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Sample records for long-term safety evaluation

  1. An inventory of European data sources for the long-term safety evaluation of methylphenidate.

    PubMed

    Murray, Macey L; Insuk, Suppachai; Banaschewski, Tobias; Neubert, Antje C; McCarthy, Suzanne; Buitelaar, Jan K; Coghill, David; Dittmann, Ralf W; Konrad, Kerstin; Panei, Pietro; Rosenthal, Eric; Sonuga-Barke, Edmund J; Wong, Ian C K

    2013-10-01

    To compile an inventory of European healthcare databases with potential to study long-term effects of methylphenidate (MPH) in patients with attention deficit hyperactivity disorder (ADHD). Potential databases were identified through expert opinion, the website of the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance, and literature search. An online survey was conducted among database providers/coordinators to ascertain the databases' appropriateness for inclusion into the inventory. It included questions about database characteristics, sample size, availability of information on drug exposure, clinical data and accessibility. Forty-two databases from 11 countries were identified and their coordinators invited to participate; responses were obtained for 22 (52.4 %) databases of which 15 record ADHD diagnoses. Eleven had sufficient data on ADHD diagnosis, drug exposure, and at least one type of outcome information (symptoms/clinical events, weight, height, blood pressure, heart rate) to assess MPH safety. These were Aarhus University Prescription Database, Danish National Birth Cohort (Denmark); German Health Interview and Examination Survey for Children and Adolescents; Health Search Database Thales, Italian ADHD Register, Lombardy Region ADHD Database (Italy); Avon Longitudinal Study of Parents and Children, General Practice Research Database, The Health Improvement Network, QResearch (UK) and IMS Disease Analyzer (UK, Germany, France). Of the 20 databases with no responses, information on seven from publications and/or websites was obtained; Pedianet and the Integrated Primary Care Information database were considered suitable. Many European healthcare databases can be used for multinational long-term safety studies of MPH. Methodological research is underway to investigate the feasibility of their pooling and analysis. PMID:23508655

  2. An inventory of European data sources for the long-term safety evaluation of methylphenidate.

    PubMed

    Murray, Macey L; Insuk, Suppachai; Banaschewski, Tobias; Neubert, Antje C; McCarthy, Suzanne; Buitelaar, Jan K; Coghill, David; Dittmann, Ralf W; Konrad, Kerstin; Panei, Pietro; Rosenthal, Eric; Sonuga-Barke, Edmund J; Wong, Ian C K

    2013-10-01

    To compile an inventory of European healthcare databases with potential to study long-term effects of methylphenidate (MPH) in patients with attention deficit hyperactivity disorder (ADHD). Potential databases were identified through expert opinion, the website of the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance, and literature search. An online survey was conducted among database providers/coordinators to ascertain the databases' appropriateness for inclusion into the inventory. It included questions about database characteristics, sample size, availability of information on drug exposure, clinical data and accessibility. Forty-two databases from 11 countries were identified and their coordinators invited to participate; responses were obtained for 22 (52.4 %) databases of which 15 record ADHD diagnoses. Eleven had sufficient data on ADHD diagnosis, drug exposure, and at least one type of outcome information (symptoms/clinical events, weight, height, blood pressure, heart rate) to assess MPH safety. These were Aarhus University Prescription Database, Danish National Birth Cohort (Denmark); German Health Interview and Examination Survey for Children and Adolescents; Health Search Database Thales, Italian ADHD Register, Lombardy Region ADHD Database (Italy); Avon Longitudinal Study of Parents and Children, General Practice Research Database, The Health Improvement Network, QResearch (UK) and IMS Disease Analyzer (UK, Germany, France). Of the 20 databases with no responses, information on seven from publications and/or websites was obtained; Pedianet and the Integrated Primary Care Information database were considered suitable. Many European healthcare databases can be used for multinational long-term safety studies of MPH. Methodological research is underway to investigate the feasibility of their pooling and analysis.

  3. Evaluating the Long-Term Safety of a Repository at Yucca Mountain 

    SciTech Connect

    Van Luik, Abe

    2009-07-17

    Regulations require that the repository be evaluated for its health and safety effects for 10,000 years for the Site Recommendation process. Regulations also require potential impacts to be evaluated for up to a million years in an Environmental Impact Statement. The Yucca Mountain Project is in the midst of the Site Recommendation process. The Total System Performance Assessment (TSPA) that supports the Site Recommendation evaluated safety for these required periods of time. Results showed it likely that a repository at this site could meet the licensing requirements promulgated by the Nuclear Regulatory Commission. The TSPA is the tool that integrates the results of many years of scientific investigations with design information to allow evaluations of potential far-future impacts of building a Yucca Mountain repository. Knowledge created in several branches of physics is part of the scientific basis of the TSPA that supports the Site Recommendation process.

  4. Long-term safety evaluation of a novel oxygen-coordinated niacin-bound chromium (III) complex.

    PubMed

    Shara, Michael; Kincaid, Anthony E; Limpach, Aimee L; Sandstrom, Robert; Barrett, Laura; Norton, Neil; Bramble, J D; Yasmin, Taharat; Tran, Janet; Chatterjee, Archana; Bagchi, Manashi; Bagchi, Debasis

    2007-07-01

    Chromium (III) is an essential micronutrient required for normal protein, fat and carbohydrate metabolism, as well as helps insulin metabolize fat, turn protein into muscle and convert sugar into energy. A broad spectrum of research investigations including in vitro, in vivo and clinical studies demonstrated the beneficial effects of novel oxygen- coordinated niacin-bound chromium (III) complex (NBC) in promoting glucose-insulin sensitivity, lipid profile, cardioprotective ability and lean body mass. This study examined the long-term safety of NBC by orally administering either 0 or 25 ppm or the human equivalency dose of 1000 microg elemental chromium (III) as NBC per day for 52 consecutive weeks to male and female Sprague-Dawley rats. Animals of each group and each gender were sacrificed on 26, 39, or 52 weeks of treatment. Body weight, physical and ocular health, feed and water intake, selected organ weights as such and as a percentage of liver and brain weight, hepatic lipid peroxidation and DNA fragmentation, hematology and clinical chemistry, and histopathological evaluations were conducted. At 26, 39, or 52 weeks of treatment, body weight gain was significantly reduced by 7.7%, 8.1% and 14.9% in male rats, and 5.5%, 11.4% and 9.6% in female rats, respectively, in the NBC treatment groups. No significant changes were observed in hepatic lipid peroxidation and DNA fragmentation, hematology and clinical chemistry, and histopathological evaluation between control and NBC groups at these time points. These findings, thus far, are in agreement with the subchronic studies in terms of the safety of NBC. PMID:17555823

  5. Safety of long-term PPI therapy.

    PubMed

    Reimer, Christina

    2013-06-01

    Proton pump inhibitors have become the mainstay of medical treatment of acid-related disorders. Long-term use is becoming increasingly common, in some cases without a proper indication. A large number of mainly observational studies on a very wide range of possible associations have been published in the past decade and are critically reviewed in this article and the existing evidence is evaluated and translated into possible clinical consequences. Based on the existing evidence the benefits of PPI treatment seem to outweigh potential risks in the large majority of patients especially if PPI use is based on a relevant indication. The concern for complications should primarily be directed at elderly, malnourished with significant co-morbidity. In this population an increased risk for enteric infections, fractures and nutritional deficiencies might have clinical consequences and should lead to a careful evaluation of the indication for PPI treatment. PMID:23998981

  6. Safety of long-term large doses of aspartame.

    PubMed

    Leon, A S; Hunninghake, D B; Bell, C; Rassin, D K; Tephly, T R

    1989-10-01

    Safety of long-term administration of 75 mg/kg of aspartame per day was evaluated with the use of a randomized, double-blind, placebo-controlled, parallel-group design in 108 male and female volunteers aged 18 to 62 years. Subjects received either aspartame or placebo in capsule form three times daily for 24 weeks. No persistent changes over time were noted in either group in vital signs; body weight; results of standard laboratory tests; fasting blood levels of aspartame's constituent amino acids (aspartic acid and phenylalanine), other amino acids, and methanol; or blood formate levels and 24-hour urinary excretion of formate. There also were no statistically significant differences between groups in the number of subjects experiencing symptoms or in the number of symptoms per subject. These results further document the safety of the long-term consumption of aspartame at doses equivalent to the amount of aspartame in approximately 10 L of beverage per day.

  7. Evaluating Long-Term Disability Insurance Plans.

    ERIC Educational Resources Information Center

    Powell, Jan

    1992-01-01

    This report analyzes the factors involved in reviewing benefits and services of employer-sponsored group long-term disability plans for higher education institutions. Opening sections describe the evolution of disability insurance and its shape today. Further sections looks at the complex nature of "value" within a plan, relationship between plan…

  8. Long-term safety and efficacy of continuous intrathecal baclofen.

    PubMed

    Campbell, William M; Ferrel, Anne; McLaughlin, John F; Grant, Gerald A; Loeser, John D; Graubert, Catherine; Bjornson, Kristie

    2002-10-01

    Long-term continuous intrathecal baclofen (CITB) infusion is a treatment option used to manage otherwise intractable spasticity and is delivered via an implantable pump. The purpose of this single-center multidisciplinary review was to report on the long-term safety and efficacy of CITB in the treatment of 21 children with intractable severe spasticity of cerebral origin. Nineteen recipients had spastic quadriplegia and two had spastic diplegia. Seven recipients had level IV severity on the Gross Motor Functional Classification System and 14 had level V. Median age at implantation was 12 years (range 4 to 20). Fifteen recipients were male, 6 were female. Seventeen recipients were alive at the end of the follow-up period (31 to 78 months; mean 53, SD 4). The Ashworth scale showed a substantial decrease in spasticity in the upper and lower extremities at 6 months and at the most recent follow-up. The Gross Motor Function Measure and Pediatric Evaluation of Disability Inventory showed no functional change. Most treatment goals were at least partly achieved. Caregivers reported a reduction in use of oral medication for spasticity, and improvements in comfort, function, and ease of care. Caregiver satisfaction was high. During 80 recipient-years of pump operation, 153 treatment-associated adverse events occurred: 27 of these were device-related. There were four deaths unrelated to CITE, including one from acute pancreatitis. Our findings might assist in establishing patient selection criteria and treatment goals, improving patient follow-up, and monitoring adverse events. PMID:12418790

  9. Long-term safety evaluation of bimatoprost ophthalmic solution 0.03%: a pooled analysis of six double-masked, randomized, active-controlled clinical trials

    PubMed Central

    Wirta, David; VanDenburgh, Amanda M; Weng, Emily; Whitcup, Scott M; Kurstjens, Sef; Beddingfield, Frederick C

    2011-01-01

    Background: Bimatoprost ophthalmic solution 0.03% was approved in the US for reducing intraoccular pressure (IOP) based on two double-masked, active-controlled clinical trials. Four additional long-term studies (≥12 months) were conducted; however, the aggregate safety profile of the six studies has not been reported. Methods: Adverse events (AEs) were pooled from six double-masked, active-controlled, long-term clinical trials in which subjects received bimatoprost 0.03% once daily (QD) or twice daily (BID) as an eyedrop. AE terms were converted to MedDRA (V.11.0) Preferred Terms and analyzed. Results: In total, 1409 patients received more than one dose of bimatoprost 0.03% QD or BID. Most AEs were mild in severity and reported by 86.7% (QD) and 94.8% (BID) of subjects (≤12 months of treatment). AEs reported through month 12 (aggregate incidence of ≥5%) were conjunctival hyperemia, increased eyelash growth, eye pruritus, periocular skin hyperpigmentation, eye irritation, dry eye, and hypertrichosis. AE onset was generally reported within four months of treatment. The cumulative incidence of common AEs in the QD treatment group at 24–48 months was similar to that measured at 12 months of treatment. Conclusion: Bimatoprost 0.03% has a favorable safety and tolerability profile as characterized by six long-term studies. Common AEs were due to the known pharmacological activity of bimatoprost and reversible with treatment cessation. PMID:21691584

  10. Evaluating Aspects of Online Medication Safety in Long-Term Follow-Up of 136 Internet Pharmacies: Illegal Rogue Online Pharmacies Flourish and Are Long-Lived

    PubMed Central

    2013-01-01

    Background A growing number of online pharmacies have been established worldwide. Among them are numerous illegal websites selling medicine without valid medical prescriptions or distributing substandard or counterfeit drugs. Only a limited number of studies have been published on Internet pharmacies with regard to patient safety, professionalism, long-term follow-up, and pharmaceutical legitimacy verification. Objective In this study, we selected, evaluated, and followed 136 Internet pharmacy websites aiming to identify indicators of professional online pharmacy service and online medication safety. Methods An Internet search was performed by simulating the needs of potential customers of online pharmacies. A total of 136 Internet pharmacy websites were assessed and followed for four years. According to the LegitScript database, relevant characteristics such as longevity, time of continuous operation, geographical location, displayed contact information, prescription requirement, medical information exchange, and pharmaceutical legitimacy verification were recorded and evaluated. Results The number of active Internet pharmacy websites decreased; 23 of 136 (16.9%) online pharmacies ceased operating within 12 months and only 67 monitored websites (49.3%) were accessible at the end of the four-year observation period. However, not all operated continuously, as about one-fifth (31/136) of all observed online pharmacy websites were inaccessible provisionally. Thus, only 56 (41.2%) Internet-based pharmacies were continuously operational. Thirty-one of the 136 online pharmacies (22.8%) had not provided any contact details, while only 59 (43.4%) displayed all necessary contact information on the website. We found that the declared physical location claims did not correspond to the area of domain registration (according to IP address) for most websites. Although the majority (120/136, 88.2%) of the examined Internet pharmacies distributed various prescription

  11. Combination therapy of hydroxycarbamide with anagrelide in patients with essential thrombocythemia in the evaluation of Xagrid® efficacy and long-term safety study

    PubMed Central

    Gugliotta, Luigi; Besses, Carlos; Griesshammer, Martin; Harrison, Claire; Kiladjian, Jean-Jacques; Coll, Ruth; Smith, Jonathan; Abhyankar, Brihad; Birgegård, Gunnar

    2014-01-01

    Available information is limited regarding the use of cytoreductive combination therapy in high-risk patients with essential thrombocythemia. This analysis aims to evaluate the clinical relevance and patterns of cytoreductive combination treatment in European high-risk patients with essential thrombocythemia in the Evaluation of Xagrid® Efficacy and Long-term Safety study. Of 3643 patients, 347 (9.5%) received combination therapy. Data were recorded at each 6-month update. Of 347 patients who received combination therapy, 304 (87.6%) received hydroxycarbamide + anagrelide. Monotherapies received before this combination were hydroxycarbamide (n=167, 54.9%) and anagrelide (n=123, 40.5%). Median weekly doses of hydroxycarbamide and anagrelide were: 7000 and 10.5 mg when used as prior monotherapy; 3500 and 7.0 mg when used as add-on treatment. Overall, median platelet counts were 581×109/L and 411×109/L before and after starting hydroxycarbamide + anagrelide, respectively. In patients with paired data (n=153), the number of patients with platelet counts less than 400×109/L increased from 33 (21.6%) to 74 (48.4%; P<0.0001), and with platelet counts less than 600×109/L, from 82 (53.6%) to 132 (86.3%; P<0.0001). Hydroxycarbamide + anagrelide was discontinued in 158 patients: 76 (48.1%) stopped hydroxycarbamide, 59 (37.3%) stopped anagrelide, 19 (12.0%) stopped both and 4 (2.5%) had another therapy added. The most frequent reasons for discontinuation were intolerance/side-effects, lack of efficacy, and therapeutic strategy. Combination therapy, usually hydroxycarbamide + anagrelide, is used in approximately 10% of all high-risk patients with essential thrombocythemia and may be a useful approach in treating patients for whom monotherapy is unsatisfactory. (Clinicaltrials.gov identifier:NCT00567502) PMID:24334294

  12. Long-term safety concerns with proton pump inhibitors.

    PubMed

    Ali, Tauseef; Roberts, David Neil; Tierney, William M

    2009-10-01

    Proton pump inhibitors (PPIs) are among the most widely prescribed medications worldwide. Their use has resulted in dramatic improvements in treatment of peptic ulcer disease and gastroesophageal reflux disease. Despite an acceptable safety profile, mounting data demonstrate concerns about the long-term use of PPIs. To provide a comprehensive review regarding the concerns of long-term PPI use, a literature search was performed to identify pertinent original and review articles. Despite study shortcomings, the collective body of information overwhelmingly suggests an increased risk of infectious complications and nutritional deficiencies. Data regarding any increased risk in gastric or colon malignancy are less convincing. PPIs have revolutionized the management and complications of acid-related disorders with a high margin of safety; however, with the data available, efforts to reduce the dosing of or discontinue the use of PPIs must be reassessed frequently.

  13. The long-term safety of antiepileptic drugs.

    PubMed

    Gaitatzis, Athanasios; Sander, Josemir W

    2013-06-01

    Antiepileptic drugs (AEDs) are used by millions of people worldwide for the treatment of epilepsy, as well as in many other neurological and psychiatric conditions. They are frequently associated with adverse effects (AEs), which have an impact on the tolerability and success of treatment. Half the people who develop intolerable AEs discontinue treatment early on after initiation, while the majority of people will continue to be exposed to their effects for long periods of time. The long-term safety of AEDs reflects their potential for chronic, cumulative dose effects; rare, but potentially serious late idiosyncratic effects; late, dose-related effects; and delayed, teratogenic or neurodevelopmental effects. These AEs can affect every body system and are usually insidious. With the exception of delayed effects, most other late or chronic AEs are reversible. To date, there is no clear evidence of a carcinogenic effect of AEDs in humans. While physicians are aware of the long-term AEs of old AEDs (the traditional liver enzyme-inducing AEDs and valproate), information about AEs of new AEDs (such as lamotrigine, levetiracetam, oxcarbazepine, topiramate or zonisamide), particularly of their teratogenic effects, has emerged over the years. Sporadic publications have raised issues about AEs of the newer AEDs eslicarbazepine, retigabine, rufinamide, lacosamide and perampanel but their long-term safety profiles may take years to be fully appreciated. Physicians should not only be aware of the late and chronic AEs of AEDs but should systematically enquire and screen for these according to the individual AED AE profile. Care should be taken for individuals with comorbid conditions that may render them more susceptible to specific AEs. Prevention and appropriate management of long-term AED AEs is expected to improve adherence to treatment, quality of life and control of epilepsy. PMID:23673774

  14. Comparative long-term preclinical safety evaluation of two glatiramoid compounds (glatiramer Acetate, Copaxone(R), and TV-5010, protiramer) in rats and monkeys.

    PubMed

    Ramot, Yuval; Rosenstock, Moti; Klinger, Ety; Bursztyn, Dizza; Nyska, Abraham; Shinar, Doron M

    2012-01-01

    Glatiramer acetate (GA), the active ingredient in Copaxone®, is a complex mixture of polypeptides used for the treatment of relapsing remitting multiple sclerosis. Glatiramoids are related mixtures that may differ in some characteristics of the prototype molecule. Our aim is to describe the long-term toxicity studies with protiramer (TV-5010), a new glatiramoid, in comparison with similar studies conducted with GA. The toxicity of twice-weekly subcutaneous injections of protiramer to Sprague-Dawley rats (twenty-six weeks) and cynomolgus monkeys (fifty-two weeks) was compared with similar studies done with daily subcutaneous injections of GA. Daily treatment with GA was safe and well tolerated, without systemic effects or death. Protiramer administration was not as well tolerated as GA and led to dose- and time-related mortalities, probably mediated through severe injection-site lesions both in rats and in monkeys. Bridging fibrosis in the liver and severe progressive nephropathy were seen in rats. A dose-related increase in eosinophils was observed in monkeys. The protiramer toxicity studies show that minor variations in the manufacturing of glatiramoids may lead to significant toxic effects. It is therefore essential that the safety of any new glatiramoid be studied in long-term preclinical studies before exposing humans. PMID:22083585

  15. Long-term safety and efficacy of teriflunomide

    PubMed Central

    Comi, Giancarlo; Freedman, Mark S.; Miller, Aaron E.; Kappos, Ludwig; Bouchard, Jean-Pierre; Lebrun-Frenay, Christine; Mares, Jan; Benamor, Myriam; Thangavelu, Karthinathan; Liang, Jinjun; Truffinet, Philippe; Lawson, Victoria J.; Wolinsky, Jerry S.

    2016-01-01

    Objective: To report safety and efficacy outcomes from up to 9 years of treatment with teriflunomide in an extension (NCT00803049) of the pivotal phase 3 Teriflunomide Multiple Sclerosis Oral (TEMSO) trial (NCT00134563). Methods: A total of 742 patients entered the extension. Teriflunomide-treated patients continued the original dose; those previously receiving placebo were randomized 1:1 to teriflunomide 14 mg or 7 mg. Results: By June 2013, median (maximum) teriflunomide exposure exceeded 190 (325) weeks per patient; 468 patients (63%) remained on treatment. Teriflunomide was well-tolerated with continued exposure. The most common adverse events (AEs) matched those in the core study. In extension year 1, first AEs of transient liver enzyme increases or reversible hair thinning were generally attributable to patients switching from placebo to teriflunomide. Approximately 11% of patients discontinued treatment owing to AEs. Twenty percent of patients experienced serious AEs. There were 3 deaths unrelated to teriflunomide. Soon after the extension started, annualized relapse rates and gadolinium-enhancing T1 lesion counts fell in patients switching from placebo to teriflunomide, remaining low thereafter. Disability remained stable in all treatment groups (median Expanded Disability Status Scale score ≤2.5; probability of 12-week disability progression ≤0.48). Conclusions: In the TEMSO extension, safety observations were consistent with the core trial, with no new or unexpected AEs in patients receiving teriflunomide for up to 9 years. Disease activity decreased in patients switching from placebo and remained low in patients continuing on teriflunomide. Classification of evidence: This study provides Class III evidence that long-term treatment with teriflunomide is well-tolerated and efficacy of teriflunomide is maintained long-term. PMID:26865517

  16. Long term follow-up study to evaluate immunogenicity and safety of a single dose of live attenuated hepatitis a vaccine in children.

    PubMed

    Mitra, Monjori; Shah, Nitin; Faridi, Mma; Ghosh, Apurba; Sankaranarayanan, V S; Aggarwal, Anju; Chatterjee, Suparna; Bhattacharyya, Nisha; Kadhe, Ganesh; Vishnoi, Gaurav; Mane, Amey

    2015-01-01

    Worldwide, viral hepatitis continues to be a cause of considerable morbidity and mortality. Mass immunization with a single dose of live attenuated HAV has been shown to significantly reduce disease burden in the community. This was a phase IV, 5-year follow up study carried out at 4 centers (Kolkata, Delhi, Mumbai and Chennai) across India. The subjects with antibody titer <20 mIU/mL at baseline were evaluated for long term immunogenicity. Of the 503 subjects enrolled, 349 subjects were baseline seronegative with an anti-HAV antibody titer <20 mIU/mL. Overall, 343 subjects could be followed up at some point of time during this 5 y post vaccination period. In the last year (60 months) of follow-up, 108 subjects (97.3%) of 111 subjects (who came for follow-up at the end of 5 y) had a protective antibody titer (anti-HAV antibody titer >20 mIU/mL). The seroconversion rates considering seroprotection levels of anti-HAV antibody titer >20 mIU/mL, following vaccination starting from 6 weeks, 6 months, 12 months, 24 months, 36 months, 48 months and 60 months were 95.1%, 97.9%, 98.3%, 96.2%, 97.8%, 92.6% and 97.3%, respectively. The geometric mean concentration (GMC) over the years increased from 64.9 mIU/mL at 6 weeks to 38.1 mIU/mL and 135.2 mIU/mL at 6 months and 12 months, respectively and was maintained at 127.1 mIU/mL at 60 months. In conclusion, the result of this 5-year follow up study showed that the single dose of live attenuated vaccine is well tolerated and provides long-term immunogenicity in healthy Indian children.

  17. Demonstrating the Safety of Long-Term Dry Storage - 13468

    SciTech Connect

    McCullum, Rod; Brookmire, Tom; Kessler, John; Leblang, Suzanne; Levin, Adam; Martin, Zita; Nesbit, Steve; Nichol, Marc; Pickens, Terry

    2013-07-01

    Commercial nuclear plants in the United States were originally designed with the expectation that used nuclear fuel would be moved directly from the reactor pools and transported off site for either reprocessing or direct geologic disposal. However, Federal programs intended to meet this expectation were never able to develop the capability to remove used fuel from reactor sites - and these programs remain stalled to this day. Therefore, in the 1980's, with reactor pools reaching capacity limits, industry began developing dry cask storage technology to provide for additional on-site storage. Use of this technology has expanded significantly since then, and has today become a standard part of plant operations at most US nuclear sites. As this expansion was underway, Federal programs remained stalled, and it became evident that dry cask systems would be in use longer than originally envisioned. In response to this challenge, a strong technical basis supporting the long term dry storage safety has been developed. However, this is not a static situation. The technical basis must be able to address future challenges. Industry is responding to one such challenge - the increasing prevalence of high burnup (HBU) used fuel and the need to provide long term storage assurance for these fuels equivalent to that which has existed for lower burnup fuels over the past 25 years. This response includes a confirmatory demonstration program designed to address the aging characteristics of HBU fuel and set a precedent for a learning approach to aging management that will have broad applicability across the used fuel storage landscape. (authors)

  18. Long-term botulinum toxin efficacy, safety, and immunogenicity.

    PubMed

    Mejia, Nicte I; Vuong, Kevin Dat; Jankovic, Joseph

    2005-05-01

    To determine the long-term efficacy of botulinum toxin (BTX) treatments, we analyzed longitudinal follow-up data on 45 patients (32 women; mean age, 68.8 years) currently followed in the Baylor College of Medicine Movement Disorders Clinic, who have received BTX treatments continuously for at least 12 years (mean 15.8 +/- 1.5 years). Their mean response rating after the last injection, based one a previously described scale 0-to-4 scale (0 = no effect; 4 = marked improvement) was 3.7 +/- 0.6 and the mean total duration of response was 15.4 +/- 3.4 weeks. Although the latency and total duration of the response to treatment have not changed over time, the peak duration of response (P < 0.005) and dose per visit (P < 0.0001) have increased since the initial visit. Furthermore, global rating (P < 0.02) and peak effect (P < 0.05) have improved. In total, 20 adverse events occurred in 16 of 45 (35.6%) patients after their initial visit and 11 adverse events in 10 of 45 (22.2%) patients at their most recent injection visit. Antibody (Ab) testing was carried out in 22 patients due to nonresponsiveness; blocking Abs were confirmed by the mouse protection assay in 4 of 22 (18%) patients. Of the Ab-negative patients, 16 resumed responsiveness after dose adjustments and 2 persisted as nonrespondents. Except for 1 patient, the 4 Ab-positive and the 2 clinical nonresponders are being treated with BTX-B. This longest reported follow-up of BTX injections confirms the long-term efficacy and safety of this treatment.

  19. Acute And Long-Term Bioeffects And Lamp Safety

    NASA Astrophysics Data System (ADS)

    Andersen, F. Alan

    1980-10-01

    Knowledge of both acute and chronic biological effects is currently used to evaluate lamp safety. In some cases, a quantitative basis for avoiding exposures greater than a certain value can be stated. In other cases, however, only a qualitative estimate of the hazard is available. In a discussion that uses mercury vapor lamps, tanning booths, and sodium vapor lamps as examples, the interplay between the two types of data leading to an evaluation of lamp safety is described.

  20. PLUME-SCALER-EVALUATING LONG-TERM MONITORING WELL NETWORKS

    EPA Science Inventory

    EPA's Subsurface Protection and Remediation Division is developing a new computer application called PLUME-SCALER to evaluate long term monitoring well networks using typically available historical site water level data. PLUME-SCALER can be used to determine if there are enough ...

  1. Long-Term Effectiveness and Safety of Dexmethylphenidate Extended-Release Capsules in Adult ADHD

    ERIC Educational Resources Information Center

    Adler, Lenard A.; Spencer, Thomas; McGough, James J.; Jiang, Hai; Muniz, Rafael

    2009-01-01

    Objective: This study evaluates dexmethylphenidate extended release (d-MPH-ER) in adults with ADHD. Method: Following a 5-week, randomized, controlled, fixed-dose study of d-MPH-ER 20 to 40 mg/d, 170 adults entered a 6-month open-label extension (OLE) to assess long-term safety, with flexible dosing of 20 to 40 mg/d. Exploratory effectiveness…

  2. Evaluating the care of patients with long term conditions

    PubMed Central

    Ahluwalia, Sanjiv

    2014-01-01

    Approaches to evaluating the care of patients with long-term conditions first need to be framed around defining outcomes that ‘matter to people’, rather than those that are focused on disease and easily measurable. Secondly, approaches to evaluating such care should be organised with the ability to ‘deliver what matters to people’ – such models of care must allow for the opportunity to maximise the impact of primary care. Finally, any approach to evaluation must also ‘enable the delivery of what matters to people’, including approaches to promote self-care, well-being and interprofessional workforce development organised around educational networks. PMID:25949734

  3. Economic evaluation in long-term clinical trials.

    PubMed

    Hlatky, Mark A; Boothroyd, Derek B; Johnstone, Iain M

    2002-10-15

    Economic endpoints have been increasingly included in long-term clinical trials, but they pose several methodologic challenges, including how best to collect, describe, analyse and interpret medical cost data. Cost of care can be measured by converting billed charges, performing detailed micro-costing studies, or by measuring use of key resources and assigning cost weights to each resource. The latter method is most commonly used, with cost weights based either on empirical regression models or administratively determined reimbursement rates. In long-term studies, monetary units should be adjusted to reflect cost inflation and discounting. The temporal pattern of accumulating costs can be described using a modification of the Kaplan-Meier curve. Regression analyses to evaluate factors associated with cost are best performed on the log of costs due to their typically skewed distribution.Cost-effectiveness analysis attempts to measure the value of a new therapy by calculating the difference in cost between the new therapy and the standard therapy, divided by the difference in benefit between the new therapy and the standard therapy. The cost-effectiveness ratio based on the results of a randomized trial may change substantially with longer follow-up intervals, particularly for therapies that are initially expensive but eventually improve survival. A model that projects long-term patterns of cost and survival expected beyond the end of completed follow-up can provide an important perspective in the setting of limited trial duration.

  4. Economic evaluation in long-term clinical trials.

    PubMed

    Hlatky, Mark A; Boothroyd, Derek B; Johnstone, Iain M

    2002-10-15

    Economic endpoints have been increasingly included in long-term clinical trials, but they pose several methodologic challenges, including how best to collect, describe, analyse and interpret medical cost data. Cost of care can be measured by converting billed charges, performing detailed micro-costing studies, or by measuring use of key resources and assigning cost weights to each resource. The latter method is most commonly used, with cost weights based either on empirical regression models or administratively determined reimbursement rates. In long-term studies, monetary units should be adjusted to reflect cost inflation and discounting. The temporal pattern of accumulating costs can be described using a modification of the Kaplan-Meier curve. Regression analyses to evaluate factors associated with cost are best performed on the log of costs due to their typically skewed distribution.Cost-effectiveness analysis attempts to measure the value of a new therapy by calculating the difference in cost between the new therapy and the standard therapy, divided by the difference in benefit between the new therapy and the standard therapy. The cost-effectiveness ratio based on the results of a randomized trial may change substantially with longer follow-up intervals, particularly for therapies that are initially expensive but eventually improve survival. A model that projects long-term patterns of cost and survival expected beyond the end of completed follow-up can provide an important perspective in the setting of limited trial duration. PMID:12325104

  5. Assessment of GE food safety using '-omics' techniques and long-term animal feeding studies.

    PubMed

    Ricroch, Agnès E

    2013-05-25

    Despite the fact that a thorough, lengthy and costly evaluation of genetically engineered (GE) crop plants (including compositional analysis and toxicological tests) is imposed before marketing some European citizens remain sceptical of the safety of GE food and feed. In this context, are additional tests necessary? If so, what can we learn from them? To address these questions, we examined data from 60 recent high-throughput '-omics' comparisons between GE and non-GE crop lines and 17 recent long-term animal feeding studies (longer than the classical 90-day subchronic toxicological tests), as well as 16 multigenerational studies on animals. The '-omics' comparisons revealed that the genetic modification has less impact on plant gene expression and composition than that of conventional plant breeding. Moreover, environmental factors (such as field location, sampling time, or agricultural practices) have a greater impact than transgenesis. None of these '-omics' profiling studies has raised new safety concerns about GE varieties; neither did the long-term and multigenerational studies on animals. Therefore, there is no need to perform such long-term studies in a case-by-case approach, unless reasonable doubt still exists after conducting a 90-day feeding test. In addition, plant compositional analysis and '-omics' profiling do not indicate that toxicological tests should be mandatory. We discuss what complementary fundamental studies should be performed and how to choose the most efficient experimental design to assess risks associated with new GE traits. The possible need to update the current regulatory framework is discussed.

  6. Long-term safety and effectiveness of tanezumab as treatment for chronic low back pain.

    PubMed

    Gimbel, Joseph S; Kivitz, Alan J; Bramson, Candace; Nemeth, Mary Anne; Keller, David S; Brown, Mark T; West, Christine R; Verburg, Kenneth M

    2014-09-01

    A noncontrolled, randomized, multicenter study (NCT00924664) evaluated long-term safety and effectiveness of tanezumab in patients with chronic low back pain following a randomized placebo- and active-controlled parent study that evaluated analgesic efficacy. Patients were randomized to tanezumab 10mg (n=321) or 20mg (n=527) administered at 8-week intervals via 3 intravenous injections followed by 4 subcutaneous injections. Effectiveness analyses included change from parent study baseline in Brief Pain Inventory Short Form, Roland Morris Disability Questionnaire, and Patient's Global Assessment of low back pain. Safety assessments included adverse event documentation, physical/neurological examinations, and laboratory tests. Mean treatment duration during the extension study was 194 and 202 days with tanezumab 10 and 20mg, respectively. Both tanezumab doses provided similar and sustained improvements in all effectiveness outcomes. The most frequently reported adverse events were arthralgia, paresthesia, and hypoesthesia. Adverse events initially described as osteonecrosis were reported in 6 patients (tanezumab 10mg, n=2; tanezumab 20mg, n=4); 9 additional patients (tanezumab 10mg, n=7; tanezumab 20mg, n=2) underwent total joint replacement (TJR). A blinded, independent adjudication committee reviewed all 6 patients with reported osteonecrosis and 4 of the 9 patients undergoing TJR. Adjudication outcomes were osteonecrosis (n=0), worsening osteoarthritis (n=5; 1 rapidly progressive), and another diagnosis or indeterminate (n=5). Tanezumab 10mg had better tolerability than tanezumab 20mg, and may represent an effective long-term treatment for chronic low back pain.

  7. SULFURIC ACID REMOVAL PROCESS EVALUATION: LONG-TERM RESULTS

    SciTech Connect

    Gary M. Blythe; Richard McMillan

    2002-07-03

    longer-term (approximately 25-day) full-scale tests on two different units. The longer-term tests were conducted to confirm the effectiveness of the sorbents tested over extended operation on two different boilers, and to determine balance-of-plant impacts. The first long-term test was conducted on FirstEnergy's BMP, Unit 3, and the second test was conducted on AEP's Gavin Plant, Unit 1. The Gavin Plant testing provided an opportunity to evaluate the effects of sorbent injected into the furnace on SO{sub 3} formed across an operating SCR reactor. This report presents the results from those long-term tests. The tests determined the effectiveness of injecting commercially available magnesium hydroxide slurry (Gavin Plant) and byproduct magnesium hydroxide slurry (both Gavin Plant and BMP) for sulfuric acid control. The results show that injecting either slurry could achieve up to 70 to 75% overall sulfuric acid removal. At BMP, this overall removal was limited by the need to maintain acceptable electrostatic precipitator (ESP) particulate control performance. At Gavin Plant, the overall sulfuric acid removal was limited because the furnace injected sorbent was less effective at removing SO{sub 3} formed across the SCR system installed on the unit for NOX control than at removing SO{sub 3} formed in the furnace. The long-term tests also determined balance-of-plant impacts from slurry injection during the two tests. These include impacts on boiler back-end temperatures and pressure drops, SCR catalyst properties, ESP performance, removal of other flue gas species, and flue gas opacity. For the most part the balance-of-plant impacts were neutral to positive, although adverse effects on ESP performance became an issue during the BMP test.

  8. Long-term safety of mepolizumab for the treatment of hypereosinophilic syndromes

    PubMed Central

    Roufosse, Florence E; Kahn, Jean-Emmanuel; Gleich, Gerald J; Schwartz, Lawrence B; Singh, Anish D; Rosenwasser, Lanny J; Denburg, Judah A; Ring, Johannes; Rothenberg, Marc E; Sheikh, Javed; Haig, Ann E; Mallett, Stephen A; Templeton, Deborah N; Ortega, Hector G; Klion, Amy D

    2012-01-01

    Background Hypereosinophilic syndromes (HES) are chronic disorders that require long-term therapy to suppress eosinophilia and clinical manifestations. Corticosteroids are usually effective, yet many patients become corticosteroid-refractory or develop corticosteroid toxicity. Mepolizumab, a humanised monoclonal anti-interleukin-5 antibody, demonstrated corticosteroid-sparing effects in a double-blind, placebo-controlled study of FIP1L1/PDGFRA-negative, corticosteroid-responsive subjects with HES. Objective To evaluate long-term safety and efficacy of mepolizumab (750 mg) in HES. Methods MHE100901 is an open-label extension study. The primary endpoint was the frequency of adverse events (AEs). Optimal dosing frequency, corticosteroid-sparing effect of mepolizumab, and development of anti-mepolizumab antibodies were also explored. Results Seventy-eight subjects received 1–66 mepolizumab infusions each (including mepolizumab infusions received in the placebo-controlled trial). Mean exposure was 251 weeks (range 4–302). The most common dosing interval was 9–12 weeks. The incidence of AEs was 932 events per 100 subject-years in the first year, declining to 461 events per 100 subject-years after 48 months. Serious AEs, including one death, were reported by the investigator as possibly due to mepolizumab in three subjects. The median daily prednisone dose decreased from 20.0 to 0 mg in the first 24 weeks. The median average daily dose for all subjects over the course of the study was 1.8 mg. Sixty-two percent of subjects were prednisone-free without other HES medications for ≥12 consecutive weeks. No neutralizing antibodies were detected. Twenty-four subjects withdrew prior to study completion for death (n=4), lack of efficacy (n=6), or other reasons. Conclusion Mepolizumab was well tolerated and effective as a long-term corticosteroid-sparing agent in PDGFRA-negative HES. PMID:23040887

  9. Long-term safety and efficacy of insulin degludec in the management of type 2 diabetes

    PubMed Central

    Thuillier, Philippe; Alavi, Zarrin; Kerlan, Véronique

    2015-01-01

    Insulin degludec (IDeg) is a novel antiglycemic agent belonging to the therapeutic class of ultra-long duration basal insulin analogs. Its half-life and duration of action are 25 hours and 42 hours, respectively. This pharmacodynamic profile leads to a strict dosing schedule, ie, IDeg is injected at the same time each day to ensure optimal biological action and consistent glycemic control. According to the literature, IDeg provides glycemic control and nocturnal hypoglycemia reduction comparable with other long-acting analogs in type 2 diabetes mellitus. The risk of severe hypoglycemic episodes seems also to be reduced when using IDeg therapy; however, long-term follow-up is warranted for monitoring of possible but relatively infrequent adverse events. IDeg is also available in combination with aspart insulin and with liraglutide. The above preparations have been approved by the European Medicines Agency and other national health authorities. In 2012, the US Food and Drug Administration asked for a complementary study on IDeg-associated cardiovascular risk. Future prospective evaluation of large cohorts of patients with type 2 diabetes mellitus treated with IDeg, with long-term follow-up, can provide further relevant information on the safety of IDeg therapy. PMID:26457056

  10. Long-term efficacy and safety of a generic atorvastatin in usual clinical care setting.

    PubMed

    Ong, L M; Punithavathi, N; Lena, Y L L; Mahanim, O; Leekha, S

    2011-08-01

    A multicentre study was conducted to assess the long term efficacy and safety of a generic atorvastatin in the treatment of primary hypercholesterolaemia. Eighty five patients who received 10mg or 20 mg of atorvastatin for 8 weeks depending on target cholesterol goal were followed up by their own physicians and had final evaluation at 52 weeks. Reduction in mean low density Lipoprotein (LDL-C) was 36.5%, 37.9% and 32.2% at weeks 4, 8 and 52 respectively. LDL-C target was maintained in 81% and 69% of patients at week 8 and 52 respectively without drug related serious adverse events. Generic atorvastatin is safe and effective in usual clinical care setting. PMID:22111443

  11. Tocilizumab in refractory rheumatoid arthritis: long-term efficacy, safety, and tolerability beyond 2 years

    PubMed Central

    Farah, Ziad; Ali, Sabreen; Price-Kuehne, Fiona; Mackworth-Young, Charles G

    2016-01-01

    Objectives To evaluate the long-term efficacy and safety of tocilizumab (TCZ) in clinical patients with rheumatoid arthritis (RA) refractory to synthetic disease-modifying antirheumatic drugs, anti-tumor necrosis factor agents, and B-cell depletion therapy with rituximab (RTX). Methods We conducted a single-center retrospective study of 22 patients with RA treated with TCZ. We collected data including demographics and medication histories. We recorded clinical parameters including tender joint counts and swollen joint counts, and laboratory parameters including inflammatory makers and lipid profiles over regular intervals of TCZ treatment. Results In all, 22 patients with RA were included, 20 of whom were female. The median age at the first dose of TCZ was 62 years (range: 35–75 years). The mean duration of the disease from diagnosis with RA to May 2015 was 15.7 years (range: 6–30 years). A total of 15 out of 22 patients remained on TCZ at the end of the study, and in all, there was an improvement in markers of disease activity following initiating TCZ. The effect was sustained for a mean of 35 months (SD±15.5 months, range: 9–72 months). Of the 17 patients who failed to respond to RTX previously, 12 patients remained on TCZ. In all, eight out of 22 patients developed adverse events, five of whom discontinued TCZ. In contrast to previously documented short-term data, TCZ did not result in a statistically significant (P<0.05) long-term deterioration in lipid profile for any of the lipid parameters measured in our cohort (mean ± SD at initiation of TCZ to most recent follow-up: total cholesterol 5.25±1.05 to 5.28±0.77 mmol/L, high-density lipoprotein 1.72±0.54 to 1.67±0.43 mmol/L, low-density lipoprotein 3.05±0.98 to 2.98±0.81 mmol/L, and cholesterol to high-density lipoprotein ratio 3.41±1.23 to 3.40±1.22). Conclusion The efficacy of TCZ in patients with RA refractory to disease-modifying drugs, including anti-tumor necrosis factor blockade and RTX

  12. Long-term safety and efficacy of romiplostim for treatment of immune thrombocytopenia

    PubMed Central

    Vishnu, Prakash; Aboulafia, David M

    2016-01-01

    Inhibition of platelet production and mediated by antiplatelet antibodies is a well-known mechanism causing low platelet counts in immune thrombocytopenia (ITP). Use of thrombopoietin receptor agonists increases platelet counts and decreases the risk of bleeding in patients with ITP. Two such thrombopoietin receptor agonists, romiplostim and eltrombopag, are approved by the US Food and Drug Administration to treat thrombocytopenia in adults, and most recently, children with persistent or chronic ITP. This review focuses on the efficacy data and safety analysis of the pooled data from the clinical trials evaluating romiplostim for treatment of adults with ITP. The rates of hemorrhage, thrombosis, hematologic and nonhematologic cancers, and myelodysplastic syndrome were not overrepresented among the groups who received romiplostim versus placebo or other standard-of-care treatments. Yet, as after-market experience with thrombopoietin receptor agonists increases, there are emerging reports of increased incidence of thrombosis and bone marrow reticulin among patients who are treated with long-term use of these agents. Ongoing clinical research will continue to evaluate romiplostim’s efficacy and safety in other primary and secondary thrombocytopenic states. PMID:27307776

  13. Safety, Tolerability, and Compliance with Long-Term Antimalarial Chemoprophylaxis in American Soldiers in Afghanistan.

    PubMed

    Saunders, David L; Garges, Eric; Manning, Jessica E; Bennett, Kent; Schaffer, Sarah; Kosmowski, Andrew J; Magill, Alan J

    2015-09-01

    Long-term antimalarial chemoprophylaxis is currently used by deployed U.S. military personnel. Previous small, short-term efficacy studies have shown variable rates of side effects among patients taking various forms of chemoprophylaxis, though reliable safety and tolerability data on long-term use are limited. We conducted a survey of troops returning to Fort Drum, NY following a 12-month deployment to Operation Enduring Freedom, Afghanistan from 2006 to 2007. Of the 2,351 respondents, 95% reported taking at least one form of prophylaxis during their deployment, and 90% were deployed for > 10 months. Compliance with daily doxycycline was poor (60%) compared with 80% with weekly mefloquine (MQ). Adverse events (AEs) were reported by approximately 30% with both MQ and doxycycline, with 10% discontinuing doxycycline compared with 4% of MQ users. Only 6% and 31% of soldiers reported use of bed nets and skin repellents, respectively. Compliance with long-term malaria prophylaxis was poor, and there were substantial tolerability issues based on these anonymous survey results, though fewer with MQ than doxycycline. Given few long-term antimalarial chemoprophylaxis options, there is an unmet medical need for new antimalarials safe for long-term use. PMID:26123954

  14. Safety, Tolerability, and Compliance with Long-Term Antimalarial Chemoprophylaxis in American Soldiers in Afghanistan.

    PubMed

    Saunders, David L; Garges, Eric; Manning, Jessica E; Bennett, Kent; Schaffer, Sarah; Kosmowski, Andrew J; Magill, Alan J

    2015-09-01

    Long-term antimalarial chemoprophylaxis is currently used by deployed U.S. military personnel. Previous small, short-term efficacy studies have shown variable rates of side effects among patients taking various forms of chemoprophylaxis, though reliable safety and tolerability data on long-term use are limited. We conducted a survey of troops returning to Fort Drum, NY following a 12-month deployment to Operation Enduring Freedom, Afghanistan from 2006 to 2007. Of the 2,351 respondents, 95% reported taking at least one form of prophylaxis during their deployment, and 90% were deployed for > 10 months. Compliance with daily doxycycline was poor (60%) compared with 80% with weekly mefloquine (MQ). Adverse events (AEs) were reported by approximately 30% with both MQ and doxycycline, with 10% discontinuing doxycycline compared with 4% of MQ users. Only 6% and 31% of soldiers reported use of bed nets and skin repellents, respectively. Compliance with long-term malaria prophylaxis was poor, and there were substantial tolerability issues based on these anonymous survey results, though fewer with MQ than doxycycline. Given few long-term antimalarial chemoprophylaxis options, there is an unmet medical need for new antimalarials safe for long-term use.

  15. Resilience Engineering in Critical Long Term Aerospace Software Systems: A New Approach to Spacecraft Software Safety

    NASA Astrophysics Data System (ADS)

    Dulo, D. A.

    Safety critical software systems permeate spacecraft, and in a long term venture like a starship would be pervasive in every system of the spacecraft. Yet software failure today continues to plague both the systems and the organizations that develop them resulting in the loss of life, time, money, and valuable system platforms. A starship cannot afford this type of software failure in long journeys away from home. A single software failure could have catastrophic results for the spaceship and the crew onboard. This paper will offer a new approach to developing safe reliable software systems through focusing not on the traditional safety/reliability engineering paradigms but rather by focusing on a new paradigm: Resilience and Failure Obviation Engineering. The foremost objective of this approach is the obviation of failure, coupled with the ability of a software system to prevent or adapt to complex changing conditions in real time as a safety valve should failure occur to ensure safe system continuity. Through this approach, safety is ensured through foresight to anticipate failure and to adapt to risk in real time before failure occurs. In a starship, this type of software engineering is vital. Through software developed in a resilient manner, a starship would have reduced or eliminated software failure, and would have the ability to rapidly adapt should a software system become unstable or unsafe. As a result, long term software safety, reliability, and resilience would be present for a successful long term starship mission.

  16. Evaluation of the long-term results of trabectome surgery.

    PubMed

    Yildirim, Yildiray; Kar, Taner; Duzgun, Eyup; Sagdic, Sercan Koray; Ayata, Ali; Unal, Melih Hamdi

    2016-10-01

    The aim of this study was to investigate the safety and efficacy of ab interno trabeculectomy which is a minimally invasive glaucoma surgery, in the late period, performed via trabectome instrument. A total of 70 eyes followed up with a diagnosis of open-angle glaucoma (OAG) and undertaken trabectome surgery were included in the study. Preoperative and postoperative intraocular pressures (IOPs), number of the drugs used, and complications were retrospectively investigated and the data were evaluated. The criteria of success were accepted as an IOP value ≤21 mmHg or ≥30 % reduction in IOP and no need for a second operation. Mean IOP was decreased by 38 % from a preoperative value of 28.77 ± 5.34 to 17.62 ± 2.81 mmHg at the end of 18 months. Likewise, mean drug usage was decreased by 48 % from a preoperative value of 3.3 ± 1.01 to 1.7 ± 1.16 at the end of 18 months. Both decreases were statistically significant (p < 0.05). Postoperative success rates were 82.8 % in the 6th month, 81.4 % in the 9th month, 77.1 % in the 12th month, and 70 % in the 18th month. Most common complication observed was intraoperative reflux hemorrhage and no serious complication was observed. Trabectome surgery is an effective and safe method in early-stage open-angle glaucoma types that cannot be controlled despite maximal medical therapy. This procedure is a proper surgical option in patients targeted for moderate IOP without the need for a topical medication or with less drug usage.

  17. Long-term Efficacy and Safety of Sitagliptin in Elderly Patients with Type 2 Diabetes Mellitus.

    PubMed

    Tada, Yuko; Kanazawa, Ippei; Notsu, Masakazu; Tanaka, Ken-Ichiro; Kiyohara, Nobuaki; Sasaki, Motofumi; Sugimoto, Toshitsugu

    2016-01-01

    Objective We herein conducted a retrospective study to evaluate the long-term efficacy and safety of sitagliptin treatment in elderly patients with type 2 diabetes mellitus. Methods We analyzed the changes in glycemic control in 112 Japanese type 2 diabetes patients over 65 years of age treated with 50 mg/day sitagliptin. Hemoglobin A1c (HbA1c) levels, liver and kidney functions, and usage of hypoglycemic agents were recorded for 24 months. Results HbA1c levels were significantly decreased, and the significance of HbA1c reduction was maintained during the observation period [from 7.7±1.1% to 7.2±0.7% (p<0.001) at the end of observational period]. The %change in HbA1c levels was significantly and negatively correlated with the baseline HbA1c levels (r=-0.51, p<0.001), but not with age, duration of diabetes, or the estimated glomerular filtration rate (eGFR). No patient experienced severe hypoglycemia episodes, and aspartate transaminase, alanine transaminase, gamma-glutamyl transpeptidase, and the eGFR remained unchanged. The dose of sulfonylurea was finally decreased in 72% of patients treated with sulfonylurea. Conclusion Sitagliptin treatment continually decreases the HbA1c level for 24 months and is useful to reduce the dose of sulfonylurea in elderly patients with type 2 diabetes. PMID:27181532

  18. Open-Label, Long-Term Safety Study of Cevimeline in the Treatment of Postirradiation Xerostomia

    SciTech Connect

    Chambers, Mark S. Jones, Christopher Uwe; Biel, Merrill A.; Weber, Randal S.; Hodge, Kenneth M.; Chen, Y.; Holland, John M.; Ship, Jonathan; Vitti, Robert; Armstrong, Ingrid; Garden, Adam S.; Haddad, Robert

    2007-12-01

    Purpose: To assess the safety of long-term cevimeline treatment of radiation-induced xerostomia in patients with head-and-neck cancer; and to assess the efficacy of cevimeline in these patients. Methods and Materials: A total of 255 adults with head-and-neck cancer who had received more than 40 Gy of radiation 4 months or more before entry and had clinically significant salivary gland dysfunction received cevimeline hydrochloride 45 mg t.i.d. orally for 52 weeks. Adverse events (AEs), their severity, and their relationship to the study medication were assessed by each investigator. The efficacy assessment was based on subjects' global evaluation of oral dryness on a scale of 0 (none) to 3 (severe). Results: Overall, 175 subjects (68.6%) experienced expected treatment-related AEs, most mild to moderate. The most frequent was increased sweating (47.5%), followed by dyspepsia (9.4%), nausea (8.2%), and diarrhea (6.3%). Fifteen subjects (5.9%) experienced Grade 3 treatment-related AEs, of which the most frequent was increased sweating. Eighteen subjects (7.1%) reported at least one serious AE, and 45 subjects (17.6%) discontinued study medication because of an AE. The global efficacy evaluation at the last study visit showed that cevimeline improved dry mouth in most subjects (59.2%). Significant improvement was seen at each study visit in the mean change from baseline of the numeric global evaluation score (p < 0.0001). Conclusions: Cevimeline 45 mg t.i.d. was generally well tolerated over a period of 52 weeks in subjects with xerostomia secondary to radiotherapy for cancer in the head-and-neck region.

  19. A randomized, double-blinded, placebo-controlled study to evaluate the efficacy and safety of venlafaxine extended release and a long-term extension study for patients with major depressive disorder in Japan

    PubMed Central

    Higuchi, Teruhiko; Kamijima, Kunitoshi; Nakagome, Kazuyuki; Asami, Yuko; Kuribayashi, Kazuhiko; Imaeda, Takayuki

    2016-01-01

    The aim of this study was to assess antidepressant efficacy and safety of venlafaxine extended release in Japanese patients with major depressive disorder (MDD). We carried out a double-blinded, placebo-controlled, randomized study using fixed (75 mg/day) and flexible (75–225 mg/day, most patients attained to 225 mg/day) doses, followed by the long-term, open-labeled, extension study. Outpatients aged at least 20 years diagnosed with MDD were included. The primary efficacy measure was change from baseline in the Hamilton Rating Scale for Depression (HAM-D17) score at week 8; secondary efficacy measures included the Montgomery–Åsberg Depression Rating Scale, the Quick Inventory of Depressive Symptomatology self-report version, HAM-D6, and Clinical Global Impression scales in the double-blinded study. Overall, 538 patients were randomized; significant differences were observed in the primary efficacy variable in the fixed-dose group (−10.76; P=0.031), but not in the flexible-dose (−10.37; P=0.106) group compared with placebo (−9.25). However, the flexible-dose group showed significant efficacy in several secondary measures. Treatment-related adverse events in the treatment period were 51.7 and 67.8% in the fixed-dose and flexible-dose groups, respectively, versus 38.8% with placebo. Throughout the study period, no Japanese-specific adverse events were observed. Thus, venlafaxine extended release was efficacious and safe for MDD treatment in Japan. PMID:26513202

  20. A randomized, double-blinded, placebo-controlled study to evaluate the efficacy and safety of venlafaxine extended release and a long-term extension study for patients with major depressive disorder in Japan.

    PubMed

    Higuchi, Teruhiko; Kamijima, Kunitoshi; Nakagome, Kazuyuki; Itamura, Rio; Asami, Yuko; Kuribayashi, Kazuhiko; Imaeda, Takayuki

    2016-01-01

    The aim of this study was to assess antidepressant efficacy and safety of venlafaxine extended release in Japanese patients with major depressive disorder (MDD). We carried out a double-blinded, placebo-controlled, randomized study using fixed (75 mg/day) and flexible (75-225 mg/day, most patients attained to 225 mg/day) doses, followed by the long-term, open-labeled, extension study. Outpatients aged at least 20 years diagnosed with MDD were included. The primary efficacy measure was change from baseline in the Hamilton Rating Scale for Depression (HAM-D17) score at week 8; secondary efficacy measures included the Montgomery-Åsberg Depression Rating Scale, the Quick Inventory of Depressive Symptomatology self-report version, HAM-D6, and Clinical Global Impression scales in the double-blinded study. Overall, 538 patients were randomized; significant differences were observed in the primary efficacy variable in the fixed-dose group (-10.76; P=0.031), but not in the flexible-dose (-10.37; P=0.106) group compared with placebo (-9.25). However, the flexible-dose group showed significant efficacy in several secondary measures. Treatment-related adverse events in the treatment period were 51.7 and 67.8% in the fixed-dose and flexible-dose groups, respectively, versus 38.8% with placebo. Throughout the study period, no Japanese-specific adverse events were observed. Thus, venlafaxine extended release was efficacious and safe for MDD treatment in Japan.

  1. Safety of long-term use of linezolid: results of an open-label study

    PubMed Central

    Vazquez, Jose A; Arnold, Anthony C; Swanson, Robert N; Biswas, Pinaki; Bassetti, Matteo

    2016-01-01

    Objective The objective of this study was to assess the long-term safety of linezolid in patients with chronic infections requiring treatment for ≥6 weeks. Enhanced monitoring for optic neuropathy was included to characterize the early development of this side effect and to identify ophthalmologic tests that might be valuable in early detection of this event. Methods This was a multicenter, open-label, pilot study of patients aged ≥18 years on long-term linezolid therapy. Matched control patients were included for baseline assessment comparison. Patients were assessed at study entry, monthly while on treatment, at the end of treatment, and 30 days following the last dose. Aggregate ocular safety data were reviewed. Response to treatment was reported. Results The study was terminated owing to slow enrollment. Twenty-four patients received linezolid; nine patients were included as matched controls. Linezolid was prescribed for a median of 80.5 days (range, 50–254 days). In patients with a reported clinical outcome, the majority were considered improved or cured. Common treatment-related adverse events (AEs) included anemia, peripheral neuropathy, polyneuropathy, vomiting, and asthenia, and were consistent with the known safety profile. Most AEs resolved or stabilized with discontinuation of treatment. Results of ophthalmologic tests in the one case adjudicated as probable linezolid-associated optic neuropathy revealed abnormal color vision, characteristic changes in the optic disk, and central scotomas in each eye. Conclusion In our small population, linezolid was generally well tolerated and AEs were consistent with the known safety profile. Extensive ophthalmologic testing of all 24 linezolid-treated patients identified one case adjudicated as probable, linezolid-associated optic neuropathy. PMID:27621644

  2. Safety of long-term use of linezolid: results of an open-label study

    PubMed Central

    Vazquez, Jose A; Arnold, Anthony C; Swanson, Robert N; Biswas, Pinaki; Bassetti, Matteo

    2016-01-01

    Objective The objective of this study was to assess the long-term safety of linezolid in patients with chronic infections requiring treatment for ≥6 weeks. Enhanced monitoring for optic neuropathy was included to characterize the early development of this side effect and to identify ophthalmologic tests that might be valuable in early detection of this event. Methods This was a multicenter, open-label, pilot study of patients aged ≥18 years on long-term linezolid therapy. Matched control patients were included for baseline assessment comparison. Patients were assessed at study entry, monthly while on treatment, at the end of treatment, and 30 days following the last dose. Aggregate ocular safety data were reviewed. Response to treatment was reported. Results The study was terminated owing to slow enrollment. Twenty-four patients received linezolid; nine patients were included as matched controls. Linezolid was prescribed for a median of 80.5 days (range, 50–254 days). In patients with a reported clinical outcome, the majority were considered improved or cured. Common treatment-related adverse events (AEs) included anemia, peripheral neuropathy, polyneuropathy, vomiting, and asthenia, and were consistent with the known safety profile. Most AEs resolved or stabilized with discontinuation of treatment. Results of ophthalmologic tests in the one case adjudicated as probable linezolid-associated optic neuropathy revealed abnormal color vision, characteristic changes in the optic disk, and central scotomas in each eye. Conclusion In our small population, linezolid was generally well tolerated and AEs were consistent with the known safety profile. Extensive ophthalmologic testing of all 24 linezolid-treated patients identified one case adjudicated as probable, linezolid-associated optic neuropathy.

  3. Long-Term Safety and Effectiveness of the 'OptEase' Vena Cava Filter

    SciTech Connect

    Kalva, Sanjeeva P.; Marentis, Theodore C.; Yeddula, Kalpana; Somarouthu, Bhanusupriya; Wicky, Stephan; Stecker, Michael S.

    2011-04-15

    Purpose: To assess the long-term safety and effectiveness of the OptEase inferior vena cava (IVC) filter. Materials and Methods: In this Institutional Review Board-approved, retrospective study, we reviewed data of 71 patients who received an OptEase filter at our institution from 2002 to 2007. Thirty-nine (55%) patients had symptoms of venous thromboembolism before filter placement. The indications for filter included contraindication to anticoagulation in 31 (44%) patients, prophylaxis against pulmonary embolism (PE) in 29 (41%) patients, and failure of anticoagulation in 11 (15%) patients. Procedure-related complications, such as symptomatic post-filter PE, deep venous thrombosis (DVT), IVC occlusion, and incidental imaging-evident filter-related complications, were recorded. Safety was assessed by the occurrence of filter-related complications during placement and follow-up. Effectiveness was assessed by the occurrence of post-filter PE. Results: Sixty-five (92%) filters were placed under fluoroscopy, and 6 (8%) were placed using intravascular ultrasound guidance. Seventy (99%) filters were placed successfully. Seven (10%) filters were placed in the suprarenal cava. Retrieval was attempted in 14 (20%) patients, and 12 filters were successfully retrieved. Clinical follow-up was available for 20 {+-} 21 months. Symptoms of postfilter PE and DVT occurred in 15% (n = 11) and 10% (n = 7) patients, respectively. None of these patients had computed tomography (CT)-proven PE, and only one had ultrasound-proven new DVT. One patient had symptomatic IVC occlusion. Follow-up abdominal CT in 20 patients showed thrombus in the filter in two of them. There were no instances of filter migration, filter tilt, or caval wall penetration. Conclusion: The OptEase filter appears to have an acceptable long-term safety profile. The filter was effective against PE.

  4. Parametric Analysis of PWR Spent Fuel Depletion Parameters for Long-Term-Disposal Criticality Safety

    SciTech Connect

    DeHart, M.D.

    1999-08-01

    Utilization of burnup credit in criticality safety analysis for long-term disposal of spent nuclear fuel allows improved design efficiency and reduced cost due to the large mass of fissile material that will be present in the repository. Burnup-credit calculations are based on depletion calculations that provide a conservative estimate of spent fuel contents (in terms of criticality potential), followed by criticality calculations to assess the value of the effective neutron multiplication factor (k(sub)eff) for the a spent fuel cask or a fuel configuration under a variety of probabilistically derived events. In order to ensure that the depletion calculation is conservative, it is necessary to both qualify and quantify assumptions that can be made in depletion models.

  5. [Further enhance the long-term myopia control efficacy and safety of orthokeratology].

    PubMed

    Xie, Peiying

    2014-01-01

    Strategies and methods of myopia prevention and control has been more and more. In recent years optical correction method is focusing on promoting the retinal mid-peripheral myopic defocus, improving the visual quality and promoting the accommodative function. Among the all, orthokeratology is the most notable optometry technology. This article will combine research progress both local and international achievements, the present situation of the domestic popularized the technique, and the existing problems. From the realistic approach, keep improving, the pursuit of stability, the pursuit of harmony and eliminate the false five aspects, to discuss how to promote orthokeratology for the myopia control with long-term stably efficacy and safety. How to promote the harmony and cooperation between doctors, patients and manufactures. And how to correctly guide the orthokeratology Having both specification and continued development. PMID:24709125

  6. Safety of long-term dietary supplementation with L-arginine in pigs.

    PubMed

    Hu, Shengdi; Li, Xilong; Rezaei, Reza; Meininger, Cynthia J; McNeal, Catherine J; Wu, Guoyao

    2015-05-01

    This study was conducted with a swine model to determine the safety of long-term dietary supplementation with L-arginine-HCl or L-arginine free base. Beginning at 30 days of age, pigs were fed a corn- and soybean meal-based diet (31.5 g/kg body weight/day) supplemented with 0, 1.21, 1.81 or 2.42 % L-arginine-HCl (Experiment 1) or with 0, 1, 1.5 or 2 % L-arginine (Experiment 2). The supplemental doses of 0, 1, 1.5, and 2 % L-arginine provided pigs with 0, 315, 473, and 630 mg L-arginine/kg body weight/day, respectively, which were equivalent to 0, 286, 430, and 573 mg L-arginine/kg body weight/day, respectively, in humans. At 121 days of age (91 days after initiation of supplementation), blood samples were obtained from the jugular vein of pigs at 1 and 4 h after feeding for hematological and clinical chemistry tests. Dietary supplementation with L-arginine increased plasma concentrations of arginine, ornithine, proline, albumin and reticulocytes, while reducing plasma concentrations of ammonia, free fatty acids, triglyceride, cholesterol, and neutrophils. L-Arginine supplementation enhanced protein gain and reduced white-fat deposition in the body. Other variables in standard hematology and clinical chemistry tests, serum concentrations of insulin, growth hormone and insulin-like growth factor-I did not differ among all the groups of pigs. These results indicate that dietary supplementation with L-arginine (up to 630 mg/kg body weight/day) is safe in pigs for at least 91 days. Our findings help guide clinical studies to determine the safety of long-term oral administration of L-arginine to humans.

  7. Long-term efficacy, safety, and patient acceptability of ibandronate in the treatment of postmenopausal osteoporosis.

    PubMed

    Inderjeeth, Charles A; Glendenning, Paul; Ratnagobal, Shoba; Inderjeeth, Diren Che; Ondhia, Chandni

    2015-01-01

    Several second-generation bisphosphonates (BPs) are approved in osteoporosis treatment. Efficacy and safety depends on potency of farnesyl pyrophosphate synthase (FPPS) inhibition, hydroxyapatite affinity, compliance and adherence. The latter may be influenced by frequency and route of administration. A literature search using "ibandronate", "postmenopausal osteoporosis", "fracture", and "bone mineral density" (BMD) revealed 168 publications. The Phase III BONE study, using low dose 2.5 mg daily oral ibandronate demonstrated 49% relative risk reduction (RRR) in clinical vertebral fracture after 3 years. Non-vertebral fracture (NVF) reduction was demonstrated in a subgroup (pretreatment T-score ≤ -3.0; RRR 69%) and a meta-analysis of high annual doses (150 mg oral monthly or intravenous equivalent of ibandronate; RRR 38%). Hip fracture reduction was not demonstrated. Long-term treatment efficacy has been confirmed over 5 years. Long term safety is comparable to placebo over 3 years apart from flu-like symptoms which are more common with oral monthly and intravenous treatments. No cases of atypical femoral fracture or osteonecrosis of the jaw have been reported in randomized controlled trial studies. Ibandronate inhibits FPPS more than alendronate but less than other BPs which could explain rate of action onset. Ibandronate has a higher affinity for hydroxyapatite compared with risedronate but less than other BPs which could affect skeletal distribution and rate of action offset. High doses (150 mg oral monthly or intravenous equivalent) were superior to low doses (oral 2.5 mg daily) according to 1 year BMD change. Data are limited by patient selection, statistical power, under-dosing, and absence of placebo groups in high dose studies. Ibandronate treatment offers different doses and modalities of administration which could translate into higher adherence rates, an important factor when the two main limitations of BP treatment are initiation and adherence rates

  8. Improving Service Quality in Long-term Care Hospitals: National Evaluation on Long-term Care Hospitals and Employees Perception of Quality Dimensions

    PubMed Central

    Kim, Jinkyung; Han, Woosok

    2012-01-01

    Objectives To investigate predictors for specific dimensions of service quality perceived by hospital employees in long-term care hospitals. Methods Data collected from a survey of 298 hospital employees in 18 long-term care hospitals were analysed. Multivariate ordinary least squares regression analysis with hospital fixed effects was used to determine the predictors of service quality using respondents’ and organizational characteristics. Results The most significant predictors of employee-perceived service quality were job satisfaction and degree of consent on national evaluation criteria. National evaluation results on long-term care hospitals and work environment also had positive effects on service quality. Conclusion The findings of the study show that organizational characteristics are significant determinants of service quality in long-term care hospitals. Assessment of the extent to which hospitals address factors related to employeeperceived quality of services could be the first step in quality improvement activities. Results have implications for efforts to improve service quality in longterm care hospitals and designing more comprehensive national evaluation criteria. PMID:24159497

  9. Long-term efficacy and safety of ramosetron in the treatment of diarrhea-predominant irritable bowel syndrome

    PubMed Central

    Chiba, Toshimi; Yamamoto, Kazunari; Sato, Shoko; Suzuki, Kazuyuki

    2013-01-01

    Irritable bowel syndrome (IBS) is a functional disease with persisting gastrointestinal symptoms that has been classified into four subtypes. Serotonin (5-hydroxytryptamine [5-HT]) plays important physiological roles in the contraction and relaxation of smooth muscle. Intraluminal distension of the intestine is known to stimulate the release of endogenous 5-HT from enterochromaffin cells, activating 5-HT3 receptors located on primary afferent neurons and leading to increases in intestinal secretions and peristaltic activity. Ramosetron, a potent and selective 5-HT3-receptor antagonist, has been in development for use in patients suffering from diarrhea-predominant IBS. In a double-blind, placebo-controlled, parallel-group study of 418 patients with diarrhea-predominant IBS-D, once-daily 5 μg and 10 μg doses of ramosetron increased the monthly responder rates of IBS symptoms compared to placebo. In a 12-week randomized controlled trial of 539 patients, a positive response to treatment was reported by 47% of a once-daily 5 μg dose of ramosetron-treated individuals compared to 27% of patients receiving placebo (P<0.001). Furthermore, the responder rate was increased in the oral administration of 5 μg of ramosetron for at least 28 weeks (up to 52 weeks), and long-term efficacy for overall improvement of IBS symptoms was also demonstrated. The rate was further increased subsequently. Adverse events were reported by 7% in ramosetron treatment. No serious adverse events, eg, severe constipation or ischemic colitis, were reported for long-term treatment with ramosetron. In conclusion, further studies to evaluate the long-term efficacy and safety of ramosetron are warranted in the form of randomized controlled trials. PMID:23922505

  10. Long-Term Marine Traffic Monitoring for Environmental Safety in the Aegean Sea

    NASA Astrophysics Data System (ADS)

    Giannakopoulos, T.; Gyftakis, S.; Charou, E.; Perantonis, S.; Nivolianitou, Z.; Koromila, I.; Makrygiorgos, A.

    2015-04-01

    The Aegean Sea is characterized by an extremely high marine safety risk, mainly due to the significant increase of the traffic of tankers from and to the Black Sea that pass through narrow straits formed by the 1600 Greek islands. Reducing the risk of a ship accident is therefore vital to all socio-economic and environmental sectors. This paper presents an online long-term marine traffic monitoring work-flow that focuses on extracting aggregated vessel risks using spatiotemporal analysis of multilayer information: vessel trajectories, vessel data, meteorological data, bathymetric / hydrographic data as well as information regarding environmentally important areas (e.g. protected high-risk areas, etc.). A web interface that enables user-friendly spatiotemporal queries is implemented at the frontend, while a series of data mining functionalities extracts aggregated statistics regarding: (a) marine risks and accident probabilities for particular areas (b) trajectories clustering information (c) general marine statistics (cargo types, etc.) and (d) correlation between spatial environmental importance and marine traffic risk. Towards this end, a set of data clustering and probabilistic graphical modelling techniques has been adopted.

  11. Long-term efficacy and safety of raltegravir in the management of HIV infection.

    PubMed

    Liedtke, Michelle D; Tomlin, C Ryan; Lockhart, Staci M; Miller, Misty M; Rathbun, R Chris

    2014-01-01

    Raltegravir is an integrase strand-transfer inhibitor approved for the treatment of HIV infection. It was the first medication in a novel class of antiretroviral agents to be approved for use in the United States in 2007. Raltegravir exhibits potent activity against wild-type HIV-1, but resistance development has been noted through three different pathways. It is metabolized primarily through uridine diphosphate glucuronosyltransferase 1A1 and has a single inactive glucuronide metabolite. Raltegravir is not a substrate, inhibitor, or inducer of cytochrome P450 enzymes and exhibits low potential for drug-drug interactions; however, strong uridine diphosphate glucuronosyltransferase 1A1 inhibitors or inducers can alter the pharmacokinetics of raltegravir. It is well tolerated, and the most commonly reported adverse effects include headache, nausea, and diarrhea. Serious adverse effects with raltegravir are rare but include rhabdomyolysis and severe skin and hypersensitivity reactions. It has been approved for use in both treatment-naïve and treatment-experienced patients and is a preferred first-line agent in both United States and European HIV treatment guidelines. Although initial approval was granted on 48-week data, 5-year clinical data have recently been published. This article reviews the data supporting long-term efficacy and safety of raltegravir in the treatment of HIV infection.

  12. Long-term safety and efficacy of sustained eculizumab treatment in patients with paroxysmal nocturnal haemoglobinuria

    PubMed Central

    Hillmen, Peter; Muus, Petra; Röth, Alexander; Elebute, Modupe O; Risitano, Antonio M; Schrezenmeier, Hubert; Szer, Jeffrey; Browne, Paul; Maciejewski, Jaroslaw P; Schubert, Jörg; Urbano-Ispizua, Alvaro; de Castro, Carlos; Socié, Gérard; Brodsky, Robert A

    2013-01-01

    Paroxysmal nocturnal haemoglobinuria (PNH) is characterized by chronic, uncontrolled complement activation resulting in elevated intravascular haemolysis and morbidities, including fatigue, dyspnoea, abdominal pain, pulmonary hypertension, thrombotic events (TEs) and chronic kidney disease (CKD). The long-term safety and efficacy of eculizumab, a humanized monoclonal antibody that inhibits terminal complement activation, was investigated in 195 patients over 66 months. Four patient deaths were reported, all unrelated to treatment, resulting in a 3-year survival estimate of 97·6%. All patients showed a reduction in lactate dehydrogenase levels, which was sustained over the course of treatment (median reduction of 86·9% at 36 months), reflecting inhibition of chronic haemolysis. TEs decreased by 81·8%, with 96·4% of patients remaining free of TEs. Patients also showed a time-dependent improvement in renal function: 93·1% of patients exhibited improvement or stabilization in CKD score at 36 months. Transfusion independence increased by 90·0% from baseline, with the number of red blood cell units transfused decreasing by 54·7%. Eculizumab was well tolerated, with no evidence of cumulative toxicity and a decreasing occurrence of adverse events over time. Eculizumab has a substantial impact on the symptoms and complications of PNH and results a significant improvement in patient survival. PMID:23617322

  13. Long-term efficacy and safety of raltegravir in the management of HIV infection

    PubMed Central

    Liedtke, Michelle D; Tomlin, C Ryan; Lockhart, Staci M; Miller, Misty M; Rathbun, R Chris

    2014-01-01

    Raltegravir is an integrase strand-transfer inhibitor approved for the treatment of HIV infection. It was the first medication in a novel class of antiretroviral agents to be approved for use in the United States in 2007. Raltegravir exhibits potent activity against wild-type HIV-1, but resistance development has been noted through three different pathways. It is metabolized primarily through uridine diphosphate glucuronosyltransferase 1A1 and has a single inactive glucuronide metabolite. Raltegravir is not a substrate, inhibitor, or inducer of cytochrome P450 enzymes and exhibits low potential for drug–drug interactions; however, strong uridine diphosphate glucuronosyltransferase 1A1 inhibitors or inducers can alter the pharmacokinetics of raltegravir. It is well tolerated, and the most commonly reported adverse effects include headache, nausea, and diarrhea. Serious adverse effects with raltegravir are rare but include rhabdomyolysis and severe skin and hypersensitivity reactions. It has been approved for use in both treatment-naïve and treatment-experienced patients and is a preferred first-line agent in both United States and European HIV treatment guidelines. Although initial approval was granted on 48-week data, 5-year clinical data have recently been published. This article reviews the data supporting long-term efficacy and safety of raltegravir in the treatment of HIV infection. PMID:24672249

  14. Evaluating the Long-Term Impacts of AmeriCorps Service on Participants. PRGS Dissertation

    ERIC Educational Resources Information Center

    Epstein, Diana

    2009-01-01

    Since 1993, over 500,000 people have served in AmeriCorps national service programs. This dissertation evaluates the long-term impacts of AmeriCorps service on participants, particularly in the areas of civic engagement, future volunteerism, appreciation of diversity, and a number of other job and life skills. It fills a gap by using both…

  15. Evaluating long-term trends in littoral benthic macroinvertebrate communities of lakes recovering from acid deposition.

    PubMed

    Lento, Jennifer; Dillon, Peter J; Somers, Keith M

    2012-12-01

    The Mann-Kendall test has been proposed as a nonparametric method to evaluate trends in long-term water quality datasets with missing values, serial correlation, and non-normality. However, this test has rarely been used to evaluate long-term trends in biological data. In this study, we used the Mann-Kendall test to evaluate trends in 15 years of data on benthic macroinvertebrate communities from 17 Precambrian Shield lakes. We also used the van Belle and Hughes test of trend homogeneity to assess whether common among-lake temporal trends existed. We assumed that evidence of a common regional trend among lakes would support the hypothesis of long-term biological recovery from past acidification. We found decreasing proportions of Chironomidae and increasing proportions of Ephemeroptera, Plecoptera, and Trichoptera (EPT) in both single-lake and multi-lake trend analysis. Moreover, six of the nine lakes with significant trends in more than one benthos metric displayed a significant decrease in Chironomidae and increase in EPT concurrently, indicating a shift towards more acid-sensitive taxa. Weak trends in several of the biological metrics indicated that recovery in these lakes has been impeded. Results of this study indicate that the Mann-Kendall and van Belle and Hughes trend tests are useful statistical tools to evaluate long-term patterns in biological data.

  16. Evaluating long-term trends in littoral benthic macroinvertebrate communities of lakes recovering from acid deposition.

    PubMed

    Lento, Jennifer; Dillon, Peter J; Somers, Keith M

    2012-12-01

    The Mann-Kendall test has been proposed as a nonparametric method to evaluate trends in long-term water quality datasets with missing values, serial correlation, and non-normality. However, this test has rarely been used to evaluate long-term trends in biological data. In this study, we used the Mann-Kendall test to evaluate trends in 15 years of data on benthic macroinvertebrate communities from 17 Precambrian Shield lakes. We also used the van Belle and Hughes test of trend homogeneity to assess whether common among-lake temporal trends existed. We assumed that evidence of a common regional trend among lakes would support the hypothesis of long-term biological recovery from past acidification. We found decreasing proportions of Chironomidae and increasing proportions of Ephemeroptera, Plecoptera, and Trichoptera (EPT) in both single-lake and multi-lake trend analysis. Moreover, six of the nine lakes with significant trends in more than one benthos metric displayed a significant decrease in Chironomidae and increase in EPT concurrently, indicating a shift towards more acid-sensitive taxa. Weak trends in several of the biological metrics indicated that recovery in these lakes has been impeded. Results of this study indicate that the Mann-Kendall and van Belle and Hughes trend tests are useful statistical tools to evaluate long-term patterns in biological data. PMID:22193633

  17. Monitoring the Long-Term Effectiveness of Integrated Safety Management System (ISMS) Implementation Through Use of a Performance Dashboard Process

    SciTech Connect

    Michael D. Kinney and William D. Barrick

    2008-09-01

    This session will examine a method developed by Federal and Contractor personnel at the U.S. Department of Energy, National Nuclear Security Administration Nevada Site Office (NNSA/NSO) to examine long-term maintenance of DOE Integrated Safety Management System (ISMS) criteria, including safety culture attributes, as well as identification of process improvement opportunities. This process was initially developed in the summer of 2000 and has since been expanded to recognize the importance of safety culture attributes, and associated safety culture elements, as defined in DOE M 450.4-1, “Integrated Safety Management System Manual.” This process has proven to significantly enhance collective awareness of the importance of long-term ISMS implementation as well as support commitments by NNSA/NSO personnel to examine the continued effectiveness of ISMS processes.

  18. The safety and long-term efficacy of zonisamide as adjunctive therapy for focal epilepsy.

    PubMed

    Schulze-Bonhage, Andreas

    2015-01-01

    Epilepsy is a chronic disease which affects 1% of the population worldwide. As treatment is required for many years or decades, the long-term efficacy and tolerability of antiepileptic drugs are particularly important. Zonisamide (ZNS) is a second-generation antiepileptic drug with a unique structure and multiple mechanisms of action. Here, recently published long-term outcomes of patient cohorts with focal epilepsy undergoing ZNS treatment are discussed. Whereas ZNS monotherapy maintains similar seizure control efficacy to carbamazepine after 2 years of treatment, seizure-free rates are low in pharmacoresistant patients undergoing late adjunctive therapy. In preselected patient populations derived from double-blind studies, long-term seizure reduction and responder rates support sustained ZNS efficacy, good adherence and long-term retention. Adverse effects include somnolence and weight decrease, but data suggest that long-term treatment with ZNS is safe with only rare newly occurring adverse effects, and good long-term tolerability also regarding mood, behavior, cognition and bone maturation.

  19. Towards a common benchmark for long-term process control and monitoring performance evaluation.

    PubMed

    Rosen, C; Jeppsson, U; Vanrolleghem, P A

    2004-01-01

    The COST/IWA benchmark simulation model has been available for seven years. Its primary purpose has been to create a platform for control strategy benchmarking of biological wastewater treatment processes. The fact that the benchmark has resulted in more than 100 publications, not only in Europe but also worldwide, demonstrates the interest for such a tool in the research community. In this paper, an extension of the benchmark simulation model no. 1 (BSM1) is proposed. It aims at facilitating evaluation of two closely related operational tasks: long-term control strategy performance and process monitoring performance. The motivation for the extension is that these two tasks typically act on longer time scales. The extension proposed here consists of 1) prolonging the evaluation period to one year (including influent files), 2) specifying time varying process parameters and 3) including sensor and actuator failures. The prolonged evaluation period is necessary to obtain a relevant and realistic assessment of the effects of such disturbances. Also, a prolonged evaluation period allows for a number of long-term control actions/handles that cannot be evaluated in a realistic fashion in the one week BSM1 evaluation period. In the paper, models for influent file design, parameter changes and sensor failures, initialization procedure and evaluation criteria are discussed. Important remaining topics, for which consensus is required, are identified. The potential of a long-term benchmark is illustrated with an example of process monitoring algorithm benchmarking.

  20. Hydrodynamic evaluation of long term impacts of climate change and coastal effluents in the Arabian Gulf.

    PubMed

    Elhakeem, Abubaker; Elshorbagy, Walid

    2015-12-30

    A comprehensive basin wide hydrodynamic evaluation has been carried out to assess the long term impacts of climate change and coastal effluents on the salinity and seawater temperature of the Arabian Gulf (AG) using Delft3D-Flow model. The long term impacts of climate change scenarios A2 and B1 of the IPCC-AR4 on the AG hydrodynamics were evaluated. Using the current capacity and production rates of coastal desalination, power, and refinery plants, two projection scenarios until the year 2080 with 30 year intervals were developed namely the realistic and the optimistic discharge scenarios. Simulations of the individual climate change scenarios ascertained overall increase of the AG salinity and temperature and decrease of precipitation. The changes varied spatially with different scenarios as per the depth, proximity to exchange with ocean water, flushing, vertical mixing, and flow restriction. The individual tested scenarios of coastal projected discharges showed significant effects but within 10-20 km from the outfalls.

  1. Radioembolization for Neuroendocrine Liver Metastases: Safety, Imaging, and Long-Term Outcomes

    SciTech Connect

    Memon, Khairuddin; Lewandowski, Robert J.; Mulcahy, Mary F.; Riaz, Ahsun; Ryu, Robert K.; Sato, Kent T.; Gupta, Ramona; Nikolaidis, Paul; Miller, Frank H.; Yaghmai, Vahid; Gates, Vanessa L.; Atassi, Bassel; Newman, Steven; Omary, Reed A.; Benson, Al B.; Salem, Riad

    2012-07-01

    Purpose: To present long-term outcomes on the safety and efficacy of Yttrium-90 radioembolization in the treatment of unresectable hepatic neuroendocrine metastases refractory to standard-of-care therapy. Methods and Materials: This study was approved by our institutional review board and was compliant with the Health Insurance Portability and Accountability Act. Forty patients with hepatic neuroendocrine metastases were treated with {sup 90}Y radioembolization at a single center. Toxicity was assessed using National Cancer Institute Common Terminology Criteria v3.0. Response to therapy was assessed by World Health Organization (WHO) guidelines for size and European Association for the Study of the Liver disease (EASL) guidelines for necrosis. Time to response and overall survival were calculated using the Kaplan-Meier method. Univariate and multivariate analyses were performed. Results: The median dose was 113 Gy (29-299 Gy). Clinical toxicities included fatigue (63%), nausea/vomiting (40%), abdominal pain (18%), fever (8%), diarrhea and weight loss (5%); Grade 3 and 4 bilirubin toxicities were experienced by 2 patients and 1 patient, respectively. Different responses were noted by WHO (complete response, 1.2%; partial response, 62.7%) and EASL (complete response, 20.5%; partial response, 43.4%). Median time to response was 4 and 4.9 months by lesion and patient, respectively. The 1-, 2-, and 3-year overall survival rates were 72.5%, 62.5%, and 45%, respectively. Eastern Cooperative Oncology Group (ECOG) performance score 0 (p < 0.0001), tumor burden {<=}25% (p = 0.0019), albumin {>=}3.5 g/dL (p = 0.017), and bilirubin {<=}1.2 mg/dL (p = 0.002) prognosticated survival on univariate analysis; only ECOG performance score 0 and bilirubin {<=}1.2 mg/dL prognosticated better survival outcome on multivariate analysis (p = 0.0001 and p = 0.02). Conclusion: Yttrium-90 therapy for hepatic neuroendocrine metastases leads to satisfactory tumor response and patient survival

  2. Evaluation of the measurement uncertainty in automated long-term sampling of PCDD/PCDFs.

    PubMed

    Vicaretti, M; D'Emilia, G; Mosca, S; Guerriero, E; Rotatori, M

    2013-12-01

    Since the publication of the first version of European standard EN-1948 in 1996, long-term sampling equipment has been improved to a high standard for the sampling and analysis of polychlorodibenzo-p-dioxin (PCDD)/polychlorodibenzofuran (PCDF) emissions from industrial sources. The current automated PCDD/PCDF sampling systems enable to extend the measurement time from 6-8 h to 15-30 days in order to have data values better representative of the real pollutant emission of the plant in the long period. EN-1948:2006 is still the European technical reference standard for the determination of PCDD/PCDF from stationary source emissions. In this paper, a methodology to estimate the measurement uncertainty of long-term automated sampling is presented. The methodology has been tested on a set of high concentration sampling data resulting from a specific experience; it is proposed with the intent that it is to be applied on further similar studies and generalized. A comparison between short-term sampling data resulting from manual and automated parallel measurements has been considered also in order to verify the feasibility and usefulness of automated systems and to establish correlations between results of the two methods to use a manual method for calibration of automatic long-term one. The uncertainty components of the manual method are analyzed, following the requirements of EN-1948-3:2006, allowing to have a preliminary evaluation of the corresponding uncertainty components of the automated system. Then, a comparison between experimental data coming from parallel sampling campaigns carried out in short- and long-term sampling periods is realized. Long-term sampling is more reliable to monitor PCDD/PCDF emissions than occasional short-term sampling. Automated sampling systems can assure very useful emission data both in short and long sampling periods. Despite this, due to the different application of the long-term sampling systems, the automated results could not be

  3. Model-based prediction of the acute and long-term safety profile of naproxen in rats

    PubMed Central

    Sahota, Tarjinder; Sanderson, Ian; Danhof, Meindert; Della Pasqua, Oscar

    2015-01-01

    Background and Purpose Despite the increasing importance of biomarkers as predictors of drug effects, toxicology protocols continue to rely on the experimental evidence of adverse events (AEs) as a basis for establishing the link between indicators of safety and drug exposure. Furthermore, biomarkers may facilitate the translation of findings from animals to humans. Combined with a model-based approach, biomarker data have the potential to predict long-term effects arising from prolonged drug exposure. Here, we used naproxen as a paradigm to explore the feasibility of a biomarker-guided approach for the prediction of long-term AEs in humans. Experimental Approach An experimental toxicology protocol was set up for evaluating the effects of naproxen in rats, in which four active doses were tested (7.5, 15, 40 and 80 mg·kg−1). In addition to AE monitoring and histology, a few blood samples were also collected for the assessment of drug exposure, TXB2 and PGE2 levels. Non-linear mixed effects modelling was used to analyse the data and identify covariate factors on the incidence and severity of AEs. Key Results Modelling results showed that besides drug exposure, maximum PGE2 inhibition and treatment duration were also predictors of gastrointestinal ulceration. Although PGE2 levels were clearly linked to the incidence rates, it appeared that ulceration severity is better predicted by measures of drug exposure. Conclusions and Implications These results show that the use of a model-based approach provides the opportunity to integrate pharmacokinetics, pharmacodynamics and toxicity data, enabling optimization of the design, analysis and interpretation of toxicology experiments. PMID:25884765

  4. Swallowing outcome after TORS for sleep apnea: short- and long-term evaluation.

    PubMed

    Eesa, Mohamed; Montevecchi, Filippo; Hendawy, Ehsan; D'Agostino, Giovanni; Meccariello, Giuseppe; Vicini, Claudio

    2015-06-01

    The aim of this study was to evaluate outcomes related to swallowing function in patients who underwent transoral robotic surgery (TORS) for sleep apnea on both short- and long-term scales. 78 patients who underwent TORS for sleep apnea between 2011 and 2014 were followed up for an average period of 20 ± 7.12 months (range 7-32 months), then swallowing outcomes determined by MD Anderson Dysphagia Inventory (MDADI) questionnaire, gastrografin fluoroscopy imaging results, nasogastric tube dependence and subjectively by recording the patients' complaints were analyzed and reported. Minimal insignificant short-term impact on swallowing function (4.58 ± 7.03 preoperative MDADI score versus 5.18 ± 8.32 post-operative) (p = 0.56) was registered. Mean time for start of oral feeding was 1.05 ± 0.25 days (average, 1-3). In no case nasogastric tube feeding was required. Only five patients (6 %) showed significant aspiration on gastrografin fluoroscopy examination after 1 week; there was no significant correlation between the volume of tissue removed from both tongue base and epiglottis to the incidence of aspiration as shown by gastrografin fluoroscopy examination (p = 0.72). No long-term swallowing complaint was registered. Patients who underwent TORS tongue base reduction and supraglottoplasty for sleep apnea proved to have a reasonable short-term swallowing outcomes with no long-term sequelae.

  5. Evaluation of Long-Term Migration Testing from Can Coatings into Food Simulants: Polyester Coatings.

    PubMed

    Paseiro-Cerrato, Rafael; Noonan, Gregory O; Begley, Timothy H

    2016-03-23

    FDA guidance for food contact substances recommends that for food packaging intended for use at sterilized, high temperature processed, or retorted conditions, a migration test with a retort step at 121 °C for 2 h followed by a 10 day migration test at 40 °C should be performed. These conditions are in intended to simulate processing and long-term storage. However, can coatings may be in contact with food for years, and there are very few data evaluating if this short-term testing accurately simulates migration over extended time periods. A long-term migration test at 40 °C with retorted and non-retorted polyester cans using several food simulants (water, 3% acetic acid, 10% ethanol, 50% ethanol, and isooctane) was conducted to verify whether traditional migration testing protocols accurately predict migration from food contact materials used for extended time periods. Time points were from 1 day to 515 days. HPLC-MS/MS was used to analyze polyester monomers, and oligomer migration was monitored using HPLC-DAD/CAD and HPLC-MS. Concentrations of monomers and oligomers increased during the migration experiments, especially in ethanol food simulants. The data suggest that current FDA migration protocols may need to be modified to address changes in migrants as a result of long-term storage conditions.

  6. Long term effect and safety of Wharton's jelly-derived mesenchymal stem cells on type 2 diabetes

    PubMed Central

    Hu, Jianxia; Wang, Yangang; Gong, Huimin; Yu, Chundong; Guo, Caihong; Wang, Fang; Yan, Shengli; Xu, Hongmei

    2016-01-01

    Cellular therapies offer novel opportunities for the treatment of type 2 diabetes mellitus (T2DM). The present study evaluated the long-term efficacy and safety of infusion of Wharton's jelly-derived mesenchymal stem cells (WJ-MSC) on T2DM. A total of 61 patients with T2DM were randomly divided into two groups on the basis of basal therapy; patients in group I were administered WJ-MSC intravenous infusion twice, with a four-week interval, and patients in group II were treated with normal saline as control. During the 36-month follow-up period, the occurrence of any adverse effects and the results of clinical and laboratory examinations were recorded and evaluated. The lack of acute or chronic adverse effects in group I was consistent with group II.. Blood glucose, glycosylated hemoglobin, C-peptide, homeostasis model assessment of pancreatic islet β-cell function and incidence of diabetic complications in group I were significantly improved, as compared with group II during the 36-month follow-up. The results of the present study demonstrated that infusion of WJ-MSC improved the function of islet β-cells and reduced the incidence of diabetic complications, although the precise mechanisms are yet to be elucidated. The infusion of WJ-MSC may be an effective option for the treatment of patients with type 2 diabetes. PMID:27588104

  7. Depot-medroxyprogesterone acetate injection (Depo-Provera): a highly effective contraceptive option with proven long-term safety.

    PubMed

    Westhoff, Carolyn

    2003-08-01

    Depot-medroxyprogesterone acetate (Depo-Provera(R)) is a highly effective, nondaily hormonal contraceptive option that has been available in the United States for a decade, and worldwide for 40 years. Benefits and risks of hormonal therapy are often under scrutiny; however, long-term clinical experience has established the safety of this long-acting contraceptive. This article reviews the contraceptive efficacy, potential noncontraceptive health benefits and long-term safety of with regard to risk of cardiovascular events, breast and gynecologic malignancy and osteopenia. Comparisons with other hormonal contraceptives are made as clinically appropriate. Common patient management issues, including effects on menstrual cycle, body weight and mood, are also addressed. Finally, this review provides recommendations for appropriate patient selection.

  8. Prolonged-release melatonin for insomnia – an open-label long-term study of efficacy, safety, and withdrawal

    PubMed Central

    Lemoine, Patrick; Garfinkel, Doron; Laudon, Moshe; Nir, Tali; Zisapel, Nava

    2011-01-01

    Background Prolonged-release melatonin (PRM) 2 mg is indicated for insomnia in patients aged 55 years and older. A recent double-blind placebo-controlled study demonstrated 6-month efficacy and safety of PRM in insomnia patients aged 18–80 and lack of withdrawal and rebound symptoms upon discontinuation. Objective To investigate the efficacy, safety, and withdrawal phenomena associated with 6–12 months PRM treatment. Methods Data from a prospective 6–12-month open-label study of 244 community dwelling adults with primary insomnia, who had participated in a placebo-controlled, double-blind dose-ranging trial of PRM. Patients received PRM nightly, followed by a 2-week withdrawal period. Main outcome measures were patient-reported sleep quality ratings (diary), adverse events, vital signs, and laboratory tests recorded at each visit, and withdrawal symptoms (CHESS-84 [Check-list Evaluation of Somatic Symptoms]). Nocturnal urinary 6-sulfatoxymelatonin excretion, a measure of the endogenous melatonin production, was assessed upon discontinuing long-term PRM. Results Of the 244 patients, 36 dropped out, 112 completed 6 months of treatment, and the other 96 completed 12 months of treatment. The mean number of nights by which patients reported sleep quality as “good” or “very good” was significantly higher during PRM than before treatment. There was no evidence of tolerance to PRM. Discontinuation of PRM was not associated with rebound insomnia or withdrawal symptoms; on the contrary, residual benefit was observed. PRM was well tolerated, and there was no suppression of endogenous melatonin production. Conclusion Results support the efficacy and safety of PRM in primary insomnia patients aged 20–80 throughout 6–12 months of continuous therapy. PRM discontinuation even after 12 months was not associated with adverse events, withdrawal symptoms, or suppression of endogenous melatonin production. PMID:21845053

  9. Advanced Evaluation of the Long-Term Stability of Oxygen Evolution Electrocatalysts.

    PubMed

    Maljusch, Artjom; Conradi, Oliver; Hoch, Sascha; Blug, Matthias; Schuhmann, Wolfgang

    2016-08-01

    Evaluation of the long-term stability of electrocatalysts is typically performed using galvanostatic polarization at a predefined current density. A stable or insignificant increase in the applied potential is usually interpreted as high long-term stability of the tested catalyst. However, effects such as (i) electrochemical degradation of a catalyst due to its oxidation, (ii) blocking of the catalyst surface by evolved gas bubbles, and (iii) detachment of the catalyst from the electrode surface may lead to a decrease of the catalyst's active surface area being exposed to the electrolyte. In order to separate these effects and to evaluate the true electrochemical degradation of electrocatalysts, an advanced evaluation protocol based on subsequently performed electrochemical impedance, double layer capacitance, cyclic voltammetry, and galvanostatic polarization measurements was developed and used to evaluate the degradation of IrO2 particles drop-coated on glassy carbon rotating disk electrode using Nafion as a binder. A flow-through electrochemical cell was developed enabling circulation of the electrolyte leading to an efficient removal of evolved oxygen bubbles even at high current densities of up to 250 mA/cm(2). The degradation rate of IrO2 was evaluated over 225 test cycles (0.733 ± 0.022 mV/h) with a total duration of galvanostatic polarization measurements of over 55 h. PMID:27398712

  10. Long-term (52 weeks) safety and tolerability of umeclidinium in Japanese patients with chronic obstructive pulmonary disease.

    PubMed

    Yamagata, Eiji; Soutome, Toru; Hashimoto, Kenichi; Mihara, Kazuko; Tohda, Yuji

    2016-05-01

    Objective Umeclidinium bromide (UMEC) 62.5 μg is a long-acting muscarinic antagonist (LAMA) that is administered once daily via inhalation for chronic obstructive pulmonary disease (COPD) treatment. The objective of this study was to evaluate the safety and tolerability of long-term treatment with UMEC 125 μg in Japanese patients with COPD. Methods This was a 52 week, multicenter, open-label study to evaluate the safety and tolerability of UMEC 125 μg once daily delivered via a novel dry powder inhaler (nDPI) in Japanese patients with COPD. The primary endpoint was the incidence and severity of all adverse events (AEs) throughout the 52 week treatment period. Clinical trial registration number ClinicalTrials.gov identifier is NCT01702363. Results A total of 153 patients were enrolled in the study. Of these, 131 patients started treatment with UMEC 125 μg, and 111 patients (85%) completed the study. AEs did not differ greatly in incidence over the various time periods (Weeks 0 to 12, 13 to 24, 25 to 36, and 37 to 52 of treatment) and did not increase with continued treatment. The incidence of drug-related AEs associated with the pharmacological effects of LAMAs (including constipation, blurred vision, and thirst) was low. Serious adverse events (SAEs) during the treatment period were reported in 17 patients (13%). SAEs reported in more than one patient were COPD exacerbation and pneumonia (3 patients each, 2%). One SAE of angina pectoris was considered to be drug related. No fatalities were reported during this study. Conclusions No new AEs were identified beyond those attributable to the pharmacological effects of LAMAs. UMEC 125 μg was well tolerated over 52 weeks of treatment in Japanese patients with COPD. PMID:26782971

  11. Polysomnographic and long-term video electroencephalographic evaluation of cases presenting with parasomnias.

    PubMed

    Yiş, Uluç; Kurul, Semra Hiz; Öztura, Ibrahim; Ecevit, Mustafa Cenk; Dirik, Eray

    2013-09-01

    The aim of this study is to evaluate the clinical, electroencephalographic and polysomnographic features of patients presenting with parasomnias. Cases who were admitted for differentiating parasomnias from epilepsy were included in the study. Clinical features of cases were recorded and routine sleep electroencephalography was obtained from all cases. Cases whose symptoms strongly suggested nocturnal seizure underwent all night video electroencephalography monitoring. Polysomnography was obtained to evaluate the quality of breathing from patients whose symptoms suggested obstructive sleep apnea. Twenty-three patients with no neurological disorder were included in the study. The mean age of the patients was 11.7 ± 2.8 [7-17] years. Twelve patients (52 %) presented with sleep terrors and 11 patients (48 %) presented with sleep walking. All of the patients underwent a routine sleep electroencephalographic study and 15 patients (65 %) whose symptoms strongly suggested nocturnal epilepsy underwent long-term video electroencephalographic evaluation. Ten patients (43 %) underwent polysomnographic study. Three patients (20 %) who underwent long-term video electroencephalographic evaluation were diagnosed to have nocturnal frontal lobe epilepsy and two patients (20 %) who underwent polysomnography had pathological sleep apnea. Eleven patients (48 %) had a psychiatric disorder like major depression, anxiety disorder, hyperactivity disorder and obsessive-compulsive disorder. Childhood cases presenting with parasomnias should be searched for nocturnal epileptic disorders, sleep disordered breathing and psychiatric disorders. PMID:23135782

  12. Long-term safety of antiresorptive treatment: bone material, matrix and mineralization aspects

    PubMed Central

    Misof, Barbara M; Fratzl-Zelman, Nadja; Paschalis, Eleftherios P; Roschger, Paul; Klaushofer, Klaus

    2015-01-01

    It is well established that long-term antiresorptive use is effective in the reduction of fracture risk in high bone turnover osteoporosis. Nevertheless, during recent years, concerns emerged that longer bone turnover reduction might favor the occurrence of fatigue fractures. However, the underlying mechanisms for both beneficial and suspected adverse effects are not fully understood yet. There is some evidence that their effects on the bone material characteristics have an important role. In principle, the composition and nanostructure of bone material, for example, collagen cross-links and mineral content and crystallinity, is highly dependent on tissue age. Bone turnover determines the age distribution of the bone structural units (BSUs) present in bone, which in turn is decisive for its intrinsic material properties. It is noteworthy that the effects of bone turnover reduction on bone material were observed to be dependent on the duration of the antiresorptive therapy. During the first 2–3 years, significant decreases in the heterogeneity of material properties such as mineralization of the BSUs have been observed. In the long term (5–10 years), the mineralization pattern reverts towards normal heterogeneity and degree of mineralization, with no signs of hypermineralization in the bone matrix. Nevertheless, it has been hypothesized that the occurrence of fatigue fractures (such as atypical femoral fractures) might be linked to a reduced ability of microdamage repair under antiresorptive therapy. The present article examines results from clinical studies after antiresorptive, in particular long-term, therapy with the aforementioned potentially positive or negative effects on bone material. PMID:25709811

  13. In Vivo Transplantation of Enteric Neural Crest Cells into Mouse Gut; Engraftment, Functional Integration and Long-Term Safety

    PubMed Central

    Cooper, Julie E.; McCann, Conor J.; Natarajan, Dipa; Choudhury, Shanas; Boesmans, Werend; Delalande, Jean-Marie; Vanden Berghe, Pieter; Burns, Alan J.; Thapar, Nikhil

    2016-01-01

    Objectives Enteric neuropathies are severe gastrointestinal disorders with unsatisfactory outcomes. We aimed to investigate the potential of enteric neural stem cell therapy approaches for such disorders by transplanting mouse enteric neural crest cells (ENCCs) into ganglionic and aganglionic mouse gut in vivo and analysing functional integration and long-term safety. Design Neurospheres generated from yellow fluorescent protein (YFP) expressing ENCCs selected from postnatal Wnt1-cre;R26R-YFP/YFP murine gut were transplanted into ganglionic hindgut of wild-type littermates or aganglionic hindgut of Ednrbtm1Ywa mice (lacking functional endothelin receptor type-B). Intestines were then assessed for ENCC integration and differentiation using immunohistochemistry, cell function using calcium imaging, and long-term safety using PCR to detect off-target YFP expression. Results YFP+ ENCCs engrafted, proliferated and differentiated into enteric neurons and glia within recipient ganglionic gut. Transplanted cells and their projections spread along the endogenous myenteric plexus to form branching networks. Electrical point stimulation of endogenous nerve fibres resulted in calcium transients (F/F0 = 1.16±0.01;43 cells, n = 6) in YFP+ transplanted ENCCs (abolished with TTX). Long-term follow-up (24 months) showed transplanted ENCCs did not give rise to tumours or spread to other organs (PCR negative in extraintestinal sites). In aganglionic gut ENCCs similarly spread and differentiated to form neuronal and glial networks with projections closely associated with endogenous neural networks of the transition zone. Conclusions Transplanted ENCCs successfully engrafted into recipient ganglionic and aganglionic gut showing appropriate spread, localisation and, importantly, functional integration without any long-term safety issues. This study provides key support for the development and use of enteric neural stem cell therapies. PMID:26824433

  14. Long Term Stability Evaluation of Prostacyclin Released from Biomedical Device Through Turbiscan Lab Expert

    PubMed Central

    Celia, Christian; Locatelli, Marcello; Cilurzo, Felisa; Cosco, Donato; Gentile, Emanuela; Scalise, Daniela; Carafa, Maria; Ventura, Cinzia Anna; Fleury, Mathias; Tisserand, Christelle; Barbacane, Renato C.; Fresta, Massimo; Marzio, Luisa Di; Paolino, Donatella

    2015-01-01

    Therapeutic guidelines indicate prostacyclin as the first line of treatment in inflammation and vascular diseases. Prostacyclins prevent formation of the platelet plug involved in primary hemostasis by inhibiting platelet activation and, combined with thromboxane, are effective vasodilators in vascular damage. Trans-Atlantic Inter-Society Consensus Document on Management of Peripheral Arterial Disease II guidelines indicates prostacyclins; in particular, Iloprost, as the first therapeutic option for treating peripheral arterial disease. However, therapeutic efficacy of Iloprost has witnessed several drawbacks that have occurred in patients receiving repeated weekly administration of the drug by intravenous infusions. Adverse reactions arose under perfusion with Iloprost for 6 h and patient compliance was drastically decreased. Biomedical devices could provide a suitable alternative to overcome these drawbacks. In particular, elastomeric pumps, filled with Iloprost isotonic solution, could slowly release the drug, thus decreasing its side effects, representing a valid alternative to hospitalization of patients affected by peripheral arterial disease. However, the home therapy treatment of patients requires long-term stability of Iloprost in solution-loaded elastomeric pumps. The aim of this work was to investigate the long-term stability of Iloprost isotonic solution in biomedical devices using Turbiscan technology. Turbiscan Lab Expert (L’Union, France) predicts the long-term stability of suspensions, emulsions and colloidal formulations by measuring backscattering and transmission of particulates dispersed in solution. The formulations were evaluated by measuring the variation of physical-chemical properties of colloids and suspensions as a function of backscattering and transmission modifications. In addition, the release profile of Iloprost isotonic solution from the biomedical device was evaluated. PMID:25381994

  15. Long-term evaluation of a liquid crystal polymer (LCP)-based retinal prosthesis

    NASA Astrophysics Data System (ADS)

    Jeong, Joonsoo; Bae, So Hyun; Seo, Jong-Mo; Chung, Hum; Kim, Sung June

    2016-04-01

    Objective. The aim of this study is to evaluate the long-term reliability of a recently presented liquid crystal polymer (LCP) -based retinal prosthesis in vitro as well as in vivo. Because an all-polymer implant introduces another intrinsic leak type due to gas permeation, for which the traditional helium leak test for metallic packages was not designed to quantify, a new method to investigate its durability is required. Approach. We designed and carried out a series of reliability tests specifically for all-polymer implants by quantitatively investigating moisture ingress through various pathways of the polymer surface, and the polymer-polymer and polymer-metal adhesions. Moisture permeation through the bulk material was estimated by analytic calculation, while water ingress through the adhesively sealed LCP-LCP and LCP-metal interfaces was investigated using the separate parts of an electrode array and a package in an accelerated aging condition. In vivo tests were done in rabbits to examine the long-term biocompatibility and implantation stability by fundus observation and optical coherence tomography (OCT) imaging. Main results. The analytic calculation estimated good barrier properties of the LCP. Samples of the LCP-based electrode array failed after 114 days in 87 °C saline as a result of water penetration through the LCP-metal interface. An eye-conformable LCP package survived for 87 days in an accelerated condition at 87 °C. The in vivo results confirmed that no adverse effects were observed around the retina 2.5 years after the implantation of the device. Significance. These long-term evaluation results show the potential for the chronic use of LCP-based biomedical implants to provide an alternative to traditional metallic packages.

  16. Detecting long-term growth trends using tree rings: a critical evaluation of methods.

    PubMed

    Peters, Richard L; Groenendijk, Peter; Vlam, Mart; Zuidema, Pieter A

    2015-05-01

    Tree-ring analysis is often used to assess long-term trends in tree growth. A variety of growth-trend detection methods (GDMs) exist to disentangle age/size trends in growth from long-term growth changes. However, these detrending methods strongly differ in approach, with possible implications for their output. Here, we critically evaluate the consistency, sensitivity, reliability and accuracy of four most widely used GDMs: conservative detrending (CD) applies mathematical functions to correct for decreasing ring widths with age; basal area correction (BAC) transforms diameter into basal area growth; regional curve standardization (RCS) detrends individual tree-ring series using average age/size trends; and size class isolation (SCI) calculates growth trends within separate size classes. First, we evaluated whether these GDMs produce consistent results applied to an empirical tree-ring data set of Melia azedarach, a tropical tree species from Thailand. Three GDMs yielded similar results - a growth decline over time - but the widely used CD method did not detect any change. Second, we assessed the sensitivity (probability of correct growth-trend detection), reliability (100% minus probability of detecting false trends) and accuracy (whether the strength of imposed trends is correctly detected) of these GDMs, by applying them to simulated growth trajectories with different imposed trends: no trend, strong trends (-6% and +6% change per decade) and weak trends (-2%, +2%). All methods except CD, showed high sensitivity, reliability and accuracy to detect strong imposed trends. However, these were considerably lower in the weak or no-trend scenarios. BAC showed good sensitivity and accuracy, but low reliability, indicating uncertainty of trend detection using this method. Our study reveals that the choice of GDM influences results of growth-trend studies. We recommend applying multiple methods when analysing trends and encourage performing sensitivity and reliability

  17. Detecting long-term growth trends using tree rings: a critical evaluation of methods.

    PubMed

    Peters, Richard L; Groenendijk, Peter; Vlam, Mart; Zuidema, Pieter A

    2015-05-01

    Tree-ring analysis is often used to assess long-term trends in tree growth. A variety of growth-trend detection methods (GDMs) exist to disentangle age/size trends in growth from long-term growth changes. However, these detrending methods strongly differ in approach, with possible implications for their output. Here, we critically evaluate the consistency, sensitivity, reliability and accuracy of four most widely used GDMs: conservative detrending (CD) applies mathematical functions to correct for decreasing ring widths with age; basal area correction (BAC) transforms diameter into basal area growth; regional curve standardization (RCS) detrends individual tree-ring series using average age/size trends; and size class isolation (SCI) calculates growth trends within separate size classes. First, we evaluated whether these GDMs produce consistent results applied to an empirical tree-ring data set of Melia azedarach, a tropical tree species from Thailand. Three GDMs yielded similar results - a growth decline over time - but the widely used CD method did not detect any change. Second, we assessed the sensitivity (probability of correct growth-trend detection), reliability (100% minus probability of detecting false trends) and accuracy (whether the strength of imposed trends is correctly detected) of these GDMs, by applying them to simulated growth trajectories with different imposed trends: no trend, strong trends (-6% and +6% change per decade) and weak trends (-2%, +2%). All methods except CD, showed high sensitivity, reliability and accuracy to detect strong imposed trends. However, these were considerably lower in the weak or no-trend scenarios. BAC showed good sensitivity and accuracy, but low reliability, indicating uncertainty of trend detection using this method. Our study reveals that the choice of GDM influences results of growth-trend studies. We recommend applying multiple methods when analysing trends and encourage performing sensitivity and reliability

  18. Long-Term Benefits of Prompts to Use Safety Belts among Drivers Exiting Senior Communities

    ERIC Educational Resources Information Center

    Cox, Cory D.; Cox, Brian S.; Cox, Daniel J.

    2005-01-01

    Senior drivers are vulnerable to automobile crashes and subsequent injury and death. Safety belts reduce health risks associated with auto crashes. Therefore, it is important to encourage senior drivers to wear safety belts while driving. Using a repeated baseline design (AAB), we previously reported that motivating signs boosted safety belt usage…

  19. Short-term and long-term safety and tolerability of interferon β-1b in multiple sclerosis.

    PubMed

    Reder, Anthony T; Oger, Joel F; Kappos, Ludwig; O'Connor, Paul; Rametta, Mark

    2014-05-01

    Clinical trials have generated a wealth of data on the safety profile of interferon β-1b for patients with multiple sclerosis (MS). In general, interferon β-1b has not been associated with serious or life-threatening side effects during long-term treatment. Flu-like symptoms, injection site reactions, depression, and elevated liver transaminases were the most common adverse events in clinical trials. This review will discuss the rates of these and other common adverse events observed in 3 clinical trials of interferon β-1b: BENEFIT, BEYOND, and the 16-year Long-Term Follow-up (LTF) of the pivotal interferon β-1b trial in MS, as well as how these adverse events may influence patient and physician decision making when selecting a disease-modifying therapy. In addition, we will discuss the effects of interferon β-1b on mortality in the 16-year and 21-year LTF studies. PMID:25876467

  20. Long-term cardiovascular evaluation of patients with Hodgkin's disease treated by thoracic mantle radiation therapy

    SciTech Connect

    Applefeld, M.M.; Slawson, R.G.; Spicer, K.M.; Singleton, R.T.; Wesley, M.N.; Wiernik, P.H.

    1982-04-01

    The long-term cardiac effects of anterior-weighted thoracic mantle field radiotherapy were assessed in 25 patients treated for Hodgkin's disease. These patients underwent an evaluation that included a careful history and physical examination, ECG, M-mode echocardiogram, exercise ECG-gated radionuclide ventriculography, and cardiac catheterization. In these 25 patients evaluated 37-144 months (median, 96) after completion of thoracic mantle radiotherapy, eight had constrictive pericarditis; eight had occult constrictive pericarditis; three had an abnormal response to fluid challenge; three had suspected or proven occlusive coronary artery disease; and one each had a cardiomyopathy and diminished functional capacity on exercise testing. Only one patient appears to be normal after evaluation. The clinical spectrum of delayed-appearing radiation-induced cardiac disease in patients treated by anterior-weighted thoracic mantle fields and our suggestions for its treatment are discussed.

  1. Long-term safety of polypropylene knots under scleral flaps for transsclerally sutured posterior chamber lenses.

    PubMed Central

    Van Meter, W S

    1997-01-01

    PURPOSE: To evaluate the safety of polypropylene knots used in TS-SPCL combined with PK and AV over time. METHOD: A retrospective review of 26 consecutive cases of TS-SPCL by one surgeon (WSVM) with at least 12 months follow-up (mean 26, range 12-62). All patients had a double strand polypropylene knot buried under partial thickness scleral flaps at 2 and 8 o'clock. Knots were rotated into the globe (R) in 10 cases, and could not be buried (N) in 13 cases, and in 3 cases 1 knot was buried. RESULTS: No cases of suture erosion occurred in R or N. One or more polypropylene sutures were visible in 17 patients (8 R, 9 T) at last exam. Twenty-three of 52 knots were rotated into the globe, and 70% of rotated knots were not even visible at the slit lamp at final visit. There was no evidence of conjunctival erosion in any patient. There was no lens dislocation and no endophthalmitis. CONCLUSION: The combination of partial thickness scleral flaps with double strand polypropylene knots reduces the incidence of suture erosion through the conjunctive if knots cannot be rotated into the globe. Images FIGURE 1 FIGURE 2 FIGURE 3 PMID:9440177

  2. Long-term hydrolytic capacity evaluation of a thermophilic anaerobic digester treating sewage sludge.

    PubMed

    Donoso-Bravo, Andres; Pérez-Elvira, Sara; Wouwer, Alain Vande; Fdz-Polanco, Fernando

    2012-01-01

    This study presents an evaluation of the hydrolytic activity of a continuous thermophilic anaerobic reactor in long-term operation. The hydrolytic coefficient was estimated by fitting a three-reaction model of the anaerobic digestion process with experimental data obtained from a pilot thermophilic digester operated for about 2 years. The model fitting and the cross-validation indicate that this model can represent the behavior of the system in a proper way; moreover, the results show a variation of the hydrolytic capacity of the system throughout the evaluation period. The increase in the hydrolytic coefficient is in agreement with the increase in the organic load applied to the reactor, which shows the capacity of the continuous reactor to select populations according to the input conditions of the system.

  3. Evaluating multimodel variability of humidity over Europe using long term GPS network and ground base datasets

    NASA Astrophysics Data System (ADS)

    Bastin, Sophie; Bock, Olivier; Parracho, Ana

    2016-04-01

    Thanks to efforts made to reanalyse observed data to produce long-term homogenized datasets of new parameters or multi-parameters in recent years, we can better characterize, evaluate and analyse the water cycle in models at different scales. In this paper, a few MED-CORDEX simulations covering the ERA-interim period are evaluated against reprocessed IWV from GPS datasets over the European domain, from 1995 to 2008. The humidity is an important component of the water cycle, and models often have difficulties representing it. The high quality, consistent, long-term IWV dataset recently produced from GPS at more than 100 stations over Europe, with about half of the stations having nearly 15 years of data over the period from 1995 to 2010 is therefore used to evaluate the simulated IWV at seasonal, interannual and possibly diurnal time scales. Regional features are then identified, corresponding to different climate regimes. Other datasets, such as reanalysis of multi-parameters observed at one site (SIRTA, Palaiseau, France) over more than 10 years, or more regional networks are used to explain the dispersion of IWV among the different models and their biases against observations. The relationship between IWV and surface temperature is also evaluated locally to assess how much the sources of humidity from advection or surface fluxes are enough to reach the total capacity of the atmosphere in humidity when temperature increases. Over arid areas, this relation can depart from the Clausius-Clapeyron relation when temperature becomes too high. The ability of models to reproduce this relation during present climate is of high importance to estimate future climate.

  4. Long-term safety and efficacy of telmisartan/amlodipine single pill combination in the treatment of hypertension

    PubMed Central

    Billecke, Scott S; Marcovitz, Pamela A

    2013-01-01

    The use of multiple drug regimens is increasingly recognized as a tacit requirement for the management of hypertension, a necessity fueled in part by rising rates of metabolic syndrome and diabetes. By targeting complementary pathways, combinations of antihypertensive drugs can be applied to provide effective blood pressure control while minimizing side effects and reducing exposure to high doses of individual medications. In addition, combination therapies, including angiotensin converting enzyme (ACE) inhibitors and calcium channel blockers (CCBs), have the added benefit of reducing cardiovascular mortality and morbidity over other dual therapies while providing equivalent blood pressure control. It is possible that angiotensin receptor blockers (ARBs), which unlike ACE inhibitors are minimally affected by upregulation of alternative pathways for angiotensin II accumulation following long-term treatment, would also provide such outcome benefits. At issue, however, is maintaining patient compliance, as adding medications is known to reduce adherence to treatment regimens. The purpose of this review is to summarize existing trial data for the long-term safety and efficacy of a recent addition to the armamentarium of dual-antihypertensive therapeutic options, the telmisartan/amlodipine single pill combination. The areas where long-term data are lacking, notably clinical information regarding minorities and women, will also be discussed. PMID:23662062

  5. Evaluation of the long-term efficacy and safety of an imidacloprid 10%/flumethrin 4.5% polymer matrix collar (Seresto®) in dogs and cats naturally infested with fleas and/or ticks in multicentre clinical field studies in Europe

    PubMed Central

    2012-01-01

    Background The objective of these two GCP multicentre European clinical field studies was to evaluate the long-term efficacy and safety of a new imidacloprid/flumethrin collar (Seresto®, Bayer AnimalHealth, Investigational Veterinary Product(IVP)) in dogs and cats naturally infested with fleas and/or ticks in comparison to a dimpylat collar ("Ungezieferband fuer Hunde/fuer Katzen", Beaphar, Control Product (CP)). Methods 232 (IVP) and 81 (CP) cats and 271(IVP) and 129 (CP) dogs were treated with either product according to label claims and formed the safety population. Flea and tick counts were conducted in monthly intervals for up to 8 months in the efficacy subpopulation consisting of 118 (IVP) + 47 (CP) cats and 197 (IVP) + 94 (CP) dogs. Efficacy was calculated as reduction of infestation rate within the same treatment group and statistically compared between the two treatment groups. Results Preventive efficacy against fleas in cats/dogs varied in the IVP group between 97.4%/94.1% and 100%/100% (overall mean: 98.3%/96.7%) throughout the 8 month period and in the CP group between 57.1%/28.2% and 96.1%/67.8% (overall mean: 79.3%/57.9%). Preventive efficacy against ticks in cats/dogs varied in the IVP group between 94.0%/91.2% and 100%/100% (overall mean: 98.4%/94.7%) throughout the 8 month period and in the CP group between 90.7%/79.9% and 100%/88.0% (overall mean: 96.9%/85.6%). The IVP group was statistically non-inferior to the CP group, and on various assessment days, statistical superiority was proven for flea and tick count reduction in dogs and cats. Both treatments proved to be safe in dogs and cats with mainly minor local observations at the application site. There was moreover, no incidence of any mechanical problem with the collar in dogs and cats during the entire study period. Conclusions The imidacloprid/flumethrin collar proved to reduce tick counts by at least 90% and flea counts by at least 95% for a period of at least 7-8 months in cats and dogs

  6. Sustainable development and next generation's health: a long-term perspective about the consequences of today's activities for food safety.

    PubMed

    Frazzoli, Chiara; Petrini, Carlo; Mantovani, Alberto

    2009-01-01

    Development is defined sustainable when it meets the needs of the present without compromising the ability of future generations to meet their own needs. Pivoting on social, environmental and economic aspects of food chain sustainability, this paper presents the concept of sustainable food safety based on the prevention of risks and burden of poor health for generations to come. Under this respect, the assessment of long-term, transgenerational risks is still hampered by serious scientific uncertainties. Critical issues to the development of a sustainable food safety framework may include: endocrine disrupters as emerging contaminants that specifically target developing organisms; toxicological risks assessment in Countries at the turning point of development; translating knowledge into toxicity indexes to support risk management approaches, such as hazard analysis and critical control points (HACCP); the interplay between chemical hazards and social determinants. Efforts towards the comprehensive knowledge and management of key factors of sustainable food safety appear critical to the effectiveness of the overall sustainability policies.

  7. Long-term efficacy and safety of tocilizumab in giant cell arteritis and large vessel vasculitis

    PubMed Central

    Evans, Jobie; Steel, Lauren; Borg, Frances; Dasgupta, Bhaskar

    2016-01-01

    Giant cell arteritis (GCA) is a chronic systemic vasculitis affecting large-sized and medium-sized vessels. Glucocorticoids are currently the mainstay of treatment for GCA and associated large vessel vasculitis (LVV) but are associated with frequent adverse events. Methotrexate has only demonstrated a modest benefit while anti-TNF biological agents (infliximab and etanercept) have been inefficacious. Elevated levels of interleukin-6 (IL-6), a proinflammatory cytokine, has been associated with GCA. Tocilizumab (TCZ), a humanised antihuman IL-6 receptor antibody, has been used successfully in several reports as a treatment for GCA and LVV. We report the potentially long-term successful use of TCZ in 8 cases of refractory LVV. All of our patients achieved a good clinical response to TCZ and C reactive protein reduced from an average of 70.3 to 2.5. In all cases, the glucocorticoid dose was reduced, from an average of 24.6 mg prednisolone prior to TCZ treatment to 4.7 mg, indicating that TCZ may enable a reduction in glucocorticoid-associated adverse events. However, regular TCZ administration was needed for disease control in most cases. TCZ was discontinued in one case due to the development of an empyema indicating the need for careful monitoring of infection when using this treatment. PMID:26819753

  8. Criteria for the evaluation and certification of long-term digital archives in the earth sciences

    NASA Astrophysics Data System (ADS)

    Klump, Jens

    2010-05-01

    Digital information has become an indispensable part of our cultural and scientific heritage. Scientific findings, historical documents and cultural achievements are to a rapidly increasing extent being presented in electronic form - in many cases exclusively so. However, besides the invaluable advantages offered by this form, it also carries a serious disadvantage: users need to invest a great deal of technical effort in accessing the information. Also, the underlying technology is still undergoing further development at an exceptionally fast pace. The rapid obsolescence of the technology required to read the information combined with the frequently imperceptible physical decay of the media themselves represents a serious threat to preservation of the information content. Many data sets in earth science research are from observations that cannot be repeated. This makes these digital assets particularly valuable. Therefore, these data should be kept and made available for re-use long after the end of the project from which they originated. Since research projects only run for a relatively short period of time, it is advisable to shift the burden of responsibility for long-term data curation from the individual researcher to a trusted data repository or archive. But what makes a trusted data repository? Each trusted digital repository has its own targets and specifications. The trustworthiness of digital repositories can be tested and assessed on the basis of a criteria catalogue. This is the main focus of the work of the nestor working group "Trusted repositories - Certification". It identifies criteria which permit the trustworthiness of a digital repository to be evaluated, both at the organisational and technical levels. The criteria are defined in close collaboration with a wide range of different memory organisations, producers of information, experts and other interested parties. This open approach ensures a high degree of universal validity, suitability for

  9. Gasbuggy, New Mexico Long-Term Hydrologic Monitoring Program Evaluation Report

    SciTech Connect

    2009-06-01

    This report summarizes an evaluation of the Long-Term Hydrologic Monitoring Program (LTHMP) that has been conducted since 1972 at the Gasbuggy, New Mexico underground nuclear detonation site. The nuclear testing was conducted by the U.S. Atomic Energy Commission under the Plowshare program, which is discussed in greater detail in Appendix A. The detonation at Gasbuggy took place in 1967, 4,240 feet below ground surface, and was designed to fracture the host rock of a low-permeability natural gas-bearing formation in an effort to improve gas production. The site has historically been managed under the Nevada Offsites Project. These underground nuclear detonation sites are within the United States but outside of the Nevada Test Site where most of the experimental nuclear detonations conducted by the U.S. Government took place. Gasbuggy is managed by the U.S. Department of Energy (DOE) Office of Legacy Management (LM ).

  10. Climate considerations in long-term safety assessments for nuclear waste repositories.

    PubMed

    Näslund, Jens-Ove; Brandefelt, Jenny; Liljedahl, Lillemor Claesson

    2013-05-01

    For a deep geological repository for spent nuclear fuel planned in Sweden, the safety assessment covers up to 1 million years. Climate scenarios range from high-end global warming for the coming 100 000 years, through deep permafrost, to large ice sheets during glacial conditions. In contrast, in an existing repository for short-lived waste the activity decays to low levels within a few tens of thousands of years. The shorter assessment period, 100 000 years, requires more focus on climate development over the coming tens of thousands of years, including the earliest possibility for permafrost growth and freezing of the engineered system. The handling of climate and climate change in safety assessments must be tailor-made for each repository concept and waste type. However, due to the uncertain future climate development on these vast time scales, all safety assessments for nuclear waste repositories require a range of possible climate scenarios.

  11. Comparison of Long-Term Safety and Efficacy Outcomes after Drug-Eluting and Bare-Metal Stent Use across Racial Groups: insights from NHLBI Dynamic Registry

    PubMed Central

    Olafiranye, Oladipupo; Vlachos, Helen; Mulukutla, Suresh R.; Marroquin, Oscar; Selzer, Faith; Kelsey, Sheryl F.; Williams, David O.; Strollo, Patrick J.; Reis, Steven E.; Lee, Joon S.; Smith, AJ. Conrad

    2015-01-01

    Background Long-term data on outcomes after percutaneous coronary intervention (PCI) with drug-eluting stent (DES) and bare-metal stent (BMS) across racial groups are limited, and minorities are under-represented in existing clinical trials. Whether DES has better long-term clinical outcomes compared to BMS across racial groups remains to be established. Accordingly, we assessed whether longer-term clinical outcomes are better with DES compared to BMS across racial groups. Methods Using the multicenter National Heart, Lung, and Blood Institute (NHLBI)-sponsored Dynamic Registry, 2-year safety (death, MI) and efficacy (repeat revascularization) outcomes of 3,326 patients who underwent PCI with DES versus BMS were evaluated. Results With propensity-score adjusted analysis, the use of DES, compared to BMS, was associated with a lower risk for death or MI at 2 years for both blacks (adjusted Hazard Ratio (aHR)=0.41, 95% CI 0.25–0.69, p<0.001) and whites (aHR=0.67, 95% CI 0.51–0.90, p=0.007). DES use was associated with a significant 24% lower risk of repeat revascularization in whites (aHR=0.76, 95% CI 0.60–0.97, p=0.03) and with nominal 34% lower risk in blacks (aHR=0.66, 95% CI 0.39–1.13, p=0.13). Conclusion Use of DES in PCI was associated with better long-term safety outcomes across racial groups. Compared to BMS, DES was more effective in reducing repeat revascularization in whites and blacks, but this benefit was attenuated after statistical adjustment in blacks. These findings indicate that DES is superior to BMS in all patients regardless of race. Further studies are needed to determine long-term outcomes across racial groups with newer generation stents. PMID:25697874

  12. Evaluation of focused multipolar stimulation for cochlear implants in long-term deafened cats

    NASA Astrophysics Data System (ADS)

    George, Shefin S.; Wise, Andrew K.; Fallon, James B.; Shepherd, Robert K.

    2015-06-01

    Objective. Focused multipolar (FMP) stimulation has been shown to produce restricted neural activation using intracochlear stimulation in animals with a normal population of spiral ganglion neurons (SGNs). However, in a clinical setting, the widespread loss of SGNs and peripheral fibres following deafness is expected to influence the effectiveness of FMP. Approach. We compared the efficacy of FMP stimulation to both monopolar (MP) and tripolar (TP) stimulation in long-term deafened cat cochleae (n = 8). Unlike our previous study, these cochleae contained <10% of the normal SGN population adjacent to the electrode array. We also evaluated the effect of electrode position on stimulation modes by using either modiolar facing or lateral wall facing half-band electrodes. The spread of neural activity across the inferior colliculus, a major nucleus within the central auditory pathway, was used as a measure of spatial selectivity. Main results. In cochleae with significant SGN degeneration, we observed that FMP and TP stimulation resulted in greater spatial selectivity than MP stimulation (p < 0.001). However, thresholds were significantly higher for FMP and TP stimulation compared to MP stimulation (p < 0.001). No difference between FMP and TP stimulation was found in any measures. The high threshold levels for FMP stimulation was significantly reduced without compromising spatial selectivity by varying the degree of current focusing (referred as ‘partial-FMP’ stimulation). Spatial selectivity of all stimulation modes was unaffected by the electrode position. Finally, spatial selectivity in long-term deafened cochleae was significantly less than that of cochleae with normal SGN population (George S S et al 2014 J. Neural Eng. 11 065003). Significance. The present results indicate that the greater spatial selectivity of FMP and TP stimulation over MP stimulation is maintained in cochleae with significant neural degeneration and is not adversely affected by electrode

  13. Long-term safety and efficacy of dutasteride in the treatment of male patients with androgenetic alopecia.

    PubMed

    Tsunemi, Yuichiro; Irisawa, Ryokichi; Yoshiie, Hiromu; Brotherton, Betsy; Ito, Hisahiro; Tsuboi, Ryoji; Kawashima, Makoto; Manyak, Michael

    2016-09-01

    Androgenetic alopecia is an androgen-induced pattern of progressive hair loss, which occurs in genetically predisposed people. This study aimed to determine long-term safety, tolerability and efficacy of dutasteride 0.5 mg, an inhibitor of 5-α-reductase, in Japanese male patients with androgenetic alopecia. This was a multicenter, open-label, prospective outpatient study (clinicaltrials.gov NCT01831791, GSK identifier ARI114264) in which patients took dutasteride 0.5 mg p.o. once daily for 52 weeks. Primary end-points included adverse event assessment, incidence of drug-related adverse event and premature discontinuations. Secondary end-points included hair growth, hair restoration and global improvement in hair. A total of 120 patients were enrolled, of whom 110 completed 52 weeks of treatment. Nasopharyngitis, erectile dysfunction and decreased libido were the most frequently reported adverse events and most adverse events were mild. Drug-related adverse events were reported with an incidence of 17%, none of which led to study withdrawal. Hair growth (mean target area hair count at week 52), hair restoration (mean target area hair width at week 52) and global appearance of hair (mean of the median score at week 52) improved from baseline during the study. As a potential future treatment option for male androgenetic alopecia, dutasteride 0.5 mg exhibited long-term safety, tolerability and efficacy within this study population. PMID:26893187

  14. Evaluation of microbial activity for long-term performance assessments of deep geologic nuclear waste repositories.

    SciTech Connect

    Francis, Arokiasamy J.; Wang, Yifeng

    2005-06-01

    Microorganisms are ubiquitous in subsurface environments and play a major role in the biogeochemical recycling of various elements. In this paper, we have developed a general approach for a systematic evaluation of microbial impact on the long-term performance of the repository. We have demonstrated that data on microbial population alone are not sufficient for the evaluation of microbial impact on repository performance and a sensible approach for such evaluation must be based on the consideration of environmental constraints on microbial reaction pathways. We have applied our approach to both the Yucca Mountain (YM) repository and the Waste Isolation Pilot Plant (WIPP). We have demonstrated that the effect of microbial activity on the near-field chemistry in the Yucca Mountain repository is negligible because of limited nutrient supply and harsh environmental conditions created by waste emplacement. Whereas for the WIPP, we have shown that, due to the presence of a large quantity of organic materials and nutrients in the wastes, a significant microbial activity can potentially be stimulated and its impact on repository performance can be evaluated with carefully designed incubation experiments coupled with performance assessment calculations. The impact of microbial gas generation on disposal room chemistry in the WIPP can be mitigated by introducing MgO as a backfill material.

  15. Evaluation of the long-term performance of six alternative disposal methods for LLRW

    SciTech Connect

    Kossik, R.; Sharp, G.; Chau, T.

    1995-12-31

    The State of New York has carried out a comparison of six alternative disposal methods for low-level radioactive waste (LLRW). An important part of these evaluations involved quantitatively analyzing the long-term (10,000 yr) performance of the methods with respect to dose to humans, radionuclide concentrations in the environment, and cumulative release from the facility. Four near-surface methods (covered above-grade vault, uncovered above-grade vault, below-grade vault, augered holes) and two mine methods (vertical shaft mine and drift mine) were evaluated. Each method was analyzed for several generic site conditions applicable for the state. The evaluations were carried out using RIP (Repository Integration Program), an integrated, total system performance assessment computer code which has been applied to radioactive waste disposal facilities both in the U.S. (Yucca Mountain, WIPP) and worldwide. The evaluations indicate that mines in intact low-permeability rock and near-surface facilities with engineered covers generally have a high potential to perform well (within regulatory limits). Uncovered above-grade vaults and mines in highly fractured crystalline rock, however, have a high potential to perform poorly, exceeding regulatory limits.

  16. Long-term safety of abatacept in patients with rheumatoid arthritis.

    PubMed

    Atzeni, Fabiola; Sarzi-Puttini, Piercarlo; Mutti, Alessandra; Bugatti, Serena; Cavagna, Lorenzo; Caporali, Roberto

    2013-10-01

    Abatacept is a selective T cell co-stimulation modulator that was first approved by the Italian Medicines Agency and reimbursed by the Italian National Health Service when used to treat active rheumatoid arthritis "not sufficiently responsive to other disease-modifying anti-rheumatic drugs (DMARDs) including at least one TNF inhibitor", and is now also approved as a first line biological agent. The aim of this review is to summarise the safety data collected in clinical trials and observational studies.

  17. Glatiramer acetate: long-term safety and efficacy in relapsing-remitting multiple sclerosis.

    PubMed

    Boster, Aaron L; Ford, Corey C; Neudorfer, Orit; Gilgun-Sherki, Yossi

    2015-06-01

    Glatiramer acetate (GA) is approved for relapsing-remitting multiple sclerosis in 57 countries worldwide, with more than 2 million patient-years of exposure and over 20 years of continuous clinical use without new safety concerns. GA has an overall favorable risk-benefit profile: 30% reduced annual relapse rate and decreased brain lesion activity. In clinically definite MS or clinically isolated syndrome, GA slows brain atrophy, which may be related to its unique anti-inflammatory and neuroprotective mechanisms of action. Early treatment with GA delays the onset of clinically definite MS more effectively than late treatment in clinically isolated syndrome. GA is not associated with immunosuppression, autoimmune disease, infections or development of neutralizing antibodies. A new three-times-weekly formulation of GA is available to potentially reduce the incidence of injection-related side effects. Other safety advantages of GA include its pregnancy rating (Category B) and limited uncontrolled data suggesting that tolerability is similar in children with MS. PMID:25924547

  18. Long-term clinical evaluation of fixed dentures--two to fifteen years after insertion.

    PubMed

    Hubálková, H; Charvát, J; Dostálová, T; Linetskiy, I

    2005-01-01

    Fixed denture durability is characterized as a period of time for which a dental appliance satisfies functional and esthetic requirements. First of all, its durability is based on the properties of materials it is made of, and depends, at the same time, on the characteristics of biological environment, in which the denture is placed. The purpose of this study was a long-term monitoring of changes taking place in the fixed dental constructions during their application in the oral cavity. These changes were to be evaluated for different types of materials used for fixed dentures manufacturing, namely metal alloys, ceramics, and plastics. A set of 454 full crowns from 134 patients divided in 6 clinical studies was examined and both qualitative and quantitative changes evaluated after 2 and 8 to 15 years after cementation. Clinical assessment adopted the United States Public Health Service System criteria. Alloys of precious metals veneered with ceramics are considered the optimal method of choice for both high precision of execution and consideration of future changes brought on by the use of the dentures. PMID:16007909

  19. EVALUATION OF RADIONUCLIDE ACCUMULATION IN SOIL DUE TO LONG-TERM IRRIGATION

    SciTech Connect

    De Wesley Wu

    2006-04-16

    Radionuclide accumulation in soil due to long-term irrigation is an important part of the model for predicting radiation dose in a long period of time. The model usually assumes an equilibrium condition in soil with a constant irrigation rate, so that radionuclide concentration in soil does not change with time and can be analytically solved. This method is currently being used for the dose assessment in the Yucca Mountain project, which requires evaluating radiation dose for a period of 10,000 years. There are several issues associated with the method: (1) time required for the equilibrium condition, (2) validity of constant irrigation rate, (3) agricultural land use for a long period of time, and (4) variation of a radionuclide concentration in water. These issues are evaluated using a numerical method with a simple model built in the GoldSim software. Some key radionuclides, Tc-99, Np-237, Pu-239, and Am-241 are selected as representative radionuclides. The results indicate that the equilibrium model is acceptable except for a radionuclide that requires long time to accumulate in soil and that its concentration in water changes dramatically with time (i.e. a sharp peak). Then the calculated dose for that radionuclide could be overestimated using the current equilibrium method.

  20. Long-term performance evaluation of wood fibre fills. Final report

    SciTech Connect

    Kilian, A.P.; Ferry, C.D.

    1992-08-01

    The paper presents the results of a research project to determine the long-term performance of wood fiber embankments, that were constructed by the Washington State Department of Transportation (WSDOT) beginning in 1972. At the time of their construction, concern existed that wood fiber fills would only provide a 15 to 20 year service life. Performance of existing wood fiber fills was evaluated based on the quality of the wood fiber material, quality of the effluent, and condition of the pavement. A visual classification system rating the wood fiber from fresh to completely decomposed was developed and used in order to establish a criteria from which all wood fiber material could be rated. Visual examination in conjunction with laboratory tests were used as determining aspects for the effluent quality. The WSDOT Pavement Management System was used to evaluate relative pavement performance. Site descriptions are presented giving specific characteristics and properties of the fills inventoried. An analysis of this information was done to determine the effectiveness of the fills. Over half the wood fiber samples were found to be nearly fresh or fresh and none were found to be completely decomposed. In all but one case, the pavement quality over the wood fiber fills surpassed the comparative highway segment rating indicating the wood fill's performance exceeded that of the surrounding area.

  1. Evaluating Clouds in Long-Term Cloud-Resolving Model Simulations with Observational Data

    NASA Technical Reports Server (NTRS)

    Zeng, Xiping; Tao, Wei-Kuo; Zhang, Minghua; Peters-Lidard, Christa; Lang, Stephen; Simpson, Joanne; Kumar, Sujay; Xie, Shaocheng; Eastman, Joseph L.; Shie, Chung-Lin; Geiger, James V.

    2006-01-01

    Two 20-day, continental midlatitude cases are simulated with a three-dimensional (3D) cloud-resolving model (CRM) and compared to Atmospheric Radiation Measurement (ARM) data. This evaluation of long-term cloud-resolving model simulations focuses on the evaluation of clouds and surface fluxes. All numerical experiments, as compared to observations, simulate surface precipitation well but over-predict clouds, especially in the upper troposphere. The sensitivity of cloud properties to dimensionality and other factors is studied to isolate the origins of the over prediction of clouds. Due to the difference in buoyancy damping between 2D and 3D models, surface precipitation fluctuates rapidly with time, and spurious dehumidification occurs near the tropopause in the 2D CRM. Surface fluxes from a land data assimilation system are compared with ARM observations. They are used in place of the ARM surface fluxes to test the sensitivity of simulated clouds to surface fluxes. Summertime simulations show that surface fluxes from the assimilation system bring about a better simulation of diurnal cloud variation in the lower troposphere.

  2. Long-term leaching test of incinerator bottom ash: Evaluation of Cu partition

    SciTech Connect

    Lin, Cheng-Fang Wu, Chung-Hsin; Liu, Yen-Chiun

    2007-07-01

    Two types of leaching tests were performed on the bottom ash from municipal solid waste incinerators. A short-term batch test specified by the America Nuclear Society (ANS) and long-term column tests with acetic acid (pH 5.2) as leaching solution were used to evaluate copper leachability. The Cu leaching after the 5-d ANS test is about 1% of the original Cu content of 5300 mg/kg. Upon addition of a stabilizing agent, the Cu leaching quantity is reduced; the extent of reduction depends on the type of chemical used (phosphate, carbonate and sulfide). The 1.6% Na{sub 2}S addition showed negligible Cu leaching, and Na{sub 2}S was, therefore, used in subsequent column tests. The 30-d column test indicates a steady increase of Cu leaching amount with time and reaches about 1.5% of the original Cu content after 30 d. A 180-d column test further increased the Cu leaching to about 5.1% of the original Cu content, whereas no appreciable Cu leaching was found with the addition of 1.6% Na{sub 2}S. A sequential extraction was conducted on the raw ash, ash with the addition of Na{sub 2}S and the residue ash after 30 d of operation to characterize Cu affinity for different solid fractions. The data were used to evaluate the fate of Cu through these interactions.

  3. Long-term safety and efficacy of etanercept in the treatment of ankylosing spondylitis.

    PubMed

    Senabre-Gallego, José Miguel; Santos-Ramírez, Carlos; Santos-Soler, Gregorio; Salas-Heredia, Esteban; Sánchez-Barrioluengo, Mabel; Barber, Xavier; Rosas, José

    2013-01-01

    To date, anti-tumor necrosis factor alfa (anti-TNF-α) therapy is the only alternative to nonsteroidal anti-inflammatory drugs for the treatment of ankylosing spondylitis. Etanercept is a soluble TNF receptor, with a mode of action and pharmacokinetics different to those of antibodies and distinctive efficacy and safety. Etanercept has demonstrated efficacy in the treatment of ankylosing spondylitis, with or without radiographic sacroiliitis, and other manifestations of the disease, including peripheral arthritis, enthesitis, and psoriasis. Etanercept is not efficacious in inflammatory bowel disease, and its efficacy in the treatment of uveitis appears to be lower than that of other anti-TNF drugs. Studies of etanercept confirmed regression of bone edema on magnetic resonance imaging of the spine and sacroiliac joint, but failed to reduce radiographic progression, as do the other anti-TNF drugs. It seems that a proportion of patients remain in disease remission when the etanercept dose is reduced or administration intervals are extended. Etanercept is generally well tolerated with an acceptable safety profile in the treatment of ankylosing spondylitis. The most common adverse effect of etanercept treatment is injection site reactions, which are generally self-limiting. Reactivation of tuberculosis, reactivation of hepatitis B virus infection, congestive heart failure, demyelinating neurologic disorders, hematologic disorders like aplastic anemia and pancytopenia, vasculitis, immunogenicity, and exacerbation or induction of psoriasis are class effects of all the anti-TNF drugs, and have been seen in patients with ankylosing spondylitis. However, etanercept is less likely to induce reactivation of tuberculosis than the other anti-TNF drugs and it has been suggested that etanercept might be less immunogenic, especially in ankylosing spondylitis. Acute uveitis, Crohn's disease, and sarcoidosis are other adverse events that have been rarely associated with etanercept

  4. Long-term safety and efficacy of etanercept in the treatment of ankylosing spondylitis

    PubMed Central

    Senabre-Gallego, José Miguel; Santos-Ramírez, Carlos; Santos-Soler, Gregorio; Salas-Heredia, Esteban; Sánchez-Barrioluengo, Mabel; Barber, Xavier; Rosas, José

    2013-01-01

    To date, anti-tumor necrosis factor alfa (anti-TNF-α) therapy is the only alternative to nonsteroidal anti-inflammatory drugs for the treatment of ankylosing spondylitis. Etanercept is a soluble TNF receptor, with a mode of action and pharmacokinetics different to those of antibodies and distinctive efficacy and safety. Etanercept has demonstrated efficacy in the treatment of ankylosing spondylitis, with or without radiographic sacroiliitis, and other manifestations of the disease, including peripheral arthritis, enthesitis, and psoriasis. Etanercept is not efficacious in inflammatory bowel disease, and its efficacy in the treatment of uveitis appears to be lower than that of other anti-TNF drugs. Studies of etanercept confirmed regression of bone edema on magnetic resonance imaging of the spine and sacroiliac joint, but failed to reduce radiographic progression, as do the other anti-TNF drugs. It seems that a proportion of patients remain in disease remission when the etanercept dose is reduced or administration intervals are extended. Etanercept is generally well tolerated with an acceptable safety profile in the treatment of ankylosing spondylitis. The most common adverse effect of etanercept treatment is injection site reactions, which are generally self-limiting. Reactivation of tuberculosis, reactivation of hepatitis B virus infection, congestive heart failure, demyelinating neurologic disorders, hematologic disorders like aplastic anemia and pancytopenia, vasculitis, immunogenicity, and exacerbation or induction of psoriasis are class effects of all the anti-TNF drugs, and have been seen in patients with ankylosing spondylitis. However, etanercept is less likely to induce reactivation of tuberculosis than the other anti-TNF drugs and it has been suggested that etanercept might be less immunogenic, especially in ankylosing spondylitis. Acute uveitis, Crohn’s disease, and sarcoidosis are other adverse events that have been rarely associated with etanercept

  5. The evaluation of the National Long Term Care Demonstration. 3. Recruitment and characteristics of channeling clients.

    PubMed

    Applebaum, R A

    1988-04-01

    The National Long Term Care Demonstration (channeling) was designed to provide coordinated community-based long-term care services to those older persons at high risk of nursing home placement. A key component of the program was the process established to accomplish this targeting effort. In this article, the outreach and eligibility procedures developed in the demonstration are described. Characteristics of channeling clients are compared to those of clients from other long-term care demonstrations, a national nursing home sample, and a simulated national sample of functionally impaired older persons. Results indicate that the channeling clients were quite frail, more so than the clients served in most of the other long-term care demonstrations, but were younger, slightly less disabled, and more likely to be married than a national sample of nursing home residents.

  6. Evaluating the clinical and physiological effects of long term ultraviolet B radiation on guinea pigs (Cavia porcellus).

    PubMed

    Watson, Megan K; Stern, Adam W; Labelle, Amber L; Joslyn, Stephen; Fan, Timothy M; Leister, Katie; Kohles, Micah; Marshall, Kemba; Mitchell, Mark A

    2014-01-01

    Vitamin D is an important hormone in vertebrates. Most animals acquire this hormone through their diet, secondary to exposure to ultraviolet B (UVB) radiation, or a combination thereof. The objectives for this research were to evaluate the clinical and physiologic effects of artificial UVB light supplementation on guinea pigs (Cavia porcellus) and to evaluate the long-term safety of artificial UVB light supplementation over the course of six months. Twelve juvenile acromelanic Hartley guinea pigs were randomly assigned to one of two treatment groups: Group A was exposed to 12 hours of artificial UVB radiation daily and Group B received only ambient fluorescent light for 12 hours daily. Animals in both groups were offered the same diet and housed under the same conditions. Blood samples were collected every three weeks to measure blood chemistry values, parathyroid hormone, ionized calcium, and serum 25-hydroxyvitamin D3 (25-OHD3) levels. Serial ophthalmologic examinations, computed tomography scans, and dual energy x-ray absorptiometry scans were performed during the course of the study. At the end of the study the animals were euthanized and necropsied. Mean ± SD serum 25-OHD3 concentrations differed significantly in the guinea pigs (p<0.0001) between the UVB supplementation group (101.49±21.81 nmol/L) and the control group (36.33±24.42 nmol/L). An increased corneal thickness in both eyes was also found in the UVB supplementation compared to the control group (right eye [OD]: p<0.0001; left eye [OS]: p<0.0001). There were no apparent negative clinical or pathologic side effects noted between the groups. This study found that exposing guinea pigs to UVB radiation long term significantly increased their circulating serum 25-OHD3 levels, and that this increase was sustainable over time. Providing guinea pigs exposure to UVB may be an important husbandry consideration that is not currently recommended. PMID:25517408

  7. Evaluating the Clinical and Physiological Effects of Long Term Ultraviolet B Radiation on Guinea Pigs (Cavia porcellus)

    PubMed Central

    Watson, Megan K.; Stern, Adam W.; Labelle, Amber L.; Joslyn, Stephen; Fan, Timothy M.; Leister, Katie; Kohles, Micah; Marshall, Kemba; Mitchell, Mark A.

    2014-01-01

    Vitamin D is an important hormone in vertebrates. Most animals acquire this hormone through their diet, secondary to exposure to ultraviolet B (UVB) radiation, or a combination thereof. The objectives for this research were to evaluate the clinical and physiologic effects of artificial UVB light supplementation on guinea pigs (Cavia porcellus) and to evaluate the long-term safety of artificial UVB light supplementation over the course of six months. Twelve juvenile acromelanic Hartley guinea pigs were randomly assigned to one of two treatment groups: Group A was exposed to 12 hours of artificial UVB radiation daily and Group B received only ambient fluorescent light for 12 hours daily. Animals in both groups were offered the same diet and housed under the same conditions. Blood samples were collected every three weeks to measure blood chemistry values, parathyroid hormone, ionized calcium, and serum 25-hydroxyvitamin D3 (25-OHD3) levels. Serial ophthalmologic examinations, computed tomography scans, and dual energy x-ray absorptiometry scans were performed during the course of the study. At the end of the study the animals were euthanized and necropsied. Mean ± SD serum 25-OHD3 concentrations differed significantly in the guinea pigs (p<0.0001) between the UVB supplementation group (101.49±21.81 nmol/L) and the control group (36.33±24.42 nmol/L). An increased corneal thickness in both eyes was also found in the UVB supplementation compared to the control group (right eye [OD]: p<0.0001; left eye [OS]: p<0.0001). There were no apparent negative clinical or pathologic side effects noted between the groups. This study found that exposing guinea pigs to UVB radiation long term significantly increased their circulating serum 25-OHD3 levels, and that this increase was sustainable over time. Providing guinea pigs exposure to UVB may be an important husbandry consideration that is not currently recommended. PMID:25517408

  8. Long-term endurance and safety of elosulfase alfa enzyme replacement therapy in patients with Morquio A syndrome.

    PubMed

    Hendriksz, Christian J; Parini, Rossella; AlSayed, Moeenaldeen D; Raiman, Julian; Giugliani, Roberto; Solano Villarreal, Martha L; Mitchell, John J; Burton, Barbara K; Guelbert, Norberto; Stewart, Fiona; Hughes, Derralynn A; Berger, Kenneth I; Slasor, Peter; Matousek, Robert; Jurecki, Elaina; Shaywitz, Adam J; Harmatz, Paul R

    2016-09-01

    Long-term efficacy and safety of elosulfase alfa enzyme replacement therapy were evaluated in Morquio A patients over 96weeks (reaching 120weeks in total from pre-treatment baseline) in an open-label, multi-center, phase III extension study. During this extension of a 24-week placebo-controlled phase III study, all patients initially received 2.0mg/kg elosulfase alfa either weekly or every other week, prior to establishment of 2.0mg/kg/week as the recommended dose, at which point all patients received weekly treatment. Efficacy measures were compared to baseline of the initial 24-week study, enabling analyses of changes over 120weeks. In addition to performing analyses for the entire intent-to-treat (ITT) population (N=173), analyses were also performed for a modified per-protocol (MPP) population (N=124), which excluded patients who had orthopedic surgery during the extension study or were non-compliant with the study protocol (as determined by ≥20% missed infusions). Six-minute walk test (6MWT) was the primary efficacy measure; three-minute stair climb test (3MSCT) and normalized urine keratan sulfate (uKS) were secondary efficacy measures. Mean (SE) change from baseline to Week 120 in 6MWT distance was 32.0 (11.3)m and 39.9 (10.1)m for patients receiving elosulfase alfa at 2.0mg/kg/week throughout the study (N=56) and 15.1 (7.1)m and 31.7 (6.8)m in all patients combined, regardless of dosing regimen, for the ITT and MPP populations, respectively. Further analyses revealed that durability of 6MWT improvements was not impacted by baseline 6MWT distance, use of a walking aid, or age. Mean (SE) change at Week 120 in the 3MSCT was 5.5 (1.9) and 6.7 (2.0)stairs/min for patients receiving elosulfase alfa at 2.0mg/kg/week throughout the study and 4.3 (1.2) and 6.8 (1.3)stairs/min in all patients combined, regardless of dosing regimen, for the ITT and MPP populations, respectively Across all patients, mean (SE) change at Week 120 in normalized uKS was -59.4 (1.8)% and

  9. Safety and Long-Term Performance of Lithium-ion Pouch Cells

    NASA Technical Reports Server (NTRS)

    Jeevarajan, Judith

    2012-01-01

    Lithium-ion batteries have the highest energy density of the batteries available in the commercial market today. Although most lithium-ion cell designs use a metal can design, this has changed significantly in recent years. Cell designs are offered in the pouch format as they offer better volumetric and gravimetric energy densities and in some cases, higher tolerance to abuse or off-nominal conditions. In the past decade, several state-of-the-art lithium-ion pouch cell designs have been tested. The pouch cell designs have become more robust in the past two years but there are still a few issues that need to be looked into for optimization. The pouch cells seem to have a tendency to swell when left in storage under ambient conditions. The cells also swell under overvoltage and undervoltage conditions. A significant issue that has been observed is the swelling of the cells under a vacuum condition which could lead to deformation of the cell pouch after this exposure. This last factor would be very critical in the use of these cell designs for space applications as vacuum exposure is used to check for cell and battery leaks before it is flown into space. In rare cases, corrosion of the aluminum layer of the pouches has been observed in stored cells. Pouch material analysis has been carried out in an effort to understand the strength of the pouches and determine if this is a factor in the corrosion as well as unsafe condition of the cells as deformation of the inner layers of the pouch could occur when the cells swell under the various conditions described above. Pouch materials are typically aluminized plastic, made up of a layer of Al sandwiched between one or more layers of polymeric material. Deformations or cell manufacturing processes could lead to a compromise of the inner polymeric layer/s of the pouch leading to the corrosion of the Al layer in the aluminized pouch material. The safety of the pouch cell designs has been determined for cells from various

  10. Long-term safety and effectiveness of sildenafil citrate in men with erectile dysfunction

    PubMed Central

    McMurray, James G; Feldman, Robert A; Auerbach, Stephen M; DeRiesthal, Herb; Wilson, Neal

    2007-01-01

    Because sildenafil citrate is a treatment, not a cure, for erectile dysfunction (ED), many men may choose to use it for an extended period. Men with ED who had previously completed 1 of 4 double-blind trials with short-term open-label extension (combined duration, 0.9–1.2 years) were eligible for this 4-year, open-label, extension study, which assessed the safety and effectiveness of flexible doses (25, 50, and 100 mg sildenafil) used as needed. Adverse events that were serious or led to dosing changes or discontinuation (temporary or permanent) were recorded. Many of the 979 participants (mean age, 58 [range, 27–82] years; mean ED duration, 4.5 years) had concomitant hypertension (28%), diabetes (22%), or hyperlipidemia (14%). Overall, 37 (3.8%) had treatment-related adverse events (none serious) requiring dosage change or discontinuation and 62 (6.3%) discontinued because of insufficient response. At each yearly assessment, more than 94% of participants responded affirmatively to the questions: “Are you satisfied with the effect of treatment on your erections?” and “If yes, has treatment improved your ability to engage in sexual activity?” These results argue against the loss of tolerability or the development of tachyphylaxis over a prolonged period of as needed, flexible-dose sildenafil treatment of men with ED. PMID:18516312

  11. Effects of approach and services under differential response on long term child safety and welfare.

    PubMed

    Loman, L Anthony; Siegel, Gary L

    2015-01-01

    An outcome analysis was conducted based on an extended follow-up of the implementation of differential response program reforms in Child Protective Services offices in 10 counties in a Midwestern U.S. State. Random assignment was conducted of families that were first determined to be appropriate for family assessments. Experimental families (n=2,382) were each assigned to a non-forensic family assessment, and control families (n=2,247) each received a forensic investigation. Families were assigned continuously over a 15-month period and then tracked from 45 to 60 months from the date of assignment. Detailed information on services provided and family responses was obtained via two subsamples of experimental and control families. Measures of family engagement and service reception and utilization were utilized to determine instrumental outcomes introduced through family assessments. Improved family engagement and increased and broadened services were found to have occurred, and it was theorized that these changes mediated extended outcomes. Extended outcomes included reductions of rates of subsequent screened-in reports of child maltreatment, proportions of families that experienced child removals, and instances of new safety threats and problems in parenting. Differences in outcomes were found among the participating counties with 4 counties accounting for most outcome differences. The relationships between instrumental and extended outcomes were discussed with suggestions for further research. PMID:24957562

  12. Long-term evaluation of home-based pulmonary rehabilitation in patients with COPD

    PubMed Central

    Grosbois, Jean Marie; Gicquello, Alice; Langlois, Carole; Le Rouzic, Olivier; Bart, Frédéric; Wallaert, Benoit; Chenivesse, Cécile

    2015-01-01

    Introduction Personalized, global pulmonary rehabilitation (PR) management of patients with COPD is effective, regardless of the place in which this rehabilitation is provided. The objective of this retrospective observational study was to study the long-term outcome of exercise capacity and quality of life during management of patients with COPD treated by home-based PR. Methods Home-based PR was administered to 211 patients with COPD (mean age, 62.3±11.1 years; mean forced expiratory volume in 1 second, 41.5%±17.7%). Home-based PR was chosen because of the distance of the patient’s home from the PR center and the patient’s preference. Each patient was individually managed by a team member once a week for 8 weeks with unsupervised continuation of physical exercises on the other days of the week according to an individual action plan. Exercise conditioning, therapeutic patient education, and self-management were included in the PR program. The home assessment comprised evaluation of the patient’s exercise capacity by a 6-minute stepper test, Timed Up and Go test, ten times sit-to-stand test, Hospital Anxiety and Depression score, and quality of life (Visual Simplified Respiratory Questionnaire, VQ11, Maugeri Respiratory Failure 28). Results No incidents or accidents were observed during the course of home-based PR. The 6-minute stepper test was significantly improved after completion of the program, at 6 months and 12 months, whereas the Timed Up and Go and ten times sit-to-stand test were improved after PR and at 6 months but not at 12 months. Hospital Anxiety and Depression and quality of life scores improved after PR, and this improvement persisted at 6 months and 12 months. Conclusion Home-based PR for unselected patients with COPD is effective in the short term, and this effectiveness is maintained in the medium term (6 months) and long term (12 months). Home-based PR is an alternative to outpatient management provided all activities, such as exercise

  13. An evaluation of persistence of treatment effects during long-term treatment of destructive behavior.

    PubMed

    Wacker, David P; Harding, Jay W; Berg, Wendy K; Lee, John F; Schieltz, Kelly M; Padilla, Yaniz C; Nevin, John A; Shahan, Timothy A

    2011-09-01

    Eight young children who displayed destructive behavior maintained, at least in part, by negative reinforcement received long-term functional communication training (FCT). During FCT, the children completed a portion of a task and then touched a communication card attached to a microswitch to obtain brief breaks. Prior to and intermittently throughout FCT, extinction probes were conducted within a withdrawal design in which task completion, manding, and destructive behavior were placed on extinction to evaluate the relative persistence of appropriate and destructive behavior over the course of treatment. FCT continued until appropriate behavior persisted and destructive behavior failed to recur at baseline levels during extinction probes. The completion of FCT was followed by four challenges to the persistence of treatment effects conducted within mixed- or multiple-schedule designs: (a) extended extinction sessions (from 5 to 15 min), (b) introduction of a novel task, (c) removal of the microswitch and communication card, and (d) a mixed schedule of reinforcement in which both appropriate and destructive behavior produced reinforcement. The results showed that although FCT often resulted in quick reductions in destructive behavior and increases in appropriate behavior, destructive behavior often recurred during the extinction probes conducted during the initial treatment. When the effects of treatment persisted during the extinction probes, the remaining challenges to treatment effects resulted in only mild to moderate disruptions in behavior. These results are consistent with the quantitative predictions of behavioral momentum theory and may provide an alternative definition of maintenance as constituting behavioral persistence.

  14. An evaluation of persistence of treatment effects during long-term treatment of destructive behavior.

    PubMed

    Wacker, David P; Harding, Jay W; Berg, Wendy K; Lee, John F; Schieltz, Kelly M; Padilla, Yaniz C; Nevin, John A; Shahan, Timothy A

    2011-09-01

    Eight young children who displayed destructive behavior maintained, at least in part, by negative reinforcement received long-term functional communication training (FCT). During FCT, the children completed a portion of a task and then touched a communication card attached to a microswitch to obtain brief breaks. Prior to and intermittently throughout FCT, extinction probes were conducted within a withdrawal design in which task completion, manding, and destructive behavior were placed on extinction to evaluate the relative persistence of appropriate and destructive behavior over the course of treatment. FCT continued until appropriate behavior persisted and destructive behavior failed to recur at baseline levels during extinction probes. The completion of FCT was followed by four challenges to the persistence of treatment effects conducted within mixed- or multiple-schedule designs: (a) extended extinction sessions (from 5 to 15 min), (b) introduction of a novel task, (c) removal of the microswitch and communication card, and (d) a mixed schedule of reinforcement in which both appropriate and destructive behavior produced reinforcement. The results showed that although FCT often resulted in quick reductions in destructive behavior and increases in appropriate behavior, destructive behavior often recurred during the extinction probes conducted during the initial treatment. When the effects of treatment persisted during the extinction probes, the remaining challenges to treatment effects resulted in only mild to moderate disruptions in behavior. These results are consistent with the quantitative predictions of behavioral momentum theory and may provide an alternative definition of maintenance as constituting behavioral persistence. PMID:21909168

  15. Preventing child obesity: a long-term evaluation of the HENRY approach.

    PubMed

    Brown, Rebecca E; Willis, Thomas A; Aspinall, Nichola; Candida, Hunt; George, Jackie; Rudolf, Mary C J

    2013-07-01

    Childhood obesity has reached epidemic levels, yet many health professionals lack confidence in working with parents around lifestyle change. HENRY (Health Exercise Nutrition for the Really Young) aims to tackle this through training practitioners to work more effectively with parents of preschoolers around obesity and lifestyle issues.We evaluated the long-term impact of HENRY training on health professionals' knowledge, skills and confidence in tackling obesity prevention. All practitioners trained 2007-11 (n = 1601) were invited to complete an online survey. 237 emails (14.8%) were undeliverable; 354 (26.0%) of the remainder completed the survey. A majority (67%) reported using knowledge and skills gained on a regular basis in their professional lives. Sessions on the importance of empathy and key parenting skills were considered particularly useful, with 78% and 74% respectively reporting regular use of these skills. Effects on respondents' personal lives were also reported: 61% applied the knowledge and skills at home, identifying for example, more shared family mealtimes and reduced portion sizes. The impact endures, with 71% of those undergoing training > 12 months ago, stating that they continued to use concepts in their professional lives. The findings suggest that brief training can have a sustained impact on practitioners' professional and personal lives.

  16. Trauma emergency unit: long-term evaluation of a quality assurance programme

    PubMed Central

    Gagneux, E.; Lombrail, P.; Vichard, P.

    1998-01-01

    OBJECTIVE: Long-term evaluation of a quality assurance programme (after an assessment in 1993). DESIGN: Review of medical records. SETTING: Emergency area of an orthopaedic, trauma, and plastic surgery unit in a French teaching hospital (Besancon). SUBJECTS: 1187 consecutive ambulatory patients' records, from July 1995. MAIN MEASURES: Occurrence of near adverse events (at risk events causing situations which could lead to the occurrence of an adverse event). RESULTS: 71 near adverse events were identified (5.9% of the ambulatory visits). There was a significant decrease in the rate of near adverse events between 1993 (9.9% (2056 ambulatory visits, 204 near adverse events)), and 1995 (5.9% (1187 ambulatory visits, 71 near adverse events)), and significant change in the proportion of each category of adverse event (decrease in departures from prevention protocols). CONCLUSIONS: Despite their limitations, the effectiveness and efficiency of quality assurance programmes seem to be real and valuable. Maintaining quality improvement requires conditions which include some of the basic principles of total quality management (leadership, participatory management, openness, continuous feed back). The organisation of this unit as a specialised trauma centre was also a determining factor in the feasibility of a quality assurance programme (specialisation and small size, high activity volume, management of the complete care process). Quality assurance is an important initial step towards quality improvement, that should precede consideration of a total quality management programme. PMID:10178144

  17. Preventing child obesity: a long-term evaluation of the HENRY approach.

    PubMed

    Brown, Rebecca E; Willis, Thomas A; Aspinall, Nichola; Candida, Hunt; George, Jackie; Rudolf, Mary C J

    2013-07-01

    Childhood obesity has reached epidemic levels, yet many health professionals lack confidence in working with parents around lifestyle change. HENRY (Health Exercise Nutrition for the Really Young) aims to tackle this through training practitioners to work more effectively with parents of preschoolers around obesity and lifestyle issues.We evaluated the long-term impact of HENRY training on health professionals' knowledge, skills and confidence in tackling obesity prevention. All practitioners trained 2007-11 (n = 1601) were invited to complete an online survey. 237 emails (14.8%) were undeliverable; 354 (26.0%) of the remainder completed the survey. A majority (67%) reported using knowledge and skills gained on a regular basis in their professional lives. Sessions on the importance of empathy and key parenting skills were considered particularly useful, with 78% and 74% respectively reporting regular use of these skills. Effects on respondents' personal lives were also reported: 61% applied the knowledge and skills at home, identifying for example, more shared family mealtimes and reduced portion sizes. The impact endures, with 71% of those undergoing training > 12 months ago, stating that they continued to use concepts in their professional lives. The findings suggest that brief training can have a sustained impact on practitioners' professional and personal lives. PMID:23914474

  18. Long-term evaluation of myoblast seeded patches implanted on infarcted rat hearts.

    PubMed

    Giraud, Marie-Noëlle; Flueckiger, Remy; Cook, Stéphane; Ayuni, Erick; Siepe, Matthias; Carrel, Thierry; Tevaearai, Hendrik

    2010-06-01

    Cell transplantation presents great potential for treatment of patients with severe heart failure. However, its clinical application was revealed to be more challenging than initially expected in experimental studies. Further investigations need to be undertaken to define the optimal treatment conditions. We previously reported on the epicardial implantation of a bio-engineered construct of skeletal myoblast-seeded polyurethane and its preventive effect on progression toward heart failure. In the present study, we present a long-term evaluation of this functional outcome. Left anterior descending coronary ligation was performed in female Lewis rats. Two weeks later, animals were treated with either epicardial implantation of biograft, acellular scaffold, sham operation, or direct intramyocardial skeletal myoblast injection. Functional assessments were performed with serial echocardiographies every 3 months and end point left ventricle pressure was assessed. Hearts were then harvested for histological examinations. Myocardial infarction induced a slow and progressive reduction in fractional shortening after 3 months. Progression toward heart failure was significantly prevented for up to 6 months after injection of myoblasts and for up to 9 months following biograft implantation. Nevertheless, this effect vanished after 12 months, with immunohistological examinations revealing an absence of the transplanted myoblasts within the scaffold. We demonstrated that tissue therapy is superior to cell therapy for stabilization of heart function. However, beneficial effects are transient.

  19. [Regional evaluation of long-term care facilities for the elderly].

    PubMed

    Lezin, B; Burnouf, L; Grimbert, I; Collignon, A; Thouin, A

    2002-06-01

    The increase in the total number of very elderly people demands the precision and specification of the needs of long-term care structures in the coming years. A survey conducted in Lower-Normandy is presented and described. Questionnaires were sent to directors of residence homes and nursing homes in order to investigate their operations and their problems. The increase in the number of spaces to foresee seems moderate if the progressive trend remains unchanged (+1% per year until the year 2010), but within the same timeframe, the demographic decline in the number of potential family helpers and home health workers to take care of the elderly in their homes, coupled with the establishment of a new state allowance for dependent people, could alter the situation. Furthermore, more than 50% of nursing homes and residence homes for the elderly are in need of significant improvements: a reduction in the number of shared rooms (52.5% of nursing homes) and the development of equipment to meet the needs of the handicapped and disabled. The means in personnel and staff qualifications are particularly heterogeneous and difficulties in coping with dependency are reported most everywhere. The application of the 1999 decree stipulating the approval of these structures based upon thorough evaluations of available services is urgently needed. PMID:12375526

  20. Long-term efficacy, safety and durability of Juvéderm® XC.

    PubMed

    Ballin, Annelyse C; Cazzaniga, Alex; Brandt, Fredric S

    2013-01-01

    Over the last decade, there has been increasing interest in minimally invasive cosmetic treatments, especially for facial rejuvenation. Next to botulinum toxin injection, the injection of soft tissue fillers is the second most frequent minimally invasive procedure performed in the USA. Hyaluronic acid (HA) is the most commonly used dermal filler. One of patients' main concerns about filler injections pertains to pain and discomfort. Topical anesthetics, nerve blocks, and/or the incorporation of lidocaine to the filler have been applied in order to reduce distress and pain. Despite nerve blocks being an effective form of anesthesia, they may distort the area to be treated, as well as lengthen and complicate the procedure. Studies have shown that the incorporation of lidocaine to HA fillers significantly reduces pain and discomfort. Yet, one of the dilemmas about the addition of lidocaine solution to HA fillers is the possible alteration of the physical characteristics of the product by negatively impacting the efficacy and/or duration of the filler. The concern is that the addition of lidocaine could dilute the product, creating less correction per mL, changing the product's viscosity and consequently the "lifting" ability. Also, this dilution could reduce the product's duration. There may be a difference between a physician adding an aqueous solution into a lidocaine-free version of HA and the pre-incorporated lidocaine version of HA. An aqueous solution might dilute the product, while the pre-incorporated powder lidocaine appears to avoid this problem. Juvéderm® XC is manufactured with powder lidocaine 0.3%; it is associated with significantly less injection pain than Juvéderm® and other lidocaine-free versions of HA. Studies have shown that lidocaine enhances treatment comfort and optimizes the injection experience while maintaining a similar safety and effectiveness profile. Regarding the longevity, further study is necessary to determine if there is any

  1. Mathematical models as tools for probing long-term safety of CO2 storage

    SciTech Connect

    Pruess, Karsten; Birkholzer, Jens; Zhou, Quanlin

    2009-02-01

    Subsurface reservoirs being considered for storing CO{sub 2} include saline aquifers, oil and gas reservoirs, and unmineable coal seams (Baines and Worden, 2004; IPCC, 2005). By far the greatest storage capacity is in saline aquifers (Dooley et al., 2004), and our discussion will focus primarily on CO{sub 2} storage in saline formations. Most issues for safety and security of CO{sub 2} storage arise from the fact that, at typical temperature and pressure conditions encountered in terrestrial crust, CO{sub 2} is less dense than aqueous fluids. Accordingly, CO{sub 2} will experience an upward buoyancy force in most subsurface environments, and will tend to migrate upwards whenever (sub-)vertical permeable pathways are available, such as fracture zones, faults, or improperly abandoned wells (Bachu, 2008; Pruess, 2008a, b; Tsang et al., 2008). CO{sub 2} injection will increase fluid pressures in the target formation, thereby altering effective stress distributions, and potentially triggering movement along fractures and faults that could increase their permeability and reduce the effectiveness of a caprock in containing CO{sub 2} (Rutqvist et al., 2008; Chiaramonte et al., 2008). Induced seismicity as a consequence of fluid injection is also a concern (Healy et al., 1968; Raleigh et al., 1976; Majer et al., 2007). Dissolution of CO{sub 2} in the aqueous phase generates carbonic acid, which may induce chemical corrosion (dissolution) of minerals with associated increase in formation porosity and permeability, and may also mediate sequestration of CO{sub 2} as solid carbonate (Gaus et al., 2008). Chemical dissolution of caprock minerals could promote leakage of CO{sub 2} from a storage reservoir (Gherardi et al., 2007). Chemical dissolution and geomechanical effects could reinforce one another in compromising CO{sub 2} containment. Additional issues arise from the potential of CO{sub 2} to mobilize hazardous chemical species (Kharaka et al., 2006), and from migration of

  2. Acute and long-term safety and tolerability of risperidone in children with autism.

    PubMed

    Aman, Michael G; Arnold, L Eugene; McDougle, Christopher J; Vitiello, Benedetto; Scahill, Lawrence; Davies, Mark; McCracken, James T; Tierney, Elaine; Nash, Patricia L; Posey, David J; Chuang, Shirley; Martin, Andres; Shah, Bhavik; Gonzalez, Nilda M; Swiezy, Naomi B; Ritz, Louise; Koenig, Kathleen; McGough, James; Ghuman, Jaswinder K; Lindsay, Ronald L

    2005-12-01

    Treatment-emergent adverse events (AEs) were monitored during an 8-week, double-blind, placebo-controlled trial of risperidone (0.5-3.5 mg/day) in 101 children and adolescents with a lifetime diagnosis of autistic disorder. In addition, 37 placebo nonresponders received open-label risperidone for another 8 weeks. Of all the risperidone responders (n=65), 63 entered an open extension of another 16 weeks (6 months total risperidone exposure), and 32 of them were rerandomized to either continued risperidone therapy (n=16) or gradual replacement with placebo (n=16) over 8 weeks. We collected the following measures of safety and tolerability: (1) laboratory blood assessments (CBC with differential, electrolytes, and liver function tests) and urinalyses, (2) vital signs, (3) Side Effects Review of AEs thought to be associated with risperidone, (4) sleep records, (5) Simpson Angus Neurological Rating Scale (SARS), (6) Abnormal Involuntary Movement Scale (AIMS), and (7) height and weight. No clinically significant changes were found on the lab tests. During the 8-week acute trial, the most common AEs on the Side Effects Review, scored as moderate or higher, were as follows (placebo and risperidone, respectively): Somnolence (12% and 37%), enuresis (29% and 33%), excessive appetite (10% and 33%), rhinitis (8% and 16%), difficulty waking (8% and 12%), and constipation (12% and 10%). "Difficulty falling asleep" and anxiety actually favored the risperidone condition at statistically significant levels. The same AEs tended to recur through 6 months of treatment, although often at reduced levels. Using Centers for Disease Control (CDC) standardized scores, both weight and body mass index (BMI) increased with risperidone during the acute trial (0.5 and 0.6 SDs, respectively, for risperidone; 0.0 and 0.1 SDs, respectively, for placebo) and into open-label extension (0.19 and 0.16 SDs, respectively), although the amount of gain decelerated with time. Extrapyramidal symptoms, as

  3. Long-term efficacy and safety of polyalkylimide gel for the treatment of HIV-associated lipoatrophy.

    PubMed

    Antoniou, Tony; Raboud, Janet M; Kovacs, Colin; Diong, Christina; Brunetta, Jason; Smith, Graham; Halpenny, Roberta; Beninger, Francis; Loutfy, Mona R

    2009-10-01

    The long-term safety and efficacy of products used in the correction of HIV-associated facial lipoatrophy (FLA) are largely unknown. The purpose of this study was to describe the long-term efficacy and safety of polyalkylimide gel (PAIG) in the treatment of HIV-associated FLA. In this open-label, randomized, single-center study, 31 HIV-positive individuals (median age 48 years (interquartile ranges (IQR) 45, 55, 97% male) with FLA were randomized to immediate (week 0 and six) or delayed (week 12 and 18) PAIG injections. Week 96 endpoints included change in FLA severity scores (FLSS) (five-point scale), proportion of patients with adverse events, and changes in quality of life, depression and anxiety using validated surveys. Results at week 96 were available for 28 patients. Adverse events, including swelling, redness, bruising and pain, were mild, and resolved after a median of three days following the injection. At week 96, median changes in physician and patient FLSS scores were -2 (IQR -3, -1; p<0.001 vs. baseline) and -2 (IQR -2, -1; p<0.001 vs. baseline), respectively. Physician and patient FLSS scores were not significantly different between the groups at week 96. Significant improvements in patient's anxiety (p<0.001), depression (p<0.001) and mental health (p=0.01) were observed from baseline to week 96. In conclusion, treatment with PAIG was associated with sustained improvements in both the physical and psychological components of FLA through 96 weeks of follow-up.

  4. Evaluation of the antipsychotic medication review process at four long-term facilities in Alberta

    PubMed Central

    Birney, Arden; Charland, Paola; Cole, Mollie; Aslam Arain, Mubashir

    2016-01-01

    Purpose The goal of this evaluation was to understand how four long-term care (LTC) facilities in Alberta have implemented medication reviews for the Appropriate Use of Antipsychotics (AUA) initiative. We aimed to determine how interprofessional (IP) collaboration was incorporated in the antipsychotic medication reviews and how the reviews had been sustained. Methods Four LTC facilities in Alberta participated in this evaluation. We conducted semistructured interviews with 18 facility staff and observed one antipsychotic medication review at each facility. We analyzed data according to the following key components that we identified as relevant to the antipsychotic medication reviews: the structure of the reviews, IP interactions between the staff members, and strategies for sustaining the reviews. Results The duration of antipsychotic medication reviews ranged from 1 to 1.5 hours. The number of professions in attendance ranged from 3 to 9; a pharmacist led the review at two sites, while a registered nurse led the review at one site and a nurse practitioner at the remaining site. The number of residents discussed during the review ranged from 6 to 20. The process at some facilities was highly IP, demonstrating each of the six IP competencies. Other facilities conducted the review in a less IP manner due to challenges of physician involvement and staff workload, particularly of health care aides. Facilities that had an nurse practitioner on site were more efficient with the process of implementing recommendations resulting from the medication reviews. Conclusion The LTC facilities were successful in implementing the medication review process and the process seemed to be sustainable. A few challenges were observed in the implementation process at two facilities. IP practice moved forward the goals of the AUA initiative to reduce the inappropriate use of antipsychotics. PMID:27785044

  5. Evaluating and ranking threats to the long-term persistence of polar bears

    USGS Publications Warehouse

    Atwood, Todd C.; Marcot, Bruce G.; Douglas, David C.; Amstrup, Steven C.; Rode, Karyn D.; Durner, George M.; Bromaghin, Jeffrey F.

    2015-01-01

    The polar bear (Ursus maritimus) was listed as a globally threatened species under the U.S. Endangered Species Act (ESA) in 2008, mostly due to the significant threat to their future population viability from rapidly declining Arctic sea ice. A core mandate of the ESA is the development of a recovery plan that identifies steps to maintain viable populations of a listed species. A substantive evaluation of the relative influence of putative threats to population persistence is helpful to recovery planning. Because management actions must often be taken in the face of substantial information gaps, a formalized evaluation hypothesizing potential stressors and their relationships with population persistence can improve identification of relevant conservation actions. To this end, we updated a Bayesian network model previously used to forecast the future status of polar bears worldwide. We used new information on actual and predicted sea ice loss and polar bear responses to evaluate the relative influence of plausible threats and their mitigation through management actions on the persistence of polar bears in four ecoregions. We found that polar bear outcomes worsened over time through the end of the century under both stabilized and unabated greenhouse gas (GHG) emission pathways. Under the unabated pathway (i.e., RCP 8.5), the time it took for polar bear populations in two of four ecoregions to reach a dominant probability of greatly decreased was hastened by about 25 years. Under the stabilized GHG emission pathway (i.e., RCP 4.5), where GHG emissions peak around the year 2040, the polar bear population in the Archipelago Ecoregion of High Arctic Canada never reached a dominant probability of greatly decreased, reinforcing earlier suggestions of this ecoregion’s potential to serve as a long-term refugium. The most influential drivers of adverse polar bear outcomes were declines to overall sea ice conditions and to the marine prey base. Improved sea ice conditions

  6. 76 FR 68769 - Bridging the Idea Development Evaluation Assessment and Long-Term Initiative and Total Product...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-07

    ...-Term Initiative and Total Product Life Cycle Approaches for Evidence Development for Surgical Medical... Evaluation Assessment and Long-Term (IDEAL) initiative and Total Product Life Cycle (TPLC) frameworks related... device life cycle; and Integrating innovation, evaluation, and dissemination pathways for medical...

  7. Longitudinal study to assess the safety and efficacy of a live-attenuated SHIV vaccine in long term immunized rhesus macaques

    SciTech Connect

    Yankee, Thomas M. Sheffer, Darlene; Liu Zhengian; Dhillon, Sukhbir; Jia Fenglan; Chebloune, Yahia; Stephens, Edward B.; Narayan, Opendra

    2009-01-05

    Live-attenuated viruses derived from SIV and SHIV have provided the most consistent protection against challenge with pathogenic viruses, but concerns regarding their long-term safety and efficacy have hampered their clinical usefulness. We report a longitudinal study in which we evaluated the long-term safety and efficacy of {delta}vpuSHIV{sub PPC}, a live virus vaccine derived from SHIV{sub PPC}. Macaques were administered two inoculations of {delta}vpuSHIV{sub PPC}, three years apart, and followed for eight years. None of the five vaccinated macaques developed an AIDS-like disease from the vaccine. At eight years, macaques were challenged with pathogenic SIV and SHIV. None of the four macaques with detectable cellular-mediated immunity prior to challenge had detectable viral RNA in the plasma. This study demonstrates that multiple inoculations of a live vaccine virus can be used safely and can significantly extend the efficacy of the vaccine, as compared to a single inoculation, which is efficacious for approximately three years.

  8. Long-Term Impact of Community-Based Information, Education and Communication Activities on Food Hygiene and Food Safety Behaviors in Vietnam: A Longitudinal Study

    PubMed Central

    Takanashi, Kumiko; Quyen, Dao To; Le Hoa, Nguyen Thi; Khan, Nguyen Cong; Yasuoka, Junko; Jimba, Masamine

    2013-01-01

    Background Ingestion of contaminated water or food is a major contributor to childhood diarrhea in developing countries. In Vietnam, the use of community-based information, education and communication (IEC) activities could be a sustainable strategy to improve food hygiene and food safety behaviors. This study thus examined the long-term impact of community-based IEC activities on food hygiene and food safety behaviors. Methods In this longitudinal study, we interviewed caregivers of children aged between six months and four years in suburban Hanoi. Baseline data were collected in January 2006 (n = 125). After conducting IEC interventions, we collected a 1st set of evaluation data in January 2007 (n = 132). To examine the long-term impact of the interventions, we then collected a 2nd set of evaluation data in January 2008 (n = 185). Changes in childhood diarrhea prevalence, IEC coverage, and food hygiene and food safety behaviors were assessed over a two-year period using bivariate and logistic regression analyses. Effective IEC channels were determined through multiple linear regression analysis. Results Childhood diarrhea was significantly reduced from 21.6% at baseline to 7.6% at the 1st post-intervention evaluation (P = 0.002), and to 5.9% at the 2nd evaluation. Among 17 food hygiene and food safety behaviors measured, a total of 11 behaviors were improved or maintained by the 2nd evaluation. Handwashing after toilet use was significantly improved at both evaluation points. Overall, 3 food safety behaviors and 7 food hygiene behaviors were found to have significantly improved at the 1st and at the 2nd evaluations, respectively. Flip chart communication administered by community groups was identified to be the most effective IEC channel for effecting behavior change (P = 0.018). Conclusions Flip chart communication administered by community groups is effective for improving multiple food hygiene and food safety behaviors in sustainable ways

  9. Long-term geochemical evaluation of the coastal Chicot aquifer system, Louisiana, USA

    NASA Astrophysics Data System (ADS)

    Borrok, David M.; Broussard, Whitney P.

    2016-02-01

    Groundwater is increasingly being overdrafted in the Gulf and Atlantic Coastal regions of the United States. Geochemical data associated with groundwater in these aquifers can provide important information on changes in salinity, recharge, and reaction pathways that can be used to improve water management strategies. Here we evaluated long-term geochemical changes associated with the 23,000 km2 Chicot aquifer system in Louisiana, USA. The Chicot aquifer is currently being overdrafted by about 1,320,000 m3 per day. We compiled selected bulk geochemical data from samples collected from 20 wells in the Chicot aquifer from 1993 to 2015. Oxygen and hydrogen isotope measurements were additionally completed for the 2014 samples. We identified three zones of groundwater with distinctive geochemical character; (1) A groundwater recharge zone in the northern part of the study area with low pH, low salinity, and low temperature relative to other groundwater samples, (2) a groundwater recharge zone in the southeastern part of the study area with low temperature, high alkalinity, and higher Ca and Mg concentrations compared to the other groundwater samples, and (3) groundwater in the southwestern part of the aquifer system with high salinity, high temperature, and a ∼1:1 Na/Cl ratio. The geochemistry of these regions has been relatively stable over the last ∼20 years. However, in the drought year of 2011, the estimated extent of zones with elevated salinity increased substantially. Geochemical evidence suggests that there was increased infiltration of deeper, more salt-rich waters into the shallower Chicot aquifer.

  10. Comprehensive evaluation of long-term trends in occupational exposure: Part 1. Description of the database

    PubMed Central

    Symanski, E.; Kupper, L. L.; Rappaport, S. M.

    1998-01-01

    OBJECTIVES: To conduct a comprehensive evaluation of long term changes in occupational exposure among a broad cross section of industries worldwide. METHODS: A review of the scientific literature identified studies that reported historical changes in exposure. About 700 sets of data from 119 published and several unpublished sources were compiled. Data were published over a 30 year period in 25 journals that spanned a range of disciplines. For each data set, the average exposure level was compiled for each period and details on the contaminant, the industry and location, changes in the threshold limit value (TLV), as well as the type of sampling method were recorded. Spearman rank correlation coefficients were used to identify monotonic changes in exposure over time and simple linear regression analyses were used to characterise trends in exposure. RESULTS: About 78% of the natural log transformed data showed linear trends towards lower exposure levels whereas 22% indicated increasing trends. (The Spearman rank correlation analyses produced a similar breakdown between exposures monotonically increasing or decreasing over time.) Although the rates of reduction for the data showing downward trends ranged from -1% to -62% per year, most exposures declined at rates between -4% and -14% per year (the interquartile range), with a median value of -8% per year. Exposures seemed to increase at rates that were slightly lower than those of exposures which have declined over time. Data sets that showed downward (versus upward) trends were influenced by several factors including type and carcinogenicity of the contaminant, type of monitoring, historical changes in the threshold limit values (TLVs), and period of sampling. CONCLUSIONS: This review supports the notion that occupational exposures are generally lower today than they were years or decades ago. However, such trends seem to have been affected by factors related to the contaminant, as well as to the period and type of

  11. DEVELOMENT AND EVALUATION OF A MODEL FOR ESTIMATING LONG-TERM AVERAGE OZONE EXPOSURES TO CHILDREN

    EPA Science Inventory

    Long-term average exposures of school-age children can be modelled using longitudinal measurements collected during the Harvard Southern California Chronic Ozone Exposure Study over a 12-month period: June, 1995-May, 1996. The data base contains over 200 young children with perso...

  12. An Evaluation of the Long-Term Effectiveness of a Women's Leadership Development Program

    ERIC Educational Resources Information Center

    Ericksen, Kirsten S.

    2009-01-01

    The purpose of this study was to investigate the Women's Institute for Leadership Development (W.I.L.D.) program to determine the immediate and long-term impact as defined by the alumni program participants from three cohorts (2008, 2005, 2003). A secondary focus of the career transition decision-making of recent W.I.L.D. participants was also…

  13. Evaluating the Impact of Supplemental Instruction on Short- and Long-Term Retention of Course Content

    ERIC Educational Resources Information Center

    Price, Jodi; Lumpkin, Amber G.; Seemann, Eric A.; Bell, Diana Calhoun

    2012-01-01

    Findings from prior research in various content domains have indicated that Peer Assisted Study Sessions (PASS) attendees earned higher final grades than non-attendees. However, what makes PASS effective remains unknown; for example, PASS could improve short-term retention but hinder long-term maintenance of course content given that some methods…

  14. Evaluation of long-term bedload virtual velocity in gravel-bed rivers (Ardenne, Belgium)

    NASA Astrophysics Data System (ADS)

    Houbrechts, Geoffrey; Levecq, Yannick; Peeters, Alexandre; Hallot, Eric; Van Campenhout, Jean; Denis, Anne-Cécile; Petit, François

    2015-12-01

    In many gravel-bed rivers, bed material transfer has been interrupted or perturbed by anthropogenic activities. Currently, restoration projects are being conducted in many countries in order to re-establish bedload continuity. However, until now, few studies have provided indications of the velocity of bed material over the long-term (at least decade to century time-scale). In the context of river restoration projects (e.g. weir removal, addition of spawning gravel), these data are nevertheless crucial to predict the downstream propagation of the geomorphological and biological benefits (e.g. supply-transport equilibrium, morphological and substratum diversity). In our study, PIT-tag tracers were used in eight medium-sized gravel-bed rivers (Ardenne Region, Belgium) to propose a flow competence relationship based on specific stream power, on the one hand, and to determine the long-term virtual velocity of the bed material corresponding to the median diameter (D50) of the surface layer of riffles, on the other hand. After each flow event that exceeded the threshold for sediment entrainment, tagged particles were sought and located, even when they were buried in the subsurface layer. Afterwards, all of the data were used to estimate the virtual velocity of the bed material over the long-term using three approaches. Finally, the results were compared with long-term transport estimations based on iron slag dispersed by the rivers since the end of the middle ages.

  15. An Evaluation of Persistence of Treatment Effects during Long-Term Treatment of Destructive Behavior

    ERIC Educational Resources Information Center

    Wacker, David P.; Harding, Jay W.; Berg, Wendy K.; Lee, John F.; Schieltz, Kelly M.; Padilla, Yaniz C.; Nevin, John A.; Shahan, Timothy A.

    2011-01-01

    Eight young children who displayed destructive behavior maintained, at least in part, by negative reinforcement received long-term functional communication training (FCT). During FCT, the children completed a portion of a task and then touched a communication card attached to a microswitch to obtain brief breaks. Prior to and intermittently…

  16. Evaluation of Self-Assessment Tests for Predicting Long-Term Knowledge Retention.

    ERIC Educational Resources Information Center

    Russo, John, Jr.; And Others

    1985-01-01

    To determine if posttests administered immediately following a continuing pharmacy education (CPE) program are reliable predictors of long-term knowledge retention, a portion of three posttests used in three successive CPE programs was readministered to attendees of those programs 8 to 21 weeks later. Posttests do not reliably assess long-term…

  17. Evaluation of long-term water-level declines in basalt aquifers near Mosier, Oregon

    USGS Publications Warehouse

    Burns, Erick R.; Morgan, David S.; Lee, Karl K.; Haynes, Jonathan V.; Conlon, Terrence D.

    2012-01-01

    are not sustainable, (2) well construction practices that have resulted in leakage from aquifers into springs and streams, and (3) reduction in aquifer recharge resulting from long-term climate variations. Historical well construction practices, specifically open, unlined, uncased boreholes that result in cross-connecting (or commingling) multiple aquifers, allow water to flow between these aquifers. Water flowing along the path of least resistance, through commingled boreholes, allows the drainage of aquifers that previously stored water more efficiently. The study area is in the eastern foothills of the Cascade Range in north central Oregon in a transitional zone between the High Cascades to the west and the Columbia Plateau to the east. The 78-square mile (mi2) area is defined by the drainages of three streams - Mosier Creek (51.8 mi2), Rock Creek (13.9 mi2), and Rowena Creek (6.9 mi2) - plus a small area that drains directly to the Columbia River.The three major components of the study are: (1) a 2-year intensive data collection period to augment previous streamflow and groundwater-level measurements, (2) precipitation-runoff modeling of the watersheds to determine the amount of recharge to the aquifer system, and (3) groundwater-flow modeling and analysis to evaluate the cause of groundwater-level declines and to evaluate possible water resource management strategies. Data collection included the following: 1. Water-level measurements were made in 37 wells. Bi-monthly or quarterly measurements were made in 30 wells, and continuous water-level monitoring instruments were installed in 7 wells. The measurements principally were made to capture the seasonal patterns in the groundwater system, and to augment the available long-term record. 2. Groundwater pumping was measured, reported, or estimated from irrigation, municipal and domestic wells. Flowmeters were installed on 74 percent of all high-capacity irrigation wells in the study area. 3. Borehole geophysical data

  18. Evaluation of Late Adverse Events in Long-Term Wilms' Tumor Survivors

    SciTech Connect

    Dijk, Irma van; Oldenburger, Foppe; Cardous-Ubbink, Mathilde C.; Geenen, Maud M.

    2010-10-01

    Purpose: To evaluate the prevalence and severity of adverse events (AEs) and treatment-related risk factors in long-term Wilms' tumor (WT) survivors, with special attention to radiotherapy. Methods and Materials: The single-center study cohort consisted of 185 WT survivors treated between 1966 and 1996, who survived at least 5 years after diagnosis. All survivors were invited to a late-effects clinic for medical assessment of AEs. AEs were graded for severity in a standardized manner. Detailed radiotherapy data enabled us to calculate the equivalent dose in 2 Gy fractions (EQD{sub 2}) to compare radiation doses in a uniform way. Risk factors were evaluated with multivariate logistic regression analysis. Results: Medical follow-up was complete for 98% of survivors (median follow-up, 18.9 years; median attained age, 22.9 years); 123 survivors had 462 AEs, of which 392 had Grade 1 or 2 events. Radiotherapy to flank/abdomen increased the risk of any AE (OR, 1.08 Gy{sup -1} [CI, 1.04-1.13]). Furthermore, radiotherapy to flank/abdomen was associated with orthopedic events (OR, 1.09 Gy{sup -1} [CI, 1.05-1.13]) and second tumors (OR, 1.11 Gy{sup -1} [CI, 1.03-1.19]). Chest irradiation increased the risk of pulmonary events (OR, 1.14 Gy{sup -1} [CI, 1.06-1.21]). Both flank/abdominal and chest irradiation were associated with cardiovascular events (OR, 1.05 Gy{sup -1} [CI, 1.00-1.10], OR, 1.06 Gy{sup -1} [CI, 1.01-1.12]) and tissue hypoplasia (OR, 1.17 Gy{sup -1} [CI, 1.10-1.24], OR 1.10 Gy{sup -1} [CI, 1.03-1.18]). Conclusion: The majority of AEs, overall as well as in irradiated survivors, were mild to moderate. Nevertheless, the large amount of AEs emphasizes the importance of follow-up programs for WT survivors.

  19. Evaluation of Long Term Effect of RV Apical Pacing on Global LV Function by Echocardiography

    PubMed Central

    Tilkar, Mahendra; Jain, Siddhant; Mondal, Subrata; Sarkar, Piyabi; Modi, Nitin

    2016-01-01

    Introduction We very often face pacemaker implanted patients during follow-up with shortness of breath and effort intolerance inspite of normal clinical parameters. Aim The aim of our study is to evaluate the cause of effort intolerance and probable cause of sub-clinical Congestive Cardiac Failure (CCF) in a case of long term Right Ventricular (RV) apical pacing on global Left Ventricular (LV) function non- invasively by echocardiography. Materials and Methods We studied 54 patients (Male 42, Female 12) of complete heart block (CHB) with RV apical pacing (40 VVI and 14 DCP). Mean duration of pacing was 58+4 months. All patients underwent 24 hours Holter monitoring to determine the percentage of ventricular pacing beats. 2-D Echocardiography was done to assess the regional wall motion of abnormality and global LV ejection fraction by modified Simpson’s rule. These methods were coupled with the Doppler derived Myocardial Performance Index (MPI), tissue Doppler imaging, and mechanical regional dyssynchrony with 3-D Echocardiography. Data were analysed from 54 RV- apical paced patients and compared with age and body surface area of 60 controlled subjects (Male 46, Female 14). Results Evaluation of LV function in 54 patients demonstrated regional wall motion abnormality and Doppler study revealed both LV systolic and diastolic dysfunction compare with control subjects (regional wall motion abnormality 80±6% vs 30±3% with p-value<0.0001) which is proportional to the percentage of ventricular pacing beats (mean paced beat 78%). Global LVEF 50±4% vs 60±2% (p-valve <0.0001) and MPI 0.46 ±0.12 v/s 0.36±0.09 (p-value <0.0001). Conclusion RV–apical pacing induces iatrogenic electrical dyssynchrony which leads to remodeling of LV and produces mechanical dyssynchrony which is responsible for LV dysfunction. Alternate site of RV pacing and/or biventricular pacing should be done to maintain biventricular electrical synchrony which will preserve the LV function. PMID

  20. Evaluating Indicator-Based Methods of "Measuring Long-Term Impacts of a Science Center on Its Community"

    ERIC Educational Resources Information Center

    Jensen, Eric Allen

    2016-01-01

    This article addresses some of the challenges faced when attempting to evaluate the long-term impact of informal science learning interventions. To contribute to the methodological development of informal science learning research, we critically examine (Falk and Needham (2011) "Journal of Research in Science Teaching," 48: 1-12.) study…

  1. Long-Term Effects of Outpatient Geriatric Evaluation and Management on Health Care Utilization, Cost, and Survival

    ERIC Educational Resources Information Center

    Engelhardt, Joseph B.; Toseland, Ronald W.; Gao, Jian; Banks, Steven

    2006-01-01

    Purpose: The long-term effectiveness and efficiency of an outpatient geriatric evaluation and management (GEM) program was compared to usual primary care (UPC). Design and Method: A randomized controlled group design was used. Health care utilization, cost of care, and survival were assessed during a 48-month period among a sample of 160 male…

  2. Comprehensive evaluation of long-term hydrological data sets: Constraints of the Budyko framework

    NASA Astrophysics Data System (ADS)

    Greve, Peter; Orlowsky, Boris; Seneviratne, Sonia I.

    2013-04-01

    An accurate estimate of the climatological land water balance is essential for a wide range of socio-economical issues. Despite the simplicity of the underlying water balance equation, its individual variables are of complex nature. Global estimates, either derived from observations or from models, of precipitation (P ) and especially evapotranspiration (ET) are characterized by high uncertainties. This leads to inconsistent results in determining conditions related to the land water balance and its components. In this study, we consider the Budyko framework as a constraint to evaluate long-term hydrological data sets within the period from 1984 to 2005. The Budyko framework is a well established empirically based relationsship between ET-P and Ep-P , with Ep being the potential evaporation. We use estimates of ET associated with the LandFlux-EVAL initiative (Mueller et. al., 2012), either derived from observations, CMIP5 models or land-surface models (LSMs) driven with observation-based forcing or atmospheric reanalyses. Data sets of P comprise all commonly used global observation-based estimates. Ep is determined by methods of differing complexity with recent global temperature and radiation data sets. Based on this comprehensive synthesis of data sets and methods to determine Ep, more than 2000 possible combinations for ET-P in conjunction with Ep-P are created. All combinations are validated against the Budyko curve and against physical limits within the Budyko phase space. For this purpose we develop an error measure based on the root mean square error which combines both constraints. We find that uncertainties are mainly induced by the ET data sets. In particular, reanalysis and CMIP5 data sets are characterized by low realism. The realism of LSMs is further not primarily controlled by the forcing, as different LSMs driven with the same forcing show significantly different error measures. Our comprehensive approach is thus suitable to detect uncertainties

  3. Proboscis lateralis: a rare craniofacial anomaly, reconstruction, and long-term evaluation.

    PubMed

    David, Lisa R; Sanger, Claire; Fisher, David; Argenta, Louis C

    2008-07-01

    Proboscis lateralis is a rare spontaneous congenital anomaly that results from a failure of normal embryological nasal development. The ensuing deformity consists of imbrication of the nasal soft tissues into a tubelike proboscis and can be associated with ipsilateral heminasal aplasia, choanal atresia, and multiple other abnormalities. A case report of a patient with proboscis lateralis is presented, with a 27-year follow-up detailing the complexities of long-term surgical management. After 15 major surgical interventions, there is relatively normal facial symmetry, but abnormalities remain with the underlying craniofacial skeleton and nasopharyngeal airway. Proboscis lateralis is not an isolated soft tissue abnormality but is a craniofacial defect that requires a long-term multidisciplinary approach to the surgical timing and treatment with lifelong follow-up. PMID:18650742

  4. [Evaluation of a long-term sensomotor deficit after neonatal rat brain ischemia/hypoxia].

    PubMed

    Silachev, D N; Shubina, M I; Iankauskas, S S; Mkrtchian, V P; Manskikh, V N; Guliaev, M V; Zorov, D B

    2013-01-01

    The application of magnetic resonance imaging method showed that ischemia/hypoxia of the brain of neonatal rats made by the protocol suggested by Levine-Rice induces one-sided lesions in the areas of cerebral cortex, striatum and hippocampus. Unilateral ischemic injury leads to a long-term sensorimotor and behavioral distortions within 90-115 days after the operation which has been tested in animals by the battery of tests including Cylinder, Beam-walking, Staircase and Limb-placing test. Chosen battery of tests in combination with magnetic resonance imaging allows to reliably estimate the long-term sensorimotor recovery in adult animals suffered an injury in neonatal age. PMID:24450172

  5. Evaluating the Long-Term Performance of Geosynethic Clay Liners Exposed to Freeze-Thaw

    SciTech Connect

    Robert K. Podgorney; Jesse E. Bennett

    2006-02-01

    Geosynethic clay liners have become an increasingly common component in landfill liner and cover systems since their introduction in the early 1980’s. An important consideration for landfills and covers constructed in the frost zone of cold climates is the possible deterioration in performance due to freeze-thaw cycling over the design life of the liner or cover system, which can be up to 1,000 years. The literature contains several examples showing that geosynethic clay liners can withstand a limited number of freeze-thaw events, but data on long-term performance are lacking The objective of this study was to examine the long-term performance of geosynethic clay liners exposed to repeated freeze-thaw cycles, encompassing their application as a final cover as well as a bottom liner. Laboratory analysis of hydraulic conductivity was performed after as many as 150 freeze-thaw cycles, with no appreciable changes observed. Based upon an analytical heat transfer analysis, this equates to [at least] 150 years of field service for placement depths greater then approximately 30 cm below the surface of the liner. The long-term insusceptibility of GCLs to increased hydraulic conductivity as a response to repeated freeze-thaw cycling is largely due to the self-healing characteristics of the sodium bentonite used in their construction. GCLs perform well and maintain efficiency as a barrier to flow after 150 freeze-thaw cycles. Other factors, such as permeant chemistry, physical disturbance, desiccation, etc., may be much more important factors to consider when planning for the long-term performance of GCLs.

  6. Gracilis myocutaneous flap: evaluation of potential risk factors and long-term donor-site morbidity.

    PubMed

    Papadopoulos, Othon; Konofaos, Petros; Georgiou, Panos; Chrisostomidis, Chrisostomos; Tsantoulas, Zacharias; Karypidis, Dimitrios; Kostakis, Alkiviadis

    2011-09-01

    This study reviewed our experience with the gracilis myocutaneous (GMC) flap, potential risk factors for flap necrosis, and long-term morbidity at the donor-site. From 1993 to 2002, 29 GMC flaps were harvested from 27 patients (pedicled n = 21 and free n = 8). The overall incidence of flap necrosis was 13.79% (partial (n = 2) and total (n = 2) necrosis). Flap necrosis was correlated with body mass index >25 (P = 0.022), with smoking (P = 0.04 9) and with radiation therapy at the recipient site (P = 0.020). The long-term morbidity at the donor-site was low, except for scar appearance (17.24%), thigh contour deformity (58.62%), and hypoesthesia (17.24%). Significant age and gender differences were seen for ranking of scar ugliness, with females (P = 0.0061) and younger patients (age ≤55) (P = 0.046) assigned higher values. Significant age differences were seen for ranking of thigh contour deformity, with younger patients assigned higher values (P = 0.0012). In conclusion, patient overweight, smoking, and previous radiation therapy at the recipient site may be the "potential risk factors" for flap necrosis. The long-term morbidity at the donor-site was low, which was in agreement with previous reported studies. A larger series would be the subject of a future study.

  7. Long-Term Safety and Adverse Events of Risperidone in Children, Adolescents, and Adults with Pervasive Developmental Disorders

    ERIC Educational Resources Information Center

    Hellings, Jessica A.; Cardona, Alicia M.; Schroeder, Stephen R.

    2010-01-01

    The objective of this study was to examine long-term adverse events of risperidone in 19 children, adolescents, and adults with Pervasive Developmental Disorders and intellectual disability, continuing risperidone for a mean of 186.5 weeks, following a 46-week risperidone study. Nineteen individuals continued long-term follow-up after our…

  8. Long-term efficacy and safety of mipomersen in patients with familial hypercholesterolaemia: 2-year interim results of an open-label extension

    PubMed Central

    Santos, Raul D.; Duell, P. Barton; East, Cara; Guyton, John R.; Moriarty, Patrick M.; Chin, Wai; Mittleman, Robert S.

    2015-01-01

    Aims To evaluate the efficacy and safety of extended dosing with mipomersen in patients with familial hypercholesterolaemia (HC) taking maximally tolerated lipid-lowering therapy. Methods and results A planned interim analysis of an ongoing, open-label extension trial in patients (n = 141) with familial HC receiving a subcutaneous injection of 200 mg mipomersen weekly plus maximally tolerated lipid-lowering therapy for up to 104 weeks. The mean changes in low-density lipoprotein cholesterol (LDL-C) from baseline to weeks 26 (n = 130), 52 (n = 111), 76 (n = 66), and 104 (n = 53) were −28, −27, −27, and −28%; and in apolipoprotein B −29, −28, −30, and −31%, respectively. Reductions in total cholesterol, non-high-density lipoprotein-cholesterol, and lipoprotein(a) were comparable with decreases in LDL-C and apolipoprotein B levels. Mean high-density lipoprotein cholesterol increased from baseline by 7 and 6% at weeks 26 and 52, respectively. The long-term safety profile of mipomersen was similar to that reported in the associated randomized placebo-controlled Phase 3 trials. Adverse events included injection site reactions and flu-like symptoms. There was an incremental increase in the median liver fat during the initial 6–12 months that appeared to diminish with continued mipomersen exposure beyond 1 year and returned towards baseline 24 weeks after last drug dose suggestive of adaptation. The median alanine aminotransferase level showed a similar trend over time. Conclusion Long-term treatment with mipomersen for up to 104 weeks provided sustained reductions in all atherosclerotic lipoproteins measured and a safety profile consistent with prior controlled trials in these high-risk patient populations. Clinicaltrials.gov NCT00694109. PMID:24366918

  9. Long-term engraftment of single genetically modified human epidermal holoclones enables safety pre-assessment of cutaneous gene therapy.

    PubMed

    Larcher, Fernando; Dellambra, Elena; Rico, Laura; Bondanza, Sergio; Murillas, Rodolfo; Cattoglio, Claudia; Mavilio, Fulvio; Jorcano, José L; Zambruno, Giovanna; Del Rio, Marcela

    2007-09-01

    Predicting the risks of permanent gene therapy approaches involving the use of integrative gene-targeting vectors has become a critical issue after the unfortunate episode of a clinical trial in children with X-linked severe combined immunodeficiency (X-SCID). Safety pre-assessment of single isolated gene-targeted stem cells or their derivative clones able to regenerate their tissue of origin would be a major asset in addressing untoward gene therapy effects in advance. Human epidermal stem cells, which have extensive proliferative potential in vitro, theoretically offer such a possibility as a method of assessment. By means of optimized organotypic culture and grafting methods, we demonstrate the long-term in vivo regenerative capacity of single gene-targeted human epidermal stem cell clones (holoclones). Both histopathological analysis of holoclone-derived grafts in immunodeficient mice and retroviral insertion site mapping performed in the holoclone in vitro and after grafting provide proof of the feasibility of pre-assessing genotoxicity risks in isolated stem cells before transplantation into patients. Our results provide an experimental basis for previously untested assumptions about the in vivo behavior of epidermal stem cells prospectively isolated in vitro and pave the way for a safer approach to cutaneous gene therapy.

  10. Long-term follow-up of MCL patients treated with single-agent ibrutinib: updated safety and efficacy results

    PubMed Central

    Blum, Kristie A.; Martin, Peter; Goy, Andre; Auer, Rebecca; Kahl, Brad S.; Jurczak, Wojciech; Advani, Ranjana H.; Romaguera, Jorge E.; Williams, Michael E.; Barrientos, Jacqueline C.; Chmielowska, Ewa; Radford, John; Stilgenbauer, Stephan; Dreyling, Martin; Jedrzejczak, Wieslaw Wiktor; Johnson, Peter; Spurgeon, Stephen E.; Zhang, Liang; Baher, Linda; Cheng, Mei; Lee, Dana; Beaupre, Darrin M.; Rule, Simon

    2015-01-01

    Ibrutinib, an oral inhibitor of Bruton tyrosine kinase, is approved for patients with mantle cell lymphoma (MCL) who have received one prior therapy. We report the updated safety and efficacy results from the multicenter, open-label phase 2 registration trial of ibrutinib (median 26.7-month follow-up). Patients (N = 111) received oral ibrutinib 560 mg once daily, and those with stable disease or better could enter a long-term extension study. The primary end point was overall response rate (ORR). The median patient age was 68 years (range, 40-84), with a median of 3 prior therapies (range, 1-5). The median treatment duration was 8.3 months; 46% of patients were treated for >12 months, and 22% were treated for ≥2 years. The ORR was 67% (23% complete response), with a median duration of response of 17.5 months. The 24-month progression-free survival and overall survival rates were 31% (95% confidence interval [CI], 22.3-40.4) and 47% (95% CI, 37.1-56.9), respectively. The most common adverse events (AEs) in >30% of patients included diarrhea (54%), fatigue (50%), nausea (33%), and dyspnea (32%). The most frequent grade ≥3 infections included pneumonia (8%), urinary tract infection (4%), and cellulitis (3%). Grade ≥3 bleeding events in ≥2% of patients were hematuria (2%) and subdural hematoma (2%). Common all-grade hematologic AEs were thrombocytopenia (22%), neutropenia (19%), and anemia (18%). The prevalence of infection, diarrhea, and bleeding was highest for the first 6 months of therapy and less thereafter. With longer follow-up, ibrutinib continues to demonstrate durable responses and favorable safety in relapsed/refractory MCL. The trial is registered to www.ClinicalTrials.gov as #NCT01236391. PMID:26059948

  11. Evaluation of long-term gas hydrate production testing locations on the Alaska north slope

    USGS Publications Warehouse

    Collett, T.S.; Boswell, R.; Lee, M.W.; Anderson, B.J.; Rose, K.; Lewis, K.A.

    2011-01-01

    The results of short duration formation tests in northern Alaska and Canada have further documented the energy resource potential of gas hydrates and justified the need for long-term gas hydrate production testing. Additional data acquisition and long-term production testing could improve the understanding of the response of naturally-occurring gas hydrate to depressurization-induced or thermal-, chemical-, and/or mechanical-stimulated dissociation of gas hydrate into producible gas. The Eileen gas hydrate accumulation located in the Greater Prudhoe Bay area in northern Alaska has become a focal point for gas hydrate geologic and production studies. BP Exploration (Alaska) Incorporated and ConocoPhillips have each established research partnerships with U.S. Department of Energy to assess the production potential of gas hydrates in northern Alaska. A critical goal of these efforts is to identify the most suitable site for production testing. A total of seven potential locations in the Prudhoe Bay, Kuparuk, and Milne Point production units were identified and assessed relative to their suitability as a long-term gas hydrate production test site. The test site assessment criteria included the analysis of the geologic risk associated with encountering reservoirs for gas hydrate testing. The site selection process also dealt with the assessment of the operational/logistical risk associated with each of the potential test sites. From this review, a site in the Prudhoe Bay production unit was determined to be the best location for extended gas hydrate production testing. The work presented in this report identifies the key features of the potential test site in the Greater Prudhoe Bay area, and provides new information on the nature of gas hydrate occurrence and potential impact of production testing on existing infrastructure at the most favorable sites. These data were obtained from well log analysis, geological correlation and mapping, and numerical simulation

  12. Evaluation of long-term gas hydrate production testing locations on the Alaska North Slope

    USGS Publications Warehouse

    Collett, Timothy; Boswell, Ray; Lee, Myung W.; Anderson, Brian J.; Rose, Kelly K.; Lewis, Kristen A.

    2011-01-01

    The results of short duration formation tests in northern Alaska and Canada have further documented the energy resource potential of gas hydrates and justified the need for long-term gas hydrate production testing. Additional data acquisition and long-term production testing could improve the understanding of the response of naturally-occurring gas hydrate to depressurization-induced or thermal-, chemical-, and/or mechanical-stimulated dissociation of gas hydrate into producible gas. The Eileen gas hydrate accumulation located in the Greater Prudhoe Bay area in northern Alaska has become a focal point for gas hydrate geologic and production studies. BP Exploration (Alaska) Incorporated and ConocoPhillips have each established research partnerships with U.S. Department of Energy to assess the production potential of gas hydrates in northern Alaska. A critical goal of these efforts is to identify the most suitable site for production testing. A total of seven potential locations in the Prudhoe Bay, Kuparuk, and Milne Point production units were identified and assessed relative to their suitability as a long-term gas hydrate production test site. The test site assessment criteria included the analysis of the geologic risk associated with encountering reservoirs for gas hydrate testing. The site selection process also dealt with the assessment of the operational/logistical risk associated with each of the potential test sites. From this review, a site in the Prudhoe Bay production unit was determined to be the best location for extended gas hydrate production testing. The work presented in this report identifies the key features of the potential test site in the Greater Prudhoe Bay area, and provides new information on the nature of gas hydrate occurrence and potential impact of production testing on existing infrastructure at the most favorable sites. These data were obtained from well log analysis, geological correlation and mapping, and numerical simulation.

  13. Evaluation of long-term gas hydrate production testing locations on the Alaska North Slope

    USGS Publications Warehouse

    Collett, Timothy S.; Boswell, Ray; Lee, Myung W.; Anderson, Brian J.; Rose, Kelly K.; Lewis, Kristen A.

    2012-01-01

    The results of short-duration formation tests in northern Alaska and Canada have further documented the energy-resource potential of gas hydrates and have justified the need for long-term gas-hydrate-production testing. Additional data acquisition and long-term production testing could improve the understanding of the response of naturally occurring gas hydrate to depressurization-induced or thermal-, chemical-, or mechanical-stimulated dissociation of gas hydrate into producible gas. The Eileen gashydrate accumulation located in the Greater Prudhoe Bay area in northern Alaska has become a focal point for gas-hydrate geologic and production studies. BP Exploration (Alaska) Incorporated and ConocoPhillips have each established research partnerships with the US Department of Energy to assess the production potential of gas hydrates in northern Alaska. A critical goal of these efforts is to identify the most suitable site for production testing. A total of seven potential locations in the Prudhoe Bay, Kuparuk River, and Milne Point production units were identified and assessed relative to their suitability as a long-term gas-hydrate-production test sites. The test-site-assessment criteria included the analysis of the geologic risk associated with encountering reservoirs for gas-hydrate testing. The site-selection process also dealt with the assessment of the operational/logistical risk associated with each of the potential test sites. From this review, a site in the Prudhoe Bay production unit was determined to be the best location for extended gas-hydrate-production testing. The work presented in this report identifies the key features of the potential test site in the Greater Prudhoe Bay area and provides new information on the nature of gas-hydrate occurrence and the potential impact of production testing on existing infrastructure at the most favorable sites. These data were obtained from well-log analysis, geological correlation and mapping, and numerical

  14. Evaluation of the body composition and fat distribution in long-term users of hormone replacement therapy.

    PubMed

    Perrone, G; Liu, Y; Capri, O; Critelli, C; Barillaro, F; Galoppi, P; Zichella, L

    1999-01-01

    The aim of the study was to evaluate the body composition and fat distribution in long-term users of hormonal replacement therapy (HRT). 18 healthy menopausal women, long-term users of HRT (transdermal estradiol 50 microg continuously administered and 10 mg/day of medroxyprogesterone acetate for 12 days/month) and 18 healthy menopausal women, who had never used HRT were included in the study. Age, menopausal age, parity, weight and height (body mass index, weight/height2), and lifestyle habits were similar. Waist and hip circumference, body composition and waist/hip ratio were measured and the results were analyzed. No significant difference was demonstrated in fat and water percentage, and waist/hip ratio. Nevertheless, the waist circumference of long-term HRT users was significantly lower than that of non-users. In conclusion, abdominal fat in long-term HRT users is lower than that of non-users of similar age, menopausal age and body mass index.

  15. Combined liposuction and excision of lipomas: long-term evaluation of a large sample of patients.

    PubMed

    Copeland-Halperin, Libby R; Pimpinella, Vincenza; Copeland, Michelle

    2015-01-01

    Background. Lipomas are benign tumors of mature fat cells. They can be removed by liposuction, yet this technique is seldom employed because of concerns that removal may be incomplete and recurrence may be more frequent than after conventional excision. Objectives. We assessed the short- and long-term clinical outcomes and recurrence of combined liposuction and limited surgical excision of subcutaneous lipomas. Methods. From 2003 to 2012, 25 patients with 48 lipomas were treated with liposuction followed by direct excision through the same incision to remove residual lipomatous tissue. Initial postoperative follow-up ranged from 1 week to 3 months, and long-term outcomes, complications, and recurrence were surveyed 1 to 10 years postoperatively. Results. Lipomas on the head, neck, trunk, and extremities ranged from 1 to 15 cm in diameter. Early postoperative hematoma and seromas were managed by aspiration. Among 23 survey respondents (92%), patients were uniformly pleased with the cosmetic results; none reported recurrent lipoma. Conclusions. The combination of liposuction and excision is a safe alternative for lipoma removal; malignancy and recurrence are uncommon. Liposuction performed through a small incision provides satisfactory aesthetic results in most cases. Once reduced in size, residual lipomatous and capsular tissue can be removed without expanding the incision. These favorable outcomes support wider application of this technique in appropriate cases. PMID:25694827

  16. Combined Liposuction and Excision of Lipomas: Long-Term Evaluation of a Large Sample of Patients

    PubMed Central

    Copeland-Halperin, Libby R.; Pimpinella, Vincenza

    2015-01-01

    Background. Lipomas are benign tumors of mature fat cells. They can be removed by liposuction, yet this technique is seldom employed because of concerns that removal may be incomplete and recurrence may be more frequent than after conventional excision. Objectives. We assessed the short- and long-term clinical outcomes and recurrence of combined liposuction and limited surgical excision of subcutaneous lipomas. Methods. From 2003 to 2012, 25 patients with 48 lipomas were treated with liposuction followed by direct excision through the same incision to remove residual lipomatous tissue. Initial postoperative follow-up ranged from 1 week to 3 months, and long-term outcomes, complications, and recurrence were surveyed 1 to 10 years postoperatively. Results. Lipomas on the head, neck, trunk, and extremities ranged from 1 to 15 cm in diameter. Early postoperative hematoma and seromas were managed by aspiration. Among 23 survey respondents (92%), patients were uniformly pleased with the cosmetic results; none reported recurrent lipoma. Conclusions. The combination of liposuction and excision is a safe alternative for lipoma removal; malignancy and recurrence are uncommon. Liposuction performed through a small incision provides satisfactory aesthetic results in most cases. Once reduced in size, residual lipomatous and capsular tissue can be removed without expanding the incision. These favorable outcomes support wider application of this technique in appropriate cases. PMID:25694827

  17. Application to Evaluation of Hydrological Time Series Forecasting for Long-Term Runoff Simulation

    NASA Astrophysics Data System (ADS)

    Yoon, Sun-Kwon; Moon, Young-Il; Oh, Tae-Suk; Moon, Jang-Won; Kim, Seong-Sil

    2010-05-01

    Hydrological system forecasting, which is the short term runoff historical data during the limited period in dam site, is a conditional precedent of hydrological persistence by stochastic analysis. We have forecasted the monthly hydrological system from Andong dam basin data that is the rainfall, evaporation, and runoff, using the seasonal ARIMA (autoregressive integrated moving average) model. Also we have conducted long term runoff simulations through the forecasted results of TANK model and ARIMA+TANK model. It has been taking for three steps, which is model identification, model estimation and model diagnostic checking, to modeling for time series data to processing typical Box and Jenkins method. Therefore, time series data analysis carry out the model distinguished from ACF (autocorrelation function), PACF (partial autocorrelation function), AIC (akaike's bayesian criterion) and SBC (schwartz's bayesian criterion). Model diagnostic checking has been performed to portmanteau test, residual test and model identification by ML (maximum likelihood) method. The results of analysis have been concurred to the observation data, and it has been considered for application to possibility on the stochastic model for dam inflow forecasting. Thus, the method presented in this study suggests a help to water resource mid- and long-term strategy establishment to application for runoff simulations through the forecasting variables of hydrological time series on the relatively short holding runoff data in an object basins.

  18. Long-term evaluation of the degradation behavior of three apatite-forming calcium phosphate cements.

    PubMed

    An, Jie; Liao, Hongbing; Kucko, Nathan W; Herber, Ralf-Peter; Wolke, Joop G C; van den Beucken, Jeroen J J P; Jansen, John A; Leeuwenburgh, Sander C G

    2016-05-01

    Calcium phosphate cements (CPCs) are injectable bone substitutes with a long clinical history because of their biocompatibility and osteoconductivity. Nevertheless, their cohesion upon injection into perfused bone defects as well as their long-term degradation behavior remain major clinical challenges. Therefore, the long-term degradation behavior of two types of α-tricalcium phosphate-based, apatite-forming CPCs was compared to a commercially available apatite-forming cement, that is HydroSet™ . Carboxyl methylcellulose (CMC) was used as cohesion promotor to improve handling properties of the two experimental cements, whereas poly (d, l-lactic-co-glycolic) acid (PLGA) microparticles were added to introduce macroporosity and stimulate CPC degradation. All three CPCs were injected into defects drilled into rabbit femoral condyles and explanted after 4, 12, or 26 weeks, after which the bone response was assessed both qualitatively and quantitatively. CPCs without PLGA microparticles degraded only at the periphery of the implants, while the residual CPC volume was close to 90%. On the contrary, bone ingrowth was observed not only at the periphery of the CPC, but also throughout the center of the implants after 26 weeks of implantation for the PLGA-containing CPCs with a residual CPC volume of approximately 55%. In conclusion, it was shown that CPC containing CMC and PLGA was able to induce partial degradation of apatite-forming CPCs and concomitant replacement by bone tissue. PMID:26743230

  19. Long-term efficacy, tolerability and safety of nalmefene as-needed in patients with alcohol dependence: A 1-year, randomised controlled study.

    PubMed

    van den Brink, Wim; Sørensen, Per; Torup, Lars; Mann, Karl; Gual, Antoni

    2014-08-01

    This study evaluated the long-term efficacy and safety of nalmefene treatment in reducing alcohol consumption. We randomised (1:3) 675 alcohol-dependent patients ≥ 18 years of age to 52 weeks of as-needed treatment with placebo or nalmefene 18 mg/day: A total of 112 patients (68%) in the placebo group and 310 (62%) in the nalmefene group completed the study. At month 6, the co-primary outcome variables showed no statistically-significant differences between the treatment groups; but at month 13, nalmefene was more effective than placebo, both in the reduction of the number of heavy drinking days (HDDs) (- 1.6 days/month (95% CI - 2.9; - 0.3); p = 0.017) and the reduction of total alcohol consumption (TAC) (- 6.5 g/day last month (95% CI - 12.5; - 0.4); p = 0.036). In a subgroup analysis of patients with high/very high drinking risk levels at screening and at randomisation (the target population), there was a significant effect in favour of nalmefene on TAC at month 6, and on both HDD and TAC at month 13. Improvements in Clinical Global Impression and liver enzymes were greater with nalmefene, compared to placebo. Most adverse events were mild or moderate, and transient; adverse events, including those leading to dropout, were more common with nalmefene. This study provides evidence for the long-term safety and efficacy of nalmefene as-needed in alcohol-dependent patients whom continue to drink heavily, following a brief intervention.

  20. Safety and long-term effect of the probiotic FK-23 in patients with hepatitis C virus infection

    PubMed Central

    OO, Khin May; LWIN, Aye Aye; KYAW, Yi Yi; TUN, Win Maw; FUKADA, Kazutake; GOSHIMA, Akiko; SHIMADA, Takashi; OKADA, Shigeru

    2016-01-01

    A clinical trial was conducted on 39 adult HCV-positive subjects to determine the safety and long-term effect of the probiotic FK-23 (heat-treated Enterococcus faecalis strain FK-23). Asymptomatic anti-HCV positive adults who fulfilled the selection criteria and gave voluntary consent were recruited from attendees of the Hepatitis Carrier Clinic, Department of Medical Research (Lower Myanmar). Each subject was given 2,700 mg of FK-23 per day by oral route. Blood samples were taken at enrollment and every 3 months and tested for alanine aminotransferase (ALT) and aspartate transaminase (AST). Viral load, urea, total protein, hemoglobin and platelet count were determined every 6 months. Among the subjects, 23 completed 36 months, 31 completed 24 months, 35 completed 12 months and 37 completed 6 months of probiotic therapy. Significant decreases in mean ALT levels were observed at 3 months (34. 9 ± 15.1 IU/l) as compared with the initial level (64.8 ± 17.5 IU/l) and persisted up to 36 months (43.7 ± 25.2 IU/l). Decrease of AST was detected after 9 months (46.2 ± 21.7 IU/l) of probiotic therapy as compared with the initial level (64.3 ± 28.7 IU/l). FK-23 was safe based on the stable levels of biochemical and hematological parameters and the absence of untoward side effects. The FK-23 preparation was well tolerated and accepted by the subjects. PMID:27508113

  1. Safety and long-term effect of the probiotic FK-23 in patients with hepatitis C virus infection.

    PubMed

    Oo, Khin May; Lwin, Aye Aye; Kyaw, Yi Yi; Tun, Win Maw; Fukada, Kazutake; Goshima, Akiko; Shimada, Takashi; Okada, Shigeru

    2016-01-01

    A clinical trial was conducted on 39 adult HCV-positive subjects to determine the safety and long-term effect of the probiotic FK-23 (heat-treated Enterococcus faecalis strain FK-23). Asymptomatic anti-HCV positive adults who fulfilled the selection criteria and gave voluntary consent were recruited from attendees of the Hepatitis Carrier Clinic, Department of Medical Research (Lower Myanmar). Each subject was given 2,700 mg of FK-23 per day by oral route. Blood samples were taken at enrollment and every 3 months and tested for alanine aminotransferase (ALT) and aspartate transaminase (AST). Viral load, urea, total protein, hemoglobin and platelet count were determined every 6 months. Among the subjects, 23 completed 36 months, 31 completed 24 months, 35 completed 12 months and 37 completed 6 months of probiotic therapy. Significant decreases in mean ALT levels were observed at 3 months (34. 9 ± 15.1 IU/l) as compared with the initial level (64.8 ± 17.5 IU/l) and persisted up to 36 months (43.7 ± 25.2 IU/l). Decrease of AST was detected after 9 months (46.2 ± 21.7 IU/l) of probiotic therapy as compared with the initial level (64.3 ± 28.7 IU/l). FK-23 was safe based on the stable levels of biochemical and hematological parameters and the absence of untoward side effects. The FK-23 preparation was well tolerated and accepted by the subjects. PMID:27508113

  2. Experimental evaluation of stable long term operation of semiconductor magnetic sensors at ITER relevant environment

    NASA Astrophysics Data System (ADS)

    Bolshakova, I.; Belyaev, S.; Bulavin, M.; Brudnyi, V.; Chekanov, V.; Coccorese, V.; Duran, I.; Gerasimov, S.; Holyaka, R.; Kargin, N.; Konopleva, R.; Kost, Ya.; Kuech, T.; Kulikov, S.; Makido, O.; Moreau, Ph; Murari, A.; Quercia, A.; Shurygin, F.; Strikhanov, M.; Timoshyn, S.; Vasil'evskii, I.; Vinichenko, A.

    2015-08-01

    The paper deals with radiation resistant sensors and their associated measuring instrumentation developed in the course of R and D activities carried out in the framework of an international collaboration. The first trial tests of three-dimensional (3D) probes with Hall sensors have been performed in European tokamaks TORE SUPRA (2004) and JET (2005). Later in 2009 six sets of 3D probes were installed in JET and now continue to operate. The statistical analysis performed in 2014 on the basis of the JET database have demonstrated stable long term operation of all 18 sensors of 3D probes. The results of measurements conducted at the neutron fluxes of nuclear reactors have demonstrated the operability of the sensors up to high neutron fluences of F  >  1018n • cm-2 that exceeds the maximum one for the locations of steady state sensors in ITER over its total lifetime.

  3. Long-Term Follow-Up of a Revascularized Immature Necrotic Tooth Evaluated by CBCT

    PubMed Central

    She, C. M. L.; Cheung, G. S. P.; Zhang, C. F.

    2016-01-01

    This case study reports the successful treatment of an immature upper premolar with periapical pathosis and sinus tract using revascularization technique. Clinical and radiographic examination demonstrated the recovery of vitality, continued root development, and periapical healing at the 7-month follow-up. In addition, severe calcification of the canal was noted at the 36-month follow-up. At the 66-month follow-up, cone-beam computed tomography (CBCT) revealed complete periapical healing, apical closure, increase in root length and thickness of dentin, and severe calcification of the root canal. Even though the nature of tissue within the root canal is unknown, revascularization appears to give good clinical and radiographic success. This case report highlights that severe calcification of the canal is one of the long-term outcomes of revascularized root canals. PMID:26949550

  4. Long-term environmental effects and flight service evaluation of composite materials

    SciTech Connect

    Dexter, H.B.

    1987-01-01

    Results of a NASA-Langley sponsored research program to establish the long term effects of realistic flight environments and ground based exposure on advanced composite materials are presented. The effects of moisture, ultraviolet radiation, aircraft fuels and fluids, sustained stress, and fatigue loading are reported. Residual strength and stiffness as a function of exposure time and exposure location are reported for seven different material systems after 10 years of worldwide outdoor exposure. Flight service results of over 300 composite components installed on rotorcraft and transport aircraft are included. Over 4 million total component flight hours were accumulated on various aircraft since initiation of flight service in 1973. Service performance, maintenance characteristics, and residual strength of numerous composite components installed on commercial and military aircraft are reported as a function of flight hours and years in service. Residual strength test results of graphite/epoxy spoilers with 10 years of worldwide service and over 28,000 flight hours are reported.

  5. Evaluating long-term performance of in situ vitrified waste forms: Methodology and results

    SciTech Connect

    McGrail, B.P.; Olson, K.M.

    1992-11-01

    In situ vitrification (ISV) is an emerging technology for the remediation of hazardous and radioactive waste sites. The concept relies on the principle of Joule heating to raise the temperature of a soil between an array of electrodes above the melting temperature. After cooling, the melt solidifies into a massive glass and crystalline block similar to naturally occurring obsidian. Determining the long-term performance of ISV products in a changing regulatory environment requires a fundamental understanding of the mechanisms controlling the dissolution behavior of the material. A series of experiments was performed to determine the dissolution behavior of samples produced from the ISV processing of typical soils from the Idaho National Engineering Laboratory subsurface disposal area. Dissolution rate constant measurements were completed at 90{degrees}C over the pH range 2 to 11 for one sample obtained from a field test of the ISV process.

  6. Evaluating long-term performance of in situ vitrified waste forms: Methodology and results

    SciTech Connect

    McGrail, B.P.; Olson, K.M.

    1992-11-01

    In situ vitrification (ISV) is an emerging technology for the remediation of hazardous and radioactive waste sites. The concept relies on the principle of Joule heating to raise the temperature of a soil between an array of electrodes above the melting temperature. After cooling, the melt solidifies into a massive glass and crystalline block similar to naturally occurring obsidian. Determining the long-term performance of ISV products in a changing regulatory environment requires a fundamental understanding of the mechanisms controlling the dissolution behavior of the material. A series of experiments was performed to determine the dissolution behavior of samples produced from the ISV processing of typical soils from the Idaho National Engineering Laboratory subsurface disposal area. Dissolution rate constant measurements were completed at 90[degrees]C over the pH range 2 to 11 for one sample obtained from a field test of the ISV process.

  7. Evaluation of low-dosage environmental mutagens with a long-term, cultured epithelial cell line

    SciTech Connect

    Li, C.S.; Lin, R.H.

    1996-12-31

    Polycyclic or polynuclear aromatic hydrocarbons (PAHs) are a group of compounds consisting of at least two fused aromatic rings and are common environmental contaminants in soil, water, and air. Additionally, some PAHs are considered to be mutagenic, carcinogenic, and cytotoxic compounds. BaA (Benz(a)anthracene) and BaP (Benzo(a)pyrene) are the two major unsubstituted PAHs identified by the USEPA as priority pollutants. BaA is suspected to be a human carcinogen by the US Department of Health and Human Services, whereas BaP is regarded as an animal carcinogen. It is estimated that the emission concentrations of BaA and BaP from mainstream cigarette smoke are 20-70 ng per g cigarette and 20-40 ng per g cigarette, respectively, with an average sidestream to mainstream weight ratio of 3. In addition, BaA and BaP are also the main emissions from diesel particulate extracts with mean concentrations of 500 ppm and 40 ppm, respectively. From a recent report concerning PAHs in urban areas all over the world, the airborne concentration of BaP was typically found to be in the range of 1-20 ng/m{sup 3} in Europe and 1 ng/m{sup 3} in the U.S.A. For BaA, the concentrations commonly ranged from I to 50 ng/m{sup 3} in Europe and from 0.1 to 1 ng/m{sup 3} in the U.S.A. Therefore, the long term exposure to these two compounds may cause health effects. This study examines long-term cultured epithelial cell lines exposed to BaP or BaA, in vitro, and the frequency of HGPRT mutants. 19 refs., 3 figs.

  8. Robustness-based evaluation of long-term river basin planning under climate change

    NASA Astrophysics Data System (ADS)

    Taner, M. U.; Ray, P. A.; Brown, C. M.

    2015-12-01

    This work develops a bottom-up, multi-stage planning framework for the sustainable development of river basin systems under deep climate uncertainty. The research focuses on whether and when it is desirable to invest for costly water infrastructure projects, and how to select among a set of project alternatives in order achieve the desired economic benefits with a relatively low level of risk. The proposed framework begins with identifying a set of climate conditions to represent the future vulnerability domain of the system using simulation analysis. The conditions identified in the simulation analysis are then used to develop a scenario-tree, to represent the manner in which the uncertainties may evolve over the course of the planning period. Next, optimal decisions are repeatedly explored through a multi-stage optimization model, by varying the probability weights employed in the scenario-tree. The resulting vector of optimal decisions are post-processed to identify robust choices that are least sensitive to the scenario probabilities. The proposed planning framework is illustrated for the Niger Basin, over a 45-year planning period from 2015 to 2060. The Niger Basin is a transboundary system facing a series of challenges including endemic poverty, inadequate infrastructure and weak adaptive capacity to climate variability and change. The case study assesses long-term economic benefits from four new dam projects, and from a range of expansions across the eleven irrigation zones. The climate scenarios are obtained by first generating new climate variability realizations from a stochastic weather generator, and then placing climate change factors on the generated climate realizations. Basin runoff response to climate scenarios are simulated by a series of monthly, two-compartment water balance models. Long-term economic benefits are estimated from the sectors of irrigated agriculture, hydropower, navigation, fishing, and environmental protection, using a mixed

  9. Evaluating Long-term Outcomes of NHS Stop Smoking Services (ELONS): a prospective cohort study.

    PubMed Central

    Dobbie, Fiona; Hiscock, Rosemary; Leonardi-Bee, Jo; Murray, Susan; Shahab, Lion; Aveyard, Paul; Coleman, Tim; McEwen, Andy; McRobbie, Hayden; Purves, Richard; Bauld, Linda

    2015-01-01

    BACKGROUND NHS Stop Smoking Services (SSSs) provide free at the point of use treatment for smokers who would like to stop. Since their inception in 1999 they have evolved to offer a variety of support options. Given the changes that have happened in the provision of services and the ongoing need for evidence on effectiveness, the Evaluating Long-term Outcomes for NHS Stop Smoking Services (ELONS) study was commissioned. OBJECTIVES The main aim of the study was to explore the factors that determine longer-term abstinence from smoking following intervention by SSSs. There were also a number of additional objectives. DESIGN The ELONS study was an observational study with two main stages: secondary analysis of routine data collected by SSSs and a prospective cohort study of service clients. The prospective study had additional elements on client satisfaction, well-being and longer-term nicotine replacement therapy (NRT) use. SETTING The setting for the study was SSSs in England. For the secondary analysis, routine data from 49 services were obtained. For the prospective study and its added elements, nine services were involved. The target population was clients of these services. PARTICIPANTS There were 202,804 cases included in secondary analysis and 3075 in the prospective study. INTERVENTIONS A combination of behavioural support and stop smoking medication delivered by SSS practitioners. MAIN OUTCOME MEASURES Abstinence from smoking at 4 and 52 weeks after setting a quit date, validated by a carbon monoxide (CO) breath test. RESULTS Just over 4 in 10 smokers (41%) recruited to the prospective study were biochemically validated as abstinent from smoking at 4 weeks (which was broadly comparable with findings from the secondary analysis of routine service data, where self-reported 4-week quit rates were 48%, falling to 34% when biochemical validation had occurred). At the 1-year follow-up, 8% of prospective study clients were CO validated as abstinent from smoking

  10. Long-term organ damage accrual and safety in patients with SLE treated with belimumab plus standard of care

    PubMed Central

    Urowitz, M; van Vollenhoven, R; Aranow, C; Fettiplace, J; Oldham, M; Wilson, B; Molta, C; Roth, D; Gordon, D

    2016-01-01

    Objective To examine long-term organ damage and safety following treatment with belimumab plus standard of care (SoC) in patients with systemic lupus erythematosus (SLE). Methods Pooled data were examined from two ongoing open-label studies that enrolled patients who completed BLISS-52 or BLISS-76. Patients received belimumab every four weeks plus SoC. SLICC Damage Index (SDI) values were assessed every 48 weeks (study years) following belimumab initiation (baseline). The primary endpoint was change in SDI from baseline at study years 5–6. Incidences of adverse events (AEs) were reported for the entire study period. Results The modified intent-to-treat (MITT) population comprised 998 patients. At baseline, 940 (94.2%) were female, mean (SD) age was 38.7 (11.49) years, and disease duration was 6.7 (6.24) years. The mean (SD) SELENA-SLEDAI and SDI scores were 8.2 (4.18) and 0.7 (1.19), respectively; 411 (41.2%) patients had organ damage (SDI = 1: 235 (23.5%); SDI ≥ 2: 176 (17.6%)) prior to belimumab. A total of 427 (42.8%) patients withdrew overall; the most common reasons were patient request (16.8%) and AEs (8.5%). The mean (SD) change in SDI was +0.2 (0.48) at study years 5–6 (n = 403); 343 (85.1%) patients had no change from baseline in SDI score (SDI +1: 46 (11.4%), SDI +2: 13 (3.2%), SDI +3: 1 (0.2%)). Of patients without organ damage at baseline, 211/241 (87.6%) had no change in SDI and the mean change (SD) in SDI was +0.2 (0.44). Of patients with organ damage at baseline, 132/162 (81.5%) had no change in SDI and the mean (SD) change in SDI was +0.2 (0.53). The probability of not having a worsening in SDI score was 0.88 (95% CI: 0.85, 0.91) and 0.75 (0.67, 0.81) in those without and with baseline damage, respectively (post hoc analysis). Drug-related AEs were reported for 433 (43.4%) patients; infections/infestations (282, 28.3%) and gastrointestinal disorders (139, 13.9%) were the most common. Conclusion Patients with SLE treated with long-term

  11. Accelerated forgetting? An evaluation on the use of long-term forgetting rates in patients with memory problems

    PubMed Central

    Geurts, Sofie; van der Werf, Sieberen P.; Kessels, Roy P. C.

    2015-01-01

    The main focus of this review was to evaluate whether long-term forgetting rates (delayed tests, days, to weeks, after initial learning) are more sensitive measures than standard delayed recall measures to detect memory problems in various patient groups. It has been suggested that accelerated forgetting might be characteristic for epilepsy patients, but little research has been performed in other populations. Here, we identified eleven studies in a wide range of brain injured patient groups, whose long-term forgetting patterns were compared to those of healthy controls. Signs of accelerated forgetting were found in three studies. The results of eight studies showed normal forgetting over time for the patient groups. However, most of the studies used only a recognition procedure, after optimizing initial learning. Based on these results, we recommend the use of a combined recall and recognition procedure to examine accelerated forgetting and we discuss the relevance of standard and optimized learning procedures in clinical practice. PMID:26106343

  12. Transplantation of a horseshoe kidney from a living donor: Case report, long term outcome and donor safety

    PubMed Central

    Justo-Janeiro, Jaime Manuel; Orozco, Eduardo Prado; Reyes, Francisco J.Roberto Enríquez; de la Rosa Paredes, René; de Lara Cisneros, Luis G.Vázquez; Espinosa, Alfonso Lozano; Naylor, Jesús Mier

    2015-01-01

    Introduction The use of a horseshoe kidney in renal transplant remains controversial, when it is found in the evaluation of a living donor, anatomical, surgical and ethical issues are involved. Presentation of Case An uncomplicated horseshoe kidney was detected in a 51-year-old woman who was the only suitable donor for her 30-year-old son. Kidneys were fused in the inferior pole and no vascular or urinary abnormalities were detected during imaging evaluation. The surgical procedure was approved by the hospital transplant committee. A laparotomy was performed by means of a medial upper incision. The isthmus of the kidney was divided using a harmonic scalpel and the left segment was used; it had 2 arteries too distant to create a common one, thus anastomosed separately. The renal vein was side-to-side anastomosed to the right external iliac vein and a Lich-Gregoir ureteral implant was made. There were no intraoperative or postoperative complications in the donor who currently remains asymptomatic. Recipient developed a delayed graft function (DGF), and was discharged on the 12th day after surgery. After 24 months of surgery, renal function has remained stable with a serum creatinine of 128 μmol/L (1.45 mg/dL). Discussion There are 7 reports of a horseshoe kidney from living donors in 8 patients without morbidity and a good long term outcome of all recipients. Conclusion If we anticipate a low operative risk and there is a suitable anatomy, we may consider the use of horseshoe kidneys from living donors a viable alternative. PMID:26299249

  13. Safety and efficacy of long-term combination therapy with bezafibrate and ezetimibe in patients with dyslipidemia in the prospective, observational J-COMPATIBLE study

    PubMed Central

    2013-01-01

    Background There are numerous reports describing the efficacy of fenofibrate in combination with ezetimibe for treating dyslipidemia. In contrast, a study combining bezafibrate and ezetimibe has not yet been conducted. In this study, we examined the safety, including the risk of gallstone formation, and the efficacy of long-term combination therapy with bezafibrate and ezetimibe for treating dyslipidemia. Methods Dyslipidemic patients treated with 400 mg/day bezafibrate in combination with 10 mg/day ezetimibe for the first time were eligible. We selected 157 institutions in Japan and conducted a 12-month prospective observational study, with patients enrolled on the day they started combination therapy. Safety of the combination was examined in terms of the type, onset, and severity of adverse drug reactions (ADRs). Efficacy was evaluated in terms of the changes in low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), triglyceride (TG), and non-HDL cholesterol (non-HDL-C) levels from the start of combination therapy (baseline) to the last observation carried forward (LOCF). Lipid levels were assessed at 1, 3, 6, and 12 months after starting combination therapy. Results We enrolled 665 patients in this observational study. Safety was evaluated in 659, and ADRs occurred in 42 patients (6.4%). The most frequent ADRs were blood creatine phosphokinase increase (1.5%) and myalgia (0.8%). Asymptomatic gallstones were observed in four patients (0.6%). Effectiveness was evaluated in 622 patients. LDL-C, HDL-C, TG, and non-HDL-C levels improved significantly from baseline to LOCF by −17.4%, 8.8%, –40.5%, and −21.6%, respectively (all, p < 0.001). Lipid levels also improved from baseline to each evaluation time-point. Conclusions Bezafibrate in combination with ezetimibe is safe and effective, and is potentially useful for comprehensive management of dyslipidemia. PMID:24195788

  14. An evaluation of two incontinence skin care protocols in a long-term care setting.

    PubMed

    Lewis-Byers, Kari; Thayer, Debra

    2002-12-01

    Caring for the skin of patients with incontinence is an essential activity in long-term care. A prospective descriptive study to compare the effect of two skin care protocols on skin condition, pain, and caregiver time was conducted. Thirty-two (32) skilled nursing facility residents with incontinence participated in the 3-week study. Patients were randomly assigned to a standard care regimen (soap and water cleansing after each incontinence episode, followed by application of a moisturizing lotion) or study care protocol (no-rinse skin cleanser after each episode and application of a barrier cream with durable properties after the first incontinence episode of each shift). Number and type of incontinence episodes, skin condition, pain, and caregiver time spent were assessed. Skin integrity was maintained in the majority of control (69%) and study group (72%) patients and improvement occurred in 8% of control and 17% of the study group (NS). Study protocol procedures took less time to complete than control procedures (a savings of 79 minutes/patient/day). A positive correlation between pain intensity and level of skin impairment was observed (r = 0.88). The results of this study suggest that at this facility, use of soap, water, and a moisturizer may be less effective and more time-consuming than using a no-rinse cleanser and a durable barrier product.

  15. Evaluation of a long-term hindcast simulation for the Columbia River estuary

    NASA Astrophysics Data System (ADS)

    Kärnä, Tuomas; Baptista, António M.

    2016-03-01

    In order to simulate the biogeochemical function of estuaries across the land-ocean continuum, circulation models must represent a cascade of complex physical processes spanning several spatial and temporal scales. Furthermore, governing physical processes tend to vary under different flow regimes, in response to external forcings. Model validation must therefore cover all relevant flow regimes and span sufficiently long time to represent transient and slowly-varying phenomena. We focus in a multi-year hindcast simulation of the Columbia River estuary - a mesotidal, river-dominated estuary that is also influenced by coastal upwelling in an Eastern Boundary Current system. Model skill is assessed against long-term observational time series, covering the lower estuary (for salinity) as well as most of the tidal river (for water temperature and elevation). In addition, high-resolution profiles of velocity and salinity are used to study salt transport mechanisms at a single station. Results indicate that the model captures the estuarine dynamics of the system, but the skill depends on the flow regime: In general the model performs far better during spring tides (i.e., under partially mixed or time-dependent salt wedge regimes) than under neap tides (i.e., salt wedge and strongly stratified regimes). While the model accurately represents tidal salt transport mechanisms, it tends to underestimate gravitational transport which becomes more important under neap tide conditions. Furthermore, the skill decreases during high river discharge periods, because the model has difficulty capturing the extremely strong stratification characteristic to those periods.

  16. Evaluating the feasibility of biological waste processing for long term space missions

    NASA Technical Reports Server (NTRS)

    Garland, J. L.; Alazraki, M. P.; Atkinson, C. F.; Finger, B. W.; Sager, J. C. (Principal Investigator)

    1998-01-01

    Recycling waste products during orbital (e.g., International Space Station) and planetary missions (e.g., lunar base, Mars transit mission, Martian base) will reduce storage and resupply costs. Wastes streams on the space station will include human hygiene water, urine, faeces, and trash. Longer term missions will contain human waste and inedible plant material from plant growth systems used for atmospheric regeneration, food production, and water recycling. The feasibility of biological and physical-chemical waste recycling is being investigated as part of National Aeronautics and Space Administration's (NASA) Advanced Life Support (ALS) Program. In-vessel composting has lower manpower requirements, lower water and volume requirements, and greater potential for sanitization of human waste compared to alternative bioreactor designs such as continuously stirred tank reactors (CSTR). Residual solids from the process (i.e. compost) could be used a biological air filter, a plant nutrient source, and a carbon sink. Potential in-vessel composting designs for both near- and long-term space missions are presented and discussed with respect to the unique aspects of space-based systems.

  17. Evaluating the feasibility of biological waste processing for long term space missions.

    PubMed

    Garland, J L; Alazraki, M P; Atkinson, C F; Finger, B W

    1998-01-01

    Recycling waste products during orbital (e.g., International Space Station) and planetary missions (e.g., lunar base, Mars transit mission, Martian base) will reduce storage and resupply costs. Wastes streams on the space station will include human hygiene water, urine, faeces, and trash. Longer term missions will contain human waste and inedible plant material from plant growth systems used for atmospheric regeneration, food production, and water recycling. The feasibility of biological and physical-chemical waste recycling is being investigated as part of National Aeronautics and Space Administration's (NASA) Advanced Life Support (ALS) Program. In-vessel composting has lower manpower requirements, lower water and volume requirements, and greater potential for sanitization of human waste compared to alternative bioreactor designs such as continuously stirred tank reactors (CSTR). Residual solids from the process (i.e. compost) could be used a biological air filter, a plant nutrient source, and a carbon sink. Potential in-vessel composting designs for both near- and long-term space missions are presented and discussed with respect to the unique aspects of space-based systems. PMID:11541774

  18. Evaluating the feasibility of biological waste processing for long term space missions.

    PubMed

    Garland, J L; Alazraki, M P; Atkinson, C F; Finger, B W

    1998-01-01

    Recycling waste products during orbital (e.g., International Space Station) and planetary missions (e.g., lunar base, Mars transit mission, Martian base) will reduce storage and resupply costs. Wastes streams on the space station will include human hygiene water, urine, faeces, and trash. Longer term missions will contain human waste and inedible plant material from plant growth systems used for atmospheric regeneration, food production, and water recycling. The feasibility of biological and physical-chemical waste recycling is being investigated as part of National Aeronautics and Space Administration's (NASA) Advanced Life Support (ALS) Program. In-vessel composting has lower manpower requirements, lower water and volume requirements, and greater potential for sanitization of human waste compared to alternative bioreactor designs such as continuously stirred tank reactors (CSTR). Residual solids from the process (i.e. compost) could be used a biological air filter, a plant nutrient source, and a carbon sink. Potential in-vessel composting designs for both near- and long-term space missions are presented and discussed with respect to the unique aspects of space-based systems.

  19. Development and long-term in vivo evaluation of a biodegradable urethane-doped polyester elastomer.

    PubMed

    Dey, Jagannath; Tran, Richard T; Shen, Jinhui; Tang, Liping; Yang, Jian

    2011-12-12

    We have recently reported upon the development of crosslinked urethane-doped polyester (CUPE) network elastomers, which was motivated by the desire to overcome the drawbacks presented by crosslinked network polyesters and biodegradable polyurethanes for soft tissue engineering applications. Although the effect of the isocyanate content and post-polymerization conditions on the material structure-property relationship was examined in detail, the ability of the diol component to modulate the material properties was only studied briefly. Herein, we present a detailed report on the development of CUPE polymers synthesized using diols 4, 6, 8, 10, or 12 methylene units in length in order to investigate what role the diol component plays on the resulting material's physical properties, and assess their long-term biological performance in vivo. An increase in the diol length was shown to affect the physical properties of the CUPE polymers primarily through lowered polymeric crosslinking densities and elevated material hydrophobicity. The use of longer chain diols resulted in CUPE polymers with increased molecular weights resulting in higher tensile strength and elasticity, while also increasing the material hydrophobicity to lower bulk swelling and prolong the polymer degradation rates. Although the number of methylene units largely affected the physical properties of CUPE, the choice of diol did not affect the overall polymer cell/tissue-compatibility both in vitro and in vivo. In conclusion, we have established the diol component as an important parameter in controlling the structure-property relationship of the polymer in addition to diisocyanate concentration and post-polymerization conditions. Expanding the family of CUPE polymers increases the choices of biodegradable elastomers for tissue engineering applications.

  20. Evaluation of urinary bladder fibrogenesis in a mouse model of long-term ketamine injection.

    PubMed

    Shen, Cheng-Huang; Wang, Shou-Chieh; Wang, Shou-Tsung; Lin, Shu-Mei; Wu, Jiann-Der; Lin, Chang-Te; Liu, Yi-Wen

    2016-09-01

    Long-term ketamine abuse has been shown to affect the lower urinary tract and result in interstitial cystitis-like syndrome. However, the causative mechanism of ketamine-induced dysfunction remains unclear. The present study aimed to investigate the physiological, histological and molecular changes on ketamine‑associated cystitis (KC) in a mouse model. Both male and female Balb/c mice were separately distributed into the control group (normal saline) and ketamine group, which received ketamine hydrochloride (100 mg/kg/day) daily by intraperitoneal injection for a total period of 20 weeks. In each group, the urine was analyzed by gas chromatography‑mass spectrometry to measure the concentration of ketamine and its metabolites. Urinary frequency and urine volume were examined to investigate the urinary voiding functions. Mice bladders were excised for cDNA microarray and hematoxylin and eosin (HE) staining. The ketamine and metabolites were detected only in ketamine‑treated mice urine. The voiding interval was reduced in the male mice group after 20 week ketamine administration. Additionally, the result of cDNA array analysis revealed a number of gene expression levels involved in chronic wound healing response and collagen accumulation, which were closely associated with fibrosis progression in the connective tissue. In HE staining of the bladder tissue, the ketamine-injected mice exhibited prominently denser blood vessel distribution in the submucosal layer. Based on the evidence in the present study, a mechanism that delineates fibrosis formation of urinary bladder induced by the pathogenesis of ketamine abuse can be constructed. PMID:27431428

  1. Long-term Evaluation of Radiation-Induced Optic Neuropathy After Single-Fraction Stereotactic Radiosurgery

    SciTech Connect

    Leavitt, Jacqueline A.; Stafford, Scott L.; Link, Michael J.; Pollock, Bruce E.

    2013-11-01

    Purpose: To determine the long-term risk of radiation-induced optic neuropathy (RION) in patients having single-fraction stereotactic radiosurgery (SRS) for benign skull base tumors. Methods and Materials: Retrospective review of 222 patients having Gamma Knife radiosurgery for benign tumors adjacent to the anterior visual pathway (AVP) between 1991 and 1999. Excluded were patients with prior or concurrent external beam radiation therapy or SRS. One hundred twenty-nine patients (58%) had undergone previous surgery. Tumor types included confirmed World Health Organization grade 1 or presumed cavernous sinus meningioma (n=143), pituitary adenoma (n=72), and craniopharyngioma (n=7). The maximum dose to the AVP was ≤8.0 Gy (n=126), 8.1-10.0 Gy (n=39), 10.1-12.0 Gy (n=47), and >12 Gy (n=10). Results: The mean clinical and imaging follow-up periods were 83 and 123 months, respectively. One patient (0.5%) who received a maximum radiation dose of 12.8 Gy to the AVP developed unilateral blindness 18 months after SRS. The chance of RION according to the maximum radiation dose received by the AVP was 0 (95% confidence interval [CI] 0-3.6%), 0 (95% CI 0-10.7%), 0 (95% CI 0-9.0%), and 10% (95% CI 0-43.0%) for patients receiving ≤8 Gy, 8.1-10.0 Gy, 10.1-12.0 Gy, and >12 Gy, respectively. The overall risk of RION in patients receiving >8 Gy to the AVP was 1.0% (95% CI 0-6.2%). Conclusions: The risk of RION after single-fraction SRS in patients with benign skull base tumors who have no prior radiation exposure is very low if the maximum dose to the AVP is ≤12 Gy. Physicians performing single-fraction SRS should remain cautious when treating lesions adjacent to the AVP, especially when the maximum dose exceeds 10 Gy.

  2. Development and long-term in vivo evaluation of a biodegradable urethane-doped polyester elastomer

    PubMed Central

    Dey, Jagannath; Tran, Richard T.; Shen, Jinhui; Tang, Liping; Yang, Jian

    2011-01-01

    We have recently reported upon the development of crosslinked urethane-doped polyester (CUPE) network elastomers, which was motivated by the desire to overcome the drawbacks presented by crosslinked network polyesters and biodegradable polyurethanes for soft tissue engineering applications. Although the effect of the isocyanate content and post-polymerization conditions on the material structure-property relationship was examined in detail, the ability of the diol component to modulate the material properties was only studied briefly. Herein, we present a detailed report on the development of CUPE polymers synthesized using diols 4, 6, 8, 10, or 12 methylene units in length in order to investigate what role the diol component plays on the resulting material’s physical properties, and assess their long-term biological performance in vivo. An increase in the diol length was shown to affect the physical properties of the CUPE polymers primarily through lowered polymeric crosslinking densities and elevated material hydrophobicity. The use of longer chain diols resulted in CUPE polymers with increased molecular weights resulting in higher tensile strength and elasticity, while also increasing the material hydrophobicity to lower bulk swelling and prolong the polymer degradation rates. Although the number of methylene units largely affected the physical properties of CUPE, the choice of diol did not affect the overall polymer cell/tissue-compatibility both in vitro and in vivo. In conclusion, we have established the diol component as an important parameter in controlling the structure-property relationship of the polymer in addition to diisocyanate concentration and post-polymerization conditions. Expanding the family of CUPE polymers increases the choices of biodegradable elastomers for tissue engineering applications. PMID:22184499

  3. Evaluation of urinary bladder fibrogenesis in a mouse model of long-term ketamine injection

    PubMed Central

    Shen, Cheng-Huang; Wang, Shou-Chieh; Wang, Shou-Tsung; Lin, Shu-Mei; Wu, Jiann-Der; Lin, Chang-Te; Liu, Yi-Wen

    2016-01-01

    Long-term ketamine abuse has been shown to affect the lower urinary tract and result in interstitial cystitis-like syndrome. However, the causative mechanism of ketamine-induced dysfunction remains unclear. The present study aimed to investigate the physiological, histological and molecular changes on ketamine-associated cystitis (KC) in a mouse model. Both male and female Balb/c mice were separately distributed into the control group (normal saline) and ketamine group, which received ketamine hydrochloride (100 mg/kg/day) daily by intraperitoneal injection for a total period of 20 weeks. In each group, the urine was analyzed by gas chromatography-mass spectrometry to measure the concentration of ketamine and its metabolites. Urinary frequency and urine volume were examined to investigate the urinary voiding functions. Mice bladders were excised for cDNA microarray and hematoxylin and eosin (HE) staining. The ketamine and metabolites were detected only in ketamine-treated mice urine. The voiding interval was reduced in the male mice group after 20 week ketamine administration. Additionally, the result of cDNA array analysis revealed a number of gene expression levels involved in chronic wound healing response and collagen accumulation, which were closely associated with fibrosis progression in the connective tissue. In HE staining of the bladder tissue, the ketamine-injected mice exhibited prominently denser blood vessel distribution in the submucosal layer. Based on the evidence in the present study, a mechanism that delineates fibrosis formation of urinary bladder induced by the pathogenesis of ketamine abuse can be constructed. PMID:27431428

  4. Evaluating the adequacy of climate change information to support long-term water resource planning

    NASA Astrophysics Data System (ADS)

    Brekke, L. D.; Clark, M. P.; Gutmann, E. D.; Pruitt, T.; Mizukami, N.; Mendoza, P. A.; Rasmussen, R.; Arnold, J.; Raff, D. A.; Rajagopalan, B.

    2013-12-01

    The National Center for Atmospheric Research (NCAR), the Department of Interior's Bureau of Reclamation (Reclamation) and the U.S. Army Corps of Engineers (USACE) are partnering to understand appropriate applications of downscaling methods and hydrologic analysis used to produce projections of hydroclimate impacts used in long-term water resources planning and management. The overall objectives of this project are to determine the extent to which the portrayal of hydroclimate impacts depends on methodological choices, understand why different methods produce different results, and provide guidance on the suitability of different methods to provide state-of-the-art intelligence for water resources planning and management. Research questions include: (1) How does the portrayal of hydrologic impacts under climate change depend on the chosen downscaling method and resolution (i.e. dynamical downscaling using regional climate models versus non-dynamical downscaling using statistical or empirical methods)? (2) How does the portrayal of hydrologic impacts under climate change depend on the choice/configuration of hydrologic model(s) used for impact assessment and the parameter estimation strategy? This presentation provides a synthesis of methods and key findings. Main results are (i) high-resolution dynamic downscaling using a model such as the Weather Research and Forecasting model (WRF) is required to properly capture precipitation processes over complex terrain in the Colorado Headwaters region, and climate change scenarios from the 4-km WRF simulations are very different from current guidance being provided to water managers; (ii) WRF simulations at 12-km and 36-km have poor correspondence to observations, and very different change signals to the 4-km WRF simulations; (iii) the statistical downscaling methods examined struggle to adequately capture daily precipitation characteristics that are important to hydrologic impacts, such as wet-day frequency and spatial

  5. The evaluation of the National Long Term Care Demonstration. 1. An overview of the channeling demonstration and its evaluation.

    PubMed

    Carcagno, G J; Kemper, P

    1988-04-01

    The channeling demonstration sought to substitute community care for nursing home care to reduce long-term care costs and improve the quality of life of elderly clients and the family members and friends who care for them. Two interventions were tested, each in five sites; both had comprehensive case management at their core. One model added a small amount of additional funding for direct community services to fill the gaps in the existing system; the other substantially expanded coverage of community services regardless of categorical eligibility under existing programs. The demonstration was evaluated using a randomized experimental design to test the effects of channeling on use of community care, nursing homes, hospitals, and informal caregiving, and on measures of the quality of life of clients and their informal caregivers. Data were obtained from interviews with clients and informal caregivers; service use and cost records came from Medicare, Medicaid, channeling, and providers; and death records for an 18-month follow-up period were examined.

  6. Long-term evaluation of 'BARC 68Ge/68Ga generator' based on the nanoceria-polyacrylonitrile composite sorbent.

    PubMed

    Chakravarty, Rubel; Chakraborty, Sudipta; Ram, Ramu; Dash, Ashutosh; Pillai, M R A

    2013-10-01

    This article describes the long-term evaluation of a nanoceria-polyacrylonitrile (CeO2-PAN) composite sorbent-based (68)Ge/(68)Ga generator reported. This generator used the new CeO2-PAN composite sorbent for preparation of the (68)Ge/(68)Ga generator. Since this sorbent has not been previously evaluated, a thorough long-term evaluation of the performance of the generator is necessary to ensure its applicability for clinical practice. The performance of the generator was evaluated in terms of (68)Ga yield, (68)Ge breakthrough, radioactive concentration of the (68)Ga solution, and suitability of the (68)Ga for the preparation of (68)Ga-labeled tracers. The (68)Ge/(68)Ga generator was able to provide a (68)Ga activity with consistent yields (>70%) and having acceptable radionuclidic (<10(-4)% of (68)Ge breakthrough), radiochemical, and chemical purities for an extended period of time. The eluted (68)GaCl3 is useful for the majority of the (68)Ga complexation chemistry. PMID:23745686

  7. Long-term evaluation of 'BARC 68Ge/68Ga generator' based on the nanoceria-polyacrylonitrile composite sorbent.

    PubMed

    Chakravarty, Rubel; Chakraborty, Sudipta; Ram, Ramu; Dash, Ashutosh; Pillai, M R A

    2013-10-01

    This article describes the long-term evaluation of a nanoceria-polyacrylonitrile (CeO2-PAN) composite sorbent-based (68)Ge/(68)Ga generator reported. This generator used the new CeO2-PAN composite sorbent for preparation of the (68)Ge/(68)Ga generator. Since this sorbent has not been previously evaluated, a thorough long-term evaluation of the performance of the generator is necessary to ensure its applicability for clinical practice. The performance of the generator was evaluated in terms of (68)Ga yield, (68)Ge breakthrough, radioactive concentration of the (68)Ga solution, and suitability of the (68)Ga for the preparation of (68)Ga-labeled tracers. The (68)Ge/(68)Ga generator was able to provide a (68)Ga activity with consistent yields (>70%) and having acceptable radionuclidic (<10(-4)% of (68)Ge breakthrough), radiochemical, and chemical purities for an extended period of time. The eluted (68)GaCl3 is useful for the majority of the (68)Ga complexation chemistry.

  8. Evaluating, Migrating, and Consolidating Databases and Applications for Long-Term Surveillance and Maintenance Activities at the Rocky Flats Site

    SciTech Connect

    Surovchak, S.; Marutzky, S.; Thompson, B.; Miller, K.; Labonte, E.

    2006-07-01

    The U.S. Department of Energy (DOE) Office of Legacy Management (LM) is assuming responsibilities for long-term surveillance and maintenance (LTS and M) activities at the Rocky Flats Environmental Technology Site (RFETS) during fiscal year 2006. During the transition, LM is consolidating databases and applications that support these various functions into a few applications which will streamline future management and retrieval of data. This paper discussed the process of evaluating, migrating, and consolidating these databases and applications for LTS and M activities and provides lessons learned that will benefit future transitions. (authors)

  9. Long-Term Care

    MedlinePlus

    ... this page please turn Javascript on. Long-Term Care What Is Long-Term Care? Long-term care involves a variety of services ... the Escape (Esc) button on your keyboard.) Most Care Provided at Home Long-term care is provided ...

  10. Long-term efficacy and safety of once-daily mesalazine granules for the treatment of active ulcerative colitis.

    PubMed

    Böhm, Stephan Karl; Kruis, Wolfgang

    2014-01-01

    demonstrated that OD administration of 5-ASA is as effective as conventional dosing in mild to moderate active UC. The three 5-ASA products MMX, Salofalk(®), and Pentasa(®) employed in those studies so far have not shown differences in efficacy between OD and conventional dosing. No differences regarding safety outcomes have been detected between OD and conventional dosing, including incidence of adverse events, serious adverse events, or withdrawal from treatment due to an adverse event. Although the majority of patients prefer OD dosing to conventional dosing, it was not possible to detect differences in adherence between OD and multiple dose regimens in the clinical trial setting. Well-designed and controlled large-scale community-based studies are necessary to further investigate and prove the point of improved long-term adherence and treatment efficacy in OD dosing.

  11. Long-term efficacy and safety of once-daily mesalazine granules for the treatment of active ulcerative colitis

    PubMed Central

    Böhm, Stephan Karl; Kruis, Wolfgang

    2014-01-01

    demonstrated that OD administration of 5-ASA is as effective as conventional dosing in mild to moderate active UC. The three 5-ASA products MMX, Salofalk®, and Pentasa® employed in those studies so far have not shown differences in efficacy between OD and conventional dosing. No differences regarding safety outcomes have been detected between OD and conventional dosing, including incidence of adverse events, serious adverse events, or withdrawal from treatment due to an adverse event. Although the majority of patients prefer OD dosing to conventional dosing, it was not possible to detect differences in adherence between OD and multiple dose regimens in the clinical trial setting. Well-designed and controlled large-scale community-based studies are necessary to further investigate and prove the point of improved long-term adherence and treatment efficacy in OD dosing. PMID:25285021

  12. Morphological Evaluation of Proximal Anastomosis by PAS-Port® System in Patients with Long-Term Patent Grafts

    PubMed Central

    Fujii, Takeshiro; Hara, Masanori; Sasaki, Yuki; Katayanagi, Tomoyuki; Okuma, Shinnosuke; Watanabe, Yoshinori

    2014-01-01

    Purpose: We examined grafts employing for morphological analysis of early and long-term results on proximal anastomosis with the PAS-Port®. Methods: One hundred and four patients treated by OPCAB with PAS-Port® were performed postoperative MDCT. Morphological evaluation of the proximal anastomotic region was classified into three groups (A; graft was anastomosed almost perpendicularly to the aortic wall, B; graft was same type A, but subsequently curved to form an acute angle with the aortic wall, C; graft take off acute angle with the aortic wall) evaluated on planar and sagittal sections. Results: One hundred twenty-six PAS-Port® were used. Patency rate was 99.0% at discharge, 94.7% at 1 year, and no blockages were detected thereafter in patients examined. The morphology rate was A 50.6%, B 15.3% and C 34.1% on planar sections, and A 58.8%, B 10.6% and C 30.6% on sagittal sections. Conclusion: The morphological evaluation of grafts revealed the degree of freedom in graft design to be relatively high and long-term patency posed no particular problem even if the layout of the proximal anastomotic region involved a relatively acute angle. The PAS-Port® was considered to be a highly reliable device which performed appropriate proximal anastomosis and improved the patency of vein grafting to the aortic wall. PMID:25078547

  13. Evaluation of the long-term energy analysis program used for the 1978 EIA Administrator's Report to Congress

    SciTech Connect

    Peelle, R. W.; Weisbin, C. R.; Alsmiller, Jr., R. G.

    1981-10-01

    An evaluation of the Long-Term Energy Analysis Program (LEAP), a computer model of the energy portion of the US economy that was used for the 1995-2020 projections in its 1978 Annual Report to Congress, is presented. An overview of the 1978 version, LEAP Model 22C, is followed by an analysis of the important results needed by its users. The model is then evaluated on the basis of: (1) the adequacy of its documentation; (2) the local experience in operating the model; (3) the adequacy of the numerical techniques used; (4) the soundness of the economic and technical foundations of the model equations; and (5) the degree to which the computer program has been verified. To show which parameters strongly influence the results and to approach the question of whether the model can project important results with sufficient accuracy to support qualitative conclusions, the numerical sensitivities of some important results to model input parameters are described. The input data are categorized and discussed, and uncertainties are given for some parameters as examples. From this background and from the relation of LEAP to other available approaches for long-term energy modeling, an overall evaluation is given of the model's suitability for use by the EIA.

  14. Long-term safety and efficacy of dalfampridine for walking impairment in patients with multiple sclerosis: Results of open-label extensions of two Phase 3 clinical trials

    PubMed Central

    Goodman, Andrew D; Bethoux, Francois; Brown, Theodore R; Schapiro, Randall T; Cohen, Ron; Marinucci, Lawrence N; Henney, Herbert R

    2015-01-01

    Background: In Phase 3 double-blind trials (MS-F203 and MS-F204), dalfampridine extended release tablets 10 mg twice daily (dalfampridine-ER; prolonged-release fampridine in Europe; fampridine modified or sustained release elsewhere) improved walking speed relative to placebo in patients with multiple sclerosis (MS). Objectives: Evaluation of long-term safety and efficacy of dalfampridine-ER in open-label extensions (MS-F203EXT, MS-F204EXT). Methods: Patients received dalfampridine-ER 10 mg twice daily; and had Timed 25-Foot Walk (T25FW) assessments at 2, 14 and 26 weeks, and then every 6 months. Subjects were categorized as dalfampridine-ER responders or non-responders, based on their treatment response in the double-blind parent trials that assessed T25FW. Results: We had 269 patients enter MS-F203EXT and 154 patients complete it; for a maximum exposure of 5 years. We had 214 patients enter MS-F204EXT and 146 complete it; for a maximum exposure of 3.3 years. No new safety signals emerged and dalfampridine-ER tolerability was consistent with the double-blind phase. Improvements in walking speed were lost after dalfampridine-ER was discontinued in the parent trial, but returned by the 2-week assessment after re-initiation of the drug. Throughout the extensions, mean improvement in walking speed declined, but remained improved, among the double-blind responders as compared with non-responders. Conclusions: The dalfamipridine-ER safety profile was consistent with the parent trials. Although walking speed decreased over time, dalfampridine-ER responders continued to show improved walking speed, which was sustained compared with non-responders. PMID:25583832

  15. Evaluation and prediction of long-term environmental effects of nonmetallic materials, second phase

    NASA Technical Reports Server (NTRS)

    1983-01-01

    Changes in the functional properties of a number of nonmetallic materials were evaluated experimentally as a function of simulated space environments and to use such data to develop models for accelerated test methods useful for predicting such behavioral changes. The effects of changed particle irradiations on candidate space materials are evaluated.

  16. Dynamic Evaluation of Long-Term Air Quality Model Simulations Over the Northeastern U.S.

    EPA Science Inventory

    Dynamic model evaluation assesses a modeling system's ability to reproduce changes in air quality induced by changes in meteorology and/or emissions. In this paper, we illustrate various approaches to dynamic mode evaluation utilizing 18 years of air quality simulations perform...

  17. Long-term safety and tolerability of saxagliptin add-on therapy in older patients (aged ≥65 years) with type 2 diabetes

    PubMed Central

    Iqbal, Nayyar; Allen, Elsie; Öhman, Peter

    2014-01-01

    Background Treatment decisions for older patients with type 2 diabetes mellitus must balance glycemic control and adverse event risk. The objective of this study was to evaluate the long-term safety and tolerability of saxagliptin 5 mg as add-on therapy to common antihyperglycemic drugs in patients aged ≥65 years and <65 years. Methods Pooled adverse event data from three placebo-controlled trials of 76–206 weeks’ duration in older (≥65 years) and younger (<65 years) patients receiving saxagliptin 5 mg or matching placebo added to metformin, glyburide, or a thiazolidinedione were analyzed. Measurements were calculated from day of first dose to specified event or last dose and included time at risk for adverse events, treatment-related adverse events, serious adverse events, adverse events leading to discontinuation, and events of special interest. Weighted incidence rates (number of events/total time) and incidence rate ratios (saxagliptin/placebo) with 95% confidence intervals were calculated (Mantel-Haenszel test). Results A total of 205 older (mean age 69 years; saxagliptin, n=99; placebo, n=106) and 1,055 younger (mean age 52 years; saxagliptin, n=531; placebo, n=524) patients were assessed. Regardless of age category, the adverse event incidence rates were generally similar between treatments, with confidence intervals for incidence rate ratios bridging 1. Treatment-related adverse events occurred in 36 older patients receiving saxagliptin versus 32 receiving placebo (incidence rate 34.1 versus 27.1 per 100 person-years) and in 150 younger patients in both treatment groups (incidence rate 24.0 versus 27.8 per 100 person-years). With saxagliptin versus placebo, serious adverse events occurred in eight versus 14 older (incidence rate 5.7 versus 9.9 per 100 person-years) and 49 versus 44 younger patients (incidence rate 6.5 versus 6.6 per 100 person-years). There were two deaths (one patient ≥65 years) with saxagliptin and six (none aged ≥65 years

  18. Long-term reproducibility optimization of an x-ray process for bone architectural evaluation during osteoporosis

    NASA Astrophysics Data System (ADS)

    Fidouh, Fouad; Harba, Rachid; Jacquet, Gérard; Loussot, Thierry; Lespessailles, Eric

    1999-01-01

    Non-invasive and in vivo assessment of bone architectural changes at high resolution is of considerable interest in osteoporosis. In this note, the use of an x-ray acquisition system in the evaluation of the architectural quality of trabecular bone by radiographic texture analysis is optimized to achieve good long-term reproducibility. First, radiographic and digitization processes are modelled and defined. Procedures to make radiographs and their digital images are fixed. Then, measurements of the modulation transfer function (MTF) of the entire acquisition chain were completed. These measurements provide an MTF in excess of 30% at a spatial frequency of 2.5 lp/mm. Also, results of a fractal texture analysis made on digital images of calcaneus radiographs show a mean coefficient of variation of 2.07%. These data show that good long-term reproducibility can make the x-ray acquisition system efficient for patient follow-up, or evaluation of treatment regimes for osteoporosis. Finally, it is shown that fractal texture parameters are statistically different in an osteoporotic population and in a control group. Therefore, this system should also be of medical interest.

  19. Evaluating Long-Term Complex Professional Development: Using a Variation of the Cohort Control Design

    ERIC Educational Resources Information Center

    Sample Mcmeeking, Laura B.; Cobb, R. Brian; Basile, Carole

    2010-01-01

    This paper introduces a variation on the post-test only cohort control design and addresses questions concerning both the methodological credibility and the practical utility of employing this design variation in evaluations of large-scale complex professional development programmes in mathematics education. The original design and design…

  20. Evaluating measures to assess soil health in long-term agroecosystem trials

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Monitoring and assessing soil health is an important component of any land management system with a vision of sustaining soil resources. Soil organic matter(SOM)characteristics are key to soil health and responsive to tillage regime and crop management. As metrics of soil health, we evaluated surfac...

  1. PERFORMANCE EVALUATION AT A LONG-TERM FOOD PROCESSING LAND TREATMENT SITE

    EPA Science Inventory

    The objective of this project was to determine the performance of a full scale, operating overland flow land (GEL) treatment system treating nonhazardous waste. Performance was evaluated in terms of treatment of the applied waste and the environmental impact of the system, partic...

  2. Evaluating Long-Term Effects of the Golden Lion Tamarin Environmental Education Program in Brazil

    ERIC Educational Resources Information Center

    Engels, Christine Archer; Jacobson, Susan K.

    2007-01-01

    The authors evaluated the environmental education program of the Golden Lion Tamarin Association in Brazil by comparing results of a 2001 survey with baseline data from 1986. Responses of 666 residents and results from 4 focus groups revealed an increase in public support for the tamarin and its habitat and an increase in general environmental…

  3. Long-term efficacy and safety of otilonium bromide in the management of irritable bowel syndrome: a literature review

    PubMed Central

    Triantafillidis, John K; Malgarinos, George

    2014-01-01

    Irritable bowel syndrome (IBS) is a very common functional gastrointestinal disorder characterized by abdominal pain or discomfort and altered bowel habits. The disease affects a large part of the world population. The clinical course is mostly characterized by a cyclic recurrence of symptoms. Therefore, IBS patients should receive, as an initial therapeutic approach, a short course of treatment, and long-term treatment should be reserved for those patients with recurrent symptoms. The available clinical trials show that significant improvement of the symptoms over placebo could be achieved with various drugs, although this improvement is frequently time dependent and with high relapse rates after the cessation of the treatment. In a proportion of patients, clinically obvious relapse could appear long after stopping the treatment. Some of the available pharmacologic agents, including otilonium bromide (OB), are able to significantly prolong the time to the appearance of relapse, compared with placebo. As a consequence, some authors suggest that a cyclic treatment could be of benefit. Antispasmodic drugs have been used for many years in an effort to control the symptoms of IBS. OB is a poorly absorbed spasmolytic drug, exerting significantly greater control of the symptoms of IBS compared with placebo. Recent data suggest that the drug could effectively be used for the long-term management of patients with IBS. The aim of this review is to provide the reader with an evidence-based overview of the efficacy and tolerability of OB in the long-term management of IBS patients, based on the results of the clinical trials published so far. PMID:24741324

  4. Long-term prospective evaluation of intestinal anastomosis using stainless steel staples in 14 dogs

    PubMed Central

    Benlloch-Gonzalez, Manuel; Gomes, Eymeric; Bouvy, Bernard; Poncet, Cyrill

    2015-01-01

    This prospective clinical study evaluated the use, complications, and clinical and ultrasonographic follow-ups of end-to-end intestinal anastomoses with skin staples in naturally occurring diseases in canine small and large intestines. Intestinal anastomoses were performed in 14 dogs and pre-, peri-, and postoperative data were recorded. Postoperative clinical and ultrasound evaluations were performed at regular intervals for 1 year. The mean time taken to construct the anastomosis was 5 min. There were no intraoperative complications. Hemorrhage and colonic stricture were the main postoperative complications. Staple loss occurred in 2 cases. Absence of wall layering and focal wall thickening were observed in all cases at each ultrasonographic follow-up. Hyperechoic fat was observed in all but 1 of the cases at month 1. Nine dogs were alive with normal digestive function at the end of the study. The skin stapler technique enabled rapid construction of consistent anastomoses with inexpensive stapling material. PMID:26130833

  5. [An evaluation of the long-term results of palatopharyngeal closure function after velopharyngeal ring ligation].

    PubMed

    Zhang, S; Wei, F; Zhang, P

    1997-08-01

    16 cases were selected randomly from a group of 36 postoperative patients who underwent velopharyngeal ring ligation 16 years ago for evaluation of pronunciation, pharyngeal radiography, and electric endostroboskop to evaluate the patients' velopharygeal closure function. It was found that the pronunciation function of 93% patients were in good status. The results showed that centripetal force of velopharyngeal ring ligation made the velopharyngeal cavity reduced from the right to left and from anterior to posterior sides. It was good for sphincter of velopharyngeal moving, which could reduce the space of pharyngeal cavity and add the length of soft palate. The velopharyngeal closure was improved, which produced a good condition for the recovery of pronunciation function, at the same time, the change of pharyngeal cavity adapts to the patient's growth without limiting the growth and development of nasovelopharyngeal. PMID:11480008

  6. Long-term evaluation of porous PEGT/PBT implants for soft tissue augmentation.

    PubMed

    Lamme, Evert N; Druecke, Daniel; Pieper, Jeroen; May, Paul S; Kaim, Peter; Jacobsen, Frank; Steinau, Hans-Ulrich; Steinstraesser, Lars

    2008-01-01

    Porous PEGT/PBT implants with different physico-chemical characteristics were evaluated to identify its potential as biodegradable and biofunctional soft tissue filler. Implants (50 x 10 x 5 mm3) were implanted subcutaneously in mini-pigs and tissue response, tissue volume generated and its consistency were assessed quantitatively with a 52 weeks follow-up. The absence of wound edema, skin irritation, and chronic inflammation demonstrated biocompatibility of all implants evaluated. The hydrophobic implants induced the mildest foreign body response, generated highest amount of connective tissue and demonstrated a decrease in copolymer MW of 34-37% compared to 90% decrease of the hydrophilic implants. The rate and extent of copolymer fragmentation seems to be the determining factor of success of soft tissue augmentation using porous PEGT/PBT copolymer implants. PMID:18089674

  7. Clinical evaluation of direct composite restoration done for midline diastema closure – long-term study

    PubMed Central

    Prabhu, R.; Bhaskaran, S.; Geetha Prabhu, K. R.; Eswaran, M. A.; Phanikrishna, G.; Deepthi, B.

    2015-01-01

    Purpose of the Study: The aim of this study was to evaluate clinically the performance of composite resin used to restore midline diastema between the maxillary and mandibular central incisors. Methodology: Direct composite restorations were done for 45 patients with midline diastema between the maxillary and mandibular central incisors. Standard protocols were followed for the placement of composite resin for the diastema closure, and recall visits were made for every 6 months for a period of 60 months for evaluation of the success of these restorations made. Qualified dental personnel examined the restorations made. Results: Clinical evaluations were done after the restorations had been in place for an average of 6 months. Results indicate that none of the restorations were totally lost, and resulting in a 91% overall retention rate for the period of 60 months. About 62% of the restorations made had no noticeable color difference with that of the adjacent tooth, and gingival health indicated 73% of the sample was without any signs of inflammation. Conclusions: Composites restored for diastemas exhibit satisfactory survival rates placed with recommended placement protocols and without occlusal loading. PMID:26538917

  8. Experiences in long-term evaluation of mercury emission monitoring systems

    SciTech Connect

    Chin-Min Cheng; Hung-Ta Lin; Qiang Wang; Chien-Wei Chen; Chia-Wei Wang; Ming-Chung Liu; Chi-Kuan Chen; Wei-Ping Pan

    2008-09-15

    Six mercury continuous emission monitoring (CEM) systems provided by two leading mercury (Hg) CEM system manufacturers were tested at five coal combustion utilities. The linearity, response time, day-to-day stability, efficiency of the Hg speciation modules, and ease of use were evaluated by following procedures specified in the Code of Federal Regulation Title 40 Part 75 (40 CFR Part 75). Mercury monitoring results from Hg CEM systems were compared to an EPA-recognized reference method. A sorbent trap sampling system was also evaluated in this study to compare the relative accuracy to the reference method as well as to Hg CEM systems. A conceptual protocol proposed by U.S. EPA (Method 30A) for using an Hg CEM system as the reference method for the Hg relative accuracy (RA) test was also followed to evaluate the workability of the protocol. This paper discusses the operational experience obtained from these field studies and the remaining challenges to overcome while using Hg CEM systems and the sorbent trap method for continuous Hg emission monitoring. 3 refs., 5 figs., 11 tabs.

  9. Evaluation of long term effects of thermal effluents on stream biota

    SciTech Connect

    Sublette, J.E.

    1980-10-01

    In order to evaluate the effects of energy related developments in aquatic ecosystems, a normal water data base must be established. One approach used is the selection of indicator communities on species with fairly well known environmental tolerances and requirements. The Chironomidae (Order Diptera) dominate the macrobenthic assemblages of many streams. The group offers great potential for water quality assessment. The studies in this report determine the species composition of Chironomidae at stream sites in New Mexico, across the relationship of species composition to water quality parameters, and map karyotypes for the chironomus decorus group. (ACR)

  10. Evaluation and prediction of long-term environmental effects of nonmetallic materials

    NASA Technical Reports Server (NTRS)

    Papazian, H.

    1985-01-01

    The properties of a number of nonmetallic materials were evaluated experimentally in simulated space environments in order to develop models for accelerated test methods useful for predicting such behavioral changes. Graphite-epoxy composites were exposed to thermal cycling. Adhesive foam tapes were subjected to a vacuum environment. Metal-matrix composites were tested for baseline data. Predictive modeling designed to include strength and aging effects on composites, polymeric films, and metals under such space conditions (including the atomic oxygen environment) is discussed. The Korel 8031-00 high strength adhesive foam tape was shown to be superior to the other two tested.

  11. Economic evaluation of the use of point-of-care devices in patients with long term oral anticoagulation.

    PubMed

    Gerkens, Sophie; Gailly, Jeannine; Obyn, Caroline; Devriese, Stephan; Cleemput, Irina

    2012-10-01

    To examine the cost and cost-effectiveness of the use of point-of-care (POC) devices by the general practitioner (GP), in anticoagulation clinic or by the patient in self-testing (PST) and self-management (PSM), compared with standard laboratory testing to realize international normalized ratio tests for patients on long term anticoagulation therapy. An economic evaluation was performed from the Belgian health care payer's perspective using a Markov model. Outcomes data were derived from a meta-analysis and cost data were derived from claims databases. Several scenarios were tested based on number of tests and GP's contacts and probabilistic sensitivity analysis was used to handle uncertainty. Evidence on the impact of POC on mortality was only found for PSM. Therefore, a cost-effectiveness analysis was performed for PSM and for other strategies, only a cost comparison was done. With an unchanged number of tests, POC is cost-saving compared to laboratory testing (probability > 70%). In scenarios where POC induces more tests, results were different: with 52 tests/year, only PSM kept a probability of remaining cost-saving superior to 50%. Except in the case of 100% of GP consultations maintained and 52 tests/year performed, PSM resulted in significantly more "life years gained" (LYG) than usual care and was on average cost-saving. The organisation of long term oral anticoagulation monitoring should be directed towards PSM and, to a lesser extent, PST for selected and trained patients. PMID:22437654

  12. Evaluating long-term annual sediment yield estimating potential of GIS interfaced MUSLE model on two micro-watersheds.

    PubMed

    Arekhi, Saleh

    2008-01-15

    Use of an event scale MUSLE model for obtaining accurate long-term annual sediment yield estimates from micro-watersheds was evaluated. Such estimates are extremely important for designing appropriate soil/water conserving measures. For easy extraction and inputting of model input parameters, the proposed model was interfaced to an Arc-View/Spatial Analyst geographic information system. Application of this GIS interfaced MUSLE model on two gauged (pine and oak forest) hilly micro-watersheds viz., Salla Rautella (0.47 km2) and Naula (0.42 km2), in Almora district of Uttaranchal, India showed that it could estimate annual sediment yields with absolute mean relative errors ranging between 12-14%. Even long-term average sediment yields for Salla Rautella (observed: 9.58 tons and estimated: 10.92 tons) and Naula: (Observed: 23.89 tons and estimated: 26.61 tons) micro-watersheds could be quite realistically simulated by the proposed model. PMID:18817202

  13. Preparation and evaluation of biocompatible long-term radiopaque microspheres based on polyvinyl alcohol and lipiodol for embolization.

    PubMed

    Meng, Wen-Jing; Lu, Xiao-Jing; Wang, Huan; Fan, Tian-Yuan; Cui, Dai-Chao; Zhang, Shui-Sheng; Zheng, Zhuo-Zhao; Guan, Hai-Tao; Song, Li; Zou, Ying-Hua

    2015-08-01

    The aim of this work was to develop long-term radiopaque microspheres (LRMs) by entrapping lipiodol in biocompatible polyvinyl alcohol with multiple emulsions chemical crosslinking method. The high content of lipiodol (0.366 g/mL) was hardly released from LRMs in vitro and the radiopacity could maintain at least 3 months after subcutaneous injection in mice without weakening. A series of tests was performed to evaluate the feasibility of LRMs for embolization. LRMs were proved to be smooth, spherical, and well dispersed with diameter range of 100-1200 μm. Young's modulus of LRMs was 55.39 ± 9.10 kPa and LRMs could be easily delivered through catheter without aggregating or clogging. No toxicity of LRMs was found to mouse L929 fibroblasts cells and only moderate inflammatory in surrounding tissue of mice was found after subcutaneous injection of LRMs. After LRMs were embolized in renal artery of a rabbit, the distribution and radiopacity of LRMs in vivo were easily detectable by X-ray fluoroscopy and computed tomography (CT) imaging, respectively. More accurate distribution of LRMs in embolized kidney and vessels could be detected by high-revolution visualization of micro-CT ex vivo. In conclusion, the LRMs were proved to be biocompatible and provide long-term radiopacity with good physical and mechanical properties for embolization.

  14. Evaluation of somatic hybrids of potato with Solanum stenotomum after a long-term in vitro conservation.

    PubMed

    Fock, Isabelle; Collonnier, Cécile; Lavergne, Danielle; Vaniet, Sébastien; Ambroise, Annick; Luisetti, Jacques; Kodja, Hippolyte; Sihachakr, Darasinh

    2007-01-01

    Somatic hybrids of potato with a cultivated relative, Solanum stenotomum also called Solanum tuberosum Stenotomum group, were evaluated for their physiological and agronomical characteristics as well as the stability of the introgressed resistance to bacterial wilt, caused by Ralstonia solanacearum, after a long-term in vitro conservation for more than 5 years. Analysis of photosynthesis showed that the PEPC/Rubisco ratio remained lower than 0.5 for all vitroplants of potato and the somatic hybrids, except for the relative species. This indicates that the carbon metabolism is heterotrophic (ratio>1) for S. stenotomum, and autotrophic for potato and the somatic hybrids (ratio<1). In both in vitro and greenhouse conditions, potato and the somatic hybrids produced few bigger tubers, while many small tubers were obtained from the relative. The hybrid tubers were morphologically intermediate. The starch content of hybrid tubers was much lower than that of potato, but similar to that of the relative species. Interestingly, the level of bacterial resistance, introgressed from S. stenotomum into potato, was shown to be very stable and remained as high as that of the relative after a long-term period of in vitro conservation.

  15. Long-term evaluation of the performance of four point-of-use water filters.

    PubMed

    Pérez-Vidal, Andrea; Diaz-Gómez, Jaime; Castellanos-Rozo, Jose; Usaquen-Perilla, Olga Lucía

    2016-07-01

    Despite technological advances water supply quality and poor access to safe water remain a major problem in developing countries, especially in rural areas. Point-of-use (POU) water treatment has been shown to be a viable option to produce safe drinking water quality. The aim of this study was to evaluate, under laboratory conditions over 14 months, the performance of four household filtration systems: membrane filter (MF), one-candle ceramic filter (1CCF), two-candle ceramic filter (2CCF) and pot ceramic filter (PCF). The evaluation was made using spiked water having the required concentrations of turbidity, Escherichia coli and Total Dissolved Solids (TDS). The results show that all systems have high removal efficiencies for turbidity (98-99%), and E. coli 4-5 Log Reduction Value (LRV). The poorest efficiency was for TDS (9-18%). The MF and the CCF displayed no significant difference in efficiencies for these parameters. The PCF had less significant differences for turbidity removal than the other systems. The average filtration rate for all systems decreased during the operation time. The CPF showed the major potential to be used in rural communities mainly for its low operational level and maintenance requirements as well as its local craftsmanship. It was observed that the efficiency of the systems is highly sensitive to cleaning and maintenance activities and therefore, the system sustainability will depend considerably on the training and education of the potential users.

  16. Retrospective Evaluation of the Long-Term CSEP-Italy Earthquake Forecasts

    NASA Astrophysics Data System (ADS)

    Werner, M. J.; Zechar, J. D.; Marzocchi, W.; Wiemer, S.

    2010-12-01

    On 1 August 2009, the global Collaboratory for the Study of Earthquake Predictability (CSEP) launched a prospective and comparative earthquake predictability experiment in Italy. The goal of the CSEP-Italy experiment is to test earthquake occurrence hypotheses that have been formalized as probabilistic earthquake forecasts over temporal scales that range from days to years. In the first round of forecast submissions, members of the CSEP-Italy Working Group presented eighteen five-year and ten-year earthquake forecasts to the European CSEP Testing Center at ETH Zurich. We considered the twelve time-independent earthquake forecasts among this set and evaluated them with respect to past seismicity data from two Italian earthquake catalogs. Here, we present the results of tests that measure the consistency of the forecasts with the past observations. Besides being an evaluation of the submitted time-independent forecasts, this exercise provided insight into a number of important issues in predictability experiments with regard to the specification of the forecasts, the performance of the tests, and the trade-off between the robustness of results and experiment duration.

  17. Long-term evaluation of the performance of four point-of-use water filters.

    PubMed

    Pérez-Vidal, Andrea; Diaz-Gómez, Jaime; Castellanos-Rozo, Jose; Usaquen-Perilla, Olga Lucía

    2016-07-01

    Despite technological advances water supply quality and poor access to safe water remain a major problem in developing countries, especially in rural areas. Point-of-use (POU) water treatment has been shown to be a viable option to produce safe drinking water quality. The aim of this study was to evaluate, under laboratory conditions over 14 months, the performance of four household filtration systems: membrane filter (MF), one-candle ceramic filter (1CCF), two-candle ceramic filter (2CCF) and pot ceramic filter (PCF). The evaluation was made using spiked water having the required concentrations of turbidity, Escherichia coli and Total Dissolved Solids (TDS). The results show that all systems have high removal efficiencies for turbidity (98-99%), and E. coli 4-5 Log Reduction Value (LRV). The poorest efficiency was for TDS (9-18%). The MF and the CCF displayed no significant difference in efficiencies for these parameters. The PCF had less significant differences for turbidity removal than the other systems. The average filtration rate for all systems decreased during the operation time. The CPF showed the major potential to be used in rural communities mainly for its low operational level and maintenance requirements as well as its local craftsmanship. It was observed that the efficiency of the systems is highly sensitive to cleaning and maintenance activities and therefore, the system sustainability will depend considerably on the training and education of the potential users. PMID:27105031

  18. An evaluation of long-term preservation methods for brown bear (Ursus arctos) faecal DNA samples

    USGS Publications Warehouse

    Murphy, M.A.; Waits, L.P.; Kendall, K.C.; Wasser, S.K.; Higbee, J.A.; Bogden, R.

    2002-01-01

    Relatively few large-scale faecal DNA studies have been initiated due to difficulties in amplifying low quality and quantity DNA template. To improve brown bear faecal DNA PCR amplification success rates and to determine post collection sample longevity, five preservation methods were evaluated: 90% ethanol, DETs buffer, silica-dried, oven-dried stored at room temperature, and oven-dried stored at -20??C. Preservation effectiveness was evaluated for 50 faecal samples by PCR amplification of a mitochondrial DNA (mtDNA) locus (???146 bp) and a nuclear DNA (nDNA) locus (???200 bp) at time points of one week, one month, three months and six months. Preservation method and storage time significantly impacted mtDNA and nDNA amplification success rates. For mtDNA, all preservation methods had ??? 75% success at one week, but storage time had a significant impact on the effectiveness of the silica preservation method. Ethanol preserved samples had the highest success rates for both mtDNA (86.5%) and nDNA (84%). Nuclear DNA amplification success rates ranged from 26-88%, and storage time had a significant impact on all methods but ethanol. Preservation method and storage time should be important considerations for researchers planning projects utilizing faecal DNA. We recommend preservation of faecal samples in 90% ethanol when feasible, although when collecting in remote field conditions or for both DNA and hormone assays a dry collection method may be advantageous.

  19. Using probabilities of enterococci exceedance and logistic regression to evaluate long term weekly beach monitoring data.

    PubMed

    Aranda, Diana; Lopez, Jose V; Solo-Gabriele, Helena M; Fleisher, Jay M

    2016-02-01

    Recreational water quality surveillance involves comparing bacterial levels to set threshold values to determine beach closure. Bacterial levels can be predicted through models which are traditionally based upon multiple linear regression. The objective of this study was to evaluate exceedance probabilities, as opposed to bacterial levels, as an alternate method to express beach risk. Data were incorporated into a logistic regression for the purpose of identifying environmental parameters most closely correlated with exceedance probabilities. The analysis was based on 7,422 historical sample data points from the years 2000-2010 for 15 South Florida beach sample sites. Probability analyses showed which beaches in the dataset were most susceptible to exceedances. No yearly trends were observed nor were any relationships apparent with monthly rainfall or hurricanes. Results from logistic regression analyses found that among the environmental parameters evaluated, tide was most closely associated with exceedances, with exceedances 2.475 times more likely to occur at high tide compared to low tide. The logistic regression methodology proved useful for predicting future exceedances at a beach location in terms of probability and modeling water quality environmental parameters with dependence on a binary response. This methodology can be used by beach managers for allocating resources when sampling more than one beach. PMID:26837832

  20. Using probabilities of enterococci exceedance and logistic regression to evaluate long term weekly beach monitoring data.

    PubMed

    Aranda, Diana; Lopez, Jose V; Solo-Gabriele, Helena M; Fleisher, Jay M

    2016-02-01

    Recreational water quality surveillance involves comparing bacterial levels to set threshold values to determine beach closure. Bacterial levels can be predicted through models which are traditionally based upon multiple linear regression. The objective of this study was to evaluate exceedance probabilities, as opposed to bacterial levels, as an alternate method to express beach risk. Data were incorporated into a logistic regression for the purpose of identifying environmental parameters most closely correlated with exceedance probabilities. The analysis was based on 7,422 historical sample data points from the years 2000-2010 for 15 South Florida beach sample sites. Probability analyses showed which beaches in the dataset were most susceptible to exceedances. No yearly trends were observed nor were any relationships apparent with monthly rainfall or hurricanes. Results from logistic regression analyses found that among the environmental parameters evaluated, tide was most closely associated with exceedances, with exceedances 2.475 times more likely to occur at high tide compared to low tide. The logistic regression methodology proved useful for predicting future exceedances at a beach location in terms of probability and modeling water quality environmental parameters with dependence on a binary response. This methodology can be used by beach managers for allocating resources when sampling more than one beach.

  1. Life-long diseases need life-long treatment: long-term safety of ciclosporin in canine atopic dermatitis.

    PubMed

    Nuttall, Tim; Reece, Douglas; Roberts, Elizabeth

    2014-03-01

    Ciclosporin (Atopica; Novartis Animal Health) has been licensed for canine atopic dermatitis (AD) since 2002. Adverse events (AEs) have been reported in 55 per cent of 759 dogs in 15 clinical trials, but are rare in pharmacovigilance data (71.81 AEs/million capsules sold). Gastrointestinal reactions were most common, but were mild and rarely required intervention. Other AEs were rare (≤1 per cent in clinical trials; <10/million capsules sold). Hirsutism, gingival hyperplasia and hyperplastic dermatitis were rarely significant and resolved on dose reduction. Ciclosporin decreases staphylococcal and Malassezia infections in AD, and at the recommended dose is not a risk factor for other infections, neoplasia, renal failure or hypertension. The impact on glucose and calcium metabolism is not clinically significant for normal dogs. Concomitant treatment with most drugs is safe. Effects on cytochrome P450 and MDR1 P-glycoprotein activity may elevate plasma ciclosporin concentrations, but short-term changes are not clinically significant. Monitoring of complete blood counts, urinalysis or ciclosporin levels is not justified except with higher than recommended doses and/or long-term concurrent immunosuppressive drugs. Ciclosporin is not a contraindication for killed (including rabies) vaccines, but the licensed recommendation is that live vaccination is avoided during treatment. In conclusion, ciclosporin has a positive risk-benefit profile for the long-term management of canine AD. PMID:24682696

  2. Life-long diseases need life-long treatment: long-term safety of ciclosporin in canine atopic dermatitis

    PubMed Central

    Nuttall, Tim; Reece, Douglas; Roberts, Elizabeth

    2014-01-01

    Ciclosporin (Atopica; Novartis Animal Health) has been licensed for canine atopic dermatitis (AD) since 2002. Adverse events (AEs) have been reported in 55 per cent of 759 dogs in 15 clinical trials, but are rare in pharmacovigilance data (71.81 AEs/million capsules sold). Gastrointestinal reactions were most common, but were mild and rarely required intervention. Other AEs were rare (≤1 per cent in clinical trials; <10/million capsules sold). Hirsutism, gingival hyperplasia and hyperplastic dermatitis were rarely significant and resolved on dose reduction. Ciclosporin decreases staphylococcal and Malassezia infections in AD, and at the recommended dose is not a risk factor for other infections, neoplasia, renal failure or hypertension. The impact on glucose and calcium metabolism is not clinically significant for normal dogs. Concomitant treatment with most drugs is safe. Effects on cytochrome P450 and MDR1 P-glycoprotein activity may elevate plasma ciclosporin concentrations, but short-term changes are not clinically significant. Monitoring of complete blood counts, urinalysis or ciclosporin levels is not justified except with higher than recommended doses and/or long-term concurrent immunosuppressive drugs. Ciclosporin is not a contraindication for killed (including rabies) vaccines, but the licensed recommendation is that live vaccination is avoided during treatment. In conclusion, ciclosporin has a positive risk-benefit profile for the long-term management of canine AD. PMID:24682696

  3. A performance evaluation of coating systems for long term aqueous immersion service

    SciTech Connect

    Pawel, S.J.

    1994-11-08

    The static immersion of coated steel panels in various media representative of chemical and waste processes around the Oak Ridge Y-12 Plant was terminated after 16 months exposure for evaluation of coating performance and comparison with observations collected following 1, 6, and 11 months exposure. In each environment, a wide range of coating performance was observed, including some coatings unsuitable for use in the test environment (despite the high recommendation of the vendor). Further, coating performance as a function of time suggests a test duration of at least several months is required to fully assess candidate coating performance for specific applications. The performance of many coatings, particularly in the most alkaline environment, was adversely affected by the imposition of supplemental cathodic protection on the coated test panels.

  4. Long-term evaluation of Leber's hereditary optic neuropathy-like symptoms in rotenone administered rats.

    PubMed

    Zhang, Li; Liu, Laura; Philip, Ann L; Martinez, Juan C; Guttierez, Juan C; Marella, Mathieu; Patki, Gaurav; Matsuno-Yagi, Akemi; Yagi, Takao; Thomas, Biju B

    2015-01-12

    Leber's hereditary optic neuropathy (LHON) is an inherited disorder affecting the retinal ganglion cells (RGCs) and their axons that lead to the loss of central vision. This study is aimed at evaluating the LHON symptoms in rats administered with rotenone microspheres into the superior colliculus (SC). Optical coherence tomography (OCT) analysis showed substantial loss of retinal nerve fiber layer (RNFL) thickness in rotenone injected rats. Optokinetic testing in rotenone treated rats showed decrease in head-tracking response. Electrophysiological mapping of the SC surface demonstrated attenuation of visually evoked responses; however, no changes were observed in the ERG data. The progressive pattern of disease manifestation in rotenone administered rats demonstrated several similarities with human disease symptoms. These rats with LHON-like symptoms can serve as a model for future investigators to design and implement reliable tests to assess the beneficial effects of therapeutic interventions for LHON disease.

  5. Evaluation of Long-Term Calibrations of the AVHRR Visible Radiances

    NASA Technical Reports Server (NTRS)

    Rossow, William B.; Ferrier, Joseph

    2015-01-01

    Two systematic calibrations have been compiled for the visible radiances measured by the series of AVHRR instruments flown on the NOAA operational polar weather satellites: one by the International Satellite Cloud Climatology Project (ISCCP), anchored on NASA ER-2 underflights in the 1980s and early 1990s and covering the period 1981-2009, and one by the PATMOS-x project, anchored on comparisons to the MODIS instruments on the Aqua and Terra satellites in the 2000s and covering the period 1979-2010 (this result also includes calibration for the near-IR channels). Both methods have had to extend their anchor calibrations over a long series of instruments using different vicarious approaches, so a comparison provides an opportunity to evaluate how well this extension works by cross-checking the results at the anchor points. The basic result of this comparison is that for the ''afternoon'' series of AVHRRs, the calibrations agree to within their mutual uncertainties. However, this retrospective evaluation also shows that the representation of the time variations can be simplified. The ISCCP procedure had much more difficulty extending the calibration to the ''morning'' series of AVHRRs with the calibrations for NOAA-15 and NOAA-17 exceeding the estimated uncertainties. Given the general agreement, a new calibration for all AVHRR visible radiances (except TIROS-N, NOAA-6, NOAA-19, and MetOp-A) is proposed that is based on the average of the best linear fits to the two time records. The estimated uncertainty of these calibrations is 63% absolute (scaled radiance units).

  6. Long term evaluation of mesenchymal stem cell therapy in a feline model of chronic allergic asthma

    PubMed Central

    Trzil, Julie E; Masseau, Isabelle; Webb, Tracy L; Chang, Chee-hoon; Dodam, John R; Cohn, Leah A; Liu, Hong; Quimby, Jessica M; Dow, Steven W; Reinero, Carol R

    2014-01-01

    Background Mesenchymal stem cells (MSCs) decrease airway eosinophilia, airway hyperresponsiveness (AHR), and remodeling in murine models of acutely induced asthma. We hypothesized that MSCs would diminish these hallmark features in a chronic feline asthma model. Objective To document effects of allogeneic, adipose-derived MSCs on airway inflammation, airway hyperresponsiveness (AHR), and remodeling over time and investigate mechanisms by which MSCs alter local and systemic immunologic responses in chronic experimental feline allergic asthma. Methods Cats with chronic, experimentally-induced asthma received six intravenous infusions of MSCs (0.36–2.5X10E7 MSCs/infusion) or placebo bimonthly at the time of study enrollment. Cats were evaluated at baseline and longitudinally for one year. Outcome measures included: bronchoalveolar lavage fluid cytology to assess airway eosinophilia; pulmonary mechanics and clinical scoring to assess AHR; and thoracic computed tomographic (CT) scans to assess structural changes (airway remodeling). CT scans were evaluated using a scoring system for lung attenuation (LA) and bronchial wall thickening (BWT). To assess mechanisms of MSC action, immunologic assays including allergen-specific IgE, cellular IL-10 production, and allergen-specific lymphocyte proliferation were performed. Results There were no differences between treatment groups or over time with respect to airway eosinophilia or AHR. However, significantly lower LA and BWT scores were noted in CT images of MSC-treated animals compared to placebo-treated cats at month 8 of the study (LA p=0.0311; BWT p=0.0489). No differences were noted between groups in the immunologic assays. Conclusions and Clinical Relevance When administered after development of chronic allergic feline asthma, MSCs failed to reduce airway inflammation and AHR. However, repeated administration of MSCs at the start of study did reduce computed tomographic measures of airway remodeling by month 8, though

  7. Discriminative evaluative conditioning in the long-term after severe accidental injury.

    PubMed

    Oe, Misari; Schumacher, Sonja; Schnyder, Ulrich; Mueller-Pfeiffer, Christoph; Wilhelm, Frank H; Kuelen, Eveline; Martin-Soelch, Chantal

    2016-06-30

    Impairments in classical fear conditioning and deficits in discriminative learning are observed in posttraumatic stress disorder (PTSD). However, it is unknown whether similar impairments can be found with types of discriminative learning other than classical conditioning, such as evaluative conditioning (EC), in which the valence of a stimulus can be transferred to other stimuli. In this study, we investigated whether EC is also influenced by traumatic experiences independently of presence of PTSD. We tested 14 accident survivors with remitted PTSD, 14 survivors without PTSD, and 16 non-trauma controls. We used behavioral measures, psychophysiological indicators, and subjective ratings for tasks. General effects of learning were observed across groups and conditioning/extinction. Trauma controls had slower reaction times (RTs) to the aversive conditioned stimulus compared to appetitive conditioned and neutral stimuli, as well as slower RTs and increased accuracy during conditioning than during extinction. Remitted PTSD participants showed opposite results, demonstrating decreased accuracy and slower RTs during conditioning as compared to during extinction. No discriminative effect was found in the non-trauma controls and the remitted PTSD participants. These results suggest that a traumatic experience influences EC, and that this influence differs between individuals who have and have not developed PTSD after traumatic exposure. PMID:27107667

  8. Bacterial decomposition of coral mucus as evaluated by long-term and quantitative observation

    NASA Astrophysics Data System (ADS)

    Tanaka, Y.; Ogawa, H.; Miyajima, T.

    2011-06-01

    Coral mucus released from Acropora formosa and Montipora digitata was incubated with bacteria under dark conditions for 1 year to evaluate the quantitative degradability. All the mucus samples showed a similar decomposition pattern: about 80% of total organic carbon (TOC) in the mucus was mineralized within 1 month, while some mucus was slowly decomposed over the 1 year. Regression analysis using an exponential curve considering three degradability pools (labile, semilabile, and refractory) fitted the changes of the TOC concentrations very well ( r 2 > 0.99). Compiling the data on the two coral species, the labile organic C in the coral mucus had mineralization rates of 10-18% d-1 and accounted for 79-87% of the initial TOC in the mucus. Semilabile organic C had mineralization rates of 0.3-1.6% d-1 and accounted for 11-18% of the initial TOC. Refractory organic C accounted for 6% at most. These results suggest that not all coral mucus is rapidly decomposed by bacteria but some mucus remains as semilabile and refractory organic matter for several months.

  9. Evaluation of long-term sedation in cheetah (Acinonyx jubatus) with perphenazine enanthate and zuclopenthixol acetate.

    PubMed

    Huber, C; Walzer, C; Slotta-Bachmayr, L

    2001-09-01

    Two long-acting neuroleptics were used to tranquilize nine captive cheetahs (Acinonyx jubatus). Perphenazine enanthate (3.0 mg/kg) and zuclopenthixol acetate (0.6 mg/kg) were each administered to separate groups of three cheetahs in a double blind trial. Both products were administered together to a third group of three animals at the same dosages. Behavioral effect, duration of effect, and possible side effects were observed by a predefined protocol. Under standardized holding conditions, the cheetahs were observed 5 days before drug administration and 14 days after administration. Daily activity was defined and statistically evaluated by a U-test. A significant reduction of activity was observed after administration in all three trials. Zuclopenthixol acetate at 0.6 mg/kg alone and in combination with perphenazine enanthate caused inappetence, ataxia, extra pyramidal reactions, akathisia, and prolapse of the third eyelid. Zuclopenthixol acetate should not be used in cheetahs. Perphenazine enanthate did not cause inappetence, reduced appetite, or any of the previously mentioned side effects when used alone. It produced satisfactory tranquilization and is suitable and safe for cheetahs at 3.0 mg/kg. This dosage should be varied depending on health, age, and temperament of the individual cheetah.

  10. Discriminative evaluative conditioning in the long-term after severe accidental injury.

    PubMed

    Oe, Misari; Schumacher, Sonja; Schnyder, Ulrich; Mueller-Pfeiffer, Christoph; Wilhelm, Frank H; Kuelen, Eveline; Martin-Soelch, Chantal

    2016-06-30

    Impairments in classical fear conditioning and deficits in discriminative learning are observed in posttraumatic stress disorder (PTSD). However, it is unknown whether similar impairments can be found with types of discriminative learning other than classical conditioning, such as evaluative conditioning (EC), in which the valence of a stimulus can be transferred to other stimuli. In this study, we investigated whether EC is also influenced by traumatic experiences independently of presence of PTSD. We tested 14 accident survivors with remitted PTSD, 14 survivors without PTSD, and 16 non-trauma controls. We used behavioral measures, psychophysiological indicators, and subjective ratings for tasks. General effects of learning were observed across groups and conditioning/extinction. Trauma controls had slower reaction times (RTs) to the aversive conditioned stimulus compared to appetitive conditioned and neutral stimuli, as well as slower RTs and increased accuracy during conditioning than during extinction. Remitted PTSD participants showed opposite results, demonstrating decreased accuracy and slower RTs during conditioning as compared to during extinction. No discriminative effect was found in the non-trauma controls and the remitted PTSD participants. These results suggest that a traumatic experience influences EC, and that this influence differs between individuals who have and have not developed PTSD after traumatic exposure.

  11. [Requirements for long-term follow-up on efficacy and safety of advanced therapy medicinal products. Risk management and traceability].

    PubMed

    Klug, B; Reinhardt, J; Schröder, C

    2010-01-01

    Advanced therapy medicinal products (ATMPs) are an innovative treatment option. To promote timely access of the innovative medicinal product and to safeguard public health, new elements have been introduced into legislation. A key element of the ATMP regulation is the requirement for long-term follow-up on safety and efficacy of patients enrolled in clinical trials with ATMPs, which is beyond the routine requirements on pharmacovigilance. For gene therapy medicinal products, a guideline on long-term follow-up, which lays down the technical requirements, is available. A further key element of the ATMP regulation is the traceability of the starting materials used to manufacture the ATMP. A common European coding system is imperative to ensure the traceability of starting materials, especially across the borders of European Member States.

  12. Empirical evaluation of the conceptual model underpinning a regional aquatic long-term monitoring program using causal modelling

    USGS Publications Warehouse

    Irvine, Kathryn M.; Miller, Scott; Al-Chokhachy, Robert K.; Archer, Erik; Roper, Brett B.; Kershner, Jeffrey L.

    2015-01-01

    Conceptual models are an integral facet of long-term monitoring programs. Proposed linkages between drivers, stressors, and ecological indicators are identified within the conceptual model of most mandated programs. We empirically evaluate a conceptual model developed for a regional aquatic and riparian monitoring program using causal models (i.e., Bayesian path analysis). We assess whether data gathered for regional status and trend estimation can also provide insights on why a stream may deviate from reference conditions. We target the hypothesized causal pathways for how anthropogenic drivers of road density, percent grazing, and percent forest within a catchment affect instream biological condition. We found instream temperature and fine sediments in arid sites and only fine sediments in mesic sites accounted for a significant portion of the maximum possible variation explainable in biological condition among managed sites. However, the biological significance of the direct effects of anthropogenic drivers on instream temperature and fine sediments were minimal or not detected. Consequently, there was weak to no biological support for causal pathways related to anthropogenic drivers’ impact on biological condition. With weak biological and statistical effect sizes, ignoring environmental contextual variables and covariates that explain natural heterogeneity would have resulted in no evidence of human impacts on biological integrity in some instances. For programs targeting the effects of anthropogenic activities, it is imperative to identify both land use practices and mechanisms that have led to degraded conditions (i.e., moving beyond simple status and trend estimation). Our empirical evaluation of the conceptual model underpinning the long-term monitoring program provided an opportunity for learning and, consequently, we discuss survey design elements that require modification to achieve question driven monitoring, a necessary step in the practice of

  13. Decellularized Allogeneic Heart Valves Demonstrate Self-Regeneration Potential after a Long-Term Preclinical Evaluation

    PubMed Central

    Iop, Laura; Bonetti, Antonella; Naso, Filippo; Rizzo, Stefania; Cagnin, Stefano; Bianco, Roberto; Lin, Carlo Dal; Martini, Paolo; Poser, Helen; Franci, Paolo; Lanfranchi, Gerolamo; Busetto, Roberto; Spina, Michel; Basso, Cristina; Marchini, Maurizio; Gandaglia, Alessandro

    2014-01-01

    Tissue-engineered heart valves are proposed as novel viable replacements granting longer durability and growth potential. However, they require extensive in vitro cell-conditioning in bioreactor before implantation. Here, the propensity of non-preconditioned decellularized heart valves to spontaneous in body self-regeneration was investigated in a large animal model. Decellularized porcine aortic valves were evaluated for right ventricular outflow tract (RVOT) reconstruction in Vietnamese Pigs (n = 11) with 6 (n = 5) and 15 (n = 6) follow-up months. Repositioned native valves (n = 2 for each time) were considered as control. Tissue and cell components from explanted valves were investigated by histology, immunohistochemistry, electron microscopy, and gene expression. Most substitutes constantly demonstrated in vivo adequate hemodynamic performances and ex vivo progressive repopulation during the 15 implantation months without signs of calcifications, fibrosis and/or thrombosis, as revealed by histological, immunohistochemical, ultrastructural, metabolic and transcriptomic profiles. Colonizing cells displayed native-like phenotypes and actively synthesized novel extracellular matrix elements, as collagen and elastin fibers. New mature blood vessels, i.e. capillaries and vasa vasorum, were identified in repopulated valves especially in the medial and adventitial tunicae of regenerated arterial walls. Such findings correlated to the up-regulated vascular gene transcription. Neoinnervation hallmarks were appreciated at histological and ultrastructural levels. Macrophage populations with reparative M2 phenotype were highly represented in repopulated valves. Indeed, no aspects of adverse/immune reaction were revealed in immunohistochemical and transcriptomic patterns. Among differentiated elements, several cells were identified expressing typical stem cell markers of embryonic, hematopoietic, neural and mesenchymal lineages in significantly higher number

  14. Decellularized allogeneic heart valves demonstrate self-regeneration potential after a long-term preclinical evaluation.

    PubMed

    Iop, Laura; Bonetti, Antonella; Naso, Filippo; Rizzo, Stefania; Cagnin, Stefano; Bianco, Roberto; Dal Lin, Carlo; Martini, Paolo; Poser, Helen; Franci, Paolo; Lanfranchi, Gerolamo; Busetto, Roberto; Spina, Michel; Basso, Cristina; Marchini, Maurizio; Gandaglia, Alessandro; Ortolani, Fulvia; Gerosa, Gino

    2014-01-01

    Tissue-engineered heart valves are proposed as novel viable replacements granting longer durability and growth potential. However, they require extensive in vitro cell-conditioning in bioreactor before implantation. Here, the propensity of non-preconditioned decellularized heart valves to spontaneous in body self-regeneration was investigated in a large animal model. Decellularized porcine aortic valves were evaluated for right ventricular outflow tract (RVOT) reconstruction in Vietnamese Pigs (n = 11) with 6 (n = 5) and 15 (n = 6) follow-up months. Repositioned native valves (n = 2 for each time) were considered as control. Tissue and cell components from explanted valves were investigated by histology, immunohistochemistry, electron microscopy, and gene expression. Most substitutes constantly demonstrated in vivo adequate hemodynamic performances and ex vivo progressive repopulation during the 15 implantation months without signs of calcifications, fibrosis and/or thrombosis, as revealed by histological, immunohistochemical, ultrastructural, metabolic and transcriptomic profiles. Colonizing cells displayed native-like phenotypes and actively synthesized novel extracellular matrix elements, as collagen and elastin fibers. New mature blood vessels, i.e. capillaries and vasa vasorum, were identified in repopulated valves especially in the medial and adventitial tunicae of regenerated arterial walls. Such findings correlated to the up-regulated vascular gene transcription. Neoinnervation hallmarks were appreciated at histological and ultrastructural levels. Macrophage populations with reparative M2 phenotype were highly represented in repopulated valves. Indeed, no aspects of adverse/immune reaction were revealed in immunohistochemical and transcriptomic patterns. Among differentiated elements, several cells were identified expressing typical stem cell markers of embryonic, hematopoietic, neural and mesenchymal lineages in significantly higher number

  15. Evaluation of long-term occupational exposure to styrene vapor on olfactory function.

    PubMed

    Dalton, Pamela; Lees, Peter S J; Gould, Michele; Dilks, Daniel; Stefaniak, Aleksandr; Bader, Michael; Ihrig, Andreas; Triebig, Gerhard

    2007-10-01

    The primary sensory neurons of the olfactory system are chronically exposed to the ambient environment and may therefore be susceptible to damage from occupational exposure to many volatile chemicals. To investigate whether occupational exposure to styrene was associated with olfactory impairment, we examined olfactory function in 2 groups: workers in a German reinforced-plastics boat-manufacturing facility having a minimum of 2 years of styrene exposure (15-25 ppm as calculated from urinary metabolite concentrations, with historical exposures up to 85 ppm) and a group of age-matched workers from the same facility with lower styrene exposures. The results were also compared with normative data previously collected from healthy, unexposed individuals. Multiple measures of olfactory function were evaluated using a standardized battery of clinical assessments from the Monell-Jefferson Chemosensory Clinical Research Center that included tests of threshold sensitivity for phenylethyl alcohol (PEA) and odor identification ability. Thresholds for styrene were also obtained as a measure of occupational olfactory adaptation. Styrene exposure history was calculated through the use of past biological monitoring results for urinary metabolites of styrene (mandelic acid [MA], phenylglyoxylic acid [PGA]); current exposure was determined for each individual using passive air sampling for styrene and biological monitoring for styrene urinary metabolites. Current mean effective styrene exposure during the day of olfactory testing for the group of workers who worked directly with styrene resins was 18 ppm styrene (standard deviation [SD] = 14), 371 g/g creatinine MA + PGA (SD = 289) and that of the group of workers with lower exposures was 4.8 ppm (SD = 5.2), 93 g/g creatinine MA+PGA (SD = 100). Historic annual average exposures for all workers were greater by a factor of up to 6x. No differences unequivocally attributable to exposure status were observed between the Exposed and

  16. Long-term evaluation of single crystal sapphire implants as abutments in fixed prosthodontics.

    PubMed

    Fartash, B; Arvidson, K

    1997-02-01

    49 patients participated in a prospective study of treatment of total or partial edentulism with fixed prosthodontics supported by Bioceram sapphire implants. 15 patients were treated for maxillary or mandibular edentulism, and 7 for a missing maxillary anterior tooth. The remaining 27 patients, with Applegate-Kennedy Class I-IV residual dentitions, were treated with fixed bridges supported by free-standing implants, or bridges supported by teeth and implants. Implant success, prosthesis stability, radiographic marginal bone level as well as parameters for peri-implant health were evaluated. The study began in 1982, and clinical treatment of the last patients was completed in 1988, i.e., a follow-up period ranging from 7 to 13 years. Of the patients treated for total mandibular edentulism, one implant fractured after 6 years in situ. The bone implant score (BIS) values for those implants were at the time for the bridge cementation 63.5 +/- 1.4 and at 1, 2, 3 and 5 year follow-ups 62.1 +/- 1.4, 61.9 +/- 1.5, 61.5 +/- 1.6, and 60.95 +/- 1.3, respectively. The success rate was 100%, 100% and 97.7% for the mandible at 3, 5 and 10 years, respectively. Of the 7 edentulous patients treated with maxillary fixed bridges, 6 implants in 1 patient had to be removed after 1 year in service. Another 2 patients lost all their implants, 6 each, after 36 months. 6 implants in the 4th patient did not fulfil the criteria for success and were rated as failures at the four year follow-up. The success rate was thus 58.1%, 44.2% and 44.2% for the maxilla at 3, 5 and 10 year follow-ups, respectively. Of the 7 patients in whom single missing teeth were replaced, 1 implant in the premolar region was lost during the 1st year post-operatively, but no other complications or changes in BIS were observed. Of the 27 patients treated for partial edentulism (56 implants total) 1 implant, of a 4-unit free standing maxillary bridge fractured after 6 years and was later replaced. There were no

  17. Multicenter field trial on possible health effects of toluene. III. Evaluation of effects after long-term exposure.

    PubMed

    Gericke, C; Hanke, B; Beckmann, G; Baltes, M M; Kühl, K P; Neubert, D

    2001-11-15

    In rotogravure industry, contributing considerably to mass color printing of catalogues and magazines, toluene is still extensively used as paint solvent, and many printers have been exposed to this chemical for several decades. Information on adverse health effects associated with long-term toluene exposure is still controversial. In a multi-center study, adverse health effects possibly associated with long-term toluene exposure were evaluated. In 12 rotogravure factories, 1226 male volunteers were recruited, and sufficient information on exposure and on medical data was compiled for about 1077 of them. Evaluations included: physical examination, standard tests of psycho-physiological and psycho-motoric performances, self-report of subjective symptoms, and data on a variety of laboratory blood tests. The medical data were correlated with the length (months) of toluene exposure, and a rough estimate of the extent of exposure (i.e. highly exposed printers and their helpers versus employees working at locations with low or negligible toluene exposure). A small reference group (n=109) was selected from companies of the paper industry. When linear regression curves were calculated (test results versus duration of exposure), extremely low overall coefficients of determination (r(2) adj.) of a few percent were estimated within the data clouds, with sometimes statistically significant P-values. Closer analyses revealed a strong influence of the confounding factor age, no clustering of abnormal values of highly toluene-exposed volunteers, and the vast majority or all values of the highly and long-term toluene-exposed participants staying within the reference ranges. Thus, no medical relevance of P-values <0.05 could be recognized in this evaluation, and there may have been some border-line deviations or results largely occurring by chance in the large trial. In a small cluster of the many rotogravure printers toluene-exposed for more than 20 years, the highest systolic

  18. Evaluating for long-term impact of an environmental education program at the Kalinzu Forest Reserve, Uganda.

    PubMed

    Kuhar, C W; Bettinger, T L; Lehnhardt, K; Tracy, Osuo; Cox, D

    2010-05-01

    Although the importance of evaluating the effectiveness of conservation education programs cannot be underestimated, few evaluations of these programs and their resulting impact on the environment have been conducted. A partnership between scientists, educators, and local administrators on an evaluation program has been developed to evaluate a model of education program evaluation that includes short- and long-term evaluation of (1) knowledge and attitude change, (2) behavior change, and (3) positive biological impact. Previous work has shown short-term knowledge retention from this education program. In the current study follow-up evaluations were collected from students at 14 schools outside the Kalinzu Forest Reserve, Uganda. By comparing performance 30 days, 1 year and 2 years after the initial program we demonstrate that knowledge gain from this program is not transient. However, although knowledge is a prerequisite for appropriate conservation actions it does not guarantee appropriate behaviors will be performed. Anecdotal evidence of behavior change and positive biological impact is discussed within the context of the challenges with changing behavior and evaluating the true biological impacts of those behaviors. Ultimately, conservation professionals will need to partner with educators and social scientists to effectively measure the impact of conservation education and human-based conservation programs on primate populations and their habitat.

  19. NDT evaluation of long-term bond durability of CFRP-structural systems applied to RC highway bridges

    NASA Astrophysics Data System (ADS)

    Crawford, Kenneth C.

    2016-06-01

    The long-term durability of CFRP structural systems applied to reinforced-concrete (RC) highway bridges is a function of the system bond behavior over time. The sustained structural load performance of strengthened bridges depends on the carbon fiber-reinforced polymer (CFRP) laminates remaining 100 % bonded to concrete bridge members. Periodic testing of the CFRP-concrete bond condition is necessary to sustain load performance. The objective of this paper is to present a non-destructive testing (NDT) method designed to evaluate the bond condition and long-term durability of CFRP laminate (plate) systems applied to RC highway bridges. Using the impact-echo principle, a mobile mechanical device using light impact hammers moving along the length of a bonded CFRP plate produces unique acoustic frequencies which are a function of existing CFRP plate-concrete bond conditions. The purpose of this method is to test and locate CFRP plates de-bonded from bridge structural members to identify associated deterioration in bridge load performance. Laboratory tests of this NDT device on a CFRP plate bonded to concrete with staged voids (de-laminations) produced different frequencies for bonded and de-bonded areas of the plate. The spectra (bands) of frequencies obtained in these tests show a correlation to the CFRP-concrete bond condition and identify bonded and de-bonded areas of the plate. The results of these tests indicate that this NDT impact machine, with design improvements, can potentially provide bridge engineers a means to rapidly evaluate long lengths of CFRP laminates applied to multiple highway bridges within a national transportation infrastructure.

  20. Evolution of the air pollution in SW Germany evaluated by the long-term air quality index LAQx

    NASA Astrophysics Data System (ADS)

    Mayer, Helmut; Holst, Jutta; Schindler, Dirk; Ahrens, Dieter

    The air quality index LAQx ( Long-term Air Quality Inde x), which has been recently developed to evaluate the long-term integral air quality related to well-being and health of people, was applied to analyse the evolution of air pollution from 1985 to 2005 at different urban and rural sites in SW Germany. The LAQx method including the air pollutants taken into account is briefly discussed. LAQx is grouped into six classes according to the German school grade system, i.e. LAQx class 1 indicates a very good air quality, while very poor air quality is described by LAQx class 6. For an additional differentiation, the six LAQx classes are subdivided into LAQx values based on the decimal system. In accordance with the trends of the air pollutants taken into account in LAQx, the results show decreasing LAQx values at urban sites, which reflect an improvement of the integral air quality. In 1985 it was very poor and poor, respectively, whereas it reached the sufficient and satisfying level in 2005. For the rural sites, where LAQx could be determined only from 1995 to 2005, it fluctuated around a mean level indicating good to satisfying air quality but without any decreasing tendency. Differences of LAQx between the investigated sites were primarily caused by different local emission conditions. The trend of decreasing LAQx values, i.e. improvement of the integral air quality, was modified by distinctly higher LAQx values in years characterised by a relatively high portion of consecutive extremely hot summer days like during the heat waves in 2003 in Central Europe, which particularly increased the ozone concentration.

  1. In vitro evaluation of the long-term stability of polyimide as a material for neural implants.

    PubMed

    Rubehn, Birthe; Stieglitz, Thomas

    2010-05-01

    In order to be used as a material for neural prostheses, polyimide has to withstand the body environment over years. To obtain more information about the long-term stability of this material, we tested three commercially available polyimides (PI2611 - HD-Microsystems (type: BPDA-PPD), U-Varnish-S - UBE (type: BPDA-PPD), Durimide 7510 - Fujifilm (type: information not provided)). Specimens were stored in phosphate buffered saline (PBS) at 37 degrees C to simulate body temperature and at elevated temperatures of 60 degrees C and 85 degrees C to accelerate aging. During the course of 20 months, stress-strain curves were measured monthly by tensile testing. From these curves the Young's modulus, the stress and strain at break, the stress at 10% strain as well as the fracture energy were extracted and used to characterize and to statistically evaluate the mechanical material properties. Mass loss was determined by weighing polyimide foils (Upilex25S - UBE) and optical measurements were conducted to examine changes in chemical structure and crystallinity. At 37 degrees C and 60 degrees C no change in material behavior could be observed, except for an increase of the Young's modulus of the BPDA-PPD type stored at 60 degrees C. This demonstrates the long-term stability of all tested polyimides with respect to PBS. All extracted quantities mentioned above, as well as the mass, decreased in specimens stored in PBS at 85 degrees C. As a comparison, BPDA-PPD type specimens stored at 85 degrees C in deionized water showed no change in any property but behaved similarly to the reference material.

  2. Evaluation of the stability of arsenic immobilized by microbial sulfate reduction using TCLP extractions and long-term leaching techniques.

    PubMed

    Jong, Tony; Parry, David L

    2005-07-01

    An investigation was conducted to evaluate the stability or leachability of arsenic immobilized by microbial sulfate reduction. Anoxic solid-phase samples taken from a bioreactor previously used to treat metal and As contaminated water using sulfate reducing bacteria (SRB) were subjected to the toxicity characteristic leaching procedure (TCLP) and long-term column leaching tests. The results from TCLP experiments showed that the concentration of As leached from solid-phase sulfide material (SSM) samples after an 18 h extraction time was <300 microgl(-1), which is below the current maximum Australian TCLP leachate value for As, and thus would not be characterized as a hazardous waste. In terms of percent total As leached, this was equivalent to <8.5% for SSM samples initially containing 61.3 mgkg(-1) As. The levels of As extracted by the TCLP was found to be significantly lowered or underestimated in the presence of dissolved oxygen, with As concentrations increasing with decreasing headspace-to-leachant volume ratios. The concentration of As was also consistently higher in nitrogen purged extractions compared to those performed in air. This was attributed to the dissolution of Fe-sulfide precipitates and subsequent oxidation of Fe(II) ions and precipitation of ferric(hydr)oxides, resulting in the adsorption of soluble As and corresponding decrease in As concentrations. According to the experimental data, it is recommended that TCLP tests for As leachability should be performed at least in zero-headspace vessels or preferably under nitrogen to minimize the oxidation of Fe(II) to ferric(hydr)oxides. In long-term leaching studies (approximately 68 days), it was found that the low solubility of the SSM ensured that rate of release of As was relatively slow, and the resulting leachate concentrations of As were below the current Australian guideline concentration for arsenic in drinking water.

  3. Long-term efficacy and safety of bosutinib in patients with advanced leukemia following resistance/intolerance to imatinib and other tyrosine kinase inhibitors.

    PubMed

    Gambacorti-Passerini, Carlo; Kantarjian, Hagop M; Kim, Dong-Wook; Khoury, Hanna J; Turkina, Anna G; Brümmendorf, Tim H; Matczak, Ewa; Bardy-Bouxin, Nathalie; Shapiro, Mark; Turnbull, Kathleen; Leip, Eric; Cortes, Jorge E

    2015-09-01

    Long-term efficacy and safety of bosutinib (≥4 years follow-up from last enrolled patient) were evaluated in an ongoing phase 1/2 study in the advanced leukemia cohort with prior treatment failure (accelerated-phase [AP, n = 79] chronic myeloid leukemia [CML], blast-phase [BP, n = 64] CML, acute lymphoblastic leukemia [ALL, n = 24]). Fourteen AP, 2 BP, and 1 ALL patient remained on bosutinib at 4 years (vs. 38, 8, 1 at 1 year); median (range) treatment durations: 10.2 (0.1-88.6), 2.8 (0.03-55.9), 0.97 (0.3-89.2) months. Among AP and BP patients, 57% and 28% newly attained or maintained baseline overall hematologic response (OHR); 40% and 37% attained/maintained major cytogenetic response (MCyR) by 4 years (most by 12 months). In responders at 1 versus 4 years, Kaplan-Meier (KM) probabilities of maintaining OHR were 78% versus 49% (AP) and 28% versus 19% (BP); KM probabilities of maintaining MCyR were 65% versus 49% (AP) and 21% versus 21% (BP). Most common AEs (AP, BP) were gastrointestinal (96%; 83%), primarily diarrhea (85%; 64%), which was typically low grade (maximum grade 1/2: 81%; 59%) and transient; no patient discontinued due to diarrhea. Serious AEs occurred in 44 (56%) AP and 37 (58%) BP patients, most commonly pneumonia (n = 9) for AP and pyrexia (n = 6) for BP; 11 and 13 died within 30 days of last dose (2 considered bosutinib-related [AP] per investigator). Responses were durable in ∼50% AP responders at 4 years (∼25% BP patients responded at year 1, suggesting possible bridge-to-transplant role in BP patients); toxicity was manageable. PMID:26040495

  4. Long-term evaluation of eyes with central corneal thickness <400 μm following laser in situ keratomileusis

    PubMed Central

    Djodeyre, Mohammad Reza; Beltran, Jaime; Ortega-Usobiaga, Julio; Gonzalez-Lopez, Felix; Ruiz-Rizaldos, Ana Isabel; Baviera, Julio

    2016-01-01

    Purpose To study long-term refractive and visual outcomes of laser in situ keratomileusis (LASIK) in eyes with a postoperative thin central cornea. Methods In this retrospective observational case series, we studied 282 myopic eyes with a normal preoperative topographic pattern and postoperative thin corneas (<400 μm) that had at least 3 years of follow-up after LASIK in three private clinics. The main outcome measures were safety, efficacy, predictability, percent tissue altered, and complications. Results The mean postoperative central corneal thickness was 392.05 μm (range: 363.00–399.00 μm). After a mean follow-up of 6.89±2.35 years (standard deviation), the safety index was 1.17, the efficacy index was 0.94, and predictability (±1.00 diopter [D]) was 73.49. The mean residual stromal bed thickness was 317.34±13.75 μm (range: 275–356 μm), the mean flap thickness was 74.76±13.57 μm (range: 55–124 μm), and the mean percent tissue altered was 37.12%±3.62% (range: 27.25%–49.26%). No major complications were recorded. Conclusion LASIK with a resultant central cornea thickness <400 μm seems to be effective, safe, and predictable provided that preoperative topography is normal and the residual stromal bed thickness is >275 μm. PMID:27099459

  5. Key Performance Criteria Affecting the Most the Safety of a Nuclear Waste Long Term Storage : A Case Study Commissioned by CEA

    SciTech Connect

    Marvy, A.; Lioure, A; Heriard-Dubreuil, G.; Gadbois, S.; Schneider, T.; Schieber, C.

    2003-02-24

    As part of the work scope set in the French law on high level long lived waste R&D passed in 1991, CEA is conducting a research program to establish the scientific basis and assess the feasibility of long term storage as an option for the safe management of nuclear waste for periods as long as centuries. This goal is a significant departure from the current industrial practice where storage facilities are usually built to last only a few decades. From a technical viewpoint such an extension in time seems feasible provided care and maintenance is exercised. Considering such long periods of time, the risk for Society of loosing oversight and control of such a facility is real, which triggers the question of whether and how long term storage safety can be actually achieved. Therefore CEA commissioned a study (1) in which MUTADIS Consultants (2) and CEPN (3) were both involved. The case study looks into several past and actual human enterprises conducted over significant periods o f time, one of them dating back to the end of the 18th century, and all identified out of the nuclear field. Then-prevailing societal behavior and organizational structures are screened out to show how they were or are still able to cope with similar oversight and control goals. As a result, the study group formulated a set of performance criteria relating to issues like responsibility, securing funds, legal and legislative implications, economic sustainable development, all being areas which are not traditionally considered as far as technical studies are concerned. These criteria can be most useful from the design stage onward, first in an attempt to define the facility construction and operating guiding principles, and thereafter to substantiate the safety case for long term storage and get geared to the public dialogue on that undertaking should it become a reality.

  6. Environmental management: Integrating ecological evaluation, remediation, restoration, natural resource damage assessment and long-term stewardship on contaminated lands

    PubMed Central

    Burger, Joanna

    2014-01-01

    Ecological evaluation is essential for remediation, restoration, and Natural Resource Damage Assessment (NRDA), and forms the basis for many management practices. These include determining status and trends of biological, physical, or chemical/radiological conditions, conducting environmental impact assessments, performing remedial actions should remediation fail, managing ecosystems and wildlife, and assessing the efficacy of remediation, restoration, and long-term stewardship. The objective of this paper is to explore the meanings of these assessments, examine the relationships among them, and suggest methods of integration that will move environmental management forward. While remediation, restoration, and NRDA, among others, are often conducted separately, it is important to integrate them for contaminated land where the risks to ecoreceptors (including humans) can be high, and the potential damage to functioning ecosystems great. Ecological evaluations can range from inventories of local plants and animals, determinations of reproductive success of particular species, levels of contaminants in organisms, kinds and levels of effects, and environmental impact assessments, to very formal ecological risk assessments for a chemical or other stressor. Such evaluations can range from the individual species to populations, communities, ecosystems or the landscape scale. Ecological evaluations serve as the basis for making decisions about the levels and kinds of remediation, the levels and kinds of restoration possible, and the degree and kinds of natural resource injuries that have occurred because of contamination. Many different disciplines are involved in ecological evaluation, including biologists, conservationists, foresters, restoration ecologists, ecological engineers, economists, hydrologist, and geologists. Since ecological evaluation forms the basis for so many different types of environmental management, it seems reasonable to integrate management options

  7. Environmental management: integrating ecological evaluation, remediation, restoration, natural resource damage assessment and long-term stewardship on contaminated lands.

    PubMed

    Burger, Joanna

    2008-08-01

    Ecological evaluation is essential for remediation, restoration, and Natural Resource Damage Assessment (NRDA), and forms the basis for many management practices. These include determining status and trends of biological, physical, or chemical/radiological conditions, conducting environmental impact assessments, performing remedial actions should remediation fail, managing ecosystems and wildlife, and assessing the efficacy of remediation, restoration, and long-term stewardship. The objective of this paper is to explore the meanings of these assessments, examine the relationships among them, and suggest methods of integration that will move environmental management forward. While remediation, restoration, and NRDA, among others, are often conducted separately, it is important to integrate them for contaminated land where the risks to ecoreceptors (including humans) can be high, and the potential damage to functioning ecosystems great. Ecological evaluations can range from inventories of local plants and animals, determinations of reproductive success of particular species, levels of contaminants in organisms, kinds and levels of effects, and environmental impact assessments, to very formal ecological risk assessments for a chemical or other stressor. Such evaluations can range from the individual species to populations, communities, ecosystems or the landscape scale. Ecological evaluations serve as the basis for making decisions about the levels and kinds of remediation, the levels and kinds of restoration possible, and the degree and kinds of natural resource injuries that have occurred because of contamination. Many different disciplines are involved in ecological evaluation, including biologists, conservationists, foresters, restoration ecologists, ecological engineers, economists, hydrologist, and geologists. Since ecological evaluation forms the basis for so many different types of environmental management, it seems reasonable to integrate management options

  8. Use of caesium-137 data to evaluate SHETRAN simulated long-term erosion patterns in arable lands

    NASA Astrophysics Data System (ADS)

    Norouzi Banis, Y.; Bathurst, J. C.; Walling, D. E.

    2004-07-01

    The caesium-137 method of quantifying soil erosion is used to provide field data for validating the capability of the SHETRAN modelling system for predicting long-term (30-year) erosion rates and their spatial variability. Simulations were carried out for two arable farm sites (area 3-5 ha) in central England for which average annual erosion rates of 6.5 and 10.4 t ha-1 year-1 had already been determined using caesium-137 measurements. These rates were compared with a range of simulated values representing the uncertainty in model output derived from uncertainty in the evaluation of model parameters. A successful validation was achieved in that the simulation range contained the measured rate at both sites, whereas the spatial variability was reproduced excellently at one site and partially at the other. The results indicate that, as the caesium-137 technique measures the erosion caused by all the processes acting at a site, it is relevant to hydrologically based models such as SHETRAN only if erosion by wind, agricultural activities and other processes not represented in the model are insignificant. The results also indicate a need to reduce the uncertainty in model parameter evaluation. More generally, the caesium-137 technique is shown to provide field data that improve the severity of the validation procedure (accounting for internal as well as outlet conditions) and that add spatial variability to magnitude as a condition for identifying unrealistic parameter sets when seeking to reduce simulation uncertainty.

  9. Evaluating methods for estimating space-time paths of individuals in calculating long-term personal exposure to air pollution

    NASA Astrophysics Data System (ADS)

    Schmitz, Oliver; Soenario, Ivan; Vaartjes, Ilonca; Strak, Maciek; Hoek, Gerard; Brunekreef, Bert; Dijst, Martin; Karssenberg, Derek

    2016-04-01

    Air pollution is one of the major concerns for human health. Associations between air pollution and health are often calculated using long-term (i.e. years to decades) information on personal exposure for each individual in a cohort. Personal exposure is the air pollution aggregated along the space-time path visited by an individual. As air pollution may vary considerably in space and time, for instance due to motorised traffic, the estimation of the spatio-temporal location of a persons' space-time path is important to identify the personal exposure. However, long term exposure is mostly calculated using the air pollution concentration at the x, y location of someone's home which does not consider that individuals are mobile (commuting, recreation, relocation). This assumption is often made as it is a major challenge to estimate space-time paths for all individuals in large cohorts, mostly because limited information on mobility of individuals is available. We address this issue by evaluating multiple approaches for the calculation of space-time paths, thereby estimating the personal exposure along these space-time paths with hyper resolution air pollution maps at national scale. This allows us to evaluate the effect of the space-time path and resulting personal exposure. Air pollution (e.g. NO2, PM10) was mapped for the entire Netherlands at a resolution of 5×5 m2 using the land use regression models developed in the European Study of Cohorts for Air Pollution Effects (ESCAPE, http://escapeproject.eu/) and the open source software PCRaster (http://www.pcraster.eu). The models use predictor variables like population density, land use, and traffic related data sets, and are able to model spatial variation and within-city variability of annual average concentration values. We approximated space-time paths for all individuals in a cohort using various aggregations, including those representing space-time paths as the outline of a persons' home or associated parcel

  10. Long-term efficacy and safety of all-trans retinoic acid/arsenic trioxide-based therapy in newly diagnosed acute promyelocytic leukemia.

    PubMed

    Hu, Jiong; Liu, Yuan-Fang; Wu, Chuan-Feng; Xu, Fang; Shen, Zhi-Xiang; Zhu, Yong-Mei; Li, Jun-Min; Tang, Wei; Zhao, Wei-Li; Wu, Wen; Sun, Hui-Ping; Chen, Qiu-Sheng; Chen, Bing; Zhou, Guang-Biao; Zelent, Arthur; Waxman, Samuel; Wang, Zhen-Yi; Chen, Sai-Juan; Chen, Zhu

    2009-03-01

    All-trans retinoic acid (ATRA)/arsenic trioxide (ATO) combination-based therapy has benefitted newly diagnosed acute promyelocytic leukemia (APL) in short-term studies, but the long-term efficacy and safety remained unclear. From April 2001, we have followed 85 patients administrated ATRA/ATO with a median follow-up of 70 months. Eighty patients (94.1%) entered complete remission (CR). Kaplan-Meier estimates of the 5-year event-free survival (EFS) and overall survival (OS) for all patients were 89.2% +/- 3.4% and 91.7% +/- 3.0%, respectively, and the 5-year relapse-free survival (RFS) and OS for patients who achieved CR (n = 80) were 94.8% +/- 2.5% and 97.4% +/- 1.8%, respectively. Upon ATRA/ATO, prognosis was not influenced by initial white blood cell count, distinct PML-RARalpha types, or FLT3 mutations. The toxicity profile was mild and reversible. No secondary carcinoma was observed, and 24 months after the last dose of ATRA/ATO, patients had urine arsenic concentrations well below the safety limit. These results demonstrate the high efficacy and minimal toxicity of ATRA/ATO treatment for newly diagnosed APL in long-term follow-up, suggesting a potential frontline therapy for de novo APL.

  11. Handling glacially induced faults in the assessment of the long term safety of a repository for spent nuclear fuel at Forsmark, Sweden

    NASA Astrophysics Data System (ADS)

    Munier, R.

    2011-12-01

    Located deep into the Baltic shield, far from active plate boundaries and volcanism, Swedish bedrock is characterised by a low frequency of earthquakes of small magnitudes. Yet, faults, predominantly in the Lapland region, offsetting the quarternary regolith ten meters or more, reveal that Swedish bedrock suffered from substantial earthquake activity in connection to the retreat of the latest continental glacier, Weichsel. Storage of nuclear wastes, hazardous for hundreds of thousand years, requires, firstly, isolation of radionuclides and, secondly, retardation of the nuclides should the barriers fail. Swedish regulations require that safety is demonstrated for a period of a million years. Consequently, the repository must be designed to resist the impact of several continental glaciers. Large, glacially induced, earthquakes near the repository have the potential of triggering slip along fractures across the canisters containing the nuclear wastes, thereby simultaneously jeopardising isolation, retardation and, hence, long term safety. It has therefore been crucial to assess the impact of such intraplate earthquake upon the primary functions of the repository. We conclude that, by appropriate design of the repository, the negative impact of earthquakes on long term safety can be considerably lessened. We were, additionally, able to demonstrate compliance with Swedish regulations in our safety assessment, SR-Site, submitted to the authorities earlier this year. However, the assessment required a number of critical assumptions, e.g. concerning the strain rate and the fracture properties of the rock, many of which are subject of current research in the geoscientific community. By a conservative approach, though, we judge to have adequately propagated critical uncertainties through the assessment and bound the uncertainty space.

  12. Evaluation of performance of a BLSS model in long-term operation in dynamic and steady states

    NASA Astrophysics Data System (ADS)

    Gros, Jean-Bernard; Tikhomirov, Alex; Ushakova, Sofya; Velitchko, Vladimir; Tikhomirova, Natalia; Lasseur, Christophe

    Evaluation of performance of a BLSS model, including higher plants for food production and biodegradation of human waste, in long-term operation in dynamic and steady states was performed. The model system was conceived for supplying vegetarian food and oxygen to 0.07 human. The following data were obtained in steady-state operating conditions. Average rate of wheat, chufa, radish, lettuce and Salicornia edible biomass accumulation were 8.7, 5.5, 0.6, 0.6 and metricconverterProductID2.5 g2.5 g per day respectively. Thus, to mimic the vegetarian edible biomass consumption by a human it was necessary to withdraw 17.9 g/d from total mass ex-change. Simultaneously, human mineralized exometabolites (artificial mineralized urine, AMU) in the amount of approximately 7% of a daily norm were introduced into the nutrient solu-tion for irrigation of the plants cultivated on a neutral substrate (expanded clay aggregate). The estimated value of 5.8 g/d of wheat and Salicornia inedible biomass was introduced in the soil-like substrate (SLS) to fully meet the plants need in nitrogen. The rest of wheat and Salicornia inedible biomass, 5.7 g/d, was stored. Thus in all, 23.6g of vegetarian dry matter had been stored. Assuming edible biomass is eaten up by the human, the closure coefficient of the vegetarian biomass inclusion into matter recycling amounted to 88%. The analysis of the long-term model operation showed that the main factors limiting increase of recycling processes were the following: a) Partly unbalanced mineral composition of daily human waste with daily needs of plants culti-` vated in the system. Thus, when fully satisfied with respect to nitrogen, the plants experienced a lack of macro elements such as P, Mg and Ca by more than 50%; b) Partly unbalanced mineral composition of edible biomass of the plants cultivated in the SLS with that of inedible biomass of the plants cultivated by hydroponic method on neutral substrate introduced in the SLS; c) Accumulation of

  13. Long-Term Results from Evaluation of Advanced New Construction Packages in Test Homes: Lake Elsinore, Californi

    SciTech Connect

    Stecher, D.; Brozyna, K.

    2013-08-01

    This report presents the long-term evaluation results from a hot-dry climate project that examines the room-to-room temperature conditions that exist in a high performance envelope, the performance of a simplified air distribution system, and a comparison of modeled energy performance with measured energy use. The project, a prototype house built by K. Hovnanian Homes’ Ontario Group, is located in Lake Elsinore, Riverside County, California, and achieves a 50% level of whole house source energy savings with respect to the Building America (BA) Benchmark Definition 2009 (Hendron and Engebrecht 2010). Temperature measurements in three rooms indicate that the temperature difference between the measured locations and the thermostat were within recommendations 90.3% of the time in heating mode and 99.3% of the time in cooling mode. The air distribution system is operating efficiently with average delivered temperatures adequate to facilitate proper heating and cooling and only minor average temperature differences observed between the system’s plenum and farthest register. Monitored energy use results for the house indicate that it is using less energy than predicted from modeling. A breakdown of energy use according to end use determined little agreement between comparable values.

  14. Long-Term Results from Evaluation of Advanced New Construction Packages in Test Homes: Lake Elsinore, California

    SciTech Connect

    Stecher, D.; Brozyna, K.

    2013-08-01

    This report presents the long-term evaluation results from a hot-dry climate project that examines the room-to-room temperature conditions that exist in a high performance envelope, the performance of a simplified air distribution system, and a comparison of modeled energy performance with measured energy use. The project, a prototype house built by K. Hovnanian Homes' Ontario Group, is located in Lake Elsinore, Riverside County, California, and achieves a 50% level of whole house source energy savings with respect to the Building America (BA) Benchmark Definition 2009 (Hendron and Engebrecht 2010). Temperature measurements in three rooms indicate that the temperature difference between the measured locations and the thermostat were within recommendations 90.3% of the time in heating mode and 99.3% of the time in cooling mode. The air distribution system is operating efficiently with average delivered temperatures adequate to facilitate proper heating and cooling and only minor average temperature differences observed between the system's plenum and farthest register. Monitored energy use results for the house indicate that it is using less energy than predicted from modeling. A breakdown of energy use according to end use determined little agreement between comparable values.

  15. Evaluation of the Universal Viral Transport system for long-term storage of virus specimens for microbial forensics.

    PubMed

    Hosokawa-Muto, Junji; Fujinami, Yoshihito; Mizuno, Natsuko

    2015-08-01

    Forensic microbial specimens, including bacteria and viruses, are collected at biocrime and bioterrorism scenes. Although it is preferable that the pathogens in these samples are alive and kept in a steady state, the samples may be stored for prolonged periods before analysis. Therefore, it is important to understand the effects of storage conditions on the pathogens contained within such samples. To evaluate the capacity to preserve viable virus and the viral genome, influenza virus was added to the transport medium of the Universal Viral Transport system and stored for over 3 months at various temperatures, after which virus titrations and quantitative analysis of the influenza hemagglutinin gene were performed. Although viable viruses became undetectable 29 days after the medium was stored at room temperature, viruses in the medium stored at 4°C were viable even after 99 days. A quantitative PCR analysis indicated that the hemagglutinin gene was maintained for 99 days at both 4°C and room temperature. Therefore, long-term storage at 4°C has little effect on viable virus and viral genes, so the Universal Viral Transport system can be useful for microbial forensics. This study provides important information for the handling of forensic virus specimens.

  16. Chiral HPLC versus chiral SFC: evaluation of long-term stability and selectivity of Chiralcel OD using various eluents.

    PubMed

    Lynam, K G; Nicolas, E C

    1993-01-01

    The long-term stability of Chiralcel OD columns under varying HPLC and SFC conditions was evaluated. Two new columns from the same supplier lot were procured, and one was installed in an HPLC system, and the other was installed in an SFC system. Enantiomeric mixtures of trans-stilbene oxide and carbobenzyloxy phenylalaninol were repeatedly injected in both systems over several days. For HPLC, hexane was the primary solvent used, along with IPA, EtOH, MeOH/IPA, or EtOH/TFA modifier. Carbon dioxide was the primary SFC solvent, together with the similar modifiers as the HPLC. Column performance was monitored by measuring resolution, theoretical plate number, and alpha between enantiomeric peaks. It was observed that, when the eluent strengths were adjusted to provide comparable retention times, the Chiralcel OD gave superior enantiomeric resolution when used in the SFC than the HPLC. Equilibration in between solvents was faster with SFC. The columns were demonstrated to be quite stable in both systems. PMID:8123734

  17. Long-term safety of tiotropium delivered by Respimat® SoftMist™ Inhaler: patient selection and special considerations

    PubMed Central

    Tan, Ching Kuo; Say, Gui Quan; Geake, James B

    2016-01-01

    Tiotropium bromide is a long-acting inhaled muscarinic antagonist used in patients with chronic respiratory disease. It has been available since 2002 as a single-dose dry powder formulation via the HandiHaler® dry powder inhaler (DPI) device, and since 2007 as the Respimat® SoftMist™ Inhaler (SMI). The latter is a novel method of medication delivery that utilizes a multidose aqueous solution to deliver the drug as a fine mist. Potential benefits include more efficient drug deposition throughout the respiratory tract, reduced systemic exposure, and greater ease of use and patient satisfaction compared with the use of HandiHaler DPI. Although tiotropium bromide delivered via the HandiHaler DPI has been clearly shown to improve lung function, dyspnea, and quality of life and to reduce exacerbations in patients with chronic obstructive pulmonary disease (COPD), there is accumulating evidence regarding the use of tiotropium HandiHaler in other respiratory diseases characterized by airflow limitation, such as asthma and cystic fibrosis. Developed more recently, tiotropium delivered via the Respimat SMI appears to have a similar efficacy and safety profile to the HandiHaler DPI, and early data raising the possibility of safety concerns with its use in COPD have been refuted by more recent evidence. The benefits over the HandiHaler DPI, however, remain unclear. This paper will review the evidence for tiotropium delivered via the Respimat SMI inhaler, in particular as an alternative to the HandiHaler DPI, and will focus on the safety profile for each of the chronic lung diseases in which it has been trialed, as well as an approach to appropriate patient selection. PMID:27703365

  18. Evaluation of biostimulation and Tween 80 addition for the bioremediation of long-term DDT-contaminated soil.

    PubMed

    Betancur-Corredor, Bibiana; Pino, Nancy J; Cardona, Santiago; Peñuela, Gustavo A

    2015-02-01

    The bioremediation of a long-term contaminated soil through biostimulation and surfactant addition was evaluated. The concentrations of 1,1,1-trichloro-2,2-bis(4-chlorophenyl) ethane (DDT) and its metabolites 1,1-dichloro-2,2-bis(4-chlorophenyl) ethane (DDD) and 1,1-dichloro-2,2-bis(4-chlorophenyl) ethylene (DDE) were monitored during an 8-week remediation process. Physicochemical characterization of the treated soil was performed before and after the bioremediation process. The isolation and identification of predominant microorganisms during the remediation process were also carried out. The efficiency of detoxification was evaluated after each bioremediation protocol. Humidity and pH and the heterotrophic microorganism count were monitored weekly. The DDT concentration was reduced by 79% after 8 weeks via biostimulation with surfactant addition (B+S) and 94.3% via biostimulation alone (B). Likewise, the concentrations of the metabolites DDE and DDD were reduced to levels below the quantification limits. The microorganisms isolated during bioremediation were identified as Bacillus thuringiensis, Flavobacterium sp., Cuprivadius sp., Variovorax soli, Phenylobacterium sp. and Lysobacter sp., among others. Analysis with scanning electron microscopy (SEM) allowed visualization of the colonization patterns of soil particles. The toxicity of the soil before and after bioremediation was evaluated using Vibrio fischeri as a bioluminescent sensor. A decrease in the toxic potential of the soil was verified by the increase of the concentration/effect relationship EC50 to 26.9% and 27.2% for B+S and B, respectively, compared to 0.4% obtained for the soil before treatment and 2.5% by natural attenuation after 8 weeks of treatment.

  19. Evaluation of biostimulation and Tween 80 addition for the bioremediation of long-term DDT-contaminated soil.

    PubMed

    Betancur-Corredor, Bibiana; Pino, Nancy J; Cardona, Santiago; Peñuela, Gustavo A

    2015-02-01

    The bioremediation of a long-term contaminated soil through biostimulation and surfactant addition was evaluated. The concentrations of 1,1,1-trichloro-2,2-bis(4-chlorophenyl) ethane (DDT) and its metabolites 1,1-dichloro-2,2-bis(4-chlorophenyl) ethane (DDD) and 1,1-dichloro-2,2-bis(4-chlorophenyl) ethylene (DDE) were monitored during an 8-week remediation process. Physicochemical characterization of the treated soil was performed before and after the bioremediation process. The isolation and identification of predominant microorganisms during the remediation process were also carried out. The efficiency of detoxification was evaluated after each bioremediation protocol. Humidity and pH and the heterotrophic microorganism count were monitored weekly. The DDT concentration was reduced by 79% after 8 weeks via biostimulation with surfactant addition (B+S) and 94.3% via biostimulation alone (B). Likewise, the concentrations of the metabolites DDE and DDD were reduced to levels below the quantification limits. The microorganisms isolated during bioremediation were identified as Bacillus thuringiensis, Flavobacterium sp., Cuprivadius sp., Variovorax soli, Phenylobacterium sp. and Lysobacter sp., among others. Analysis with scanning electron microscopy (SEM) allowed visualization of the colonization patterns of soil particles. The toxicity of the soil before and after bioremediation was evaluated using Vibrio fischeri as a bioluminescent sensor. A decrease in the toxic potential of the soil was verified by the increase of the concentration/effect relationship EC50 to 26.9% and 27.2% for B+S and B, respectively, compared to 0.4% obtained for the soil before treatment and 2.5% by natural attenuation after 8 weeks of treatment. PMID:25662244

  20. The evaluation of flap growth and long-term results of pediatric mandible reconstructions using free fibular flaps.

    PubMed

    Temiz, Gökhan; Bilkay, Ufuk; Tiftikçioğlu, Yiğit Özer; Mezili, Candan Tevfik; Songür, Ecmel

    2015-05-01

    Currently, the free fibular flap is well accepted as the first choice for mandibular reconstruction. Achieving functional results in pediatric patients requires a different approach than that employed for mature patients. Because the pediatric craniofacial skeleton continues to grow, reconstruction is more challenging, and the long-term results can be different from those of adult patients. In this study, we sought to measure flap growth objectively in our series. Ten pediatric patients who underwent reconstruction with free fibular flaps were retrospectively reviewed. Flap growth was evaluated by comparing the intraoperative photographs with photographs of the control panoramic mandibular radiographs taken using photo-anthropometric techniques. The measurements were converted to proportionality indices (PI), and these indices were compared. Subsequent complications and functional results were also evaluated. The mean patient age was 11.8 years, and the mean follow up was 57.7 months. The mean preoperative PI value was 10.74  ±  2.47. The mean postoperative PI value was 12.52  ±  2.34. The mean difference between the preoperative and postoperative PI values was -1.78 ± 0.53. These photo-anthropometric data clearly illustrated the growth of the fibular flaps (P = 0.001). None of these patients exhibited nonunion of the fractures; however, one patient experienced a delayed union, one had chronic temporomandibular joint pain, and one had chronic temporomandibular joint luxation. In two patients, the inter-incisive measurements were below the third percentile, and two additional patients had grade 2 eating abilities, which can be regarded as poor. All of the patients had symmetric mandibular contours. Free fibular flaps continue to grow in pediatric patients. This flap is a "workhorse" flap in children because it adapts to the craniofacial skeleton via its ability to grow, and this ability results in subsequent good cosmetic and functional results. PMID

  1. Evaluation of encapsulation and passivation of InGaAs/InP DHBT devices for long-term reliability

    NASA Astrophysics Data System (ADS)

    Kopf, R. F.; Hamm, R. A.; Ryan, R. W.; Burm, J.; Tate, A.; Chen, Y.-K.; Georgiou, G.; Lang, D. V.; Ren, F.

    1998-08-01

    Device encapsulation and passivation are critical for long-term reliability and stability. Several encapsulation techniques were evaluated in terms of degradation of electrical characteristics, gap filling under the mesa structures, and adhesion to the semiconductor and metal surfaces. These included plasma enhanced chemical vapor deposited (PECVD) SiO2, electron cyclotron resonance CVD SiNx, spin-on glass, benzocyclobutene, and polyimide. Damage from plasma exposure caused gain degradation in the devices. Spin-on coatings cause little to no gain degradation, provided that there is minimal stress in the cured film. SOG and BCB films have acceptable adhesion properties and were excellent for gap filling. Polyimide films have excellent adhesion properties, however, they were poor at gap filling and had a great deal of shrinkage during curing. Device passivation was evaluated using double heterojunction bipolar transistor structures with either an abrupt or graded emitter-base junction. Abrupt junction devices had the self-aligned base metal directly on the p+ InGaAs base. Graded junction devices had the base metal on top of graded InGaAsP layers, which the metal was diffused through, to make contact to the base region. Abrupt junction devices stressed at an initial JE of 90 kA/cm2 at a VCE of 2V at 25°C degraded 20% within 70 h of operation, whereas, the graded junction devices show no degradation in dc characteristics after operation for over 500 h. Typical common emitter current gain was 50. An ft of 80 and fmax of 155 GHz were achieved for 2×4 µm2 emitter size devices.

  2. Assessment of long-term safety and efficacy of intranasal mesenchymal stem cell treatment for neonatal brain injury in the mouse

    PubMed Central

    Donega, Vanessa; Nijboer, Cora H.; van Velthoven, Cindy T. J.; Youssef, Sameh A.; de Bruin, Alain; van Bel, Frank; Kavelaars, Annemieke; Heijnen, Cobi J.

    2015-01-01

    Background: For clinical translation, we assessed whether intranasal mesenchymal stem cell (MSC) treatment after hypoxia–ischemia (HI) induces neoplasia in the brain or periphery at 14 mo. Furthermore, the long-term effects of MSCs on behavior and lesion size were determined. Method: HI was induced in 9-d-old mice. Pups received an intranasal administration of 0.5 × 106 MSCs or vehicle at 10 d post-HI. Full macroscopical and microscopical pathological analysis of 39 organs per mouse was performed. Sensorimotor behavior was assessed in the cylinder-rearing test at 10 d, 28 d, 6 mo, and 9 mo. Cognition was measured with the novel object recognition test at 3 and 14 mo post-HI. Lesion size was determined by analyzing mouse-anti-microtubule-associated protein 2 (MAP2) and mouse-anti-myelin basic protein (MBP) staining at 5 wk and 14 mo. Results: At 14 mo post-HI, we did not observe any neoplasia in the nasal turbinates, brain, or other organs of HI mice treated with MSCs. Furthermore, our results show that MSC-induced improvement of sensorimotor and cognitive function is long lasting. In contrast, HI-vehicle mice showed severe behavioral impairment. Recovery of MAP2- and MBP-positive area lasted up to 14 mo following MSC treatment. Conclusion: Our results provide strong evidence of the long-term safety and positive effects of MSC treatment following neonatal HI in mice. PMID:26270577

  3. Long-Term Efficacy and Safety of Repeated Intravescial OnabotulinumtoxinA Injections Plus Hydrodistention in the Treatment of Interstitial Cystitis/Bladder Pain Syndrome

    PubMed Central

    Lee, Cheng-Ling; Kuo, Hann-Chorng

    2015-01-01

    Intravesical onabotulinumtoxinA (BoNT-A) injection can relieve symptoms of interstitial cystitis/bladder pain syndrome (IC/BPS), but lacks sustainability. Repeated injections have been shown to provide a superior outcome to a single injection, but data on long-term efficacy and safety is limited. In this prospective study, we enrolled patients with refractory IC/BPS, and treated them with 100 U of BoNT-A injection plus hydrodistention followed by repeated injections every six months for up to two years or until the patient wished to discontinue. A “top-up” dose was offered after the fourth injection. Of these 104 participants, 56.7% completed four BoNT-A injections and 34% voluntarily received the fifth injection due to exacerbated IC symptoms. With a follow-up period of up to 79 months, O’Leary-Sant symptom and problem indexes (ICSI, ICPI, OSS), pain visual analogue scale (VAS) functional bladder capacity, frequency episodes, and global response assessment (GRA) all showed significant improvement (p < 0.0001). Those who received repeated injections had a better success rate during the long-term follow-up period. The incidence of adverse events did not rise with the increasing number of BoNT-A injections. A higher pre-treatment ICSI and ICPI score was predictive for successful response to repeated intravesical BoNT-A injections plus hydrodistention. PMID:26506388

  4. Long-term Satellite NDVI Data Sets: Evaluating Their Ability to Detect Ecosystem Functional Changes in South America

    PubMed Central

    Baldi, Germán; Nosetto, Marcelo D.; Aragón, Roxana; Aversa, Fernando; Paruelo, José M.; Jobbágy, Esteban G.

    2008-01-01

    In the last decades, South American ecosystems underwent important functional modifications due to climate alterations and direct human intervention on land use and land cover. Among remotely sensed data sets, NOAA-AVHRR “Normalized Difference Vegetation Index” (NDVI) represents one of the most powerful tools to evaluate these changes thanks to their extended temporal coverage. In this paper we explored the possibilities and limitations of three commonly used NOAA-AVHRR NDVI series (PAL, GIMMS and FASIR) to detect ecosystem functional changes in the South American continent. We performed pixel-based linear regressions for four NDVI variables (average annual, maximum annual, minimum annual and intra-annual coefficient of variation) for the 1982-1999 period and (1) analyzed the convergences and divergences of significant multi-annual trends identified across all series, (2) explored the degree of aggregation of the trends using the O-ring statistic, and (3) evaluated observed trends using independent information on ecosystem functional changes in five focal regions. Several differences arose in terms of the patterns of change (the sign, localization and total number of pixels with changes). FASIR presented the highest proportion of changing pixels (32.7%) and GIMMS the lowest (16.2%). PAL and FASIR data sets showed the highest agreement, with a convergence of detected trends on 71.2% of the pixels. Even though positive and negative changes showed substantial spatial aggregation, important differences in the scale of aggregation emerged among the series, with GIMMS showing the smaller scale (≤11 pixels). The independent evaluations suggest higher accuracy in the detection of ecosystem changes among PAL and FASIR series than with GIMMS, as they detected trends that match expected shifts. In fact, this last series eliminated most of the long term patterns over the continent. For example, in the “Eastern Paraguay” and “Uruguay River margins” focal regions

  5. Diffuse large B-cell lymphoma associated with the use of biologic and other investigational agents: the importance of long-term post-marketing safety surveillance.

    PubMed

    Goddard, Allison; Borovicka, Judy H; West, Dennis P; Evens, Andrew M; Laumann, Anne

    2011-01-01

    This case report describes a patient who developed diffuse large B-cell lymphoma (DLBCL) after receiving courses of two investigational biologic agents and cyclosporine followed by more than four years of subcutaneous efalizumab for the treatment of extensive chronic plaque psoriasis. Three years later, the patient remains free of lymphoma and his psoriasis is well controlled with thrice-weekly narrow-band ultraviolet phototherapy. This case emphasizes the importance of continued long-term post-marketing safety surveillance and the early reporting of all possible serious side effects, including cancers, related to the use of any newly available product. In particular, surveillance should focus on the immunomodulating biologic agents in order to identify possible dangerous sequelae.

  6. Long-Term Safety of Repeated Blood-Brain Barrier Opening via Focused Ultrasound with Microbubbles in Non-Human Primates Performing a Cognitive Task.

    PubMed

    Downs, Matthew E; Buch, Amanda; Sierra, Carlos; Karakatsani, Maria Eleni; Teichert, Tobias; Chen, Shangshang; Konofagou, Elisa E; Ferrera, Vincent P

    2015-01-01

    Focused Ultrasound (FUS) coupled with intravenous administration of microbubbles (MB) is a non-invasive technique that has been shown to reliably open (increase the permeability of) the blood-brain barrier (BBB) in multiple in vivo models including non-human primates (NHP). This procedure has shown promise for clinical and basic science applications, yet the safety and potential neurological effects of long term application in NHP requires further investigation under parameters shown to be efficacious in that species (500 kHz, 200-400 kPa, 4-5 μm MB, 2 minute sonication). In this study, we repeatedly opened the BBB in the caudate and putamen regions of the basal ganglia of 4 NHP using FUS with systemically-administered MB over 4-20 months. We assessed the safety of the FUS with MB procedure using MRI to detect edema or hemorrhaging in the brain. Contrast enhanced T1-weighted MRI sequences showed a 98% success rate for openings in the targeted regions. T2-weighted and SWI sequences indicated a lack edema in the majority of the cases. We investigated potential neurological effects of the FUS with MB procedure through quantitative cognitive testing of' visual, cognitive, motivational, and motor function using a random dot motion task with reward magnitude bias presented on a touchpanel display. Reaction times during the task significantly increased on the day of the FUS with MB procedure. This increase returned to baseline within 4-5 days after the procedure. Visual motion discrimination thresholds were unaffected. Our results indicate FUS with MB can be a safe method for repeated opening of the BBB at the basal ganglia in NHP for up to 20 months without any long-term negative physiological or neurological effects with the parameters used. PMID:25945493

  7. Long-Term Safety of Repeated Blood-Brain Barrier Opening via Focused Ultrasound with Microbubbles in Non-Human Primates Performing a Cognitive Task

    PubMed Central

    Downs, Matthew E.; Buch, Amanda; Sierra, Carlos; Karakatsani, Maria Eleni; Chen, Shangshang; Konofagou, Elisa E.; Ferrera, Vincent P.

    2015-01-01

    Focused Ultrasound (FUS) coupled with intravenous administration of microbubbles (MB) is a non-invasive technique that has been shown to reliably open (increase the permeability of) the blood-brain barrier (BBB) in multiple in vivo models including non-human primates (NHP). This procedure has shown promise for clinical and basic science applications, yet the safety and potential neurological effects of long term application in NHP requires further investigation under parameters shown to be efficacious in that species (500kHz, 200–400 kPa, 4–5μm MB, 2 minute sonication). In this study, we repeatedly opened the BBB in the caudate and putamen regions of the basal ganglia of 4 NHP using FUS with systemically-administered MB over 4–20 months. We assessed the safety of the FUS with MB procedure using MRI to detect edema or hemorrhaging in the brain. Contrast enhanced T1-weighted MRI sequences showed a 98% success rate for openings in the targeted regions. T2-weighted and SWI sequences indicated a lack edema in the majority of the cases. We investigated potential neurological effects of the FUS with MB procedure through quantitative cognitive testing of’ visual, cognitive, motivational, and motor function using a random dot motion task with reward magnitude bias presented on a touchpanel display. Reaction times during the task significantly increased on the day of the FUS with MB procedure. This increase returned to baseline within 4–5 days after the procedure. Visual motion discrimination thresholds were unaffected. Our results indicate FUS with MB can be a safe method for repeated opening of the BBB at the basal ganglia in NHP for up to 20 months without any long-term negative physiological or neurological effects with the parameters used. PMID:25945493

  8. Long-Term Safety of Repeated Blood-Brain Barrier Opening via Focused Ultrasound with Microbubbles in Non-Human Primates Performing a Cognitive Task.

    PubMed

    Downs, Matthew E; Buch, Amanda; Sierra, Carlos; Karakatsani, Maria Eleni; Teichert, Tobias; Chen, Shangshang; Konofagou, Elisa E; Ferrera, Vincent P

    2015-01-01

    Focused Ultrasound (FUS) coupled with intravenous administration of microbubbles (MB) is a non-invasive technique that has been shown to reliably open (increase the permeability of) the blood-brain barrier (BBB) in multiple in vivo models including non-human primates (NHP). This procedure has shown promise for clinical and basic science applications, yet the safety and potential neurological effects of long term application in NHP requires further investigation under parameters shown to be efficacious in that species (500 kHz, 200-400 kPa, 4-5 μm MB, 2 minute sonication). In this study, we repeatedly opened the BBB in the caudate and putamen regions of the basal ganglia of 4 NHP using FUS with systemically-administered MB over 4-20 months. We assessed the safety of the FUS with MB procedure using MRI to detect edema or hemorrhaging in the brain. Contrast enhanced T1-weighted MRI sequences showed a 98% success rate for openings in the targeted regions. T2-weighted and SWI sequences indicated a lack edema in the majority of the cases. We investigated potential neurological effects of the FUS with MB procedure through quantitative cognitive testing of' visual, cognitive, motivational, and motor function using a random dot motion task with reward magnitude bias presented on a touchpanel display. Reaction times during the task significantly increased on the day of the FUS with MB procedure. This increase returned to baseline within 4-5 days after the procedure. Visual motion discrimination thresholds were unaffected. Our results indicate FUS with MB can be a safe method for repeated opening of the BBB at the basal ganglia in NHP for up to 20 months without any long-term negative physiological or neurological effects with the parameters used.

  9. Long-Term Safety of Subcutaneous Abatacept in Rheumatoid Arthritis: Integrated Analysis of Clinical Trial Data Representing More Than Four Years of Treatment

    PubMed Central

    Alten, Rieke; Kaine, Jeffrey; Keystone, Edward; Nash, Peter; Delaet, Ingrid; Genovese, Mark C

    2014-01-01

    Objective To investigate the safety of long-term subcutaneous (SC) abatacept treatment using integrated clinical trial data obtained in patients with rheumatoid arthritis refractory to traditional disease-modifying antirheumatic drugs. Methods Data from the double-blind and open-label phases of 5 clinical trials of SC abatacept were pooled. The overall and 6-month incidence rates were calculated as events per 100 patient-years of exposure. Results This analysis included 1,879 patients with 4,214.6 patient-years of exposure to SC abatacept. The mean ± SD length of exposure was 27.3 ± 9.1 months. The reported incidence rate of serious infections was 1.79 (95% confidence interval [95% CI] 1.42–2.24); the most frequent infections were pneumonia (incidence rate 0.36 [95% CI 0.22–0.59]), urinary tract infection (incidence rate 0.14 [95% CI 0.06–0.32]), and gastroenteritis (incidence rate 0.10 [95% CI 0.04–0.25]). Tuberculosis occurred rarely (incidence rate 0.09 [95% CI 0.04–0.25]). The reported incidence rate of malignancies was 1.32 (95% CI 1.01–1.72), and the most common was solid organ malignancy (incidence rate 0.69 [95% CI 0.48–0.99]). The incidence rate of autoimmune events was 1.37 (95% CI 1.06–1.78), and the most frequent events were psoriasis (incidence rate 0.33 [95% CI 0.20–0.56]) and Sjögren's syndrome (incidence rate 0.24 [95% CI 0.13–0.44]). The reported incidence rate of local injection site reactions was 1.72 (95% CI 1.36–2.17); these events occurred primarily during the first 6 months of treatment, and almost all were of mild or moderate intensity. The incidence rates of serious infections, malignancies, autoimmune events, and injection site reactions did not increase over time. Conclusion Long-term treatment with SC abatacept was associated with low incidence rates of serious infections, malignancies, and autoimmune events and was well tolerated, with infrequent injection site reactions. These findings are consistent with those

  10. Evaluation of Chemistry-Climate Model Results using Long-Term Satellite and Ground-Based Data

    NASA Technical Reports Server (NTRS)

    Stolarski, Richard S.

    2005-01-01

    Chemistry-climate models attempt to bring together our best knowledge of the key processes that govern the composition of the atmosphere and its response to changes in forcing. We test these models on a process by process basis by comparing model results to data from many sources. A more difficult task is testing the model response to changes. One way to do this is to use the natural and anthropogenic experiments that have been done on the atmosphere and are continuing to be done. These include the volcanic eruptions of El Chichon and Pinatubo, the solar cycle, and the injection of chlorine and bromine from CFCs and methyl bromide. The test of the model's response to these experiments is their ability to produce the long-term variations in ozone and the trace gases that affect ozone. We now have more than 25 years of satellite ozone data. We have more than 15 years of satellite and ground-based data of HC1, HN03, and many other gases. I will discuss the testing of models using long-term satellite data sets, long-term measurements from the Network for Detection of Stratospheric Change (NDSC) , long-term ground-based measurements of ozone.

  11. Ductal Carcinoma In Situ With Microinvasion: Prognostic Implications, Long-Term Outcomes, and Role of Axillary Evaluation

    SciTech Connect

    Parikh, Rahul R.; Haffty, Bruce G.; Lannin, Donald; Moran, Meena S.

    2012-01-01

    Purpose: To compare the clinical-pathologic features and long-term outcomes for women with ductal carcinoma in situ (DCIS) vs. DCIS with microinvasion (DCISM) treated with breast conservation therapy (BCT), to assess the impact of microinvasion. Patients and Methods: A total of 393 patients with DCIS/DCISM from our database were analyzed to assess differences in clinical-pathologic features and outcomes for the two cohorts. Results: The median follow-up was 8.94 years, and the mean age was 55.8 years for the entire group. The DCISM cohort was comprised of 72 of 393 patients (18.3%). Surgical evaluation of the axilla was performed in 58.3% (n = 42) of DCISM vs. 18.1% (n = 58) of DCIS, with only 1 of 42 DCISM (2.3%) vs. 0 of 58 DCIS with axillary metastasis. Surgical axillary evaluation was not an independent predictor of local-regional relapse (LRR), distant relapse-free survival (DRFS), or overall survival (OS) in Cox proportional hazards analysis (p > 0.05). For the DCIS vs. DCISM groups, respectively, the 10-year breast relapse-free survival was 89.0% vs. 90.7% (p = 0.36), DRFS was 98.5% vs. 97.9% (p = 0.78), and OS was 93.2% vs. 95.7% (p = 0.95). The presence of microinvasion did not correlate with LRR, age, presentation, race, family history, margin status, and use of adjuvant hormonal therapy (all p > 0.05). In univariate analysis, pathology (DCIS vs. DCISM) was not an independent predictor of LRR (hazard ratio [HR], 1.58; 95% confidence interval [CI], 0.58-4.30; p = 0.36), DRFS (HR, 0.72; 95% CI, 0.07-6.95; p = 0.77), or OS (HR, 1.03; 95% CI, 0.28-3.82; p = 0.95). Conclusions: Our data imply that the natural history of DCISM closely resembles that of DCIS, with a low incidence of local-regional and distant failures. On the basis of our large dataset, the incidence of axillary metastasis in DCISM appears to be small and not appear to correlate to outcomes, and thus, microinvasion alone should not be the sole criterion for more aggressive treatment.

  12. Long-term safety and efficacy of once-daily topical brimonidine tartrate gel 0.5% for the treatment of moderate to severe facial erythema of rosacea: results of a 1-year open-label study.

    PubMed

    Moore, Angela; Kempers, Steven; Murakawa, George; Weiss, Jonathan; Tauscher, Amanda; Swinyer, Leonard; Liu, Hong; Leoni, Matthew

    2014-01-01

    Once-daily topical brimonidine tartrate (BT) gel 0.5% was shown to be efficacious and safe for the treatment of erythema of rosacea in previous studies including a 4-week treatment phase. In the present 1-year study, we aimed to assess the long-term safety and efficacy of the treatment. Subjects with moderate to severe erythema of rosacea were instructed to apply topical BT gel 0.5% once daily for 12 months. Severity of erythema and adverse events (AEs) were evaluated. Approximately 345 subject years of exposure to BT gel 0.5% was achieved in the study. The incidence of AEs and AEs judged to be related to the study drug was higher at the beginning and decreased over the course of the study. Similar safety profiles were observed between the subjects who had received or not received concomitant therapies for the inflammatory lesions of rosacea. Effect of topical BT gel 0.5% on erythema severity was observed after the first application and the durability of the effect was maintained until the end of the study at month 12, with no tachyphylaxis observed. In conclusion, once-daily topical BT gel 0.5% is safe and consistently effective for the long-term treatment of moderate to severe erythema of rosacea, even in the presence of concomitant therapies for the inflammatory lesions of rosacea.

  13. Locking-In Effects Due to Early Interventions? An Evaluation of a Multidisciplinary Screening Programs for Avoiding Long-Term Sickness

    ERIC Educational Resources Information Center

    Johansson, Per; Lindahl, Erica

    2012-01-01

    Objective: In this article, we estimate the effect of a multidisciplinary collaboration program on the length of sickness absence. The intention with the program was to avoid long-term sickness absence by providing an early and holistic evaluation of the sick-listed individuals' conditions. The target group was individuals who were at risk of…

  14. ENVIRONMENTAL RESEARCH BRIEF: LONG-TERM PERFORMANCE OF PERMEABLE REACTIVE BARRIERS USING ZERO-VALENT IRON: AN EVALUATION AT TWO SITES

    EPA Science Inventory

    Geochemical and microbiological factors that control long-term performance of subsurface permeable reactive barriers were evaluated at the Elizabeth City, NC and the Denver Federal Center, CO sites. These groundwater treatment systems use zero-valent iron filings to intercept an...

  15. Long-Term Outcomes of an Australian Universal Prevention Trial of Anxiety and Depression Symptoms in Children and Youth: An Evaluation of the Friends Program

    ERIC Educational Resources Information Center

    Barrett, Paula M.; Farrell, Lara J.; Ollendick, Thomas H.; Dadds, Mark

    2006-01-01

    This study evaluated the long-term effectiveness of the FRIENDS Program in reducing anxiety and depression in a sample of children from Grade 6 and Grade 9 in comparison to a control condition. Longitudinal data for Lock and Barrett's (2003) universal prevention trial is presented, along with data from 12-month follow-up to 24- and 36-month…

  16. Evaluating the Effectiveness of Intervention in Long-Term Aphasia Post-Stroke: The Experience from CHANT (Communication Hub for Aphasia in North Tyneside)

    ERIC Educational Resources Information Center

    Mumby, Katharyn; Whitworth, Anne

    2012-01-01

    Background: Despite recognition of the need for increased long-term support for people with aphasia following stroke, there remains limited evidence for effective service-level interventions. Aims: To evaluate the outcomes and experiences of people participating in the Communication Hub for Aphasia in North Tyneside (CHANT), a 2-year partnership…

  17. Long-term Geochemical Transport Simulation to Evaluate Ambient Chemical Conditions at Horonobe URL Site, Hokkaido, Japan

    NASA Astrophysics Data System (ADS)

    Yamamoto, H.; Shimo, M.; Fujiwara, Y.; Kunimaru, T.; Xu, T.; Laaksoharju, M.

    2005-12-01

    JNC (Japan Nuclear Cycle Development Institute) has been planning an underground research laboratory (URL) in Horonobe, northern Hokkaido, Japan. In this study, long-term evolution of groundwater chemistry was simulated to evaluate ambient chemical conditions around the Horonobe URL site. The study area is about 8km by 4km and 2km deep region centered on the URL, in which the geology mainly consists of Pliocene diatomaceous argillaceous formations. Hydro-geochemical investigations using deep boreholes in about 3km by 3km area have suggested that groundwater chemistry around the site has been formed through the mixing of shallow fresh water and deep saline water. The deep groundwater has high salinity and differs from the present seawater in that it is highly reduced and has low pH, high bicarbonate and low magnesium concentration. Prior to the simulation, a computer code M3 (Laaksoharju et al. 1999) was used to model that the groundwater composition is affected by a two end-member mixing system. Next, the simulation of chemical changes during the intrusion of fresh water from land surface into deep saline water in the past 0.1 Ma was performed. A non-isothermal multiphase reactive geochemical transport simulation code TOUGHREACT (Xu and Press, 2001) was employed to solve the complex interplay of mass transport and chemical reaction in groundwater such as mineral dissolution/precipitation and ion exchange. The simulator was applied to a site-scale 3D geological structure model in which surface topography, the structures of geologic formations and a major fault were embedded. The results suggest that: 1) the spatial patterns of salinity and major constituents observed are in the site are generally consistent with a scenario of the intrusion of the surface fresh water into the deep saline water; 2) freshening of the deep saline water increases pH by cation exchange; 3) redox front migrates as oxidized water infiltrates from surface but is strongly buffered by reducing

  18. Field Evaluations of Sampling Methods for Long-Term Monitoring of Upland Ecosystems on the Colorado Plateau

    USGS Publications Warehouse

    Miller, Mark E.; Witwicki, Dana L.; Mann, Rebecca K.; Tancreto, Nicole J.

    2007-01-01

    To inform planning for long-term ecological monitoring, we sampled vegetation and soil-surface attributes across a range of terrestrial ecosystems (physiognomic types) in seven National Park Service units on the Colorado Plateau. Primary objectives were (1) to evaluate a suite of sampling methods according to measures of repeatability, efficiency, and impacts on plot conditions; and (2) to characterize within- and among-plot variability in monitoring measures. This work was designed to support NPS staff in selecting the combination of methods that best meets their monitoring objectives and resource constraints. We found no differences among cover-estimation techniques in terms of repeatability between observers (measurement precision). Estimates for total live understory canopy cover, cover of individual species, and cover of soil-surface features were highly repeatable between observers for 10-m2 quadrats, 1-m2 quadrats, and line-point intercept sampling methods. Estimates of shrub and tree density in 10-m2 quadrats also were repeatable between observers, although sample sizes for were small for many species. At 10 of 11 ecological sites, we found that sampling with 10-m2 quadrats was the most efficient cover-estimation technique with respect to within-plot variability in cover estimates and numbers of subsamples required to estimate plot-level cover with 20 percent precision. According to these same measures, sampling with 1-m2 quadrats was the least efficient cover-estimation technique at eight of 11 ecological sites. The line-point technique was most efficient at eight of 11 ecological sites in terms of the amount of time required to estimate total plot-level cover with 20 percent precision - largely because 10-m2 quadrats were more time consuming and 1-m2 quadrats had greater within-plot variability relative to line-point sampling. However, there was no statistical difference among methods with respect to median subsampling times for 20 percent precision

  19. An Evaluation of Long-Term Performance of Liner Systems for Low-Level Waste Disposal Facilities

    SciTech Connect

    Arthur S. Rood; Annette L. Schafer; A. Jeffrey Sondrup

    2011-03-01

    Traditional liner systems consisting of a geosynthetic membrane underlying a waste disposal facility coupled with a leachate collection system have been proposed as a means of containing releases of low-level radioactive waste within the confines of the disposal facility and thereby eliminating migration of radionuclides into the vadose zone and groundwater. However, this type of hydraulic containment liner system is only effective as long as the leachate collection system remains functional or an overlying cover limits the total infiltration to the volumetric pore space of the disposal system. If either the leachate collection system fails, or the overlying cover becomes less effective during the 1,000’s of years of facility lifetime, the liner may fill with water and release contaminated water in a preferential or focused manner. If the height of the liner extends above the waste, the waste will become submerged which could increase the release rate and concentration of the leachate. If the liner extends near land surface, there is the potential for contamination reaching land surface creating a direct exposure pathway. Alternative protective liner systems can be engineered that eliminate radionuclide releases to the vadose zone during operations and minimizing long term migration of radionuclides from the disposal facility into the vadose zone and aquifer. Non-traditional systems include waste containerization in steel or composite materials. This type of system would promote drainage of clean infiltrating water through the facility without contacting the waste. Other alternatives include geochemical barriers designed to transmit water while adsorbing radionuclides beneath the facility. Facility performance for a hypothetical disposal facility has been compared for the hydraulic and steel containerization liner alternatives. Results were compared in terms of meeting the DOE Order 435.1 low-level waste performance objective of 25 mrem/yr all-pathways dose

  20. Long-Term Evaluation of the AMSR-E Soil Moisture Product Over the Walnut Gulch Watershed, AZ

    NASA Astrophysics Data System (ADS)

    Bolten, J. D.; Jackson, T. J.; Lakshmi, V.; Cosh, M. H.; Drusch, M.

    2005-12-01

    The Advanced Microwave Scanning Radiometer -Earth Observing System (AMSR-E) was launched aboard NASA's Aqua satellite on May 4th, 2002. Quantitative estimates of soil moisture using the AMSR-E provided data have required routine radiometric data calibration and validation using comparisons of satellite observations, extended targets and field campaigns. The currently applied NASA EOS Aqua ASMR-E soil moisture algorithm is based on a change detection approach using polarization ratios (PR) of the calibrated AMSR-E channel brightness temperatures. To date, the accuracy of the soil moisture algorithm has been investigated on short time scales during field campaigns such as the Soil Moisture Experiments in 2004 (SMEX04). Results have indicated self-consistency and calibration stability of the observed brightness temperatures; however the performance of the moisture retrieval algorithm has been poor. The primary objective of this study is to evaluate the quality of the current version of the AMSR-E soil moisture product for a three year period over the Walnut Gulch Experimental Watershed (150 km2) near Tombstone, AZ; the northern study area of SMEX04. This watershed is equipped with hourly and daily recording of precipitation, soil moisture and temperature via a network of raingages and a USDA-NRCS Soil Climate Analysis Network (SCAN) site. Surface wetting and drying are easily distinguished in this area due to the moderately-vegetated terrain and seasonally intense precipitation events. Validation of AMSR-E derived soil moisture is performed from June 2002 to June 2005 using watershed averages of precipitation, and soil moisture and temperature data from the SCAN site supported by a surface soil moisture network. Long-term assessment of soil moisture algorithm performance is investigated by comparing temporal variations of moisture estimates with seasonal changes and precipitation events. Further comparisons are made with a standard soil dataset from the European

  1. Evaluation of autofluorescent property of hemoglobin-advanced glycation end product as a long-term glycemic index of diabetes.

    PubMed

    Gopalkrishnapillai, Bijukumar; Nadanathangam, Vigneshwaran; Karmakar, Nivedita; Anand, Sneh; Misra, Anoop

    2003-04-01

    Current methods for measuring long-term glycemia in patients with diabetes are HbA(1c) and advanced glycation end products (AGEs), which are estimated by phenyl boronate affinity chromatography and competitive enzyme-linked immunosorbent assay, respectively. In this study, we hypothesize that the intrinsic fluorescence property of hemoglobin-AGE (Hb-AGE) may be a simple, accurate, and therefore better index for long-term glycemic status due to its highly specific nature and longer half-life. To establish this contention, in vitro and in vivo experiments were carried out. The former was performed by incubating commercially available hemoglobin with 5 and 20 mmol/l glucose and the latter through experimentally induced (streptozotocin) diabetes in an animal model (male Wistar rats) to identify the new fluorophore formed due to the nonenzymatic glycosylation of hemoglobin. An adduct exhibiting fluorescence at 308/345 nm of excitation/emission wavelengths has been identified and its time-dependent formation established. Under in vitro conditions, the first appearance of the new fluorophore was noticed only after a period of 2 months, whereas under in vivo conditions, it increased significantly after 2 months of hyperglycemia. Consistent with the observations, studies on patients with type 2 diabetes demonstrated an elevated level of this new fluorescent adduct in patients with persisting high levels of plasma glucose for >2 months. Based on the results obtained, Hb-AGE appears to be an efficient fluorescence-based biosensing molecule for the long-term monitoring of glycemic control in diabetes.

  2. Long-Term Efficacy and Patterns of Failure After Accelerated Partial Breast Irradiation: A Molecular Assay-Based Clonality Evaluation

    SciTech Connect

    Vicini, Frank A. . E-mail: fvicini@beaumont.edu; Antonucci, J. Vito; Wallace, Michelle R.N.; Gilbert, Samuel; Goldstein, Neal S.; Kestin, Larry; Chen, Peter; Kunzman, Jonathan; Boike, Thomas; Benitez, Pamela; Martinez, Alvaro

    2007-06-01

    Purpose: To determine the long-term efficacy and cosmetic results of accelerated partial breast irradiation (APBI) by reviewing our institution's experience. Methods and Materials: A total of 199 patients with early-stage breast cancer were treated prospectively with adjuvant APBI after lumpectomy using interstitial brachytherapy. All patients had negative margins, 82% had Stage I disease, median tumor size was 1.1 cm, and 12% had positive lymph nodes. The median follow-up for surviving patients was 8.6 years. Fifty-three patients (27%) have been followed for {>=}10 years. Results: Six ipsilateral breast tumor recurrences (IBTRs) were observed, for a 5-year and 10-year actuarial rate of 1.6% and 3.8%, respectively. A total of three regional nodal failures were observed, for a 10-year actuarial rate of 1.6%. Five contralateral breast cancers developed, for a 5- and 10-year actuarial rate of 2.2% and 5.2%, respectively. The type of IBTR (clonally related vs. clonally distinct) was analyzed using a polymerase chain reaction-based loss of heterozygosity assay. Eighty-three percent of IBTRs (n = 5) were classified as clonally related. Multiple clinical, pathologic, and treatment-related factors were analyzed for an association with the development of an IBTR, regional nodal failure, or contralateral breast cancer. On multivariate analysis, no variable was associated with any of these events. Cosmetic results were rated as excellent/good in 99% of patients. Conclusions: Long-term results with APBI using interstitial brachytherapy continue to demonstrate excellent long-term local and regional control rates and cosmetic results. According to a polymerase chain reaction-based loss of heterozygosity assay, 83% of recurrences were classified as clonally related.

  3. Working together in placing the long term interests of the child at the heart of the DSD evaluation.

    PubMed

    Magritte, Ellie

    2012-12-01

    This paper articulates a number of important but often ignored questions that families have during and following the diagnosis of a child with a DSD. Recounting a personal birth experience, it illustrates the urgent need for more psychological and educational support during and following diagnosis and gender assignment. Finally, the paper describes some practical strategies for raising a child living with genital difference. It urges everyone involved in the care of children with a DSD to support parents in looking beyond initial anxiety and worry and always to place the child's long term wellbeing at the very heart of the clinical decision-making and care. PMID:22981141

  4. Long-Term Outcomes of Cultivated Limbal Epithelial Transplantation: Evaluation and Comparison of Results in Children and Adults

    PubMed Central

    Ganger, Anita; Vanathi, M.; Mohanty, Sujata; Tandon, Radhika

    2015-01-01

    Purpose. To compare the long-term clinical outcomes of cultivated limbal epithelial transplantation (CLET) in children and adults with limbal stem cell deficiency. Design. Retrospective case series. Methods. Case records of patients with limbal stem cell deficiency (LSCD) who underwent CLET from April 2004 to December 2014 were studied. Outcome measures were compared in terms of anatomical success and visual improvement. Parameters for total anatomical success were avascular, epithelized, and clinically stable corneal surface without conjunctivalization, whereas partial anatomical success was considered when mild vascularization (sparing centre of cornea) and mild conjunctivalization were noted along with complete epithelization. Results. A total of 62 cases underwent the CLET procedure: 38 (61.3%) were children and 24 (38.7%) were adults. Patients with unilateral LSCD (33 children and 21 adults) had autografts and those with bilateral LSCD (5 children and 3 adults) had allografts. Amongst the 54 autografts partial and total anatomical success were noted in 21.2% and 66.6% children, respectively, and 19.0% and 80.9% in adults, respectively (p value 0.23). Visual improvement of 1 line and ≥2 lines was seen in 57.5% and 21.2% children, respectively, and 38% and 38% in adults, respectively (p value 0.31). Conclusion. Cultivated limbal epithelial transplantation gives good long-term results in patients with LSCD and the outcomes are comparable in children and adults. PMID:26770973

  5. Study on the postprandial blood glucose suppression effect of D-psicose in borderline diabetes and the safety of long-term ingestion by normal human subjects.

    PubMed

    Hayashi, Noriko; Iida, Tetsuo; Yamada, Takako; Okuma, Kazuhiro; Takehara, Isao; Yamamoto, Takashi; Yamada, Koji; Tokuda, Masaaki

    2010-01-01

    This clinical study was conducted to investigate the safety and effect of D-psicose on postprandial blood glucose levels in adult men and women, including borderline diabetes patients. A randomized double-blind placebo-controlled crossover experiment of single ingestion was conducted on 26 subjects who consumed zero or 5 g of D-psicose in tea with a standard meal. The blood glucose levels at fasting and 30, 60, 90, and 120 min after the meal were compared. The blood glucose level was significantly lower 30 and 60 min after the meal with D-psicose (p<0.01, p<0.05), and a significant decrease was also shown in the area under the curve (p<0.01). The results suggest that D-psicose had an effect to suppress the postprandial blood glucose elevation mainly in borderline diabetes cases. A randomized double-blind placebo-controlled parallel-group experiment of long-term ingestion was conducted on 17 normal subjects who took 5 g of D-psicose or D-glucose with meals three times a day for 12 continuous weeks. Neither any abnormal effects nor clinical problems caused by the continuous ingestion of D-psicose were found.

  6. Microdiscectomy for the treatment of lumbar disc herniation: an evaluation of reoperations and long-term outcomes.

    PubMed

    Aichmair, Alexander; Du, Jerry Y; Shue, Jennifer; Evangelisti, Gisberto; Sama, Andrew A; Hughes, Alexander P; Lebl, Darren R; Burket, Jayme C; Cammisa, Frank P; Girardi, Federico P

    2014-10-01

    Design Retrospective case series. Objective The objective of this study was to assess the reoperation rate after microdiscectomy for the treatment of lumbar disc herniation (LDH) in patients with ≥ 5-year follow-up and identify demographic, perioperative, and outcome-related differences between patients with and without a reoperation. Methods The medical records, operative reports, and office notes of patients who had undergone microdiscectomy at a single institution between March 1994 and December 2007 were reviewed and long-term follow-up was assessed via a telephone questionnaire. Results Forty patients (M:24, F:16) with an average age at surgery of 39.9 ± 12.5 years (range: 18-80) underwent microdiscectomy at the levels L5-S1 (n = 28, 70%), L4-L5 (n = 9, 22.5%), L3-L4 (n = 2, 5.0%), and L1-L2 (n = 1, 2.5%). After an average of 40.4 ± 40.1 months (range: 1-128), 25% of patients (10/40) required further spine surgery related to the initial microdiscectomy. At an average postoperative follow-up of 11.1 ± 4.0 years (range: 5-19), additional symptoms apart from back and leg pain were reported more frequently by patients who underwent a reoperation (p = 0.005). Patient satisfaction was significantly higher in patients who did not undergo a reoperation (p = 0.041). For the Oswestry disability index, pain intensity (p = 0.036), and pain-related sleep disturbances (p = 0.006) were reported to be more severe in the reoperation group. Conclusions Microdiscectomy for the treatment of LDH results in a favorable long-term outcome in the majority of cases. The reoperation rate was higher in our series than reported in previous investigations with shorter follow-up. Although there were no statistically significant pre-/perioperative differences between patients with and without reoperation, our findings suggest a difference in self-reported long-term outcome measures. PMID:25278881

  7. Evaluation of the long-term variability of seawater salinity and temperature in response to natural and anthropogenic stressors in the Arabian Gulf.

    PubMed

    Elhakeem, Abubaker; Elshorbagy, Walid

    2013-11-15

    Evaluating the long-term variability of the seawater salinity and temperature due to climate change is a limiting economical and operational factor in planning the design of new and expansion of existing desalination plants. This need is amplified in the Arabian Gulf due to the natural arid climate and anthropological stresses related to energy exploration and ongoing major developments. The lack of data in this region further adds additional dimension to the problem. The present work represents a systematic innovative approach to evaluate the anticipated long-term changes in the seawater salinity and temperature under the stresses of projected climate change and massive industrial effluents using statistical correlation and hydrodynamic simulation. The proposed approach employs the direct relation between the net freshwater losses (evaporation) entrenched with the investigated stressors and the mean sea salinity and sea temperature variation of an inverse estuary to formulate the statistical correlation and the hydrodynamic simulation conditions.

  8. Long-term evaluation of the fate of sulfur mustard on dry and humid soils, asphalt, and concrete.

    PubMed

    Mizrahi, Dana M; Goldvaser, Michael; Columbus, Ishay

    2011-04-15

    The long-term fate of the blister agent sulfur mustard (HD, bis(2-chloroethyl)sulfide) was determined in a variety of commercial and natural matrices. HD was found to be extremely stable in dry matrices for over a year. The addition of 5% water to the matrices induced slow degradation of HD, which lasted several months. The major degradation product in sands and asphalt was found to be a sulfonium salt, S[CH(2)CH(2)S(+)(CH(2)CH(2)OH)(2)](2) (H-2TG). Red loam soil, which has not been examined before, exhibited strong interaction with HD, both in dry form and in the presence of water. Humid red loam soil gave rise to unique oxidative degradation products. On humid concrete HD degraded to a complex mixture of products, including vinyls. This may be attributed to the basic sites incorporated in concrete.

  9. Long-term evaluation of the fate of sulfur mustard on dry and humid soils, asphalt, and concrete.

    PubMed

    Mizrahi, Dana M; Goldvaser, Michael; Columbus, Ishay

    2011-04-15

    The long-term fate of the blister agent sulfur mustard (HD, bis(2-chloroethyl)sulfide) was determined in a variety of commercial and natural matrices. HD was found to be extremely stable in dry matrices for over a year. The addition of 5% water to the matrices induced slow degradation of HD, which lasted several months. The major degradation product in sands and asphalt was found to be a sulfonium salt, S[CH(2)CH(2)S(+)(CH(2)CH(2)OH)(2)](2) (H-2TG). Red loam soil, which has not been examined before, exhibited strong interaction with HD, both in dry form and in the presence of water. Humid red loam soil gave rise to unique oxidative degradation products. On humid concrete HD degraded to a complex mixture of products, including vinyls. This may be attributed to the basic sites incorporated in concrete. PMID:21438603

  10. Carbon sequestration strategies for crop- and grasslands evaluated in long-term field experiments in Northern Europe

    NASA Astrophysics Data System (ADS)

    Kätterer, Thomas; Bolinder, Martin; Börjesson, Gunnar; Kirchmann, Holger

    2013-04-01

    Improved management of grass- and croplands is a win-win strategy resulting in both increased soil fertility and carbon sequestration. We quantified the effect of N fertilization, organic amendments and ley-arable rotations versus continuous annual cropping systems on soil carbon stocks by analyzing data from long-term field experiments in Nordic countries. Increasing net primary production was found to be the main driver for higher soil carbon storage. Mineral N fertilization increased soil carbon stocks by about 1-2 kg C ha-1 for each kg of N applied to cropland. Ley-arable rotations, being a combination of annual and perennial crops, are expected to have C stocks intermediate between continuous grass- and croplands. A summary of data from 15 long-term sites showed that on average 0.5 Mg ha-1 yr-1 (range 0.3 to 1.1; median 0.4 Mg ha-1 yr-1) more carbon was retained in soils in ley-arable compared to exclusively annual systems, depending on species composition, management, soil depth and the duration of the studies. We also quantified the effect of organic amendments on soil carbon stocks. Retention factors calculated for straw, manure, sawdust, peat, sewage sludge and composted household waste varied widely from about 15% for above-ground crop residues to about 90% for composted household waste. We also emphasize that increased soil carbon stocks not always lead to carbon sequestration of atmospheric CO2 and discuss misunderstandings related to mitigation options earlier proposed for carbon sequestration such as organic farming, manure application, residue handling or application of biochar. Finally, the consequences of different land use and management are discussed, taking into account two critical boundaries - the limited area of agricultural land on Earth and requirements to produce sufficient food, fibres and energy for a growing population.

  11. Evaluating long-term effects of heroin-assisted treatment: the results of a 6-year follow-up.

    PubMed

    Güttinger, Franziska; Gschwend, Patrick; Schulte, Bernd; Rehm, Jürgen; Uchtenhagen, Ambros

    2003-04-01

    Since January 1994, heroin-assisted treatment for opiate addicts has been available in Switzerland. This is the first report of the long-term effects of this form of treatment. The report examines subjects who entered a study involving medical prescription of opiates (Projekt zur ärztlichen Verschreibung von Betäubungsmitteln; PROVE) in Switzerland between January 1994 and March 1995 (n = 366). Opiates were dispensed in eight treatment centres. A follow-up was conducted 6 years after treatment entry. Two groups were assessed: clients who have continuously been on heroin-assisted treatment since entry into the PROVE study or who re-entered this treatment, and ex-clients who had discontinued heroin-assisted treatment at the time of follow-up. Two kinds of comparisons were conducted. Firstly, conditions at treatment entry were compared to 6-year follow-up outcomes, and secondly, outcomes were compared between clients still on heroin-assisted treatment and those who had been discharged. It was found that 46% of the clients still alive were on heroin-assisted treatment at the time of follow-up. A comparison of the present living conditions showed very little difference between those in treatment and those who had terminated treatment. Compared to the situation at entry, the results of the follow-up showed a significant decrease in the use of illegal substances, illegal income and most other variables concerning social conditions, but they also showed an increase in unemployment and reliance on social benefits. Heroin-assisted treatment is thus efficacious in the long-term course of treatment and is still effective after termination of treatment with respect to living conditions and use of illicit substances.

  12. Evaluation of the Long-Term Anti-Human Papillomavirus 6 (HPV6), 11, 16, and 18 Immune Responses Generated by the Quadrivalent HPV Vaccine

    PubMed Central

    Saah, Alfred; Munk, Christian; Tryggvadottir, Laufey; Enerly, Espen; Hortlund, Maria; Sigurdardottir, Lara G.; Vuocolo, Scott; Kjaer, Susanne K.; Dillner, Joakim

    2015-01-01

    This quadrivalent human papillomavirus (qHPV) (HPV6, -11, -16, and -18) vaccine long-term follow-up (LTFU) study is an ongoing extension of a pivotal clinical study (FUTURE II) taking place in the Nordic region. The LTFU study was designed to evaluate the effectiveness, immunogenicity, and safety of the qHPV vaccine (Gardasil) for at least 10 years following completion of the base study. The current report presents immunogenicity data from testing samples of the year 5 LTFU visit (approximately 9 years after vaccination). FUTURE II vaccination arm subjects, who consented to being followed in the LTFU, donated serum at regular intervals and in 2012. Anti-HPV6, -11, -16, and -18 antibodies were detected by the competitive Luminex immunoassay (cLIA), and in addition, serum samples from 2012 were analyzed by the total IgG Luminex immunoassay (LIA) (n = 1,598). cLIA geometric mean titers (GMTs) remained between 70% and 93% of their month 48 value depending on HPV type. For all HPV types, the lower bound of the 95% confidence interval (CI) for the year 9 GMTs remained above the serostatus cutoff value. The proportion of subjects who remained seropositive based on the IgG LIA was higher than the proportion based on cLIA, especially for anti-HPV18. As expected, the anti-HPV serum IgG and cLIA responses were strongly correlated for all HPV types. Anti-HPV GMTs and the proportion of vaccinated individuals who are seropositive remain high for up to 9 years of follow-up after vaccination. PMID:26084514

  13. Long-Term Efficacy, Tolerability, and Renal Safety of Atazanavir/Ritonavir-based Antiretroviral Therapy in a Cohort of Treatment-Naïve Patients with HIV-1 Infection: the REMAIN Study

    PubMed Central

    Teófilo, Eugénio; Rocha-Pereira, Nuno; Kuhlmann, Birger; Antela, Antonio; Knechten, Heribert; Santos, Jesús; Jiménez-Expósito, Maria Jesús

    2016-01-01

    Background: Boosted protease inhibitors (PIs), including ritonavir-boosted atazanavir (ATV/r), are a recommended option for the initial treatment of HIV-1 infection based upon clinical trial data; however, long-term real-life clinical data are limited. Objective: We evaluated the long-term use of ATV/r as a component of antiretroviral combination therapy in the real-life setting in the REMAIN study. Methods: This was an observational cohort study conducted at sites across Germany, Portugal, and Spain. Retrospective historical and prospective longitudinal follow-up data were extracted every six months from medical records of HIV-infected treatment-naïve patients aged ≥ 18 years initiating a first-line ATV/r-containing regimen. Results: Eligible patients (n = 517) were followed up for a median of 3.4 years. The proportion remaining on ATV/r at 5 years was 51.5% with an estimated Kaplan-Meier median time to treatment discontinuation of 4.9 years. Principal reasons for discontinuation were adverse events (15.9%; 8.9% due to hyperbilirubinemia) and virologic failure (6.8%). The Kaplan-Meier probability of not having virologic failure (HIV-1 RNA < 50 copies/mL) was 0.79 (95% CI: 0.75, 0.83) at five years. No treatment-emergent major PI resistance occurred. ATV/r was generally well tolerated during long-term treatment with no significant changes in estimated glomerular filtration rate over five years. Conclusions: In a real-life clinical setting over five years, treatment-naïve patients with HIV-1 infection initiating an ATV/r-based regimen showed sustained virologic suppression, an overall treatment persistence rate of 51.5%, an absence of treatment-emergent major PI resistance mutations at virologic failure, a long-term safety profile consistent with that observed in clinical trials, and no significant decline in renal function. PMID:26899539

  14. Evaluation of Long-term Agroecosystem Management on Changes in Subsurface vs. Surface Soil Carbon Fractions and Dynamics

    NASA Astrophysics Data System (ADS)

    Wolfe, D.; Beem-Miller, J.; Kong, A.; Comstock, J.; Sherpa, S.; Wine, E.; Mallorino, A.

    2013-12-01

    Most studies of terrestrial soil organic carbon (SOC) have focused on the upper soil profile (e.g., 0-30 cm), so our knowledge of C dynamics in deeper layers is incomplete. Here, we examine the depth-dependent mechanisms and constraints by which management of the upper soil profile for optimum crop yield in agroecosystems can influence SOC fractions and change in both the surface and subsurface. Our study includes continuous corn systems under long-term conventional tillage (CT) vs no-tillage (NT) at Willsboro, New York (NY) (Kingsbury silty loam soil; 19 y) and Chazy, NY (Raynham silt loam; 38 y), and long-term crop rotation experiments under CT at Algona, Iowa (IA) (Clarion loam; 11 y) and Kanawha, IA (Canisteo clay loam; 57 y). Rotations in IA compared continuous corn to corn rotations with soybean, alfalfa, and/or oats. Cores were collected in 2011 and 2012 at 0-10, 10-20, 20-30, 30-50 and 50-75 cm, and analyzed for bulk density, soil texture, percent organic matter, total C and nitrogen (N), soil inorganic C, and active C (permanganate oxidizable C, POXC). Recent studies have documented that POXC is closely correlated with heavy, small-sized particulate organic C, reflecting a relatively processed and stable pool of labile C that is well-suited to assess land management effects on C dynamics. Overall, cumulative SOC stocks (0-75 cm) in the IA and NY soils ranged from 109.9-168.8 MgC ha-1, and 37.8-104.1 MgC ha-1, respectively. The proportion of total SOC stocks that occurred in the subsurface (30-75 cm) ranged from 39-44% in the IA soils, compared to 16-26% in NY. Across all sites and management we found no examples of statistically significant SOC change below 30 cm, although this may be in part an artifact of greater variability and smaller absolute values of C concentration at depth. SOC data were correlated with POXC measurements, although depth- and site-specific discrepancies in these two measures were observed. For example, POXC was relatively

  15. Evaluation of pre-breeding reproductive tract scoring as a predictor of long term reproductive performance in beef heifers.

    PubMed

    Holm, D E; Nielen, M; Jorritsma, R; Irons, P C; Thompson, P N

    2015-01-01

    In a 7-year longitudinal study 292 Bovelder beef cows in a restricted breeding system in South Africa were observed from 1 to 2 days before their first breeding season, when reproductive tract scoring (RTS, scored from 1 to 5) was performed, until weaning their 5th calves. The objective was to determine whether pre-breeding RTS in heifers is a valid tool to predict long-term reproductive performance. Outcomes measured were failure to show oestrus during the first 24 days of the first 50-day AI season (24-day anoestrus), failure to become pregnant during each yearly artificial insemination (AI) season (reproductive failure), number of days from the start of each AI season to calving, and number of years to reproductive failure. The effect of RTS on each outcome was adjusted for year of birth, pre-breeding age, BW and body condition score (BCS), and for 24-day anoestrus, bull, gestation length, previous days to calving and previous cow efficiency index, the latter two in the case of the 2nd to the 5th calving season. During their first breeding season, heifers with RTS 1 and 2 combined were more likely to be in anoestrus for the first 24 days (OR=3.0, 95% CI 1.5, 6.4, P=0.003), and were also more likely to fail to become pregnant even after adjusting for 24-day anoestrus (OR=2.1, 95% CI 1.1, 3.9, P=0.025), compared to those with RTS 4 and 5 combined. Animals with RTS 1 and 2 combined were at increased risk of early reproductive failure compared to those with RTS 4 and 5 combined (HR=1.4, 95% CI 1.0, 1.9, P=0.045) although RTS was not associated with calving rate or days to calving after the second calving season. Low RTS at a threshold of 1 had consistent specificity of ≥94% for both 24-day anoestrus and pregnancy failure, however its predictive value was lower in the age cohort with a higher prevalence of anoestrus. We conclude that RTS is a valid management tool for culling decisions intended to improve long-term reproductive success in a seasonal breeding system

  16. Determination of epileptic focus side in mesial temporal lobe epilepsy using long-term noninvasive fNIRS/EEG monitoring for presurgical evaluation

    PubMed Central

    Rizki, Edmi Edison; Uga, Minako; Dan, Ippeita; Dan, Haruka; Tsuzuki, Daisuke; Yokota, Hidenori; Oguro, Keiji; Watanabe, Eiju

    2015-01-01

    Abstract. Noninvasive localization of an epileptogenic zone is a fundamental step for presurgical evaluation of epileptic patients. Here, we applied long-term simultaneous functional near-infrared spectroscopy (fNIRS)/electroencephalogram (EEG) monitoring for focus diagnosis in patients with mesial temporal lobe epilepsy (MTLE). Six MTLE patients underwent long-term (8–16 h per day for 4 days) fNIRS/EEG monitoring for the occurrence of spontaneous seizures. Four spontaneous seizures were successfully recorded out of the six patients. To determine oxy-Hb amplitude, the period-average values of oxy-Hb across 20 s from the EEG- or clinically defined epileptic onset were calculated for both hemispheres from the simultaneously recorded fNIRS data. The average oxy-Hb values for the temporal lobe at the earlier EEG- or clinically defined epileptic onsets were greater for the epileptic side than for the contralateral side after EEG activity suppression, spike train, and clinical seizure in all four cases. The true laterality was determined based on the relief of seizures by selective amygdalo-hippocampectomy. Thus, oxy-Hb amplitude could be a reliable measure for determining the epileptic focus side. Long-term simultaneous fNIRS/EEG measurement serves as an effective tool for recording spontaneous seizures. Cerebral hemodynamic measurement by fNIRS would serve as a valuable supplementary noninvasive measurement method for presurgical evaluation of MTLE. PMID:26158007

  17. Long-Term Safety and Efficacy of Atazanavir-Based Therapy in HIV-Infected Infants, Children and Adolescents: The Pediatric AIDS Clinical Trials Group Protocol 1020A

    PubMed Central

    Rutstein, Richard M.; Samson, Pearl; Fenton, Terry; Fletcher, Courtney V.; Kiser, Jennifer J.; Mofenson, Lynne M.; Smith, Elizabeth; Graham, Bobbie; Mathew, Marina; Aldrovani, Grace

    2014-01-01

    Background Atazanavir is an attractive option for the treatment of Pediatric HIV infection, based on once daily dosing and the availability of a formulation appropriate for younger children. PACTG 1020A was a phase I/II open label study of atazanavir (ATV) (with/without ritonavir [RTV] boosting)-based treatment of HIV-infected children; here we report the long-term safety and virologic and immunologic responses. Methods Antiretroviral-naïve and experienced children, ages 91 days to 21 years, with baseline plasma HIV RNA >5000 copies/ml (cpm) were enrolled at sites in the United States and South Africa. Results Of 195 children enrolled 142 (73%) subjects received ATV-based regimens at the final protocol recommended dose. 58% were treatment naive. Overall, at week 24, 84/139 subjects (60.4%) and at week 48, 83/142 (58.5%), had HIV RNA ≤400 cpm. At week 48, 69.5% of naïve and 43.3% of experienced subjects had HIV RNA ≤400 cpm; median CD4 increase was 196.5 cells/mm3. The primary adverse event was increased serum bilirubin; 9% of subjects had levels > 5.1 times upper limit of normal and 1.4% noted jaundice. 3% of subjects experienced Grade 2 or 3 prolongation in PR or QTc intervals. At week 48, there was a 15% increase in total cholesterol (TC), with TC >199 mg/dL increasing from 1% at baseline to 5.7%. Conclusions Use of once-daily ATV, with/without RTV, was safe and well tolerated in children, with acceptable levels of viral suppression and CD4 count increase. The primary adverse event, as expected, was an increase in bilirubin levels. PMID:25232777

  18. An open-label, long-term study examining the safety and tolerability of pregabalin in Japanese patients with central neuropathic pain

    PubMed Central

    Onouchi, Kenji; Koga, Hiroaki; Yokoyama, Kazumasa; Yoshiyama, Tamotsu

    2014-01-01

    Purpose Studies of pregabalin for the treatment of central neuropathic pain have been limited to double-blind trials of 4–17 weeks in duration. The purpose of this study was to assess the long-term safety and tolerability of pregabalin in Japanese patients with central neuropathic pain. The efficacy of pregabalin was also assessed as a secondary measure. Patients and methods This was a 53-week, multicenter, open-label trial of pregabalin (150–600 mg/day) in Japanese patients with central neuropathic pain due to spinal cord injury, multiple sclerosis, or cerebral stroke. Results A total of 103 patients received pregabalin (post-stroke =60; spinal cord injury =38; and multiple sclerosis =5). A majority of patients (87.4%) experienced one or more treatment-related adverse events, most commonly somnolence, weight gain, dizziness, or peripheral edema. The adverse event profile was similar to that seen in other indications of pregabalin. Most treatment-related adverse events were mild (89.1%) or moderate (9.2%) in intensity. Pregabalin treatment improved total score, sensory pain, affective pain, visual analog scale (VAS), and present pain intensity scores on the Short-Form McGill Pain Questionnaire (SF-MPQ) and ten-item modified Brief Pain Inventory (mBPI-10) total score at endpoint compared with baseline. Improvements in SF-MPQ VAS and mBPI-10 total scores were evident in all patient subpopulations. Mean changes from baseline in SF-MPQ VAS and mBPI-10 scores at endpoint were −20.1 and −1.4, respectively. Conclusion These findings demonstrate that pregabalin is generally well tolerated and provides sustained efficacy over a 53-week treatment period in patients with chronic central neuropathic pain. PMID:25114584

  19. Post Hoc Evaluation of Long-Term Goals for Energy Savings in the Buildings Sector: Lessons from Hindsight

    SciTech Connect

    Anderson, Dave M. ); Hostick, Donna J. )

    2003-04-28

    This report is one of two that re-examines the forecasted impact of individual programs currently within the Buildings Technology Program (BT) and the Weatherization and Intergovernmental Program (WIP) that appeared in the FY2000 Presidential Budget request. This report outlines the effects of re-estimating the FY 2000 budget request based on overlaying project data from subsequent years essentially revised out-year forecasts of project benefits. It shows that year-to-year long-term projections of primary energy savings can vary widely as models improve and programs change. Note that the FY2000 budget request was originally analyzed under the former Office of Building Technology, State and Community Programs (BTS), where BT and WIP were previously combined. Throughout the document, reference will be made to the predecessor of the BT and WIP programs, BTS, as FY2000 reflected that organization. A companion report develops potential methods for allowing inherent risk to be captured in the project benefits analysis. The point estimates in this paper are not influenced by uncertainty or risk. That report develops potential methods for allowing inherent risk to affect the benefits analysis via Monte Carlo simulation.

  20. Isotropic Versus Bipolar Functionalized Biomimetic Artificial Basement Membranes and Their Evaluation in Long-Term Human Cell Co-Culture.

    PubMed

    Rossi, Angela; Wistlich, Laura; Heffels, Karl-Heinz; Walles, Heike; Groll, Jürgen

    2016-08-01

    In addition to dividing tissues into compartments, basement membranes are crucial as cell substrates and to regulate cellular behavior. The development of artificial basement membranes is indispensable for the ultimate formation of functional engineered tissues; however, pose a challenge due to their complex structure. Herein, biodegradable electrospun polyester meshes are presented, exhibiting isotropic or bipolar bioactivation as a biomimetic and biofunctional model of the natural basement membrane. In a one-step preparation process, reactive star-shaped prepolymer additives, which generate a hydrophilic fiber surface, are electrospun with cell-adhesion-mediating peptides, derived from major components of the basement membrane. Human skin cells adhere to the functionalized meshes, and long-term co-culture experiments confirm that the artificial basement membranes recapitulate and preserve tissue specific functions. Several layers of immortalized human keratinocytes grow on the membranes, differentiating toward the surface and expressing typical epithelial markers. Fibroblasts migrate into the reticular lamina mimicking part of the mesh. Both cells types begin to produce extracellular matrix proteins and to remodel the initial membrane. It is shown at the example of skin that the artificial basement membrane design provokes biomimetic responses of different cell types and can thus be used as basis for the future development of basement membrane containing tissues. PMID:27283510

  1. Evaluating the long-term performance of low-cost adsorbents using small-scale adsorption column experiments.

    PubMed

    Callery, O; Healy, M G; Rognard, F; Barthelemy, L; Brennan, R B

    2016-09-15

    This study investigated a novel method of predicting the long-term phosphorus removal performance of large-scale adsorption filters, using data derived from short-term, small-scale column experiments. The filter media investigated were low-cost adsorbents such as aluminum sulfate drinking water treatment residual, ferric sulfate drinking water treatment residual, and fine and coarse crushed concretes. Small-bore adsorption columns were loaded with synthetic wastewater, and treated column effluent volume was plotted against the mass of phosphorus adsorbed per unit mass of filter media. It was observed that the curve described by the data strongly resembled that of a standard adsorption isotherm created from batch adsorption data. Consequently, it was hypothesized that an equation following the form of the Freundlich isotherm would describe the relationship between filter loading and media saturation. Moreover, the relationship between filter loading and effluent concentration could also be derived from this equation. The proposed model was demonstrated to accurately predict the performance of large-scale adsorption filters over a period of up to three months with a very high degree of accuracy. Furthermore, the coefficients necessary to produce said model could be determined from just 24 h of small-scale experimental data. PMID:27295617

  2. Isotropic Versus Bipolar Functionalized Biomimetic Artificial Basement Membranes and Their Evaluation in Long-Term Human Cell Co-Culture.

    PubMed

    Rossi, Angela; Wistlich, Laura; Heffels, Karl-Heinz; Walles, Heike; Groll, Jürgen

    2016-08-01

    In addition to dividing tissues into compartments, basement membranes are crucial as cell substrates and to regulate cellular behavior. The development of artificial basement membranes is indispensable for the ultimate formation of functional engineered tissues; however, pose a challenge due to their complex structure. Herein, biodegradable electrospun polyester meshes are presented, exhibiting isotropic or bipolar bioactivation as a biomimetic and biofunctional model of the natural basement membrane. In a one-step preparation process, reactive star-shaped prepolymer additives, which generate a hydrophilic fiber surface, are electrospun with cell-adhesion-mediating peptides, derived from major components of the basement membrane. Human skin cells adhere to the functionalized meshes, and long-term co-culture experiments confirm that the artificial basement membranes recapitulate and preserve tissue specific functions. Several layers of immortalized human keratinocytes grow on the membranes, differentiating toward the surface and expressing typical epithelial markers. Fibroblasts migrate into the reticular lamina mimicking part of the mesh. Both cells types begin to produce extracellular matrix proteins and to remodel the initial membrane. It is shown at the example of skin that the artificial basement membrane design provokes biomimetic responses of different cell types and can thus be used as basis for the future development of basement membrane containing tissues.

  3. Evaluating a theory of stress and adjustment when predicting long-term psychosocial outcome after brain injury.

    PubMed

    Rutterford, Neil A; Wood, Rodger L

    2006-05-01

    Kendall and Terry (1996) include many psychosocial predictors in their theoretical model that explains individual differences in psychosocial adjustment (Lazarus & Folkman, 1984). The model depicts appraisal and coping variables as mediating relationships between situation factors, environmental and personal resources, and multidimensional outcome. The aim of this study was to explore these theoretical relationships at very late stages of recovery from traumatic brain injury. A total of 131 participants who were more than 10 years post-injury (mean = 15.31 years) completed several psychosocial measures relating to outcome dimensions comprising employment, community integration, life satisfaction, quality of life (QoL), and emotion. There was no evidence that appraisal and coping variables mediated relationships between psychosocial and any of the outcome variables. However, when appraisal and coping variables were combined with psychosocial variables as direct predictors of outcome, every outcome except employment status was reliably predicted, accounting for between 31 and 46% of the variance. Personality significantly influenced all predicted outcomes. Self-efficacy contributed to the prediction of all outcomes except QoL. Data did not support for the theory of stress and adjustment as a framework for explaining the nature of predictive relationships between psychosocial variables and very long-term, multidimensional outcome after brain injury.

  4. Evaluation of long-term community recovery from Hurricane Andrew: sources of assistance received by population sub-groups.

    PubMed

    McDonnell, S; Troiano, R P; Barker, N; Noji, E; Hlady, W G; Hopkins, R

    1995-12-01

    Two three-stage cluster surveys were conducted in South Dade County, Florida, 14 months apart, to assess recovery following Hurricane Andrew. Response rates were 75 per cent and 84 per cent. Sources of assistance used in recovery from Hurricane Andrew differed according to race, per capita income, ethnicity, and education. Reports of improved living situation post-hurricane were not associated with receiving relief assistance, but reports of a worse situation were associated with loss of income, being exploited, or job loss. The number of households reporting problems with crime and community violence doubled between the two surveys. Disaster relief efforts had less impact on subjective long-term recovery than did job or income loss or housing repair difficulties. Existing sources of assistance were used more often than specific post-hurricane relief resources. The demographic make-up of a community may determine which are the most effective means to inform them after a disaster and what sources of assistance may be useful.

  5. Long-term safety, efficacy and side-effects of continuous subcutaneous insulin infusion treatment for type 1 (insulin-dependent) diabetes mellitus: a one centre experience.

    PubMed

    Chantelau, E; Spraul, M; Mühlhauser, I; Gause, R; Berger, M

    1989-07-01

    A follow-up study of 116 Type 1 (insulin-dependent) diabetic patients on long-term continuous subcutaneous insulin infusion was conducted after 4.5 +/- 0.2 years. The average HbA1c-value of these patients decreased by 1% to 6.7 +/- 0.1% during this observation period. Typical side effects of continuous subcutaneous insulin infusion such as skin inflammation at the catheter insertion site occurred with similar frequency as has been reported previously by other authors. Diabetic ketoacidosis (0.14 per patient year) and disabling hypoglycaemia (0.1 per patient year, including 0.05 hypoglycaemic coma per patient-year) occurred at substantially lower rates than in other comparable studies with Type 1 diabetic patients at a similar degree of metabolic control. Subgroup evaluation suggested that a normal (less than 5.6%) HbA1c-value at follow-up was associated with increased incidence of disabling hypoglycaemia, whereas poor metabolic control (HbA1c greater than 7.5%) was associated with increased rates of skin complications and hospital treatment for ketoacidosis. Thus, under the policies of this diabetes centre, continuous subcutaneous insulin infusion has proved to be beneficial to a large proportion of experienced adult Type 1 diabetic patients, who voluntarily had opted for, and continued with, this particular mode of insulin treatment.

  6. Long-term clinical evaluation of fracture and pulp injury following glass-ionomer cement or composite resin applied as a base filling in teeth restored with amalgam.

    PubMed

    De C Luz, M A; Ciaramicoli-Rodrigues, M T; Garone Netto, N; De Lima, A C

    2001-07-01

    The aim of this research was to analyse the long-term clinical behaviour of two dental materials applied as filling under silver amalgam restorations: glass-ionomer cement (GIC) and composite resin with adhesive system (CR). In this study, 117 posterior teeth (29 premolars and 88 molars) were selected with carious lesions which resulted in great loss of dentin and cusps with unsupported enamel. After caries removal, cavities were prepared and totally filled with GIC or with CR. In a following visit, new cavities were prepared, leaving the employed filling material as a base and support for the enamel, which were then restored with silver amalgam. Restorations were evaluated periodically after 6 months and up to 5 years. Both fracture and pulpal involvement rates were low. Although differences could be observed in the behaviour of the materials, statistical survival estimation showed that the performances of GIC and CR as filling material were similar. There was a significant association both between kind of tooth (molar or premolar) and long-term survival of the restorations; and between degree of unsupported enamel and the same long-term survival. Our results confirmed that the technique in which GIC or CR are used as filling under silver amalgam restorations is clinically acceptable. PMID:11422695

  7. Evaluating the long-term hydrology of an evapotranspiration-capillary barrier with a 1000 year design life

    NASA Astrophysics Data System (ADS)

    Zhang, Z. Fred

    2016-06-01

    A surface barrier is a commonly used technology for isolation of subsurface contaminants. Surface barriers for isolating radioactive waste are expected to perform for centuries to millennia, yet there are very few data for field-scale surface barriers for periods approaching a decade or longer. The Prototype Hanford Barrier (PHB) with a design life of 1000 years was constructed over an existing radioactive waste site in 1994 to demonstrate its long-term performance. The primary element of the PHB is an evapotranspiration-capillary (ETC) barrier in which precipitation water is stored in a fine-textured soil layer and later released to the atmosphere via evapotranspiration. To address the barrier performance under extreme conditions, this study included an enhanced precipitation stress test from 1995 to 1997 to determine barrier response to extreme precipitation events. During this period a 1000 year 24 h return rainstorm was simulated in March every year. The loss of vegetation on barrier hydrology was tested with a controlled fire test in 2008. The 19 year monitoring record shows that the store-and-release mechanism worked as well as or better than the design criterion. Average drainage from the ETC barrier amounted to an average of 0.005 mm yr-1, which is well below the design criterion of 0.5 mm yr-1. After a simulated wildfire, the naturally reestablished vegetation and increased evaporation combined to release the stored water and summer precipitation to the atmosphere such that drainage did not occur in the 5 years subsequent to the fire.

  8. Evaluation of the use of oseltamivir prophylaxis in the control of influenza outbreaks in long-term care facilities in Alberta, Canada: a retrospective provincial database analysis

    PubMed Central

    Ye, Ming; Jacobs, Angela; Khan, Muhammad Naeem; Jaipaul, Joy; Oda, Joanna; Johnson, Marcia; Doroshenko, Alexander

    2016-01-01

    Objectives To evaluate the impact of oseltamivir prophylaxis in the management and control of influenza outbreaks in long-term care facilities in Alberta, Canada. Setting and participants Long-term care facilities where 127 influenza outbreaks were reported to public health authorities in Alberta, Canada, during two influenza seasons from 2013 to 2015. Design and outcome measures Using routinely collected surveillance and administrative data, we examined the association between decision-making time for oseltamivir recommendation as prophylaxis strategy for influenza outbreaks in long-term care facilities (explanatory variable) and the duration of an influenza outbreak, the postprophylaxis risk of influenza-like illness and hospitalisation among residents of long-term care facilities in Alberta (outcome variables) using multivariable linear and Poisson regression models. Results Oseltamivir prophylaxis decision-making time was positively associated with the postintervention duration of an outbreak, with a 1-day delay in making decision on oseltamivir prophylaxis associated with 2.22 (95% CI 1.37 to 3.06) more days of the duration of an outbreak after controlling for potential confounding effect of the number of residents at risk at intervention, outbreak progression time, prevalence of influenza-like illness during outbreak progression, facility location, presence of mixed strain and based on optimal timing of oseltamivir prophylaxis. Although not statistically significant, a 1-day delay in making decision on oseltamivir prophylaxis was associated with a 5% (95% CI −1% to 11%) increase in the postintervention risk of influenza-like illness, and a 6% (95% CI −8% to 22%) increase in the postintervention risk of hospitalisation after controlling for the same potential confounders. Conclusions Our study demonstrated benefits of using oseltamivir prophylaxis to shorten the duration of influenza outbreaks; however, there were no significant differences in the

  9. Evaluation of long-term side effects after shock-wave lithotripsy for renal calculi using a third generation electromagnetic lithotripter.

    PubMed

    Pirola, Giacomo Maria; Micali, Salvatore; Sighinolfi, Maria Chiara; Martorana, Eugenio; Territo, Angelo; Puliatti, Stefano; Bianchi, Giampaolo

    2016-10-01

    To assess the incidence of long-term side effects after shock-wave lithotripsy treatment performed with an electromagnetic Dornier Lithotripter S device. A specific follow-up was undertaken on a cohort of 100 selected patients that underwent SWL for a single renal stone in our center from 2002 to 2004. Previous and current data were compared using the Student t test. Factors associated with the incidence of hypertension and diabetes mellitus were determined. Ten years after treatment, mean serum creatinine level and glomerular filtration rate remained similar to previous values (serum creatinine level: 0.96 ± 0.22 vs. 0.92 ± 0.19 mg/dL; glomerular filtration rate: 92.8 ± 17.8 vs. 88.1 ± 21.7 mL/min). There were marked increases in blood cholesterol, blood pressure, and blood glucose levels, while smoking decreased. Age, glomerular filtration rate, body mass index, blood glucose and blood pressure at the time of treatment were significantly associated with the presence of hypertension and diabetes mellitus at follow-up; blood cholesterol was associated with diabetes mellitus development. After 10 years, overall renal function appeared to have been unaffected by shock-wave lithotripsy treatment. The increased rate of hypertension and diabetes mellitus were consistent with the incidence in the global population. This is the first report on the long-term safety of a third generation electromagnetic lithotripter, and indicates that there are no long-term sequelae.

  10. Evaluation of long-term side effects after shock-wave lithotripsy for renal calculi using a third generation electromagnetic lithotripter.

    PubMed

    Pirola, Giacomo Maria; Micali, Salvatore; Sighinolfi, Maria Chiara; Martorana, Eugenio; Territo, Angelo; Puliatti, Stefano; Bianchi, Giampaolo

    2016-10-01

    To assess the incidence of long-term side effects after shock-wave lithotripsy treatment performed with an electromagnetic Dornier Lithotripter S device. A specific follow-up was undertaken on a cohort of 100 selected patients that underwent SWL for a single renal stone in our center from 2002 to 2004. Previous and current data were compared using the Student t test. Factors associated with the incidence of hypertension and diabetes mellitus were determined. Ten years after treatment, mean serum creatinine level and glomerular filtration rate remained similar to previous values (serum creatinine level: 0.96 ± 0.22 vs. 0.92 ± 0.19 mg/dL; glomerular filtration rate: 92.8 ± 17.8 vs. 88.1 ± 21.7 mL/min). There were marked increases in blood cholesterol, blood pressure, and blood glucose levels, while smoking decreased. Age, glomerular filtration rate, body mass index, blood glucose and blood pressure at the time of treatment were significantly associated with the presence of hypertension and diabetes mellitus at follow-up; blood cholesterol was associated with diabetes mellitus development. After 10 years, overall renal function appeared to have been unaffected by shock-wave lithotripsy treatment. The increased rate of hypertension and diabetes mellitus were consistent with the incidence in the global population. This is the first report on the long-term safety of a third generation electromagnetic lithotripter, and indicates that there are no long-term sequelae. PMID:26968731

  11. Long-Term Efficacy, Safety, and Pharmacokinetics of Drisapersen in Duchenne Muscular Dystrophy: Results from an Open-Label Extension Study

    PubMed Central

    Goemans, Nathalie M.; Tulinius, Már; van den Hauwe, Marleen; Kroksmark, Anna-Karin; Buyse, Gunnar; Wilson, Rosamund J.; van Deutekom, Judith C.; de Kimpe, Sjef J.; Lourbakos, Afrodite; Campion, Giles

    2016-01-01

    Background Drisapersen induces exon 51 skipping during dystrophin pre-mRNA splicing and allows synthesis of partially functional dystrophin in Duchenne muscular dystrophy (DMD) patients with amenable mutations. Methods This 188-week open-label extension of the dose-escalation study assessed the long-term efficacy, safety, and pharmacokinetics of drisapersen (PRO051/GSK2402968), 6 mg/kg subcutaneously, in 12 DMD subjects. Dosing was once weekly for 72 weeks. All subjects had a planned treatment interruption (weeks 73–80), followed by intermittent dosing (weeks 81–188). Results Subjects received a median (range) total dose of 5.93 (5.10 to 6.02) mg/kg drisapersen. After 177 weeks (last efficacy assessment), median (mean [SD]) six-minute walk distance (6MWD) improved by 8 (-24.5 [161]) meters for the 10 subjects able to complete the 6MWD at baseline (mean age [SD]: 9.5 [1.9] years). These statistics include 2 subjects unable to complete the test at later visits and who scored “zero”. When only the 8 ambulant subjects at week 177 were taken into account, a median (mean [SD]) increase of 64 (33 [121]) meters in 6MWD was observed. Of 7 subjects walking ≥330 m at extension baseline, 5 walked farther at week 177. Of 3 subjects walking <330 m, 2 lost ambulation, while 1 declined overall but walked farther at some visits. Over the 188 weeks, the most common adverse events were injection-site reactions, raised urinary α1-microglobulin and proteinuria. Dystrophin expression was detected in all muscle biopsies obtained at week 68 or 72. Conclusion Drisapersen was generally well tolerated over 188 weeks. Possible renal effects, thrombocytopenia and injection-site reactions warrant continued monitoring. Improvements in the 6MWD at 12 weeks were sustained after 3.4 years of dosing for most patients. For a small, uncontrolled study, the outcomes are encouraging, as natural history studies would anticipate a decline of over 100 meters over a 3-year period in a comparable

  12. Rationale for a long-term evaluation of the consequences of potentially life-threatening maternal conditions and maternal "near-miss" incidents using a multidimensional approach.

    PubMed

    Pacagnella, Rodolfo C; Cecatti, Jose G; Camargo, Rodrigo P; Silveira, Carla; Zanardi, Dulce T; Souza, Joao P; Parpinelli, Mary A; Haddad, Samira M

    2010-08-01

    Recent advances in health care mean that women survive severe conditions and events related to pregnancy that would previously have resulted in death. Therefore, a greater number of women will experience significant maternal morbidity with significant consequences. Little is known, however, about these long-term consequences. Some investigators have evaluated the repercussions of severe biological or traumatic events, and have reported that survivors are at an increased risk of death in the five years after the event. In addition, they continue to experience both organic and emotional problems such as clinical, cardiac, respiratory, and neurological complications, as well as anxiety and depression, following discharge from hospital. Following a maternal "near-miss" incident, various life domains may be affected (organic, mental, cognitive, and social function), and these must be evaluated in addition to the related economic issues and quality of life. However, because of the diversity of methods and instruments used to evaluate possible repercussions, comparisons between the few studies available on the subject are difficult. An in-depth debate should be initiated to discuss the methodological aspects of such investigation. We propose a conceptual and methodological discussion on the long-term repercussions of severe maternal morbidity based on the evaluation of the following variables: reproductive health, quality of life, posttraumatic stress syndrome, sexual function, postpartum depression, daily functioning, and the physical, neurological, and psychomotor development of the children born after a complicated pregnancy.

  13. CRUISE- Evaluating Enhanced Crew Autonomy Concepts On-Board the ISS as a Preparation for Future Long Term Crewed Space Missions

    NASA Astrophysics Data System (ADS)

    Matevska, Jasminka; Sievi, Sonja; Plassmeier, Frank; Gries, Florian; Wolff, Mikael; Melody, John

    2014-08-01

    The Crew User Interface System Enhancement (CRUISE) system demonstrates concepts for increased crew autonomy and improved usability in microgravity with respect to the execution of operational procedures in order to prepare for future long term crewed space missions. As a main focus two software components/building blocks were addressed: 1. Flight software user interface elements embedded in traditional operational crew procedures. 2. Voice navigation, as an additional user interaction modality, for an astronaut manual hands-on task. The system was evaluated in the frame of an International Space Station (ISS) on-board experiment, which was carried out in the European science laboratory Columbus early 2013.

  14. Evaluation of the Long-Term Segmentation of the Wasatch Fault Footwall Using (U-Th)/He Thermochronometry

    NASA Astrophysics Data System (ADS)

    Taylor, A. R.; Armstrong, P. A.; Farley, K. A.

    2001-12-01

    The Wasatch fault zone (WFZ) is a 350-km-long normal fault system that is separated into ten segments based on its surface fault trace and topographic salients in the footwall Wasatch Mountains. The presence of the topographic salients, E-W striking fault zones that cut across the Wasatch, and apparent changes in depth of exposure of footwall rocks at the segment boundaries suggest these boundaries partition long-term footwall uplift and exhumation between the segments. To determine low-temperature ( ~65° C) cooling ages and infer exhumation rates within and between footwall segments, we measured multiple, single-grain laser (U-Th)/He ages on 11 footwall samples collected from the five central segments at a common elevation ( ~1500 m) along the range front. Pooled ages from this study average 5.3 +/-1.2 Ma for most of the Wasatch Front. Age ranges within segments, arranged north to south, are as follows. Two samples from the Brigham City segment yield average sample ages of 4.5+/-1.3 to 5.7+/-1.2 Ma. Four samples from the Weber segment have ages of 3.8+/-0.3 to 6.4+/-1.7 Ma, with the youngest ages in the center of the segment. Two samples from the northern Salt Lake segment yield ages of 3.4+/-1.1 to 5.2+/-1.2 Ma. Two closely spaced samples from the Provo segment and one from the Nephi segment yield ages of 6.4+/-1.2 Ma. Typical age variations within and between segments are relatively small with overlapping uncertainties, except on the Salt Lake segment, where several multiple-grain furnace (U-Th)/He ages from the Cottonwood Intrusive Belt (CIB) in the southern Salt Lake segment (Armstrong et. al. AGU, 1999) are about half those of the rest of the segment and the Wasatch Front average. The relatively consistent late Miocene to early Pliocene ages along nearly 200 km of the WFZ suggest similar exhumation rates along most of the Wasatch front for the last ~6 Ma. With the exception of the CIB, simple calculations assuming monotonic cooling and typical geothermal

  15. Is fire a long term sink or source of atmospheric carbon? A comprehensive evaluation of a boreal forest fire

    NASA Astrophysics Data System (ADS)

    Santin, C.; Doerr, S. H.; Preston, C.; Bryant, R.

    2012-12-01

    -fire fuel assessment, ii) fire behaviour monitoring and iii) immediate post-fire fuel and PyC inventory. Before the fire, fuel characteristics were established and the site was instrumented with auto-logging thermocouples to provide temperature-duration profiles during burning. Also, different types of PyC were placed on the ground to determine PyC loss during the fire. Immediately after fire, the various post-burn PyC products and stores were sampled. Total PyC was quantified and the chemical recalcitrance of the different PyC forms found was determined. The results obtained will be discussed in the context of PyC production, and its different forms and quantities, with respect to (i) fire characteristics and fuel consumed, and (ii) the long term carbon balance in this boreal forest environment for recurring fire-regrowth cycles under current and predicted future climatic conditions.

  16. Long-term evaluation of combined prolonged-release oxycodone and naloxone in patients with moderate-to-severe chronic pain: pooled analysis of extension phases of two Phase III trials

    PubMed Central

    Blagden, M; Hafer, J; Duerr, H; Hopp, M; Bosse, B

    2014-01-01

    Background While opioids provide effective analgesia, opioid-induced constipation (OIC) can severely impact quality of life and treatment compliance. This pooled analysis evaluated the maintenance of efficacy and safety during long-term treatment with combined oxycodone/naloxone prolonged-release tablets (OXN PR) in adults with moderate-to-severe chronic pain. Methods Patients (N = 474) received open-label OXN PR during 52-week extension phases of two studies, having completed 12-week, double-blind, randomized treatment with oxycodone prolonged-release tablets (Oxy PR) or OXN PR. Analgesia and bowel function were assessed at each study visit using ‘Average pain over last 24 h scale and Bowel Function Index (BFI), respectively. Treatment Satisfaction Questionnaire for Medication was assessed at study end only. Key Results Improvement in bowel function was particularly marked in patients who switched from Oxy PR in the double-blind phase to OXN PR during the extension phase, resulting in a clinically meaningful reduction (≥12 points) in BFI score: at the start of the extension phases, mean (SD) BFI score was 44.3 (28.13), and was 29.8 (26.36) for patients who had received OXN PR in the double-blind phase. One week later, BFI scores were similar for the two groups (26.5 [24.40] and 27.5 [25.60], respectively), as was observed throughout the following months. Fewer than 10% of patients received laxatives regularly. Mean 24-h pain scores were low and stable throughout the extension phases. No unexpected adverse events were observed. Conclusions & Inferences Pooled data demonstrate OXN PR is an effective long-term therapy for patients with chronic non-cancer pain, and can address symptoms of OIC. No new safety issues were observed which were attributable to the long-term administration of OXN PR. PMID:25346155

  17. A new animal model for evaluation of long-term growth rate over one month by rhGH/PLGA microcapsule formulations.

    PubMed

    Takada, Shigeyuki; Kurokawa, Tomofumi; Misaki, Masafumi; Taira, Keiko; Yamagata, Yutaka

    2003-07-01

    A new animal model to evaluate the long-term growth rate produced by a sustained-release formulation of recombinant human growth hormone (rhGH) over one month was developed and the usefulness of our microcapsule formulations was demonstrated in this model. Long-term pharmacological effects by subcutaneous injection of microcapsules for sustained release of rhGH were evaluated in hypophysectomized (Hpx) rats treated with immunosuppressive agent along with hormone supplement. Copoly(DL-lactic/glycolic)acid (PLGA) microcapsules for sustained release of rhGH, a two-week sustained-release formulation (rhGH-SR-2W) and a one-month sustained-release formulation (rhGH-SR-1M), were prepared by a solid-in-oil-in-water emulsion solvent evaporation technique. Body-weight gain, body-length gain and serum levels of rat insulin-like growth factor-I (rIGF-I) induced by subcutaneous injection of rhGH-SR were compared with those by daily injections of rhGH solution in Hpx rats for 35 days. Serum IGF-I levels in Hpx rats after the injection of rhGH-SR2W microcapsules were higher than those after daily injections of rhGH solution. Body-length gain, a new parameter, after single injection of rhGH-SR-1M microcapsules demonstrated the higher growth rate than that after daily injections of rhGH solution for 35 days. Thus, single injection of rhGH-SR microcapsules demonstrated long-term pharmacological effects greater than those by daily injections of rhGH solution in a newly developed model, immunosuppressed Hpx rats. PMID:12906752

  18. Long-term evaluation and cross-checking of two geometric calibrations of kV and MV imaging systems for Linacs.

    PubMed

    Chiu, Tsuicheng D; Yan, Yulong; Foster, Ryan; Mao, Weihua

    2015-01-01

    Geometric or mechanical accuracy of kV and MV imaging systems of two Varian TrueBeam linacs have been monitored by two geomertirc calibration systems, Varian IsoCal geometric calibration system and home-developed gQA system. Results of both systems are cross-checked and the long-term geometric stabilities of linacs are evaluated. Two geometric calibration methodologies have been used to assess kV and MV imaging systems and their coincidence periodically on two TrueBeam linacs for about one year. Both systems analyze kV or MV projection images of special designed phantoms to retrieve geometric parameters of the imaging systems. The isocenters — laser isocenter and centers of rotations of kV imager and EPID — are then calculated, based on results of multiple projections from different angles. Long-term calibration results from both systems are compared for cross-checking. There are 24 sessions of side-by-side calibrations performed by both systems on two TrueBeam linacs. All the disagreements of isocenters between two calibrations systems are less than 1 mm with ± 0.1 mm SD. Most of the large disagreements occurred in vertical direction (AP direction), with an averaged disagreement of 0.45 mm. The average disagreements of isocenters are 0.09 mm in other directions. Additional to long-term calibration monitoring, for the accuracy test, special tests were performed by misaligning QA phantoms on purpose (5 mm away from setup isocenter in AP, SI, and lateral directions) to test the liability performance of both systems with the known deviations. The errors are within 0.5 mm. Both geometric calibration systems, IsoCal and gQA, are capable of detecting geometric deviations of kV and MV imaging systems of linacs. The long-term evaluation also shows that the deviations of geometric parameters and the geometric accuracies of both linacs are small and very consistent during the one-year study period. PMID:26218992

  19. Bipolar Electrochemistry for Concurrently Evaluating the Stability of Anode and Cathode Electrocatalysts and the Overall Cell Performance during Long-Term Water Electrolysis.

    PubMed

    Eßmann, Vera; Barwe, Stefan; Masa, Justus; Schuhmann, Wolfgang

    2016-09-01

    Electrochemical efficiency and stability are among the most important characteristics of electrocatalysts. These parameters are usually evaluated separately for the anodic and cathodic half-cell reactions in a three-electrode system or by measuring the overall cell voltage between the anode and cathode as a function of current or time. Here, we demonstrate how bipolar electrochemistry can be exploited to evaluate the efficiency of electrocatalysts for full electrochemical water splitting while simultaneously and independently monitoring the individual performance and stability of the half-cell electrocatalysts. Using a closed bipolar electrochemistry setup, all important parameters such as overvoltage, half-cell potential, and catalyst stability can be derived from a single galvanostatic experiment. In the proposed experiment, none of the half-reactions is limiting on the other, making it possible to precisely monitor the contribution of the individual half-cell reactions on the durability of the cell performance. The proposed approach was successfully employed to investigate the long-term performance of a bifunctional water splitting catalyst, specifically amorphous cobalt boride (Co2B), and the durability of the electrocatalyst at the anode and cathode during water electrolysis. Additionally, by periodically alternating the polarization applied to the bipolar electrode (BE) modified with a bifunctional oxygen electrocatalyst, it was possible to explicitly follow the contributions of the oxygen reduction (ORR) and the oxygen evolution (OER) half-reactions on the overall long-term durability of the bifunctional OER/ORR electrocatalyst. PMID:27469162

  20. Nurse-led educative consultation setting personalized tertiary prevention goals after cardiovascular rehabilitation: evaluation of patient satisfaction and long-term effects.

    PubMed

    Dedoncker, Anne; Lejeune, Corinne; Dupont, Catherine; Antoine, Daniel; Laurent, Yves; Casillas, Jean-Marie; Gremeaux, Vincent

    2012-01-01

    This study aimed to evaluate the perception and long-term effects of an educative consultation performed before cardiac rehabilitation discharge. The patient and the referring nurse summed up the educative interventions, and filled a personalized form summarizing tertiary prevention goals. Fifty patients were contacted by mail at 11 ± 1 months, and called at 4.2 ± 0.2 years after discharge, to evaluate their satisfaction and assess cardiovascular risk factors (CVRF) control. Mail response rate was 82%, and 90% of patients believed that it had encouraged them to adopt a healthier lifestyle. Almost half the number of patients declared that they considered the nurse intervention as positive. Telephone response rate was 54%. Most long-term effects were better than usually reported in the field of multidisciplinary secondary prevention of CVRF. Patients felt that this educational action was positive, even though highlighting this role of nurses seems necessary. Additional controlled trials are needed to provide rigorous validation of this strategy.

  1. Bipolar Electrochemistry for Concurrently Evaluating the Stability of Anode and Cathode Electrocatalysts and the Overall Cell Performance during Long-Term Water Electrolysis.

    PubMed

    Eßmann, Vera; Barwe, Stefan; Masa, Justus; Schuhmann, Wolfgang

    2016-09-01

    Electrochemical efficiency and stability are among the most important characteristics of electrocatalysts. These parameters are usually evaluated separately for the anodic and cathodic half-cell reactions in a three-electrode system or by measuring the overall cell voltage between the anode and cathode as a function of current or time. Here, we demonstrate how bipolar electrochemistry can be exploited to evaluate the efficiency of electrocatalysts for full electrochemical water splitting while simultaneously and independently monitoring the individual performance and stability of the half-cell electrocatalysts. Using a closed bipolar electrochemistry setup, all important parameters such as overvoltage, half-cell potential, and catalyst stability can be derived from a single galvanostatic experiment. In the proposed experiment, none of the half-reactions is limiting on the other, making it possible to precisely monitor the contribution of the individual half-cell reactions on the durability of the cell performance. The proposed approach was successfully employed to investigate the long-term performance of a bifunctional water splitting catalyst, specifically amorphous cobalt boride (Co2B), and the durability of the electrocatalyst at the anode and cathode during water electrolysis. Additionally, by periodically alternating the polarization applied to the bipolar electrode (BE) modified with a bifunctional oxygen electrocatalyst, it was possible to explicitly follow the contributions of the oxygen reduction (ORR) and the oxygen evolution (OER) half-reactions on the overall long-term durability of the bifunctional OER/ORR electrocatalyst.

  2. Ionizer assisted air filtration for collection of submicron and ultrafine particles-evaluation of long-term performance and influencing factors.

    PubMed

    Shi, Bingbing; Ekberg, Lars

    2015-06-01

    Previous research has demonstrated that unipolar ionization can enhance the filter performance to collect airborne particles, aeroallergens, and airborne microorganisms, without affecting the filter pressure drop. However, there is a lack of research on the long-term system performance as well as the influence of environmental and operational parameters. In this paper, both field and laboratory tests were carried out to evaluate the long-term particle collection efficiency of a synthetic filter of class M6 with and without ionization. The effect of air velocity, temperature, relative humidity, and particle concentration were further investigated in laboratory tests. Results showed that ionization enhanced the filtration efficiency by 40%-units during most of the operation time. When the ionization system was managed by periodically switching the ionizer polarity, the filtration efficiency against PM0.3-0.5 was maintained above 50% during half a year. Furthermore, the pressure drop of the ionizer-assisted M6 filter was 25-30% lower than that of a filter of class F7. The evaluation of various influencing factors demonstrated that (1) air moisture reduced the increase of filtration efficiency; (2) higher upstream particle concentration and air velocity decreased the filtration efficiency; and (3) the air temperature had very limited effect on the filtration efficiency.

  3. Multimodal optical studies of single and clustered colloidal quantum dots for the long-term optical property evaluation of quantum dot-based molecular imaging phantoms

    PubMed Central

    Kang, HyeongGon; Clarke, Matthew L.; Lacerda, Silvia H. De Paoli; Karim, Alamgir; Pease, Leonard F.; Hwang, Jeeseong

    2012-01-01

    Understanding the optical properties of clustered quantum dots (QDs) is essential to the design of QD-based optical phantoms for molecular imaging. Single and clustered core/shell colloidal QDs of dimers, trimers, and tetramers are self-assembled, separated, and preferentially collected using electrospray differential mobility analysis (ES-DMA) with electrostatic deposition. Multimodal optical characterization and analysis of their dynamical photoluminescence (PL) properties enables the long-term evaluation of the physicochemical and optical properties of QDs in a single or a clustered state. A multimodal time-correlated spectroscopic confocal microscope capable of simultaneously measuring the time evolution of PL intensity fluctuation, PL lifetime, and emission spectra reveals the long-term dynamic optical properties of interacting QDs in individual dimeric clusters of QDs. This new method will benefit research into the quantitative interpretation of fluorescence intensity and lifetime results in QD-based molecular imaging techniques. The process of photooxidation leads to coupling of the QDs in a dimer, leading to unique optical properties when compared to an isolated QD. These results guide the design and evaluation of QD-based phantom materials for the validation of the PL measurements for quantitative molecular imaging of biological samples labeled with QD probes. PMID:22741078

  4. Evaluation of Long-Term Cloud-Resolving Model Simulations Using Satellite Radiance Observations and Multi-Frequency Satellite Simulators

    NASA Technical Reports Server (NTRS)

    Matsui, Toshihisa; Zeng, Xiping; Tao, Wei-Kuo; Masunaga, Hirohiko; Olson, William S.; Lang, Stephen

    2008-01-01

    This paper proposes a methodology known as the Tropical Rainfall Measuring Mission (TRMM) Triple-Sensor Three-step Evaluation Framework (T3EF) for the systematic evaluation of precipitating cloud types and microphysics in a cloud-resolving model (CRM). T3EF utilizes multi-frequency satellite simulators and novel statistics of multi-frequency radiance and backscattering signals observed from the TRMM satellite. Specifically, T3EF compares CRM and satellite observations in the form of combined probability distributions of precipitation radar (PR) reflectivity, polarization-corrected microwave brightness temperature (Tb), and infrared Tb to evaluate the candidate CRM. T3EF is used to evaluate the Goddard Cumulus Ensemble (GCE) model for cases involving the South China Sea Monsoon Experiment (SCSMEX) and Kwajalein Experiment (KWAJEX). This evaluation reveals that the GCE properly captures the satellite-measured frequencies of different precipitating cloud types in the SCSMEX case but underestimates the frequencies of deep convective and deep stratiform types in the KWAJEX case. Moreover, the GCE tends to simulate excessively large and abundant frozen condensates in deep convective clouds as inferred from the overestimated GCE-simulated radar reflectivities and microwave Tb depressions. Unveiling the detailed errors in the GCE s performance provides the best direction for model improvements.

  5. Evaluation of a new tablet formulation of deferasirox to reduce chronic iron overload after long-term blood transfusions

    PubMed Central

    Chalmers, Anna W; Shammo, Jamile M

    2016-01-01

    Transfusion-dependent anemia is a common feature in a wide array of hematological disorders, including thalassemia, sickle cell disease, aplastic anemia, myelofibrosis, and myelo-dysplastic syndromes. In the absence of a physiological mechanism to excrete excess iron, chronic transfusions ultimately cause iron overload. Without correction, iron overload can lead to end-organ damage, resulting in cardiac, hepatic, and endocrine dysfunction/failure. Iron chelating agents are utilized to reduce iron overload, as they form a complex with iron, leading to its clearance. Iron chelation has been proven to decrease organ dysfunction and improve survival in certain transfusion-dependent anemias, such as β-thalassemia. Several chelating agents have been approved by the United States Food and Drug Administration for the treatment of iron overload, including deferoxamine, deferiprone, and deferasirox. A variety of factors have to be considered when choosing an iron chelator, including dosing schedule, route of administration, tolerability, and side effect profile. Deferasirox is an orally administered iron chelator with proven efficacy and safety in multiple hematological disorders. There are two formulations of deferasirox, a tablet for suspension, and a new tablet form. This paper is intended to provide an overview of iron overload, with a focus on deferasirox, and its recently approved formulation Jadenu® for the reduction of transfusional iron overload in hematological disorders. PMID:26929633

  6. Clozapine Treatment of Childhood-Onset Schizophrenia: Evaluation of Effectiveness, Adverse Effects, and Long-Term Outcome

    ERIC Educational Resources Information Center

    Sporn, Alexandra L.; Vermani, Anoop; Greenstein, Deanna K.; Bobb, Aaron J.; Spencer, Edgar P.; Clasen, Liv S.; Tossell, Julia W.; Stayer, Catherine C.; Gochman, Peter A.; Lenane, Marge C.; Rapoport, Judith L.; Gogtay, Nitin

    2007-01-01

    Objective: Clozapine is a unique atypical antipsychotic with superior efficacy in treatment-resistant schizophrenia. Plasma concentration of clozapine and its major metabolite N-desmethylclozapine (NDMC) as well as the ratio of NDMC to clozapine have been reported to be predictors of clozapine response. Here we evaluate these as well as other…

  7. Evaluating the Role of Job Site Supervisors in the Long-Term Employment of Persons with Severe Disabilities.

    ERIC Educational Resources Information Center

    Rusch, Frank R.; And Others

    The purpose of this study was to identify job site supervisors' opinions regarding job placement, training, evaluation, and job maintenance of persons with disabilities. In order to assess the role of job site supervisors, 10 supervisors in businesses that employed individuals with handicaps were interviewed. Employment sites represented four…

  8. Structuring Long-Term Faculty Training According to Needs Exhibited by Students' Written Comments in Course Evaluations

    ERIC Educational Resources Information Center

    Fulkerth, Robert

    2014-01-01

    A comprehensive adjunct faculty training program is described, whose aim is to improve student perceptions of courses and programs in a private, not-for-profit MBA and Law degree granting university in San Francisco, The program is somewhat novel in that it uses (a) student input from open-ended responses on course evaluations to determine faculty…

  9. Clinical efficacy, radiographic and safety findings through 2 years of golimumab treatment in patients with active psoriatic arthritis: results from a long-term extension of the randomised, placebo-controlled GO-REVEAL study

    PubMed Central

    Kavanaugh, Arthur; McInnes, Iain B; Mease, Philip J; Krueger, Gerald G; Gladman, Dafna D; van der Heijde, Désirée; Mudivarthy, Surekha; Xu, Weichun; Mack, Michael; Xu, Zhenhua; Beutler, Anna

    2013-01-01

    Objectives To assess long-term golimumab efficacy/safety in patients with active psoriatic arthritis (PsA). Methods Adult PsA patients (≥3 swollen, ≥3 tender joints, active psoriasis) were randomly assigned to subcutaneous injections of placebo, golimumab 50 mg or 100 mg every 4 weeks (q4wks) through week 20. All patients received golimumab 50 or 100 mg beginning week 24. Findings through 2 years are reported. Efficacy evaluations included ≥20% improvement in American College of Rheumatology (ACR20) response, good/moderate response in Disease Activity Scores incorporating 28 joints and C-reactive protein (DAS28-CRP), ≥75% improvement in Psoriasis Area and Severity Index (PASI75) and changes in PsA-modified Sharp/van der Heijde scores (SHS). Results Golimumab treatment through 2 years was effective in maintaining clinical response (response rates: ACR20 63%–70%, DAS28-CRP 77%–86%, PASI75 56%–72%) and inhibiting radiographic progression (mean change in PsA-modified SHS in golimumab-treated patients: −0.36), with no clear difference between doses. No new safety signals were identified through 2 years. With the study's tuberculosis screening and prophylactic measures, no patient developed active tuberculosis through 2 years. Conclusions Golimumab 50 and 100 mg for up to 2 years yielded sustained clinical and radiographic efficacy when administered to patients with active PsA. Increasing the golimumab dose from 50 to 100 mg q4wks added limited benefit. Golimumab safety through up to 2 years was consistent with other antitumour necrosis factor α agents used to treat PsA. Treatment of patients with latent tuberculosis identified at baseline appeared to be effective in inhibiting the development of active tuberculosis. PMID:23161902

  10. Long-term efficacy and safety of rabeprazole in patients taking low-dose aspirin with a history of peptic ulcers: a phase 2/3, randomized, parallel-group, multicenter, extension clinical trial

    PubMed Central

    Fujishiro, Mitsuhiro; Higuchi, Kazuhide; Kato, Mototsugu; Kinoshita, Yoshikazu; Iwakiri, Ryuichi; Watanabe, Toshio; Takeuchi, Toshihisa; Sugisaki, Nobuyuki; Okada, Yasushi; Ogawa, Hisao; Arakawa, Tetsuo; Fujimoto, Kazuma

    2015-01-01

    A 24-week, double-blind, clinical trial of rabeprazole for the prevention of recurrent peptic ulcers caused by low-dose aspirin (LDA) has been reported, but trials for longer than 24 weeks have not been reported. The aim of this study is to assess the long-term efficacy and safety of rabeprazole for preventing peptic ulcer recurrence on LDA therapy. Eligible patients had a history of peptic ulcers on long-term LDA (81 or 100 mg/day) therapy. Patients with no recurrence of peptic ulcers at the end of the 24-week double-blind phase with rabeprazole (10- or 5-mg once daily) or teprenone (50 mg three times daily) entered the extension phase. Rabeprazole doses were maintained for a maximum of 76 weeks, including the double-blind 24-week period and the extension phase period (long-term rabeprazole 10- and 5-mg groups). Teprenone was randomly switched to rabeprazole 10 or 5 mg for a maximum of 52 weeks in the extension phase (newly-initiated rabeprazole 10- and 5-mg groups). The full analysis set consisted of 151 and 150 subjects in the long-term rabeprazole 10- and 5-mg groups, respectively, and the cumulative recurrence rates of peptic ulcers were 2.2 and 3.7%, respectively. Recurrent peptic ulcers were not observed in the newly-initiated rabeprazole 10- and 5-mg groups. No bleeding ulcers were reported. No clinically significant safety findings, including cardiovascular events, emerged. The use of long-term rabeprazole 10- and 5-mg once daily prevents the recurrence of peptic ulcers in subjects on low-dose aspirin therapy, and both were well-tolerated. PMID:26060354

  11. Development and application of a procedure for evaluating the long-term integrity of membranes for the anaerobic fluidized membrane bioreactor (AFMBR).

    PubMed

    Shin, Chungheon; Kim, Kihyun; McCarty, Perry L; Kim, Jeonghwan; Bae, Jaeho

    2016-01-01

    A bench-scale short-term test, developed to predict the long-term integrity of membranes with potential for use in anaerobic fluidized-bed membrane bioreactors, was used to evaluate several commercial hollow-fiber membranes. It was found that membrane performance varied widely, some membranes failing much more rapidly than others. Also found was that larger sizes of the fluidized media, in this case granular activated carbon (GAC), severely affected membrane structural integrity more than did smaller sizes, as did the method used for membrane attachment. Within the limits studied, the GAC packing ratio had only a minor impact. A decrease in membrane permeability that sometimes resulted during the testing and was caused by the deposition of fine GAC particles could be eliminated without membrane damage through simultaneous chemical cleaning and sonication. This new testing procedure should be useful for selecting membranes and reactor operating conditions to better ensure long-term operating performance of anaerobic fluidized-bed membrane bioreactors. PMID:27438251

  12. Views from Within a Narrative: Evaluating Long-Term Human-Robot Interaction in a Naturalistic Environment Using Open-Ended Scenarios.

    PubMed

    Syrdal, Dag Sverre; Dautenhahn, Kerstin; Koay, Kheng Lee; Ho, Wan Ching

    2014-01-01

    This article describes the prototyping of human-robot interactions in the University of Hertfordshire (UH) Robot House. Twelve participants took part in a long-term study in which they interacted with robots in the UH Robot House once a week for a period of 10 weeks. A prototyping method using the narrative framing technique allowed participants to engage with the robots in episodic interactions that were framed using narrative to convey the impression of a continuous long-term interaction. The goal was to examine how participants responded to the scenarios and the robots as well as specific robot behaviours, such as agent migration and expressive behaviours. Evaluation of the robots and the scenarios were elicited using several measures, including the standardised System Usability Scale, an ad hoc Scenario Acceptance Scale, as well as single-item Likert scales, open-ended questionnaire items and a debriefing interview. Results suggest that participants felt that the use of this prototyping technique allowed them insight into the use of the robot, and that they accepted the use of the robot within the scenario.

  13. Sustained efficacy, immunogenicity, and safety of the HPV-16/18 AS04-adjuvanted vaccine: final analysis of a long-term follow-up study up to 9.4 years post-vaccination.

    PubMed

    Naud, Paulo S; Roteli-Martins, Cecilia M; De Carvalho, Newton S; Teixeira, Julio C; de Borba, Paola C; Sanchez, Nervo; Zahaf, Toufik; Catteau, Gregory; Geeraerts, Brecht; Descamps, Dominique

    2014-01-01

    HPV-023 (NCT00518336; ClinicalTrial.gov) is a long-term follow-up of an initial double-blind, randomized (1:1), placebo-controlled study (HPV-001, NCT00689741) evaluating the efficacy against human papillomavirus (HPV)-16/18 infection and associated cyto-histopathological abnormalities, persistence of immunogenicity, and safety of the HPV-16/18 AS04-adjuvanted vaccine. Among the women, aged 15-25 years, enrolled in HPV-001 and who participated in the follow-up study HPV-007 (NCT00120848), a subset of 437 women from five Brazilian centers participated in this 36-month long-term follow-up (HPV-023) for a total of 113 months (9.4 years). During HPV-023, anti-HPV-16/18 antibodies were measured annually by enzyme-linked immunosorbent assay (ELISA) and pseudovirion-based neutralisation assay (PBNA). Cervical samples were tested for HPV DNA every 6 months, and cyto-pathological examinations were performed annually. During HPV-023, no new HPV-16/18-associated infections and cyto-histopathological abnormalities occurred in the vaccine group. Vaccine efficacy (VE) against HPV-16/18 incident infection was 100% (95%CI: 66.1, 100). Over the 113 months (9.4 years), VE was 95.6% (86.2, 99.1; 3/50 cases in vaccine and placebo groups, respectively) against incident infection, 100% (84·1, 100; 0/21) against 6-month persistent infection (PI); 100% (61·4, 100; 0/10) against 12-month PI; 97·1% (82.5, 99.9; 1/30) against ≥ ASC-US; 95·0% (68.0, 99.9; 1/18) against ≥ LSIL; 100% (45.2, 100; 0/8) against CIN1+; and 100% (-128.1, 100; 0/3) against CIN2+ associated with HPV-16/18. All vaccinees remained seropositive to HPV-16/18, with antibody titers remaining several folds above natural infection levels, as measured by ELISA and PBNA. There were no safety concerns. To date, these data represent the longest follow-up reported for a licensed HPV vaccine. PMID:25424918

  14. Long-term evaluation of the needle surface wax condition of Pinus sylvestris around different industries in Lithuania.

    PubMed

    Kupcinskiene, Eugenija; Huttunen, Satu

    2005-10-01

    The aim of our study was to evaluate the annual dynamics of needle surface wax erosion and wettability in Scots pines exposed to a gradient of industrial pollutants emitted from the main factories of Lithuania: a nitrogen fertilizer factory, an oil refinery and a cement factory. Decreased emissions (in the case of the oil refinery and the cement factory) were reflected in the increased structural surface area (SSA, i.e. area covered by tubular waxes) on the needles. The nearly constant amount of emissions from the nitrogen fertilizer factory within the 1994-2000 period corresponded to negligible annual differences in SSA. Annual changes in the hydrophobicity of needles on the investigated transects were small. Despite the decreased pollution within the 7-year period, industrial emissions are still causing significantly accelerated wax erosion and increased wettability in needles sampled from the stands most heavily affected by pollutants. PMID:16005772

  15. Long-term evaluation of the needle surface wax condition of Pinus sylvestris around different industries in Lithuania.

    PubMed

    Kupcinskiene, Eugenija; Huttunen, Satu

    2005-10-01

    The aim of our study was to evaluate the annual dynamics of needle surface wax erosion and wettability in Scots pines exposed to a gradient of industrial pollutants emitted from the main factories of Lithuania: a nitrogen fertilizer factory, an oil refinery and a cement factory. Decreased emissions (in the case of the oil refinery and the cement factory) were reflected in the increased structural surface area (SSA, i.e. area covered by tubular waxes) on the needles. The nearly constant amount of emissions from the nitrogen fertilizer factory within the 1994-2000 period corresponded to negligible annual differences in SSA. Annual changes in the hydrophobicity of needles on the investigated transects were small. Despite the decreased pollution within the 7-year period, industrial emissions are still causing significantly accelerated wax erosion and increased wettability in needles sampled from the stands most heavily affected by pollutants.

  16. Evaluation of the 96/4 PLDLLA polymer resorbable lumbar interbody cage in a long term animal model.

    PubMed

    Lazennec, Jean Y; Madi, Abdallah; Rousseau, Marc A; Roger, Bernard; Saillant, Gérard

    2006-10-01

    Arthrodesis using interbody cages has demonstrated high fusion rates. However, permanent cages are exposed to stress-shielding, corrosion, and may require explanation when necessary. Polylactic acid (PLA) bioresorbable cages are developed for avoiding these problems, but significant tissue reaction has been reported with 70/30 PLDLLA in some preclinical animal studies. The objective was to evaluate 96/4 PLDLLA cages in a sheep model over 3 years. Sixteen sheeps underwent one level anterior lumbar interbody fusion using 96/4 PLDLLA cages, filled and surrounded with cancellous bone graft from the iliac crest. Six groups of three animals were killed after 3, 6, 9, 12, 24, and 36 months. Harvested lumbar spine had radiographic, MRI, and CT evaluation and histological analysis. Histological results: cage swelling and slight signs of fragmentation associated to fibrocartilaginous tissue apposition at 3 months; bone remodeling around the cage with direct apposition of the mineralization front at 6 months; active cage degradation and complete fusion around the cage at 9 months; cage fragmentation and partial replacement by bone tissue at 12 months; bone bridges in and around the cage at 24 months; full resorption and intervertebral fusion at 36 months. Radiological results: partial arthrodesis at 3 months; definite peripheral arthrodesis at 6 months; similar aspect at 9 months; significant cage resorption at 12 months; definite inner and outer fusion at 24 months; complete cage resorption and calcification at the location of the cage at 36 months confirmed histological observations. Radiographic, CT scan, MRI, and histological data were consistent for showing progressive resorption of 96/4 PLDLLA, interbody fusion, and bone remodeling, with no significant signs of local intolerance reaction. These results are promising and suggest further development of 96/4 PLDLLA cages. PMID:16736199

  17. Long-Term Histopathologic and IVUS Evaluations of a Novel Coiled Sheet Stent in Porcine Carotid Arteries

    SciTech Connect

    Kaneda, Hideaki; Ikeno, Fumiaki Lyons, Jennifer; Rezaee, Mehrdad; Yeung, Alan C.; Fitzgerald, Peter J.

    2006-06-15

    Carotid angioplasty with stent placement has been proposed as an alternative method for revascularization of carotid artery stenosis. A novel stent with a laser-cut, rolled sheet of Nitinol (EndoTex Interventional Systems, Inc., Cupertino, CA) has been developed to customize treatment of stenotic lesions in carotid arteries utilizing a single stent, designed to adapt to multiple diameters and to tapered or nontapered configurations. The purpose of this study is to evaluate the conformability and vascular response to a novel stent in a chronic porcine carotid model using serial three-dimensional intravascular ultrasound (IVUS) analysis as well as histological examination. Ten Yucatan pigs underwent stent implantation in both normal carotid arteries with adjunctive balloon angioplasty. Three-dimensional IVUS analysis was performed before stent implantation, after adjunctive balloon angioplasty, and at follow-up [1 month (n = 6), 3 months (n = 6), or 6 months (n = 8)]. Histological examination (injury score, percent plaque obstruction, and qualitative analysis) was also performed. All stents were successfully deployed and well apposed in different sized vessels (lumen area range: 19-30 mm{sup 2}). Volumetric IVUS analysis showed no significant difference between the lumen areas before stent implantation and after adjunctive balloon angioplasty and no stent area change at each follow-up point compared to immediately postprocedure. Histological examination revealed minimal injury and neointimal hyperplasia at each follow-up point. In the chronic porcine carotid model, the novel stent system demonstrated good conformability, resulting in minimal vessel injury and neointimal formation.

  18. An evaluation of image quality metrics aiming to validate long term stability and the performance of NUC methods

    NASA Astrophysics Data System (ADS)

    Svensson, Thomas

    2013-06-01

    Spatial noise added to temporal noise will affect both the detection and the classification ability of staring image sensors. The spatial noise is due to non-uniform pixels and is also called fixed pattern noise (FPN), though it is not totally static but varies slowly in time, which is due to sensor drift. The sensor drift is mainly due to variability in the ambient temperature and hence the temperature of camera elements, which may be a concern in field trials and the subsequent analysis of the image data. The performance of a non-uniformity correction (NUC) depends on the characteristics of the spatial noise in the image data, in addition to the correction method. In this paper six different quality metrics are studied, aiming to quantify the non-uniformity in collected image data and to validate the performance of a set of NUC methods. The set of methods has been applied on various kinds of real image data recorded with three different imaging sensors in the infrared spectral region, where image data may be severely distorted by fixed pattern noise. Calculated image quality metrics for image data have been compared with results from a visual evaluation. A conclusion is that image quality metrics are useful tools that enable an objective rating of image quality.

  19. Evaluation of a long-term oral health program by carers of children and adults with intellectual disabilities.

    PubMed

    Faulks, D; Hennequin, M

    2000-01-01

    The oral health program presented here was undertaken in three French centers for persons with special needs. The program aimed to educate the carers about dental disease, to motivate them with regard to prevention, and to improve the oral hygiene and oral health of the residents. This study evaluated the impact of the program in terms of change in attitudes and behavior expressed by the carers by means of a questionnaire. Following demonstration of oral hygiene techniques on an individual basis, the number of residents who had their teeth cleaned more than once a day rose from 24% to 52% (p < 0.05). The percentage of carers able to clean both posterior and anterior teeth of their key residents increased from 24% to 60% (p < 0.05), and the percentage finding tooth cleaning easy increased from 36% to 60% (non-significant). The intervention was thus deemed moderately successful, although the carers continued to take better care of their own oral health than that of the residents. The need for ongoing training is emphasized, both for the carers of those with special needs and for the dental profession. The lack of a validated means of measuring the impact of such interventions on care providers for this population is discussed. PMID:11203899

  20. Bayesian evaluation of a physiologically-based pharmacokinetic (PBPK) model of long-term kinetics of metal nanoparticles in rats.

    PubMed

    Sweeney, Lisa M; MacCalman, Laura; Haber, Lynne T; Kuempel, Eileen D; Tran, C Lang

    2015-10-01

    Biomathematical modeling quantitatively describes the disposition of metal nanoparticles in lungs and other organs of rats. In a preliminary model, adjustable parameters were calibrated to each of three data sets using a deterministic approach, with optimal values varying among the different data sets. In the current effort, Bayesian population analysis using Markov chain Monte Carlo (MCMC) simulation was used to recalibrate the model while improving assessments of parameter variability and uncertainty. The previously-developed model structure and some physiological parameter values were modified to improve physiological realism. The data from one of the three previously-identified studies and from two other studies were used for model calibration. The data from the one study that adequately characterized mass balance were used to generate parameter distributions. When data from a second study of the same nanomaterial (iridium) were added, the level of agreement was still acceptable. Addition of another data set (for silver nanoparticles) led to substantially lower precision in parameter estimates and large discrepancies between the model predictions and experimental data for silver nanoparticles. Additional toxicokinetic data are needed to further evaluate the model structure and performance and to reduce uncertainty in the kinetic processes governing in vivo disposition of metal nanoparticles. PMID:26145831

  1. gamma. -irradiated sewage solids in diets for sheep: nutritive evaluations and long-term assessments of possible toxicants

    SciTech Connect

    Sanson, D.W.

    1983-01-01

    Air-dried solids from primary (undigested) sewage sludge were collected at Las Cruces, New Mexico (a non-industrial town with population about 50,000). Bagged sewage solids were ..gamma..-irradiated (1 megarad dosage) to kill parasites and pathogenic organisms and evaluated as prospective feedstuffs for sheep. Pelleted, complete diets for gestating-lactating fine-wool ewes and for their growing-finishing lambs were formulated to be isonitrogenous with either 3.5% cottonseed meal (conventional diet) or 7% sewage solids (experimental diet). Digestibility of organic matter and crude protein, and biological value of nitrogen, did not differ (P > .05) between diets, as determined with wethers. Wether lambs fed to slaughter with conventional or experimental diets did not differ (P > .05) in rate of gain, carcass characteristics, element concentrations in blood and serum chemistry profiles, although liver Cu and kidney Pb levels were increased (P < .05) about 1.6-fold by sewage solids. Element contents of spleen and muscles did not differ (P > .05) due to diets. These studies confirm previous research at New Mexico State University which indicates that dried solids from municipal (primary) sludge provide nutritive benefits to sheep with risks of toxicity and heavy metal accumulation that appear tolerable where managed properly.

  2. Evaluation of long-term surface-retrieved cloud droplet number concentration with in situ aircraft observations

    NASA Astrophysics Data System (ADS)

    Lim, Kyo-Sun Sunny; Riihimaki, Laura; Comstock, Jennifer M.; Schmid, Beat; Sivaraman, Chitra; Shi, Yan; McFarquhar, Greg M.

    2016-03-01

    A new operational retrieval of cloud droplet number concentration (ND) at cloud base has been produced from surface remote sensors at the Atmospheric Radiation Measurement (ARM) Southern Great Plains site for 13 years from January 1998 to January 2011. The retrieval is based on surface radiometer measurements of cloud optical depth from the multifilter rotating shadow band radiometer and liquid water path from the microwave radiometer (MWR). It is only applicable for single-layered overcast warm (stratus or stratocumulus) clouds. Evaluation with in situ aircraft measurements during the extended-term aircraft field campaign, Routine ARM Aerial Facility (AAF) Clouds with Low Optical Water Depths (CLOWD) Optical Radiative Observations (RACORO), shows that the retrieved ND robustly reproduces the primary mode of the in situ measured probability density function (PDF) but produces too wide a distribution, primarily caused by frequent high cloud droplet number concentration. Our analysis shows that the error in the MWR retrievals at low liquid water paths is one possible reason for this deficiency. Modification through the diagnosed liquid water path from the coordinate solution improves not only the PDF of the retrieved ND but also the relationship between the cloud droplet number concentration and cloud droplet effective radius. Consideration of entrainment effects rather than assuming an adiabatic cloud improves the values of the ND retrieval by reducing the magnitude of cloud droplet number concentration. Aircraft measurements and retrieval comparisons suggest that retrieving the vertical distribution of cloud droplet number concentration and effective radius is feasible with an improvement of the parameter representing the mixing effects between environment and clouds and with a better understanding of the effect of mixing degree on cloud properties.

  3. Evaluation of Long-term Vitamin E Insufficiency or Excess on Bone Mass, Density and Microarchitecture in Rodents

    PubMed Central

    Iwaniec, Urszula T.; Turner, Russell T.; Smith, Brenda J.; Stoecker, Barbara J.; Rust, Allison; Zhang, Bo; Vasu, Vihas T.; Gohil, Kishorchandra; Cross, Carroll E.; Traber, Maret G.

    2013-01-01

    High dietary α-tocopherol levels reportedly result in osteopenia in growing rats, while α-tocopherol deficiency in α-tocopherol transfer protein knockout (α-TTP KO) mice results in increased cancellous bone mass. Since osteoporosis is a disease associated primarily with aging, we hypothesized that age-related bone loss would be attenuated in α-TTP KO mice. Cancellous and cortical bone mass and microarchitecture were assessed using dual energy x-ray absorptiometry and micro-computed tomography in 2-year-old α-TTP KO and wildtype (WT) male and female mice fed DL-α-tocopherol acetate. In contrast to our expectations, differences in cancellous bone were not detected between WT and α-TTP KO mice in either gender and α-TTP KO males had lower (p < 0.05) cortical bone mass than WT males. We therefore evaluated bone mass, density and microarchitecture in proximal femur of skeletally mature (8.5-months-old) male Sprague-Dawley rats fed diets containing low (15 IU/kg), adequate (75 IU/kg), or high (500 IU/kg diet) DL-α-tocopherol acetate for 13 weeks. Low dietary α-tocopherol did not increase bone mass. Furthermore, no reductions in cancellous or cortical bone mass were detected with high dietary α-tocopherol. Failure to detect increased bone mass in aged α-TTP KO mice or bone changes in skeletally mature rats fed either low or high levels of α-tocopherol does not support the hypothesis that α-tocopherol has a negative impact on bone mass, density or microarchitecture in rodents. PMID:24051180

  4. Long-term ocean simulations in FESOM: evaluation and application in studying the impact of Greenland Ice Sheet melting

    NASA Astrophysics Data System (ADS)

    Wang, Xuezhu; Wang, Qiang; Sidorenko, Dmitry; Danilov, Sergey; Schröter, Jens; Jung, Thomas

    2012-12-01

    The Finite Element Sea-ice Ocean Model (FESOM) is formulated on unstructured meshes and offers geometrical flexibility which is difficult to achieve on traditional structured grids. In this work, the performance of FESOM in the North Atlantic and Arctic Ocean on large time scales is evaluated in a hindcast experiment. A water-hosing experiment is also conducted to study the model sensitivity to increased freshwater input from Greenland Ice Sheet (GrIS) melting in a 0.1-Sv discharge rate scenario. The variability of the Atlantic Meridional Overturning Circulation (AMOC) in the hindcast experiment can be explained by the variability of the thermohaline forcing over deep convection sites. The model also reproduces realistic freshwater content variability and sea ice extent in the Arctic Ocean. The anomalous freshwater in the water-hosing experiment leads to significant changes in the ocean circulation and local dynamical sea level (DSL). The most pronounced DSL rise is in the northwest North Atlantic as shown in previous studies, and also in the Arctic Ocean. The released GrIS freshwater mainly remains in the North Atlantic, Arctic Ocean and the west South Atlantic after 120 model years. The pattern of ocean freshening is similar to that of the GrIS water distribution, but changes in ocean circulation also contribute to the ocean salinity change. The changes in Arctic and sub-Arctic sea level modify exchanges between the Arctic Ocean and subpolar seas, and hence the role of the Arctic Ocean in the global climate. Not only the strength of the AMOC, but also the strength of its decadal variability is notably reduced by the anomalous freshwater input. A comparison of FESOM with results from previous studies shows that FESOM can simulate past ocean state and the impact of increased GrIS melting well.

  5. Towards an assistive peripheral visual prosthesis for long-term treatment of retinitis pigmentosa: evaluating mobility performance in immersive simulations

    NASA Astrophysics Data System (ADS)

    Zapf, Marc Patrick H.; Boon, Mei-Ying; Matteucci, Paul B.; Lovell, Nigel H.; Suaning, Gregg J.

    2015-06-01

    Objective. The prospective efficacy of a future peripheral retinal prosthesis complementing residual vision to raise mobility performance in non-end stage retinitis pigmentosa (RP) was evaluated using simulated prosthetic vision (SPV). Approach. Normally sighted volunteers were fitted with a wide-angle head-mounted display and carried out mobility tasks in photorealistic virtual pedestrian scenarios. Circumvention of low-lying obstacles, path following, and navigating around static and moving pedestrians were performed either with central simulated residual vision of 10° alone or enhanced by assistive SPV in the lower and lateral peripheral visual field (VF). Three layouts of assistive vision corresponding to hypothetical electrode array layouts were compared, emphasizing higher visual acuity, a wider visual angle, or eccentricity-dependent acuity across an intermediate angle. Movement speed, task time, distance walked and collisions with the environment were analysed as performance measures. Main results. Circumvention of low-lying obstacles was improved with all tested configurations of assistive SPV. Higher-acuity assistive vision allowed for greatest improvement in walking speeds—14% above that of plain residual vision, while only wide-angle and eccentricity-dependent vision significantly reduced the number of collisions—both by 21%. Navigating around pedestrians, there were significant reductions in collisions with static pedestrians by 33% and task time by 7.7% with the higher-acuity layout. Following a path, higher-acuity assistive vision increased walking speed by 9%, and decreased collisions with stationary cars by 18%. Significance. The ability of assistive peripheral prosthetic vision to improve mobility performance in persons with constricted VFs has been demonstrated. In a prospective peripheral visual prosthesis, electrode array designs need to be carefully tailored to the scope of tasks in which a device aims to assist. We posit that maximum

  6. PEGylated liposomes of anastrozole for long-term treatment of breast cancer: in vitro and in vivo evaluation.

    PubMed

    Shavi, Gopal Venkatesh; Sreenivasa Reddy, Meka; Raghavendra, Ramesh; Nayak, Usha Yogendra; Kumar, Averineni Ranjith; Deshpande, Praful Balavant; Udupa, Nayanabhirama; Behl, Gautam; Dave, Vivek; Kushwaha, Kriti

    2016-01-01

    The aim of present study was to develop conventional and PEGylated (long circulating), liposomes containing anastrozole (ANS) for effective treatment of breast cancer. ANS is a third-generation non-steroidal aromatase inhibitor of the triazole class used for the treatment of advanced and late-stage breast cancer in post-menopausal women. Under such disease conditions the median duration of therapy should be prolonged until tumor regression ends (>31 months). Liposomes were prepared by the thin film hydration method by using ANS and various lipids such as soyaphosphatidyl choline, cholesterol and methoxy polyethylene glycol distearoyl ethanolamine in different concentration ratios and evaluated for physical characteristics, in vitro drug release and stability. Optimized formulations of liposome were studied for in vitro cytotoxic activity against the BT-549 and MCF-7 cell lines and in vivo behavior in Wistar rats. Preformulation studies, both Fourier transform infrared study and differential scanning calorimetry analysis showed no interaction between the drug and the excipients used in the formulations. The optimized formulations AL-07 and AL-09 liposomes showed encapsulation efficiencies in the range 65.12 ± 1.05% to 69.85 ± 3.2% with desired mean particle size distribution of 101.1 ± 5.9 and 120.2 ± 2.8 nm and zeta potentials of -43.7 ± 4.7 and -62.9 ± 3.5 mV. All the optimized formulations followed Higuchi-matrix release kinetics and when plotted in accordance with the Korsemeyer-Peppas method, the n-value 0.5 < n < 1.0 suggests an anomalous (non-Fickian) transport. Likewise, the PEGylated liposomes showed greater tumor growth inhibition on BT-549 and MCF-7 cell lines from in vitro cytotoxicity studies (p < 0.05). Pharmacokinetic study of conventional and PEGylated liposomes in Wistar rats demonstrated a 3.33- and 20.28-fold increase in AUC(0-∞) values when compared to pure drug (p < 0.001). Among the formulations

  7. Pooled analysis of large and long-term safety data from the human papillomavirus-16/18-AS04-adjuvanted vaccine clinical trial programme

    PubMed Central

    Angelo, Maria-Genalin; David, Marie-Pierre; Zima, Julia; Baril, Laurence; Dubin, Gary; Arellano, Felix; Struyf, Frank

    2014-01-01

    Purpose The purpose of this study is to further evaluate the safety of the human papillomavirus (HPV)-16/18-AS04-adjuvanted vaccine (HPV-16/18-vaccine Cervarix®, GlaxoSmithKline, Belgium) through a pooled analysis of data from 42 completed/ongoing clinical studies. Methods Unsolicited adverse events (AEs) were reported for 30 days after each dose. Medically significant conditions, serious AEs (SAEs), potential immune-mediated diseases (pIMDs) and pregnancy outcomes were captured until study completion. Events leading to subject withdrawal were reviewed. Relative risks compared incidences of spontaneous abortion and pIMDs in controlled studies. Results Thirty one thousand one hundred seventy-three adolescent girls/women received HPV-16/18-vaccine alone (HPV group), 2166 received HPV-16/18-vaccine coadministered with another vaccine and 24 241 were controls. Mean follow-up was 39 months (range 0–113.3). Incidences of unsolicited AEs reported within 30 days after any dose were similar between HPV and Control groups (30.8%/29.7%). During the entire study period, reports of medically significant conditions (25.0%/28.3%) and SAEs (7.9%/9.3%) were also similarly distributed between groups. Deaths were rare: HPV (alone/coadministered) n = 25, controls n = 20 (n = 18 in blinded groups). pIMDs within 1 year were reported by 0.2% of HPV-16/18 vaccinees and controls. For each pIMD event category, no increased relative risks were reported for HPV-16/18 vaccinees versus controls. Coadministration did not change the overall safety profile. Pregnancy outcomes and withdrawal rates were similar between groups. Conclusions Analysis of safety data arising from 57 580 subjects and 96 704 HPV-16/18-vaccine doses shows that the incidences and distribution of AEs were similar among HPV-16/18-vaccine recipients and controls. No new safety signals were identified. The data confirm previous findings that HPV-16/18-vaccine has an acceptable benefit-risk profile in adolescent girls and

  8. Mann-Kendall Test for Analysis of Groundwater Contaminant Plume Stability and Evaluation of Sampling Frequency for Long-Term Monitoring - 13233

    SciTech Connect

    Walker, Jeffrey R.; Harrison, Toby R.

    2013-07-01

    This paper describes a spreadsheet-based approach for applying the Mann-Kendall (MK) Test to identify statistically significant increasing or decreasing concentration trends, stable concentration trends (not increasing or decreasing), and indeterminate concentration trends (no trend) defined by time-series groundwater monitoring data for inorganic, organic, or radiological contaminants. The approach has been applied in support of ongoing long-term monitoring (LTM) of groundwater contamination at the U.S. Department of Energy (DOE) Y-12 National Security Complex (Y-12) in Oak Ridge, Tennessee and elsewhere on the DOE Oak Ridge Reservation (ORR), and has proven effective at minimizing subjective bias in the evaluation and interpretation of contaminant concentration trend data. Application of the approach for the purposes of optimizing groundwater sampling frequency for LTM also is outlined. (authors)

  9. Long term follow-up concerning safety and efficacy of novel adhesion prophylactic agent for laparoscopic myomectomy in the prospective randomized ADBEE study.

    PubMed

    Cezar, Cristina; Tchartchian, Garri; Korell, Matthias; Ziegler, Nicole; Senshu, Kazuhisa; De Wilde, Maya Sophie; Herrmann, Anja; Larbig, Angelika; De Wilde, Rudy Leon

    2016-08-01

    We conducted a prospective randomized single blind - subject study in the University Clinic of Gynecology of Pius-Hospital Oldenburg. The primary objective of the ADBEE study was to assess the safety and manageability of ADBLOCK when used as an adjunct to laparoscopic surgery for the primary of myomas in women wishing to improve pregnancy outcomes. The study population included 32 women aged between 18-45 years, in good general health condition, who have not completed their family planning and who are undergoing primary ('virgin') laparoscopic myomectomy with an aim to improve pregnancy outcomes. The patients were randomized in 2 groups, ADBLOCK arm with 21 patients and surgery only arm with 11 patients. The study was single blind - subject and the investigators were blinded to treatment group assignment until completion of uterine suturing and prior to removal of the endoscope. A vigorous follow-up of subjects was organized, focusing on its two critical characteristics: completeness and duration. Completeness represented the percentage of subjects who returned to every planed follow - up appointments. The patients were evaluated in a specific period of time, which defined the duration of follow-up. Safety of the ADBLOCK was estimated after analyzing and documentation of any adverse events occurred, clinical and physical examination of patients as well as evaluation of laboratory measures. There were 25 adverse events reported in ADBLOCK treatment group and 12 events in NO-ADBLOCK group over the 24-months treatment. All adverse events in both treatment arms were not anticipated, with all events in the ADBLOCK group being resolved. At 28 days, there was no significant difference in proportion of events between the two treatments (p = 0.440). Overall, the number of events reported was low and the severity of events was generally mild with an unlikely or no relationship to treatment. There were no unanticipated device related adverse events seen in both treatment

  10. Evaluating litter decomposition and soil organic matter dynamics in earth system models: contrasting analysis of long-term litter decomposition and steady-state soil carbon

    NASA Astrophysics Data System (ADS)

    Bonan, G. B.; Wieder, W. R.

    2012-12-01

    litterfall and model-derived climatic decomposition index. While comparison with the LIDET 10-year litterbag study reveals sharp contrasts between CLM4 and DAYCENT, simulations of steady-state soil carbon show less difference between models. Both CLM4 and DAYCENT significantly underestimate soil carbon. Sensitivity analyses highlight causes of the low soil carbon bias. The terrestrial biogeochemistry of earth system models must be critically tested with observations, and the consequences of particular model choices must be documented. Long-term litter decomposition experiments such as LIDET provide a real-world process-oriented benchmark to evaluate models and can critically inform model development. Analysis of steady-state soil carbon estimates reveal additional, but here different, inferences about model performance.

  11. Effectiveness and Safety of Spot Scanning Proton Radiation Therapy for Chordomas and Chondrosarcomas of the Skull Base: First Long-Term Report

    SciTech Connect

    Ares, Carmen; Hug, Eugen B.; Lomax, Antony J.; Bolsi, Alessandra; Timmermann, Beate; Rutz, Hans Peter; Schuller, Jan C.; Pedroni, Eros; Goitein, Gudrun

    2009-11-15

    Purpose: To evaluate effectiveness and safety of spot-scanning-based proton radiotherapy (PT) in skull-base chordomas and chondrosarcomas. Methods and Materials: Between October 1998 and November 2005, 64 patients with skull-base chordomas (n = 42) and chondrosarcomas (n = 22) were treated at Paul Scherrer Institute with PT using spot-scanning technique. Median total dose for chordomas was 73.5 Gy(RBE) and 68.4 Gy(RBE) for chondrosarcomas at 1.8-2.0 Gy(RBE) dose per fraction. Local control (LC), disease specific survival (DSS), and overall survival (OS) rates were calculated. Toxicity was assessed according to CTCAE, v. 3.0. Results: Mean follow-up period was 38 months (range, 14-92 months). Five patients with chordoma and one patient with chondrosarcoma experienced local recurrence. Actuarial 5-year LC rates were 81% for chordomas and 94% for chondrosarcomas. Brainstem compression at the time of PT (p = 0.007) and gross tumor volume >25 mL (p = 0.03) were associated with lower LC rates. Five years rates of DSS and OS were 81% and 62% for chordomas and 100% and 91% for chondrosarcomas, respectively. High-grade late toxicity consisted of one patient with Grade 3 and one patient with Grade 4 unilateral optic neuropathy, and two patients with Grade 3 central nervous system necrosis. No patient experienced brainstem toxicity. Actuarial 5-year freedom from high-grade toxicity was 94%. Conclusions: Our data indicate safety and efficacy of spot-scanning based PT for skull-base chordomas and chondrosarcomas. With target definition, dose prescription and normal organ tolerance levels similar to passive-scattering based PT series, complication-free, tumor control and survival rates are at present comparable.

  12. Efficacy and Safety of a Hyaluronic Acid Filler to Correct Aesthetically Detracting or Deficient Features of the Asian Nose: A Prospective, Open-Label, Long-Term Study

    PubMed Central

    Liew, Steven; Scamp, Terrence; de Maio, Mauricio; Halstead, Michael; Johnston, Nicole; Silberberg, Michael; Rogers, John D.

    2016-01-01

    Background There is increasing interest among patients and plastic surgeons for alternatives to rhinoplasty, a common surgical procedure performed in Asia. Objectives To evaluate the safety, efficacy, and longevity of a hyaluronic acid filler in the correction of aesthetically detracting or deficient features of the Asian nose. Methods Twenty-nine carefully screened Asian patients had their noses corrected with the study filler (Juvéderm VOLUMA [Allergan plc, Dublin, Ireland] with lidocaine injectable gel), reflecting individualized treatment goals and utilizing a standardized injection procedure, and were followed for over 12 months. Results A clinically meaningful correction (≥1 grade improvement on the Assessment of Aesthetic Improvement Scale) was achieved in 27 (93.1%) patients at the first follow-up visit. This was maintained in 28 (96.6%) patients at the final visit, based on the independent assessments of a central non-injecting physician and the patients. At this final visit, 23 (79.3%) patients were satisfied or very satisfied with the study filler and 25 (86.2%) would recommend it to others. In this small series of patients, there were no serious adverse events (AEs), with all treatment-related AEs being mild to moderate, transient injection site reactions, unrelated to the study filler. Conclusions Using specific eligibility criteria, individualized treatment goals, and a standardized injection procedure, the study filler corrected aesthetically detracting or deficient features of the Asian nose, with the therapeutic effects lasting for over 12 months, consistent with a high degree of patient satisfaction. This study supports the safety and efficacy of this HA filler for specific nose augmentation procedures in selected Asian patients. Level of Evidence: 3 Therapeutic PMID:27301371

  13. TREATMENT EFFECTS OF WST11 VASCULAR TARGETED PHOTODYNAMIC THERAPY IN UROTHELIAL CELL CARCINOMA AND FEASIBILITY, SAFETY, AND LONG TERM OUTCOMES IN THE UPPER URINARY TRACT OF SWINE

    PubMed Central

    Murray, Katie S; Winter, Ashley G; Corradi, Renato Beluco; LaRosa, Stephen; Jebiwott, Sylvia; Somma, Alexander; Takaki, Haruyuki; Srimathveeravalli, Govindarajan; Lepherd, Michelle; Monette, Sebastien; Kim, Kwanghee; Scherz, Avigdor; Coleman, Jonathan A

    2016-01-01

    Purpose Surgical management of upper tract urothelial carcinoma requires removal of kidney and ureter, compromising renal function. Non-surgical alternatives have potentially prohibitive safety concerns. We examine the feasibility and safety of ablation of the ureter and renal pelvis using endoluminal vascular-targeted photodynamic therapy in a porcine model and report efficacy of WST11 vascular-targeted photodynamic therapy in a murine model. Materials and Methods Following approval, we performed 28 endoluminal ablations in the ureters and renal pelvis of 18 swine. Intravenous infusion of WST11 (4mg/kg) followed by laser illumination (10 minutes) was performed via percutaneous access or retrograde ureteroscopic approach. Animals were followed clinically with laboratory testing, imaging and histology was evaluated at several post-ablation time points. A murine xenograft was created with the 5637 human urothelial cell carcinoma line to determine sensitivity to this therapy. Results At 24 hours, 50 mW/cm laser fluence produced superficial necrosis of the ureter and deeper necrosis (penetrating the muscularis propria or adventitia) was produced by treatment with 200 mW/cm in the ureter and renal pelvis. At 4 weeks, superficial urothelium had regenerated over the treatment site. No symptomatic obstruction, clinically relevant hydronephrosis, or abnormality of lab testing was noted up to 4 weeks. In mice, 80% had no evidence of tumor at 19 days after WST11 vascular-targeted photodynamic therapy. Conclusions Urothelial cell carcinoma appears to be sensitive to WST11 vascular-targeted photodynamic therapy. Depth of WST11 vascular-targeted photodynamic therapy treatment effects can be modulated in a dose-dependent manner by titration of light intensity. Moreover, this treatment modality, applied to the porcine upper urinary tract, is feasible via antegrade and retrograde access. PMID:26860792

  14. Evaluation of a deposit in the vicinity of the PBU L-106 Site, North Slope, Alaska, for a potential long-term test of gas production from hydrates

    SciTech Connect

    Moridis, G.J.; Reagan, M.T.; Boyle, K.L.; Zhang, K.

    2010-05-01

    As part of the effort to investigate the technical feasibility of gas production from hydrate deposits, a long-term field test (lasting 18-24 months) is under consideration in a project led by the U.S. Department of Energy. We evaluate a candidate deposit involving the C-Unit in the vicinity of the PBU-L106 site in North Slope, Alaska. This deposit is stratigraphically bounded by impermeable shale top and bottom boundaries (Class 3), and is characterized by high intrinsic permeabilities, high porosity, high hydrate saturation, and a hydrostatic pressure distribution. The C-unit deposit is composed of two hydrate-bearing strata separated by a 30-ft-thick shale interlayer, and its temperatrure across its boundaries ranges between 5 and 6.5 C. We investigate by means of numerical simulation involving very fine grids the production potential of these two deposits using both vertical and horizontal wells. We also explore the sensitivity of production to key parameters such as the hydrate saturation, the formation permeability, and the permeability of the bounding shale layers. Finally, we compare the production performance of the C-Unit at the PBU-L106 site to that of the D-Unit accumulation at the Mount Elbert site, a thinner, single-layer Class 3 deposit on the North Slope of Alaska that is shallower, less-pressurized and colder (2.3-2.6 C). The results indicate that production from horizontal wells may be orders of magnitude larger than that from vertical ones. Additionally, production increases with the formation permeability, and with a decreasing permeability of the boundaries. The effect of the hydrate saturation on production is complex and depends on the time frame of production. Because of higher production, the PBU-L106 deposit appears to have an advantage as a candidate for the long-term test.

  15. Metabonomics evaluation of urine from rats administered with phorate under long-term and low-level exposure by ultra-performance liquid chromatography-mass spectrometry.

    PubMed

    Sun, Xiaowei; Xu, Wei; Zeng, Yan; Hou, Yurong; Guo, Lin; Zhao, Xiujuan; Sun, Changhao

    2014-02-01

    The purpose of this study was to investigate the toxic effect of long-term and low-level exposure to phorate using a metabonomics approach based on ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). Male Wistar rats were given phorate daily in drinking water at low doses of 0.05, 0.15 or 0.45 mg kg⁻¹ body weight (BW) for 24 weeks consecutively. Rats in the control group were given an equivalent volume of drinking water. Compared with the control group, serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (TBIL), urea nitrogen (BUN) and creatinine (CR) were increased in the middle- and high-dose groups whereas albumin (ALB) and cholinesterase (CHE) were decreased. Urine metabonomics profiles were analyzed by UPLC-MS. Compared with the control group, 12 metabolites were significantly changed in phorate-treated groups. In the negative mode, metabolite intensities of uric acid, suberic acid and citric acid were significantly decreased in the middle- and high-dose groups, whereas indoxyl sulfic acid (indican) and cholic acid were increased. In the positive mode, uric acid, creatinine, kynurenic acid and xanthurenic acid were significantly decreased in the middle- and high-dose groups, but 7-methylguanine (N⁷G) was increased. In both negative and positive modes, diethylthiophosphate (DETP) was significantly increased, which was considered as a biomarker of exposure to phorate. In conclusion, long-term and low-level exposure to phorate can cause disturbances in energy-related metabolism, liver and kidney function, the antioxidant system, and DNA damage. Moreover, more information can be provided on the evaluation of toxicity of phorate using metabonomics combined with clinical chemistry.

  16. Evaluating litter decomposition in earth system models with long-term litterbag experiments: an example using the Community Land Model version 4 (CLM4).

    PubMed

    Bonan, Gordon B; Hartman, Melannie D; Parton, William J; Wieder, William R

    2013-03-01

    Decomposition is a large term in the global carbon budget, but models of the earth system that simulate carbon cycle-climate feedbacks are largely untested with respect to litter decomposition. We tested the litter decomposition parameterization of the community land model version 4 (CLM4), the terrestrial component of the community earth system model, with data from the long-term intersite decomposition experiment team (LIDET). The LIDET dataset is a 10-year study of litter decomposition at multiple sites across North America and Central America. We performed 10-year litter decomposition simulations comparable with LIDET for 9 litter types and 20 sites in tundra, grassland, and boreal, conifer, deciduous, and tropical forest biomes using the LIDET-provided climatic decomposition index to constrain temperature and moisture effects on decomposition. We performed additional simulations with DAYCENT, a version of the CENTURY model, to ask how well an established ecosystem model matches the observations. The results show large discrepancy between the laboratory microcosm studies used to parameterize the CLM4 litter decomposition and the LIDET field study. Simulated carbon loss is more rapid than the observations across all sites, and nitrogen immobilization is biased high. Closer agreement with the observations requires much lower decomposition rates, obtained with the assumption that soil mineral nitrogen severely limits decomposition. DAYCENT better replicates the observations, for both carbon mass remaining and nitrogen, independent of nitrogen limitation. CLM4 has low soil carbon in global earth system simulations. These results suggest that this bias arises, in part, from too rapid litter decomposition. More broadly, the terrestrial biogeochemistry of earth system models must be critically tested with observations, and the consequences of particular model choices must be documented. Long-term litter decomposition experiments such as LIDET provide a real

  17. Evaluation of pesticide monitoring strategies in agricultural streams based on the toxic-unit concept--experiences from long-term measurements.

    PubMed

    Bundschuh, Mirco; Goedkoop, Willem; Kreuger, Jenny

    2014-06-15

    The European Water Framework Directive requires surface water bodies to have a good chemical and ecological status. Although relatively few pesticides are included in the list of priority pollutants, they pose, due to their intrinsic biological activity, a significant risk for the integrity of aquatic ecosystems. In this context, the pesticide (up to 128 pesticides including some transformation products) exposure pattern in four agricultural streams and two rivers was determined from 2002 to 2011 under the umbrella of the Swedish national monitoring program employing time-proportional and grab sampling strategies, respectively. After transforming the measured pesticide concentrations into toxic units, the European Uniform Principles for algae (chronic), invertebrates and fish (both acute), which are partly employed as benchmark for pesticide regulation, were only occasionally (<2%) exceeded. Moreover, this evaluation showed no long-term trends over the years. However, recent publications suggested that those thresholds are not protective for ecosystem structure and function, indicating a risk of up to 20% and 35% of the samples from the agricultural streams and the rivers, respectively. Moreover, the monitoring data show a continuous but rather low toxic potential of pesticides for all three trophic levels throughout the year, which suggests pesticides as an evolutionary force in agriculturally impacted aquatic ecosystems. However, the flow-triggered sampling, which was implemented as an additional sampling strategy in one of the agricultural streams starting in 2006, displayed an up to 7-fold underestimation of the maximum concentration in terms of toxic units for daphnids and fish during run-off events. The present study thus underpins that the optimal sampling design for pesticide monitoring strongly depends on its overall purpose. If the long-term exposure pattern is of concern a time-proportional composite sampling strategy is recommended, while for an

  18. Long-term environmental stewardship.

    SciTech Connect

    Nagy, Michael David

    2010-08-01

    The purpose of this Supplemental Information Source Document is to effectively describe Long-Term Environmental Stewardship (LTES) at Sandia National Laboratories/New Mexico (SNL/NM). More specifically, this document describes the LTES and Long-Term Stewardship (LTS) Programs, distinguishes between the LTES and LTS Programs, and summarizes the current status of the Environmental Restoration (ER) Project.

  19. Presynaptic long-term plasticity

    PubMed Central

    Yang, Ying; Calakos, Nicole

    2013-01-01

    Long-term synaptic plasticity is a major cellular substrate for learning, memory, and behavioral adaptation. Although early examples of long-term synaptic plasticity described a mechanism by which postsynaptic signal transduction was potentiated, it is now apparent that there is a vast array of mechanisms for long-term synaptic plasticity that involve modifications to either or both the presynaptic terminal and postsynaptic site. In this article, we discuss current and evolving approaches to identify presynaptic mechanisms as well as discuss their limitations. We next provide examples of the diverse circuits in which presynaptic forms of long-term synaptic plasticity have been described and discuss the potential contribution this form of plasticity might add to circuit function. Finally, we examine the present evidence for the molecular pathways and cellular events underlying presynaptic long-term synaptic plasticity. PMID:24146648

  20. A long-term noninterventional safety study of adjunctive lacosamide therapy in patients with epilepsy and uncontrolled partial-onset seizures.

    PubMed

    Steinhoff, Bernhard J; Eckhardt, Klaus; Doty, Pamela; De Backer, Marc; Brunnert, Marcus; Schulze-Bonhage, Andreas

    2016-05-01

    This noninterventional, observational, postauthorization safety study (SP0942, NCT00771927) evaluated the incidence of predefined cardiovascular- (CV) and psychiatric-related treatment-emergent adverse events (TEAEs), in patients with epilepsy and uncontrolled partial-onset seizures, when initiating adjunctive therapy with lacosamide or another approved antiepileptic drug (AED) according to standard medical practice. Active recording of predefined TEAEs of interest took place at three-monthly recommended visits for up to 12months. Of 1004 patients who received at least one dose of adjunctive AEDs, 511 initially added lacosamide therapy, 493 added another AED, 69 were ≥65years of age, and 72 took concomitant antiarrhythmic drugs. Patients in the lacosamide cohort had a higher median frequency of partial-onset seizures (6.0 versus 3.5 per 28days) despite taking more concomitant AEDs (84.9% versus 66.9% took ≥2) at baseline. Patients who added lacosamide took a modal dose of 200mg/day over the treatment period (n=501), and 50.1% (256/511) completed 12months of treatment. Fifty-one point nine percent (256/493) of patients who added another AED completed the study, with the most commonly added AED being levetiracetam (28.4%). Four patients (0.8%) in each cohort, all <65years of age, reported predefined CV-related TEAEs. None were considered serious or led to discontinuation. One event each of sinus bradycardia (lacosamide), atrioventricular block first degree (lacosamide), and syncope (other AED) were judged to be treatment-related. Another patient in the other AED cohort reported bradycardia while taking concomitant antiarrhythmic drugs. Predefined psychiatric-related TEAEs were reported by 21 patients (4.1%) in the lacosamide cohort and 27 patients (5.5%) in the other AED cohort. Depression was the most common to be treatment-related (7/11 and 12/18 of patients reporting treatment-related psychiatric TEAEs, respectively). Serious psychiatric-related TEAEs were

  1. Long-term plutonium storage: Design concepts

    SciTech Connect

    Wilkey, D.D.; Wood, W.T.; Guenther, C.D.

    1994-08-01

    An important part of the Department of Energy (DOE) Weapons Complex Reconfiguration (WCR) Program is the development of facilities for long-term storage of plutonium. The WCR design goals are to provide storage for metals, oxides, pits, and fuel-grade plutonium, including material being held as part of the Strategic Reserve and excess material. Major activities associated with plutonium storage are sorting the plutonium inventory, material handling and storage support, shipping and receiving, and surveillance of material in storage for both safety evaluations and safeguards and security. A variety of methods for plutonium storage have been used, both within the DOE weapons complex and by external organizations. This paper discusses the advantages and disadvantages of proposed storage concepts based upon functional criteria. The concepts discussed include floor wells, vertical and horizontal sleeves, warehouse storage on vertical racks, and modular storage units. Issues/factors considered in determining a preferred design include operational efficiency, maintenance and repair, environmental impact, radiation and criticality safety, safeguards and security, heat removal, waste minimization, international inspection requirements, and construction and operational costs.

  2. Long-Term (1-Year) Safety and Efficacy of a Single 6-mL Injection of Hylan G-F 20 in Indian Patients with Symptomatic Knee Osteoarthritis

    PubMed Central

    Pal, Sarvajeet; Thuppal, Sreedhar; Reddy, K.J; Avasthi, Sachin; Aggarwal, Anish; Bansal, Himanshu; Mohanasundaram, Senthilnathan; Bailleul, Francois

    2014-01-01

    Introduction: The prevalence of symptomatic knee osteoarthritis (OA) among Asians ≥65 years is estimated to double by 2040. This study was designed to evaluate the safety and efficacy of a single, 6-mL intra-articular injection of hylan G-F 20 in Indian patients with knee OA at 26 weeks through to 52 weeks. Methods: This study was an open-label, multicentre, phase 4 clinical trial. Enrolled patients (N=394) were ≥30 years old with Kellgren-Lawrence grade 1–3 OA; all patients received hylan G-F 20. WOMAC, SF-12, PTGA, and COGA scores, and OA medication use were evaluated at weeks 1, 4, 12, 26, 39, and 52 (initial treatment phase). At 26, 39, or 52 weeks, eligible patients could participate in a repeat treatment phase. McNemar-Bowkers, paired t-tests and ANOVA analyses were performed (alpha=0.05). Results: At 26 weeks, statistically significant changes from baseline were observed in all efficacy parameters, including the primary efficacy endpoint of WOMAC A1 (p<0.0001). Improvements continued for 52 weeks. No significant changes occurred in concomitant medication use. Eleven patients (2.8%) were re-injected at week 26 or 52. After repeat injection, statistically significant decreases were observed in WOMAC A1, WOMAC C and PTGA scores (p≤0.028). Twenty-three (5.8%) patients reported 26 local target knee AEs. Conclusion: Among Indian patients within this study, a 6-mL hylan G-F 20 injection was well tolerated and effective in treating symptomatic knee OA with significant long-term (1 year) improvement of outcomes. When needed, repeat treatment was safe and efficacious for 4 weeks. Trial Registration: Clinical Trial Registry of India (CTRI/2010/091/000052) www.ctri.nic.in/Clinicaltrials/login.php. PMID:25328555

  3. Modeling the impact of climate change in Germany with biosphere models for long-term safety assessment of nuclear waste repositories.

    PubMed

    Staudt, C; Semiochkina, N; Kaiser, J C; Pröhl, G

    2013-01-01

    Biosphere models are used to evaluate the exposure of populations to radionuclides from a deep geological repository. Since the time frame for assessments of long-time disposal safety is 1 million years, potential future climate changes need to be accounted for. Potential future climate conditions were defined for northern Germany according to model results from the BIOCLIM project. Nine present day reference climate regions were defined to cover those future climate conditions. A biosphere model was developed according to the BIOMASS methodology of the IAEA and model parameters were adjusted to the conditions at the reference climate regions. The model includes exposure pathways common to those reference climate regions in a stylized biosphere and relevant to the exposure of a hypothetical self-sustaining population at the site of potential radionuclide contamination from a deep geological repository. The end points of the model are Biosphere Dose Conversion factors (BDCF) for a range of radionuclides and scenarios normalized for a constant radionuclide concentration in near-surface groundwater. Model results suggest an increased exposure of in dry climate regions with a high impact of drinking water consumption rates and the amount of irrigation water used for agriculture.

  4. Safety and efficacy of long-term esomeprazole 20 mg in Japanese patients with a history of peptic ulcer receiving daily non-steroidal anti-inflammatory drugs

    PubMed Central

    2013-01-01

    Background Non-steroidal anti-inflammatory drugs (NSAIDs) are an effective and common treatment for chronic pain disorders, but long-term use is associated with risk of potentially life-threatening gastrointestinal adverse events (AEs). The proton pump inhibitor esomeprazole has been found to be effective for gastroprotection in NSAID users, but few long-term studies have been conducted in Japan. Methods This was an open-label, multicentre, single-arm, prospective 1-year study of treatment with esomeprazole (20 mg once daily) in Japanese patients (aged ≥20 years) with endoscopic evidence of previous peptic ulcer and receiving daily oral NSAID therapy (at a stable dose) for a chronic condition. Eligibility was not dictated by type of oral NSAID. The primary objective was to determine long-term safety and tolerability of esomeprazole. Efficacy for prevention of peptic ulcers was also determined (Kaplan-Meier method). All statistical analyses were descriptive. Results A total of 130 patients (73.1% women, mean age 62.1 years, 43.8% Helicobacter pylori-positive) received treatment with esomeprazole in addition to long-term NSAID therapy (most commonly for rheumatoid arthritis [n=42] and osteoarthritis [n=34]). Loxoprofen, meloxicam and diclofenac were the most commonly used NSAIDs; cyclo-oxygenase (COX)-2 selective agents were used by 16.2% of patients (n=21). Long-term compliance with esomeprazole (capsule counts) was >75% for the majority of patients. Although 16.9% of patients (n=22) experienced AEs judged to be possibly related to treatment with esomeprazole, they were mostly mild and transient. The most commonly reported possibly treatment-related AEs were abnormal hepatic function, headache, increased γ-glutamyltransferase levels and muscle spasms (2 patients each). Overall, 95.9% (95% confidence interval: 92.3, 99.4) of patients remained ulcer free at 1 year. Conclusion Long-term treatment with esomeprazole (20 mg once daily) is well tolerated and

  5. A Multicentre Prospective Evaluation of the Impact of Renal Insufficiency on In-hospital and Long-term Mortality of Patients with Acute ST-elevation Myocardial Infarction

    PubMed Central

    Li, Chao; Hu, Dayi; Shi, Xubo; Li, Li; Yang, Jingang; Song, Li; Ma, Changsheng

    2015-01-01

    Background: Numerous previous studies have shown that renal insufficiency (RI) in patients with acute coronary syndrome is associated with poor cardiovascular outcomes. These studies do not well address the impact of RI on the long-term outcome of patients with acute ST-elevation myocardial infarction (STEMI) in China. The aim of this study was to investigate the association of admission RI and inhospital and long-term mortality of patients with acute STEMI. Methods: This was a multicenter, observational, prospective-cohort study. 718 consecutive patients were admitted to 19 hospitals in Beijing within 24 hours of onset of STEMI, between January 1,2006 and December 31,2006. Estimation of glomerular filtration rate (eGFR) was calculated using the modified abbreviated modification of diet in renal disease equation-based on the Chinese chronic kidney disease patients. The patients were categorized according to eGFR, as normal renal dysfunction (eGFR ≥ 90 ml∙min-1∙1.73 m-2), mild RI (60 ml∙min-1∙1.73 m-2 ≤ eGFR < 90 ml∙min-1∙1.73 m-2) and moderate or severe RI (eGFR < 60 ml∙min-1∙1.73 m-2). The association between RI and inhospital and 6-year mortality of was evaluated. Results: Seven hundred and eighteen patients with STEMI were evaluated. There were 551 men and 167 women with a mean age of 61.0 ± 13.0 years. Two hundred and eighty patients (39.0%) had RI, in which 61 patients (8.5%) reached the level of moderate or severe RI. Patients with RI were more often female, elderly, hypertensive, and more patients had heart failure and stroke with higher killip class. Patients with RI were less likely to present with chest pain. The inhospital mortality (1.4% vs. 5.9% vs. 22.9%, P < 0.001), 6-year all-cause mortality (9.5% vs. 19.8 vs. 45.2%, P < 0.001) and 6-year cardiac mortality (2.9% vs. 12.2% vs. 23.8%, P < 0.001) were markedly increased in patients with RI. After adjusting for other confounding factors, classification of admission renal function

  6. Long-term effects of dredging operations program. long-term evaluation of plants and animals colonizing contaminated estuarine dredged material placed in both upland and wetland environments. Final report

    SciTech Connect

    Brandon, D.L.; Lee, C.R.; Simmers, J.W.; Skogerboe, J.G.; Wilhelm, G.S.

    1991-09-01

    Contaminated sediment was dredged from Black Rock Harbor, Connecticut, in October 1983 and placed in aquatic, upland, and wetland environments as part of the Field Verification Program (FVP), conducted during the period 1981-1986. Laboratory tests were conducted on the sediment prior to dredging to evaluate potential contaminant mobility under each of the disposal alternatives. Prior to dredging for upland disposal and wetland creation at the FVP field site, upland tests (i.e., plant and earthworm bioassays) and wetland tests (i.e., plant, sandworm, snail, and mussel bioassays) were conducted. Laboratory test results were sub-subsequently field verified at the field test site at Tongue Point, Bridgeport, CT. The results of the upland disposal and wetland creation portions of the FVP, and the changes occurring since completion of the FVP for each disposal environment, are summarized herein. The emphasis of this report is on the contaminant mobility of heavy metals. This interim report includes data collected through 1989. Contaminant mobility and the progressive development of the upland and wetland ecosystems at this site will be evaluated until September 1985.

  7. Design of, and first data from, PATRO Children, a multicentre, noninterventional study of the long-term efficacy and safety of Omnitrope® in children requiring growth hormone treatment

    PubMed Central

    Pfäffle, Roland; Schwab, Karl Otfried; Marginean, Otilia; Walczak, Mieczyslaw; Szalecki, Mieczyslaw; Schuck, Ellen; Zucchini, Stefano

    2013-01-01

    Objective: To describe the rationale, design and first data from PATRO Children, a postmarketing surveillance of the long-term efficacy and safety of somatropin (Omnitrope®) for the treatment of children requiring growth hormone treatment. Methods: PATRO Children is a multicentre, open, longitudinal, noninterventional study being conducted in children’s hospitals and specialised endocrinology clinics. The primary objective is to assess the long-term safety of Omnitrope® in routine clinical practice. Eligible patients are infants, children and adolescents (male or female) who are receiving treatment with Omnitrope® and who have provided informed consent. Patients who have been treated with another recombinant human growth hormone (rhGH) product before starting Omnitrope® are eligible for inclusion. All adverse events (AEs) are monitored and recorded, with particular emphasis on: long-term safety; the recording of malignancies; the occurrence and clinical impact of anti-hGH antibodies; the development of diabetes during Omnitrope® treatment in children short for gestational age (SGA); safety issues in patients with Prader–Willi syndrome (PWS). Efficacy assessments include auxological parameters, plus insulin-like growth factor-1 and insulin-like growth factor binding protein-3. Results: As of September 2012, 1837 patients were enrolled in the study from 184 sites in 10 European countries. To date, efficacy data are reassuring and consistent with previous studies. In addition, there have been no confirmed cases of diabetes occurring under Omnitrope® treatment, no reports of malignancy and no safety issues in PWS patients. Conclusions: The efficacy and safety profile of Omnitrope® in the PATRO Children study so far are as expected. The ongoing study will extend the safety database for Omnitrope®, and rhGH products more generally, in paediatric indications. Of particular interest, PATRO Children will add important information on the diabetogenic potential of

  8. Long term complications of diabetes

    MedlinePlus

    ... this page: //medlineplus.gov/ency/patientinstructions/000327.htm Long term complications of diabetes To use the sharing ... sores and infections. If it goes on too long, your toes, foot, or leg may need to ...

  9. Abdominal Pain, Long-Term

    MedlinePlus

    MENU Return to Web version Abdominal Pain, Long-term See complete list of charts. Ongoing or recurrent abdominal pain, also called chronic pain, may be difficult to diagnose, causing frustration for ...

  10. Long-term biomass research

    SciTech Connect

    Not Available

    1981-03-01

    Some of DOE's long term R and D programs for biomass are summarized in this article. These include research efforts in the fields of anaerobic digestion, energy farming, short rotation cultivation and aquatic farming. (DMC)

  11. Long-term efficacy and safety of oxycodone–naloxone prolonged release in geriatric patients with moderate-to-severe chronic noncancer pain: a 52-week open-label extension phase study

    PubMed Central

    Guerriero, Fabio; Roberto, Anna; Greco, Maria Teresa; Sgarlata, Carmelo; Rollone, Marco; Corli, Oscar

    2016-01-01

    Background Two-thirds of older people suffer from chronic pain and finding valid treatment options is essential. In this 1-yearlong investigation, we evaluated the efficacy and safety of prolonged-release oxycodone–naloxone (OXN-PR) in patients aged ≥70 (mean 81.7) years. Methods In this open-label prospective study, patients with moderate-to-severe noncancer chronic pain were prescribed OXN-PR for 1 year. The primary endpoint was the proportion of patients who achieved ≥30% reduction in pain intensity after 52 weeks of treatment, without worsening bowel function. The scheduled visits were at baseline (T0), after 4 weeks (T4), and after 52 weeks (T52). Results Fifty patients completed the study. The primary endpoint was achieved in 78% of patients at T4 and 96% at T52 (P<0.0001). Pain intensity, measured on a 0–10 numerical rating scale, decreased from 6.0 at T0 to 2.8 at T4 and to 1.7 at T52 (P<0.0001). Mean daily dose of oxycodone increased from 10 to 14.4 mg (T4) and finally to 17.4 mg (T52). Bowel Function Index from 35.1 to 28.7 at T52. No changes were observed in cognitive functions (Mini-Mental State Examination evaluation), while daily functioning improved (Barthel Index from 53.1 to 61.0, P<0.0001). The Screener and Opioid Assessment for Patients with Pain-Revised score at 52 weeks was 2.6 (standard deviation 1.6), indicating a low risk of aberrant medication-related behavior. In general, OXN-PR was well tolerated. Conclusion This study of the long-term treatment of chronic pain in a geriatric population with OXN-PR shows satisfying analgesic effects achieved with a stable low daily dose, coupled with a good safety profile and, in particular, with a reduction of constipation, often present during opioid therapy. Our findings support the indications of the American Geriatrics Society, suggesting the use of opioids to treat pain in older people not responsive to acetaminophen or nonsteroidal anti-inflammatory drugs. PMID:27143857

  12. Long term treatment of polymyalgia rheumatica with deflazacort.

    PubMed Central

    Cimmino, M A; Moggiana, G; Montecucco, C; Caporali, R; Accardo, S

    1994-01-01

    OBJECTIVES--To evaluate the long term efficacy and tolerability of deflazacort, a corticosteroid reputed to have only minor side effects, in the treatment of polymyalgia rheumatica (PMR). METHODS--In a prospective open study, deflazacort was administered at an average initial dose of 21.8 mg/day for a mean period of 19 months in 40 patients with PMR. RESULTS--A highly significant improvement of clinical and laboratory parameters occurred one month after therapy onset. This improvement persisted for the whole study period. Laboratory parameters of tolerability did not change during the study. Mild to moderate steroid-related side effects occurred in 57.9% of the patients. CONCLUSIONS--Deflazacort is effective in the treatment of PMR. Its long term safety profile may be superior to that of other corticosteroids. PMID:8017988

  13. Long-term home care research.

    PubMed

    Green, J H

    1989-11-01

    The population of seniors is growing and health service reimbursement is shrinking. Long-term home health care services were developed with an assumption that the services would decrease costs. This assumption has not been validated. What has been recognized is that long-term home health care targets a new and growing population of frail seniors who need services but are probably not at risk for institutionalization. The impact of long-term home care services on the health status and quality of life of seniors and caregivers has been limited by outcome measurement problems. There are indications that the services improved life satisfaction and reduced services needs, but further evaluations need to replicate the outcomes. In effect, long-term outcomes have not been sufficiently explored. Further research also needs to assist us in identifying outcomes for certain services with precise target populations. Public policy questions are ahead. Should a program that can increase costs, has demonstrated some but not dramatic impacts on quality of life and health status, and has the possibility of expansion, be funded? The question is obviously debatable. From a nursing perspective of health promotion and prevention, the answer is "yes." Funding should be continued in conjunction with increased research on the program impacts. In Kane's (1988) analysis of the Channeling experiments, she summarized the situation effectively: Knowing these facts, we are now in a position to reformulate public policies to design a system of long-term care that satisfies the preferences of consumers and protects them from catastrophic long-term expenses, while promoting the triple virtues of acceptable, quality, equitable access, and defensible costs. . . Nothing in the Channeling results should prevent us from going ahead and trying to develop both community based and institutionally based long-term services in which this country can take pride.

  14. Evaluation of the resilience of a full-scale down-flow hanging sponge reactor to long-term outages at a sewage treatment plant in India.

    PubMed

    Onodera, Takashi; Takayama, Daisuke; Ohashi, Akiyoshi; Yamaguchi, Takashi; Uemura, Shigeki; Harada, Hideki

    2016-10-01

    Resilience to process outages is an essential requirement for sustainable wastewater treatment systems in developing countries. In this study, we evaluated the ability of a full-scale down-flow hanging sponge (DHS) reactor to recover after a 10-day outage. The DHS tested in this study uses polyurethane sponge as packing material. This full-scale DHS reactor has been tested over a period of about 4 years in India with a flow rate of 500 m(3)/day. Water was not supplied to the DHS reactor that was subjected to the 10-day outage; however, the biomass did not dry out because the sponge was able to retain enough water. Soon after the reactor was restarted, a small quantity of biomass, amounting to only 0.1% of the total retained biomass, was eluted. The DHS effluent achieved satisfactory removal of suspended solids, chemical oxygen demand, and ammonium nitrogen within 90, 45, and 90 min, respectively. Conversely, fecal coliforms in the DHS effluent did not reach satisfactory levels within 540 min; instead, the normal levels of fecal coliforms were achieved within 3 days. Overall, the tests demonstrated that the DHS reactor was sufficiently robust to withstand long-term outages and achieved steady state soon after restart. This reinforces the suitability of this technology for developing countries. PMID:27450993

  15. Evaluation of the resilience of a full-scale down-flow hanging sponge reactor to long-term outages at a sewage treatment plant in India.

    PubMed

    Onodera, Takashi; Takayama, Daisuke; Ohashi, Akiyoshi; Yamaguchi, Takashi; Uemura, Shigeki; Harada, Hideki

    2016-10-01

    Resilience to process outages is an essential requirement for sustainable wastewater treatment systems in developing countries. In this study, we evaluated the ability of a full-scale down-flow hanging sponge (DHS) reactor to recover after a 10-day outage. The DHS tested in this study uses polyurethane sponge as packing material. This full-scale DHS reactor has been tested over a period of about 4 years in India with a flow rate of 500 m(3)/day. Water was not supplied to the DHS reactor that was subjected to the 10-day outage; however, the biomass did not dry out because the sponge was able to retain enough water. Soon after the reactor was restarted, a small quantity of biomass, amounting to only 0.1% of the total retained biomass, was eluted. The DHS effluent achieved satisfactory removal of suspended solids, chemical oxygen demand, and ammonium nitrogen within 90, 45, and 90 min, respectively. Conversely, fecal coliforms in the DHS effluent did not reach satisfactory levels within 540 min; instead, the normal levels of fecal coliforms were achieved within 3 days. Overall, the tests demonstrated that the DHS reactor was sufficiently robust to withstand long-term outages and achieved steady state soon after restart. This reinforces the suitability of this technology for developing countries.

  16. Evaluation of long-term corrosion durability and self-healing ability of scratched coating systems on carbon steel in a marine environment

    NASA Astrophysics Data System (ADS)

    Zhao, Xia; Chen, Changwei; Xu, Weichen; Zhu, Qingjun; Ge, Chengyue; Hou, Baorong

    2016-09-01

    Defects in protective-coating systems on steel surfaces are inevitable in practical engineering applications. A composite coating system, including a primer, middle coat and topcoat, were used to protect carbon steel from corrosion in a marine environment. Two environmental additives, glass fibers and thiourea, were applied in the middle coat to modify the coating system. The long-term corrosion durability and self-healing ability of the scratched coating system were evaluated by multiple methods. Results of the electrochemical technologies indicated that the coating system that contained 0.5 wt.% fibers and 0.5 wt.% thiourea presented good corrosion protection and self-healing for carbon steel when immersed in 3.5% NaCl for 120 d. Evolution of localized corrosion factors with time, as obtained from the current distribution showed that fibers combined with thiourea could inhibit the occurrence of local corrosion in scratched coating systems and retarded the corrosion development significantly. Surface characterization suggested that adequate thiourea could be absorbed uniformly on fibers for a long time to play an important role in protecting the carbon steel. Finally, schematic models were established to demonstrate the action of fibers and thiourea on the exposed surface of the carbon steel and the scratched coating system in the entire deterioration process.

  17. A modelling approach to evaluate the long-term effect of soil texture on spring wheat productivity under a rain-fed condition.

    PubMed

    He, Yong; Hou, Lingling; Wang, Hong; Hu, Kelin; McConkey, Brian

    2014-01-01

    Soil surface texture is an important environmental factor that influences crop productivity because of its direct effect on soil water and complex interactions with other environmental factors. Using 30-year data, an agricultural system model (DSSAT-CERES-Wheat) was calibrated and validated. After validation, the modelled yield and water use (WU) of spring wheat (Triticum aestivum L.) from two soil textures (silt loam and clay) under rain-fed condition were analyzed. Regression analysis showed that wheat grown in silt loam soil is more sensitive to WU than wheat grown in clay soil, indicating that the wheat grown in clay soil has higher drought tolerance than that grown in silt loam. Yield variation can be explained by WU other than by precipitation use (PU). These results demonstrated that the DSSAT-CERES-Wheat model can be used to evaluate the WU of different soil textures and assess the feasibility of wheat production under various conditions. These outcomes can improve our understanding of the long-term effect of soil texture on spring wheat productivity in rain-fed condition. PMID:25074796

  18. [Effects of long-term fertilization on reddish paddy soil quality and its evaluation in a typical double-rice cropping region of China].

    PubMed

    Nie, Jun; Yang, Zeng-Ping; Zheng, Sheng-Xian; Liao, Yu-Lin; Xie, Jian; Xiang, Yan-Wen

    2010-06-01

    In order to quantify the effects of 27 years application of chemical fertilizers, pig manure, and rice straw on the reddish paddy soil quality in double rice cropping region, the indices of soil bulk density, porosity, maximum water holding capacity, normalized mean weight diameter, pH, cation exchange capacity, available nutrients, organic matter, microbial biomass C, enzyme activities, and rice yield were selected as the evaluation indicators, and classified into four functional groups, i. e., resistance to physical degradation, plant nutrients supply and storage, resistance to biochemical degradation, and sustaining of crop productivity. The soil quality index (SQI) was calculated based on the four functional groups. The results showed that the SQI ranged from 0.544 in treatment CK to 0.729 in treatment NPK plus rice straw. Treatments PK, NP, and NK induced soil degradation, compared to treatment NPK. The deficiencies of soil P and K were the main limiting factors for the double rice productivity in reddish paddy soil area. Even though 30 t x hm(-2) x a(-1) of pig manure and 4.2 t x hm(-2) x a(-1) of rice straw were applied, the soil P and K were still not adequate for the requirement of rice growth. There was no obvious effect of long-term application of lime on the reddish paddy soil quality. The combined application of NPK with organic manure was an important and effective measure in improving soil quality in double rice cropping regions of Southern China. PMID:20873620

  19. Evaluation of Passive Samplers for Long-Term Monitoring of Organic Compounds in the Untreated Drinking Water Supply for the City of Eugene, Oregon, September-October 2007

    USGS Publications Warehouse

    McCarthy, Kathleen A.; Alvarez, David A.; Anderson, Chauncey W.; Cranor, Walter L.; Perkins, Stephanie D.; Schroeder, Vickie

    2009-01-01

    Two types of passive samplers, polar organic chemical integrative samplers (POCIS) and semipermeable membrane devices (SPMDs), were deployed at three sites in the McKenzie River basin during September-October 2007. The McKenzie River is the source of drinking water for the city of Eugene, Oregon, and the work presented here was designed to evaluate the use of POCIS and SMPDs as part of a long-term monitoring plan for the river. Various compounds were detected in extracts from the POCIS and SPMDs, indicating that some compounds of concern are present in the McKenzie River basin, including the intake for the drinking water plant. However, most concentrations were near the quantitation limits of the analytical methods used - generally at subnanogram per liter concentrations - and would not have been detectable with conventional water sampling and analysis methods. These results indicate that both POCIS and SPMDs are well suited to monitor organic compounds in the McKenzie River basin.

  20. A modelling approach to evaluate the long-term effect of soil texture on spring wheat productivity under a rain-fed condition.

    PubMed

    He, Yong; Hou, Lingling; Wang, Hong; Hu, Kelin; McConkey, Brian

    2014-07-30

    Soil surface texture is an important environmental factor that influences crop productivity because of its direct effect on soil water and complex interactions with other environmental factors. Using 30-year data, an agricultural system model (DSSAT-CERES-Wheat) was calibrated and validated. After validation, the modelled yield and water use (WU) of spring wheat (Triticum aestivum L.) from two soil textures (silt loam and clay) under rain-fed condition were analyzed. Regression analysis showed that wheat grown in silt loam soil is more sensitive to WU than wheat grown in clay soil, indicating that the wheat grown in clay soil has higher drought tolerance than that grown in silt loam. Yield variation can be explained by WU other than by precipitation use (PU). These results demonstrated that the DSSAT-CERES-Wheat model can be used to evaluate the WU of different soil textures and assess the feasibility of wheat production under various conditions. These outcomes can improve our understanding of the long-term effect of soil texture on spring wheat productivity in rain-fed condition.

  1. Long-term consequences of non-intentional flows of substances: Modelling non-intentional flows of lead in the Dutch economic system and evaluating their environmental consequences

    SciTech Connect

    Elshkaki, Ayman Voet, Ester van der; Holderbeke, Mirja van; Timmermans, Veerle

    2009-06-15

    Substances may enter the economy and the environment through both intentional and non-intentional flows. These non-intentional flows, including the occurrence of substances as pollutants in mixed primary resources (metal ores, phosphate ores and fossil fuels) and their presence in re-used waste streams from intentional use may have environmental and economic consequences in terms of pollution and resource availability. On the one hand, these non-intentional flows may cause pollution problems. On the other hand, these flows have the potential to be a secondary source of substances. This article aims to quantify and model the non-intentional flows of lead, to evaluate their long-term environmental consequences, and compare these consequences to those of the intentional flows of lead. To meet this goal, the model combines all the sources of non-intentional flows of lead within one model, which also includes the intentional flows. Application of the model shows that the non-intentional flows of lead related to waste streams associated with intentional use are decreasing over time, due to the increased attention given to waste management. However, as contaminants in mixed primary resources application, lead flows are increasing as demand for these applications is increasing.

  2. A modelling approach to evaluate the long-term effect of soil texture on spring wheat productivity under a rain-fed condition

    PubMed Central

    He, Yong; Hou, Lingling; Wang, Hong; Hu, Kelin; McConkey, Brian

    2014-01-01

    Soil surface texture is an important environmental factor that influences crop productivity because of its direct effect on soil water and complex interactions with other environmental factors. Using 30-year data, an agricultural system model (DSSAT-CERES-Wheat) was calibrated and validated. After validation, the modelled yield and water use (WU) of spring wheat (Triticum aestivum L.) from two soil textures (silt loam and clay) under rain-fed condition were analyzed. Regression analysis showed that wheat grown in silt loam soil is more sensitive to WU than wheat grown in clay soil, indicating that the wheat grown in clay soil has higher drought tolerance than that grown in silt loam. Yield variation can be explained by WU other than by precipitation use (PU). These results demonstrated that the DSSAT-CERES-Wheat model can be used to evaluate the WU of different soil textures and assess the feasibility of wheat production under various conditions. These outcomes can improve our understanding of the long-term effect of soil texture on spring wheat productivity in rain-fed condition. PMID:25074796

  3. Upscaling SOC changes from long term field experiments to regional level - evaluation of agri-environmental measures on their contribution to mitigate climate change

    NASA Astrophysics Data System (ADS)

    Freudenschuss, Alexandra; Sedy, Katrin; Spiegel, Heide; Zethner, Gerhard

    2010-05-01

    Several agri-environment measures in Austria are presumed to also mitigate climate change. These are mainly measures that lead to an increase or stabilization of soil organic carbon (SOC) in arable soils, like e.g. organic farming, legumes and cover crops in the crop rotation as well as the application of organic fertilizers. A reduction of mineral fertiliser application may also reduce greenhouse gas emissions. The results of the study aim to evaluate different agricultural practices on their impact on SOC changes. Data from long term field experiments in Austria with different tillage systems and incorporation rates of crop residues and manure are used to determine effects of agricultural practices on SOC changes. Management factors that compare results from different activities on cropland are calculated and compared with international data. Furthermore these data are used to verify results gained from the application of humus balance model (VDLUFA). For the upscaling of potential SOC changes at regional level (federal states of Austria) data of the IACS - Integrated Administrative Control System are applied in the humus balance model. In order to cover the range of possible SOC changes three different approaches of the humus balance model are introduced and the results will be presented.

  4. Evaluation of guanfacine as a potential medication for alcohol use disorder in long-term drinking rats: behavioral and electrophysiological findings.

    PubMed

    Fredriksson, Ida; Jayaram-Lindström, Nitya; Wirf, Malin; Nylander, Erik; Nyström, Erica; Jardemark, Kent; Steensland, Pia

    2015-03-13

    One of the main treatment challenges in alcohol use disorder (AUD) is the high rate of craving in combination with decreased cognitive functioning including impaired decision making and impulse control that often lead to relapse. Recent studies show that guanfacine, an α-2-adrenoceptor agonist and FDA-approved ADHD medication, attenuates stress-induced relapse of several drugs of abuse including alcohol. Here we evaluated guanfacine's effects on voluntary alcohol intake, the alcohol deprivation effect (ADE), alcohol seeking behavior, and cue/priming-induced reinstatement in Wistar rats that had voluntarily consumed alcohol for at least 2 months before treatment. In addition, guanfacine's ability to regulate glutamatergic neurotransmission was evaluated through electrophysiological recordings in medial prefrontal cortex (mPFC) slices prepared from long-term drinking rats (and alcohol-naive controls) that had received three daily guanfacine (0.6 mg/kg/day) or vehicle injections in vivo. Guanfacine decreased alcohol intake in high, but not low, alcohol-consuming rats and the effects were generally more long lasting than that of the AUD medication naltrexone. Repeated guanfacine treatment induced a long-lasting decrease in alcohol intake, persistent up to five drinking sessions after the last injection. In addition, guanfacine attenuated the ADE as well as alcohol seeking and cue/priming-induced reinstatement of alcohol seeking. Finally, subchronic guanfacine treatment normalized an alcohol-induced dysregulated glutamatergic neurotransmission in the mPFC. These results support previous studies showing that guanfacine has the ability to improve prefrontal connectivity through modulation of the glutamatergic system. Together with the fact that guanfacine appears to be clinically safe, these results merit evaluation of guanfacine's clinical efficacy in AUD individuals.

  5. Evaluation of long-term stability of mesiodistal axial inclinations of maxillary molars through panoramic radiographs in subjects treated with Pendulum appliance

    PubMed Central

    Rocha, Caroline Andrade; de Almeida, Renato Rodrigues; Henriques, José Fernando Castanha; Flores-Mir, Carlos; de Almeida, Marcio Rodrigues

    2016-01-01

    Objective: To evaluate the stability of mesiodistal inclination of maxillary molars produced by a pendulum appliance, five years after completion of orthodontic treatment. Angulation changes were compared to an untreated sample. Methods: The sample consisted of 20 patients (14 females and 6 males) with Class II, Division 1 malocclusion that was treated through molar distalization with a pendulum appliance followed by cervical headgear and full fixed appliances. Maxillary molar inclination was evaluated through panoramic radiograph. The mean age at pretreatment was 14.3 ± 1.6 years, whereas at immediate post-treatment it was 18.6 ± 1.8 years, and at long-term post-treatment it was 23.8 ± 2.0 years. A control group of 16 untreated individuals with untreated normocclusion ranging in age from 12 to 17 years old were used as comparison group. Data were statistically analyzed with independent t-tests and ANOVA test followed by Tukey post-hoc tests. Results: Statistically significant differences were found between T1(94.50) and T2 (98.80) as well as between T2 and T3 (94.70) for maxillary first molars. Maxillary second molars did not show any statistically significant positional changes during the evaluated time periods T1 (107.50), T2 (109.30) and T3 (106.90). Conclusion: Although maxillary first molars underwent distal crown inclination immediately after treatment, approximately five years thereafter their roots tended to upright close to the pretreatment positions. PMID:27007764

  6. IN VIVO EVALUATION OF SKIN IRRITATION POTENTIAL, MELASMA AND SEBUM CONTENT FOLLOWING LONG TERM APPLICATION OF SKIN CARE CREAM IN HEALTHY ADULTS, USING NON-INVASIVE BIOMETROLOGICAL TECHNIQUES.

    PubMed

    Arshad, Atif I; Khan, Shoaib H M; Akhtar, Naveed; Mahmood, Asif; Sarfraz, Rai Muhammad

    2016-01-01

    The present investigation was conducted to evaluate non-invasively, various functional skin parameters i.e., irritation potential, melasma and sebum contents following long term application of topical cream (w/o) loaded with 2% methanolic extract of Ananas comosus L. versus placebo control (base) in healthy adults. Healthy human volunteers (n = 11, aged 20-30 years) were recruited for investigation and written informed consent was taken from each volunteer. In this single blinded study every volunteer applied formulation on one side of face and placebo on the other side of face twice daily for a period of 12 weeks (three months). Different skin parameters i.e., skin irritancy, melasma, and sebum contents were measured on both sides of face at baseline and after two weeks interval, using photometric device Mexameter and Sebumeter in a draught free room with modulated conditions of temperature (22-25°C) and humidity (55-60%). It was evident from the results that no primary skin irritancy was observed with patch test. Besides, statistical interpretation indicates that treatment with formulation is superior to placebo because it significantly (p ≤ 0.05) reduced the skin irritancy, melasma and sebum secretions throughout the study and reaching maximum -20.76 ± 0.89, -54.2 ± 0.37 and -40.71 ± 0.75%, respectively, at the end of study period. Antioxidant activity of extract was 92% compared to standard antioxidant. Conclusively, active cream loaded with fruit extract was well tolerated by all the volunteers and suitable to treat contact dermatitis, greasy skin, acne and seborrheic dermatitis and augmenting beauty and attraction by depigmentation of human skin. So, in the future, there is need to clinically evaluate these formulations in patients with compromised skin functions i.e., contact dermatitis, melasma, and acne vulgaris in order to explore the actual potential of this fruit. PMID:27008816

  7. IN VIVO EVALUATION OF SKIN IRRITATION POTENTIAL, MELASMA AND SEBUM CONTENT FOLLOWING LONG TERM APPLICATION OF SKIN CARE CREAM IN HEALTHY ADULTS, USING NON-INVASIVE BIOMETROLOGICAL TECHNIQUES.

    PubMed

    Arshad, Atif I; Khan, Shoaib H M; Akhtar, Naveed; Mahmood, Asif; Sarfraz, Rai Muhammad

    2016-01-01

    The present investigation was conducted to evaluate non-invasively, various functional skin parameters i.e., irritation potential, melasma and sebum contents following long term application of topical cream (w/o) loaded with 2% methanolic extract of Ananas comosus L. versus placebo control (base) in healthy adults. Healthy human volunteers (n = 11, aged 20-30 years) were recruited for investigation and written informed consent was taken from each volunteer. In this single blinded study every volunteer applied formulation on one side of face and placebo on the other side of face twice daily for a period of 12 weeks (three months). Different skin parameters i.e., skin irritancy, melasma, and sebum contents were measured on both sides of face at baseline and after two weeks interval, using photometric device Mexameter and Sebumeter in a draught free room with modulated conditions of temperature (22-25°C) and humidity (55-60%). It was evident from the results that no primary skin irritancy was observed with patch test. Besides, statistical interpretation indicates that treatment with formulation is superior to placebo because it significantly (p ≤ 0.05) reduced the skin irritancy, melasma and sebum secretions throughout the study and reaching maximum -20.76 ± 0.89, -54.2 ± 0.37 and -40.71 ± 0.75%, respectively, at the end of study period. Antioxidant activity of extract was 92% compared to standard antioxidant. Conclusively, active cream loaded with fruit extract was well tolerated by all the volunteers and suitable to treat contact dermatitis, greasy skin, acne and seborrheic dermatitis and augmenting beauty and attraction by depigmentation of human skin. So, in the future, there is need to clinically evaluate these formulations in patients with compromised skin functions i.e., contact dermatitis, melasma, and acne vulgaris in order to explore the actual potential of this fruit.

  8. Long-Term Follow-Up of the E1199 Phase III Trial Evaluating the Role of Taxane and Schedule in Operable Breast Cancer

    PubMed Central

    Sparano, Joseph A.; Zhao, Fengmin; Martino, Silvana; Ligibel, Jennifer A.; Perez, Edith A.; Saphner, Tom; Wolff, Antonio C.; Sledge, George W.; Wood, William C.; Davidson, Nancy E.

    2015-01-01

    Purpose To determine long-term outcomes in a clinical trial evaluating the role of taxane type and schedule in operable breast cancer and evaluate the impact of obesity and black race on outcome. Patients and Methods A total of 4,954 eligible women with stage II to III breast cancer treated with four cycles of doxorubicin plus cyclophosphamide were randomly assigned to receive paclitaxel or docetaxel every 3 weeks for four doses or weekly for 12 doses using a 2 × 2 factorial design. The primary end point was disease-free survival (DFS). Results are expressed as hazard ratios (HRs) from Cox proportional hazards models. All P values are two sided. Results When compared with the standard every-3-week paclitaxel arm, after a median follow-up of 12.1 years, DFS significantly improved and overall survival (OS) marginally improved only for the weekly paclitaxel (HR, 0.84; P = .011 and HR, 0.87; P = .09, respectively) and every-3-week docetaxel arms (HR, 0.79; P = .001 and HR, 0.86; P = .054, respectively). Weekly paclitaxel improved DFS and OS (HR, 0.69; P = .010 and HR, 0.69; P = .019, respectively) in triple-negative breast cancer. For hormone receptor–positive, human epidermal growth factor receptor 2–nonoverexpressing disease, no experimental arm improved OS, and black race and obesity were associated with increased risk of breast cancer recurrence and death. Conclusion Improved outcomes initially observed for weekly paclitaxel were qualitatively similar but quantitatively less pronounced with longer follow-up, although exploratory analysis suggested substantial benefit in triple-negative disease. Further research is required to understand why obesity and race influence clinical outcome in hormone receptor–positive disease. PMID:26077235

  9. Short- and long-term clinical evaluation of post-operative sensitivity of a new resin-based restorative material and self-etching primer.

    PubMed

    Gordan, Valeria V; Mjör, Ivar A

    2002-01-01

    This study evaluated the post-operative sensitivity of posterior restorations restored with a resin-based restorative material and a self-etching primer. Forty-six restorations, 28 Class I and 18 Class II were placed by two clinicians in 25 patients. After cavity preparations were completed under rubber dam isolation, they were restored using a self-etching primer (Fluorobond, Shofu Inc, Kyoto, Japan) and a resin-based restorative material (Beautifil, Shofu Inc, Kyoto, Japan). Patients were contacted on days 2 and 7 post-operatively and questioned regarding the presence of sensitivity, the stimuli that created sensitivity, the length of time the sensitivity lasted and its intensity using a rating scale from slight to severe. If sensitivity was experienced on day 7, patients were also contacted on days 14, 30 and 90 to assess the degree of sensitivity. All patients were recalled after 6-, 12- and 24-months for further evaluation of any sensitivity experienced. Chi-Square and Fisher's Exact Test were used for statistical analysis. At day 2, six restorations were sensitive to cold with no statistical difference (p > 0.05) from the restorations that were not sensitive. At day 7, only two restorations were sensitive. No sensitivity was present after day 14, which was also confirmed at the six-month recall. No correlation could be established among the duration of the sensitivity, the degree of pain and the causes that initiated sensitivity (p > 0.05). At one-year recall, one restoration was replaced due to post-operative sensitivity that started after the six-month recall. No sensitivity was noted at the 24-month recall. No correlation (p > 0.05) was found between sensitive restorations and those with a normal response throughout the study. The study showed that Fluorobond self-etching primer and Beautifil resin-based restorative material, when placed in posterior restorations, do not result in long-term post-operative sensitivity.

  10. Evaluation of impact factors on PM2.5 based on long-term chemical components analyses in the megacity Beijing, China.

    PubMed

    Chen, Yuan; Schleicher, Nina; Cen, Kuang; Liu, Xiuli; Yu, Yang; Zibat, Volker; Dietze, Volker; Fricker, Mathieu; Kaminski, Uwe; Chen, Yizhen; Chai, Fahe; Norra, Stefan

    2016-07-01

    Nine years of sampling and analyses of fine particles (PM2.5) were performed in Beijing from 2005 to 2013. Twenty-seven chemical elements and black carbon (BC) in PM2.5 were analyzed in order to study chemical characteristics and temporal distribution of Beijing aerosols. Principle component analysis defined different types of elemental sources, based on which, the influences of a variety of anthropogenic activities including governmental intervention measures and natural sources on air quality were evaluated. For the first time, Ga is used as a tracer element for heating activities mainly using coal in Beijing, due to its correlation with BC and coal combustion, as well as its concentration variation between the heating- and non-heating periods. The traffic restrictions effectively reduced emissions of relevant heavy metals such as As, Cd, Sn and Sb. The expected long-term effectiveness of the steel smelters relocation was not observed due to the nearby relocation with increased capacity. Firework display during every Chinese spring festival season and special events such as the Olympic Games resulted in several times higher concentrations of K, Sr and Ba than other days and thus they were proposed as tracers for firework display. The impacts of all these factors were quantified and evaluated. Sand dust or dust storms induced higher concentrations of geogenic elements in PM2.5 compared to non-dust days. Sustainable mitigation measures, such as traffic restrictions, are necessary to be continued and improved to obtain more "blue sky" days in the future.

  11. Evaluation of impact factors on PM2.5 based on long-term chemical components analyses in the megacity Beijing, China.

    PubMed

    Chen, Yuan; Schleicher, Nina; Cen, Kuang; Liu, Xiuli; Yu, Yang; Zibat, Volker; Dietze, Volker; Fricker, Mathieu; Kaminski, Uwe; Chen, Yizhen; Chai, Fahe; Norra, Stefan

    2016-07-01

    Nine years of sampling and analyses of fine particles (PM2.5) were performed in Beijing from 2005 to 2013. Twenty-seven chemical elements and black carbon (BC) in PM2.5 were analyzed in order to study chemical characteristics and temporal distribution of Beijing aerosols. Principle component analysis defined different types of elemental sources, based on which, the influences of a variety of anthropogenic activities including governmental intervention measures and natural sources on air quality were evaluated. For the first time, Ga is used as a tracer element for heating activities mainly using coal in Beijing, due to its correlation with BC and coal combustion, as well as its concentration variation between the heating- and non-heating periods. The traffic restrictions effectively reduced emissions of relevant heavy metals such as As, Cd, Sn and Sb. The expected long-term effectiveness of the steel smelters relocation was not observed due to the nearby relocation with increased capacity. Firework display during every Chinese spring festival season and special events such as the Olympic Games resulted in several times higher concentrations of K, Sr and Ba than other days and thus they were proposed as tracers for firework display. The impacts of all these factors were quantified and evaluated. Sand dust or dust storms induced higher concentrations of geogenic elements in PM2.5 compared to non-dust days. Sustainable mitigation measures, such as traffic restrictions, are necessary to be continued and improved to obtain more "blue sky" days in the future. PMID:27115848

  12. Integrated analysis of long-term safety in patients with chronic immune thrombocytopaenia (ITP) treated with the thrombopoietin (TPO) receptor agonist romiplostim.

    PubMed

    Cines, Douglas B; Gernsheimer, Terry; Wasser, Jeffrey; Godeau, Bertrand; Provan, Drew; Lyons, Roger; Altomare, Ivy; Wang, Xuena; Lopez, Angela

    2015-09-01

    A safety analysis of pooled data from clinical studies of romiplostim, a thrombopoietin (TPO) receptor agonist, in which patients with immune thrombocytopaenia (ITP) received romiplostim, placebo, or medical standard of care (SOC) Rodeghiero et al. (Eur J Haematol 91:423-436, 2013), has been updated. Included are data from 14 trials spanning 2002-2011; placebo- and SOC-arm data are pooled. Most patients (n = 1059) were female (61 %) and Caucasian (85 %); 38 % had undergone splenectomy; 23 were children. Mean (SD) baseline platelet count was 20.6 (16.5) × 10(9)/L. Mean (SD) weekly dose of romiplostim was 4.2 (2.8) µg/kg; total exposure was 1520 patient-years. Overall, 921 patients received romiplostim only, 65 received placebo/SOC only, and 73 received placebo/SOC followed by romiplostim. Rates of haemorrhage (romiplostim, 205/100 patient-years; placebo/SOC, 263/100), thrombosis (both, 5.5/100 patient-years), haematological malignancy/myelodysplastic syndrome (romiplostim, 0.5/100 patient-years; placebo/SOC, 2.7/100), and non-haematological tumours (romiplostim, 2.2/100 patient-years; placebo/SOC, 3.6/100) were comparable among groups. Bone marrow reticulin was reported in 17 patients and collagen in one patient receiving romiplostim; one patient receiving placebo/SOC had reticulin reported. Three patients developed neutralizing antibodies to romiplostim, but not to endogenous TPO. This integrated analysis of the safety profile of romiplostim in patients with ITP is consistent with previously reported studies; no new safety concerns emerged.

  13. Acarologic risk of exposure to Borrelia burgdorferi spirochaetes: long-term evaluations in north-western California, with implications for Lyme borreliosis risk-assessment models.

    PubMed

    Eisen, L; Eisen, R J; Chang, C-C; Mun, J; Lane, R S

    2004-03-01

    Over a 5-year period (1997-2001) the population densities of Ixodes pacificus Cooley & Kohls (Acari: Ixodidae) nymphs infected with spirochaetes of Borrelia burgdorferi sensu lato (s.l.) were evaluated in areas of 2000 ha at two localities (CHR, nine sites; HREC, seven sites) 25 km apart in Mendocino County, north-western California. The 5-year median density of infected nymphs was significantly higher at CHR than at HREC (0.51 vs. 0.09 per 100 m(2) and site-specific yearly densities exceeding one infected nymph per 100 m2 were 10-fold more likely to occur at CHR than at HREC. The importance of long-term data in acarologic risk assessment was demonstrated by significantly higher median yearly densities of infected nymphs at CHR from 1997 to 1999, whereas both areas had similar densities during 2000-2001. Overall, the causative agent of Lyme borreliosis in North America, B. burgdorferi Johnson et al. sensu stricto (s.s.) accounted for 76% of 46 genetically characterized B. burgdorferi s.l. infections from I. pacificus nymphs. Tremendous variability in acarologic risk was recorded within both areas: yearly densities of infected nymphs varied 11-97-fold between sites at CHR and 8-30-fold at HREC. Part of this variation could be explained by environmental traits, most notably deer usage. However, correlations between environmental factors and density of infected nymphs (for CHR and HREC combined) did not necessarily apply when these areas were considered separately. Thus, a Lyme borreliosis ecology model developed in one of these areas needs testing in the other area. PMID:15009444

  14. Prognostic usefulness of left ventricular hypertrophy by electrocardiography in patients with atrial fibrillation (from the Randomized Evaluation of Long-Term Anticoagulant Therapy Study).

    PubMed

    Verdecchia, Paolo; Reboldi, Gianpaolo; Di Pasquale, Giuseppe; Mazzotta, Giovanni; Ambrosio, Giuseppe; Yang, Sean; Pogue, Janice; Wallentin, Lars; Ezekowitz, Michael D; Connolly, Stuart J; Yusuf, Salim

    2014-02-15

    It is unknown whether left ventricular hypertrophy (LVH) diagnosis by electrocardiography improves risk stratification in patients with atrial fibrillation (AF). We investigated the prognostic impact of LVH diagnosis by electrocardiography in a large sample of anticoagulated patients with AF included in the Randomized Evaluation of Long-Term Anticoagulant Therapy (RE-LY) Study. We defined electrographic LVH (ECG-LVH) by strain pattern or Cornell voltage (R wave in aVL plus S wave in V3) >2.0 mV (women) or >2.4 mV (men). LVH prevalence was 22.7%. During a median follow-up of 2.0 years, 303 patients developed a stroke, 778 died (497 from cardiovascular causes), and 140 developed a myocardial infarction. LVH was associated with a greater risk of stroke (1.99% vs 1.32% per year, hazard ratio [HR] 1.51, 95% confidence interval [CI] 1.18 to 1.93, p <0.001), cardiovascular death (4.52% vs 1.80% per year, HR 2.56, 95% CI 2.14 to 3.06, p <0.0001), all-cause death (6.03% vs 3.11% per year, HR 1.95, 95% CI 1.68 to 2.26, p <0.0001), and myocardial infarction (1.11% vs 0.55% per year, HR 2.07, 95% CI 1.47 to 2.92, p <0.0001). In multivariate analysis, the prognostic value of LVH was additive to CHA2DS2-VASc score and other covariates. The category-free net reclassification index and integrated discrimination improvement increased significantly after adding LVH to multivariate models. In conclusion, our study demonstrates for the first time that ECG-LVH, a simple and easily accessible prognostic indicator, improves risk stratification in anticoagulated patients with AF.

  15. Meteorological detrending of primary and secondary pollutant concentrations: Method application and evaluation using long-term (2000-2012) data in Atlanta

    NASA Astrophysics Data System (ADS)

    Henneman, Lucas R. F.; Holmes, Heather A.; Mulholland, James A.; Russell, Armistead G.

    2015-10-01

    The effectiveness of air pollution regulations and controls are evaluated based on measured air pollutant concentrations. Air pollution levels, however, are highly sensitive to both emissions and meteorological fluctuations. Therefore, an assessment of the change in air pollutant levels due to emissions controls must account for these meteorological fluctuations. Two empirical methods to quantify the impact of meteorology on pollutant levels are discussed and applied to the 13-year time period between 2000 and 2012 in Atlanta, GA. The methods employ Kolmogorov-Zurbenko filters and linear regressions to detrended pollutant signals into long-term, seasonal, weekly, short-term, and white-noise components. The methods differ in how changes in weekly and holiday emissions are accounted for. Both can provide meteorological adjustments on a daily basis for future use in acute health analyses. The meteorological impact on daily signals of ozone, NOx, CO, SO2, PM2.5, and PM species are quantified. Analyses show that the substantial decreases in seasonal averages of NOx and SO2 correspond with controls implemented in the metropolitan Atlanta area. Detrending allows for the impacts of some controls to be observed with averaging times of as little as 3 months. Annual average concentrations of NOx, SO2, and CO have all fallen by at least 50% since 2000. Reductions in NOx levels, however, do not lead to uniform reductions in ozone. While average detrended summer average maximum daily average 8 h ozone (MDA8h O3) levels fell by 4% (2.2 ± 2 ppb) between 2000 and 2012, winter averages have increased by 12% (3.8 ± 1.4 ppb), providing further evidence that high ozone levels are NOx-limited and lower ozone concentrations are NOx-inhibited. High ozone days (with MDA8h O3 greater than 60 ppb) decreased both in number and in magnitude over the study period.

  16. Analyses of fecal and hair glucocorticoids to evaluate short- and long-term stress and recovery of Asiatic black bears (Ursus thibetanus) removed from bile farms in China.

    PubMed

    Malcolm, K D; McShea, W J; Van Deelen, T R; Bacon, H J; Liu, F; Putman, S; Zhu, X; Brown, J L

    2013-05-01

    Demand for traditional Chinese medicines has given rise to the practice of maintaining Asiatic black bears (Ursus thibetanus) in captivity to harvest bile. We evaluated hypothalamic-pituitary-adrenal (HPA) activity in Asiatic black bears on a bile farm in China by measuring cortisol in hair. We also monitored hair and fecal glucocorticoid metabolites as bears acclimated to improved husbandry at the Animals Asia Foundation China Bear Rescue Center (CBRC) after removal from other bile farms. Fecal samples were collected twice weekly for ~1 year, and hair was obtained from bears upon arrival at the CBRC and again ≥163 days later. Paired hair samples showed declines in cortisol concentrations of 12-88% in 38 of 45 (84%, p<0.001) bears after arrival and acclimation at the rehabilitation facility. Concentrations of cortisol in hair from bears on the bile farm were similar to initial concentrations upon arrival at the CBRC but were higher than those collected after bears had been at the CBRC for ≥163 days. Fecal glucocorticoid concentrations varied across months and were highest in April and declined through December, possibly reflecting seasonal patterns, responses to the arrival and socialization of new bears at the CBRC, and/or annual metabolic change. Data from segmental analysis of hair supports the first of these explanations. Our findings indicate that bears produced elevated concentrations of glucocorticoids on bile farms, and that activity of the HPA axis declined following relocation. Thus, hair cortisol analyses are particularly well suited to long-term, retrospective assessments of glucocorticoids in ursids. By contrast, fecal measures were not clearly associated with rehabilitation, but rather reflected more subtle endocrine changes, possibly related to seasonality. PMID:23416358

  17. Evaluation of the drug release patterns and long term stability of aqueous and organic coated pellets by using blends of enteric and gastrointestinal insoluble polymers.

    PubMed

    Kranz, H; Gutsche, S

    2009-10-01

    The major aim of this study was to identify an efficient tool to adjust drug release patterns from aqueous and organic ethylcellulose (a gastrointestinal insoluble polymer) coated pellets and to evaluate the long term stability of the film coatings. Drug release was monitored during open and closed storage at 25 degrees C/60% RH (ambient conditions) and 40 degrees C/75% RH (stress conditions) for up to 24 months. Release of vatalanib succinate, a poorly soluble drug that demonstrates pH-dependent solubility, from pure ethylcellulose coated pellets was slow irrespectively of the type of coating and release medium. By addition of the enteric polymer methacrylic acid/ethyl acrylate copolymer (applied as aqueous Kollicoat MAE 30 DP dispersion or organic solution of Kollicoat MAE 100 P) to ethylcellulose broad ranges of drug release patterns could be achieved. For aqueous film coatings the addition of Kollicoat MAE 30 DP to ethylcellulose dispersions resulted in unaltered drug release kinetics during closed storage at ambient and stress conditions. The storage stabilizing effect of the added enteric polymer might be explained by the more hydrophilic nature of Kollicoat MAE 30 DP compared to ethylcellulose trapping water during film formation and improving polymer particle coalescence. However, during open storage of aqueous coated ethylcellulose:Kollicoat MAE 30 DP pellets at stress conditions drug release decreased due to further gradual polymer particle coalescence. In contrast, drug release rates from organic coated ethylcellulose:Kollicoat MAE 100 P pellets stored at ambient and stress conditions did not change which could be explained by differences in the film formation process. This clearly indicates that the presented concept of the addition of methacrylic acid/ethyl acrylate copolymer to ethylcellulose film coatings in combination with an organic coating process is able to achieve broad ranges of drug release patterns and to overcome storage instability. PMID

  18. Evaluation of an integrated system for classification, assessment and comparison of services for long-term care in Europe: the eDESDE-LTC study

    PubMed Central

    2013-01-01

    Background The harmonization of European health systems brings with it a need for tools to allow the standardized collection of information about medical care. A common coding system and standards for the description of services are needed to allow local data to be incorporated into evidence-informed policy, and to permit equity and mobility to be assessed. The aim of this project has been to design such a classification and a related tool for the coding of services for Long Term Care (DESDE-LTC), based on the European Service Mapping Schedule (ESMS). Methods The development of DESDE-LTC followed an iterative process using nominal groups in 6 European countries. 54 researchers and stakeholders in health and social services contributed to this process. In order to classify services, we use the minimal organization unit or “Basic Stable Input of Care” (BSIC), coded by its principal function or “Main Type of Care” (MTC). The evaluation of the tool included an analysis of feasibility, consistency, ontology, inter-rater reliability, Boolean Factor Analysis, and a preliminary impact analysis (screening, scoping and appraisal). Results DESDE-LTC includes an alpha-numerical coding system, a glossary and an assessment instrument for mapping and counting LTC. It shows high feasibility, consistency, inter-rater reliability and face, content and construct validity. DESDE-LTC is ontologically consistent. It is regarded by experts as useful and relevant for evidence-informed decision making. Conclusion DESDE-LTC contributes to establishing a common terminology, taxonomy and coding of LTC services in a European context, and a standard procedure for data collection and international comparison. PMID:23768163

  19. Mesophilic and thermophilic biofiltration of gaseous toluene in a long-term operation: performance evaluation, biomass accumulation, mass balance analysis and isolation identification.

    PubMed

    Wang, Can; Kong, Xin; Zhang, Xin-Yue

    2012-08-30

    A thermophilic biofilter (TBF) was developed to treat high temperature gaseous toluene (55°C). The performance of TBF was evaluated under various operating conditions, including different inlet concentrations and gas flow rates, and compared with a control mesophilic biofilter (MBF). Furthermore, the leachate, biomass accumulation and pressure drop of filter bed were investigated. The experimental results showed that the TBF achieved high performance removal efficiencies of 90% when the inlet loading was lower than 100 gm(-3)h(-1). Increasing inlet loading resulted in lower performance of TBF compared with MBF. However, the biomass in TBF, in the long-term operation, showed a slow accumulation process than MBF. The specific growth rates of microorganism were 0.0011 day(-1) and 0.0015 day(-1) for TBF and MBF, respectively. The slow growth process in TBF further resulted in a lower pressure drop of filter bed (0.1-0.5 kPa) than that of MBF (7-10 kPa). The leachate from TBF presented a neutral pH and presented a higher TOC contents than those from MBF. The results of three-dimensional fluorescence spectra suggested that the products of toluene biodegradation included some organic acids. A carbon mass balance analysis showed that 47.1% of the removed toluene was converted to biomass in MBF, which was higher than that of MBF with 30.5%. Finally, 16s rRNA gene sequences indicated the dominant microorganisms in the TBF including Brevibacillus sp. and Anoxybacillus sp., while Delftia sp. and Stenotrophomonas sp. in the MBF.

  20. Comprehensive Validation and Evaluation of JPSS VIIRS Land Surface Albedo (LSA): Field Measurements Validation, Inter-comparisons, Long-term Monitoring, and Temporal Filtering

    NASA Astrophysics Data System (ADS)

    Zhou, Y.

    2015-12-01

    Land surface albedo (LSA), part of the Visible Infrared Imaging Radiometer Suite (VIIRS) surface albedo environmental data record (EDR), is an essential variable regulating shortwave energy exchange between the land surface and the atmosphere. Currently, the bright pixel sub-algorithm (BPSA), which estimates LSA directly from VIIRS top-of-atmosphere (TOA) reflectance through simulation of atmospheric radiative transfer, is used to generate LSA products. In order to provide a better assessment of the VIIRS LSA data, this study performed comprehensive validation and evaluation in four aspects: 1) Comparing VIIRS LSA with global field measurements including Surfard, BSRN, GC-net, etc. Result shows VIIRS albedo has an overall bias of 0.004 and root mean square error (RMSE) of 0.024 against those ground sites. 2) Inter-comparing VIIRS LSA with albedo derived from other data source to see the discrepancies of albedo estimation among different sensors. Result shows that VIIRS LSA has a high agreement with high resolution albedo maps derived from Landsat data (bias = 0.003, RMSE = 0.019), and the 16-day mean VIIRS albedo agrees well with MODIS blue-sky albedo (bias = 0.001 and RMSE = 0.019). 3) Establishing a long-term monitoring tool for VIIRS LSA to regularly detect the global albedo change and related disturbances. It provides an important way for investigating global land processes. 4) Developing a temporal filter algorithm to fill gaps on the albedo time series and make it smooth, and more applicable for end users.

  1. An Initial Evaluation of a Long-Term, Sustainable, Integrated Community-Based Physical Activity Program for Adults with Intellectual Disability

    ERIC Educational Resources Information Center

    Lante, Kerrie A.; Walkley, Jeff W.; Gamble, Merrilyn; Vassos, Maria V.

    2011-01-01

    Background: Physical activity (PA) programs for adults with intellectual disability (ID) have positive impacts, at least in the short term. No research has been reported on the effect of long-term engagement in PA programs for adults with ID. This paper explores the physical and psychosocial benefits gained by two individuals with mild ID who…

  2. The High-Skilled VET Practitioner: Interim Findings from the Evaluation of the Long-Term Impacts of the Framing the Future Projects in 1999-2000.

    ERIC Educational Resources Information Center

    Mitchell, John; Wood, Sarah; Young, Susan

    Research was conducted in 2000-01 on the long-term impacts of the 200 projects funded by Australia's Framing the Future in 1999 and of the 250 conducted in 2000. Two main research methodologies (case study investigations and a survey) were used for the study. Case study investigations were conducted with the Deaf Education Network in Sydney; South…

  3. IN SITU SOURCE TREATMENT OF CR(VI) USING A FE(II)-BASED REDUCTANT BLEND: LONG-TERM MONITORING AND EVALUATION

    EPA Science Inventory

    The long-term effectiveness of a FeSO4 + Na2S2O4 reductant solution blend for in situ saturated zone treatment of dissolved and solid phase Cr(VI) in a high pH chromite ore processing solid waste (COPSW) fill material was investigated. Two field pilot injection studies were cond...

  4. Clinical efficacy, radiographic and safety findings through 5 years of subcutaneous golimumab treatment in patients with active psoriatic arthritis: results from a long-term extension of a randomised, placebo-controlled trial (the GO-REVEAL study)

    PubMed Central

    Kavanaugh, Arthur; McInnes, Iain B; Mease, Philip; Krueger, Gerald G; Gladman, Dafna; van der Heijde, Désirée; Zhou, Yiying; Lu, Jiandong; Leu, Jocelyn H; Goldstein, Neil; Beutler, Anna

    2014-01-01

    Objectives Assess golimumab's long-term efficacy/safety in psoriatic arthritis (PsA). Methods Adults with active PsA (≥3 swollen and tender joints, active psoriasis) were randomly assigned to subcutaneous placebo, golimumab 50 mg, or golimumab 100 mg every 4 weeks (q4wks) through wk20. All patients received golimumab 50 mg or 100 mg q4wks from wk24 forward. Methotrexate was allowed and taken by approximately half the patients. Findings through 5 years are reported herein. Efficacy assessments included ≥20% improvement in American College of Rheumatology (ACR20) response, C-reactive-protein-based, 28-joint-count Disease Activity Score (DAS28-CRP) response, ≥75% improvement in Psoriasis Area and Severity Index (PASI75) scores, and PsA-modified Sharp/van der Heijde scores (SHSs). Results 126/405 (31%) randomised patients discontinued treatment through wk252. Golimumab was effective in maintaining clinical improvement through year-5 (ACR20: 62.8–69.9%, DAS28-CRP: 75.2-84.9% for randomised patients; PASI75: 60.8–72.2% among randomised patients with ≥3% body surface area involvement) and inhibiting radiographic progression (mean changes in PsA-modified SHS: 0.1–0.3) among patients with radiographic data. While concomitant methotrexate did not affect ACR20/PASI75, it appeared to reduce radiographic progression. No new safety signals were identified. Antibodies-to-golimumab occurred in 1.8%/10.0% of patients with/without methotrexate). Conclusions Long-term golimumab safety/efficacy in PsA was demonstrated through 5 years. Trial registration number NCT00265096. PMID:24748630

  5. Long-term efficacy, safety, and tolerability of rilpivirine (RPV, TMC278) in HIV type 1-infected antiretroviral-naive patients: week 192 results from a phase IIb randomized trial.

    PubMed

    Wilkin, Aimee; Pozniak, Anton L; Morales-Ramirez, Javier; Lupo, Sergio H; Santoscoy, Mario; Grinsztejn, Beatriz; Ruxrungtham, Kiat; Rimsky, Laurence T; Vanveggel, Simon; Boven, Katia

    2012-05-01

    TMC278-C204 (NCT00110305), a 96-week trial of the nonnucleoside reverse transcription inhibitor (NNRTI) rilpivirine (RPV, TMC278) in 368 HIV-1-infected, treatment-naive patients, was extended to investigate long-term safety and efficacy. Week 192 analysis results are presented. This was a long-term follow-up of a Phase IIb, randomized trial. No significant RPV dose-response relationships with respect to the primary endpoint (composite ITT-TLOVR algorithm) were observed at week 48 or 96. All RPV-treated patients were switched to open-label 75 mg qd at week 96 and then to 25 mg qd, the Phase III dose, at approximately week 144 as it gave the best benefit-risk balance. All control patients continued receiving open-label efavirenz (EFV) 600 mg qd. At week 192, 59% of RPV- and 61% of EFV-treated patients maintained confirmed viral load <50 copies/ml (ITT-TLOVR algorithm). The mean changes from baseline in CD4 cell count were similar in both groups (RPV: 210 cells/mm(3) vs. EFV: 225 cells/mm(3)). No new safety concerns were noted between week 48 and 192. In the week 192 analysis, RPV compared with EFV was associated with a lower overall incidence of grade 2-4 adverse events (AEs) at least possibly related to treatment, including rash (p<0.001) and neurologic AEs (p<0.05 Fisher's exact test, post hoc analyses) Incidences of serious AEs, grade 3 or 4 AEs, and discontinuations due to AEs were similar across groups. Increases in total cholesterol, LDL-cholesterol, HDL-cholesterol, and triglycerides were significantly lower with RPV than with EFV. RPV continued to show sustained efficacy similar to EFV at week 192 with a generally more favorable safety profile. PMID:21902621

  6. Long-term parenteral nutrition

    PubMed Central

    Ladefoged, Karin; Jarnum, Stig

    1978-01-01

    Nineteen patients (11 women and eight men) aged 20-68 received long-term parenteral nutrition, mostly at home, for six to 63 months (mean 19 months). Indications for LTPN were extensive, active Crohn's disease in three patients, intestinocutaneous fistulas in three, and short-bowel syndrome in the remaining 13 patients. Subclavian or intra-atrial (Broviac) catheters were most commonly used, for which the average life was four and seven months respectively. Complications of long-term parenteral nutrition included pneumothorax in four out of 48 subclavian vein punctures. Catheter-induced thrombosis of central veins was shown by phlebography 17 times in nine patients, and eight episodes of total occlusion occurred. Two of these patients had pulmonary infarction. Nineteen episodes of catheter sepsis occurred in 11 patients, but only one was fatal. Complications related to intestinal disease included intra-abdominal abscesses and intestinal fistulas, and disturbances of liver function. Five patients died, though in only two was death related to long-term parenteral nutrition. One of these patients died from catheter sepsis, the other had subdural haematoma possibly caused by anticoagulant treatment. Eight of the 14 surviving patients still needed parenteral nutrition. All received a disability pension, but six had an acceptable quality of life with almost normal social activities. Despite problems such as difficulties in maintaining standardised infusion programmes, it was concluded that long-term parenteral nutrition at home is practicable and consistent with an acceptable quality of life. ImagesFIG 2 PMID:98199

  7. Long-term evaluation of three satellite ocean color algorithms for identifying harmful algal blooms (Karenia brevis) along the west coast of Florida: A matchup assessment

    PubMed Central

    Carvalho, Gustavo A.; Minnett, Peter J.; Banzon, Viva F.; Baringer, Warner; Heil, Cynthia A.

    2011-01-01

    We present a simple algorithm to identify Karenia brevis blooms in the Gulf of Mexico along the west coast of Florida in satellite imagery. It is based on an empirical analysis of collocated matchups of satellite and in situ measurements. The results of this Empirical Approach is compared to those of a Bio-optical Technique – taken from the published literature – and the Operational Method currently implemented by the NOAA Harmful Algal Bloom Forecasting System for K. brevis blooms. These three algorithms are evaluated using a multi-year MODIS data set (from July, 2002 to October, 2006) and a long-term in situ database. Matchup pairs, consisting of remotely-sensed ocean color parameters and near-coincident field measurements of K. brevis concentration, are used to assess the accuracy of the algorithms. Fair evaluation of the algorithms was only possible in the central west Florida shelf (i.e. between 25.75°N and 28.25°N) during the boreal Summer and Fall months (i.e. July to December) due to the availability of valid cloud-free matchups. Even though the predictive values of the three algorithms are similar, the statistical measure of success in red tide identification (defined as cell counts in excess of 1.5 × 104 cells L−1) varied considerably (sensitivity—Empirical: 86%; Bio-optical: 77%; Operational: 26%), as did their effectiveness in identifying non-bloom cases (specificity—Empirical: 53%; Bio-optical: 65%; Operational: 84%). As the Operational Method had an elevated frequency of false-negative cases (i.e. presented low accuracy in detecting known red tides), and because of the considerable overlap between the optical characteristics of the red tide and non-bloom population, only the other two algorithms underwent a procedure for further inspecting possible detection improvements. Both optimized versions of the Empirical and Bio-optical algorithms performed similarly, being equally specific and sensitive (~70% for both) and showing low levels of

  8. Long-term evaluation of three satellite ocean color algorithms for identifying harmful algal blooms (Karenia brevis) along the west coast of Florida: A matchup assessment.

    PubMed

    Carvalho, Gustavo A; Minnett, Peter J; Banzon, Viva F; Baringer, Warner; Heil, Cynthia A

    2011-01-17

    We present a simple algorithm to identify Karenia brevis blooms in the Gulf of Mexico along the west coast of Florida in satellite imagery. It is based on an empirical analysis of collocated matchups of satellite and in situ measurements. The results of this Empirical Approach is compared to those of a Bio-optical Technique - taken from the published literature - and the Operational Method currently implemented by the NOAA Harmful Algal Bloom Forecasting System for K. brevis blooms. These three algorithms are evaluated using a multi-year MODIS data set (from July, 2002 to October, 2006) and a long-term in situ database. Matchup pairs, consisting of remotely-sensed ocean color parameters and near-coincident field measurements of K. brevis concentration, are used to assess the accuracy of the algorithms. Fair evaluation of the algorithms was only possible in the central west Florida shelf (i.e. between 25.75°N and 28.25°N) during the boreal Summer and Fall months (i.e. July to December) due to the availability of valid cloud-free matchups. Even though the predictive values of the three algorithms are similar, the statistical measure of success in red tide identification (defined as cell counts in excess of 1.5 × 10(4) cells L(-1)) varied considerably (sensitivity-Empirical: 86%; Bio-optical: 77%; Operational: 26%), as did their effectiveness in identifying non-bloom cases (specificity-Empirical: 53%; Bio-optical: 65%; Operational: 84%). As the Operational Method had an elevated frequency of false-negative cases (i.e. presented low accuracy in detecting known red tides), and because of the considerable overlap between the optical characteristics of the red tide and non-bloom population, only the other two algorithms underwent a procedure for further inspecting possible detection improvements. Both optimized versions of the Empirical and Bio-optical algorithms performed similarly, being equally specific and sensitive (~70% for both) and showing low levels of

  9. Long-term evaluation of three satellite ocean color algorithms for identifying harmful algal blooms (Karenia brevis) along the west coast of Florida: A matchup assessment.

    PubMed

    Carvalho, Gustavo A; Minnett, Peter J; Banzon, Viva F; Baringer, Warner; Heil, Cynthia A

    2011-01-17

    We present a simple algorithm to identify Karenia brevis blooms in the Gulf of Mexico along the west coast of Florida in satellite imagery. It is based on an empirical analysis of collocated matchups of satellite and in situ measurements. The results of this Empirical Approach is compared to those of a Bio-optical Technique - taken from the published literature - and the Operational Method currently implemented by the NOAA Harmful Algal Bloom Forecasting System for K. brevis blooms. These three algorithms are evaluated using a multi-year MODIS data set (from July, 2002 to October, 2006) and a long-term in situ database. Matchup pairs, consisting of remotely-sensed ocean color parameters and near-coincident field measurements of K. brevis concentration, are used to assess the accuracy of the algorithms. Fair evaluation of the algorithms was only possible in the central west Florida shelf (i.e. between 25.75°N and 28.25°N) during the boreal Summer and Fall months (i.e. July to December) due to the availability of valid cloud-free matchups. Even though the predictive values of the three algorithms are similar, the statistical measure of success in red tide identification (defined as cell counts in excess of 1.5 × 10(4) cells L(-1)) varied considerably (sensitivity-Empirical: 86%; Bio-optical: 77%; Operational: 26%), as did their effectiveness in identifying non-bloom cases (specificity-Empirical: 53%; Bio-optical: 65%; Operational: 84%). As the Operational Method had an elevated frequency of false-negative cases (i.e. presented low accuracy in detecting known red tides), and because of the considerable overlap between the optical characteristics of the red tide and non-bloom population, only the other two algorithms underwent a procedure for further inspecting possible detection improvements. Both optimized versions of the Empirical and Bio-optical algorithms performed similarly, being equally specific and sensitive (~70% for both) and showing low levels of

  10. Safety, long-term results, and predictors of recurrence after complete endocardial ventricular tachycardia substrate ablation in patients with previous myocardial infarction.

    PubMed

    Arenal, Ángel; Hernández, Jesús; Calvo, David; Ceballos, Cecilia; Atéa, Leonardo; Datino, Tomás; Atienza, Felipe; González-Torrecilla, Esteban; Eídelman, Gabriél; Miracle, Ángel; Avila, Pablo; Bermejo, Javier; Fernández-Avilés, Francisco

    2013-02-15

    Conduction channels and electrograms with isolated component/late potentials are sensitive markers of the substrate of post-myocardial infarction sustained monomorphic ventricular tachycardia (VT). Ablation of all conduction channels and isolated component/late potentials (complete endocardial VT substrate ablation [CEVTSA]) during sinus rhythm could simplify and facilitate the ablation procedure, mainly in patients without references for clinical VT substrate identification. The aim of this study was to assess the safety, efficacy, and predictors of VT recurrence after CEVTSA. Electroanatomic mapping and CEVTSA were performed in 59 post-myocardial infarction patients (mean age 67 ± 9 years, mean left ventricular ejection fraction 30 ± 11%), 24 of whom did not have clinical VT substrate references. The mean areas of scar (≤1.5 mV) and dense scar (≤0.5 mV) were 76 ± 42 and 34 ± 24 cm(2), respectively; isolated component/late potentials and conduction channels were identified and ablated in 97% and 83% of patients (mean ablation area 14 ± 10 cm(2)). No life-threatening complications occurred during the procedure. After 1 year and at the end of follow-up (mean 39 ± 21 months), 81% and 58% of patients were free of VT. No differences were observed between patients with and without specific clinical VT substrate identification. Univariate analysis identified the left ventricular ejection fraction, VT cycle length (VTCL), infarct location (inferior vs anterior), and dense scar area as predictors of VT recurrence, and Cox analysis identified VTCL (hazard ratio 0.42, p <0.001) and dense scar area (hazard ratio 2.65, p <0.0006) as independent predictors. No patients with dense scar area ≤25 cm(2) and VTCL >350 ms had recurrences. In conclusion, CEVTSA is safe and effective, even in patients without clinical VT substrate identification. Scar area and VTCL are valuable predictors of VT recurrence.

  11. Long-term data archiving

    SciTech Connect

    Moore, David Steven

    2009-01-01

    Long term data archiving has much value for chemists, not only to retain access to research and product development records, but also to enable new developments and new discoveries. There are some recent regulatory requirements (e.g., FDA 21 CFR Part 11), but good science and good business both benefit regardless. A particular example of the benefits of and need for long term data archiving is the management of data from spectroscopic laboratory instruments. The sheer amount of spectroscopic data is increasing at a scary rate, and the pressures to archive come from the expense to create the data (or recreate it if it is lost) as well as its high information content. The goal of long-term data archiving is to save and organize instrument data files as well as any needed meta data (such as sample ID, LIMS information, operator, date, time, instrument conditions, sample type, excitation details, environmental parameters, etc.). This editorial explores the issues involved in long-term data archiving using the example of Raman spectral databases. There are at present several such databases, including common data format libraries and proprietary libraries. However, such databases and libraries should ultimately satisfy stringent criteria for long term data archiving, including readability for long times into the future, robustness to changes in computer hardware and operating systems, and use of public domain data formats. The latter criterion implies the data format should be platform independent and the tools to create the data format should be easily and publicly obtainable or developable. Several examples of attempts at spectral libraries exist, such as the ASTM ANDI format, and the JCAMP-DX format. On the other hand, proprietary library spectra can be exchanged and manipulated using proprietary tools. As the above examples have deficiencies according to the three long term data archiving criteria, Extensible Markup Language (XML; a product of the World Wide Web

  12. Decision-analytic modeling to evaluate the long-term effectiveness and cost-effectiveness of HPV-DNA testing in primary cervical cancer screening in Germany

    PubMed Central

    Sroczynski, Gaby; Schnell-Inderst, Petra; Mühlberger, Nikolai; Lang, Katharina; Aidelsburger, Pamela; Wasem, Jürgen; Mittendorf, Thomas; Engel, Jutta; Hillemanns, Peter; Petry, Karl Ulrich; Krämer, Alexander; Siebert, Uwe

    2010-01-01

    Background Persistent infections with high-risk types of human papillomavirus (HPV) are associated with the development of cervical neoplasia. Compared to cytology HPV testing is more sensitive in detecting high-grade cervical cancer precursors, but with lower specificity. HPV based primary screening for cervical cancer is currently discussed in Germany. Decisions should be based on a systematic evaluation of the long-term effectiveness and cost-effectiveness of HPV based primary screening. Research questions What is the long-term clinical effectiveness (reduction in lifetime risk of cervical cancer and death due to cervical cancer, life years gained) of HPV testing and what is the cost-effectiveness in Euro per life year gained (LYG) of including HPV testing in primary cervical cancer screening in the German health care context? How can the screening program be improved with respect to test combination, age at start and end of screening and screening interval and which recommendations should be made for the German health care context? Methods A previously published and validated decision-analytic model for the German health care context was extended and adapted to the natural history of HPV infection and cervical cancer in order to evaluate different screening strategies that differ by screening interval, and tests, including cytology alone, HPV testing alone or in combination with cytology, and HPV testing with cytology triage for HPV-positive women. German clinical, epidemiological and economic data were used. In the absence of individual data, screening adherence was modelled independently from screening history. Test accuracy data were retrieved from international meta-analyses. Predicted outcomes included reduction in lifetime-risk for cervical cancer cases and deaths, life expectancy, lifetime costs, and discounted incremental cost-effectiveness ratios (ICER). The perspective of the third party payer and 3% annual discount rate were adopted. Extensive

  13. A multicentre, open-label, follow-on study to assess the long-term maintenance of effect, tolerance and safety of THC/CBD oromucosal spray in the management of neuropathic pain.

    PubMed

    Hoggart, B; Ratcliffe, S; Ehler, E; Simpson, K H; Hovorka, J; Lejčko, J; Taylor, L; Lauder, H; Serpell, M

    2015-01-01

    Peripheral neuropathic pain (PNP) poses a significant clinical challenge. The long-term efficacy of delta-9-tetrahydrocannabinol (THC)/cannabidiol (CBD) oromucosal spray was investigated in this 38-week open-label extension study. In total, 380 patients with PNP associated with diabetes or allodynia entered this study from two parent randomised, controlled trials. Patients received THC/CBD spray for a further 38 weeks in addition to their current analgesic therapy. Neuropathic pain severity was the primary efficacy measure using a pain 0-10 numerical rating scale (NRS). Additional efficacy, safety and tolerability outcomes were also investigated. In total, 234 patients completed the study (62 %). The pain NRS showed a decrease in score over time in patients from a mean of 6.9 points (baseline in the parent studies) to a mean of 4.2 points (end of open-label follow-up). The proportion of patients who reported at least a clinically relevant 30 % improvement in pain continued to increase with time (up to 9 months); at least half of all patients reported a 30 % improvement at all time points. Improvements were observed for all secondary efficacy outcomes, including sleep quality 0-10 NRS scores, neuropathic pain scale scores, subject global impression of change and EQ-5D questionnaire scores. THC/CBD spray was well tolerated for the study duration and patients did not seek to increase their dose with time, with no new safety concerns arising from long-term use. In this previously difficult to manage patient population, THC/CBD spray was beneficial for the majority of patients with PNP associated with diabetes or allodynia.

  14. The past versus the present, 1980-2004: reduction of mean initial low-dose, long-term glucocorticoid therapy in rheumatoid arthritis from 10.3 to 3.6 mg/day, concomitant with early methotrexate, with long-term effectiveness and safety of less than 5 mg/day.

    PubMed

    Pincus, Theodore; Sokka, Tuulikki; Cutolo, Maurizio

    2015-01-01

    Quantitative observations are presented concerning treatment with glucocorticoids of 308 patients with rheumatoid arthritis (RA) at a weekly academic rheumatology setting over 25 years from 1980 to 2004. A database of all visits included medications and multidimensional health assessment questionnaire scores for physical function, pain and routine assessment of patient index data (RAPID3; and a surrogate RAPID3-EST), completed by each patient at each visit in routine care. Over the 5-year periods of 1980-1984, 1985-1989, 1990-1994, 1995-1999 and 2000-2004, the mean initial prednisone daily dose declined from 10.3 to 6.5, 5.1, 4.1 and 3.6 mg/day, as initial doses were >5 mg/day in 49, 16, 7, 7 and 3% of patients, 5 mg/day in 51, 80, 70, 26 and 10%, and <5 mg/day in 0, 4, 23, 67 and 86%. Reduction of prednisone doses in the respective five-year periods was accompanied by increased and earlier use of methotrexate as the first disease-modifying antirheumatic drug (DMARD) in 10, 26, 57, 71 and 78%, and methotrexate treatment in 10, 26, 74, 82 and 92% of patients within the first year of disease. Higher methotrexate doses in the respective five-year periods were used after 1990, along with lower prednisone doses. Most patients were treated indefinitely with both low-dose prednisone and methotrexate; 80% continued both medications for more than 5 years. The primary adverse events were skin-thinning and bruising. New hypertension, diabetes and cataracts were seen in fewer than 10% of patients. While efficacy and safety cannot be analyzed definitively from observational data, the data suggest that many patients with RA might be treated effectively with weekly low-dose methotrexate along with initial and long-term, low-dose prednisone of <5 mg/day. PMID:25228430

  15. Evaluation of the CENTURY model using long-term fertilization trials under corn-wheat cropping systems in the typical croplands of China.

    PubMed

    Cong, Rihuan; Wang, Xiujun; Xu, Minggang; Ogle, Stephen M; Parton, William J

    2014-01-01

    Soil organic matter models are widely used to study soil organic carbon (SOC) dynamics. Here, we used the CENTURY model to simulate SOC in wheat-corn cropping systems at three long-term fertilization trials. Our study indicates that CENTURY can simulate fertilization effects on SOC dynamics under different climate and soil conditions. The normalized root mean square error is less than 15% for all the treatments. Soil carbon presents various changes under different fertilization management. Treatment with straw return would enhance SOC to a relatively stable level whereas chemical fertilization affects SOC differently across the three sites. After running CENTURY over the period of 1990-2050, the SOC levels are predicted to increase from 31.8 to 52.1 Mg ha-1 across the three sites. We estimate that the carbon sequestration potential between 1990 and 2050 would be 9.4-35.7 Mg ha-1 under the current high manure application at the three sites. Analysis of SOC in each carbon pool indicates that long-term fertilization enhances the slow pool proportion but decreases the passive pool proportion. Model results suggest that change in the slow carbon pool is the major driver of the overall trends in SOC stocks under long-term fertilization.

  16. An evaluation study of the determinants of future perspective and global Quality of Life in Spanish long-term premenopausal early-stage breast cancer survivors

    PubMed Central

    Illarramendi, Jose Juan; Salgado, Esteban; de la Cruz, Susana; Asin, Gemma; Manterola, Ana; Ibañez, Berta; Zarandona, Uxue; Dominguez, Miguel Angel; Vera, Ruth

    2016-01-01

    Aim of the study Quality of life (QL) is important in premenopausal long-term breast cancer survivors. In this study we assessed QL and factors associated with future perspective and global QL in premenopausal early-stage long-term breast cancer survivors from Spain. Material and methods 243 premenopausal stage I-IIIA relapse-free breast cancer patients who had received surgery 5–20 years previously completed EORTC QLQ-C30 and QLQ-BR23 questionnaires once during follow-up. Univariate and multivariate logistic regression analyses were performed. Results QL mean scores were high in most areas (> 80 in functioning; < 20 in symptoms). The main factors for future perspective were emotional and social functioning, fatigue, breast symptom, and body image. The main factors for global QL were fatigue, pain and physical functioning, and emotional and social functioning. The best logistic model to explain future perspective associated high emotional and social functioning and low breast symptoms with a lower risk of low future perspective (R2 = 0.56). Higher scores in physical and emotional functioning and lower scores in fatigue were associated with a lower risk of low global QL (R2 = 0.50). Conclusions Psychological, social, and physical factors were found to be possible determinants of global QL and future perspective. QL in premenopausal early-stage long-term breast cancer survivors may benefit from multidisciplinary treatment. PMID:27358597

  17. Evaluation of the CENTURY Model Using Long-Term Fertilization Trials under Corn-Wheat Cropping Systems in the Typical Croplands of China

    PubMed Central

    Cong, Rihuan; Wang, Xiujun; Xu, Minggang; Ogle, Stephen M.; Parton, William J.

    2014-01-01

    Soil organic matter models are widely used to study soil organic carbon (SOC) dynamics. Here, we used the CENTURY model to simulate SOC in wheat-corn cropping systems at three long-term fertilization trials. Our study indicates that CENTURY can simulate fertilization effects on SOC dynamics under different climate and soil conditions. The normalized root mean square error is less than 15% for all the treatments. Soil carbon presents various changes under different fertilization management. Treatment with straw return would enhance SOC to a relatively stable level whereas chemical fertilization affects SOC differently across the three sites. After running CENTURY over the period of 1990–2050, the SOC levels are predicted to increase from 31.8 to 52.1 Mg ha−1 across the three sites. We estimate that the carbon sequestration potential between 1990 and 2050 would be 9.4–35.7 Mg ha−1 under the current high manure application at the three sites. Analysis of SOC in each carbon pool indicates that long-term fertilization enhances the slow pool proportion but decreases the passive pool proportion. Model results suggest that change in the slow carbon pool is the major driver of the overall trends in SOC stocks under long-term fertilization. PMID:24751981

  18. Pesticide residues in leafy vegetables, stalk and stem vegetables from South Korea: a long-term study on safety and health risk assessment.

    PubMed

    Park, Duck Woong; Kim, Kwang Gon; Choi, Eun Ah; Kang, Gyeong Ri; Kim, Tae Sun; Yang, Yong Shik; Moon, Su Jin; Ha, Dong Ryong; Kim, Eun Sun; Cho, Bae Sik

    2016-01-01

    South Korea has a unique food culture. South Koreans enjoy wrapping meat and eating or making kimchi (traditionally fermented Korean food) and eating using raw leafy vegetables, stalk and stem vegetables. Therefore, there is a high chance of being exposed to pesticide residues of vegetables. The objective of this study was to investigate pesticide residues in leafy vegetables, stalk and stem vegetables from South Korea. A total of 8496 samples were mainly collected from Gwangju and Jeonnam area (the largest production region of leafy vegetables, stalk and stem vegetables) in South Korea from 2010 to 2014. A total of 230 pesticides were used for multi-residue analysis of pesticides. Among 8496 samples, 61 different pesticides (1029 times) were detected in 890 samples, of which 118 samples (1.4%) exceeded the Korea maximum residue limits (MRLs). Samples exceeding the MRLs were mostly found in leafy vegetables (brassica lee ssp. namai, leafy lettuce, spinach, perilla leaves, crown daisy, marsh mallow, aster scaber, pimpinella brachycarpa) and Chinese chive. Procymidone, dimethomorph and azoxystrobin were the most frequently found pesticides. A risk assessment of pesticides exceeding the MRLs was evaluated by calculating the estimated daily intake (EDI) and the acceptable daily intake (ADI). The ratio of EDI to ADI was 0.003-30.4%.

  19. Pesticide residues in leafy vegetables, stalk and stem vegetables from South Korea: a long-term study on safety and health risk assessment.

    PubMed

    Park, Duck Woong; Kim, Kwang Gon; Choi, Eun Ah; Kang, Gyeong Ri; Kim, Tae Sun; Yang, Yong Shik; Moon, Su Jin; Ha, Dong Ryong; Kim, Eun Sun; Cho, Bae Sik

    2016-01-01

    South Korea has a unique food culture. South Koreans enjoy wrapping meat and eating or making kimchi (traditionally fermented Korean food) and eating using raw leafy vegetables, stalk and stem vegetables. Therefore, there is a high chance of being exposed to pesticide residues of vegetables. The objective of this study was to investigate pesticide residues in leafy vegetables, stalk and stem vegetables from South Korea. A total of 8496 samples were mainly collected from Gwangju and Jeonnam area (the largest production region of leafy vegetables, stalk and stem vegetables) in South Korea from 2010 to 2014. A total of 230 pesticides were used for multi-residue analysis of pesticides. Among 8496 samples, 61 different pesticides (1029 times) were detected in 890 samples, of which 118 samples (1.4%) exceeded the Korea maximum residue limits (MRLs). Samples exceeding the MRLs were mostly found in leafy vegetables (brassica lee ssp. namai, leafy lettuce, spinach, perilla leaves, crown daisy, marsh mallow, aster scaber, pimpinella brachycarpa) and Chinese chive. Procymidone, dimethomorph and azoxystrobin were the most frequently found pesticides. A risk assessment of pesticides exceeding the MRLs was evaluated by calculating the estimated daily intake (EDI) and the acceptable daily intake (ADI). The ratio of EDI to ADI was 0.003-30.4%. PMID:26571090

  20. Performance considerations in long-term spaceflight

    NASA Technical Reports Server (NTRS)

    Akins, F. R.

    1979-01-01

    Maintenance of skilled performance during extended space flight is of critical importance to both the health and safety of crew members and to the overall success of mission goals. An examination of long term effects and performance requirements is therefore a factor of immense importance to the planning of future missions. Factors that were investigated include: definition of performance categories to be investigated; methods for assessing and predicting performance levels; in-flight factors which can affect performance; and factors pertinent to the maintenance of skilled performance.

  1. OSLER and ODYSSEY LONG TERM: PCSK9 inhibitors on the right track of reducing cardiovascular events.

    PubMed

    Hassan, Mohamed

    2015-01-01

    Proprotein convertase subtilisin kexin 9 (PCSK9) inhibitors have emerged as a novel treatment option in patients with hypercholesterolemia. Evolocumab and alirocumab have achieved consistent and significant (around 60%) reduction in low-density lipoprotein cholesterol (LDL-C) levels when added to statin therapy in short term studies. The Open-Label Study of Long-term Evaluation Against LDL-C (OSLER), and The Long-term Safety and Tolerability of Alirocumab in High Cardiovascular Risk Patients with Hypercholesterolemia Not Adequately Controlled with Their Lipid Modifying Therapy (ODYSSEY LONG TERM) studies are two phase 3, multicentre, randomized, placebo controlled studies that were conducted to evaluate the long term efficacy and safety of evolocumab and alirocumab respectively in reducing lipids and cardiovascular (CV) events. Both studies demonstrated additional 48-53% reduction of CV events when added to statin therapy. Most adverse events occurred with similar frequency in the two groups; however the rate of neurocognitive adverse events was higher with evolocumab and alirocumab than with placebo. These data provide strong support for the notion that lower LDL-C goal is better, and may confirm the role of PCSK9 inhibitors as a new frontier in lipid management. The results of larger long-term outcome studies are still awaited.

  2. OSLER and ODYSSEY LONG TERM: PCSK9 inhibitors on the right track of reducing cardiovascular events

    PubMed Central

    Hassan, Mohamed

    2015-01-01

    Proprotein convertase subtilisin kexin 9 (PCSK9) inhibitors have emerged as a novel treatment option in patients with hypercholesterolemia. Evolocumab and alirocumab have achieved consistent and significant (around 60%) reduction in low-density lipoprotein cholesterol (LDL-C) levels when added to statin therapy in short term studies. The Open-Label Study of Long-term Evaluation Against LDL-C (OSLER), and The Long-term Safety and Tolerability of Alirocumab in High Cardiovascular Risk Patients with Hypercholesterolemia Not Adequately Controlled with Their Lipid Modifying Therapy (ODYSSEY LONG TERM) studies are two phase 3, multicentre, randomized, placebo controlled studies that were conducted to evaluate the long term efficacy and safety of evolocumab and alirocumab respectively in reducing lipids and cardiovascular (CV) events. Both studies demonstrated additional 48–53% reduction of CV events when added to statin therapy. Most adverse events occurred with similar frequency in the two groups; however the rate of neurocognitive adverse events was higher with evolocumab and alirocumab than with placebo. These data provide strong support for the notion that lower LDL-C goal is better, and may confirm the role of PCSK9 inhibitors as a new frontier in lipid management. The results of larger long-term outcome studies are still awaited. PMID:26566525

  3. OSLER and ODYSSEY LONG TERM: PCSK9 inhibitors on the right track of reducing cardiovascular events.

    PubMed

    Hassan, Mohamed

    2015-01-01

    Proprotein convertase subtilisin kexin 9 (PCSK9) inhibitors have emerged as a novel treatment option in patients with hypercholesterolemia. Evolocumab and alirocumab have achieved consistent and significant (around 60%) reduction in low-density lipoprotein cholesterol (LDL-C) levels when added to statin therapy in short term studies. The Open-Label Study of Long-term Evaluation Against LDL-C (OSLER), and The Long-term Safety and Tolerability of Alirocumab in High Cardiovascular Risk Patients with Hypercholesterolemia Not Adequately Controlled with Their Lipid Modifying Therapy (ODYSSEY LONG TERM) studies are two phase 3, multicentre, randomized, placebo controlled studies that were conducted to evaluate the long term efficacy and safety of evolocumab and alirocumab respectively in reducing lipids and cardiovascular (CV) events. Both studies demonstrated additional 48-53% reduction of CV events when added to statin therapy. Most adverse events occurred with similar frequency in the two groups; however the rate of neurocognitive adverse events was higher with evolocumab and alirocumab than with placebo. These data provide strong support for the notion that lower LDL-C goal is better, and may confirm the role of PCSK9 inhibitors as a new frontier in lipid management. The results of larger long-term outcome studies are still awaited. PMID:26566525

  4. What Is Essential in Developmental Evaluation? On Integrity, Fidelity, Adultery, Abstinence, Impotence, Long-Term Commitment, Integrity, and Sensitivity in Implementing Evaluation Models

    ERIC Educational Resources Information Center

    Patton, Michael Quinn

    2016-01-01

    Fidelity concerns the extent to which a specific evaluation sufficiently incorporates the core characteristics of the overall approach to justify labeling that evaluation by its designated name. Fidelity has traditionally meant implementing a model in exactly the same way each time following the prescribed steps and procedures. The essential…

  5. Long-term EEG in children.

    PubMed

    Montavont, A; Kaminska, A; Soufflet, C; Taussig, D

    2015-03-01

    Long-term video-EEG corresponds to a recording ranging from 1 to 24 h or even longer. It is indicated in the following situations: diagnosis of epileptic syndromes or unclassified epilepsy, pre-surgical evaluation for drug-resistant epilepsy, follow-up of epilepsy or in cases of paroxysmal symptoms whose etiology remains uncertain. There are some specificities related to paediatric care: a dedicated pediatric unit; continuous monitoring covering at least a full 24-hour period, especially in the context of pre-surgical evaluation; the requirement of presence by the parents, technician or nurse; and stronger attachment of electrodes (cup electrodes), the number of which is adapted to the age of the child. The chosen duration of the monitoring also depends on the frequency of seizures or paroxysmal events. The polygraphy must be adapted to the type and topography of movements. It is essential to have at least an electrocardiography (ECG) channel, respiratory sensor and electromyography (EMG) on both deltoids. There is no age limit for performing long-term video-EEG even in newborns and infants; nevertheless because of scalp fragility, strict surveillance of the baby's skin condition is required. In the specific context of pre-surgical evaluation, long-term video-EEG must record all types of seizures observed in the child. This monitoring is essential in order to develop hypotheses regarding the seizure onset zone, based on electroclinical correlations, which should be adapted to the child's age and the psychomotor development.

  6. Simulation of Long-Term Carbon and Nitrogen Dynamics in Grassland-Based Dairy Farming Systems to Evaluate Mitigation Strategies for Nutrient Losses.

    PubMed

    Shah, Ghulam Abbas; Groot, Jeroen C J; Shah, Ghulam Mustafa; Lantinga, Egbert A

    2013-01-01

    Many measures have been proposed to mitigate gaseous emissions and other nutrient losses from agroecosystems, which can have large detrimental effects for the quality of soils, water and air, and contribute to eutrophication and global warming. Due to complexities in farm management, biological interactions and emission measurements, most experiments focus on analysis of short-term effects of isolated mitigation practices. Here we present a model that allows simulating long-term effects at the whole-farm level of combined measures related to grassland management, animal housing and manure handling after excretion, during storage and after field application. The model describes the dynamics of pools of organic carbon and nitrogen (N), and of inorganic N, as affected by farm management in grassland-based dairy systems. We assessed the long-term effects of delayed grass mowing, housing type (cubicle and sloping floor barns, resulting in production of slurry and solid cattle manure, respectively), manure additives, contrasting manure storage methods and irrigation after application of covered manure. Simulations demonstrated that individually applied practices often result in compensatory loss pathways. For instance, methods to reduce ammonia emissions during storage like roofing or covering of manure led to larger losses through ammonia volatilization, nitrate leaching or denitrification after application, unless extra measures like irrigation were used. A strategy of combined management practices of delayed mowing and fertilization with solid cattle manure that is treated with zeolite, stored under an impermeable sheet and irrigated after application was effective to increase soil carbon stocks, increase feed self-sufficiency and reduce losses by ammonia volatilization and soil N losses. Although long-term datasets (>25 years) of farm nutrient dynamics and loss flows are not available to validate the model, the model is firmly based on knowledge of processes and

  7. Environmental evaluation of alternatives for long-term management of Defense high-level radioactive wastes at the Idaho Chemical Processing Plant

    SciTech Connect

    Not Available

    1982-09-01

    The U.S. Department of Energy (DOE) is considering the selection of a strategy for the long-term management of the defense high-level wastes at the Idaho Chemical Processing Plant (ICPP). This report describes the environmental impacts of alternative strategies. These alternative strategies include leaving the calcine in its present form at the Idaho National Engineering Laboratory (INEL), or retrieving and modifying the calcine to a more durable waste form and disposing of it either at the INEL or in an offsite repository. This report addresses only the alternatives for a program to manage the high-level waste generated at the ICPP. 24 figures, 60 tables.

  8. A Meta-analysis to Evaluate the Predictive Validity of the Braden Scale for Pressure Ulcer Risk Assessment in Long-term Care.

    PubMed

    Chen, Hong-Lin; Shen, Wang-Qin; Liu, Peng

    2016-09-01

    Although it is among the most commonly used pressure ulcer risk assessment tools, the Braden Scale may lack strong predictive validity when used in the long-term care setting. A meta-analysis was conducted of English-language articles published in the PubMed database and Web of Science from the indices' inception through July 2015 to assess the predictive validity of the Braden Scale for pressure ulcers in long-term care residents. Search terms included pressure ulcer, pressure sore, bedsore, decubitus, long-term care, nursing home, skilled nursing facility, hospice, and Braden. Data extracted from the publications included sample and setting characteristics and predictive value indices. The pooled sensitivities, specificities, diagnostic odds ratios (DOR), and constructed summary receiver operating characteristic (SROC) curves were calculated. Eight studies (2 prospective cohorts and 6 cross-sectional studies) with 41 489 residents met selection criteria for inclusion in the analysis. The pooled sensitivity and specificity were 0.80 (95% CI: 0.79-0.81) and 0.42 (95% CI: 0.42-0.43), respectively, yielding a combined DOR of 5.66 (95% CI: 3.77-8.48). The area under the ROC curve (AUC) was 0.7686 ± 0.0478 (95% CI: 0.6749-0.8623), and the overall diagnostic accuracy (Q*) was 0.7090 ± 0.0402 (95% CI: 0.6302-0.7878). Significant heterogeneity was noted among the included studies; Q value was 302.54 (P = 0.000), and I2 for pooled sensitivity, pooled specificity, and pooled DOR was 97.4%, 98.7% and 96.4%, respectively. Meta-regression analysis showed no heterogeneity was noted among Braden scale cut-offs (P = 0.123) and pressure ulcer prevalence P = 0.547). The evidence showed the Braden Scale has moderate predictive validity and low predictive specificity for pressure ulcers in long-term care residents. The development and testing of new risk assessment scales for this population is warranted. PMID:27668477

  9. Long-term safety of ivermectin 1% cream vs azelaic acid 15% gel in treating inflammatory lesions of rosacea: results of two 40-week controlled, investigator-blinded trials.

    PubMed

    Stein Gold, Linda; Kircik, Leon; Fowler, Joseph; Jackson, J Mark; Tan, Jerry; Draelos, Zoe; Fleischer, Alan; Appell, Melanie; Steinhoff, Martin; Lynde, Charles; Sugarman, Jeffrey; Liu, Hong; Jacovella, Jean

    2014-11-01

    Papulopustular rosacea (PPR) is characterized by facial erythema and inflammatory lesions believed to be primarily caused by dysregulation of the innate immune system. More recent evidence also suggests that Demodex folliculorum mites may contribute to the etiology of PPR. Ivermectin (IVM) 1% cream is a novel topical treatment developed to treat PPR. Two phase 3 trials have demonstrated that IVM 1% cream was significantly better than vehicle at investigator global assessment (IGA) success rate and lesion reductions and that it was safe and well tolerated. Two 40-week extension studies of those trials were conducted to assess the long-term safety of IVM 1% cream vs azelaic acid (AzA) 15% gel. Subjects originally treated with IVM 1% continued on IVM 1% and those originally treated with vehicle switched to AzA 15% gel. IVM 1% cream was safe throughout the study with a lower incidence of related adverse events (AEs) compared to AzA 15% gel. No subjects in the IVM 1% cream group discontinued either study due to a related AE. IVM 1% also continued to be efficacious during the 40-week extension studies as the percentage of subjects with IGA scores of clear or almost clear was higher at the end of the study compared to baseline. The results of these 40-week extension studies support the use of IVM 1% cream as a long-term therapy for PPR as IVM 1% cream was shown to be safe and effective for up to 52 weeks of total treatment. PMID:25607706

  10. Session 6: Infant nutrition: future research developments in Europe EARNEST, the early nutrition programming project: EARly Nutrition programming - long-term Efficacy and Safety Trials and integrated epidemiological, genetic, animal, consumer and economic research.

    PubMed

    Fewtrell, M S

    2007-08-01

    Increasing evidence from lifetime experimental studies in animals and observational and experimental studies in human subjects suggests that pre- and postnatal nutrition programme long-term health. However, key unanswered questions remain on the extent of early-life programming in contemporary European populations, relevant nutritional exposures, critical time periods, mechanisms and the effectiveness of interventions to prevent or reverse programming effects. The EARly Nutrition programming - long-term Efficacy and Safety Trials and integrated epidemiological, genetic, animal, consumer and economic research (EARNEST) consortium brings together a multi-disciplinary team of scientists from European research institutions in an integrated programme of work that includes experimental studies in human subjects, modern prospective observational studies and mechanistic animal work including physiological studies, cell-culture models and molecular techniques. Theme 1 tests early nutritional programming of disease in human subjects, measuring disease markers in childhood and early adulthood in nineteen randomised controlled trials of nutritional interventions in pregnancy and infancy. Theme 2 examines associations between early nutrition and later outcomes in large modern European population-based prospective studies, with detailed measures of diet in pregnancy and early life. Theme 3 uses animal, cellular and molecular techniques to study lifetime effects of early nutrition. Biomedical studies are complemented by studies of the social and economic importance of programming (themes 4 and 5), and themes encouraging integration, communication, training and wealth creation. The project aims to: help formulate policies on the composition and testing of infant foods; improve the nutritional value of infant formulas; identify interventions to prevent and reverse adverse early nutritional programming. In addition, it has the potential to develop new products through industrial

  11. The interRAI Pediatric Home Care (PEDS HC) Assessment: Evaluating the Long-term Community-Based Service and Support Needs of Children Facing Special Healthcare Challenges

    PubMed Central

    Phillips, Charles D; Hawes, Catherine

    2015-01-01

    The vast majority of assessment instruments developed to assess children facing special healthcare challenges were constructed to assess children within a limited age range or children who face specific conditions or impairments. In contrast, the interRAI Pediatric Home Care (PEDS HC) Assessment Form was specifically designed to assess the long-term community-based service and support needs of children and youth aged from four to 20 years who face a wide range of chronic physical or behavioral health challenges. Initial research indicates that PEDS HC items exhibit good predictive validity—explaining significant proportions of the variance in parents’ perceptions of needs, case managers’ service authorizations, and Medicaid program expenditures for long-term community-based services and supports. In addition, PEDS HC items have been used to construct scales that summarize the strengths and needs of children facing special healthcare challenges. Versions of the PEDS HC are now being used in Medicaid programs in three states in the United States. PMID:26401100

  12. Evaluating soil quality under a long-term integrated tillage-water-nutrient experiment with intensive rice-wheat rotation in a semi-arid Inceptisol, India.

    PubMed

    Bhaduri, Debarati; Purakayastha, T J; Patra, A K; Chakraborty, Debashis

    2014-04-01

    Long-term sustainability and a declining trend in productivity of rice-wheat rotation in the Indo-Gangetic plain, often direct towards the changes in soil quality parameters. Soil quality is decided through few sensitive soil physical, chemical and biological indicators as it cannot be measured directly. The present investigation was carried out to develop a valid soil quality index through some chosen indicators under long-term influences of tillage, water and nutrient-management practices in a rice-wheat cropping system. The experiment consisted of two tillage treatments, three irrigation treatments, and nine nutrient management treatments for both rice and wheat, was continued for 8 years. The index was developed using expert-opinion based conceptual framework model. After harvest of rice, the CFSQI-P (productivity) was higher under puddled situation, whereas CFSQI-EP (environmental protection) was more under non-puddled condition and 3-days of drainage was found promising for all the indices. No-tillage practice always showed higher soil quality index. The treatments either receiving full organics (100% N) or 25% substitution of fertilizer N with organics showed higher soil quality indices. Puddling, irrigation after 3 days of drainage and substitution of 25% recommended fertilizer N dose with FYM in rice could be practiced for maintaining or enhancing soil quality. No-tillage, two irrigations, and domestic sewage sludge in wheat can safely be recommended for achieving higher soil quality. PMID:24310369

  13. Evaluating soil quality under a long-term integrated tillage-water-nutrient experiment with intensive rice-wheat rotation in a semi-arid Inceptisol, India.

    PubMed

    Bhaduri, Debarati; Purakayastha, T J; Patra, A K; Chakraborty, Debashis

    2014-04-01

    Long-term sustainability and a declining trend in productivity of rice-wheat rotation in the Indo-Gangetic plain, often direct towards the changes in soil quality parameters. Soil quality is decided through few sensitive soil physical, chemical and biological indicators as it cannot be measured directly. The present investigation was carried out to develop a valid soil quality index through some chosen indicators under long-term influences of tillage, water and nutrient-management practices in a rice-wheat cropping system. The experiment consisted of two tillage treatments, three irrigation treatments, and nine nutrient management treatments for both rice and wheat, was continued for 8 years. The index was developed using expert-opinion based conceptual framework model. After harvest of rice, the CFSQI-P (productivity) was higher under puddled situation, whereas CFSQI-EP (environmental protection) was more under non-puddled condition and 3-days of drainage was found promising for all the indices. No-tillage practice always showed higher soil quality index. The treatments either receiving full organics (100% N) or 25% substitution of fertilizer N with organics showed higher soil quality indices. Puddling, irrigation after 3 days of drainage and substitution of 25% recommended fertilizer N dose with FYM in rice could be practiced for maintaining or enhancing soil quality. No-tillage, two irrigations, and domestic sewage sludge in wheat can safely be recommended for achieving higher soil quality.

  14. Developmental Dyslexia and Explicit Long-Term Memory

    ERIC Educational Resources Information Center

    Menghini, Deny; Carlesimo, Giovanni Augusto; Marotta, Luigi; Finzi, Alessandra; Vicari, Stefano

    2010-01-01

    The reduced verbal long-term memory capacities often reported in dyslexics are generally interpreted as a consequence of their deficit in phonological coding. The present study was aimed at evaluating whether the learning deficit exhibited by dyslexics was restricted only to the verbal component of the long-term memory abilities or also involved…

  15. Evaluating the predictability of terrestrial ecosystem carbon fluxes integrating long term eddy-covariance and biometric observations with multi-model ensembles (Invited)

    NASA Astrophysics Data System (ADS)

    Carvalhais, N.; van Oijen, M.; Keenan, T. F.; Macbean, N. L.; Peylin, P. P.; Rammig, A.; Rolinski, S.; Thum, T.; Granier, A.; Loustau, D.; Schuermann, G. J.; Zaehle, S.; Beer, C.; Mahecha, M. D.; Richardson, A. D.; Reichstein, M.

    2013-12-01

    Discrepancies between future projections of land carbon fluxes originate from different process representations, but also from differences in model parameterization. Model parameters are typically drawn from disparate literature sources, individual site measurements, or expert judgment, allowing for large variability in the actual parameters used and thus model functional responses. In addition, differences in meteorological forcing datasets and modeling setups may contribute strongly to differences at inter-annual and longer time scales. Along with the known differences in the mean model behavior under future climate scenarios, there are likely also differences in model responses to increased climate variability, and extreme events, which have yet to be assessed. In this study we developed an in situ model data fusion experiment to explore the contribution of diverse long-term observations in addressing the divergence of modeled projections of ecosystem water and carbon fluxes until 2100, along with responses to climate variability and extreme events. We focus on two forest sites in France - Hesse and Le Bray - for which carbon and water fluxes have been observed for more than ten years using eddy covariance methodology. The consolidated set of eddy covariance observations and respective uncertainties is complemented with biometric information on aboveground biomass, biomass increments and soil carbon stocks. These datasets are simultaneously used as constraints in the inverse parameter optimization of an ensemble of terrestrial biogeochemical models ranging from specific forest models to generic land surface schemes, namely: BASFOR, FöBAAR, JSBACH, LPJ and ORCHIDEE. The experimental setup includes the harmonization of the optimization by forcing and constraining the models with the same observations, and through a common cost function. The set of multiple constraints ensures that the models simulate the responses of ecosystem fluxes to environmental conditions

  16. Titanium for long-term tritium storage

    SciTech Connect

    Heung, L.K.

    1994-12-01

    Due to the reduction of nuclear weapon stockpile, there will be an excess of tritium returned from the field. The excess tritium needs to be stored for future use, which might be several years away. A safe and cost effective means for long term storage of tritium is needed. Storing tritium in a solid metal tritide is preferred to storing tritium as a gas, because a metal tritide can store tritium in a compact form and the stored tritium will not be released until heat is applied to increase its temperature to several hundred degrees centigrade. Storing tritium as a tritide is safer and more cost effective than as a gas. Several candidate metal hydride materials have been evaluated for long term tritium storage. They include uranium, La-Ni-Al alloys, zirconium and titanium. The criteria used include material cost, radioactivity, stability to air, storage capacity, storage pressure, loading and unloading conditions, and helium retention. Titanium has the best combination of properties and is recommended for long term tritium storage.

  17. Infective endocarditis: determinants of long term outcome

    PubMed Central

    Netzer, R O M; Altwegg, S C; Zollinger, E; Täuber, M; Carrel, T; Seiler, C

    2002-01-01

    Objective: To evaluate predictors of long term prognosis in infective endocarditis. Design: Retrospective cohort study. Setting: Tertiary care centre. Patients: 212 consecutive patients with infective endocarditis between 1980 and 1995 Main outcome measures: Overall and cardiac mortality; event-free survival; and the following events: recurrence, need for late valve surgery, bleeding and embolic complications, cerebral dysfunction, congestive heart failure. Results: During a mean follow up period of 89 months (range 1–244 months), 56% of patients died. In 180 hospital survivors, overall and cardiac mortality amounted to 45% and 24%, respectively. By multivariate analysis, early surgical treatment, infection by streptococci, age < 55 years, absence of congestive heart failure, and > 6 symptoms or signs of endocarditis during active infection were predictive of improved overall long term survival. Independent determinants of event-free survival were infection by streptococci and age < 55 years. Event-free survival was 17% at the end of follow up both in medically–surgically treated patients and in medically treated patients. Conclusions: Long term survival following infective endocarditis is 50% after 10 years and is predicted by early surgical treatment, age < 55 years, lack of congestive heart failure, and the initial presence of more symptoms of endocarditis. PMID:12067947

  18. Long-Term, Open-Label, Safety Study of Edivoxetine 12 to 18 mg Once Daily as Adjunctive Treatment for Patients With Major Depressive Disorder Who Are Partial Responders to Selective Serotonin Reuptake Inhibitor Treatment.

    PubMed

    Ball, Susan G; Atkinson, Sarah; Sparks, JonDavid; Bangs, Mark; Goldberger, Celine; Dubé, Sanjay

    2015-06-01

    Long-term safety, tolerability, and efficacy of adjunctive edivoxetine hydrochloride (hereafter edivoxetine), a highly selective and potent norepinephrine reuptake inhibitor, was assessed in patients with major depressive disorder (MDD) experiencing partial response to selective serotonin reuptake inhibitor treatment. Data are from a multicenter, 54-week, open-label trial of adjunctive edivoxetine 12 to 18 mg once daily in patients with MDD who had experienced partial response by history to 6 or more weeks of current selective serotonin reuptake inhibitor therapy and who had a 17-item GRID Hamilton Rating Scale for Depression total score 16 or higher at study entry. Safety measures included discontinuation rate, treatment-emergent adverse events, serious adverse events, and vital signs. Efficacy measures included the Montgomery-Åsberg Depression Rating Scale. Of 608 patients, 328 (54%) completed the open-label adjunctive treatment. Study discontinuation due to adverse events occurred in 17.0%, and there were 13 serious adverse events (1 death). Treatment-emergent adverse events 5% or higher were nausea, hyperhidrosis, constipation, headache, dry mouth, dizziness, vomiting, insomnia, and upper respiratory tract infection. Mean increases were observed in systolic blood pressure (range, 0.0-2.3 mm Hg), diastolic blood pressure (range, 1.9-3.3 mm Hg), and pulse (range, 5.9-8.4 beats per minute). Mean improvements on the Montgomery-Åsberg Depression Rating Scale (-17.0) were observed from baseline to week 54. The safety profile from this study provides an overview of outcomes associated with edivoxetine and norepinephrine reuptake inhibition as an adjunctive treatment in patients with MDD who were treated up to 1 year. PMID:25815754

  19. Long-term space flights - personal impressions

    NASA Astrophysics Data System (ADS)

    Polyakov, V. V.

    During a final 4-month stage of a 1-year space flight of cosmonauts Titov and Manarov, a physician, Valery Polyakov was included on a crew for the purpose of evaluating their health, correcting physical status to prepare for the spacecraft reentry and landing operations. The complex program of scientific investigations and experiments performed by the physician included an evaluation of adaptation reactions of the human body at different stages of space mission using clinicophysiological and biochemical methods; testing of alternative regimes of exercise and new countermeasures to prevent an unfavourable effect of long-term weightlessness.

  20. Evaluation of H2O2 prophylaxis of bacteriuria in patients with long-term indwelling Foley catheters: a randomized controlled study.

    PubMed

    Sweet, D E; Goodpasture, H C; Holl, K; Smart, S; Alexander, H; Hedari, A

    1985-07-01

    Since the long-term catheterized patient is at significant risk of urinary tract infection, and the catheter drainage bags of these patients are at significant risk of becoming reservoirs for nosocomial pathogens, we carried out a randomized, controlled study to determine the efficacy of intermittent drainage bag instillation of hydrogen peroxide (H2O2) in patients requiring indwelling Foley catheters for 5 days or more. Herein we report the effects of this technique on the rates of catheter and bag bacteriuria, the duration to positive culture, the temporal relationships observed, and the spectrum of organisms recovered. Bag source bacteriuria was found with the same frequency in both control and H2O2 groups. H2O2 did reduce contamination of the drainage bag but did not reduce catheter-associated bacteriuria or frequency of symptomatic urinary tract infection. Furthermore, H2O2 did not reduce the frequency of bag contamination with most of the common nosocomial urinary pathogens.

  1. Evaluation of Neural Response Telemetry (NRT™) with focus on long-term rate adaptation over a wide range of stimulation rates.

    PubMed

    Huarte, Alicia; Ramos, Angel; Morera, Constantino; Garcia-Ibáñez, Luis; Battmer, Rolf; Dillier, Norbert; Wesarg, Thomas; Müller-Deile, Joachim; Hey, Mattias; Offeciers, Erwin; von Wallenberg, Ernst; Coudert, Chrystelle; Killian, Matthijs

    2014-05-01

    Custom Sound EP™ (CSEP) is an advanced flexible software tool dedicated to recording of electrically evoked compound action potentials (ECAPs) in Nucleus® recipients using Neural Response Telemetry™ (NRT™). European multi-centre studies of the Freedom™ cochlear implant system confirmed that CSEP offers tools to effectively record ECAP thresholds, amplitude growth functions, recovery functions, spread of excitation functions, and rate adaptation functions and an automated algorithm (AutoNRT™) to measure threshold profiles. This paper reports on rate adaptation measurements. Rate adaptation of ECAP amplitudes can successfully be measured up to rates of 495 pulses per second (pps) by repeating conventional ECAP measurements and over a wide range of rates up to 8000 pps using the masked response extraction technique. Rate adaptation did not show a predictable relationship with speech perception and coding strategy channel rate preference. The masked response extraction method offers opportunities to study long-term rate adaptation with well-defined and controlled stimulation paradigms. PMID:24559068

  2. Evaluation of the leucine incorporation technique for detection of pollution-induced community tolerance to copper in a long-term agricultural field trial with urban waste fertilizers.

    PubMed

    Lekfeldt, Jonas Duus Stevens; Magid, Jakob; Holm, Peter E; Nybroe, Ole; Brandt, Kristian Koefoed

    2014-11-01

    Copper (Cu) is known to accumulate in agricultural soils receiving urban waste products as fertilizers. We here report the use of the leucine incorporation technique to determine pollution-induced community tolerance (Leu-PICT) to Cu in a long-term agricultural field trial. A significantly increased bacterial community tolerance to Cu was observed for soils amended with organic waste fertilizers and was positively correlated with total soil Cu. However, metal speciation and whole-cell bacterial biosensor analysis demonstrated that the observed PICT responses could be explained entirely by Cu speciation and bioavailability artifacts during Leu-PICT detection. Hence, the agricultural application of urban wastes (sewage sludge or composted municipal waste) simulating more than 100 years of use did not result in sufficient accumulation of Cu to select for Cu resistance. Our findings also have implications for previously published PICT field studies and demonstrate that stringent PICT detection criteria are needed for field identification of specific toxicants.

  3. Electronic nose and chiral-capillary electrophoresis in evaluation of the quality changes in commercial green tea leaves during a long-term storage.

    PubMed

    Mirasoli, Mara; Gotti, Roberto; Di Fusco, Massimo; Leoni, Alberto; Colliva, Carolina; Roda, Aldo

    2014-11-01

    Electronic nose and capillary electrophoresis were applied in quality control of green tea samples subjected to long-term storage. Twelve representative green teas were considered, available as an "aged" (tea leaves stored during a long-term period of two years) and/or "not aged" (fresh products) samples. Their infusions were analyzed by an electronic nose, equipped with an array of six metal oxide semiconductor (MOS) sensors to obtain olfactive fingerprints of the volatile compounds in the infusions headspace. Upon training and chemometric analysis of acquired data (linear discriminant analysis), the electronic nose was found to be able in correctly classifying unknown samples as "aged" or "not aged". Concomitantly, the infusion samples were analyzed by Cyclodextrin-modified Micellar Electrokinetic Chromatography (CD-MEKC) for determination of catechins. The analysis of seven most represented catechins and the methylxanthines theobromine and caffeine revealed a general loss of the polyphenols in each of the considered aged samples (up to 45%, w/w). In addition, the applied enantioselective method based on (2-hydroxypropyl)-β-cyclodextrin (HP-βCD) as chiral selector, was exploited for the estimation of (+)-Gallocatechin in the presence of (-)-Gallocatechin; the latter, as the non-native enantiomer, can be associated to the epimerisation of (-)-Epigallocatechin and was assumed as a marker occurring in case of uncorrected storage conditions of tea leaves. Interestingly, it was observed that epimerization did not significantly occur during aging. The application of CD-MEKC and electronic nose allowed for a fast characterization of green teas taking into account that the aroma is a decisive parameter for the acceptance of the product, whereas the catechins content is associated to the biological value.

  4. Behavioral and physiological effects of a single injection of rat interferon-alpha on male Sprague-Dawley rats: a long-term evaluation.

    PubMed

    Kentner, A C; Miguelez, M; James, J S; Bielajew, C

    2006-06-20

    Interferon-alpha (IFN-alpha) is a cytokine used as a first line of defense against diseases such as cancer and hepatitis C. However, reports indicate that its effectiveness as a treatment is countered by central nervous system (CNS) disruptions in patients. Our work explored the possibility that it may also cause long-term behavioral disruptions by chronicling the behavioral and physiological disturbances associated with a single injection of vehicle, 10, 100, or 1,000 units of IFN-alpha in male Sprague-Dawley rats (n = 5/dose). Following 1 day of locomotor baseline collection, we monitored sickness behaviors (ptosis, piloerection, lethargy, and sleep), food and water intake, body weight, temperature, and motor activity. Observations were recorded 4 days prior to and 4 days following the IFN-alpha injection. Temperature and sickness behaviors were recorded three times daily at 9:00, 15:00, and 21:00 h, and all other indices, once daily. On the injection day, temperature values were highest in the animals receiving the 10-unit IFN-alpha dose 15 min and 13 h post-injection. In the case of sickness behaviors, a significant increase was observed in piloerection in all IFN-alpha groups at each time point measured, while the scores of the rats in the vehicle condition remained unchanged between pre- and post-injection days. Analyses of overall sickness behaviors during morning and night observation periods indicated increased scores in all IFN-alpha groups following injection. Cumulatively, these data suggest that a single IFN-alpha exposure may elicit long-term behavioral disruptions and that its consequences should be thoroughly investigated for its use in clinical populations.

  5. TRAIL and TRAIL receptors splice variants during long-term interferon β treatment of patients with multiple sclerosis: evaluation as biomarkers for therapeutic response

    PubMed Central

    López-Gómez, Carlos; Oliver-Martos, Begoña; Pinto-Medel, María-Jesús; Suardiaz, Margarita; Reyes-Garrido, Virginia; Urbaneja, Patricia; Fernández, Óscar; Leyva, Laura

    2016-01-01

    Objective We aimed to assess the effects of interferon β (IFNβ) treatment on the expression of the splice variants of the Tumour necrosis factor-Related Apoptosis Inducing Ligand (TRAIL) and its receptors in different cell subpopulations (CD14+, CD4+ and CD8+) from patients with multiple sclerosis (MS), and to determine whether this expression discriminated responders from non-responders to IFNβ therapy. Methods We examined mRNA expression of the TRAIL and TRAIL receptors variants in patients with MS, at baseline and after one year of IFNβ therapy, according to responsiveness to this drug. Results Long-term therapy with IFNβ increased the expression of TRAIL-α in T cell subsets exclusively from responders and decreased the expression of the isoform 2 of TRAILR-2 in monocytes from responders as well as non-responders. Lower expression of TRAIL-α, and higher expression of TRAIL-β in monocytes and T cells, was found before the onset of IFNβ therapy in patients who will subsequently become responders. Baseline expression of TRAILR-1 was also significantly higher in monocytes and CD4+ T cells from responders. Conclusions The present study shows that long-term IFNβ treatment has a direct influence on TRAIL-α and TRAILR-2 isoform 2 expression. Besides, receiver operating characteristic analysis revealed that the baseline expression of TRAIL-α in monocytes and T cells, and that of TRAILR-1 in monocytes and CD4+ T cells, showed a predictive value of the clinical response to IFNβ therapy, pointing to a role of TRAIL system in the mechanism of action of IFNβ in MS that will need further investigation. PMID:25736057

  6. Target and non-target analysis of migrants from PVC-coated cans using UHPLC-Q-Orbitrap MS: evaluation of long-term migration testing.

    PubMed

    Vaclavikova, Marta; Paseiro-Cerrato, Rafael; Vaclavik, Lukas; Noonan, Gregory O; DeVries, Jonathan; Begley, Timothy H

    2016-01-01

    A simple, rapid and sensitive method for analyzing multi-target and non-target additives in polyvinyl chloride (PVC) food can coatings using ultra-high-performance liquid chromatography coupled to quadrupole-orbital ion-trap mass spectrometry was developed. This procedure was used to study the behaviour of a cross-linking agent, benzoguanamine (BGA), two slip agents, oleamide and erucamide, and 18 other commonly used plasticisers including phthalates, adipates, sebacates, acetyl tributyl citrate and epoxidised soybean or linseed oils. This optimised method was used to detect these analytes in food simulants (water and 3% acetic acid) in a long-term migration test of PVC-coated food cans for a period ranging from 1 day to 1.5 years at 40°C. Although very low detection limits (5 ng ml(-1)) were obtained for the majority of compounds, none of the monitored plasticisers and slip agents was detected in simulants extracted from cans over the period of the test. However, the presence of BGA in both aqueous food simulants was confirmed based on high-resolution mass spectrometry, product ion spectra and analysis of a reference standard. The BGA concentration in both simulants continued to increase with storage time: after 1.5 years storage in aqueous food simulants at 40°C, BGA was detected at concentrations up to 84 µg dm(-2). We believe this is the first study describing the long-term migration capacity of BGA from any vinyl coating material intended for use in PVC-coated food cans. Our results may have implications for migration test protocols for food cans that will be stored for extended time periods. PMID:26744815

  7. Long-term culture of human corticotropin-secreting adenomas on extracellular matrix and evaluation of serum-free conditions. Secretory aspects.

    PubMed

    Westphal, M; Jaquet, P; Wilson, C B

    1986-01-01

    Tissues from 12 human corticotropin-secreting adenomas, obtained during surgery for Cushing's disease (CD, ten cases) or Nelson's Syndrome (NS, two cases), were exclusively mechanically dispersed. Single cells and cell aggregates were plated on extracellular matrix derived from bovine corneal endothelia. Functional responses to physiological stimuli were analyzed by measuring human beta-endorphin (beta h-EP) immunoreactivity (IR) by radioimmunoassay in the culture medium. All adenomas responded with stimulated secretory activity to arginine vasopressin (AVP), corticotropin-releasing factor (CRF), or both. Cortisol higher than 10(-8) M suppressed basal secretion and CRF- or AVP-stimulated beta h-EP-IR secretion. There was no consistent difference in response of the cells when cultured in medium containing 10% fetal calf serum (FCS) or in serum-free conditions. A change of cells from serum to serum-free conditions usually resulted in 10%-50% reduction in the basal secretion level that remained stable for at least 2 weeks and, in one case (NS), 10 weeks. In cells maintained in medium supplemented with 5% serum obtained from the respective patients 40 min after adenoma removal, basal secretion was suppressed to 60% of the baseline level in a 10% FCS control. Long-term incubation with CRF (10(-9) M) showed sustained stimulation of hormone secretion. No remarkable cell proliferation was observed under basal conditions or during long-term, low-dose incubation with cholera toxin (10(-12) M) in two cases (CD), or CRF (10(-9) M) in two cases (NS, CD). Parallel beta-EP-IR and adrenocorticotropin secretion was verified in selected cases.

  8. Target and non-target analysis of migrants from PVC-coated cans using UHPLC-Q-Orbitrap MS: evaluation of long-term migration testing.

    PubMed

    Vaclavikova, Marta; Paseiro-Cerrato, Rafael; Vaclavik, Lukas; Noonan, Gregory O; DeVries, Jonathan; Begley, Timothy H

    2016-01-01

    A simple, rapid and sensitive method for analyzing multi-target and non-target additives in polyvinyl chloride (PVC) food can coatings using ultra-high-performance liquid chromatography coupled to quadrupole-orbital ion-trap mass spectrometry was developed. This procedure was used to study the behaviour of a cross-linking agent, benzoguanamine (BGA), two slip agents, oleamide and erucamide, and 18 other commonly used plasticisers including phthalates, adipates, sebacates, acetyl tributyl citrate and epoxidised soybean or linseed oils. This optimised method was used to detect these analytes in food simulants (water and 3% acetic acid) in a long-term migration test of PVC-coated food cans for a period ranging from 1 day to 1.5 years at 40°C. Although very low detection limits (5 ng ml(-1)) were obtained for the majority of compounds, none of the monitored plasticisers and slip agents was detected in simulants extracted from cans over the period of the test. However, the presence of BGA in both aqueous food simulants was confirmed based on high-resolution mass spectrometry, product ion spectra and analysis of a reference standard. The BGA concentration in both simulants continued to increase with storage time: after 1.5 years storage in aqueous food simulants at 40°C, BGA was detected at concentrations up to 84 µg dm(-2). We believe this is the first study describing the long-term migration capacity of BGA from any vinyl coating material intended for use in PVC-coated food cans. Our results may have implications for migration test protocols for food cans that will be stored for extended time periods.

  9. Long-term neurodevelopmental and cardiovascular outcome after intrauterine transfusions for fetal anaemia: a review.

    PubMed

    Lindenburg, Irene T M; van Klink, Jeanine M; Smits-Wintjens, Vivianne E H J; van Kamp, Inge L; Oepkes, Dick; Lopriore, Enrico

    2013-09-01

    Perinatal survival rates after intrauterine transfusions (IUT) for red cell alloimmunisation now exceed 90%, which demonstrates the safety and efficacy of one of the most successful procedures in fetal therapy. However, improved perinatal survival could lead to an increased number of children with long-term disabilities. The importance of long-term follow-up studies in fetal therapy lies in both the necessity of evaluation of antenatal management as well as in evidence-based preconceptional and prenatal counselling. This review describes the possible long-term cardiovascular and neurodevelopmental sequelae after IUT treatment for different indications including red cell alloimmunisation, parvovirus B19 infection, fetomaternal haemorrhage and twin anaemia-polycythaemia sequence.

  10. Influence of cover crops and crop residue treatment on soil organic carbon stocks evaluated in Swedish long-term field experiments

    NASA Astrophysics Data System (ADS)

    Poeplau, Christopher; Bolinder, Martin A.; Börjesson, Gunnar; Kätterer, Thomas

    2015-04-01

    Soil organic carbon (SOC) stocks in agricultural soils are strongly controlled by management. In this study we quantified the effect of cover crops and crop residue management on SOC stocks in Swedish long-term experiments. Eight pairs of cover crop (undersown ryegrass) vs. no cover crop were investigated in Swedish long-term field experiments (16 to 24 years). Yields of the main crop were not affected by the cover crop. Cover crops significantly increased SOC stocks, with a mean carbon sequestration rate in all experiments (excluding one) of 0.32±0.29 Mg C ha-1 yr-1. Interestingly, this sequestration is similar to that estimated for a U.S.experiment, where ryegrass growth is much less temperature- and light-limited than under Swedish conditions. This sequestration rate is also the same as that recently reported for many other cover crops in a global meta-analysis but less than SOC changes in ley-dominated rotations which under Nordic conditions were shown to accumulate in average 0.5 Mg C ha-1 yr-1 more carbon compared to exclusively annual cropping systems. Thus, originally introduced in agricultural rotations to reduce nitrate leaching, cover crops are also an effective practice to increase SOC stocks, even at relatively high latitudes. The effect of crop residue treatment was studied in 16 pairs of straw incorporated (SI) vs. straw removed (SR) treatments in six Swedish long-term field experiments. Data series on SOC with 5-28 sampling dates during 27-53 years were analysed using ICBM, a dynamic SOC model. At five out of six sites, the humification coefficient for straw (hlitter; the fraction of straw C that is entering the slow C pool) was much smaller (0-0.09) than the ICBM default h-value for plant material estimated in previous studies (0.125). The derived hlitter-values and thus the stabilization of straw-derived carbon increased significantly with clay content. For an Italian site (with five pairs of SI vs. SR) that was used for model validation we found

  11. The Fukushima nuclear accident and the pale grass blue butterfly: evaluating biological effects of long-term low-dose exposures

    PubMed Central

    2013-01-01

    Background On August 9th 2012, we published an original research article in Scientific Reports, concluding that artificial radionuclides released from the Fukushima Dai-ichi Nuclear Power Plant exerted genetically and physiologically adverse effects on the pale grass blue butterfly Zizeeria maha in the Fukushima area. Immediately following publication, many questions and comments were generated from all over the world. Here, we have clarified points made in the original paper and answered questions posed by the readers. Results The following points were clarified. (1) There are many advantages to using the pale grass blue butterfly as an indicator species. (2) The forewings of the individuals collected in Fukushima were significantly smaller than in the northern and southern localities. (3) We observed growth retardation in the butterflies from the Fukushima area. (4) The aberrant colour patterns in the butterflies obtained in the Fukushima area were different from the colour patterns induced by temperature and sibling crosses but similar to those induced by external and internal exposures to the artificial radionuclides and by a chemical mutagen, suggesting that genetic mutations caused the aberrations. (5) This species of butterfly has been plentiful in Fukushima area for at least half a century. We here present specimens collected from Fukushima Prefecture before the accident. (6) Mutation accumulation was detected by the increase in the abnormality rates from May 2011 to September 2011. (7) The abnormal traits were heritable. (8) Our sampling localities were not affected by the tsunami. (9) We used a high enough number of samples to obtain statistically significant results. (10) The standard rearing method was followed, producing normal adults in the control groups. (11) The exposure experiments successfully reproduced the results of the field work. This species of butterfly is vulnerable to long-term low-dose internal and external exposures; however, insect

  12. The Long-term Management of Used Nuclear Fuel in Canada: A Geoscientific Prespective

    NASA Astrophysics Data System (ADS)

    Belfadhel, B.

    2009-05-01

    The Nuclear Waste Management Organization (NWMO) is responsible for implementing Adaptive Phased Management, the approach selected by the Government of Canada for long-term management of used nuclear fuel waste generated by Canadian nuclear reactors. In support of this objective, NWMO is pursuing an active technical research and development program in areas such as repository engineering, repository geoscience and repository safety. The geoscience work program is designed to develop a geoscientific basis for understanding long-term geosphere barrier performance, as well as building confidence in deep geological repository safety in both sedimentary and crystalline settings. This is achieved through a multidisciplinary approach involving the coordinated effort of research groups drawn from universities, consultants, and international nuclear waste management organizations. The main objectives of the program are to: develop tools and methods to improve NWMO's geosphere characterization capabilities and develop readiness for evaluating potential candidate sites in willing host communities; advance the understanding of long-term physical and geochemical evolution of the geosphere at time scales relevant to repository safety; and improve numerical methods to assess the geosphere evolution and its response to long-term perturbations. The paper provides an overview of the geoscience issues and challenges associated with the development of deep geological repositories and key activities that the NWMO is pursuing to address them.

  13. Long Term Analysis for the BAM device

    NASA Astrophysics Data System (ADS)

    Bonino, D.; Gardiol, D.

    2011-02-01

    Algorithms aimed at the evaluation of critical quantities are based on models with many parameters, which values are estimated from data. The knowledge, with high accuracy, of these values and the control of their temporal evolution are important features. In this work, we focus on the latter subject, and we show a proposed pipeline for the BAM (Basic Angle Monitoring) Long Term Analysis, aimed at the study of the calibration parameters of the BAM device and of the Basic Angle variation, searching for unwanted trends, cyclic features, or other potential unexpected behaviours.

  14. Long-term results of hypofractionated stereotactic radiotherapy with CyberKnife for growth hormone-secreting pituitary adenoma: evaluation by the Cortina consensus.

    PubMed

    Iwata, Hiromitsu; Sato, Kengo; Nomura, Ryutaro; Tabei, Yusuke; Suzuki, Ichiro; Yokota, Naoki; Inoue, Mitsuhiro; Ohta, Seiji; Yamada, Shozo; Shibamoto, Yuta

    2016-06-01

    The aim of the present study was to evaluate the safety and feasibility of hypofractionated stereotactic radiotherapy (SRT) with CyberKnife for growth hormone-secreting pituitary adenoma (GH-PA). Fifty-two patients with GH-PA were treated with hypofractionated SRT between September 2001 and October 2012. Eight patients had clinically silent GH-PA and 44 were symptomatic. Only 1 patient was inoperable. The other patients had recurrent or postoperative residual tumors on MRI. All patients had received pharmacotherapy prior to SRT with a somatostatin analog, dopamine agonist, and/or GH receptor antagonist. The marginal doses were 17.4-26.8 Gy for the 3-fraction schedule and 20.0-32.0 Gy for the 5-fraction schedule. Endocrinological remission was assessed by the Cortina consensus criteria 2010 (random GH <1 ng/ml or nadir GH after an oral glucose tolerance test <0.4 ng/ml and normalization of age- and sex-adjusted insulin-like growth factor-1). The median follow-up period was 60 months (range 27-137). The 5-year overall survival, local control, and disease-free survival rates were 100, 100, and 96 %, respectively. Nine patients (5 clinically silent and 4 symptomatic patients) satisfied the Cortina criteria without receiving further pharmacotherapy, whereas the remaining 43 patients did not. No post-SRT grade 2 or higher visual disorder occurred. Symptomatic post-SRT hypopituitarism was observed in 1 patient. CyberKnife hypofractionated SRT is safe and effective when judged by imaging findings for GH-PA. However, it may be difficult to satisfy the Cortina consensus criteria in most symptomatic patients with SRT alone. Further investigations of optimal treatments are warranted. PMID:26961771

  15. Evaluation of larvicides in developing management guidelines for long-term control of pest blackflies (Diptera: Simuliidae) along the Orange River, South Africa.

    PubMed

    Palmer, R W; Rivers-Moore, N A

    2008-12-01

    In 2000 and 2001 Orange River levels were higher than normal: associated serious outbreaks of blackfly had a substantial detrimental impact on the local economy. The poor control was attributed to the suspected development of larval resistance to temephos. A long-term solution to blackfly control, through the identification of a suitable replacement to temephos for use during high flow conditions, was proposed. This study, however, failed to identify or register a suitable larvicide for use during high flow conditions. Although permethrin was highly effective against blackfly larvae, it was rejected because of its detrimental impacts on non-target fauna. Various formulations of locally produced dry Bacillus thuringiensis var. israelensis (B.t.i.) were tested, but these were ineffective against blackflies. The study also confirmed that resistance to temephos has developed among Simulium chutteri in the middle and lower Orange River. The feasibility of "reversing" the resistance to temephos through the use of the synergist piperonyl butoxide (PBO) was investigated, but the results were not favourable. Furthermore, PBO was highly toxic to blackflies and non-target organisms, and was not recommended for further testing. This means that B.t.i. currently remains the only symptomatic measure of treatment currently applied. Although resistance to B.t.i. has not been reported for blackflies elsewhere in South Africa, there is a need to remain vigilant and to implement an operational strategy that minimizes the risks of resistance developing.

  16. Performance evaluation, microbial enzymatic activity and microbial community of a sequencing batch reactor under long-term exposure to cerium dioxide nanoparticles.

    PubMed

    Wang, Sen; Gao, Mengchun; Li, Zhiwei; She, Zonglian; Wu, Juan; Zheng, Dong; Guo, Liang; Zhao, Yangguo; Gao, Feng; Wang, Xuejiao

    2016-11-01

    The performance, microbial enzymatic activity and microbial community of a sequencing batch reactor (SBR) were investigated under long-term exposure to cerium dioxide nanoparticles (CeO2 NPs). The COD removal kept a stable value at 0-5mg/L CeO2 NPs and then decreased at 10-60mg/L CeO2 NPs. The NH4(+)-N removal had no obvious changes at 0-30mg/L CeO2 NPs, and a minor decrease appeared at 60mg/L CeO2 NPs. Compared to 0mg/L CeO2 NPs, the phosphorus removal showed a decrease at 2mg/L CeO2 NPs and slightly increased at 5-60mg/L CeO2 NPs. The nitrogen and phosphorus removal rates had similar variation trends to the microbial enzymatic activities. The variations of reactive oxygen species (ROS) and lactate dehydrogenase (LDH) indicated that high CeO2 NPs concentration could result in the biotoxicity to activated sludge. The presence of CeO2 NPs had obvious effect on the microbial richness and diversity of activated sludge. PMID:27584902

  17. Cone Beam Computed Tomography Evaluation of the Diagnosis, Treatment Planning, and Long-Term Followup of Large Periapical Lesions Treated by Endodontic Surgery: Two Case Reports

    PubMed Central

    Shekhar, Vijay; Shashikala, K.

    2013-01-01

    The aim of this case report is to present two cases where cone beam computed tomography (CBCT) was used for the diagnosis, treatment planning, and followup of large periapical lesions in relation to maxillary anterior teeth treated by endodontic surgery. Periapical disease may be detected sooner using CBCT, and their true size, extent, nature, and position can be assessed. It allows clinician to select the most relevant views of the area of interest resulting in improved detection of periapical lesions. CBCT scan may provide a better, more accurate, and faster method to differentially diagnose a solid (granuloma) from a fluid-filled lesion or cavity (cyst). In the present case report, endodontic treatment was performed for both the cases followed by endodontic surgery. Biopsy was done to establish the confirmatory histopathological diagnosis of the periapical lesions. Long-term assessment of the periapical healing following surgery was done in all the three dimensions using CBCT and was found to be more accurate than IOPA radiography. It was concluded that CBCT was a useful modality in making the diagnosis and treatment plan and assessing the outcome of endodontic surgery for large periapical lesions. PMID:23762646

  18. Evaluation of precipitates used in strainer head loss testing : Part III. Long-term aluminum hydroxide precipitation tests in borated water.

    SciTech Connect

    Bahn, C. B.; Kasza, K. E.; Shack, W. J.; Natesan, K.; Klein, P.

    2011-05-01

    Long-term aluminum (Al) hydroxide precipitation tests were conducted in slightly alkaline solutions containing 2500 ppm boron. The solution temperature was cycled to obtain a temperature history more representative of emergency core cooling system temperatures after a loss-of-coolant accident. The observed Al precipitation boundary was close to predicted results for amorphous precipitates, which are higher than the solubility expected for crystalline forms. Bench-scale and loop head loss test results under various conditions were successfully combined into single map in a temperature - 'pH + p[Al]{sub T}' domain, which yielded two bounding lines for Al hydroxide solubility in borated alkaline water that depend on whether or not loop head loss tests with Al alloy coupons are included. Precipitates were observed to form either as fine, cloudy suspensions, which showed very little tendency to settle, or as flocculated precipitates. The flocculation tendency of the precipitates can be qualitatively explained by a colloid stability theory or a phase diagram for protein solutions.

  19. Long Term Surface Salinity Measurements

    NASA Technical Reports Server (NTRS)

    Schmitt, Raymond W.; Brown, Neil L.

    2005-01-01

    Our long-term goal is to establish a reliable system for monitoring surface salinity around the global ocean. Salinity is a strong indicator of the freshwater cycle and has a great influence on upper ocean stratification. Global salinity measurements have potential to improve climate forecasts if an observation system can be developed. This project is developing a new internal field conductivity cell that can be protected from biological fouling for two years. Combined with a temperature sensor, this foul-proof cell can be deployed widely on surface drifters. A reliable in-situ network of surface salinity sensors will be an important adjunct to the salinity sensing satellite AQUARIUS to be deployed by NASA in 2009. A new internal-field conductivity cell has been developed by N Brown, along with new electronics. This sensor system has been combined with a temperature sensor to make a conductivity - temperature (UT) sensor suitable for deployment on drifters. The basic sensor concepts have been proven on a high resolution CTD. A simpler (lower cost) circuit has been built for this application. A protection mechanism for the conductivity cell that includes antifouling protection has also been designed and built. Mr. A.Walsh of our commercial partner E-Paint has designed and delivered time-release formulations of antifoulants for our application. Mr. G. Williams of partner Clearwater Instrumentation advised on power and communication issues and supplied surface drifters for testing.

  20. Long-