015-01-01

This article provides a comparison between genomic medicine and forensic genetics in Mexico, in light of recent depictions of the nation as a ‘país de gordos’ (country of the fat) and a ‘país de muertos’ (country of the dead). We examine the continuities and ruptures in the public image of genetics in these two areas of attention, health and security, focusing especially on how the relevant publics of genetic science are assembled in each case. Publics of biomedical and forensic genetics are assembled through processes of recruitment and interpellation, in ways that modulate current theorizations of co-production. The comparison also provides a vista onto discussions regarding the involvement of genetics in regimes of governance and citizenship and about the relationship between the state and biopower in a context of perceived health crisis and war-like violence. PMID:27479997

Robotic technology in surgery: current status in 2008.

PubMed

Murphy, Declan G; Hall, Rohan; Tong, Raymond; Goel, Rajiv; Costello, Anthony J

2008-12-01

There is increasing patient and surgeon interest in robotic-assisted surgery, particularly with the proliferation of da Vinci surgical systems (Intuitive Surgical, Sunnyvale, CA, USA) throughout the world. There is much debate over the usefulness and cost-effectiveness of these systems. The currently available robotic surgical technology is described. Published data relating to the da Vinci system are reviewed and the current status of surgical robotics within Australia and New Zealand is assessed. The first da Vinci system in Australia and New Zealand was installed in 2003. Four systems had been installed by 2006 and seven systems are currently in use. Most of these are based in private hospitals. Technical advantages of this system include 3-D vision, enhanced dexterity and improved ergonomics when compared with standard laparoscopic surgery. Most procedures currently carried out are urological, with cardiac, gynaecological and general surgeons also using this system. The number of patients undergoing robotic-assisted surgery in Australia and New Zealand has increased fivefold in the past 4 years. The most common procedure carried out is robotic-assisted laparoscopic radical prostatectomy. Published data suggest that robotic-assisted surgery is feasible and safe although the installation and recurring costs remain high. There is increasing acceptance of robotic-assisted surgery, especially for urological procedures. The da Vinci surgical system is becoming more widely available in Australia and New Zealand. Other surgical specialties will probably use this technology. Significant costs are associated with robotic technology and it is not yet widely available to public patients.

Using transcranial direct-current stimulation (tDCS) to understand cognitive processing.

PubMed

Reinhart, Robert M G; Cosman, Josh D; Fukuda, Keisuke; Woodman, Geoffrey F

2017-01-01

Noninvasive brain stimulation methods are becoming increasingly common tools in the kit of the cognitive scientist. In particular, transcranial direct-current stimulation (tDCS) is showing great promise as a tool to causally manipulate the brain and understand how information is processed. The popularity of this method of brain stimulation is based on the fact that it is safe, inexpensive, its effects are long lasting, and you can increase the likelihood that neurons will fire near one electrode and decrease the likelihood that neurons will fire near another. However, this method of manipulating the brain to draw causal inferences is not without complication. Because tDCS methods continue to be refined and are not yet standardized, there are reports in the literature that show some striking inconsistencies. Primary among the complications of the technique is that the tDCS method uses two or more electrodes to pass current and all of these electrodes will have effects on the tissue underneath them. In this tutorial, we will share what we have learned about using tDCS to manipulate how the brain perceives, attends, remembers, and responds to information from our environment. Our goal is to provide a starting point for new users of tDCS and spur discussion of the standardization of methods to enhance replicability.

75 FR 69468 - Metlife Moosic, PA, Metlife Clarks Summit, PA; Notice of Affirmative Determination Regarding...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-12

... DEPARTMENT OF LABOR Employment and Training Administration [TA-W-73,210; TA-W-73,210A] Metlife Moosic, PA, Metlife Clarks Summit, PA; Notice of Affirmative Determination Regarding Application for Reconsideration By application dated August 2, 2010, the petitioners requested administrative reconsideration of...

Hepatitis B Virus Infection in Tanzania: Current Status and Challenges

PubMed Central

Bakshi, Fatma A.; Jaka, Hyasinta

2018-01-01

Hepatitis B is one of the most common infectious diseases in the world with high prevalence in most of sub-Saharan Africa countries. The complexity in its diagnosis and treatment poses a significant management challenge in the resource-limited settings including Tanzania, where most of the tests and drugs are either unavailable or unaffordable. This mini review aims at demonstrating the current status of the disease in the country and discussing the concomitant challenges in diagnosis, treatment, and prevention. PMID:29666656

Review: Current clinical applications of chimeric antigen receptor (CAR) modified T cells

PubMed Central

Geyer, Mark B.; Brentjens, Renier J.

2016-01-01

The past several years have been marked by extraordinary advances in clinical applications of immunotherapy. In particular, adoptive cellular therapy utilizing chimeric antigen receptor (CAR) modified T cells targeted to CD19 has demonstrated substantial clinical efficacy in children and adults with relapsed or refractory B cell acute lymphoblastic leukemia (B-ALL), and durable clinical benefit in a smaller subset of patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or B cell non-Hodgkin lymphoma (B-NHL). Early phase clinical trials are presently assessing CAR T cell safety and efficacy in additional malignancies. Herein, we discuss clinical results from the largest series to date investigating CD19-targeted CAR T cells in B-ALL, CLL, and B-NHL, including discussion of differences in CAR T cell design and production and treatment approach, as well as clinical efficacy, nature of severe cytokine release syndrome and neurologic toxicities, and CAR T cell expansion and persistence. We additionally review the current and forthcoming use of CAR T cells in multiple myeloma and several solid tumors, and highlight challenges and opportunities afforded by the current state of CAR T cell therapies, including strategies to overcome inhibitory aspects of the tumor microenvironment and enhance antitumor efficacy. PMID:27592405

Transcranial direct current stimulation (tDCS) neuromodulatory effects on mechanical hyperalgesia and cortical BDNF levels in ovariectomized rats.

PubMed

da Silva Moreira, Sônia Fátima; Medeiros, Liciane Fernandes; de Souza, Andressa; de Oliveira, Carla; Scarabelot, Vanessa Leal; Fregni, Felipe; Caumo, Wolnei; Torres, Iraci L S

2016-01-15

Epidemiological studies show that painful disorders are more prevalent in women than in men, and the transcranial direct current stimulation (tDCS) technique has been tested in chronic pain states. We explored the effect of tDCS on pain behavior and brain-derived neurotrophic factor (BDNF) levels in ovariectomized rats. Forty-five female Wistar adult rats were distributed into five groups: control (CT), ovariectomy + tDCS (OT), ovariectomy + sham tDCS (OS), sham ovariectomy + tDCS (ST), and sham ovariectomy+shamtDCS (SS). The rats were subjected to cathodal tDCS. The vaginal cytology and the estradiol levels confirmed the hormonal status. In addition, nociceptive behavior was evaluated using the tail-flick, von Frey, and hot-plate tests, as well as the BDNF levels in the serum, hypothalamus, hippocampus, spinal cord, and cerebral cortex. One-way analysis of variance (ANOVA) or two-way ANOVA was used for statistical analysis, followed by the Bonferroni, and P-value b 0.05 was considered significant. The ovariectomized animals presented a hypersensitivity response in the hot-plate (P b 0.01) and von Frey (P b 0.05) tests, as well as increased serum BDNF (P b 0.05) and decreased hypothalamic BDNF (P b 0.01) levels. The OT, OS, ST, and SS groups showed decreased hippocampal BDNF levels as compared with the control group (P b 0.001). The interaction between tDCS and ovariectomy on the cortical BDNF levels (P b 0.01) was observed. The ovariectomy induced nociceptive hypersensitivity and altered serum and hypothalamic BDNF levels. The cathodal tDCS partially reversed nociceptive hypersensitivity.

Current Status and Future Prospects of Upper-Secondary Vocational Education in Taiwan.

ERIC Educational Resources Information Center

Lee, Lung-Sheng Steven

The current status and prospects of upper secondary vocational education (USVE) in Taiwan were reviewed. The following were among the key findings: (1) in Taiwan, USVE is offered in all vocational high schools (VHS), the occupational programs in all comprehensive high schools (CHS), and some senior high schools (SHS); (2) students in VHS…

Closing the Gaps in Offshore P&A: Lessons Learned From the North Sea

NASA Astrophysics Data System (ADS)

Torsater, M.

2017-12-01

This talk will give an overview of the major challenges related to offshore well plugging and abandonment (P&A) with examples from the North Sea. The talk will outline why today's P&A operations are so time consuming and expensive, and it will point out current technology gaps and issues related to standards and regulations in the North Sea countries. Emerging P&A solutions will be discussed, and results from large ongoing research projects in Norway will be shared. Special emphasis will be given to promising new concepts, such as using creeping shale formations as permanent well barriers, and using thermal methods for removal of tubing and casing. The long-term aspects of well plugging will also be discussed, together with methods available for minimizing leakage risk.

8 CFR 212.16 - Applications for exercise of discretion relating to T nonimmigrant status.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 8 Aliens and Nationality 1 2011-01-01 2011-01-01 false Applications for exercise of discretion... INADMISSIBLE ALIENS; PAROLE § 212.16 Applications for exercise of discretion relating to T nonimmigrant status. (a) Filing the waiver application. An alien applying for the exercise of discretion under section 212...

8 CFR 212.16 - Applications for exercise of discretion relating to T nonimmigrant status.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 8 Aliens and Nationality 1 2014-01-01 2014-01-01 false Applications for exercise of discretion... INADMISSIBLE ALIENS; PAROLE § 212.16 Applications for exercise of discretion relating to T nonimmigrant status. (a) Filing the waiver application. An alien applying for the exercise of discretion under section 212...

8 CFR 212.16 - Applications for exercise of discretion relating to T nonimmigrant status.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 8 Aliens and Nationality 1 2012-01-01 2012-01-01 false Applications for exercise of discretion... INADMISSIBLE ALIENS; PAROLE § 212.16 Applications for exercise of discretion relating to T nonimmigrant status. (a) Filing the waiver application. An alien applying for the exercise of discretion under section 212...

8 CFR 212.16 - Applications for exercise of discretion relating to T nonimmigrant status.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 8 Aliens and Nationality 1 2013-01-01 2013-01-01 false Applications for exercise of discretion... INADMISSIBLE ALIENS; PAROLE § 212.16 Applications for exercise of discretion relating to T nonimmigrant status. (a) Filing the waiver application. An alien applying for the exercise of discretion under section 212...

8 CFR 212.16 - Applications for exercise of discretion relating to T nonimmigrant status.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 8 Aliens and Nationality 1 2010-01-01 2010-01-01 false Applications for exercise of discretion... INADMISSIBLE ALIENS; PAROLE § 212.16 Applications for exercise of discretion relating to T nonimmigrant status. (a) Filing the waiver application. An alien applying for the exercise of discretion under section 212...

Development of improved vaccines against whooping cough: current status.

PubMed

Marzouqi, Ibrahim; Richmond, Peter; Fry, Scott; Wetherall, John; Mukkur, Trilochan

2010-07-01

Prior to the introduction of killed whole cell pertussis vaccine [wP] in the 1940s, whooping cough was a major cause of infant death worldwide. Widespread vaccination of children with this vaccine caused a significant reduction in mortality. However in the 1990s and now more recently, there has been a resurgence of pertussis in several countries even in populations previously vaccinated with an acellular pertussis vaccine [aP]. In this review, we describe the epidemiology of whooping cough, the vast array of virulence factors produced by this pathogen potentially contributing to the resurgence of pertussis even in previously vaccinated populations of infants and children, history of whooping cough prophylaxis, possible mechanisms of immunity, lack of availability of a suitable non-toxic adjuvant capable of inducing both arms of the immune response, and the current status of development of improved vaccines with potential to induce longer-lasting protection, than is currently possible with the wP or aP vaccines, against whooping cough.

FORENSIC PSYCHIATRY IN INDIA CURRENT STATUS AND FUTURE DEVELOPMENT

PubMed Central

Shah, L.P.

1999-01-01

Forensic psychiatry is a developing superspeciality in India and other SAARC countries. After a brief historical review, the paper describes the current status of forensic psychiatry in India and compares it with the development in this field in Europe and America. It takes the stock of current scenario in three different areas viz., i) legal and clinical ii) teaching and training and Hi) research. It deliberates on need for teaching this subject at the undergraduate and the postgraduate medical and legal courses and necessity of full time consultants devoted to the practice of forensic psychiatry. It focuses on the recent developments in the field of forensic psychiatry like enactment of Narcotic and Psychotropic Substance Act (1985), Mental Health Act (1987), Juvenile Justice Act (1989), Act for the Disabled (1994) and the Consumer Protection Act (1986). The paper also recommends some strategies for teaching, training, research and future developments in this field. PMID:21455388

32 CFR 701.120 - Processing requests that cite or imply PA, Freedom of Information (FOIA), or PA/FOIA.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Privacy Program § 701.120 Processing requests that cite or imply PA, Freedom of Information (FOIA), or PA... maximum release of information allowed under the Acts. (d) Processing time limits. DON activities shall... 32 National Defense 5 2010-07-01 2010-07-01 false Processing requests that cite or imply PA...

Metrology of airborne and liquid-borne nanoparticles: current status and future needs

NASA Astrophysics Data System (ADS)

Ehara, Kensei; Sakurai, Hiromu

2010-04-01

The current status and future needs of nanoparticle metrology are discussed, particularly with respect to measurements of size, size distribution and number concentration of airborne and liquid-borne nanoparticles. Possible classification of types of measurement standards is proposed, and the role of each type of standard, including the feasibility of its establishment, is examined. A desirable interplay between measurement standards and documentary standards in establishing the traceability chain in particle measurements is suggested. Particle-related calibration services currently provided by our laboratory at the National Institute of Advanced Industrial Science and Technology are also described.

Different TCR-induced T lymphocyte responses are potentiated by stiffness with variable sensitivity

PubMed Central

Saitakis, Michael; Dogniaux, Stéphanie; Goudot, Christel; Bufi, Nathalie; Asnacios, Sophie; Maurin, Mathieu; Randriamampita, Clotilde; Asnacios, Atef; Hivroz, Claire

2017-01-01

T cells are mechanosensitive but the effect of stiffness on their functions is still debated. We characterize herein how human primary CD4+ T cell functions are affected by stiffness within the physiological Young’s modulus range of 0.5 kPa to 100 kPa. Stiffness modulates T lymphocyte migration and morphological changes induced by TCR/CD3 triggering. Stiffness also increases TCR-induced immune system, metabolism and cell-cycle-related genes. Yet, upon TCR/CD3 stimulation, while cytokine production increases within a wide range of stiffness, from hundreds of Pa to hundreds of kPa, T cell metabolic properties and cell cycle progression are only increased by the highest stiffness tested (100 kPa). Finally, mechanical properties of adherent antigen-presenting cells modulate cytokine production by T cells. Together, these results reveal that T cells discriminate between the wide range of stiffness values found in the body and adapt their responses accordingly. DOI: http://dx.doi.org/10.7554/eLife.23190.001 PMID:28594327

A Current Source Method For t(sub q) Measurement of Fast Switching Thyristors

NASA Technical Reports Server (NTRS)

Niedra, Janis M.

2006-01-01

A current source driven circuit has been constructed to measure the turn-off time (t(sub q)) of fast-switching SiC thyristors. This circuit operates from a single power supply and a dual channel pulse generator to provide adjustment of forward current, magnitude and duration of reverse applied voltage, and rate of rise of reapplied forward voltage. Values of t(sub q) down to 100 ns can be resolved.

Vitamin D Status Is Positively Correlated with Regulatory T Cell Function in Patients with Multiple Sclerosis

PubMed Central

Smolders, Joost; Thewissen, Mariëlle; Peelen, Evelyn; Menheere, Paul; Cohen Tervaert, Jan Willem; Damoiseaux, Jan; Hupperts, Raymond

2009-01-01

Background In several autoimmune diseases, including multiple sclerosis (MS), a compromised regulatory T cell (Treg) function is believed to be critically involved in the disease process. In vitro, the biologically active metabolite of vitamin D has been shown to promote Treg development. A poor vitamin D status has been linked with MS incidence and MS disease activity. In the present study, we assess a potential in vivo correlation between vitamin D status and Treg function in relapsing remitting MS (RRMS) patients. Methodology/Principal Findings Serum levels of 25-hydroxyvitamin D (25(OH)D) were measured in 29 RRMS patients. The number of circulating Tregs was assessed by flow-cytometry, and their functionality was tested in vitro in a CFSE-based proliferation suppression assay. Additionally, the intracellular cytokine profile of T helper cells was determined directly ex-vivo by flow-cytometry. Serum levels of 25(OH)D correlated positively with the ability of Tregs to suppress T cell proliferation (R = 0.590, P = 0.002). No correlation between 25(OH)D levels and the number of Tregs was found. The IFN-γ/IL-4 ratio (Th1/Th2-balance) was more directed towards IL-4 in patients with favourable 25(OH)D levels (R = −0.435, P = 0.023). Conclusions/Significance These results show an association of high 25(OH)D levels with an improved Treg function, and with skewing of the Th1/Th2 balance towards Th2. These findings suggest that vitamin D is an important promoter of T cell regulation in vivo in MS patients. It is tempting to speculate that our results may not only hold for MS, but also for other autoimmune diseases. Future intervention studies will show whether modulation of vitamin D status results in modulation of the T cell response and subsequent amelioration of disease activity. PMID:19675671

[Current status of bone/cartilage tissue engineering towards clinical applications].

PubMed

Ohgushi, Hajime

2014-10-01

Osteo/chondrogenic differentiation capabilities are seen after in vivo implantation of mesenchymal stem cells (MSCs), which are currently used for the patients having bone/cartilage defects. Importantly, the differentiation capabilities are induced by culturing technology, resulting in in vitro bone/cartilage formation. Especially, the in vitro bone tissue is useful for bone tissue regeneration. For cartilage regeneration, culture expanded chondrocytes derived from patient's normal cartilage are also used for the patients having cartilage damages. Recently, the cultured chondrocytes embedded in atelocollagen gel are obtainable as tissue engineered products distributed by Japan Tissue Engineering Co. Ltd. The products are available in the well-regulated hospitals by qualified orthopedic surgeons. The criteria for these hospitals/surgeons have been established. This review paper focuses on current status of bone/cartilage tissue engineering towards clinical applications in Japan.

The ILLIAC IV memory system: Current status and future possibilities

NASA Technical Reports Server (NTRS)

Stevenson, D. K.

1978-01-01

The future needs of researchers who will use the Illiac were examined and the requirements they will place on the memory system were evaluated. Various alternatives to replacing critical memory components were considered with regard to cost, risk, system impact, software requirements, and implementation schedules. The current system, its performance and status, and the limitations it places on possible enhancements are discussed as well as the planned enhancements to the Illiac processor. After a brief technology survey, different implementations are presented for each system memory component. Three different memory systems are proposed to meet the identified needs of the Illiac user community. These three alternatives differ considerably with respect to storage capacity and accessing capabilities, but they all offer significant improvements over the current system. The proposed systems and their relative merits are analyzed.

Tele-yoga for Chronic Pain: Current Status and Future Directions.

PubMed

Mathersul, Danielle C; Mahoney, Louise A; Bayley, Peter J

2018-01-01

Pain is a pervasive, debilitating disorder that is resistant to long-term pharmacological interventions. Although psychological therapies such as cognitive behavior therapy demonstrate moderate efficacy, many individuals continue to have ongoing difficulties following treatment. There is a current trend to establish complementary and integrative health interventions for chronic pain, for which yoga has been found to have exciting potential. Nevertheless, an important consideration within the field is accessibility to adequate care. Telehealth can be used to provide real-time interactive video conferencing leading to increased access to health care for individuals located remotely or who otherwise have difficulty accessing services, perhaps through issues of mobility or proximity of adequate services. This article assesses the current status and feasibility of implementing tele-yoga for chronic pain. Methodological limitations and recommendations for future research are discussed.

The Japanese artificial organs scene: current status.

PubMed

Mitamura, Yoshinori; Murabayashi, Shun

2005-08-01

Artificial organs and regenerative medicine are the subjects of very active research and development (R&D) in Japan and various artificial organs are widely used in patients. Results of the R&D are presented at the annual conference of the Japanese Society for Artificial Organs (JSAO). Progress in the fields of artificial organs and regenerative medicine are reviewed annually in the Japanese Journal of Artificial Organs. The official English-language journal of JSAO, Journal of Artificial Organs, also publishes many original articles by Japanese researchers. Although the annual conference and the publications of JSAO provide the world with update information on artificial organs and regenerative medicine in Japan, the information is not always understood appropriately in the rest of the world, mainly due to language problems. This article therefore introduces the current status of artificial organs and regenerative medicine in Japan. Artificial hearts and metabolic support systems are reviewed here and other interesting areas such as regenerative medicine can be found elsewhere.

Current status of GALS setup in JINR

NASA Astrophysics Data System (ADS)

Zemlyanoy, S.; Avvakumov, K.; Fedosseev, V.; Bark, R.; Blazczak, Z.; Janas, Z.

2017-11-01

This is a brief report on the current status of the new GAs cell based Laser ionization Setup (GALS) at the Flerov Laboratory for Nuclear Reactions (FLNR) of the Joint Institute for Nuclear Research (JINR) in Dubna. GALS will exploit available beams from the U-400M cyclotron in low energy multi-nucleon transfer reactions to study exotic neutron-rich nuclei located in the "north-east" region of nuclear map. Products from 4.5 to 9 MeV/nucleon heavy-ion collisions, such as 136Xe on 208Pb, are thermalized and neutralized in a high pressure gas cell and subsequently selectively laser re-ionized. In order to choose the best scheme of ion extraction the results of computer simulations of two different systems are presented. The first off- and online experiment will be performed on osmium atoms that is regarded as a most convenient element for producing isotopes with neutron number in the vicinity of the magic N = 126.

Current Status of Messenger RNA Delivery Systems.

PubMed

Stanton, Matthew G

2018-06-01

Messenger RNA is emerging as a highly versatile biological construct for creation of impactful medicines. mRNA vaccines directed toward infectious disease and cancer are in clinical development with encouraging early reads on tolerability and efficacy. The use of mRNA to direct intense but transient expression of paracrine factors is finding utility in reprogramming progenitor cells for wound healing and cardiac regeneration and for stimulation of antitumor immune responses, at least preclinically as we await clinical results. The use of mRNA for prolonged and repeated expression of proteins and enzymes to treat rare, typically monogenic disease is nearing clinical entry. These uses of mRNA require delivery solutions, and the application of and improvement to existing nanoparticle nucleic acid delivery systems have jump started the pace of development and reenergized the field of particle based nucleic acid delivery. The current status of mRNA delivery is reviewed in this article with an eye toward clinical tractability.

Interventional Radiology of Male Varicocele: Current Status

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

Iaccarino, Vittorio, E-mail: vittorio.iaccarino@unina.it; Venetucci, Pietro

2012-12-15

Varicocele is a fairly common condition in male individuals. Although a minor disease, it may cause infertility and testicular pain. Consequently, it has high health and social impact. Here we review the current status of interventional radiology of male varicocele. We describe the radiological anatomy of gonadal veins and the clinical aspects of male varicocele, particularly the physical examination, which includes a new clinical and ultrasound Doppler maneuver. The surgical and radiological treatment options are also described with the focus on retrograde and antegrade sclerotherapy, together with our long experience with these procedures. Last, we compare the outcomes, recurrence andmore » persistence rates, complications, procedure time and cost-effectiveness of each method. It clearly emerges from this analysis that there is a need for randomized multicentre trials designed to compare the various surgical and percutaneous techniques, all of which are aimed at occlusion of the anterior pampiniform plexus.« less

Comprehensive Test Ban Treaty (CTBT): Current Status

NASA Astrophysics Data System (ADS)

Chaturvedi, Ram

2003-04-01

After an effort of nearly a half century the CTBT was approved by the U.N. on September 10, 1996. Out of 185 member nations (at the time), 158 voted in favor, 3 against, and the remaining either abstained or were diplomatically absent. In spite of such an overwhelming support of the international community, the CTBT may well remain on paper. The reason being that one of the opposing nations, India, is considered a "threshold Nuclear Nation" and must approve the treaty to enter into force according to the rules of Conference of Disarmament (CD). India's U.N. representative said that her country would "never sign this unequal treaty, not now, not later." "Unequal" because it does not provide a time table for elimination of the existing nuclear weapons, testing of weapons, etc., which favor nuclear states. This paper will provide details of the above issues and the current status of the CTBT.

Clinical Research with Transcranial Direct Current Stimulation (tDCS): Challenges and Future Directions

PubMed Central

Brunoni, Andre Russowsky; Nitsche, Michael A.; Bolognini, Nadia; Bikson, Marom; Wagner, Tim; Merabet, Lotfi; Edwards, Dylan J.; Valero-Cabre, Antoni; Rotenberg, Alexander; Pascual-Leone, Alvaro; Ferrucci, Roberta; Priori, Alberto; Boggio, Paulo; Fregni, Felipe

2011-01-01

Background Transcranial direct current stimulation (tDCS) is a neuromodulatory technique that delivers low-intensity, direct current to cortical areas facilitating or inhibiting spontaneous neuronal activity. In the past ten years, tDCS physiological mechanisms of action have been intensively investigated giving support for the investigation of its applications in clinical neuropsychiatry and rehabilitation. However, new methodological, ethical, and regulatory issues emerge when translating the findings of preclinical and phase I studies into phase II and III clinical studies. The aim of this comprehensive review is to discuss the key challenges of this process and possible methods to address them. Methods We convened a workgroup of researchers in the field to review, discuss and provide updates and key challenges of neuromodulation use for clinical research. Main Findings/Discussion We reviewed several basic and clinical studies in the field and identified potential limitations, taking into account the particularities of the technique. We review and discuss the findings into four topics: (i) mechanisms of action of tDCS, parameters of use and computer-based human brain modeling investigating electric current fields and magnitude induced by tDCS; (ii) methodological aspects related to the clinical research of tDCS as divided according to study phase (i.e., preclinical, phase I, phase II and phase III studies); (iii) ethical and regulatory concerns; (iv) future directions regarding novel approaches, novel devices, and future studies involving tDCS. Finally, we propose some alternative methods to facilitate clinical research on tDCS. PMID:22037126

Wind turbines: current status, obstacles, trends and technologies

NASA Astrophysics Data System (ADS)

Konstantinidis, E. I.; Botsaris, P. N.

2016-11-01

The last decade the installation of wind farms around the world is spreading rapidly and wind energy has become a significant factor for promoting sustainable development. The scope of the present study is to indicate the present status of global wind power expansion as well as the current state of the art in the field of wind turbine technology. The RAM (reliability/availability/maintenance) section is also examined and the Levelized Cost of Energy for onshore/ offshore electricity production is presented. Negative consequences that go with the rapid expansion of wind power like accidents, environmental effects, etc. are highlighted. Especially visual impact to the landscape and noise pollution are some factors that provoke social reactions. Moreover, the complicated and long permitted process of a wind power plant, the high capital cost of the investment and the grid instability due to the intermittent nature of wind, are also significant obstacles in the development of the wind energy production. The current trends in the field of research and development of onshore and offshore wind power production are analyzed. Finally the present study is trying to achieve an estimation of where the wind industry targets for the years to come.

PaTrx1 and PaTrx3, two cytosolic thioredoxins of the filamentous ascomycete Podospora anserina involved in sexual development and cell degeneration.

PubMed

Malagnac, Fabienne; Klapholz, Benjamin; Silar, Philippe

2007-12-01

In various organisms, thioredoxins are known to be involved in the reduction of protein disulfide bonds and in protecting the cell from oxidative stress. Genes encoding thioredoxins were found by searching the complete genome sequence of the filamentous ascomycete Podospora anserina. Among them, PaTrx1, PaTrx2, and PaTrx3 are predicted to be canonical cytosolic proteins without additional domains. Targeted disruption of PaTrx1, PaTrx2, and PaTrx3 shows that PaTrx1 is the major thioredoxin involved in sulfur metabolism. Deletions have no effect on peroxide resistance; however, data show that either PaTrx1 or PaTrx3 is necessary for sexual reproduction and for the development of the crippled growth cell degeneration (CG), processes that also required the PaMpk1 mitogen-activated protein kinase (MAPK) pathway. Since PaTrx1 PaTrx3 mutants show not an enhancement but rather an impairment in CG, it seems unlikely that PaTrx1 and PaTrx3 thioredoxins participate in the inhibition of this MAPK pathway. Altogether, these results underscore a role for thioredoxins in fungal development.

Phosphatidic acid (PA) binds PP2AA1 to regulate PP2A activity and PIN1 polar localization.

PubMed

Gao, Hong-Bo; Chu, Yu-Jia; Xue, Hong-Wei

2013-09-01

Phospholipase D (PLD) exerts broad biological functions in eukaryotes through regulating downstream effectors by its product, phosphatidic acid (PA). Protein kinases and phosphatases, such as mammalian target of rapamycin (mTOR), Protein Phosphatase 1 (PP1) and Protein Phosphatase 2C (PP2C), are PA-binding proteins that execute crucial regulatory functions in both animals and plants. PA participates in many signaling pathways by modulating the enzymatic activity and/or subcellular localization of bound proteins. In this study, we demonstrated that PLD-derived PA interacts with the scaffolding A1 subunit of Protein Phosphatase 2A (PP2A) and regulates PP2A-mediated PIN1 dephosphorylation in Arabidopsis. Genetic and pharmacological studies showed that both PA and PP2A participate in the regulation of auxin distribution. In addition, both the phosphorylation status and polar localization of PIN1 protein were affected by PLD inhibitors. Exogenous PA triggered the membrane accumulation of PP2AA1 and enhanced the PP2A activity at membrane, while PLD inhibition resulted in the reduced endosomal localization and perinuclear aggregation of PP2AA1. These results demonstrate the important role of PLD-derived PA in normal PP2A-mediated PIN dephosphorylation and reveal a novel mechanism, in which PA recruits PP2AA1 to the membrane system and regulates PP2A function on membrane-targeted proteins. As PA and PP2A are conserved among eukaryotes, other organisms might use similar mechanisms to mediate multiple biological processes.

Community-based dental education: history, current status, and future.

PubMed

Formicola, Allan J; Bailit, Howard L

2012-01-01

This article examines the history, current status, and future direction of community-based dental education (CBDE). The key issues addressed include the reasons that dentistry developed a different clinical education model than the other health professions; how government programs, private medical foundations, and early adopter schools influenced the development of CBDE; the societal and financial factors that are leading more schools to increase the time that senior dental students spend in community programs; the impact of CBDE on school finances and faculty and student perceptions; and the reasons that CBDE is likely to become a core part of the clinical education of all dental graduates.

Block-structured grids for complex aerodynamic configurations: Current status

NASA Technical Reports Server (NTRS)

Vatsa, Veer N.; Sanetrik, Mark D.; Parlette, Edward B.

1995-01-01

The status of CFD methods based on the use of block-structured grids for analyzing viscous flows over complex configurations is examined. The objective of the present study is to make a realistic assessment of the usability of such grids for routine computations typically encountered in the aerospace industry. It is recognized at the very outset that the total turnaround time, from the moment the configuration is identified until the computational results have been obtained and postprocessed, is more important than just the computational time. Pertinent examples will be cited to demonstrate the feasibility of solving flow over practical configurations of current interest on block-structured grids.

CT myocardial perfusion imaging: current status and future perspectives.

PubMed

Yang, Dong Hyun; Kim, Young-Hak

2017-07-01

Computed tomography myocardial perfusion (CTP) combined with coronary computed tomography angiography (CCTA) may constitute a "1-stop shop" for the noninvasive diagnosis of hemodynamically significant coronary stenosis during a single CT examination. CTP shows high diagnostic performance and provides incremental value over CCTA for the detection of hemodynamically significant coronary stenosis in patients with a high Agatston calcium score or coronary artery stents. Future studies should determine the optimal protocol and clinical value of CTP for guiding revascularization strategy and prognostication. In this article, we review the current status and future perspectives of CTP, focusing on technical considerations, clinical applications, and future research topics.

The Global Ecosystem Dynamics Investigation: Current Status

NASA Astrophysics Data System (ADS)

Dubayah, R.

2016-12-01

Spaceborne lidar has been identified as a key technology by the international ecosystem science community because it enables accurate estimates of canopy structure and biomass, forms the basis for fusion approaches with existing and planned missions, such as the NASA's ICESat2, ECOSTRESS and OCO3 missions, and extends the capabilities of radar missions such as the NASA-ISRO SAR, Tandem-X and the ESA BIOMASS missions. The Global Ecosystem Dynamics Investigation (GEDI) is a space-based lidar instrument scheduled for launch in late 2018. From its vantage point on the International Space Station, GEDI will provide high-resolution observations of forest vertical structure. These data will be used to address three core science questions: What is the aboveground carbon balance of the land surface? What role will the land surface play in mitigating atmospheric CO2 in the coming decades? How does ecosystem structure affect habitat quality and biodiversity? GEDI informs these science questions by making billions of lidar waveform observations per year. These canopy measurements are then used to estimate biomass and in fusion with radar and other remote sensing data to quantify changes in biomass resulting from disturbance and recovery. GEDI further marries ecosystem structure from lidar with ecosystem and habitat modeling to evaluate the impact of changes in land use and climate on carbon sequestration and biodiversity. In this talk we present an overview of the GEDI mission and its current implementation status. We first review its major science objectives and planned data sets. We then summarize GEDI algorithms and our approach to calibration and validation. Lastly, we provide the status of the instrument hardware build, as well as expected technical performance details.

Early Childhood Inclusion in the United States: Goals, Current Status, and Future Directions

ERIC Educational Resources Information Center

Guralnick, Michael J.; Bruder, Mary Beth

2016-01-01

The current status and future directions of early childhood inclusion in the United States are discussed from the perspective of 4 key goals: access, accommodations and feasibility, developmental progress, and social integration. Recommendations are put forward to promote inclusion goals emphasizing administrative structures, personnel…

[Current approaches to evaluating the anatomic and functional status of the cornea].

PubMed

Avetisov, S E; Borodina, N V; Kobzova, M V; Musaeva, G M

2010-01-01

The review provides data on current methods for evaluating the anatomic and functional status of the cornea (light refraction, light transmission, and biomechanical properties, in particular). It analyzes the main advantages and disadvantages of basic (biomicroscopy, endothelial microscopy, ophthalmometry, topography, and pachymetry) and special (confocal microscopy, optical coherence tomography, ultrasound biomicroscopy, aberrometry, bidirectional corneal applanation, and keratoesthesiometry) studies.

Using transcranial direct-current stimulation (tDCS) to understand cognitive processing

PubMed Central

Reinhart, Robert M.G.; Cosman, Josh D.; Fukuda, Keisuke; Woodman, Geoffrey F.

2017-01-01

Noninvasive brain stimulation methods are becoming increasingly common tools in the kit of the cognitive scientist. In particular, transcranial direct-current stimulation (tDCS) is showing great promise as a tool to causally manipulate the brain and understand how information is processed. The popularity of this method of brain stimulation is based on the fact that it is safe, inexpensive, its effects are long lasting, and you can increase the likelihood that neurons will fire near one electrode and decrease the likelihood that neurons will fire near another. However, this method of manipulating the brain to draw causal inferences is not without complication. Because tDCS methods continue to be refined and are not yet standardized, there are reports in the literature that show some striking inconsistencies. Primary among the complications of the technique is that the tDCS method uses two or more electrodes to pass current and all of these electrodes will have effects on the tissue underneath them. In this tutorial, we will share what we have learned about using tDCS to manipulate how the brain perceives, attends, remembers, and responds to information from our environment. Our goal is to provide a starting point for new users of tDCS and spur discussion of the standardization of methods to enhance replicability. PMID:27804033

Current status of SK-Gd project and EGADS

NASA Astrophysics Data System (ADS)

Xu, Chenyuan; Super-Kamiokande Collaboration

2016-05-01

Supernova Relic Neutrino (SRN) has not been observed yet because of its low event rate and high background. By adding gadolinium into water Cherenkov detector, inverse beta decay will have two signals, the prompt one is positron signal and the delayed one is a ~8 MeV gamma cascade from neutron capture on gadolinium. By this way, background for SRN can be largely reduced by detecting prompt and delayed signals coincidently, and Super-K will also have the ability to distinguish neutrino and anti-neutrino. SK-Gd is a R&D project proposed to dissolve gadolinium into Super-K. As a part of it, EGADS, a 200 ton water Cherenkov detector was built in Kamioka mine. Current status of SK-Gd project and the physics work being performed in EGADS will be presented here.

Effect of low frequency ultrasound on combined rt-PA and eptifibatide thrombolysis in human clots.

PubMed

Meunier, Jason M; Holland, Christy K; Pancioli, Arthur M; Lindsell, Christopher J; Shaw, George J

2009-01-01

Fibrinolytics such as recombinant tissue plasminogen activator (rt-PA) are used to treat thrombotic disease such as acute myocardial infarction (AMI) and ischemic stroke. Interest in increasing efficacy and reducing side effects has led to the study of adjuncts such as GP IIb-IIIa inhibitors and ultrasound (US) enhanced thrombolysis. Currently, GP IIb-IIIa inhibitor and fibrinolytic treatment are often used in AMI, and are under investigation for stroke treatment. However, little is known of the efficacy of combined GP IIb-IIIa inhibitor, fibrinolytic and ultrasound treatment. We measure the lytic efficacy of rt-PA, eptifibatide (Epf) and 120 kHz ultrasound treatment in an in-vitro human clot model. Blood was drawn from 15 subjects after IRB approval. Clots were made in 20 microL pipettes, and placed in a water tank for microscopic visualization during lytic treatment. Clots were exposed to control, rt-PA (rt-PA), eptifibatide (Epf), or rt-PA+eptifibatide (rt-PA + Epf), with (+US) or without (-US) ultrasound for 30 minutes at 37 degrees C in human plasma. Clot lysis was measured over time, using a microscopic imaging technique. The fractional clot loss (FCL) and initial lytic rate (LR) were used to quantify lytic efficacy. LR values for (- US) treated clots were 0.8+/-0.1(control), 1.8+/-0.3 (Epf), 1.5+/-0.2 (rt-PA), and 1.3+/-0.4 (rt-PA + Epf) (% clot width/minute) respectively. In comparison, the (+ US) group exhibited LR values of 1.6+/-0.2 (control), 4.3+/-0.4 (Epf), 6.3+/-0.4 (rt-PA), and 4.6+/-0.6 (rt-PA + Epf). For (- US) treated clots, FCL was 6.0+/-0.8 (control), 9.2+/-2.5 (Epf), 15.6+/-1.7 (rt-PA), and 28.0+/-2.2% (rt-PA + Epf) respectively. FCL for (+ US) clots was 13.5+/-2.4 (control), 20.7+/-6.4 (Epf), 44.4+/-3.6 (rt-PA) and 30.3+/-3.6% (rt-PA + Epf) respectively. Although the addition of eptifibatide enhances the in-vitro lytic efficacy of rt-PA in the absence of ultrasound, the efficacy of ultrasound and rt-PA is greater than that of combined

WISM - A Wideband Instrument for Snow Measurement: Past Accomplishments, Current Status, and Path Forward

NASA Technical Reports Server (NTRS)

Bonds, Quenton; Racette, Paul; Durham, Tim (Principal Investigator)

2016-01-01

Presented are the prior accomplishments, current status and path forward for GSFC's Wideband Instrument for Snow Measurement (WISM). This work is a high level overview of the project, presented via Webinar to the IEEE young professionals.

Tele-yoga for Chronic Pain: Current Status and Future Directions

PubMed Central

Mahoney, Louise A; Bayley, Peter J

2018-01-01

Pain is a pervasive, debilitating disorder that is resistant to long-term pharmacological interventions. Although psychological therapies such as cognitive behavior therapy demonstrate moderate efficacy, many individuals continue to have ongoing difficulties following treatment. There is a current trend to establish complementary and integrative health interventions for chronic pain, for which yoga has been found to have exciting potential. Nevertheless, an important consideration within the field is accessibility to adequate care. Telehealth can be used to provide real-time interactive video conferencing leading to increased access to health care for individuals located remotely or who otherwise have difficulty accessing services, perhaps through issues of mobility or proximity of adequate services. This article assesses the current status and feasibility of implementing tele-yoga for chronic pain. Methodological limitations and recommendations for future research are discussed. PMID:29637012

Relationship between periodontal status and intellectual function among community-dwelling elderly persons.

PubMed

Moriya, Shingo; Tei, Kanchu; Toyoshita, Yoshifumi; Koshino, Hisashi; Inoue, Nobuo; Miura, Hiroko

2012-06-01

The aim of this study was to indicate the relationship between periodontal status and intellectual function in the elderly. Periodontal status has been shown to be related to demographic, socioeconomic, and psychological status. Intellectual function is a significant indicator of health status. Nevertheless, the relationship between periodontal status and intellectual function has not been elucidated in detail among the elderly. A total of 152 community-dwelling elderly persons, aged 70-74 years, were enrolled in the study. Periodontal status was evaluated using the WHO Community Periodontal Index of Treatment Needs (CPITN). Intellectual function was assessed by four neuropsychological tests: Raven's Coloured Progressive Matrices (RCPM) test, the Verbal Paired Associates 1 (VerPA) task and the Visual Paired Associates 1 (VirPA) task, extracted from the Wechsler Memory Scale Revised Edition, and the Block Design subtest, extracted from the Wechsler Adult Intelligence Scales, Third Edition. Correlations between CPITN and each test were examined using Spearman rank correlation coefficients. The ordinal regression model was constructed with CPITN as the dependent variable and neuropsychological test as the principal independent variable to adjust for demographic factors, general health, lifestyle and oral health behaviour. Significant correlations were found between the RCPM test, the VerPA task, the Visual Paired Associates 1 and CPITN. In the ordinal regression model, CPITN was significantly related to measures of RCPM after adjusting for demographic factors, general health status, lifestyle and oral health behaviour. Intellectual function is considered a significant indicator of periodontal status among community-dwelling elderly persons. © 2011 The Gerodontology Society and John Wiley & Sons A/S.

Current status and future trends in turbine application of thermal barrier coatings

NASA Technical Reports Server (NTRS)

Sheffler, Keith D.; Gupta, Dinesh K.

1988-01-01

This paper provides an overview of the current status and future trends in application of thermal barrier coatings (TBC) to turbine components, and in particular to high turbine airfoils. Included are descriptions of the favorable results achieved to date with bill-of-material applications of plasma deposited TBC, and recent experience with developmental coatings applied by electron beam-physical vapor deposition.

Current status of taeniasis in Thailand.

PubMed

Anantaphruti, Malinee Thairungroj

2013-02-01

Taeniasis is prevalent in all regions of Thailand, except the South. Infections were more frequently found in males than females of any age from 7-83 years. Taenia saginata is the most common species throughout the country. Taenia asiatica was reported only in the province of Kanchanaburi in the Central region. Co-infections, with Taenia solium and T. asiatica or T. solium and T. saginata, were found. Hybridization between T. asiatica and T. saginata is evidence that co-infection is never found between these 2 species. Finding more than 1 worm in a single patient was not entirely rare. Genetic variation was found without correlation to its geographic distribution in T. saginata, whereas no variation was found in T. asiatica.

Current Status of Taeniasis in Thailand

PubMed Central

2013-01-01

Taeniasis is prevalent in all regions of Thailand, except the South. Infections were more frequently found in males than females of any age from 7-83 years. Taenia saginata is the most common species throughout the country. Taenia asiatica was reported only in the province of Kanchanaburi in the Central region. Co-infections, with Taenia solium and T. asiatica or T. solium and T. saginata, were found. Hybridization between T. asiatica and T. saginata is evidence that co-infection is never found between these 2 species. Finding more than 1 worm in a single patient was not entirely rare. Genetic variation was found without correlation to its geographic distribution in T. saginata, whereas no variation was found in T. asiatica. PMID:23467328

Current Status and Future Agenda for the Theory, Research, and Practice of Childhood Career Development

ERIC Educational Resources Information Center

Schultheiss, Donna E. Palladino

2008-01-01

This article reviews the current status and a future agenda for childhood career development theory, research, and practice. The fragmented nature of the current state of the literature is noted, and a call is made for a reexamination and reconsideration of the childhood developmental pathways of life's work. It is suggested that the study of…

Status of high temperature superconductor cable and fault current limiter projects at American Superconductor

NASA Astrophysics Data System (ADS)

Maguire, J. F.; Yuan, J.

2009-10-01

This paper will describe the status of three key programs currently underway at American Superconductor Corp. The first program is the LIPA project which is a transmission voltage high temperature superconducting cable program, with funding support from the US Department of Energy. The 600 m cable, capable of carrying 574 MVA, was successfully installed and commissioned in LIPA grid on April 22, 2008. An overview of the project, system level design details and operational data will be provided. In addition, the status of the newly awarded LIPA II project will be described. The second program is Project Hydra, with funding support from the US Department of Homeland Security, to design, develop and demonstrate an HTS cable with fault current limiting functionality. The cable is 300 m long and is being designed to carry 96 MVA at a distribution level voltage of 13.8 kV. The cable will be permanently installed and energized in Manhattan, New York in 2010. The initial status of Project Hydra will be presented. The final program to be discussed is a transmission voltage, high temperature superconducting fault current limiter funded by the US DOE. The project encompasses the design, construction and test of a 115 kV FCL for power transmission within a time frame of 4-5 years. Installation and testing are planned for a Southern California Edison substation. A project overview and progress under the first phase will be reported.

Current status of chirality in agrochemicals.

PubMed

Jeschke, Peter

2018-04-27

The agrochemical industry is continuously searching for new pesticides to develop products with optimal efficacy, lower application rates in the field, increased selectivity, favorable toxicological and environmental safety, enhanced user friendliness and better economic viability. One strategy to achieve these ambitious goals makes use of the unique properties of molecules containing asymmetric centers. In the past, many natural products and their congeners have been a source of inspiration for designing new active ingredients, and the molecular structure of the resulting molecules have become increasingly complex. 30% contain fragments with asymmetric centers. However, despite the enormous progress that has been made in catalytic asymmetric processes over the last decade, only few agrochemicals are produced in enantiomerically pure or enriched form on an industrial scale. Since 2007, around 43% of the 44 launched products (insecticides, acaricides, fungicides, nematicides, and herbicides) contain one or more asymmetric centers in the molecule (≈ 47 %) and most of them were launched as racemic mixtures of enantiomers or diastereomers. This review gives an overview of the current status of chiral agrochemicals launched over the past 10 years and describes the inherently connected challenges of modern agricultural chemistry by managing important aspects resulting from stereochemistry of these innovative products. This article is protected by copyright. All rights reserved.

PaTrx1 and PaTrx3, Two Cytosolic Thioredoxins of the Filamentous Ascomycete Podospora anserina Involved in Sexual Development and Cell Degeneration▿ †

PubMed Central

Malagnac, Fabienne; Klapholz, Benjamin; Silar, Philippe

2007-01-01

In various organisms, thioredoxins are known to be involved in the reduction of protein disulfide bonds and in protecting the cell from oxidative stress. Genes encoding thioredoxins were found by searching the complete genome sequence of the filamentous ascomycete Podospora anserina. Among them, PaTrx1, PaTrx2, and PaTrx3 are predicted to be canonical cytosolic proteins without additional domains. Targeted disruption of PaTrx1, PaTrx2, and PaTrx3 shows that PaTrx1 is the major thioredoxin involved in sulfur metabolism. Deletions have no effect on peroxide resistance; however, data show that either PaTrx1 or PaTrx3 is necessary for sexual reproduction and for the development of the crippled growth cell degeneration (CG), processes that also required the PaMpk1 mitogen-activated protein kinase (MAPK) pathway. Since PaTrx1 PaTrx3 mutants show not an enhancement but rather an impairment in CG, it seems unlikely that PaTrx1 and PaTrx3 thioredoxins participate in the inhibition of this MAPK pathway. Altogether, these results underscore a role for thioredoxins in fungal development. PMID:17933907

Contrast-enhanced endoscopic ultrasonography: advance and current status

PubMed Central

2014-01-01

Endoscopic ultrasonography (EUS) technology has undergone a great deal of progress along with the color and power Doppler imaging, three-dimensional imaging, electronic scanning, tissue harmonic imaging, and elastography, and one of the most important developments is the ability to acquire contrast-enhanced images. The blood flow in small vessels and the parenchymal microvasculature of the target lesion can be observed non-invasively by contrast-enhanced EUS (CE-EUS). Through a hemodynamic analysis, CE-EUS permits the diagnosis of various gastrointestinal diseases and differential diagnoses between benign and malignant tumors. Recently, mechanical innovations and the development of contrast agents have increased the use of CE-EUS in the diagnostic field, as well as for the assessment of the efficacy of therapeutic agents. The advances in and the current status of CE-EUS are discussed in this review. PMID:25038805

Cacao biotechnology: current status and future prospects.

PubMed

Wickramasuriya, Anushka M; Dunwell, Jim M

2018-01-01

Theobroma cacao-The Food of the Gods, provides the raw material for the multibillion dollar chocolate industry and is also the main source of income for about 6 million smallholders around the world. Additionally, cocoa beans have a number of other nonfood uses in the pharmaceutical and cosmetic industries. Specifically, the potential health benefits of cocoa have received increasing attention as it is rich in polyphenols, particularly flavonoids. At present, the demand for cocoa and cocoa-based products in Asia is growing particularly rapidly and chocolate manufacturers are increasing investment in this region. However, in many Asian countries, cocoa production is hampered due to many reasons including technological, political and socio-economic issues. This review provides an overview of the present status of global cocoa production and recent advances in biotechnological applications for cacao improvement, with special emphasis on genetics/genomics, in vitro embryogenesis and genetic transformation. In addition, in order to obtain an insight into the latest innovations in the commercial sector, a survey was conducted on granted patents relating to T. cacao biotechnology. © 2017 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

Environmental Programs: Status of Work and Current Priorities for FY13

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

Jones, Patricia

2012-08-17

Presentation outline is: Mission/overview, Regulatory framework, Current status of cleanup, Shift in priorities to address highest risk, Removal of above-ground waste, Continued focus on protecting water resources, and Priorities for fiscal year 2013. LANL's Environmental Mission is to: (1) Repack and ship legacy transuranic waste containers; (2) Investigate and remediate Cold War (legacy) hazardous and radioactive waste areas; (3) Demolish unused buildings; (4) Disposition solid waste from Laboratory operations; and (5) Lifecycle cost nearly $3 billion.

Holographic Methods Of Dynamic Particulate Measurements ¬â€?Current Status

NASA Astrophysics Data System (ADS)

Thompson, Brian J.

1983-03-01

The field of holographic particulate measurements continues to be very active with many new applications in such diverse fields as bubble chamber recording and contaminant measurements in small vials. The methods have also been extended to measure velocity distributions of particles within a volume, particularly by the application of subsequent image processing methods. These techniques could be coupled with hybrid systems to become near real time. The current status of these more recent developments is reviewed.

Recent Results from ArgoNeuT and Status of MicroBooNE

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

Szelc, Andrzej

2015-07-10

Liquid Argon Time Projection Chamber (LArTPC) detectors hold the key to answering the outstanding questions about the role of neutrinos in the Standard Model of Particle physics and beyond. Their fine granularity combined with calorimetric capabilities allows for precision measurements that answering these questions will require. Here, we discuss the recent results from the ArgoNeuT experiment as well as the status and prospects for MicroBooNE, both a part of the US-based LArTPC neutrino program.

Loss or Inhibition of uPA or MMP-9 Attenuates LV Remodeling and Dysfunction after Acute Pressure Overload in Mice

PubMed Central

Heymans, Stephane; Lupu, Florea; Terclavers, Sven; Vanwetswinkel, Bjorn; Herbert, Jean-Marc; Baker, Andrew; Collen, Desire; Carmeliet, Peter; Moons, Lieve

2005-01-01

Left ventricular (LV) hypertrophy is a natural response of the heart to increased pressure loading, but accompanying fibrosis and dilatation may result in irreversible life-threatening heart failure. Matrix metalloproteinases (MMPs) have been invoked in various cardiac diseases, however, direct genetic evidence for a role of the plasminogen activator (PA) and MMP systems in pressure overload-induced LV hypertrophy and in heart failure is lacking. Therefore, the consequences of transverse aortic banding (TAB) were analyzed in mice lacking tissue-type PA (t-PA−/−), urokinase-type PA (u-PA−/−), or gelatinase-B (MMP-9−/−), and in wild-type (WT) mice after adenoviral gene transfer of the PA-inhibitor PAI-1 or the MMP-inhibitor TIMP-1. TAB elevated LV pressure comparably in all genotypes. In WT and t-PA−/− mice, cardiomyocyte hypertrophy was associated with myocardial fibrosis, LV dilatation and dysfunction, and pump failure after 7 weeks. In contrast, in u-PA−/− mice or in WT mice after PAI-1- and TIMP-1-gene transfer, cardiomyocyte hypertrophy was moderate and only minimally associated with cardiac fibrosis and LV dilatation, resulting in better preservation of pump function. Deficiency of MMP-9 had an intermediate effect. These findings suggest that the use of u-PA- or MMP-inhibitors might preserve cardiac pump function in LV pressure overloading. PMID:15631996

Genetic cancer vaccines: current status and perspectives.

PubMed

Aurisicchio, Luigi; Ciliberto, Gennaro

2012-08-01

The recent approval of the first therapeutic cancer vaccine by the US Regulatory Agency represents a breakthrough event in the history of cancer treatment. The past scepticism towards this type of therapeutic intervention is now replaced by great expectations. The field is now moving towards the development of alternative vaccination technologies, which are capable of generating stronger, more durable and efficient immune responses against specific tumour-associated antigens (TAAs) in combination with cheaper and more standardised manufacturing. In this context, genetic vaccines are emerging among the most promising methodologies. Several evidences point to combinations of different genetic immunisation modalities (heterologous prime/boost) as a powerful approach to induce superior immune responses and achieve greater clinical efficacy. In this review, we provide an overview of the current status of development of genetic cancer vaccines with particular emphasis on adenoviral vector prime/DNA boost vaccination schedules. We believe that therapeutic genetic cancer vaccines have the strong potential to become an established therapeutic modality for cancer in next coming years, in a manner similar to what have now become monoclonal antibodies.

Transcranial direct current stimulation and power spectral parameters: a tDCS/EEG co-registration study

PubMed Central

Mangia, Anna L.; Pirini, Marco; Cappello, Angelo

2014-01-01

Transcranial direct current stimulation (tDCS) delivers low electric currents to the brain through the scalp. Constant electric currents induce shifts in neuronal membrane excitability, resulting in secondary changes in cortical activity. Concomitant electroencephalography (EEG) monitoring during tDCS can provide valuable information on the tDCS mechanisms of action. This study examined the effects of anodal tDCS on spontaneous cortical activity in a resting brain to disclose possible modulation of spontaneous oscillatory brain activity. EEG activity was measured in ten healthy subjects during and after a session of anodal stimulation of the postero-parietal cortex to detect the tDCS-induced alterations. Changes in the theta, alpha, beta, and gamma power bands were investigated. Three main findings emerged: (1) an increase in theta band activity during the first minutes of stimulation; (2) an increase in alpha and beta power during and after stimulation; (3) a widespread activation in several brain regions. PMID:25147519

Joint Relationship Between Physical Activity, Weight Status, and Motor Skills in Children Aged 3 to 10 Years.

PubMed

DuBose, Katrina D; Gross McMillan, Amy; Wood, Aaron P; Sisson, Susan B

2018-06-01

While the relationships between physical activity (PA), obesity, and motor skills have been independently examined by previous research, this study explored both independent and combined relationships between children's PA, weight status, and motor skills within a multiple regression analysis. We measured height and weight and calculated body mass index (BMI) z scores for 96 children (3-10 years of age). We measured motor skills using the Movement Assessment Battery for Children-2nd edition (MABC-2), and we measured PA levels through accelerometry. Children with more time in moderate and moderate-to-vigorous PA had higher Total motor skill scores on the MABC-2. Further, children with higher moderate PA levels had higher Balance scores and those with moderate-to-vigorous PA demonstrated higher Aiming and Catching scores. Among children with healthier BMIs, more time spent in PA, regardless of intensity, was related to higher Aiming and Catching scores. Among children with BMI scores suggestive of overweight/obesity, both moderate and moderate-to-vigorous PA were positively related to Balance scores. In conclusion, while BMI z scores were not directly related to motor skills, PA levels were positively related to motor skills, and weight status mediated the relationship between PA and specific components of motor skills.

SENIEUR status of the originating cell donor negates certain 'anti-immunosenescence' effects of ebselen and N-acetyl cysteine in human T cell clone cultures.

PubMed

Marthandan, Shiva; Freeburn, Robin; Steinbrecht, Susanne; Pawelec, Graham; Barnett, Yvonne

2014-01-01

Damage to T cells of the immune system by reactive oxygen species may result in altered cell function or cell death and thereby potentially impact upon the efficacy of a subsequent immune response. Here, we assess the impact of the antioxidants Ebselen and N-acetyl cysteine on a range of biological markers in human T cells derived from a SENIEUR status donor. In addition, the impact of these antioxidants on different MAP kinase pathways in T cells from donors of different ages was also examined. T cell clones were derived from healthy 26, 45 and SENIEUR status 80 year old people and the impact of titrated concentrations of Ebselen or N-acetyl cysteine on their proliferation and in vitro lifespan, GSH:GSSG ratio as well as levels of oxidative DNA damage and on MAP kinase signaling pathways was examined. In this investigation neither Ebselen nor N-acetyl cysteine supplementation had any impact on the biological endpoints examined in the T cells derived from the SENIEUR status 80 year old donor. This is in contrast to the anti-immunosenescent effects of these antioxidants on T cells from donors of 26 or 45 years of age. The analysis of MAP kinases showed that pro-apoptotic pathways become activated in T cells with increasing in vitro age and that Ebselen or N-acetyl cysteine could decrease activation (phosphorylation) in T cells from 26 or 45 year old donors, but not from the SENIEUR status 80 year old donor. The results of this investigation demonstrate that the biological phenotype of SENIEUR status derived human T cells negates the anti-immunosenescence effects of Ebselen and also N-acetyl cysteine. The results highlight the importance of pre-antioxidant intervention evaluation to determine risk-benefit.

Effect of Low Frequency Ultrasound on Combined rt-PA and Eptifibatide Thrombolysis in Human Clots

PubMed Central

Meunier, Jason M.; Holland, Christy K.; Pancioli, Arthur M.; Lindsell, Christopher J.; Shaw, George J.

2009-01-01

Introduction Fibrinolytics such as recombinant tissue plasminogen activator (rt-PA) are used to treat thrombotic disease such as acute myocardial infarction (AMI) and ischemic stroke. Interest in increasing efficacy and reducing side effects has led to the study of adjuncts such as GP IIb-IIIa inhibitors and ultrasound (US) enhanced thrombolysis. Currently, GP IIb-IIIa inhibitor and fibrinolytic treatment are often used in AMI, and are under investigation for stroke treatment. However, little is known of the efficacy of combined GP IIb-IIIa inhibitor, fibrinolytic and ultrasound treatment. We measure the lytic efficacy of rt-PA, eptifibatide (Epf) and 120 kHz ultrasound treatment in an in-vitro human clot model. Materials and Methods Blood was drawn from 15 subjects after IRB approval. Clots were made in 20 μL pipettes, and placed in a water tank for microscopic visualization during lytic treatment. Clots were exposed to control, rt-PA (rt-PA), eptifibatide (Epf), or rt-PA+eptifibatide (rt-PA+Epf), with or without ultrasound for 30 minutes at 37°C in human plasma. Clot lysis was measured over time, using a microscopic imaging technique. The fractional clot loss (FCL) and initial lytic rate (LR) were used to quantify lytic efficacy. Results and Conclusions LR values for (−US) treated clots were 0.8±0.1(control), 1.8±0.3 (Epf), 1.5±0.2 (rt-PA), and 1.3±0.4 (rt-PA+Epf) (% clot width/minute) respectively. In comparison, the (+US) group exhibited LR values of 1.6±0.2 (control), 4.3±0.4 (Epf), 6.3±0.4 (rt-PA), and 4.6±0.6 (rt-PA+Epf). For (−US) treated clots, FCL was 6.0±0.8 (control), 9.2±2.5 (Epf), 15.6±1.7 (rt-PA), and 28.0±2.2% (rt-PA+Epf) respectively. FCL for (+US) clots was 13.5±2.4 (control), 20.7±6.4 (Epf), 44.4±3.6 (rt-PA) and 30.3±3.6% (rt-PA+Epf) respectively. Although the addition of eptifibatide enhances the in-vitro lytic efficacy of rt-PA in the absence of ultrasound, the efficacy of ultrasound and rt-PA is greater than that of

White Paper: Interventional MRI: Current Status and Potential for Development Considering Economic Perspectives, Part 1: General Application.

PubMed

Barkhausen, Jörg; Kahn, Thomas; Krombach, Gabriele A; Kuhl, Christiane K; Lotz, Joachim; Maintz, David; Ricke, Jens; Schönberg, Stefan O; Vogl, Thomas J; Wacker, Frank K

2017-07-01

children with congenital heart defects and for atrial ablation at individual centers. Greater application can be expected in the future.. Citation format · Barkhausen J, Kahn T, Krombach GA et al. White Paper: Interventional MRI: Current Status and Potential for Development Considering Economic Perspectives, Part 1: General Application. Fortschr Röntgenstr 2017; 189: 611 - 623. © Georg Thieme Verlag KG Stuttgart · New York.

First-cut design of an all-superconducting 100-T direct current magnet

PubMed Central

Iwasa, Yukikazu; Hahn, Seungyong

2013-01-01

A 100-T magnetic field has heretofore been available only in pulse mode. This first-cut design demonstrates that a 100-T DC magnet (100 T) is possible. We base our design on: Gadolinium-based coated superconductor; a nested-coil formation, each a stack of double-pancake coils with the no-insulation technique; a band of high-strength steel over each coil; and a 12-T radial-field limit. The 100 T, a 20 mm cold bore, 6-m diameter, 17-m height, with a total of 12 500-km long superconductor, stores an energy of 122 GJ at its 4.2-K operating current of 2400 A. It requires a 4.2-K cooling power of 300 W. PMID:24399859

First-cut design of an all-superconducting 100-T direct current magnet.

PubMed

Iwasa, Yukikazu; Hahn, Seungyong

2013-12-16

A 100-T magnetic field has heretofore been available only in pulse mode. This first-cut design demonstrates that a 100-T DC magnet (100 T) is possible. We base our design on: Gadolinium-based coated superconductor; a nested-coil formation, each a stack of double-pancake coils with the no-insulation technique; a band of high-strength steel over each coil; and a 12-T radial-field limit. The 100 T, a 20 mm cold bore, 6-m diameter, 17-m height, with a total of 12 500-km long superconductor, stores an energy of 122 GJ at its 4.2-K operating current of 2400 A. It requires a 4.2-K cooling power of 300 W.

Association of outdoor recreation availability with physical activity and weight status in Minnesota youth.

PubMed

Wilhelm Stanis, Sonja A; Oftedal, Andrew; Schneider, Ingrid

2014-03-01

Examine macro-level associations of youth physical activity (PA) and weight status with availability of outdoor recreation resources (i.e., parkland, forestland, natural preserves, nonmotorized trails, and motorized trails) across counties in Minnesota. Hierarchical regression models examined if availability of recreation resources significantly improved prediction of PA and weight status of 9th and 12th grade boys and girls (2010) across Minnesota counties. The inclusion of county-level densities of recreational land variables did not produce a significant increase in R(2) for any of the models predicting 9th grade outcomes, yet county-level densities of recreational trails did significantly increase R(2) for both levels of PA and weight status. In contrast, the inclusion of recreational trails did not produce any significant increases in R(2) for 12th grade outcomes, although the inclusion of recreational land did significantly increase the R(2) for 12th grade girls achieving 30min of PA 5 or more days of the week. Findings indicate that various recreational land and trail types may have different impacts on and associations with PA and health outcomes. As such, it is important that future studies focus not only on parks, but also on other types of recreational lands and trails as well. Copyright © 2013 Elsevier Inc. All rights reserved.

The relations between driving behavior, physical activity and weight status among Canadian adults.

PubMed

Swanson, Kenda C; McCormack, Gavin R

2012-03-01

Evidence regarding the relative contributions of physical activity (PA) and driving behavior on weight status is limited. This study examined the associations between driving and PA behavior and weight status among Canadian adults. A random cross-section of Calgarian adults (n = 1026) completed a telephone-interview and a self-administered questionnaire. Weekly physical activity time, daily driving time, BMI, motor vehicle access, and demographic characteristics were captured. Logistic regression was used to estimate associations between driving minutes (0-209, 219-419, 420-839, 840-1679, and ≥ 1680 min/week), motor vehicle access, sufficient PA (210 min/week of moderate-intensity PA or 90 min/week of vigorous-intensity PA), and the likelihood of being 1) overweight/obese vs. healthy weight and 2) obese only vs. healthy/overweight. Compared with driving ≤ 209 min/week, driving 840 to 1679 min/week significantly (P < .05) increased the likelihood of being overweight/obese (OR 2.08). Insufficient PA was positively associated with being overweight/obese (OR 1.43). Each hour/week of driving was associated with a 1.6% reduction in the odds of achieving sufficient PA. A 3-fold increase (OR 3.73) in the likelihood of overweight was found among insufficiently active individuals who drove 210 to 419 min/week compared with sufficiently active individuals who drove ≤ 209 min/week. Interventions that decrease driving time and increase PA participation may be important for reducing weight among Canadian adults.

Nutritional status and its association with physical fitness, physical activity and parasitological indicators in youths from rural Mozambique.

PubMed

Nhantumbo, Leonardo; Ribeiro Maia, José António; dos Santos, Fernanda Karina; Jani, Ilesh V; Gudo, Eduardo Samo; Katzmarzyk, Peter T; Prista, António

2013-01-01

Little information exists about the relationship of nutritional status and motor performance conditional on asymptomatic parasitemia in rural African children. The aims of this study were to (1) determine if malnourished youths from rural African areas have lower levels of physical fitness (PF) and physical activity (PA) compared to normal weight youths, (2) verify the biological relevance of anthropometric criteria used to classify nutritional status in youth, and (3) determine the prevalence of parasitological indicators, and its association with nutritional status and PF. The sample comprised 794 youths (6-17 years) from Calanga, a rural community in Mozambique. PF tests were selected from standardized test batteries, and PA was estimated by accelerometry. Nutritional status was defined according to WHO recommendations for stunting, wasting and normal weight. Parasitological indicators were determined based on stool specimens' analysis. In general terms the normal group out-performed the other nutritional groups (stunted and wasted) for PF. However, no significant differences were found for PA among nutritional groups. There were also no significant differences in prevalence of intestinal parasites. Nutritional status was not associated with PA levels or the prevalence of parasitological indicators in youth, but was related to physical performance. Copyright © 2013 Wiley Periodicals, Inc.

Current status of managing food allergies in schools in Seoul, Korea.

PubMed

Kim, Soyoung; Yoon, Jihyun; Kwon, Sooyoun; Kim, Jihyun; Han, Youngshin

2012-12-01

Recently the need to manage food allergies in schools has been growing. This study aimed to examine the current status of managing food allergies in schools in Seoul, Korea. A questionnaire survey was conducted in cooperation with the School Dietician Association during April 2009. Among the participating 154 schools, a total of 109 (71%) were determining students' food allergy status through parental surveys based on self-reported food allergies. A total of 72 (47%) had experienced student visits to a school health room due to food allergies within one year before the survey. Over 80 percent of the schools relied on self-care only without any school-wide measures for food allergies in place. Among the 890 menu items most frequently served in school lunch programs, a total of 664 (75%) were found to contain more than one food allergen. It is highly suggested that preventive plans and treatment measures should be established to manage food allergies in schools.

Transcranial Direct Current Stimulation (tDCS): A Beginner's Guide for Design and Implementation

PubMed Central

Thair, Hayley; Holloway, Amy L.; Newport, Roger; Smith, Alastair D.

2017-01-01

Transcranial direct current stimulation (tDCS) is a popular brain stimulation method that is used to modulate cortical excitability, producing facilitatory or inhibitory effects upon a variety of behaviors. There is, however, a current lack of consensus between studies, with many results suggesting that polarity-specific effects are difficult to obtain. This article explores some of these differences and highlights the experimental parameters that may underlie their occurrence. We provide a general, practical snapshot of tDCS methodology, including what it is used for, how to use it, and considerations for designing an effective and safe experiment. Our aim is to equip researchers who are new to tDCS with the essential knowledge so that they can make informed and well-rounded decisions when designing and running successful experiments. By summarizing the varied approaches, stimulation parameters, and outcomes, this article should help inform future tDCS research in a variety of fields. PMID:29213226

The current status of research on the structure of evaluative space

PubMed Central

Norris, Catherine J.; Gollan, Jackie; Berntson, Gary G.; Cacioppo, John T.

2009-01-01

The structure of evaluative space shapes emotional life. Although behavior may be constrained to a single bipolar dimension, for example as defined by the opposing movements of approach and withdrawal, the mechanisms underlying the affect system must be capable of an astonishing range of emotional experience and expression. The model of evaluative space (ESM; J. T. Cacioppo, W. L. Gardner, & G. G. Berntson, 1997, 1999) proposes that behavioral predispositions are the ultimate output of the affect system, which is defined by operating characteristics that differ both for positivity and negativity, as well as across levels of the nervous system. In this article, we outline the current status of theory and research on the structure of evaluative space. First, we summarize the basic tenets of the model, as well as recent research supporting these ideas and counterarguments that have been raised by other theorists. To address these counterarguments, we discuss the postulates of affective oscillation and calibration, two mechanistic features of the affect system proposed to underlie the durability and adaptability of affect. We summarize empirical support for the functional consequences of the principles of affective oscillation and calibration, with a focus on how oscillation and the “stickiness” of affect can lead to the emergence of ambivalence, whereas affective calibration and the flexibility of the affect system produce asymmetries in affective processing (e.g., the negativity bias). Finally, we consider the clinical implications of disorder in the structure of evaluative space for the comprehension and treatment of depression and anxiety. PMID:20346389

Homogeneous Studies of Transiting Extrasolar Planets: Current Status and Future Plans

NASA Astrophysics Data System (ADS)

Taylor, John

2011-09-01

We now know of over 500 planets orbiting stars other than our Sun. The jewels in the crown are the transiting planets, for these are the only ones whose masses and radii are measurable. They are fundamental for our understanding of the formation, evolution, structure and atmospheric properties of extrasolar planets. However, their characterization is not straightforward, requiring extremely high-precision photometry and spectroscopy as well as input from theoretical stellar models. I summarize the motivation and current status of a project to measure the physical properties of all known transiting planetary systems using homogeneous techniques (Southworth 2008, 2009, 2010, 2011 in preparation). Careful attention is paid to the treatment of limb darkening, contaminating light, correlated noise, numerical integration, orbital eccentricity and orientation, systematic errors from theoretical stellar models, and empirical constraints. Complete error budgets are calculated for each system and can be used to determine which type of observation would be most useful for improving the parameter measurements. Known correlations between the orbital periods, masses, surface gravities, and equilibrium temperatures of transiting planets can be explored more safely due to the homogeneity of the properties. I give a sneak preview of Homogeneous Studies Paper 4, which includes the properties of thirty transiting planetary systems observed by the CoRoT, Kepler and Deep Impact space missions. Future opportunities are discussed, plus remaining problems with our understanding of transiting planets. I acknowledge funding from the UK STFC in the form of an Advanced Fellowship.

Current status of endoscopic submucosal dissection for early gastric cancer in Korea: role and benefits.

PubMed

Kim, Sang Gyun; Lyu, Da Hyun; Park, Chan Mi; Lee, Na Rae; Kim, Jiyoung; Cha, Youngju; Jung, Hwoon-Yong

2018-06-21

This study was aimed to investigate the current clinical status of endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) in Korea based on a National Health Insurance (NHI) database between 2011 and 2014. The claims data of ESD for EGC in Korean NHI were reviewed using material codes of Health Insurance Review and Assessment Service between November 2011 and December 2014. The current clinical status was analyzed in terms of treatment pattern, in-hospital length of stay (LOS), total medical costs, and en bloc resection rate according to the hospital type. A total of 23,828 cases of ESD for EGC were evaluated. ESD was performed in 67.4% of cases in tertiary care hospitals, 31.8% in general hospitals, and 0.8% in hospitals, respectively. The median LOS was 5 days, and total median medical costs was approximately 1,300 US dollars. En bloc resection rate was 99%; 8.5% of cases underwent additional treatment within 90 days ESD, and 5.5% in 91 to 365 days after ESD. The clinical status was not significantly different according to the year and hospital type. A majority of ESD for EGC were performed in tertiary care hospitals in Korea. The clinical status showed excellent clinical outcomes and did not differ by the year and between the types of hospitals in Korea.

WIMP dark matter candidates and searches-current status and future prospects.

PubMed

Roszkowski, Leszek; Sessolo, Enrico Maria; Trojanowski, Sebastian

2018-06-01

We review several current aspects of dark matter theory and experiment. We overview the present experimental status, which includes current bounds and recent claims and hints of a possible signal in a wide range of experiments: direct detection in underground laboratories, gamma-ray, cosmic ray, x-ray, neutrino telescopes, and the LHC. We briefly review several possible particle candidates for a weakly interactive massive particle (WIMP) and dark matter that have recently been considered in the literature. We pay particular attention to the lightest neutralino of supersymmetry as it remains the best motivated candidate for dark matter and also shows excellent detection prospects. Finally we briefly review some alternative scenarios that can considerably alter properties and prospects for the detection of dark matter obtained within the standard thermal WIMP paradigm.

WIMP dark matter candidates and searches—current status and future prospects

NASA Astrophysics Data System (ADS)

Roszkowski, Leszek; Sessolo, Enrico Maria; Trojanowski, Sebastian

2018-06-01

We review several current aspects of dark matter theory and experiment. We overview the present experimental status, which includes current bounds and recent claims and hints of a possible signal in a wide range of experiments: direct detection in underground laboratories, gamma-ray, cosmic ray, x-ray, neutrino telescopes, and the LHC. We briefly review several possible particle candidates for a weakly interactive massive particle (WIMP) and dark matter that have recently been considered in the literature. We pay particular attention to the lightest neutralino of supersymmetry as it remains the best motivated candidate for dark matter and also shows excellent detection prospects. Finally we briefly review some alternative scenarios that can considerably alter properties and prospects for the detection of dark matter obtained within the standard thermal WIMP paradigm.

Adoptive T-cell therapies for refractory/relapsed leukemia and lymphoma: current strategies and recent advances

PubMed Central

McLaughlin, Lauren; Cruz, C. Russell; Bollard, Catherine M.

2015-01-01

Despite significant advancements in the treatment and outcome of hematologic malignancies, prognosis remains poor for patients who have relapsed or refractory disease. Adoptive T-cell immunotherapy offers novel therapeutics that attempt to utilize the noted graft versus leukemia effect. While CD19 chimeric antigen receptor (CAR)-modified T cells have thus far been the most clinically successful application of adoptive T immunotherapy, further work with antigen specific T cells and CARs that recognize other targets have helped diversify the field to treat a broad spectrum of hematologic malignancies. This article will focus primarily on therapies currently in the clinical trial phase as well as current downfalls or limitations. PMID:26622998

GeMS: Gemini Mcao System: current status and commissioning plans

NASA Astrophysics Data System (ADS)

Boccas, Maxime; Rigaut, François; Gratadour, Damien; d'Orgeville, Céline; Bec, Matthieu; Daruich, Felipe; Perez, Gabriel; Arriagada, Gustavo; Bombino, Stacy; Carter, Chris; Cavedoni, Chas; Collao, Fabian; Collins, Paul; Diaz, Pablo; Ebbers, Angelic; Galvez, Ramon; Gausachs, Gaston; Hardash, Steve; James, Eric; Karewicz, Stan; Lazo, Manuel; Maltes, Diego; Mouser, Ron; Rogers, Rolando; Rojas, Roberto; Sheehan, Michael; Trancho, Gelys; Vergara, Vicente; Vucina, Tomislav

2008-07-01

The Gemini Multi-Conjugate Adaptive Optics project was launched in April 1999 to become the Gemini South AO facility in Chile. The system includes 5 laser guide stars, 3 natural guide stars and 3 deformable mirrors optically conjugated at 0, 4.5 and 9km to achieve near-uniform atmospheric compensation over a 1 arc minute square field of view. Sub-contracted systems with vendors were started as early as October 2001 and were all delivered by July 2007, but for the 50W laser (due around September 2008). The in-house development began in January 2006, and is expected to be completed by the end of 2008 to continue with integration and testing (I&T) on the telescope. The on-sky commissioning phase is scheduled to start during the first half of 2009. In this general overview, we will first describe the status of each subsystem with their major requirements, risk areas and achieved performance. Next we will present our plan to complete the project by reviewing the remaining steps through I&T and commissioning on the telescope, both during day-time and at night-time. Finally, we will summarize some management activities like schedules, resources and conclude with some lessons learned.

Peanut-specific type 1 regulatory T cells induced in vitro from allergic subjects are functionally impaired.

PubMed

Pellerin, Laurence; Jenks, Jennifer Anne; Chinthrajah, Sharon; Dominguez, Tina; Block, Whitney; Zhou, Xiaoying; Noshirvan, Arram; Gregori, Silvia; Roncarolo, Maria Grazia; Nadeau, Kari Christine; Bacchetta, Rosa

2018-01-01

Peanut allergy (PA) is a life-threatening condition that lacks regulator-approved treatment. Regulatory T type 1 (T R 1) cells are potent suppressors of immune responses and can be induced in vivo upon repeated antigen exposure or in vitro by using tolerogenic dendritic cells. Whether oral immunotherapy (OIT) leads to antigen-specific T R 1 cell induction has not been established. We sought to determine whether peanut-specific T R 1 cells can be generated in vitro from peripheral blood of patients with PA at baseline or during OIT and whether they are functional compared with peanut-specific T R 1 cells induced from healthy control (HC) subjects. Tolerogenic dendritic cells were differentiated in the presence of IL-10 from PBMCs of patients with PA and HC subjects pulsed with the main peanut allergens of Arachis hypogaea, Ara h 1 and 2, and used as antigen-presenting cells for autologous CD4 + T cells (CD4 + T cells coincubated with tolerogenic dendritic cells pulsed with the main peanut allergens [pea-T10 cells]). Pea-T10 cells were characterized by the presence of CD49b + lymphocyte-activation gene 3 (LAG3) + T R 1 cells, antigen-specific proliferative responses, and cytokine production. CD49b + LAG3 + T R 1 cells were induced in pea-T10 cells at comparable percentages from HC subjects and patients with PA. Despite their antigen specificity, pea-T10 cells of patients with PA with or without OIT, as compared with those of HC subjects, were not anergic and had high T H 2 cytokine production upon peanut-specific restimulation. Peanut-specific T R 1 cells can be induced from HC subjects and patients with PA, but those from patients with PA are functionally defective independent of OIT. The unfavorable T R 1/T H 2 ratio is discussed as a possible cause of PA T R 1 cell impairment. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Cartilage magnetic resonance imaging techniques at 3 T: current status and future directions.

PubMed

Thakkar, Rashmi S; Subhawong, Ty; Carrino, John A; Chhabra, Avneesh

2011-04-01

Magnetic resonance imaging (MRI) remains the imaging modality of choice for morphological and compositional evaluation of the articular cartilage. Accurate detection and characterization of cartilage lesions are necessary to guide the medical and surgical therapy and are also critical for longitudinal studies of the cartilage. Recent work using 3.0-T MRI systems shows promise in improving detection and characterization of the cartilage lesions, particularly with increasing use of high-resolution and high-contrast 3-dimensional sequences, which allow detailed morphological assessment of cartilage in arbitrary imaging planes. In addition, implementation of biochemical sequences in clinically feasible scan times has a potential in the early detection of cartilage lesions before they become morphologically apparent. This article discusses relative advantages and disadvantages of various commonly used as well as experimental MRI techniques to directly assess the morphology and indirectly evaluate the biochemical composition of the articular cartilage.

Palliative Care Social Work In India: Current Status and Future Directions

PubMed Central

Ragesh, G; Zacharias, Lithin; Thomas, Priya Treesa

2017-01-01

Palliative care (PC) involves total care for persons suffering from life-threatening illnesses and their families. Social work as a profession and an academic discipline is gaining momentum in India for the past few decades. A large number of professional social workers are working with individuals, families, and communities to provide PC in India. Authors have presented the current status of PC social work interventions and discussed the future directions in the practice, research, and training in PC and end-of-life care. PMID:28216870

Association of School-Based Physical Activity Opportunities, Socioeconomic Status, and Third-Grade Reading

ERIC Educational Resources Information Center

Kern, Ben D.; Graber, Kim C.; Shen, Sa; Hillman, Charles H.; McLoughlin, Gabriella

2018-01-01

Background: Socioeconomic status (SES) is the most accurate predictor of academic performance in US schools. Third-grade reading is highly predictive of high school graduation. Chronic physical activity (PA) is shown to improve cognition and academic performance. We hypothesized that school-based PA opportunities (recess and physical education)…

Transcranial Alternating Current Stimulation (tACS) Enhances Mental Rotation Performance during and after Stimulation

PubMed Central

Kasten, Florian H.; Herrmann, Christoph S.

2017-01-01

Transcranial alternating current stimulation (tACS) has been repeatedly demonstrated to modulate endogenous brain oscillations in a frequency specific manner. Thus, it is a promising tool to uncover causal relationships between brain oscillations and behavior or perception. While tACS has been shown to elicit a physiological aftereffect for up to 70 min, it remains unclear whether the effect can still be elicited if subjects perform a complex task interacting with the stimulated frequency band. In addition, it has not yet been investigated whether the aftereffect is behaviorally relevant. In the current experiment, participants performed a Shepard-like mental rotation task for 80 min. After 10 min of baseline measurement, participants received either 20 min of tACS at their individual alpha frequency (IAF) or sham stimulation (30 s tACS in the beginning of the stimulation period). Afterwards another 50 min of post-stimulation EEG were recorded. Task performance and EEG were acquired during the whole experiment. While there were no effects of tACS on reaction times or event-related-potentials (ERPs), results revealed an increase in mental rotation performance in the stimulation group as compared to sham both during and after stimulation. This was accompanied by increased ongoing alpha power and coherence as well as event-related-desynchronization (ERD) in the alpha band in the stimulation group. The current study demonstrates a behavioral and physiological aftereffect of tACS in parallel. This indicates that it is possible to elicit aftereffects of tACS during tasks interacting with the alpha band. Therefore, the tACS aftereffect is suitable to achieve an experimental manipulation. PMID:28197084

The Canadian Precipitation Analysis (CaPA): Evaluation of the statistical interpolation scheme

NASA Astrophysics Data System (ADS)

Evans, Andrea; Rasmussen, Peter; Fortin, Vincent

2013-04-01

CaPA (Canadian Precipitation Analysis) is a data assimilation system which employs statistical interpolation to combine observed precipitation with gridded precipitation fields produced by Environment Canada's Global Environmental Multiscale (GEM) climate model into a final gridded precipitation analysis. Precipitation is important in many fields and applications, including agricultural water management projects, flood control programs, and hydroelectric power generation planning. Precipitation is a key input to hydrological models, and there is a desire to have access to the best available information about precipitation in time and space. The principal goal of CaPA is to produce this type of information. In order to perform the necessary statistical interpolation, CaPA requires the estimation of a semi-variogram. This semi-variogram is used to describe the spatial correlations between precipitation innovations, defined as the observed precipitation amounts minus the GEM forecasted amounts predicted at the observation locations. Currently, CaPA uses a single isotropic variogram across the entire analysis domain. The present project investigates the implications of this choice by first conducting a basic variographic analysis of precipitation innovation data across the Canadian prairies, with specific interest in identifying and quantifying potential anisotropy within the domain. This focus is further expanded by identifying the effect of storm type on the variogram. The ultimate goal of the variographic analysis is to develop improved semi-variograms for CaPA that better capture the spatial complexities of precipitation over the Canadian prairies. CaPA presently applies a Box-Cox data transformation to both the observations and the GEM data, prior to the calculation of the innovations. The data transformation is necessary to satisfy the normal distribution assumption, but introduces a significant bias. The second part of the investigation aims at devising a bias

Improving Interference Control in ADHD Patients with Transcranial Direct Current Stimulation (tDCS).

PubMed

Breitling, Carolin; Zaehle, Tino; Dannhauer, Moritz; Bonath, Björn; Tegelbeckers, Jana; Flechtner, Hans-Henning; Krauel, Kerstin

2016-01-01

The use of transcranial direct current stimulation (tDCS) in patients with attention deficit hyperactivity disorder (ADHD) has been suggested as a promising alternative to psychopharmacological treatment approaches due to its local and network effects on brain activation. In the current study, we investigated the impact of tDCS over the right inferior frontal gyrus (rIFG) on interference control in 21 male adolescents with ADHD and 21 age matched healthy controls aged 13-17 years, who underwent three separate sessions of tDCS (anodal, cathodal, and sham) while completing a Flanker task. Even though anodal stimulation appeared to diminish commission errors in the ADHD group, the overall analysis revealed no significant effect of tDCS. Since participants showed a considerable learning effect from the first to the second session, performance in the first session was separately analyzed. ADHD patients receiving sham stimulation in the first session showed impaired interference control compared to healthy control participants whereas ADHD patients who were exposed to anodal stimulation, showed comparable performance levels (commission errors, reaction time variability) to the control group. These results suggest that anodal tDCS of the right inferior frontal gyrus could improve interference control in patients with ADHD.

Current Status of Standardization of Inhalant Allergen Extracts in Korea

PubMed Central

Jeong, Kyoung Yong; Lee, Jae-Hyun; Kim, Eun-Jin; Lee, Joo-Shil; Cho, Sang-Heon; Hong, Soo-Jong

2014-01-01

Allergy diagnosis and immunotherapy in Korea rely mostly on imported allergen extracts. However, some allergens that are not important in Western countries are not commercially available, and even the same species of allergen source often displays differences in allergenicity due to amino acid sequence polymorphisms. Therefore, it is essential to prepare allergen extracts that reflect regional characteristics. Allergen standardization has been performed since 2009 with the support of the Korea Center for Disease Control and Prevention. Here, we summarize the current status of allergen standardization, focusing on the house dust mite and cockroach. Pollen allergens that are under investigation are also briefly described. PMID:24843793

The MAO NASU Plate Archive Database. Current Status and Perspectives

NASA Astrophysics Data System (ADS)

Pakuliak, L. K.; Sergeeva, T. P.

2006-04-01

The preliminary online version of the database of the MAO NASU plate archive is constructed on the basis of the relational database management system MySQL and permits an easy supplement of database with new collections of astronegatives, provides a high flexibility in constructing SQL-queries for data search optimization, PHP Basic Authorization protected access to administrative interface and wide range of search parameters. The current status of the database will be reported and the brief description of the search engine and means of the database integrity support will be given. Methods and means of the data verification and tasks for the further development will be discussed.

Current status of brachytherapy in Korea: a national survey of radiation oncologists

PubMed Central

Kim, Joo-Young; Park, Won; Kim, Young Seok

2016-01-01

Objective The aim of the present study was to acquire information on brachytherapy resources in Korea through a national survey of radiation oncologists. Methods Between October 2014 and January 2015, a questionnaire on the current status of brachytherapy was distributed to all 86 radiation oncology departments in Korea. The questionnaire was divided into sections querying general information on human resources, brachytherapy equipment, and suggestions for future directions of brachytherapy policy in Korea. Results The response rate of the survey was 88.3%. The average number of radiation oncologists per center was 2.3. At the time of survey, 28 centers (36.8%) provided brachytherapy to patients. Among the 28 brachytherapy centers, 15 (53.5%) were located in in the capital Seoul and its surrounding metropolitan areas. All brachytherapy centers had a high-dose rate system using 192Ir (26 centers) or 60Co (two centers). Among the 26 centers using 192Ir sources, 11 treated fewer than 40 patients per year. In the two centers using 60Co sources, the number of patients per year was 16 and 120, respectively. The most frequently cited difficulties in performing brachytherapy were cost related. A total of 21 centers had a plan to sustain the current brachytherapy system, and four centers noted plans to upgrade their brachytherapy system. Two centers stated that they were considering discontinuation of brachytherapy due to cost burdens of radioisotope source replacement. Conclusion The present study illustrated the current status of brachytherapy in Korea. Financial difficulties were the major barriers to the practice of brachytherapy. PMID:27102244

Current status of brachytherapy in Korea: a national survey of radiation oncologists.

PubMed

Kim, Haeyoung; Kim, Joo Young; Kim, Juree; Park, Won; Kim, Young Seok; Kim, Hak Jae; Kim, Yong Bae

2016-07-01

The aim of the present study was to acquire information on brachytherapy resources in Korea through a national survey of radiation oncologists. Between October 2014 and January 2015, a questionnaire on the current status of brachytherapy was distributed to all 86 radiation oncology departments in Korea. The questionnaire was divided into sections querying general information on human resources, brachytherapy equipment, and suggestions for future directions of brachytherapy policy in Korea. The response rate of the survey was 88.3%. The average number of radiation oncologists per center was 2.3. At the time of survey, 28 centers (36.8%) provided brachytherapy to patients. Among the 28 brachytherapy centers, 15 (53.5%) were located in in the capital Seoul and its surrounding metropolitan areas. All brachytherapy centers had a high-dose rate system using (192)Ir (26 centers) or (60)Co (two centers). Among the 26 centers using (192)Ir sources, 11 treated fewer than 40 patients per year. In the two centers using (60)Co sources, the number of patients per year was 16 and 120, respectively. The most frequently cited difficulties in performing brachytherapy were cost related. A total of 21 centers had a plan to sustain the current brachytherapy system, and four centers noted plans to upgrade their brachytherapy system. Two centers stated that they were considering discontinuation of brachytherapy due to cost burdens of radioisotope source replacement. The present study illustrated the current status of brachytherapy in Korea. Financial difficulties were the major barriers to the practice of brachytherapy.

The current status and trend of clinical pharmacology in developing countries

PubMed Central

2013-01-01

Background Several international forums for promoting clinical pharmacology in developing countries have been held since 1980, and several clinical pharmacology programmes targeting developing countries were instituted such that the status of clinical pharmacology in developing countries is not where it was 50 years ago. Therefore, a survey and an appraisal of the literature on the current status of clinical pharmacology in developing countries were undertaken with a hope that it would enable development of appropriate strategies for further promotion of clinical pharmacology in these countries. Methods First, nine determinants (or enabling factors) for running a successful clinical pharmacology programme were identified, i.e., disease burden, drug situation, economic growth, clinical pharmacology activities, recognition, human capital, government support, international collaboration, and support for traditional/alternative medicines. These factors were then evaluated with regard to their current status in the developing countries that responded to an electronic questionnaire, and their historical perspective, using the literature appraisal. From these, a projected trend was constructed with recommendations on the way forward. Results Clinical pharmacology services, research and teaching in developing countries have improved over the past 50 years with over 90% of countries having the appropriate policies for regulation and rational use of medicines in place. Unfortunately, policy implementation remains a challenge, owing to a worsening disease burden and drug situation, versus fewer clinical pharmacologists and other competing priorities for the national budgets. This has led to a preference for training ‘a physician clinical pharmacologist’ in programmes emphasizing local relevancy and for a shorter time, and the training of other professionals in therapeutics for endemic diseases (task shifting), as the most promising strategies of ensuring rational use of

What are the factors associated with physical activity (PA) participation in community dwelling adults with dementia? A systematic review of PA correlates.

PubMed

Stubbs, Brendon; Eggermont, Laura; Soundy, Andrew; Probst, Michel; Vandenbulcke, Mathieu; Vancampfort, Davy

2014-01-01

PA shows promise as a modifiable lifestyle intervention to benefit pathological symptoms of dementia. However, little is known about the factors associated with participation in PA in community dwelling adults with dementia. A systematic review was undertaken to identify PA correlates. Two independent reviewers searched major electronic databases and extracted data on studies reporting quantitative correlates of PA participation in community dwelling adults with dementia. PA correlates were analyzed using the summary code approach within the socio-ecological model. Out of a potential of 118 articles, 12 met the eligibility criteria encompassing 752 participants. We conducted secondary analysis on nine data sets. Increased energy intake, resting metabolic rate, fat free mass, gait speed, global motor function, overall health related quality of life (HRQOL), physical HRQOL, higher levels of social functioning and reduced apathy were positively associated with PA. Taking ≥ four medications, dizziness, lower activities of daily living (ADL) function, a history of falls, less waking hours in the day, more autonomic problems and delirium were negatively associated with PA. Increasing age and lower global cognition were not consistently associated with PA participation. It is surprising that increasing age and lower global cognition do not appear to influence PA participation. All significant correlates should be confirmed in prospective studies with particular focus on the relationship of PA and gait speed, ADL function, falls history and dietary intake and the progression of frailty and nursing home admission as a priority. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

[Current status and potential perspectives in classical radiotherapy technology].

PubMed

Dabić-Stanković, Kata M; Stanković, Jovan B; Radosević-Jelić, Ljiljana M

2004-01-01

After purchase of radiotherapy equipment in 2003, classic radiation therapy in Serbia will reach the highest world level. In order to define the highest standards in radiation technology, we analyzed the current status and potential perspectives of radiation therapy. An analysis of present situation in the USA, assumed as the most developed in the world, was done. Available data, collected in the last 3 years (equipment assortment, therapy modalities, workload and manpower) for 284 radiotherapy centers, out of potential 2050, were analyzed. Results were presented as crude percentage and matched to point current status. The analysis showed that CLINAC accelerators are the most popular (82.7%), as well as, ADAC (43.7%) and Focus (CMS) (27.4%) systems for therapy planning. Movement towards virtual simulation is evident (59.3%), although classic "simulation" is not fully eliminated from the radiotherapy chain. The most popular brachytherapy afterloader is Microselectron HDR (71%). About 64.4% centers use IMPAC communication/verification/record system that seems more open than Varis. All centers practice modern radiotherapy modalities and techniques (CPRT, IMRT, SRS/SRT, TBI, IORT, IVBHRT, HDR BHRT, etc.). CT and MRI availability is out of question, but PET is available in 3% of centers, however this percentage is rapidly growing. Up to 350 new patients per year are treated by one accelerator (about 35 pts. a day). Centers are relatively small and utilize 2-3 accelerators on average. Average FTE staffing norm is 4 radiation oncologists, 2-3 medical radiotherapy physicists, about 3 certified medical dosimetrists and about 6 radiotherapy technologists. In the past 5 years relative stagnation in classic radiotherapy has been observed. In spite of substantial investments in technology and consequent improvements, as well as wide introduction of computers in radiotherapy, radiotherapy results have not changed significantly. Vendor developement strategies do not point that

Phosphatidic acid (PA)-preferring phospholipase A1 regulates mitochondrial dynamics.

PubMed

Baba, Takashi; Kashiwagi, Yuriko; Arimitsu, Nagisa; Kogure, Takeshi; Edo, Ayumi; Maruyama, Tomohiro; Nakao, Kazuki; Nakanishi, Hiroki; Kinoshita, Makoto; Frohman, Michael A; Yamamoto, Akitsugu; Tani, Katsuko

2014-04-18

Recent studies have suggested that phosphatidic acid (PA), a cone-shaped phospholipid that can generate negative curvature of lipid membranes, participates in mitochondrial fusion. However, precise mechanisms underling the production and consumption of PA on the mitochondrial surface are not fully understood. Phosphatidic acid-preferring phospholipase A1 (PA-PLA1)/DDHD1 is the first identified intracellular phospholipase A1 and preferentially hydrolyzes PA in vitro. Its cellular and physiological functions have not been elucidated. In this study, we show that PA-PLA1 regulates mitochondrial dynamics. PA-PLA1, when ectopically expressed in HeLa cells, induced mitochondrial fragmentation, whereas its depletion caused mitochondrial elongation. The effects of PA-PLA1 on mitochondrial morphology appear to counteract those of MitoPLD, a mitochondrion-localized phospholipase D that produces PA from cardiolipin. Consistent with high levels of expression of PA-PLA1 in testis, PA-PLA1 knock-out mice have a defect in sperm formation. In PA-PLA1-deficient sperm, the mitochondrial structure is disorganized, and an abnormal gap structure exists between the middle and principal pieces. A flagellum is bent at that position, leading to a loss of motility. Our results suggest a possible mechanism of PA regulation of the mitochondrial membrane and demonstrate an in vivo function of PA-PLA1 in the organization of mitochondria during spermiogenesis.

Current status of the HAL/S compiler on the Modcomp classic 7870 computer

NASA Technical Reports Server (NTRS)

Lytle, P. J.

1981-01-01

A brief history of the HAL/S language, including the experience of other users of the language at the Jet Propulsion Laboratory is presented. The current status of the compiler, as implemented on the Modcomp 7870 Classi computer, and future applications in the Deep Space Network (DSN) are discussed. The primary applications in the DSN will be in the Mark IVA network.

Tranexamic Acid and Trauma: Current Status and Knowledge Gaps with Recommended Research Priorities

DTIC Science & Technology

2013-01-01

Review Article TRANEXAMIC ACID AND TRAUMA: CURRENT STATUS AND KNOWLEDGE GAPS WITH RECOMMENDED RESEARCH PRIORITIES Anthony E. Pusateri,* Richard B...on the use of tranexamic acid (TXA) for trauma reported important survival benefits. Subsequently, successful use of TXA for combat casualties in...refinement of practice guidelines over time. KEYWORDS— Tranexamic acid , trauma, efficacy, safety, research requirements INTRODUCTION Tranexamic acid (TXA

In-vivo Imaging of Magnetic Fields Induced by Transcranial Direct Current Stimulation (tDCS) in Human Brain using MRI

NASA Astrophysics Data System (ADS)

Jog, Mayank V.; Smith, Robert X.; Jann, Kay; Dunn, Walter; Lafon, Belen; Truong, Dennis; Wu, Allan; Parra, Lucas; Bikson, Marom; Wang, Danny J. J.

2016-10-01

Transcranial direct current stimulation (tDCS) is an emerging non-invasive neuromodulation technique that applies mA currents at the scalp to modulate cortical excitability. Here, we present a novel magnetic resonance imaging (MRI) technique, which detects magnetic fields induced by tDCS currents. This technique is based on Ampere’s law and exploits the linear relationship between direct current and induced magnetic fields. Following validation on a phantom with a known path of electric current and induced magnetic field, the proposed MRI technique was applied to a human limb (to demonstrate in-vivo feasibility using simple biological tissue) and human heads (to demonstrate feasibility in standard tDCS applications). The results show that the proposed technique detects tDCS induced magnetic fields as small as a nanotesla at millimeter spatial resolution. Through measurements of magnetic fields linearly proportional to the applied tDCS current, our approach opens a new avenue for direct in-vivo visualization of tDCS target engagement.

[Construction of lentiviral mediated CyPA siRNA and its functions in non-small cell lung cancer].

PubMed

FENG, Yan-ming; WU, Yi-ming; TU, Xin-ming; XU, Zheng-shun; WU, Wei-dong

2010-02-01

To construct a lentiviral-vector-mediated CyPA small interference RNA (siRNA) and study its function in non-small cell lung cancer. First, four target sequences were selected according to CyPA mRNA sequence, the complementary DNA contained both sense and antisense oligonucleotides were designed, synthesized and cloned into the pGCL-GFP vector, which contained U6 promoter and green fluorescent protein (GFP). The resulting lentiviral vector containing CyPA shRNA was named Lv-shCyPA, and it was confirmed by PCR and sequencing. Next, it was cotransfected by Lipofectamine 2000 along with pHelper1.0 and pHelper 2.0 into 293T cells to package lentivirus particles. At the same time, the packed virus infected non-small cell lung cancer cell (A549), the level of CyPA protein at 5 d after infection was detected by Western Blot to screen the target of CyPA. A549 were infected with Lv-shCyPA and grown as xenografts in severe combined immunodeficient mice. Cell cycle and apoptosis were measured by FCM. It was confirmed by PCR and DNA sequencing that lentiviral-vector-mediated CyPA siRNA (Lv-shCyPA) producing CyPA shRNA was constructed successfully. The titer of concentrated virus were 1 x 10(7) TU/ml. Flow cytometric analysis demonstrated G2-M phase (11.40% +/- 0.68%) was decreased relatively in A549/LvshCyPA compared with control groups (14.52% +/- 1.19%) (P<0.05). The apoptosis rate of A549/Lv-shCyPA (5.01% +/- 0.5%) was higher than control groups (0.35% +/- 0.17%) (P<0.05). Visible tumors were only detectable at 6th day after inoculated by A549/Lv-shCyPA. The xenograft tumors of A549/Lv-shCyPA remarkably delayed tumor growth and remained at a similarly small average size at 38th days after inoculation compared with the control group (P < 0.05). Lentiviral-vector-mediated siRNA technique effectively inhibits the expression of CyPA, induces the NSCLC cell apoptosis, inhibits the tumor growth. Elucidation of the precise role of CypA in these pathways may lead to new targeted

Pseudomonas aeruginosa phage PaP1 DNA polymerase is an A-family DNA polymerase demonstrating ssDNA and dsDNA 3'-5' exonuclease activity.

PubMed

Liu, Binyan; Gu, Shiling; Liang, Nengsong; Xiong, Mei; Xue, Qizhen; Lu, Shuguang; Hu, Fuquan; Zhang, Huidong

2016-08-01

Most phages contain DNA polymerases, which are essential for DNA replication and propagation in infected host bacteria. However, our knowledge on phage-encoded DNA polymerases remains limited. This study investigated the function of a novel DNA polymerase of PaP1, which is the lytic phage of Pseudomonas aeruginosa. PaP1 encodes its sole DNA polymerase called Gp90 that was predicted as an A-family DNA polymerase with polymerase and 3'-5' exonuclease activities. The sequence of Gp90 is homologous but not identical to that of other A-family DNA polymerases, such as T7 DNA polymerases (Pol) and DNA Pol I. The purified Gp90 demonstrated a polymerase activity. The processivity of Gp90 in DNA replication and its efficiency in single-dNTP incorporation are similar to those of T7 Pol with processive thioredoxin (T7 Pol/trx). Gp90 can degrade ssDNA and dsDNA in 3'-5' direction at a similar rate, which is considerably lower than that of T7 Pol/trx. The optimized conditions for polymerization were a temperature of 37 °C and a buffer consisting of 40 mM Tris-HCl (pH 8.0), 30 mM MgCl2, and 200 mM NaCl. These studies on DNA polymerase encoded by PaP1 help advance our knowledge on phage-encoded DNA polymerases and elucidate PaP1 propagation in infected P. aeruginosa.

The EuPA Biobank Initiative: Meeting the future challenges of biobanking in proteomics & systems medicine.

PubMed

Wheelock, Åsa M; Paulson, Linda; Litton, Jan-Eric

2015-09-08

In this News & Reviews Discussion, the recently launched EuPA (European Proteomics Association) Biobank Initiative is introduced in the context of current and future challenges in biobanking. The purpose of the initiative is to provide a forumand knowledge platform for integrating the extensive experiences collected by the EuPA community, and link it to the European and international biobanking communities at large. The specific impact of providing a forum and easy access to this type of information to the EuPA community is the potential of improving the quality of future sample collections and biobanks, the quality of the research produced from these sample collections, as well as the output and productivity from existing biobanks. The underutilization of biobanks has recently been identified as an emerging issue of biobankingworldwide. Measures to improve our ability to locate and access appropriate sample collections for a wide range of research purposes may enhance both the scientific quality and biobank sustainability, thereby contributing to the important task of moving our research beyond basic findings and mere publications, into clinical practice. This manuscript is intended as a Discussion piece, and represents a recollection of the presentation under the “EuPA Initiative” session at HUPO/EuPA 2014 in Madrid. The launch of the EuPA (European Proteomics Association) Biobank Initiative in the context of current and future challenges in biobanking is discussed. The purpose of the initiative is to provide a forum and knowledge base for integrating the extensive experiences collected by the EuPA community, and link it to the European and international biobanking communities at large. The specific impact of providing a forumand easy access to this type of information to the EuPA community is the potential of improving the quality of future sample collections and biobanks, the quality of the research produced from these sample collections, aswell as the

Utilization management in radiology, part 1: rationale, history, and current status.

PubMed

Duszak, Richard; Berlin, Jonathan W

2012-10-01

Previous growth in the utilization of medical imaging has led to numerous efforts to reduce associated spending. Although these have historically been directed toward unit cost reductions, recent interest has emerged by various stakeholders in curbing inappropriate utilization. Radiology benefits managers have widespread market penetration and have been promoted largely by the payer community as effective mechanisms to curb increases in imaging volume. The provider community has tended to favor real-time order entry decision support systems. These have demonstrated comparable effectiveness to radiology benefits managers in early projects but currently have only limited market penetration. In this first of a two-part series, the rationale for the development of utilization management programs will be discussed and their history and current status reviewed. Copyright © 2012 American College of Radiology. Published by Elsevier Inc. All rights reserved.

Neurovirulence safety testing of mumps vaccines--historical perspective and current status.

PubMed

Rubin, S A; Afzal, M A

2011-04-05

Many live, attenuated viral vaccines are derived from wild type viruses with known neurovirulent properties. To assure the absence of residual neurotoxicity, pre-clinical neurovirulence safety testing of candidate vaccines is performed. For mumps virus, a highly neurotropic virus, neurovirulence safety testing is performed in monkeys. However, laboratory studies suggest an inability of this test to correctly discern among virus strains of varying neurovirulence potential in man, and, further, some vaccines found to be neuroattenuated in monkeys were later found to be neurovirulent in humans when administered in large numbers. Over the past decade, concerted efforts have been made to replace monkey-based neurovirulence safety testing with more informative, alternative methods. This review summarizes the current status of mumps vaccine neurovirulence safety testing and insights into models currently approved and those under development. Published by Elsevier Ltd.

Structure-based drug discovery for combating influenza virus by targeting the PA-PB1 interaction.

PubMed

Watanabe, Ken; Ishikawa, Takeshi; Otaki, Hiroki; Mizuta, Satoshi; Hamada, Tsuyoshi; Nakagaki, Takehiro; Ishibashi, Daisuke; Urata, Shuzo; Yasuda, Jiro; Tanaka, Yoshimasa; Nishida, Noriyuki

2017-08-25

Influenza virus infections are serious public health concerns throughout the world. The development of compounds with novel mechanisms of action is urgently required due to the emergence of viruses with resistance to the currently-approved anti-influenza viral drugs. We performed in silico screening using a structure-based drug discovery algorithm called Nagasaki University Docking Engine (NUDE), which is optimised for a GPU-based supercomputer (DEstination for Gpu Intensive MAchine; DEGIMA), by targeting influenza viral PA protein. The compounds selected by NUDE were tested for anti-influenza virus activity using a cell-based assay. The most potent compound, designated as PA-49, is a medium-sized quinolinone derivative bearing a tetrazole moiety, and it inhibited the replication of influenza virus A/WSN/33 at a half maximal inhibitory concentration of 0.47 μM. PA-49 has the ability to bind PA and its anti-influenza activity was promising against various influenza strains, including a clinical isolate of A(H1N1)pdm09 and type B viruses. The docking simulation suggested that PA-49 interrupts the PA-PB1 interface where important amino acids are mostly conserved in the virus strains tested, suggesting the strain independent utility. Because our NUDE/DEGIMA system is rapid and efficient, it may help effective drug discovery against the influenza virus and other emerging viruses.

Imaging transcranial direct current stimulation (tDCS) of the prefrontal cortex-correlation or causality in stimulation-mediated effects?

PubMed

Wörsching, Jana; Padberg, Frank; Ertl-Wagner, Birgit; Kumpf, Ulrike; Kirsch, Beatrice; Keeser, Daniel

2016-10-01

Transcranial current stimulation approaches include neurophysiologically distinct non-invasive brain stimulation techniques widely applied in basic, translational and clinical research: transcranial direct current stimulation (tDCS), oscillating transcranial direct current stimulation (otDCS), transcranial alternating current stimulation (tACS) and transcranial random noise stimulation (tRNS). Prefrontal tDCS seems to be an especially promising tool for clinical practice. In order to effectively modulate relevant neural circuits, systematic research on prefrontal tDCS is needed that uses neuroimaging and neurophysiology measures to specifically target and adjust this method to physiological requirements. This review therefore analyses the various neuroimaging methods used in combination with prefrontal tDCS in healthy and psychiatric populations. First, we provide a systematic overview on applications, computational models and studies combining neuroimaging or neurophysiological measures with tDCS. Second, we categorise these studies in terms of their experimental designs and show that many studies do not vary the experimental conditions to the extent required to demonstrate specific relations between tDCS and its behavioural or neurophysiological effects. Finally, to support best-practice tDCS research we provide a methodological framework for orientation among experimental designs. Copyright © 2016 Elsevier Ltd. All rights reserved.

Optimization of Catheter Based rtPA Thrombolysis in a Novel In Vitro Clot Model for Intracerebral Hemorrhage

PubMed Central

Masomi-Bornwasser, Julia; Müller-Werkmeister, Hendrik; Kantelhardt, Sven Rainer; König, Jochem; Kempski, Oliver; Giese, Alf

2017-01-01

Hematoma lysis with recombinant tissue plasminogen activator (rtPA) has emerged as an alternative therapy for spontaneous intracerebral hemorrhage (ICH). Optimal dose and schedule are still unclear. The aim of this study was to create a reliable in vitro blood clot model for investigation of optimal drug dose and timing. An in vitro clot model was established, using 25 mL and 50 mL of human blood. Catheters were placed into the clots and three groups, using intraclot application of rtPA, placebo, and catheter alone, were analyzed. Dose-response relationship, repetition, and duration of rtPA treatment and its effectiveness in aged clots were investigated. A significant relative end weight difference was found in rtPA treated clots compared to catheter alone (p = 0.002) and placebo treated clots (p < 0.001). Dose-response analysis revealed 95% effective dose around 1 mg rtPA in 25 and 50 mL clots. Approximately 80% of relative clot lysis could be achieved after 15 min incubation. Lysis of aged clots was less effective. A new clot model for in vitro investigation was established. Our data suggest that current protocols for rtPA based ICH therapy may be optimized by using less rtPA at shorter incubation times. PMID:28459065

Optimization of Catheter Based rtPA Thrombolysis in a Novel In Vitro Clot Model for Intracerebral Hemorrhage.

PubMed

Keric, Naureen; Masomi-Bornwasser, Julia; Müller-Werkmeister, Hendrik; Kantelhardt, Sven Rainer; König, Jochem; Kempski, Oliver; Giese, Alf

2017-01-01

Hematoma lysis with recombinant tissue plasminogen activator (rtPA) has emerged as an alternative therapy for spontaneous intracerebral hemorrhage (ICH). Optimal dose and schedule are still unclear. The aim of this study was to create a reliable in vitro blood clot model for investigation of optimal drug dose and timing. An in vitro clot model was established, using 25 mL and 50 mL of human blood. Catheters were placed into the clots and three groups, using intraclot application of rtPA, placebo, and catheter alone, were analyzed. Dose-response relationship, repetition, and duration of rtPA treatment and its effectiveness in aged clots were investigated. A significant relative end weight difference was found in rtPA treated clots compared to catheter alone ( p = 0.002) and placebo treated clots ( p < 0.001). Dose-response analysis revealed 95% effective dose around 1 mg rtPA in 25 and 50 mL clots. Approximately 80% of relative clot lysis could be achieved after 15 min incubation. Lysis of aged clots was less effective. A new clot model for in vitro investigation was established. Our data suggest that current protocols for rtPA based ICH therapy may be optimized by using less rtPA at shorter incubation times.

Influence of Concurrent Finger Movements on Transcranial Direct Current Stimulation (tDCS)-Induced Aftereffects.

PubMed

Shirota, Yuichiro; Terney, Daniella; Antal, Andrea; Paulus, Walter

2017-01-01

Transcranial direct current stimulation (tDCS) has been reported to have bidirectional influence on the amplitude of motor-evoked potentials (MEPs) in resting participants in a polarity-specific manner: anodal tDCS increased and cathodal tDCS decreased them. More recently, the effects of tDCS have been shown to depend on a number of additional factors. We investigated whether a small variety of movements involving target and non-target muscles could differentially modify the efficacy of tDCS. MEPs were elicited from the right first dorsal interosseous muscle, defined as the target muscle, by single pulse transcranial magnetic stimulation (TMS) over the primary motor cortex (M1). During M1 tDCS, which lasted for 10 min applying anodal, cathodal, or sham condition, the participants were instructed to squeeze a ball with their right hand (Task 1), to move their right index finger only in the medial (Task 2), in the lateral direction (Task 3), or in medial and lateral direction alternatively (Task 4). Anodal tDCS reduced MEP amplitudes measured in Task 1 and Task 2, but to a lesser extent in the latter. In Task 3, anodal tDCS led to greater MEP amplitudes than cathodal stimulation. Alternating movements resulted in no effect of tDCS on MEP amplitude (Task 4). The results are congruent with the current notion that the aftereffects of tDCS are highly variable relying on a number of factors including the type of movements executed during stimulation.

In Vitro and In Vivo Evaluations of Nano-Hydroxyapatite/Polyamide 66/Glass Fibre (n-HA/PA66/GF) as a Novel Bioactive Bone Screw

PubMed Central

Su, Bao; Peng, Xiaohua; Jiang, Dianming; Wu, Jun; Qiao, Bo; Li, Weichao; Qi, Xiaotong

2013-01-01

In this study, we prepared nano-hydroxyapatite/polyamide 66/glass fibre (n-HA/PA66/GF) bioactive bone screws. The microstructure, morphology and coating of the screws were characterised, and the adhesion, proliferation and viability of MC3T3-E1 cells on n-HA/PA66/GF scaffolds were determined using scanning electron microscope, CCK-8 assays and cellular immunofluorescence analysis. The results confirmed that n-HA/PA66/GF scaffolds were biocompatible and had no negative effect on MC3T3-E1 cells in vitro. To investigate the in vivo biocompatibility, internal fixation properties and osteogenesis of the bioactive screws, both n-HA/PA66/GF screws and metallic screws were used to repair intercondylar femur fractures in dogs. General photography, CT examination, micro-CT examination, histological staining and biomechanical assays were performed at 4, 8, 12 and 24 weeks after operation. The n-HA/PA66/GF screws exhibited good biocompatibility, high mechanical strength and extensive osteogenesis in the host bone. Moreover, 24 weeks after implantation, the maximum push-out load of the bioactive screws was greater than that of the metallic screws. As shown by their good cytocompatibility, excellent biomechanical strength and fast formation and ingrowth of new bone, n-HA/PA66/GF screws are thus suitable for orthopaedic clinical applications. PMID:23861888

Regulated Proteolytic Processing of Reelin through Interplay of Tissue Plasminogen Activator (tPA), ADAMTS-4, ADAMTS-5, and Their Modulators

PubMed Central

Krstic, Dimitrije; Rodriguez, Myriam; Knuesel, Irene

2012-01-01

The extracellular signaling protein Reelin, indispensable for proper neuronal migration and cortical layering during development, is also expressed in the adult brain where it modulates synaptic functions. It has been shown that proteolytic processing of Reelin decreases its signaling activity and promotes Reelin aggregation in vitro, and that proteolytic processing is affected in various neurological disorders, including Alzheimer's disease (AD). However, neither the pathophysiological significance of dysregulated Reelin cleavage, nor the involved proteases and their modulators are known. Here we identified the serine protease tissue plasminogen activator (tPA) and two matrix metalloproteinases, ADAMTS-4 and ADAMTS-5, as Reelin cleaving enzymes. Moreover, we assessed the influence of several endogenous protease inhibitors, including tissue inhibitors of metalloproteinases (TIMPs), α-2-Macroglobulin, and multiple serpins, as well as matrix metalloproteinase 9 (MMP-9) on Reelin cleavage, and described their complex interplay in the regulation of this process. Finally, we could demonstrate that in the murine hippocampus, the expression levels and localization of Reelin proteases largely overlap with that of Reelin. While this pattern remained stable during normal aging, changes in their protein levels coincided with accelerated Reelin aggregation in a mouse model of AD. PMID:23082219

Antigen-Specific CD8 Lytic Phenotype Induced by Sipuleucel-T in Hormone-Sensitive or Castration-Resistant Prostate Cancer and Association With Overall Survival.

PubMed

Antonarakis, Emmanuel S; Small, Eric J; Petrylak, Daniel; Quinn, David I; Kibel, Adam S; Chang, Nancy; Dearstyne, Erica; Harmon, Matthew; Campogan, Dwayne; Haynes, Heather; Vu, Tuyen; Sheikh, Nadeem A; Drake, Charles G

2018-06-01

Sipuleucel-T is FDA-approved for the treatment of metastatic castration-resistant prostate cancer (mCRPC) based on the IMPACT trial showing a 4.1-month benefit in median overall survival (OS) for patients receiving sipuleucel-T vs control. Although efficacy of sipuleucel-T is well-established, its mechanism remains incompletely understood. Patient samples from three sipuleucel-T trials were assessed for peripheral cellular immune responses to the immunogen PA2024 and the target antigen prostatic acid phosphatase (PAP). PAP- and PA2024-specific proliferative and cytolytic responses were characterized to delineate sipuleucel-T-induced immune responses. To quantify potential cytotoxic T lymphocyte (CTL) activity, cell-surface CD107a expression on PAP- or PA2024-specific CD8+ T cells was measured in sipuleucel-T-treated patient and healthy volunteer samples. Increased PA2024-specific CD4+ (p=0.030) and CD8+ (p=0.052) T-cell proliferation from baseline to week 6 was observed (N=14) post-sipuleucel-T, with greater magnitude of PA2024-specific responses compared to PAP. PAP- and PA2024-CTL activity (CD107a positivity) significantly increased at weeks 6 and 26 after sipuleucel-T treatment (p<0.0001; N=22). At 26 weeks post-sipuleucel-T, OS correlated with the magnitude of PAP (Pearson's R, 0.52; p=0.013) or PA2024 (Pearson's R, 0.67; p=0.0006) CTL activity. Higher PA2024-CTL activity at week 26 was significantly associated with longer OS using tertile analysis (p=0.0005; N=22), with PA2024 responses correlating with PAP responses at week 26 (R=0.90; p=1.53E -08 ). This study is the first to report PAP-specific CD8+ T-cell responses elicited by sipuleucel-T treatment. Increased and persistent potential PA2024-specific CTL activity correlated with PAP-specific CTL activity and associated with improved OS following sipuleucel-T treatment. Copyright ©2018, American Association for Cancer Research.

Greater effect of stroke thrombolysis in the presence of arterial obstruction.

PubMed

De Silva, Deidre A; Churilov, Leonid; Olivot, Jean-Marc; Christensen, Soren; Lansberg, Maarten G; Mlynash, Michael; Campbell, Bruce C V; Desmond, Patricia; Straka, Matus; Bammer, Roland; Albers, Gregory W; Davis, Stephen M; Donnan, Geoffrey A

2011-10-01

Recanalization of arterial obstruction is associated with improved clinical outcomes. There are no controlled data demonstrating whether arterial obstruction status predicts the treatment effect of intravenous (IV) tissue plasminogen activator (tPA). We aimed to determine if the presence of arterial obstruction improves the treatment effect of IV tPA over placebo in attenuating infarct growth. We analyzed 175 ischemic stroke patients treated in the 3-6 hour time window from the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET) trial (randomized to IV tPA or placebo) and Diffusion and perfusion imaging Evaluation For Understanding Stroke Evolution (DEFUSE) study (all treated with IV tPA). Infarct growth was calculated as the difference between baseline diffusion-weighted imaging (DWI) and final T2 lesion volumes. Baseline arterial obstruction of large intracranial arteries was graded on magnetic resonance angiography (MRA). Among the 116 patients with adequate baseline MRA and final lesion assessment, 72 had arterial obstruction (48 tPA, 24 placebo) and 44 no arterial obstruction (33 tPA, 11 placebo). Infarct growth was lower in the tPA than placebo group (median difference 26ml, 95% confidence interval [CI], 1-50) in patients with arterial obstruction, but was similar in patients with no arterial obstruction (median difference 5ml, 95%CI, -3 to 9). Infarct growth attenuation with tPA over placebo treatment was greater among patients with arterial obstruction than those without arterial obstruction by a median of 32ml (95%CI, 21-43, p < 0.001). The treatment effect of IV tPA over placebo was greater with baseline arterial obstruction, supporting arterial obstruction status as a consideration in selecting patients more likely to benefit from IV thrombolysis. Copyright © 2011 American Neurological Association.

Pseudo and conditional score approach to joint analysis of current count and current status data.

PubMed

Wen, Chi-Chung; Chen, Yi-Hau

2018-04-17

We develop a joint analysis approach for recurrent and nonrecurrent event processes subject to case I interval censorship, which are also known in literature as current count and current status data, respectively. We use a shared frailty to link the recurrent and nonrecurrent event processes, while leaving the distribution of the frailty fully unspecified. Conditional on the frailty, the recurrent event is assumed to follow a nonhomogeneous Poisson process, and the mean function of the recurrent event and the survival function of the nonrecurrent event are assumed to follow some general form of semiparametric transformation models. Estimation of the models is based on the pseudo-likelihood and the conditional score techniques. The resulting estimators for the regression parameters and the unspecified baseline functions are shown to be consistent with rates of square and cubic roots of the sample size, respectively. Asymptotic normality with closed-form asymptotic variance is derived for the estimator of the regression parameters. We apply the proposed method to a fracture-osteoporosis survey data to identify risk factors jointly for fracture and osteoporosis in elders, while accounting for association between the two events within a subject. © 2018, The International Biometric Society.

Synthesis and characterization of semiaromatic copolyamide 10T/1014 with high performance and flexibility.

PubMed

Feng, Wutong; Wang, Pingli; Zou, Guangji; Ren, Zhonglai; Ji, Junhui

2018-01-01

Poly (decamethylene terephthalamide) (PA10T) is a kind of engineering plastics with high strength and high modulus, but one of its disadvantages is its low elongation at break. In order to improve the flexibility of PA10T, one aliphatic comonomer with a long alkyl chain is introduced to the molecular chain of PA10T. Then long chain semiaromatic copolyamides 10T/1014 were synthesized with different contents of 1014 units by polycondensation reaction of 1,10-diaminodecane, terephthalic acid and 1,12-dodecanedicarboxylic acid in deionized water. The intrinsic viscosities of the resultant polyamides ranged from 0.90 to 1.03 dL/g were obtained. The chemical and crystal structures of the copolymers were characterized by FTIR, 1 H-NMR and WAXD. These copolyamides exhibited outstanding thermal properties with melting points range of 306-295 °C and degradation temperatures range of 479-472 °C at maximum degradation rate, and also have a wider processing window than PA10T. The tensile strength of PA10T/1014 copolymers decreased gradually from 80.02 to 72.95 MPa as the content of 1014 units increasing from 5 to 20 mol %, while the elongation at break increased significantly from 57 to 150%. The moisture content of 10T/1014 copolyamides decreased with increasing the 1014 unit contents. It suggests that 10T/1014 copolyamides could be a kind of promising heat-resistant engineering thermoplastic in the future applications.

Intestinal parasitic infections in relation to HIV/AIDS status, diarrhea and CD4 T-cell count.

PubMed

Assefa, Shimelis; Erko, Berhanu; Medhin, Girmay; Assefa, Zelalem; Shimelis, Techalew

2009-09-18

HIV infection has been modifying both the epidemiology and outcome of parasitic infections. Hence, this study was undertaken to determine the prevalence of intestinal parasitic infection among people with and without HIV infection and its association with diarrhea and CD4 T-cell count. A cross-sectional study was conducted at Hawassa Teaching and Referral Hospital focusing on HIV positive individuals, who gave blood for CD4 T-cell count at their first enrollment and clients tested HIV negative from November, 2008 to March, 2009. Data on socio-demographic factors and diarrhea status were obtained by interviewing 378 consecutive participants (214 HIV positive and 164 HIV negative). Stool samples were collected from all study subjects and examined for parasites using direct, formol-ether and modified acid fast stain techniques. The prevalence of any intestinal parasitic infection was significantly higher among HIV positive participants. Specifically, rate of infection with Cryptosporidium, I. belli, and S. stercoralis were higher, particularly in those with CD4 count less than 200 cells/microL. Diarrhea was more frequent also at the same lower CD4 T-cell counts. Immunodeficiency increased the risk of having opportunistic parasites and diarrhea. Therefore; raising patient immune status and screening at least for those treatable parasites is important.

Biofuels in transport sector of Latvia: experience, current status and barriers

NASA Astrophysics Data System (ADS)

Smigins, R.; Shipkovs, P.

2014-02-01

During the last 10 years biofuel production and utilization in the European Union have become more extensive owing to support provided by the relevant EU Directives. Achievement of the main targets defined by Directives was not simple, being confronted with various barriers. Latvia is one of the EU member-countries that have set an ambitious goal as to the production of biofuel and its use in transport. The authors summarize the major achievements of the country in this area and analyze the main barriers to implementation of biofuels in the transport sector, providing an outlook on the current status of the bioenergy and the transport situation in Latvia. Pēdējo 10 gadu laikā biodegvielu ražošana un izmantošana ES ir kļuvusi daudz plašāka, pateicoties spēcīgam Direktīvu atbalstam. Galveno Direktīvu definēto mērķu sasniegšana nebija viegla un saskārās ar dažādiem sarežģījumiem. Latvija ir viena no ES valstīm, kas uzstādīja ambiciozu mērķi biodegvielu ražošanā un tālākā šīs degvielas izmantošanā transportā. Dotais raksts dod ieskatu galvenajos valsts sasniegumos šajā sfērā, kā arī analizē galvenās barjeras, kas traucē biodegvielu ieviešanu transporta sektorā. Tāpat tiek dots ieskats uz valsts esošo situāciju enerģētikā un transportā.

Improving Interference Control in ADHD Patients with Transcranial Direct Current Stimulation (tDCS)

PubMed Central

Breitling, Carolin; Zaehle, Tino; Dannhauer, Moritz; Bonath, Björn; Tegelbeckers, Jana; Flechtner, Hans-Henning; Krauel, Kerstin

2016-01-01

The use of transcranial direct current stimulation (tDCS) in patients with attention deficit hyperactivity disorder (ADHD) has been suggested as a promising alternative to psychopharmacological treatment approaches due to its local and network effects on brain activation. In the current study, we investigated the impact of tDCS over the right inferior frontal gyrus (rIFG) on interference control in 21 male adolescents with ADHD and 21 age matched healthy controls aged 13–17 years, who underwent three separate sessions of tDCS (anodal, cathodal, and sham) while completing a Flanker task. Even though anodal stimulation appeared to diminish commission errors in the ADHD group, the overall analysis revealed no significant effect of tDCS. Since participants showed a considerable learning effect from the first to the second session, performance in the first session was separately analyzed. ADHD patients receiving sham stimulation in the first session showed impaired interference control compared to healthy control participants whereas ADHD patients who were exposed to anodal stimulation, showed comparable performance levels (commission errors, reaction time variability) to the control group. These results suggest that anodal tDCS of the right inferior frontal gyrus could improve interference control in patients with ADHD. PMID:27147964

Single-cell profiling of peanut-responsive T cells in patients with peanut allergy reveals heterogeneous effector TH2 subsets.

PubMed

Chiang, David; Chen, Xintong; Jones, Stacie M; Wood, Robert A; Sicherer, Scott H; Burks, A Wesley; Leung, Donald Y M; Agashe, Charuta; Grishin, Alexander; Dawson, Peter; Davidson, Wendy F; Newman, Leah; Sebra, Robert; Merad, Miriam; Sampson, Hugh A; Losic, Bojan; Berin, M Cecilia

2018-06-01

The contribution of phenotypic variation of peanut-specific T cells to clinical allergy or tolerance to peanut is not well understood. Our objective was to comprehensively phenotype peanut-specific T cells in the peripheral blood of subjects with and without peanut allergy (PA). We obtained samples from patients with PA, including a cohort undergoing baseline peanut challenges for an immunotherapy trial (Consortium of Food Allergy Research [CoFAR] 6). Subjects were confirmed as having PA, or if they passed a 1-g peanut challenge, they were termed high-threshold subjects. Healthy control (HC) subjects were also recruited. Peanut-responsive T cells were identified based on CD154 expression after 6 to 18 hours of stimulation with peanut extract. Cells were analyzed by using flow cytometry and single-cell RNA sequencing. Patients with PA had tissue- and follicle-homing peanut-responsive CD4 + T cells with a heterogeneous pattern of T H 2 differentiation, whereas control subjects had undetectable T-cell responses to peanut. The PA group had a delayed and IL-2-dependent upregulation of CD154 on cells expressing regulatory T (Treg) cell markers, which was absent in HC or high-threshold subjects. Depletion of Treg cells enhanced cytokine production in HC subjects and patients with PA in vitro, but cytokines associated with highly differentiated T H 2 cells were more resistant to Treg cell suppression in patients with PA. Analysis of gene expression by means of single-cell RNA sequencing identified T cells with highly correlated expression of IL4, IL5, IL9, IL13, and the IL-25 receptor IL17RB. These results demonstrate the presence of highly differentiated T H 2 cells producing T H 2-associated cytokines with functions beyond IgE class-switching in patients with PA. A multifunctional T H 2 response was more evident than a Treg cell deficit among peanut-responsive T cells. Copyright © 2018 American Academy of Allergy, Asthma & Immunology. All rights reserved.

Current status of the western gray squirrel population in the Puget Trough, Washington.

Treesearch

R. Bayrakci; A.B. Carey; T.M. Wilson

2001-01-01

The Puget Trough population of Washington’s state-threatened western gray squirrel is centered in Oregon white oak ecotones adjacent to conifer forests and prairies on the Fort Lewis Military Reservation. Our goal was to determine the current status of western gray squirrels in this region. In 1998, we found five western gray squirrels in 538 hours of foot surveys in...

Age, Sex & Nutritional Status Modify CD4+T-Cell Recovery Rate in HIV/Tuberculosis Co-infected Patients on cART

PubMed Central

Ezeamama, Amara E; Mupere, Ezekiel; Oloya, James; Martinez, Leonardo; Kakaire, Robert; Yin, Xiaoping; Sekandi, Juliet N; Whalen, Christopher C

2015-01-01

Background We examined baseline age and combination antiretroviral therapy (cART) as determinants of CD4+T-cell recovery during six months of tuberculosis (TB) therapy with/without cART. We determined whether this association was modified by patient sex and nutritional status. Methods This longitudinal analysis included 208 immune-competent, non-pregnant, ART-naive HIV-positive patients from Uganda with a first episode of pulmonary TB. CD4+T-cell count was measured using flow cytometry. Age was defined as ≤24, 25–29, 30–34, 35–39 vs. ≥ 40 years. Nutritional status was defined as normal (>18.5kg/m2) vs. underweight (≤18.5kg/m2) using body mass index (BMI). Multivariate random-effects linear mixed models were fitted to estimate differences in CD4+T-cell recovery in relation to specified determinants. Results cART was associated with a monthly rise of 15.7 cells/μL (p<0.001). Overall, age was not associated with CD4+T-cell recovery during TB therapy (p=0.655). However, among patients on cART, age-associated CD4+T-cell recovery rate varied by sex and nutritional status such that age <40 vs. ≥ 40 years predicted superior absolute CD4+T-cell recovery among females (p=0.006) and among patients with BMI≥18.5kg/m2 (p<0.001). Conclusions TB infected HIV-positive patients ≥ 40 years have a slower rate of immune restoration given cART-particularly if BMI>18.5kg/m2 or female. They may benefit from increased monitoring and nutritional support during cART. PMID:25910854

Current Status of the LOFAR EoR Key Science Project

NASA Astrophysics Data System (ADS)

Koopmans, L. V. E.; LOFAR EoR KSP Team

2018-05-01

A short status update on the LOFAR Epoch of Reionization (EoR) Key Science Project (KSP) is given, regarding data acquisition, data processing and analysis, and current power-spectrum limits on the redshifted 21-cm signal of neutral hydrogen at redshifts z = 8 - 10. With caution, we present a preliminary astrophysical analysis of ~60 hr of processed LOFAR data and their resulting power spectrum, showing that potentially already interesting limits on X-ray heating during the Cosmic Dawn can already be gained. This is by no means the final analysis of this sub-set of data, but illustrates the future potential when all nearly 3000 hr of data in hand on two EoR windows will have been processed.

Current status of surrogacy in Japan and uterine transplantation research.

PubMed

Kisu, Iori; Banno, Kouji; Mihara, Makoto; Iida, Takuya; Yoshimura, Yasunori

2011-10-01

Recent advances in assisted reproductive technology (ART) have made it possible to circumvent many causes of male and female infertility. The right to have a child by ART has been respected for infertile couples. However, there are currently no legal regulations concerning ART in Japan, and this has resulted in social and ethical problems. Surrogacy involves particularly complex medical, ethical, social, and legal issues, and is frequently focused on as a major social concern. Uterine transplantation (UTx) is a potential alternative for young women with uterine factor infertility due to hysterectomy for treatment of a malignant uterine tumor or massive blood loss after delivery, or because of a congenital disease such as Mayer-Rokitansky-Küster syndrome. UTx has been examined in experimental animals as a basis for establishment of fecundity for young women with uterine factor infertility. In this review, we focus on surrogacy in Japan and UTx research, and discuss the current status and concerns in this field. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

The current status and portability of our sequence handling software.

PubMed Central

Staden, R

1986-01-01

I describe the current status of our sequence analysis software. The package contains a comprehensive suite of programs for managing large shotgun sequencing projects, a program containing 61 functions for analysing single sequences and a program for comparing pairs of sequences for similarity. The programs that have been described before have been improved by the addition of new functions and by being made very much easier to use. The major interactive programs have 125 pages of online help available from within them. Several new programs are described including screen editing of aligned gel readings for shotgun sequencing projects; a method to highlight errors in aligned gel readings, new methods for searching for putative signals in sequences. We use the programs on a VAX computer but the whole package has been rewritten to make it easy to transport it to other machines. I believe the programs will now run on any machine with a FORTRAN77 compiler and sufficient memory. We are currently putting the programs onto an IBM PC XT/AT and another micro running under UNIX. PMID:3511446

Current status and future prospects of Japanese national project on coated conductor development and its applications

NASA Astrophysics Data System (ADS)

Shiohara, Y.; Yoshizumi, M.; Izumi, T.; Yamada, Y.

2008-09-01

Four years of the current five-year national project since 2003 for development of coated conductors using Y-system superconductors have passed and lots of remarkable results have been achieved. In this paper, the current status and the future prospect of this project are reviewed. The current national project comprises several groups of national laboratories, universities and private companies. The group of high performance tape development, consisting of Fujikura and SRL-NCCC, has worked on the tape by PLD-REBCO superconducting tapes on the PLD-CeO 2/IBAD-GZO buffered substrates. The high product of Ic and L equal to 112,166 A m was achieved in the 368 m-304.8 A GdBCO tape whose Ic value is mostly above 350 A/cm-w. The performance under the magnetic fields was also improved up to 42 A at 3 T in a GdBCO short film with doping of ZrO 2. About 61 m long GdBCO tape with ZrO 2 doping showed a high Ic value of 220 A at self field and 30 A at 3 T. On the other hand, the other group focusing on the low production cost has worked on processes of TFA-MOD and MOCVD, etc. The extremely high Ic value of 735 A/cm-w was attained in the TFA-MOD films on PLD-CeO 2/IBAD-GZO/Hastelloy C276 substrate by means of using the effect of Ba-poor nominal composition. In the efforts for long tape production, 200 m long tapes with high Ic values of 200 A/cm-w and 205 A/cm-w were obtained by MOD-YBCO/PLD-CeO 2/IBAD-GZO/Hastelloy C276 and PLD-HoBCO on buffered NiW substrate, respectively. The Ic × L value of the MOD-derived tape was 40,000 A m, which is the highest value in the world by the MOD process. Based on the above achievements on the coated conductor process development, two new additional goals were set in the project. One is the development for the extremely low cost tape and another is the development of the basic technologies for making the electric power devices including cables, transformers, motors, current-limiters and cryocoolers. Some of the new themes already revealed the

75 FR 12732 - Foreign-Trade Zone Subzone 33E-Mount Pleasant, PA; Temporary/Interim Manufacturing Authority; DNP...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-17

... DEPARTMENT OF COMMERCE Foreign-Trade Zones Board [T-2-2009] Foreign-Trade Zone Subzone 33E--Mount Pleasant, PA; Temporary/ Interim Manufacturing Authority; DNP IMS America Corporation (Thermal Transfer...) authority, on behalf of DNP IMS America Corporation to manufacture thermal transfer ribbon printer rolls...

Cross-cultural adaptation of the assistive technology device - Predisposition assessment (ATD PA) for use in Brazil (ATD PA Br).

PubMed

Alves, Ana Cristina de Jesus; Matsukura, Thelma Simões; Scherer, Marcia J

2017-02-01

The purpose of this study is to conduct a cross-cultural adaptation of the Assistive Technology Device Predisposition Assessment (ATD PA) for use in Brazil. The selection of the Assistive Technology Device Predisposition Assessment (ATD PA) was determined by previous literature reviews of articles published in 2014 and 2016 in six databases with the terms "assistive device" or "assistive technology" or "self-help device" combined with "evidence-based practice" or "framework" or "measurement scale" or "model and outcome assessment". This review indicated that the conceptual model of Assistive Technology (AT) most discussed in the literature was the Matching Person and Technology (MPT) model, and this finding determined the selection of ATD PA as an assessment within the MPT portfolio of measures. The procedures for cross-cultural adaptation were as follows: Equivalence of Concept, Semantic and Operational. Five experts were asked to translate 725 items and these translations were evaluated and a high level of agreement was demonstrated. The Portuguese version, Avaliação de Tecnologia Assistiva - Predisposição ao Uso - ATD PA Br, was derived from the original version in English (ATD PA). The ATD PA Br will support professionals and people with disabilities in Brazil to better select AT devices according to the clients' needs. Implications for rehabilitation Provides a systematic way of selecting assistive technology devices for the use of individuals with disabilities according to the Brazilian reality. A systematic way of selecting the assistive technology that can help decrease the abandonment of the assistive technology use. The use of the Matching Person and Technology theorical model and of the assessment ATD PA Br is essential to guide the researches and clinical practice in Brazil.

A review on current status of antiviral siRNA.

PubMed

Qureshi, Abid; Tantray, Vaqar Gani; Kirmani, Altaf Rehman; Ahangar, Abdul Ghani

2018-04-15

Viral diseases like influenza, AIDS, hepatitis, and Ebola cause severe epidemics worldwide. Along with their resistant strains, new pathogenic viruses continue to be discovered so creating an ongoing need for new antiviral treatments. RNA interference is a cellular gene-silencing phenomenon in which sequence-specific degradation of target mRNA is achieved by means of complementary short interfering RNA (siRNA) molecules. Short interfering RNA technology affords a potential tractable strategy to combat viral pathogenesis because siRNAs are specific, easy to design, and can be directed against multiple strains of a virus by targeting their conserved gene regions. In this review, we briefly summarize the current status of siRNA therapy for representative examples from different virus families. In addition, other aspects like their design, delivery, medical significance, bioinformatics resources, and limitations are also discussed. Copyright © 2018 John Wiley & Sons, Ltd.

Microbiological risk factors in dentistry. Current status of knowledge.

PubMed

Szymańska, Jolanta

2005-01-01

Dentists belong to a professional group potentially exposed to harmful biological factors which most often are infectious microorganisms, less frequently - allergenic or toxic microorganisms. The fundamental routes of spreading harmful microorganisms in a dental surgery are: blood-borne, saliva-droplet, direct contact with a patient and with infected equipment, and water-droplet infections. In this paper, the current status of knowledge on microbiological hazards in a dentist's work is presented. Groups of microorganisms, such as prions, viruses, bacteria, fungi and protozoa, to which a dentist is, or may be exposed, are discussed. Epidemiological assessment of microbiological hazards in a dentist's work was performed and the basic principles of prevention formulated. Special attention was given to microflora in dental unit waterlines, and the biofilm persisting in them, as a source of occupational hazards specific for a dentist's workplace.

PERSISTENT CURRENT EFFECT IN 15-16 T NB3SN ACCELERATOR DIPOLES AND ITS CORRECTION

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

Kashikhin, V. V.; Zlobin, A. V.

2016-11-08

Nb3Sn magnets with operating fields of 15-16 T are considered for the LHC Energy Doubler and a future Very High Energy pp Collider. Due to large coil volume, high critical current density and large superconducting (SC) filament size the persistent current effect is very large in Nb3Sn dipoles al low fields. This paper presents the results of analysis of the persistent current effect in the 15 T Nb3Sn dipole demonstrator being developed at FNAL, and describes different possibilities of its correction including passive SC wires, iron shims and coil geometry.

Effects of preoperative and postoperative enteral nutrition on postoperative nutritional status and immune function of gastric cancer patients.

PubMed

Ding, Dayong; Feng, Ye; Song, Bin; Gao, Shuohui; Zhao, Jisheng

2015-03-01

Effects of preoperative one week enteral nutrition (EN) support on the postoperative nutritional status, immune function and inflammatory response of gastric cancer patients were investigated. 106 cases of gastric cancer patients were randomly divided into preoperative one week EN group (trial group) and early postoperative EN group (control group), which were continuously treated with EN support until the postoperative 9th day according to different treatment protocols. All the patients were checked for their body weight, skinfold thickness, upper arm circumference, white blood cell count (WBC), albumin (ALB), prealbumin (PA), C-reactive protein (CRP), humoral immunity (IgA, IgG), T cell subsets (CD4, CD8 and CD4/CD8), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), etc. on the preoperative and the postoperative 1st and 10th day, respectively. PA and IgG levels of the experimental group were higher than those of the control group on the postoperative 10th day, whereas IL-6 level of the experimental group was lower than that of the control group. EN support for preoperative gastric cancer patients will improve the postoperative nutritional status and immune function, alleviate inflammatory response, and facilitate the recovery of patients.

Spatial and polarity precision of concentric high-definition transcranial direct current stimulation (HD-tDCS)

NASA Astrophysics Data System (ADS)

Alam, Mahtab; Truong, Dennis Q.; Khadka, Niranjan; Bikson, Marom

2016-06-01

Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulation technique that applies low amplitude current via electrodes placed on the scalp. Rather than directly eliciting a neuronal response, tDCS is believed to modulate excitability—enhancing or suppressing neuronal activity in regions of the brain depending on the polarity of stimulation. The specificity of tDCS to any therapeutic application derives in part from how electrode configuration determines the brain regions that are stimulated. Conventional tDCS uses two relatively large pads (>25 cm2) whereas high-definition tDCS (HD-tDCS) uses arrays of smaller electrodes to enhance brain targeting. The 4  ×  1 concentric ring HD-tDCS (one center electrode surrounded by four returns) has been explored in application where focal targeting of cortex is desired. Here, we considered optimization of concentric ring HD-tDCS for targeting: the role of electrodes in the ring and the ring’s diameter. Finite element models predicted cortical electric field generated during tDCS. High resolution MRIs were segmented into seven tissue/material masks of varying conductivities. Computer aided design (CAD) model of electrodes, gel, and sponge pads were incorporated into the segmentation. Volume meshes were generated and the Laplace equation (\

Current Status of Endovascular Treatment for Vasospasm following Subarachnoid Hemorrhage: Analysis of JR-NET2

PubMed Central

HAYASHI, Kentaro; HIRAO, Tomohito; SAKAI, Nobuyuki; NAGATA, Izumi

2014-01-01

Endovascular treatments are employed for cerebral vasospasm following subarachnoid hemorrhage, which is not responded to the medical treatments. However, the effect or complication of the treatments is not known well. Here, we analyzed the data of Japanese Registry of Neuroendovascular Therapy 2 (JRNET2) and revealed current status of the endovascular treatment for the cerebral vasospasm. JR-NET2 is conducted from January 1, 2007 to December 31, 2009. Information on the clinical status, imaging studies, treatment methods, the results of treatment, and status 30 days later were recorded. Totally 645 treatments for 480 patients (mean age, 59.4 years; 72.7% woman) were included. Factors related to the neurological improvement and treatment related complications were statistically analyzed. Treatments for ruptured cerebral aneurysm were direct surgery for 366 cases and endovascular treatment for 253 cases. The timing of the endovascular treatment for the cerebral vasospasm was within 3 hours in 209 cases, 3–6 hours in 158 cases, and more than 6 hours in 158 cases. Intra-arterial vasodilator was employed for the 495 cases and percutaneous transluminal angioplasty for 140 cases. Neurological improvement was observed in 372 cases and radiological improvement was seen in 623 cases. The treatment related complication occurred in 20 cases (3.1%), including 6 cases of intracranial hemorrhage, 5 cases of cerebral ischemia, a case of puncture site trouble, and 8 cases of others. Statistical analysis showed early treatment was related to the neurological improvement. Current status of endovascular treatment for cerebral vasospasm was revealed. Endovascular treatment was effective for vasospasm especially was performed early. PMID:24257541

Current status of endovascular treatment for vasospasm following subarachnoid hemorrhage: analysis of JR-NET2.

PubMed

Hayashi, Kentaro; Hirao, Tomohito; Sakai, Nobuyuki; Nagata, Izumi

2014-01-01

Endovascular treatments are employed for cerebral vasospasm following subarachnoid hemorrhage, which is not responded to the medical treatments. However, the effect or complication of the treatments is not known well. Here, we analyzed the data of Japanese Registry of Neuroendovascular Therapy 2 (JR-NET2) and revealed current status of the endovascular treatment for the cerebral vasospasm. JR-NET2 is conducted from January 1, 2007 to December 31, 2009. Information on the clinical status, imaging studies, treatment methods, the results of treatment, and status 30 days later were recorded. Totally 645 treatments for 480 patients (mean age, 59.4 years; 72.7% woman) were included. Factors related to the neurological improvement and treatment related complications were statistically analyzed. Treatments for ruptured cerebral aneurysm were direct surgery for 366 cases and endovascular treatment for 253 cases. The timing of the endovascular treatment for the cerebral vasospasm was within 3 hours in 209 cases, 3-6 hours in 158 cases, and more than 6 hours in 158 cases. Intra-arterial vasodilator was employed for the 495 cases and percutaneous transluminal angioplasty for 140 cases. Neurological improvement was observed in 372 cases and radiological improvement was seen in 623 cases. The treatment related complication occurred in 20 cases (3.1%), including 6 cases of intracranial hemorrhage, 5 cases of cerebral ischemia, a case of puncture site trouble, and 8 cases of others. Statistical analysis showed early treatment was related to the neurological improvement. Current status of endovascular treatment for cerebral vasospasm was revealed. Endovascular treatment was effective for vasospasm especially was performed early.

Current Status of Endovascular Treatment for Vasospasm following Subarachnoid Hemorrhage: Analysis of JR-NET2.

PubMed

Hayashi, Kentaro; Hirao, Tomohito; Sakai, Nobuyuki; Nagata, Izumi

2014-01-01

Endovascular treatments are employed for cerebral vasospasm following subarachnoid hemorrhage, which is not responded to the medical treatments. However, the effect or complication of the treatments is not known well. Here, we analyzed the data of Japanese Registry of Neuroendovascular Therapy 2 (JR-NET2) and revealed current status of the endovascular treatment for the cerebral vasospasm. JR-NET2 is conducted from January 1, 2007 to December 31, 2009. Information on the clinical status, imaging studies, treatment methods, the results of treatment, and status 30 days later were recorded. Totally 645 treatments for 480 patients (mean age, 59.4 years; 72.7% woman) were included. Factors related to the neurological improvement and treatment related complications were statistically analyzed. Treatments for ruptured cerebral aneurysm were direct surgery for 366 cases and endovascular treatment for 253 cases. The timing of the endovascular treatment for the cerebral vasospasm was within 3 hours in 209 cases, 3–6 hours in 158 cases, and more than 6 hours in 158 cases. Intra-arterial vasodilator was employed for the 495 cases and percutaneous transluminal angioplasty for 140 cases. Neurological improvement was observed in 372 cases and radiological improvement was seen in 623 cases. The treatment related complication occurred in 20 cases (3.1%), including 6 cases of intracranial hemorrhage, 5 cases of cerebral ischemia, a case of puncture site trouble, and 8 cases of others. Statistical analysis showed early treatment was related to the neurological improvement. Current status of endovascular treatment for cerebral vasospasm was revealed. Endovascular treatment was effective for vasospasm especially was performed early.

Academic drug discovery: current status and prospects.

PubMed

Everett, Jeremy R

2015-01-01

The contraction in pharmaceutical drug discovery operations in the past decade has been counter-balanced by a significant rise in the number of academic drug discovery groups. In addition, pharmaceutical companies that used to operate in completely independent, vertically integrated operations for drug discovery, are now collaborating more with each other, and with academic groups. We are in a new era of drug discovery. This review provides an overview of the current status of academic drug discovery groups, their achievements and the challenges they face, together with perspectives on ways to achieve improved outcomes. Academic groups have made important contributions to drug discovery, from its earliest days and continue to do so today. However, modern drug discovery and development is exceedingly complex, and has high failure rates, principally because human biology is complex and poorly understood. Academic drug discovery groups need to play to their strengths and not just copy what has gone before. However, there are lessons to be learnt from the experiences of the industrial drug discoverers and four areas are highlighted for attention: i) increased validation of targets; ii) elimination of false hits from high throughput screening (HTS); iii) increasing the quality of molecular probes; and iv) investing in a high-quality informatics infrastructure.

The Impact of ExoS on Pseudomonas aeruginosa Internalization by Epithelial Cells Is Independent of fleQ and Correlates with Bistability of Type Three Secretion System Gene Expression

PubMed Central

Kroken, Abby R.; Chen, Camille K.; Evans, David J.; Yahr, Timothy L.

2018-01-01

ABSTRACT Pseudomonas aeruginosa is internalized into multiple types of epithelial cell in vitro and in vivo and yet is often regarded as an exclusively extracellular pathogen. Paradoxically, ExoS, a type three secretion system (T3SS) effector, has antiphagocytic activities but is required for intracellular survival of P. aeruginosa and its occupation of bleb niches in epithelial cells. Here, we addressed mechanisms for this dichotomy using invasive (ExoS-expressing) P. aeruginosa and corresponding effector-null isogenic T3SS mutants, effector-null mutants of cytotoxic P. aeruginosa with and without ExoS transformation, antibiotic exclusion assays, and imaging using a T3SS-GFP reporter. Except for effector-null PA103, all strains were internalized while encoding ExoS. Intracellular bacteria showed T3SS activation that continued in replicating daughter cells. Correcting the fleQ mutation in effector-null PA103 promoted internalization by >10-fold with or without ExoS. Conversely, mutating fleQ in PAO1 reduced internalization by >10-fold, also with or without ExoS. Effector-null PA103 remained less well internalized than PAO1 matched for fleQ status, but only with ExoS expression, suggesting additional differences between these strains. Quantifying T3SS activation using GFP fluorescence and quantitative reverse transcription-PCR (qRT-PCR) showed that T3SS expression was hyperinducible for strain PA103ΔexoUT versus other isolates and was unrelated to fleQ status. These findings support the principle that P. aeruginosa is not exclusively an extracellular pathogen, with internalization influenced by the relative proportions of T3SS-positive and T3SS-negative bacteria in the population during host cell interaction. These data also challenge current thinking about T3SS effector delivery into host cells and suggest that T3SS bistability is an important consideration in studying P. aeruginosa pathogenesis. PMID:29717012

Assimilation of radar quantitative precipitation estimations in the Canadian Precipitation Analysis (CaPA)

NASA Astrophysics Data System (ADS)

Fortin, Vincent; Roy, Guy; Donaldson, Norman; Mahidjiba, Ahmed

2015-12-01

The Canadian Precipitation Analysis (CaPA) is a data analysis system used operationally at the Canadian Meteorological Center (CMC) since April 2011 to produce gridded 6-h and 24-h precipitation accumulations in near real-time on a regular grid covering all of North America. The current resolution of the product is 10-km. Due to the low density of the observational network in most of Canada, the system relies on a background field provided by the Regional Deterministic Prediction System (RDPS) of Environment Canada, which is a short-term weather forecasting system for North America. For this reason, the North American configuration of CaPA is known as the Regional Deterministic Precipitation Analysis (RDPA). Early in the development of the CaPA system, weather radar reflectivity was identified as a very promising additional data source for the precipitation analysis, but necessary quality control procedures and bias-correction algorithms were lacking for the radar data. After three years of development and testing, a new version of CaPA-RDPA system was implemented in November 2014 at CMC. This version is able to assimilate radar quantitative precipitation estimates (QPEs) from all 31 operational Canadian weather radars. The radar QPE is used as an observation source and not as a background field, and is subject to a strict quality control procedure, like any other observation source. The November 2014 upgrade to CaPA-RDPA was implemented at the same time as an upgrade to the RDPS system, which brought minor changes to the skill and bias of CaPA-RDPA. This paper uses the frequency bias indicator (FBI), the equitable threat score (ETS) and the departure from the partial mean (DPM) in order to assess the improvements to CaPA-RDPA brought by the assimilation of radar QPE. Verification focuses on the 6-h accumulations, and is done against a network of 65 synoptic stations (approximately two stations per radar) that were withheld from the station data assimilated by CaPA

Current Status of Nephron-Sparing Surgery (NSS) in the Management of Renal Tumours.

PubMed

Venkatramani, Vivek; Swain, Sanjaya; Satyanarayana, Ramgopal; Parekh, Dipen J

2017-06-01

Nephron-sparing surgery has emerged as the surgical treatment of choice for small renal masses over the past two decades, replacing the traditional teaching of radical nephrectomy for renal cell carcinoma. With time, there has been an evolution in the techniques and indications for partial nephrectomy. This review summarizes the current status of nephron-sparing surgery for renal carcinoma and also deals with the future of this procedure.

Joint T1 and brain fiber log-demons registration using currents to model geometry.

PubMed

Siless, Viviana; Glaunès, Joan; Guevara, Pamela; Mangin, Jean-François; Poupon, Cyril; Le Bihan, Denis; Thirion, Bertrand; Fillard, Pierre

2012-01-01

We present an extension of the diffeomorphic Geometric Demons algorithm which combines the iconic registration with geometric constraints. Our algorithm works in the log-domain space, so that one can efficiently compute the deformation field of the geometry. We represent the shape of objects of interest in the space of currents which is sensitive to both location and geometric structure of objects. Currents provides a distance between geometric structures that can be defined without specifying explicit point-to-point correspondences. We demonstrate this framework by registering simultaneously T1 images and 65 fiber bundles consistently extracted in 12 subjects and compare it against non-linear T1, tensor, and multi-modal T1 + Fractional Anisotropy (FA) registration algorithms. Results show the superiority of the Log-domain Geometric Demons over their purely iconic counterparts.

Veterinary pharmacology: history, current status and future prospects.

PubMed

Lees, P; Fink-Gremmels, J; Toutain, P L

2013-04-01

Veterinary therapeutics, based on the art of Materia Medica, has been practised for countless centuries, but the science of veterinary pharmacology is of very recent origin. This review traces the contribution of Materia Medica to veterinary therapeutics from the Egyptian period through to the Age of Enlightenment. The first tentative steps in the development of the science of veterinary pharmacology were taken in the 18th century, but it was not until the mid 20th century that the science replaced the art of Materia Medica. This review traces the 20th century developments in veterinary pharmacology, with emphasis on the explosion of knowledge in the 35 year period to 2010. The range of factors which have influenced the current status of the discipline are reviewed. Future developments are considered from the perspectives of what might be regarded as desirable and those innovations that might be anticipated. We end with words of encouragement for young colleagues intent upon pursuing a career in veterinary pharmacology. © 2013 Blackwell Publishing Ltd.

Synthesis and characterization of semiaromatic copolyamide 10T/1014 with high performance and flexibility

PubMed Central

Feng, Wutong; Zou, Guangji; Ren, Zhonglai; Ji, Junhui

2018-01-01

Abstract Poly (decamethylene terephthalamide) (PA10T) is a kind of engineering plastics with high strength and high modulus, but one of its disadvantages is its low elongation at break. In order to improve the flexibility of PA10T, one aliphatic comonomer with a long alkyl chain is introduced to the molecular chain of PA10T. Then long chain semiaromatic copolyamides 10T/1014 were synthesized with different contents of 1014 units by polycondensation reaction of 1,10-diaminodecane, terephthalic acid and 1,12-dodecanedicarboxylic acid in deionized water. The intrinsic viscosities of the resultant polyamides ranged from 0.90 to 1.03 dL/g were obtained. The chemical and crystal structures of the copolymers were characterized by FTIR, 1H-NMR and WAXD. These copolyamides exhibited outstanding thermal properties with melting points range of 306–295 °C and degradation temperatures range of 479–472 °C at maximum degradation rate, and also have a wider processing window than PA10T. The tensile strength of PA10T/1014 copolymers decreased gradually from 80.02 to 72.95 MPa as the content of 1014 units increasing from 5 to 20 mol %, while the elongation at break increased significantly from 57 to 150%. The moisture content of 10T/1014 copolyamides decreased with increasing the 1014 unit contents. It suggests that 10T/1014 copolyamides could be a kind of promising heat-resistant engineering thermoplastic in the future applications. PMID:29706846

Ventilator-associated pneumonia: current status and future recommendations.

PubMed

Efrati, Shai; Deutsch, Israel; Antonelli, Massimo; Hockey, Peter M; Rozenblum, Ronen; Gurman, Gabriel M

2010-04-01

Ventilator-associated pneumonia (VAP) is a common hazardous complication in ICU patients. The aim of the current review is to give an update on the current status and future recommendations for VAP prevention. This article gives an updated review of the current literature on VAP. The first part briefly reviews pathogenesis and epidemiology while the second includes an in-depth review of evidence-based practice guidelines (EBPG) and new technologies developed for prevention of VAP. VAP remains a frequent and costly complication of critical illness with a pooled relative risk of 9-27% and mortality of 25-50%. Strikingly, VAP adds an estimated cost of more than $40,000 to a typical hospital admission. An important aetiological mechanism of VAP is gross or micro-aspiration of oropharyngeal organisms around the cuff of the endotracheal tube (ETT) into the distal bronchi. Prevention of VAP is preferable. Preventative measures can be divided into two main groups: the implemen- tation of EBPGs and use of device-based technologies. EBPGs have been authored jointly by the American Thoracic Society and the Infectious Diseases Society of America. The Canadian Critical Care Trials group also published VAP Guidelines in 2008. Their recommendations are detailed in this review. The current device-based technologies include drainage of subglottic secretions, silver coated ETTs aiming to influence the internal bio-layer of the ETT, better sealing of the lower airways with ultrathin cuffs and loops for optimal cuff pressure control. EBPG consensus includes: elevation of the head of the bed, use of daily "sedation vacations" and decontamination of the oropharynx. Technological solutions should aim to use the most comprehensive combination of subglottic suction of secretions, optimization of ETT cuff pressure and ultrathin cuffs. VAP is a type of hospital-acquired pneumonia that develops more than 48 h after endotracheal intubation. Its incidence is estimated to be 9-27%, with a

Transcranial direct current stimulation (tDCS) modulation of picture naming and word reading: A meta-analysis of single session tDCS applied to healthy participants.

PubMed

Westwood, Samuel J; Romani, Cristina

2017-09-01

Recent reviews quantifying the effects of single sessions of transcranial direct current stimulation (or tDCS) in healthy volunteers find only minor effects on cognition despite the popularity of this technique. Here, we wanted to quantify the effects of tDCS on language production tasks that measure word reading and picture naming. We reviewed 14 papers measuring tDCS effects across a total of 96 conditions to a) quantify effects of conventional stimulation on language regions (i.e., left hemisphere anodal tDCS administered to temporal/frontal areas) under normal conditions or under conditions of cognitive (semantic) interference; b) identify parameters which may moderate the size of the tDCS effect within conventional stimulation protocols (e.g., online vs offline, high vs. low current densities, and short vs. long durations), as well as within types of stimulation not typically explored by previous reviews (i.e., right hemisphere anodal tDCS or left/right hemisphere cathodal tDCS). In all analyses there was no significant effect of tDCS, but we did find a small but significant effect of time and duration of stimulation with stronger effects for offline stimulation and for shorter durations (< 15min). We also found some indication of publication bias towards reporting positive effects. We encourage further experimentation in order resolve the disparity between the current popularity of tDCS and its poor efficacy in healthy participants. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Provider perceptions of barriers to the emergency use of tPA for acute ischemic stroke: a qualitative study.

PubMed

Meurer, William J; Majersik, Jennifer J; Frederiksen, Shirley M; Kade, Allison M; Sandretto, Annette M; Scott, Phillip A

2011-05-06

Only 1-3% of ischemic stroke patients receive thrombolytic therapy. Provider barriers to adhering with guidelines recommending tPA delivery in acute stroke are not well known. The main objective of this study was to describe barriers to thrombolytic use in acute stroke care. Twenty-four hospitals were randomly selected and matched into 12 pairs. Barrier assessment occurred at intervention sites only, and utilized focus groups and structured interviews. A pre-specified taxonomy was employed to characterize barriers. Two investigators independently assigned themes to transcribed responses. Seven facilitators (three emergency physicians, two nurses, and two study coordinators) conducted focus groups and interviews of emergency physicians (65), nurses (62), neurologists (15), radiologists (12), hospital administrators (12), and three others (hospitalists and pharmacist). The following themes represented the most important external barriers: environmental and patient factors. Important barriers internal to the clinician included familiarity with and motivation to adhere to the guidelines, lack of self-efficacy and outcome expectancy. The following themes were not substantial barriers: lack of awareness of the existence of acute stroke guidelines, presence of conflicting guidelines, and lack of agreement with the guidelines. Healthcare providers perceive environmental and patient-related factors as the primary barriers to adherence with acute stroke treatment guidelines. Interventions focused on increasing physician familiarity with and motivation to follow guidelines may be of highest yield in improving adherence. Improving self-efficacy in performing guideline concordant care may also be useful.

The Effects of Transcranial Direct Current Stimulation (tDCS) on Multitasking Throughput Capacity

PubMed Central

Nelson, Justin; McKinley, Richard A.; Phillips, Chandler; McIntire, Lindsey; Goodyear, Chuck; Kreiner, Aerial; Monforton, Lanie

2016-01-01

Background: Multitasking has become an integral attribute associated with military operations within the past several decades. As the amount of information that needs to be processed during these high level multitasking environments exceeds the human operators' capabilities, the information throughput capacity reaches an asymptotic limit. At this point, the human operator can no longer effectively process and respond to the incoming information resulting in a plateau or decline in performance. The objective of the study was to evaluate the efficacy of a non-invasive brain stimulation technique known as transcranial direct current stimulation (tDCS) applied to a scalp location over the left dorsolateral prefrontal cortex (lDLPFC) to improve information processing capabilities during a multitasking environment. Methods: The study consisted of 20 participants from Wright-Patterson Air Force Base (16 male and 4 female) with an average age of 31.1 (SD = 4.5). Participants were randomly assigned into two groups, each consisting of eight males and two females. Group one received 2 mA of anodal tDCS and group two received sham tDCS over the lDLPFC on their testing day. Results: The findings indicate that anodal tDCS significantly improves the participants' information processing capability resulting in improved performance compared to sham tDCS. For example, the multitasking throughput capacity for the sham tDCS group plateaued near 1.0 bits/s at the higher baud input (2.0 bits/s) whereas the anodal tDCS group plateaued near 1.3 bits/s. Conclusion: The findings provided new evidence that tDCS has the ability to augment and enhance multitasking capability in a human operator. Future research should be conducted to determine the longevity of the enhancement of transcranial direct current stimulation on multitasking performance, which has yet to be accomplished. PMID:27965553

The Effects of Transcranial Direct Current Stimulation (tDCS) on Multitasking Throughput Capacity.

PubMed

Nelson, Justin; McKinley, Richard A; Phillips, Chandler; McIntire, Lindsey; Goodyear, Chuck; Kreiner, Aerial; Monforton, Lanie

2016-01-01

Background: Multitasking has become an integral attribute associated with military operations within the past several decades. As the amount of information that needs to be processed during these high level multitasking environments exceeds the human operators' capabilities, the information throughput capacity reaches an asymptotic limit. At this point, the human operator can no longer effectively process and respond to the incoming information resulting in a plateau or decline in performance. The objective of the study was to evaluate the efficacy of a non-invasive brain stimulation technique known as transcranial direct current stimulation (tDCS) applied to a scalp location over the left dorsolateral prefrontal cortex (lDLPFC) to improve information processing capabilities during a multitasking environment. Methods: The study consisted of 20 participants from Wright-Patterson Air Force Base (16 male and 4 female) with an average age of 31.1 (SD = 4.5). Participants were randomly assigned into two groups, each consisting of eight males and two females. Group one received 2 mA of anodal tDCS and group two received sham tDCS over the lDLPFC on their testing day. Results: The findings indicate that anodal tDCS significantly improves the participants' information processing capability resulting in improved performance compared to sham tDCS. For example, the multitasking throughput capacity for the sham tDCS group plateaued near 1.0 bits/s at the higher baud input (2.0 bits/s) whereas the anodal tDCS group plateaued near 1.3 bits/s. Conclusion: The findings provided new evidence that tDCS has the ability to augment and enhance multitasking capability in a human operator. Future research should be conducted to determine the longevity of the enhancement of transcranial direct current stimulation on multitasking performance, which has yet to be accomplished.

Current status of the expanded GRAPES collaboration experiment at Ooty in India

NASA Astrophysics Data System (ADS)

Gupta, S.K.; Anita, H.M.; Iyer, A.; Jagadeesan, P.; Jain, A.; Karthikeyan, S.; Manoharan, P.K.; Mohanty, P.K.; Nayak, P.K.; Rao, B.S.; Ravindran, K.C.; Tanaka, H.; Tonwar, S.C.; Ogio, S.; Okuda, T.; Oshima, A.; Shimizu, N.; Yoshikoshi, T.; Badruddin; Hasan, R.; Ahmad, Shakeel; Mishra, A.P.; Shrivastava, P.K.; Koul, R.; Shah, G.N.; Mir, T.A.; Mufti, S.; Raha, S.; Ghosh, S.; Joarder, P.; Saha, S.; Boruah, K.; Datta, P.; Boruah, P.K.; Baruah, A.G.; Baishya, R.; Saikia, J.; Banerjee, D.; Subramanian, P.; Bhadra, A.; Kumar, S.; Agarwal, R.; Dubey, S.K.; Bhattacharjee, P.

GRAPES-3 experiment employs a high-density array of scintillators and a large area tracking muon telescope. The GRAPES collaboration is being expanded with addition of several major facilities. These include a Cerenkov telescope and low frequency dipole array for the measurement of shower energy. Addition of several modules of muon telescopes to cover a larger area, expansion of the scintillator array with greater separation between detectors. Installation of a neutron monitor is also planned. The current status of the experiment would be summarized.

Nutritional quality of breakfast and physical activity independently predict the literacy and numeracy scores of children after adjusting for socioeconomic status.

PubMed

O'Dea, Jennifer A; Mugridge, Anna C

2012-12-01

Health-related behaviors [physical activity (PA), nutritional quality of breakfast and sleep]; personal variables (self-esteem, attitudes to PA and gender) and socioeconomic status (SES) (school SES and parental education), were examined in relation to literacy and numeracy scores of 824 grade 3-7 children. Participants completed a questionnaire, and their national literacy and numeracy test scores were retrieved. Mothers (N = 755) completed a telephone interview. Students of highest school SES, maternal education, nutritional quality of breakfast, more sedentary time and female gender had higher literacy scores. SES, maternal education, male gender and total minutes of daily PA were predictors of numeracy with an interaction between greater total PA in boys and greater numeracy. Even though the socioeconomic factors that have predicted children's academic achievement for many decades are still clearly set in place, there are also other modifiable health influences that affect literacy and numeracy and are independent of SES. The current findings provide evidence for health educators and school administrators who may garner support for both breakfast programs and daily school PA for the dual purposes of health promotion as well as for the improvement of literacy and numeracy in settings in which social class may be acting against the educational interests of disadvantaged children.

Computational modeling of transcranial direct current stimulation (tDCS) in obesity: Impact of head fat and dose guidelines☆

PubMed Central

Truong, Dennis Q.; Magerowski, Greta; Blackburn, George L.; Bikson, Marom; Alonso-Alonso, Miguel

2013-01-01

Recent studies show that acute neuromodulation of the prefrontal cortex with transcranial direct current stimulation (tDCS) can decrease food craving, attentional bias to food, and actual food intake. These data suggest potential clinical applications for tDCS in the field of obesity. However, optimal stimulation parameters in obese individuals are uncertain. One fundamental concern is whether a thick, low-conductivity layer of subcutaneous fat around the head can affect current density distribution and require dose adjustments during tDCS administration. The aim of this study was to investigate the role of head fat on the distribution of current during tDCS and evaluate whether dosing standards for tDCS developed for adult individuals in general are adequate for the obese population. We used MRI-derived high-resolution computational models that delineated fat layers in five human heads from subjects with body mass index (BMI) ranging from “normal-lean” to “super-obese” (20.9 to 53.5 kg/m2). Data derived from these simulations suggest that head fat influences tDCS current density across the brain, but its relative contribution is small when other components of head anatomy are added. Current density variability between subjects does not appear to have a direct and/or simple link to BMI. These results indicate that guidelines for the use of tDCS can be extrapolated to obese subjects without sacrificing efficacy and/or treatment safety; the recommended standard parameters can lead to the delivery of adequate current flow to induce neuromodulation of brain activity in the obese population. PMID:24159560

Modulation of Brain Activity with Noninvasive Transcranial Direct Current Stimulation (tDCS): Clinical Applications and Safety Concerns

PubMed Central

Zhao, Haichao; Qiao, Lei; Fan, Dongqiong; Zhang, Shuyue; Turel, Ofir; Li, Yonghui; Li, Jun; Xue, Gui; Chen, Antao; He, Qinghua

2017-01-01

Transcranial direct current stimulation (tDCS) is a widely-used tool to induce neuroplasticity and modulate cortical function by applying weak direct current over the scalp. In this review, we first introduce the underlying mechanism of action, the brief history from discovery to clinical scientific research, electrode positioning and montages, and parameter setup of tDCS. Then, we review tDCS application in clinical samples including people with drug addiction, major depression disorder, Alzheimer's disease, as well as in children. This review covers the typical characteristics and the underlying neural mechanisms of tDCS treatment in such studies. This is followed by a discussion of safety, especially when the current intensity is increased or the stimulation duration is prolonged. Given such concerns, we provide detailed suggestions regarding safety procedures for tDCS operation. Lastly, future research directions are discussed. They include foci on the development of multi-tech combination with tDCS such as with TMS and fMRI; long-term behavioral and morphological changes; possible applications in other research domains, and more animal research to deepen the understanding of the biological and physiological mechanisms of tDCS stimulation. PMID:28539894

Inhomogeneous cosmology and backreaction: Current status and future prospects

NASA Astrophysics Data System (ADS)

Bolejko, Krzysztof; Korzyński, Mikołaj

Astronomical observations reveal hierarchical structures in the universe, from galaxies, groups of galaxies, clusters and superclusters, to filaments and voids. On the largest scales, it seems that some kind of statistical homogeneity can be observed. As a result, modern cosmological models are based on spatially homogeneous and isotropic solutions of the Einstein equations, and the evolution of the universe is approximated by the Friedmann equations. In parallel to standard homogeneous cosmology, the field of inhomogeneous cosmology and backreaction is being developed. This field investigates whether small scale inhomogeneities via nonlinear effects can backreact and alter the properties of the universe on its largest scales, leading to a non-Friedmannian evolution. This paper presents the current status of inhomogeneous cosmology and backreaction. It also discusses future prospects of the field of inhomogeneous cosmology, which is based on a survey of 50 academics working in the field of inhomogeneous cosmology.

Clinical utility of level-of-evidence-1 disease forecast cancer biomarkers uPA and its inhibitor PAI-1.

PubMed

Schmitt, Manfred; Mengele, Karin; Napieralski, Rudolf; Magdolen, Viktor; Reuning, Ute; Gkazepis, Apostolos; Sweep, Fred; Brünner, Nils; Foekens, John; Harbeck, Nadia

2010-11-01

The prognostic and/or predictive value of the cancer biomarkers, urokinase-type plasminogen activator (uPA) and its inhibitor (plasminogen activator inhibitor [PAI]-1), determined by ELISA in tumor-tissue extracts, was demonstrated for several cancer types in numerous clinically relevant retrospective or prospective studies, including a multicenter breast cancer therapy trial (Chemo-N0). Consequently, for the first time ever for any cancer biomarker for breast cancer, uPA and PAI-1 have reached the highest level of evidence, level-of-evidence-1. At present, two other breast cancer therapy trials, NNBC-3 and Plan B, also incorporating uPA and PAI-1 as treatment-assignment tools are in effect. Furthermore, small synthetic molecules targeting uPA are currently in Phase II clinical trials in patients afflicted with advanced cancer of the ovary, breast or pancreas.

The Effect of Transcranial Direct Current Stimulation (tDCS) Electrode Size and Current Intensity on Motor Cortical Excitability: Evidence From Single and Repeated Sessions.

PubMed

Ho, Kerrie-Anne; Taylor, Janet L; Chew, Taariq; Gálvez, Verònica; Alonzo, Angelo; Bai, Siwei; Dokos, Socrates; Loo, Colleen K

2016-01-01

Current density is considered an important factor in determining the outcomes of tDCS, and is determined by the current intensity and electrode size. Previous studies examining the effect of these parameters on motor cortical excitability with small sample sizes reported mixed results. This study examined the effect of current intensity (1 mA, 2 mA) and electrode size (16 cm(2), 35 cm(2)) on motor cortical excitability over single and repeated tDCS sessions. Data from seven studies in 89 healthy participants were pooled for analysis. Single-session data were analyzed using mixed effects models and repeated-session data were analyzed using mixed design analyses of variance. Computational modeling was used to examine the electric field generated. The magnitude of increases in excitability after anodal tDCS was modest. For single-session tDCS, the 35 cm(2) electrodes produced greater increases in cortical excitability compared to the 16 cm(2) electrodes. There were no differences in the magnitude of cortical excitation produced by 1 mA and 2 mA tDCS. The repeated-sessions data also showed that there were greater increases in excitability with the 35 cm(2) electrodes. Further, repeated sessions of tDCS with the 35 cm(2) electrodes resulted in a cumulative increase in cortical excitability. Computational modeling predicted higher electric field at the motor hotspot for the 35 cm(2) electrodes. 2 mA tDCS does not necessarily produce larger effects than 1 mA tDCS in healthy participants. Careful consideration should be given to the exact positioning, size and orientation of tDCS electrodes relative to cortical regions. Copyright © 2016 Elsevier Inc. All rights reserved.

[Current status of hepatitis B immunization and strengthened immune memory among first-year middle school students in Tianjin].

PubMed

Shan, Ai-lan; Li, Chao; Wu, Wei-shen; He, Hai-yan; Liu, Yong; Liu, Peng; Xie, Xiao-hua

2010-06-01

To investigate the immunization status of hepatitis B vaccine who were inoculated at birth, HBV infections and the vaccine booster effect in the first-year middle school students (12 - 14 years old). A cluster, stratified simplified random sampling method was administrated. The sample size was at least 218, which was calculated by Epi Info 3.3.2 software at 53% the minimum acceptable anti-HBs positive rate and 95% confidence level. A total of 250 and 236 students participated in the infection status and booster immunization effects investigation. The HBsAg, anti-HBs and anti-HBc IgG were detected by Enzyme-linked immunosorbent assay (ELISA). HBV DNA was detected by fluorescence quantitative PCR, and the diagnostic test kit were produced respectively by ABBOTT, Diasorin and Beijing Wantai Biological Pharmacy Enterprise Co. For the immunization status before booster: the positive rate of anti-HBs was 62.80% (157/250), the GMT was 73.79 IU/L; the currently HBV infection rate (HBsAg and anti-HBc positive) was 2.80% (7/250). After injection, the anti-HBs positive rate was 94.92% (224/236). Compared with the before booster results, the significant difference was observed (χ(2) = 73.92, P = 0.00). The GMT was 521.15 IU/L, comparing with the before booster results, there was significant difference (t = 15.98, P = 0.00). The anti-HBs conversion rate (from negative to positive) was 91.86% (79/86) after immune-enhancement; of which, 11 students got the second dose of booster vaccine who are no-responders after first injection, in addition 8 students got the anti-HBs. It is an effective method to put the first-year middle school students into the immune-enhancement program, so as to improve the immunization memory effect and avoid the loss of protective antibodies.

The Current Status of Statewide Networks.

ERIC Educational Resources Information Center

Frazier, Deneen; Kurshan, Barbara

1994-01-01

Describes the status of educational telecommunications networks operated and funded by state government agencies to support K-12 programs. Summaries of a 1993 survey and other recent studies are presented together with recommendations for network infrastructure, instruction, transport, funding, and evaluation development. (Contains 12 references.)…

Weight status, gender, and race/ethnicity: are there differences in meeting recommended health behavior guidelines for adolescents?

PubMed

Minges, Karl E; Chao, Ariana; Nam, Soohyun; Grey, Margaret; Whittemore, Robin

2015-04-01

Healthy behaviors including limited screen time (ST), high physical activity (PA), and adequate fruits and vegetables consumption (FV) are recommended for adolescents, but it is unclear how gender, race/ethnicity, and weight status relate to these public health guidelines in diverse urban adolescents. Participants (N = 384) were recruited from three public high schools in or near New Haven, Connecticut. Descriptive statistics and logistic regression analyses were conducted. Most adolescents exceeded recommended levels of ST (70.5%) and did not meet guidelines for PA (87.2%) and FV (72.6%). Only 3.5% of the sample met all three guidelines. Boys were more likely to meet guidelines for PA (p < .01), while girls were engaged in less ST (p < .001). Black, non-Latinos were less likely to meet PA guidelines (p < .05). There were no significant differences in meeting ST, PA, or FV guidelines by weight status for the overall sample or when stratified by gender or race/ethnicity. We found alarmingly low levels of healthy behaviors in normal weight and overweight/obese adolescents. © The Author(s) 2014.