Sample records for long-term extension study

  1. Assessing coronal laxity in extension and flexion at a minimum of 10 years after primary total knee arthroplasty.

    PubMed

    Yoshihara, Yasushi; Arai, Yuji; Nakagawa, Shuji; Inoue, Hiroaki; Ueshima, Keiichiro; Fujiwara, Hiroyoshi; Oda, Ryo; Taniguchi, Daigo; Kubo, Toshikazu

    2016-08-01

    Favourable long-term results after total knee arthroplasty (TKA) require appropriate soft tissue balance. However, the relationships between long-term results after TKA surgery and mediolateral laxities at extension and at 90° flexion remain unknown. This study therefore quantitatively assessed ligament balance at extension and at 90° knee flexion at least 10 years after primary TKA, as well as clarifying the relationships between long-term outcomes and mediolateral laxities. This study included 49 knees (19 CR type and 30 PS type) of 33 patients followed up for at least 10 years after TKA at our hospital. Plain radiographs were obtained with about 150 N of varus or valgus stress using a Telos arthrometer at extension. At 90° flexion, epicondylar views were obtained under a 1.5-kg load and with about 10 kg of varus or valgus stress. Lateral laxity of about 5° was observed in both extension and flexion, with total laxities of varus and valgus stress each less than 10°. Postoperative clinical outcomes were good, with significant improvements in extension angle, femorotibial angle, and KSS, and no loosening in any knee. Good long-term results of TKA can be obtained with a lateral laxity of about 5°, equivalent to that of healthy knees. III.

  2. Long Term Deck Deterioration : final report.

    DOT National Transportation Integrated Search

    1990-09-01

    In May of 1981 the Oregon State Highway Division was asked by the Federal Highway Administration to participate in a long term deck deterioration study. The study, an extension of an earlier study was finalized in 1979, was to run through 1990. Revie...

  3. Temporal variations in the potential hydrological performance of extensive green roof systems

    NASA Astrophysics Data System (ADS)

    De-Ville, Simon; Menon, Manoj; Stovin, Virginia

    2018-03-01

    Existing literature provides contradictory information about variation in potential green roof hydrological performance over time. This study has evaluated a long-term hydrological monitoring record from a series of extensive green roof test beds to identify long-term evolutions and sub-annual (seasonal) variations in potential hydrological performance. Monitoring of nine differently-configured extensive green roof test beds took place over a period of 6 years in Sheffield, UK. Long-term evolutions and sub-annual trends in maximum potential retention performance were identified through physical monitoring of substrate field capacity over time. An independent evaluation of temporal variations in detention performance was undertaken through the fitting of reservoir-routing model parameters. Aggregation of the resulting retention and detention variations permitted the prediction of extensive green roof hydrological performance in response to a 1-in-30-year 1-h summer design storm for Sheffield, UK, which facilitated the comparison of multi and sub-annual hydrological performance variations. Sub-annual (seasonal) variation was found to be significantly greater than long-term evolution. Potential retention performance increased by up to 12% after 5-years, whilst the maximum sub-annual variation in potential retention was 27%. For vegetated roof configurations, a 4% long-term improvement was observed for detention performance, compared to a maximum 63% sub-annual variation. Consistent long-term reductions in detention performance were observed in unvegetated roof configurations, with a non-standard expanded-clay substrate experiencing a 45% reduction in peak attenuation over 5-years. Conventional roof configurations exhibit stable long-term hydrological performance, but are nonetheless subject to sub-annual variation.

  4. Long-term efficacy and safety of lamotrigine monotherapy in Japanese and South Korean pediatric patients with newly diagnosed typical absence seizures: An open-label extension study.

    PubMed

    Yasumoto, Sawa; Ohtsuka, Yoko; Sato, Katsuaki; Kurata, Atsuyo; Numachi, Yotaro; Shimizu, Masahiro

    2018-05-31

    To investigate the efficacy and safety of long-term lamotrigine (LTG) monotherapy in Japanese and South Korean pediatric patients with newly diagnosed typical absence seizures. Six Japanese patients and one South Korean patient were enrolled in the extension phase of the study after completing the 12-week maintenance phase of an open-label clinical study of LTG monotherapy. During the extension phase, patients underwent efficacy and safety evaluation every 12 weeks. Of the seven patients, six patients completed the extension phase. The seizure-free rate confirmed by hyperventilation (HV)-electroencephalography ranged from 71.4% to 100.0% at each visit up to Week 168 of the extension phase. Similar effects were confirmed by HV-clinical signs and seizure diaries. Although no unexpected adverse events were observed, one Japanese patient was withdrawn from the extension phase due to mild drug-related rash developed 842 days after the start of LTG. Although the number of patients is limited, long-term LTG monotherapy appeared to be effective and generally well tolerated in Japanese and South Korean pediatric patients with typical absence seizures. Copyright © 2018 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  5. Subregion-Specific p300 Conditional Knock-Out Mice Exhibit Long-Term Memory Impairments

    ERIC Educational Resources Information Center

    Oliveira, Ana M. M.; Estevez, Marcel A.; Hawk, Joshua D.; Grimes, Shannon; Brindle, Paul K.; Abel, Ted

    2011-01-01

    Histone acetylation plays a critical role during long-term memory formation. Several studies have demonstrated that the histone acetyltransferase (HAT) CBP is required during long-term memory formation, but the involvement of other HAT proteins has not been extensively investigated. The HATs CBP and p300 have at least 400 described interacting…

  6. Comparative study of different stochastic weather generators for long-term climate data simulation

    USDA-ARS?s Scientific Manuscript database

    Climate is one of the single most important factors affecting watershed ecosystems and water resources. The effect of climate variability and change has been studied extensively in some places; in many places, however, assessments are hampered by limited availability of long term continuous climate ...

  7. Interaction of Inhibitory and Facilitatory Effects of Conditioning Trials on Long-Term Memory Formation

    ERIC Educational Resources Information Center

    Hosono, Shouhei; Matsumoto, Yukihisa; Mizunami, Makoto

    2016-01-01

    Animals learn through experience and consolidate the memories into long-time storage. Conditioning parameters to induce protein synthesis-dependent long-term memory (LTM) have been the subject of extensive studies in many animals. Here we found a case in which a conditioning trial inhibits or facilitates LTM formation depending on the intervals…

  8. The need for accurate long-term measurements of water vapor in the upper troposphere and lower stratosphere with global coverage.

    PubMed

    Müller, Rolf; Kunz, Anne; Hurst, Dale F; Rolf, Christian; Krämer, Martina; Riese, Martin

    2016-02-01

    Water vapor is the most important greenhouse gas in the atmosphere although changes in carbon dioxide constitute the "control knob" for surface temperatures. While the latter fact is well recognized, resulting in extensive space-borne and ground-based measurement programs for carbon dioxide as detailed in the studies by Keeling et al. (1996), Kuze et al. (2009), and Liu et al. (2014), the need for an accurate characterization of the long-term changes in upper tropospheric and lower stratospheric (UTLS) water vapor has not yet resulted in sufficiently extensive long-term international measurement programs (although first steps have been taken). Here, we argue for the implementation of a long-term balloon-borne measurement program for UTLS water vapor covering the entire globe that will likely have to be sustained for hundreds of years.

  9. Description of the Fork Mountain long-term soil productivity study: site characterization

    Treesearch

    Mary Beth Adams; James Burger; Lucian Zelazny; John Baumgras

    2004-01-01

    The effects of air pollution and timber harvesting on soil resources continue to be an important issue in eastern hardwood forests. This publication describes the Fork Mountain Long-term Soil Productivity Study (LTSP), located on the Fernow Experimental Forest, WV, and the pretreatment stand, soil and climatic conditions. Extensive vegetation surveys, biomass...

  10. Early intervention with tafamidis provides long-term (5.5-year) delay of neurologic progression in transthyretin hereditary amyloid polyneuropathy.

    PubMed

    Waddington Cruz, Márcia; Amass, Leslie; Keohane, Denis; Schwartz, Jeffrey; Li, Huihua; Gundapaneni, Balarama

    2016-09-01

    Transthyretin hereditary amyloid polyneuropathy, also traditionally known as transthyretin familial amyloid polyneuropathy (ATTR-FAP), is a rare, relentless, fatal hereditary disorder. Tafamidis, an oral, non-NSAID, highly specific transthyretin stabilizer, demonstrated safety and efficacy in slowing neuropathy progression in early-stage ATTRV30M-FAP in a 1.5-year, randomized, double-blind, placebo-controlled trial, and 1-year open-label extension study, with a second long-term open-label extension study ongoing. Subgroup analysis of the effectiveness of tafamidis in the pivotal study and its open-label extensions revealed a relatively cohesive cohort of patients with mild neuropathy (i.e. Neuropathy Impairment Score for Lower Limbs [NIS-LL] ≤ 10) at the start of active treatment. Early treatment with tafamidis for up to 5.5 years (≥1 dose of tafamidis meglumine 20 mg once daily during the original trial or after switching from placebo in its extension) resulted in sustained delay in neurologic progression and long-term preservation of nutritional status in this cohort. Mean (95% CI) changes from baseline in NIS-LL and mBMI were 5.3 (1.6, 9.1) points and -7.8 (-44.3, 28.8) kg/m 2 × g/L at 5.5 years, respectively. No new safety issues or side effects were identified. These data represent the longest prospective evaluation of tafamidis to date, confirm a favorable safety profile, and underscore the long-term benefits of early intervention with tafamidis. ClincalTrials.gov Identifier: NCT00409175, NCT00791492, and NCT00925002.

  11. 21 CFR 310.303 - Continuation of long-term studies, records, and reports on certain drugs for which new drug...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... approved for marketing unless it has been shown to be safe and effective for its intended use(s). After... effectiveness of long-term use of such drugs, extensive animal and clinical tests are required as a condition of...

  12. 10 years of denosumab treatment in postmenopausal women with osteoporosis: results from the phase 3 randomised FREEDOM trial and open-label extension.

    PubMed

    Bone, Henry G; Wagman, Rachel B; Brandi, Maria L; Brown, Jacques P; Chapurlat, Roland; Cummings, Steven R; Czerwiński, Edward; Fahrleitner-Pammer, Astrid; Kendler, David L; Lippuner, Kurt; Reginster, Jean-Yves; Roux, Christian; Malouf, Jorge; Bradley, Michelle N; Daizadeh, Nadia S; Wang, Andrea; Dakin, Paula; Pannacciulli, Nicola; Dempster, David W; Papapoulos, Socrates

    2017-07-01

    Long-term safety and efficacy of osteoporosis treatment are important because of the chronic nature of the disease. We aimed to assess the long-term safety and efficacy of denosumab, which is widely used for the treatment of postmenopausal women with osteoporosis. In the multicentre, randomised, double-blind, placebo-controlled, phase 3 FREEDOM trial, postmenopausal women aged 60-90 years with osteoporosis were enrolled in 214 centres in North America, Europe, Latin America, and Australasia and were randomly assigned (1:1) to receive 60 mg subcutaneous denosumab or placebo every 6 months for 3 years. All participants who completed the FREEDOM trial without discontinuing treatment or missing more than one dose of investigational product were eligible to enrol in the open-label, 7-year extension, in which all participants received denosumab. The data represent up to 10 years of denosumab exposure for women who received 3 years of denosumab in FREEDOM and continued in the extension (long-term group), and up to 7 years for women who received 3 years of placebo and transitioned to denosumab in the extension (crossover group). The primary outcome was safety monitoring, comprising assessments of adverse event incidence and serious adverse event incidence, changes in safety laboratory analytes (ie, serum chemistry and haematology), and participant incidence of denosumab antibody formation. Secondary outcomes included new vertebral, hip, and non-vertebral fractures as well as bone mineral density (BMD) at the lumbar spine, total hip, femoral neck, and one-third radius. Analyses were done according to the randomised FREEDOM treatment assignments. All participants who received at least one dose of investigational product in FREEDOM or the extension were included in the combined safety analyses. All participants who enrolled in the extension with observed data were included in the efficacy analyses. The FREEDOM trial (NCT00089791) and its extension (NCT00523341) are both registered with ClinicalTrials.gov. Between Aug 3, 2004, and June 1, 2005, 7808 women were enrolled in the FREEDOM study. 5928 (76%) women were eligible for enrolment in the extension, and of these, 4550 (77%) were enrolled (2343 long-term, 2207 crossover) between Aug 7, 2007, and June 20, 2008. 2626 women (1343 long-term; 1283 crossover) completed the extension. The yearly exposure-adjusted participant incidence of adverse events for all individuals receiving denosumab decreased from 165·3 to 95·9 per 100 participant-years over the course of 10 years. Serious adverse event rates were generally stable over time, varying between 11·5 and 14·4 per 100 participant-years. One atypical femoral fracture occurred in each group during the extension. Seven cases of osteonecrosis of the jaw were reported in the long-term group and six cases in the crossover group. The yearly incidence of new vertebral fractures (ranging from 0·90% to 1·86%) and non-vertebral fractures (ranging from 0·84% to 2·55%) remained low during the extension, similar to rates observed in the denosumab group during the first three years of the FREEDOM study, and lower than rates projected for a virtual long-term placebo cohort. In the long-term group, BMD increased from FREEDOM baseline by 21·7% at the lumbar spine, 9·2% at total hip, 9·0% at femoral neck, and 2·7% at the one-third radius. In the crossover group, BMD increased from extension baseline by 16·5% at the lumbar spine, 7·4% at total hip, 7·1% at femoral neck, and 2·3% at one-third radius. Denosumab treatment for up to 10 years was associated with low rates of adverse events, low fracture incidence compared with that observed during the original trial, and continued increases in BMD without plateau. Amgen. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. OECD/NEA study on the economics of the long-term operation of nuclear power plants

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

    Lokhov, A.; Cameron, R.

    2012-07-01

    The OECD Nuclear Energy Agency (NEA) established the Ad hoc expert group on the Economics of Long-term Operation (LTO) of Nuclear Power Plants. The primary aim of this group is to collect and analyse technical and economic data on the upgrade and lifetime extension experience in OECD countries, and to assess the likely applications for future extensions. This paper describes the key elements of the methodology of economic assessment of LTO and initial findings for selected NEA member countries. (authors)

  14. Long-Term Autobiographical Memory for Legal Involvement: Individual and Sociocontextual Predictors

    ERIC Educational Resources Information Center

    Quas, Jodi A.; Alexander, Kristen Weede; Goodman, Gail S.; Ghetti, Simona; Edelstein, Robin S.; Redlich, Allison

    2010-01-01

    We examined adults' long-term autobiographical memory for a dramatic life event-participating as a child victim in a criminal prosecution because of alleged sexual abuse. The study is unique in several ways, including that we had extensive documentation concerning the sexual abuse allegations, the children's involvement in their legal case, and…

  15. Expanding the Reach of Extension to Underserved Audiences through Study Circles in Rural Idaho

    ERIC Educational Resources Information Center

    Cummins, Melissa; Petty, Barbara; Hansen, Lyle; Hoffman, Katie; Wittman, Grace

    2012-01-01

    Extension educators expanded the reach of their programming to underserved audiences through the implementation of Study Circles in rural Southern Idaho. Study Circles gave educators entry into communities by establishing relationships necessary for long-term change. Study Circle discussions in rural Southern Idaho led to stronger relationships…

  16. Long commuting time, extensive overtime, and sympathodominant state assessed in terms of short-term heart rate variability among male white-collar workers in the Tokyo megalopolis.

    PubMed

    Kageyama, T; Nishikido, N; Kobayashi, T; Kurokawa, Y; Kaneko, T; Kabuto, M

    1998-07-01

    To investigate the possible effects of long commuting time and extensive overtime on daytime cardiac autonomic activity, the short-term heart rate variability (HRV) both at supine rest and at standing rest of 223 male white-collar workers in the Tokyo Megalopolis was examined. Workers with a one-way commute of 90 min or more exhibited decreased vagal activity at supine rest and increased sympathetic activity regardless of posture, and those doing overtime of 60 h/month or more exhibited decreased vagal activity and increased sympathetic activity at standing rest. These findings suggest that chronic stress or fatigue resulting from long commuting time or extensive overtime caused these individuals to be in a sympathodominant state. Although these shifts in autonomic activities are not direct indicators of disease, it can be hypothesized that they can induce cardiovascular abnormalities or dysfunctions related to the onset of heart disease. Assessment of the daily and weekly variations in HRV as a function of daily life activities (such as working, commuting, sleeping, and exercising) among workers in Asia-Pacific urban areas might be one way of studying the possible effects of long commuting time, and extensive overtime, on health.

  17. Early intervention with tafamidis provides long-term (5.5-year) delay of neurologic progression in transthyretin hereditary amyloid polyneuropathy

    PubMed Central

    Waddington Cruz, Márcia; Amass, Leslie; Keohane, Denis; Schwartz, Jeffrey; Li, Huihua; Gundapaneni, Balarama

    2016-01-01

    Abstract Transthyretin hereditary amyloid polyneuropathy, also traditionally known as transthyretin familial amyloid polyneuropathy (ATTR-FAP), is a rare, relentless, fatal hereditary disorder. Tafamidis, an oral, non-NSAID, highly specific transthyretin stabilizer, demonstrated safety and efficacy in slowing neuropathy progression in early-stage ATTRV30M-FAP in a 1.5-year, randomized, double-blind, placebo-controlled trial, and 1-year open-label extension study, with a second long-term open-label extension study ongoing. Subgroup analysis of the effectiveness of tafamidis in the pivotal study and its open-label extensions revealed a relatively cohesive cohort of patients with mild neuropathy (i.e. Neuropathy Impairment Score for Lower Limbs [NIS-LL] ≤ 10) at the start of active treatment. Early treatment with tafamidis for up to 5.5 years (≥1 dose of tafamidis meglumine 20 mg once daily during the original trial or after switching from placebo in its extension) resulted in sustained delay in neurologic progression and long-term preservation of nutritional status in this cohort. Mean (95% CI) changes from baseline in NIS-LL and mBMI were 5.3 (1.6, 9.1) points and −7.8 (−44.3, 28.8) kg/m2 × g/L at 5.5 years, respectively. No new safety issues or side effects were identified. These data represent the longest prospective evaluation of tafamidis to date, confirm a favorable safety profile, and underscore the long-term benefits of early intervention with tafamidis. Trial Registration: ClincalTrials.gov Identifier: NCT00409175, NCT00791492, and NCT00925002. PMID:27494299

  18. Tofacitinib, an oral Janus kinase inhibitor, for the treatment of chronic plaque psoriasis: Long-term efficacy and safety results from 2 randomized phase-III studies and 1 open-label long-term extension study.

    PubMed

    Papp, Kim A; Krueger, James G; Feldman, Steven R; Langley, Richard G; Thaci, Diamant; Torii, Hideshi; Tyring, Stephen; Wolk, Robert; Gardner, Annie; Mebus, Charles; Tan, Huaming; Luo, Yingchun; Gupta, Pankaj; Mallbris, Lotus; Tatulych, Svitlana

    2016-05-01

    Tofacitinib is an oral Janus kinase inhibitor being investigated for psoriasis. We sought to report longer-term tofacitinib efficacy and safety in patients with moderate to severe psoriasis. Data from 2 identical phase-III studies, Oral-treatment Psoriasis Trial Pivotal 1 and 2, were pooled with data from these patients in an ongoing open-label long-term extension study. Patients (n = 1861) were randomized 2:2:1 to tofacitinib 5 mg, 10 mg, or placebo twice daily (BID). At week 16, placebo patients were rerandomized to tofacitinib. Pivotal study participants could enroll into the long-term extension where they received tofacitinib at 10 mg BID for 3 months, after which dosing could be 5 or 10 mg BID. At week 28, the proportions of patients randomized to tofacitinib 5 and 10 mg BID achieving 75% or greater reduction in Psoriasis Area and Severity Index score from baseline were 55.6% and 68.8%, and achieving Physician Global Assessment of clear or almost clear were 54.7% and 65.9%. Efficacy was maintained in most patients through 24 months. Serious adverse events and discontinuations because of adverse events were reported in less than 11% of patients over 33 months of tofacitinib exposure. There was no dose comparison beyond week 52. Oral tofacitinib demonstrated sustained efficacy in patients with psoriasis through 2 years, with 10 mg BID providing greater efficacy than 5 mg BID. No unexpected safety findings were observed. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  19. 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…

  20. Update on long-term treatment with bisphosphonates for postmenopausal osteoporosis: a systematic review.

    PubMed

    Eriksen, Erik F; Díez-Pérez, Adolfo; Boonen, Steven

    2014-01-01

    Osteoporosis is a progressive skeletal disorder that requires long-term treatment. However, there is little guidance regarding optimal treatment duration and what the treatment discontinuation and retreatment criteria should be. Given that bisphosphonates are the most commonly prescribed class of agent for the treatment of osteoporosis, we reviewed the long-term data relating to these therapies and discussed the considerations for using bisphosphonates in postmenopausal women with osteoporosis. A PubMed search, using the search terms 'bisphosphonate', 'postmenopausal osteoporosis' and 'long term' and/or 'extension' was conducted in January 2013. Results from nine controlled studies that prospectively assessed alendronate, risedronate, ibandronate or zoledronic acid in women with postmenopausal osteoporosis were reviewed. Clinical studies in postmenopausal women with osteoporosis showed that long-term use of bisphosphonates resulted in persistent antifracture and bone mineral density (BMD) increasing effects beyond 3 years of treatment. No unexpected adverse events were identified in these studies and the long-term tolerability profiles of bisphosphonates remain favorable. Data from the withdrawal extension studies of alendronate and zoledronic acid also showed that residual fracture benefits were seen in patients who discontinued treatment for 3 to 5 years after an initial 3- to 5-year treatment period. BMD monitoring and fracture risk assessments should be conducted regularly to determine whether treatment could be stopped or should be reinitiated. Patients exhibiting T-scores<-2.5 or who have suffered a new fracture while on treatment should continue treatment, while patients with T-scores>-2.5 could be considered for discontinuation of active treatment while undergoing continued monitoring of their bone health. The duration and potential discontinuation of treatment should be personalized for individual patients based on their response to treatment, fracture risk and comorbidities. © 2013. Published by Elsevier Inc. All rights reserved.

  1. TV EDUCATIONAL FUNCTION OF THE COLLEGES OF AGRICULTURE AND HOME ECONOMICS. EXTENSION STUDY, NUMBER 9. PARTS I - VII.

    ERIC Educational Resources Information Center

    ALEXANDER, FRANK D.; AND OTHERS

    WITH THE NEED TO PROVIDE LONG-TERM FINANCIAL SUPPORT FOR ITS TV FILM CENTER, THE DEPARTMENT OF EXTENSION TEACHING AND INFORMATION AT NEW YORK STATE COLLEGES OF AGRICULTURE AND HOME ECONOMICS AT CORNELL UNIVERSITY IN COOPERATION WITH THE OFFICE OF EXTENSION STUDIES INITIATED IN JULY 1963 A PROJECT TO ASCERTAIN (1) VIEWPOINTS RELATIVE TO OFF-CAMPUS…

  2. Comparing Safety and Efficacy of "Third-Generation" Antiepileptic Drugs: Long-Term Extension and Post-marketing Treatment.

    PubMed

    Kwok, Charlotte S; Johnson, Emily L; Krauss, Gregory L

    2017-11-01

    Four "third-generation" antiepileptic drugs (AEDs) were approved for adjunctive treatment of refractory focal onset seizures during the past 10 years. Long-term efficacy and safety of the drugs were demonstrated in large extension studies and in reports of subgroups of patients not studied in pivotal trials. Reviewing extension study and post-marketing outcome series for the four newer AEDs-lacosamide, perampanel, eslicarbazepine acetate and brivaracetam-can guide clinicians in treating and monitoring patients. AED extension studies evaluate treatment retention, drug tolerability, and drug safety during individualized treatment with flexible dosing and thus provide information not available in rigid pivotal trials. Patient retention in the studies ranged from 75 to 80% at 1 year and from 36 to 68% at 2-year treatment intervals. Safety findings were generally similar to those of pivotal trials, with no major safety risks identified and with several specific adverse drug effects, such as hyponatremia, reported. The third-generation AEDs, some through new mechanisms and others with improved tolerability compared to related AEDs, provide new options in efficacy and tolerability.

  3. A United States perspective on long-term management of areas contaminated with radioactive materials.

    PubMed

    Jones, C Rick

    2004-01-01

    The US has far-reaching and extensive experience in the long-term management of areas contaminated with radioactive materials. This experience base includes the Department of Energy's continued follow-up with Hiroshima and Nagasaki from the 1940s at the Radiological Effects Research Foundation in Hiroshima, Japan, the long-term management of the Marshall Islands Programme, the clean-up of the US nuclear weapons complex and the ongoing management of accident sites such as in Palomares, Spain. This paper discusses the lessons learnt and best practices gained from this far-reaching and extensive experience in the long-term management of areas contaminated with radioactive materials. Copyright 2004 Oxford University Press

  4. The Effect of Three or Six Years of Denosumab Exposure in Women With Postmenopausal Osteoporosis: Results From the FREEDOM Extension

    PubMed Central

    Chapurlat, Roland; Brandi, Maria-Luisa; Brown, Jacques P.; Czerwiński, Edward; Krieg, Marc-Antoine; Mellström, Dan; Radominski, Sebastião C.; Reginster, Jean-Yves; Resch, Heinrich; Ivorra, Jose A. Román; Roux, Christian; Vittinghoff, Eric; Daizadeh, Nadia S.; Wang, Andrea; Bradley, Michelle N.; Franchimont, Nathalie; Geller, Michelle L.; Wagman, Rachel B.; Cummings, Steven R.; Papapoulos, Socrates

    2013-01-01

    Context: The Fracture Reduction Evaluation of Denosumab in Osteoporosis Every 6 Months (FREEDOM) extension is evaluating the long-term efficacy and safety of denosumab for up to 10 years. Objective: The objective of the study was to report results from the first 3 years of the extension, representing up to 6 years of denosumab exposure. Design, Setting, and Participants: This was a multicenter, international, open-label study of 4550 women. Intervention: Women from the FREEDOM denosumab group received 3 more years of denosumab for a total of 6 years (long-term) and women from the FREEDOM placebo group received 3 years of denosumab (crossover). Main Outcome Measures: Bone turnover markers (BTMs), bone mineral density (BMD), fracture, and safety data are reported. Results: Reductions in BTMs were maintained (long-term) or achieved rapidly (crossover) after denosumab administration. In the long-term group, BMD further increased for cumulative 6-year gains of 15.2% (lumbar spine) and 7.5% (total hip). During the first 3 years of denosumab treatment, the crossover group had significant gains in lumbar spine (9.4%) and total hip (4.8%) BMD, similar to the long-term group during the 3-year FREEDOM trial. In the long-term group, fracture incidences remained low and below the rates projected for a virtual placebo cohort. In the crossover group, 3-year incidences of new vertebral and nonvertebral fractures were similar to those of the FREEDOM denosumab group. Incidence rates of adverse events did not increase over time. Six participants had events of osteonecrosis of the jaw confirmed by adjudication. One participant had a fracture adjudicated as consistent with atypical femoral fracture. Conclusion: Denosumab treatment for 6 years remained well tolerated, maintained reduced bone turnover, and continued to increase BMD. Fracture incidence remained low. PMID:23979955

  5. Teaching an Old Game New Tricks: Long-Term Feedback on a Re-Designed Online Role Play

    ERIC Educational Resources Information Center

    Hardy, Mat; Totman, Sally

    2017-01-01

    Despite an extensive history of use in teaching Political Science subjects, long-term scholarly studies of online role plays are uncommon. This paper redresses that balance by presenting five years of data on the Middle East Politics Simulation. This online role play has been run since the 1990s and underwent significant technical upgrade in…

  6. Fluoxetine for the Treatment of Childhood Anxiety Disorders: Open-Label, Long-Term Extension to a Controlled Trial

    ERIC Educational Resources Information Center

    Clark, Duncan B.; Birmaher, Boris; Axelson, David; Monk, Kelly; Kalas, Catherine; Ehmann, Mary; Bridge, Jeffrey; Wood, D. Scott; Muthen, Bengt; Brent, David

    2005-01-01

    Objective: To assess the efficacy of fluoxetine for the long-term treatment of children and adolescents with anxiety disorders, including generalized anxiety disorder, separation anxiety disorder, and/or social phobia. Method: Children and adolescents (7-17 years old) with anxiety disorders were studied in open treatment for 1 year after they…

  7. 76 FR 68493 - Extension of the Designation of Nicaragua for Temporary Protected Status and Automatic Extension...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-04

    ... long-term recovery has been the recurrence of these environmental disasters and ensuing damage in the.... SUPPLEMENTARY INFORMATION: Abbreviations and Terms Used in This Document Act--Immigration and Nationality Act... United States and may obtain work authorization, so long as they continue to meet the requirements of TPS...

  8. Behavior Change Strategies for Successful Long-Term Weight Loss: Focusing on Dietary and Physical Activity Adherence, Not Weight Loss

    ERIC Educational Resources Information Center

    Hongu, Nobuko; Kataura, Martha P.; Block, Linda M.

    2011-01-01

    This article helps Extension professionals guide individuals in a successful long-term weight loss program. A program should focus on behavioral changes (improving eating habits and physical activity), not just weight loss. In order to do this, Extension professionals should implement behavior change strategies that motivate individuals to…

  9. Long-term management of type 2 diabetes with glucagon-like peptide-1 receptor agonists.

    PubMed

    Courtney, Hamish; Nayar, Rahul; Rajeswaran, Chinnadorai; Jandhyala, Ravi

    2017-01-01

    Continuously reducing excess blood glucose is a primary goal for the management of type 2 diabetes (T2D). Most patients with T2D require glucose-lowering medications to achieve and maintain adequate glycemic control; however, treatment failure may occur, limiting treatment options. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are an emerging therapeutic class that can be prescribed for patients instead of basal insulin after the failure of oral therapies. Recent studies have focused on the durability and tolerability of long-term GLP-1RA therapy. This review summarizes the key efficacy and safety findings from prospective phase 3 clinical studies of at least 76 weeks' duration for the GLP-1RAs currently approved in the United States and the European Union (albiglutide, dulaglutide, exenatide twice daily [BID], exenatide once weekly [QW], liraglutide, and lixisenatide). Currently, most of the long-term data are from uncontrolled extension studies, and continuous patient benefit has been observed for up to 3 years with multiple GLP-1RAs. Four-year comparative data demonstrated a longer time to treatment failure for exenatide BID than for sulfonylurea, and 3-year comparative extension data demonstrated greater glycated hemoglobin (HbA1c) reductions and weight loss with exenatide QW than with insulin glargine. Currently, the longest extension study for a GLP-1RA is the DURATION-1 study of exenatide QW, with >7 years of clinical data available. Data from DURATION-1 demonstrated that continuous HbA1c reductions and weight loss were observed for the patients continuing on the treatment, with no unexpected adverse events. Taken together, these data support GLP-1RAs as a long-term noninsulin treatment option after the failure of oral therapies.

  10. Short- and long-term clinical outcomes of use of beta-interferon or glatiramer acetate for people with clinically isolated syndrome: a systematic review of randomised controlled trials and network meta-analysis.

    PubMed

    Armoiry, X; Kan, A; Melendez-Torres, G J; Court, R; Sutcliffe, P; Auguste, P; Madan, J; Counsell, C; Clarke, A

    2018-05-01

    Beta-interferon (IFN-β) and glatiramer acetate (GA) have been evaluated in people with clinically isolated syndrome (CIS) with the aim to delay a second clinical attack and a diagnosis of clinically definite multiple sclerosis (CDMS). We systematically reviewed trials evaluating the short- and long-term clinical effectiveness of these drugs in CIS. We searched multiple electronic databases. We selected randomised controlled studies (RCTs) conducted in CIS patients and where the interventions were IFN-β and GA. Main outcomes were time to CDMS, and discontinuation due to adverse events (AE). We compared interventions using random-effect network meta-analyses (NMA). We also reported outcomes from long-term open-label extension (OLE) studies. We identified five primary studies. Four had open-label extensions following double-blind periods comparing outcomes between early vs delayed DMT. Short-term clinical results (double-blind period) showed that all drugs delayed CDMS compared to placebo. Indirect comparisons did not suggest superiority of any one active drug over another. We could not undertake a NMA for discontinuation due to AE. Long-term clinical results (OLE studies) showed that the risk of developing CDMS was consistently reduced across studies after early DMT treatment compared to delayed DMT (HR = 0.64, 95% CI 0.55, 0.74). No data supported the benefit of DMTs in reducing the time to, and magnitude of, disability progression. Meta-analyses confirmed that IFN-β and GA delay time to CDMS compared to placebo. In the absence of evidence that early DMTs can reduce disability progression, future research is needed to better identify patients most likely to benefit from long-term DMTs.

  11. Long-Term Tolerability and Effectiveness of Once-Daily Mixed Amphetamine Salts (Adderall XR) in Children with ADHD

    ERIC Educational Resources Information Center

    McGough, James J.; Biederman, Joseph; Wigal, Sharon B.; Lopez, Frank A.; McCracken, James T.; Spencer, Thomas; Zhang, Yuxin; Tulloch, Simon J.

    2005-01-01

    Objective: To evaluate the long-term tolerability and effectiveness of extended-release mixed amphetamine salts (MAS XR; Adderall XR[R]) in children with attention-deficit/hyperactivity disorder (ADHD). Method: This was a 24-month, multicenter, open-label extension of TWO placebo-controlled studies of MAS XR in children with ADHD aged 6 to 12…

  12. Aortic cusp extension valvuloplasty with or without tricuspidization in children and adolescents: long-term results and freedom from aortic valve replacement.

    PubMed

    Polimenakos, Anastasios C; Sathanandam, Shyam; Elzein, Chawki; Barth, Mary J; Higgins, Robert S D; Ilbawi, Michel N

    2010-04-01

    Aortic cusp extension valvuloplasty is increasingly used in the management of children and adolescents with aortic stenosis or regurgitation. The durability of this approach and the freedom from valve replacement are not well defined. A study was undertaken to investigate outcomes. From July 1987 to November 2008, 142 patients aged less than 19 years underwent aortic cusp extension valvuloplasty in the form of pericardial cusp extension and tricuspidization (when needed). Three patients with truncus arteriosus and severe truncal valve insufficiency were excluded. From the available follow-up data of 139 patients, 50 had bicuspid aortic valves, 40 had congenital aortic valve stenosis, 41 had combined congenital aortic valve stenosis/insufficiency, and 8 had other diagnoses. Median follow-up was 14.4 years (0.1-21.4). Long-term mortality and freedom from aortic valve replacement were studied. There were no early, intermediate, or late deaths. Z-values of left ventricular end-diastolic dimension, aortic annulus, aortic sinus diameter, and sinotubular junction diameter before aortic valve replacement were 4.2 +/- 3.11, 2.3 +/- 1.25, 4.4 +/- 1.23, and 1.84 +/- 1.28, respectively. During the follow-up period, 64 patients underwent aortic valve reinterventions. The Ross procedure was performed in 32 of 139 patients (23%) undergoing aortic cusp extension valvuloplasty. Other aortic valve replacements were undertaken after 16 aortic cusp extension valvuloplasties (11.5%). Freedom from a second aortic cusp extension valvuloplasty or aortic valve replacement at 18 years was 82.1% +/- 4.2% and 60.0% +/- 7.2%, respectively. Aortic cusp extension valvuloplasty is a safe and effective surgical option with excellent survival and good long-term outcomes in children and adolescents. The procedure provides acceptable durability and satisfactory freedom from aortic valve replacement. Copyright 2010 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

  13. Long-Term Monitoring of Pavement Maintenance Materials Test Sites

    DOT National Transportation Integrated Search

    1998-06-01

    The Strategic Highway Research Program's {SHRP) H-106 pothole repair experiment was part of the most extensive pavement maintenance experiment ever conducted. Started under SHRP and continued under the Long-Term Pavement Performance program's Long-Te...

  14. 77 FR 58116 - Commission Information Collection Activities (FERC-732); Comment Request; Extension

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-19

    ... Rate Schedules and Tariffs: Long-Term Firm Transmission Rights in Organized Electricity Markets. DATES... Tariffs: Long-Term Firm Transmission Rights in Organized Electricity Markets. OMB Control No.:1902-0245... organized electricity markets to make available long-term firm transmission rights that satisfy each of the...

  15. Early nutrition and health: short- and long-term outcomes.

    PubMed

    Gruszfeld, Dariusz; Socha, Piotr

    2013-01-01

    Maternal diet, nutritional status during pregnancy, and the early diet of the offspring play an important role in later health. The short- and long-term outcomes of early nutrition have been extensively studied in recent decades. One of the most commonly investigated nutritional interventions is breastfeeding, which is associated with a number of positive short- and long-term outcomes. A short-term effect of breastfeeding is reduced morbidity and mortality in children from poor living conditions and in preterm infants. Breastfeeding is associated with better cognitive development and also has a long-term protective effect on obesity risk, prevalence of type 2 diabetes, and a lowering effect on blood pressure. Selected nutrients have undergone extensive investigation to show their role in disease prevention or improved development, e.g. protein intake in infancy seems to be associated with a later risk of obesity or docosahexaenoic acid supplementation has a positive impact on cognitive function. Another consideration is the fast catch-up growth in small for gestational age infants as an important factor associated with adult risk of cardiovascular problems. On the other hand, high protein and energy intake seems to be positively associated with some indicators of cognitive development. Most of the evidence comes from observational studies that cannot exclude potential confounders. Animal studies demonstrate causality but should not be directly extrapolated to humans. The number of randomized controlled studies is increasing but long-term follow-ups are necessary to obtain convincing results. The majority of these trials compare different infant formula compositions and macro- or micronutrient supplementation. One of the major questions is to define a critical (or opportunity) window and a mechanism of nutritional influence on several health outcomes. Copyright © 2013 S. Karger AG, Basel.

  16. Long-term effects of the iron-based phosphate binder, sucroferric oxyhydroxide, in dialysis patients.

    PubMed

    Floege, Jürgen; Covic, Adrian C; Ketteler, Markus; Mann, Johannes F E; Rastogi, Anjay; Spinowitz, Bruce; Chong, Edward M F; Gaillard, Sylvain; Lisk, Laura J; Sprague, Stuart M

    2015-06-01

    Hyperphosphatemia necessitates the use of phosphate binders in most dialysis patients. Long-term efficacy and tolerability of the iron-based phosphate binder, sucroferric oxyhydroxide (previously known as PA21), was compared with that of sevelamer carbonate (sevelamer) in an open-label Phase III extension study. In the initial Phase III study, hemo- or peritoneal dialysis patients with hyperphosphatemia were randomized 2:1 to receive sucroferric oxyhydroxide 1.0-3.0 g/day (2-6 tablets/day; n = 710) or sevelamer 2.4-14.4 g/day (3-18 tablets/day; n = 349) for 24 weeks. Eligible patients could enter the 28-week extension study, continuing the same treatment and dose they were receiving at the end of the initial study. Overall, 644 patients were available for efficacy analysis (n = 384 sucroferric oxyhydroxide; n = 260 sevelamer). Serum phosphorus concentrations were maintained during the extension study. Mean ± standard deviation (SD) change in serum phosphorus concentrations from extension study baseline to Week 52 end point was 0.02 ± 0.52 mmol/L with sucroferric oxyhydroxide and 0.09 ± 0.58 mmol/L with sevelamer. Mean serum phosphorus concentrations remained within Kidney Disease Outcomes Quality Initiative target range (1.13-1.78 mmol/L) for both treatment groups. Mean (SD) daily tablet number over the 28-week extension study was lower for sucroferric oxyhydroxide (4.0 ± 1.5) versus sevelamer (10.1 ± 6.6). Patient adherence was 86.2% with sucroferric oxyhydroxide versus 76.9% with sevelamer. Mean serum ferritin concentrations increased over the extension study in both treatment groups, but transferrin saturation (TSAT), iron and hemoglobin concentrations were generally stable. Gastrointestinal-related adverse events were similar and occurred early with both treatments, but decreased over time. The serum phosphorus-lowering effect of sucroferric oxyhydroxide was maintained over 1 year and associated with a lower pill burden, compared with sevelamer. Sucroferric oxyhydroxide was generally well tolerated long-term and there was no evidence of iron accumulation. © The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA.

  17. Long-term results after treatment of extensive odontogenic cysts of the jaws: a review.

    PubMed

    Wakolbinger, Robert; Beck-Mannagetta, Johann

    2016-01-01

    The aim was to perform a literature review concerning long-term results after treatment of extensive cysts of the jaws. The following databases were searched: MEDLINE, Cochrane CENTRAL, Cochrane Database of Systematic Reviews, The Cochrane Library, and EMBASE. Case reports and abstracts were excluded. Three hundred fifty-six articles were found, of which 30 were included. Only the minority of the studies reported long-term results. Most authors did not distinguish between temporary complications and permanent deficiencies (incomplete bone healing, permanent sensory deficits). Based on this review, it is recommended to consider primary decompression or marsupialization ± later definitive surgery for the treatment of extensive jaw cysts in order to achieve satisfying clinical results. Complications (occurring within the first 6 months postoperatively, e.g., infection) and remaining deficits (after a minimum of 6 months and not changing over time, e.g., bony or sensory deficit) should be clearly separated from each other. Knowledge of permanent deficits and bone healing after different therapeutic approaches is important for decision making. Patients should be informed not only about complications but also about the risk of permanent deficits for each method.

  18. Long term potentiation, but not depression, in interlamellar hippocampus CA1.

    PubMed

    Sun, Duk-Gyu; Kang, Hyeri; Tetteh, Hannah; Su, Junfeng; Lee, Jihwan; Park, Sung-Won; He, Jufang; Jo, Jihoon; Yang, Sungchil; Yang, Sunggu

    2018-03-26

    Synaptic plasticity in the lamellar CA3 to CA1 circuitry has been extensively studied while interlamellar CA1 to CA1 connections have not yet received much attention. One of our earlier studies demonstrated that axons of CA1 pyramidal neurons project to neighboring CA1 neurons, implicating information transfer along a longitudinal interlamellar network. Still, it remains unclear whether long-term synaptic plasticity is present within this longitudinal CA1 network. Here, we investigate long-term synaptic plasticity between CA1 pyramidal cells, using in vitro and in vivo extracellular recordings and 3D holography glutamate uncaging. We found that the CA1-CA1 network exhibits NMDA receptor-dependent long-term potentiation (LTP) without direction or layer selectivity. By contrast, we find no significant long-term depression (LTD) under various LTD induction protocols. These results implicate unique synaptic properties in the longitudinal projection suggesting that the interlamellar CA1 network could be a promising structure for hippocampus-related information processing and brain diseases.

  19. Reduced insulin-like growth factor-I serum levels in formerly obese women subjected to laparoscopic-adjustable gastric banding or diet-induced long-term caloric restriction.

    PubMed

    Mitterberger, Maria C; Mattesich, Monika; Klaver, Elise; Piza-Katzer, Hildegunde; Zwerschke, Werner

    2011-11-01

    Life-span extension in laboratory rodents induced by long-term caloric restriction correlates with decreased serum insulin-like growth factor-I (IGF-I) levels. Reduced activity of the growth hormone/IGF-I signaling system slows aging and increases longevity in mutant mouse models. In the present study, we show that long-term caloric restriction achieved by two different interventions for 4 years, either laparoscopic-adjustable gastric banding or reducing diet, leads to reduced IGF-I serum levels in formerly obese women relative to normal-weight women eating ad libitum. Moreover, we present evidence that the long-term caloric restriction interventions reduce fasting growth hormone serum levels. The present study indicates that the activity of the growth hormone/IGF-I axis is reduced in long-term calorically restricted formerly obese humans. Furthermore, our findings suggest that the duration and severity of the caloric restriction intervention are important for the outcome on the growth hormone/IGF-I axis in humans.

  20. Effects of long-term self-massage at the musculotendinous junction on hamstring extensibility, stiffness, stretch tolerance, and structural indices: A randomized controlled trial.

    PubMed

    Akazawa, Naoki; Okawa, Naomi; Kishi, Masaki; Nakatani, Kiyoshi; Nishikawa, Katsuya; Tokumura, Daichi; Matsui, Yuji; Moriyama, Hideki

    2016-09-01

    The purpose of this study was to examine the effect of long-term self-massage at the musculotendinous junction on hamstring extensibility, stiffness, stretch tolerance, and structural indices. Single-blind, randomized, controlled trial. Laboratory. Thirty-seven healthy men. The right or left leg of each participant was randomly assigned to the massage group, and the other leg was assigned to the control group. The participants conducted self-massage at the musculotendinous junction for 3 min daily, five times per week, for 12 weeks. Hamstring extensibility, stiffness, stretch tolerance, and structural indices were measured by a blinded examiner prior to the massage intervention and after 6 and 12 weeks of intervention. The maximum hip flexion angle (HFA) and the maximum passive pressure after 6 and 12 weeks of intervention in the massage group were significantly higher than prior to intervention. The visual analog scale (for pain perception) at maximum HFA, the stiffness of the hamstring, and the structural indices did not differ in either group over the 12 week period. Our results suggest that long-term self-massage at the musculotendinous junction increases hamstring extensibility by improving stretch tolerance. However, this intervention does not change hamstring stiffness. University Hospital Medical Information Network registration number UMIN000011233. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Sustained weight loss in patients treated with mifepristone for Cushing's syndrome: a follow-up analysis of the SEISMIC study and long-term extension.

    PubMed

    Fein, Henry G; Vaughan, T Brooks; Kushner, Harvey; Cram, David; Nguyen, Dat

    2015-10-27

    Overweight and obesity are common among patients with Cushing's syndrome (CS) and may persist in some patients even after ostensibly curative surgery, contributing to cardiometabolic dysfunction and increased cardiovascular risk. Mifepristone, a selective glucocorticoid receptor antagonist, was effective in controlling hyperglycemia in a 24-week trial of adults (N = 50) with endogenous CS and associated type 2 diabetes mellitus/impaired glucose tolerance or hypertension who had failed or were not candidates for surgery (SEISMIC, Study of the Efficacy and Safety of Mifepristone in the Treatment of Endogenous Cushing's Syndrome). This analysis examines long-term weight change among patients who received mifepristone in SEISMIC and enrolled in a long-term safety extension (LTE) study. Patients completing the 24-week SEISMIC study and subsequent 6-week off-drug safety evaluation were invited to enroll in the LTE study. Mifepristone doses at the end of SEISMIC were the LTE starting doses. Body weight measures were reviewed at baseline and week 24 of SEISMIC and at LTE month 6, 12, 18, 24, and final visit (last observation collected during the LTE study). Of the 30 patients enrolled in the LTE, evaluable weight data were available for 29 (20/29 female; mean age of 44.7 ± 11.2 years). These patients received mifepristone for a median of 29.2 months (range 8.4-41.9). Mean ± SD weight from SEISMIC baseline to LTE final visit decreased by 10.3 ± 16.3 kg (mean 105.4 ± 34.3 kg to 95.1 ± 32.9 kg), a 9.3 % decrease from baseline weight (P = 0.0008). Of the 29 LTE patients, 18 (62.1 %) lost ≥ 5 % of body weight by the end of the initial 24-week treatment period; this ≥5 % weight loss persisted in 83.3 % (15/18) at LTE final visit. Ten patients (34.5 %) lost ≥ 10 % of initial body weight by week 24 of SEISMIC, which persisted in 80 % at LTE final visit. No new safety signals were detected with long-term mifepristone use. Clinically meaningful weight loss achieved during a 24-week study of mifepristone for CS persisted for two additional years in patients who remained on therapy. Long-term treatment with mifepristone appears to have a beneficial effect on weight in patients with endogenous CS. NCT00569582 (SEISMIC); NCT00936741 (Long-Term Extension).

  2. Long-term tolerability and maintenance of therapeutic response to sodium oxybate in an open-label extension study in patients with fibromyalgia

    PubMed Central

    2013-01-01

    Introduction The long-term safety and therapeutic response of sodium oxybate (SXB) in fibromyalgia syndrome (FM) patients were assessed for a combined period of up to 1 year in a prospective, multicenter, open-label, extension study in patients completing 1 of 2 phase 3 randomized, double-blind, controlled, 14-week trials that examined the efficacy and safety of SXB 4.5 g, SXB 6 g, and placebo for treatment of FM. Methods This extension study comprised an additional 38 weeks of treatment and was carried out at 130 clinical sites in 7 countries. Initial entry criteria for the previous 2 double-blind clinical trials required that patients aged ≥ 18 years met the American College of Rheumatology 1990 criteria for FM, had a body mass index (BMI) < 40 kg/m2, and had a score ≥ 50 on a 100-mm pain visual analog scale (VAS) at baseline. All patients began treatment in the extension study with SXB 4.5 g/night (administered in 2 equally divided doses) for at least 1 week, followed by possible serial 1.5 g/night dose increases to 9 g/night (maximum) or reductions to 4.5 g/night (minimum). Results Of the 560 FM patients enrolled in this extension study, 319 (57.0%) completed the study. The main reason for early discontinuation was adverse events (AEs; 23.0% of patients). Patients were primarily middle-aged (mean 46.9 ± 10.8 years), female (91.1%), white (91.4%), with a mean duration of FM symptoms of 9.9 ± 8.7 years. Serious AEs were experienced by 3.6% of patients. The most frequently reported AEs (incidence ≥ 5% at any dose or overall) were nausea, headache, dizziness, nasopharyngitis, vomiting, sinusitis, diarrhea, anxiety, insomnia, influenza, somnolence, upper respiratory tract infection, muscle spasms, urinary tract infection, and gastroenteritis viral. Maintenance of SXB therapeutic response was demonstrated with continued improvement from controlled-study baseline in pain VAS, Fibromyalgia Impact Questionnaire (FIQ) total scores, and other measures. Responder analyses showed that 68.8% of patients achieved ≥ 30% reduction in pain VAS and 69.7% achieved ≥ 30% reduction in FIQ total score at study endpoint. Conclusions The long-term safety profile of SXB in FM patients was similar to that in the previously reported controlled clinical trials. Improvement in pain and other FM clinical domains was maintained during long-term use. Trial registration ClinicalTrials.gov NCT00423605. PMID:24286114

  3. Long-term tolerability and maintenance of therapeutic response to sodium oxybate in an open-label extension study in patients with fibromyalgia.

    PubMed

    Spaeth, Michael; Alegre, Cayetano; Perrot, Serge; Wang, Youyu; Guinta, Diane R; Alvarez-Horine, Sarah; Russell, Irwin

    2013-11-11

    The long-term safety and therapeutic response of sodium oxybate (SXB) in fibromyalgia syndrome (FM) patients were assessed for a combined period of up to 1 year in a prospective, multicenter, open-label, extension study in patients completing 1 of 2 phase 3 randomized, double-blind, controlled, 14-week trials that examined the efficacy and safety of SXB 4.5 g, SXB 6 g, and placebo for treatment of FM. This extension study comprised an additional 38 weeks of treatment and was carried out at 130 clinical sites in 7 countries. Initial entry criteria for the previous 2 double-blind clinical trials required that patients aged ≥ 18 years met the American College of Rheumatology 1990 criteria for FM, had a body mass index (BMI) < 40 kg/m2, and had a score ≥ 50 on a 100-mm pain visual analog scale (VAS) at baseline. All patients began treatment in the extension study with SXB 4.5 g/night (administered in 2 equally divided doses) for at least 1 week, followed by possible serial 1.5 g/night dose increases to 9 g/night (maximum) or reductions to 4.5 g/night (minimum). Of the 560 FM patients enrolled in this extension study, 319 (57.0%) completed the study. The main reason for early discontinuation was adverse events (AEs; 23.0% of patients). Patients were primarily middle-aged (mean 46.9 ± 10.8 years), female (91.1%), white (91.4%), with a mean duration of FM symptoms of 9.9 ± 8.7 years. Serious AEs were experienced by 3.6% of patients. The most frequently reported AEs (incidence ≥ 5% at any dose or overall) were nausea, headache, dizziness, nasopharyngitis, vomiting, sinusitis, diarrhea, anxiety, insomnia, influenza, somnolence, upper respiratory tract infection, muscle spasms, urinary tract infection, and gastroenteritis viral. Maintenance of SXB therapeutic response was demonstrated with continued improvement from controlled-study baseline in pain VAS, Fibromyalgia Impact Questionnaire (FIQ) total scores, and other measures. Responder analyses showed that 68.8% of patients achieved ≥ 30% reduction in pain VAS and 69.7% achieved ≥ 30% reduction in FIQ total score at study endpoint. The long-term safety profile of SXB in FM patients was similar to that in the previously reported controlled clinical trials. Improvement in pain and other FM clinical domains was maintained during long-term use. ClinicalTrials.gov NCT00423605.

  4. 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.

  5. Evaluation of long term health-related quality of life in extensive burns: a 12-year experience in a burn center.

    PubMed

    Xie, Bing; Xiao, Shi-chu; Zhu, Shi-hui; Xia, Zhao-fan

    2012-05-01

    We sought to evaluate the long term health-related quality of life (HRQOL) in patients survived severely extensive burn and identify their clinical predicting factors correlated with HRQOL. A cross-sectional study was conducted in 20 patients survived more than 2 years with extensive burn involving ≥70% total body surface area (TBSA) between 1997 and 2009 in a burn center in Shanghai. Short Form-36 Medical Outcomes Survey (SF-36), Brief Version of Burn Specific Health Scale (BSHS-B) and Michigan Hand Outcome Questionnaire (MHQ) were used for the present evaluation. SF-36 scores were compared with a healthy Chinese population, and linear correlation analysis was performed to screen the clinical relating factors predicting physical and mental component summary (PCS and MCS) scores from SF-36. HRQOL scores from SF-36 were significantly lower in the domains of physical functioning, role limitations due to physical problems, pain, social functioning and role limitations due to emotional problems compared with population norms. Multiple linear regression analysis demonstrated that only return to work (RTW) predicted improved PCS. While age at injury, facial burns, skin grafting and length of hospital stay were correlated with MCS. Work, body image and heat sensitivity obtained the lowest BSHS-B scores in all 9 domains. Improvements of HRQOL could still be seen in BSHS-B scores in domains of simple abilities, hand function, work and affect even after a quite long interval between burns and testing. Hand function of extensive burn patients obtained relatively poor MHQ scores, especially in those without RTW. Patients with extensive burns have a poorer quality of life compared with that of general population. Relatively poor physical and psychological problems still exist even after a long period. Meanwhile, a trend of gradual improvements was noted. This information will aid clinicians in decision-making of comprehensive systematic regimens for long term rehabilitation and psychosocial treatment. Copyright © 2011 Elsevier Ltd and ISBI. All rights reserved.

  6. Long-Term Modulation of Electrical Synapses in the Mammalian Thalamus

    NASA Astrophysics Data System (ADS)

    Landisman, Carole E.; Connors, Barry W.

    2005-12-01

    Electrical synapses are common between inhibitory neurons in the mammalian thalamus and neocortex. Synaptic modulation, which allows flexibility of communication between neurons, has been studied extensively at chemical synapses, but modulation of electrical synapses in the mammalian brain has barely been examined. We found that the activation of metabotropic glutamate receptors, via endogenous neurotransmitter or by agonist, causes long-term reduction of electrical synapse strength between the inhibitory neurons of the rat thalamic reticular nucleus.

  7. Phenological responses of Icelandic subarctic grasslands to short-term and long-term natural soil warming.

    PubMed

    Leblans, Niki I W; Sigurdsson, Bjarni D; Vicca, Sara; Fu, Yongshuo; Penuelas, Josep; Janssens, Ivan A

    2017-11-01

    The phenology of vegetation, particularly the length of the growing season (LOS; i.e., the period from greenup to senescence), is highly sensitive to climate change, which could imply potent feedbacks to the climate system, for example, by altering the ecosystem carbon (C) balance. In recent decades, the largest extensions of LOS have been reported at high northern latitudes, but further warming-induced LOS extensions may be constrained by too short photoperiod or unfulfilled chilling requirements. Here, we studied subarctic grasslands, which cover a vast area and contain large C stocks, but for which LOS changes under further warming are highly uncertain. We measured LOS extensions of Icelandic subarctic grasslands along natural geothermal soil warming gradients of different age (short term, where the measurements started after 5 years of warming and long term, i.e., warmed since ≥50 years) using ground-level measurements of normalized difference vegetation index. We found that LOS linearly extended with on average 2.1 days per °C soil warming up to the highest soil warming levels (ca. +10°C) and that LOS had the potential to extend at least 1 month. This indicates that the warming impact on LOS in these subarctic grasslands will likely not saturate in the near future. A similar response to short- and long-term warming indicated a strong physiological control of the phenological response of the subarctic grasslands to warming and suggested that genetic adaptations and community changes were likely of minor importance. We conclude that the warming-driven extension of the LOSs of these subarctic grasslands did not saturate up to +10°C warming, and hence that growing seasons of high-latitude grasslands are likely to continue lengthening with future warming (unless genetic adaptations or species shifts do occur). This persistence of the warming-induced extension of LOS has important implications for the C-sink potential of subarctic grasslands under climate change. © 2017 John Wiley & Sons Ltd.

  8. Long-Term Follow Up of Patients with Mild-to-Moderate Alzheimer's Disease Treated with Bapineuzumab in a Phase III, Open-Label, Extension Study.

    PubMed

    Salloway, Stephen P; Sperling, Reisa; Fox, Nick C; Sabbagh, Marwan N; Honig, Lawrence S; Porsteinsson, Anton P; Rofael, Hany; Ketter, Nzeera; Wang, Daniel; Liu, Enchi; Carr, Stephen; Black, Ronald S; Brashear, H Robert

    2018-06-08

    A 3-year extension of two Phase III parent studies of intravenous (IV) bapineuzumab in patients with mild-to-moderate Alzheimer's disease dementia (apolipoprotein (APOE) ɛ4 carriers and noncarriers) is summarized. The primary and secondary objectives were to evaluate the long-term safety, tolerability, and maintenance of efficacy of bapineuzumab. A multicenter study in patients who had participated in double-blind placebo-controlled parent studies. Patients enrolled in the extension study were assigned to receive IV infusions of bapineuzumab (0.5 or 1.0 mg/kg) every 13 weeks until termination but were blinded to whether they had received bapineuzumab or placebo in the parent studies. A total of 1,462 (688 were APOEɛ4 carriers and 774 were noncarriers) patients were enrolled. Extension-onset adverse events occurred in >81% of the patients in each dose group. Fall, urinary tract infection, agitation, and ARIA-E occurred in ≥10% of participants. The incidence proportion of ARIA-E was higher among carriers and noncarriers who received bapineuzumab for the first time in the extension study (11.8% and 5.4%, respectively) versus those who were previously exposed in the parent studies (5.1% and 1.3%, respectively). After 6 to 12 months exposure to bapineuzumab IV in the extension study, similar deterioration of cognition and function occurred with no significant differences between the dose groups. Infusion of bapineuzumab 0.5 or 1.0 mg/kg every 13 weeks for up to 3 years was generally well tolerated, with a safety and tolerability profile similar to that in previous studies.

  9. The influence of disturbance events on survival and dispersal rates of Florida box turtles

    USGS Publications Warehouse

    Dodd, C.K.; Ozgul, A.; Oli, M.K.

    2006-01-01

    Disturbances have the potential to cause long-term effects to ecosystem structure and function, and they may affect individual species in different ways. Long-lived vertebrates such as turtles may be at risk from such events, inasmuch as their life histories preclude rapid recovery should extensive mortality occur. We applied capture–mark–recapture models to assess disturbance effects on a population of Florida box turtles (Terrapene carolina bauri) on Egmont Key, Florida, USA. Near the midpoint of the study, a series of physical disturbances affected the island, from salt water overwash associated with several tropical storms to extensive removal of nonindigenous vegetation. These disturbances allowed us to examine demographic responses of the turtle population and to determine if they affected dispersal throughout the island. Adult survival rates did not vary significantly either between sexes or among years of the study. Survival rates did not vary significantly between juvenile and adult turtles, or among years of the study. Furthermore, neither adult nor juvenile survival rates differed significantly between pre- and post-disturbance. However, dispersal rates varied significantly among the four major study sites, and dispersal rates were higher during the pre-disturbance sampling periods compared to post-disturbance. Our results suggest few long-term effects on the demography of the turtle population. Florida box turtles responded to tropical storms and vegetation control by moving to favorable habitats minimally affected by the disturbances and remaining there. As long as turtles and perhaps other long-lived vertebrates can disperse to non-disturbed habitat, and high levels of mortality do not occur in a population, a long life span may allow them to wait out the impact of disturbance with potentially little effect on long-term population processes.

  10. Five Years of Cenosumab Exposure in Women With Postmenopausal Osteoporosis: Results From the First Two Years of the FREEDOM Extension

    PubMed Central

    Papapoulos, Socrates; Chapurlat, Roland; Libanati, Cesar; Brandi, Maria Luisa; Brown, Jacques P; Czerwiński, Edward; Krieg, Marc-Antoine; Man, Zulema; Mellström, Dan; Radominski, Sebastião C; Reginster, Jean-Yves; Resch, Heinrich; Ivorra, José A Román; Roux, Christian; Vittinghoff, Eric; Austin, Matthew; Daizadeh, Nadia; Bradley, Michelle N; Grauer, Andreas; Cummings, Steven R; Bone, Henry G

    2012-01-01

    The 3-year FREEDOM trial assessed the efficacy and safety of 60 mg denosumab every 6 months for the treatment of postmenopausal women with osteoporosis. Participants who completed the FREEDOM trial were eligible to enter an extension to continue the evaluation of denosumab efficacy and safety for up to 10 years. For the extension results presented here, women from the FREEDOM denosumab group had 2 more years of denosumab treatment (long-term group) and those from the FREEDOM placebo group had 2 years of denosumab exposure (cross-over group). We report results for bone turnover markers (BTMs), bone mineral density (BMD), fracture rates, and safety. A total of 4550 women enrolled in the extension (2343 long-term; 2207 cross-over). Reductions in BTMs were maintained (long-term group) or occurred rapidly (cross-over group) following denosumab administration. In the long-term group, lumbar spine and total hip BMD increased further, resulting in 5-year gains of 13.7% and 7.0%, respectively. In the cross-over group, BMD increased at the lumbar spine (7.7%) and total hip (4.0%) during the 2-year denosumab treatment. Yearly fracture incidences for both groups were below rates observed in the FREEDOM placebo group and below rates projected for a “virtual untreated twin” cohort. Adverse events did not increase with long-term denosumab administration. Two adverse events in the cross-over group were adjudicated as consistent with osteonecrosis of the jaw. Five-year denosumab treatment of women with postmenopausal osteoporosis maintained BTM reduction and increased BMD, and was associated with low fracture rates and a favorable risk/benefit profile. © 2012 American Society for Bone and Mineral Research PMID:22113951

  11. Modeling ecohydrologic processes at Hubbard Brook: Initial results for Watershed 6 stream discharge and chemistry

    EPA Science Inventory

    The Hubbard Brook Long Term Ecological Research site has produced some of the most extensive and long-running databases on the hydrology, biology and chemistry of forest ecosystem responses to climate and forest harvest. We used these long-term databases to calibrate and apply G...

  12. Examination of Health Effects and Long-Term Impacts of Deployments of Multiple Tag Types on Blue, Humpback, and Gray Whales in the Eastern North Pacific

    DTIC Science & Technology

    2014-09-30

    Deployments of Multiple Tag Types on Blue, Humpback , and Gray Whales in the Eastern North Pacific John Calambokidis Cascadia Research Collective...of large whales including blue, humpback , and gray whales by conducting long term follow up of previously tagged individuals in the eastern North...blue, humpback , and gray whales in the eastern North Pacific and our extensive monitoring of these populations. Despite extensive use of implant tags

  13. Examination of Health Effects and Long-Term Impacts of Deployments of Multiple Tag Types on Blue, Humpback, and Gray Whales in the Eastern North Pacific

    DTIC Science & Technology

    2013-09-30

    Deployments of Multiple Tag Types on Blue, Humpback , and Gray Whales in the Eastern North Pacific John Calambokidis Cascadia Research Collective 218...large whales including blue, humpback , and gray whales by conducting long term follow up of previously tagged individuals in the eastern North Pacific... humpback , and gray whales in the eastern North Pacific and our extensive monitoring of these populations. Despite extensive use of implant tags for more

  14. The Effects of Valbenazine in Participants with Tardive Dyskinesia: Results of the 1-Year KINECT 3 Extension Study.

    PubMed

    Factor, Stewart A; Remington, Gary; Comella, Cynthia L; Correll, Christoph U; Burke, Joshua; Jimenez, Roland; Liang, Grace S; O'Brien, Christopher F

    Valbenazine, a highly selective vesicular monoamine transporter 2 inhibitor, is approved for the treatment of tardive dyskinesia. This is the first report of long-term effects in adults with tardive dyskinesia. Participants with a DSM-IV diagnosis of schizophrenia, schizoaffective disorder, or a mood disorder who completed the 6-week, double-blind, placebo-controlled period of KINECT 3 were eligible to enter the 42-week valbenazine extension (VE) period and subsequent 4-week washout period. The extension phase was conducted from December 16, 2014, to August 3, 2016. Participants who received placebo and entered the VE period were re-randomized 1:1 to valbenazine 80 or 40 mg while others continued valbenazine at the KINECT 3 dose. Safety assessments included treatment-emergent adverse events (TEAEs) and scales for suicidal ideation/behavior, treatment-emergent akathisia or parkinsonism, and psychiatric symptoms. Efficacy assessments included the Abnormal Involuntary Movement Scale (AIMS) and Clinical Global Impression of Change-Tardive Dyskinesia (CGI-TD). 198 participants entered the VE period, 124 (62.6%) completed treatment (week 48), and 121 (61.1%) completed the follow-up visit after washout (week 52). During the VE period, 69.2% of participants had ≥ 1 TEAE, 14.6% had a serious TEAE, and 15.7% discontinued due to a TEAE. During washout, 13.1% of participants experienced a TEAE. No apparent risk for suicidal ideation or behavior was found. Long-term valbenazine treatment did not appear to induce or worsen akathisia or parkinsonism. Participants generally remained psychiatrically stable during the study. AIMS and CGI-TD measures indicated sustained tardive dyskinesia improvement, with scores returning toward baseline after 4 weeks of valbenazine washout. The long-term safety and tolerability of valbenazine were generally favorable, and maintenance of treatment effect was apparent with both doses during this long-term study. ClinicalTrials.gov identifier: NCT02274558. © Copyright 2017 Physicians Postgraduate Press, Inc.

  15. Long-term priming of neighbours biases the word recognition process: evidence from a lexical decision task.

    PubMed

    Wagenmakers, Eric-Jan; Raaijmakers, Jeroen G W

    2006-12-01

    The role of orthographically similar words (i.e., neighbours) in the word recognition process has been studied extensively using short-term priming paradigms (e.g., Colombo, 1986). Here we demonstrate that long-term effects of neighbour priming can also be obtained. Experiment 1 showed that prior study of a neighbour (e.g., TANGO) increased later lexical decision performance for similar words (e.g., MANGO), but decreased performance for similar pseudowords (e.g., LANGO). Experiment 2 replicated this bias effect and showed that the increase in lexical decision performance due to neighbour priming is selectively due to words from a relatively sparse neighbourhood. Explanations of the bias effect in terms of lexical activation and episodic memory retrieval are discussed.

  16. Total En Bloc Spondylectomy for Locally Aggressive Vertebral Hemangioma Causing Neurological Deficits

    PubMed Central

    Ogawa, Ryo; Hikata, Tomohiro; Fujita, Nobuyuki; Iwanami, Akio; Watanabe, Kota; Ishii, Ken; Nakamura, Masaya; Toyama, Yoshiaki; Matsumoto, Morio

    2015-01-01

    Vertebral hemangiomas are common; however, aggressive vertebral hemangiomas with extraosseous extensions causing neurological deficits are rare. The treatment for this subtype of hemangioma remains controversial, since there are few reports on long-term clinical outcomes or tumor recurrence rates. We describe a case of aggressive vertebral hemangioma treated by total en bloc spondylectomy, with a literature review focusing on long-term recurrence. A 52-year-old male with a two-month history of numbness in the bilateral lower extremities was referred to our hospital. Imaging studies showed a tumor originating in the T9 vertebra and extending to the T8 and T10 vertebrae, with extraosseous extension causing spinal-cord compression. Ten months after onset, the patient presented with progressive paraparesis and hypalgesia. Total en bloc spondylectomy was performed, and pathology was consistent with cavernous hemangioma. Motor and sensory deficits improved significantly, and no signs of recurrence are seen at 2.5 years after operation. A review of literature revealed a recurrence rate of 12.7% (10/79 cases). The available evidence indicates satisfactory long-term outcomes for total tumor resection without adjuvant radiotherapy. PMID:25918662

  17. 75 FR 33769 - Manufacturing Extension Partnership (MEP) Availability of Funds for Projects To Develop and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-15

    ... to the long-term economic stability of the region. Please see the NIST MEP Web site, http://www.nist... region, and contribute to the long-term economic stability of the region. Competitive projects will use...

  18. Symbol Labelling Improves Advantageous Decision-Making on the Iowa Gambling Task in People with Intellectual Disabilities

    ERIC Educational Resources Information Center

    Dymond, Simon; Bailey, Rebecca; Willner, Paul; Parry, Rhonwen

    2010-01-01

    Individuals with intellectual and developmental disabilities often have difficulties foregoing short-term loss for long-term gain. The Iowa Gambling Task (IGT) has been extensively adopted as a laboratory measure of this ability. In the present study, we undertook the first investigation with people with intellectual disabilities using a…

  19. Comparison of laparoscopic jejunostomy tube to percutaneous endoscopic gastrostomy tube with jejunal extension: long-term durability and nutritional outcomes.

    PubMed

    Haskins, Ivy N; Strong, Andrew T; Baginsky, Mary; Sharma, Gautam; Karafa, Matthew; Ponsky, Jeffrey L; Rodriguez, John H; Kroh, Matthew D

    2018-05-01

    Enteral access through the jejunum is indicated when patients cannot tolerate oral intake or gastric feeding. While multiple approaches for feeding jejunal access exist, few studies have compared the efficacy of these techniques. The purpose of this study was to investigate the long-term durability, re-intervention rates, and nutritional outcomes following percutaneous endoscopic gastrostomy tubes with jejunal extension tubes (PEG-JET) versus laparoscopic jejunostomy tubes (j-tubes). Retrospective chart review was performed on all patients who underwent PEG-JET or laparoscopic jejunostomy tube placement from January 2005 through December 2015 at our institution. Thirty-day and long-term outcomes were compared between the two groups. A total of 105 patients underwent PEG-JET and 307 patients underwent laparoscopic j-tube placement during the defined study period. In terms of 30-day outcomes, patients who underwent PEG-JET placement were significantly more likely to experience a tube dislodgement event (p = 0.005) and undergo a re-intervention (p < 0.001). Patients who had a laparoscopic j-tube placed were significantly more likely to meet their enteral feeding goals (p = 0.002) and less likely to require nutritional supplementation with total parenteral nutrition (TPN) (p < 0.001). With regard to long-term outcomes, patients who underwent PEG-JET placement were significantly more likely to experience tube occlusion (p < 0.001) and require an endoscopic or surgical tube re-intervention (p < 0.001). Patients who underwent laparoscopic j-tube placement were significantly more likely to experience a tube site leak (p = 0.015) but were less likely to require nutritional supplementation with TPN (p = 0.001). Laparoscopic jejunostomy tubes provide more durable long-term enteral access compared to PEG-JET. Consideration should be given to laparoscopic jejunostomy tube placement in eligible patients who cannot tolerate oral intake or gastric enteral feeding.

  20. STS-65 Earth observation of Omo River Delta, Lake Turkana in Ethiopia / Kenya

    NASA Technical Reports Server (NTRS)

    1994-01-01

    STS-65 Earth observation taken aboard Columbia, Orbiter Vehicle (OV) 102, is of Omo River Delta and Lake Turkana in Ethiopia / Kenya. The Omo Delta at the north end of Lake Turkana (Rudolph) is one of the long-term environmental study sites of the Space Shuttle program. The environmental interest in this instance is the documentation of the delta's extension into the lake. This delta extension, or aggradation, is felt to be the result of large-scale soil erosion in the recently deforested areas of Ethiopia in the watershed of the Omo River. Using digitized, rectified, machine-classified, and mensurated NASA photography, it has been determined that the Omo Delta has increased in area by approximately 400% to about 1,800 square kilometers since it was first photographed during the Gemini program in 1965. This photograph documents the long-term and increasing turbidity of Lake Turkana and the continuing delta extension southward by both the northwest and northeast distributaries of the Om

  1. Long-Term Safety and Efficacy of Fulranumab in Patients With Moderate-to-Severe Osteoarthritis Pain: A Phase II Randomized, Double-Blind, Placebo-Controlled Extension Study.

    PubMed

    Sanga, Panna; Katz, Nathaniel; Polverejan, Elena; Wang, Steven; Kelly, Kathleen M; Haeussler, Juergen; Thipphawong, John

    2017-04-01

    To evaluate the long-term safety and efficacy of fulranumab in patients with knee or hip pain caused by moderate-to-severe chronic osteoarthritis (OA). In this phase II double-blind, placebo-controlled extension study, patients who were randomized in equal proportions to receive subcutaneous doses of either placebo or fulranumab (1 mg every 4 weeks, 3 mg every 8 weeks, 3 mg every 4 weeks, 6 mg every 8 weeks, or 10 mg every 8 weeks) in the 12-week double-blind efficacy phase and who completed this double-blind efficacy phase were eligible to continue the dosage throughout a 92-week double-blind extension phase, followed by a 24-week posttreatment follow-up period. Safety assessments included evaluation of treatment-emergent adverse events (TEAEs), pre-identified AEs of interest, and joint replacements. Efficacy assessments included changes from baseline to the end of the double-blind extension phase in scores on the patient's global assessment and the pain and physical function subscales of the Western Ontario and McMaster Universities Osteoarthritis Index. Overall, 401 of the 423 patients who completed the 12-week double-blind efficacy phase entered the extension study. Long-term sustained improvements were observed in all efficacy parameters following fulranumab treatment (1 mg every 4 weeks, 3 mg every 4 weeks, and 10 mg every 8 weeks) as compared with placebo. Similar percentages of patients in both groups experienced TEAEs (88% taking placebo and 91% taking fulranumab; all phases). Across all fulranumab groups, arthralgia (21%) and OA (18%) (e.g., exacerbation of OA pain) were the most common TEAEs. The most common serious TEAEs were the requirement for knee (10%) and hip (7%) arthroplasty, with 80% occurring during the posttreatment follow-up period. Neurologic-related TEAEs (28%; all phases) were generally mild-to-moderate. Overall, 81 joint replacements were performed in 71 patients (8 [11%] receiving placebo and 63 [89%] receiving fulranumab); 15 patients (21%) had rapid progression of OA (RPOA). All cases of RPOA occurred in fulranumab-treated patients who were concurrently receiving nonsteroidal antiinflammatory drugs and occurred in joints with preexisting OA. Long-term treatment with fulranumab was generally well-tolerated and efficacious. RPOA was observed as a safety signal. Future studies are warranted to demonstrate whether the risk of RPOA can be reduced in patients taking fulranumab. © 2016, American College of Rheumatology.

  2. Green Infrastructure for CSO Control in Kansas City, Missouri

    EPA Science Inventory

    Kansas City Water Services Department (WSD) conducted extensive modeling and economic studies of its combined sewer system over the last 5 years, for submittal of its long term control plan to EPA. These studies and recent funding opportunities have provided the impetus for sele...

  3. Orbital transfer vehicle concept definition and systems analysis study. Volume 11: Study extension 2 results

    NASA Technical Reports Server (NTRS)

    Willcockson, W. H.

    1988-01-01

    Work conducted in the second extension of the Phase A Orbit Transfer Vehicle Concept Definition and Systems Analysis Study is summarized. Four major tasks were identified: (1) define an initial OTV program consistent with near term Civil Space Leadership Initiative missions; (2) develop program evolution to long term advanced missions; (3) investigate the implications of current STS safety policy on an Aft Cargo Carrier based OTV; and (4) expand the analysis of high entry velocity aeroassist. An increased emphasis on the breath of OTV applications was undertaken to show the need for the program on the basis of the expansion of the nation's capabilities in space.

  4. 76 FR 17419 - Agency Information Collection Activities; Proposed Collection; Comment Request; Extension of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-29

    ... Title III and Minor Revisions to the Certification of Long-Term Care Ombudsman Program Expenditures... Certification of Long-Term Care Ombudsman Program Expenditures provides statutorily required information... DEPARTMENT OF HEALTH AND HUMAN SERVICES Administration on Aging Agency Information Collection...

  5. Long-term (up to 4.5 years) treatment with fingolimod in multiple sclerosis: results from the extension of the randomised TRANSFORMS study.

    PubMed

    Cohen, Jeffrey A; Khatri, Bhupendra; Barkhof, Frederik; Comi, Giancarlo; Hartung, Hans-Peter; Montalban, Xavier; Pelletier, Jean; Stites, Tracy; Ritter, Shannon; von Rosenstiel, Philipp; Tomic, Davorka; Kappos, Ludwig

    2016-05-01

    The 12-month (M), phase 3, double-blind, randomised TRANSFORMS study demonstrated significant benefits of fingolimod 0.5 or 1.25 mg over interferon β-1a (IFNβ-1a) in patients with relapsing-remitting multiple sclerosis. We report the results of long-term (up to 4.5 years) extension of TRANSFORMS. Patients randomised to fingolimod (0.5/1.25 mg) in the core phase continued the same dose (continuous-fingolimod) in the extension, whereas those on IFNβ-1a were re-randomised (1:1) to fingolimod (IFN-switch; IFN: 0.5/1.25 mg). Outcomes included annualised relapse rate (ARR), confirmed disability progression and MRI measures. Results are presented here for the continuous-fingolimod 0.5 mg and pooled IFN-switch groups. Of the 1027 patients who entered the extension, 772 (75.2%) completed the study. From baseline to the end of the study (EOS), ARR in patients on continuous-fingolimod 0.5 mg was significantly lower than in the IFN-switch group (M0-EOS: 0.17 vs 0.27). After switching to fingolimod (M0-12 vs M13-EOS), patients initially treated with IFN had a 50% reduction in ARR (0.40 vs 0.20), reduced MRI activity and a lower rate of brain volume loss. In a post hoc analysis, the proportion of IFN-switch patients with no evidence of disease activity increased by approximately 50% in the first year after switching to fingolimod treatment (44.3% to 66.0%). The safety profile was consistent with that observed in the core phase. These results support a continued effect of long-term fingolimod therapy in maintaining a low rate of disease activity and sustained improved efficacy after switching from IFNβ-1a to fingolimod. NCT00340834. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  6. Control of the Onboard Microgravity Environment and Extension of the Service Life of the Long-Term Space Station

    NASA Astrophysics Data System (ADS)

    Titov, V. A.

    2018-03-01

    The problem of control of the on-board microgravity environment in order to extend the service life of the long-term space station has been discussed. Software developed for the ISS and the results of identifying dynamic models and external impacts based on telemetry data have been presented. Proposals for controlling the onboard microgravity environment for future long-term space stations have been formulated.

  7. Degradation of Chlorophenols by Alcaligenes eutrophus JMP134(pJP4) in Bleached Kraft Mill Effluent

    PubMed Central

    Valenzuela, J.; Bumann, U.; Cespedes, R.; Padilla, L.; Gonzalez, B.

    1997-01-01

    The ability of Alcaligenes eutrophus JMP134(pJP4) to degrade 2,4-dichlorophenoxyacetic acid, 2,4,6-trichlorophenol, and other chlorophenols in a bleached kraft mill effluent was studied. The efficiency of degradation and the survival of strain JMP134 and indigenous microorganisms in short-term batch or long-term semicontinuous incubations performed in microcosms were assessed. After 6 days of incubation, 2,4-dichlorophenoxyacetate (400 ppm) or 2,4,6-trichlorophenol (40 to 100 ppm) were extensively degraded (70 to 100%). In short-term batch incubations, indigenous microorganisms were unable to degrade such of compounds. Degradation of 2,4,6-trichlorophenol by strain JMP134 was significantly lower at 200 to 400 ppm of compound. This strain was also able to degrade 2,4-dichlorophenoxyacetate, 2,4,6-trichlorophenol, 4-chlorophenol, and 2,4,5-trichlorophenol when bleached Kraft mill effluent was amended with mixtures of these compounds. On the other hand, the chlorophenol concentration and the indigenous microorganisms inhibited the growth and survival of the strain in short-term incubations. In long-term (>1-month) incubations, strain JMP134 was unable to maintain a large, stable population, although extensive 2,4,6-trichlorophenol degradation was still observed. The latter is probably due to acclimation of the indigenous microorganisms to degrade 2,4,6-trichlorophenol. Acclimation was observed only in long-term, semicontinuous microcosms. PMID:16535488

  8. Childhood Neurodevelopmental Disorders and Violent Criminality: A Sibling Control Study

    ERIC Educational Resources Information Center

    Lundström, Sebastian; Forsman, Mats; Larsson, Henrik; Kerekes, Nora; Serlachius, Eva; Långström, Niklas; Lichtenstein, Paul

    2014-01-01

    The longitudinal relationship between attention deficit hyperactivity disorder (ADHD) and violent criminality has been extensively documented, while long-term effects of autism spectrum disorders (ASDs), tic disorders (TDs), and obsessive compulsive disorder (OCD) on criminality have been scarcely studied. Using population-based registers of all…

  9. Graphene as a long-term metal oxidation barrier: worse than nothing.

    PubMed

    Schriver, Maria; Regan, William; Gannett, Will J; Zaniewski, Anna M; Crommie, Michael F; Zettl, Alex

    2013-07-23

    Anticorrosion and antioxidation surface treatments such as paint or anodization are a foundational component in nearly all industries. Graphene, a single-atom-thick sheet of carbon with impressive impermeability to gases, seems to hold promise as an effective anticorrosion barrier, and recent work supports this hope. We perform a complete study of the short- and long-term performance of graphene coatings for Cu and Si substrates. Our work reveals that although graphene indeed offers effective short-term oxidation protection, over long time scales it promotes more extensive wet corrosion than that seen for an initially bare, unprotected Cu surface. This surprising result has important implications for future scientific studies and industrial applications. In addition to informing any future work on graphene as a protective coating, the results presented here have implications for graphene's performance in a wide range of applications.

  10. Long-term analysis of Zostera noltei: A retrospective approach for understanding seagrasses' dynamics.

    PubMed

    Calleja, Felipe; Galván, Cristina; Silió-Calzada, Ana; Juanes, José A; Ondiviela, Bárbara

    2017-09-01

    Long-term studies are necessary to establish trends and to understand seagrasses' spatial and temporal dynamic. Nevertheless, this type of research is scarce, as the required databases are often unavailable. The objectives of this study are to create a method for mapping the seagrass Zostera noltei using remote sensing techniques, and to apply it to the characterization of the meadows' extension trend and the potential drivers of change. A time series was created using a novel method based on remote sensing techniques that proved to be adequate for mapping the seagrass in the emerged intertidal. The meadows seem to have a decreasing trend between 1984 and the early 2000s, followed by an increasing tendency that represents a recovery in the extension area of the species. This 30-year analysis demonstrated the Z. noltei's recovery in the study site, similar to that in other estuaries nearby and contrary to the worldwide decreasing behavior of seagrasses. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Long-Term Phonological Knowledge Supports Serial Ordering in Working Memory

    ERIC Educational Resources Information Center

    Nakayama, Masataka; Tanida, Yuki; Saito, Satoru

    2015-01-01

    Serial ordering mechanisms have been investigated extensively in psychology and psycholinguistics. It has also been demonstrated repeatedly that long-term phonological knowledge contributes to serial ordering. However, the mechanisms that contribute to serial ordering have yet to be fully understood. To understand these mechanisms, we demonstrate…

  12. Motivations of Volunteer Leaders in an Extension Exercise Program

    ERIC Educational Resources Information Center

    Washburn, Lisa T.; Cornell, Carol E.; Traywick, LaVona; Felix, Holly C.; Phillips, Martha

    2015-01-01

    This article describes findings from a qualitative study of volunteer leaders in the StrongWomen strength training program in Arkansas. The study explored reasons volunteers initially agreed to serve, perceptions of volunteer role, and motivations for continuing to lead strength training groups long-term. Findings suggest a combination of factors…

  13. Cyclic Nucleotide-Gated Channels, Calmodulin, Adenylyl Cyclase, and Calcium/Calmodulin-Dependent Protein Kinase II Are Required for Late, but Not Early, Long-Term Memory Formation in the Honeybee

    ERIC Educational Resources Information Center

    Matsumoto, Yukihisa; Sandoz, Jean-Christophe; Devaud, Jean-Marc; Lormant, Flore; Mizunami, Makoto; Giurfa, Martin

    2014-01-01

    Memory is a dynamic process that allows encoding, storage, and retrieval of information acquired through individual experience. In the honeybee "Apis mellifera," olfactory conditioning of the proboscis extension response (PER) has shown that besides short-term memory (STM) and mid-term memory (MTM), two phases of long-term memory (LTM)…

  14. Positive Socialization Mechanisms in Secure and Insecure Parent-Child Dyads: Two Longitudinal Studies

    ERIC Educational Resources Information Center

    Kochanska, Grazyna; Woodard, Jarilyn; Kim, Sanghag; Koenig, Jamie L.; Yoon, Jeung Eun; Barry, Robin A.

    2010-01-01

    Background: Implications of early attachment have been extensively studied, but little is known about its long-term indirect sequelae, where early security organization moderates future parent-child relationships, serving as a catalyst for adaptive and maladaptive processes. Two longitudinal multi-trait multi-method studies examined whether early…

  15. Decomposition rate comparisons between frequently burned and unburned areas of uneven-aged loblolly pine stands in southeastern Arkansas

    Treesearch

    Miclele Renschin; Hal O. Leichty; Michael G. Shelton

    2001-01-01

    Although fire has been used extensively over long periods of time in loblolly pine (Pinis taeda L.) ecosystems, little is known concerning the effects of frequent fire use on nutrient cycling and decomposition. To better understand the long-term effects of fire on these processes, foliar litter decomposition rates were quantified in a study...

  16. Long-term studies of dopamine agonists.

    PubMed

    Hubble, Jean P

    2002-02-26

    Dopamine agonists have long been used as adjunctive therapy for the treatment of Parkinson's disease (PD). In more recent years these drugs have also been proved safe and effective as initial therapy in lieu of levodopa in the treatment of PD. Long-term levodopa therapy is associated with motor complications, including fluctuating response patterns and dyskinesia. By initially introducing a dopamine agonist as symptomatic drug therapy, it may be possible to postpone the use of levodopa and delay or prevent the development of motor complications. Recently, four clinical trials have explored this hypothesis by comparing the long-term response and side effects of levodopa with dopamine agonist therapy. The drugs studied have included ropinirole, pramipexole, cabergoline, and pergolide. In each of these projects, the occurrence of motor complications, such as wearing off and dyskinesia, was significantly less in the subjects assigned to initiation of therapy with a dopamine agonist. The addition of levodopa could be postponed by many months or even several years. Therefore, these long-term studies of dopamine agonists support the initiation of a dopamine agonist instead of levodopa in an effort to postpone levodopa-related motor complications. This therapeutic approach may be particularly appropriate in PD patients with a long treatment horizon on the basis of age and general good health. The extension phase of the long-term study comparing pramipexole with levodopa is ongoing, and follow-up information may help to establish the value of this treatment strategy.

  17. Decreased muscle strength is associated with impaired long-term functional outcome after intramedullary nailing of femoral shaft fracture.

    PubMed

    Larsen, P; Elsoe, R; Graven-Nielsen, T; Laessoe, U; Rasmussen, S

    2015-12-01

    To examine the long-term outcome after intramedullary nailing of femoral diaphysial fractures measured as disease-specific patient reported function, walking ability, muscle strength, pain and quality of life (QOL). Cross-sectional study. Retrospective review and follow-up with clinical examination of 48 patients treated with intramedullary nailing after femoral shaft fracture between 2007 and 2010. The patients underwent a clinical examination and assessment of walking ability, maximal muscle strength during knee flexion and extension and hip abduction. Hip disability and Osteoarthritis Outcome Score (HOOS) and questionnaire evaluating QOL (Eq5D-5L) were completed by patients. Fourty-eight patients agreed to participate. Mean time for follow-up was 4.7 years. The mean HOOS scores were 84.9 (Pain), 86.6 (ADL), 85.0 (Symptoms), 72.6 (QOL), and 69.1 (Sport). The mean muscle strength of knee flexion with the injured leg (226.0 N) was significantly lower then knee flexion with the non-injured leg (259.5 N, P < 0.0001). Likewise for knee extension (335.2 vs 406.4 N, P < 0.001) and hip abduction (129.2 vs 156.0 N, P < 0.001). Significant association between HOOS and an increase in the difference in muscle strength were observed as well as between worse HOOS outcome and increasing body mass index. This study showed that decreased muscle strength for knee flexion, knee extension and hip abduction was associated with worse long-term functional outcome measured with a disease-specific questionnaire (HOOS) after intramedullary nailing of femoral shaft fracture.

  18. Determining Extension's Role in Controversial Issues: Content, Process, Neither, or Both?

    ERIC Educational Resources Information Center

    Goerlich, Dan; Walker, Martha A.

    2015-01-01

    Controversial issues offer Extension faculty opportunities to facilitate community dialogue and apply conflict resolution strategies to help communities achieve higher ground. Handled appropriately, the long-term benefits to the community, the Extension organization, and the faculty member of facilitating public issues outweigh the costs. This…

  19. The Role of Public Extension in Introducing Environment-Friendly Farming Methods in Turkey.

    ERIC Educational Resources Information Center

    Kumuk, T.; Akgungor, S.

    1995-01-01

    Currently, the Turkish extension service plays a minimal role in reducing adverse environmental effects of farming methods. Public investment in research and extension on sustainable agriculture is needed to ensure long-term production practices that maintain the food supply without damaging the environment. (SK)

  20. Long-term efficacy and safety of certolizumab pegol in Japanese rheumatoid arthritis patients with an inadequate response to methotrexate: 52-week results from an open-label extension of the J-RAPID study

    PubMed Central

    Tanaka, Yoshiya; Yamamoto, Kazuhiko; Takeuchi, Tsutomu; Yamanaka, Hisashi; Ishiguro, Naoki; Eguchi, Katsumi; Watanabe, Akira; Origasa, Hideki; Shoji, Toshiharu; Miyasaka, Nobuyuki; Koike, Takao

    2014-01-01

    Abstract Objectives. To evaluate the long-term efficacy and safety of certolizumab pegol (CZP) plus methotrexate treatment and to assess the efficacy of two CZP maintenance dosing schedules in Japanese rheumatoid arthritis (RA) patients with an inadequate response to methotrexate. Methods. J-RAPID double-blind patients were entered into an open-label extension (OLE) study. Patients withdrawn due to lack of efficacy at 16 weeks and double-blind completers without a week-24 American College of Rheumatology (ACR) 20 response received CZP 200 mg every other week (Q2W) plus methotrexate. Double-blind completers with week-24 ACR20 responses were randomized to CZP 200 mg Q2W plus methotrexate or CZP 400 mg every 4 weeks plus methotrexate. Results. The ACR20/ACR50/ACR70 response rates of double-blind completers (n = 204) were 89.7%/67.2%/36.3% at OLE entry and 95.6%/84.8%/58.3% at 52 weeks, respectively. Other clinical, functional and radiographic outcomes were sustained with long-term CZP plus methotrexate. Long-term treatment with CZP was well-tolerated with no new unexpected adverse events observed. The efficacy and safety of CZP treatment were similar between the two dosing schedules. Conclusions. Continued CZP administration with methotrexate maintained efficacy over 52 weeks and was well-tolerated for Japanese RA patients. No obvious differences in clinical efficacy and safety were observed between the two dosing schedules, giving flexibility in maintenance administration schedules. PMID:24593170

  1. Dissecting the Components of Long-Term Potentiation

    PubMed Central

    Blundon, Jay A.; Zakharenko, Stanislav S.

    2009-01-01

    The formation of memories relies on plastic changes at synapses between neurons. Although the mechanisms of synaptic plasticity have been studied extensively over several decades, many aspects of this process remain controversial. The cellular locus of expression of long-term potentiation (LTP), a major form of synaptic plasticity, is one of the most important unresolved phenomena. In this article, we summarize some recent advances in this area made possible by the development of new imaging tools. These studies have demonstrated that LTP is compound in nature and consists of both presynaptic and postsynaptic components. We also review some features of presynaptic and postsynaptic changes during compound LTP. PMID:18940785

  2. Mechanistic approach to the pathophysiology of target organ damage in hypertension from studies in a human model with characteristics opposite to hypertension: Bartter's and Gitelman's syndromes.

    PubMed

    Calò, L A; Maiolino, G

    2015-07-01

    Extensive studies using Bartter's/Gitelman's syndrome patients have provided insights into the angiotensin II (Ang II) signaling pathways involved in the regulation of vascular tone and cardiovascular-renal remodeling. The renin-angiotensin-aldosterone system is activated in these syndromes, however, patients do not develop hypertension and cardiovascular remodeling and clinically manifest conditions opposite to hypertension. The short- and the long-term signaling of Ang II remains an important matter of investigation to shed light on mechanisms responsible for the pathophysiology of hypertension and its long-term complications. The long-term signaling of Ang II is involved in the pathophysiology of cardiovascular-renal remodeling and inflammatory responses in which the balance between RhoA/Rho kinase pathway and NO system plays a crucial role. In this brief review, the results of our studies in Bartter's and Gitelman's syndromes are reported on these processes. The information obtained from these studies can clarify, confirm or be used to extend the biochemical mechanisms responsible for the pathophysiology of hypertension and its long-term complications and could offer further chances to identify additional potential significant targets of therapy.

  3. Systematic review and meta-analysis of serious infections with tofacitinib and biologic disease-modifying antirheumatic drug treatment in rheumatoid arthritis clinical trials.

    PubMed

    Strand, Vibeke; Ahadieh, Sima; French, Jonathan; Geier, Jamie; Krishnaswami, Sriram; Menon, Sujatha; Checchio, Tina; Tensfeldt, Thomas G; Hoffman, Elaine; Riese, Richard; Boy, Mary; Gómez-Reino, Juan J

    2015-12-15

    Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). Tofacitinib modulates the signaling of cytokines that are integral to lymphocyte activation, proliferation, and function. Thus, tofacitinib therapy may result in suppression of multiple elements of the immune response. Serious infections have been reported in tofacitinib RA trials. However, limited head-to-head comparator data were available within the tofacitinib RA development program to directly compare rates of serious infections with tofacitinib relative to biologic agents, and specifically adalimumab (employed as an active control agent in two randomized controlled trials of tofacitinib). A systematic literature search of data from interventional randomized controlled trials and long-term extension studies with biologics in RA was carried out. Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) consensus was followed for reporting results of the review and meta-analysis. Incidence rates (unique patients with events/100 patient-years) for each therapy were estimated based on data from randomized controlled trials and long-term extension studies using a random-effects model. Relative and absolute risk comparisons versus placebo used Mantel-Haenszel methods. The search produced 657 hits. In total, 66 randomized controlled trials and 22 long-term extension studies met the selection criteria. Estimated incidence rates (95% confidence intervals [CIs]) for abatacept, rituximab, tocilizumab, and tumor necrosis factor inhibitors were 3.04 (2.49, 3.72), 3.72 (2.99, 4.62), 5.45 (4.26, 6.96), and 4.90 (4.41, 5.44), respectively. Incidence rates (95% CIs) for tofacitinib 5 and 10 mg twice daily (BID) in phase 3 trials were 3.02 (2.25, 4.05) and 3.00 (2.24, 4.02), respectively. Corresponding incidence rates in long-term extension studies were 2.50 (2.05, 3.04) and 3.19 (2.74, 3.72). The risk ratios (95% CIs) versus placebo for tofacitinib 5 and 10 mg BID were 2.21 (0.60, 8.14) and 2.02 (0.56, 7.28), respectively. Risk differences (95% CIs) versus placebo for tofacitinib 5 and 10 mg BID were 0.38% (-0.24%, 0.99%) and 0.40% (-0.22%, 1.02%), respectively. In interventional studies, the risk of serious infections with tofacitinib is comparable to published rates for biologic disease-modifying antirheumatic drugs in patients with moderate to severely active RA.

  4. Assessment of safety and efficacy of long-term treatment with combination lumacaftor and ivacaftor therapy in patients with cystic fibrosis homozygous for the F508del-CFTR mutation (PROGRESS): a phase 3, extension study.

    PubMed

    Konstan, Michael W; McKone, Edward F; Moss, Richard B; Marigowda, Gautham; Tian, Simon; Waltz, David; Huang, Xiaohong; Lubarsky, Barry; Rubin, Jaime; Millar, Stefanie J; Pasta, David J; Mayer-Hamblett, Nicole; Goss, Christopher H; Morgan, Wayne; Sawicki, Gregory S

    2017-02-01

    The 24-week safety and efficacy of lumacaftor/ivacaftor combination therapy was shown in two randomised controlled trials (RCTs)-TRAFFIC and TRANSPORT-in patients with cystic fibrosis who were aged 12 years or older and homozygous for the F508del-CFTR mutation. We aimed to assess the long-term safety and efficacy of extended lumacaftor/ivacaftor therapy in this group of patients in PROGRESS, the long-term extension of TRAFFIC and TRANSPORT. PROGRESS was a phase 3, parallel-group, multicentre, 96-week study of patients who completed TRAFFIC or TRANSPORT in 191 sites in 15 countries. Patients were eligible if they were at least 12 years old with cystic fibrosis and homozygous for the F508del-CFTR mutation. Exclusion criteria included any comorbidity or laboratory abnormality that, in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering the study drug to the participant, history of drug intolerance, and history of poor compliance with the study drug. Patients who previously received active treatment in TRANSPORT or TRAFFIC remained on the same dose in PROGRESS. Patients who had received placebo in TRANSPORT or TRAFFIC were randomly assigned (1:1) to receive lumacaftor (400 mg every 12 h)/ivacaftor (250 mg every 12 h) or lumacaftor (600 mg once daily)/ivacaftor (250 mg every 12 h). The primary outcome was to assess the long-term safety of combined therapy. The estimated annual rate of decline in percent predicted FEV 1 (ppFEV 1 ) in treated patients was compared with that of a matched registry cohort. Efficacy analyses were based on modified intention-to-treat, such that data were included for all patients who were randomly assigned and received at least one dose of study drug. This study is registered with ClinicalTrials.gov, number NCT01931839. Between Oct 24, 2013, and April 7, 2016, 1030 patients from the TRANSPORT and TRAFFIC studies enrolled in PROGRESS, and 1029 received at least one dose of study drug. 340 patients continued treatment with lumacaftor 400 mg every 12 h/ivacaftor 250 mg every 12 h; 176 patients who had received placebo in the TRANSPORT or TRAFFIC studies initiated treatment with lumacaftor 400 mg every 12 h/ivacaftor 250 mg every 12 h, the commercially available dose, for which data are presented. The most common adverse events were infective pulmonary exacerbations, cough, increased sputum, and haemoptysis. Modest blood pressure increases seen in TRAFFIC and TRANSPORT were also observed in PROGRESS. For patients continuing treatment, the mean change from baseline in ppFEV 1 was 0·5 (95% CI -0·4 to 1·5) at extension week 72 and 0·5 (-0·7 to 1·6) at extension week 96; change in BMI was 0·69 (0·56 to 0·81) at extension week 72 and 0·96 (0·81 to 1·11) at extension week 96. The annualised pulmonary exacerbation rate in patients continuing treatment through extension week 96 (0·65, 0·56 to 0·75) remained lower than the placebo rate in TRAFFIC and TRANSPORT. The annualised rate of ppFEV 1 decline was reduced in lumacaftor/ivacaftor-treated patients compared with matched controls (-1·33, -1·80 to -0·85 vs -2·29, -2·56 to -2·03). The efficacy and safety profile of the lumacaftor 600 mg once daily/ivacaftor 250 mg every 12 h groups was generally similar to that of the lumacaftor 400 mg every 12 h/ivacaftor 250 mg every 12 h groups. The long-term safety profile of lumacaftor/ivacaftor combination therapy was consistent with previous RCTs. Benefits continued to be observed with longer-term treatment, and lumacaftor/ivacaftor was associated with a 42% slower rate of ppFEV 1 decline than in matched registry controls. Vertex Pharmaceuticals Incorporated. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Modified Direct-Type Septal Extension Grafts: Their Stability and Usefulness in Asian Rhinoplasty.

    PubMed

    Han, So-Eun; Han, Kihwan; Choi, Jaehoon; Yun, Tae Bin

    2017-03-01

    In Asian rhinoplasty, many autogenous cartilage grafts are required for correction of the nasal tip and columella, but the amount has limitations. A modified direct-type septal extension graft, in continuity with the entire caudal border of the septal cartilage with an edge-to-edge coaptation, can effectively and concomitantly correct the nasal tip and columella deformities using a limited amount of septal cartilage graft. The purpose of this study was to evaluate long-term cosmetic outcomes and stability from the modified direct extension grafts. Fifty-seven patients with a follow-up of more than 1 year were enrolled in the study. A total of 11 measurement items were evaluated from basal and right lateral views by photogrammetry using standardized clinical photographic techniques. The overall mean follow-up period was 20.4 months. When comparing the preoperative and postoperative values, the nasal tip projection, nasal bridge length, nasal tip angle, height of nose, and the columellar labial angle increased significantly; additionally, the soft nose width index, width between ac-ac index, nostril axis inclination, columellar length (Rt-Lt), and the alar length (Rt-Lt) decreased significantly. No resorption, buckling, or displacement of the graft was observed during the follow-up period. The modified direct extension graft demonstrated a marked aesthetic improvement in the nasal tip and columella, and it provided long-term stability. Therefore, the modified direct extension graft is useful for correction of the nasal tip and columella in Asian rhinoplasty.

  6. A Survey of Current Literature on Sampling, Sample Handling, and Long Term Storage for Environmental Materials.

    ERIC Educational Resources Information Center

    Maienthal, E. J.; Becker, D. A.

    This report presents the results of an extensive literature survey undertaken to establish optimum sampling, sample handling and long-term storage techniques for a wide variety of environmental samples to retain sample integrity. The components of interest are trace elements, organics, pesticides, radionuclides and microbiologicals. A bibliography…

  7. Hippocampal damage causes retrograde but not anterograde memory loss for context fear discrimination in rats.

    PubMed

    Lee, Justin Q; Sutherland, Robert J; McDonald, Robert J

    2017-09-01

    There is a substantial body of evidence that the hippocampus (HPC) plays and essential role in context discrimination in rodents. Studies reporting anterograde amnesia (AA) used repeated, alternating, distributed conditioning and extinction sessions to measure context fear discrimination. In addition, there is uncertainty about the extent of damage to the HPC. Here, we induced conditioned fear prior to discrimination tests and rats sustained extensive, quantified pre- or post-training HPC damage. Unlike previous work, we found that extensive HPC damage spares context discrimination, we observed no AA. There must be a non-HPC system that can acquire long-term memories that support context fear discrimination. Post-training HPC damage caused retrograde amnesia (RA) for context discrimination, even when rats are fear conditioned for multiple sessions. We discuss the implications of these findings for understanding the role of HPC in long-term memory. © 2017 Wiley Periodicals, Inc.

  8. The clinical implications of poly implant prothèse breast implants: an overview.

    PubMed

    Wazir, Umar; Kasem, Abdul; Mokbel, Kefah

    2015-01-01

    Mammary implants marketed by Poly Implant Prothèse (PIP) were found to contain industrial grade silicone and this caused heightened anxiety and extensive publicity regarding their safety in humans. These implants were used in a large number of patients worldwide for augmentation or breast reconstruction. We reviewed articles identified by searches of Medline, PubMed, Embase, and Google Scholar databases up to May 2014 using the terms: "PIP", "Poly Implant Prothèse", "breast implants" and "augmentation mammoplasty" "siloxanes" or "silicone". In addition the websites of regulating bodies in Europe, USA, and Australia were searched for reports related to PIP mammary implants. PIP mammary implants are more likely to rupture than other implants and can cause adverse effects in the short to the medium term related to the symptoms of rupture such as pain, lumps in the breast and axilla and anxiety. Based on peer-reviewed published studies we have calculated an overall rupture rate of 14.5% (383/2,635) for PIP implants. However, there is no evidence that PIP implant rupture causes long-term adverse health effects in humans so far. Silicone lymphadenopathy represents a foreign body reaction and should be treated conservatively. The long-term adverse effects usually arise from inappropriate extensive surgery, such as axillary lymph node dissection or extensive resection of breast tissue due to silicone leakage.

  9. The Clinical Implications of Poly Implant Prothèse Breast Implants: An Overview

    PubMed Central

    Wazir, Umar; Kasem, Abdul

    2015-01-01

    Mammary implants marketed by Poly Implant Prothèse (PIP) were found to contain industrial grade silicone and this caused heightened anxiety and extensive publicity regarding their safety in humans. These implants were used in a large number of patients worldwide for augmentation or breast reconstruction. We reviewed articles identified by searches of Medline, PubMed, Embase, and Google Scholar databases up to May 2014 using the terms: "PIP", "Poly Implant Prothèse", "breast implants" and "augmentation mammoplasty" "siloxanes" or "silicone". In addition the websites of regulating bodies in Europe, USA, and Australia were searched for reports related to PIP mammary implants. PIP mammary implants are more likely to rupture than other implants and can cause adverse effects in the short to the medium term related to the symptoms of rupture such as pain, lumps in the breast and axilla and anxiety. Based on peer-reviewed published studies we have calculated an overall rupture rate of 14.5% (383/2,635) for PIP implants. However, there is no evidence that PIP implant rupture causes long-term adverse health effects in humans so far. Silicone lymphadenopathy represents a foreign body reaction and should be treated conservatively. The long-term adverse effects usually arise from inappropriate extensive surgery, such as axillary lymph node dissection or extensive resection of breast tissue due to silicone leakage. PMID:25606483

  10. Response of Solar Irradiance to Sunspot-area Variations

    NASA Astrophysics Data System (ADS)

    Dudok de Wit, T.; Kopp, G.; Shapiro, A.; Witzke, V.; Kretzschmar, M.

    2018-02-01

    One of the important open questions in solar irradiance studies is whether long-term variability (i.e., on timescales of years and beyond) can be reconstructed by means of models that describe short-term variability (i.e., days) using solar proxies as inputs. Preminger & Walton showed that the relationship between spectral solar irradiance and proxies of magnetic-flux emergence, such as the daily sunspot area, can be described in the framework of linear system theory by means of the impulse response. We significantly refine that empirical model by removing spurious solar-rotational effects and by including an additional term that captures long-term variations. Our results show that long-term variability cannot be reconstructed from the short-term response of the spectral irradiance, which questions the extension of solar proxy models to these timescales. In addition, we find that the solar response is nonlinear in a way that cannot be corrected simply by applying a rescaling to a sunspot area.

  11. Candidacy for Bilateral Hearing Aids: A Retrospective Multicenter Study

    ERIC Educational Resources Information Center

    Boymans, Monique; Goverts, S. Theo; Kramer, Sophia E.; Festen, Joost M.; Dreschler, Wouter A.

    2009-01-01

    Purpose: The goal of this study was to find factors for refining candidacy criteria for bilateral hearing aid fittings. Clinical files of 1,000 consecutive hearing aid fittings were analyzed. Method: Case history, audiometric, and rehabilitation data were collected from clinical files, and an extensive questionnaire on long-term outcome measures…

  12. The Longitudinal Effect of Bilingual Immersion Schooling on Cognitive Control and Intelligence

    ERIC Educational Resources Information Center

    Woumans, Evy; Surmont, Jill; Struys, Esli; Duyck, Wouter

    2016-01-01

    Throughout the past century, the effects of bilingualism on general cognition have been extensively explored. Studies evolved from a negative to a more positive perspective, but longitudinal assessments of effects of bilingualism are scarce. This study investigated the long-term effect of becoming a bilingual on the development of general…

  13. Potential Impact of Clean Air Act Regulations on Nitrogen Fate and Transport in the Neuse River Basin: a Modeling Investigation Using CMAQ and SWAT

    EPA Science Inventory

    There has been extensive analysis of Clean Air Act Amendment (CAAA) regulation impacts to changes in atmospheric nitrogen deposition; however, few studies have focused on watershed nitrogen transfer particularly regarding long-term predictions. In this study, we investigated impa...

  14. Predictive factors of long-term colorectal cancer survival after ultrasound-controlled ablation of hepatic metastases.

    PubMed

    Hernández-Socorro, Carmen Rosa; Saavedra, Pedro; Ramírez Felipe, José; Bohn Sarmiento, Uriel; Ruiz-Santana, Sergio

    2017-04-21

    The risk factors associated to long-term survival were assessed in patients with liver metastases of colorectal carcinoma undergoing ablative therapies. Single-centre cohort study, retrospectively analysed and prospectively collected consecutive patients with unresectable metastatic liver disease of colorectal carcinoma treated with ablative therapies between 1996 and 2013. Factors associated with survival time were identified using Cox's proportional hazard model with time-dependent covariates. A forward variable selection based on Akaike information criterion was performed. Relative risk and 95% confidence intervals for each factor were calculated. Statistical significance was set as P<.05. Seventy-five patients with liver metastases of colorectal cancer, with a mean age of 65.6 (10.3) underwent 106 treatments. Variables selected were good quality of life (RR 0.308, 95% CI 0.150-0.632) and tumour extension (RR 3.070, 95% CI 1.776-5.308). The median overall survival was 18.5 months (95% CI 17.4-24.4). The survival prognosis in median was 13.5 vs. 23.4 months for patients with and without tumour extension, and 23.0 vs. 12.8 months for patients with good and fair or poor quality of life, respectively. Good quality of life and tumour extension were the only statistically significant predictors of long-term survival in patients of colorectal carcinoma with liver metastatic disease undergoing ablative treatment with ultrasound. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  15. Long-term Immunogenicity of Elosulfase Alfa in the Treatment of Morquio A Syndrome: Results From MOR-005, a Phase III Extension Study.

    PubMed

    Long, Brian; Tompkins, Troy; Decker, Celeste; Jesaitis, Lynne; Khan, Shahid; Slasor, Peter; Harmatz, Paul; O'Neill, Charles A; Schweighardt, Becky

    2017-01-01

    Elosulfase alfa is an enzyme replacement therapy for the treatment of Morquio A syndrome (mucopolysaccharidosis IVA), a lysosomal storage disorder caused by a deficiency of the enzyme N-acetylgalactose-amine-6-sulfatase. We previously reported immunogenicity data from our 24-week placebo-controlled Phase III study, MOR-004. Here, we report the long-term immunogenicity profile of elosulfase alfa from MOR-005, the Phase III extension trial to assess potential correlations between antidrug antibodies and efficacy and safety profile outcomes throughout 120 weeks of treatment. The long-term immunogenicity of elosulfase alfa was evaluated in patients with Morquio A syndrome in an open-label extension study for a total of 120 weeks. All patients received 2.0 mg/kg elosulfase alfa either weekly or every other week before establishment of 2.0 mg/kg/wk as the recommended dose, at which time all patients received weekly treatment. Efficacy measures were compared with those from the MOR-004 baseline, enabling analysis of changes over 120 weeks. The primary efficacy measure was the change from baseline in 6-minute walk test. Secondary measures included changes from baseline in 3-minute stair climb test and normalized urine keratan sulfate, a pharmacodynamic metric. All patients treated with elosulfase alfa developed antidrug total antibodies (TAb) by week 24 of MOR-004. In the extension study, all patients, including those who had previously received placebo, were TAb positive by study week 36 (MOR-005 week 12). All patients remained TAb positive throughout the study, and TAb titers were similar across treatment groups at week 120. Nearly all patients tested positive for neutralizing antibodies (NAb) at least once, with incidence of NAb positivity peaking at 85.9% at study week 36, then steadily declining to 66.0% at study week 120. In all treatment groups, mean urine keratan sulfate remained below treatment-naive baseline despite the presence of antidrug antibodies. No relationship was observed between TAb titers or NAb positivity and changes in urine keratan sulfate, 6-minute walk test, or 3-minute stair climb test from baseline to week 120. No consistent associations were detected between antidrug antibodies and the occurrence of hypersensitivity adverse events or anaphylaxis over the course of the study. Immunogenicity results from this long-term study are consistent with previously reported 24-week results. Despite the sustained presence of antidrug antibodies, elosulfase alfa was well tolerated, and patients continued to benefit from treatment through week 120. No associations were detected between higher TAb titers or NAb positivity and reduced treatment effect or worsened safety profile measures. ClinicalTrials.gov identifier: NCT01415427. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  16. Long-Term Effects of an Extensive Cognitive Training on Personality Development.

    PubMed

    Sander, Julia; Schmiedek, Florian; Brose, Annette; Wagner, Gert G; Specht, Jule

    2017-08-01

    Previous research found that cognitive training increases the Big Five personality trait Openness to Experience during and some weeks after the intervention. The present study investigated whether long-term changes happen in Openness to Experience and other personality traits after an extensive cognitive training of memory and perceptual speed. The intervention group consisted of 204 adults (20-31 years and 65-80 years; 50% female) who received daily 1-hour cognitive training sessions for about 100 days. The control group consisted of 86 adults (21-29 years and 65-82 years; 51% female) who received no cognitive training. All participants answered the NEO Five-Factor Inventory before and 2 years after the cognitive training. Latent change models were applied that controlled for age group (young vs. old) and gender. In the long run, the cognitive training did not affect changes in any facet of Openness to Experience. This was true for young and old participants as well as for men and women. Instead, the cognitive training lowered the general increase of Conscientiousness. Even an extensive cognitive training on memory and perceptual speed does not serve as a sufficient intervention for enduring changes in Openness to Experiences or one of its facets. © 2016 Wiley Periodicals, Inc.

  17. Long-term Safety and Efficacy of Tapentadol Extended Release Following up to 2 Years of Treatment in Patients With Moderate to Severe, Chronic Pain: Results of an Open-label Extension Trial.

    PubMed

    Buynak, Robert; Rappaport, Stephen A; Rod, Kevin; Arsenault, Pierre; Heisig, Fabian; Rauschkolb, Christine; Etropolski, Mila

    2015-11-01

    Tapentadol extended release (ER) has demonstrated efficacy and safety for the management of moderate to severe, chronic pain in adults. This study evaluated the long-term safety and tolerability of tapentadol ER in patients with chronic osteoarthritis or low back pain. Patients were enrolled in this 1-year, open-label extension study after completing one of two 15-week, placebo-controlled studies of tapentadol ER and oxycodone controlled release (CR) for osteoarthritis knee pain (NCT00421928) or low back pain (NCT00449176), a 7-week crossover study between tapentadol immediate release and tapentadol ER for low back pain (NCT00594516), or a 1-year safety study of tapentadol ER and oxycodone CR for osteoarthritis or low back pain (NCT00361504). After titrating the drug to an optimal dose, patients received tapentadol ER (100-250 mg BID) for up to 1 year (after finishing treatment in the preceding studies); patients who were previously treated with tapentadol ER in the 1-year safety study received tapentadol ER continuously for up to 2 years in total. Of the 1,154 patients in the safety population, 82.7% were aged >65 years and 57.9% were female; 50.1% had mild baseline pain intensity. Mean (SD) pain intensity scores (11-point numerical rating scale) were 3.9 (2.38) at baseline (end of preceding study) and 3.7 (2.42) at end point, indicating that pain relief was maintained during the extension study. Improvements in measures of quality of life (eg, EuroQol-5 Dimension and the 36-item Short Form Health Survey [SF-36]) health status questionnaires) achieved during the preceding studies were maintained during the open-label extension study. Tapentadol ER was associated with a safety and tolerability profile comparable to that observed in the preceding studies. The most common treatment-emergent adverse events (incidence ≥10%; n = 1154) were headache (13.1%), nausea (11.8%), and constipation (11.1%). Similar efficacy and tolerability results were shown for patients who received up to 2 years of tapentadol ER treatment. Pain relief and improvements in quality of life achieved during the preceding studies were maintained throughout this extension study, during which tapentadol ER was well tolerated for the long-term treatment of chronic osteoarthritis or low back pain over up to 2 years of treatment. (ClinicalTrials.gov identifier: NCT00487435.). Copyright © 2015. Published by Elsevier Inc.

  18. Recovery and reproduction of an Antarctic tardigrade retrieved from a moss sample frozen for over 30 years.

    PubMed

    Tsujimoto, Megumu; Imura, Satoshi; Kanda, Hiroshi

    2016-02-01

    Long-term survival has been one of the most studied of the extraordinary physiological characteristics of cryptobiosis in micrometazoans such as nematodes, tardigrades and rotifers. In the available studies of long-term survival of micrometazoans, instances of survival have been the primary observation, and recovery conditions of animals or subsequent reproduction are generally not reported. We therefore documented recovery conditions and reproduction immediately following revival of tardigrades retrieved from a frozen moss sample collected in Antarctica in 1983 and stored at -20 °C for 30.5 years. We recorded recovery of two individuals and development of a separate egg of the Antarctic tardigrade, Acutuncus antarcticus, providing the longest records of survival for tardigrades as animals or eggs. One of the two resuscitated individuals and the hatchling successfully reproduced repeatedly after their recovery from long-term cryptobiosis. This considerable extension of the known length of long-term survival of tardigrades recorded in our study is interpreted as being associated with the minimum oxidative damage likely to have resulted from storage under stable frozen conditions. The long recovery times of the revived tardigrades observed is suggestive of the requirement for repair of damage accrued over 30 years of cryptobiosis. Further more detailed studies will improve understanding of mechanisms and conditions underlying the long-term survival of cryptobiotic organisms. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  19. Global biodiversity monitoring: from data sources to essential biodiversity variables

    USGS Publications Warehouse

    Proenca, Vania; Martin, Laura J.; Pereira, Henrique M.; Fernandez, Miguel; McRae, Louise; Belnap, Jayne; Böhm, Monika; Brummitt, Neil; Garcia-Moreno, Jaime; Gregory, Richard D.; Honrado, Joao P; Jürgens, Norbert; Opige, Michael; Schmeller, Dirk S.; Tiago, Patricia; van Sway, Chris A

    2016-01-01

    Essential Biodiversity Variables (EBVs) consolidate information from varied biodiversity observation sources. Here we demonstrate the links between data sources, EBVs and indicators and discuss how different sources of biodiversity observations can be harnessed to inform EBVs. We classify sources of primary observations into four types: extensive and intensive monitoring schemes, ecological field studies and satellite remote sensing. We characterize their geographic, taxonomic and temporal coverage. Ecological field studies and intensive monitoring schemes inform a wide range of EBVs, but the former tend to deliver short-term data, while the geographic coverage of the latter is limited. In contrast, extensive monitoring schemes mostly inform the population abundance EBV, but deliver long-term data across an extensive network of sites. Satellite remote sensing is particularly suited to providing information on ecosystem function and structure EBVs. Biases behind data sources may affect the representativeness of global biodiversity datasets. To improve them, researchers must assess data sources and then develop strategies to compensate for identified gaps. We draw on the population abundance dataset informing the Living Planet Index (LPI) to illustrate the effects of data sources on EBV representativeness. We find that long-term monitoring schemes informing the LPI are still scarce outside of Europe and North America and that ecological field studies play a key role in covering that gap. Achieving representative EBV datasets will depend both on the ability to integrate available data, through data harmonization and modeling efforts, and on the establishment of new monitoring programs to address critical data gaps.

  20. Duration of anti-resorptive therapy for osteoporosis.

    PubMed

    Adler, Robert A

    2016-02-01

    Osteoporotic fractures are common, and available medications reduce fracture risk by up to half. However, because the most commonly used drugs, bisphosphonates, have side effects that may be related to duration of therapy and because long-term efficacy has not been established, the optimal length of treatment has not been determined. Based on two long-term studies and extensive clinical experience, a plan is provided to treat patients at risk for 5 years with re-assessment every 2 years thereafter. Assessment tools are limited, but for each individual, the potential risks and benefits of continuing, discontinuing, re-instituting, or changing therapy can be estimated.

  1. Long-term chemical carcinogenesis experiments for identifying potential human cancer hazards: collective database of the National Cancer Institute and National Toxicology Program (1976-1991).

    PubMed Central

    Huff, J; Haseman, J

    1991-01-01

    The carcinogenicity database used for this paper originated in the late 1960s by the National Cancer Institute (NCI) and since 1978 has been continued and made more comprehensive by the National Toxicology Program (NTP). The extensive files contain, among other sets of information, detailed pathology data on more than 400 long-term (most often 24-month) chemical carcinogenesis studies, comprising nearly 1600 individual experiments having at least 10 million tissue sections that have been evaluated for toxicity and carcinogenicity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1820269

  2. Maternity Leave and Mothers' Long-Term Sickness Absence: Evidence From West Germany.

    PubMed

    Guertzgen, Nicole; Hank, Karsten

    2018-04-01

    Exploiting unique German administrative data, we estimate the association between an expansion in maternity leave duration from two to six months in 1979 and mothers' postbirth long-term sickness absence over a period of three decades after childbirth. Adopting a difference-in-difference approach, we first assess the reform's labor market effects and, subsequently, prebirth and postbirth maternal long-term sickness absence, accounting for the potential role of the reform in mothers' selection into employment. Consistent with previous research, our estimates show that the leave extension caused mothers to significantly delay their return to work within the first year after childbirth. We then provide difference-in-difference estimates for the number and length of spells of long-term sickness absence among returned mothers. Our findings suggest that among those returned, mothers subject to the leave extension exhibit a higher incidence of long-term sickness absence compared with mothers who gave birth before the reform. This also holds true after we control for observable differences in prebirth illness histories. At the same time, we find no pronounced effects on mothers' medium-run labor market attachment following the short-run delay in return to work, which might rationalize a negative causal health effect. Breaking down the results by mothers' prebirth health status suggests that the higher incidence of long-term sickness absence among mothers subject to the reform may be explained by the fact that the reform facilitated the reentry of a negative health selection into the labor market.

  3. The role of elasticity in simulating long-term tectonic extension

    NASA Astrophysics Data System (ADS)

    Olive, Jean-Arthur; Behn, Mark D.; Mittelstaedt, Eric; Ito, Garrett; Klein, Benjamin Z.

    2016-05-01

    While elasticity is a defining characteristic of the Earth's lithosphere, it is often ignored in numerical models of long-term tectonic processes in favour of a simpler viscoplastic description. Here we assess the consequences of this assumption on a well-studied geodynamic problem: the growth of normal faults at an extensional plate boundary. We conduct 2-D numerical simulations of extension in elastoplastic and viscoplastic layers using a finite difference, particle-in-cell numerical approach. Our models simulate a range of faulted layer thicknesses and extension rates, allowing us to quantify the role of elasticity on three key observables: fault-induced topography, fault rotation, and fault life span. In agreement with earlier studies, simulations carried out in elastoplastic layers produce rate-independent lithospheric flexure accompanied by rapid fault rotation and an inverse relationship between fault life span and faulted layer thickness. By contrast, models carried out with a viscoplastic lithosphere produce results that may qualitatively resemble the elastoplastic case, but depend strongly on the product of extension rate and layer viscosity U × ηL. When this product is high, fault growth initially generates little deformation of the footwall and hanging wall blocks, resulting in unrealistic, rigid block-offset in topography across the fault. This configuration progressively transitions into a regime where topographic decay associated with flexure is fully accommodated within the numerical domain. In addition, high U × ηL favours the sequential growth of multiple short-offset faults as opposed to a large-offset detachment. We interpret these results by comparing them to an analytical model for the fault-induced flexure of a thin viscous plate. The key to understanding the viscoplastic model results lies in the rate-dependence of the flexural wavelength of a viscous plate, and the strain rate dependence of the force increase associated with footwall and hanging wall bending. This behaviour produces unrealistic deformation patterns that can hinder the geological relevance of long-term rifting models that assume a viscoplastic rheology.

  4. Long-Term Exercise in Older Adults: 4-Year Outcomes of Music-Based Multitask Training

    PubMed Central

    Herrmann, François R.; Fielding, Roger A.; Reid, Kieran F.; Rizzoli, René; Trombetti, Andrea

    2016-01-01

    Prospective controlled evidence supporting the efficacy of long-term exercise to prevent physical decline and reduce falls in old age is lacking. The present study aimed to assess the effects of long-term music-based multitask exercise (i.e., Jaques-Dalcroze eurhythmics) on physical function and fall risk in older adults. A 3-year follow-up extension of a 1-year randomized controlled trial (NCT01107288) was conducted in Geneva (Switzerland), in which 134 community-dwellers aged ≥65 years at increased risk of falls received a 6-month music-based multitask exercise program. Four years following original trial enrolment, 52 subjects (baseline mean ± SD age, 75 ± 8 years) who (i) have maintained exercise program participation through the 4-year follow-up visit (“long-term intervention group”, n = 23) or (ii) have discontinued participation following original trial completion (“control group”, n = 29) were studied. They were reassessed in a blind fashion, using the same procedures as at baseline. At 4 years, linear mixed-effects models showed significant gait (gait speed, P = 0.006) and balance (one-legged stance time, P = 0.015) improvements in the long-term intervention group, compared with the control group. Also, long-term intervention subjects did better on Timed Up & Go, Five-Times-Sit-to-Stand and handgrip strength tests, than controls (P < 0.05, for all comparisons). Furthermore, the exercise program reduced the risk of falling (relative risk, 0.69; 95 % confidence interval, 0.5–0.9; P = 0.008). These findings suggest that long-term maintenance of a music-based multitask exercise program is a promising strategy to prevent age-related physical decline in older adults. They also highlight the efficacy of sustained long-term adherence to exercise for falls prevention. PMID:25148876

  5. Assessing the Long-Term Impacts of Water Quality Outreach and Education Efforts on Agricultural Landowners

    ERIC Educational Resources Information Center

    Jackson-Smith, Douglas B.; McEvoy, Jamie P.

    2011-01-01

    We assess the long-term effectiveness of outreach and education efforts associated with a water quality improvement project in a watershed located in northern Utah, USA. Conducted 15 years after the original project began, our research examines the lasting impacts of different extension activities on landowners' motivations to participate and…

  6. Tofacitinib, an oral Janus kinase inhibitor, as monotherapy or with background methotrexate, in Japanese patients with rheumatoid arthritis: an open-label, long-term extension study.

    PubMed

    Yamanaka, Hisashi; Tanaka, Yoshiya; Takeuchi, Tsutomu; Sugiyama, Naonobu; Yuasa, Hirotoshi; Toyoizumi, Shigeyuki; Morishima, Yosuke; Hirose, Tomohiro; Zwillich, Samuel

    2016-01-28

    Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis. Here, tofacitinib safety and efficacy data from a long-term extension study in Japanese patients are presented. Study A3921041 was a multi-centre, open-label, long-term extension study that included Japanese patients who had participated in a prior Phase 2 or Phase 3 study of tofacitinib as monotherapy or with background methotrexate. Patients received tofacitinib 5 mg twice daily (BID) or tofacitinib 10 mg BID. Dose adjustment of tofacitinib during treatment period, and concomitant usage of disease-modifying antirheumatic drugs including methotrexate after week 12 were permitted. Primary endpoints were adverse events, laboratory parameters and vital signs. Secondary efficacy endpoints included American College of Rheumatology (ACR)20/50/70 response rates, Disease Activity Score (DAS)28-4(erythrocyte sedimentation rate (ESR))<2.6 response rate (DAS-defined remission) and Health Assessment Questionnaire-Disability Index (HAQ-DI) score. Safety and efficacy data were assessed throughout the study. A total of 486 patients were recruited and treated (1439.9 patient-years of exposure). 308 patients completed the study. Median (range) duration of treatment in this extension study was 1185 (5-2016) days. 476 patients (97.9 %) experienced adverse events; the majority of which (97.8 %) were of mild or moderate severity. The two most common treatment-emergent adverse events were nasopharyngitis (n = 293, 60.3 %) and herpes zoster (n = 94, 19.3 %). For all tofacitinib-treated patients, the incidence rate (patients with events per 100 patient-years) was 10.7 for serious adverse events, 3.3 for serious infections, 7.4 for herpes zoster (serious and non-serious) and 1.2 for malignancies (excluding non-melanoma skin cancer). Mean changes from baseline (start of the index study) in laboratory parameters were consistent with those seen in previously reported studies of tofacitinib. ACR20/50/70 response rates, DAS-defined remission rates and HAQ-DI scores were sustained through to study completion. Tofacitinib (with or without background methotrexate) demonstrated a stable safety profile and sustained efficacy in Japanese patients with active rheumatoid arthritis. The risk of herpes zoster appears to be higher in Japanese patients treated with tofacitinib than in the global population. Clinicaltrials.gov NCT00661661 . Registered 7 February 2008.

  7. Relationship between Defenses, Personality, and Affect during a Stress Task in Normal Adolescents

    ERIC Educational Resources Information Center

    Steiner, Hans; Erickson, Sarah J.; MacLean, Peggy; Medic, Sanja; Plattner, Belinda; Koopman, Cheryl

    2007-01-01

    Objective: Although there are extensive data on the relationship between personality and stress reactivity in adults, there is little comparable empirical research with adolescents. This study examines the simultaneous relationships between long term functioning (personality, defenses) and observed stress reactivity (affect) in adolescents.…

  8. Fragile X Syndrome: An Aging Perspective

    ERIC Educational Resources Information Center

    Schneider, Andrea; Ligsay, Andrew; Hagerman, Randi J.

    2013-01-01

    Cognitive and behavioral correlates of molecular variations related to the FMR1 gene have been studied rather extensively, but research about the long-term outcome in individuals with fragile X spectrum disorders remains sparse. In this review, we present an overview of aging research and recent findings in regard to cellular and clinical…

  9. An Open-label Extension Study to Assess the Long-term Safety and Efficacy of ISIS 301012 (Mipomersen) in Patients With Familial Hypercholesterolemia or Severe-Hypercholesterolemia

    ClinicalTrials.gov

    2016-08-01

    Lipid Metabolism, Inborn Errors; Hypercholesterolemia, Autosomal Dominant; Hyperlipidemias; Metabolic Diseases; Hyperlipoproteinemia Type II; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Infant, Newborn, Diseases; Metabolic Disorder; Congenital Abnormalities; Hypercholesterolemia; Hyperlipoproteinemias; Dyslipidemias; Lipid Metabolism Disorders

  10. Video traffic characteristics of modern encoding standards: H.264/AVC with SVC and MVC extensions and H.265/HEVC.

    PubMed

    Seeling, Patrick; Reisslein, Martin

    2014-01-01

    Video encoding for multimedia services over communication networks has significantly advanced in recent years with the development of the highly efficient and flexible H.264/AVC video coding standard and its SVC extension. The emerging H.265/HEVC video coding standard as well as 3D video coding further advance video coding for multimedia communications. This paper first gives an overview of these new video coding standards and then examines their implications for multimedia communications by studying the traffic characteristics of long videos encoded with the new coding standards. We review video coding advances from MPEG-2 and MPEG-4 Part 2 to H.264/AVC and its SVC and MVC extensions as well as H.265/HEVC. For single-layer (nonscalable) video, we compare H.265/HEVC and H.264/AVC in terms of video traffic and statistical multiplexing characteristics. Our study is the first to examine the H.265/HEVC traffic variability for long videos. We also illustrate the video traffic characteristics and statistical multiplexing of scalable video encoded with the SVC extension of H.264/AVC as well as 3D video encoded with the MVC extension of H.264/AVC.

  11. Video Traffic Characteristics of Modern Encoding Standards: H.264/AVC with SVC and MVC Extensions and H.265/HEVC

    PubMed Central

    2014-01-01

    Video encoding for multimedia services over communication networks has significantly advanced in recent years with the development of the highly efficient and flexible H.264/AVC video coding standard and its SVC extension. The emerging H.265/HEVC video coding standard as well as 3D video coding further advance video coding for multimedia communications. This paper first gives an overview of these new video coding standards and then examines their implications for multimedia communications by studying the traffic characteristics of long videos encoded with the new coding standards. We review video coding advances from MPEG-2 and MPEG-4 Part 2 to H.264/AVC and its SVC and MVC extensions as well as H.265/HEVC. For single-layer (nonscalable) video, we compare H.265/HEVC and H.264/AVC in terms of video traffic and statistical multiplexing characteristics. Our study is the first to examine the H.265/HEVC traffic variability for long videos. We also illustrate the video traffic characteristics and statistical multiplexing of scalable video encoded with the SVC extension of H.264/AVC as well as 3D video encoded with the MVC extension of H.264/AVC. PMID:24701145

  12. Nature's Notebook and Extension: Engaging Citizen-Scientists and 4-H Youth to Observe a Changing Environment

    ERIC Educational Resources Information Center

    Posthumus, Erin E.; Barnett, LoriAnne; Crimmins, Theresa M.; Kish, George R.; Sheftall, Will; Stancioff, Esperanza; Warren, Peter

    2013-01-01

    Extension, with its access to long-term volunteers, has the unique ability to teach citizen scientists about the connection between climate variability and the resulting effects on plants, animals, and thus, humans. The USA National Phenology Network's Nature's Notebook on-line program provides a science learning tool for Extension's Master…

  13. Self-concept and quality of object relations as predictors of outcome in short- and long-term psychotherapy.

    PubMed

    Lindfors, Olavi; Knekt, Paul; Heinonen, Erkki; Virtala, Esa

    2014-01-01

    Quality of object relations and self-concept reflect clinically relevant aspects of personality functioning, but their prediction as suitability factors for psychotherapies of different lengths has not been compared. This study compared their prediction on psychiatric symptoms and work ability in short- and long-term psychotherapy. Altogether 326 patients, 20-46 years of age, with mood and/or anxiety disorder, were randomized to short-term (solution-focused or short-term psychodynamic) psychotherapy and long-term psychodynamic psychotherapy. The Quality of Object Relations Scale (QORS) and the Structural Analysis of Social Behavior (SASB) self-concept questionnaire were measured at baseline, and their prediction on outcome during the 3-year follow-up was assessed by the Symptom Check List Global Severity Index and the Anxiety Scale, the Beck Depression Inventory and by the Work Ability Index, Social Adjustment Scale work subscale and the Perceived Psychological Functioning scale. Negative self-concept strongly and self-controlling characteristics modestly predicted better 3-year outcomes in long-term therapy, after faster early gains in short-term therapy. Patients with a more positive or self-emancipating self-concept, or more mature object relations, experienced more extensive benefits after long-term psychotherapy. The importance of length vs. long-term therapy technique on the differences found is not known. Patients with mild to moderate personality pathology, indicated by poor self-concept, seem to benefit more from long-term than short-term psychotherapy, in reducing risk of depression. Long-term therapy may also be indicated for patients with relatively good psychological functioning. More research is needed on the relative importance of these characteristics in comparison with other patient-related factors. © 2013 Published by Elsevier B.V.

  14. Maternal Behavior Modifications during Pretense and Their Long-Term Effects on Toddlers' Understanding of Pretense

    ERIC Educational Resources Information Center

    Nakamichi, Naoko

    2015-01-01

    Recent studies indicate the need to investigate the sources of toddlers' understanding of another person's pretense. The present study is a cultural and longitudinal extension of the work of Lillard and Witherington (2004), who claimed that mothers modify their behaviors during pretense and that the some of these behavior modifications help their…

  15. Neurosciences research in space - Future directions

    NASA Technical Reports Server (NTRS)

    Sulzman, Frank M.; Wolfe, James W.

    1991-01-01

    In order to gain a better understanding of the effects of long-duration space missions on the central nervous system, near-term research, to take place from 1990-1995, will be directed at investigating the acute effects of microgravity and the 'space adaptation syndrome'. These include experiments scheduled for the Spacelab Life Sciences 1 which is designed to evaluate changes in the visual, vestibular, and proprioceptive systems. An extensive series of experiments, collectively termed Microgravity Vestibular Investigations (MVI), is also planned for the IML-1 mission to be flown in 1992. The IML-2 mission will emphasize behavior and performance, biological rhythms, and further vestibular studies. Mid-term goals, projected to be achieved from 1995-2000, include the use of new technology such as magnetic recording techniques. Long-term goals are also discussed including studies dealing with neuronal plasticity and sensory substitution, augmentation, and robotic telepresence.

  16. Evidence of Non-extensivity in Earth's Ambient Noise

    NASA Astrophysics Data System (ADS)

    Koutalonis, Ioannis; Vallianatos, Filippos

    2017-12-01

    The study of ambient seismic noise is one of the important scientific and practical research challenges, due to its use in a number of geophysical applications. In this work, we describe Earth's ambient noise fluctuations in terms of non-extensive statistical physics. We found that Earth's ambient noise increments follow the q-Gaussian distribution. This indicates that Earth's ambient noise's fluctuations are not random and present long-term memory effects that could be described in terms of Tsallis entropy. Our results suggest that q values depend on the time length used and that the non-extensive parameter, q, converges to value q → 1 for short-time windows and a saturation value of q ≈ 1.33 for longer ones. The results are discussed from the point of view of superstatistics introduced by Beck [Contin Mech Thermodyn 16(3):293-304, 2004] and connects the q values with the system's degrees of freedom. Our work indicates that the converged (maximum) value is q = 1.33 and is related to 5 degrees of freedom.

  17. Long-Term Memory for Place Learning Is Facilitated by Expression of cAMP Response Element-Binding Protein in the Dorsal Hippocampus

    ERIC Educational Resources Information Center

    Brightwell, Jennifer J.; Smith, Clayton A.; Neve, Rachael L.; Colombo, Paul J.

    2007-01-01

    Extensive research has shown that the hippocampus is necessary for consolidation of long-term spatial memory in rodents. We reported previously that rats using a place strategy to solve a cross maze task showed sustained phosphorylation of hippocampus cyclic AMP response element-binding protein (CREB), a transcription factor implicated in…

  18. Long-term soil accumulation of chromium, copper, and arsenic adjacent to preservative-treated wood.

    Treesearch

    S. Lebow; D. Foster; J. Evans

    2004-01-01

    Chromated copper arsenate (CCA) treated wood has been used extensively in outdoor applications. The Environmental Protection Agency (EPA) and CCA producers recently reached an agreement to limit future use of CCA for some types of applications. One area of concern is the long-term accumulation of leached CCA in soil adjacent to treated wood structures. Interpreting...

  19. An open-label study to evaluate the long-term safety and efficacy of lanadelumab for prevention of attacks in hereditary angioedema: design of the HELP study extension.

    PubMed

    Riedl, Marc A; Bernstein, Jonathan A; Craig, Timothy; Banerji, Aleena; Magerl, Markus; Cicardi, Marco; Longhurst, Hilary J; Shennak, Mustafa M; Yang, William H; Schranz, Jennifer; Baptista, Jovanna; Busse, Paula J

    2017-01-01

    Hereditary angioedema (HAE) is characterized by recurrent attacks of subcutaneous or submucosal edema. Attacks are unpredictable, debilitating, and have a significant impact on quality of life. Patients may be prescribed prophylactic therapy to prevent angioedema attacks. Current prophylactic treatments may be difficult to administer (i.e., intravenously), require frequent administrations or are not well tolerated, and breakthrough attacks may still occur frequently. Lanadelumab is a subcutaneously-administered monoclonal antibody inhibitor of plasma kallikrein in clinical development for prophylaxis of hereditary angioedema attacks. A Phase 1b study supported its efficacy in preventing attacks. A Phase 3, randomized, double-blind, placebo-controlled, parallel-arm study has been completed and an open-label extension is currently ongoing. The primary objective of the open-label extension is to evaluate the long-term safety of repeated subcutaneous administrations of lanadelumab in patients with type I/II HAE. Secondary objectives include evaluation of efficacy and time to first angioedema attack to determine outer bounds of the dosing interval. The study will also evaluate immunogenicity, pharmacokinetics/pharmacodynamics, quality of life, characteristics of breakthrough attacks, ease of self-administration, and safety/efficacy in patients who switch to lanadelumab from another prophylactic therapy. The open-label extension will enroll patients who completed the double-blind study ("rollover patients") and those who did not participate in the double-blind study ("non-rollover patients"), which includes patients who may or may not be currently using another prophylactic therapy. Rollover patients will receive a single 300 mg dose of lanadelumab on Day 0 and the second dose after the patient's first confirmed angioedema attack. Thereafter, lanadelumab will be administered every 2 weeks. Non-rollover patients will receive 300 mg lanadelumab every 2 weeks regardless of the first attack. All patients will receive their last dose on Day 350 (maximum of 26 doses), and will then undergo a 4-week follow-up. Prevention of attacks can reduce the burden of illness associated with HAE. Prophylactic therapy requires extended, repeated dosing and the results of this study will provide important data on the long-term safety and efficacy of lanadelumab, a monoclonal antibody inhibitor of plasma kallikrein for subcutaneous administration for the treatment of HAE. Trial registration NCT02741596.

  20. Long term benefits of stabilizing soil subgrades

    DOT National Transportation Integrated Search

    2002-06-01

    Chemical admixtures have been used extensively since the mid-eighties in Kentucky to improve bearing strengths of soil subgrades. Most pavements in Kentucky are constructed on clayey soils. Although short-term observations at a small number of sites ...

  1. Long-term Outcomes of Mitral Valve Repair Versus Replacement for Degenerative Disease: A Systematic Review

    PubMed Central

    McNeely, Christian A; Vassileva, Christina M

    2015-01-01

    The short-term advantage of mitral valve repair versus replacement for degenerative disease has been extensively documented. These advantages include lower operative mortality, improved survival, better preservation of left-ventricular function, shorter post-operative hospital stay, lower total costs, and fewer valve-related complications, including thromboembolism, anticoagulation-related bleeding events and late prosthetic dysfunction. More recent written data are available indicating the long-term advantage of repair versus replacement. While at some institutions, the repair rate for degenerative disease may exceed 90%, the national average in 2007 was only 69%. Making direct comparisons between mitral valve repair and replacement using the available studies does present some challenges however, as there are often differences in baseline characteristics between patient groups as well as other dissimilarities between studies. The purpose of this review is to systematically summarize the long-term survival and reoperation data of mitral valve repair versus replacement for degenerative disease. A PubMed search was done and resulted in 12 studies that met our study criteria for comparing mitral valve repair versus replacement for degenerative disease. A systematic review was then conducted abstracting survival and reoperation data. PMID:25158683

  2. Clinicopathologic characteristics associated with long-term survival in advanced epithelial ovarian cancer: an NRG Oncology/Gynecologic Oncology Group ancillary data study.

    PubMed

    Hamilton, C A; Miller, A; Casablanca, Y; Horowitz, N S; Rungruang, B; Krivak, T C; Richard, S D; Rodriguez, N; Birrer, M J; Backes, F J; Geller, M A; Quinn, M; Goodheart, M J; Mutch, D G; Kavanagh, J J; Maxwell, G L; Bookman, M A

    2018-02-01

    To identify clinicopathologic factors associated with 10-year overall survival in epithelial ovarian cancer (EOC) and primary peritoneal cancer (PPC), and to develop a predictive model identifying long-term survivors. Demographic, surgical, and clinicopathologic data were abstracted from GOG 182 records. The association between clinical variables and long-term survival (LTS) (>10years) was assessed using multivariable regression analysis. Bootstrap methods were used to develop predictive models from known prognostic clinical factors and predictive accuracy was quantified using optimism-adjusted area under the receiver operating characteristic curve (AUC). The analysis dataset included 3010 evaluable patients, of whom 195 survived greater than ten years. These patients were more likely to have better performance status, endometrioid histology, stage III (rather than stage IV) disease, absence of ascites, less extensive preoperative disease distribution, microscopic disease residual following cyoreduction (R0), and decreased complexity of surgery (p<0.01). Multivariable regression analysis revealed that lower CA-125 levels, absence of ascites, stage, and R0 were significant independent predictors of LTS. A predictive model created using these variables had an AUC=0.729, which outperformed any of the individual predictors. The absence of ascites, a low CA-125, stage, and R0 at the time of cytoreduction are factors associated with LTS when controlling for other confounders. An extensively annotated clinicopathologic prediction model for LTS fell short of clinical utility suggesting that prognostic molecular profiles are needed to better predict which patients are likely to be long-term survivors. Published by Elsevier Inc.

  3. Clinicopathologic characteristics associated with long-term survival in advanced epithelial ovarian cancer: an NRG Oncology/Gynecologic Oncology Group ancillary data study

    PubMed Central

    Hamilton, C. A.; Miller, A.; Casablanca, Y.; Horowitz, N. S.; Rungruang, B.; Krivak, T. C.; Richard, S. D.; Rodriguez, N.; Birrer, M.J.; Backes, F.J.; Geller, M.A.; Quinn, M.; Goodheart, M.J.; Mutch, D.G.; Kavanagh, J.J.; Maxwell, G. L.; Bookman, M. A.

    2018-01-01

    Objective To identify clinicopathologic factors associated with 10-year overall survival in epithelial ovarian cancer (EOC) and primary peritoneal cancer (PPC), and to develop a predictive model identifying long-term survivors. Methods Demographic, surgical, and clinicopathologic data were abstracted from GOG 182 records. The association between clinical variables and long-term survival (LTS) (>10 years) was assessed using multivariable regression analysis. Bootstrap methods were used to develop predictive models from known prognostic clinical factors and predictive accuracy was quantified using optimism-adjusted area under the receiver operating characteristic curve (AUC). Results The analysis dataset included 3,010 evaluable patients, of whom 195 survived greater than ten years. These patients were more likely to have better performance status, endometrioid histology, stage III (rather than stage IV) disease, absence of ascites, less extensive preoperative disease distribution, microscopic disease residual following cyoreduction (R0), and decreased complexity of surgery (p<0.01). Multivariable regression analysis revealed that lower CA-125 levels, absence of ascites, stage, and R0 were significant independent predictors of LTS. A predictive model created using these variables had an AUC=0.729, which outperformed any of the individual predictors. Conclusions The absence of ascites, a low CA-125, stage, and R0 at the time of cytoreduction are factors associated with LTS when controlling for other confounders. An extensively annotated clinicopathologic prediction model for LTS fell short of clinical utility suggesting that prognostic molecular profiles are needed to better predict which patients are likely to be long-term survivors. PMID:29195926

  4. Evaluation of the Dawson College Shooting Psychological Intervention: Moving Toward a Multimodal Extensive Plan

    PubMed Central

    Séguin, Monique; Chawky, Nadia; Lesage, Alain; Boyer, Richard; Guay, Stéphane; Bleau, Pierre; Miquelon, Paule; Szkrumelak, Nadia; Steiner, Warren; Roy, Denise

    2013-01-01

    In 2006, following the shooting at Dawson College, the authorities implemented an intervention plan. This provided an opportunity to analyze the responses to services offered, and afforded a learning opportunity, which led to the proposal of an extensive multimodal short- and long-term psychological plan for future needs. Both quantitative and qualitative data were gathered 18 months after the event, involving the participation of 948 students and staff. Mental health problems and the perception of services offered after the shooting were investigated, using standardized measures. Second, focus groups and individual interviews were conducted among a subgroup of participants (support team members; teachers and employees; students and parents) and permitted to gather data on services received and services required. Individual report of events, the extent of psychological impact and services offered and received were analyzed in terms of the following dimensions: intervention philosophy, training, ongoing offer of services and finally, detection and outreach. A significant incidence of disorders and a high rate of exacerbation of preexisting mental disorders were observed within the 18 months following the shooting. Postimmediate and short-term intervention appeared adequate, but the long-term collective vision toward community support and availability of mental health services were lacking. Lessons learned from this evaluation and other school shootings suggest that preparedness and long-term community responses are often overlooked. A multimodal extensive plan is proposed based on a theoretical model from which interventions strategies could be drawn. PMID:24795790

  5. Marital history, health and mortality among older men and women in England and Wales.

    PubMed

    Grundy, Emily M D; Tomassini, Cecilia

    2010-09-15

    Health benefits of marriage have long been recognised and extensively studied but previous research has yielded inconsistent results for older people, particularly older women. At older ages accumulated benefits or disadvantages of past marital experience, as well as current marital status, may be relevant, but fewer studies have considered effects of marital history. Possible effects of parity, and the extent to which these may contribute to marital status differentials in health, have also been rarely considered. We use data from the Office for National Statistics Longitudinal Study, a large record linkage study of 1% of the population of England & Wales, to analyse associations between marital history 1971-1991 and subsequent self-reported limiting long-term illness and mortality in a cohort of some 75,000 men and women aged 60-79 in 1991. We investigate whether prior marital status and time in current marital status influenced risks of mortality or long term illness using Poisson regression to analyse mortality differentials 1991-2001 and logistic regression to analyse differences in proportions reporting limiting long-term illness in 1991 and 2001. Co-variates included indicators of socio-economic status at two or three points of the adult life course and, for women, number of children borne (parity). Relative to men in long-term first marriages, never-married men, widowers with varying durations of widowerhood, men divorced for between 10 and twenty years, and men in long-term remarriages had raised mortality 1991-2001. Men in long-term remarriages and those divorced or widowed since 1971 had higher odds of long-term illness in 1991; in 2001 the long-term remarried were the only group with significantly raised odds of long-term illness. Among women, the long-term remarried also had higher odds of reporting long-term illness in 1991 and in 2001 and those remarried and previously divorced had raised odds of long-term illness and raised mortality 1991-2001; this latter effect was not significant in models including parity. All widows had raised mortality 1991-2001 but associations between widowhood of varying durations and long-term illness in 1991 or 2001 were not significant once socio-economic status was controlled. Some groups of divorced women had higher mortality risks 1991-2001 and raised odds of long-term illness in 1991. Results for never-married women showed a divergence between associations with mortality and with long-term illness. In models controlling for socio-economic status, mortality risk was raised but the association with 1991 long-term illness was not significant and in 2001 never-married women had lower odds of reporting long-term illness than women in long-term first marriages. Formally taking account of selective survival in the 20 years prior to entry to the study population had minor effects on results. Results were consistent with previous studies in showing that the relationship between marital experience and later life health and mortality is considerably modified by socio-economic factors, and additionally showed that taking women's parity into account further moderated associations. Considering marital history rather than simply current marital status provided some insights into differentials between, for example, remarried people according to prior marital status and time remarried, but these groups were relatively small and there were some disadvantages of the approach in terms of loss of statistical power. Consideration of past histories is likely to be more important for later born cohorts whose partnership experiences have been less stable and more heterogeneous.

  6. [Research progress of larger flexion gap than extension gap in total knee arthroplasty].

    PubMed

    Zhang, Weisong; Hao, Dingjun

    2017-05-01

    To summarize the progress of larger flexion gap than extension gap in total knee arthro-plasty (TKA). The domestic and foreign related literature about larger flexion gap than extension gap in TKA, and its impact factors, biomechanical and kinematic features, and clinical results were summarized. During TKA, to adjust the relations of flexion gap and extension gap is one of the key factors of successful operation. The biomechanical, kinematic, and clinical researches show that properly larger flexion gap than extension gap can improve both the postoperative knee range of motion and the satisfaction of patients, but does not affect the stability of the knee joint. However, there are also contrary findings. So adjustment of flexion gap and extension gap during TKA is still in dispute. Larger flexion gap than extension gap in TKA is a new joint space theory, and long-term clinical efficacy, operation skills, and related complications still need further study.

  7. The full metallic double-pigtail ureteral stent: Review of the clinical outcome and current status

    PubMed Central

    Kallidonis, Panagiotis S.; Georgiopoulos, Ioannis S.; Kyriazis, Iason D.; Kontogiannis, Stavros; Al-Aown, Abdulrahman M.; Liatsikos, Evangelos N.

    2015-01-01

    The full metallic double-J ureteral stent (MS) was introduced as a method for providing long-term drainage in malignant ureteral obstruction. Experimental evaluation of the MS revealed that its mechanical features allow efficient drainage in difficult cases, which could not be managed by the insertion of a standard polymeric double-J stent. Clinical experience with the MS showed controversial results. Careful patient selection results in efficient long-term management of malignant ureteral obstruction. The use of the MS should also be considered in selected benign cases. Major complications are uncommon and the minor complications should not hinder its use. Experience in pediatric patients is limited and warrants additional study. The cost-effectiveness of the MS seems to be appropriate for long-term treatment. Further investigation with comparative clinical trials would document the outcome more extensively and establish the indications as well as the selection criteria for the MS. PMID:25624569

  8. Long-term efficacy of rasagiline in early Parkinson's disease.

    PubMed

    Lew, Mark F; Hauser, Robert A; Hurtig, Howard I; Ondo, William G; Wojcieszek, Joanne; Goren, Tamar; Fitzer-Attas, Cheryl J

    2010-06-01

    This study was designed to follow the long-term efficacy, safety, and tolerability of rasagiline for Parkinson's disease (PD) with data collected from all patients who had ever taken rasagiline during the 12-month TEMPO monotherapy trial (N = 398) and subsequent open-label extension. Patients were followed for up to 6.5 years with a mean of 3.5 +/- 2.1 years. After 12 months, additional PD medications were added as required. Of patients remaining in the trial at 2 years, 46% were maintained on rasagiline monotherapy. The majority of patients received a dopamine agonist prior to levodopa as the first additional dopaminergic agent. Analysis using a Kaplan-Meier method indicated that by 5.4 years only 25% of patients progressed to Hoehn & Yahr stage III. Rasagiline was well tolerated, with 11.3% of patients (45/398) withdrawing because of an adverse event. Rasagiline therapy for PD was effective, well tolerated, and safe in this long-term trial.

  9. Delayed Consequences of Acute Kidney Injury

    PubMed Central

    Parr, Sharidan K; Siew, Edward D

    2016-01-01

    Acute kidney injury (AKI) is an increasingly common complication of hospitalization and acute illness. Experimental data indicate that AKI may cause permanent kidney damage through tubulointerstitial fibrosis and progressive nephron loss, while also lowering the threshold for subsequent injury. Furthermore, preclinical data suggest that AKI may also cause distant organ dysfunction. The extension of these findings to human studies suggests long-term consequences of AKI including, but not limited to recurrent AKI, progressive kidney disease, elevated blood pressure, cardiovascular events, and mortality. As the number of AKI survivors increases, the need to better understand the mechanisms driving these processes becomes paramount. Optimizing care for AKI survivors will require understanding the short- and long-term risks associated with AKI, identifying patients at highest risk for poor outcomes, and testing interventions that target modifiable risk factors. In this review, we examine the literature describing the association between AKI and long-term outcomes and highlight opportunities for further research and potential intervention. PMID:27113695

  10. The long-term demographic role of community-based family planning in rural Bangladesh.

    PubMed

    Phillips, J F; Hossain, M B; Arends-Kuenning, M

    1996-01-01

    Experimental studies demonstrating the effectiveness of nonclinical distribution of contraceptives are typically conducted in settings where contraceptive use is low and unmet need is extensive. Determining the long-term role of active outreach programs after initial demand is met represents an increasingly important policy issue in Asia, where contraceptive prevalence is high and fixed service points are conveniently available. This article examines the long-term rationale for household family planning in Bangladesh-where growing use of contraceptives, rapid fertility decline, and normative change in reproductive preferences are in progress, bringing into question the rationale for large-scale deployment of paid outreach workers. Longitudinal data are analyzed that record outreach encounters and contraceptive use dynamics in a large rural population. Findings demonstrate that outreach has a continuing impact on program effectiveness, even after a decade of household visitation. The policy implications of this finding are reviewed.

  11. Histone Deacetylase Inhibition Induces Odor Preference Memory Extension and Maintains Enhanced AMPA Receptor Expression in the Rat Pup Model

    ERIC Educational Resources Information Center

    Bhattacharya, Sriya; Mukherjee, Bandhan; Doré, Jules J. E.; Yuan, Qi; Harley, Carolyn W.; McLean, John H.

    2017-01-01

    Histone deacetylase (HDAC) plays a role in synaptic plasticity and long-term memory formation. We hypothesized that trichostatin-A (TSA), an HDAC inhibitor, would promote long-term odor preference memory and maintain enhanced GluA1 receptor levels that have been hypothesized to support memory. We used an early odor preference learning model in…

  12. Long-term nitrogen dynamics of Coweeta forested watersheds in the southeastern United States of America

    Treesearch

    Wayne T. Swank; James M. Vose

    2001-01-01

    We analyzed long-term (23 years) data of inorganic N deposition and loss for an extensive network of mature mixed hardwood covered watersheds in the southern Appalachians of North Carolina to assess trends and dynamics of N in baseline ecosystems. We also assessed watershed N saturation in the context of altered N cycles and stream inorganic N responses associated with...

  13. Implications of prognostic factors and risk groups in the management of differentiated thyroid cancer.

    PubMed

    Shaha, Ashok R

    2004-03-01

    The outcome in differentiated thyroid cancer generally depends on the stage of the disease at the time of presentation; prognostic factors such as age, grade, size, extension, or distant metastasis; and risk groups (eg, low or high risk). The author has reviewed a large number of patients with differentiated thyroid cancer to analyze their hypothesis and to confirm that various risk groups have a major implication in relation to extent of the treatment and outcome. Differentiated thyroid cancers make up 90% of all thyroid tumors. The prognostic factors are well defined, such as age, size of the tumor, extrathyroidal extension, presence of distant metastasis, histological appearance, and grade of the tumor. The author has previously divided the risk groups into low-, intermediate-, and high-risk categories based on prognostic factors. The study describes the author's treatment approach related to the extent of thyroidectomy and adjuvant therapy based on various risk groups and the long-term survival. Retrospective. In a retrospective review of 1038 patients with differentiated thyroid carcinoma, various prognostic factors were studied by univariate and multivariate analysis. The significant prognostic factors were studied in detail and, based on these prognostic factors, the patients were divided into low-, intermediate- and high-risk groups. The survival curves were plotted by Kaplan-Meier method. The long-term survivals in low-, intermediate- and high-risk groups were 99%, 87%, and 57% respectively. Based on these risk groups, a decision tree was made regarding extent of thyroidectomy and adjuvant treatment. In the high-risk group and selected patients in the intermediate-risk group, aggressive surgery including removal of all gross disease and extrathyroidal extension with postoperative radioactive iodine ablation is recommended. In the low-risk group and selected patients in the intermediate-risk group, lobectomy appears to be satisfactory with excellent long-term outcome. The surgical treatment offers the best long-term results in low-risk patients, and the role of adjuvant treatment in this group is questionable. The decisions in the management of well-differentiated thyroid cancer should be based on various prognostic factors and risk groups. The long-term survival in the low-risk group is excellent, and consideration should be given to conservative surgical resection depending on the extent of the disease. In the high-risk group and selected patients in the intermediate-risk group, total thyroidectomy with radioactive ablation is warranted. A consideration may be given to external-beam radiation therapy in selected high-risk patients. It is apparent, based on the author's clinical experience and critical retrospective analysis, that the author's hypothesis that risk groups are extremely important in the long-term outcome of patients with differentiated thyroid cancer is correct. Based on various risk groups, the author currently is able to guide the treatment policies for thyroid cancer.

  14. GH treatment to final height produces similar height gains in patients with SHOX deficiency and Turner syndrome: results of a multicenter trial.

    PubMed

    Blum, Werner F; Ross, Judith L; Zimmermann, Alan G; Quigley, Charmian A; Child, Christopher J; Kalifa, Gabriel; Deal, Cheri; Drop, Stenvert L S; Rappold, Gudrun; Cutler, Gordon B

    2013-08-01

    Growth impairment in short stature homeobox-containing gene (SHOX) deficiency and Turner syndrome share a similar etiology. Because of the established effect of GH treatment on height in patients with Turner syndrome, we hypothesized that GH therapy would also stimulate growth in patients with SHOX deficiency. Our objectives were to evaluate long-term efficacy of GH treatment in short patients with SHOX deficiency and to compare the effect on final (adult) height (FH) in patients with SHOX deficiency and Turner syndrome. A prospective, multinational, open-label, randomized 3-arm study consisting of a 2-year control period and a subsequent extension period to FH. The treatment groups were 1) SHOX-D-C/GH (untreated during the control period, GH-treated during the extension), 2) SHOX-D-GH/GH, and 3) Turner-GH/GH (GH-treated during both study periods). Short-statured prepubertal patients with genetically confirmed SHOX deficiency (n = 49) or Turner syndrome (n = 24) who participated in the extension. Depending on the study arm, patients received a daily sc injection of 0.05 mg/kg recombinant human GH from start of the study or start of the extension until attainment of FH or study closure. Height SD score gain from start of GH treatment to FH was similar between the combined SHOX-deficient groups (n = 28, 1.34 ± 0.18 [least-squares mean ± SE]) and the Turner group (n = 19, 1.32 ± 0.22). In this FH population, 57% of the patients with SHOX deficiency and 32% of the patients with Turner syndrome achieved a FH greater than -2 SD score. GH treatment in short children with SHOX deficiency showed similar long-term efficacy as seen in girls with Turner syndrome.

  15. Two-Year Safety and Efficacy Experience in Patients with Methotrexate-Resistant Active Rheumatoid Arthritis Treated with Etanercept and Conventional Disease-Modifying Anti-rheumatic Drugs in the Latin American Region.

    PubMed

    Machado, Daniel A; Guzman, Renato; Xavier, Ricardo M; Simon, Jesus A; Mele, Linda; Shen, Qi; Pedersen, Ronald; Kotak, Sameer; Vlahos, Bonnie

    2016-01-01

    Although long-term data are available from biologic studies in North American/European populations with rheumatoid arthritis (RA), long-term findings in Latin American RA populations are limited. To examine long-term safety/efficacy of etanercept, methotrexate, and/or other disease-modifying anti-rheumatic drugs (DMARDs) in Latin American patients with moderate-to-severe active RA. In the first phase of this open-label study, patients were randomized to etanercept 50 mg weekly plus methotrexate or conventional DMARD (hydroxychloroquine or sulfasalazine) plus methotrexate for 24 weeks. At the start of the second phase (week 24), investigators selected a treatment regimen that included any combination/dosage of etanercept, methotrexate, hydroxychloroquine, or sulfasalazine based on previous treatment response, preference, and local product labeling, and was continued for the 104-week extension. In the extension, in the group previously randomized to etanercept-plus-methotrexate therapy, etanercept was continued in 259/260 patients; methotrexate continued in 260/260; and hydroxychloroquine and sulfasalazine added in 8/260 and 3/260, respectively. In the group previously randomized to conventional DMARD-plus-methotrexate therapy, conventional DMARD was discontinued in 86/126 and etanercept added in 105/126. Among etanercept-exposed patients (total exposure, 798.1 patient-year [PY]), rates of adverse events, serious adverse events, and serious infections per PY were 1.7, 0.07, and 0.02 events per PY. In both groups, after treatment modification was permitted, clinical response rates and improvements in clinical/patient-reported outcomes from baseline were sustained to week 128. After investigators were permitted to modify treatment, etanercept was part of the treatment regimen in 95% of patients. Continuation or addition of etanercept in the 2-year extension resulted in a consistently good risk:benefit profile. Open-Label Study Comparing Etanercept to Conventional Disease Modifying Antirheumatic Drug (DMARD) Therapy; ClinicalTrials.gov, number NCT00848354; https://clinicaltrials.gov/ct2/show/NCT00848354.

  16. Ferric maltol therapy for iron deficiency anaemia in patients with inflammatory bowel disease: long-term extension data from a Phase 3 study.

    PubMed

    Schmidt, C; Ahmad, T; Tulassay, Z; Baumgart, D C; Bokemeyer, B; Howaldt, S; Stallmach, A; Büning, C

    2016-08-01

    Ferric maltol was effective and well-tolerated in iron deficiency anaemia patients with inflammatory bowel disease during a 12-week placebo-controlled trial. To perform a Phase 3 extension study evaluating long-term efficacy and safety with ferric maltol in inflammatory bowel disease patients in whom oral ferrous therapies had failed to correct iron deficiency anaemia. After 12 weeks of randomised, double-blind treatment, patients with iron deficiency anaemia and mild-to-moderate ulcerative colitis or Crohn's disease received open-label ferric maltol 30 mg b.d. for 52 weeks. 111 patients completed randomised treatment and 97 entered the open-label ferric maltol extension. In patients randomised to ferric maltol ('continued'; n = 50), mean ± s.d. haemoglobin increased by 3.07 ± 1.46 g/dL between baseline and Week 64. In patients randomised to placebo ('switch'; n = 47), haemoglobin increased by 2.19 ± 1.61 g/dL. Normal haemoglobin was achieved in high proportions of both continued and switch patients (89% and 83% at Week 64, respectively). Serum ferritin increased from 8.9 μg/L (baseline) to 26.0 μg/L (Week 12) in ferric maltol-treated patients, and to 57.4 μg/L amongst all patients at Week 64. In total, 80% of patients reported ≥1 adverse event by Week 64. Adverse events considered related to ferric maltol were recorded in 27/111 (24%) patients: 8/18 discontinuations due to adverse events were treatment-related. One patient was withdrawn due to increased ulcerative colitis activity. Normal haemoglobin was observed in ≥80% of patients from weeks 20-64 of long-term ferric maltol treatment, with concomitant increases in iron storage parameters. Ferric maltol was well-tolerated throughout this 64-week study. © 2016 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.

  17. [Long-term results after multiple trauma with ISS ≥ 25. Outcome and predictors of quality of life].

    PubMed

    Simmel, S; Drisch, S; Haag, S; Bühren, V

    2013-09-01

    The survival chances of multiple trauma patients have continually improved over the last decades; therefore, it is often not a question of whether a patient survives a severe accident but rather how the patient survives. In a retrospective study 127 patients were questioned regarding quality of life and health and possible influencing factors using the POLO chart an average of 70 months after suffering severe trauma (ISS Ø 35.6). The quality of life of severely injured patients is significantly reduced compared with the normal population even years after the trauma. In addition to four pretraumatic factors (older age, female gender, low education and previous illnesses) four posttraumatic variables (difficulties with authorities/institutions and unemployment as a consequence of the accident, long duration and subjectively inadequate treatment in hospital) were identified that have a negative impact on long-term quality of life. The self-reported quality of life after multiple trauma no longer permanently achieves the original level despite extensive rehabilitation measures. Post-traumatic factors have a greater impact on the long-term quality of life than the injury severity. A long-term care and specialized rehabilitation services are needed to improve outcome further.

  18. Riociguat for the treatment of chronic thromboembolic pulmonary hypertension: a long-term extension study (CHEST-2).

    PubMed

    Simonneau, Gérald; D'Armini, Andrea M; Ghofrani, Hossein-Ardeschir; Grimminger, Friedrich; Hoeper, Marius M; Jansa, Pavel; Kim, Nick H; Wang, Chen; Wilkins, Martin R; Fritsch, Arno; Davie, Neil; Colorado, Pablo; Mayer, Eckhard

    2015-05-01

    Riociguat is a soluble guanylate cyclase stimulator approved for the treatment of inoperable and persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH). In the 16-week CHEST-1 study, riociguat showed a favourable benefit-risk profile and improved several clinically relevant end-points in patients with CTEPH. The CHEST-2 open-label extension evaluated the long-term safety and efficacy of riociguat. Eligible patients from CHEST-1 received riociguat individually adjusted up to a maximum dose of 2.5 mg three times daily. The primary objective was the safety and tolerability of riociguat; exploratory efficacy end-points included 6-min walking distance (6MWD) and World Health Organization (WHO) functional class (FC). Overall, 237 patients entered CHEST-2 and 211 (89%) were ongoing at this interim analysis (March 2013). The safety profile of riociguat in CHEST-2 was similar to CHEST-1, with no new safety signals. Improvements in 6MWD and WHO FC observed in CHEST-1 persisted for up to 1 year in CHEST-2. In the observed population at 1 year, mean±sd 6MWD had changed by +51±62 m (n=172) versus CHEST-1 baseline (n=237), and WHO FC had improved/stabilised/worsened in 47/50/3% of patients (n=176) versus CHEST-1 baseline (n=236). Long-term riociguat had a favourable benefit-risk profile and apparently showed sustained benefits in exercise and functional capacity for up to 1 year. Copyright ©ERS 2015.

  19. Getting to the Bottom Line: How Using Evaluation Results to Enhance Extension Programs Can Lead to Greater Levels of Accountability

    ERIC Educational Resources Information Center

    Lamm, Alexa J.; Israel, Glenn D.; Harder, Amy

    2011-01-01

    Extension has enhanced the lives of U.S. citizens through adult education in a myriad of ways. However, as budgets get tighter, accountability becomes increasingly more important. Over the years, Extension has reported low level impacts rather than the long-term successes that those working within the system know are occurring. Without enhanced…

  20. 76 FR 33766 - Agency Information Collection Activities; Submission for OMB Review; Comment Request; Extension...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-09

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Administration on Aging Agency Information Collection Activities; Submission for OMB Review; Comment Request; Extension of Certification of Maintenance of Effort for the Title III and Minor Revisions to the Certification of Long-Term Care Ombudsman Program...

  1. Organic selenium supplementation increases mercury excretion and decreases oxidative damage in long-term mercury-exposed residents from Wanshan, China.

    PubMed

    Li, Yu-Feng; Dong, Zeqin; Chen, Chunying; Li, Bai; Gao, Yuxi; Qu, Liya; Wang, Tianchen; Fu, Xin; Zhao, Yuliang; Chai, Zhifang

    2012-10-16

    Due to a long history of extensive mercury mining and smelting activities, local residents in Wanshan, China, are suffering from elevated mercury exposure. The objective of the present study was to study the effects of oral supplementation with selenium-enriched yeast in these long-term mercury-exposed populations. One hundred and three volunteers from Wanshan area were recruited and 53 of them were supplemented with 100 μg of organic selenium daily as selenium-enriched yeast while 50 of them were supplemented with the nonselenium-enriched yeast for 3 months. The effects of selenium supplementation on urinary mercury, selenium, and oxidative stress-related biomarkers including malondialdehyde and 8-hydroxy-2-deoxyguanosine were assessed. This 3-month selenium supplementation trial indicated that organic selenium supplementation could increase mercury excretion and decrease urinary malondialdehyde and 8-hydroxy-2-deoxyguanosine levels in local residents.

  2. Pimecrolimus in atopic dermatitis: Consensus on safety and the need to allow use in infants

    PubMed Central

    Luger, Thomas; Boguniewicz, Mark; Carr, Warner; Cork, Michael; Deleuran, Mette; Eichenfield, Lawrence; Eigenmann, Philippe; Fölster-Holst, Regina; Gelmetti, Carlo; Gollnick, Harald; Hamelmann, Eckard; Hebert, Adelaide A; Muraro, Antonella; Oranje, Arnold P; Paller, Amy S; Paul, Carle; Puig, Luis; Ring, Johannes; Siegfried, Elaine; Spergel, Jonathan M; Stingl, Georg; Taieb, Alain; Torrelo, Antonio; Werfel, Thomas; Wahn, Ulrich

    2015-01-01

    Atopic dermatitis (AD) is a distressing dermatological disease, which is highly prevalent during infancy, can persist into later life and requires long-term management with anti-inflammatory compounds. The introduction of the topical calcineurin inhibitors (TCIs), tacrolimus and pimecrolimus, more than 10 yr ago was a major breakthrough for the topical anti-inflammatory treatment of AD. Pimecrolimus 1% is approved for second-line use in children (≥2 yr old) and adults with mild-to-moderate AD. The age restriction was emphasized in a boxed warning added by the FDA in January 2006, which also highlights the lack of long-term safety data and the theoretical risk of skin malignancy and lymphoma. Since then, pimecrolimus has been extensively investigated in short- and long-term studies including over 4000 infants (<2 yr old). These studies showed that pimecrolimus effectively treats AD in infants, with sustained improvement with long-term intermittent use. Unlike topical corticosteroids, long-term TCI use does not carry the risks of skin atrophy, impaired epidermal barrier function or enhanced percutaneous absorption, and so is suitable for AD treatment especially in sensitive skin areas. Most importantly, the studies of pimecrolimus in infants provided no evidence for systemic immunosuppression, and a comprehensive body of evidence from clinical studies, post-marketing surveillance and epidemiological investigations does not support potential safety concerns. In conclusion, the authors consider that the labelling restrictions regarding the use of pimecrolimus in infants are no longer justified and recommend that the validity of the boxed warning for TCIs should be reconsidered. PMID:25557211

  3. No difference in long-term trunk muscle strength, cross-sectional area, and density in patients with chronic low back pain 7 to 11 years after lumbar fusion versus cognitive intervention and exercises.

    PubMed

    Froholdt, Anne; Holm, Inger; Keller, Anne; Gunderson, Ragnhild B; Reikeraas, Olav; Brox, Jens I

    2011-08-01

    Reduced muscle strength and density observed at 1 year after lumbar fusion may deteriorate more in the long term. To compare the long-term effect of lumbar fusion and cognitive intervention and exercises on muscle strength, cross-sectional area, density, and self-rated function in patients with chronic low back pain (CLBP) and disc degeneration. Randomized controlled study with a follow-up examination at 8.5 years (range, 7-11 years). Patients with CLBP and disc degeneration randomized to either instrumented posterolateral fusion of one or both of the two lower lumbar levels or a 3-week cognitive intervention and exercise program were included. Isokinetic muscle strength was measured by a Cybex 6000 (Cybex-Lumex, Inc., Ronkonkoma, NY, USA). All patients had previous experience with the test procedure. The back extension (E) flexion (F) muscles were tested, and the E/F ratios were calculated. Cross-sectional area and density of the back muscles were measured at the L3-L4 segment by computed tomography. Patients rated their function by the General Function Score. Trunk muscle strength, cross-sectional area, density, and self-rated function. Fifty-five patients (90%) were included at long-term follow-up. There were no significant differences in cross-sectional area, density, muscle strength, or self-rated function between the two groups. The cognitive intervention and exercise group increased trunk muscle extension significantly (p<.05), and both groups performed significantly better on trunk muscle flexion tests (p<.01) at long-term follow-up. On average, self-rated function improved by 56%, cross-sectional area was reduced by 8.5%, and muscle density was reduced by 27%. Although this study did not assess the morphology of muscles likely damaged by surgery, trunk muscle strength and cross-sectional area above the surgical levels are not different between those who had lumbar fusion or cognitive intervention and exercises at 7- to 11-year follow-up. Copyright © 2011 Elsevier Inc. All rights reserved.

  4. Long Term Trend Analysis and Assessment of Water Quality in the Penchala River, Malaysia

    NASA Astrophysics Data System (ADS)

    Chow, M. F.; Haris, H. B.; Mohd Sidek, L. B.

    2014-12-01

    Rapid urban expansion produces negative impacts on the natural environment, especially river water quality. Studies assessing long term changes of water quality have been recognized as a key tool for understanding ongoing processes in watersheds and for providing an essential background for evaluation of rapid changes within industrialized and populated urban areas. Unfortunately, only limited studies are available for developing countries such as Malaysia. Thus, a long term study was conducted to evaluate water quality trends at Pencala river basin that has undergone extensive land use changes related to industrial, agricultural and urban activities. Fifteen physical and chemical variables were analysed in river water samples collected every month over a period of 13 years, between 1997 and 2009. The trend study was performed using the Mann-Kendall Seasonal test and the Sen's Slope estimator. Results revealed that most water quality parameters showed a downward trend for yearly average concentration. The water quality index (WQI) for Pencala River was improved from Class V to Class IV, according to National Water Quality Standards for Malaysia. BOD, COD, NH3-N and SS show trends toward decreasing concentrations over time. The improvements seen in water quality appear to be the result of improved wastewater treatment and other water quality improvement efforts achieved through government initiative. Continued long-term and high frequency monitoring is necessary to establish plans and policies for effective water resources management.

  5. Integration of devices into long-term condition management: a synthesis of qualitative studies.

    PubMed

    Gately, Claire; Rogers, Anne; Kirk, Susan; McNally, Rosalind

    2008-06-01

    Understanding peoples' responses to and ability to incorporate technology for managing long-term conditions into their everyday lives is relevant for informing the development and implementation of new technologies as part of future long-term condition management in domestic environments. Future research and theory building can be facilitated by the synthesis of existing qualitative studies. A systematic search for qualitative studies of health technologies at home was undertaken on OVID CINAHL, OVID Medline and CSA databases for the period 1996-2006. Studies (n = 12) that met the inclusion criteria were synthesized and their analyses subjected to qualitative meta-synthesis. Analyses clustered into five themes: (1) managing multiple uncertainties; (2) the reconstruction of identity; (3) the struggle to remain autonomous while allowing dependence; (4) coming to terms with living a technology-assisted life; and (5) the usability of devices. These translated into a line of argument synthesis in which technology takes on the status of a personified ;other' around which a set of personal and relational attributions are subsequently constructed. These allow the extension of existing illness work to incorporate new technologies. Ambivalence about the value of technologies that are designed to assist with the management of a long-term condition reflects experiences of the disruptive effects of health technologies on personal identities and strategies of managing illness. At the same time, they are highly valued because they provided new opportunities to complete aspects of illness work that were previously impossible.

  6. The Relationship between Treatment Attendance, Adherence, and Outcome in a Caregiver-Mediated Intervention for Low-Resourced Families of Young Children with Autism Spectrum Disorder

    ERIC Educational Resources Information Center

    Carr, Themba; Shih, Wendy; Lawton, Kathy; Lord, Catherine; King, Bryan; Kasari, Connie

    2016-01-01

    Rates of participation in intervention research have not been extensively studied within autism spectrum disorder. Such research is important given the benefit of early intervention on long-term prognosis for children with autism spectrum disorder. The goals of this study were to examine how family demographic factors predicted treatment…

  7. The Influence of Science Knowledge Structures on Children's Success in Solving Academic Problems.

    ERIC Educational Resources Information Center

    Champagne, Audrey B.; And Others

    Presented is a study of eighth-grade students' academic problem-solving ability based on their knowledge structures, or their information stored in semantic or long-term memory. The authors describe a technique that they developed to probe knowledge structures with an extension of the card-sort method. The method, known as the Concept Structure…

  8. Juvenile Justice Teachers' Job Satisfaction: A Comparison of Teachers in Three States

    ERIC Educational Resources Information Center

    Houchins, David E.; Shippen, Margaret E.; McKeand, Kim; Viel-Ruma, Kim; Jolivete, Kristine; Guarino, Anthony J.

    2010-01-01

    The purpose of this study was to examine the differences in the perceptions of juvenile justice teachers in Georgia, Louisiana, and Ohio. Juvenile justice teachers (n = 542) completed an extensive attrition and retention survey with a 98% response rate. Comparisons were made between states, type of facility (short or long-term), gender, and…

  9. Invasive forest defoliator contributes to the impending downward trend of oak dominance in eastern North America

    Treesearch

    Randall S. Morin; Andrew M. Liebhold

    2016-01-01

    Disturbanceby non-native insect species can be an important ecological driver shaping long-term changes in vegetation and plant species composition. While impacts of gypsy moth (Lymatria dispar L.) outbreaks in North American forests have been extensively studied, the results are quite inconsistent, particularly with respect to the amount of tree...

  10. The Effect of Local Limitations on General State Aid in Illinois.

    ERIC Educational Resources Information Center

    Bush, Erik

    2002-01-01

    Study to determine if a substantive relationship exits between the progression of a federal Tax Increment Financing (TIF) district, the long-term effects of the state Property Tax Extension Limitation Law (PTELL), and the General State Aid funding of school districts in Illinois. Finds that both TIF and PTELL lead to an increase in General State…

  11. Using Long-Term Time-Lapse Imaging of Mammalian Cell Cycle Progression for Laboratory Instruction and Analysis

    ERIC Educational Resources Information Center

    Hinchcliffe, Edward H.

    2005-01-01

    Cinemicrography--the capture of moving cellular sequences through the microscope--has been influential in revealing the dynamic nature of cellular behavior. One of the more dramatic cellular events is mitosis, the division of sister chromatids into two daughter cells. Mitosis has been extensively studied in a variety of organisms, both…

  12. The hardwood ecosystem experiment: extension and outreach

    Treesearch

    Brian J. MacGowan; Lenny D. Farlee; Robert N. Chapman

    2013-01-01

    The Hardwood Ecosystem Experiment (HEE) in Indiana is a long-term, large-scale experimental study of forest management and its impacts on plants and animals. Information from the HEE should and will be made available to a diverse group of potential users. This paper summarizes educational efforts during the pre-treatment period and highlights potential mechanisms and...

  13. A methodology for incorporating fuel price impacts into short-term transit ridership forecasts.

    DOT National Transportation Integrated Search

    2009-08-01

    Anticipating changes to public transportation ridership demand is important to planning for and meeting : service goals and maintaining system viability. These changes may occur in the short- or long-term; : extensive academic work has focused on bet...

  14. The Valley without Birds.

    ERIC Educational Resources Information Center

    Breslin, Patrick

    1988-01-01

    Describes cooperative campaign by central Chilean farmers to reduce use of dangerous chemicals. Describes cooperative's rural extension program targeting misuse of pesticides. Describes concern of chemical danger to local and foreign consumers. Cooperative's effort described as balancing short-term economic gains with long-term health and…

  15. Characterization and limits of a cold-atom Sagnac interferometer

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

    Gauguet, A.; Canuel, B.; Leveque, T.

    2009-12-15

    We present the full evaluation of a cold-atom gyroscope based on atom interferometry. We have performed extensive studies to determine the systematic errors, scale factor and sensitivity. We demonstrate that the acceleration noise can be efficiently removed from the rotation signal, allowing us to reach the fundamental limit of the quantum projection noise for short term measurements. The technical limits to the long term sensitivity and accuracy have been identified, clearing the way for the next generation of ultrasensitive atom gyroscopes.

  16. SAVY-4000 Surveillance and Life Extension Program Fiscal Year 2013 Annual Report

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

    Stone, Timothy A.; Blair, Michael W.; Weis, Eric

    2014-03-03

    The Packaging Surveillance Program section of the DOE M441.1-1 /sup>1, Nuclear Material Packaging Manual (DOE, 2008) requires DOE contractors to “ensure that a surveillance program is established and implemented to ensure the nuclear material storage package continues to meet its design criteria.” In order to ensure continuing safe storage of nuclear material and the maximization of risk reduction, TA-55 has established a Surveillance Program to ensure storage container integrity for operations within its specified design life. The LANL SAVY-4000 Field Surveillance Plan2 defines the near-term field surveillance plan for SAVY-4000 containers as required by the Manual. A long-term surveillance planmore » will be established based on the results of the first several years of surveillance and the results of the lifetime extension studies as defined in the Accelerated Aging Plan3. This report details progress in positioning the Surveillance Program for successful implementation in FY14 and status of the Design Life Extension Program in terms of its implementation and data collection for FY13.« less

  17. LIMK1 regulates long-term memory and synaptic plasticity via the transcriptional factor CREB.

    PubMed

    Todorovski, Zarko; Asrar, Suhail; Liu, Jackie; Saw, Ner Mu Nar; Joshi, Krutika; Cortez, Miguel A; Snead, O Carter; Xie, Wei; Jia, Zhengping

    2015-04-01

    Deletion of the LIMK1 gene is associated with Williams syndrome, a unique neurodevelopmental disorder characterized by severe defects in visuospatial cognition and long-term memory (LTM). However, whether LIMK1 contributes to these deficits remains elusive. Here, we show that LIMK1-knockout (LIMK1(-/-)) mice are drastically impaired in LTM but not short-term memory (STM). In addition, LIMK1(-/-) mice are selectively defective in late-phase long-term potentiation (L-LTP), a form of long-lasting synaptic plasticity specifically required for the formation of LTM. Furthermore, we show that LIMK1 interacts and regulates the activity of cyclic AMP response element-binding protein (CREB), an extensively studied transcriptional factor critical for LTM. Importantly, both L-LTP and LTM deficits in LIMK1(-/-) mice are rescued by increasing the activity of CREB. These results provide strong evidence that LIMK1 deletion is sufficient to lead to an LTM deficit and that this deficit is attributable to CREB hypofunction. Our study has identified a direct gene-phenotype link in mice and provides a potential strategy to restore LTM in patients with Williams syndrome through the enhancement of CREB activity in the adult brain. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  18. [Assessment of production of eggs of Eastern Baltic cod (Gadus morhua callarias L.) on the basis of long-term ichthyoplankton data].

    PubMed

    Karaseva, E M

    2011-01-01

    Proceeding from long-term data on the numbers of eggs of cod in ichthyoplankton, the total annual production of cod eggs at four main spawning grounds of the Baltic Sea was calculated. It was shown that the long-term fluctuations of cod egg production were positively related to the dynamics of the volume of waters coming to the Baltic Sea in years of the North Sea advections. It is suggested that this dependence was determined by a set of adaptations providing the extension of cod reproduction upon the improvement of the environment.

  19. Variability of Changjiang Diluted Water revealed by a 45-year long-term ocean hindcast and Self-Organizing Maps analysis

    NASA Astrophysics Data System (ADS)

    Zeng, Xiangming; He, Ruoying; Zong, Haibo

    2017-08-01

    Based on long-term realistic ocean circulation hindcast for in the Bohai, Yellow, and East China Seas, 45 years (1961-2005) of sea surface salinity data were analyzed using Self-Organizing Maps (SOM) to have a better understanding of the Changjiang Diluted Water (CDW) variation. Three spatial patterns were revealed by the SOM: normal, transition, and extension. The normal pattern mainly occurs from December to May while the CDW hugs China's east coast closely and flows southward. The extension pattern is dominant from June to October when the CDW extends northwestward toward Jeju Island in an omega shape. The transition pattern prevails for the rest of the year. Pattern-averaged temperature, circulation, and chlorophyll-a concentration show significant differences. CDW area and its eastern most extension were explored as a function of the Changjiang runoff and regional upwelling index. We found that Changjiang runoff and upwelling index can be reasonable predictors for the overall CDW area, while ambient circulation determines the distribution and structure of the CDW, and thus the CDW eastern most extension.

  20. Three decades of recurrent declines and recoveries in corals belie ongoing change in fish assemblages

    NASA Astrophysics Data System (ADS)

    Lamy, T.; Galzin, R.; Kulbicki, M.; Lison de Loma, T.; Claudet, J.

    2016-03-01

    Coral reefs are increasingly being altered by a myriad of anthropogenic activities and natural disturbances. Long-term studies offer unique opportunities to understand how multiple and recurrent disturbances can influence coral reef resilience and long-term dynamics. While the long-term dynamics of coral assemblages have been extensively documented, the long-term dynamics of coral reef fish assemblages have received less attention. Here, we describe the changes in fish assemblages on Tiahura reef, Moorea, from 1979 to 2011. During this 33-yr period, Tiahura was exposed to multiple disturbances (crown-of-thorns seastar outbreaks and cyclones) that caused recurrent declines and recoveries of coral cover and changes in the dominant coral genera. These shifts in coral composition were associated with long-term cascading effects on fish assemblages. The composition and trophic structure of fish assemblages continuously shifted without returning to their initial composition, whereas fish species richness remained stable, albeit with a small increase over time. We detected nonlinear responses of fish density when corals were most degraded. When coral cover dropped below 10 % following a severe crown-of-thorns sea star outbreak, the density of most fish trophic groups sharply decreased. Our study shows that historical contingency may potentially be an important but largely underestimated factor explaining the contemporary structure of reef fish assemblages and suggests that temporal stability in their structure and function should not necessarily be the target of management strategies that aim at increasing or maintaining coral reef resilience.

  1. An open-label extension long-term study of the safety and efficacy of aripiprazole for irritability in children and adolescents with autistic disorder in Japan.

    PubMed

    Ichikawa, Hironobu; Hiratani, Michio; Yasuhara, Akihiro; Tsujii, Noa; Oshimo, Takashi; Ono, Hiroaki; Tadori, Yoshihiro

    2018-02-01

    The purpose of this study was to evaluate the long-term safety and efficacy of aripiprazole in treating irritability in pediatric patients (6-17 years) with autistic disorder (AD) in Japan. In this open-label extension study, patients who had completed a previous randomized, double-blind, placebo-controlled 8-week study were enrolled and were flexibly dosed with aripiprazole (1-15 mg/day) until the new indication of irritability in pediatric autism spectrum disorder was approved in Japan. Seventy (81%) out of 86 enrolled patients completed week-48 assessments. The mean duration of treatment was 694.9 days. The mean daily dose of aripiprazole over the treatment period was 7.2 mg and the mean of the final dose was 8.5 mg. The most common treatment-emergent adverse events (TEAE; ≥20%) included nasopharyngitis, somnolence, influenza, and increased weight. The majority of these TEAE were mild or moderate in severity, and there were no deaths, and no clinically relevant findings in laboratory values except prolactin decrease, vital signs, height, or ECG parameters. At week 48 (observed case), the mean change from baseline in the Irritability subscale score for the Aberrant Behavior Checklist Japanese Version was -6.3 in prior placebo patients and -2.6 in prior aripiprazole patients. Aripiprazole was generally safe, well tolerated, and effective in the long-term treatment of irritability associated with AD in Japanese pediatric patients. © 2017 The Authors. Psychiatry and Clinical Neurosciences published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Psychiatry and Neurology.

  2. Simultaneous Control of PTH and Ca×P Is Sustained over Three Years of Treatment with Cinacalcet HCl

    PubMed Central

    Evenepoel, Pieter; Curzi, Mario P.; González, Maria Teresa; Husserl, Fred E.; Kopyt, Nelson; Sterling, Lulu Ren; Mix, Chris; Wong, Gordon

    2009-01-01

    Background & objectives: Chronic kidney disease (CKD) is commonly complicated by secondary hyperparathyroidism (SHPT), leading to increased risk of morbidity and mortality. SHPT is a progressive disease often requiring long-term therapy to control parathyroid hormone (PTH) and mineral imbalances. Vitamin D sterols and phosphate binders, used as traditional therapies to lower PTH and phosphorus, may provide inadequate long-term control for many dialysis patients. Cinacalcet, by simultaneously lowering PTH, calcium, phosphorus, and calcium-phosphorus levels, may maintain PTH and mineral balance in these individuals. However, as with traditional therapies, long-term data are limited. Design, setting, participants, & measurement: Dialysis subjects from at least one of five lead-in studies (double-blind placebo-controlled, including one extension trial) completing up to 52 wk of either cinacalcet or placebo were eligible for this open-label extension study, including an 8-wk dose titration (initiated at 30 mg/d), followed by 24-wk maintenance and up to 132 wk of follow-up. Final efficacy analysis was at week 180. Results: Three hundred thirty-four of 589 enrolled subjects received cinacalcet from the beginning of the lead-in study. Weekly median PTH values were ≤300 pg/ml (weeks 16 through 180) and median Ca×P values were ≤55 mg2/dl2 (weeks 4 through 180). Similar results were exhibited in the 255 subjects who initially received placebo. Among the patients exposed to cinacalcet from the beginning of the lead-in study, 3% of subjects exhibited treatment-related serious adverse events. Conclusions: Cinacalcet effectively maintained PTH, Ca and P reductions in dialysis subjects for up to 180 wk. PMID:19696213

  3. Changes in plasma ACTH levels and corticotroph tumor size in patients with Cushing's disease during long-term treatment with the glucocorticoid receptor antagonist mifepristone.

    PubMed

    Fleseriu, Maria; Findling, James W; Koch, Christian A; Schlaffer, Sven-Martin; Buchfelder, Michael; Gross, Coleman

    2014-10-01

    Pituitary effects of long-term therapy with mifepristone, a glucocorticoid receptor antagonist, in Cushing's disease (CD) patients are not well understood. Our objective was to report changes in ACTH and pituitary magnetic resonance imaging (MRI) findings during long-term use of mifepristone in CD patients. The Study of the Efficacy and Safety of Mifepristone in the Treatment of Endogenous Cushing's Syndrome (SEISMIC) was a 24-week, open-label study of mifepristone, and its long-term extension (LTE) is a multicenter U.S. study. Forty-three CD patients (mean age 45.3 years) were enrolled in SEISMIC with 27 continuing into the LTE study. Mifepristone (300-1200 mg) was administered once daily. ACTH and pituitary MRI were assessed at baseline and at regular intervals during treatment. A ≥2-fold increase in ACTH was observed in 72% of patients treated for a median duration of 11.3 months. The mean peak increase in ACTH was 2.76 ± 1.65-fold during SEISMIC, and mean ACTH concentrations remained stable during the LTE. ACTH was directly correlated with mifepristone dose and declined to near baseline levels after mifepristone discontinuation. Tumor regressed in 2 patients and progressed in 3 patients with macroadenomas. An additional microadenoma was identified after 25 months of treatment after a baseline tumor-negative MRI. In the largest prospective study to date, long-term mifepristone treatment increased ACTH in approximately two-thirds of patients with CD. ACTH elevations were observed within the first few weeks of treatment, were dose-dependent, and generally remained stable over time. Corticotroph tumor progression and regression may occur over time, but patients may have significant increases in ACTH levels without evidence of tumor growth.

  4. Food for thought: a pilot study of the pros and cons of changing eating patterns within cognitive-behavioural therapy for the eating disorders.

    PubMed

    Waller, Glenn; Evans, Jane; Pugh, Matthew

    2013-09-01

    Evidence-based cognitive-behavioural therapy (CBT) for the eating disorders has an early focus on behavioural changes around food intake. However, patients' anxiety around such change might account for why they often seem unmotivated in treatment. In order to determine the impact of changing intake, this pilot study of patients with bulimic disorders (N = 19) or anorexia nervosa (N = 9) used a mixed quantitative and qualitative design to retrospectively examine their perspectives of the short- and long-term pros and cons of such change. As expected, change was seen negatively in the short-term (with particularly high numbers reporting anxiety), but there were few reports of long-term negative outcomes. In contrast, there were both short- and long-term benefits of changing eating. The patients described what was helpful in making changes and what they had learned as a result. In both cases, their descriptions mapped closely onto the content and process of evidence-based CBT for the eating disorders. Although there is a need for more extensive research, these findings suggest that patients (and therapists) might benefit from being aware of the contrast between the short- and the long-term pros and cons of changing eating within CBT for the eating disorders. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. [Which rehabilitation for which low back pain?].

    PubMed

    Poiraudeau, S; Lefèvre-Colau, M M; Mayoux-Benhamou, M A; Revel, M

    2000-10-15

    Many rehabilitation technics for low back pain are available. Their aims are short time pain decrease, muscular strengthening in flexion or extension, increased hip and lumbar spine mobility, improved lumbar and pelvic proprioceptive sensibility, improved general fitness. During the past ten years, studies meeting widely accepted validity and applicability for therapeutic trials have addressed the clinical efficacy of rehabilitation in low back pain patients. Most studies assessing the back school approach have found no benefit. Spinal extension and flexion programs have yielded short-time improvements, without difference between the two methods. There is now strong evidence that functional restoration programs provide long-term benefits including better social and occupational outcomes.

  6. Ulcerative proctitis: an update on the pharmacotherapy and management.

    PubMed

    Gecse, Krisztina B; Lakatos, Peter L

    2014-08-01

    Ulcerative colitis (UC) presents as proctitis in approximately a quarter of the patients. It may progress into left-sided or extensive colitis in up to 50% of cases upon long-term follow-up. Currently available data on ulcerative proctitis are summarized and critically reviewed. Extensive literature search (MEDLINE) was performed to identify relevant articles up to March 2014. The short-term goal of the treatment in UC is to induce remission, whereas long-term goals are to maintain remission and prevent disease progression. Topically administered 5-aminosalicylates (5-ASA) and corticosteroids are effective in the treatment of proctitis, although they seem to be underused in everyday practice. Locally administered 5-ASA preparations are more effective than oral compounds. The combination of topical and oral 5-ASA and steroids should be considered for escalation of treatment. Refractory patients should be re-evaluated to exclude for compliance failures, infections or proximal disease extent. True refractory or steroid-dependent patients may require immunomodulators or biological therapy. Alternative medicine can be used complementarily, while experimental approaches are reserved for patients failing conventional medication. Proctocolectomy may be the last resort of treatment. Upon long-term, 5-ASA maintenance treatment is indicated in all UC cases to prevent relapse and disease progression.

  7. Perioperative and Long-Term Smoking Behaviors in Cosmetic Surgery Patients.

    PubMed

    Van Slyke, Aaron C; Carr, Michael; Knox, Aaron D C; Genoway, Krista; Carr, Nicholas J

    2017-09-01

    Many plastic surgeons advocate smoking cessation before patients undergo cosmetic surgery with extensive soft-tissue dissection. Smoking cessation rates after cosmetic surgery are unknown. The preoperative consultation may be an opportunity to promote long-term smoking cessation. This is a retrospective, cross-sectional cohort study. All patients over an 8-year study period who smoked before their preoperative consultation; who quit 2 weeks before surgery; and who subsequently underwent rhytidectomy, abdominoplasty, or mastopexy were included. Patients were asked to complete a Web-based survey at long-term follow-up. Eighty-five smokers were included, and 47 patients completed the survey, for a response rate of 55.3 percent. Average follow-up was 63.3 months. Five respondents were social smokers and thus excluded. Of the 42 daily smokers, 17 patients (40.5 percent) were no longer smoking cigarettes on a daily basis at long-term follow-up. Of these 17 patients, 10 (23.8 percent) had not smoked since their operation. A total of 24 patients (57.1 percent) had reduced their cigarette consumption by any amount, and 70.8 percent (17 of 24) of these patients agreed that discussing adverse surgical outcomes related to smoking influenced their ability to quit/reduce. Twenty-one of 42 patients (50.0 percent) admitted that they were not compliant with the preoperative smoking cessation instructions. This is the first report to investigate long-term smoking cessation from a cosmetic surgery practice. The authors have shown a positive association between smoking cessation and cosmetic surgery. Requesting a period of cessation before cosmetic surgery may promote long-lasting smoking cessation.

  8. Long-term conditioning of deep-seated rockslides in deglaciated valleys: the Spriana case study

    NASA Astrophysics Data System (ADS)

    Agliardi, Federico; Crosta, Giovanni B.

    2015-04-01

    Deep-seated rockslides in alpine valleys evolve over long time under the action of multiple triggers. Early Warning based on monitoring is often the only effective approach to cope with these landslides, but it requires an improved understanding of mechanisms interplaying over long time. Deep-seated rockslides are often characterized by long-term 'creep' and seasonal displacement components, contributing to measured displacement patterns which are often modelled as rockslide responses to hydrologic perturbations. Although this hydro-mechanical modelling approach fits the behaviour of disrupted rockslide masses with well-developed shear zones, it is often insufficient to explain the initial onset and the long-term components of creep movements of deep-seated rockslides. This outlines the need to link long-term evolution of rock slopes and their sensitivity to triggers. We discuss the Spriana rockslide, affecting the steep left-hand flank of Val Malenco (italian Central Alps). Documented instabilities date back to 1912, whereas the rockslide underwent major acceleration stages in 1960 and 1977-78 and later minor reactivations. We reviewed a large amount of data collected since 1978 by extensive geotechnical site investigation (borehole drilling, exploratory adits, and seismic refraction) and monitoring activities (ground surface and deep displacements, pore pressures) motivated by potential catastrophic collapse threatening the city of Sondrio area. We performed rock mass characterization based on laboratory studies on intact rock samples, field surveys and drillcore logging. These data allowed re-evaluating the geological model of the Spriana rockslide, which is a compound slide of up to 50 Mm3 of slope debris and fractured gneiss, with multiple shear failure zones up to 90 m deep. Two main scarps developed in different stages, suggesting progressive failure processes. The rockslide creeps at slow rates of 0.4-3 cm/a, and undergoes acceleration stages (weeks to months) during increased water recharge periods. Heavily fractured rock masses occur below rockslide base up to 150 m in depth, suggesting extensive rock mass damage pre-dating rockslide onset. Groundwater monitoring shows that this fractured layer hosts a perched water table characterized by annual fluctuations up to 3 m. To gain insights in the long-term slope evolution we performed 2D Finite-Element multi-stage stress-strain and seepage modelling, accounting for post-LGM deglaciation, damage and related changes in slope strength and hydrology. Results validated using investigation data show that rockslide onset would have been unlikely without the strong preconditioning of long-term damage related to deglaciation. This led to a two-layer hydro-mechanical slope differentiation, with a fractured upper layer hosting a perched water table that favoured rockslide onset. Once structured, the rockslide became more sensitive to short-term hydrologic triggers, with displacement rates increasing in response to groundwater recharge related to critical values of antecedent (7 to 30 days) rainfall. Our results outline the importance of accounting for long-term slope evolution when dealing with rockslides evolving over 102-103 year timescales, and point to the need of modelling approaches able to relate changing hydro-mechanical properties of slopes to long-term damage processes.

  9. The long-term problems of contaminated land: Sources, impacts and countermeasures

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

    Baes, C.F. III

    1986-11-01

    This report examines the various sources of radiological land contamination; its extent; its impacts on man, agriculture, and the environment; countermeasures for mitigating exposures; radiological standards; alternatives for achieving land decontamination and cleanup; and possible alternatives for utilizing the land. The major potential sources of extensive long-term land contamination with radionuclides, in order of decreasing extent, are nuclear war, detonation of a single nuclear weapon (e.g., a terrorist act), serious reactor accidents, and nonfission nuclear weapons accidents that disperse the nuclear fuels (termed ''broken arrows'').

  10. Effect of Xyloglucan Oligosaccharides on Growth, Viscoelastic Properties, and Long-Term Extension of Pea Shoots.

    PubMed Central

    Cutillas-Iturralde, A.; Lorences, E. P.

    1997-01-01

    The growth-promoting effect of xyloglucan-derived oligosaccharides was investigated using a bioassay with entire pea (Pisum sativum L., var Alaska) shoots. After a 24-h incubation period at 25[deg]C, xyloglucan oligosaccharide (XGO) solutions with concentrations of 10-6 M notably increased the growth rate of pea shoots, whereas the same oligosaccharides at 10-7 M were less effective. To investigate the possible correlation between growth rate changes in the XGO-treated shoots and changes in the wall mechanical properties of their growing regions (third internodes), we used a short-term creep assay. The promotion of elongation by XGOs was reflected in an enhancement of the viscoelasticity of the growing regions of the shoots. To show whether this effect on wall viscoelastic properties was the cause or a consequence of their growth promotion, we tested the effect of XGOs on the long-term extension of isolated cell walls. We characterized an acid-induced extension in isolated cell walls from pea shoots that was not inhibited by preincubation in neutral buffers. Exogenously added XGOs did not alter the pattern of pea segment extension at any pH tested, indicating that XGOs have no direct effect on cell wall viscoelasticity. Finally, preincubation of pea segments in neutral buffers with XGOs enhanced their capacity to extend under acidic conditions. This finding suggests that XGOs at a neutral pH can act via transglycosylation, weakening the wall matrix and making the wall more responsive to other mechanisms of acid-induced extension as an expansin-mediated extension. PMID:12223593

  11. Hodgkin's lymphoma rectosigmoid in a patient with ulcerative colitis on long-term azathioprine therapy

    PubMed Central

    Khuroo, Mehnaaz S

    2014-01-01

    Hodgkin's lymphoma complicating chronic ulcerative colitis is extremely rare. We report a case of extranodal Hodgkin's lymphoma involving rectosigmoid in a patient of chronic ulcerative colitis on long-term azathioprine. A 67-year-old man presented with extensive ulcerative colitis, on follow-up since September 2005. He received long-term steroids, mesalamine and azathioprine. Serial surveillance colonoscopic examinations and colonic biopsies were performed. Surveillance colonoscopy performed 8 years after the onset of disease showed multiple deep ulcers and nodular masses involving the rectum and sigmoid colon. Histological examination of rectosigmoid biopsies showed classic Hodgkin's disease. Azathioprine was withdrawn. He received mechlorethamine, vincristine, procarbazine and prednisone (MOPP) chemotherapy protocol and was planned for total colectomy in follow-up. We believe patients with ulcerative colitis on long-term azathioprine should be on vigil for development of lymphomas by protocol surveillance colonoscopic examinations and biopsies. The risk of lymphoma in such patients is small and outweighs the benefits of long-term azathioprine therapy. PMID:24849639

  12. Condition and fate of logged forests in the Brazilian Amazon.

    Treesearch

    Gregory P. Asner; Eben N. Broadbent; Paulo J. C. Oliveira; Michael Keller; David E. Knapp; Jose N. M. Silva

    2006-01-01

    The long-term viability of a forest industry in the Amazon region of Brazil depends on the maintenance of adequate timber volume and growth in healthy forests. Using extensive high-resolution satellite analyses, we studied the forest damage caused by recent logging operations and the likelihood that logged forests would be cleared within 4 years after timber harvest....

  13. Capital Improvements Programming: A Proposal for a Revised Process to Develop the Annual Capital Budget for the Orleans Parish School Board. Revised.

    ERIC Educational Resources Information Center

    Ducote, Kenneth J.

    A study by the United States General Accounting Office found that successful organizations incorporate in their capital budgeting process extensive links between planning and budgeting, up-to-date information on existing capital facilities, and consideration of long-term effects in making capital budgeting decisions. This paper recommends the…

  14. The Overgeneralization of Linear Models among University Students' Mathematical Productions: A Long-Term Study

    ERIC Educational Resources Information Center

    Esteley, Cristina B.; Villarreal, Monica E.; Alagia, Humberto R.

    2010-01-01

    Over the past several years, we have been exploring and researching a phenomenon that occurs among undergraduate students that we called extension of linear models to non-linear contexts or overgeneralization of linear models. This phenomenon appears when some students use linear representations in situations that are non-linear. In a first phase,…

  15. Microstructural Changes in Inconel ® 740 After Long-Term Aging in the Presence and Absence of Stress

    DOE PAGES

    Unocic, Kinga A.; Shingledecker, John Paul; Tortorelli, Peter F.

    2014-11-18

    The Ni-based alloy, Inconel ® 740, is being extensively examined for use in advanced ultrasupercritical steam boilers because its precipitation-strengthened microstructure appears to offer the necessary creep strength under the high temperatures and pressures (up to 760°C and 35 MPa) needed for high efficiency power generation. However, because this application requires extremely long lifetimes under these conditions (up to 30 years), long-term microstructure stability is a major concern. In this study, results from microstructural analyses of Inconel 740 specimens aged at 700 and 750°C in the presence and absence of creep loading for times up to ~31,000 h are presented.more » The primary focus was on the development of the eta η (Ni 3Ti) phase and coarsening of coherent γ'-Ni 3(Al,Ti) precipitates and its depletion near eta/matrix interfaces. Finally, however, despite these processes, Inconel 740 showed adequate long-term microstructural stability to assure adequate creep strength for the intended application.« less

  16. Effect of the long-term care prevention project on the motor functions and daily life activities of the elderly.

    PubMed

    Wada, Yoshihiro; Sakuraba, Keisyoku; Kubota, Atsushi

    2015-01-01

    [Purpose] The purpose of this study was to verify the effects of the long-term care prevention project and develop an effective program. [Subjects] A total of 81 elderly people (age, 79 ± 5.1 years; height, 149.2 ± 9.2 cm; weight, 54.2 ± 11.4 kg). [Methods] Grip, knee extension muscular strength, 10 m walking speed, and Timed Up and Go time were measured for evaluation of motor functions, and the "Locomo 25", a 25-question risk assessment questionnaire, was used as the judgment criterion for evaluation of daily life activities, with measurements being taken at the beginning of the project and after three months. [Results] In the motor functions evaluation, significant differences were observed in 10 m walking speed, Timed Up and Go time, and knee extension strength. In the daily life activities evaluation, scores for pain, rising movement, standing movement, indoor walking, outdoor walking, and fear of falling were significantly reduced. In addition, a significant correlation was also observed between motor functions and daily life activities. [Conclusion] The result of this study indicated that the long-term care prevention project is effective in maintaining or improving muscular strength and mitigating pain in the elderly and that it is an effective program for maintaining daily life activities. We were also able to show that it would be effective to develop programs with a low exercise intensity that can be performed on a continuing by the elderly.

  17. Pimecrolimus in atopic dermatitis: consensus on safety and the need to allow use in infants.

    PubMed

    Luger, Thomas; Boguniewicz, Mark; Carr, Warner; Cork, Michael; Deleuran, Mette; Eichenfield, Lawrence; Eigenmann, Philippe; Fölster-Holst, Regina; Gelmetti, Carlo; Gollnick, Harald; Hamelmann, Eckard; Hebert, Adelaide A; Muraro, Antonella; Oranje, Arnold P; Paller, Amy S; Paul, Carle; Puig, Luis; Ring, Johannes; Siegfried, Elaine; Spergel, Jonathan M; Stingl, Georg; Taieb, Alain; Torrelo, Antonio; Werfel, Thomas; Wahn, Ulrich

    2015-06-01

    Atopic dermatitis (AD) is a distressing dermatological disease, which is highly prevalent during infancy, can persist into later life and requires long-term management with anti-inflammatory compounds. The introduction of the topical calcineurin inhibitors (TCIs), tacrolimus and pimecrolimus, more than 10 yr ago was a major breakthrough for the topical anti-inflammatory treatment of AD. Pimecrolimus 1% is approved for second-line use in children (≥2 yr old) and adults with mild-to-moderate AD. The age restriction was emphasized in a boxed warning added by the FDA in January 2006, which also highlights the lack of long-term safety data and the theoretical risk of skin malignancy and lymphoma. Since then, pimecrolimus has been extensively investigated in short- and long-term studies including over 4000 infants (<2 yr old). These studies showed that pimecrolimus effectively treats AD in infants, with sustained improvement with long-term intermittent use. Unlike topical corticosteroids, long-term TCI use does not carry the risks of skin atrophy, impaired epidermal barrier function or enhanced percutaneous absorption, and so is suitable for AD treatment especially in sensitive skin areas. Most importantly, the studies of pimecrolimus in infants provided no evidence for systemic immunosuppression, and a comprehensive body of evidence from clinical studies, post-marketing surveillance and epidemiological investigations does not support potential safety concerns. In conclusion, the authors consider that the labelling restrictions regarding the use of pimecrolimus in infants are no longer justified and recommend that the validity of the boxed warning for TCIs should be reconsidered. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. No Magic, Little Sleep, and Lots of Luck: Reflections from a Long-Serving University President

    ERIC Educational Resources Information Center

    Trachtenberg, Stephen Joel

    2006-01-01

    Financial misdeeds, athletics scandals, and votes of "no confidence." How does a president escape all of these and hold office for the long haul? And "why" does one serve for an extensive term? In this article, the author explores these questions as he looks back on his long tenure at The George Washington University. He…

  19. Primary care management of patients following bariatric surgery.

    PubMed

    Doolen, Jessica L; Miller, Sally K

    2005-11-01

    To evaluate the nutritional, psychosocial, and other primary care issues faced by nurse practitioners (NPs) and their patients in the long-term management of the increasing population of patients who have had bariatric surgery. An extensive review of the literature provides the foundation for development of assessment and management strategies highlighted in a case study. Management of the patient after bariatric surgery does not end with successful surgical healing. Numerous long-term implications, including significant psychosocial and nutritional issues, require the informed attention of the primary care provider for the rest of the life span. Each year an increasing number of obese patients pursue a surgical solution to obesity, up to an estimated 100,000 in 2004. Numerous long-term health implications are specific to this population. NPs can improve the quality of primary care to these patients by being informed regarding the different procedures and their impact on physiologic phenomena, and the psychosocial issues inherent to extreme weight loss.

  20. Epoxide-functionalization of polyethyleneimine for synthesis of stable carbon dioxide adsorbent in temperature swing adsorption

    PubMed Central

    Choi, Woosung; Min, Kyungmin; Kim, Chaehoon; Ko, Young Soo; Jeon, Jae Wan; Seo, Hwimin; Park, Yong-Ki; Choi, Minkee

    2016-01-01

    Amine-containing adsorbents have been extensively investigated for post-combustion carbon dioxide capture due to their ability to chemisorb low-concentration carbon dioxide from a wet flue gas. However, earlier studies have focused primarily on the carbon dioxide uptake of adsorbents, and have not demonstrated effective adsorbent regeneration and long-term stability under such conditions. Here, we report the versatile and scalable synthesis of a functionalized-polyethyleneimine (PEI)/silica adsorbent which simultaneously exhibits a large working capacity (2.2 mmol g−1) and long-term stability in a practical temperature swing adsorption process (regeneration under 100% carbon dioxide at 120 °C), enabling the separation of concentrated carbon dioxide. We demonstrate that the functionalization of PEI with 1,2-epoxybutane reduces the heat of adsorption and facilitates carbon dioxide desorption (>99%) during regeneration compared with unmodified PEI (76%). Moreover, the functionalization significantly improves long-term adsorbent stability over repeated temperature swing adsorption cycles due to the suppression of urea formation and oxidative amine degradation. PMID:27572662

  1. Temporary practice pause then resumption (TPPR) study design: an extension of the withdrawal study design to complementary and alternative medicine mind and body interventions (CAM-MABI).

    PubMed

    Braun, M Miles

    2013-10-01

    Study of complementary and alternative medicine's mind and body interventions (CAM-MABI) is hindered not only by the inability to mask participants and their teachers to the study intervention but also by the major practical hurdles of long-term study of practices that can be lifelong. Two other important methodological problems are that study of newly trained practitioners cannot directly address long-term practice, and that long-term practitioners likely self-select in ways that make finding appropriate controls (or a comparison group) challenging. The temporary practice pause then resumption study design (TPPR) introduced here is a new tool that extends the withdrawal study design, established in the field of drug evaluation, to the field of CAM-MABI. With the exception of the inability to mask, TPPR can address the other methodological problems noted above. Of great interest to investigators will likely be measures in practitioners of CAM-MABI that change with temporary pausing of CAM-MABI practice, followed by return of the measures to pre-pause levels with resumption of practice; this would suggest a link of the practice to measured changes. Such findings using this tool may enhance our insight into fundamental biological processes, leading to beneficial practical applications.

  2. A controlled survey of less typical long-term consequences after an extensive waterborne epidemic.

    PubMed

    Laine, Janne; Laine, Outi; Lumio, Jukka; Antonen, Jaakko; Toikkanen, Salla; Virtanen, Mikko J; Kuusi, Markku

    2017-02-21

    Extensive backflow of treated wastewater caused household water contamination in a Finnish town in 2007. The drinking water of 9 500 residents became heavily polluted with faecal microbes, resulting in a large gastroenteritis epidemic. Cases of reactive arthritis, milder joint symptoms and prolonged gastrointestinal symptoms were observed after the outbreak. A follow-up survey was performed to study less familiar long-term health consequences within a year from the outbreak. The contaminated group comprised a sample of residents of the area with polluted water supply (N = 323) and the control group a sample of residents in a nearby municipality (N = 186). The presence of 20 general symptoms or complaints was inquired by a mail survey. Quarterly prevalence of each symptom or complaint was measured. Twelve of these proceeded to further analysis. The response rate was 53% (323/615) in the contaminated group and 54% (186/343) in the control group. Rash, eye irritation, heartburn and weight loss were more prevalent in the contaminated group during the first year quarter. In the last year quarter, only eye irritation was significantly more common in the contaminated group. The excess prevalence of four complaints at the first year quarter can be explained by acute gastroenteritis or intensive water chlorination. The excess prevalence of eye irritation at the fourth year quarter cannot be explained by chlorination anymore but might be a sign of co-existing reactive joint disease. In general, long-term consequences of the outbreak can be considered minor in terms of the surveyed symptoms or complaints.

  3. Long-term changes in cognitive bias and coping response as a result of chronic unpredictable stress during adolescence.

    PubMed

    Chaby, Lauren E; Cavigelli, Sonia A; White, Amanda; Wang, Kayllie; Braithwaite, Victoria A

    2013-01-01

    Animals that experience adverse events in early life often have life-long changes to their physiology and behavior. Long-term effects of stress during early life have been studied extensively, but less attention has been given to the consequences of negative experiences solely during the adolescent phase. Adolescence is a particularly sensitive period of life when regulation of the glucocorticoid "stress" hormone response matures and specific regions in the brain undergo considerable change. Aversive experiences during this time might, therefore, be expected to generate long-term consequences for the adult phenotype. Here we investigated the long-term effects of exposure to chronic unpredictable stress during adolescence on adult decision-making, coping response, cognitive bias, and exploratory behavior in rats. Rats exposed to chronic unpredictable stress (e.g., isolation, crowding, cage tilt) were compared to control animals that were maintained in standard, predictable conditions throughout development. Unpredictable stress during adolescence resulted in a suite of long-term behavioral and cognitive changes including a negative cognitive bias [F (1, 12) = 5.000, P < 0.05], altered coping response [T (1, 14) = 2.216, P = 0.04], and accelerated decision-making [T (1, 14) = 3.245, P = 0.01]. Exposure to chronic stress during adolescence also caused a short-term increase in boldness behaviors; in a novel object test 15 days after the last stressor, animals exposed to chronic unpredictable stress had decreased latencies to leave a familiar shelter and approach a novel object [T (1, 14) = 2.240, P = 0.04; T (1, 14) = 2.419, P = 0.03, respectively]. The results showed that stress during adolescence has long-term impacts on behavior and cognition that affect the interpretation of ambiguous stimuli, behavioral response to adverse events, and how animals make decisions.

  4. Macroeconomic Scenario Building for Strategic National Defense Planning

    DTIC Science & Technology

    2001-12-01

    can be disastrous. The rapid destruction of the hedge fund Long Term Capital Management in the fall of 1998 is a case in point. This fund traded...extensively in derivatives and arbitrage with use of heavy leverage. Their use of computer models developed by the crème of academia, including Nobel...historical norms of arbitrage trading and bond yields broke down. In five weeks the Long Term Capital’s portfolio imploded under the weight of its leverage

  5. Home garden plums

    USDA-ARS?s Scientific Manuscript database

    The paper is to provide extension information on plums for home owners in Georgia and other Southeastern states. It includes seven sections: introduction, varieties, planting, pruning, fertilization, pests/diseases, and long term care....

  6. Extensive and systematic rewiring of histone post-translational modifications in cancer model systems.

    PubMed

    Noberini, Roberta; Osti, Daniela; Miccolo, Claudia; Richichi, Cristina; Lupia, Michela; Corleone, Giacomo; Hong, Sung-Pil; Colombo, Piergiuseppe; Pollo, Bianca; Fornasari, Lorenzo; Pruneri, Giancarlo; Magnani, Luca; Cavallaro, Ugo; Chiocca, Susanna; Minucci, Saverio; Pelicci, Giuliana; Bonaldi, Tiziana

    2018-05-04

    Histone post-translational modifications (PTMs) generate a complex combinatorial code that regulates gene expression and nuclear functions, and whose deregulation has been documented in different types of cancers. Therefore, the availability of relevant culture models that can be manipulated and that retain the epigenetic features of the tissue of origin is absolutely crucial for studying the epigenetic mechanisms underlying cancer and testing epigenetic drugs. In this study, we took advantage of quantitative mass spectrometry to comprehensively profile histone PTMs in patient tumor tissues, primary cultures and cell lines from three representative tumor models, breast cancer, glioblastoma and ovarian cancer, revealing an extensive and systematic rewiring of histone marks in cell culture conditions, which includes a decrease of H3K27me2/me3, H3K79me1/me2 and H3K9ac/K14ac, and an increase of H3K36me1/me2. While some changes occur in short-term primary cultures, most of them are instead time-dependent and appear only in long-term cultures. Remarkably, such changes mostly revert in cell line- and primary cell-derived in vivo xenograft models. Taken together, these results support the use of xenografts as the most representative models of in vivo epigenetic processes, suggesting caution when using cultured cells, in particular cell lines and long-term primary cultures, for epigenetic investigations.

  7. Extensive and systematic rewiring of histone post-translational modifications in cancer model systems

    PubMed Central

    Noberini, Roberta; Osti, Daniela; Miccolo, Claudia; Richichi, Cristina; Lupia, Michela; Corleone, Giacomo; Hong, Sung-Pil; Colombo, Piergiuseppe; Pollo, Bianca; Fornasari, Lorenzo; Pruneri, Giancarlo; Magnani, Luca; Cavallaro, Ugo; Chiocca, Susanna; Minucci, Saverio; Pelicci, Giuliana; Bonaldi, Tiziana

    2018-01-01

    Abstract Histone post-translational modifications (PTMs) generate a complex combinatorial code that regulates gene expression and nuclear functions, and whose deregulation has been documented in different types of cancers. Therefore, the availability of relevant culture models that can be manipulated and that retain the epigenetic features of the tissue of origin is absolutely crucial for studying the epigenetic mechanisms underlying cancer and testing epigenetic drugs. In this study, we took advantage of quantitative mass spectrometry to comprehensively profile histone PTMs in patient tumor tissues, primary cultures and cell lines from three representative tumor models, breast cancer, glioblastoma and ovarian cancer, revealing an extensive and systematic rewiring of histone marks in cell culture conditions, which includes a decrease of H3K27me2/me3, H3K79me1/me2 and H3K9ac/K14ac, and an increase of H3K36me1/me2. While some changes occur in short-term primary cultures, most of them are instead time-dependent and appear only in long-term cultures. Remarkably, such changes mostly revert in cell line- and primary cell-derived in vivo xenograft models. Taken together, these results support the use of xenografts as the most representative models of in vivo epigenetic processes, suggesting caution when using cultured cells, in particular cell lines and long-term primary cultures, for epigenetic investigations. PMID:29618087

  8. Diagnosis and management of a retrobulbar abscess of periapical origin in a domestic rabbit.

    PubMed

    Ward, Michelle L

    2006-09-01

    Retrobulbar abscessation is the most common orbital disease of rabbits, and the lesions are notoriously difficult to treat successfully. This article describes the diagnosis, surgical treatment, and long-term management of an extensive abscess located within the right maxilla and retrobulbar space of a domestic rabbit. Preoperative assessment and long-term monitoring were achieved with a combination of radiography, ophthalmic ultrasonography, and CT. Extraoral rigid endoscopy via a fenestration in the maxilla was used to facilitate surgical debridement of the lesion, and extraction of multiple cheek teeth has been fundamental to achieving control. The long-term use of topical and systemic antibiotic preparations and nonsteroidal anti-inflammatory medication is discussed.

  9. Quadriplegia after parathyroidectomy in a hemodialysis patient.

    PubMed

    Wang, Yu-Chieh; Huang, Shih-Yu; Lin, Ho-Tien; Hu, Jenkin-S; Chan, Kwok-Hon; Tsou, Mei-Yung

    2011-03-01

    We present a case of post-operative iatrogenic quadriplegia, which occurred after subtotal parathyroidectomy. This patient was on long-term hemodialysis for 7 years. The need of prolonged neck extension for this procedure was probably the main risk factor for the spinal cord injury. Systemic hypotension which contributed to the injury in this case, should be anticipated and promptly treated to prevent further damage. Spinal deformities associated with end-stage renal disease may make such patients more susceptible. Since appropriate precautions against potential neurologic damage can be undertaken, we suggest that evaluating carefully for the pre-existing spinal stenosis before a procedure requiring prominent and prolonged hyper-extension of the neck, especially in long-term hemodialysis patients is of paramount importance. Copyright © 2011. Published by Elsevier B.V.

  10. Cultural Implications of Human Resource Development.

    ERIC Educational Resources Information Center

    Hiranpruk, Chaiskran

    A discussion of the cultural effects of economic and, by extension, human resource development in Southeast Asia looks at short- and long-term implications. It is suggested that in the short term, increased competition will affect distribution of wealth, which can promote materialism and corruption. The introduction of labor-saving technology may…

  11. Application of a motivation-behavioral skills protocol in gingival lichen planus: a short-term study.

    PubMed

    López-Jornet, Pia; Camacho-Alonso, Fabio

    2010-10-01

    The main objective of the present study was to assess the efficacy of a motivation–behavioral skills protocol for plaque control in patients with gingival lichen planus. A pre- and post-test descriptive clinical study was made of 40 consecutive white patients with gingival lichen planus: five males (12.5%) and 35 females (87.5%); mean age: 57 years. A motivation–behavioral skills protocol for oral hygiene was applied, with the determination of gingival scores (gingival index, plaque extension, and Community Periodontal Index of Treatment Needs [CPITN]) and patient evaluation after 4 and 8 weeks. The clinical parameters in relation to the different forms of gingival lichen planus showed statistically significant improvements for gingival index, plaque extension, and CPITN (P <0.001) as determined 4 and 8 weeks after starting the program. The application of an active prevention program in patients with gingival lichen planus is important because it offers benefits for periodontal health. However, more long-term studies are needed to confirm the results obtained.

  12. Use of clinical and computed tomography findings to assess long-term unsatisfactory outcome after femoral head and neck ostectomy in four large breed dogs.

    PubMed

    Ober, Ciprian; Pestean, Cosmin; Bel, Lucia; Taulescu, Marian; Milgram, Joshua; Todor, Adrian; Ungur, Rodica; Leșu, Mirela; Oana, Liviu

    2018-05-10

    Femoral head and neck ostectomy (FHNO) is a salvage surgical procedure intended to eliminate hip joint laxity associated pain in the immature dog, or pain due to secondary osteoarthritis in the mature dog. The outcome of the procedure is associated with the size of the dog but the cause of a generally poorer outcome in larger breeds has not been determined. The objective of this study was to assess the long-term results of FHNO associated with unsatisfactory functional outcome by means of clinical examination and computed tomography (CT) scanning. Four large mixed breed dogs underwent FHNO in different veterinary clinics. Clinical and CT scanning evaluations were carried out long time after the procedures had been done. Hip pain, muscle atrophy, decreased range of motion and chronic lameness were observed at clinical examination. Extensive remodelling, unacceptable bone-on-bone contact with bony proliferation involving the femoral neck and acetabulum, but also excessive removal with bone lysis were observed by CT scanning. Revision osteotomy was performed in one dog. Deep gluteal muscle interposition was used, but no improvements were observed postoperatively. This is the first report on the evaluation of three-dimensional CT reconstructions of the late bone remodelling associated with poor clinical outcome in large dogs. The study shows that FHNO could lead to severe functional deficits in large breed dogs. An extensive follow-study is necessary to more accurately determine the frequency of such complications.

  13. Real-time strategy video game experience and structural connectivity - A diffusion tensor imaging study.

    PubMed

    Kowalczyk, Natalia; Shi, Feng; Magnuski, Mikolaj; Skorko, Maciek; Dobrowolski, Pawel; Kossowski, Bartosz; Marchewka, Artur; Bielecki, Maksymilian; Kossut, Malgorzata; Brzezicka, Aneta

    2018-06-20

    Experienced video game players exhibit superior performance in visuospatial cognition when compared to non-players. However, very little is known about the relation between video game experience and structural brain plasticity. To address this issue, a direct comparison of the white matter brain structure in RTS (real time strategy) video game players (VGPs) and non-players (NVGPs) was performed. We hypothesized that RTS experience can enhance connectivity within and between occipital and parietal regions, as these regions are likely to be involved in the spatial and visual abilities that are trained while playing RTS games. The possible influence of long-term RTS game play experience on brain structural connections was investigated using diffusion tensor imaging (DTI) and a region of interest (ROI) approach in order to describe the experience-related plasticity of white matter. Our results revealed significantly more total white matter connections between occipital and parietal areas and within occipital areas in RTS players compared to NVGPs. Additionally, the RTS group had an altered topological organization of their structural network, expressed in local efficiency within the occipito-parietal subnetwork. Furthermore, the positive association between network metrics and time spent playing RTS games suggests a close relationship between extensive, long-term RTS game play and neuroplastic changes. These results indicate that long-term and extensive RTS game experience induces alterations along axons that link structures of the occipito-parietal loop involved in spatial and visual processing. © 2018 Wiley Periodicals, Inc.

  14. Assessment of long-term donor-site morbidity after harvesting the latissimus dorsi flap for neonatal myelomeningocele repair.

    PubMed

    Osinga, R; Mazzone, L; Meuli, M; Meuli-Simmen, C; von Campe, A

    2014-08-01

    The latissimus dorsi flap (LDF) has been employed very successfully over decades to cover large soft-tissue defects. Its donor-site morbidity has been extensively investigated in adults - but not in children - and is considered to be nonrestrictive. The aim of this long-term study was to assess donor-site morbidity with the modified Constant score more than 8 years after coverage of large myelomeningocele (MMC) defects with a reverse latissimus dorsi flap. Within the first days after birth, the reverse latissimus dorsi muscle flap was used uni- or bilaterally in three neonates to cover a large MMC defect. Bilateral shoulder function was tested more than 8 years postoperatively according to the modified Constant score. The mean age at follow-up was 11.7 years. None of the patients experienced any pain or shoulder restrictions during normal daily activities. They all managed to position both of their arms comfortably above the head. Forward flexion was normal in all patients as was abduction and external rotation. Dorsal extension was minimally reduced on the operated side. Internal rotation was symmetric in all patients; the extent of active movement varied from excellent to poor. Our long-term data suggest that there is no specific and significant impairment of shoulder function after using the distally pedicled reverse LDF for neonatal MMC repair. Copyright © 2014 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

  15. The Effects of Hypertension on Cognitive Function in Children and Adolescents

    PubMed Central

    Cha, Stephen D.; Patel, Hiren P.; Hains, David S.; Mahan, John D.

    2012-01-01

    Hypertension (HTN) is found in about 3-4% of the pediatric population with long-term risks of end organ damage if untreated or poorly controlled. Although children with HTN are being more frequently screened for end organ damage (i.e., LVH), the cognitive effects of HTN and methods to screen for cognitive dysfunction have not been extensively explored. In recent years, there have been a small number of studies that have provided important insights that can guide future research in this area. These studies show that HTN can be associated with headaches, restlessness, sleep disturbance, anxiety, depression, decreased attention, and also poor executive functioning. By increasing the utilization of cognitive tests in hypertensive children and adolescents, important cognitive defects secondary to HTN may be detected. More research is needed in the area, and the results of future studies could have far reaching implications for long-term outcomes in hypertensive children and adolescents. PMID:22518186

  16. Epidemiologic methods lessons learned from environmental public health disasters: Chernobyl, the World Trade Center, Bhopal, and Graniteville, South Carolina.

    PubMed

    Svendsen, Erik R; Runkle, Jennifer R; Dhara, Venkata Ramana; Lin, Shao; Naboka, Marina; Mousseau, Timothy A; Bennett, Charles

    2012-08-01

    Environmental public health disasters involving hazardous contaminants may have devastating effects. While much is known about their immediate devastation, far less is known about long-term impacts of these disasters. Extensive latent and chronic long-term public health effects may occur. Careful evaluation of contaminant exposures and long-term health outcomes within the constraints imposed by limited financial resources is essential. Here, we review epidemiologic methods lessons learned from conducting long-term evaluations of four environmental public health disasters involving hazardous contaminants at Chernobyl, the World Trade Center, Bhopal, and Graniteville (South Carolina, USA). We found several lessons learned which have direct implications for the on-going disaster recovery work following the Fukushima radiation disaster or for future disasters. These lessons should prove useful in understanding and mitigating latent health effects that may result from the nuclear reactor accident in Japan or future environmental public health disasters.

  17. Zonisamide and renal calculi in patients with epilepsy: how big an issue?

    PubMed

    Wroe, Stephen

    2007-08-01

    To determine the prevalence of renal calculi in patients treated with zonisamide during randomized, controlled and open-label clinical trials, and from post-marketing surveillance data. Reports of renal calculi from four placebo-controlled double-blind trials of zonisamide, their long-term open-label treatment extension phases, and the US/European zonisamide clinical trial programme were reviewed. One double-blind study and its extension included routine ultrasound screening to identify asymptomatic calculi. Post-marketing surveillance data were also investigated, as was concomitant treatment with topiramate. No symptomatic renal calculi were reported during four randomized double-blind, placebo-controlled trials involving 848 subjects (including 498 zonisamide recipients) treated for up to 3 months. In long-term extension studies with treatment for up to 24 months, symptomatic renal calculi were reported in 9/626 (1.4%) patients. Pooled safety data from all US/European clinical trials identified 15/1296 (1.2%) patients with symptomatic renal calculi during treatment for up to 8.7 years. Post-marketing surveillance revealed nine cases from 59 667 patient-years of exposure in the USA, and 14 from 709 294 patient-years of exposure in Japan; only one case occurred during concomitant topiramate and zonisamide treatment. No imbalance in electrolyte levels was found from 35 patients receiving such co-treatment in clinical trials. The available data suggest that the risk of developing renal calculi during zonisamide treatment is low. Data are insufficient to determine whether concomitant treatment with topiramate increases the risk of renal stones.

  18. Considerations for long-term anticoagulant therapy in patients with venous thromboembolism in the novel oral anticoagulant era.

    PubMed

    Toth, Peter P

    2016-01-01

    Patients who have had a venous thromboembolic event are generally advised to receive anticoagulant treatment for 3 months or longer to prevent a recurrent episode. Current guidelines recommend initial heparin and an oral vitamin K antagonist (VKA) for long-term anticoagulation. However, because of the well-described disadvantages of VKAs, including extensive food and drug interactions and the need for regular anticoagulation monitoring, novel oral anticoagulants (NOACs) have become an attractive option in recent years. These agents are given at fixed doses and do not require routine coagulation-time monitoring. The NOACs are discussed in this review with regard to the needs of patients on long-term anticoagulation. Current guidelines from Europe and North America that refer to the treatment of deep vein thrombosis and/or pulmonary embolism are included, as well as published randomized Phase III clinical trials of NOACs. PubMed searches were used for sourcing case studies of long-term anticoagulant treatment, and results were filtered for human application and screened for relevance. NOAC-based therapy showed a similar efficacy and safety profile to heparins/VKAs but without the need for regular anticoagulation monitoring or dietary adjustments, and can be taken as a fixed-dose regimen once or twice daily. This represents a significant step forward in facilitating the management of long-term anticoagulation therapy. Furthermore, in the EINSTEIN studies, improved patient satisfaction was documented with the NOAC rivaroxaban, which may result in better adherence to therapy and an overall reduction in the incidence of recurrent venous thromboembolism.

  19. A Long-term Slip Model for the San Ramón Fault, Santiago de Chile, from Tectonically Reconcilable Boundary Conditions

    NASA Astrophysics Data System (ADS)

    Aron, F.; Estay, N.; Cembrano, J. M.; Yanez, G. A.

    2016-12-01

    We constructed a 3D Boundary Elements model simulating subduction of the Nazca plate underneath South America, from 29° to 38° S, to compute long-term surface deformation and slip rates on crustal faults imbedded in the upper-plate wedge of the Andean orogen. We tested our model on the San Ramón Fault (SRF), a major E-dipping, thrust structure limiting the western front of the Main Cordillera with surface expression along the entire, 40 km long, extension of the Santiago de Chile basin. Long-lived thrusting has produced more than 2 km of differential uplift of the mountains. Given its proximity to the country's largest city, this potentially seismogenic fault —dormant during historic times— has drawn increasing public attention. We used earthquake hypocenters captured over a one-year seismic deployment, 2D resistivity profiles, and published geologic cross-sections to determine the geometry of the SRF. The base of the lithosphere and plate interface surfaces were defined based on average Andean values and the Slab1.0 model. The simulation reproduces plate convergence and mechanic decoupling of the lithospheric plates across the subduction seismic cycle using mixed boundary conditions. Relative plate motion is achieved prescribing uniform, far-field horizontal displacement over the depth extension of both the oceanic and continental lithospheric plates. Long-term deformation is carried out in two steps. First, the modeled surfaces are allowed to slip freely emulating continuous slip on the subduction megathrust; subsequently, zero displacement is prescribed on the locking zone of the megathrust down to 40 km depth, while keeping the rest of the surfaces traction free, mimicking interseismic conditions. Long-term slip rate fields obtained for the SRF range between 0.1 and 1% the plate convergence rate, with maximum values near the surface. Interestingly, at an estimated 76-77 mm/yr relative plate motion velocity, those rates agree well with what has been reported on studies at one paleoseismic trench site across the fault. These results might contribute to determining possible seismic scenarios for Santiago but perhaps more importantly, our approach could be use in estimations of long-term slip rates and surface deformation due to other crustal structures with unknown displacement history.

  20. Let Peter Rabbit Play in the Garden: Using Beatrix Potter's Work to Integrate Ecological Literacy into Montessori Classrooms

    ERIC Educational Resources Information Center

    Johnson, Kelly

    2015-01-01

    Kelly Johnson introduces a series of lessons that incorporate literacy, observation, botany, history, place studies, writing, and art, with a long-term eco-literacy goal of connectedness and a conservation ethic. Johnson's initial idea to use Beatrix Potter as a model in the Lower Elementary classroom came after extensively researching…

  1. Two-Year Safety and Efficacy Experience in Patients with Methotrexate-Resistant Active Rheumatoid Arthritis Treated with Etanercept and Conventional Disease-Modifying Anti-rheumatic Drugs in the Latin American Region

    PubMed Central

    Machado, Daniel A.; Guzman, Renato; Xavier, Ricardo M.; Simon, Jesus A.; Mele, Linda; Shen, Qi; Pedersen, Ronald; Kotak, Sameer; Vlahos, Bonnie

    2016-01-01

    Background: Although long-term data are available from biologic studies in North American/European populations with rheumatoid arthritis (RA), long-term findings in Latin American RA populations are limited. Objective: To examine long-term safety/efficacy of etanercept, methotrexate, and/or other disease-modifying anti-rheumatic drugs (DMARDs) in Latin American patients with moderate-to-severe active RA. Methods: In the first phase of this open-label study, patients were randomized to etanercept 50 mg weekly plus methotrexate or conventional DMARD (hydroxychloroquine or sulfasalazine) plus methotrexate for 24 weeks. At the start of the second phase (week 24), investigators selected a treatment regimen that included any combination/dosage of etanercept, methotrexate, hydroxychloroquine, or sulfasalazine based on previous treatment response, preference, and local product labeling, and was continued for the 104-week extension. Results: In the extension, in the group previously randomized to etanercept-plus-methotrexate therapy, etanercept was continued in 259/260 patients; methotrexate continued in 260/260; and hydroxychloroquine and sulfasalazine added in 8/260 and 3/260, respectively. In the group previously randomized to conventional DMARD-plus-methotrexate therapy, conventional DMARD was discontinued in 86/126 and etanercept added in 105/126. Among etanercept-exposed patients (total exposure, 798.1 patient-year [PY]), rates of adverse events, serious adverse events, and serious infections per PY were 1.7, 0.07, and 0.02 events per PY. In both groups, after treatment modification was permitted, clinical response rates and improvements in clinical/patient-reported outcomes from baseline were sustained to week 128. Conclusion: After investigators were permitted to modify treatment, etanercept was part of the treatment regimen in 95% of patients. Continuation or addition of etanercept in the 2-year extension resulted in a consistently good risk:benefit profile. Trial Registration: Open-Label Study Comparing Etanercept to Conventional Disease Modifying Antirheumatic Drug (DMARD) Therapy; ClinicalTrials.gov, number NCT00848354; https://clinicaltrials.gov/ct2/show/NCT00848354 PMID:27006728

  2. The Qatar Biobank: background and methods.

    PubMed

    Al Kuwari, Hanan; Al Thani, Asma; Al Marri, Ajayeb; Al Kaabi, Abdulla; Abderrahim, Hadi; Afifi, Nahla; Qafoud, Fatima; Chan, Queenie; Tzoulaki, Ioanna; Downey, Paul; Ward, Heather; Murphy, Neil; Riboli, Elio; Elliott, Paul

    2015-12-03

    The Qatar Biobank aims to collect extensive lifestyle, clinical, and biological information from up to 60,000 men and women Qatari nationals and long-term residents (individuals living in the country for ≥15 years) aged ≥18 years (approximately one-fifth of all Qatari citizens), to follow up these same individuals over the long term to record any subsequent disease, and hence to study the causes and progression of disease, and disease burden, in the Qatari population. Between the 11(th)-December-2012 and 20(th)-February-2014, 1209 participants were recruited into the pilot study of the Qatar Biobank. At recruitment, extensive phenotype information was collected from each participant, including information/measurements of socio-demographic factors, prevalent health conditions, diet, lifestyle, anthropometry, body composition, bone health, cognitive function, grip strength, retinal imaging, total body dual energy X-ray absorptiometry, and measurements of cardiovascular and respiratory function. Blood, urine, and saliva were collected and stored for future research use. A panel of 66 clinical biomarkers was routinely measured on fresh blood samples in all participants. Rates of recruitment are to be progressively increased in the coming period and the recruitment base widened to achieve a cohort of consented individuals broadly representative of the eligible Qatari population. In addition, it is planned to add additional measures in sub-samples of the cohort, including Magnetic Resonance Imaging (MRI) of the brain, heart and abdomen. The mean time for collection of the extensive phenotypic information and biological samples from each participant at the baseline recruitment visit was 179 min. The 1209 pilot study participants (506 men and 703 women) were aged between 28-80 years (median 39 years); 899 (74.4%) were Qatari nationals and 310 (25.6%) were long-term residents. Approximately two-thirds of pilot participants were educated to graduate level or above. The pilot has proven that recruitment of volunteers into the Qatar Biobank project with intensive baseline measurements of behavioural, physical, and clinical characteristics is well accepted and logistically feasible. Qatar Biobank will provide a powerful resource to investigate the major determinants of ill-health and well-being in Qatar, providing valuable insights into the current and future public health burden that faces the country.

  3. Logo Effects on Brand Extension Evaluations from the Electrophysiological Perspective.

    PubMed

    Shang, Qian; Pei, Guanxiong; Dai, Shenyi; Wang, Xiaoyi

    2017-01-01

    Brand extension typically has two strategies: brand name extension (BN) and brand logo extension (BL). The current study explored which strategy (BN or BL) better enhanced the success of dissimilar brand extension and product promotion in enterprises. Event-related potentials (ERPs) were used to investigate electrophysiological processes when subjects evaluated their acceptance of the brand extension using a combined picture of S1 and S2. S1 was a famous brand presented by two identity signs (brand name and brand logo). S2 was a picture of an extension product that belonged to a dissimilar product category than S1. The behavior data showed that BL was more acceptable than BN in the dissimilar brand extension. The neurophysiology process was reflected by a less negative N2 component and a larger P300 component in the BL than in the BN. We suggested that N2 reflected a whole conflict between the brand-product combination and the long-term memory and that P300 could be regarded as the reflection of the categorization process in the working memory.

  4. Logo Effects on Brand Extension Evaluations from the Electrophysiological Perspective

    PubMed Central

    Shang, Qian; Pei, Guanxiong; Dai, Shenyi; Wang, Xiaoyi

    2017-01-01

    Brand extension typically has two strategies: brand name extension (BN) and brand logo extension (BL). The current study explored which strategy (BN or BL) better enhanced the success of dissimilar brand extension and product promotion in enterprises. Event-related potentials (ERPs) were used to investigate electrophysiological processes when subjects evaluated their acceptance of the brand extension using a combined picture of S1 and S2. S1 was a famous brand presented by two identity signs (brand name and brand logo). S2 was a picture of an extension product that belonged to a dissimilar product category than S1. The behavior data showed that BL was more acceptable than BN in the dissimilar brand extension. The neurophysiology process was reflected by a less negative N2 component and a larger P300 component in the BL than in the BN. We suggested that N2 reflected a whole conflict between the brand-product combination and the long-term memory and that P300 could be regarded as the reflection of the categorization process in the working memory. PMID:28337121

  5. Alteration in certain enzymological parameters of an Indian major carp, Cirrhinus mrigala exposed to short- and long-term exposure of clofibric acid and diclofenac.

    PubMed

    Saravanan, Manoharan; Ramesh, Mathan; Petkam, Rakpong

    2013-12-01

    The extensive use of pharmaceuticals in human and veterinary medicine may enter the aquatic environment and pose a serious threat to non-target aquatic organisms like fish. In this study, Indian major carp Cirrhinus mrigala was exposed to different concentrations (1, 10 and 100 μg L⁻¹) of most commonly used pharmaceutical drugs clofibric acid (CA) and diclofenac (DCF) to evaluate its impacts on certain enzymological parameters during short- and long-term exposures. During short-term (96 h) exposure period, plasma glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT) and gill Na⁺/K⁺-ATPase activity were significantly altered at all concentrations of both the CA- and DCF-treated fish. In long-term exposure (35 days), gill Na⁺/K⁺-ATPase activity was found to be significantly increased at all concentration of CA and DCF exposures throughout the study period (except at the end of 7th day in 10 and 100 µg L⁻¹) . However, a biphasic trend was observed in plasma GOT and GPT activity when compared to the control groups. In both short- and long-term exposure, a significant (P < 0.01 and P < 0.05) changes were observed in all enzymological parameters of fish C. mrigala exposed to different concentrations of CA and DCF. The alterations of these enzymological parameters can be effectively used as potential biomarkers in monitoring of pharmaceutical toxicity in aquatic environment and organisms.

  6. Bone quality and the immediate loading of implants-critical aspects based on literature, research, and clinical experience.

    PubMed

    Romanos, Georgios E

    2009-06-01

    Immediate loading of oral implants has been extensively described in the international literature and the requirements for long-term success are evaluated. The author presents here the critical aspects of the criteria for success as well as describes the characteristics of an implant macro- and microdesign for immediate loading to control the periimplant crestal bone loss and secure the long-term stability. Information from the literature and the clinical experience will be presented.

  7. Clinical relevance of the effects of reach-to-grasp training using trunk restraint in individuals with hemiparesis poststroke: A systematic review.

    PubMed

    Greisberger, Andrea; Aviv, Hanna; Garbade, Sven F; Diermayr, Gudrun

    2016-04-28

    To evaluate the evidence for, and clinical relevance of, immediate and long-term effects of trunk restraint during reach-to-grasp training poststroke on movement patterns and functional abilities within the framework of the International Classification of Functioning, Disability and Health. PubMed, Web of Science, CINAHL, Embase, PEDro, Cochrane Library (publication dates January 1985 to March 2015). Randomized controlled trials comparing training using trunk restraint with any other exercise training. Data were extracted by one researcher and checked by two other researchers. The Cochrane Collaboration's tool for assessing risk of bias and the Physiotherapy Evidence Database scale were used by two researchers to assess study quality and risk of bias. Eight studies met the inclusion criteria. Five studies found better recovery of movement patterns (trunk displacement, elbow extension, and/or shoulder flexion - body function/structure) at post-test in the experimental compared with the control groups. Functional abilities (activity/participation) improved more in the experimental groups in 3 studies at post-test. Long-term effects were found in one study after 4 weeks. Trunk restraint has immediate and some long-term effects in adults with chronic stroke. However, these effects are not consistently clinically relevant when referring to minimal detectable change or minimal clinically important difference values.

  8. Long-term outcome in BRAF(V600E) melanoma patients treated with vemurafenib: Patterns of disease progression and clinical management of limited progression.

    PubMed

    Puzanov, Igor; Amaravadi, Ravi K; McArthur, Grant A; Flaherty, Keith T; Chapman, Paul B; Sosman, Jeffrey A; Ribas, Antoni; Shackleton, Mark; Hwu, Patrick; Chmielowski, Bartosz; Nolop, Keith B; Lin, Paul S; Kim, Kevin B

    2015-07-01

    Vemurafenib induces tumour regression in most patients with BRAF(V600E)-mutant melanoma; eventually, most experience progressive disease (PD). Long-term follow-up of patients with BRAF(V600E) melanoma treated in the phase 1 vemurafenib trial is reported. Patients received vemurafenib 240-1120 mg (dose escalation cohort) or 960 mg (extension cohort) orally twice daily. Clinical response was evaluated every 8 weeks by Response Evaluation Criteria In Solid Tumors (RECIST). Patients with PD amenable to local therapy (surgery or radiotherapy) were allowed to continue vemurafenib after progression. Overall survival (OS) from time of treatment initiation and from PD was estimated. Sites of PD were recorded. Forty-eight patients (escalation cohort, n = 16; extension cohort, n = 32) received therapeutic doses of vemurafenib (⩾ 240 mg twice daily). Forty-four patients had PD by the time of this analysis and four remained progression free (follow-up time, 1.2-56.1 months). Median OS was 14 months (range, 1.2-56.1); 3- and 4-year melanoma-specific survival rate in the extension cohort was 26% and 19%, respectively. Median OS was 26.0 months (range, 7.7-56.1) among 20 patients who continued vemurafenib after local therapy. Median treatment duration beyond initial PD was 3.8 months (range, 1.1-26.6). In the extension cohort, six and five patients were alive after 3 and 4 years, respectively, on vemurafenib monotherapy. Some patients with melanoma achieved long-term survival with vemurafenib monotherapy. Continuation of vemurafenib after PD might be beneficial in some patients because remaining disease might continue to respond to BRAF inhibition. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. A comparison of four streamflow record extension techniques

    USGS Publications Warehouse

    Hirsch, Robert M.

    1982-01-01

    One approach to developing time series of streamflow, which may be used for simulation and optimization studies of water resources development activities, is to extend an existing gage record in time by exploiting the interstation correlation between the station of interest and some nearby (long-term) base station. Four methods of extension are described, and their properties are explored. The methods are regression (REG), regression plus noise (RPN), and two new methods, maintenance of variance extension types 1 and 2 (MOVE.l, MOVE.2). MOVE.l is equivalent to a method which is widely used in psychology, biometrics, and geomorphology and which has been called by various names, e.g., ‘line of organic correlation,’ ‘reduced major axis,’ ‘unique solution,’ and ‘equivalence line.’ The methods are examined for bias and standard error of estimate of moments and order statistics, and an empirical examination is made of the preservation of historic low-flow characteristics using 50-year-long monthly records from seven streams. The REG and RPN methods are shown to have serious deficiencies as record extension techniques. MOVE.2 is shown to be marginally better than MOVE.l, according to the various comparisons of bias and accuracy.

  10. A Comparison of Four Streamflow Record Extension Techniques

    NASA Astrophysics Data System (ADS)

    Hirsch, Robert M.

    1982-08-01

    One approach to developing time series of streamflow, which may be used for simulation and optimization studies of water resources development activities, is to extend an existing gage record in time by exploiting the interstation correlation between the station of interest and some nearby (long-term) base station. Four methods of extension are described, and their properties are explored. The methods are regression (REG), regression plus noise (RPN), and two new methods, maintenance of variance extension types 1 and 2 (MOVE.l, MOVE.2). MOVE.l is equivalent to a method which is widely used in psychology, biometrics, and geomorphology and which has been called by various names, e.g., `line of organic correlation,' `reduced major axis,' `unique solution,' and `equivalence line.' The methods are examined for bias and standard error of estimate of moments and order statistics, and an empirical examination is made of the preservation of historic low-flow characteristics using 50-year-long monthly records from seven streams. The REG and RPN methods are shown to have serious deficiencies as record extension techniques. MOVE.2 is shown to be marginally better than MOVE.l, according to the various comparisons of bias and accuracy.

  11. Platelet-Derived Growth Factor Promotes Periodontal Regeneration in Localized Osseous Defects: 36-Month Extension Results From a Randomized, Controlled, Double-Masked Clinical Trial

    PubMed Central

    Nevins, Myron; Kao, Richard T.; McGuire, Michael K.; McClain, Pamela K.; Hinrichs, James E.; McAllister, Bradley S.; Reddy, Michael S.; Nevins, Marc L.; Genco, Robert J.; Lynch, Samuel E.; Giannobile, William V.

    2017-01-01

    Background Recombinant human platelet-derived growth factor (rhPDGF) is safe and effective for the treatment of periodontal defects in short-term studies up to 6 months in duration. We now provide results from a 36-month extension study of a multicenter, randomized, controlled clinical trial evaluating the effect and long-term stability of PDGF-BB treatment in patients with localized severe periodontal osseous defects. Methods A total of 135 participants were enrolled fromsix clinical centers for an extension trial. Eighty-three individuals completed the study at 36 months and were included in the analysis. The study investigated the local application of β-tricalcium phosphate scaffold matrix with or without two different dose levels of PDGF (0.3 or 1.0 mg/mL PDGF-BB) in patients possessing one localized periodontal osseous defect. Composite analysis for clinical and radiographic evidence of treatment success was defined as percentage of cases with clinical attachment level (CAL) ≥2.7mmand linear bone growth (LBG) ≥1.1 mm. Results The participants exceeding this composite outcome benchmark in the 0.3 mg/mL rhPDGF-BB group went from 62.2% at 12 months, 75.9% at 24 months, to 87.0% at 36 months compared with 39.5%, 48.3%, and 53.8%, respectively, in the scaffold control group at these same time points (P <0.05). Although there were no significant increases in CAL and LBG at 36 months among all groups, there were continued increases in CAL gain, LBG, and percentage bone fill over time, suggesting overall stability of the regenerative response. Conclusion PDGF-BB in a synthetic scaffold matrix promotes long-term stable clinical and radiographic improvements as measured by composite outcomes for CAL gain and LBG for patients possessing localized periodontal defects (ClinicalTrials.gov no. CT01530126). PMID:22612364

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

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

    Marvy, A.; Lioure, A; Heriard-Dubreuil, G.

    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 periodsmore » 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.« less

  13. 43 CFR 3135.1-5 - Extension of lease.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... MANAGEMENT, DEPARTMENT OF THE INTERIOR MINERALS MANAGEMENT (3000) OIL AND GAS LEASING: NATIONAL PETROLEUM...) The term of a lease shall be extended beyond its primary term: (1) So long as oil or gas is produced from the lease in paying quantities; (2) If the BLM has determined in writing that oil or gas is...

  14. 43 CFR 3135.1-5 - Extension of lease.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... MANAGEMENT, DEPARTMENT OF THE INTERIOR MINERALS MANAGEMENT (3000) OIL AND GAS LEASING: NATIONAL PETROLEUM...) The term of a lease shall be extended beyond its primary term: (1) So long as oil or gas is produced from the lease in paying quantities; (2) If the BLM has determined in writing that oil or gas is...

  15. 43 CFR 3135.1-5 - Extension of lease.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... MANAGEMENT, DEPARTMENT OF THE INTERIOR MINERALS MANAGEMENT (3000) OIL AND GAS LEASING: NATIONAL PETROLEUM...) The term of a lease shall be extended beyond its primary term: (1) So long as oil or gas is produced from the lease in paying quantities; (2) If the BLM has determined in writing that oil or gas is...

  16. Interaction of inhibitory and facilitatory effects of conditioning trials on long-term memory formation

    PubMed Central

    Hosono, Shouhei; Matsumoto, Yukihisa

    2016-01-01

    Animals learn through experience and consolidate the memories into long-time storage. Conditioning parameters to induce protein synthesis-dependent long-term memory (LTM) have been the subject of extensive studies in many animals. Here we found a case in which a conditioning trial inhibits or facilitates LTM formation depending on the intervals from preceding trials. We studied the effects of conditioning parameters on LTM formation in olfactory conditioning of maxillary-palpi extension response with sucrose reward in the cockroach Periplaneta americana. We found, at first, that translation- and transcription-dependent LTM forms 1 h after training, the fastest so far reported in insects. Second, we observed that multiple-trial training with an intertrial interval (ITI) of 20 or 30 sec, often called massed training, is more effective than spaced training for LTM formation, an observation that differs from the results of most studies in other animals. Third, we found that a conditioning trial inhibits LTM formation when the intervals from preceding trials were in the range of 10–16 min. This inhibitory effect is pairing-specific and is not due to decreased motivation for learning (overtraining effect). To our knowledge, no similar inhibition of LTM formation by a conditioning trial has been reported in any animals. We propose a model to account for the effects of trial number and ITIs on LTM formation. Olfactory conditioning in cockroaches should provide pertinent materials in which to study neuronal and molecular mechanisms underlying the inhibitory and facilitatory processes for LTM formation. PMID:27918270

  17. Microcircuits in the Nervous System

    ERIC Educational Resources Information Center

    Shepherd, Gordon M.

    1978-01-01

    Nerve circuits are usually analyzed in terms of the axon, the long fiber of the nerve cell. It now appears that there are many circuits involving only the nerve cell's shorter extensions, the dendrites. (Author/BB)

  18. Sustained, long-term renal stabilization after 54 months of agalsidase beta therapy in patients with Fabry disease.

    PubMed

    Germain, Dominique P; Waldek, Stephen; Banikazemi, Maryam; Bushinsky, David A; Charrow, Joel; Desnick, Robert J; Lee, Philip; Loew, Thomas; Vedder, Anouk C; Abichandani, Rekha; Wilcox, William R; Guffon, Nathalie

    2007-05-01

    Fabry disease, an inherited deficiency of the lysosomal enzyme alpha-galactosidase A, causes progressive intralysosomal accumulation of globotriaosylceramide (GL-3) and premature death from renal, cardiac, and cerebrovascular manifestations. To determine the long-term safety and efficacy of recombinant human alpha-galactosidase A, an open-label, phase III extension study was conducted, involving 58 patients who had classic Fabry disease and completed a 20-wk, double-blind, randomized, placebo-controlled, phase III study of agalsidase beta and were transitioned to an extension trial to receive biweekly 1 mg/kg agalsidase beta for up to an additional 54 mo. GL-3 accumulation was evaluated in the capillary endothelia of the skin, kidney, and heart. Renal function was assessed. By month 54, all patients with optional kidney biopsies (n = 8) maintained complete GL-3 clearance in renal capillary endothelial cells and multiple cell types. Continued, complete clearance of skin (31 of 36) and heart (six of eight) capillary endothelium was demonstrated. Mean plasma GL-3 levels remained decreased in the normal range. Median serum creatinine and estimated GFR remained stable (normal) in patients with renal data at month 54 (n = 41). Six patients had renal disease progression; most (four of six) were older than 40 yr and had significant proteinuria at baseline and evidence of sclerotic glomeruli pretreatment. Adverse events were generally mild and unrelated to treatment. The most common treatment-related adverse events were infusion-associated reactions, which decreased over time. Long-term agalsidase beta therapy stabilizes renal function in patients without renal involvement at baseline, maintains reduction of plasma GL-3, and sustains GL-3 clearance in capillary endothelial cells and multiple renal cell types.

  19. Durability of Therapeutic Response With Long-Term Aripiprazole Lauroxil Treatment Following Successful Resolution of an Acute Episode of Schizophrenia.

    PubMed

    McEvoy, Joseph P; Risinger, Robert; Mykhnyak, Serhiy; Du, Yangchun; Liu, Chih-Chin; Stanford, Arielle D; Weiden, Peter J

    To evaluate durability of therapeutic effect of long-term treatment with aripiprazole lauroxil in patients with schizophrenia following successful treatment of an acute psychotic episode. This post hoc analysis assessed long-term outcomes for a subgroup of patients who entered a 52-week extension study after being successfully stabilized with one of 2 doses of aripiprazole lauroxil (441 or 882 mg) in a pivotal 12-week, placebo-controlled, randomized clinical trial. Durability of therapeutic effect was measured by the proportion of patients completing the 1-year course of aripiprazole lauroxil, the trajectories of the Positive and Negative Syndrome Scale (PANSS) total and the Clinical Global Impression-Severity (CGI-S) item scores beyond the first 12 weeks, and the likelihood of remission at any follow-up point. In total, 181 patients treated with aripiprazole lauroxil entered the extension study; 73% and 66% of patients from the 441 mg and 882 mg groups, respectively, completed all 13 aripiprazole lauroxil treatments scheduled every 4 weeks over 52 weeks. Both groups continued on a positive trajectory of symptom improvements (P < .0001 for reductions in PANSS total and CGI-S scores from week 12 to end of follow-up). Most patients (74% and 68% in the aripiprazole lauroxil 441 mg and 882 mg groups, respectively) achieved remission during follow-up. These post hoc analyses of a subgroup of patients demonstrate the continued therapeutic efficacy of aripiprazole lauroxil after successful treatment of an acute episode of schizophrenia. Both the 441 mg and 882 mg groups had similar retention rates, degree of symptom improvement, and likelihood of remission. ClinicalTrials.gov identifier: NCT01469039; European Clinical Trials Database (EudraCT) numbers: 2012-003445-15 and 2012-003996-20​​​​. © Copyright 2017 Physicians Postgraduate Press, Inc.

  20. The influence of time horizon on results of cost-effectiveness analyses.

    PubMed

    Kim, David D; Wilkinson, Colby L; Pope, Elle F; Chambers, James D; Cohen, Joshua T; Neumann, Peter J

    2017-12-01

    Debates persist on the appropriate time horizon from a payer's perspective and how the time horizon in cost-effectiveness analysis (CEA) influences the value assessment. We systematically reviewed the Tufts Medical Center CEA Registry and identified US-based studies that used a payer perspective from 2005-2014. We classified the identified CEAs as short-term (time horizon ≤ 5 years) and long-term (> 5 years), and examined associations between study characteristics and the specified time horizon. We also developed case studies with selected interventions to further explore the relationship between time horizon and projected costs, benefits, and incremental cost-effectiveness ratios (ICER). Among 782 identified studies that met our inclusion criteria, 552 studies (71%) utilized a long-term time horizon while 198 studies (25%) used a short-term horizon. Among studies that employed multiple time horizons, the extension of the time horizon yielded more favorable ICERs in 19 cases and less favorable ICERs in 4 cases. Case studies showed the use of a longer time horizon also yielded more favorable ICERs. The assumed time horizon in CEAs can substantially influence the value assessment of medical interventions. To capture all consequences, we encourage the use of time horizons that extend sufficiently into the future.

  1. Use long short-term memory to enhance Internet of Things for combined sewer overflow monitoring

    NASA Astrophysics Data System (ADS)

    Zhang, Duo; Lindholm, Geir; Ratnaweera, Harsha

    2018-01-01

    Combined sewer overflow causes severe water pollution, urban flooding and reduced treatment plant efficiency. Understanding the behavior of CSO structures is vital for urban flooding prevention and overflow control. Neural networks have been extensively applied in water resource related fields. In this study, we collect data from an Internet of Things monitoring CSO structure and build different neural network models for simulating and predicting the water level of the CSO structure. Through a comparison of four different neural networks, namely multilayer perceptron (MLP), wavelet neural network (WNN), long short-term memory (LSTM) and gated recurrent unit (GRU), the LSTM and GRU present superior capabilities for multi-step-ahead time series prediction. Furthermore, GRU achieves prediction performances similar to LSTM with a quicker learning curve.

  2. Lessons learned from long-term ecosystem research and monitoring in alpine and subalpine basins of the Colorado Rocky Mountains, USA

    USGS Publications Warehouse

    Baron, Jill S.

    2001-01-01

    Long-term ecosystem research and monitoring was begun in the Loch Vale watershed of Rocky Mountain National Park in 1983, after extensive survey work to identify the best location. Then, as now, our scientific objectives were to understand natural biogeochemical cycles and variability, so that we could differentiate ecosystem changes from human-caused disturbances, such as atmospheric deposition of pollutants and climate change. We have learned many lessons, often through our mistakes, that are worth passing on. Clear scientific objectives, even for long-term monitoring, are essential. Standardized methods, including rigorous quality assurance procedures should be adhered to from the beginning of the program. All data, even those collected routinely for background records, should be scrutinized and summarized at least once a year. Freely share basic information such as weather, hydrologic, chemical, and descriptive records with other researchers who can build upon your efforts. Use many tools when asking complex ecological questions, in order to minimize bias toward specific results. Publish frequently; long-term studies do not imply there are no interim conclusions or interesting findings. Interpret findings frequently to policy makers and citizens; increased understanding of the environment and human-caused changes may improve natural resource management, and build support for ecological research. And finally, be persistent. Long-term ecological research can be frustrating and difficult to maintain, yet is often the best way to observe and understand ecological change on a meaningful time scale.

  3. Simple surface engineering of polydimethylsiloxane with polydopamine for stabilized mesenchymal stem cell adhesion and multipotency

    PubMed Central

    Chuah, Yon Jin; Koh, Yi Ting; Lim, Kaiyang; Menon, Nishanth V.; Wu, Yingnan; Kang, Yuejun

    2015-01-01

    Polydimethylsiloxane (PDMS) has been extensively exploited to study stem cell physiology in the field of mechanobiology and microfluidic chips due to their transparency, low cost and ease of fabrication. However, its intrinsic high hydrophobicity renders a surface incompatible for prolonged cell adhesion and proliferation. Plasma-treated or protein-coated PDMS shows some improvement but these strategies are often short-lived with either cell aggregates formation or cell sheet dissociation. Recently, chemical functionalization of PDMS surfaces has proved to be able to stabilize long-term culture but the chemicals and procedures involved are not user- and eco-friendly. Herein, we aim to tailor greener and biocompatible PDMS surfaces by developing a one-step bio-inspired polydopamine coating strategy to stabilize long-term bone marrow stromal cell culture on PDMS substrates. Characterization of the polydopamine-coated PDMS surfaces has revealed changes in surface wettability and presence of hydroxyl and secondary amines as compared to uncoated surfaces. These changes in PDMS surface profile contribute to the stability in BMSCs adhesion, proliferation and multipotency. This simple methodology can significantly enhance the biocompatibility of PDMS-based microfluidic devices for long-term cell analysis or mechanobiological studies. PMID:26647719

  4. Long-Term Safety and Efficacy of Enzyme Replacement Therapyfor Fabry Disease

    PubMed Central

    Wilcox, William R.; Banikazemi, Maryam; Guffon, Nathalie; Waldek, Stephen; Lee, Philip; Linthorst, Gabor E.; Desnick, Robert J.; Germain, Dominique P.

    2004-01-01

    Elsewhere, we reported the safety and efficacy results of a multicenter phase 3 trial of recombinant human α-galactosidase A (rh-αGalA) replacement in patients with Fabry disease. All 58 patients who were enrolled in the 20-wk phase 3 double-blind, randomized, and placebo-controlled study received subsequently 1 mg/kg of rh-αGalA (agalsidase beta, Fabrazyme, Genzyme Corporation) biweekly in an ongoing open-label extension study. Evidence of long-term efficacy, even in patients who developed IgG antibodies against rh-αGalA, included the continuously normal mean plasma globotriaosylceramide (GL-3) levels during 30 mo of the extension study and the sustained capillary endothelial GL-3 clearance in 98% (39/40) of patients who had a skin biopsy taken after treatment for 30 mo (original placebo group) or 36 mo (original enzyme-treated group). The mean serum creatinine level and estimated glomerular filtration rate also remained stable after 30–36 mo of treatment. Infusion-associated reactions decreased over time, as did anti-rh-αGalA IgG antibody titers. Among seroconverted patients, after 30–36 mo of treatment, seven patients tolerized (no detectable IgG antibody), and 59% had ⩾4-fold reductions in antibody titers. As of 30 mo into the extension trial, three patients were withdrawn from the study because of positive serum IgE or skin tests; however, all have been rechallenged successfully at the time of this report. Thus, enzyme replacement therapy for 30–36 mo with agalsidase beta resulted in continuously decreased plasma GL-3 levels, sustained endothelial GL-3 clearance, stable kidney function, and a favorable safety profile. PMID:15154115

  5. Long-term safety and efficacy of enzyme replacement therapy for Fabry disease.

    PubMed

    Wilcox, William R; Banikazemi, Maryam; Guffon, Nathalie; Waldek, Stephen; Lee, Philip; Linthorst, Gabor E; Desnick, Robert J; Germain, Dominique P

    2004-07-01

    Elsewhere, we reported the safety and efficacy results of a multicenter phase 3 trial of recombinant human alpha -galactosidase A (rh-alpha GalA) replacement in patients with Fabry disease. All 58 patients who were enrolled in the 20-wk phase 3 double-blind, randomized, and placebo-controlled study received subsequently 1 mg/kg of rh-alpha GalA (agalsidase beta, Fabrazyme, Genzyme Corporation) biweekly in an ongoing open-label extension study. Evidence of long-term efficacy, even in patients who developed IgG antibodies against rh- alpha GalA, included the continuously normal mean plasma globotriaosylceramide (GL-3) levels during 30 mo of the extension study and the sustained capillary endothelial GL-3 clearance in 98% (39/40) of patients who had a skin biopsy taken after treatment for 30 mo (original placebo group) or 36 mo (original enzyme-treated group). The mean serum creatinine level and estimated glomerular filtration rate also remained stable after 30-36 mo of treatment. Infusion-associated reactions decreased over time, as did anti-rh- alpha GalA IgG antibody titers. Among seroconverted patients, after 30-36 mo of treatment, seven patients tolerized (no detectable IgG antibody), and 59% had > or =4-fold reductions in antibody titers. As of 30 mo into the extension trial, three patients were withdrawn from the study because of positive serum IgE or skin tests; however, all have been rechallenged successfully at the time of this report. Thus, enzyme replacement therapy for 30-36 mo with agalsidase beta resulted in continuously decreased plasma GL-3 levels, sustained endothelial GL-3 clearance, stable kidney function, and a favorable safety profile.

  6. Simulating ungulate herbivory across forest landscapes: A browsing extension for LANDIS-II

    USGS Publications Warehouse

    DeJager, Nathan R.; Drohan, Patrick J.; Miranda, Brian M.; Sturtevant, Brian R.; Stout, Susan L.; Royo, Alejandro; Gustafson, Eric J.; Romanski, Mark C.

    2017-01-01

    Browsing ungulates alter forest productivity and vegetation succession through selective foraging on species that often dominate early succession. However, the long-term and large-scale effects of browsing on forest succession are not possible to project without the use of simulation models. To explore the effects of ungulates on succession in a spatially explicit manner, we developed a Browse Extension that simulates the effects of browsing ungulates on the growth and survival of plant species cohorts within the LANDIS-II spatially dynamic forest landscape simulation model framework. We demonstrate the capabilities of the new extension and explore the spatial effects of ungulates on forest composition and dynamics using two case studies. The first case study examined the long-term effects of persistently high white-tailed deer browsing rates in the northern hardwood forests of the Allegheny National Forest, USA. In the second case study, we incorporated a dynamic ungulate population model to simulate interactions between the moose population and boreal forest landscape of Isle Royale National Park, USA. In both model applications, browsing reduced total aboveground live biomass and caused shifts in forest composition. Simulations that included effects of browsing resulted in successional patterns that were more similar to those observed in the study regions compared to simulations that did not incorporate browsing effects. Further, model estimates of moose population density and available forage biomass were similar to previously published field estimates at Isle Royale and in other moose-boreal forest systems. Our simulations suggest that neglecting effects of browsing when modeling forest succession in ecosystems known to be influenced by ungulates may result in flawed predictions of aboveground biomass and tree species composition.

  7. Long-term tolerability of ethinylestradiol 20 μg/drospirenone 3 mg in a flexible extended regimen: results from a randomised, controlled, multicentre study.

    PubMed

    Klipping, Christine; Duijkers, Ingrid; Fortier, Michel P; Marr, Joachim; Trummer, Dietmar; Elliesen, Jörg

    2012-04-01

    This study was designed to assess the long-term safety and tolerability of a new flexible extended regimen of ethinylestradiol (EE) 20 μg/drospirenone (DRSP) 3 mg, which allows management of intracyclic (breakthrough) bleeding [flexible management of intracyclic (breakthrough) bleeding (MIB)], in comparison to conventional 28-day and fixed extended regimens. In this Phase III, multicentre, open-label study, women (aged 18-35 years) were randomised to EE/DRSP in the following regimens: flexible(MIB) (24-120 days' active hormonal intake followed by a 4-day tablet-free interval), conventional 28-day (24 days' active hormonal intake followed by a 4-day hormone-free interval) or fixed extended (120 days' uninterrupted active hormonal intake followed by a 4-day tablet-free interval) during a 1-year comparative phase. Thereafter, women entered a 1-year safety extension phase in which the majority received the flexible(MIB) regimen. Safety/tolerability outcomes were measured over 2 years. A separate analysis of certain safety parameters (endometrial, hormonal, lipid, haemostatic and metabolic variables) was conducted at two of the study centres. Results were analysed in 1067 and 783 women in the comparative and safety extension phases. Overall, 56.3% of women experienced ≥1 adverse event (AE) in the safety extension phase. Serious AEs occurred in 3.0%, 1.4% and 3.3% of women receiving the flexible(MIB), conventional and fixed extended regimens, respectively. No unexpected endometrial, hormonal, lipid, haemostatic or metabolic findings occurred with any of the three regimens. EE/DRSP in a flexible extended regimen with management of intracyclic (breakthrough) bleeding is well-tolerated and, when administered for up to 2 years, has a good safety profile comparable to other estrogen/progestogen oral contraceptives.

  8. Additional EIPC Study Analysis: Interim Report on High Priority Topics

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

    Hadley, Stanton W

    Between 2010 and 2012 the Eastern Interconnection Planning Collaborative (EIPC) conducted a major long-term resource and transmission study of the Eastern Interconnection (EI). With guidance from a Stakeholder Steering Committee (SSC) that included representatives from the Eastern Interconnection States Planning Council (EISPC) among others, the project was conducted in two phases. Phase 1 involved a long-term capacity expansion analysis that involved creation of eight major futures plus 72 sensitivities. Three scenarios were selected for more extensive transmission- focused evaluation in Phase 2. Five power flow analyses, nine production cost model runs (including six sensitivities), and three capital cost estimations weremore » developed during this second phase. The results from Phase 1 and 2 provided a wealth of data that could be examined further to address energy-related questions. A list of 13 topics was developed for further analysis; this paper discusses the first five.« less

  9. Chemical stabilization of metals and arsenic in contaminated soils using oxides--a review.

    PubMed

    Komárek, Michael; Vaněk, Aleš; Ettler, Vojtěch

    2013-01-01

    Oxides and their precursors have been extensively studied, either singly or in combination with other amendments promoting sorption, for in situ stabilization of metals and As in contaminated soils. This remediation option aims at reducing the available fraction of metal(loid)s, notably in the root zone, and thus lowering the risks associated with their leaching, ecotoxicity, plant uptake and human exposure. This review summarizes literature data on mechanisms involved in the immobilization process and presents results from laboratory and field experiments, including the subsequent influence on higher plants and aided phytostabilization. Despite the partial successes in the field, recent knowledge highlights the importance of long-term and large-scale field studies evaluating the stability of the oxide-based amendments in the treated soils and their efficiency in the long-term. Copyright © 2012 Elsevier Ltd. All rights reserved.

  10. Variability in electromagnetic field levels over time, and Monte-Carlo simulation of exposure parameters.

    PubMed

    Pachón-García, F T; Paniagua-Sánchez, J M; Rufo-Pérez, M; Jiménez-Barco, A

    2014-12-01

    This article analyses the electric field levels around medium-wave transmitters, delimiting the temporal variability of the levels received at a pre-established reception point. One extensively used dosimetric criterion is to consider historical levels of the field recorded over a certain period of time so as to provide an overall perspective of radio-frequency electric field exposure in a particular environment. This aspect is the focus of the present study, in which the measurements will be synthesised in the form of exposure coefficients. Two measurement campaigns were conducted: one short term (10 days) and the other long term (1 y). The short-term data were used to study which probability density functions best approximate the measured levels. The long-term data were used to compute the principal statistics that characterise the field values over a year. The data that form the focus of the study are the peak traces, since these are the most representative from the standpoint of exposure. The deviations found were around 6 % for short periods and 12 % for long periods. The information from the two campaigns was used to develop and implement a computer application based on the Monte Carlo method to simulate values of the field, allowing one to carry out robust statistics. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  11. Assessment of vaccine testing at three laboratories using the guinea pig model of tuberculosis.

    PubMed

    Grover, Ajay; Troudt, Jolynn; Arnett, Kimberly; Izzo, Linda; Lucas, Megan; Strain, Katie; McFarland, Christine; Hall, Yper; McMurray, David; Williams, Ann; Dobos, Karen; Izzo, Angelo

    2012-01-01

    The guinea pig model of tuberculosis is used extensively in different locations to assess the efficacy of novel tuberculosis vaccines during pre-clinical development. Two key assays are used to measure protection against virulent challenge: a 30 day post-infection assessment of mycobacterial burden and long-term post-infection survival and pathology analysis. To determine the consistency and robustness of the guinea pig model for testing vaccines, a comparative assessment between three sites that are currently involved in testing tuberculosis vaccines from external providers was performed. Each site was asked to test two "subunit" type vaccines in their routine animal model as if testing vaccines from a provider. All sites performed a 30 day study, and one site also performed a long-term survival/pathology study. Despite some differences in experimental approach between the sites, such as the origin of the Mycobacterium tuberculosis strain and the type of aerosol exposure device used to infect the animals and the source of the guinea pigs, the data obtained between sites were consistent in regard to the ability of each "vaccine" tested to reduce the mycobacterial burden. The observations also showed that there was good concurrence between the results of short-term and long-term studies. This validation exercise means that efficacy data can be compared between sites. Copyright © 2011 Elsevier Ltd. All rights reserved.

  12. Managing Osteoporosis Patients after Long-Term Bisphosphonate Treatment

    PubMed Central

    Adler, Robert A.; Fuleihan, Ghada El-Hajj; Bauer, Douglas C.; Camacho, Pauline M.; Clarke, Bart L.; Clines, Gregory A.; Compston, Juliet E.; Drake, Matthew T.; Edwards, Beatrice J.; Favus, Murray J.; Greenspan, Susan L.; McKinney, Ross; Pignolo, Robert J.; Sellmeyer, Deborah E.

    2016-01-01

    Bisphosphonates (BPs) are the most commonly used medications for osteoporosis, but optimal duration of therapy is unknown. This ASBMR report provides guidance on BP therapy duration with a risk benefit perspective. Two trials provided evidence for long-term BP use. In the Fracture Intervention Trial Long-term Extension (FLEX), postmenopausal women receiving alendronate for 10 years had fewer clinical vertebral fractures than those switched to placebo after 5 years. In the HORIZON extension, women who received 6 annual infusions of zoledronic acid had fewer morphometric vertebral fractures compared with those switched to placebo after 3 years. Low hip T-score between −2 and −2.5 in FLEX and below −2.5 in HORIZON extension predicted a beneficial response to continued therapy. Hence, the Task Force suggests that after 5 years of oral BP or 3 years of intravenous BP, women should be reassessed. Women with previous major osteoporotic fracture, those who fracture on therapy, or others at high risk should generally continue therapy for up to 10 years (oral) or 6 years (intravenous), with periodic risk-benefit evaluation. Older women, those with a low hip T-score or high fracture risk score are considered high risk. The risk of osteonecrosis of the jaw and atypical femoral fracture increases with BP therapy duration, but such rare events are far outweighed by fracture risk reduction with BPs in high risk patients. For women not at high fracture risk after 3–5 years of BP treatment, a drug holiday of 2–3 years can be considered, with periodic reassessment. The algorithm provided for long term BP use is based on limited evidence in mostly Caucasian postmenopausal women and only for vertebral fracture reduction. It is probably applicable to men and patients with glucocorticoid-induced osteoporosis, with some adaptations. It is unlikely that future osteoporosis trials will provide data for formulating definitive recommendations. PMID:26350171

  13. Changes in Plasma ACTH Levels and Corticotroph Tumor Size in Patients With Cushing's Disease During Long-term Treatment With the Glucocorticoid Receptor Antagonist Mifepristone

    PubMed Central

    Findling, James W.; Koch, Christian A.; Schlaffer, Sven-Martin; Buchfelder, Michael; Gross, Coleman

    2014-01-01

    Context: Pituitary effects of long-term therapy with mifepristone, a glucocorticoid receptor antagonist, in Cushing's disease (CD) patients are not well understood. Objective: Our objective was to report changes in ACTH and pituitary magnetic resonance imaging (MRI) findings during long-term use of mifepristone in CD patients. Design and Setting: The Study of the Efficacy and Safety of Mifepristone in the Treatment of Endogenous Cushing's Syndrome (SEISMIC) was a 24-week, open-label study of mifepristone, and its long-term extension (LTE) is a multicenter U.S. study. Patients: Forty-three CD patients (mean age 45.3 years) were enrolled in SEISMIC with 27 continuing into the LTE study. Interventions: Mifepristone (300–1200 mg) was administered once daily. Main Outcome Measures: ACTH and pituitary MRI were assessed at baseline and at regular intervals during treatment. Results: A ≥2-fold increase in ACTH was observed in 72% of patients treated for a median duration of 11.3 months. The mean peak increase in ACTH was 2.76 ± 1.65-fold during SEISMIC, and mean ACTH concentrations remained stable during the LTE. ACTH was directly correlated with mifepristone dose and declined to near baseline levels after mifepristone discontinuation. Tumor regressed in 2 patients and progressed in 3 patients with macroadenomas. An additional microadenoma was identified after 25 months of treatment after a baseline tumor-negative MRI. Conclusions: In the largest prospective study to date, long-term mifepristone treatment increased ACTH in approximately two-thirds of patients with CD. ACTH elevations were observed within the first few weeks of treatment, were dose-dependent, and generally remained stable over time. Corticotroph tumor progression and regression may occur over time, but patients may have significant increases in ACTH levels without evidence of tumor growth. PMID:25013998

  14. Providing long-term trend and gravimetric factor at Chandler period from superconducting gravimeter records by using Singular Spectrum Analysis along with its multivariate extension

    NASA Astrophysics Data System (ADS)

    Gruszczynska, M.; Rosat, S.; Klos, A.; Bogusz, J.

    2017-12-01

    In this study, Singular Spectrum Analysis (SSA) along with its multivariate extension MSSA (Multichannel SSA) were used to estimate long-term trend and gravimetric factor at the Chandler wobble frequency from superconducting gravimeter (SG) records. We have used data from seven stations located worldwide and contributing to the International Geodynamics and Earth Tides Service (IGETS). The timespan ranged from 15 to 19 years. Before applying SSA and MSSA, we had removed local tides, atmospheric (ECMWF data), hydrological (MERRA2 products) loadings and non-tidal ocean loading (ECCO2 products) effects. In the first part of analysis, we used the SSA approach in order to estimate the long-term trends from SG observations. We use the technique based on the classical Karhunen-Loève spectral decomposition of time series into long-term trend, oscillations and noise. In the second part, we present the determination of common time-varying pole tide (annual and Chandler wobble) to estimate gravimetric factor from SG time series using the MSSA approach. The presented method takes advantage over traditional methods like Least Squares Estimation by determining common modes of variability which reflect common geophysical field. We adopted a 6-year lag-window as the optimal length to extract common seasonal signals and the Chandler components of the Earth polar motion. The signals characterized by annual and Chandler wobble account for approximately 62% of the total variance of residual SG data. Then, we estimated the amplitude factors and phase lags of Chandler wobble with respect to the IERS (International Earth Rotation and Reference Systems Service) polar motion observations. The resulting gravimetric factors at the Chandler Wobble period are finally compared with previously estimates. A robust estimate of the gravimetric Earth response to the Chandlerian component of the polar motion is required to better constrain the mantle anelasticity at this frequency and hence the attenuation models of the Earth interior.

  15. An approach to counteracting long-term microgravity-induced muscle atrophy

    NASA Technical Reports Server (NTRS)

    Tesch, P. A.; Buchanan, P.; Dudley, G. A.

    1990-01-01

    To find means of alleviating muscle atrophy induced by long-term microgravity, the effects of a 19-week-long heavy-resistance training regime (using either concentric muscle actions only or concentric and eccentric muscle actions) on the strengths of the exercised knee extensor muscle group were investigated in two groups of male human subjects performing two types of training exercises: supine leg press or/and seated knee extension. Results show that a training program in which both the concentric and the eccentric muscle action was performed led to substantially greater increases in maximal muscle strength than when only concentric exercises were performed.

  16. Long-term efficacy and safety of ustekinumab for Crohn's disease through the second year of therapy.

    PubMed

    Sandborn, W J; Rutgeerts, P; Gasink, C; Jacobstein, D; Zou, B; Johanns, J; Sands, B E; Hanauer, S B; Targan, S; Ghosh, S; de Villiers, W J S; Colombel, J-F; Feagan, B G

    2018-05-24

    In Phase 3 studies of ustekinumab, a fully human monoclonal IL-12/23p40 antibody approved for moderate-to-severe Crohn's disease, patients entered a long-term extension after completing 8 weeks of induction and 44 weeks of maintenance treatment. Efficacy through 92 weeks and safety through 96 weeks of IM-UNITI maintenance are reported. UNITI-1 (TNF-antagonist failures) and UNITI-2 (conventional therapy failures) patients (N = 1281) entered IM-UNITI, including 397 ustekinumab intravenous induction responders randomised to subcutaneous ustekinumab 90 mg every 12 weeks, every 8 weeks, or placebo and 884 nonrandomised patients. Dose-adjustment to 90 mg every 8 weeks occurred in patients randomised to 90 mg every 12 weeks and placebo patients with loss of response (Weeks 8-32). All Week 44 completers could enter the long-term extension without further dose adjustment. Placebo patients discontinued following study unblinding. A total of 718 patients (all treated) entered the long-term extension (298 randomised and 420 not randomised). Overall, 86.5% (621/718) completed Week 96. The proportions of randomised patients in clinical remission were generally maintained from Week 44 through 92 in ustekinumab 90 mg every 12 weeks (77.4% to 72.6%), every 8 weeks (84.1% to 74.4%), and prior dose adjustment groups (63.4% to 53.5%). At Week 92, the proportions of patients in clinical remission were similar in the ustekinumab 90 mg every 12 weeks and every 8 weeks groups and lower in patients with prior dose adjustment. Proportions of patients in clinical remission at Week 92 for all treated every 8 weeks (64.4%) and every 12 weeks (64.3%) groups were lower than randomised every 8 weeks (74.4%) and every 12 weeks (72.6%) groups, but similarly maintained. Safety events (per hundred patient-years) were similar among all placebo and ustekinumab patients (Week 0-96), including adverse events (484.39 vs 447.76), serious adverse events (19.24 vs 18.82), and serious infections (4.09 vs 4.02). No dose effect was observed. Subcutaneous ustekinumab maintained clinical response and remission through Week 92. No new safety signals were observed. ClinicalTrials.gov number NCT01369355. © 2018 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.

  17. Linear extension rates of massive corals from the Dry Tortugas National Park (DRTO), Florida

    USGS Publications Warehouse

    Muslic, Adis; Flannery, Jennifer A.; Reich, Christopher D.; Umberger, Daniel K.; Smoak, Joseph M.; Poore, Richard Z.

    2013-01-01

    Colonies of three coral species, Montastraea faveolata, Diploria strigosa, and Siderastrea siderea, located in the Dry Tortugas National Park (DRTO), Florida, were sampled and analyzed to evaluate annual linear extension rates. Montastraea faveolata had the highest average linear extension and variability in (DRTO: C2 = 0.67 centimeters/year (cm yr-1) ± 0.04, B3 = 0.85 cm yr-1 ± 0.07), followed by D. strigosa (DRTO: C1 = 0.73 cm yr-1 ± 0.04; MK = 0.59 cm yr-1 ± 0.06) and S. siderea (DRTO: A1 = 0.41 cm yr-1 ± 0.03). Intercolony comparison of M. faveolata from DRTO yielded a significant correlation (r = 0.34, df = 67, P = 0.005) and similar long-term patterns. DRTO S. siderea core A1 showed an overall increasing trend (r = 0.61, df = 119, P < 0.0001) in extension rates that correlated significantly with International Comprehensive Ocean/Atmosphere Data Set annual sea-surface temperature (r = 0.42, df = 115, P < 0.0001) and an air temperature record from Key West (r = 0.37, df = 111, P < 0.0001). In conclusion, annual linear extension rates are species specific and potentially influence by long-term variability in sea-surface temperature.

  18. Help-Seeking Response to Subjective Memory Complaints in Older Adults: Toward a Conceptual Model

    ERIC Educational Resources Information Center

    Begum, Aysha; Whitley, Rob; Banerjee, Sube; Matthews, David; Stewart, Robert; Morgan, Craig

    2013-01-01

    Purpose: Subjective memory complaint is a term used to refer older adults who report memory problems. Extensive literature exists on its etiology and impact on long-term cognitive decline, and some physicians consider it important in the early detection of dementia. Despite the salient features reported by both patients and clinicians, few people…

  19. 75 FR 32951 - Determination of Regulatory Review Period for Purposes of Patent Extension; PROMACTA

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-10

    ... Patent Term Restoration Act of 1984 (Public Law 98-417) and the Generic Animal Drug and Patent Term... years so long as the patented item (human drug product, animal drug product, medical device, food... and an approval phase. For human drug products, the testing phase begins when the exemption to permit...

  20. 75 FR 9227 - Determination of Regulatory Review Period for Purposes of Patent Extension; FIRMAGON

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-01

    ... Patent Term Restoration Act of 1984 (Public Law 98-417) and the Generic Animal Drug and Patent Term... years so long as the patented item (human drug product, animal drug product, medical device, food... and an approval phase. For human drug products, the testing phase begins when the exemption to permit...

  1. Analysis of the yeast short-term Crabtree effect and its origin

    PubMed Central

    Hagman, Arne; Säll, Torbjörn; Piškur, Jure

    2014-01-01

    The short-term Crabtree effect is defined as the immediate occurrence of aerobic alcoholic fermentation in response to provision of a pulse of excess sugar to sugar-limited yeast cultures. Here we have characterized ten yeast species with a clearly defined phylogenetic relationship. Yeast species were cultivated under glucose-limited conditions, and we studied their general carbon metabolism in response to a glucose pulse. We generated an extensive collection of data on glucose and oxygen consumption, and ethanol and carbon dioxide generation. We conclude that the Pichia,Debaryomyces,Eremothecium and Kluyveromyces marxianus yeasts do not exhibit any significant ethanol formation, while Kluyveromyces lactis behaves as an intermediate yeast, and Lachancea,Torulaspora,Vanderwaltozyma and Saccharomyces yeasts exhibit rapid ethanol accumulation. Based on the present data and our previous data relating to the presence of the long-term Crabtree effect in over 40 yeast species, we speculate that the origin of the short-term effect may coincide with the origin of the long-term Crabtree effect in the Saccharomycetales lineage, occurring ∼ 150 million years ago. PMID:25161062

  2. Long-term functional outcome after surgical repair of cranial cruciate ligament disease in dogs.

    PubMed

    Mölsä, Sari H; Hyytiäinen, Heli K; Hielm-Björkman, Anna K; Laitinen-Vapaavuori, Outi M

    2014-11-19

    Cranial cruciate ligament (CCL) rupture is a very common cause of pelvic limb lameness in dogs. Few studies, using objective and validated outcome evaluation methods, have been published to evaluate long-term (>1 year) outcome after CCL repair. A group of 47 dogs with CCL rupture treated with intracapsular, extracapsular, and osteotomy techniques, and 21 healthy control dogs were enrolled in this study. To evaluate long-term surgical outcome, at a minimum of 1.5 years after unilateral CCL surgery, force plate, orthopedic, radiographic, and physiotherapeutic examinations, including evaluation of active range of motion (AROM), symmetry of thrust from the ground, symmetry of muscle mass, and static weight bearing (SWB) of pelvic limbs, and goniometry of the stifle and tarsal joints, were done. At a mean of 2.8 ± 0.9 years after surgery, no significant differences were found in average ground reaction forces or SWB between the surgically treated and control dog limbs, when dogs with no other orthopedic findings were included (n = 21). However, in surgically treated limbs, approximately 30% of the dogs had decreased static or dynamic weight bearing when symmetry of weight bearing was evaluated, 40-50% of dogs showed limitations of AROM in sitting position, and two-thirds of dogs had weakness in thrust from the ground. The stifle joint extension angles were lower (P <0.001) and flexion angles higher (P <0.001) in surgically treated than in contralateral joints, when dogs with no contralateral stifle problems were included (n = 33). In dogs treated using the intracapsular technique, the distribution percentage per limb of peak vertical force (DPVF) in surgically treated limbs was significantly lower than in dogs treated with osteotomy techniques (P =0.044). The average long-term dynamic and static weight bearing of the surgically treated limbs returned to the level of healthy limbs. However, extension and flexion angles of the surgically treated stifles remained inferior to healthy joints, and impairment of AROM and weakness in thrust from the ground in the surgically treated limbs were frequently present. Ground reaction forces may be inadequate as a sole method for assessing functional outcome after cranial cruciate ligament repair.

  3. Ageing and moisture uptake in polymethyl methacrylate (PMMA) bone cements☆

    PubMed Central

    Ayre, Wayne Nishio; Denyer, Stephen P.; Evans, Samuel L.

    2014-01-01

    Bone cements are extensively employed in orthopaedics for joint arthroplasty, however implant failure in the form of aseptic loosening is known to occur after long-term use. The exact mechanism causing this is not well understood, however it is thought to arise from a combination of fatigue and chemical degradation resulting from the hostile in vivo environment. In this study, two commercial bone cements were aged in an isotonic fluid at physiological temperatures and changes in moisture uptake, microstructure and mechanical and fatigue properties were studied. Initial penetration of water into the cement followed Fickian diffusion and was thought to be caused by vacancies created by leaching monomer. An increase in weight of approximately 2% was experienced after 30 days ageing and was accompanied by hydrolysis of poly(methyl methacrylate) (PMMA) in the outermost layers of the cement. This molecular change and the plasticising effect of water resulted in reduced mechanical and fatigue properties over time. Cement ageing is therefore thought to be a key contributor in the long-term failure of cemented joint replacements. The results from this study have highlighted the need to develop cements capable of withstanding long-term degradation and for more accurate test methods, which fully account for physiological ageing. PMID:24445003

  4. Ageing and moisture uptake in polymethyl methacrylate (PMMA) bone cements.

    PubMed

    Ayre, Wayne Nishio; Denyer, Stephen P; Evans, Samuel L

    2014-04-01

    Bone cements are extensively employed in orthopaedics for joint arthroplasty, however implant failure in the form of aseptic loosening is known to occur after long-term use. The exact mechanism causing this is not well understood, however it is thought to arise from a combination of fatigue and chemical degradation resulting from the hostile in vivo environment. In this study, two commercial bone cements were aged in an isotonic fluid at physiological temperatures and changes in moisture uptake, microstructure and mechanical and fatigue properties were studied. Initial penetration of water into the cement followed Fickian diffusion and was thought to be caused by vacancies created by leaching monomer. An increase in weight of approximately 2% was experienced after 30 days ageing and was accompanied by hydrolysis of poly(methyl methacrylate) (PMMA) in the outermost layers of the cement. This molecular change and the plasticising effect of water resulted in reduced mechanical and fatigue properties over time. Cement ageing is therefore thought to be a key contributor in the long-term failure of cemented joint replacements. The results from this study have highlighted the need to develop cements capable of withstanding long-term degradation and for more accurate test methods, which fully account for physiological ageing. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

  5. Ileocolic junction resection in dogs and cats: 18 cases.

    PubMed

    Fernandez, Yordan; Seth, Mayank; Murgia, Daniela; Puig, Jordi

    2017-12-01

    There is limited veterinary literature about dogs or cats with ileocolic junction resection and its long-term follow-up. To evaluate the long-term outcome in a cohort of dogs and cats that underwent resection of the ileocolic junction without extensive (≥50%) small or large bowel resection. Medical records of dogs and cats that had the ileocolic junction resected were reviewed. Follow-up information was obtained either by telephone interview or e-mail correspondence with the referring veterinary surgeons. Nine dogs and nine cats were included. The most common cause of ileocolic junction resection was intussusception in dogs (5/9) and neoplasia in cats (6/9). Two dogs with ileocolic junction lymphoma died postoperatively. Only 2 of 15 animals, for which long-term follow-up information was available, had soft stools. However, three dogs with suspected chronic enteropathy required long-term treatment with hypoallergenic diets alone or in combination with medical treatment to avoid the development of diarrhoea. Four of 6 cats with ileocolic junction neoplasia were euthanised as a consequence of progressive disease. Dogs and cats undergoing ileocolic junction resection and surviving the perioperative period may have a good long-term outcome with mild or absent clinical signs but long-term medical management may be required.

  6. Long term changes in Intrinsic Water Use Efficiency, the palaoe record derived from stable carbon isotope measurements from tree rings.

    NASA Astrophysics Data System (ADS)

    Gagen, Mary; McCarroll, Danny; Loader, Neil; Young, Giles; Robertson, Iain

    2015-04-01

    Stable carbon isotope (δ13C) measurements from the annual rings of trees are increasingly used to explore long term changes in plant-carbon-water relations, via changes in intrinsic water use efficiency (iWUE); the ratio of photosynthetic rate to stomatal conductance. Many studies report a significant increase in iWEU since industrialisation, which tracks rising global atmospheric CO2. Such changes are logical are trees are known to change their stomatal geometry, number and action in response to rising CO2. However, which increasing iWUE suggests physiological changes which should lead to increased growth increasing iWUE is rarely matched by enhanced tree growth when tree rings are measured, despite increases of up to 30% in iWUE over the recent past (van der Sleen et al 2015). Explanations for the mismatch between iWUE and tree growth records encompass questions over the veracity of δ13C records for recording physiological change (Silva and Howarth 2013), suggestions that moisture stress in warming climates becomes a limit to growth and prevents opportunistic use of rising CO2 by trees (Andreu-Hayles et al 2011) and questions regarding the use of tree ring width, which does not record tree height gain, to record growth. Here we present an extensive range of long term iWUE records, derived broadly from the temperate, high latitude and one tropical forest site to explore the palaeoclimatic perspective on the iWUE-fertilization conundrum in a spatio temporally extensive manner.

  7. Experimental program to determine long term characteristics of the MDE pressure transducers

    NASA Technical Reports Server (NTRS)

    Parker, C. D.

    1973-01-01

    The pressure cell sensors developed for the Pioneer 10/G meteoroid detection experiments (MDE) were investigated to enhance their application and their potential as a sensor in other MDE applications. Their Paschen characteristics were also investigated, and the effects of variations in geometry, Ni-63 platings (for initial ionizations) and sealing pressures were determined. The effects of extensive pre-flight testing and proton and heavy ion space radiation were investigated. Flight-quality pressure panels/cells were committed to long term testing to demonstrate their suitability for the Pioneer 10/G Missions.

  8. Short-Term, Intermittent Fasting Induces Long-Lasting Gut Health and TOR-Independent Lifespan Extension.

    PubMed

    Catterson, James H; Khericha, Mobina; Dyson, Miranda C; Vincent, Alec J; Callard, Rebecca; Haveron, Steven M; Rajasingam, Arjunan; Ahmad, Mumtaz; Partridge, Linda

    2018-06-04

    Intermittent fasting (IF) can improve function and health during aging in laboratory model organisms, but the mechanisms at work await elucidation. We subjected fruit flies (Drosophila melanogaster) to varying degrees of IF and found that just one month of a 2-day fed:5-day fasted IF regime at the beginning of adulthood was sufficient to extend lifespan. This long-lasting, beneficial effect of early IF was not due to reduced fecundity. Starvation resistance and resistance to oxidative and xenobiotic stress were increased after IF. Early-life IF also led to higher lipid content in 60-day-old flies, a potential explanation for increased longevity. Guts of flies 40 days post-IF showed a significant reduction in age-related pathologies and improved gut barrier function. Improved gut health was also associated with reduced relative bacterial abundance. Early IF thus induced profound long-term changes. Pharmacological and genetic epistasis analysis showed that IF acted independently of the TOR pathway because rapamycin and IF acted additively to extend lifespan, and global expression of a constitutively active S6K did not attenuate the IF-induced lifespan extension. We conclude that short-term IF during early life can induce long-lasting beneficial effects, with robust increase in lifespan in a TOR-independent manner, probably at least in part by preserving gut health. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  9. Low acetaldehyde collection efficiencies for 24-hour sampling with 2,4-dinitrophenylhydrazine (DNPH)-coated solid sorbents.

    PubMed

    Herrington, Jason S; Fan, Zhi-Hua Tina; Lioy, Paul J; Zhang, Junfeng Jim

    2007-01-15

    Airborne aldehyde and ketone (carbonyl) sampling methodologies based on derivatization with 2,4-dinitrophenylhydrazine (DNPH)-coated solid sorbents could unequivocally be considered the "gold" standard. Originally developed in the late 1970s, these methods have been extensively evaluated and developed up to the present day. However, these methods have been inadequately evaluated for the long-term (i.e., 24 h or greater) sampling collection efficiency (CE) of carbonyls other than formaldehyde. The current body of literature fails to demonstrate that DNPH-coated solid sorbent sampling methods have acceptable CEs for the long-term sampling of carbonyls other than formaldehyde. Despite this, such methods are widely used to report the concentrations of multiple carbonyls from long-term sampling, assuming approximately 100% CEs. Laboratory experiments were conducted in this study to evaluate the long-term formaldehyde and acetaldehyde sampling CEs for several commonly used DNPH-coated solid sorbents. Results from sampling known concentrations of formaldehyde and acetaldehyde generated in a dynamic atmosphere generation system demonstrate that the 24-hour formaldehyde sampling CEs ranged from 83 to 133%, confirming the findings made in previous studies. However, the 24-hour acetaldehyde sampling CEs ranged from 1 to 62%. Attempts to increase the acetaldehyde CEs by adding acid to the samples post sampling were unsuccessful. These results indicate that assuming approximately 100% CEs for 24-hour acetaldehyde sampling, as commonly done with DNPH-coated solid sorbent methods, would substantially under estimate acetaldehyde concentrations.

  10. [Potential therapeutic usefulness of cannabis and cannabinoids].

    PubMed

    Lorenzo Fernández, P

    2000-01-01

    Diseases in which Cannabis and cannabinoids have demonstrated some medicinal putative properties are: nausea and vomiting associated with cancer chemotherapy, muscle spasticity (multiple sclerosis, movement disorders), pain, anorexia, epilepsy, glaucoma, bronchial asthma, neuroegenerative diseases, cancer, etc. Although some of the current data comes from clinical controlled essays, the majority are based on anecdotic reports. Basic pharmacokinetic and pharmacodynamic studies and more extensive controlled clinical essays with higher number of patients and long term studies are necessary to consider these compounds useful since a therapeutical point of view.

  11. Epidemiologic Methods Lessons Learned from Environmental Public Health Disasters: Chernobyl, the World Trade Center, Bhopal, and Graniteville, South Carolina

    PubMed Central

    Svendsen, Erik R.; Runkle, Jennifer R.; Dhara, Venkata Ramana; Lin, Shao; Naboka, Marina; Mousseau, Timothy A.; Bennett, Charles

    2012-01-01

    Background: Environmental public health disasters involving hazardous contaminants may have devastating effects. While much is known about their immediate devastation, far less is known about long-term impacts of these disasters. Extensive latent and chronic long-term public health effects may occur. Careful evaluation of contaminant exposures and long-term health outcomes within the constraints imposed by limited financial resources is essential. Methods: Here, we review epidemiologic methods lessons learned from conducting long-term evaluations of four environmental public health disasters involving hazardous contaminants at Chernobyl, the World Trade Center, Bhopal, and Graniteville (South Carolina, USA). Findings: We found several lessons learned which have direct implications for the on-going disaster recovery work following the Fukushima radiation disaster or for future disasters. Interpretation: These lessons should prove useful in understanding and mitigating latent health effects that may result from the nuclear reactor accident in Japan or future environmental public health disasters. PMID:23066404

  12. Cumulative effects of climate change and ice-wedge degradation, Prudhoe Bay oilfield Alaska

    NASA Astrophysics Data System (ADS)

    Walker, D. A.; Kanevskiy, M. Z.; Shur, Y.; Raynolds, M. K.; Buchhorn, M.

    2016-12-01

    Development of Arctic oil & gas resources requires extensive networks of roads, pipelines and other forms of infrastructure. The Prudhoe Bay Oilfield is the largest Arctic oilfield in North America with a long, well-documented history. In a previous publication we analyzed the historical record of high-resolution aerial photos to document the long-term changes to infrastructure extent (1949-2010) for the entire oilfield, and an integrated-geoecological-historical-change-mapping (IGHCM) approach to document terrain changes within 22-km2 areas of the oilfield. We reported the recent widespread expansion of thermokarst, starting in about 1989. Here we examine the annual air-photo record to better pinpoint the years of major change. We also conducted detailed field studies of roadside changes using topographic surveys and soil, vegetation and ice-wedge coring studies. Both sites exhibit extensive ice-wedge degradation that is caused by a combination of a long-term warming trend a series of exceptionally warm summers, and infrastructure-related factors that melted the tops of ice wedges. Near-road thermokarst is enhanced by warmer soils associated with road dust, roadside flooding, near-road pipelines, communication cables, and altered snow regimes. These strongly affect roadside ecosystems and the infrastructure itself. Changes to ecosystems include altered hydrology with the drying of polygon centers and the formation of well-developed high-centered polygons occurs in some areas. Other areas develop extensive flooding and erosion of ice-wedge troughs. An unexpected result of flooding is the stabilization of ice-wedge degradation in some areas because the increased productivity of sedges in the flooded areas is producing large amounts of organic material that protects the tops of ice wedges from further degradation. The large increases in productivity in roadside areas also attract large flocks of waterfowl. Changes to the soils with the addition of thick layers of dust cause decreases in the plant diversity. There are also broad social and economic implications. For example, a flood along the Dalton Highway in 2015 caused extensive degradation of ice wedges, major damage to the Dalton Highway and affected transportation to and from the oilfield for several weeks in Spring 2015.

  13. Thermal and physicochemical properties important for the long term behavior of nuclear waste glasses

    NASA Astrophysics Data System (ADS)

    Matzke, Hj.; Vernaz, E.

    High level nuclear waste from reprocessing of spent nuclear fuel has to be solidified in a stable matrix for safe long-time storage. Vitrification in borosilicate glasses is the technique accepted worldwide as the best combination of engineering constraints from fabrication and physicochemical properties of the matrix. A number of different glasses was developed in different national programs. The criteria and the reasons for selecting the final compositions are described briefly. Emphasis is placed on the French product R7T7 and on thermal and physicochemical properties though glasses developed in other national projects (e.g., the German product GP 98/12, etc.) are also treated. The basic physical and mechanical properties and the chemical durability of the glass in contact with water are described. The basic mechanisms of aqueous corrosion are discussed and the evolving modelling of the leaching process is dealt with, as well as effects of container material, backfill, etc. The thermal behavior has also been studied and extensive data exist on diffusion of glass constituents (Na) and of interesting elements of the waste such as the alkalis Rb and Cs or the actinides U and Pu, as well as on crystallization processes in the glass during storage at elevated temperatures. Emphasis is placed on the radiation stability of the glasses, based on extensive studies using short-lived actinides (e.g., 244Cm) or ion implantation to produce the damage expected during long storage at an accelerated rate. The radiation stability is shown to be very good, if realistic damage conditions are used. The knowledge accumulated in the past years is used to evaluate and predict the long-term evolution of the glass under storage conditions.

  14. Long-term safety and efficacy of deferasirox (Exjade®) for up to 5 years in transfusional iron-overloaded patients with sickle cell disease

    PubMed Central

    Vichinsky, Elliott; Bernaudin, Françoise; Forni, Gian Luca; Gardner, Renee; Hassell, Kathryn; Heeney, Matthew M; Inusa, Baba; Kutlar, Abdullah; Lane, Peter; Mathias, Liesl; Porter, John; Tebbi, Cameron; Wilson, Felicia; Griffel, Louis; Deng, Wei; Giannone, Vanessa; Coates, Thomas

    2011-01-01

    To date, there is a lack of long-term safety and efficacy data for iron chelation therapy in transfusion-dependent patients with sickle cell disease (SCD). To evaluate the long-term safety and efficacy of deferasirox (a once-daily oral iron chelator), patients with SCD completing a 1-year, Phase II, randomized, deferoxamine (DFO)-controlled study entered a 4-year extension, continuing to receive deferasirox, or switching from DFO to deferasirox. Average actual deferasirox dose was 19·4 ± 6·3 mg/kg per d. Of 185 patients who received at least one deferasirox dose, 33·5% completed the 5-year study. The most common reasons for discontinuation were withdrawal of consent (23·8%), lost to follow-up (9·2%) and adverse events (AEs) (7·6%). Investigator-assessed drug-related AEs were predominantly gastrointestinal [including nausea (14·6%), diarrhoea (10·8%)], mild-to-moderate and transient in nature. Creatinine clearance remained within the normal range throughout the study. Despite conservative initial dosing, serum ferritin levels in patients with ≥4 years deferasirox exposure significantly decreased by −591 μg/l (95% confidence intervals, −1411, −280 μg/l; P=0·027; n=67). Long-term deferasirox treatment for up to 5 years had a clinically acceptable safety profile, including maintenance of normal renal function, in patients with SCD. Iron burden was substantially reduced with appropriate dosing in patients treated for at least 4 years. PMID:21592110

  15. Long-term safety and efficacy of deferasirox (Exjade) for up to 5 years in transfusional iron-overloaded patients with sickle cell disease.

    PubMed

    Vichinsky, Elliott; Bernaudin, Françoise; Forni, Gian Luca; Gardner, Renee; Hassell, Kathryn; Heeney, Matthew M; Inusa, Baba; Kutlar, Abdullah; Lane, Peter; Mathias, Liesl; Porter, John; Tebbi, Cameron; Wilson, Felicia; Griffel, Louis; Deng, Wei; Giannone, Vanessa; Coates, Thomas

    2011-08-01

    To date, there is a lack of long-term safety and efficacy data for iron chelation therapy in transfusion-dependent patients with sickle cell disease (SCD). To evaluate the long-term safety and efficacy of deferasirox (a once-daily oral iron chelator), patients with SCD completing a 1-year, Phase II, randomized, deferoxamine (DFO)-controlled study entered a 4-year extension, continuing to receive deferasirox, or switching from DFO to deferasirox. Average actual deferasirox dose was 19·4 ± 6·3 mg/kg per d. Of 185 patients who received at least one deferasirox dose, 33·5% completed the 5-year study. The most common reasons for discontinuation were withdrawal of consent (23·8%), lost to follow-up (9·2%) and adverse events (AEs) (7·6%). Investigator-assessed drug-related AEs were predominantly gastrointestinal [including nausea (14·6%), diarrhoea (10·8%)], mild-to-moderate and transient in nature. Creatinine clearance remained within the normal range throughout the study. Despite conservative initial dosing, serum ferritin levels in patients with ≥ 4 years deferasirox exposure significantly decreased by -591 μg/l (95% confidence intervals, -1411, -280 μg/l; P = 0·027; n = 67). Long-term deferasirox treatment for up to 5 years had a clinically acceptable safety profile, including maintenance of normal renal function, in patients with SCD. Iron burden was substantially reduced with appropriate dosing in patients treated for at least 4 years. © 2011 Blackwell Publishing Ltd.

  16. Outcomes of bacterial meningitis in children.

    PubMed

    Briand, C; Levy, C; Baumie, F; Joao, L; Béchet, S; Carbonnelle, E; Grimprel, E; Cohen, R; Gaudelus, J; de Pontual, L

    2016-06-01

    Pediatricians are well aware of the immediate risks of bacterial meningitis in children. However, the long-term outcome of the disease has not been extensively studied. We aimed: (i) to evaluate the duration and quality of the long-term follow-up of children diagnosed with bacterial meningitis in a general pediatric department, (ii) to estimate the incidence of sequelae at the various stages of follow-up, and (iii) to compare our data with that of other studies. We conducted a retrospective study and included 34 children (3 months-15 years) who had been hospitalized for bacterial meningitis in the pediatric department of a University Hospital between January 1st, 2001 and December 31st, 2013. Overall, 32% of patients presented with sequelae and 15% with seizures. Only one patient presented with hearing loss, but 23.5% of patients did not have any hearing test performed. Seven patients had a neuropsychological assessment performed and no severe neuropsychological sequela was observed in this group. The average follow-up duration increased during the study period (from 23 to 49months). The long-term follow-up modalities observed in other studies were highly variable. Assessing the incidence and severity of sequelae was therefore difficult. A standardized follow-up should be implemented by way of a national surveillance network of children presenting with bacterial meningitis. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  17. Effects of hurricane disturbance on stream water concentrations and fluxes in eight tropical forest watersheds of the Luquillo Experimental Forest, Puerto Rico.

    Treesearch

    DOUGLAS. A. SCHAEFER; WILLIAM H. McDOWELL; FREDRICK N. SCATENA; CLYDE E. ASBURY

    2000-01-01

    Stream water chemistry responds substantially to watershed disturbances, but hurricane effects have not been extensively investigated in tropical regions. This study presents a long-term (2.5±11 y) weekly record of stream water chemistry on eight forested watersheds (catchment basins) in the Luquillo Mountains of Puerto Rico. This includes a period before and at least...

  18. Long-term outcome of percutaneous alcohol embolization combined with percutaneous vertebroplasty in aggressive vertebral hemangiomas with epidural extension.

    PubMed

    Premat, Kévin; Clarençon, Frédéric; Cormier, Évelyne; Mahtout, Jugurtha; Bonaccorsi, Raphaël; Degos, Vincent; Chiras, Jacques

    2017-07-01

    To evaluate, on a long-term basis, the safety and effectiveness of percutaneous alcohol embolization (PAE) combined with percutaneous vertebroplasty (PVP) as a sole treatment for aggressive vertebral haemangiomas (AVHs) with epidural extension. From 1996 to 2015, 26 consecutive patients (15 women [58%] and 11 men; mean age 51.8 years [range: 19-75 years]) underwent PAE combined with PVP (performed at day 15) for the treatment of 27 AVHs with epidural extension. Clinical outcome was evaluated with a mean delay of 88.3 ± 53.3 months (range: 22-217 months). The primary endpoint was pain relief evaluated with a visual analogue scale (VAS). Pre-procedure mean VAS score was 7.23 ± 1.3 and significantly improved at last follow-up (m = 3.11 ± 1.9; p < 0.001). Ten patients (38.5%) remained asymptomatic. Eighty-eight percent of the patients with neurosensory disorders had complete regression of these symptoms. Two of the three patients with motor deficit did not show any improvement. No major complication was recorded. PAE combined with PVP is a minimally invasive safe and effective therapeutic approach for AVH with epidural involvement, even on long-term clinical outcome. This technique appears mainly effective for pain and neurosensory symptoms, but seems less effective for motor deficit relief. • Combination of PAE with PVP is a safe technique. • PAE combined with PVP is an effective treatment for sensory symptoms. • This strategy seems less effective in patients with motor deficits.

  19. Technology Solutions Case Study: Long-Term Monitoring of Mini-Split Ductless Heat Pumps in the Northeast, Devens and Easthampton, Massachusetts

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

    None

    Transformations, Inc., has extensive experience building high-performance homes - production and custom - in a variety of Massachusetts locations and uses mini-split heat pumps (MSHPs) for space conditioning in most of its homes. The use of MSHPs for simplified space-conditioning distribution provides significant first-cost savings, which offsets the increased investment in the building enclosure. In this project, the U.S. Department of Energy Building America team Building Science Corporation evaluated the long-term performance of MSHPs in 8 homes during a period of 3 years. The work examined electrical use of MSHPs, distributions of interior temperatures and humidity when using simplified (two-point)more » heating systems in high-performance housing, and the impact of open-door/closed-door status on temperature distributions.« less

  20. Oral manifestations of paracoccidioidomycosis. Report of 21 cases from Argentina.

    PubMed

    Godoy, H; Reichart, P A

    2003-01-01

    The present study describes 21 Argentinian patients living in the province of Corrientes, who had developed oral manifestations due to Paracoccidioides brasiliensis infection. Of these, 20 patients were men and one a woman. Patients were of an average age of 39 years (range 25 to 72 years). Approximately, 76.2% of the patients were farmers. Gingival lesions were observed in 76%. Also, the tongue (71%) and the lips (62%) were frequently affected. Cytological smears and histopathology showed the characteristic fungal cells with the characteristic granulomatous inflammatory reaction consisting of lymphocytes, epithelioid cells and giant cells of the Langhans type. All patients except one had detectable pulmonary involvement. Therapy consists of long-term administration of itraconazole. Oral manifestations of paracoccidioidomycosis are characteristic in their clinical presentation. Early diagnosis and adequate therapy may prevent extensive tissue destructions. Long-term follow-up is mandatory.

  1. Long-Term Phenological Shifts in Raptor Migration and Climate

    PubMed Central

    Jaffré, Mikaël; Beaugrand, Grégory; Goberville, Éric; Jiguet, Frédéric; Kjellén, Nils; Troost, Gerard; Dubois, Philippe J.; Leprêtre, Alain; Luczak, Christophe

    2013-01-01

    Climate change is having a discernible effect on many biological and ecological processes. Among observed changes, modifications in bird phenology have been widely documented. However, most studies have interpreted phenological shifts as gradual biological adjustments in response to the alteration of the thermal regime. Here we analysed a long-term dataset (1980-2010) of short-distance migratory raptors in five European regions. We revealed that the responses of these birds to climate-induced changes in autumn temperatures are abrupt and synchronous at a continental scale. We found that when the temperatures increased, birds delayed their mean passage date of autumn migration. Such delay, in addition to an earlier spring migration, suggests that a significant warming may induce an extension of the breeding-area residence time of migratory raptors, which may eventually lead to residency. PMID:24223888

  2. Long-term abstinent alcoholics have normal memory.

    PubMed

    Reed, R J; Grant, I; Rourke, S B

    1992-08-01

    It is generally believed that many non-Korsakoff alcoholics have subtle defects in memory. To determine whether such defects vary as a function of length of abstinence (LOA), we performed extensive memory testing with: (1) recently detoxified (n = 31; LOA-29 days); (2) intermediate-term abstinent (n = 28; LOA = 1.9 years); (3) long-term abstinent (n = 32; LOA-7.0 years) alcoholics; and (4) nonalcoholic controls (n = 37). All subjects were matched on age and education. Alcoholics were matched on years of alcoholic drinking. Memory measures were divided into the following domains: verbal learning, verbal recall, visual learning, visual recall, and paired associate learning. A series of MANOVAs were conducted that revealed a significant relationship between visual learning and length of abstinence, and a significant interaction between age and length of abstinence on visual recall. Long-term abstinent subjects were not significantly different from controls on any test. We conclude that memory disturbance demonstrable among recently detoxified alcoholics in the early weeks of their abstinence is not evident in demographically matched long-term abstinent alcoholics with similar drinking histories.

  3. 75 FR 21299 - Determination of Regulatory Review Period for Purposes of Patent Extension; VIMPAT-NDA 22-254

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-23

    ... Patent Term Restoration Act of 1984 (Public Law 98-417) and the Generic Animal Drug and Patent Term... years so long as the patented item (human drug product, animal drug product, medical device, food... and an approval phase. For human drug products, the testing phase begins when the exemption to permit...

  4. 75 FR 21298 - Determination of Regulatory Review Period for Purposes of Patent Extension; VIMPAT -NDA 22-253

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-23

    ... Patent Term Restoration Act of 1984 (Public Law 98-417) and the Generic Animal Drug and Patent Term... years so long as the patented item (human drug product, animal drug product, medical device, food... and an approval phase. For human drug products, the testing phase begins when the exemption to permit...

  5. Agroecology for the Shrinking City

    EPA Science Inventory

    Many cities are experiencing long-term declines in population and economic activity. As a result, frameworks for urban sustainability need to address the unique challenges and opportunities of such shrinking cities. Shrinking, particularly in the U.S., has led to extensive vacant...

  6. Long-term Effectiveness of Cathodic Protection Systems on Highway Structures

    DOT National Transportation Integrated Search

    2003-07-01

    The Federal Highway Administration (FHWA) has concluded, on the basis of extensive research, that cathodic protection (CP), the technology used to mitigate corrosion of metals embedded in concrete, is the only rehabilitation technique that has proven...

  7. Origins of house mice in ecological niches created by settled hunter-gatherers in the Levant 15,000 y ago

    PubMed Central

    Weissbrod, Lior; Marshall, Fiona B.; Valla, François R.; Khalaily, Hamoudi; Bar-Oz, Guy; Auffray, Jean-Christophe; Vigne, Jean-Denis; Cucchi, Thomas

    2017-01-01

    Reductions in hunter-gatherer mobility during the Late Pleistocene influenced settlement ecologies, altered human relations with animal communities, and played a pivotal role in domestication. The influence of variability in human mobility on selection dynamics and ecological interactions in human settlements has not been extensively explored, however. This study of mice in modern African villages and changing mice molar shapes in a 200,000-y-long sequence from the Levant demonstrates competitive advantages for commensal mice in long-term settlements. Mice from African pastoral households provide a referential model for habitat partitioning among mice taxa in settlements of varying durations. The data reveal the earliest known commensal niche for house mice in long-term forager settlements 15,000 y ago. Competitive dynamics and the presence and abundance of mice continued to fluctuate with human mobility through the terminal Pleistocene. At the Natufian site of Ain Mallaha, house mice displaced less commensal wild mice during periods of heavy occupational pressure but were outcompeted when mobility increased. Changing food webs and ecological dynamics in long-term settlements allowed house mice to establish durable commensal populations that expanded with human societies. This study demonstrates the changing magnitude of cultural niche construction with varying human mobility and the extent of environmental influence before the advent of farming. PMID:28348225

  8. Origins of house mice in ecological niches created by settled hunter-gatherers in the Levant 15,000 y ago.

    PubMed

    Weissbrod, Lior; Marshall, Fiona B; Valla, François R; Khalaily, Hamoudi; Bar-Oz, Guy; Auffray, Jean-Christophe; Vigne, Jean-Denis; Cucchi, Thomas

    2017-04-18

    Reductions in hunter-gatherer mobility during the Late Pleistocene influenced settlement ecologies, altered human relations with animal communities, and played a pivotal role in domestication. The influence of variability in human mobility on selection dynamics and ecological interactions in human settlements has not been extensively explored, however. This study of mice in modern African villages and changing mice molar shapes in a 200,000-y-long sequence from the Levant demonstrates competitive advantages for commensal mice in long-term settlements. Mice from African pastoral households provide a referential model for habitat partitioning among mice taxa in settlements of varying durations. The data reveal the earliest known commensal niche for house mice in long-term forager settlements 15,000 y ago. Competitive dynamics and the presence and abundance of mice continued to fluctuate with human mobility through the terminal Pleistocene. At the Natufian site of Ain Mallaha, house mice displaced less commensal wild mice during periods of heavy occupational pressure but were outcompeted when mobility increased. Changing food webs and ecological dynamics in long-term settlements allowed house mice to establish durable commensal populations that expanded with human societies. This study demonstrates the changing magnitude of cultural niche construction with varying human mobility and the extent of environmental influence before the advent of farming.

  9. Long-term safety of once-daily, dual-release hydrocortisone in patients with adrenal insufficiency: a phase 3b, open-label, extension study

    PubMed Central

    Nilsson, Anna G; Bergthorsdottir, Ragnhildur; Burman, Pia; Dahlqvist, Per; Ekman, Bertil; Engström, Britt Edén; Ragnarsson, Oskar; Skrtic, Stanko; Wahlberg, Jeanette; Achenbach, Heinrich; Uddin, Sharif; Marelli, Claudio

    2017-01-01

    Objective To investigate the long-term safety and tolerability of a once-daily, dual-release hydrocortisone (DR-HC) tablet as oral glucocorticoid replacement therapy in patients with primary adrenal insufficiency (AI). Design Prospective, open-label, multicenter, 5-year extension study of DR-HC conducted at five university clinics in Sweden. Methods Seventy-one adult patients diagnosed with primary AI who were receiving stable glucocorticoid replacement therapy were recruited. Safety and tolerability outcomes included adverse events (AEs), intercurrent illness episodes, laboratory parameters and vital signs. Quality of life (QoL) was evaluated using generic questionnaires. Results Total DR-HC exposure was 328 patient-treatment years. Seventy patients reported 1060 AEs (323 per 100 patient-years); 85% were considered unrelated to DR-HC by the investigator. The most common AEs were nasopharyngitis (70%), fatigue (52%) and gastroenteritis (48%). Of 65 serious AEs reported by 32 patients (20 per 100 patient-years), four were considered to be possibly related to DR-HC: acute AI (n = 2), gastritis (n = 1) and syncope (n = 1). Two deaths were reported (fall from height and subarachnoid hemorrhage), both considered to be unrelated to DR-HC. From baseline to 5 years, intercurrent illness episodes remained relatively stable (mean 2.6–5.4 episodes per patient per year), fasting plasma glucose (0.7 mmol/L; P < 0.0001) and HDL cholesterol (0.2 mmol/L; P < 0.0001) increased and patient-/investigator-assessed tolerability improved. QoL total scores were unchanged but worsening physical functioning was recorded (P = 0.008). Conclusions In the first prospective study evaluating the long-term safety of glucocorticoid replacement therapy in patients with primary AI, DR-HC was well tolerated with no safety concerns observed during 5-year treatment. PMID:28292927

  10. Jump performance and augmented feedback: immediate benefits and long-term training effects.

    PubMed

    Keller, Martin; Lauber, Benedikt; Gehring, Dominic; Leukel, Christian; Taube, Wolfgang

    2014-08-01

    Drop jumps and their adaptations to training have been extensively investigated. However, the influence of augmented feedback (aF) on stretch-shortening cycle (SSC) was not scrutinized so far despite the well-known positive effects of aF on motor performance and motor learning. The aim of the present study was therefore to investigate the effects of aF by evaluating immediate within-session effects and long-term adaptations. 34 participants were assigned to three groups that trained drop jumps with different relative frequencies of aF about their jump height: 100%, 50%, or 0%. A significant within-session effect of aF on jump height was observed before and also after the training period (pre: +4.6%; post: +2.6%). In the long-term (comparing pre- to post-measurement), the 100% group showed the greatest increase in jump height (+14%), followed by the 50% (+10%) and the 0% group (+6%). The importance of aF on drop jumps is therefore twofold: (i) to immediately increase jump performance and (ii) to improve long-term training efficacy. In contrast to the proposition of the guidance hypothesis, high frequency of aF seems to be beneficial when maximizing SSC-performance. As jump height cannot be quantified without objective technical measures it is recommended to include them into daily training. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. Biogeography and organic matter removal shape long-term effects of timber harvesting on forest soil microbial communities.

    PubMed

    Wilhelm, Roland C; Cardenas, Erick; Maas, Kendra R; Leung, Hilary; McNeil, Larisa; Berch, Shannon; Chapman, William; Hope, Graeme; Kranabetter, J M; Dubé, Stephane; Busse, Matt; Fleming, Robert; Hazlett, Paul; Webster, Kara L; Morris, David; Scott, D Andrew; Mohn, William W

    2017-11-01

    The growing demand for renewable, carbon-neutral materials and energy is leading to intensified forest land-use. The long-term ecological challenges associated with maintaining soil fertility in managed forests are not yet known, in part due to the complexity of soil microbial communities and the heterogeneity of forest soils. This study determined the long-term effects of timber harvesting, accompanied by varied organic matter (OM) removal, on bacterial and fungal soil populations in 11- to 17-year-old reforested coniferous plantations at 18 sites across North America. Analysis of highly replicated 16 S rRNA gene and ITS region pyrotag libraries and shotgun metagenomes demonstrated consistent changes in microbial communities in harvested plots that included the expansion of desiccation- and heat-tolerant organisms and decline in diversity of ectomycorrhizal fungi. However, the majority of taxa, including the most abundant and cosmopolitan groups, were unaffected by harvesting. Shifts in microbial populations that corresponded to increased temperature and soil dryness were moderated by OM retention, which also selected for sub-populations of fungal decomposers. Biogeographical differences in the distribution of taxa as well as local edaphic and environmental conditions produced substantial variation in the effects of harvesting. This extensive molecular-based investigation of forest soil advances our understanding of forest disturbance and lays the foundation for monitoring long-term impacts of timber harvesting.

  12. [THE REGULATING EFFECT OF DIPEPTIDES ON CELL PROLIFERATION IN NERVE TISSUE CULTURE IN MAMMALS AND ON ASSOCIATIVE LEARNING IN INSECTS].

    PubMed

    Chalisova, N I; Zachepilo, T G; Kamyshev, N G; Lopatina, N G

    2015-01-01

    The effect of dipeptides AspPro and AspSer and of their composing amino acids (asparagine acid--Asp, proline--Pro, serin--Ser) on the proliferative activity in the explants of cortex and subcortical structures of the rat brain and on the functional activity of CNS of the honeybee was studied. The square index defined as a proportion of the whole explant square to the square of its central zone was determined. The number of bees responded with the conditional reaction (proboscis extension in the direction to aromatized solution) after 1 min (short-term memory) and 180 min (long-term memory) was detected after single learning procedure. Both dipeptides, as well as the asparagine acid, stimulated an increase of the growth zone of the subcortical structure explants in rats and of the number of honeybees with retention of conditional reaction in the short-term/long-term memory independently of the effect of the second member of the dipeptide. The unidirectionality of the effect suggests the existence of common mechanisms of reception and signal transduction established during evolution that require the further study.

  13. Childhood and adolescent obesity and long-term cognitive consequences during aging.

    PubMed

    Wang, Jun; Freire, Daniel; Knable, Lindsay; Zhao, Wei; Gong, Bing; Mazzola, Paolo; Ho, Lap; Levine, Samara; Pasinetti, Giulio M

    2015-04-01

    The prevalence of childhood/adolescent obesity and insulin resistance has reached an epidemic level. Obesity's immediate clinical impacts have been extensively studied; however, current clinical evidence underscores the long-term implications. The current study explored the impacts of brief childhood/adolescent obesity and insulin resistance on cognitive function in later life. To mimic childhood/adolescent obesity and insulin resistance, we exposed 9-week-old C57BL/6J mice to a high-fat diet for 15 weeks, after which the mice exhibited diet-induced obesity and insulin resistance. We then put these mice back on a normal low-fat diet, after which the mice exhibited normal body weight and glucose tolerance. However, a spatial memory test in the forms of the Morris water maze (MWM) and contextual fear conditioning at 85 weeks of age showed that these mice had severe deficits in learning and long-term memory consolidation. Mechanistic investigations identified increased expression of histone deacetylases 5, accompanied by reduced expression of brain-derived neurotrophic factor, in the brains 61 weeks after the mice had been off the high-fat diet. Electrophysiology studies showed that hippocampal slices isolated from these mice are more susceptible to synaptic impairments compared with slices isolated from the control mice. We demonstrated that a 15-week occurrence of obesity and insulin resistance during childhood/adolescence induces irreversible epigenetic modifications in the brain that persist following restoration of normal metabolic homeostasis, leading to brain synaptic dysfunction during aging. Our study provides experimental evidence that limited early-life exposure to obesity and insulin resistance may have long-term deleterious consequences in the brain, contributing to the onset/progression of cognitive dysfunction during aging. © 2014 Wiley Periodicals, Inc.

  14. Vedolizumab Induces Long-term Mucosal Healing in Patients With Crohn's Disease and Ulcerative Colitis.

    PubMed

    Noman, Maja; Ferrante, Marc; Bisschops, Raf; De Hertogh, Gert; Van den Broeck, Karolien; Rans, Karen; Rutgeerts, Paul; Vermeire, Séverine; Van Assche, Gert

    2017-09-01

    Vedolizumab has proven efficacy in inflammatory bowel disease [IBD], but long-term mucosal healing in Crohn's disease [CD], as well as the incidence of colorectal neoplasia in IBD, among patients treated with vedolizumab have not been studied. We aimed to document mucosal healing and to explore the risk of colorectal neoplasia with vedolizumab maintenance therapy. Surveillance colonoscopy was prospectively scheduled for patients with longstanding ulcerative coltis [UC] or CD at a tertiary referral centre, in the open-label extension phase (vedolizumab 300 mg intravenously [IV] every 4 weeks) of the Gemini studies [GEMINI LTS, study number NCT00790933]. Mayo score ≤ 1 or ulcer disappearance [in CD] was defined as mucosal healing. Targeted biopsies were graded for inflammation and dysplasia. Of 68 patients [29 CD/39 UC] treated for ≥ 1 year [median 3.2 years, range 1.1-6.1], 58 [24 CD/34 UC] were endoscopically monitored. Durable endoscopic healing corrected by non-responder imputation was found in 7/24, 29% [CD] and 17/34, 50% [UC]. Combined histological and mucosal healing was observed in 5/24 [CD] and 11/34 [UC] of those with endoscopic healing. Low-grade dysplasia was detected in 10% of patients and high-grade dysplasia in the resection specimen of one patient with biopsy-proven low-grade dysplasia. Long-term endoscopic and histological healing was observed in a proportion of patients treated with vedolizumab long-term. The dysplasia risk with vedolizumab deserves further study. Copyright © 2017 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com

  15. Biogeochemical Research Priorities for Sustainable Biofuel and Bioenergy Feedstock Production in the Americas.

    PubMed

    Gollany, Hero T; Titus, Brian D; Scott, D Andrew; Asbjornsen, Heidi; Resh, Sigrid C; Chimner, Rodney A; Kaczmarek, Donald J; Leite, Luiz F C; Ferreira, Ana C C; Rod, Kenton A; Hilbert, Jorge; Galdos, Marcelo V; Cisz, Michelle E

    2015-12-01

    Rapid expansion in biomass production for biofuels and bioenergy in the Americas is increasing demand on the ecosystem resources required to sustain soil and site productivity. We review the current state of knowledge and highlight gaps in research on biogeochemical processes and ecosystem sustainability related to biomass production. Biomass production systems incrementally remove greater quantities of organic matter, which in turn affects soil organic matter and associated carbon and nutrient storage (and hence long-term soil productivity) and off-site impacts. While these consequences have been extensively studied for some crops and sites, the ongoing and impending impacts of biomass removal require management strategies for ensuring that soil properties and functions are sustained for all combinations of crops, soils, sites, climates, and management systems, and that impacts of biomass management (including off-site impacts) are environmentally acceptable. In a changing global environment, knowledge of cumulative impacts will also become increasingly important. Long-term experiments are essential for key crops, soils, and management systems because short-term results do not necessarily reflect long-term impacts, although improved modeling capability may help to predict these impacts. Identification and validation of soil sustainability indicators for both site prescriptions and spatial applications would better inform commercial and policy decisions. In an increasingly inter-related but constrained global context, researchers should engage across inter-disciplinary, inter-agency, and international lines to better ensure the long-term soil productivity across a range of scales, from site to landscape.

  16. Lung volume reduction surgery for emphysema.

    PubMed

    Flaherty, K R; Martinez, F J

    2000-12-01

    Over the past decades, extensive literature has been published regarding surgical therapies for advanced COPD. Lung-volume reduction surgery would be an option for a significantly larger number of patients than classic bullectomy or lung transplantation. Unfortunately, the initial enthusiasm has been tempered by major questions regarding the optimal surgical approach, safety, firm selection criteria, and confirmation of long-term benefits. In fact, the long-term follow-up reported in patients undergoing classical bullectomy should serve to caution against unbridled enthusiasm for the indiscriminate application of LVRS. Those with the worst long-term outcome despite favourable short-term improvements after bullectomy have consistently been those with the lowest pulmonary function and significant emphysema in the remaining lung who appear remarkably similar to those being evaluated for LVRS. With this in mind, the National Heart, Lung and Blood Institute partnered with the Health Care Finance Administration to establish a multicenter, prospective, randomized study of intensive medical management, including pulmonary rehabilitation versus the same plus bilateral (by MS or VATS), known as the National Emphysema Treatment Trial. The primary objectives are to determine whether LVRS improves survival and exercise capacity. The secondary objectives will examine effects on pulmonary function and HRQL, compare surgical techniques, examine selection criteria for optimal response, identify criteria to determine those who are at prohibitive surgical risk, and examine long-term cost effectiveness. It is hoped that data collected from this novel, multicenter collaboration will place the role of LVRS in a clearer perspective for the physician caring for patients with advanced emphysema.

  17. Decadal and seasonal changes in temperature, salinity, nitrate, and chlorophyll in inshore and offshore waters along southeast Australia

    NASA Astrophysics Data System (ADS)

    Kelly, Paige; Clementson, Lesley; Lyne, Vincent

    2015-06-01

    Sixty years of oceanographic in situ data at Port Hacking (34°S) and Maria Island (42°S) and 15 years of satellite-derived chlorophyll a (chl a) in inshore and offshore waters of southeast Australia show changes in the seasonality and trend of water properties consistent with long-term intensification and southerly extensions of East Australian Current (EAC) water. Decadal analyses reveal that the EAC extension water at Maria Island increased gradually from the 1940s to 1980s, followed by a rapid increase since the 1990s. This acceleration coincided with enhanced winter nitrate, implying increased injections of subantarctic water at Maria Island. Satellite-derived chl a at six coastal sites and offshore companion sites in the western Tasman Sea showed significant inshore-offshore variations in seasonal cycle and long-term trend. After 2004-2005, the Maria Island seasonal cycle became increasingly similar to those of Bass Strait and St. Helens, suggesting that the EAC extension water was extending further southward. Comparative analyses of inshore-offshore sites showed that the presence of EAC extension water declined offshore. Seasonal cycles at Maria Island show a recent shift away from the traditional spring bloom, toward increased winter biomass, and enhanced primary productivity consistent with extensions of warm, energetic EAC extension water and more frequent injections of cooler, fresher nitrate-replete waters. Overall, we find complex temporal, latitudinal, and inshore-offshore changes in multiple water masses, particularly at Maria Island, and changes in primary productivity that will profoundly impact fisheries and ecosystems.

  18. Extensive piano practicing has regionally specific effects on white matter development.

    PubMed

    Bengtsson, Sara L; Nagy, Zoltán; Skare, Stefan; Forsman, Lea; Forssberg, Hans; Ullén, Fredrik

    2005-09-01

    Using diffusion tensor imaging, we investigated effects of piano practicing in childhood, adolescence and adulthood on white matter, and found positive correlations between practicing and fiber tract organization in different regions for each age period. For childhood, practicing correlations were extensive and included the pyramidal tract, which was more structured in pianists than in non-musicians. Long-term training within critical developmental periods may thus induce regionally specific plasticity in myelinating tracts.

  19. Thin-plate spline analysis of mandibular shape changes induced by functional appliances in Class II malocclusion : A long-term evaluation.

    PubMed

    Franchi, Lorenzo; Pavoni, Chiara; Faltin, Kurt; Bigliazzi, Renato; Gazzani, Francesca; Cozza, Paola

    2016-09-01

    The purpose of this work was to evaluate the long-term morphological mandibular changes induced by functional treatment of Class II malocclusion with mandibular retrusion. Forty patients (20 females, 20 males) with Class II malocclusion consecutively treated with either a Bionator or an Activator followed by fixed appliances were compared with a control group of 40 subjects (19 females, 21 males) with untreated Class II malocclusion. Lateral cephalograms were available at the start of treatment (T1, mean age 9.9 years), at the end of treatment with functional appliances (T2, mean age 12.2 years), and for long-term follow-up (T3, mean age 18.3 years). Mandibular shape changes were analyzed on lateral cephalograms of the subjects in both groups via thin-plate spline (TPS) analysis. Shape differences were statistically analyzed by conducting permutation tests on Goodall F statistics. In the long term, both the treated and control groups exhibited significant longitudinal mandibular shape changes characterized by upward and forward dislocation of point Co associated with a vertical extension in the gonial region and backward dislocation of point B. Functional appliances induced mandible's significant posterior morphogenetic rotation over the short term. The treated and control groups demonstrated similar mandibular shape over the long term.

  20. Long-Term Post-Disturbance Forest Recovery in the Greater Yellowstone Ecosystem Analyzed Using Landsat Time Series Stack

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

    Zhao, Feng R.; Meng, Ran; Huang, Chengquan

    Forest recovery from past disturbance is an integral process of ecosystem carbon cycles, and remote sensing provides an effective tool for tracking forest disturbance and recovery over large areas. Although the disturbance products (tracking the conversion from forest to non-forest type) derived using the Landsat Time Series Stack-Vegetation Change Tracker (LTSS-VCT) algorithm have been validated extensively for mapping forest disturbances across the United States, the ability of this approach to characterize long-term post-disturbance recovery (the conversion from non-forest to forest) has yet to be assessed. Here in this study, the LTSS-VCT approach was applied to examine long-term (up to 24more » years) post-disturbance forest spectral recovery following stand-clearing disturbances (fire and harvests) in the Greater Yellowstone Ecosystem (GYE). Using high spatial resolution images from Google Earth, we validated the detectable forest recovery status mapped by VCT by year 2011. Validation results show that the VCT was able to map long-term post-disturbance forest recovery with overall accuracy of ~80% for different disturbance types and forest types in the GYE. Harvested areas in the GYE have higher percentages of forest recovery than burned areas by year 2011, and National Forests land generally has higher recovery rates compared with National Parks. The results also indicate that forest recovery is highly related with forest type, elevation and environmental variables such as soil type. Findings from this study can provide valuable insights for ecosystem modeling that aim to predict future carbon dynamics by integrating fine scale forest recovery conditions in GYE, in the face of climate change. Lastly, with the availability of the VCT product nationwide, this approach can also be applied to examine long-term post-disturbance forest recovery in other study regions across the U.S.« less

  1. Long-Term Post-Disturbance Forest Recovery in the Greater Yellowstone Ecosystem Analyzed Using Landsat Time Series Stack

    DOE PAGES

    Zhao, Feng R.; Meng, Ran; Huang, Chengquan; ...

    2016-10-29

    Forest recovery from past disturbance is an integral process of ecosystem carbon cycles, and remote sensing provides an effective tool for tracking forest disturbance and recovery over large areas. Although the disturbance products (tracking the conversion from forest to non-forest type) derived using the Landsat Time Series Stack-Vegetation Change Tracker (LTSS-VCT) algorithm have been validated extensively for mapping forest disturbances across the United States, the ability of this approach to characterize long-term post-disturbance recovery (the conversion from non-forest to forest) has yet to be assessed. Here in this study, the LTSS-VCT approach was applied to examine long-term (up to 24more » years) post-disturbance forest spectral recovery following stand-clearing disturbances (fire and harvests) in the Greater Yellowstone Ecosystem (GYE). Using high spatial resolution images from Google Earth, we validated the detectable forest recovery status mapped by VCT by year 2011. Validation results show that the VCT was able to map long-term post-disturbance forest recovery with overall accuracy of ~80% for different disturbance types and forest types in the GYE. Harvested areas in the GYE have higher percentages of forest recovery than burned areas by year 2011, and National Forests land generally has higher recovery rates compared with National Parks. The results also indicate that forest recovery is highly related with forest type, elevation and environmental variables such as soil type. Findings from this study can provide valuable insights for ecosystem modeling that aim to predict future carbon dynamics by integrating fine scale forest recovery conditions in GYE, in the face of climate change. Lastly, with the availability of the VCT product nationwide, this approach can also be applied to examine long-term post-disturbance forest recovery in other study regions across the U.S.« less

  2. Dynamics of Hippocampal Protein Expression During Long-term Spatial Memory Formation*

    PubMed Central

    Borovok, Natalia; Nesher, Elimelech; Levin, Yishai; Reichenstein, Michal; Pinhasov, Albert

    2016-01-01

    Spatial memory depends on the hippocampus, which is particularly vulnerable to aging. This vulnerability has implications for the impairment of navigation capacities in older people, who may show a marked drop in performance of spatial tasks with advancing age. Contemporary understanding of long-term memory formation relies on molecular mechanisms underlying long-term synaptic plasticity. With memory acquisition, activity-dependent changes occurring in synapses initiate multiple signal transduction pathways enhancing protein turnover. This enhancement facilitates de novo synthesis of plasticity related proteins, crucial factors for establishing persistent long-term synaptic plasticity and forming memory engrams. Extensive studies have been performed to elucidate molecular mechanisms of memory traces formation; however, the identity of plasticity related proteins is still evasive. In this study, we investigated protein turnover in mouse hippocampus during long-term spatial memory formation using the reference memory version of radial arm maze (RAM) paradigm. We identified 1592 proteins, which exhibited a complex picture of expression changes during spatial memory formation. Variable linear decomposition reduced significantly data dimensionality and enriched three principal factors responsible for variance of memory-related protein levels at (1) the initial phase of memory acquisition (165 proteins), (2) during the steep learning improvement (148 proteins), and (3) the final phase of the learning curve (123 proteins). Gene ontology and signaling pathways analysis revealed a clear correlation between memory improvement and learning phase-curbed expression profiles of proteins belonging to specific functional categories. We found differential enrichment of (1) neurotrophic factors signaling pathways, proteins regulating synaptic transmission, and actin microfilament during the first day of the learning curve; (2) transcription and translation machinery, protein trafficking, enhancement of metabolic activity, and Wnt signaling pathway during the steep phase of memory formation; and (3) cytoskeleton organization proteins. Taken together, this study clearly demonstrates dynamic assembly and disassembly of protein-protein interaction networks depending on the stage of memory formation engrams. PMID:26598641

  3. Perampanel in the management of partial-onset seizures: a review of safety, efficacy, and patient acceptability

    PubMed Central

    Schulze-Bonhage, Andreas; Hintz, Mandy

    2015-01-01

    Perampanel (PER) is a novel antiepileptic drug recently introduced for the adjunctive treatment in epilepsy patients aged 12 years or older with partial-onset seizures with or without secondary generalization in the US and Europe. Its antiepileptic action is based on noncompetitive inhibition of postsynaptic AMPA receptors, decreasing excitatory synaptic transmission. Evaluation of efficacy in three placebo-controlled randomized Phase III studies showed that add-on therapy of PER decreased seizure frequencies significantly compared to placebo at daily doses between 4 mg/day and 12 mg/day. PER’s long half-life of 105 hours allows for once-daily dosing that is favorable for patient compliance with intake. Long-term extension studies showed a 62.5%–69.6% adherence of patients after 1 year of treatment, comparing favorably with other second-generation antiepileptic drugs. Whereas these trials demonstrated an overall favorable tolerability profile of PER, nonspecific central nervous system adverse effects like somnolence, dizziness, headache, and fatigue may occur. In addition, neuropsychiatric disturbances ranging from irritability to suicidality were reported in several case reports; both placebo-controlled and prospective long-term extension trials showed a low incidence of such behavioral and psychiatric complaints. For early recognition of neuropsychiatric symptoms like depression, anxiety, and aggression, slow titration and close monitoring during drug introduction are mandatory. This allows on the one hand to recognize patients particularly susceptible to adverse effects of the drug, and on the other hand to render the drug’s full potential of seizure control available for the vast majority of patient groups tolerating the drug well. PMID:26316718

  4. Backcasting long-term climate data: evaluation of hypothesis

    NASA Astrophysics Data System (ADS)

    Saghafian, Bahram; Aghbalaghi, Sara Ghasemi; Nasseri, Mohsen

    2018-05-01

    Most often than not, incomplete datasets or short-term recorded data in vast regions impedes reliable climate and water studies. Various methods, such as simple correlation with stations having long-term time series, are practiced to infill or extend the period of observation at stations with missing or short-term data. In the current paper and for the first time, the hypothesis on the feasibility of extending the downscaling concept to backcast local observation records using large-scale atmospheric predictors is examined. Backcasting is coined here to contrast forecasting/projection; the former is implied to reconstruct in the past, while the latter represents projection in the future. To assess our hypotheses, daily and monthly statistical downscaling models were employed to reconstruct past precipitation data and lengthen the data period. Urmia and Tabriz synoptic stations, located in northwestern Iran, constituted two case study stations. SDSM and data-mining downscaling model (DMDM) daily as well as the group method of data handling (GMDH) and model tree (Mp5) monthly downscaling models were trained with National Center for Environmental Prediction (NCEP) data. After training, reconstructed precipitation data of the past was validated against observed data. Then, the data was fully extended to the 1948 to 2009 period corresponding to available NCEP data period. The results showed that DMDM performed superior in generation of monthly average precipitation compared with the SDSM, Mp5, and GMDH models, although none of the models could preserve the monthly variance. This overall confirms practical value of the proposed approach in extension of the past historic data, particularly for long-term climatological and water budget studies.

  5. Engaging Living Kidney Donors in a New Paradigm of Postdonation Care.

    PubMed

    Newell, K A; Formica, R N; Gill, J S

    2016-01-01

    Recent studies have highlighted the need for better understanding of the long-term health outcomes of living donors. Barriers to establishment of a dedicated long-term donor follow-up data system in the United States include infrastructure costs and donor retention. We propose providing all previous and future living donors with a lifelong health insurance benefit for the primary purpose of facilitating acquisition of health information after donation as an alternative to establishment of a dedicated donor follow-up data system. Donors would consent to allow collection and analysis of their medical data, and continuation of insurance coverage would require completion of regular health assessments. The extension of health insurance would be analogous to the established practice of paying people for participation in a research study and would provide a mechanism to engage donors in a new paradigm of postdonation care in which donors are actively involved in their own health maintenance. Rather than acting as an inducement for donation, providing donors with the ability to easily contribute information about their health status represents a practical strategy to acquire the long-term medical information necessary to better inform future generations of living kidney donors. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

  6. Long-Term Results of Surgery for Temporal Bone Paraganglioma

    PubMed Central

    Gjuric, Mislav; Seidinger, Lynda; Wigand, Malte Erik

    1996-01-01

    The only way to resolve the dispute about the effectiveness of surgery versus radiation therapy for glomus tympanicum and jugulare tumors is adequate long-term studies. In a retrospective study with an average follow-up period of 15 years (range 11 to 23 years) we reassessed 11 patients with glomus tympanicum tumors and 11 patients with glomus jugulare tumors. Ten of 11 patients with glomus tympanicum tumor were tumor-free after surgery. A temporary facial palsy and an external meatal wall defect were the only surgical complications. The air-bone gap postoperatively closed to within 10 dB in three patients, to within 20 dB in six patients, and to more than 30 dB in one patient. Nine of 10 patients with glomus jugulare tumor receiving complete resection were tumor-free. Less than half the patients experienced new-onset cranial nerve function loss, and all made satisfactory recovery, eliminating the need for tracheostomy or gastrostomy. In two patients, the hearing could be preserved on the preoperative level, but the majority already presented with deafness. In the long-term, surgery remains a treatment of choice for glomus tympanicum tumors. It is also an extremely effective treatment with low morbidity for glomus jugulare tumors, including those with intracranial extension. PMID:17170971

  7. Systematic review with meta-analysis: proximal disease extension in limited ulcerative colitis.

    PubMed

    Roda, G; Narula, N; Pinotti, R; Skamnelos, A; Katsanos, K H; Ungaro, R; Burisch, J; Torres, J; Colombel, J-F

    2017-06-01

    Disease extent in ulcerative colitis is one of the major factors determining prognosis over the long-term. Disease extent is dynamic and a proportion of patients presenting with limited disease progress to more extensive forms of disease over time. To perform a systematic review and meta-analysis of epidemiological studies reporting on extension of ulcerative colitis to determine frequency of disease extension in patients with limited ulcerative colitis at diagnosis. We performed a systematic literature search to identify studies on disease extension of ulcerative colitis (UC) and predictors of disease progression. Overall, 41 studies were eligible for systematic review but only 30 for meta-analysis. The overall pooled frequency of UC extension was 22.8% with colonic extension being 17.8% at 5 years and 31% at 10 years. Extension was 17.8% (95% CI 11.2-27.3) from E1 to E3, 27.5% (95% CI 7.6-45.6) from E2 to E3 and 20.8% (95% CI 11.4-26.8) from E1 to E2. Rate of extension was significantly higher in patients younger than 18 years (29.2% (CI 6.4-71.3) compared to older patients (20.2% (CI 13.0-30.1) (P<.0001). Risk of extension was significantly higher in patients from North America (37.8%) than from Europe (19.6%) (P<.0001). In this meta-analysis, approximately one quarter of patients with limited UC extend over time with most extension occurring during the first 10 years. Rate of extension depends on age at diagnosis and geographic origin. Predicting those at high risk of disease extension from diagnosis could lead to personalised therapeutic strategies. © 2017 John Wiley & Sons Ltd.

  8. Time series regression studies in environmental epidemiology.

    PubMed

    Bhaskaran, Krishnan; Gasparrini, Antonio; Hajat, Shakoor; Smeeth, Liam; Armstrong, Ben

    2013-08-01

    Time series regression studies have been widely used in environmental epidemiology, notably in investigating the short-term associations between exposures such as air pollution, weather variables or pollen, and health outcomes such as mortality, myocardial infarction or disease-specific hospital admissions. Typically, for both exposure and outcome, data are available at regular time intervals (e.g. daily pollution levels and daily mortality counts) and the aim is to explore short-term associations between them. In this article, we describe the general features of time series data, and we outline the analysis process, beginning with descriptive analysis, then focusing on issues in time series regression that differ from other regression methods: modelling short-term fluctuations in the presence of seasonal and long-term patterns, dealing with time varying confounding factors and modelling delayed ('lagged') associations between exposure and outcome. We finish with advice on model checking and sensitivity analysis, and some common extensions to the basic model.

  9. Use of autologous human mesenchymal stromal cell/fibrin clot constructs in upper limb non-unions: long-term assessment.

    PubMed

    Giannotti, Stefano; Trombi, Luisa; Bottai, Vanna; Ghilardi, Marco; D'Alessandro, Delfo; Danti, Serena; Dell'Osso, Giacomo; Guido, Giulio; Petrini, Mario

    2013-01-01

    Tissue engineering appears to be an attractive alternative to the traditional approach in the treatment of fracture non-unions. Mesenchymal stromal cells (MSCs) are considered an appealing cell source for clinical intervention. However, ex vivo cell expansion and differentiation towards the osteogenic lineage, together with the design of a suitable scaffold have yet to be optimized. Major concerns exist about the safety of MSC-based therapies, including possible abnormal overgrowth and potential cancer evolution. We examined the long-term efficacy and safety of ex vivo expanded bone marrow MSCs, embedded in autologous fibrin clots, for the healing of atrophic pseudarthrosis of the upper limb. Our research work relied on three main issues: use of an entirely autologous context (cells, serum for ex vivo cell culture, scaffold components), reduced ex vivo cell expansion, and short-term MSC osteoinduction before implantation. Bone marrow MSCs isolated from 8 patients were expanded ex vivo until passage 1 and short-term osteo-differentiated in autologous-based culture conditions. Tissue-engineered constructs designed to embed MSCs in autologous fibrin clots were locally implanted with bone grafts, calibrating their number on the extension of bone damage. Radiographic healing was evaluated with short- and long-term follow-ups (range averages: 6.7 and 76.0 months, respectively). All patients recovered limb function, with no evidence of tissue overgrowth or tumor formation. Our study indicates that highly autologous treatment can be effective and safe in the long-term healing of bone non-unions. This tissue engineering approach resulted in successful clinical and functional outcomes for all patients.

  10. Survival of Burns Involving 90% of the Total Body Surface Area After Treatment With Autologous Engineered Skin Substitutes

    DTIC Science & Technology

    2008-12-01

    during acute hospitalization, and can result in long-term morbidity from scars . In this study, autologous ESS were compared with split-thickness...meshed skin autograft treatment of two pediatric patients with burns of 90% TBSA or greater, and evaluated qualitatively for formation of scar , and...populations ( Armour et al. 2007). Availability of ESS for treatment of extensive, deep burns may reduce time to wound closure, morbidity and

  11. 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.

  12. 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

  13. Effect of dopamine agonist withdrawal after long-term therapy in prolactinomas. Studies with high-definition computerised tomography.

    PubMed

    Johnston, D G; Hall, K; Kendall-Taylor, P; Patrick, D; Watson, M; Cook, D B

    1984-07-28

    The clinical, radiological, and biochemical effects of dopamine agonist withdrawal after long-term treatment were investigated in seven women and eight men who had been treated for prolactinomas for 1.5 to 7 (mean 3.7) years. Before treatment, serum prolactin concentrations were 1473 to 115 000 mU/l, all patients had abnormal radiological findings, and six had suprasellar extensions of pituitary tumours. Treatment with either bromocriptine or pergolide relieved symptoms and suppressed prolactin secretion in most patients. The size of the residual tumour was defined by doing fourth generation computerised tomographic scans immediately before termination of therapy, and evidence of tumour re-expansion was sought on scans repeated 5-39 weeks later. After discontinuation of treatment, symptoms recurred in 13 of 15 patients and hyper-prolactinaemia redeveloped in 14. Other pituitary function tests remained unchanged or improved. In 13 of 15 patients tumour or gland size did not change after withdrawal of treatment. One man had a marginal increase in tumour size, while in another the pituitary tumour shrank. Thus, although cessation of long-term dopamine agonist therapy leads to recurrence of symptoms and hyperprolactinaemia, rapid tumour regrowth is uncommon and of small extent, and other pituitary function is not altered in the short term.

  14. Elaboration of Programmes, Programmes, Plans and Budgets of the National Libraries in Socialist Countries (37th Session, Liverpool, August 1971).

    ERIC Educational Resources Information Center

    Kanevsky, B. P.

    Long-term and short-term planning and programming and budgeting are an important part of the every-day activity of the national libraries in the socialist countries. The libraries extensively apply various types of planning ranging from current annual plans to complicated prognoses for 15-20 years ahead. These libraries display increasing…

  15. Chemical climatology of the southeastern United States, 1999-2013

    NASA Astrophysics Data System (ADS)

    Hidy, G. M.; Blanchard, C. L.; Baumann, K.; Edgerton, E.; Tanenbaum, S.; Shaw, S.; Knipping, E.; Tombach, I.; Jansen, J.; Walters, J.

    2014-06-01

    A series of experiments (the Southern Oxidant and Aerosol Study-SOAS) took place in central Alabama in June-July 2013 as part of the broader Southern Atmosphere Study (SAS). These projects were aimed at studying oxidant photochemistry and formation and impacts of aerosols at a detailed process level in a location where high biogenic organic vapor emissions interact with anthropogenic emissions, and the atmospheric chemistry occurs in a subtropical climate in North America. The majority of the ground-based experiments were located at the Southeastern Aerosol Research and Characterization (SEARCH) Centreville (CTR) site near Brent, Alabama, where extensive, unique aerometric measurements of meteorology, trace gases and particles have been made from the early 1990s through 2013. The SEARCH network data permits a characterization of temporal and spatial context of the SOAS findings. The long-term measurements show that the SOAS experiments took place during the second wettest and coolest year in the 2000-2013 period, with lower than average solar radiation. The pollution levels at CTR and other SEARCH sites were the lowest since full measurements began in 1999. This dataset provides a perspective for the SOAS program in terms of long-term average chemistry (chemical climatology) and short-term comparisons of summer average spatial variability across the Southeast at high temporal (hourly) resolution. Changes in anthropogenic gas and particle emissions between 1999 and 2013, account for the decline in pollutant concentrations at the monitoring sites in the region. The long-term and short-term data provide an opportunity to contrast SOAS results with temporally and spatially variable conditions in support for the development of tests for the robustness of SOAS findings.

  16. Revision hip arthroplasty with an extensively 
porous-coated stem - excellent long-term 
results also in severe femoral bone stock loss.

    PubMed

    Thomsen, Per B; Jensen, Niels J F; Kampmann, Jens; Bæk Hansen, Torben

    2013-01-01

    During the last 25 years uncemented hip stem revision relying on diaphyseal fixation has shown improving clinical results and stem survival. The purpose of this study was to present the long-term results of hip revision with the SOLUTION stem (DePuy, Warsaw Indiana).
Ninety-three consecutive SOLUTION hip stem revisions in 84 patients with a mean age of 69 years (range 33-86 years) were reviewed. Of these, clinical and radiographic follow-up examination by an independent observer was possible in 36 hips/29 patients after mean 14 years (range 10-18 years). Stem re-revision was documented by our own files and by the Danish Hip Arthroplasty Registry. 
Stem re-revision had been performed in two hips for aseptic loosening, one due to deep infection and in one patient due to stem fracture. The 18 years cumulative survival, free of re-revision for any reason was calculated as 94.4% (88.9-99.8)% and for aseptic loosening to 97.6% (94.3-100%). Intraoperative complications were frequent with incidence of shaft fractures (14/93) and perforations (9/93) showing a significant learning curve. Mean Harris Hip Score was 85 (range 53-99). Osseointegration was seen in 34/36 stems with two stems fibrous fixated. Stress shielding was significant associated with stem diameters ≥15 mm. Severe preoperative bone deficiency had no negative bearing on stem survival and no significant influence on osseointegration of the stem or on Harris Hip Score. 
 Femoral stem revision with an extensively porous-coated monoblock chrome-cobalt stem seems to be a reliable and reproducible technique resulting in excellent long-term survivorship and clinical outcome. It can be used in femurs with deficient bone stock.

  17. Long-term exposure to fine particulate matter, residential proximity to major roads and measures of brain structure.

    PubMed

    Wilker, Elissa H; Preis, Sarah R; Beiser, Alexa S; Wolf, Philip A; Au, Rhoda; Kloog, Itai; Li, Wenyuan; Schwartz, Joel; Koutrakis, Petros; DeCarli, Charles; Seshadri, Sudha; Mittleman, Murray A

    2015-05-01

    Long-term exposure to ambient air pollution is associated with cerebrovascular disease and cognitive impairment, but whether it is related to structural changes in the brain is not clear. We examined the associations between residential long-term exposure to ambient air pollution and markers of brain aging using magnetic resonance imaging. Framingham Offspring Study participants who attended the seventh examination were at least 60 years old and free of dementia and stroke were included. We evaluated associations between exposures (fine particulate matter [PM2.5] and residential proximity to major roadways) and measures of total cerebral brain volume, hippocampal volume, white matter hyperintensity volume (log-transformed and extensive white matter hyperintensity volume for age), and covert brain infarcts. Models were adjusted for age, clinical covariates, indicators of socioeconomic position, and temporal trends. A 2-μg/m(3) increase in PM2.5 was associated with -0.32% (95% confidence interval, -0.59 to -0.05) smaller total cerebral brain volume and 1.46 (95% confidence interval, 1.10 to 1.94) higher odds of covert brain infarcts. Living further away from a major roadway was associated with 0.10 (95% confidence interval, 0.01 to 0.19) greater log-transformed white matter hyperintensity volume for an interquartile range difference in distance, but no clear pattern of association was observed for extensive white matter. Exposure to elevated levels of PM2.5 was associated with smaller total cerebral brain volume, a marker of age-associated brain atrophy, and with higher odds of covert brain infarcts. These findings suggest that air pollution is associated with insidious effects on structural brain aging even in dementia- and stroke-free persons. © 2015 American Heart Association, Inc.

  18. A pilot study on the effect of a symbiotic mixture in irritable bowel syndrome: an open-label, partially controlled, 6-month extension of a previously published trial.

    PubMed

    Bucci, C; Tremolaterra, F; Gallotta, S; Fortunato, A; Cappello, C; Ciacci, C; Iovino, P

    2014-04-01

    In recent years, the efficacy of probiotics has received considerable attention in the treatment for irritable bowel syndrome (IBS). In this regard, a symbiotic mixture (Probinul(®)) has shown beneficial effects. The aim of this study was to extend the previously published 4-week randomized, double-blinded, placebo-controlled study of this symbiotic mixture. This is an open-label prospective, partially controlled, 6-month extension period pilot study in which patients continued to receive the symbiotic mixture (Group 1) or were switched from placebo to symbiotic mixture (Group 2) using cyclic administration (last 2 weeks/month). The primary endpoints were the overall satisfactory relief of bloating and flatulence (assessed as proportions of responders). The secondary endpoints were evaluation of the symptom severity scores (bloating, flatulence, pain and urgency) and bowel function scores (frequency, consistency and incomplete evacuation). Twenty-six IBS patients completed the 6-month extension period (13 patients in Group 1 and 13 patients in Group 2). In the per-protocol analysis, the proportions of responders across time were not significantly different in the groups but in Group 2, there was an increased percentage of responders for flatulence (p = 0.07). In addition, the score of flatulence was reduced significantly during the 6-month treatment period in Group 2 (p < 0.05), while no other significant differences were detected. Treatment with this symbiotic mixture was associated with persistence of relief from flatulence or new reduction in flatulence in the present 6-month long extension study. These results need to be more comprehensively assessed in large, long-term, randomized, placebo-controlled studies.

  19. Long-term safety and tolerability of once-daily mesalamine granules in the maintenance of remission of ulcerative colitis.

    PubMed

    Lichtenstein, Gary R; Barrett, Andrew C; Bortey, Enoch; Paterson, Craig; Forbes, William P

    2014-08-01

    Ulcerative colitis (UC), a chronic, relapsing, and remitting inflammatory bowel disease, requires long-term treatment to maintain remission. In this study, the long-term safety and tolerability of mesalamine granules (MG) therapy was evaluated in the maintenance of UC remission. Previous prospective studies evaluating different oral mesalamine formulations have not exceeded a duration of 14 months. A phase 3, multicenter, 24-month, open-label extension study evaluating MG 1.5 g once daily in patients who achieved previous remission from mild to moderate UC was performed. Eligible patients had successfully participated in 1 of 2 previous 6-month double-blind, placebo-controlled trials or were new patients in remission. Safety assessments included monitoring of adverse events (AEs) and clinical laboratory tests. Risk of UC recurrence was assessed by the occurrence of UC-related AEs. Of the 393 patients enrolled (280 from the double-blind studies; 113 new patients), 388 were included in the safety population. The most common AEs included nasopharyngitis (13.9%), headache (11.6%), and diarrhea (10.8%), and the incidence of these events was generally lower in the MG group versus historical placebo group from the double-blind studies. Pancreatic, renal, and hepatic AEs occurred in 23 patients (5.9%). The risk of UC-related AEs was low and was maintained for 24 months during the open-label study. Once-daily MG has a favorable safety profile for the maintenance of remission for up to 2 years in patients with UC.

  20. Prospective evaluation of the long-term effects of clinical voiding reeducation or voiding school for lower urinary tract conditions in children.

    PubMed

    Van den Broeck, C; de Mettelinge, T Roman; Deschepper, E; Van Laecke, E; Renson, C; Samijn, B; Hoebeke, P

    2016-02-01

    Although the short-term effects of urotherapy as a treatment strategy for lower urinary tract (LUT) conditions have been well documented, the long-term effects remain largely unknown. A better insight into the long-term effects of urotherapy could improve the clinical guidelines for children with incontinence. This study aimed to investigate the long-term effects (i.e., from 6 months to 2 years) from a clinical voiding reeducation program among children with LUT conditions. This study was a prospective continuation of the follow-up study of Hoebeke et al. (2011). Thirty-eight children (mean age 9 years) with LUT conditions completed an extensive clinical voiding reeducation program (VS). Data on medication, voiding, drinking, pelvic floor tone, uroflowmetry, and incontinence were recorded 2 years after the VS. These data were compared with the outcomes at 6 months follow-up and at intake before voiding school. Six months after voiding school, 22 children continued having daytime incontinence (ID) and/or enuresis (EN). Six of them became dry at 2 years. Conversely, 16 children were dry at 6 months, of which eight relapsed at 2 years. Whereas all parameters significantly improved 6 months after VS, further improvements from 6 months to 2 years could only be noticed for the proportion of children suffering from overactive bladder (92% at intake, 55% at 6-month follow-up and 18% at 2-year follow-up) (Figure). Fluid intake and pelvic floor tone improved after 6 months, but showed a significant relapse after 2 years (P = 0.013, P = 0.031, respectively). Hoebeke et al. (2011) concluded that results continued to improve after VS. No further improvements could be noticed 2 years after VS, although individual shifts were present. The results of the present study underline the value of long-term follow-up to detect those needing ongoing treatment to prevent relapse. Fluid intake and pelvic floor tone deteriorated from 6 months to 2 years. It could be hypothesized that inadequate fluid intake, possibly leading to decreased voided volumes, may be seen as an indicator for upcoming incontinence relapse. It could be stated that adequate fluid intake and pelvic floor tone may play a role in remaining continent for the long term. Study limitations should be considered. The study population was heterogeneous and rather small. Together with other missing values, this could have influenced the results. Close individual, long-term follow-up after clinical voiding reeducation in children is recommended in order to timely detect and prevent potential relapse. Copyright © 2015 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

  1. Stability enhancement of an atomic force microscope for long-term force measurement including cantilever modification for whole cell deformation

    NASA Astrophysics Data System (ADS)

    Weafer, P. P.; McGarry, J. P.; van Es, M. H.; Kilpatrick, J. I.; Ronan, W.; Nolan, D. R.; Jarvis, S. P.

    2012-09-01

    Atomic force microscopy (AFM) is widely used in the study of both morphology and mechanical properties of living cells under physiologically relevant conditions. However, quantitative experiments on timescales of minutes to hours are generally limited by thermal drift in the instrument, particularly in the vertical (z) direction. In addition, we demonstrate the necessity to remove all air-liquid interfaces within the system for measurements in liquid environments, which may otherwise result in perturbations in the measured deflection. These effects severely limit the use of AFM as a practical tool for the study of long-term cell behavior, where precise knowledge of the tip-sample distance is a crucial requirement. Here we present a readily implementable, cost effective method of minimizing z-drift and liquid instabilities by utilizing active temperature control combined with a customized fluid cell system. Long-term whole cell mechanical measurements were performed using this stabilized AFM by attaching a large sphere to a cantilever in order to approximate a parallel plate system. An extensive examination of the effects of sphere attachment on AFM data is presented. Profiling of cantilever bending during substrate indentation revealed that the optical lever assumption of free ended cantilevering is inappropriate when sphere constraining occurs, which applies an additional torque to the cantilevers "free" end. Here we present the steps required to accurately determine force-indentation measurements for such a scenario. Combining these readily implementable modifications, we demonstrate the ability to investigate long-term whole cell mechanics by performing strain controlled cyclic deformation of single osteoblasts.

  2. Controversies surrounding high-protein diet intake: satiating effect and kidney and bone health.

    PubMed

    Cuenca-Sánchez, Marta; Navas-Carrillo, Diana; Orenes-Piñero, Esteban

    2015-05-01

    Long-term consumption of a high-protein diet could be linked with metabolic and clinical problems, such as loss of bone mass and renal dysfunction. However, although it is well accepted that a high-protein diet may be detrimental to individuals with existing kidney dysfunction, there is little evidence that high protein intake is dangerous for healthy individuals. High-protein meals and foods are thought to have a greater satiating effect than high-carbohydrate or high-fat meals. The effect of high-protein diets on the modulation of satiety involves multiple metabolic pathways. Protein intake induces complex signals, with peptide hormones being released from the gastrointestinal tract and blood amino acids and derived metabolites being released in the blood. Protein intake also stimulates metabolic hormones that communicate information about energy status to the brain. Long-term ingestion of high amounts of protein seems to decrease food intake, body weight, and body adiposity in many well-documented studies. The aim of this article is to provide an extensive overview of the efficacy of high protein consumption in weight loss and maintenance, as well as the potential consequences in human health of long-term intake. © 2015 American Society for Nutrition.

  3. Controversies Surrounding High-Protein Diet Intake: Satiating Effect and Kidney and Bone Health12

    PubMed Central

    Cuenca-Sánchez, Marta; Navas-Carrillo, Diana; Orenes-Piñero, Esteban

    2015-01-01

    Long-term consumption of a high-protein diet could be linked with metabolic and clinical problems, such as loss of bone mass and renal dysfunction. However, although it is well accepted that a high-protein diet may be detrimental to individuals with existing kidney dysfunction, there is little evidence that high protein intake is dangerous for healthy individuals. High-protein meals and foods are thought to have a greater satiating effect than high-carbohydrate or high-fat meals. The effect of high-protein diets on the modulation of satiety involves multiple metabolic pathways. Protein intake induces complex signals, with peptide hormones being released from the gastrointestinal tract and blood amino acids and derived metabolites being released in the blood. Protein intake also stimulates metabolic hormones that communicate information about energy status to the brain. Long-term ingestion of high amounts of protein seems to decrease food intake, body weight, and body adiposity in many well-documented studies. The aim of this article is to provide an extensive overview of the efficacy of high protein consumption in weight loss and maintenance, as well as the potential consequences in human health of long-term intake. PMID:25979491

  4. How Business Cycles Affect the Healthcare Sector: A Cross-country Investigation.

    PubMed

    Cleeren, Kathleen; Lamey, Lien; Meyer, Jan-Hinrich; De Ruyter, Ko

    2016-07-01

    The long-term relationship between the general economy and healthcare expenditures has been extensively researched, to explain differences in healthcare spending between countries, but the midterm (i.e., business cycle) perspective has been overlooked. This study explores business cycle sensitivity in both public and private parts of the healthcare sector across 32 countries. Responses to the business cycle vary notably, both across spending sources and across countries. Whereas in some countries, consumers and/or governments cut back, in others, private and/or public healthcare buyers tend to spend more. We also assess long-term consequences of business cycle sensitivity and show that public cost cutting during economic downturns deflates the mortality rates, whereas private cut backs increase the long-term growth in total healthcare expenditures. Finally, multiple factors help explain variability in cyclical sensitivity. Private cost cuts during economic downturns are smaller in countries with a predominantly publicly funded healthcare system and more preventive public activities. Public cut backs during contractions are smaller in countries that rely more on tax-based resources rather than social health insurances. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  5. Neuritogenesis: A model for space radiation effects on the central nervous system

    NASA Technical Reports Server (NTRS)

    Vazquez, M. E.; Broglio, T. M.; Worgul, B. V.; Benton, E. V.

    1994-01-01

    Pivotal to the astronauts' functional integrity and survival during long space flights are the strategies to deal with space radiations. The majority of the cellular studies in this area emphasize simple endpoints such as growth related events which, although useful to understand the nature of primary cell injury, have poor predictive value for extrapolation to more complex tissues such as the central nervous system (CNS). In order to assess the radiation damage on neural cell populations, we developed an in vitro model in which neuronal differentiation, neurite extension, and synaptogenesis occur under controlled conditions. The model exploits chick embryo neural explants to study the effects of radiations on neuritogenesis. In addition, neurobiological problems associated with long-term space flights are discussed.

  6. Wound Closure and Outcome in Extensively Burned Patients Treated with Cultured Autologous Keratinocytes,

    DTIC Science & Technology

    1993-05-01

    long-term joint consequently has exerted no demonstrable effect on the contractures could be expected. Was any increase noted in this outcome of...ELECTE . , AD-A268 707 THE JOURNAL or TRAUMA so AU 3 019934 N Copyright 1993 by Wils & Printed in U.S.A. WOUND CLOSLRE AND OUTCOME IN EXTENSIVELY...Ultimate patient outcome remains dependent upon ocytes has prompted many investigators to assess the early, timely closure of the burn wound, typically

  7. Merging analytic and empirical GEO debris synchronization dynamics

    NASA Astrophysics Data System (ADS)

    Anderson, Paul V.; McKnight, Darren S.; Di Pentino, Frank; Schaub, Hanspeter

    2016-09-01

    The motion of abandoned satellites near the geostationary (GEO) region has been extensively studied, modeled, and compared to the motion of station-kept, operational satellites, providing insights into the evolution of uncontrolled orbits at GEO. Analytic developments produced a family of curves represented in the ascending node versus inclination space describing the long-term precession of the orbit plane at GEO, and forecasted the clustering of objects at the geopotential wells. However, recent investigations were undertaken to characterize apparent anomalistic behavior of GEO objects and classification of objects into related families. This paper provides a unifying summary of early bottom-up analytical theory with more recent top-down operational observations, highlighting the common linkage between these dimensions of GEO object behavior. This paper also identifies the relevance of these patterns of life tendencies for future operations at and near GEO, and discusses the long-term implications of these patterns of life for space situational awareness activities in this regime.

  8. Case Studies of Ecological Integrative Information Systems: The Luquillo and Sevilleta Information Management Systems

    NASA Astrophysics Data System (ADS)

    San Gil, Inigo; White, Marshall; Melendez, Eda; Vanderbilt, Kristin

    The thirty-year-old United States Long Term Ecological Research Network has developed extensive metadata to document their scientific data. Standard and interoperable metadata is a core component of the data-driven analytical solutions developed by this research network Content management systems offer an affordable solution for rapid deployment of metadata centered information management systems. We developed a customized integrative metadata management system based on the Drupal content management system technology. Building on knowledge and experience with the Sevilleta and Luquillo Long Term Ecological Research sites, we successfully deployed the first two medium-scale customized prototypes. In this paper, we describe the vision behind our Drupal based information management instances, and list the features offered through these Drupal based systems. We also outline the plans to expand the information services offered through these metadata centered management systems. We will conclude with the growing list of participants deploying similar instances.

  9. Benthic foraminifera show some resilience to ocean acidification in the northern Gulf of California, Mexico.

    PubMed

    Pettit, L R; Hart, M B; Medina-Sánchez, A N; Smart, C W; Rodolfo-Metalpa, R; Hall-Spencer, J M; Prol-Ledesma, R M

    2013-08-30

    Extensive CO2 vents have been discovered in the Wagner Basin, northern Gulf of California, where they create large areas with lowered seawater pH. Such areas are suitable for investigations of long-term biological effects of ocean acidification and effects of CO2 leakage from subsea carbon capture storage. Here, we show responses of benthic foraminifera to seawater pH gradients at 74-207m water depth. Living (rose Bengal stained) benthic foraminifera included Nonionella basispinata, Epistominella bradyana and Bulimina marginata. Studies on foraminifera at CO2 vents in the Mediterranean and off Papua New Guinea have shown dramatic long-term effects of acidified seawater. We found living calcareous benthic foraminifera in low pH conditions in the northern Gulf of California, although there was an impoverished species assemblage and evidence of post-mortem test dissolution. Copyright © 2013 Elsevier Ltd. All rights reserved.

  10. Long-term tolerability of ethinylestradiol 20 µg/drospirenone 3 mg in a flexible extended regimen: results from a randomised, controlled, multicentre study

    PubMed Central

    Klipping, Christine; Duijkers, Ingrid; Fortier, Michel P; Marr, Joachim; Trummer, Dietmar; Elliesen, Jörg

    2012-01-01

    Background This study was designed to assess the long-term safety and tolerability of a new flexible extended regimen of ethinylestradiol (EE) 20 μg/drospirenone (DRSP) 3 mg, which allows management of intracyclic (breakthrough) bleeding [flexible management of intracyclic (breakthrough) bleeding (MIB)], in comparison to conventional 28-day and fixed extended regimens. Study design In this Phase III, multicentre, open-label study, women (aged 18–35 years) were randomised to EE/DRSP in the following regimens: flexibleMIB (24–120 days' active hormonal intake followed by a 4-day tablet-free interval), conventional 28-day (24 days' active hormonal intake followed by a 4-day hormone-free interval) or fixed extended (120 days' uninterrupted active hormonal intake followed by a 4-day tablet-free interval) during a 1-year comparative phase. Thereafter, women entered a 1-year safety extension phase in which the majority received the flexibleMIB regimen. Safety/tolerability outcomes were measured over 2 years. A separate analysis of certain safety parameters (endometrial, hormonal, lipid, haemostatic and metabolic variables) was conducted at two of the study centres. Results Results were analysed in 1067 and 783 women in the comparative and safety extension phases. Overall, 56.3% of women experienced ≥1 adverse event (AE) in the safety extension phase. Serious AEs occurred in 3.0%, 1.4% and 3.3% of women receiving the flexibleMIB, conventional and fixed extended regimens, respectively. No unexpected endometrial, hormonal, lipid, haemostatic or metabolic findings occurred with any of the three regimens. Conclusions EE/DRSP in a flexible extended regimen with management of intracyclic (breakthrough) bleeding is well-tolerated and, when administered for up to 2 years, has a good safety profile comparable to other estrogen/progestogen oral contraceptives. PMID:22454004

  11. Forest restoration treatments have subtle long-term effects on soil C and N cycling in mixed conifer forests.

    PubMed

    Ganzlin, Peter W; Gundale, Michael J; Becknell, Rachel E; Cleveland, Cory C

    2016-07-01

    Decades of fire suppression following extensive timber harvesting have left much of the forest in the intermountain western United States exceedingly dense, and forest restoration techniques (i.e., thinning and prescribed fire) are increasingly being used in an attempt to mitigate the effects of severe wildfire, to enhance tree growth and regeneration, and to stimulate soil nutrient cycling. While many of the short-term effects of forest restoration have been established, the long-term effects on soil biogeochemical and ecosystem processes are largely unknown. We assessed the effects of commonly used forest restoration treatments (thinning, burning, and thinning + burning) on nutrient cycling and other ecosystem processes 11 yr after restoration treatments were implemented in a ponderosa pine (Pinus ponderosa var. scopulorum)/Douglas fir (Pseudotsuga menziesii var. glauca) forest at the Lubrecht Fire and Fire Surrogates Study (FFS) site in western Montana, USA. Despite short-term (<3 yr) increases in soil inorganic nitrogen (N) pools and N cycling rates following prescribed fire, long-term soil N pools and N mineralization rates showed only subtle differences from untreated control plots. Similarly, despite a persistent positive correlation between fuels consumed in prescribed burns and several metrics of N cycling, variability in inorganic N pools decreased significantly since treatments were implemented, indicating a decline in N spatial heterogeneity through time. However, rates of net nitrification remain significantly higher in a thin + burn treatment relative to other treatments. Short-term declines in forest floor carbon (C) pools have persisted in the thin + burn treatment, but there were no significant long-term differences among treatments in extractable soil phosphorus (P). Finally, despite some short-term differences, long-term foliar nutrient concentrations, litter decomposition rates, and rates of free-living N fixation in the experimental plots were not different from control plots, suggesting nutrient cycles and ecosystem processes in temperate coniferous forests are resilient to disturbance following long periods of fire suppression. Overall, this study provides forest managers and policymakers valuable information showing that the effects of these commonly used restoration prescriptions on soil nutrient cycling are ephemeral and that use of repeated treatments (i.e., frequent fire) will be necessary to ensure continued restoration success. © 2016 by the Ecological Society of America.

  12. Effective Connectivity Reveals Strategy Differences in an Expert Calculator

    PubMed Central

    Minati, Ludovico; Sigala, Natasha

    2013-01-01

    Mathematical reasoning is a core component of cognition and the study of experts defines the upper limits of human cognitive abilities, which is why we are fascinated by peak performers, such as chess masters and mental calculators. Here, we investigated the neural bases of calendrical skills, i.e. the ability to rapidly identify the weekday of a particular date, in a gifted mental calculator who does not fall in the autistic spectrum, using functional MRI. Graph-based mapping of effective connectivity, but not univariate analysis, revealed distinct anatomical location of “cortical hubs” supporting the processing of well-practiced close dates and less-practiced remote dates: the former engaged predominantly occipital and medial temporal areas, whereas the latter were associated mainly with prefrontal, orbitofrontal and anterior cingulate connectivity. These results point to the effect of extensive practice on the development of expertise and long term working memory, and demonstrate the role of frontal networks in supporting performance on less practiced calculations, which incur additional processing demands. Through the example of calendrical skills, our results demonstrate that the ability to perform complex calculations is initially supported by extensive attentional and strategic resources, which, as expertise develops, are gradually replaced by access to long term working memory for familiar material. PMID:24086291

  13. High times for cannabis: Epigenetic imprint and its legacy on brain and behavior.

    PubMed

    Szutorisz, Henrietta; Hurd, Yasmin L

    2018-02-01

    Extensive debates continue regarding marijuana (Cannabis spp), the most commonly used illicit substance in many countries worldwide. There has been an exponential increase of cannabis studies over the past two decades but the drug's long-term effects still lack in-depth scientific data. The epigenome is a critical molecular machinery with the capacity to maintain persistent alterations of gene expression and behaviors induced by cannabinoids that have been observed across the individual's lifespan and even into the subsequent generation. Though mechanistic investigations regarding the consequences of developmental cannabis exposure remain sparse, human and animal studies have begun to reveal specific epigenetic disruptions in the brain and the periphery. In this article, we focus attention on long-term disturbances in epigenetic regulation in relation to prenatal, adolescent and parental germline cannabinoid exposure. Expanding knowledge about the protracted molecular memory could help to identify novel targets to develop preventive strategies and treatments for behaviors relevant to neuropsychiatric risks associated with developmental cannabis exposure. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Additional EIPC Study Analysis. Final Report

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

    Hadley, Stanton W; Gotham, Douglas J.; Luciani, Ralph L.

    Between 2010 and 2012 the Eastern Interconnection Planning Collaborative (EIPC) conducted a major long-term resource and transmission study of the Eastern Interconnection (EI). With guidance from a Stakeholder Steering Committee (SSC) that included representatives from the Eastern Interconnection States Planning Council (EISPC) among others, the project was conducted in two phases. Phase 1 involved a long-term capacity expansion analysis that involved creation of eight major futures plus 72 sensitivities. Three scenarios were selected for more extensive transmission- focused evaluation in Phase 2. Five power flow analyses, nine production cost model runs (including six sensitivities), and three capital cost estimations weremore » developed during this second phase. The results from Phase 1 and 2 provided a wealth of data that could be examined further to address energy-related questions. A list of 14 topics was developed for further analysis. This paper brings together the earlier interim reports of the first 13 topics plus one additional topic into a single final report.« less

  15. Long-term safety and efficacy of recombinant factor VIII Fc fusion protein (rFVIIIFc) in subjects with haemophilia A.

    PubMed

    Nolan, B; Mahlangu, J; Perry, D; Young, G; Liesner, R; Konkle, B; Rangarajan, S; Brown, S; Hanabusa, H; Pasi, K J; Pabinger, I; Jackson, S; Cristiano, L M; Li, X; Pierce, G F; Allen, G

    2016-01-01

    The safety, efficacy and prolonged half-life of recombinant factor VIII Fc fusion protein (rFVIIIFc) in previously treated patients with severe haemophilia A was demonstrated in the phase 3 A-LONG and Kids A-LONG studies. Here, we report interim safety and efficacy data from the rFVIIIFc extension study, ASPIRE (ClinicalTrials.gov #NCT01454739). Eligible subjects could enrol in ASPIRE upon completing A-LONG or Kids A-LONG. There were four treatment groups: individualized prophylaxis; weekly prophylaxis; modified prophylaxis (for subjects in whom optimal treatment could not be achieved with individualized or weekly prophylaxis); and episodic treatment. The primary endpoint was development of inhibitors. A total of 150 A-LONG subjects and 61 Kids A-LONG subjects enrolled in ASPIRE. As of the interim data cut (6 January 2014), the median time on study was 80.9 (A-LONG) and 23.9 (Kids A-LONG) weeks. The majority of subjects (A-LONG, 92.0%; Kids A-LONG, 57.4%) had ≥100 cumulative rFVIIIFc exposure days. No inhibitors were observed. Adverse events were generally consistent with those expected in the general haemophilia A population. Median annualized bleeding rates (ABRs) were low with individualized [A-LONG: 0.66; Kids A-LONG: 0.00 (<6 years old), 1.54 (6 to <12 years old)], weekly (A-LONG: 2.03) and modified (A-LONG: 1.97) prophylaxis. There was no change in prophylactic infusion frequency or total weekly prophylactic dose in the majority of subjects from A-LONG and Kids A-LONG. Interim data from ASPIRE confirm the long-term safety of rFVIIIFc and the maintenance of a low ABR with extended-interval prophylactic dosing in patients with severe haemophilia A. © 2015 The Authors. Haemophilia Published by John Wiley & Sons Ltd.

  16. How the definition of acceptable antigens and epitope analysis can facilitate transplantation of highly sensitized patients with excellent long-term graft survival.

    PubMed

    Heidt, Sebastiaan; Haasnoot, Geert W; Claas, Frans H J

    2018-05-24

    Highly sensitized patients awaiting a renal transplant have a low chance of receiving an organ offer. Defining acceptable antigens and using this information for allocation purposes can vastly enhance transplantation of this subgroup of patients, which is the essence of the Eurotransplant Acceptable Mismatch program. Acceptable antigens can be determined by extensive laboratory testing, as well as on basis of human leukocyte antigen (HLA) epitope analyses. Within the Acceptable Mismatch program, there is no effect of HLA mismatches on long-term graft survival. Furthermore, patients transplanted through the Acceptable Mismatch program have similar long-term graft survival to nonsensitized patients transplanted through regular allocation. Although HLA epitope analysis is already being used for defining acceptable HLA antigens for highly sensitized patients in the Acceptable Mismatch program, increasing knowledge on HLA antibody - epitope interactions will pave the way toward the definition of acceptable epitopes for highly sensitized patients in the future. Allocation based on acceptable antigens can facilitate transplantation of highly sensitized patients with excellent long-term graft survival.

  17. Plasma soluble factor following two decades prolonged suppressive antiretroviral therapy in HIV-1-positive males: A cross-sectional study.

    PubMed

    Sperk, Maike; Zhang, Wang; Nowak, Piotr; Neogi, Ujjwal

    2018-02-01

    Acute human immunodeficiency virus (HIV) infection is associated with a marked induction of several pathways that are linked to inflammation and CD4 T-cell depletion. Many of these processes do not fully resolve on short-term combination antiretroviral therapy (cART) (<5 years), despite complete and durable suppression of viremia. The effects of long-term (>15 years) successful antiretroviral therapy (ART) and the linkage between levels of biomarkers remain unclear. Therefore, the present study aims to assess the host plasma proteome in a well-defined clinical material from HIV-1-positive male patients on successful long-term ART (>15 years) and compared them with age-matched healthy controls and treatment-naïve male patients with viremia in a cross-sectional manner.Plasma samples were obtained from 3 categories of age-matched HIV-1-positive male patients on long-term successfully (ART, n = 10) with a median (Interquartile range, IQR) of 19 (17-20) years, treatment-naïve patients with viremia (VP, n = 14), and HIV-1-negative persons (HC, n = 11). Plasma proteome was analyzed using the proximity extension assay targeting 92 factors. Statistical analyses were performed with GraphPad Prism v7, R-packages, and Qlucore Omics Explorer v3.2. Functional enrichment analysis was performed by Kyoto Encyclopedia of Genes and Genomes (KEGG), and interactions of specific molecules were identified using Path Designer integrated into Ingenuity Pathway Analysis (IPA).Group wise comparison identified 53 soluble factors, which differed between the groups (P < .05). Cluster analysis identified 13 discrete soluble factors (CD8A, CRTAM, CXCL13, EGF, CD5, CD40, CXCL9, Gal-1, IL12RB1, KLRD1, PD-1, CASP-8 and TNFRSF9) between the studied groups (adjusted P < .001). The long-term successfully ART-treated individuals clustered and networked with the HC while VPs clustered separately. All of the proinflammatory cytokines and chemokines were normalized back to levels of healthy controls in long-term successfully ART-treated individuals, but not the levels of KLRD1 and PGDFB.sKLRD1 that is involved in the regulation of natural killer cell (NK) mediated cytotoxicity, failed to be restored to the level of HIV-negative individuals despite successful long-term ART. Additional analysis of NK cells along with T-cell subsets can provide insights into the long-term effects of ART on the immune system.

  18. Microstructural Changes in Inconel 740 After Long-Term Aging in the Presence and Absence of Stress

    NASA Astrophysics Data System (ADS)

    Unocic, K. A.; Shingledecker, J. P.; Tortorelli, P. F.

    2014-12-01

    The Ni-based alloy, Inconel® 740, is being extensively examined for use in advanced ultrasupercritical steam boilers because its precipitation-strengthened microstructure appears to offer the necessary creep strength under the high temperatures and pressures (up to 760°C and 35 MPa) needed for high efficiency power generation. However, because this application requires extremely long lifetimes under these conditions (up to 30 years), long-term microstructure stability is a major concern. In this paper, results from microstructural analyses of Inconel 740 specimens aged at 700 and 750°C in the presence and absence of creep loading for times up to ~31,000 h are presented. The primary focus was on the development of the eta η (Ni3Ti) phase and coarsening of coherent γ'-Ni3(Al,Ti) precipitates and its depletion near eta/matrix interfaces. However, despite these processes, Inconel 740 showed adequate long-term microstructural stability to assure adequate creep strength for the intended application.

  19. Using modified polyetheretherketone (PEEK) as an alternative material for endocrown restorations: A short-term clinical report.

    PubMed

    Zoidis, Panagiotis; Bakiri, Eleonora; Polyzois, Gregory

    2017-03-01

    A modified polyetheretherketone (PEEK) framework material veneered with indirect light-polymerized composite resin was used as an alternative material for the fabrication of an endocrown restoration for an extensively damaged molar. The elastic modulus of the polyetheretherketone framework (4 GPa) veneered with indirect composite resin could dampen the occlusal forces protecting tooth structures better than ceramic materials. This is important in the restoration of extensively damaged molars with weak roots. Long-term clinical evidence is required before recommending the application as a substitute material. Copyright © 2016 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

  20. Basement depth and sedimentary infill from deep seismic reflection data at the western tip of the offshore Corinth Rift

    NASA Astrophysics Data System (ADS)

    Beckers, Arnaud; Tripsanas, Efthymios; Hubert-Ferrari, Aurélia; Beck, Christian; Sakellariou, Dimitris

    2015-04-01

    The Corinth rift is a young continental rift located in central Greece. The active part of the rift forms an E-W striking depression - the Gulf of Corinth - that is the deepest in its central part. Extensive seismic surveys have imaged the basin's basement and allowed to estimate the total extension across most of the Gulf except its western tip. Extension is high in the central part and decreases westward and eastward, as reflected in the present-day bathymetry. Two decades of GPS measurements have shown that the extension rate increases westwards from ~5 to 10-15 mm yr-1, but this is not consistent with the long term pattern. However, no data allowed so far to estimate the basement depth at the western tip of the Gulf, where the geodetic extension rate is the largest. Such data would allow to check the apparent inconsistency between the present rate and the long-term estimates of crustal extension. We present here an unpublished multichannel seismic line dating from 1979 and crossing the western tip of the Gulf of Corinth. The line is 22 km long and strikes WNW-ESE, from the Mornos delta to the West-Channel fault. A Maxipulse source has been used, allowing to image the basement below the synrift sedimentary infill. To the east, a ~1.6 km deep basin is imaged between the southern margin of the Gulf and an inactive south-dipping fault located between the Aigion and the Trizonia faults. The sedimentary infill consists in an alternation between basin-focused bodies made of incoherent reflections and more extensive high-amplitude reflectors. Attributing this alternation to eustatic variations give an age of 300-350 ka to the oldest well imaged deposits. Northwest of the Trizonia fault, the basement is imaged at shallower depth, i.e. ~450 m. The western tip of the seismic line reaches the Mornos delta, close to the northern shoreline. There, the depth to the basement is larger, reaching ~1.2 km. The infill is made of 3 units : on the basement lies a thin unit of incoherent reflections that may corresponds to coarse-grained fluvial deposits. A second unit of parallel, high-amplitude, low-frequency reflections could represent deeper-water deposits. The last seismic unit represents the Mornos delta coarse-grained deposits, from 0 to ~0.7 km deep. The depth of the basement deduced from this seismic line at the western tip of the Gulf of Corinth (1.2-1.6 km) is shallower than the one in the central part of the Gulf (2.5-3 km). This reinforce the inconsistency between long-term and short-term rates of extension in the Corinth Rift, which may be explained by assuming that the Western Corinth Rift initiated much later than the Central Rift. These data also allow to constrain the total displacement on the N-dipping Psathopyrgos fault, one of the major, normal, basin-bounding faults at the western tip of the Rift. The total offset would reach 2.1-2.3 km and the uplift/subsidence ratio would be ~1:1.7, implying a slip rate of 2.2-2.5 mm yr-1 based on footwall uplift rate data.

  1. 77 FR 3782 - Agency Information Collection Activities: Proposed Collection: Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-25

    ... of automated collection techniques or other forms of information technology. Proposed Project: The...)-- [Extension] The HPSL Program provides long-term, low-interest loans to students attending schools of medicine, osteopathic medicine, dentistry, veterinary medicine, optometry, podiatric medicine, and pharmacy. The NSL...

  2. The E-Book: Pipe Dream or Potential Disaster?

    ERIC Educational Resources Information Center

    Dorman, David

    1999-01-01

    Discusses the development of electronic books and considers marketing and distribution, rights management, and technical standards. Economic and institutional relationships, copyrights, Extensible Markup Language (XML), access to content, free access versus fees, preservation versus loss of control over long-term storage and access, and trusted…

  3. Category Learning by Clustering with Extension to Dynamic Environments

    DTIC Science & Technology

    2010-03-05

    and decision making when short- and long-term rewards are in conflict. In a paper published in Psychonomic Bulletin & Review , we examined whether...Navigating through Abstract Decision Spaces: Evaluating the Role of State Generalization in a Dynamic Decision-Making Task. Psychonomic Bulletin & Review , 16

  4. Summary results from long-term wake turbulence measurements at San Francisco International Airport

    DOT National Transportation Integrated Search

    2004-07-01

    This report summarizes the results of an extensive wake turbulence data collection program at the San Francisco International : Airport (SFO). Most of the landings at SFO are conducted on closely spaced parallel runways that are spaced 750 feet : bet...

  5. LUC-2-1682 long term maintenance of the Anthony Wayne Suspension Bridge main cables.

    DOT National Transportation Integrated Search

    2017-01-01

    The Anthony Wayne Bridge, Ohio's only suspension bridge, is undergoing an extensive rehabilitation. Prior to taking action to preserve the cables, ODOT must decide what measures to take to evaluate the condition of the cables, how best to rehabilitat...

  6. ACCORDION MIND: results of the observational extension of the ACCORD MIND randomised trial.

    PubMed

    Murray, Anne M; Hsu, Fang-Chi; Williamson, Jeff D; Bryan, R Nick; Gerstein, Hertzel C; Sullivan, Mark D; Miller, Michael E; Leng, Iris; Lovato, Laura L; Launer, Lenore J

    2017-01-01

    The Memory in Diabetes (MIND) substudy of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study, a double 2x2 factorial parallel-group randomised clinical trial, tested whether intensive compared with standard management of hyperglycaemia, BP or lipid levels reduced cognitive decline and brain atrophy in 2977 people with type 2 diabetes. We describe the results of the observational extension study, ACCORDION MIND (ClinicalTrials.gov registration no. NCT00182910), which aimed to measure the long-term effects of the three ACCORD interventions on cognitive and brain structure outcomes approximately 4 years after the trial ended. Participants (mean diabetes duration 10 years; mean age 62 years at baseline) received a fourth cognitive assessment and a third brain MRI, targeted at 80 months post-randomisation. Primary outcomes were performance on the Digit Symbol Substitution Test (DSST) and total brain volume (TBV). The contrast of primary interest compared glycaemic intervention groups at the ACCORDION visit; secondary contrasts were the BP and lipid interventions. Of the surviving ACCORD participants eligible for ACCORDION MIND, 1328 (68%) were re-examined at the ACCORDION follow-up visit, approximately 47 months after the intensive glycaemia intervention was stopped. The significant differences in therapeutic targets for each of the three interventions (glycaemic, BP and lipid) were not sustained. We found no significant difference in 80 month mean change from baseline in DSST scores or in TBV between the glycaemic intervention groups, or the BP and lipid interventions. Sensitivity analyses of the sites with ≥70% participation at 80 months revealed consistent results. The ACCORD interventions did not result in long-term beneficial or adverse effects on cognitive or brain MRI outcomes at approximately 80 months follow-up. Loss of separation in therapeutic targets between treatment arms and loss to follow-up may have contributed to the lack of detectable long-term effects. ClinicalTrials.gov NCT00182910.

  7. Climate-induced variations of geyser periodicity in Yellowstone National Park, USA

    USGS Publications Warehouse

    Hurwitz, S.; Kumar, A.; Taylor, R.; Heasler, H.

    2008-01-01

    The geysers of Yellowstone National Park, United States, attract millions of visitors each year, and their eruption dynamics have been the subject of extensive research for more than a century. Although many of the fundamental aspects associated with the dynamics of geyser eruptions have been elucidated, the relationship between external forcing (Earth tides, barometric pressure, and precipitation) and geyser eruption intervals (GEIs) remains a matter of ongoing debate. We present new instrumental GEI data and demonstrate, through detailed time-series analysis, that geysers respond to both long-term precipitation trends and to the seasonal hydrologic cycle. Responsiveness to long-term trends is reflected by a negative correlation between the annual averages of GEIs and stream flow in the Madison River. This response is probably associated with long-term pressure changes in the underlying hydrothermal reservoir. We relate seasonal GEI lengthening to snowmelt recharge. ?? 2008 The Geological Society of America.

  8. Phylogenetic approach to the evolution of color term systems

    PubMed Central

    Haynie, Hannah J.

    2016-01-01

    The naming of colors has long been a topic of interest in the study of human culture and cognition. Color term research has asked diverse questions about thought and communication, but no previous research has used an evolutionary framework. We show that there is broad support for the most influential theory of color term development (that most strongly represented by Berlin and Kay [Berlin B, Kay P (1969) (Univ of California Press, Berkeley, CA)]); however, we find extensive evidence for the loss (as well as gain) of color terms. We find alternative trajectories of color term evolution beyond those considered in the standard theories. These results not only refine our knowledge of how humans lexicalize the color space and how the systems change over time; they illustrate the promise of phylogenetic methods within the domain of cognitive science, and they show how language change interacts with human perception. PMID:27849594

  9. Attention-deficit hyperactivity disorder (ADHD): an updated review of the essential facts.

    PubMed

    Tarver, J; Daley, D; Sayal, K

    2014-11-01

    Attention-deficit hyperactivity disorder (ADHD) is a complex disorder that can affect individuals across the lifespan. It is associated with substantial heterogeneity in terms of aetiology, clinical presentation and treatment outcome and is the subject of extensive research. Because of this, it can be difficult for clinicians to stay up to date with the most relevant findings and know how best to respond to parents' questions and concerns about the disorder and interventions. This is a narrative review that aims to summarize key findings from recent research into ADHD and its treatment that clinicians can share with families in order to increase their knowledge about ADHD and intervention options. ADHD develops as a result of complex interplay between interdependent genetic and non-genetic factors. The disorder is associated with substantial impairments in functioning and poor long-term outcomes. Pharmacological and non-pharmacological treatment options are available for symptom management and to improve function, but functioning outcomes often fail to normalize in children with ADHD. Despite extensive advances in understanding this complex disorder, it is clear that there is still a long way to go. In particular, we address the need for future non-pharmacological interventions to be more specifically targeted for ADHD symptoms and its commonly associated functioning deficits in order to ensure the best long-term outcomes for children with ADHD. © 2014 John Wiley & Sons Ltd.

  10. Predictors of long-term outcomes in patients treated with riociguat for chronic thromboembolic pulmonary hypertension: data from the CHEST-2 open-label, randomised, long-term extension trial.

    PubMed

    Simonneau, Gérald; D'Armini, Andrea M; Ghofrani, Hossein-Ardeschir; Grimminger, Friedrich; Jansa, Pavel; Kim, Nick H; Mayer, Eckhard; Pulido, Tomas; Wang, Chen; Colorado, Pablo; Fritsch, Arno; Meier, Christian; Nikkho, Sylvia; Hoeper, Marius M

    2016-05-01

    Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare, debilitating, and life-threatening disease. We investigated associations between markers of disease severity and long-term outcomes in patients with inoperable CTEPH or persistent or recurrent pulmonary hypertension after pulmonary endarterectomy (PEA) who were receiving the soluble guanylate cyclase stimulator riociguat. We also present safety and efficacy from the final data cutoff of CHEST-2, where most patients had received riociguat for at least 2 years. Eligible patients from the CHEST-1 study entered the CHEST-2 open-label extension study, in which all patients received riociguat individually adjusted to a maximum dose of 2·5 mg three times per day. The primary endpoint was safety and tolerability. We did exploratory assessments of associations between markers of disease severity (6-min walking distance [6MWD], N-terminal prohormone of brain natriuretic peptide [NT-proBNP] concentration, and WHO functional class) at baseline and follow-up with overall survival and clinical worsening-free survival. We used Kaplan-Meier and Cox proportional hazards analyses. CHEST-2 is registered at ClinicalTrials.gov, number NCT00910429. 237 patients entered CHEST-2. At 2 years, overall survival was 93% (95% CI 89-96) and clinical worsening-free survival was 82% (77-87). A significant association with overall survival was seen for 6MWD and NT-proBNP concentration at baseline (p=0·0199 and p=0·0183, respectively) and at follow-up (p=0·0385 and p=0·0068, respectively). Change from baseline in 6MWD was also significantly associated with survival (p=0·0047). WHO functional class at baseline and follow-up showed no significant association with overall survival but was associated with clinical worsening-free survival. Riociguat was well tolerated by most patients and no new safety signals were identified. Serious adverse events were seen in 129 (54%) of 237 patients, and 14 (6%) discontinued riociguat therapy because of adverse events. Riociguat may be used long term in patients with CTEPH. 6MWD and NT-proBNP concentration are good prognostic markers. Bayer Pharma AG. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Link Worker social prescribing to improve health and well-being for people with long-term conditions: qualitative study of service user perceptions

    PubMed Central

    Moffatt, Suzanne; Steer, Mel; Lawson, Sarah; Penn, Linda; O’Brien, Nicola

    2017-01-01

    Objectives To describe the experiences of patients with long-term conditions who are referred to and engage with a Link Worker social prescribing programme and identify the impact of the Link Worker programme on health and well-being. Design Qualitative study using semistructured interviews with thematic analysis of the data. Intervention Link Worker social prescribing programme comprising personalised support to identify meaningful health and wellness goals, ongoing support to achieve agreed objectives and linkage into appropriate community services. Setting Inner-city area in West Newcastle upon Tyne, UK (population n=132 000) ranked 40th most socioeconomically deprived in England, served by 17 general practices. Participants Thirty adults with long-term conditions, 14 female, 16 male aged 40–74 years, mean age 62 years, 24 white British, 1 white Irish, 5 from black and minority ethnic communities. Results Most participants experienced multimorbidity combined with mental health problems, low self-confidence and social isolation. All were adversely affected physically, emotionally and socially by their health problems. The intervention engendered feelings of control and self-confidence, reduced social isolation and had a positive impact on health-related behaviours including weight loss, healthier eating and increased physical activity. Management of long-term conditions and mental health in the face of multimorbidity improved and participants reported greater resilience and more effective problem-solving strategies. Conclusions Findings suggest that tackling complex and long-term health problems requires an extensive holistic approach not possible in routine primary care. This model of social prescribing, which takes into account physical and mental health, and social and economic issues, was successful for patients who engaged with the service. Future research on a larger scale is required to assess when and for whom social prescribing is clinically effective and cost-effective. PMID:28713072

  12. Gained insights from combined high-frequency and long-term water quality monitoring in agricultural catchments

    NASA Astrophysics Data System (ADS)

    Jomaa, Seifeddine; Dupas, Rémi; Musolff, Andreas; Rozemeijer, Joachim; Borchardt, Dietrich; Rode, Michael

    2017-04-01

    Despite extensive efforts to reduce nitrate (NO3) transfer in agricultural areas, the NO3 concentration in rivers often changes little. To investigate the reasons for this limited response, NO3 dynamics in a 100 km2 agricultural catchment in eastern Germany was analysed from decadal to infra-hourly time scales. First, Dynamic Harmonic Regression (DHR) analysis of a 32-year (1982-2014) record of NO3 and discharge revealed that i) the long-term trend in NO3 concentration was closely related to that in discharge, suggesting that large-scale weather and climate patterns were masking the effect of improved nitrogen management on NO3 trends; ii) maximum winter and minimum summer concentrations had a persistent seasonal pattern, which was interpreted as a dynamic NO3 concentration from the soil and subsoil columns; and iii) the catchment progressively changed from chemodynamic to more chemostatic behaviour over the three decades of study, which is a sign of long-term homogenisation of NO3 concentrations in the profile. Second, infra-hourly (15 min time interval) analysis of storm-event dynamics during a typical hydrological year (2005-2006) was performed to identify periods of the year with high leaching risk and to link the latter to agricultural management practices in the catchment. Also, intra-hourly data was used to improve NO3 load estimation during storm events. An Event Response Reconstruction (ERR) model was built using NO3 concentration response descriptor variables and predictor variables deduced from discharge and precipitation records. The ERR approach significantly improved NO3 load estimates compared to linear interpolation of grab-sampling data (error was reduced from 10 to 1%). Finally, this study shows that detailed physical understanding of NO3 dynamics across time scales can be obtained only through combined analysis of long-term records and high-resolution sensor data. Hence, a joint effort is advocated between environmental authorities, who usually perform long-term monitoring, and scientific programmes, which usually perform high-resolution monitoring.

  13. Post-fire Water Quality in the Western United States: Understanding and Predicting Short and Long-term Response

    NASA Astrophysics Data System (ADS)

    Hogue, T. S.; Rust, A.

    2016-12-01

    Fire frequency is increasing across mid-elevation forests, especially in the Northern Rockies, Sierra Nevada, southern Cascades, as well as the coastal ranges in California and southern Oregon. Numerous studies have noted increased discharge, floods and debris flows after wildfire. More recent work also shows increased water yield during dry seasons for up to ten years post-fire. However, few studies have evaluated long-term water quality response in fire-impacted watersheds. The current presentation will overview recent development of an extensive database on post-fire water quality response across the western U.S. A range of water quality parameters were gathered from 271 burned watersheds through local, state and federal agencies. Short and long-term response was evaluated for watersheds with at least 5 years of pre-fire data. Over 30 watersheds showed significant increases in NO3-, NO2-, NH3, and total nitrogen loading in the initial five years after fire and remained elevated ten years after fire. The burn severity influenced the degree of nitrogen response, where more severely burned watersheds showed higher nitrogen loading than less severely burned watersheds. Dissolved and total phosphorous showed significant increases in 32 watersheds for the first five years after fire. Dissolved ions such as calcium, magnesium, and chloride were also exported from over 32 watersheds, primarily during the first five years after fire, with the majority of impacted watersheds returning to pre-fire water quality conditions after ten years. Ongoing work includes evaluating key determinants that drive short and long-term response and developing predictive models for post-fire water quality. Watersheds impacted by wildfire are known to pose significant risks for downstream communities. Understanding short and long-term water quality change that can impact regional water supplies is critical for establishing potential treatment priorities and alternative source planning.

  14. Link Worker social prescribing to improve health and well-being for people with long-term conditions: qualitative study of service user perceptions.

    PubMed

    Moffatt, Suzanne; Steer, Mel; Lawson, Sarah; Penn, Linda; O'Brien, Nicola

    2017-07-16

    To describe the experiences of patients with long-term conditions who are referred to and engage with a Link Worker social prescribing programme and identify the impact of the Link Worker programme on health and well-being. Qualitative study using semistructured interviews with thematic analysis of the data. Link Worker social prescribing programme comprising personalised support to identify meaningful health and wellness goals, ongoing support to achieve agreed objectives and linkage into appropriate community services. Inner-city area in West Newcastle upon Tyne, UK (population n=132 000) ranked 40th most socioeconomically deprived in England, served by 17 general practices. Thirty adults with long-term conditions, 14 female, 16 male aged 40-74 years, mean age 62 years, 24 white British, 1 white Irish, 5 from black and minority ethnic communities. Most participants experienced multimorbidity combined with mental health problems, low self-confidence and social isolation. All were adversely affected physically, emotionally and socially by their health problems. The intervention engendered feelings of control and self-confidence, reduced social isolation and had a positive impact on health-related behaviours including weight loss, healthier eating and increased physical activity. Management of long-term conditions and mental health in the face of multimorbidity improved and participants reported greater resilience and more effective problem-solving strategies. Findings suggest that tackling complex and long-term health problems requires an extensive holistic approach not possible in routine primary care. This model of social prescribing, which takes into account physical and mental health, and social and economic issues, was successful for patients who engaged with the service. Future research on a larger scale is required to assess when and for whom social prescribing is clinically effective and cost-effective. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  15. The role of stress in absenteeism: cortisol responsiveness among patients on long-term sick leave.

    PubMed

    Jacobsen, Henrik B; Bjørngaard, Johan Håkon; Hara, Karen W; Borchgrevink, Petter C; Woodhouse, Astrid; Landrø, Nils Inge; Harris, Anette; Stiles, Tore C

    2014-01-01

    This study aimed to (1) See whether increased or decreased variation relate to subjective reports of common somatic and psychological symptoms for a population on long-term sick leave; and (2) See if this pattern in variation is correlated with autonomic activation and psychological appraisal. Our participants (n = 87) were referred to a 3.5-week return-to-work rehabilitation program, and had been on paid sick leave >8 weeks due to musculoskeletal pain, fatigue and/or common mental disorders. An extensive survey was completed, addressing socio-demographics, somatic and psychological complaints. In addition, a physician and a psychologist examined the participants, determining baseline heart rate, medication use and SCID-I diagnoses. During the 3.5-week program, the participants completed the Trier Social Stress Test for Groups. Participants wore heart rate monitors and filled out Visual Analogue Scales during the TSST-G. Our participants presented a low cortisol variation, with mixed model analyses showing a maximal increase in free saliva cortisol of 26% (95% CI, 0.21-0.32). Simultaneously, the increase in heart rate and Visual Analogue Scales was substantial, indicating autonomic and psychological activation consistent with intense stress from the Trier Social Stress Test for Groups. The current findings are the first description of a blunted cortisol response in a heterogeneous group of patients on long-term sick leave. The results suggest lack of cortisol reactivity as a possible biological link involved in the pathway between stress, sustained activation and long-term sick leave.

  16. Isokinetic and Electromyographic Properties of Muscular Endurance in Short and Long-Term Type 2 Diabetes

    PubMed Central

    Hatef, Boshra; Ghanjal, Ali; Meftahi, Gholam Hossein; Askary-Ashtiani, Ahmadreza

    2016-01-01

    Background: Patients with type 2 diabetes mellitus (T2DM) are subject to progressive reduction of muscle mass and strength. The aim of this study was to assess muscle forces and electromyography (EMG) indices in short and long-term diabetes during an isokinetic exercise. Methods: The peak torque, work, mean power frequency (MPF) and root mean square (RMS) of knee flexors and extensors during 40 isokinetic knee extension-flexion repetitions with a velocity of 150 degree/s were recorded. 18 patients with less than 10 years with T2DM and 12 patients with equal and more than 10 years of disease were compared with 20 gender, body mass index, physical activity and peripheral circulation matched healthy controls. Results: The fatigue index and slope of line across the peak torque values of the knee flexor indicate that patients with long-term T2DM were significantly more resistant to fatigue in comparison with the two other groups (p<0.009). Whereas the MPF decrease during isokinetic protocol interact with grouping in the medial hamstring (p<0.042), but it was independent to groups in other muscles (p<0.0001). The increase of RMS after fatigue protocol interacted with sex for the medial hamstring and vastus lateralis (p<0.039) and interacted with group for the extensor muscles (p<0.045). Discussion & Conclusion: It seems that long-term T2DM cause some neuromuscular adaptations to maintain knee flexor muscle performance during functional activity especially postural control. PMID:27045412

  17. Long-term cost-effectiveness of disease management in systolic heart failure.

    PubMed

    Miller, George; Randolph, Stephen; Forkner, Emma; Smith, Brad; Galbreath, Autumn Dawn

    2009-01-01

    Although congestive heart failure (CHF) is a primary target for disease management programs, previous studies have generated mixed results regarding the effectiveness and cost savings of disease management when applied to CHF. We estimated the long-term impact of systolic heart failure disease management from the results of an 18-month clinical trial. We used data generated from the trial (starting population distributions, resource utilization, mortality rates, and transition probabilities) in a Markov model to project results of continuing the disease management program for the patients' lifetimes. Outputs included distribution of illness severity, mortality, resource consumption, and the cost of resources consumed. Both cost and effectiveness were discounted at a rate of 3% per year. Cost-effectiveness was computed as cost per quality-adjusted life year (QALY) gained. Model results were validated against trial data and indicated that, over their lifetimes, patients experienced a lifespan extension of 51 days. Combined discounted lifetime program and medical costs were $4850 higher in the disease management group than the control group, but the program had a favorable long-term discounted cost-effectiveness of $43,650/QALY. These results are robust to assumptions regarding mortality rates, the impact of aging on the cost of care, the discount rate, utility values, and the targeted population. Estimation of the clinical benefits and financial burden of disease management can be enhanced by model-based analyses to project costs and effectiveness. Our results suggest that disease management of heart failure patients can be cost-effective over the long term.

  18. Type 1 Adenylyl Cyclase is Essential for Maintenance of Remote Contextual Fear Memory

    PubMed Central

    Shan, Qiang; Chan, Guy C.-K.; Storm, Daniel R.

    2008-01-01

    Although molecular mechanisms for hippocampus-dependent memory have been extensively studied, much less is known about signaling events important for remote memory. Here we report that mice lacking type 1 adenylyl cyclase (AC1) are able to establish and retrieve remote contextual memory but unable to sustain it as long as wild type mice. Interestingly, mice over-expressing AC1 show superior remote contextual memory even though they exhibit normal hippocampus-dependent contextual memory. These data illustrate that calcium coupling to cAMP contributes to the stability of remote memory and identifies AC1 as a potential drug target site to improve long-term remote memory. PMID:19036980

  19. Will the Oxygen-Phosphorus Paradigm Persist? - Expert Views of the Future of Management and Restoration of Eutrophic Lakes

    NASA Astrophysics Data System (ADS)

    Nygrén, Nina A.; Tapio, Petri; Horppila, Jukka

    2017-11-01

    In the age of climate change, the demand and lack of pure water challenges many communities. Substantial amount of effort is put in every year to manage and restore degraded lakes while the long-term effects of those efforts are only poorly known or monitored. Oxygenation, or aeration, is used extensively for the restoration of eutrophic lakes, although many studies question whether this process improves the status of the lakes in the long-term. The desired effect of oxygenation is based on paradigmatic theories that, in the light of recent literature, might not be adequate when long-term improvements are sought. This article canvasses expert views on the feasibility of the `oxygen-phosphorus paradigm' as well as the future of the management and restoration of eutrophic lakes, based on an international, two-rounded, expert panel survey (Delphi study), employing 200 freshwater experts from 33 nationalities, contacted at three conferences on the topic. The conclusion is that the oxygen-phosphorus paradigm seems to be rather persistent. The experts considered oxygenation to be a valid short-term lake restoration method, but not without harmful side-effects. In addition, experts' low level of trust in the adequacy of the scientific knowledge on the effects of restorations and in the use of the scientific knowledge as a basis of choice of restoration methods, could be signs of a paradigm shift towards an outlook emphasizing more effective catchment management over short-term restorations. The expert panel also anticipated that reducing external nutrient loads from both point and diffuse sources will succeed in the future.

  20. Nigella sativa L. seeds modulate mood, anxiety and cognition in healthy adolescent males.

    PubMed

    Bin Sayeed, Muhammad Shahdaat; Shams, Tahiatul; Fahim Hossain, Sarder; Rahman, Md Rezowanur; Mostofa, Agm; Fahim Kadir, Mohammad; Mahmood, Sharif; Asaduzzaman, Md

    2014-02-27

    Previous studies conducted on animals linked consumption of Nigella sativa L. seeds (NS) to decreased anxiety and improved memory. The present study, which was carried out at a boarding school in Bangladesh, was designed to examine probable effect of NS on mood, anxiety and cognition in adolescent human males. Forty-eight healthy adolescent human males aged between 14 to 17 years were randomly recruited as volunteers and were randomly split into two groups: A (n=24) and B (n=24). The treatment procedure for group A and B were one capsule of 500 mg placebo and 500 mg NS respectively once daily for four weeks. All the volunteers were assessed for cognition with modified California verbal learning test-II (CVLT-II), mood with Bond-Lader scale and anxiety with State-Trait Anxiety Inventory (STAI) at the beginning and after four weeks of either NS or placebo ingestion. No parameter showed statistically significant variation between A and B in measurements in the beginning, but after 4 weeks of one capsule of NS 500 mg intake, there was statistically significant variation of mood within group B but there was not statistically significant variation between group A and B. No significant variation was found in state anxiety within groups and between group A and B but in case of trait anxiety, significant variation was found within group B but not between group A and B. In case of CVLT II, there was significant variation within B in immediate short-term recall at trial 4 and 5 whereas this difference was found only in case of trial 5 between group A and B. Within group B, short term-free recall, long-term free recall and long-term cued recall had statistical difference whereas between group A and B long-term free recall and long-term cued recall had statistical difference. No parameters had significant variation within group A after placebo intake for 4 weeks. Over the 4 weeks study period, the use of NS as a nutritional supplement been observed to- stabilize mood, decrease anxiety and modulate cognition positively. However, long term study is suggested before using NS extensively. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  1. Air pollution and subclinical airway inflammation in the SALIA cohort study

    PubMed Central

    2014-01-01

    Background The association between long-term exposure to air pollution and local inflammation in the lung has rarely been investigated in the general population of elderly subjects before. We investigated this association in a population-based cohort of elderly women from Germany. Methods In a follow-up examination of the SALIA cohort study in 2008/2009, 402 women aged 68 to 79 years from the Ruhr Area and Borken (Germany) were clinically examined. Inflammatory markers were determined in exhaled breath condensate (EBC) and in induced sputum (IS). We used traffic indicators and measured air pollutants at single monitoring stations in the study area to assess individual traffic exposure and long-term air pollution background exposure. Additionally long-term residential exposure to air pollution was estimated using land-use regression (LUR) models. We applied multiple logistic and linear regression analyses adjusted for age, indoor mould, smoking, passive smoking and socio-economic status and additionally conducted sensitivity analyses. Results Inflammatory markers showed a high variability between the individuals and were higher with higher exposure to air pollution. NO derivatives, leukotriene (LT) B4 and tumour necrosis factor-α (TNF-α) showed the strongest associations. An increase of 9.42 μg/m3 (interquartile range) in LUR modelled NO2 was associated with measureable LTB4 level (level with values above the detection limit) in EBC (odds ratio: 1.38, 95% CI: 1.02 -1.86) as well as with LTB4 in IS (%-change: 19%, 95% CI: 7% - 32%). The results remained consistent after exclusion of subpopulations with risk factors for inflammation (smoking, respiratory diseases, mould infestation) and after extension of models with additional adjustment for season of examination, mass of IS and urban/rural living as sensitivity analyses. Conclusions In this analysis of the SALIA study we found that long-term exposure to air pollutants from traffic and industrial sources was associated with an increase of several inflammatory markers in EBC and in IS. We conclude that long-term exposure to air pollution might lead to changes in the inflammatory marker profile in the lower airways in an elderly female population. PMID:24645673

  2. Historical Prediction Modeling Approach for Estimating Long-Term Concentrations of PM2.5 in Cohort Studies before the 1999 Implementation of Widespread Monitoring.

    PubMed

    Kim, Sun-Young; Olives, Casey; Sheppard, Lianne; Sampson, Paul D; Larson, Timothy V; Keller, Joshua P; Kaufman, Joel D

    2017-01-01

    Recent cohort studies have used exposure prediction models to estimate the association between long-term residential concentrations of fine particulate matter (PM2.5) and health. Because these prediction models rely on PM2.5 monitoring data, predictions for times before extensive spatial monitoring present a challenge to understanding long-term exposure effects. The U.S. Environmental Protection Agency (EPA) Federal Reference Method (FRM) network for PM2.5 was established in 1999. We evaluated a novel statistical approach to produce high-quality exposure predictions from 1980 through 2010 in the continental United States for epidemiological applications. We developed spatio-temporal prediction models using geographic predictors and annual average PM2.5 data from 1999 through 2010 from the FRM and the Interagency Monitoring of Protected Visual Environments (IMPROVE) networks. Temporal trends before 1999 were estimated by using a) extrapolation based on PM2.5 data in FRM/IMPROVE, b) PM2.5 sulfate data in the Clean Air Status and Trends Network, and c) visibility data across the Weather Bureau Army Navy network. We validated the models using PM2.5 data collected before 1999 from IMPROVE, California Air Resources Board dichotomous sampler monitoring (CARB dichot), the Children's Health Study (CHS), and the Inhalable Particulate Network (IPN). In our validation using pre-1999 data, the prediction model performed well across three trend estimation approaches when validated using IMPROVE and CHS data (R2 = 0.84-0.91) with lower R2 values in early years. Model performance using CARB dichot and IPN data was worse (R2 = 0.00-0.85) most likely because of fewer monitoring sites and inconsistent sampling methods. Our prediction modeling approach will allow health effects estimation associated with long-term exposures to PM2.5 over extended time periods ≤ 30 years. Citation: Kim SY, Olives C, Sheppard L, Sampson PD, Larson TV, Keller JP, Kaufman JD. 2017. Historical prediction modeling approach for estimating long-term concentrations of PM2.5 in cohort studies before the 1999 implementation of widespread monitoring. Environ Health Perspect 125:38-46; http://dx.doi.org/10.1289/EHP131.

  3. Long-term epidemiological studies of atomic bomb survivors in Hiroshima and Nagasaki: study populations, dosimetry and summary of health effects.

    PubMed

    Okubo, Toshiteru

    2012-10-01

    The Radiation Effects Research Foundation succeeded 28 years' worth of activities of the Atomic Bomb Casualty Commission on long-term epidemiological studies in Hiroshima and Nagasaki. It has three major cohorts of atomic bomb survivors, i.e. the Life Span Study (LSS) of 120,000 people, the In Utero Cohort of 3600 and the Second Generation Study (F(1)) of 77,000. The LSS and F(1) studies include a periodic health examination for each sub-cohort, i.e. the Adult Health Study and the F(1) Clinical Study, respectively. An extensive individual dose estimation was conducted and the system was published as the Dosimetry System established in 2002 (DS02). As results of these studies, increases of cancers in relation to dose were clearly shown. Increases of other mortality causes were also observed, including heart and respiratory diseases. There has been no evidence of genetic effects in the survivors' children, including cancer and other multi-factorial diseases. The increase in the expected mortality number in the next 10 y would allow the analyses of further details of the observed effects related to atomic bomb exposures.

  4. THE DNAPL REMEDIATION CHALLENGE: IS THERE A CASE FOR SOURCE DEPLETION?

    EPA Science Inventory

    Releases of Dense Non-Aqueous Phase Liquids (DNAPLs) at a large number of public and private sector sites in the United States pose significant challenges in site remediation and long-term site management. Extensive contamination of groundwater occurs as a result of significant ...

  5. Category Learning by Clustering with Extension to Dynamic Environments

    DTIC Science & Technology

    2010-05-03

    making when short- and long-term rewards are in conflict. In a paper published in Psychonomic Bulletin & Review , we examined whether state cues make...through Abstract Decision Spaces: Evaluating the Role of State Generalization in a Dynamic Decision-Making Task. Psychonomic Bulletin & Review , 16, 957

  6. 76 FR 58460 - Information Collection; Qualified Products List for Long-Term Retardant for Wildland Firefighting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-21

    ... organizations on the extension (with contact revision) of a currently approved information collection, Qualified... entry to the building. FOR FURTHER INFORMATION CONTACT: Cecilia Johnson, Missoula Technology and... contact revision. Abstract: The Forest Service and cooperating wildland firefighting agencies need...

  7. Toward a new understanding of legacy of early attachments for future antisocial trajectories: Evidence from two longitudinal studies

    PubMed Central

    KOCHANSKA, GRAZYNA; KIM, SANGHAG

    2013-01-01

    Early parent–child attachment has been extensively explored as a contributor to children’s future adaptive or antisocial outcomes, but the specific developmental mechanisms remain to be fully understood. We examined long-term indirect developmental sequelae of early security in two longitudinal community samples followed from infancy to early school age: the Family Study (102 mothers, fathers, and infants) and the Parent–Child Study (112 mothers and infants). Constructs at multiple levels (child characteristics, parent–child security, parental discipline, and child antisocial outcomes) were assessed using a range of methods (extensive behavioral observations in a variety of settings, informants’ ratings). Both studies supported the proposed model of infant attachment as a potent catalyst that moderates future developmental socialization trajectories, despite having few long-term main effects. In insecure dyads, a pattern of coercion emerged between children who were anger prone as toddlers and their parents, resulting in parents’ increased power-assertive discipline. Power assertion in turn predicted children’s rule-breaking conduct and a compromised capacity to delay in laboratory paradigms, as well as oppositional, disruptive, callous, and aggressive behavior rated by parents and teachers at early school age. This causal chain was absent in secure dyads, where child anger proneness was unrelated to power assertion, and power assertion was unrelated to antisocial outcomes. Early insecurity appeared to act as a catalyst for the parent–child dyad embarking on a mutually adversarial path toward antisocial outcomes, whereas security defused such a maladaptive dynamic. The possible mechanisms of those effects were proposed. PMID:22781855

  8. Monitoring the Black Hole Binary GRS 1758-258 with INTEGRAL and RXTE

    NASA Technical Reports Server (NTRS)

    Pottschmidt, Katja; Chernyakova, Masha; Lubinski, Piotr; Migliari, Simone; Smith, David M.; Zdziarski, Andrzej A.; Tomsick, John A.; Bezayiff, N.; Kreykenbohm, Ingo; Kretschmar, Peter; hide

    2008-01-01

    The microquasar GRS 1758-258 is one of only three persistent black hole binaries that spend most of their time in the hard spectral state, the other two being Cyg X-l and 1E 1741.7-2942. It therefore provides the rare opportunity for an extensive long term study of this important black hole state which is associated with strong variability and radio jet emission. INTEGRAL has been monitoring the source since the first Galactic Center Deep Exposure season in spring 2003 during two 2-3 months long Galactic Center viewing epochs each year, amounting to 11 epochs including spring of 2008. With the exception of the last epoch quasi-simultaneous RXTE monitoring observations are available as well. Here we present an analysis of the epoch averaged broad band spectra which display considerable long term variability, most notably the occurrence of two soft/off states, extreme examples for the hysteretic behavior of black hole binaries. The hard source spectrum and long exposures allow us to extend the analysis for several epochs to approximately 800 keV using PICsIT data and address the question of the presence of a non-thermal Comptonization component.

  9. Analysis of recent climatic changes in the Arabian Peninsula region

    NASA Astrophysics Data System (ADS)

    Nasrallah, H. A.; Balling, R. C.

    1996-12-01

    Interest in the potential climatic consequences of the continued buildup of anthropo-generated greenhouse gases has led many scientists to conduct extensive climate change studies at the global, hemispheric, and regional scales. In this investigation, analyses are conducted on long-term historical climate records from the Arabian Peninsula region. Over the last 100 years, temperatures in the region increased linearly by 0.63 °C. However, virtually all of this warming occurred from 1911 1935, and over the most recent 50 years, the Arabian Peninsula region has cooled slightly. In addition, the satellite-based measurements of lower-tropospheric temperatures for the region do not show any statistically significant warming over the period 1979 1991. While many other areas of the world are showing a decrease in the diurnal temperature range, the Arabian Peninsula region reveals no evidence of a long-term change in this parameter. Precipitation records for the region show a slight, statistically insignificant decrease over the past 40 years. The results from this study should complement the mass of information that has resulted from similar regional climate studies conducted in the United States, Europe, and Australia.

  10. Activity and Stability of (Pr 1-xNd x) 2NiO 4+δ as Cathodes for Oxide Fuel Cells: Part VI. The Role of Cu Dopant on the Structure and Electrochemical Properties

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

    Dogdibegovic, Emir; Yan, Jingbo; Cai, Qinsheng

    Phase instability in praseodymium nickelates is a major concern for the long-term operations of solid oxide fuel cells since it may lead to the performance degradation. In this work, praseodymium nickelates (ex. Pr 2NiO 4+δ) have been stabilized via substitution on both Pr- and Ni-sites. Systematic studies over a wide range of compositions were conducted via long-term thermal annealing studies (T ≤ 870°C) and electrochemical tests in full cells. Proposed (Pr 0.50Nd 0.50) 2Ni 1-yCu yO 4+δ compositions (y = 0.05, 0.10, 0.20, and 0.30) showed the most promising results and serve as a comprehensive extension to our previous studiesmore » in this series of papers. A stable long-term performance was obtained for temperatures up to 790°C for 500 hours at 0.80 V with a minimal tradeoff between the activity (power density of 0.8–1.0 W cm -2 at 850°C) and performance stability. A preserved parent phase and suppressed performance degradation, when compared to Pr 2NiO 4+δ, make newly developed electrodes attractive candidates for the state-of-the-art solid oxide fuel cell applications.« less

  11. Ten-Year Recovery Outcomes for Clients With Co-Occurring Schizophrenia and Substance Use Disorders

    PubMed Central

    Drake, Robert E.; McHugo, Gregory J.; Xie, Haiyi; Fox, Melinda; Packard, Joan; Helmstetter, Barbara

    2006-01-01

    The long-term courses of people with schizophrenia and of those with substance use disorder have been studied separately and extensively. The long-term course of clients with co-occurring schizophrenic and substance use disorders has, however, not been examined. This article reports 10-year outcomes for 130 clients with co-occurring schizophrenic and substance use disorders in the New Hampshire Dual Diagnosis Study. In addition, we report on 6 “recovery outcomes,” identified by dual diagnosis clients, as examples of positive coping behaviors. Longitudinal data were modeled using generalized estimating equation (GEE) methods. Participants improved steadily over 10 years in the outcome domains of symptoms, substance abuse, institutionalization, functional status, and quality of life. Further, at the 10-year follow-up, substantial proportions were above cutoffs selected by dual diagnosis clients as indicators of recovery: 62.7% were controlling symptoms of schizophrenia; 62.5% were actively attaining remissions from substance abuse; 56.8% were in independent living situations; 41.4% were competitively employed; 48.9% had regular social contacts with non–substance abusers; and 58.3% expressed overall life satisfaction. These 6 outcomes were only weakly interrelated over time, suggesting that recovery, as defined by clients, is a multidimensional concept. Overall, the 10-year findings on recovery outcomes provide a hopeful long-term perspective for dual diagnosis clients. PMID:16525088

  12. Ten-year recovery outcomes for clients with co-occurring schizophrenia and substance use disorders.

    PubMed

    Drake, Robert E; McHugo, Gregory J; Xie, Haiyi; Fox, Melinda; Packard, Joan; Helmstetter, Barbara

    2006-07-01

    The long-term courses of people with schizophrenia and of those with substance use disorder have been studied separately and extensively. The long-term course of clients with co-occurring schizophrenic and substance use disorders has, however, not been examined. This article reports 10-year outcomes for 130 clients with co-occurring schizophrenic and substance use disorders in the New Hampshire Dual Diagnosis Study. In addition, we report on 6 "recovery outcomes," identified by dual diagnosis clients, as examples of positive coping behaviors. Longitudinal data were modeled using generalized estimating equation (GEE) methods. Participants improved steadily over 10 years in the outcome domains of symptoms, substance abuse, institutionalization, functional status, and quality of life. Further, at the 10-year follow-up, substantial proportions were above cutoffs selected by dual diagnosis clients as indicators of recovery: 62.7% were controlling symptoms of schizophrenia; 62.5% were actively attaining remissions from substance abuse; 56.8% were in independent living situations; 41.4% were competitively employed; 48.9% had regular social contacts with non-substance abusers; and 58.3% expressed overall life satisfaction. These 6 outcomes were only weakly interrelated over time, suggesting that recovery, as defined by clients, is a multidimensional concept. Overall, the 10-year findings on recovery outcomes provide a hopeful long-term perspective for dual diagnosis clients.

  13. Long-term stability of self-assembled monolayers on 316L stainless steel.

    PubMed

    Kaufmann, C R; Mani, G; Marton, D; Johnson, D M; Agrawal, C M

    2010-04-01

    316L stainless steel (316L SS) has been extensively used for making orthopedic, dental and cardiovascular implants. The use of phosphonic acid self-assembled monolayers (SAMs) on 316L SS has been previously explored for potential biomedical applications. In this study, we have investigated the long-term stability of methyl (-CH(3)) and carboxylic acid (-COOH)-terminated phosphonic acid SAMs on 316L under physiological conditions. The stability of SAMs on mechanically polished and electropolished 316L SS was also investigated as a part of this study. Well-ordered and uniform -CH(3)- and -COOH-terminated SAMs were coated on mechanically polished and electropolished 316L SS surfaces. The long-term stability of SAMs on 316L SS was investigated for up to 28 days in Tris-buffered saline (TBS) at 37 degrees C using x-ray photoelectron spectroscopy, atomic force microscopy and contact angle goniometry. A significant amount of phosphonic acid molecules was desorbed from the 316L SS surfaces within 1 to 7 days of TBS immersion followed by a slow desorption of molecules over the remaining days. The -COOH-terminated SAM was found to be more stable than the -CH(3)-terminated SAM on both mechanically and electropolished surfaces. No significant differences in the desorption behavior of SAMs were observed between mechanically and electropolished 316L SS surfaces.

  14. Activity and Stability of (Pr 1-xNd x) 2NiO 4+δ as Cathodes for Oxide Fuel Cells: Part VI. The Role of Cu Dopant on the Structure and Electrochemical Properties

    DOE PAGES

    Dogdibegovic, Emir; Yan, Jingbo; Cai, Qinsheng; ...

    2017-08-12

    Phase instability in praseodymium nickelates is a major concern for the long-term operations of solid oxide fuel cells since it may lead to the performance degradation. In this work, praseodymium nickelates (ex. Pr 2NiO 4+δ) have been stabilized via substitution on both Pr- and Ni-sites. Systematic studies over a wide range of compositions were conducted via long-term thermal annealing studies (T ≤ 870°C) and electrochemical tests in full cells. Proposed (Pr 0.50Nd 0.50) 2Ni 1-yCu yO 4+δ compositions (y = 0.05, 0.10, 0.20, and 0.30) showed the most promising results and serve as a comprehensive extension to our previous studiesmore » in this series of papers. A stable long-term performance was obtained for temperatures up to 790°C for 500 hours at 0.80 V with a minimal tradeoff between the activity (power density of 0.8–1.0 W cm -2 at 850°C) and performance stability. A preserved parent phase and suppressed performance degradation, when compared to Pr 2NiO 4+δ, make newly developed electrodes attractive candidates for the state-of-the-art solid oxide fuel cell applications.« less

  15. B-52G crew noise exposure study

    NASA Astrophysics Data System (ADS)

    Decker, W. H.; Nixon, C. W.

    1985-08-01

    The B-52G aircraft produces acoustic environments that are potentially hazardous, interfere with voice communications and may degrade task performance. Numerous reports from aircrew of high noise levels at crew location have been documented for those B-52G aircraft that have been modified with the Offensive Avionics System. To alleviate and minimize the excessive noise exposures of aircrews, a study of the noise problem in the b-52G was deemed necessary. First, in-flight noise measurements were obtained at key personnel locations on a B-52G during a typical training mission. Then, extensive laboratory analyses were conducted on these in-flight noise data. The resulting noise exposure data were evaluated in terms of the various segments of and the total flight profile relative to allowable noise exposures. Finally, recommendations were developed for short term and long term approaches toward potential improvement in the B-52G noise exposure problem.

  16. Effects of postoperative administration of ketoprofen or carprofen on short- and long-term results of femoral head and neck excision in dogs.

    PubMed

    Grisneaux, Emmanuelle; Dupuis, Jacques; Pibarot, Philippe; Bonneau, Norbert H; Charette, Benoît; Blais, Diane

    2003-10-01

    To determine whether postoperative administration of ketoprofen or carprofen had any effects on short- or long-term results of femoral head and neck excision (FHNE) in dogs. Prospective randomized controlled trial. 40 client-owned, large-breed dogs undergoing FHNE and 15 healthy large-breed dogs used as controls for hip joint angle measurements and force plate analyses. Dogs undergoing FHNE were treated with ketoprofen, carprofen, or a placebo for 21 days after surgery. Hip joint abduction and extension angles were measured at the end of surgery and 120 days later. Lameness scores were assigned, and force plate analyses were performed on days 3, 15, and 120. There were no significant differences among treatment groups in regard to hip joint angles or lameness scores. Force plate analysis revealed that dogs in all 3 treatment groups bore consistently less weight on the operated limb than did control dogs for the duration of the study. Dogs receiving ketoprofen had greater peak propulsive force at a walk on day 3 and greater peak vertical force at a walk on day 15 than did dogs receiving the placebo. Treatment of an acute condition and preservation of the lesser trochanter, but not postoperative analgesic administration, were positively associated with ground reaction forces on day 120. Owners of 12 of 31 dogs indicated that the dog's gait worsened for a few days after discontinuation of analgesic administration. Administration of ketoprofen or carprofen after surgery was not associated with long-term results of FHNE, probably because of the impact of other factors. Because some owners noticed worsening of the lameness following cessation of analgesic administration in the present study, it is possible that longer administration would have improved long-term results.

  17. Long-term treatment of Cushing's disease with pasireotide: 5-year results from an open-label extension study of a Phase III trial.

    PubMed

    Petersenn, S; Salgado, L R; Schopohl, J; Portocarrero-Ortiz, L; Arnaldi, G; Lacroix, A; Scaroni, C; Ravichandran, S; Kandra, A; Biller, B M K

    2017-07-01

    Treating hypercortisolism in patients with Cushing's disease after failed surgery often requires chronic medication, underlining the need for therapies with favourable long-term efficacy and safety profiles. In a randomised, double-blind study, 162 adult patients with persistent/recurrent or de novo Cushing's disease received pasireotide. Patients with mean urinary free cortisol at/below the upper limit of normal or clinical benefit at month 12 could continue receiving pasireotide during an open-ended, open-label phase, the outcomes of which are described herein. Sixteen patients received 5 years of pasireotide treatment. Among these, median (95% confidence interval) percentage change from baseline in mean urinary free cortisol was -82.6% (-89.0, -41.9) and -81.8% (-89.8, -67.4) at months 12 and 60. Eleven patients had mean urinary free cortisol ≤ upper limit of normal at month 60. Improvements in clinical signs were sustained during long-term treatment. The safety profile of pasireotide at 5 years was similar to that reported after 12 months. Fifteen of 16 patients experienced a hyperglycaemia-related adverse event; glycated haemoglobin levels were stable between months 6 and 60. Adverse events related to hyperglycaemia, bradycardia, gallbladder/biliary tract, and liver safety were most likely to first occur by month 6; adverse event severity did not tend to worsen over time. This represents the longest prospective trial of a medical therapy for Cushing's disease to date. A subset of patients treated with pasireotide maintained biochemical and clinical improvements for 5 years, with no new safety signals emerging. These data support the use of pasireotide as an effective long-term therapy for some patients with Cushing's disease.

  18. Pacific Megatrends in Education. PREL Briefing Paper.

    ERIC Educational Resources Information Center

    Hammond, Ormond W.

    Organizations can try to see into the future by identifying and describing megatrends--the large social, economic, political, and technological changes that have long-term effects. Recognizing the extensive benefits of considering future shifts and trends in the strategic planning process, Pacific Resources for Education and Learning (PREL)…

  19. Social Science Curriculum Guide and Selected Multi-Media, 7-9.

    ERIC Educational Resources Information Center

    Gaydosh, Ronald; And Others

    GRADES OR AGES: Grades 7-9. SUBJECT MATTER: Social science; history. ORGANIZATION AND PHYSICAL APPEARANCE: The extensive introductory material includes rationale, definitions of the social science core disciplines, glossary of terms, guidelines for teaching, behavioral and long-range objectives, guide format, and descriptions of concepts. The…

  20. The School and the Democratic Environment.

    ERIC Educational Resources Information Center

    1970

    The purpose of the conference was to explore how schools can prepare students to function in a democratic society beset by unprededented demands, complexities, and inconsistencies between theory and practice. Educational reform was the long-range goal, the short-term goal being the extension of dialogue in large and small school districts leading…

  1. STEPS: Moving from Welfare to Work.

    ERIC Educational Resources Information Center

    Vail, Ann; Cummings, Merrilyn; Kratzer, Connie; Galindo, Vickie

    Cooperative extension service faculty at New Mexico State University started the Steps to Employment and Personal Success (STEPS) program to help Temporary Assistance for Needy Families (TANF) clients qualify for and maintain full-time employment and strengthen their families for long-term success. Clients are referred to STEPS by New Mexico…

  2. DESTRUCTION OF PCBS USING SULFATE RADICAL-BASED ADVANCED OXIDATION PROCESSES

    EPA Science Inventory

    Polychlorinated biphenyls (PCBs) are a class of 209 congeners that were extensively used in industrial applications during 1929 to early 1970s, The presence of PCBs in the environment poses long-term risk to public health and wildlife due to their persistent and toxic nature. Adv...

  3. LONG-TERM RECOVERY OF PCB-CONTAMINATED SEDIMENTS AT THE LAKE HARTWELL SUPERFUND SITE: PCB DECHLORINATION. 2. RATES AND EXTENT

    EPA Science Inventory

    This paper reports on extensive polychlorinated biphenyl (PCB) dechlorination measured in Lake Hartwell (Pickens County, SC) sediments. Vertical sediment cores were collected from 18 locations in Lake Hartwell (Pickens County, SC) and analyzed in 5-cm increments for PCB congeners...

  4. Newquay Treviglas School.

    ERIC Educational Resources Information Center

    Ingham, Donald

    1995-01-01

    Describes a long-term scheme to develop a pond, nature trail, and tree-planting project (in Cornwall, England). The project was designed by teams of students. Plans included a large pond, meadow area, sequential cuttings of school fields to encourage insects, butterfly garden, extensive tree plantings (including a dwindling native species), and a…

  5. Web-based Distributed Medical Information System for Chronic Viral Hepatitis

    NASA Astrophysics Data System (ADS)

    Yang, Ying; Qin, Tuan-fa; Jiang, Jian-ning; Lu, Hui; Ma, Zong-e.; Meng, Hong-chang

    2008-11-01

    To make a long-term dynamic monitoring to the chronically ill, especially patients of HBV A, we build a distributed Medical Information System for Chronic Viral Hepatitis (MISCHV). The Web-based system architecture and its function are described, and the extensive application and important role are also presented.

  6. Neural Circuitry and Plasticity Mechanisms Underlying Delay Eyeblink Conditioning

    ERIC Educational Resources Information Center

    Freeman, John H.; Steinmetz, Adam B.

    2011-01-01

    Pavlovian eyeblink conditioning has been used extensively as a model system for examining the neural mechanisms underlying associative learning. Delay eyeblink conditioning depends on the intermediate cerebellum ipsilateral to the conditioned eye. Evidence favors a two-site plasticity model within the cerebellum with long-term depression of…

  7. Historical data as a baseline for conservation: reconstructing long-term faunal extinction dynamics in Late Imperial–modern China

    PubMed Central

    Turvey, Samuel T.; Crees, Jennifer J.; Di Fonzo, Martina M. I.

    2015-01-01

    Extinction events typically represent extended processes of decline that cannot be reconstructed using short-term studies. Long-term archives are necessary to determine past baselines and the extent of human-caused biodiversity change, but the capacity of historical datasets to provide predictive power for conservation must be assessed within a robust analytical framework. Local Chinese gazetteers represent a more than 400-year country-level dataset containing abundant information on past environmental conditions and include extensive records of gibbons, which have a restricted present-day distribution but formerly occurred across much of China. Gibbons show pre-twentieth century range contraction, with significant fragmentation by the mid-eighteenth century and population loss escalating in the late nineteenth century. Isolated gibbon populations persisted for about 40 years before local extinction. Populations persisted for longer at higher elevations, and disappeared earlier from northern and eastern regions, with the biogeography of population loss consistent with the contagion model of range collapse in response to human demographic expansion spreading directionally across China. The long-term Chinese historical record can track extinction events and human interactions with the environment across much longer timescales than are usually addressed in ecology, contributing novel baselines for conservation and an increased understanding of extinction dynamics and species vulnerability or resilience to human pressures. PMID:26246553

  8. Historical data as a baseline for conservation: reconstructing long-term faunal extinction dynamics in Late Imperial-modern China.

    PubMed

    Turvey, Samuel T; Crees, Jennifer J; Di Fonzo, Martina M I

    2015-08-22

    Extinction events typically represent extended processes of decline that cannot be reconstructed using short-term studies. Long-term archives are necessary to determine past baselines and the extent of human-caused biodiversity change, but the capacity of historical datasets to provide predictive power for conservation must be assessed within a robust analytical framework. Local Chinese gazetteers represent a more than 400-year country-level dataset containing abundant information on past environmental conditions and include extensive records of gibbons, which have a restricted present-day distribution but formerly occurred across much of China. Gibbons show pre-twentieth century range contraction, with significant fragmentation by the mid-eighteenth century and population loss escalating in the late nineteenth century. Isolated gibbon populations persisted for about 40 years before local extinction. Populations persisted for longer at higher elevations, and disappeared earlier from northern and eastern regions, with the biogeography of population loss consistent with the contagion model of range collapse in response to human demographic expansion spreading directionally across China. The long-term Chinese historical record can track extinction events and human interactions with the environment across much longer timescales than are usually addressed in ecology, contributing novel baselines for conservation and an increased understanding of extinction dynamics and species vulnerability or resilience to human pressures. © 2015 The Authors.

  9. Continuity resection of the mandible after ameloblastoma - feasibility of oral rehabilitation with rhBMP-2 associated to bovine xenograft followed by implant installation.

    PubMed

    Lustosa, Romulo Maciel; Macedo, Diogo de Vasconcelos; Iwaki, Lilian Cristina Vessoni; Tolentino, Elen de Souza; Hasse, Paulo Norberto; Marson, Giordano Bruno de Oliveira; Iwaki Filho, Liogi

    2015-10-01

    Recombinant human morphogenetic protein (rhBMP) is a graft alternative for extensive mandibular reconstruction after tumor resections. However, the feasibility of rhBMP-2 to receive osseointegrated implants and prosthetic rehabilitation has been rarely reported. This study reports on a case of an extensive solid ameloblastoma along the mandibular body. The treatment consisted of resection followed by off-label use of rhBMP type 2 associated with bovine bone xenograft. Eleven months postoperatively, the patient was prosthetically rehabilitated with dental implants, without evidence of resorption or complications. The literature on mandibular reconstructions using rhBMP and their feasibility for future osseointegrated implant placement was also reviewed. Based on the presented case, the association between rhBMP-2 and a bovine bone xenograft could be considered a feasible option for the reconstruction and rehabilitation of large mandibular defects after tumor resection. According to the literature, the use of rhBMP as a graft material is encouraging, with good clinical outcome. However, there are no long-term studies demonstrating success and survival rates of implants placed in these grafts. Future investigations will be required to ascertain the long-term survival of implants in areas grafted with rhBMP. Also, there is a lack of information regarding the prosthetic rehabilitation of these patients. Copyright © 2015 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

  10. Safety and tolerability of vortioxetine (15 and 20 mg) in patients with major depressive disorder: results of an open-label, flexible-dose, 52-week extension study.

    PubMed

    Jacobsen, Paula L; Harper, Linda; Chrones, Lambros; Chan, Serena; Mahableshwarkar, Atul R

    2015-09-01

    Vortioxetine is approved for the treatment of adults with major depressive disorder. This open-label extension (OLE) study evaluated the safety and tolerability of vortioxetine in the long-term treatment of major depressive disorder patients, as well as evaluated its effectiveness using measures of depression, anxiety, and overall functioning. This was a 52-week, flexible-dose, OLE study in patients who completed one of three randomized, double-blind, placebo-controlled, 8-week vortioxetine trials. All patients were switched to 10 mg/day vortioxetine for week 1, then adjusted between 15 and 20 mg for the remainder of the study, but not downtitrated below 15 mg. Safety and tolerability were assessed on the basis of treatment-emergent adverse events (TEAEs), vital signs, laboratory values, physical examination, and the Columbia-Suicide Severity Rating Scale. Efficacy measures included the Montgomery-Åsberg Depression Rating Scale, the Hamilton Anxiety Scale, the Clinical Global Impression Scale-Severity of Illness, and the Sheehan Disability Scale. Of the 1075 patients enrolled, 1073 received at least one dose of vortioxetine and 538 (50.0%) completed the study. A total of 537 patients withdrew early, with 115 (10.7% of the original study population) withdrawing because of TEAEs. Long-term treatment with vortioxetine was well tolerated; the most common TEAEs (≥10%) were nausea and headache. Laboratory values, vital signs, and physical examinations revealed no trends of clinical concern. The mean Montgomery-Åsberg Depression Rating Scale total score was 19.9 at the start of the extension study and 9.0 after 52 weeks of treatment (observed cases). Similar improvements were observed with the Hamilton Anxiety Scale (Δ-4.2), the Clinical Global Impression Scale-Severity of Illness (Δ-1.2), and the Sheehan Disability Scale (Δ-4.7) total scores after 52 weeks of treatment (observed case). In this 52-week, flexible-dose OLE study, 15 and 20 mg vortioxetine were safe and well tolerated. After entry into this study, patients continued to show improvement in depression and anxiety symptoms, as well as overall functioning, throughout the treatment period.

  11. Dynamical Stability and Long-term Evolution of Rotating Stellar Systems

    NASA Astrophysics Data System (ADS)

    Varri, Anna L.; Vesperini, E.; McMillan, S. L. W.; Bertin, G.

    2011-05-01

    We present the first results of an extensive survey of N-body simulations designed to investigate the dynamical stability and the long-term evolution of two new families of self-consistent stellar dynamical models, characterized by the presence of internal rotation. The first family extends the well-known King models to the case of axisymmetric systems flattened by solid-body rotation while the second family is characterized by differential rotation. The equilibrium configurations thus obtained can be described in terms of two dimensionless parameters, which measure the concentration and the amount of rotation, respectively. Slowly rotating configurations are found to be dynamically stable and we followed their long-term evolution, in order to evaluate the interplay between collisional relaxation and angular momentum transport. We also studied the stability of rapidly rotating models, which are characterized by the presence of a toroidal core embedded in an otherwise quasi-spherical configuration. In both cases, a description in terms of the radial and global properties, such as the ratio between the ordered kinetic energy and the gravitational energy of the system, is provided. Because the role of angular momentum in the process of cluster formation is only partly understood, we also undertook a preliminary investigation of the violent relaxation of simple systems initially characterized by approximate solid-body rotation. The properties of the final equilibrium configurations thus obtained are compared with those of the above-described family of differentially rotating models.

  12. Long-term safety and tolerability of rotigotine transdermal system in patients with early-stage idiopathic Parkinson's disease: a prospective, open-label extension study.

    PubMed

    Elmer, Lawrence W; Surmann, Erwin; Boroojerdi, Babak; Jankovic, Joseph

    2012-06-01

    This prospective, open-label extension (SP702; NCT00594165) of a 6-month double-blind, randomized study investigated the long-term safety and tolerability of rotigotine transdermal system in early Parkinson's disease (PD). Patients with early-stage idiopathic PD received transdermal rotigotine for up to 6 years at optimal dose (up to 16 mg/24h). Adjunctive levodopa was allowed. Primary outcomes included adverse events (AEs) and extent of rotigotine exposure. Other outcomes included time to levodopa, incidence of dyskinesias, and efficacy using the Unified Parkinson's Disease Rating Scale (UPDRS) II+III total score. Of 217 patients entering the open-label study, 47% were still in the study upon closure; 24% withdrew because of AEs and 6% because of lack of efficacy. The median exposure to rotigotine was 1910 days (≈ 5 years, 3 months; range 1-2188 days). Most common AEs were somnolence (23% per patient-year), falls (17%), peripheral edema (14%), nausea (12%), and application site reactions (ASRs; 12%). 3% withdrew because of ASRs. 26% patients did not initiate levodopa; of those who did, fewer than half started levodopa in the first year. Dyskinesias were reported by 25% patients; the majority (83%) reported their first episode after initiating levodopa. Mean UPDRS II+III total scores remained below double-blind baseline for up to 2 years of open-label treatment. This is the longest interventional study of rotigotine conducted to date. Transdermal rotigotine was generally well tolerated for up to 6 years; AEs reported were similar to those observed in shorter studies and led to discontinuation in only 24% patients. Copyright © 2012 Elsevier Ltd. All rights reserved.

  13. Simultaneous monitoring of presynaptic transmitter release and postsynaptic receptor trafficking reveals an enhancement of presynaptic activity in metabotropic glutamate receptor-mediated long-term depression.

    PubMed

    Xu, Wei; Tse, Yiu Chung; Dobie, Frederick A; Baudry, Michel; Craig, Ann Marie; Wong, Tak Pan; Wang, Yu Tian

    2013-03-27

    Although the contribution of postsynaptic mechanisms to long-term synaptic plasticity has been studied extensively, understanding the contribution of presynaptic modifications to this process lags behind, primarily because of a lack of techniques with which to directly and quantifiably measure neurotransmitter release from synaptic terminals. Here, we developed a method to measure presynaptic activity through the biotinylation of vesicular transporters in vesicles fused with presynaptic membranes during neurotransmitter release. This method allowed us for the first time to selectively quantify the spontaneous or evoked release of glutamate or GABA at their respective synapses. Using this method to investigate presynaptic changes during the expression of group I metabotropic glutamate receptor (mGluR1/5)-mediated long-term depression (LTD) in cultured rat hippocampal neurons, we discovered that this form of LTD was associated with increased presynaptic release of glutamate, despite reduced miniature EPSCs measured with whole-cell recording. Moreover, we found that specific blockade of AMPA receptor (AMPAR) endocytosis with a membrane-permeable GluR2-derived peptide not only prevented the expression of LTD but also eliminated LTD-associated increase in presynaptic release. Thus, our work not only demonstrates that mGluR1/5-mediated LTD is associated with increased endocytosis of postsynaptic AMPARs but also reveals an unexpected homeostatic/compensatory increase in presynaptic release. In addition, this study indicates that biotinylation of vesicular transporters in live cultured neurons is a valuable tool for studying presynaptic function.

  14. The Argentinean network for the assessment and monitoring of Pampean shallow-lakes (PAMPA2)

    NASA Astrophysics Data System (ADS)

    Zagarese, H. E.

    2012-12-01

    The Pampa region of Argentina is an extensive wetland containing nearly 200,000 shallow-lakes. The region is under increasing agricultural pressure resulting from climate change (increased temperature and precipitation) and the substitution of cattle breeding and traditional cultures by transgenic soy. Among the many services that they provide, shallow-lakes are highly responsive to changes in climate and land use. Therefore, long-term studies of shallow-lakes provide useful clues to understand and track changes occurring in their complex watersheds. PAMPA2 is a recently funded, long-term network project, with wide geographic coverage, aimed at studying Pampean shallow-lakes. Thirteen network sites (i.e., shallow lakes) occurring along the precipitation gradient (from < 300 mm y-1 to > 1000 mm y-1) form the core of the project. The network integrates various research teams from eight universities and research centers, with a strong multidisciplinary component. The approaches combine traditional sampling; high-rate monitoring using automated sensors; and remote sensing. The network develops and manufactures most the instruments, including automated buoys and unmanned aircrafts. In this presentation, we will provide details on the structure and state of development of the PAMPA2 network, and present a long-term case study of a large Pampean shallow-lake, exemplifying the strong dependence of lake processes on weather variables. Laguna Chascomús is a large, hypertrophic shallow-lake. Chascomús is one of the PAMPA2 study sites that have been more extensively studied. In this shallow-lake, high nutrient availability permits the development of a dense microbial plankton community, which in turn translates into exceptionally high water turbidity. Phytoplankton primary production is strongly limited by light availability. As a consequence, turbidity is strongly and positively correlated to the incoming solar radiation, resulting in a remarkable seasonal pattern of water transparency. Species composition within the microbial plankton community is remarkable stable. But some important features vary seasonally. Although the microbial plankton biomass is higher around the summer solstice (SS), its phosphorous content per unit biomass is higher around the winter solstice (WS), which results in an unanticipated bimodal pattern of phosphorous concentration, with maxima occurring around the spring and fall equinoxes. Many optical characteristics also vary seasonally and suggest that, as a whole, the microbial plankton community is more autotrophic around the WS, and more heterotrophic around the SS. Life table experiments, using dominant zooplankton grazers (rotifers), indicated that the microbial food quality is higher in winter than in summer. Incoming solar radiation and temperature account for much of the lake seasonal dynamics. Shallow-lakes, such Laguna Chascomús are well suited for long-term studies and the emplacement of automated sensors. Despite the high system complexity, many processes are remarkable repeatable and reproducible at mesocosm-scales. Long-term time series of lake and weather variables will provide a strong basement for understanding climate variability, such as the cyclic changes in precipitation, which greatly affects lake depth; and the seemingly stochastic cold weather periods, producing massive winter fish kill events.

  15. Synthesis of a quarter-century of satellite and airborne altimetry records to resolve long-term ice sheet elevation change

    NASA Astrophysics Data System (ADS)

    Nilsson, J.; Paolo, F. S.; Simonsen, S.; Gardner, A. S.

    2017-12-01

    Satellite and airborne altimetry provide the longest continuous record from which the mass balance of the Antarctic ice sheet can be derived, starting with the launch of ERS-1 in 1992. Accurate knowledge of the long-term mass balance is vital for understanding the geophysical processes governing the ice sheet contribution to present day sea-level rise. However, this record is comprised of several different measurement systems, with different accuracies and varying resolution. This poses a major challenge on the interpretation and reconstruction of consistent elevation-change time series for determining long-term ice sheet trends and variability. Previous studies using data from multiple satellite altimetry missions have relied on a cross-calibration technique based on crossover bias analysis to merge records from different sensors. This methodology, though accurate, limits the spatial coverage to typical resolutions of 10-50 km, restricting the approach to regional or continental-wide studies. In this study, we present a novel framework for seamless integration of heterogeneous altimetry records, using an adaptive least-squares minimization technique. The procedure allows reconstructing time series at fine spatial (<5 km) and temporal (monthly) scales, while accounting for sensor-dependent biases and heterogeneous data quality. We synthesize altimetry records spanning the time period 1992-2016 to derive long-term time series of elevation change for the Antarctica ice sheet, including both data from the European Space Agency (ERS-1, ERS-2, Envisat and CryoSat-2) and NASA (ICESat and Operation IceBridge), with future inclusion of data from NASA's ICESat-2. Mission specific errors, estimated from independent airborne measurements and crossover analysis, are propagated to derive uncertainty bounds for each individual time series. We also perform an extensive analysis of the major corrections applied to raw satellite altimetry data to assess their overall effect on the estimated uncertainty. This methodology will allow us to determine robust long-term changes in the surface elevation of grounded Antarctic ice. Such a dataset will be invaluable to advancing ice sheet assimilation efforts and to disentangle causal mechanisms of modern ice sheet response to environmental forcing.

  16. Smoking and long-term labour market outcomes.

    PubMed

    Böckerman, Petri; Hyytinen, Ari; Kaprio, Jaakko

    2015-07-01

    To examine the long-term effects of smoking on labour market outcomes using twin data matched to register-based individual information on earnings. Twin data for Finnish men born 1945-1957 was used to remove the shared environmental and genetic factors. The results were subjected to extensive robustness testing. Lifetime cigarette consumption was measured by (cumulative) cigarette pack-years in early adulthood. The average of an individual's earnings (and, alternatively, taxable income) was measured over a subsequent 15-year period in later adulthood. Smokers have lower long-term income and earnings. For example, controlling for the shared environmental and genetic factors using the data on genetically identical twins, smoking is negatively associated with lifetime income (p=0.015). The negative association was also robust to the use of various covariates, such as education, health indicators and extraversion. Smoking is negatively related to long-term labour market outcomes. The provision of information about the indirect monetary costs of smoking may thus complement the policy efforts that aim at educating consumers about the health costs of smoking. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  17. The impact of long-term growth hormone treatment on metabolic parameters in Japanese patients with short stature born small for gestational age.

    PubMed

    Kappelgaard, Anne-Marie; Kiyomi, Fumiaki; Horikawa, Reiko; Yokoya, Susumu; Tanaka, Toshiaki

    2014-01-01

    An examination of the effects of up to 260 weeks of growth hormone (GH) therapy on metabolic parameters in Japanese children born small for gestational age (SGA). Data were analysed from a 156-week extension of a 104-week multicentre, randomised, double-blind, parallel-group trial. Sixty-five children born SGA (age 3-<8 years) received 33 μg/kg/day (n = 31, 64.5% male) or 67 μg/kg/day (n = 34, 58.8% male) GH for 260 weeks. Changes in metabolic parameters - glucose, insulin, total cholesterol, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol - were recorded. Alterations in weight, body mass index standard deviation score (BMI SDS) and vital signs were also evaluated. Over 260 weeks of GH treatment, a positive correlation between Δheight SDS and Δinsulin-like growth factor-I SDS was observed. Insulin and glucose levels were generally unaffected. Favourable changes in lipid profiles were recorded, which were maintained for the study duration. No adverse alterations in weight, BMI SDS or vital signs were noted. Long-term, continuous GH treatment in children born SGA appears to be efficacious, associated with potential benefits for several metabolic parameters and associated with no long-term safety concerns.

  18. Long-term result of cementless femoral stem in avascular necrosis of the hip.

    PubMed

    Cheung, Kin W; Chiu, Kwok H; Chung, Kwong Y

    2015-01-01

    Avascular necrosis (AVN) of the hip may have extensive involvement of the proximal femur which may affect boney ingrowth into cementless femoral stems. From 1994 to 2004, 182 total hip arthroplasties (in 144 patients, 117 AVN hips and 65 non-AVN hips) were performed using hydroxyapatite coated femoral stems. All patients were followed up prospectively. Mean age was 51 years and mean follow-up 14.7 years (range 9.7-19.1 years). Four stems were revised because of aseptic loosening, 3 in AVN group and 1 in non-AVN group. The overall mechanical failure rate was 2.2%, the mechanical failure rate in AVN and non-AVN group was 2.6% and 1.5% respectively (p = 1). The 19.1 year survival using revision for aseptic loosening as an endpoint for AVN and non-AVN patients were 97.1% and 96.2% respectively (p = 0.654). Stable boney ingrowth was present in 99.5% hips. This study represents 1 of the largest series reporting the long-term follow-up of the use of cementless femoral stems in treating AVN of the hip. We report excellent long-term survival of cementless total hip arthroplasty used in managing AVN of the hip and is comparable to that seen in non-AVN total hip arthroplasty.

  19. Developing a global psychotherapeutic approach to schizophrenia: results of a five-year follow-up.

    PubMed Central

    Alanen, Y. O.; Räkköläinen, V.; Rasimus, R.; Laakso, J.; Kaljonen, A.

    1985-01-01

    This is an account of a long-range action research project to determine indications for and effects of a comprehensive psychotherapeutic approach, including various treatment modalities, in the treatment of schizophrenics. Four diagnostic groups were established among the 100 patients. In the course of data analysis, the group of typical schizophrenics (56 percent) was contrasted to or compared with the entire series. A further diagnostic differentiation was established according to ego functioning; i.e., imminent, acute, regressive, and paranoid ego disintegrations, respectively. Patients and family members were interviewed upon admission, and again two and five years later, and the data recorded on a 163-item form from which 40 clinical and psychosocial variables were constructed after the baseline examinations. In addition to cross-tabulation, logistic regression analysis was employed. The conclusion that the follow-up study supports the effectiveness of our global psychotherapeutic approach to treating schizophrenia seems justified. Results so far indicate that five modes of therapy in addition to drug treatments are optimal for different patients. The five modes are long-term individual psychotherapy, couple or conjoint family therapy for married patients, family therapy with the family of origin, flexible short-term crisis intervention with a family focus, and extensive long-term treatment focused on social rehabilitation for the most ill-starred patients. PMID:4049919

  20. Fingolimod hydrochloride for the treatment of relapsing remitting multiple sclerosis.

    PubMed

    Thomas, Katja; Proschmann, Undine; Ziemssen, Tjalf

    2017-10-01

    Fingolimod was the first oral and the first in class disease modifying treatment in multiple sclerosis that acts as sphingosine-1-phospathe receptor agonist. Since approval in 2010 there is a growing experience with fingolimod use in clinical practice, but also next-generation sphingosin-1-receptor agonists in ongoing clinical trials. Growing evidence demonstrates additional effects beyond impact on lymphocyte circulation, highlighting further promising targets in multiple sclerosis therapy. Areas covered: Here we present a systematic review using PubMed database searching and expert opinion on fingolimod use in clinical practice. Long-term data of initial clinical trials and post-marketing evaluations including long-term efficacy, safety, tolerability and management especially within growing disease modifying treatment options and pre-treatment constellation in multiple sclerosis patients are critically discussed. Furthermore novel findings in mechanism of actions and prospective on additional use in progressive forms in multiple sclerosis are presented. Expert opinion: There is an extensive long-term experience on fingolimod use in clinical practice demonstrating the favorable benefit-risk of this drug. Using a defined risk management approach experienced MS clinicians should apply fingolimod after critical choice of patients and review of clinical aspects. Further studies are essential to discuss additional benefit in progressive forms in multiple sclerosis.

  1. A 24-Week, Open-Label Extension Study to Investigate the Long-term Safety, Tolerability, and Efficacy of 13.3 mg/24 h Rivastigmine Patch in Patients With Severe Alzheimer Disease.

    PubMed

    Farlow, Martin R; Grossberg, George T; Sadowsky, Carl H; Meng, Xiangyi; Velting, Drew M

    2015-01-01

    The long-term safety, tolerability, and efficacy of high-dose 13.3 mg/24 h rivastigmine patch in severe Alzheimer disease was evaluated in a 24-week, open-label extension to the double-blind ACTION study. Safety and tolerability, and efficacy on the Alzheimer's Disease Cooperative Study-Activities of Daily Living scale-Severe Impairment Version (ADCS-ADL-SIV), Severe Impairment Battery (SIB), and ADCS-Clinical Global Impression of Change (ADCS-CGIC) were assessed. Overall, 197 patients continued on 13.3 mg/24 h patch; 199 uptitrated from 4.6 mg/24 h to 13.3 mg/24 h patch. The incidence of adverse events (AEs), serious AEs and discontinuations due to AEs was similar in patients who continued on, and patients who uptitrated to, 13.3 mg/24 h patch (AEs: 57.9% and 59.8%; serious AEs: 16.2% and 16.1%; discontinuations: 11.2% and 12.1%, respectively). Larger mean changes from double-blind baseline were observed in patients uptitrated on the ADCS-ADL-SIV (-4.6; SD=8.7) and SIB (-7.0; SD=16.6), than those who continued on 13.3 mg/24 h patch (-3.9; SD=8.0 and -4.7; SD=16.8, respectively). ADCS-CGIC scores were comparable. There were no clinically relevant between-group differences in safety and tolerability. Greater decline was observed in patients with delayed uptitration to high-dose 13.3 mg/24 h patch than patients who continued on high-dose patch.

  2. Long-term community dynamics of small landbirds with and without exposure to extensive disturbance from military training activities.

    PubMed

    Rivers, James W; Gipson, Philip S; Althoff, Donald P; Pontius, Jeffrey S

    2010-02-01

    Military training activities are known to impact individual species, yet our understanding of how such activities influence animal communities is limited. In this study, we used long-term data in a case study approach to examine the extent to which the local small landbird community differed between a site in northeast Kansas that experienced intensive disturbance from military training activities (Ft. Riley Military Installation) and a similar, nearby site that experienced minimal human disturbance (Konza Prairie Biological Station). In addition, we characterized how the regional pool of potential colonizers influenced local community dynamics using Breeding Bird Survey data. From 1991 to 2001, most species of small terrestrial landbirds (73%) recorded during breeding surveys were found at both sites and the mean annual richness at Ft. Riley (39.0 +/- 2.86 [SD]) was very similar to that of Konza Prairie (39.4 +/- 2.01). Richness was maintained at relatively constant levels despite compositional changes because colonizations compensated local extinctions at both sites. These dynamics were driven primarily by woodland species that exhibited stochastic losses and gains and were present at a low local and regional abundance. Our results suggest that military training activities may mimic natural disturbances for some species in this area because the small landbird community did not differ markedly between sites with and sites without extensive human disturbance. Although our results suggest that military training is not associated with large changes in the avian community, additional studies are needed to determine if this pattern is found in other ecological communities.

  3. Psychiatric adverse events during treatment with brodalumab: Analysis of psoriasis clinical trials.

    PubMed

    Lebwohl, Mark G; Papp, Kim A; Marangell, Lauren B; Koo, John; Blauvelt, Andrew; Gooderham, Melinda; Wu, Jashin J; Rastogi, Shipra; Harris, Susan; Pillai, Radhakrishnan; Israel, Robert J

    2018-01-01

    Individuals with psoriasis are at increased risk for psychiatric comorbidities, including suicidal ideation and behavior (SIB). To distinguish between the underlying risk and potential for treatment-induced psychiatric adverse events in patients with psoriasis being treated with brodalumab, a fully human anti-interleukin 17 receptor A monoclonal antibody. Data were evaluated from a placebo-controlled, phase 2 clinical trial; the open-label, long-term extension of the phase 2 clinical trial; and three phase 3, randomized, double-blind, controlled clinical trials (AMAGINE-1, AMAGINE-2, and AMAGINE-3) and their open-label, long-term extensions of patients with moderate-to-severe psoriasis. The analysis included 4464 patients with 9161.8 patient-years of brodalumab exposure. The follow-up time-adjusted incidence rates of SIB events were comparable between the brodalumab and ustekinumab groups throughout the 52-week controlled phases (0.20 vs 0.60 per 100 patient-years). In the brodalumab group, 4 completed suicides were reported, 1 of which was later adjudicated as indeterminate; all patients had underlying psychiatric disorders or stressors. There was no comparator arm past week 52. Controlled study periods were not powered to detect differences in rare events such as suicide. Comparison with controls and the timing of events do not indicate a causal relationship between SIB and brodalumab treatment. Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  4. Analysis of haematological changes in tofacitinib-treated patients with rheumatoid arthritis across phase 3 and long-term extension studies.

    PubMed

    Schulze-Koops, Hendrik; Strand, Vibeke; Nduaka, Chudy; DeMasi, Ryan; Wallenstein, Gene; Kwok, Kenneth; Wang, Lisy

    2017-01-01

    Tofacitinib is an oral Janus kinase inhibitor for the treatment of RA. The aim of this analysis was to characterize changes in haematological parameters following tofacitinib treatment, and to compare changes in haemoglobin with markers of disease activity, fatigue and vitality. Changes in neutrophil counts, lymphocyte counts and haemoglobin levels were analysed in patients with RA from six phase 3 randomized controlled trials (n = 4271) of tofacitinib 5 or 10 mg bd, placebo or active comparators of up to 24 months' duration, and two long-term extension (LTE) studies (n = 4858) of tofacitinib of up to 84 months' duration. Disease activity markers included CRP and ESR. Fatigue and vitality were assessed using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) and Short Form Health Survey-36 vitality domain scores. In phase 3 studies, mean neutrophil and lymphocyte counts decreased and mean haemoglobin levels increased in all tofacitinib treatment groups. Haemoglobin levels and neutrophil counts stabilized in the LTE studies, while lymphocyte count decreases stabilized at approximately month 48. Increased haemoglobin was associated with decreased ESR and CRP levels. Clinically meaningful reductions in haemoglobin levels (⩾3 g/dl from baseline or haemoglobin ⩽7 g/dl) occurred in <1.0% of patients in all treatment groups. FACIT-F and Short Form Health Survey-36 vitality scores were weakly correlated with haemoglobin levels. Small changes in haematological parameters were seen with tofacitinib treatment, which stabilized over time in the LTE studies. Changes in haemoglobin levels, although associated with changes in ESR and CRP, were not associated with fatigue or vitality. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology.

  5. A phase 2, open-label, multicenter study of the long-term safety of siltuximab (an anti-interleukin-6 monoclonal antibody) in patients with multicentric Castleman disease.

    PubMed

    van Rhee, Frits; Casper, Corey; Voorhees, Peter M; Fayad, Luis E; van de Velde, Helgi; Vermeulen, Jessica; Qin, Xiang; Qi, Ming; Tromp, Brenda; Kurzrock, Razelle

    2015-10-06

    Multicentric Castleman disease (MCD) is a rare, systemic lymphoproliferative disorder driven by interleukin (IL)-6 overproduction. Siltuximab, an anti-IL-6 monoclonal antibody, has demonstrated durable tumor and symptomatic responses in a multinational, randomized, placebo-controlled study of MCD. This preplanned safety analysis was conducted to evaluate the long-term safety of siltuximab treatment among 19 patients with MCD who had stable disease or better and were enrolled in a phase-1 study and subsequent ongoing, open-label, phase-2 extension study. Dosing was 11 mg/kg administered intravenously every 3 weeks, per protocol, or every 6 weeks at the investigator's discretion. Safety monitoring focused on potential risks associated with the anti-IL-6 mechanism of action. Investigator-assessed disease control status was also documented. Median treatment duration for the 19 patients was 5.1 (range 3.4, 7.2) years, with 14 (74%) patients treated for >4 years. Grade-≥ 3 adverse events (AEs) reported in >1 patient included hypertension (n = 3) and nausea, cellulitis, and fatigue (n = 2 each). Grade-≥ 3 AEs at least possibly attributed to siltuximab were leukopenia, lymphopenia, and a serious AE of polycythemia (n = 1 each). Hypertriglyceridemia and hypercholesterolemia (total cholesterol) were reported in 8 and 9 patients, respectively. No disease relapses were observed, and 8 of 19 patients were able to switch to an every-6-week dosing schedule. All MCD patients in this extension study have received siltuximab for a prolonged duration (up to 7 years) without evidence of cumulative toxicity or treatment discontinuations and with few serious infections. All patients are alive, demonstrate sustained disease control, and continue to receive siltuximab.

  6. Open-label, 9-month extension study investigating the uro-selective alpha-blocker silodosin in men with LUTS associated with BPH.

    PubMed

    Osman, Nadir I; Chapple, Christopher R; Tammela, Teuvo L; Eisenhardt, Andreas; Oelke, Matthias

    2015-05-01

    To evaluate the long-term safety (primary objective) and efficacy/impact on quality of life (QoL, secondary objectives) of silodosin 8 mg once daily in men with LUTS/BPH. Men who completed the 12-week double-blind study with silodosin 8 mg, tamsulosin 0.4 mg, or placebo were offered to continue with the 9-month open-label study during which all patients received silodosin 8 mg once daily. Safety was assessed by analysing vital signs, electrocardiograms, laboratory tests, and adverse events. Efficacy was evaluated with the International Prostate Symptom Score (IPSS), IPSS voiding and storage sub-scores, IPSS-QoL, and maximum urinary flow rate (Q max). A total of 500 patients (mean age 66 years) entered the 9-month open-label study. Treatment-emergent adverse events (TEAE) were experienced by 33.4% patients. Ejaculation dysfunction was the most common TEAE (9.0%) but led to study discontinuations in only 1.6% of patients. Dizziness without orthostatic hypotension occurred in 0.8%. A marked reduction in total IPSS (-2.7 ± 3.8) was documented at the first visit of this extension phase in patients having de novo silodosin compared with lesser improvement in patients previously treated with silodosin (-0.82 ± 4.2) or tamsulosin (-0.83 ± 3.8). Improvements were maintained throughout the open-label phase. QoL also improved, with the greatest improvement in de novo silodosin patients. No relevant changes in Q max occurred. Long-term treatment with silodosin was safe and efficacious. Abnormal ejaculation was the most common TEAE, but led to treatment discontinuation in only 1.6% of patients. Orthostatic hypotension was not seen, and only a few patients experienced dizziness.

  7. The safety and tolerability of vortioxetine: Analysis of data from randomized placebo-controlled trials and open-label extension studies

    PubMed Central

    Baldwin, David S; Chrones, Lambros; Florea, Ioana; Nielsen, Rebecca; Nomikos, George G; Palo, William; Reines, Elin

    2016-01-01

    The safety and tolerability of vortioxetine in adults with major depressive disorder was assessed. Tolerability was based on the nature, incidence and severity of treatment-emergent adverse events (TEAEs) during acute (6/8) week treatment in 11 randomized, double-blind placebo-controlled short-term studies in major depressive disorder: six with an active reference. Symptoms following discontinuation were assessed through the Discontinuation-Emergent Signs and Symptoms checklist in three studies. Long-term (⩽52 weeks) tolerability was evaluated in five open-label extension studies. Patients (n =5701) were acutely treated with either placebo (n=1817), vortioxetine (5–20mg/day; n=3018), venlafaxine XR (225mg/day; n=113) or duloxetine (60mg/day; n=753). The withdrawal rate due to TEAEs during treatment with vortioxetine (5–20mg/day) was 4.5–7.8%, compared with placebo (3.6%), venlafaxine XR (14.2%) or duloxetine (8.8%). Common TEAEs (incidence ⩾5% and >2 × placebo) with vortioxetine (5–20mg/day) were nausea (20.9–31.2%) and vomiting (2.9–6.5%). For vortioxetine (5–20mg/day), the incidence of TEAEs associated with insomnia was 2.0–5.1% versus 4.0% for placebo, and with sexual dysfunction 1.6–1.8% versus 1.0% for placebo. Discontinuation symptoms as assessed by the mean Discontinuation-Emergent Signs and Symptoms total score after abrupt discontinuation were comparable to placebo in the first and second week. Vortioxetine had no effect relative to placebo on clinical laboratory parameters, body weight, heart rate or blood pressure. Vortioxetine showed no clinically relevant effect on ECG parameters, including the QTcF interval. In long-term treatment, no new types of TEAEs were seen; the mean weight gain was 0.7–0.8kg. Thus, vortioxetine (5–20mg/day) appears safe and generally well tolerated in the treatment of major depressive disorder. PMID:26864543

  8. The safety and tolerability of vortioxetine: Analysis of data from randomized placebo-controlled trials and open-label extension studies.

    PubMed

    Baldwin, David S; Chrones, Lambros; Florea, Ioana; Nielsen, Rebecca; Nomikos, George G; Palo, William; Reines, Elin

    2016-03-01

    The safety and tolerability of vortioxetine in adults with major depressive disorder was assessed. Tolerability was based on the nature, incidence and severity of treatment-emergent adverse events (TEAEs) during acute (6/8) week treatment in 11 randomized, double-blind placebo-controlled short-term studies in major depressive disorder: six with an active reference. Symptoms following discontinuation were assessed through the Discontinuation-Emergent Signs and Symptoms checklist in three studies. Long-term (⩽52 weeks) tolerability was evaluated in five open-label extension studies. Patients (n =5701) were acutely treated with either placebo (n=1817), vortioxetine (5-20mg/day; n=3018), venlafaxine XR (225mg/day; n=113) or duloxetine (60mg/day; n=753). The withdrawal rate due to TEAEs during treatment with vortioxetine (5-20mg/day) was 4.5-7.8%, compared with placebo (3.6%), venlafaxine XR (14.2%) or duloxetine (8.8%). Common TEAEs (incidence ⩾5% and >2 × placebo) with vortioxetine (5-20mg/day) were nausea (20.9-31.2%) and vomiting (2.9-6.5%). For vortioxetine (5-20mg/day), the incidence of TEAEs associated with insomnia was 2.0-5.1% versus 4.0% for placebo, and with sexual dysfunction 1.6-1.8% versus 1.0% for placebo. Discontinuation symptoms as assessed by the mean Discontinuation-Emergent Signs and Symptoms total score after abrupt discontinuation were comparable to placebo in the first and second week. Vortioxetine had no effect relative to placebo on clinical laboratory parameters, body weight, heart rate or blood pressure. Vortioxetine showed no clinically relevant effect on ECG parameters, including the QTcF interval. In long-term treatment, no new types of TEAEs were seen; the mean weight gain was 0.7-0.8kg. Thus, vortioxetine (5-20mg/day) appears safe and generally well tolerated in the treatment of major depressive disorder. © The Author(s) 2016.

  9. Western root disease model simulation versus plot remeasurement: 11 years of change in stand structure and density induced by Armillaria root disease in Central Oregon

    Treesearch

    Helen M. Maffei; Gregory M. Filip; Kristen L. Chadwick; Lance David

    2008-01-01

    The purpose of this analysis was to use long term permanent plots to evaluate the short-term predictive capability of the Western Root Disease Model extension (WRDM) of the Forest Vegetation Simulator (FVS) in central Oregon mixed-conifer forests in project planning situations. Measured (1991–2002) structure and density changes on a 100-acre unmanaged area in south-...

  10. Multi-Wavelength Monitoring of GRS 1915+105

    NASA Technical Reports Server (NTRS)

    Bandyopadhyay, R.; Martini, P.; Gerard, E.; Charles, P. A.; Wagner, R. M.; Shrader, C.; Shahbaz, T.; Mirabel, I. F.

    1997-01-01

    Since its discovery in 1992, the superluminal X-ray transient GRS 1915+105 has been extensively observed in an attempt to understand its behaviour. We present here first results from a multi-wavelength campaign undertaken from July to September 1996. This study includes X-ray data from the RXTE All Sky Monitor and BATSE, two-frequency data from the Nancay radio telescope, and infrared photometry from the 1.8 m Perkins telescope at Lowell Observatory. The first long-term well-sampled IR light curve of GRS 1915+105 is presented herein and is consistent with the interpretation of this source as a long-period binary. We compare the various light curves, searching for correlations in the behaviour of the source at differing wavelengths and for possible periodicities.

  11. Long-term outcome after resection of brainstem hemangioblastomas in von Hippel-Lindau disease

    PubMed Central

    Wind, Joshua J.; Bakhtian, Kamran D.; Sweet, Jennifer A.; Mehta, Gautam U.; Thawani, Jayesh P.; Asthagiri, Ashok R.; Oldfield, Edward H.; Lonser, Russell R.

    2016-01-01

    Object Brainstem hemangioblastomas are frequently encountered in patients with von Hippel-Lindau (VHL) disease. These tumors can cause significant morbidity, and their optimal management has not been defined. To better define the outcome and management of these tumors, the authors analyzed the long-term results in patients who underwent resection of brainstem hemangioblastomas. Methods Consecutive patients with VHL disease who underwent resection of brainstem hemangioblastomas with a follow-up of 12 months or more were included in this study. Serial functional assessments, radiographic examinations, and operative records were analyzed. Results Forty-four patients (17 male and 27 female) underwent 51 operations for resection of 71 brainstem hemangioblastomas. The most common presenting symptoms were headache, swallowing difficulties, singultus, gait difficulties, and sensory abnormalities. The mean follow-up was 5.9 ± 5.0 years (range 1.0–20.8 years). Immediately after 34 operations (66.7%), the patients remained at their preoperative functional status; they improved after 8 operations (15.7%) and worsened after 9 operations (17.6%) as measured by the McCormick scale. Eight (88.9%) of the 9 patients who were worse immediately after resection returned to their preoperative status within 6 months. Two patients experienced functional decline during long-term follow-up (beginning at 2.5 and 5 years postoperatively) caused by extensive VHL disease–associated CNS disease. Conclusions Generally, resection of symptomatic brainstem hemangioblastomas is a safe and effective management strategy in patients with VHL disease. Most patients maintain their preoperative functional status, although long-term decline in functional status may occur due to VHL disease–associated progression. PMID:20932100

  12. The long-term health of vegetarians and vegans.

    PubMed

    Appleby, Paul N; Key, Timothy J

    2016-08-01

    Vegetarians, who do not eat any meat, poultry or fish, constitute a significant minority of the world's population. Lacto-ovo-vegetarians consume dairy products and/or eggs, whereas vegans do not eat any foods derived wholly or partly from animals. Concerns over the health, environmental and economic consequences of a diet rich in meat and other animal products have focussed attention on those who exclude some or all of these foods from their diet. There has been extensive research into the nutritional adequacy of vegetarian diets, but less is known about the long-term health of vegetarians and vegans. We summarise the main findings from large cross-sectional and prospective cohort studies in western countries with a high proportion of vegetarian participants. Vegetarians have a lower prevalence of overweight and obesity and a lower risk of IHD compared with non-vegetarians from a similar background, whereas the data are equivocal for stroke. For cancer, there is some evidence that the risk for all cancer sites combined is slightly lower in vegetarians than in non-vegetarians, but findings for individual cancer sites are inconclusive. Vegetarians have also been found to have lower risks for diabetes, diverticular disease and eye cataract. Overall mortality is similar for vegetarians and comparable non-vegetarians, but vegetarian groups compare favourably with the general population. The long-term health of vegetarians appears to be generally good, and for some diseases and medical conditions it may be better than that of comparable omnivores. Much more research is needed, particularly on the long-term health of vegans.

  13. Non-invasive long-term fluorescence live imaging of Tribolium castaneum embryos.

    PubMed

    Strobl, Frederic; Stelzer, Ernst H K

    2014-06-01

    Insect development has contributed significantly to our understanding of metazoan development. However, most information has been obtained by analyzing a single species, the fruit fly Drosophila melanogaster. Embryonic development of the red flour beetle Tribolium castaneum differs fundamentally from that of Drosophila in aspects such as short-germ development, embryonic leg development, extensive extra-embryonic membrane formation and non-involuted head development. Although Tribolium has become the second most important insect model organism, previous live imaging attempts have addressed only specific questions and no long-term live imaging data of Tribolium embryogenesis have been available. By combining light sheet-based fluorescence microscopy with a novel mounting method, we achieved complete, continuous and non-invasive fluorescence live imaging of Tribolium embryogenesis at high spatiotemporal resolution. The embryos survived the 2-day or longer imaging process, developed into adults and produced fertile progeny. Our data document all morphogenetic processes from the rearrangement of the uniform blastoderm to the onset of regular muscular movement in the same embryo and in four orientations, contributing significantly to the understanding of Tribolium development. Furthermore, we created a comprehensive chronological table of Tribolium embryogenesis, integrating most previous work and providing a reference for future studies. Based on our observations, we provide evidence that serosa window closure and serosa opening, although deferred by more than 1 day, are linked. All our long-term imaging datasets are available as a resource for the community. Tribolium is only the second insect species, after Drosophila, for which non-invasive long-term fluorescence live imaging has been achieved. © 2014. Published by The Company of Biologists Ltd.

  14. Utilization of Integrated Assessment Modeling for determining geologic CO2 storage security

    NASA Astrophysics Data System (ADS)

    Pawar, R.

    2017-12-01

    Geologic storage of carbon dioxide (CO2) has been extensively studied as a potential technology to mitigate atmospheric concentration of CO2. Multiple international research & development efforts, large-scale demonstration and commercial projects are helping advance the technology. One of the critical areas of active investigation is prediction of long-term CO2 storage security and risks. A quantitative methodology for predicting a storage site's long-term performance is critical for making key decisions necessary for successful deployment of commercial scale projects where projects will require quantitative assessments of potential long-term liabilities. These predictions are challenging given that they require simulating CO2 and in-situ fluid movements as well as interactions through the primary storage reservoir, potential leakage pathways (such as wellbores, faults, etc.) and shallow resources such as groundwater aquifers. They need to take into account the inherent variability and uncertainties at geologic sites. This talk will provide an overview of an approach based on integrated assessment modeling (IAM) to predict long-term performance of a geologic storage site including, storage reservoir, potential leakage pathways and shallow groundwater aquifers. The approach utilizes reduced order models (ROMs) to capture the complex physical/chemical interactions resulting due to CO2 movement and interactions but are computationally extremely efficient. Applicability of the approach will be demonstrated through examples that are focused on key storage security questions such as what is the probability of leakage of CO2 from a storage reservoir? how does storage security vary for different geologic environments and operational conditions? how site parameter variability and uncertainties affect storage security, etc.

  15. Long-term effects of ovulation-stimulating drugs on cancer risk.

    PubMed

    Brinton, Louise

    2007-07-01

    Although nulliparity has been extensively related to the risk of ovarian, breast and endometrial cancers, with many studies showing the relationship largely attributable to infertility, treatment effects on cancer risk are poorly understood. Two early studies raised substantial concern when ovulation-stimulating drugs were linked with large increases in ovarian cancer, supporting the notion of an important aetiological role of incessant ovulation. Subsequent studies have been mainly reassuring, although some have suggested possible risk increases among nulligravid women, those with extensive follow-up, and those developing borderline tumours. Results regarding effects of fertility drugs on breast cancer risk are conflicting, with some showing no associations and others demonstrating possible risk increases, although for varying subgroups. In contrast, endometrial cancer results are more consistent, with two recent studies showing increased risks related to clomiphene usage. This is of interest given that clomiphene is structurally similar to tamoxifen, a drug extensively linked with this cancer. Given the recent marketing of fertility drugs and the fact that exposed women are only beginning to reach the cancer age range, further follow-up is necessary. This will also be important to fully resolve effects of exposures such as gonadotrophins, used more recently in conjunction with IVF.

  16. Use of GnRH agonist implants for long-term suppression of fertility in extensively managed heifers and cows.

    PubMed

    D'Occhio, Michael J; Fordyce, Geoffry; Whyte, Tim R; Jubb, Tristan F; Fitzpatrick, Lee A; Cooper, Neil J; Aspden, William J; Bolam, Matt J; Trigg, Timothy E

    2002-12-16

    The ability of gonadotrophin releasing hormone (GnRH) agonist implants to suppress ovarian activity and prevent pregnancies, long-term, was examined in heifers and cows maintained under extensive management. At three cattle stations, heifers (2-year-old) and older cows (3- to 16-year-old) were assigned to a control group that received no treatment, or were treated with high-dose (12 mg, Station A) or low-dose (8 mg, Station B and Station C) GnRH agonist implants. The respective numbers of control and GnRH agonist-treated animals (heifers + cows) at each station were: Station A, 20 and 99; Station B, 19 and 89; Station C, 20 and 76. Animals were maintained with 4% bulls and monitored for pregnancy at 2-monthly intervals for approximately 12 months. Pregnancy rates for control heifers and control cows ranged from 60-90% and 80-100%, respectively, depending on the study site. The respective number of animals (heifers + cows) treated with GnRH agonist that conceived, and days to first conception, were: Station A, 9 (9%) and 336 +/- 3 days; Station B, 8 (10%) and 244 +/- 13 days; Station C, 20 (26%) and 231 +/- 3 days. Treatment with high-dose GnRH agonist prevented pregnancies for longer (approximately 300 days) than treatment with low-dose GnRH agonist (approximately 200 days). In the majority of heifers and cows treated with GnRH agonist, ovarian follicular growth was restricted to early antral follicles (2-4mm). The findings indicate that GnRH agonist implants have considerable potential as a practical technology to suppress ovarian activity and control reproduction in female cattle maintained in extensive rangelands environments. The technology also has broader applications in diverse cattle production systems. Copyright 2002 Elsevier Science B.V.

  17. Long-term observations of boreal toads at an ARMI apex site

    Treesearch

    Paul Stephen Corn; Erin Muths; David S. Pilliod

    2011-01-01

    The U.S. Geological Survey's Amphibian Research and Monitoring Initiative (ARMI) is a national project with goals to monitor the status and trends of amphibians, conduct research on causes of declines, and provide information and support to management agencies for conservation of amphibian populations. ARMI activities are organized around extensive inventories and...

  18. Stress and the Business Communication Consultant: Academics for Hire.

    ERIC Educational Resources Information Center

    David, Carol

    1990-01-01

    Recounts how the author and 25 colleagues worked on a massive, long-term consulting project with a branch of the United States military to revise an extensive technical manual. Describes stressors of the project intrinsic to the job, the workers' roles in the organization, organizational structure, career development, and work relationships. (SR)

  19. The Economic Costs of Childhood Disability

    ERIC Educational Resources Information Center

    Stabile, Mark; Allin, Sara

    2012-01-01

    Childhood disabilities entail a range of immediate and long-term economic costs that have important implications for the well-being of the child, the family, and society but that are difficult to measure. In an extensive research review, Mark Stabile and Sara Allin examine evidence about three kinds of costs--direct, out-of-pocket costs incurred…

  20. Reducing the Risk of Posttraumatic Stress Disorder in Children Following Natural Disasters

    ERIC Educational Resources Information Center

    Mohay, Heather; Forbes, Nicole

    2009-01-01

    A significant number of children suffer long-term psychological disturbance following exposure to a natural disaster. Evidence suggests that a dose-response relationship exists, so that children and adolescents who experience the most intense or extensive exposure to the risk factors for posttraumatic stress disorder (PTSD) are likely to develop…

  1. Timber production in selectively logged tropical forests in South America.

    Treesearch

    Michael Keller; Gregory P. Asner; Geoffrey Blate; Frank McGlocklin; John Merry; Marielos Peña-Claros; Johan Zweede

    2007-01-01

    Selective logging is an extensive land-use practice in South America. Governments in the region have enacted policies to promote the establishment and maintenance of economically productive and sustainable forest industries.However, both biological and policy constraints threaten to limit the viability of the industry over the long term.Biological constraints, such as...

  2. 78 FR 16795 - Medicare and Medicaid Programs; Requirements for Long-Term Care (LTC) Facilities; Notice of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-19

    ...). We noted that research has extensively documented the pervasiveness of vulnerable populations which.... For example, if the State law requires the administrator of a NF participating in its State Medicaid...) would not be applicable. For example, if a facility's air conditioning failed during a heat wave, the...

  3. How Do Mode and Timing of Follow-up Surveys Affect Evaluation Success?

    ERIC Educational Resources Information Center

    Koundinya, Vikram; Klink, Jenna; Deming, Philip; Meyers, Andrew; Erb, Kevin

    2016-01-01

    This article presents the analysis of evaluation methods used in a well-designed and comprehensive evaluation effort of a significant Extension program. The evaluation data collection methods were analyzed by questionnaire mode and timing of follow-up surveys. Response rates from the short- and long-term follow-ups and different questionnaire…

  4. Microbiome diversity of the soybean aphid (Aphis glycines) with extensive superinfection of Arsenophonus and Wolbachia in native and invasive populations

    USDA-ARS?s Scientific Manuscript database

    The interaction among insects and microbes can lead to either symbiotic cooperation which could promote ecological and evolutionary adaptation, or a parasitic relationship through reproductive manipulation. We characterized the microbiome of the soybean aphid (Aphis glycines), with the long-term goa...

  5. Using the Sonoran Desert test site to monitor the long-term radiometric stability of the Landsat TM/ETM+ and Terra MODIS sensors

    USGS Publications Warehouse

    Angal, A.; Xiong, X.; Choi, T.; Chander, G.; Wu, A.

    2009-01-01

    Pseudo-invariant ground targets have been extensively used to monitor the long-term radiometric calibration stability of remote sensing instruments. The NASA MODIS Characterization Support Team (MCST), in collaboration with members from the U.S. Geological Survey (USGS) Earth Resources Observation and Science (EROS) Center, has previously demonstrated the use of pseudo-invariant ground sites for the long-term stability monitoring of Terra MODIS and Landsat 7 ETM+ sensors. This paper focuses on the results derived from observations made over the Sonoran Desert. Additionally, Landsat 5 TM data over the Sonoran Desert site were used to evaluate the temporal stability of this site. Top-ofatmosphere (TOA) reflectances were computed for the closely matched TM, ETM+, and MODIS spectral bands over selected regions of interest. The impacts due to different viewing geometries, or the effect of test site Bi-directional Reflectance Distribution Function (BRDF), are also presented. ?? 2009 SPIE.

  6. Three year naturalistic outcome study of panic disorder patients treated with paroxetine

    PubMed Central

    Dannon, Pinhas N; Iancu, Iulian; Cohen, Ami; Lowengrub, Katherine; Grunhaus, Leon; Kotler, Moshe

    2004-01-01

    Background This naturalistic open label follow-up study had three objectives: 1) To observe the course of illness in Panic Disorder patients receiving long-term versus intermediate-term paroxetine treatment 2) To compare the relapse rates and side-effect profile after long-term paroxetine treatment between patients with Panic Disorder and Panic Disorder with Agoraphobia. 3) To observe paroxetine's tolerability over a 24 month period. Methods 143 patients with panic disorder (PD), with or without agoraphobia, successfully finished a short-term (ie 12 week) trial of paroxetine treatment. All patients then continued to receive paroxetine maintenance therapy for a total of 12 months. At the end of this period, 72 of the patients chose to discontinue paroxetine pharmacotherapy and agreed to be monitored throughout a one year discontinuation follow-up phase. The remaining 71 patients continued on paroxetine for an additional 12 months and then were monitored, as in the first group, for another year while medication-free. The primary limitation of our study is that the subgroups of patients receiving 12 versus 24 months of maintenance paroxetine therapy were selected according to individual patient preference and therefore were not assigned in a randomized manner. Results Only 21 of 143 patients (14%) relapsed during the one year medication discontinuation follow-up phase. There were no significant differences in relapse rates between the patients who received intermediate-term (up to 12 months) paroxetine and those who chose the long-term course (24 month paroxetine treatment). 43 patients (30.1%) reported sexual dysfunction. The patients exhibited an average weight gain of 5.06 kg. All patients who eventually relapsed demonstrated significantly greater weight increase (7.3 kg) during the treatment phase. Conclusions The extension of paroxetine maintenance treatment from 12 to 24 months did not seem to further decrease the risk of relapse after medication discontinuation. Twenty-four month paroxetine treatment is accompanied by sexual side effects and weight gain similar to those observed in twelve month treatment. PMID:15191617

  7. Incidence, prevalence and risk factors for post-surgical hypocalcaemia and hypoparathyroidism

    PubMed Central

    Edafe, Ovie

    2017-01-01

    Hypocalcaemia following thyroid surgery is common and is associated with significant short and long term morbidity. Damage to or devascularisation of parathyroid glands is the predominant underlying mechanism; although other factors such as hungry bone syndrome may occasionally contribute to it in the immediate post-operative period. The reported incidence of post-surgical hypocalcaemia and/or hypoparathyroidism (PoSH) varies significantly in the literature; the variation thought to be at least partly due to differences in the definitions used. Figures on the prevalence of chronic or long term post-surgical hypocalcaemia in the population are unclear. Risk factors for PoSH have been extensively studied in recent years and may be classified into patient, disease and surgery related factors. Some risk factors are modifiable; but both modifiable and non-modifiable factors help in generating a risk profile that may be used to select patients for preventative measures and/or changes in surgical strategy. This narrative review discusses recent literature on the incidence, prevalence and risk factors for PoSH. PMID:29322023

  8. The role of transanal endorectal pull-through in the treatment of Hirschsprung's disease - a multicenter experience.

    PubMed

    Höllwarth, M E; Rivosecchi, M; Schleef, J; Deluggi, S; Fasching, G; Ceriati, E; Ciprandi, G; DePeppo, F

    2002-09-01

    The transanal approach (TAA) is a new technique for surgery of Hirschsprung's disease (HD) that was introduced by de la Torre in 1998. The purpose of this multicenter study, including experience from three Austrian and one Italian departments of peadiatric surgery, was to evaluate the role of this approach in HD in 18 children aged 1-72 months. In 14 children the TAA only was performed; in 3 an additional laparoscopy was performed and in 1 conversion to a laparotomy was necessary. One complication (abscess) occurred after laparoscopic-assisted pull-through. The postoperative recovery was rapid, no severe long-term problems were observed. The transanal pull-through technique is generally possible in most classic cases of HD with extension of the disease to the sigmoid colon. If necessary, it can be combined with laparoscopy. Our preliminary results show that the technique is safe, less invasive, and gives excellent cosmetic results, and allows rapid recovery. Long-term results are still pending.

  9. Three strategies to stabilise nearly monodispersed silver nanoparticles in aqueous solution

    NASA Astrophysics Data System (ADS)

    Stevenson, Amadeus PZ; Blanco Bea, Duani; Civit, Sergi; Antoranz Contera, Sonia; Iglesias Cerveto, Alberto; Trigueros, Sonia

    2012-02-01

    Silver nanoparticles are extensively used due to their chemical and physical properties and promising applications in areas such as medicine and electronics. Controlled synthesis of silver nanoparticles remains a major challenge due to the difficulty in producing long-term stable particles of the same size and shape in aqueous solution. To address this problem, we examine three strategies to stabilise aqueous solutions of 15 nm citrate-reduced silver nanoparticles using organic polymeric capping, bimetallic core-shell and bimetallic alloying. Our results show that these strategies drastically improve nanoparticle stability by distinct mechanisms. Additionally, we report a new role of polymer functionalisation in preventing further uncontrolled nanoparticle growth. For bimetallic nanoparticles, we attribute the presence of a higher valence metal on the surface of the nanoparticle as one of the key factors for improving their long-term stability. Stable silver-based nanoparticles, free of organic solvents, will have great potential for accelerating further environmental and nanotoxicity studies. PACS: 81.07.-b; 81.16.Be; 82.70.Dd.

  10. Cyclic fatigue and fracture in pyrolytic carbon-coated graphite mechanical heart-valve prostheses: role of small cracks in life prediction.

    PubMed

    Dauskardt, R H; Ritchie, R O; Takemoto, J K; Brendzel, A M

    1994-07-01

    A fracture-mechanics based study has performed to characterize the fracture toughness and rates of cyclic fatigue-crack growth of incipient flaws in prosthetic heart-valve components made of pyrolytic carbon-coated graphite. Such data are required to predict the safe structural lifetime of mechanical heart-valve prostheses using damage-tolerant analysis. Unlike previous studies where fatigue-crack propagation data were obtained using through-thickness, long cracks (approximately 2-20 mm long), growing in conventional (e.g., compact-tension) samples, experiments were performed on physically small cracks (approximately 100-600 microns long), initiated on the surface of the pyrolytic-carbon coating to simulate reality. Small-crack toughness results were found to agree closely with those measured conventionally with long cracks. However, similar to well-known observations in metal fatigue, it was found that based on the usual computations of the applied (far-field) driving force in terms of the maximum stress intensity, Kmax, small fatigue cracks grew at rates that exceeded those of long cracks at the same applied stress intensity, and displayed a negative dependency on Kmax; moreover, they grew at applied stress intensities less than the fatigue threshold value, below which long cracks are presumed dormant. To resolve this apparent discrepancy, it is shown that long and small crack results can be normalized, provided growth rates are characterized in terms of the total (near-tip) stress intensity (incorporating, for example, the effect of residual stress); with this achieved, in principle, either form of data can be used for life prediction of implant devices. Inspection of the long and small crack results reveals extensive scatter inherent in both forms of growth-rate data for the pyrolytic-carbon material.

  11. In-vivo data on the influence of tobacco smoke and UV light on murine skin.

    PubMed

    Pavlou, P; Rallis, M; Deliconstantinos, G; Papaioannou, G; Grando, S A

    2009-01-01

    Inhaled tobacco smoke comes in direct contact with few organs such as mouth, lungs, and stomach. Cigarette smoke (CS) in lungs has been extensively studied. However, limited data exist on its effect on skin, and there are no long-term experimental studies suggesting toxic effects on skin. Even though it is generally accepted that CS is among the main factors of skin aging, the number of experimental studies showing this aging effect is limited. We hereby studied the effect of long-term exposure to CS on the skin of hairless mice in combination with or without ultraviolet (UV) light. In addition, we investigated potential skin protection by a potent antioxidant namely procyanidine-rich French maritime pine bark extract (PBE) pycnogenol. Male and female hairless SKH-2 mice were exposed for 10 months to tobacco smoke and/or UV light in vivo, and their effects on skin were investigated. Some biophysical parameters such as development of erythema, transepidermal water loss (TEWL), and skin elasticity were measured. The results show that UV and CS may be acting synergistically, as shown by the enhanced TEWL, erythema values, epitheliomas, and squamous cell carcinomas (SCCs) observed, whereas PBE seems to protect skin against SCC.

  12. Long-term decay and possible reactivation of induced seismicity at the Basel EGS site

    NASA Astrophysics Data System (ADS)

    Kraft, Toni; Herrmann, Marcus; Karvounis, Dimitrios; Tormann, Thessa; Deichmann, Nicolas; Wiemer, Stefan

    2016-04-01

    In December 2006, an extensive fluid injection was carried out below the city of Basel, Switzerland, to stimulate a reservoir for an Enhanced Geothermal System (EGS). After six days of gradual increase of flow rate (and thus seismicity), a strongly felt ML3.4 earthquakes led to the immediate termination of the project. The well was opened subsequently and seismicity declined rapidly. The Basel EGS project might be an unsuccessful attempt in terms of energy supply, but a chance to advance the physical understanding of EGSs. The well-monitored and well-studied induced sequence allowed many new insights in terms of reservoir creation. A special observation in the nine years of monitoring is the revive of seismic activity six years after prolonged seismic decay. This renewed activity increase might relate to a gradual pressure increase due to the ultimate shut-in (closure) of the borehole about one year before. Until now, a detailed analysis of the long-term behaviour remained unexplored since a consistent catalogue did not exist. In the current study, we took advantage of the high waveform similarity within a seismic sequence and applied a multi-trace template-matching (i.e. cross-correlation) procedure to detect seismic events about one order of magnitude below the detection threshold. We detected about 100,000 events within the six-day long stimulation alone - previously, only 13,000 microearthquakes were detected. We only scanned the recordings of the deepest borehole station (2.7km). This station is very close to the 5km-deep reservoir and has the highest signal-to-noise ratio among all (borehole-)stations. Our newly obtained catalogue spans over more than nine years and features a uniform (and low) detection threshold and a uniform magnitude determination. The improved resolution of the long-term behaviour and the later seismicity increase will help to understand involved mechanisms better. More induced or natural sequences can be investigated with our procedure.

  13. Phase dynamics of single long Josephson junction in MgB2 superconductor

    NASA Astrophysics Data System (ADS)

    Chimouriya, Shanker Pd.; Ghimire, Bal Ram; Kim, Ju H.

    2018-05-01

    A system of perturbed sine Gordon equations is derived to a superconductor-insulator-superconductor (SIS) long Joseph-son junction as an extension of the Ambegaokar-Baratoff relation, following the long route of path integral formalism. A computer simulation is performed by discretizing the equations using finite difference approximation and applied to the MgB2 superconductor with SiO2 as the junction material. The solution of unperturbed sG equation is taken as the initial profile for the simulation and observed how the perturbation terms play the role to modify it. It is found initial profile deformed as time goes on. The variation of total Josephson current has also been observed. It is found that, the perturbation terms play the role for phase frustration. The phase frustration achieves quicker for high tunneling current.

  14. Biocompatibility property of 100% strontium-substituted SiO2 -Al2 O3 -P2 O5 -CaO-CaF2 glass ceramics over 26 weeks implantation in rabbit model: Histology and micro-Computed Tomography analysis.

    PubMed

    Basu, Bikramjit; Sabareeswaran, A; Shenoy, S J

    2015-08-01

    One of the desired properties for any new biomaterial composition is its long-term stability in a suitable animal model and such property cannot be appropriately assessed by performing short-term implantation studies. While hydroxyapatite (HA) or bioglass coated metallic biomaterials are being investigated for in vivo biocompatibility properties, such study is not extensively being pursued for bulk glass ceramics. In view of their inherent brittle nature, the implant stability as well as impact of long-term release of metallic ions on bone regeneration have been a major concern. In this perspective, the present article reports the results of the in vivo implantation experiments carried out using 100% strontium (Sr)-substituted glass ceramics with the nominal composition of 4.5 SiO2 -3Al2 O3 -1.5P2 O5 -3SrO-2SrF2 for 26 weeks in cylindrical bone defects in rabbit model. The combination of histological and micro-computed tomography analysis provided a qualitative and quantitative understanding of the bone regeneration around the glass ceramic implants in comparison to the highly bioactive HA bioglass implants (control). The sequential polychrome labeling of bone during in vivo osseointegration using three fluorochromes followed by fluorescence microscopy observation confirmed homogeneous bone formation around the test implants. The results of the present study unequivocally confirm the long-term implant stability as well as osteoconductive property of 100% Sr-substituted glass ceramics, which is comparable to that of a known bioactive implant, that is, HA-based bioglass. © 2014 Wiley Periodicals, Inc.

  15. A comparison of laparoscopic and open D3 lymphadenectomy for transverse colon cancer.

    PubMed

    Kwak, Han Deok; Ju, Jae Kyun; Lee, Soo Young; Kim, Chang Hyun; Kim, Young Jin; Kim, Hyeong Rok

    2017-12-01

    The type of surgery or surgical approach for transverse colon cancer treatment largely depends on the tumor location or surgeon's preference. However, extensive lymphadenectomy appears to improve the long-term outcomes of locally advanced colon cancers. This study was designed to compare the short- and long-term outcomes after surgery via the laparoscopic or open approach with radical D3 lymph node dissection in patients with stage II and III transverse colon cancer. Patients were treated for stage II and III transverse colon cancer between May 2006 and December 2014. This retrospective study evaluated data collected prospectively at a tertiary teaching hospital. Radical D3 lymphadenectomy included the principal middle colic artery nodes. The study included 144 patients among whom 118 (81.9%) underwent laparoscopic surgery. Significantly more patients in the laparoscopic group underwent extended right hemicolectomy compared with the open group (90.7 vs. 65.4%, p = 0.005). The operative time was longer in the laparoscopic group (151.3 vs. 131.2 min, p = 0.021), and the open group had a greater estimated blood loss volume (160.8 vs. 289.3 ml, p = 0.011). Although the groups differed in terms of tumor size (5.8 vs 7.9 cm, p = 0.007), other pathologic outcomes did not differ. The groups did not differ regarding postoperative parameters or disease-free, overall, and cancer-specific survivals. Despite differences in surgical methods and related factors, no long-term differences in outcomes were observed between laparoscopic and open approaches to radical D3 lymphadenectomy in patients with stage II and III transverse colon cancer.

  16. Experimental study and simulation of phosphorus purification effects of bioretention systems on urban surface runoff

    PubMed Central

    Liang, Zheng; Li, Yajiao; Li, Peng; Jiang, Chunbo

    2018-01-01

    Excessive phosphorus (P) contributes to eutrophication by degrading water quality and limiting human use of water resources. Identifying economic and convenient methods to control soluble reactive phosphorus (SRP) pollution in urban runoff is the key point of rainwater management strategies. Through three series of different tests involving influencing factors, continuous operation and intermittent operation, this study explored the purification effects of bioretention tanks under different experimental conditions, it included nine intermittent tests, single field continuous test with three groups of different fillers (Fly ash mixed with sand, Blast furnace slag, and Soil), and eight intermittent tests with single filler (Blast furnace slag mixed with sand). Among the three filler combinations studied, the filler with fly ash mixed with sand achieved the best pollution reduction efficiency. The setting of the submerged zone exerted minimal influence on the P removal of the three filler combinations. An extension of the dry period slightly promoted the P purification effect. The combination of fly ash mixed with sand demonstrated a positive purification effect on SRP during short- or long-term simulated rainfall duration. Blast furnace slag also presented a positive purification effect in the short term, although its continuous purification effect on SRP was poor in the long term. The purification abilities of soil in the short and long terms were weak. Under intermittent operations across different seasons, SRP removal was unstable, and effluent concentration processes were different. The purification effect of the bioretention system on SRP was predicted through partial least squares regression (PLS) modeling analysis. The event mean concentration removal of SRP was positively related to the adsorption capacity of filler and rainfall interval time and negatively related to submerged zones, influent concentration and volume. PMID:29742120

  17. Low-frequency stimulation cancels the high-frequency-induced long-lasting effects in the rat medial vestibular nuclei.

    PubMed

    Grassi, S; Pettorossi, V E; Zampolini, M

    1996-05-15

    In rat brainstem slices, we investigated the effects of low-frequency stimulation (LFS) of the primary vestibular afferents on the amplitude of the field potentials evoked in the medial vestibular nuclei (MVN). LFS induced long-term effects, the sign of which depended on whether the vestibular neurons were previously conditioned by HFS. In unconditioned slices, LFS evoked modifications of the responses that were similar to those observed after HFS but had a smaller extension. In fact, LFS caused long-lasting potentiation of the N1 wave in the MVN ventral portion (Vp) and long-lasting depression of the N2 wave in the MVN dorsal portion (Dp), whereas it provoked small and variable effects on the N1 wave. By contrast, when the synaptic transmission was already conditioned, LFS influenced the synaptic responses oppositely, reducing or annulling the HFS long-term effects. This phenomenon was specifically induced by LFS, because HFS was not able to cause it. The involvement of NMDA receptors in mediating the LFS long-term effects was supported by the fact that AP-5 prevented their induction. In addition, the annulment of HFS long-term effects by LFS was also demonstrated by the shift in the latency of the evoked unitary potentials after LFS. In conclusion, we suggest that the reduction of the previously induced conditioning could represent a cancellation mechanism, useful to quickly adapt the vestibular system to continuous different needs and to avoid saturation.

  18. Propofol. An overview of its pharmacology and a review of its clinical efficacy in intensive care sedation.

    PubMed

    Fulton, B; Sorkin, E M

    1995-10-01

    Propofol is a phenolic derivative that is structurally unrelated to other sedative hypnotic agents. It has been used extensively as an anaesthetic agent, particularly in procedures of short duration. More recently it has been investigated as a sedative in the intensive care unit (ICU) where it produces sedation and hypnosis in a dose-dependent manner. Propofol also provides control of stress responses and has anticonvulsant and amnesic properties. Importantly, its pharmacokinetic properties are characterised by a rapid onset and short duration of action. Noncomparative and comparative trials have evaluated the use of propofol for the sedation of mechanically ventilated patients in the ICU (postsurgical, general medical, trauma). Overall, propofol provides satisfactory sedation and is associated with good haemodynamic stability. It produces results similar to or better than those seen with midazolam or other comparator agents when the quality of sedation and/or the amount of time that patients were at adequate levels of sedation are measured. Patients sedated with propofol also tend to have a faster recovery (time to spontaneous ventilation or extubation) than patients sedated with midazolam. Although most studies did not measure time to discharge from the ICU, propofol tended to be superior to midazolam in this respect. In a few small trials in patients with head trauma or following neurosurgery, propofol was associated with adequate sedation and control of cerebral haemodynamics. The rapid recovery of patients after stopping propofol makes it an attractive option in the ICU, particularly for patients requiring only short term sedation. In short term sedation, propofol, despite its generally higher acquisition costs, has the potential to reduce overall medical costs if patients are able to be extubated and discharged from the ICU sooner. Because of the potential for hyperlipidaemia and the development of tolerance to its sedative effects, and because of the reduced need for rapid reversal of drug effects in long term sedation, the usefulness of propofol in long term situations is less well established. While experience with propofol for the sedation of patients in the ICU is extensive, there are still areas requiring further investigation. These include studies in children, trials examining cerebral and haemodynamic outcomes following long term administration and in patients with head trauma and, importantly, pharmacoeconomic investigations to determine those situations where propofol is cost effective. In the meantime, propofol is a well established treatment native to benzodiazepines and/or other hypnotics or analgesics when sedation of patients in the ICU is required. In particular, propofol possesses unique advantages over these agents in patients requiring only short term sedation.

  19. Long-term (52-week) safety and efficacy of Sacubitril/valsartan in Asian patients with hypertension.

    PubMed

    Supasyndh, Ouppatham; Sun, Ningling; Kario, Kazuomi; Hafeez, Kudsia; Zhang, Jack

    2017-05-01

    Sacubitril/valsartan (LCZ696), a first-in-class angiotensin receptor-neprilysin inhibitor, demonstrated significant reductions in office and 24 h ambulatory blood pressure (BP) over 8 weeks in Asian patients with hypertension. This 52-week extension to the 8-week core study was aimed at evaluating the long-term safety, tolerability and efficacy of sacubitril/valsartan. Patients who completed an 8-week randomized study (the core study) were enrolled in this 52-week open-label study and received sacubitril/valsartan 200 mg QD. The sacubitril/valsartan dose was uptitrated to 400 mg QD if BP was uncontrolled (>140/90 mm Hg) after 4 weeks. Subsequently, in patients with uncontrolled BP, treatment was intensified every 4 weeks with amlodipine 5-10 mg followed by hydrochlorothiazide 6.25-25 mg. Of the 341 patients enrolled, 7 (2.1%) discontinued the study drug due to adverse events (AEs). The incidence of AEs and serious AEs were 63.9 and 3.8%, respectively, and no deaths were reported in this study. The most frequent AEs were nasopharyngitis (18.2%) and dizziness (8.8%). Events that were potentially indicative of low BP were infrequent. One patient reported mild transient angioedema (lasting 2.5 h) that resolved without treatment but led to study drug discontinuation. The sacubitril/valsartan-based regimen provided clinically significant mean sitting systolic BP (msSBP) and mean sitting diastolic BP (msDBP) reductions from baseline (-24.7/-16.2 mm Hg). The overall BP control, msSBP and msDBP response rates were 75.3, 90.6 and 87.6%, respectively. Long-term use of sacubitril/valsartan was generally safe and well-tolerated in patients with hypertension and provided significant BP reductions from baseline.

  20. Rehabilitation of low back pain patients. A review.

    PubMed

    Revel, M

    1995-01-01

    Numerous methods have been developed for the rehabilitation of low back pain patients, including spinal flexion and extension exercises, lumbar spine locking in an intermediate position, enhancement of spinal and pelvic proprioceptive sensibility, swimming pool therapy, back schools, and functional restoration. Each seeks to achieve a goal assumed to be central to the prevention of a first or recurrent episode of low back pain. Goals include short-term pain relief, an improved ability to achieve self-sedation, abdominal and lumbar muscle strengthening, increased hip and lumbar spine mobility, improved lumbar and pelvic proprioceptive sensibility, intervertebral joint stabilization, lumbar posture modification and improved general fitness. Less than 30 studies meeting widely accepted validity and applicability criteria for therapeutic trials have addressed the clinical efficacy of rehabilitation in low back pain patients. Most studies of the back school approach have found no benefit. Spinal flexion and extension exercise programs have yielded short-lived improvements, with no differences across methods. There is evidence that functional restoration programs based on graded activity may provide long-term benefits including better social and occupational outcomes. We have evaluated the physical therapy methods most commonly taught to and used by physical therapists in France.

  1. Deep Recurrent Neural Network-Based Autoencoders for Acoustic Novelty Detection

    PubMed Central

    Vesperini, Fabio; Schuller, Björn

    2017-01-01

    In the emerging field of acoustic novelty detection, most research efforts are devoted to probabilistic approaches such as mixture models or state-space models. Only recent studies introduced (pseudo-)generative models for acoustic novelty detection with recurrent neural networks in the form of an autoencoder. In these approaches, auditory spectral features of the next short term frame are predicted from the previous frames by means of Long-Short Term Memory recurrent denoising autoencoders. The reconstruction error between the input and the output of the autoencoder is used as activation signal to detect novel events. There is no evidence of studies focused on comparing previous efforts to automatically recognize novel events from audio signals and giving a broad and in depth evaluation of recurrent neural network-based autoencoders. The present contribution aims to consistently evaluate our recent novel approaches to fill this white spot in the literature and provide insight by extensive evaluations carried out on three databases: A3Novelty, PASCAL CHiME, and PROMETHEUS. Besides providing an extensive analysis of novel and state-of-the-art methods, the article shows how RNN-based autoencoders outperform statistical approaches up to an absolute improvement of 16.4% average F-measure over the three databases. PMID:28182121

  2. Anomalous diffusion with linear reaction dynamics: from continuous time random walks to fractional reaction-diffusion equations.

    PubMed

    Henry, B I; Langlands, T A M; Wearne, S L

    2006-09-01

    We have revisited the problem of anomalously diffusing species, modeled at the mesoscopic level using continuous time random walks, to include linear reaction dynamics. If a constant proportion of walkers are added or removed instantaneously at the start of each step then the long time asymptotic limit yields a fractional reaction-diffusion equation with a fractional order temporal derivative operating on both the standard diffusion term and a linear reaction kinetics term. If the walkers are added or removed at a constant per capita rate during the waiting time between steps then the long time asymptotic limit has a standard linear reaction kinetics term but a fractional order temporal derivative operating on a nonstandard diffusion term. Results from the above two models are compared with a phenomenological model with standard linear reaction kinetics and a fractional order temporal derivative operating on a standard diffusion term. We have also developed further extensions of the CTRW model to include more general reaction dynamics.

  3. Observations and Modeling of Long Negative Laboratory Discharges: Identifying the Physics Important to an Electrical Spark in Air

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

    Biagi, C J; Uman, M A

    2011-12-13

    There are relatively few reports in the literature focusing on negative laboratory leaders. Most of the reports focus exclusively on the simpler positive laboratory leader that is more commonly encountered in high voltage engineering [Gorin et al., 1976; Les Renardieres Group, 1977; Gallimberti, 1979; Domens et al., 1994; Bazelyan and Raizer 1998]. The physics of the long, negative leader and its positive counterpart are similar; the two differ primarily in their extension mechanisms [Bazelyan and Raizer, 1998]. Long negative sparks extend primarily by an intermittent process termed a 'step' that requires the development of secondary leader channels separated in spacemore » from the primary leader channel. Long positive sparks typically extend continuously, although, under proper conditions, their extension can be temporarily halted and begun again, and this is sometimes viewed as a stepping process. However, it is emphasized that the nature of positive leader stepping is not like that of negative leader stepping. There are several key observational studies of the propagation of long, negative-polarity laboratory sparks in air that have aided in the understanding of the stepping mechanisms exhibited by such sparks [e.g., Gorin et al., 1976; Les Renardieres Group, 1981; Ortega et al., 1994; Reess et al., 1995; Bazelyan and Raizer, 1998; Gallimberti et al., 2002]. These reports are reviewed below in Section 2, with emphasis placed on the stepping mechanism (the space stem, pilot, and space leader). Then, in Section 3, reports pertaining to modeling of long negative leaders are summarized.« less

  4. Cellular consequences of sleep deprivation in the brain.

    PubMed

    Cirelli, Chiara

    2006-10-01

    Several recent studies have used transcriptomics approaches to characterize the molecular correlates of sleep, waking, and sleep deprivation. This analysis may help in understanding the benefits that sleep brings to the brain at the cellular level. The studies are still limited in number and focus on a few brain regions, but some consistent findings are emerging. Sleep, spontaneous wakefulness, short-term, and long-term sleep deprivation are each associated with the upregulation of hundreds of genes in the cerebral cortex and other brain areas. In fruit flies as well as in mammals, three categories of genes are consistently upregulated during waking and short-term sleep deprivation relative to sleep. They include genes involved in energy metabolism, synaptic potentiation, and the response to cellular stress. In the rat cerebral cortex, transcriptional changes associated with prolonged sleep loss differ significantly from those observed during short-term sleep deprivation. However, it is too early to draw firm conclusions relative to the molecular consequences of sleep deprivation, and more extensive studies using DNA and protein arrays are needed in different species and in different brain regions.

  5. Long-term effects of cladribine tablets on MRI activity outcomes in patients with relapsing-remitting multiple sclerosis: the CLARITY Extension study.

    PubMed

    Comi, Giancarlo; Cook, Stuart; Rammohan, Kottil; Soelberg Sorensen, Per; Vermersch, Patrick; Adeniji, Abidemi K; Dangond, Fernando; Giovannoni, Gavin

    2018-01-01

    The CLARITY and CLARITY Extension studies demonstrated that treatment of relapsing-remitting multiple sclerosis (RRMS) with cladribine tablets (CT) results in significant clinical improvements, compared with placebo. This paper presents the key magnetic resonance imaging (MRI) findings from the CLARITY Extension study. Patients who received a cumulative dose of either CT 3.5 or 5.25 mg/kg in CLARITY were rerandomized to either placebo or CT 3.5 mg/kg in CLARITY Extension. Patients from the arm that received placebo in CLARITY were assigned to CT 3.5 mg/kg. MRI assessments were carried out when patients entered CLARITY Extension and after Weeks 24, 48, 72 and 96, and in a supplemental follow-up period. At CLARITY Extension baseline, patients who received placebo during CLARITY had more T1 gadolinium-enhanced (Gd+) lesions than patients who received CT during CLARITY. These patients, who were then exposed to cladribine 3.5 mg/kg during the extension, experienced a 90.4% relative reduction (median difference -0.33, 97.5% confidence interval -0.33-0.00; p < 0.001) in T1 Gd+ lesions at the end of the extension compared with the end of CLARITY. Overall, the majority of patients in each treatment group remained free from T1 Gd+ lesions throughout CLARITY Extension. However, a small proportion of patients who were treated with cladribine in CLARITY and received placebo in CLARITY Extension showed evidence of increased MRI activity, and this was associated with a prolonged treatment gap between CLARITY and CLARITY Extension. A 2-year treatment with CT 3.5 mg/kg has a durable effect on MRI outcomes in the majority of patients, an effect that was sustained in patients who were not retreated in the subsequent 2 years after initial treatment. ClinicalTrials.gov identifier: NCT00641537 .

  6. Long-term effects of cladribine tablets on MRI activity outcomes in patients with relapsing–remitting multiple sclerosis: the CLARITY Extension study

    PubMed Central

    Comi, Giancarlo; Cook, Stuart; Rammohan, Kottil; Soelberg Sorensen, Per; Vermersch, Patrick; Adeniji, Abidemi K.; Dangond, Fernando; Giovannoni, Gavin

    2018-01-01

    Background The CLARITY and CLARITY Extension studies demonstrated that treatment of relapsing–remitting multiple sclerosis (RRMS) with cladribine tablets (CT) results in significant clinical improvements, compared with placebo. This paper presents the key magnetic resonance imaging (MRI) findings from the CLARITY Extension study. Methods Patients who received a cumulative dose of either CT 3.5 or 5.25 mg/kg in CLARITY were rerandomized to either placebo or CT 3.5 mg/kg in CLARITY Extension. Patients from the arm that received placebo in CLARITY were assigned to CT 3.5 mg/kg. MRI assessments were carried out when patients entered CLARITY Extension and after Weeks 24, 48, 72 and 96, and in a supplemental follow-up period. Results At CLARITY Extension baseline, patients who received placebo during CLARITY had more T1 gadolinium-enhanced (Gd+) lesions than patients who received CT during CLARITY. These patients, who were then exposed to cladribine 3.5 mg/kg during the extension, experienced a 90.4% relative reduction (median difference −0.33, 97.5% confidence interval −0.33–0.00; p < 0.001) in T1 Gd+ lesions at the end of the extension compared with the end of CLARITY. Overall, the majority of patients in each treatment group remained free from T1 Gd+ lesions throughout CLARITY Extension. However, a small proportion of patients who were treated with cladribine in CLARITY and received placebo in CLARITY Extension showed evidence of increased MRI activity, and this was associated with a prolonged treatment gap between CLARITY and CLARITY Extension. Conclusion A 2-year treatment with CT 3.5 mg/kg has a durable effect on MRI outcomes in the majority of patients, an effect that was sustained in patients who were not retreated in the subsequent 2 years after initial treatment. ClinicalTrials.gov identifier: NCT00641537 PMID:29399054

  7. Long-term safety and efficacy of abatacept in children with juvenile idiopathic arthritis.

    PubMed

    Ruperto, Nicolino; Lovell, Daniel J; Quartier, Pierre; Paz, Eliana; Rubio-Pérez, Nadina; Silva, Clovis A; Abud-Mendoza, Carlos; Burgos-Vargas, Ruben; Gerloni, Valeria; Melo-Gomes, Jose A; Saad-Magalhães, Claudia; Chavez-Corrales, J; Huemer, Christian; Kivitz, Alan; Blanco, Francisco J; Foeldvari, Ivan; Hofer, Michael; Horneff, Gerd; Huppertz, Hans-Iko; Job-Deslandre, Chantal; Loy, Anna; Minden, Kirsten; Punaro, Marilynn; Nunez, Alejandro Flores; Sigal, Leonard H; Block, Alan J; Nys, Marleen; Martini, Alberto; Giannini, Edward H

    2010-06-01

    We previously documented that abatacept was effective and safe in patients with juvenile idiopathic arthritis (JIA) who had not previously achieved a satisfactory clinical response with disease-modifying antirheumatic drugs or tumor necrosis factor blockade. Here, we report results from the long-term extension (LTE) phase of that study. This report describes the long-term, open-label extension phase of a double-blind, randomized, controlled withdrawal trial in 190 patients with JIA ages 6-17 years. Children were treated with 10 mg/kg abatacept administered intravenously every 4 weeks, with or without methotrexate. Efficacy results were based on data derived from the 153 patients who entered the open-label LTE phase and reflect >or=21 months (589 days) of treatment. Safety results include all available open-label data as of May 7, 2008. Of the 190 enrolled patients, 153 entered the LTE. By day 589, 90%, 88%, 75%, 57%, and 39% of patients treated with abatacept during the double-blind and LTE phases achieved responses according to the American College of Rheumatology (ACR) Pediatric 30 (Pedi 30), Pedi 50, Pedi 70, Pedi 90, and Pedi 100 criteria for improvement, respectively. Similar response rates were observed by day 589 among patients previously treated with placebo. Among patients who had not achieved an ACR Pedi 30 response at the end of the open-label lead-in phase and who proceeded directly into the LTE, 73%, 64%, 46%, 18%, and 5% achieved ACR Pedi 30, Pedi 50, Pedi 70, Pedi 90, and Pedi 100 responses, respectively, by day 589 of the LTE. No cases of tuberculosis and no malignancies were reported during the LTE. Pneumonia developed in 3 patients, and multiple sclerosis developed in 1 patient. Abatacept provided clinically significant and durable efficacy in patients with JIA, including those who did not initially achieve an ACR Pedi 30 response during the initial 4-month open-label lead-in phase.

  8. Meaningful public participation in scientific research: How to build an effective site-based long-term education program

    NASA Astrophysics Data System (ADS)

    Barnett, L.

    2013-12-01

    Many site-based educators (Wildlife Refuges, nature centers, Cooperative Extension Programs, schools, arboretums) struggle with developing and implementing cohesive long-term scientific monitoring projects into their existing outreach programming. Moreover, projects that are not meaningful to participants often have little or no sustainable long-term impact. Programs proven most effective are those which 1.) engage the participants in the study design and implementation process, 2.) answer a scientific question posed by site leaders; the data collected supports USA-NPN efforts as well as related site management and monitoring questions, 3.) are built into existing outreach and education programs, using phenology as a lens for understanding both natural and cultural history, and 4.) consistently share outcomes and results with the participants. The USA National Phenology Network's (USA-NPN) Education Program provides phenology curriculum and outreach to educators in formal, non-formal, and informal settings. Materials are designed to serve participants in grades 5-12, higher education, and adult learners. Phenology, used as a lens for place-based education, can inform science, environmental, and climate literacy, as well as other subject areas including cultural studies, art, and language arts. The USA-NPN offers consultation with site leaders on how to successfully engage site-based volunteers and students in long-term phenological studies using Nature's Notebook (NN), the professional and citizen science phenology monitoring program. USA-NPN education and educator instruction materials are designed and field-tested to demonstrate how to implement a long-term NN phenology-monitoring program at such sites. These curricula incorporate monitoring for public visitors, long-term volunteers, and school groups, while meeting the goals of USA-NPN and the site, and can be used as a model for other public participation in science programs interested in achieving similar sustainable results. Encouraging long-term data collection, interaction between educators, and offering information about how educators can ask and answer science questions is a key component to meaningfully engaging participants in long-term scientific participation. Evaluation data collected during a two-year initial implementation plan at a demonstration garden site inclusive of these four engagement strategies reflect these findings. Thirty percent of year one participants were very likely to continue NN observations while 48% of year two participants were very likely to continue with the project. Forty percent of participants were very likely to attend an advanced training on NN and 55% of second year participants responded positively. Students better understood phenology's relationship to gardening. Comments included: '...makes you more aware,' 'Very informative... motivate(s) me to record more than...when I hear the first cicada,' and 'Phenology touches everything...brings to light...connecting you already know...tests your new insights [that will] make it more meaningful.' In conclusion, effective education materials holistically and explicitly incorporate personal meaning. Directed content creation helps form an engaged participant base.

  9. Genetic features of metachronous esophageal cancer developed in Hodgkin's lymphoma or breast cancer long-term survivors: an exploratory study.

    PubMed

    Boldrin, Elisa; Rumiato, Enrica; Fassan, Matteo; Cappellesso, Rocco; Rugge, Massimo; Chiarion-Sileni, Vanna; Ruol, Alberto; Alfieri, Rita; Cagol, Matteo; Castoro, Carlo; Amadori, Alberto; Saggioro, Daniela

    2015-01-01

    Development of novel therapeutic drugs and regimens for cancer treatment has led to improvements in patient long-term survival. This success has, however, been accompanied by the increased occurrence of second primary cancers. Indeed, patients who received regional radiotherapy for Hodgkin's Lymphoma (HL) or breast cancer may develop, many years later, a solid metachronous tumor in the irradiated field. Despite extensive epidemiological studies, little information is available on the genetic changes involved in the pathogenesis of these solid therapy-related neoplasms. Using microsatellite markers located in 7 chromosomal regions frequently deleted in sporadic esophageal cancer, we investigated loss of heterozygosity (LOH) and microsatellite instability (MSI) in 46 paired (normal and tumor) samples. Twenty samples were of esophageal carcinoma developed in HL or breast cancer long-term survivors: 14 squamous cell carcinomas (ESCC) and 6 adenocarcinomas (EADC), while 26 samples, used as control, were of sporadic esophageal cancer (15 ESCC and 11 EADC). We found that, though the overall LOH frequency at the studied chromosomal regions was similar among metachronous and sporadic tumors, the latter exhibited a statistically different higher LOH frequency at 17q21.31 (p = 0.018). By stratifying for tumor histotype we observed that LOH at 3p24.1, 5q11.2 and 9p21.3 were more frequent in ESCC than in EADC suggesting a different role of the genetic determinants located nearby these regions in the development of the two esophageal cancer histotypes. Altogether, our results strengthen the genetic diversity among ESCC and EADC whether they occurred spontaneously or after therapeutic treatments. The presence of histotype-specific alterations in esophageal carcinoma arisen in HL or breast cancer long-term survivors suggests that their transformation process, though the putative different etiological origin, may retrace sporadic ESCC and EADC carcinogenesis.

  10. The FP7 ULTimateCO2 project: a study of the long term fate of CO2

    NASA Astrophysics Data System (ADS)

    Audigane, Pascal; Waldmann, Svenja; Pearce, Jonathan; Dimier, Alain; Le Gallo, Yann; Frykman, Peter; Maurand, Nicolas; Gherardi, Fabrizio; Yalamas, Thierry; Cremer, Holger; Spiers, Chris; Nussbaum, Christophe

    2014-05-01

    The objectives of the European FP7 ULTimateCO2 project are to study specific processes that could influence the long-term fate of geologically stored CO2, mainly: the trapping mechanisms occurring in the storage reservoir, the influence of fluid-rock interactions on mechanical integrity of caprock and well vicinity, and also the modifications induced at the regional scale (brine displacement, fault reactivation, hydrogeology changes...). A comprehensive approach combining laboratory experiments, numerical modeling and natural analogue studies is developed to assess all the processes mentioned above. A collection of data has been generated from natural and industrial (oil industry) analogues on the fluid flow and mechanical properties, structure, and mineralogy of faults and fractures that could affect the long-term storage capacity of underground CO2 storage sites. To address geochemical trapping at reservoir scale, an experimental approach is developed using sandstone core materials in batch reactive mode with CO2 and impurities at reservoir pressure and temperature conditions. Three inter-related lines of laboratory experiments investigate the long-term evolution of the mechanical properties and sealing integrity of fractured and faulted caprocks using Opalinus clay of Mont Terri Gallery (Switzerland), an analogue for caprock well investigated in the past for nuclear waste disposal purpose. To evaluate the interactions between CO2 (and formation fluid) and the well environment (formation, cement, casing) and to assess the consequences of these interactions on the transport properties of well materials, a 1 to 1 scale experiment has been set in the Mont Terri Gallery Opalinus clay to reproduce classical well objects (cemented annulus, casing and cement plug) perforating caprock formations. An extensive program of numerical modeling is also developed to calibrate, to reproduce and to extrapolate the experimental results at longer time scales including uncertainty assessment methods. www.ultimateco2.eu

  11. Prelimbic cortex extracellular signal-regulated kinase 1/2 activation is required for memory retrieval of long-term inhibitory avoidance.

    PubMed

    Luo, Fei; Zheng, Jian; Sun, Xuan; Deng, Wei-Ke; Li, Bao Ming; Liu, Fang

    2017-04-15

    Neural mechanism underlying memory retrieval has been extensively studied in the hippocampus and amygdala. However, little is known about the role of medial prefrontal cortex in long-term memory retrieval. We evaluate this issue in one-trial step-through inhibitory avoidance (IA) paradigm. Our results showed that, 1) inactivation of mPFC by local infusion of GABA A -receptor agonist muscimol caused severe deficits in retrieval of 1-day and 7-day but had no effects on 2-h inhibitory avoidance memory; 2) the protein level of phosphorylated-ERK1/2 in mPFC were significantly increased following retrieval of 1-day and 7-day IA memory, so did the numbers of phosphorylated-ERK (pERK) and phosphorylated-CREB (pCREB) labeled neurons; 3) intra-mPFC infusion of ERK kinase inhibitor PD98095 significantly reduced phosphorylated ERK1/2 levels and phosphorylated-ERK1/2 and phosphorylated-CREB labeled cells, and severely impaired retrieval of 7-day IA memory when the drugs were administrated 30min prior to test. The present study provides evidence that retrieval of long-lasting memory for inhibitory avoidance requires mPFC and involves the ERK-CREB signaling cascade. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Long-term safety and efficacy of canakinumab in cryopyrin-associated periodic syndrome: results from an open-label, phase III pivotal study in Japanese patients.

    PubMed

    Yokota, Shumpei; Imagawa, Tomoyuki; Nishikomori, Ryuta; Takada, Hidetoshi; Abrams, Ken; Lheritier, Karine; Heike, Toshio; Hara, Toshiro

    2017-01-01

    To assess the long-term safety and efficacy of canakinumab in Japanese patients with cryopyrin-associated periodic syndrome (CAPS). In this open-label phase 3 study, Japanese patients aged ≥2 years with CAPS received canakinumab 2-8 mg/kg subcutaneously every 8 weeks. The duration of the core treatment phase was 24 weeks followed by 22 months extension phase. The primary objective was the proportion of patients free of clinical and serologic relapse at week 24. The study enrolled 19 Japanese patients (median age, 14 years; range, 2-48 years) with CAPS [MWS, 7 (36.8%); NOMID, 12 (63.2%)] for a median of 109 weeks. Fifteen patients (79%) achieved a complete response by day 15, 18 (94.7%) by week 24 and all by week 48. At the end of the study, 18 (95%) were free from relapse and 11 (57.9%) were assessed as having no disease activity by the PGA. Thirteen (68%) patients (MWS, 4; NOMID, 9) had their canakinumab dose increased during the trial. All patients experienced at least one adverse event (AE), the most common being infections (100%) and 5 (26.3%) reported serious AEs. No deaths were reported and the only patient who discontinued the study early withdrew consent. Regular canakinumab treatment every 8 weeks at dose levels from 2-8 mg/kg, based on the clinical need, represents a successful strategy to induce rapid and complete response while maintain long-term disease control in Japanese patients with CAPS. The safety profile of canakinumab was consistent with that observed from previous studies.

  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. Hurricane impacts on the coastal environment

    USGS Publications Warehouse

    Sallenger, Abby

    1990-01-01

    In terms of insured losses, Hurricane Andrew is the most severe catastrophe in the Nation's history. Prior to the arrival of Andrew, the U.S. Geological Survey (USGS), in cooperation with the Louisiana Geological Survey (LGS), acquired an extensive body of information and data on the behavior and long-term erosion of Louisiana barrier islands. As a result, we have a clear understanding of pre-storm conditions in this area; Andrew provided an opportunity to learn in detail the impact of a very large storm on Louisiana coastal environment.

  15. Energy Product Options for Eucalyptus Species Grown as Short Rotation Woody Crops

    PubMed Central

    Rockwood, Donald L.; Rudie, Alan W.; Ralph, Sally A.; Zhu, J.Y.; Winandy, Jerrold E.

    2008-01-01

    Eucalyptus species are native to Australia but grown extensively worldwide as short rotation hardwoods for a variety of products and as ornamentals. We describe their general importance with specific emphasis on existing and emerging markets as energy products and the potential to maximize their productivity as short rotation woody crops. Using experience in Florida USA and similar locations, we document their current energy applications and assess their productivity as short-term and likely long-term energy and related products. PMID:19325808

  16. Chromium-induced kidney disease.

    PubMed

    Wedeen, R P; Qian, L F

    1991-05-01

    Kidney disease is often cited as one of the adverse effects of chromium, yet chronic renal disease due to occupational or environmental exposure to chromium has not yet been reported. Occasional cases of acute tubular necrosis (ATN) following massive absorption of chromate have been described. Chromate-induced ATN has been extensively studied in experimental animals following parenteral administration of large doses of potassium chromate (hexavalent) (15 mg/kg body weight). The chromate is selectively accumulated in the convoluted proximal tubule where necrosis occurs. An adverse long-term effect of low-dose chromium exposure on the kidneys is suggested by reports of low molecular weight (LMW) proteinuria in chromium workers. Excessive urinary excretion of beta 2-microglobulin, a specific proximal tubule brush border protein, and retinol-binding protein has been reported among chrome platers and welders. However, LMW proteinuria occurs after a variety of physiologic stresses, is usually reversible, and cannot by itself be considered evidence of chronic renal disease. Chromate-induced ATN and LMW proteinuria in chromium workers, nevertheless, raise the possibility that low-level, long-term exposure may produce persistent renal injury. The absence of evidence of chromate-induced exposure may produce persistent renal injury. The absence of evidence of chromate-induced chronic renal disease cannot be interpreted as evidence of the absence of such injury. Rather, it must be recognized that no prospective cohort or case-control study of the delayed renal effects of low-level, long-term exposure to chromium has been published.

  17. LONG TERM OPERATION ISSUES FOR ELECTRICAL CABLE SYSTEMS IN NUCLEAR POWER PLANTS

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

    Fifield, Dr Leonard S; Duckworth, Robert C; Glass III, Dr. Samuel W.

    Nuclear power plants contain hundreds of kilometers of electrical cables including cables used for power, for instrumentation, and for control. It is essential that safety-related cable systems continue to perform following a design-basis event. Wholesale replacement of electrical cables in existing plants facing licensing period renewal is both impractical and cost-prohibitive. It is therefore important to understand the long term aging of cable materials to have confidence that aged cables will perform when needed. It is equally important in support of cable aging management to develop methods to evaluate the health of installed cables and inform selective cable replacement decisions.more » The most common insulation materials for electrical cables in nuclear power plants are cross-linked polyethylene and ethylene-propylene rubber. The mechanical properties of these materials degrade over time in the presence of environmental stresses including heat, gamma irradiation, and moisture. Mechanical degradation of cable insulation beyond a certain threshold is unacceptable because it can lead to insulation cracking, exposure of energized conductors, arcing and burning or loss of the ability of the cable system to function during a design-basis accident. While thermal-, radiation-, and moisture-related degradation of polymer insulation materials has been extensively studied over the last few decades, questions remain regarding the long-term performance of cable materials in nuclear plant-specific environments. Identified knowledge gaps include an understanding of the temperature-dependence of activation energies for thermal damage and an understanding of the synergistic effects of radiation and thermal stress on polymer degradation. Many of the outstanding questions in the aging behavior of cable materials relate to the necessity of predicting long-term field degradation using accelerated aging results from the laboratory. Materials degrade faster under more extreme conditions, but extension of behavior to long term degradation under more mild conditions, such as those experienced by most installed cables in nuclear power plants, is complicated by the fact that different degradation mechanisms may be involved in extreme and mild scenarios. The discrepancy in predicted results from short term, more extreme exposure and actual results from longer term, more mild exposures can be counter intuitive. For instance, due to the attenuation of oxidation penetration in material samples rapidly aged through exposure to high temperatures, the bulk of the samples may be artificially protected from thermal aging. In another example, simultaneous exposure of cable insulation material to heat and radiation may actually lead to less damage at higher temperatures than may be observed at lower temperatures. The Light Water Reactor Sustainability program of the United States (US) Department of Energy Office (DOE) of Nuclear Energy is funding research to increase the predictive understanding of electrical cable material aging and degradation in existing nuclear power plants in support of continued safe operation of plants beyond their initial license periods. This research includes the evaluation and development of methods to assess installed cable condition.« less

  18. Aging-related impairments of hippocampal mossy fibers synapses on CA3 pyramidal cells.

    PubMed

    Villanueva-Castillo, Cindy; Tecuatl, Carolina; Herrera-López, Gabriel; Galván, Emilio J

    2017-01-01

    The network interaction between the dentate gyrus and area CA3 of the hippocampus is responsible for pattern separation, a process that underlies the formation of new memories, and which is naturally diminished in the aged brain. At the cellular level, aging is accompanied by a progression of biochemical modifications that ultimately affects its ability to generate and consolidate long-term potentiation. Although the synapse between dentate gyrus via the mossy fibers (MFs) onto CA3 neurons has been subject of extensive studies, the question of how aging affects the MF-CA3 synapse is still unsolved. Extracellular and whole-cell recordings from acute hippocampal slices of aged Wistar rats (34 ± 2 months old) show that aging is accompanied by a reduction in the interneuron-mediated inhibitory mechanisms of area CA3. Several MF-mediated forms of short-term plasticity, MF long-term potentiation and at least one of the critical signaling cascades necessary for potentiation are also compromised in the aged brain. An analysis of the spontaneous glutamatergic and gamma-aminobutyric acid-mediated currents on CA3 cells reveal a dramatic alteration in amplitude and frequency of the nonevoked events. CA3 cells also exhibited increased intrinsic excitability. Together, these results demonstrate that aging is accompanied by a decrease in the GABAergic inhibition, reduced expression of short- and long-term forms of synaptic plasticity, and increased intrinsic excitability. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Mobility of Vulnerable Elders (MOVE): study protocol to evaluate the implementation and outcomes of a mobility intervention in long-term care facilities.

    PubMed

    Slaughter, Susan E; Estabrooks, Carole A; Jones, C Allyson; Wagg, Adrian S

    2011-12-16

    Almost 90% of residents living in long-term care facilities have limited mobility which is associated with a loss of ability in activities of daily living, falls, increased risk of serious medical problems such as pressure ulcers, incontinence and a significant decline in health-related quality of life. For health workers caring for residents it may also increase the risk of injury. The effectiveness of rehabilitation to facilitate mobility has been studied with dedicated research assistants or extensively trained staff caregivers; however, few investigators have examined the effectiveness of techniques to encourage mobility by usual caregivers in long-term care facilities. This longitudinal, quasi-experimental study is designed to demonstrate the effect of the sit-to-stand activity carried out by residents in the context of daily care with health care aides. In three intervention facilities health care aides will prompt residents to repeat the sit-to-stand action on two separate occasions during each day and each evening shift as part of daily care routines. In three control facilities residents will receive usual care. Intervention and control facilities are matched on the ownership model (public, private for-profit, voluntary not-for-profit) and facility size. The dose of the mobility intervention is assessed through the use of daily documentation flowsheets in the health record. Resident outcome measures include: 1) the 30-second sit-to-stand test; 2) the Functional Independence Measure; 3) the Health Utilities Index Mark 2 and 3; and, 4) the Quality of Life - Alzheimer's Disease. There are several compelling reasons for this study: the widespread prevalence of limited mobility in this population; the rapid decline in mobility after admission to a long-term care facility; the importance of mobility to quality of life; the increased time (and therefore cost) required to care for residents with limited mobility; and, the increased risk of injury for health workers caring for residents who are unable to stand. The importance of these issues is magnified when considering the increasing number of people living in long-term care facilities and an aging population. This clinical trial is registered with ClinicalTrials.gov (trial registration number: NCT01474616).

  20. Historical Prediction Modeling Approach for Estimating Long-Term Concentrations of PM2.5 in Cohort Studies before the 1999 Implementation of Widespread Monitoring

    PubMed Central

    Kim, Sun-Young; Olives, Casey; Sheppard, Lianne; Sampson, Paul D.; Larson, Timothy V.; Keller, Joshua P.; Kaufman, Joel D.

    2016-01-01

    Introduction: Recent cohort studies have used exposure prediction models to estimate the association between long-term residential concentrations of fine particulate matter (PM2.5) and health. Because these prediction models rely on PM2.5 monitoring data, predictions for times before extensive spatial monitoring present a challenge to understanding long-term exposure effects. The U.S. Environmental Protection Agency (EPA) Federal Reference Method (FRM) network for PM2.5 was established in 1999. Objectives: We evaluated a novel statistical approach to produce high-quality exposure predictions from 1980 through 2010 in the continental United States for epidemiological applications. Methods: We developed spatio-temporal prediction models using geographic predictors and annual average PM2.5 data from 1999 through 2010 from the FRM and the Interagency Monitoring of Protected Visual Environments (IMPROVE) networks. Temporal trends before 1999 were estimated by using a) extrapolation based on PM2.5 data in FRM/IMPROVE, b) PM2.5 sulfate data in the Clean Air Status and Trends Network, and c) visibility data across the Weather Bureau Army Navy network. We validated the models using PM2.5 data collected before 1999 from IMPROVE, California Air Resources Board dichotomous sampler monitoring (CARB dichot), the Children’s Health Study (CHS), and the Inhalable Particulate Network (IPN). Results: In our validation using pre-1999 data, the prediction model performed well across three trend estimation approaches when validated using IMPROVE and CHS data (R2 = 0.84–0.91) with lower R2 values in early years. Model performance using CARB dichot and IPN data was worse (R2 = 0.00–0.85) most likely because of fewer monitoring sites and inconsistent sampling methods. Conclusions: Our prediction modeling approach will allow health effects estimation associated with long-term exposures to PM2.5 over extended time periods ≤ 30 years. Citation: Kim SY, Olives C, Sheppard L, Sampson PD, Larson TV, Keller JP, Kaufman JD. 2017. Historical prediction modeling approach for estimating long-term concentrations of PM2.5 in cohort studies before the 1999 implementation of widespread monitoring. Environ Health Perspect 125:38–46; http://dx.doi.org/10.1289/EHP131 PMID:27340825

  1. New shoreline change data and analysis for the Massachusetts shore with emphasis on Cape Cod and the islands: Mid-1800s to 1994

    USGS Publications Warehouse

    O'Connell, James F.; Thieler, E. Robert; Schupp, Courtney

    2002-01-01

    That shorelines change, oftentimes dramatically in short periods of time, is an accepted fact for those who live along the shore. However, when two-thirds or approximately 512 miles of a state's ocean-facing shore exhibits a long-term erosional trend, in some locations eroding at an average annual rate of 12 feet per year, as is the case in Massachusetts, shoreline property owners, prospective shorefront property owners, and coastal managers need to pay particular attention to the future location of the shoreline to avoid physical and economic disasters. The Woods Hole Oceanographic Institution, Sea Grant Program, the U.S. Geological Survey, and the Cape Cod Cooperative Extension recently completed an update and statistical analysis of historical shoreline change along approximately 1,000 miles of Massachusetts' ocean-facing shore, of which 754 miles were statistically analyzed (Thieler, O'Connell and Schupp, 2001; Schupp, Thieler & O'Connell, 2001). The project was funded by the Massachusetts Office of Coastal Zone Management. In general, four to five shoreline positions mapped between the mid-1800s to 1994 were used to analyze changes along the Massachusetts shore. Seventy-six shoreline change maps with accompanying data tables and a Technical Report were produced. The results of this study reveal that approximately two-thirds of the Massachusetts shore is eroding, with 68% of the shore exhibiting a long-term erosional trend, 30% showing long-term accretion, and 2% showing no net change. ln some areas, erosion rates have accelerated based on a comparison study of previous data that was conducted in 1997 (O'Connell, 1997). Ironically, coastal property that commands some of the highest real estate values in the Commonwealth also exhibits the highest consistent long-term average annual erosion rates. This paper describes the data sources used to map historic shorelines in Massachusetts, the methodology used to both plot a new shoreline and analyze the long-term historical data, and describes cautions necessary when interpreting and applying shoreline change data, with site-specific examples along the Massachusetts shore.

  2. Plasma and Dietary Antioxidant Status as Cardiovascular Disease Risk Factors: A Review of Human Studies

    PubMed Central

    Wang, Ying; Chun, Ock K.; Song, Won O.

    2013-01-01

    Extensive evidence has demonstrated that many antioxidants such as vitamin C, vitamin E, carotenoids and polyphenols have protective effects in preventing cardiovascular disease (CVD), a chronic disease that is mediated by oxidative stress and inflammation. This review focuses on evidence from prospective cohort studies and clinical trials in regard to the associations between plasma/dietary antioxidants and cardiovascular events. Long-term, large-scale, population-based cohort studies have found that higher levels of serum albumin, bilirubin, glutathione, vitamin E, vitamin C, and carotenoids were associated with a lower risk of CVD. Evidence from the cohort studies in regard to dietary antioxidants also supported the protective effects of dietary vitamin E, vitamin C, carotenoids, and polyphenols on CVD risk. However, results from large randomized controlled trials did not support long-term use of single antioxidant supplements for CVD prevention due to their null or even adverse effects on major cardiovascular events or cancer. Diet quality indexes that consider overall diet quality rather than single nutrients have been drawing increasing attention. Cohort studies and intervention studies that focused on diet patterns such as high total antioxidant capacity have documented protective effects on CVD risk. This review provides a perspective for future studies that investigate antioxidant intake and risk of CVD. PMID:23912327

  3. Long-Term Outcomes of Elagolix in Women With Endometriosis: Results From Two Extension Studies.

    PubMed

    Surrey, Eric; Taylor, Hugh S; Giudice, Linda; Lessey, Bruce A; Abrao, Mauricio S; Archer, David F; Diamond, Michael P; Johnson, Neil P; Watts, Nelson B; Gallagher, J Chris; Simon, James A; Carr, Bruce R; Dmowski, W Paul; Leyland, Nicholas; Singh, Sukhbir S; Rechberger, Tomasz; Agarwal, Sanjay K; Duan, W Rachel; Schwefel, Brittany; Thomas, James W; Peloso, Paul M; Ng, Juki; Soliman, Ahmed M; Chwalisz, Kristof

    2018-06-06

    To evaluate the efficacy and safety of elagolix, an oral, nonpeptide gonadotropin-releasing hormone antagonist, over 12 months in women with endometriosis-associated pain. Elaris Endometriosis (EM)-III and -IV were extension studies that evaluated an additional 6 months of treatment after two 6-month, double-blind, placebo-controlled phase 3 trials (12 continuous treatment months) with two elagolix doses (150 mg once daily and 200 mg twice daily). Coprimary efficacy endpoints were the proportion of responders (clinically meaningful pain reduction and stable or decreased rescue analgesic use) based on average monthly dysmenorrhea and nonmenstrual pelvic pain scores. Safety assessments included adverse events, clinical laboratory tests, and endometrial and bone mineral density assessments. The power of Elaris EM-III and -IV was based on the comparison to placebo in Elaris EM-I and -II with an expected 25% dropout rate. Between December 28, 2012, and October 31, 2014 (Elaris EM-III), and between May 27, 2014, and January 6, 2016 (Elaris EM-IV), 569 participants were enrolled. After 12 months of treatment, Elaris EM-III responder rates for dysmenorrhea were 52.1% at 150 mg once daily (Elaris EM-IV=50.8%) and 78.1% at 200 mg twice daily (Elaris EM-IV=75.9%). Elaris EM-III nonmenstrual pelvic pain responder rates were 67.8% at 150 mg once daily (Elaris EM-IV=66.4%) and 69.1% at 200 mg twice daily (Elaris EM-IV=67.2%). After 12 months of treatment, Elaris EM-III dyspareunia responder rates were 45.2% at 150 mg once daily (Elaris EM-IV=45.9%) and 60.0% at 200 mg twice daily (Elaris EM-IV=58.1%). Hot flush was the most common adverse event. Decreases from baseline in bone mineral density and increases from baseline in lipids were observed after 12 months of treatment. There were no adverse endometrial findings. Long-term elagolix treatment provided sustained reductions in dysmenorrhea, nonmenstrual pelvic pain, and dyspareunia. The safety was consistent with reduced estrogen levels and no new safety concerns were associated with long-term elagolix use. ClinicalTrials.gov, NCT01760954 and NCT02143713.

  4. The effects of chronic arsenic exposure from drinking water on the neurobehavioral development in adolescence.

    PubMed

    Tsai, Song-Yen; Chou, Hung-Yi; The, Hee-Wen; Chen, Chao-Meei; Chen, Chien-Jen

    2003-08-01

    This cross-sectional study examined the possible influence on the development of cognitive function among adolescents due to long-term arsenic exposure. Forty-nine junior school students drinking arsenic-containing well water and 60 controls matched with age, sex, education, body height, body weight, body mass index, and socioeconomic status were compared. The former was divided into two groups: high and low exposure, with mean cumulative arsenic levels of 520629.0+/-605824.2 and 13782.2+/-12886.0 ppm, respectively. Four neurobehavioral tests including continuous performance test (CPT), symbol digit (SD), pattern memory (PM) and switching attention (SA) were applied. A strong correlation between age and education caused collinearity in the multiple regression model (r=0.84, P<0.0001). Only education and sex, excluding age, were entered into the model as covariates. Pattern memory and switching attention were significantly affected by long-term cumulative exposure to arsenic after adjusting for education and sex. It is suggested that the arsenic levels in the well water may be monitored extensively, but if there is no intervention, then neurobehavioral function will not be protected. Limitations of the current study require replication of this effect in other studies to confirm this conclusion.

  5. Phase and structural transformations in VVER-440 RPV base metal after long-term operation and recovery annealing

    NASA Astrophysics Data System (ADS)

    Kuleshova, E. A.; Gurovich, B. A.; Maltsev, D. A.; Frolov, A. S.; Bukina, Z. V.; Fedotova, S. V.; Saltykov, M. A.; Krikun, E. V.; Erak, D. Yu; Zhurko, D. A.; Safonov, D. V.; Zhuchkov, G. M.

    2018-04-01

    This study was carried out to evaluate the possibility of 1st generation VVER-440 reactors lifetime extension by recovery re-annealing with the respect to base metal (BM). Comprehensive studies of the structure and properties of BM templates (samples cut from the inner surface of the shells in beltline region) of operating VVER-440 reactor (after primary standard recovery annealing 475 °C/150 h and subsequent long-term re-irradiation within reactor pressure vessel (RPV)) were conducted. These templates were also subjected to laboratory re-annealing 475 °C/150 h. TEM, SEM and APT studies of BM after laboratory re-annealing revealed significant recovery of radiation-induced hardening elements (Cu-rich precipitates and dislocation loops). Simultaneously a process of strong phosphorus accumulation at grain boundaries occurs since annealing temperature corresponds to the maximum reversible temper brittleness development. The latter is not observed for VVER-440 weld metal (WM). Comparative assessment of the properties return level for the beltline BM templates after recovery re-annealing 475 °C/150 h showed that it does not reach the one typical for beltline WM after the same annealing.

  6. Long-term association of food and nutrient intakes with cognitive and functional decline: a 13-year follow-up study of elderly French women.

    PubMed

    Vercambre, Marie-Noël; Boutron-Ruault, Marie-Christine; Ritchie, Karen; Clavel-Chapelon, Françoise; Berr, Claudine

    2009-08-01

    The objective of the present study was to determine the potential long-term impact of dietary habits on age-related decline among 4809 elderly women (born between 1925 and 1930) in the 'Etude Epidémiologique de Femmes de la Mutuelle Générale de l'Education Nationale' (E3N) study, a French epidemiological cohort. In 1993, an extensive diet history self-administered questionnaire was sent to all participants, and in 2006 another questionnaire on instrumental activities of daily living (IADL) and recent cognitive change was sent to a close relative or friend of each woman. Logistic models adjusted for socio-demographic, lifestyle and health factors were performed to evaluate associations between habitual dietary intakes and two outcomes of interest based on the informant response: recent cognitive decline and IADL impairment. Recent cognitive decline was associated with lower intakes of poultry, fish, and animal fats, as well as higher intakes of dairy desserts and ice-cream. IADL impairment was associated with a lower intake of vegetables. The odds of recent cognitive decline increased significantly with decreasing intake of soluble dietary fibre and n-3 fatty acids but with increasing intake of retinol. The odds of IADL impairment increased significantly with decreasing intakes of vitamins B2, B6 and B12. These results are consistent with a possible long-term neuroprotective effect of dietary fibre, n-3 polyunsaturated fats and B-group vitamins, and support dietary intervention to prevent cognitive decline.

  7. Characteristics of upper extremity's muscle strength in Turkish national wheelchair basketball players team.

    PubMed

    Akınoğlu, Bihter; Kocahan, Tuğba

    2017-02-01

    The objective of this study was to reveal characteristics of muscle strength of upper extremities of wheelchair (WC) basketball players and to ensure more-specific training program preparation. Isokinetic muscle strength of 12 WC basketball players were assessed by ISOMED 2000 device. The assessment protocol was evaluated at 60°/sec velocity with 5 times repeated force and at 240°/sec with 15 times repeated force. This protocol was carried out individually for shoulder flexion-extension and wrist flexion-extension movements at the right and left extremities. The flexion/extension ratio was determined to be outside of the ratios accepted as normal for primarily shoulder joint and for wrist joint. The extension movement was stronger than flexion movement in the shoulders at both velocities and the flexion movement was stronger than ex-tension movement in the wrist. The repeat times where the peak torque occurred were 2-3 repeats at 60°/sec velocity during flexion and extension movements for the wrist and shoulders, and the peak torque occurred at an average of 5-6 repeats in the shoulders at 240°/sec velocity and it occurred at 3-4 repeats in the wrist. The angles where the peak torque of the shoulder flexion and extension occurred varied between 80°-115° at both velocities, and it varied between 5°-30° angles for the wrist. As this study revealed, determination of muscle strength characteristics of WC athletes and especially using objective isokinetic devices will guide the planning of the appropriate training and exercise programs and preventing sports injuries in long term.

  8. An open-label extension study to investigate the long-term safety and tolerability of THC/CBD oromucosal spray and oromucosal THC spray in patients with terminal cancer-related pain refractory to strong opioid analgesics.

    PubMed

    Johnson, Jeremy R; Lossignol, Dominique; Burnell-Nugent, Mary; Fallon, Marie T

    2013-08-01

    Chronic pain in patients with advanced cancer poses a serious clinical challenge. The Δ9-tetrahydrocannabinol (THC)/cannabidiol (CBD) oromucosal spray (U.S. Adopted Name, nabiximols; Sativex(®)) is a novel cannabinoid formulation currently undergoing investigation as an adjuvant therapy for this treatment group. This follow-up study investigated the long-term safety and tolerability of THC/CBD spray and THC spray in relieving pain in patients with advanced cancer. In total, 43 patients with cancer-related pain experiencing inadequate analgesia despite chronic opioid dosing, who had participated in a previous three-arm (THC/CBD spray, THC spray, or placebo), two-week parent randomized controlled trial, entered this open-label, multicenter, follow-up study. Patients self-titrated THC/CBD spray (n=39) or THC spray (n=4) to symptom relief or maximum dose and were regularly reviewed for safety, tolerability, and evidence of clinical benefit. The efficacy end point of change from baseline in mean Brief Pain Inventory-Short Form scores for "pain severity" and "worst pain" domains showed a decrease (i.e., improvement) at each visit in the THC/CBD spray patients. Similarly, the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 scores showed a decrease (i.e., improvement) from baseline in the domains of insomnia, pain, and fatigue. No new safety concerns associated with the extended use of THC/CBD spray arose from this study. This study showed that the long-term use of THC/CBD spray was generally well tolerated, with no evidence of a loss of effect for the relief of cancer-related pain with long-term use. Furthermore, patients who kept using the study medication did not seek to increase their dose of this or other pain-relieving medication over time, suggesting that the adjuvant use of cannabinoids in cancer-related pain could provide useful benefit. Copyright © 2013 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.

  9. Safety and efficacy outcomes of long-term treatment up to 4 years with 5% lidocaine medicated plaster in patients with post-herpetic neuralgia.

    PubMed

    Sabatowski, Rainer; Hans, Guy; Tacken, Ingrid; Kapanadze, Sofia; Buchheister, Bettina; Baron, Ralf

    2012-08-01

    Prospective evaluation of the long-term efficacy and safety of the 5% lidocaine medicated plaster in patients with post-herpetic neuralgia (PHN). Patients with persisting pain for ≥3 months after acute herpes zoster and a baseline pain intensity of at least 4 on an 11-point numerical rating scale (NRS 0-10) were treated with 5% lidocaine medicated plasters for up to 5 years and monitored in regular intervals. Efficacy parameters are presented for the first 4 years and include patients' recall of pain relief (6-point verbal rating scale (VRS), clinical global impression of change (CGIC), patients' global impression of change PGIC), and the global evaluations of study medication. Safety parameters (clinical examination, skin evaluation, laboratory) and adverse events (AEs) were assessed at regular visits. KF10004/02. A total of 102 patients continuing from a 1 year main study period were included in an extension phase of up to 3 years. Ten patients (9.8%) dropped out due to lack of efficacy and 9 patients (8.8%) due to treatment-related AEs; 56 patients (54.9%) left the study for non-treatment-related reasons. Twenty-seven patients (26.4%) were still under treatment after a total treatment period of 4 years. On average, a pain relief of at least 4.3 (between moderate and a lot) was achieved throughout the study. At all visits the CGIC and the PGIC were much or very much improved in about 80% of patients. At the final visit, study medication was rated at least to be good by 91% of physicians and 89% of patients. Drug-related adverse events (DRAEs) were reported in 19 of 102 patients, mainly mild to moderate localized skin reactions. There were no hints for a reduced analgesic effect or an increase of DRAEs with long-term treatment. This study demonstrates that long-term treatment of ≥12 months with the 5% lidocaine medicated plaster is effective and well tolerated in PHN patients. These findings support the recommendations to use the 5% lidocaine medicated plaster as baseline therapy for localized neuropathic pain after herpes zoster infection (PHN).

  10. TREE-RING INDICES AND ISOTOPE SIGNATURES OF PINUS PONDEROSA RELATED TO HISTORIC OZONE CHANGES OUTSIDE LOS ANGELES

    EPA Science Inventory

    Ozone concentrations in the Los Angeles (LA) basin were at historic highs in the late 1970s. Since that time Clean Air regulations have helped lower ozone, but little is known of the long-term vegetation responses. Extensive research has used tree-ring indices together with the...

  11. [Long-term evolution of a patient diagnosed of small lung cancer with extension to the central nervous system].

    PubMed

    Barrado Los Arcos, M; Rico Osés, M; Errasti Viader, M; Campo Vargas, M; Zelaya Huerta, M V; Martínez López, E

    2016-01-01

    Cell lung cancer is the principal cause of cancer death in men and women. We report the case of a man diagnosed with small cell lung cancer, metastatic from the outset. The disease is stable at present, forty-seven months from dia-gnosis, after receiving different treatment modalities.

  12. The key roles of four Experimental Forests in the LTSP International Research Program

    Treesearch

    Robert F. Powers; Robert Denner; John D. Elioff; Gary O. Fiddler; Deborah Page-Dumroese; Felix Ponder; Allan E. Tiarks; Peter E. Avers; Richard G. Cline; Nelson S. Loftus

    2014-01-01

    Four Experimental Forests were pivotal in piloting the long-term soil productivity (LTSP) cooperative research program - one of the most successful and extensive collaborative science efforts yet undertaken by the USDA Forest Service. Launched on the Palustris, Challenge, Marcell, and Priest River Experimental Forests, LTSP traces to a seminal discussion during a field...

  13. An Overview of the Current Status of Southernpea Breeding Programs in the United States

    USDA-ARS?s Scientific Manuscript database

    American Horticulturists use the term southernpea when referring to any type of cowpea being grown as a vegetable crop. Several types of southernpeas, e.g., pinkeye peas, blackeye peas, crowder peas, cream peas and snap peas, have a long history of use in the southern United States. An extensive i...

  14. Long-Term Surface Transportation Extension Act of 2011

    THOMAS, 112th Congress

    Sen. Hatch, Orrin G. [R-UT

    2011-11-02

    Senate - 11/03/2011 Motion to proceed to consideration of measure under the order of 11/2/2011, not having achieved 60 votes in the affirmative, was rejected in Senate by Yea-Nay Vote. 47 - 53. Record Vote Number: 196. (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

  15. Using Evidence-Based Parenting Programs to Advance CDC Efforts in Child Maltreatment Prevention. Research Brief

    ERIC Educational Resources Information Center

    Valle, Linda Anne; Whitaker, Daniel J.; Lutzker, John R.; Filene, Jill H.; Wyatt, Jennifer M.; Cephas, Kendell C.; Hoover, D. Michele

    2004-01-01

    The Centers for Disease Control and Prevention (CDC) recognize child maltreatment as a serious public health problem with extensive short- and long-term health effects. In addition to the immediate physical and emotional effects of maltreatment, children who have experienced abuse and neglect are at increased risk of adverse health effects and…

  16. Simulating ungulate herbivory across forest landscapes: A browsing extension for LANDIS-II

    Treesearch

    Nathan R. De Jager; Patrick J. Drohan; Brian M. Miranda; Brian R. Sturtevant; Susan L. Stout; Alejandro A. Royo; Eric J. Gustafson; Mark C. Romanski

    2017-01-01

    Browsing ungulates alter forest productivity and vegetation succession through selective foraging onspecies that often dominate early succession. However, the long-term and large-scale effects of browsing on forest succession are not possible to project without the use of simulation models. To explore the effects of ungulates on succession in a spatially explicit...

  17. Continuing Injuries of Racism: Counseling in a Racist Context

    ERIC Educational Resources Information Center

    Thompson-Miller, Ruth; Feagin, Joe R.

    2007-01-01

    In this reaction article, the authors support and extend Robert T. Carter's excellent analysis of the impact of racism today on Americans of color. Drawing on their own data, they suggest important extensions of his arguments in regard to the cumulative and long-term effects of racial discrimination and other racial oppression--as well as in…

  18. Long-Term Teduglutide for the Treatment of Patients With Intestinal Failure Associated With Short Bowel Syndrome.

    PubMed

    Schwartz, Lauren K; O'Keefe, Stephen J D; Fujioka, Ken; Gabe, Simon M; Lamprecht, Georg; Pape, Ulrich-Frank; Li, Benjamin; Youssef, Nader N; Jeppesen, Palle B

    2016-02-04

    In the pivotal 24-week, phase III, placebo-controlled trial, teduglutide significantly reduced parenteral support (PS) requirements in patients with short bowel syndrome (SBS). STEPS-2 was a 2-year, open-label extension of that study designed to evaluate long-term safety and efficacy of teduglutide. Enrolled patients had completed 24 weeks of either teduglutide (TED/TED) or placebo (PBO/TED) in the initial placebo-controlled study or qualified for that study, but were not treated (NT/TED) because of full enrollment. Patients received subcutaneous teduglutide 0.05 mg/kg/day for up to 24 months (NT/TED and PBO/TED) or up to 30 months (TED/TED). Clinical response was defined as 20-100% reduction from baseline in weekly PS volume; baseline was considered the beginning of teduglutide treatment in the initial placebo-controlled study (TED/TED) or STEPS-2 (NT/TED and PBO/TED). Descriptive statistics summarized changes in efficacy and safety variables. Of 88 enrolled patients, 65 (74%) completed STEPS-2. The most common treatment-emergent adverse events were abdominal pain (34%), catheter sepsis (28%), and decreased weight (25%). Mean weight, body mass index, and serum albumin remained stable. In patients who completed the study, clinical response was achieved in 28/30 (93%) TED/TED, 16/29 (55%) PBO/TED, and 4/6 (67%) NT/TED patients. Mean PS volume reductions from baseline were 7.6 (66%), 3.1 (28%), and 4.0 (39%) l/week in the TED/TED, PBO/TED, and NT/TED groups, respectively. Thirteen patients achieved full enteral autonomy. In patients with SBS, long-term teduglutide treatment resulted in sustained, continued reductions in PS requirements. Overall health and nutritional status was maintained despite PS reductions.

  19. Long-Term Teduglutide for the Treatment of Patients With Intestinal Failure Associated With Short Bowel Syndrome

    PubMed Central

    Schwartz, Lauren K; O'Keefe, Stephen J D; Fujioka, Ken; Gabe, Simon M; Lamprecht, Georg; Pape, Ulrich-Frank; Li, Benjamin; Youssef, Nader N; Jeppesen, Palle B

    2016-01-01

    OBJECTIVES: In the pivotal 24-week, phase III, placebo-controlled trial, teduglutide significantly reduced parenteral support (PS) requirements in patients with short bowel syndrome (SBS). STEPS-2 was a 2-year, open-label extension of that study designed to evaluate long-term safety and efficacy of teduglutide. METHODS: Enrolled patients had completed 24 weeks of either teduglutide (TED/TED) or placebo (PBO/TED) in the initial placebo-controlled study or qualified for that study, but were not treated (NT/TED) because of full enrollment. Patients received subcutaneous teduglutide 0.05 mg/kg/day for up to 24 months (NT/TED and PBO/TED) or up to 30 months (TED/TED). Clinical response was defined as 20–100% reduction from baseline in weekly PS volume; baseline was considered the beginning of teduglutide treatment in the initial placebo-controlled study (TED/TED) or STEPS-2 (NT/TED and PBO/TED). Descriptive statistics summarized changes in efficacy and safety variables. RESULTS: Of 88 enrolled patients, 65 (74%) completed STEPS-2. The most common treatment-emergent adverse events were abdominal pain (34%), catheter sepsis (28%), and decreased weight (25%). Mean weight, body mass index, and serum albumin remained stable. In patients who completed the study, clinical response was achieved in 28/30 (93%) TED/TED, 16/29 (55%) PBO/TED, and 4/6 (67%) NT/TED patients. Mean PS volume reductions from baseline were 7.6 (66%), 3.1 (28%), and 4.0 (39%) l/week in the TED/TED, PBO/TED, and NT/TED groups, respectively. Thirteen patients achieved full enteral autonomy. CONCLUSIONS: In patients with SBS, long-term teduglutide treatment resulted in sustained, continued reductions in PS requirements. Overall health and nutritional status was maintained despite PS reductions. PMID:26844839

  20. Grassland responses to increased rainfall depend on the timescale of forcing.

    PubMed

    Sullivan, Martin J P; Thomsen, Meredith A; Suttle, K B

    2016-04-01

    Forecasting impacts of future climate change is an important challenge to biologists, both for understanding the consequences of different emissions trajectories and for developing adaptation measures that will minimize biodiversity loss. Existing variation provides a window into the effects of climate on species and ecosystems, but in many places does not encompass the levels or timeframes of forcing expected under directional climatic change. Experiments help us to fill in these uncertainties, simulating directional shifts to examine outcomes of new levels and sustained changes in conditions. Here, we explore the translation between short-term responses to climate variability and longer-term trajectories that emerge under directional climatic change. In a decade-long experiment, we compare effects of short-term and long-term forcings across three trophic levels in grassland plots subjected to natural and experimental variation in precipitation. For some biological responses (plant productivity), responses to long-term extension of the rainy season were consistent with short-term responses, while for others (plant species richness, abundance of invertebrate herbivores and predators), there was pronounced divergence of long-term trajectories from short-term responses. These differences between biological responses mean that sustained directional changes in climate can restructure ecological relationships characterizing a system. Importantly, a positive relationship between plant diversity and productivity turned negative under one scenario of climate change, with a similar change in the relationship between plant productivity and consumer biomass. Inferences from experiments such as this form an important part of wider efforts to understand the complexities of climate change responses. © 2016 John Wiley & Sons Ltd.

  1. DaDyn-RS: a tool for the time-dependent simulation of damage, fluid pressure and long-term instability in alpine rock slopes

    NASA Astrophysics Data System (ADS)

    Riva, Federico; Agliardi, Federico; Amitrano, David; Crosta, Giovanni B.

    2017-04-01

    Large mountain slopes in alpine environments undergo a complex long-term evolution from glacial to postglacial environments, through a transient period of paraglacial readjustment. During and after this transition, the interplay among rock strength, topographic relief, and morpho-climatic drivers varying in space and time can lead to the development of different types of slope instability, from sudden catastrophic failures to large, slow, long-lasting yet potentially catastrophic rockslides. Understanding the long-term evolution of large rock slopes requires accounting for the time-dependence of deglaciation unloading, permeability and fluid pressure distribution, displacements and failure mechanisms. In turn, this is related to a convincing description of rock mass damage processes and to their transition from a sub-critical (progressive failure) to a critical (catastrophic failure) character. Although mechanisms of damage occurrence in rocks have been extensively studied in the laboratory, the description of time-dependent damage under gravitational load and variable external actions remains difficult. In this perspective, starting from a time-dependent model conceived for laboratory rock deformation, we developed Dadyn-RS, a tool to simulate the long-term evolution of real, large rock slopes. Dadyn-RS is a 2D, FEM model programmed in Matlab, which combines damage and time-to-failure laws to reproduce both diffused damage and strain localization meanwhile tracking long-term slope displacements from primary to tertiary creep stages. We implemented in the model the ability to account for rock mass heterogeneity and property upscaling, time-dependent deglaciation, as well as damage-dependent fluid pressure occurrence and stress corrosion. We first tested DaDyn-RS performance on synthetic case studies, to investigate the effect of the different model parameters on the mechanisms and timing of long-term slope behavior. The model reproduces complex interactions between topography, deglaciation rate, mechanical properties and fluid pressure occurrence, resulting in different kinematics, damage patterns and timing of slope instabilities. We assessed the role of groundwater on slope damage and deformation mechanisms by introducing time-dependent pressure cycling within simulations. Then, we applied DaDyn-RS to real slopes located in the Italian Central Alps, affected by an active rockslide and a Deep Seated Gravitational Slope Deformation, respectively. From Last Glacial Maximum to present conditions, our model allows reproducing in an explicitly time-dependent framework the progressive development of damage-induced permeability, strain localization and shear band differentiation at different times between the Lateglacial period and the Mid-Holocene climatic transition. Different mechanisms and timings characterize different styles of slope deformations, consistently with available dating constraints. DaDyn-RS is able to account for different long-term slope dynamics, from slow creep to the delayed transition to fast-moving rockslides.

  2. 12 years' preservation of maxillary permanent incisors with cervical root fractures adjacent to aggressive periodontitis: Report of a case.

    PubMed

    Tobiska, Sandra; Krastl, Gabriel

    2018-05-17

    This case report presents long-term results following horizontal root fracture of both maxillary central incisors in a 19-year-old woman with aggressive periodontitis. Due to extensive marginal bone loss and the close proximity of the fracture lines to the bottoms of the periodontal pockets, the prognosis of both teeth was uncertain at the time of the accident. Nevertheless, a conservative treatment strategy consisting of splinting and nonsurgical periodontal therapy was initiated. Follow-up at 12 years after the start of treatment revealed a stable situation from clinical and radiologic perspectives. Permanent fixation to the adjacent teeth and regular supportive periodontal care were the basis for a favorable long-term prognosis.

  3. Effect of Water Nutrient Pollution on Long-Term Corrosion of 90:10 Copper Nickel Alloy

    PubMed Central

    Melchers, Robert E.

    2015-01-01

    Due to their good corrosion resistance, copper and copper alloys such as 90:10 Cu-Ni are used extensively in high-quality marine and industrial piping systems and also in marine, urban, and industrial environments. Their corrosion loss and pitting behaviour tends to follow a bi-modal trend rather than the classic power law. Field data for 90:10 copper nickel immersed in natural seawater are used to explore the effect of water pollution and in particular the availability of critical nutrients for microbiologically induced corrosion. It is shown, qualitatively, that increased dissolved inorganic nitrogen increases corrosion predominantly in the second, long-term, mode of the model. Other, less pronounced, influences are salinity and dissolved oxygen concentration. PMID:28793696

  4. Polarized 3He Neutron Spin Filters

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

    Sno, William Michael

    The goal of this grant to Indiana University and subcontractors at Hamilton College and Wisconsin and the associated Interagency Agreement with NIST was to extend the technique of polarized neutron scattering by the development and application of polarized 3He-based neutron spin filters. This effort was blessed with long-term support from the DOE Office of Science, which started in 2003 and continued until the end of a final no-cost extension of the last 3-year period of support in 2013. The steady support from the DOE Office of Science for this long-term development project was essential to its eventual success. Further 3Hemore » neutron spin filter development is now sited at NIST and ORNL.« less

  5. Addressing Climate Change in Long-Term Water Planning Using Robust Decisionmaking

    NASA Astrophysics Data System (ADS)

    Groves, D. G.; Lempert, R.

    2008-12-01

    Addressing climate change in long-term natural resource planning is difficult because future management conditions are deeply uncertain and the range of possible adaptation options are so extensive. These conditions pose challenges to standard optimization decision-support techniques. This talk will describe a methodology called Robust Decisionmaking (RDM) that can complement more traditional analytic approaches by utilizing screening-level water management models to evaluate large numbers of strategies against a wide range of plausible future scenarios. The presentation will describe a recent application of the methodology to evaluate climate adaptation strategies for the Inland Empire Utilities Agency in Southern California. This project found that RDM can provide a useful way for addressing climate change uncertainty and identify robust adaptation strategies.

  6. Long-term Quaternary uplift rates inferred from limestone caves in Sarawak, Malaysia

    NASA Astrophysics Data System (ADS)

    Farrant, Andrew R.; Smart, Peter L.; Whitaker, Fiona F.; Tarling, Donald H.

    1995-04-01

    The rate of long-term (2 m.y.) base-level lowering estimated in an extensive sequence of limestone caves in Sarawak, Malaysia, from uranium series, electron spin resonance, and paleomagnetic dating is 0.19 +0.03/-0.04 m/ka. This rate has remained constant over at least the last 700 ka, as shown by comparison of the number and spacing of wall notches formed during phases of interstadial and interglacial aggradation with peaks in the deep-sea oxygen isotope curve. It is argued that base-level lowering occurs in response to epirogenic uplift of the more resistant limestones due to regional denudation of the softer shales, and to flexural isostacy associated with high rates of offshore sedimentation.

  7. Tolerability and safety of Souvenaid in patients with mild Alzheimer's disease: results of multi-center, 24-week, open-label extension study.

    PubMed

    Olde Rikkert, Marcel G M; Verhey, Frans R; Blesa, Rafael; von Arnim, Christine A F; Bongers, Anke; Harrison, John; Sijben, John; Scarpini, Elio; Vandewoude, Maurits F J; Vellas, Bruno; Witkamp, Renger; Kamphuis, Patrick J G H; Scheltens, Philip

    2015-01-01

    The medical food Souvenaid, containing the specific nutrient combination Fortasyn Connect, is designed to improve synapse formation and function in patients with Alzheimer's disease (AD). Two double-blind randomized controlled trials (RCT) with Souvenaid of 12 and 24 week duration (Souvenir I and Souvenir II) showed that memory performance was improved in drug-naïve mild AD patients, whereas no effects on cognition were observed in a 24-week RCT (S-Connect) in mild to moderate AD patients using AD medication. Souvenaid was well-tolerated in all RCTs. In this 24-week open-label extension (OLE) study to the 24-week Souvenir II RCT, long-term safety and intake adherence of the medical food Souvenaid was evaluated. Patients with mild AD (n = 201) received Souvenaid once-daily during the OLE. Main outcome parameters were safety and product intake adherence. The memory domain z-score from a revised neuropsychological test battery was continued as exploratory parameter. Compared to the RCT, a similar (low) incidence and type of adverse events was observed, being mainly (68.3%) of mild intensity. Pooled data (RCT and OLE) showed that 48-week use of Souvenaid was well tolerated with high intake adherence (96.1%). Furthermore, a significant increase in the exploratory memory outcome was observed in both the active-active and control-active groups during Souvenaid intervention. Souvenaid use for up to 48-weeks was well tolerated with a favorable safety profile and high intake adherence. The findings in this OLE study warrant further investigation toward the long-term safety and efficacy of Souvenaid in a well-controlled, double-blind RCT.

  8. Oxygenated thawing and rewarming alleviate rewarming injury of cryopreserved pancreatic islets.

    PubMed

    Komatsu, Hirotake; Barriga, Alyssa; Medrano, Leonard; Omori, Keiko; Kandeel, Fouad; Mullen, Yoko

    2017-05-06

    Pancreatic islet transplantation is an effective treatment for Type 1 diabetic patients to eliminate insulin injections; however, a shortage of donor organs hinders the widespread use. Although long-term islet storage, such as cryopreservation, is considered one of the key solutions, transplantation of cryopreserved islets is still not practical due to the extensive loss during the cryopreservation-rewarming process. We have previously reported that culturing islets in a hyperoxic environment is an effective treatment to prevent islet death from the hypoxic injury during culture. In this study, we explored the effectiveness of thawing and rewarming cryopreserved islets in a hyperoxic environment. Following cryopreservation of isolated human islets, the thawing solution and culture media were prepared with or without pre-equilibration to 50% oxygen. Thawing/rewarming and the pursuant two-day culture were performed with or without oxygenation. Short-term recovery rate, defined as the volume change during cryopreservation and thawing/rewarming, was assessed. Ischemia-associated and inflammation-associated gene expressions were examined using qPCR after the initial rewarming period. Long-term recovery rate, defined as the volume change during the two-day culture after the thawing/rewarming, was also examined. Islet metabolism and function were assessed by basal oxygen consumption rate and glucose stimulated insulin secretion after long-term recovery. Oxygenated thawing/rewarming did not alter the short-term recovery rate. Inflammation-associated gene expressions were elevated by the conventional thawing/rewarming method and suppressed by the oxygenated thawing/rewarming, whereas ischemia-associated gene expressions did not change between the thawing/rewarming methods. Long-term recovery rate experiments revealed that only the combination therapy of oxygenated thawing/rewarming and oxygenated culture alleviated islet volume loss. These islets showed higher metabolism and better function among the conditions examined. Oxygenated thawing/rewarming alleviated islet volume loss, with the help of oxygenated culture. Copyright © 2017. Published by Elsevier Inc.

  9. Historical comparisons reveal multiple drivers of decadal change of an ecosystem engineer at the range edge

    PubMed Central

    Firth, Louise B; Mieszkowska, Nova; Grant, Lisa M; Bush, Laura E; Davies, Andrew J; Frost, Matthew T; Moschella, Paula S; Burrows, Michael T; Cunningham, Paul N; Dye, Stephen R; Hawkins, Stephen J

    2015-01-01

    Biogenic reefs are important for habitat provision and coastal protection. Long-term datasets on the distribution and abundance of Sabellaria alveolata (L.) are available from Britain. The aim of this study was to combine historical records and contemporary data to (1) describe spatiotemporal variation in winter temperatures, (2) document short-term and long-term changes in the distribution and abundance of S. alveolata and discuss these changes in relation to extreme weather events and recent warming, and (3) assess the potential for artificial coastal defense structures to function as habitat for S. alveolata. A semi-quantitative abundance scale (ACFOR) was used to compare broadscale, long-term and interannual abundance of S. alveolata near its range edge in NW Britain. S. alveolata disappeared from the North Wales and Wirral coastlines where it had been abundant prior to the cold winter of 1962/1963. Population declines were also observed following the recent cold winters of 2009/2010 and 2010/2011. Extensive surveys in 2004 and 2012 revealed that S. alveolata had recolonized locations from which it had previously disappeared. Furthermore, it had increased in abundance at many locations, possibly in response to recent warming. S. alveolata was recorded on the majority of artificial coastal defense structures surveyed, suggesting that the proliferation of artificial coastal defense structures along this stretch of coastline may have enabled S. alveolata to spread across stretches of unsuitable natural habitat. Long-term and broadscale contextual monitoring is essential for monitoring responses of organisms to climate change. Historical data and gray literature can be invaluable sources of information. Our results support the theory that Lusitanian species are responding positively to climate warming but also that short-term extreme weather events can have potentially devastating widespread and lasting effects on organisms. Furthermore, the proliferation of coastal defense structures has implications for phylogeography, population genetics, and connectivity of coastal populations. PMID:26355379

  10. Antibiotic prophylaxis in COPD: Why, when, and for whom?

    PubMed

    Miravitlles, Marc; Anzueto, Antonio

    2015-06-01

    One of the main goals of treatment of chronic obstructive pulmonary disease (COPD) is the prevention of exacerbations. Bronchodilators and anti-inflammatories are the first line therapy for treatment of COPD; however, these drugs are not effective in suppressing all infective exacerbations. In fact, the use of inhaled corticosteroids in patients with COPD and chronic bronchial infection may even increase the bacterial load in the airways and increase the risk of pneumonia. In this context, the use of long-term or intermittent antibiotic treatment has shown to prevent COPD exacerbations and hospitalizations. These effects may be achieved by reducing bacterial load in the airways in stable state and/or bronchial inflammation. The drugs more extensively studied are macrolides, followed by quinolones. The long-term use of antibiotics is associated with an increased risk of potentially serious adverse events and development of bacterial resistance. Therefore, the indication of long-term antibiotic therapy must be determined on a case by case basis taking into account the potential risks and benefits. In general, this treatment may be indicated in patients with severe or very severe COPD with frequent or severe exacerbations despite optimal pharmacological and non pharmacological treatment. These patients should be carefully monitored based on clinical and microbiological assessments. The most appropriate drug and regime administration, as well as the optimal duration of therapy are issues that still require further investigation. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Folic acid and sulfasalazine for colorectal carcinoma chemoprevention in patients with ulcerative colitis: the old and new evidence.

    PubMed

    Diculescu, Mircea; Ciocîrlan, Mihai; Ciocîrlan, Mirela; Piţigoi, Dan; Becheanu, Gabriel; Croitoru, Adina; Spanache, Sandu

    2003-12-01

    The purpose of the study was to assess whether folic acid supplementation and long term therapy with sulfasalazine can reduce the risk of colorectal cancer (CRC) development in longstanding extensive ulcerative colitis. A meta-analysis was performed including the last 10 years published and Medline indexed studies on this subject. 3 studies have been included concerning the protective effect of folate supplementation in development of CRC. The association of these two factors is significant (effect size r =0.124, p = 0.025). The fail-safe number of studies with an opposite result should be 4 to revert the significance. 4 studies regarding sulfasalazine's protective effect in longstanding extensive ulcerative colitis have also been evaluated. A similar significance has been obtained, r = 0.148, p = 0.0007 and a fail-safe number of studies equal to 7. The homogeneity of these studies is validated by standard tests. Both sulfasalazine therapy and folate supplementation have a protective effect in colorectal cancer development in a population of patients with longstanding ulcerative colitis. Randomized controlled trials are needed to explore these hypotheses.

  12. Delayed Complications and Long-term Management of Sulfur Mustard Poisoning: Recent Advances by Iranian Researchers (Part I of II)

    PubMed Central

    Darchini-Maragheh, Emadodin; Balali-Mood, Mahdi

    2018-01-01

    Chemical warfare agents are the most brutal weapons among the weapons of mass destruction. Sulfur mustard (SM) is a potent toxic alkylating agent known as “the King of the Battle Gases”. SM has been the most widely used chemical weapon during the wars. It was widely used in World War I. Thereafter, it was extensively employed by the Iraqi troops against the Iranian military personnel and even civilians in the border cities of Iran and Iraq in the period between 1983 and 1988. Long-term incapacitating properties, significant environmental persistence, lack of an effective antidote, and relative ease of manufacturing have kept SM a potential agent for both terrorist and military uses. Even 3 decades after SM exposure, numerous delayed complications among Iranian victims are still being reported by researchers. The most common delayed complications have been observed in the respiratory tracts of chemically injured Iranian war veterans. Also, skin lesions and eye disorders have been observed in most Iranian SM-exposed war veterans in the delayed phase of SM intoxication. Thus, extensive research has been conducted on Iranian war veterans during the past decades. Nevertheless, major gaps still continue to exist in the SM literature. Part I of this paper will discuss the delayed complications and manifestations of exposure to SM among Iranian victims of the Iran–Iraq conflict. Part II, which will appear in the next issue of Iran J Med Sci, will discuss the long-term management and therapy of SM-exposed patients. PMID:29749980

  13. Effects of hamstring stretching on passive muscle stiffness vary between hip flexion and knee extension maneuvers.

    PubMed

    Miyamoto, N; Hirata, K; Kanehisa, H

    2017-01-01

    The purpose of this study was to examine whether the effects of hamstring stretching on the passive stiffness of each of the long head of the biceps femoris (BFl), semitendinosus (ST), and semimembranosus (SM) vary between passive knee extension and hip flexion stretching maneuvers. In 12 male subjects, before and after five sets of 90 s static stretching, passive lengthening measurements where knee or hip joint was passively rotated to the maximal range of motion (ROM) were performed. During the passive lengthening, shear modulus of each muscle was measured by ultrasound shear wave elastography. Both stretching maneuvers significantly increased maximal ROM and decreased passive torque at a given joint angle. Passive knee extension stretching maneuver significantly reduced shear modulus at a given knee joint angle in all of BFl, ST, and SM. In contrast, the stretching effect by passive hip flexion maneuver was significant only in ST and SM. The present findings indicate that the effects of hamstring stretching on individual passive muscles' stiffness vary between passive knee extension and hip flexion stretching maneuvers. In terms of reducing the muscle stiffness of BFl, stretching of the hamstring should be performed by passive knee extension rather than hip flexion. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. Long-Term Farm Policy to Succeed the Agriculture and Food Act of 1981 (Research, Extension, and Teaching). Part 5. Hearings before the Subcommittee on Departmental Operations, Research, and Foreign Agriculture of the Committee on Agriculture, House of Representatives, Ninety-Eighth Congress, Second Session (June 6, 7, 12, and 13, 1984).

    ERIC Educational Resources Information Center

    Congress of the U.S., Washington, DC. House Committee on Agriculture.

    This congressional hearing is the fifth of five volumes examining various aspects of agricultural research, extension, and teaching as a prelude to determining what changes are to be made in Title XIV of the farm bill. Focuses are the U.S. Department of Agriculture (USDA) biotechnology program plans and regulatory concerns and the public benefits…

  15. Coil extensions improve line shapes by removing field distortions

    NASA Astrophysics Data System (ADS)

    Conradi, Mark S.; Altobelli, Stephen A.; McDowell, Andrew F.

    2018-06-01

    The static magnetic susceptibility of the rf coil can substantially distort the field B0 and be a dominant source of line broadening. A scaling argument shows that this may be a particular problem in microcoil NMR. We propose coil extensions to reduce the distortion. The actual rf coil is extended to a much longer overall length by abutted coil segments that do not carry rf current. The result is a long and nearly uniform sheath of copper wire, in terms of the static susceptibility. The line shape improvement is demonstrated at 43.9 MHz and in simulation calculations.

  16. MXA: a customizable HDF5-based data format for multi-dimensional data sets

    NASA Astrophysics Data System (ADS)

    Jackson, M.; Simmons, J. P.; De Graef, M.

    2010-09-01

    A new digital file format is proposed for the long-term archival storage of experimental data sets generated by serial sectioning instruments. The format is known as the multi-dimensional eXtensible Archive (MXA) format and is based on the public domain Hierarchical Data Format (HDF5). The MXA data model, its description by means of an eXtensible Markup Language (XML) file with associated Document Type Definition (DTD) are described in detail. The public domain MXA package is available through a dedicated web site (mxa.web.cmu.edu), along with implementation details and example data files.

  17. Vaginal anomalies and atresia associated with imperforate anus: diagnosis and surgical management.

    PubMed

    Pandya, Kartikey A; Koga, Hiroyuki; Okawada, Manabu; Coran, Arnold G; Yamataka, Atsuyuki; Teitelbaum, Daniel H

    2015-03-01

    The association of vaginal atresia (or Mayer-Rokitansky-Kuster-Hauser Syndrome) with imperforate anus is rare and can present significant diagnostic and therapeutic challenges. This study describes clinical characteristics, surgical treatment and outcomes in this group of complex children. Records of 20 patients were retrospectively analyzed from two pediatric surgical centers. Five patients were excluded from the long-term analysis due to inadequate information, leaving long-term follow-up in 15 patients. Mean follow-up was 10 years (range 1-31.1 years). The diagnosis of vaginal atresia was made pre-operatively in 12 out of 15 patients, and in three patients it was identified during the anoplasty. The anorectal malformations were rectoperineal (N=2), rectovestibular (N=6), recto-bladder neck (N=1) and imperforate anus without fistula (N=6). Satisfactory surgical repair was performed in 13 patients, while one continues to stool through a low perineal fistula awaiting definitive surgery and another underwent a colostomy and mucous fistula. Delayed vaginal reconstruction was due to a failure to identify the problem prior to anoplasty (N=3). Long-term results demonstrated that anorectal continence was much worse than initially appreciated, and many had associated urinary incontinence. Overall stooling score was far lower than in a separate group of children with imperforate anus without vaginal atresia (Levitt and Peña, 2007). Vaginal atresia with imperforate anus is a rare and an extensive pre-operative workup of females with imperforate anus must include assessment of vagina patency. Vaginal reconstruction and anorectal continuity can be performed in a variety of approaches, but long-term continence is often not optimal. We propose a pathway for management of this difficult genito-anorectal disorder. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Geological constraints on continental arc activity since 720 Ma: implications for the link between long-term climate variability and episodicity of continental arcs

    NASA Astrophysics Data System (ADS)

    Cao, W.; Lee, C. T.

    2016-12-01

    Continental arc volcanoes have been suggested to release more CO2 than island arc volcanoes due to decarbonation of wallrock carbonates in the continental upper plate through which the magmas traverse (Lee et al., 2013). Continental arcs may thus play an important role in long-term climate. To test this hypothesis, we compiled geological maps to reconstruct the surface distribution of granitoid plutons and the lengths of ancient continental arcs. These results were then compiled into a GIS framework and incorporated into GPlates plate reconstructions. Our results show an episodic nature of global continental arc activity since 720 Ma. The lengths of continental arcs were at minimums during most of the Cryogenian ( 720-670 Ma), the middle Paleozoic ( 460-300 Ma) and the Cenozoic ( 50-0 Ma). Arc lengths were highest during the Ediacaran ( 640-570 Ma), the early Paleozoic ( 550-430 Ma) and the entire Mesozoic with peaks in the Early Triassic ( 250-240 Ma), Late Jurassic-Early Cretaceous ( 160-130 Ma), and Late Cretaceous ( 90-65 Ma). The extensive continental arcs in the Ediacaran and early Paleozoic reflect the Pan-African events and circum-Gondwana subduction during the assembly of the Gondwana supercontinent. The Early Triassic peak is coincident with the final closure of the paleo-Asian oceans and the onset of circum-Pacific subduction associated with the assembly of the Pangea supercontinent. The Jurassic-Cretaceous peaks reflect the extensive continental arcs established in the western Pacific, North and South American Cordillera, coincident with the initial dispersal of the Pangea. Continental arcs are favored during the final assembly and the early-stage dispersal of a supercontinent. Our compilation shows a temporal match between continental arc activity and long-term climate at least since 720 Ma. For example, continental arc activity was reduced during the Cryogenian icehouse event, and enhanced during the Early Paleozoic and Jurassic-Cretaceous greenhouse events. This coherence provides further evidence that continental arcs may play an important role in controlling long-term climate evolution. CO2 degassing fluxes from continental arcs should be incorporated into global, long-term climate models. Our work provides a quantitative framework for estimating these fluxes.

  19. Modeling interactions of agriculture and groundwater nitrate contaminants: application of The STICS-Eau-Dyssée coupled models over the Seine River Basin

    NASA Astrophysics Data System (ADS)

    Tavakoly, A. A.; Habets, F.; Saleh, F.; Yang, Z. L.

    2017-12-01

    Human activities such as the cultivation of N-fixing crops, burning of fossil fuels, discharging of industrial and domestic effluents, and extensive usage of fertilizers have recently accelerated the nitrogen loading to watersheds worldwide. Increasing nitrate concentration in surface water and groundwater is a major concern in watersheds with extensive agricultural activities. Nutrient enrichment is one of the major environmental problems in the French coastal zone. To understand and predict interactions between agriculture, surface water and groundwater nitrate contaminants, this study presents a modeling framework that couples the agronomic STICS model with Eau-Dyssée, a distributed hydrologic modeling system to simulate groundwater-surface water interaction. The coupled system is implemented on the Seine River Basin with an area of 88,000 km2 to compute daily nitrate contaminants. Representing a sophisticated hydrosystem with several aquifers and including the megalopolis of Paris, the Seine River Basin is well-known as one of the most productive agricultural areas in France. The STICS-EauDyssée framework is evaluated for a long-term simulation covering 39 years (1971-2010). Model results show that the simulated nitrate highly depends on the inflow produced by surface and subsurface waters. Daily simulation shows that the model captures the seasonal variation of observations and that the overall long-term simulation of nitrate contaminant is satisfactory at the regional scale.

  20. Nanomaterial-Enabled Dry Electrodes for Electrophysiological Sensing: A Review

    NASA Astrophysics Data System (ADS)

    Yao, Shanshan; Zhu, Yong

    2016-04-01

    Long-term, continuous, and unsupervised tracking of physiological data is becoming increasingly attractive for health/wellness monitoring and ailment treatment. Nanomaterials have recently attracted extensive attention as building blocks for flexible/stretchable conductors and are thus promising candidates for electrophysiological electrodes. Here we provide a review on nanomaterial-enabled dry electrodes for electrophysiological sensing, focusing on electrocardiography (ECG). The dry electrodes can be classified into contact surface electrodes, contact-penetrating electrodes, and noncontact capacitive electrodes. Different types of electrodes including their corresponding equivalent electrode-skin interface models and the sources of the noise are first introduced, followed by a review on recent developments of dry ECG electrodes based on various nanomaterials, including metallic nanowires, metallic nanoparticles, carbon nanotubes, and graphene. Their fabrication processes and performances in terms of electrode-skin impedance, signal-to-noise ratio, resistance to motion artifacts, skin compatibility, and long-term stability are discussed.

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

    Christians, Jeffrey A.; Schulz, Philip; Tinkham, Jonathan S.

    Long-term device stability is the most pressing issue that impedes perovskite solar cell commercialization, given the achieved 22.7% efficiency. The perovskite absorber material itself has been heavily scrutinized for being prone to degradation by water, oxygen and ultraviolet light. To date, most reports characterize device stability in the absence of these extrinsic factors. Here we show that, even under the combined stresses of light (including ultraviolet light), oxygen and moisture, perovskite solar cells can retain 94% of peak efficiency despite 1,000 hours of continuous unencapsulated operation in ambient air conditions (relative humidity of 10-20%). Each interface and contact layer throughoutmore » the device stack plays an important role in the overall stability which, when appropriately modified, yields devices in which both the initial rapid decay (often termed burn-in) and the gradual slower decay are suppressed. This extensively modified device architecture and the understanding developed will lead towards durable long-term device performance.« less

  2. Fidelity study of superconductivity in extended Hubbard models

    NASA Astrophysics Data System (ADS)

    Plonka, N.; Jia, C. J.; Wang, Y.; Moritz, B.; Devereaux, T. P.

    2015-07-01

    The Hubbard model with local on-site repulsion is generally thought to possess a superconducting ground state for appropriate parameters, but the effects of more realistic long-range Coulomb interactions have not been studied extensively. We study the influence of these interactions on superconductivity by including nearest- and next-nearest-neighbor extended Hubbard interactions in addition to the usual on-site terms. Utilizing numerical exact diagonalization, we analyze the signatures of superconductivity in the ground states through the fidelity metric of quantum information theory. We find that nearest and next-nearest neighbor interactions have thresholds above which they destabilize superconductivity regardless of whether they are attractive or repulsive, seemingly due to competing charge fluctuations.

  3. Spirally-patterned pinhole arrays for long-term fluorescence cell imaging.

    PubMed

    Koo, Bon Ung; Kang, YooNa; Moon, SangJun; Lee, Won Gu

    2015-11-07

    Fluorescence cell imaging using a fluorescence microscope is an extensively used technique to examine the cell nucleus, internal structures, and other cellular molecules with fluorescence response time and intensity. However, it is difficult to perform high resolution cell imaging for a long period of time with this technique due to necrosis and apoptosis depending on the type and subcellular location of the damage caused by phototoxicity. A large number of studies have been performed to resolve this problem, but researchers have struggled to meet the challenge between cellular viability and image resolution. In this study, we employ a specially designed disc to reduce cell damage by controlling total fluorescence exposure time without deterioration of the image resolution. This approach has many advantages such as, the apparatus is simple, cost-effective, and easily integrated into the optical pathway through a conventional fluorescence microscope.

  4. Safety and Durability of Effect with Long-Term, Open-Label Droxidopa Treatment in Patients with Symptomatic Neurogenic Orthostatic Hypotension (NOH303).

    PubMed

    Isaacson, Stuart; Shill, Holly A; Vernino, Steven; Ziemann, Adam; Rowse, Gerald J

    2016-10-19

    Neurogenic orthostatic hypotension (nOH) is associated with insufficient norepinephrine release in response to postural change. The objective of this study was to evaluate the long-term safety and durability of efficacy of the norepinephrine precursor droxidopa in patients with symptomatic nOH. This multinational study consisted of 3 sequential phases: a 3-month open-label droxidopa treatment phase followed by a 2-week double-blind, placebo-controlled withdrawal phase, and a 9-month open-label extension phase in which all patients received droxidopa. Patients were adults diagnosed with symptomatic nOH associated with Parkinson's disease, multiple system atrophy, pure autonomic failure, dopamine β-hydroxylase deficiency, or nondiabetic autonomic neuropathy. Efficacy was evaluated using patient- and investigator-reported questionnaire responses and the orthostatic standing test. Safety was assessed through adverse event (AE) reports and vital signs. A total of 102 patients received treatment with droxidopa. Initial improvements from baseline in patient-reported nOH symptom severity and impact on daily activities, evaluated using the Orthostatic Hypotension Questionnaire, exceeded 50% and were maintained throughout the 12-month study. Decreased nOH severity was also reflected in clinician and patient ratings on the Clinical Global Impression questionnaire. Standing systolic and diastolic blood pressures were increased from baseline throughout the study with droxidopa treatment. The most frequently reported AEs were falls, urinary tract infection, and headache. There was a low incidence (≤2%) of cardiac AEs (eg, first-degree atrioventricular block, supraventricular extrasystoles). Long-term, open-label treatment with droxidopa for up to 12 months was generally well tolerated and provided durable improvements in nOH signs and symptoms.

  5. Low Dynamics, High Longevity and Persistence of Sessile Structural Species Dwelling on Mediterranean Coralligenous Outcrops

    PubMed Central

    Teixidó, Núria; Garrabou, Joaquim; Harmelin, Jean-George

    2011-01-01

    There is still limited understanding of the processes underlying benthic species dynamics in marine coastal habitats, which are of disproportionate importance in terms of productivity and biodiversity. The life-history traits of long-lived benthic species in these habitats are particularly poorly documented. In this study, we assessed decadal patterns of population dynamics for ten sponge and anthozoan species that play key structural roles in coralligenous outcrops (∼25 m depth) in two areas of the NW Mediterranean Sea. This study was based on examination of a unique long-term photographic series, which allowed analysis of population dynamics over extensive spatial and time spans for the very first time. Specifically, 671 individuals were censused annually over periods of 25-, 15-, and 5-years. This long-term study quantitatively revealed a common life-history pattern among the ten studied species, despite the fact they present different growth forms. Low mortality rates (3.4% yr−1 for all species combined) and infrequent recruitment events (mean value of 3.1±0.5 SE recruits yr−1) provided only a very small fraction of the new colonies required to maintain population sizes. Overall, annual mortality and recruitment rates did not differ significantly among years; however, some species displayed important mortality events and recruitment pulses, indicating variability among species. Based on the growth rates of these 10 species, we projected their longevity and, obtained a mean estimated age of 25–200 years. Finally, the low to moderate turnover rates (mean value 0.80% yr−1) observed among the coralligenous species were in agreement with their low dynamics and persistence. These results offer solid baseline data and reveal that these habitats are among the most vulnerable to the current increases of anthropogenic disturbances. PMID:21887308

  6. Safety and tolerability of vortioxetine (15 and 20 mg) in patients with major depressive disorder: results of an open-label, flexible-dose, 52-week extension study

    PubMed Central

    Jacobsen, Paula L.; Harper, Linda; Chrones, Lambros; Chan, Serena

    2015-01-01

    Vortioxetine is approved for the treatment of adults with major depressive disorder. This open-label extension (OLE) study evaluated the safety and tolerability of vortioxetine in the long-term treatment of major depressive disorder patients, as well as evaluated its effectiveness using measures of depression, anxiety, and overall functioning. This was a 52-week, flexible-dose, OLE study in patients who completed one of three randomized, double-blind, placebo-controlled, 8-week vortioxetine trials. All patients were switched to 10 mg/day vortioxetine for week 1, then adjusted between 15 and 20 mg for the remainder of the study, but not downtitrated below 15 mg. Safety and tolerability were assessed on the basis of treatment-emergent adverse events (TEAEs), vital signs, laboratory values, physical examination, and the Columbia-Suicide Severity Rating Scale. Efficacy measures included the Montgomery–Åsberg Depression Rating Scale, the Hamilton Anxiety Scale, the Clinical Global Impression Scale-Severity of Illness, and the Sheehan Disability Scale. Of the 1075 patients enrolled, 1073 received at least one dose of vortioxetine and 538 (50.0%) completed the study. A total of 537 patients withdrew early, with 115 (10.7% of the original study population) withdrawing because of TEAEs. Long-term treatment with vortioxetine was well tolerated; the most common TEAEs (≥10%) were nausea and headache. Laboratory values, vital signs, and physical examinations revealed no trends of clinical concern. The mean Montgomery–Åsberg Depression Rating Scale total score was 19.9 at the start of the extension study and 9.0 after 52 weeks of treatment (observed cases). Similar improvements were observed with the Hamilton Anxiety Scale (Δ−4.2), the Clinical Global Impression Scale-Severity of Illness (Δ−1.2), and the Sheehan Disability Scale (Δ−4.7) total scores after 52 weeks of treatment (observed case). In this 52-week, flexible-dose OLE study, 15 and 20 mg vortioxetine were safe and well tolerated. After entry into this study, patients continued to show improvement in depression and anxiety symptoms, as well as overall functioning, throughout the treatment period. PMID:26020712

  7. Management issues with exogenous steroid therapy

    PubMed Central

    Patt, Hiren; Bandgar, Tushar; Lila, Anurag; Shah, Nalini

    2013-01-01

    Glucocorticoids (GCs) are extensively used for various inflammatory and autoimmune disorders, but long term use of these agents is not without complications. Almost every GC formulations (e.g. oral, topical, inhaled, etc.) can cause systemic side effects. It can range from minor side effects (e.g. weight gain) to life-threatening effects (e.g. adrenal suppression, sepsis, etc.), which may require immediate intervention. Therefore, the decision to institute steroid therapy always requires careful consideration of the relative risk and benefit in each patient. The objectives of this study are to discuss monitoring of patients on GCs and management of the complications of GCs. PMID:24910822

  8. Relation between response to illness and compliance in haemodialysis patients.

    PubMed

    Saounatsou, M

    1999-01-01

    The treatment schedule of the haemodialysis patient has many restrictions and the long-term haemodialysis patient's response to illness is characterised by various emotional reactions. Compliance with their medical regimens remains a significant problem which influences the progress of health and by extension quality of life. The preconceived idea that a patient's response to illness may influence his adherence to medical regimen led to this study. The main variables examined were the relationship between the patient's response to illness and compliance and the relationship between compliance and age, education and the length of time on haemodialysis.

  9. The long-term hospitalization experience following military service in the 1991 Gulf War among veterans remaining on active duty, 1994–2004

    PubMed Central

    Hooper, Tomoko I; DeBakey, Samar F; Nagaraj, Barbara E; Bellis, Kimberly S; Smith, Besa; Smith, Tyler C; Gackstetter, Gary D

    2008-01-01

    Background Despite more than a decade of extensive, international efforts to characterize and understand the increased symptom and illness-reporting among veterans of the 1991 Gulf War, concern over possible long-term health effects related to this deployment continue. The purpose of this study was to describe the long-term hospitalization experience of the subset of U.S. Gulf War veterans still on active duty between 1994 and 2004. Methods Gulf War veterans on active duty rosters as of October 1, 1994, were identified (n = 211 642) and compared with veterans who had separated from military service and then assessed for attrition at three-year intervals during a 10-year follow-up period, examining demographic and military service characteristics, Gulf War exposure variables, and hospitalization data. Cox proportional hazard modeling was used to evaluate independent predictors of all-cause hospitalization among those still on active duty and to estimate cumulative probability of hospitalization, 1994–2004, by service branch. Results Members of our 1994 active duty cohort were more likely to be officers, somewhat older, and married compared with those who had separated from the military after serving in the 1991 Gulf War. Selected war-related exposures or experiences did not appear to influence separation with the exception of in-theater presence during the brief ground combat phase. Overall the top three diagnostic categories for hospitalizations were musculo-skeletal, injury and poisoning, and digestive disorders. Diseases of the circulatory system and symptoms, signs, and ill-defined conditions increased proportionately over time. In-theater hospitalization was the only significant independent predictor of long-term hospitalization risk among selected war-related exposures or experiences examined. The cumulative probability of hospitalization was highest for Army and lowest for Marines. Conclusion Our results were generally consistent with a previous hospitalization study of US Gulf War veterans for the period August 1991 to July 1999. Although lack of a comparison group for our study limits interpretation of overall findings, intra-cohort analyses showed no significant associations between long-term hospitalization and war-related exposures or experiences, with the exception of in-theater hospitalization, within our active duty subset of 1991 Gulf War veterans. PMID:18271971

  10. Effectiveness and implementation aspects of interventions for preventing falls in elderly people in long-term care facilities: a systematic review of RCTs.

    PubMed

    Neyens, Jacques C; van Haastregt, Jolanda C; Dijcks, Béatrice P; Martens, Mark; van den Heuvel, Wim J; de Witte, Luc P; Schols, Jos M

    2011-07-01

    There is extensive literature on interventions to prevent or reduce falls in elderly people. These findings, however, were based mainly on studies of community-living persons. The primary aim of the present study was to report the effectiveness and implementation aspects of interventions aimed at reducing falls in elderly residents in long-term care facilities: a systematic review of randomized controlled trials (RCTs). MEDLINE, EMBASE, CINAHL, and hand searching of reference lists of included RCTs. RCTs that assessed fall incidents (falls, fallers, recurrent fallers, fall-related injuries) among elderly residents in long-term care facilities were included in this narrative review. Two independent reviewers abstracted data: general program characteristics (setting, population, intervention program) and outcomes, detailed program characteristics (assessment, intervention content, individually tailored, multidisciplinary), and implementation aspects (feasibility, implications for practice). The CONSORT Statement 2001 Checklist was used regarding the quality of reporting RCTs. Twenty trials met the inclusion criteria. Seven trials, 4 multifactorial and 3 monofactorial, showed a significant reduction in the fall rate, the percentage of recurrent fallers, or both the fall rate and the percentage of persons sustaining femoral fractures. The positive effective programs were as follows: a comprehensive structured individual assessment with specific safety recommendations; a multidisciplinary program including general strategies tailored to the setting and strategies tailored specifically to residents; a multifaceted intervention including education, environmental adaptation, balance, resistance training, and hip protector; calcium plus vitamin D supplementation; vitamin D supplementation; a clinical medication review; and a multifactorial intervention (fall risk evaluation, specific and general interventions). In general, because of the limited number of included trials, the evidence is inconclusive for multifaceted and single interventions in long-term care facilities. Most of the reviewed studies did not find a significant positive effect on fall incidents. However, our data support the conclusions of Gillespie et al. that multifactorial interventions in long-term care populations seem more likely to be beneficial. However, single interventions (eg, targeting vitamin D insufficiency) can be effective. Furthermore, a careful approach is needed as programs to prevent falls in these settings may be ineffective or even may have adverse effects. This may occur especially when a program is not feasible for the setting in which it is implemented. Copyright © 2011 American Medical Directors Association. Published by Elsevier Inc. All rights reserved.

  11. 78 FR 66945 - Proposed Collection; 60-Day Comment request: Gulf Long-Term Follow-Up Study (GuLF STUDY)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-07

    ... Comment request: Gulf Long-Term Follow-Up Study (GuLF STUDY) Summary: In compliance with the requirement... days of the date of this publication. Proposed Collection: Gulf Long-Term Follow-Up Study (GuLF STUDY... GuLF STUDY is to investigate potential short- and long-term health effects associated with oil spill...

  12. Immune microenvironment in colorectal cancer: a new hallmark to change old paradigms.

    PubMed

    de la Cruz-Merino, Luis; Henao Carrasco, Fernando; Vicente Baz, David; Nogales Fernández, Esteban; Reina Zoilo, Juan José; Codes Manuel de Villena, Manuel; Pulido, Enrique Grande

    2011-01-01

    Impact of immune microenvironment in prognosis of solid tumors has been extensively studied in the last few years. Specifically in colorectal carcinoma, increased knowledge of the immune events around these tumors and their relation with clinical outcomes have led to consider immune microenvironment as one of the most important prognostic factors in this disease. In this review we will summarize and update the current knowledge with respect to this intriguing and complex new hallmark of cancer, paying special attention to infiltration by T-infiltrating lymphocytes and their subtypes in colorectal cancer, as well as its eventual clinical translation in terms of long-term prognosis. Finally, we suggest some possible investigational approaches based on combinatorial strategies to trigger and boost immune reaction against tumor cells.

  13. Business Students' Choice of Short-Term or Long-Term Study Abroad Opportunities

    ERIC Educational Resources Information Center

    Fitzsimmons, Stacey R.; Flanagan, David J.; Wang, Xiaodan

    2013-01-01

    Recent years have seen a proliferation of short-term study abroad opportunities. Although they are both supplementing and replacing semester-long study abroad programs, research has focused primarily on semester (long-term) programs. We draw on the theory of planned behavior (TPB) to explore factors that predict why students choose long-term and…

  14. REVEAL risk scores applied to riociguat-treated patients in PATENT-2: Impact of changes in risk score on survival.

    PubMed

    Benza, Raymond L; Farber, Harrison W; Frost, Adaani; Ghofrani, Hossein-Ardeschir; Gómez-Sánchez, Miguel A; Langleben, David; Rosenkranz, Stephan; Busse, Dennis; Meier, Christian; Nikkho, Sylvia; Hoeper, Marius M

    2018-04-01

    The Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL) risk score (RRS) calculator was developed using data derived from the REVEAL registry, and predicts survival in patients with pulmonary arterial hypertension (PAH) based on multiple patient characteristics. Herein we applied the RRS to a pivotal PAH trial database, the 12-week PATENT-1 and open-label PATENT-2 extension studies of riociguat. We examined the effect of riociguat vs placebo on RRS in PATENT-1, and investigated the prognostic implications of change in RRS during PATENT-1 on long-term outcomes in PATENT-2. RRS was calculated post hoc for baseline and Week 12 of PATENT-1, and Week 12 of PATENT-2. Patients were grouped into risk strata by RRS. Kaplan-Meier estimates were made for survival and clinical worsening-free survival in PATENT-2 to evaluate the relationship between RRS in PATENT-1 and long-term outcomes in PATENT-2. A total of 396 patients completed PATENT-1 and participated in PATENT-2. In PATENT-1, riociguat significantly improved RRS (p = 0.031) and risk stratum (p = 0.018) between baseline and Week 12 compared with placebo. RRS at baseline, and at PATENT-1 Week 12, and change in RRS during PATENT-1 were significantly associated with survival (hazard ratios for a 1-point reduction in RRS: 0.675, 0.705 and 0.804, respectively) and clinical worsening-free survival (hazard ratios of 0.736, 0.716 and 0.753, respectively) over 2 years in PATENT-2. RRS at baseline and Week 12, and change in RRS, were significant predictors of both survival and clinical worsening-free survival. These data support the long-term predictive value of the RRS in a controlled study population. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  15. Efficacy of Vismodegib (Erivedge) for Basal Cell Carcinoma Involving the Orbit and Periocular Area.

    PubMed

    Demirci, Hakan; Worden, Francis; Nelson, Christine C; Elner, Victor M; Kahana, Alon

    2015-01-01

    Evaluate the effectiveness of vismodegib in the management of basal cell carcinoma with orbital extension and/or extensive periocular involvement. Retrospective chart review of 6 consecutive patients with biopsy-proven orbital basal cell carcinoma and 2 additional patients with extensive periocular basal cell carcinoma who were treated with oral vismodegib (150 mg/day) was performed. Basal cell carcinoma extended in the orbit in 6 of 8 patients (involving orbital bones in 1 patient), and 2 of 8 patients had extensive periocular involvement (1 with basal cell nevus syndrome). Vismodegib therapy was the only treatment in 6 patients, off-label neoadjuvant in 1 patient, and adjuvant treatment in 1 patient. Orbital tumors in all 4 patients who received vismodegib as sole treatment showed partial response with a mean 83% shrinkage in tumor size after a median of 7 months of therapy. In the 2 patients receiving vismodegib as neoadjuvant or adjuvant therapies, there was complete response after a median of 7 months of therapy and no evidence of clinical recurrence after discontinuing therapy for a median of 15 months. The 2 patients with extensive periocular involvement experienced complete clinical response after a median 14 months of treatment. During treatment, the most common side effects were muscle spasm (75%) followed by alopecia (50%), dysgeusia (25%), dysosmia, and episodes of diarrhea and constipation (13%). Basal cell carcinoma with orbital extension and extensive periocular involvement responds to vismodegib therapy. The long-term prognosis remains unknown, and additional prospective studies are indicated.

  16. Stability of exotic annual grasses following restoration efforts in southern California coastal sage scrub

    Treesearch

    Robert D. Cox; Edith B. Allen

    2008-01-01

    Restoration of semi-arid shrub ecosystems often requires control of invasive grasses but the effects of these grass-control treatments on native and exotic forbs have not been investigated adequately to assess long-term stability. In southern California, coastal sage scrub (CSS) vegetation is one semi-arid shrub community that has been invaded extensively by both...

  17. Building an Evidence-Based Mental Health Program for Children with History of Early Adversity

    ERIC Educational Resources Information Center

    Kroupina, Maria; Vermeulen, Marlous; Moberg, Stephanie

    2015-01-01

    Adoption is a major intervention in a child's life, however internationally adopted (IA) children remain at risk for long-term neurodevelopmental and mental health issues due to the fact that most of them have a history of early adversity prior to their adoption. In the last 20 years, extensive research with this population has increased the…

  18. Fidelity of bats to forest sites revealed from mist-netting recaptures

    Treesearch

    Roger W. Perry

    2011-01-01

    Although site fidelity to permanent roost structures by bats is generally known, long-term fidelity to areas such as foraging or drinking sites is unknown. Furthermore, mist-net recaptures of bats over multiple years are rarely reported. Extensive mist-net surveys were conducted over the course of 8 y in the Ouachita National Forest of central Arkansas, United States...

  19. 76 FR 82320 - Extension of Public Scoping Period for the Draft Environmental Impact Statement for Adoption of a...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-30

    ... Management Plan for the Operation of Glen Canyon Dam AGENCY: Bureau of Reclamation and National Park Service... Impact Statement (EIS) for Adoption of a Long-term Experimental and Management Plan (LTEMP) for the Operation of Glen Canyon Dam to January 31, 2012. The Notice to Solicit Comments and Hold Public Scoping...

  20. Four Challenges of High-Needs Schools: Equipping Teacher Candidates to Deal with Less-than-Ideal Conditions

    ERIC Educational Resources Information Center

    Lederhouse, Jillian N.

    2008-01-01

    Although high-needs schools rarely provide extensive scaffolding for beginning educators, liberal arts colleges that are committed to the moral and intellectual development of teachers can serve a pivotal role in helping their candidates choose such schools and commit to serving in them for the long term. This article describes ways in which…

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