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Sample records for long-term enzyme replacement

  1. Murine mucopolysaccharidosis type VII: long term therapeutic effects of enzyme replacement and enzyme replacement followed by bone marrow transplantation.

    PubMed Central

    Sands, M S; Vogler, C; Torrey, A; Levy, B; Gwynn, B; Grubb, J; Sly, W S; Birkenmeier, E H

    1997-01-01

    We demonstrated previously that short term administration of recombinant beta-glucuronidase to newborn mice with mucopolysaccharidosis type VII reduced lysosomal storage in many tissues. Lysosomal storage accumulated gradually after cessation of enzyme replacement therapy. Mice alive at 1 yr of age had decreased bone deformities and less lysosomal storage in cortical neurons. Here we compare the effects of long term enzyme replacement initiated either at birth or at 6 wk of age, and of enzyme administration initiated at birth followed by syngeneic bone marrow transplantation (BMT) at 5 wk of age. Several mice from each treatment group lived to at least 1 yr of age. Liver and spleen samples had beta-glucuronidase levels ranging from 2.4 to 19.8% of normal and showed a parallel decrease in lysosomal storage. The combination of enzyme replacement therapy followed by BMT reduced lysosomal distension in meninges, corneal fibroblasts, and bone when compared with treatment with enzyme alone. Mice treated at birth had less lysosomal storage in some neurons of the brain and the skeletal dysplasia was less severe when compared to mice whose treatment was delayed until 6 wk of age. We conclude that both enzyme replacement alone and early enzyme replacement followed by BMT have long term positive effects on murine mucopolysaccharidosis type VII. In addition, treatment started at birth is far more effective than treatment initiated in young adults. PMID:9120003

  2. Modelling Gaucher disease progression: long-term enzyme replacement therapy reduces the incidence of splenectomy and bone complications

    PubMed Central

    2014-01-01

    Long-term complications and associated conditions of type 1 Gaucher Disease (GD) can include splenectomy, bone complications, pulmonary hypertension, Parkinson disease and malignancies. Enzyme replacement therapy (ERT) reverses cytopenia and reduces organomegaly. To study the effects of ERT on long-term complications and associated conditions, the course of Gaucher disease was modelled. The cohort consisted of all diagnosed GD patients in the Netherlands. Mutually exclusive disease states were defined as ‘asymptomatic’, ‘signs/symptoms’, ‘recovery’, ‘splenectomy’, ‘bone complication’, ‘multiple complications’ and ‘malignancy’. A natural history (NH) cohort was delineated based upon historical data on Dutch patients before ERT was available. Cumulative incidence curves were composed for progression from each disease state to the next. Two scenarios were applied for the ERT cohort: time to complications was calculated from A. start of ERT; B. entering the previous disease state. Median time for the development of signs and/or symptoms was 30.1 years (N = 73). In the NH cohort (N = 42), 9% had developed a bone complication after 10 years in the signs/symptoms phase, while 21% had undergone a splenectomy. In the ERT cohort (N = 29 (A), N = 28 (B)), 12% (A) or 4% (B) had developed a bone complication after 10 years in this phase and no patient was splenectomized. No patients in the NH cohort recovered, compared to 50% in the ERT cohort after 3.6 years (N = 28 (A)) or 22.4 years (N = 27 (B)) of treatment. Median time from a first to a second complication was 11 years in the NH cohort (N = 31), whereas 16 respectively 14 percent had developed a second complication after 10 years in the ERT cohort (N = 17, scenario A/B). Fourteen percent (scenario A/B) developed an associated malignancy after 10 years in the phase ‘multiple complications’ (N = 23). Associated malignancies occurred almost exclusively in advanced disease stages, therefore it

  3. Long-term outcome of enzyme-replacement therapy in advanced Fabry disease: evidence for disease progression towards serious complications

    PubMed Central

    Weidemann, F; Niemann, M; Störk, S; Breunig, F; Beer, M; Sommer, C; Herrmann, S; Ertl, G; Wanner, C

    2013-01-01

    Objective The long-term effects of enzyme-replacement therapy (ERT) in Fabry disease are unknown. Thus, the aim of this study was to determine whether ERT in patients with advanced Fabry disease affects progression towards ‘hard’ clinical end-points in comparison with the natural course of the disease. Methods A total of 40 patients with genetically proven Fabry disease (mean age 40 ± 9 years; n = 9 women) were treated prospectively with ERT for 6 years. In addition, 40 subjects from the Fabry Registry, matched for age, sex, chronic kidney disease stage and previous transient ischaemic attack (TIA), served as a comparison group. The main outcome was a composite of stroke, end-stage renal disease (ESRD) and death. Secondary outcomes included changes in myocardial left ventricular (LV) wall thickness and replacement fibrosis, change in glomerular filtration rate (GFR), new TIA and change in neuropathic pain. Results During a median follow-up of 6.0 years (bottom and top quartiles: 5.1, 7.2), 15 events occurred in 13 patients (n = 7 deaths, n = 4 cases of ESRD and n = 4 strokes). Sudden death occurred (n = 6) only in patients with documented ventricular tachycardia and myocardial replacement fibrosis. The annual progression of myocardial LV fibrosis in the entire cohort was 0.6 ± 0.7%. As a result, posterior end-diastolic wall thinning was observed (baseline, 13.2 ± 2.0 mm; follow-up, 11.4 ± 2.1 mm; P < 0.01). GFR decreased by 2.3 ± 4.6 mL min−1 per year. Three patients experienced a TIA. The major clinical symptom was neuropathic pain (n = 37), and this symptom improved in 25 patients. The event rate was not different between the ERT group and the untreated (natural history) group of the Fabry Registry. Conclusion Despite ERT, clinically meaningful events including sudden cardiac death continue to develop in patients with advanced Fabry disease. PMID:23586858

  4. Long-term effectiveness of agalsidase alfa enzyme replacement in Fabry disease: A Fabry Outcome Survey analysis

    PubMed Central

    Beck, Michael; Hughes, Derralynn; Kampmann, Christoph; Larroque, Sylvain; Mehta, Atul; Pintos-Morell, Guillem; Ramaswami, Uma; West, Michael; Wijatyk, Anna; Giugliani, Roberto

    2015-01-01

    Outcomes from 5 years of treatment with agalsidase alfa enzyme replacement therapy (ERT) for Fabry disease in patients enrolled in the Fabry Outcome Survey (FOS) were compared with published findings for untreated patients with Fabry disease. Data were extracted from FOS, a Shire-sponsored database, for comparison with data from three published studies. Outcomes evaluated were the annualized rate of change in estimated glomerular filtration rate (eGFR) and left ventricular mass indexed to height (LVMI) as well as time to and ages at a composite morbidity endpoint and at death. FOS data were extracted for 740 treated patients who were followed for a median of ~ 5 years. Compared with no treatment, patients treated with agalsidase alfa demonstrated slower decline in renal function and slower progression of left ventricular hypertrophy. Treated male patients with baseline eGFR < 60 mL/min/1.73 m2 had a mean (standard error of the mean [SEM]) annualized change in eGFR of − 2.86 (0.53) mL/min/1.73 m2/y compared with − 6.8 (1.5) in the published untreated cohort. The mean (SEM) rate of LVMI increase with treatment was 0.33 (0.10) g/m2.7/y in males and 0.48 (0.09) in females, compared with 4.07 (1.03) in untreated males and 2.31 (0.81) in untreated females. Morbidity occurred later in treated patients, with ~ 16% risk of a composite morbidity event (26% in males) after 24 months with ERT versus ~ 45% without treatment, with first events and deaths also occurring at older ages in patients administered ERT (e.g., estimated median survival in treated males was 77.5 years versus 60 years in untreated males). Findings from these retrospective comparisons of observational data and published literature support the long-term benefits of ERT with agalsidase alfa for Fabry disease in slowing the progression of renal impairment and cardiomyopathy. Treatment also appeared to delay the onset of morbidity and mortality. Interpretation of these findings should take into

  5. Long-term effectiveness of agalsidase alfa enzyme replacement in Fabry disease: A Fabry Outcome Survey analysis.

    PubMed

    Beck, Michael; Hughes, Derralynn; Kampmann, Christoph; Larroque, Sylvain; Mehta, Atul; Pintos-Morell, Guillem; Ramaswami, Uma; West, Michael; Wijatyk, Anna; Giugliani, Roberto

    2015-06-01

    Outcomes from 5 years of treatment with agalsidase alfa enzyme replacement therapy (ERT) for Fabry disease in patients enrolled in the Fabry Outcome Survey (FOS) were compared with published findings for untreated patients with Fabry disease. Data were extracted from FOS, a Shire-sponsored database, for comparison with data from three published studies. Outcomes evaluated were the annualized rate of change in estimated glomerular filtration rate (eGFR) and left ventricular mass indexed to height (LVMI) as well as time to and ages at a composite morbidity endpoint and at death. FOS data were extracted for 740 treated patients who were followed for a median of ~ 5 years. Compared with no treatment, patients treated with agalsidase alfa demonstrated slower decline in renal function and slower progression of left ventricular hypertrophy. Treated male patients with baseline eGFR < 60 mL/min/1.73 m(2) had a mean (standard error of the mean [SEM]) annualized change in eGFR of - 2.86 (0.53) mL/min/1.73 m(2)/y compared with - 6.8 (1.5) in the published untreated cohort. The mean (SEM) rate of LVMI increase with treatment was 0.33 (0.10) g/m(2.7)/y in males and 0.48 (0.09) in females, compared with 4.07 (1.03) in untreated males and 2.31 (0.81) in untreated females. Morbidity occurred later in treated patients, with ~ 16% risk of a composite morbidity event (26% in males) after 24 months with ERT versus ~ 45% without treatment, with first events and deaths also occurring at older ages in patients administered ERT (e.g., estimated median survival in treated males was 77.5 years versus 60 years in untreated males). Findings from these retrospective comparisons of observational data and published literature support the long-term benefits of ERT with agalsidase alfa for Fabry disease in slowing the progression of renal impairment and cardiomyopathy. Treatment also appeared to delay the onset of morbidity and mortality. Interpretation of these findings should take

  6. Velaglucerase alfa (VPRIV) enzyme replacement therapy in patients with Gaucher disease: Long-term data from phase III clinical trials.

    PubMed

    Hughes, Derralynn A; Gonzalez, Derlis E; Lukina, Elena A; Mehta, Atul; Kabra, Madhulika; Elstein, Deborah; Kisinovsky, Isaac; Giraldo, Pilar; Bavdekar, Ashish; Hangartner, Thomas N; Wang, Nan; Crombez, Eric; Zimran, Ari

    2015-07-01

    Type 1 Gaucher disease is an inherited lysosomal enzyme deficiency with variable age of symptom onset. Common presenting signs include thrombocytopenia, anemia, hepatosplenomegaly, bone abnormalities, and, additionally in children, growth failure. Fifty-seven patients aged 3-62 years at the baseline of two phase III trials for velaglucerase alfa treatment were enrolled in the single extension study. In the extension, they received every-other-week velaglucerase alfa intravenous infusions for 1.2-4.8 years at 60 U/kg, although 10 patients experienced dose reduction. No patient experienced a drug-related serious adverse event or withdrew due to an adverse event. One patient died following a convulsion that was reported as unrelated to the study drug. Only one patient tested positive for anti-velaglucerase alfa antibodies. Combining the experience of the initial phase III trials and the extension study, significant improvements were observed in the first 24 months from baseline in hematology variables, organ volumes, plasma biomarkers, and, in adults, the lumbar spine bone mineral density Z-score. Improvements were maintained over longer-term treatment. Velaglucerase alfa had a good long-term safety and tolerability profile, and patients continued to respond clinically, which is consistent with the results of the extension study to the phase I/II trial of velaglucerase alfa. EudraCT number 2008-001965-27; www.clinicaltrials.gov identifier NCT00635427.

  7. Velaglucerase alfa (VPRIV) enzyme replacement therapy in patients with Gaucher disease: Long-term data from phase III clinical trials

    PubMed Central

    Hughes, Derralynn A; Gonzalez, Derlis E; Lukina, Elena A; Mehta, Atul; Kabra, Madhulika; Elstein, Deborah; Kisinovsky, Isaac; Giraldo, Pilar; Bavdekar, Ashish; Hangartner, Thomas N; Wang, Nan; Crombez, Eric; Zimran, Ari

    2015-01-01

    Type 1 Gaucher disease is an inherited lysosomal enzyme deficiency with variable age of symptom onset. Common presenting signs include thrombocytopenia, anemia, hepatosplenomegaly, bone abnormalities, and, additionally in children, growth failure. Fifty-seven patients aged 3–62 years at the baseline of two phase III trials for velaglucerase alfa treatment were enrolled in the single extension study. In the extension, they received every-other-week velaglucerase alfa intravenous infusions for 1.2–4.8 years at 60 U/kg, although 10 patients experienced dose reduction. No patient experienced a drug-related serious adverse event or withdrew due to an adverse event. One patient died following a convulsion that was reported as unrelated to the study drug. Only one patient tested positive for anti-velaglucerase alfa antibodies. Combining the experience of the initial phase III trials and the extension study, significant improvements were observed in the first 24 months from baseline in hematology variables, organ volumes, plasma biomarkers, and, in adults, the lumbar spine bone mineral density Z-score. Improvements were maintained over longer-term treatment. Velaglucerase alfa had a good long-term safety and tolerability profile, and patients continued to respond clinically, which is consistent with the results of the extension study to the phase I/II trial of velaglucerase alfa. EudraCT number 2008-001965-27; http://www.clinicaltrials.gov identifier NCT00635427. Am. J. Hematol. 90:584–591, 2015. © 2015 Wiley Periodicals, Inc. PMID:25801797

  8. Targeted gene transfer into ependymal cells through intraventricular injection of AAV1 vector and long-term enzyme replacement via the CSF.

    PubMed

    Yamazaki, Yoshiyuki; Hirai, Yukihiko; Miyake, Koichi; Shimada, Takashi

    2014-07-01

    Enzyme replacement via the cerebrospinal fluid (CSF) has been shown to ameliorate neurological symptoms in model animals with neuropathic metabolic disorders. Gene therapy via the CSF offers a means to achieve a long-term sustainable supply of therapeutic proteins within the central nervous system (CNS) by setting up a continuous source of transgenic products. In the present study, a serotype 1 adeno-associated virus (AAV1) vector was injected into a lateral cerebral ventricle in adult mice to transduce the gene encoding human lysosomal enzyme arylsulfatase A (hASA) into the cells of the CNS. Widespread transduction and stable expression of hASA in the choroid plexus and ependymal cells was observed throughout the ventricles for more than 1 year after vector injection. Although humoral immunity to hASA developed after 6 weeks, which diminished the hASA levels detected in CSF from AAV1-injected mice, hASA levels in CSF were maintained for at least 12 weeks when the mice were tolerized to hASA prior of vector injection. Our results suggest that the cells lining the ventricles could potentially serve as a biological reservoir for long-term continuous secretion of lysosomal enzymes into the CSF following intracerebroventricular injection of an AAV1 vector.

  9. Oxidative and nitrative stress and pro-inflammatory cytokines in Mucopolysaccharidosis type II patients: effect of long-term enzyme replacement therapy and relation with glycosaminoglycan accumulation.

    PubMed

    Jacques, Carlos Eduardo Diaz; Donida, Bruna; Mescka, Caroline P; Rodrigues, Daiane G B; Marchetti, Desirèe P; Bitencourt, Fernanda H; Burin, Maira G; de Souza, Carolina F M; Giugliani, Roberto; Vargas, Carmen Regla

    2016-09-01

    Mucopolysaccharidosis type II (MPS II) is a lysosomal storage disease caused by a deficient activity of iduronate-2-sulfatase, leading to abnormal accumulation of glycosaminoglycans (GAG). The main treatment for MPS II is enzyme replacement therapy (ERT). Previous studies described potential benefits of six months of ERT against oxidative stress in patients. Thus, the aim of this study was to investigate oxidative, nitrative and inflammatory biomarkers in MPS II patients submitted to long term ERT. It were analyzed urine and blood samples from patients on ERT (mean time: 5.2years) and healthy controls. Patients presented increased levels of lipid peroxidation, assessed by urinary 15-F2t-isoprostane and plasmatic thiobarbituric acid-reactive substances. Concerning to protein damage, urinary di-tyrosine (di-Tyr) was increased in patients; however, sulfhydryl and carbonyl groups in plasma were not altered. It were also verified increased levels of urinary nitrate+nitrite and plasmatic nitric oxide (NO) in MPS II patients. Pro-inflammatory cytokines IL-1β and TNF-α were increased in treated patients. GAG levels were correlated to di-Tyr and nitrate+nitrite. Furthermore, IL-1β was positively correlated with TNF-α and NO. Contrastingly, we did not observed alterations in erythrocyte superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase activities, in reduced glutathione content and in the plasmatic antioxidant capacity. Although some parameters were still altered in MPS II patients, these results may suggest a protective role of long-term ERT against oxidative stress, especially upon oxidative damage to protein and enzymatic and non-enzymatic defenses. Moreover, the redox imbalance observed in treated patients seems to be GAG- and pro-inflammatory cytokine-related.

  10. Cognitive and adaptive functioning of children with infantile Pompe disease treated with enzyme replacement therapy: long-term follow-up.

    PubMed

    Spiridigliozzi, Gail A; Heller, James H; Kishnani, Priya S

    2012-02-15

    This report documents the long-term cognitive and adaptive outcome of children with infantile Pompe disease. Specifically, we describe the cognitive and adaptive functioning of seven children with classic infantile Pompe disease and two children with atypical infantile Pompe disease who have received enzyme replacement therapy (Myozyme®) for an average of 6 years, 8 months and 4 years, 1. 5 months, respectively. Multiple assessments of cognitive functioning were completed over time by means of individualized intelligence (IQ) testing. Adaptive functioning was measured by means of the Vineland Adaptive Behavior Scales-Second Edition (VABS-II). Consistent with our earlier findings regarding infants treated with ERT, children with classic infantile Pompe disease (ages 4 years, 11 months to 8 years, 11 months) were functioning at the lower end of the average range in comparison to their typical peers on their most recent IQ test. There was no evidence of a decline in their cognitive abilities over time. In contrast, the two children with atypical infantile Pompe disease (ages 5 years, 4 months and 5 years, 11 months) obtained above average IQ scores and demonstrated significant gains in IQ over time. For all children where adaptive functioning was assessed, their overall level of adaptive functioning on the VABS-II was lower than their Full Scale IQ scores on cognitive testing. Motor function appears to be an important factor impacting on reduced adaptive behavior. The implication of these findings on our understanding of a possible relationship between CNS status in children with Pompe and their adaptive and cognitive function is discussed.

  11. Progressive renal failure despite long-term biweekly enzyme replacement therapy in a patient with Fabry disease secondary to a new α-galactosidase mutation of Leu311Arg (L311R).

    PubMed

    Suzuki, Keisuke; Miura, Naoto; Kitagawa, Wataru; Suzuki, Shinkichi; Komatsuda, Atsushi; Nishikawa, Kazuhiro; Watanabe, Daisuke; Imai, Hirokazu

    2011-12-01

    A 37-year-old Japanese man affected by Fabry disease secondary to a novel mutation of Leu311Arg (L311R) in α-galactosidase demonstrated progressive renal failure despite biweekly enzyme replacement therapy (ERT) for approximately 10 years. Kidney biopsy revealed foamy glomerular epithelial cells, compatible with the typical pathologic features of Fabry disease. The patient entered a phase III study of Replagal (agalsidase alfa) in 2001, allowing him to continue ERT with biweekly dosing for almost 10 years. During 2 years of that period, he was continued on Fabrazyme (agalsidase beta) biweekly dosing. His estimated GFR was calculated to decrease by 9.9 mL/min/1.73 m(2) per year. Patients with Fabry disease have been reported to have a mean decrease in GFR of 12.2 ± 8.1 mL/min/1.73 m(2) per year. This result suggests that biweekly ERT is only mildly effective at preventing loss of kidney function.

  12. [Transformation of free radicals of gamma-irradiated enzymes during long-term storage].

    PubMed

    Ryl'tsev, V V; Virnik, R B; Dovbiĭ, E V; Filatov, V N

    1988-01-01

    The ESR method was used to study free radical processes occurring in gamma-irradiated enzymes upon their long-term storage (up to 4 years) both at room temperature and at 4 degrees C. Simultaneously, studied was the biological activity of gamma-irradiated enzymes subjected to a long-term storage. The immobilization of enzymes on dialdehyde cellulose or polycaproamine was shown to preserve their biological activity during the postirradiation storage.

  13. Comparable long-term results for porcine and pericardial prostheses after isolated aortic valve replacement

    PubMed Central

    Andreas, Martin; Wallner, Stephanie; Ruetzler, Kurt; Wiedemann, Dominik; Ehrlich, Marek; Heinze, Georg; Binder, Thomas; Moritz, Anton; Hiesmayr, Michael J.; Kocher, Alfred; Laufer, Guenther

    2015-01-01

    OBJECTIVES Outcome of aortic valve replacement may be influenced by the choice of bioprosthesis. Pericardial heart valves are described to have a favourable haemodynamic profile compared with porcine valves, although the clinical notability of this finding is still controversially debated. Herein, we compared the long-term results of two commonly implanted bioprosthesis at a single centre. METHODS All consecutive patients undergoing isolated aortic valve replacement with either a Carpentier-Edwards Magna pericardial prosthesis or a Medtronic Mosaic porcine prosthesis between 2002 and 2008 were analysed regarding preoperative characteristics, short- and long-term survival, valve-related complications and echocardiographic findings. RESULTS The Medtronic Mosaic was implanted in 163 patients and the Carpentier-Edwards Magna in 295 patients. The sizes of implanted valves were 22.4 ± 1.5 mm for the Mosaic and 21.8 ± 1.8 mm for the Magna (P = 0.001). The long-term survival rate was 76 and 56% after 5 and 10 years for the Medtronic Mosaic, which was comparable with the Carpentier-Edwards Magna (77 and 57%; P = 0.92). Overall long-term survival was comparable with an age- and sex-matched Austrian general population for both groups. Valve-related adverse events were similar between groups. The postoperative mean transvalvular gradient was significantly increased in the Mosaic group (24 ± 9 mmHg vs 17 ± 7 mmHg; P < 0.001). CONCLUSIONS Both types of aortic bioprostheses offer excellent results after isolated aortic valve replacement. Despite relevant differences in gradients, long-term survival was comparable with the expected normal survival for both bioprostheses. Patients with a porcine heart valve had a higher postoperative transvalvular gradient. PMID:25527170

  14. Long-term consequences of atrial fibrillation after aortic valve replacement.

    PubMed

    Kohno, Hiroki; Ueda, Hideki; Matsuura, Kaoru; Tamura, Yusaku; Watanabe, Michiko; Matsumiya, Goro

    2017-03-01

    Background Atrial fibrillation is a common complication after cardiac surgery, but the risk factors and long-term outcome after primary isolated aortic valve replacement remains to be clarified. Methods A single-center retrospective study was conducted on 157 patients who underwent first-time isolated aortic valve replacement between April 1999 and February 2015. Fifty-eight patients developed new-onset atrial fibrillation within 6 months postoperatively, and they were compared with patients who remained in sinus rhythm. Multivariate analyses, which incorporated the propensity score patient matching technique, were conducted to evaluate the long-term outcome of new-onset postoperative atrial fibrillation and identify patients at risk of developing this arrhythmia. Results At a mean follow-up of 52.4 months (range 8.4-200.7 months), mortality was significantly higher in patients who developed atrial fibrillation compared to those who remained in sinus rhythm (2.8%/patient-year vs. 0.2%/patient-year, respectively; p < 0.05). Patients developing atrial fibrillation were also at an independently increased risk of stroke and readmission during follow-up. Risk analysis revealed that advanced age (>70 years) and absence of a postoperative β-blocker were predictors of atrial fibrillation. Conclusions New-onset atrial fibrillation after first-time isolated aortic valve replacement correlated significantly with late morbidity and mortality. Advanced age and absence of a postoperative β-blocker may increase the incidence of atrial fibrillation.

  15. Regional analgesia for improvement of long-term functional outcome after elective large joint replacement

    PubMed Central

    Atchabahian, Arthur; Schwartz, Gary; Hall, Charles B; Lajam, Claudette M; Andreae, Michael H

    2015-01-01

    Background Regional analgesia is more effective than conventional analgesia for controlling pain and may facilitate rehabilitation after large joint replacement in the short term. It remains unclear if regional anaesthesia improves functional outcomes after joint replacement beyond three months after surgery. Objectives To assess the effects of regional anaesthesia and analgesia on long-term functional outcomes 3, 6 and 12 months after elective major joint (knee, shoulder and hip) replacement surgery. Search methods We performed an electronic search of several databases (CENTRAL, MEDLINE, EMBASE, CINAHL), and handsearched reference lists and conference abstracts. We updated our search in June 2015. Selection criteria We included randomized controlled trials (RCTs) comparing regional analgesia versus conventional analgesia in patients undergoing total shoulder, hip or knee replacement. We included studies that reported a functional outcome with a follow-up of at least three months after surgery. Data collection and analysis We used standard methodological procedures expected by Cochrane. We contacted study authors for additional information. Main results We included six studies with 350 participants followed for at least three months. All of these studies enrolled participants undergoing total knee replacement. Studies were at least partially blinded. Three studies had a high risk of performance bias and one a high risk of attrition bias, but the risk of bias was otherwise unclear or low. Only one study assessed joint function using a global score. Due to heterogeneity in outcome and reporting, we could only pool three out of six RCTs, with range of motion assessed at three months after surgery used as a surrogate for joint function. All studies had a high risk of detection bias. Using the random-effects model, there was no statistically significant difference between the experimental and control groups (mean difference 3.99 degrees, 95% confidence interval (CI)

  16. Total disc replacement in the cervical spine: a systematic review evaluating long-term safety

    PubMed Central

    Anderson, Paul A.; Hashimoto, Robin

    2012-01-01

    Study design: Systematic review. Clinical questions: What are the rates and causes of subsequent surgeries? What is the long-term complication rates following cervical artificial disc replacement (C-ADR)? How do these rates change over time? Methods: A systematic review was undertaken for articles published up to October 2011. Electronic databases and reference lists of key articles were searched to identify comparative and non-comparative studies reporting long-term (≥ 48 months) complications of C-ADR. Two independent reviewers assessed the strength of evidence using the GRADE criteria and disagreements were resolved by consensus. Results: Two RCTs reporting outcomes following C-ADR (Bryan disc, Prestige disc) versus anterior cervical discectomy and fusion (ACDF) at follow-ups of 4 to 5 years were found; five case series reporting outcomes following C-ADR at follow-ups of 4 to 8 years were identified. Secondary surgery rates were similar or slightly lower following C-ADR compared with fusion at 4 to 5 years postoperatively. In one small subset of an RCT, rates of adjacent disc heterotopic ossification were lower in C-ADR patients than in those treated with fusion. Rates of other adverse events were similar between treatment groups. Conclusions: There is low evidence on the long-term safety outcomes following C-ADR. Additional comparative studies with follow-up of at least 4 years are needed to fully understand the long-term safety outcomes of C-ADR compared with fusion. PMID:23236309

  17. Long-term hormone replacement therapy and risk of breast cancer in postmenopausal women.

    PubMed

    Newcomb, P A; Longnecker, M P; Storer, B E; Mittendorf, R; Baron, J; Clapp, R W; Bogdan, G; Willett, W C

    1995-10-15

    Despite extensive study, concerns remain about a possible association between long-term postmenopausal hormone treatment--particularly use of combination preparations--and risk of breast cancer. The authors evaluated the use of postmenopausal hormone replacement therapy in relation to breast cancer risk in a large multicenter, population-based case-control study. Women with a new diagnosis of breast cancer were identified through statewide tumor registries in Wisconsin, Massachusetts, Maine, and New Hampshire. Controls were randomly selected from population lists in each state. For this analysis of postmenopausal women, data were available from 3,130 breast cancer cases and 3,698 controls interviewed between 1989 and 1991. Replacement hormone use was not associated with breast cancer risk in women who had ever undergone this treatment (relative risk (RR) = 1.05, 95% confidence interval (CI) 0.93-1.18). Among women who had used replacement hormones for 15 years or more, there was no clear increase in risk, although the small sample size did not preclude the possibility of a modest association (RR = 1.11, 95% CI 0.87-1.43). Risk among women using progestins in combination with estrogens was similar to that in women using estrogens alone. Risk did not vary according to type of menopause, family history of breast cancer, history of benign breast disease, or alcohol intake. These results are consistent with the majority of reports which find no overall increased risk associated with the use of replacement hormones. However, in contrast to several other studies, this study did not find long-term use to be associated with increased risk. These results also do not support a hypothesized effect of combined progestin and estrogen use on the risk of breast cancer.

  18. Outcomes of long-term testosterone replacement in older hypogonadal males: a retrospective analysis.

    PubMed

    Hajjar, R R; Kaiser, F E; Morley, J E

    1997-11-01

    To determine the complications, toxicities, and compliance of long term testosterone replacement in hypogonadal males, we retrospectively assessed 45 elderly hypogonadal men receiving testosterone replacement therapy and 27 hypogonadal men taking testosterone. Hypogonadism was defined as a bioavailable testosterone serum concentration of 72 ng/dL or less. Both groups received baseline physical examinations and blood tests. The testosterone-treated group received 200 mg testosterone enanthate or cypionate im every 2 weeks, and follow-up examinations and blood samplings were performed every 3 months. The control group had a single follow-up blood test and physical examination. There was no significant difference in the initial blood tests in the two groups. At 2 yr follow-up, only the hematocrit showed a statistically significant increase in the testosterone-treated group compared to the control group (P < 0.001). A decrease in the urea nitrogen to creatinine ratio and an increase in the prostate-specific antigen concentration was not statistically significant. Eleven (24%) of the testosterone-treated subjects developed polycythemia sufficient to require phlebotomy or the temporary withholding of testosterone, one third of which occurred less than 1 yr after starting testosterone treatment. There was no significant difference in the incidence of new illness in the two groups during the 2-yr follow-up. Although self-assessment of libido was dramatically improved in the testosterone-treated group (P < 0.0001), approximately one third of the subjects discontinued therapy. In conclusion, testosterone replacement therapy appears to be well tolerated by over 84% of the subjects. Long term testosterone replacement to date appears to be a safe and effective means of treating hypogonadal elderly males, provided that frequent follow-up blood tests and examinations are performed.

  19. Stable and Continuous Long-term Enzymatic Reaction using an Enzyme-Nanofiber Composite

    SciTech Connect

    Lee, Jin Hyung; Hwang, Ee Taek; Kim, Byoung Chan; Lee, Sun Mi; Sang, Byoung-In; Choi, Yong Su; Kim, Jungbae; Gu, Man Bock

    2007-07-01

    This study shows the preparation and application of enzyme-nanofiber composites for long-term stable operation. The enzyme-nanofiber composite was prepared by coating an enzyme-aggregate, the esterase from Rhizopus oryzae, on the surface of the nanofibers. The activity and stability of the esterase-nanofiber composite was evaluated by measuring the production of p-nitrophenol from the hydrolysis of p-nitrophenyl butyrate. It was found that enzyme-nanofiber was very stable, even when the fibers were shaken in glasses, preserving 80 % of the initial activity for 100 days. In addition, the enzyme nanofiber composite was repeatedly used in 30 cycles of substrate hydrolysis and still remained active. Consequently, the esterase-nanofiber composite was finally employed to find its feasibility of long-term and stable continuous substrate hydrolysis reaction. In the sample reactor, the production of p-nitrophenol was consistent for 400 hr. Additionally, it was found that the production of p-nitrophenol proportionally decreased as the dilution rate was increased, showing the relationship between the efficiency of hydrolysis and the retention time within the reactor. This study demonstrates that the enzyme-nanofiber composite can be used in both repeated-batch and continuous modes for long-term stable operation.

  20. Manipulation under anaesthesia post total knee replacement: long term follow up.

    PubMed

    Yeoh, David; Nicolaou, Nick; Goddard, Richard; Willmott, Henry; Miles, Kim; East, Debra; Hinves, Barry; Shepperd, John; Butler-Manuel, Adrian

    2012-08-01

    A reduced range of motion post total knee replacement (TKR) is a recognised problem. Manipulation under anaesthesia (MUA) is commonly performed in the stiff post-operative TKR. Long-term results are variable in the literature. We retrospectively reviewed, prospectively collected data on 48 patients followed up since 1996 from one centre, over an average of 7.5 years, (range 1 to 10 years) and report on the long-term results. During the study period 2.3% of TKRs underwent MUA. The mean time to MUA post TKR was 12.3 weeks (range 3 to 48). Pre MUA, the mean flexion was 53°. The mean immediate passive flexion post MUA was 97°, an improvement of 44° (Range 10° to 90°, p<0.05). By 1year, the mean flexion was 87°, an improvement of 34°, (range -15° to 70°, p<0.05). At 10 years the mean flexion was 86°, (range 55° to 100°, p<0.05). We found no difference in the gain in range of motion (ROM) between knees manipulated before or after 12 weeks. Additionally, the gain was no different in stiff knees with a pre TKR ROM <90°, compared to a pre TKR ROM >90°. There were no complications as a result of MUA. However, one patient was eventually revised at 2 years secondary to low grade infection. Our findings show that MUA is a safe and effective method at improving the ROM in a stiff post-operative TKR. The improvement is maintained in the long term irrespective of time to MUA and range of motion pre TKR.

  1. Aortic valve replacement in the elderly. Risk factors and long-term results.

    PubMed Central

    Tseng, E E; Lee, C A; Cameron, D E; Stuart, R S; Greene, P S; Sussman, M S; Watkins, L; Gardner, T J; Baumgartner, W A

    1997-01-01

    OBJECTIVE: The current study was undertaken to determine long-term results of aortic valve replacement (AVR) in the elderly, to ascertain predictors of poor outcome, and to assess quality of life. SUMMARY BACKGROUND DATA: Aortic valve replacement is the procedure of choice for elderly patients with aortic valve disease. The number of patients aged 70 and older requiring AVR continues to increase. However, controversy exists as to whether surgery devoted to this subset reflect a cost-effective approach to attaining a meaningful quality of life. METHODS: This study reviews data on 247 patients aged 70 to 89 years who underwent isolated AVR between 1980 and 1995; there were 126 men (51%) and 121 women (49%). Follow-up was 97% complete (239/247 patients) for a total of 974.9 patient-years. Mean age was 76.2 +/- 4.8 years. Operative mortality and actuarial survival were determined. Patient age, gender, symptoms, associated diseases, prior conditions, New York Health Association class congestive heart failure, native valve disease, prosthetic valve type, preoperative catheterization data, and early postoperative conditions were analyzed as possible predictors of outcome. Functional recovery was evaluated using the SF-36 quality assessment tool. RESULTS: Operative mortality was 6.1% (15/247). Multivariate logistic regression showed that poor left ventricular function and preoperative pacemaker insertion were independent predictors of early mortality. After surgery, infection was predictive of early mortality. Overall actuarial survival at 1, 5, and 10 years was 89.5 +/- 2% (198 patients at risk), 69.3 +/- 3.4% (89 patients at risk), and 41.2 +/- 6% (13 patients at risk), respectively. Cox proportional hazards model showed that chronic obstructive pulmonary disease and urgency of operation were independent predictors of poor long-term survival. Postoperative renal failure also was predictive of poor outcome. Using the SF-36 quality assessment tool, elderly patients who

  2. Long-Term Behavior of Simulated Partial Lead Service Line Replacements

    PubMed Central

    St. Clair, Justin; Cartier, Clement; Triantafyllidou, Simoni; Clark, Brandi; Edwards, Marc

    2016-01-01

    Abstract In this 48-month pilot study, long-term impacts of copper:lead galvanic connections on lead release to water were assessed without confounding differences in pipe exposure prehistory or disturbances arising from cutting lead pipe. Lead release was tracked from three lead service line configurations, including (1) 100% lead, (2) traditional partial replacement with 50% copper upstream of 50% lead, and (3) 50% lead upstream of 50% copper as a function of flow rate, connection types, and sampling methodologies. Elevated lead from galvanic corrosion worsened with time, with 140% more lead release from configurations representing traditional partial replacement configurations at 14 months compared to earlier data in the first 8 months. Even when sampled consistently at moderate flow rate (8 LPM) and collecting all water passing through service lines, conditions representing traditional partial service line configurations were significantly worse (≈40%) when compared to 100% lead pipe. If sampled at a high flow rate (32 LPM) and collecting 2 L samples from service lines, 100% of samples collected from traditional partial replacement configurations exceeded thresholds posing an acute health risk versus a 0% risk for samples from 100% lead pipe. Temporary removal of lead accumulations near Pb:Cu junctions and lead deposits from other downstream plastic pipes reduced risk of partial replacements relative to that observed for 100% lead. When typical brass compression couplings were used to connect prepassivated lead pipes, lead release spiked up to 10 times higher, confirming prior concerns raised at bench and field scale regarding adverse impacts of crevices and service line disturbances on lead release. To quantify semirandom particulate lead release from service lines in future research, whole-house filters have many advantages compared to other approaches. PMID:26989344

  3. Damage evolution in acetabular replacements under long-term physiological loading conditions.

    PubMed

    Wang, J-Y; Heaton-Adegbile, P; New, A; Hussell, J G; Tong, J

    2009-05-29

    Damage development in cemented acetabular replacements has been studied in bovine pelvic bones under long-term physiological loading conditions, including normal walking, stair climbing and a combined block loading with representative routine activities. The physiological loading conditions were achieved using a specially designed hip simulator for fixation endurance testing. Damage was detected and monitored using micro-CT scanning at regular intervals of the experiments, and verified by microscopic studies post testing. The results show that debonding at the bone-cement interface defined the failure of cement fixation in all cases, and debondings initiated near the dome of the acetabulum in the superior-posterior quadrant, consistent with the high-stress region identified from the finite element analysis of implanted acetabular models Zant, N.P., Heaton-Adegbile, P., Hussell, J.G., Tong, J., 2008b. In-vitro fatigue failure of cemented acetabular replacements-a hip simulator study. Journal of Biomechanical Engineering, Transactions of the ASME, 130, 021019-1-9]; [Tong, J., Zant, N.P., Wang, J-Y., Heaton-Adegbile, P., Hussell, J.G., 2008. Fatigue in cemented acetabulum. International Journal of Fatigue, 30(8), 1366-1375].

  4. A long-term efficacy study of gene replacement therapy for RPGR-associated retinal degeneration

    PubMed Central

    Wu, Zhijian; Hiriyanna, Suja; Qian, Haohua; Mookherjee, Suddhasil; Campos, Maria M.; Gao, Chun; Fariss, Robert; Sieving, Paul A.; Li, Tiansen; Colosi, Peter; Swaroop, Anand

    2015-01-01

    Mutations in the retinitis pigmentosa GTPase regulator (RPGR) gene account for >70% of X-linked retinitis pigmentosa (XLRP) and 15–20% of all inherited retinal degeneration. Gene replacement therapy for RPGR-XLRP was hampered by the relatively slow disease progression in mouse models and by difficulties in cloning the full-length RPGR-ORF15 cDNA that includes a purine-rich 3′-coding region; however, its effectiveness has recently been demonstrated in four dogs with RPGR mutations. To advance the therapy to clinical stage, we generated new stable vectors in AAV8 or AAV9 carrying mouse and human full-length RPGR-ORF15-coding sequence and conducted a comprehensive long-term dose-efficacy study in Rpgr-knockout mice. After validating their ability to produce full-length proteins that localize to photoreceptor connecting cilia, we evaluated various vector doses in mice during a 2-year study. We demonstrate that eyes treated with a single injection of mouse or human RPGR-ORF15 vector at an optimal dose maintained the expression of RPGR-ORF15 throughout the study duration and exhibited higher electroretinogram amplitude, thicker photoreceptor layer and better targeting of opsins to outer segments compared with sham-treated eyes. Furthermore, mice that received treatment at an advanced age also showed remarkable preservation of retinal structure and function. Retinal toxicity was observed at high vector doses, highlighting the importance of careful dose optimization in future clinical experiments. Our long-term dose-efficacy study should facilitate the design of human trials with human RPGR-ORF15 vector as a clinical candidate. PMID:25877300

  5. [Long-term results of conventional aortic valve replacement for small aortic annulus].

    PubMed

    Miura, Y; Miyairi, T; Kitamura, T; Kigawa, I; Fukuda, S

    2006-04-01

    We studied cardiac function, clinical outcome and quality of life (QOL) long after aortic valve replacement for pure aortic stenosis. Forty-four patients in small group [St. Jude Medical (SJM) 17 HP, 19 A], and 69 patients in non-small group (19 HP, 21 A, 23 A) operated on from 1984 to 2004 were enrolled in this study. We assessed the clinical data, aortic pressure gradient, left ventricular mass index (LVMI), and ejection fraction (EF) by preoperative and postoperative echocardiography. Moreover to evaluate QOL after the operation, we performed SF-36 used for the evaluation of health and QOL worldwide. Mean follow-up is 7.1 +/- 4.8 years in small group, and 6.8 +/- 4.6 years in non-small group. There were 2 hospital deaths in small group, and 1 in non-small group. The actual survival rate at 10-year were 89.2% in small group, and 85.6% in non-small group. There was no significant difference in hospital mortality, LVMI, long-term survival rate, and the scores of SF-36 between the 2 groups. The use of small sized prosthetic valves in patients with small aortic annulus might be justified when there is no patient-prosthesis mismatch.

  6. The appearance of newly identified intraocular lesions in Gaucher disease type 3 despite long-term glucocerebrosidase replacement therapy

    PubMed Central

    Sawicka-Gutaj, Nadia; Machaczka, Maciej; Kulińska-Niedziela, Izabela; Bernardczyk-Meller, Jadwiga; Gutaj, Paweł; Sowiński, Jerzy; Ruchała, Marek

    2016-01-01

    Background Gaucher disease (GD) is an autosomal recessive lipid storage disorder caused by the deficient activity of the lysosomal enzyme glucocerebrosidase. The presence of central nervous system disease is a hallmark of the neuronopathic forms of GD (types 2 and 3). Intraocular lesions (e.g. corneal clouding, retinal lesions, and vitreous opacities) have been infrequently reported in GD type 3 (GD3). Moreover, there are virtually no published data on the occurrence and natural course of intraocular lesions in GD3 patients treated with enzyme replacement therapy (ERT). Case presentation We describe the case of a 26-year-old Polish male with L444P homozygous GD3 (mutation c.1448T > C in the GBA1 gene) who developed fundus lesions despite 10 years of ERT. At the age of 23 years, a spectral domain optical coherence tomography (OCT) examination was performed which disclosed the presence of discrete lesions located preretinally, intraretinally in the nerve fiber layer, and in the vitreous body. A 3-year follow-up OCT examination has not shown any significant progression of the fundus lesions. Conclusions To the best of our knowledge, this is the first published report describing the occurrence of newly identified retinal and preretinal lesions occurring during long-term ERT in GD3. We recommend that a careful ophthalmic assessment, including a dilated fundus examination, should be included as part of annual follow-up in patients with GD3. Further studies are needed to understand the nature and clinical course of these changes and whether or not these intraocular findings have any predictive value in the context of neurologic and skeletal progression in GD3. PMID:27064303

  7. Deleterious effects of glucocorticoid replacement on bone in women after long-term remission of Cushing's syndrome.

    PubMed

    Barahona, Maria-José; Sucunza, Nuria; Resmini, Eugenia; Fernández-Real, Jose-Manuel; Ricart, Wifredo; Moreno-Navarrete, Jose-Maria; Puig, Teresa; Wägner, Ana M; Rodriguez-Espinosa, José; Farrerons, Jordi; Webb, Susan M

    2009-11-01

    Endogenous hypercortisolism and high-dose and long-term glucocorticoid (GC) therapy reduce bone mass. Patients in remission after successful treatment of Cushing's syndrome (CS) often present hypoadrenalism and require long-term GC replacement. The aim of our study was to evaluate whether this GC "replacement" had any further effect on bone in women after long-term remission of CS. Thirty-seven women (mean age: 50 +/- 14 yr; 27 of pituitary and 10 of adrenal origin) with cured CS (mean time of cure: 11 +/- 6 yr), 14 with active CS, and 85 sex-, body mass index (BMI)-, and age-matched controls were enrolled. BMD and BMC were measured by DXA scanning. Bone biochemical markers were also measured. Duration and dose of GC replacement and duration of endogenous hypercortisolism were calculated. Cured and active CS patients had less BMC, BMD, and osteocalcin than controls (p < 0.01). These differences were observed in estrogen-sufficient women but not in those with estrogen deficiency. Duration of GC treatment (mean: 42 mo; range, 2-420 mo) and endogenous hypercortisolism (mean: 70 mo; range, 13-241 mo) negatively correlated with BMC and lumbar spine BMD. After regression analysis, the main predictor of abnormal BMC and BMD was the duration of GC replacement (p < 0.01). Patients treated for CS persistently have less bone mass despite long-term cure. Both duration of endogenous hypercortisolism and mainly exogenous "replacement" therapy with GC negatively affect bone mass. Thus, the additional deleterious effect of GC for the treatment of adrenal axis suppression should be considered.

  8. Repair or Replacement for Isolated Tricuspid Valve Pathology? Insights from a Surgical Analysis on Long-Term Survival

    PubMed Central

    Farag, Mina; Arif, Rawa; Sabashnikov, Anton; Zeriouh, Mohamed; Popov, Aron-Frederik; Ruhparwar, Arjang; Schmack, Bastian; Dohmen, Pascal M.; Szabó, Gábor; Karck, Matthias; Weymann, Alexander

    2017-01-01

    Background Long-term follow-up data concerning isolated tricuspid valve pathology after replacement or reconstruction is limited. Current American Heart Association guidelines equally recommend repair and replacement when surgical intervention is indicated. Our aim was to investigate and compare operative mortality and long-term survival in patients undergoing isolated tricuspid valve repair surgery versus replacement. Material/Methods Between 1995 and 2011, 109 consecutive patients underwent surgical correction of tricuspid valve pathology at our institution for varying structural pathologies. A total of 41 (37.6%) patients underwent tricuspid annuloplasty/repair (TAP) with or without ring implantation, while 68 (62.3%) patients received tricuspid valve replacement (TVR) of whom 36 (53%) were mechanical and 32 (47%) were biological prostheses. Results Early survival at 30 days after surgery was 97.6% in the TAP group and 91.1% in the TVR group. After 6 months, 89.1% in the TAP group and 87.8% in the TVR group were alive. In terms of long-term survival, there was no further mortality observed after one year post surgery in both groups (Log Rank p=0.919, Breslow p=0.834, Tarone-Ware p=0.880) in the Kaplan-Meier Survival analysis. The 1-, 5-, and 8-year survival rates were 85.8% for TAP and 87.8% for TVR group. Conclusions Surgical repair of the tricuspid valve does not show survival benefit when compared to replacement. Hence valve replacement should be considered generously in patients with reasonable suspicion that regurgitation after repair will reoccur. PMID:28236633

  9. Lunate silicone replacement arthroplasty in Kienböck's disease: a long-term follow-up.

    PubMed

    Alexander, A H; Turner, M A; Alexander, C E; Lichtman, D M

    1990-05-01

    We report a long-term follow-up (average, 5 years) of 10 patients who had lunate silicone replacement arthroplasty for treatment of Kienböck's disease. Clinical results were assessed on relief of pain, return to normal occupation, and range of motion. At 18- to 20-months follow-up, eight patients had satisfactory results, whereas at final follow-up only five of the patients had satisfactory results. Three of five patients with radiographs averaging 57 months after operation had evidence of particulate synovitis. Contrary to our previous publications on silicone replacement arthroplasty, it was concluded that the success rate for silicone replacement arthroplasty and the incidence of particulate synovitis do not warrant the continued use of silicone replacement arthroplasty as a primary treatment modality for Kienböck's disease.

  10. Implantable left ventricular assist devices: an evolving long-term cardiac replacement therapy.

    PubMed Central

    DeRose, J J; Argenziano, M; Sun, B C; Reemtsma, K; Oz, M C; Rose, E A

    1997-01-01

    OBJECTIVE: The authors' 8-year experience with both inpatient and outpatient left ventricular assist device (LVAD) support is presented to show the possibilities and limitations of long-term outpatient mechanical circulatory assistance. SUMMARY BACKGROUND DATA: The limitation of suitable cardiac donors has led to the use of LVADs as a temporizing measure for patients awaiting cardiac transplantation. The success of such devices in the short and medium term as a bridge to transplantation has led to their evaluation as a long-term destination therapy for end-stage heart disease. METHODS: Between August 1990 and February 1997, 85 patients with end-stage heart disease underwent insertion of implantable LVADs. Fifty-two patients underwent pneumatic device insertion and 32 patients received a vented electric device. RESULTS: Patients were supported for a mean of 109+/-13 days for an overall survival to transplant (54) or explant (3) of 73%. Nineteen patients were discharged from the hospital on a mean of postoperative day 41+/-4 (range, 17-68) for an outpatient support time of 108+/-30 days (range, 2-466). Of 12 patients supported after postcardiotomy cardiogenic shock, 10 (82%) survived to hospital discharge. Perioperative right ventricular failure was treated in most patients with inotropic agents and inhaled nitric oxide with only six patients requiring right ventricular assist device support. Thromboembolic rate was low (0.016 events/patient-month) despite minimal or no anticoagulation in all cases. CONCLUSIONS: Left ventricular assist device support has evolved to become an outpatient therapy with excellent survival rates and an acceptable morbidity. Accordingly, wearable LVADs should be studied as permanent treatment options for patients who are not transplant candidates. Images Figure 2. PMID:9351714

  11. Metallosis with pseudotumour formation: Long-term complication following cementless total hip replacement in a dog

    PubMed Central

    Volstad, Nicola J.; Schaefer, Susan L.; Snyder, Laura A.; Meinen, Jeffrey B.; Sample, Susannah J.

    2017-01-01

    Summary Case description A 10-year-old female Belgian Teruven dog was presented to our clinic for total hip revision following a diagnosis of implant (cup) failure with metallosis and abdominal pseudotumour formation. The patient had a cementless metal-on-polyethylene total hip replacement performed nine years prior to presentation. Clinical findings The clinical findings, including pseudotumour formation locally and at sites distant from the implant and pain associated with the joint replacement, were similar to those described in human patients with this condition. Histopathological, surgical, and radiographic findings additionally supported the diagnosis of metallosis and pseudotumour formation. Treatment and outcome Distant site pseudo tumours were surgically removed and the total hip replacement was explanted due to poor bone quality. The patient recovered uneventfully and has since resumed normal activity. Conclusion In veterinary patients with metal-on-polyethylene total hip implants, cup failure leading to metallosis and pseudotumour formation should be considered as a potential cause of ipsilateral hindlimb lameness, intra-pelvic abdominal tumours, or a combination of both. These clinical findings may occur years after total hip replacement surgery. PMID:27189390

  12. Short- and Long-Term Mortality Rates of Elderly Acute Kidney Injury Patients Who Underwent Continuous Renal Replacement Therapy

    PubMed Central

    Rhee, Harin; Jang, Keum Sook; Park, Jong Man; Kang, Jin Suk; Hwang, Na Kyoung; Kim, Il Young; Song, Sang Heon; Seong, Eun Young; Lee, Dong Won; Lee, Soo Bong; Kwak, Ihm Soo

    2016-01-01

    Background The world’s population is aging faster and the incidence of acute kidney injury (AKI) needing continuous renal replacement therapy (CRRT) is increasing in elderly population. The outcome of AKI needing CRRT in elderly patients is known to be poor. However, the definitions of elderly used in the previous literatures were diverse and, there were few data that compared the long-term mortality rates of these patients with middle aged patients. This study was aimed to evaluate this issue. Methods This study was a single-center, retrospective cohort study of patients who underwent CRRT from January 2013 to December 2015. The patients were divided into the following four age cohorts: middle-aged (55–64), young-old (65–74), middle-old (75–84), and old-old (≥85). The short- and long-term mortality rates for each age cohort were compared. Results A total of 562 patients met the inclusion criteria. The short-term mortality rate was 57.3% in the entire cohort. Compared with the middle-aged cohort, the middle-old cohort (HR 1.48 (1.09–2.02), p = 0.012) and the old-old cohort (HR 2.33 (1.30–4.19), p = 0.005) showed an increased short-term mortality rate along with an increased SOFA score, acidemia and a prolonged prothrombin time. When we analyzed the long-term mortality rate of the 238 survived patients, the middle-old cohort (HR 3.76 (1.84–7.68), p<0.001), the old-old cohort (HR 4.40(1.20–16.10), p = 0.025), a lower BMI, the presence of liver cirrhosis, the presence of congestive heart failure and a history of sepsis were independent risk factors for the prediction of long-term mortality. Conclusion Compared with the middle-aged cohort, the middle-old and the old-old cohort showed an increased short-term and long-term mortality rate. However, in the young-old cohort, neither the short-term nor the long-term mortality rate was increased. PMID:27875571

  13. Impact on lipoprotein profile after long-term testosterone replacement in hypogonadal men.

    PubMed

    Berg, G; Schreier, L; Geloso, G; Otero, P; Nagelberg, A; Levalle, O

    2002-02-01

    Testosterone serum levels may influence the lipoprotein metabolism and possibly atherogenic risk. Our aim was to investigate the effects of long-term testosterone supplementation in hypogonadal men on multiple lipoprotein markers. 18 Hypogonadal men were studied before and after 3, 6, and 18 (n = 7) months of treatment with testosterone enanthate. During treatment, serum testosterone and estradiol increased, reaching normal levels (p < 0.0001 and 0.003, respectively). This was associated with a decrease in HDL cholesterol (from 1.40 +/- 0.10 mmol/l to 1.22 +/- 0.08 mmol/l, p < 0.001) after six months at the expense of HDL2 cholesterol (p < 0.01), as well as apoprotein A1 (from 139 +/- 3.4 mg/dl to 126 +/- 3.0 mg/dl, p < 0.005). Hepatic lipase activity increased (p < 0.05) and correlated positively with testosterone (r = 0.56, p < 0.02) and negatively with HDL cholesterol (r = - 0.58, p < 0.02). Total and LDL cholesterol, triglycerides, and apoprotein B did not increase. Among the seven patients who completed 18 months of treatment, triglycerides, total cholesterol, LDL and HDL cholesterol, as well as total cholesterol/HDL cholesterol ratio values did not differ from baseline while apoprotein A1 (p < 0.03) and HDL cholesterol (p < 0.015) remained decreased and hepatic lipase unchanged. Restoration of testosterone levels in hypogonadal men in this study did not reveal unfavorable changes based on total cholesterol/HDL cholesterol and LDL cholesterol/apoprotein B ratios, which are both atherogenic risk markers. Whether the changes in light of lipoprotein metabolism will adversely influence cardiovascular risk over time remains to be determined.

  14. Long-term review of fascial replacement after excision of the carpal lunate bone.

    PubMed

    Carroll, R E

    1997-09-01

    Excision of the carpal lunate bone in Kienbock's avascular necrosis gives relief of pain. To maintain grip strength, increase range of motion, and prevent carpal collapse or shifting, this space has been filled with various materials. Forty-three patients received fascial interposition replacement, and the experience and results of 10 patients observed for 10 years or more (range, 10-34) are presented. Pain was relieved. Range of motion was increased. Carpal collapse did not occur. All patients use their hand in an unrestricted, stressful activity. The result of an operation during an extended period is documented.

  15. [Long-term intermittent renal replacement therapy at an intensive care unit].

    PubMed

    Bellomo, R; Baldwin, I; Toshio, N; Wan, L; Fealy, N; Ronco, C

    2005-01-01

    Standard intermittent hemodialysis (IHD) used for the treatment of acute renal failure (ARF) at an intensive care unit has significant biochemical and physiological drawbacks. In the past 20 years, these drawbacks have stimulated the development of continuous renal replacement therapy (CRRT) and its ever-increasing use. However, CRRT is technically complicated and requires 24-hour monitoring. In some clinics, the use of CRRT leads to that each patient is under his/her nurse's surveillance, instead 1 nurse per 2 patients as before; this change has economic consequences and may limit nursing accessibility to other patients. The procedures prolonging intermittent therapy do not require 24-hour monitoring may benefit the treatment of ARF at the intensive care therapy. In this paper the authors call such procedures for continuous intermittent renal replacement therapy. They are characterized by a number of basic principles: (1) the use of modified or standard dialysis apparatuses; (2) the application of diffuse, convection, or both; (3) a certain reduction in the rate of elimination of dissolved substances as compared with IHD; (4) more prolonged treatment: above usual 3 or 4 hours of IHD, but not more than 8-12 hours (hence the term "intermittent"); (5) the use of on-line generation dialysate or substituting fluid. Information on the effectiveness and safety of this procedure is being now compiled.

  16. Effects of long-term estrogen replacement therapy on bone turnover in periarticular tibial osteophytes in surgically postmenopausal cynomolgus monkeys.

    PubMed

    Olson, Erik J; Lindgren, Bruce R; Carlson, Cathy S

    2008-05-01

    The aims of the present study were to assess the effects of long-term estrogen replacement therapy (ERT) on size and indices of bone turnover in periarticular osteophytes in ovariectomized cynomolgus monkeys and to compare dynamic indices of bone turnover in osteophyte bone with those of subchondral bone (SCB) and epiphyseal/metaphyseal cancellous (EMC) bone. One hundred sixty-five adult female cynomolgus macaques were bilaterally ovariectomized and randomly divided into three age- and weight-matched treatment groups for a 36-month treatment period. Group 1 (OVX control) received no treatment, Group 2 (SPE) received soy phytoestrogens, and Group 3 (ERT) received conjugated equine estrogens in the diet; all monkeys were labeled with calcein before necropsy. A midcoronal, plastic-embedded section of the right proximal tibia from 20 randomly selected animals per treatment group was examined histologically. Forty-nine of the sections (OVX control, n=16; SPE, n=16; ERT, n=17) contained lateral abaxial osteophytes, and static and dynamic histomorphometry measurements were taken from osteophyte bone, SCB from the lateral tibial plateau, and EMC bone. Data were analyzed using the ANOVA and Kruskal-Wallis test, correlation and regression methods, and the Friedman and Wilcoxon signed rank test. There was no significant effect of long-term ERT on osteophyte area or on any static or dynamic histomorphometry parameters. The bone volume, trabecular number, and trabecular thickness in osteophyte bone were considerably higher than in EMC bone; whereas, trabecular separation was considerably lower in osteophyte bone. In all three treatment groups, BS/BV was significantly lower in osteophyte bone vs. EMC bone and significantly higher in osteophyte bone vs. lateral SCB. We conclude that osteophyte area and static and dynamic histomorphometry parameters within periarticular tibial osteophytes in ovariectomized cynomolgus monkeys are not significantly influenced by long-term ERT, but

  17. Estrogen metabolism genotypes, use of long-term hormone replacement therapy and risk of postmenopausal breast cancer.

    PubMed

    Cerne, Jasmina Ziva; Novakovic, Srdjan; Frkovic-Grazio, Snjezana; Pohar-Perme, Maja; Stegel, Vida; Gersak, Ksenija

    2011-08-01

    Association between long-term hormone replacement therapy (HRT) use and increased risk of breast cancer is still under debate. Functionally relevant genetic variants within the estrogen metabolic pathway may alter exposure to exogenous sex hormones and affect the risk of postmenopausal breast cancer. We investigated the associations of common polymorphisms in 4 genes encoding key proteins of the estrogen metabolic pathway, duration of HRT use and their interactions with breast cancer risk. We studied 530 breast cancer cases and 270 controls of the same age and ethnicity participating in a case-control study of postmenopausal women. Duration of HRT use was ascertained through a postal questionnaire. Genotyping was conducted for CYP1B1 (rs1056836), COMT (rs4680), GSTP1 (rs1695) and MnSOD (rs4880) polymorphisms by PCR-based RFLP and TaqMan® allelic discrimination method. Adjusted odds ratios and 95% confidence intervals were calculated using logistic regression analysis. HRT use was significantly associated with decreased breast cancer risk (p<0.001). None of the polymorphisms studied was associated with breast cancer risk. A significant interaction was observed between MnSOD 47T>C and HRT use (pinteraction=0.036); the risk of breast cancer associated with long-term vs. short-term HRT use was decreased in women homozygous for the wild-type allele and increased in women with at least one variant allele of the MnSOD 47T>C polymorphism. Our results suggest that MnSOD 47T>C polymorphism in interaction with long-term HRT use may modify the risk of breast cancer.

  18. Replacement of the ureter by an ileal loop. Quantitative aspects of long-term morphological alterations in minipigs.

    PubMed Central

    Pabst, R.; Kamran, D.

    1983-01-01

    In minipigs 1 ureter was replaced by a loop of the terminal ileum and the contralateral kidney removed. After 2.5 to 3 years the morphology of the replaced ureter was compared with the normal ileum. Independent of the 3 different operative techniques used, in about half of the pigs there was loss or flattening of the villi. In the other pigs the morphometrically determined number of intraepithelial lymphocytes, the cell density in the lamina propria and the length of the villi did not differ significantly compared with the normal ileum. There was no increase in goblet cells in the crypts. The transitional epithelium covered only a short distance at the anastomotic junctions. Peyer's patches of normal age-related size were found in the replaced ureter. Despite the long-term contact with urine instead of gut contents, in many pigs a normal amount of lymphocytes remained in the "ileal ureter". Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 PMID:6882677

  19. Effect of long-term industrial waste effluent pollution on soil enzyme activities and bacterial community composition.

    PubMed

    Subrahmanyam, Gangavarapu; Shen, Ju-Pei; Liu, Yu-Rong; Archana, Gattupalli; Zhang, Li-Mei

    2016-02-01

    Although numerous studies have addressed the influence of exogenous pollutants on microorganisms, the effect of long-term industrial waste effluent (IWE) pollution on the activity and diversity of soil bacteria was still unclear. Three soil samples characterized as uncontaminated (R1), moderately contaminated (R2), and highly contaminated (R3) receiving mixed organic and heavy metal pollutants for more than 20 years through IWE were collected along the Mahi River basin, Gujarat, western India. Basal soil respiration and in situ enzyme activities indicated an apparent deleterious effect of IWE on microbial activity and soil function. Community composition profiling of soil bacteria using 16S rRNA gene amplification and denaturing gradient gel electrophoresis (DGGE) method indicated an apparent bacterial community shift in the IWE-affected soils. Cloning and sequencing of DGGE bands revealed that the dominated bacterial phyla in polluted soil were affiliated with Firmicutes, Acidobacteria, and Actinobacteria, indicating that these bacterial phyla may have a high tolerance to pollutants. We suggested that specific bacterial phyla along with soil enzyme activities could be used as relevant biological indicators for long-term pollution assessment on soil quality. Graphical Abstract Bacterial community profiling and soil enzyme activities in long-term industrial waste effluent polluted soils.

  20. Long-term in vitro culture of bovine preantral follicles: Effect of base medium and medium replacement methods.

    PubMed

    Araújo, V R; Gastal, M O; Wischral, A; Figueiredo, J R; Gastal, E L

    2015-10-01

    Two culture media and replacement methods were compared during long-term in vitro culture of secondary follicles of cattle using α-MEM(+) or TCM-199(+) as base media. The medium replacement methods were: Conventional - removal and subsequent addition of the same amount (60μl) in a 100μl aliquot (MEM-C and TCM-C), and Small Supplementation - addition of 5μl of fresh medium to an initial small aliquot (50μl), resulting in a final volume of 125μl on the last day of culture (MEM-S and TCM-S). A total of 207 secondary follicles were cultured individually for 32 days at 38.5°C in 5% CO2 and medium replacement was performed every other day. The MEM-S treatment resulted in a larger (P<0.01) follicular diameter, greater (P<0.02) growth rate, greater (P<0.02) antrum formation, as well as greater (P<0.0001) estradiol concentrations when compared with the MEM-C treatment. The medium change methods did not affect (P>0.05) the follicular and estradiol end points for TCM-199(+). The expression of the FSHR gene was greater (P<0.03) with the TCM-C than TCM-S treatment, while the relative amounts of mRNA for IGF1 was greater (P<0.02) with MEM-S than TCM-S treatments and for VEGF was greater (P<0.02) with MEM-C than TCM-C treatment. In conclusion, the type of base medium and the effect of periodic addition of medium differentially affected follicle development, estradiol production, and gene expression. Furthermore, α-MEM(+) can be used to replace TCM-199(+) for culture of preantral follicles of cattle if progressive addition of medium is used for medium change.

  1. Mid-to long-term results of revision total hip replacement in patients aged 50 years or younger.

    PubMed

    Lee, P T H; Lakstein, D L; Lozano, B; Safir, O; Backstein, J; Gross, A E

    2014-08-01

    Revision total hip replacement (THR) for young patients is challenging because of technical complexity and the potential need for subsequent further revisions. We have assessed the survivorship, functional outcome and complications of this procedure in patients aged < 50 years through a large longitudinal series with consistent treatment algorithms. Of 132 consecutive patients (181 hips) who underwent revision THR, 102 patients (151 hips) with a mean age of 43 years (22 to 50) were reviewed at a mean follow-up of 11 years (2 to 26) post-operatively. We attempted to restore bone stock with allograft where indicated. Using further revision for any reason as an end point, the survival of the acetabular component was 71% (sd 4) and 54% (sd 7) at ten- and 20 years. The survival of the femoral component was 80% (sd 4) and 62% (sd 6) at ten- and 20 years. Complications included 11 dislocations (6.1%), ten periprosthetic fractures (5.5%), two deep infections (1.1%), four sciatic nerve palsies (2.2%; three resolved without intervention, one improved after exploration and freeing from adhesions) and one vascular injury (0.6%). The mean modified Harris Hip Score was 41 (10 to 82) pre-operatively, 77 (39 to 93) one year post-operatively and 77 (38 to 93) at the latest review. This overall perspective on the mid- to long-term results is valuable when advising young patients on the prospects of revision surgery at the time of primary replacement.

  2. Prediction of Long-term Post-operative Testosterone Replacement Requirement Based on the Pre-operative Tumor Volume and Testosterone Level in Pituitary Macroadenoma.

    PubMed

    Lee, Cheng-Chi; Chen, Chung-Ming; Lee, Shih-Tseng; Wei, Kuo-Chen; Pai, Ping-Ching; Toh, Cheng-Hong; Chuang, Chi-Cheng

    2015-11-05

    Non-functioning pituitary macroadenomas (NFPAs) are the most prevalent pituitary macroadenomas. One common symptom of NFPA is hypogonadism, which may require long-term hormone replacement. This study was designed to clarify the association between the pre-operative tumor volume, pre-operative testosterone level, intraoperative resection status and the need of long-term post-operative testosterone replacement. Between 2004 and 2012, 45 male patients with NFPAs were enrolled in this prospective study. All patients underwent transsphenoidal surgery. Hypogonadism was defined as total serum testosterone levels of <2.4 ng/mL. The tumor volume was calculated based on the pre- and post-operative magnetic resonance images. We prescribed testosterone to patients with defined hypogonadism or clinical symptoms of hypogonadism. Hormone replacement for longer than 1 year was considered as long-term therapy. The need for long-term post-operative testosterone replacement was significantly associated with larger pre-operative tumor volume (p = 0.0067), and lower pre-operative testosterone level (p = 0.0101). There was no significant difference between the gross total tumor resection and subtotal resection groups (p = 0.1059). The pre-operative tumor volume and testosterone level impact post-operative hypogonadism. By measuring the tumor volume and the testosterone level and by performing adequate tumor resection, surgeons will be able to predict post-operative hypogonadism and the need for long-term hormone replacement.

  3. Long-term follow-up of mobile-bearing total ankle replacement in patients with inflammatory joint disease.

    PubMed

    Kraal, T; van der Heide, H J L; van Poppel, B J; Fiocco, M; Nelissen, R G H H; Doets, H C

    2013-12-01

    Little is known about the long-term outcome of mobile-bearing total ankle replacement (TAR) in the treatment of end-stage arthritis of the ankle, and in particular for patients with inflammatory joint disease. The aim of this study was to assess the minimum ten-year outcome of TAR in this group of patients. We prospectively followed 76 patients (93 TARs) who underwent surgery between 1988 and 1999. No patients were lost to follow-up. At latest follow-up at a mean of 14.8 years (10.7 to 22.8), 30 patients (39 TARs) had died and the original TAR remained in situ in 28 patients (31 TARs). The cumulative incidence of failure at 15 years was 20% (95% confidence interval (CI) 11 to 28). The mean American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score of the surviving patients at latest follow-up was 80.4 (95% CI 72 to 88). In total, 21 patients (23 TARs) underwent subsequent surgery: three implant exchanges, three bearing exchanges and 17 arthrodeses. Neither design of TAR described in this study, the LCS and the Buechel-Pappas, remains currently available. However, based both on this study and on other reports, we believe that TAR using current mobile-bearing designs for patients with end-stage arthritis of the ankle due to inflammatory joint disease remains justified.

  4. Mid- to long-term outcomes of a medial-pivot system for primary total knee replacement

    PubMed Central

    Fitch, D. A.; Sedacki, K.; Yang, Y.

    2014-01-01

    Objectives This systematic review and meta-analysis was conducted to determine the mid- to long-term clinical outcomes for a medial-pivot total knee replacement (TKR) system. The objectives were to synthesise available survivorship, Knee Society Scores (KSS), and reasons for revision for this system. Methods A systematic search was conducted of two online databases to identify sources of survivorship, KSS, and reasons for revision. Survivorship results were compared with values in the National Joint Registry of England, Wales, and Northern Ireland (NJR). Results A total of eight studies that included data for 1146 TKRs performed in six countries satisfied the inclusion/exclusion criteria. Pooled component survivorship estimates were 99.2% (95% CI, 97.7 to 99.7) and 97.6% (95% CI, 95.8 to 98.6) at five and eight years, respectively. Survivorship was similar or better when compared with rates reported for all cemented TKRs combined in the NJR and was significantly better than some insert types at mid-term intervals. The weighted mean post-operative KSS was 87.9 (73.2 to 94.2), in the excellent range. Similar cumulative revision rates and KSS were reported at centres in the United States, Europe, and Asia. Conclusions The subject system was associated with survivorship and KSS similar or better than that reported for other TKR systems. Cite this article: Bone Joint Res 2014;3:297–304 PMID:25325997

  5. Long-term effects of engineered nanoparticles on enzyme activity and functional bacteria in wastewater treatment plants.

    PubMed

    Zheng, Xiong; Huang, Haining; Su, Yinglong; Wei, Yuanyuan; Chen, Yinguang

    2015-01-01

    The pervasive use of engineered nanoparticles (NPs) in a wide range of fields raises concerns about their potential environmental impacts. Previous studies confirmed that some NPs had already entered wastewater treatment plants (WWTPs). Wastewater nutrient removal depends on the metabolisms of activated sludge bacteria and their related key enzymes. Therefore, this study compared the possible influences of Al2O3, SiO2, TiO2, and ZnO NPs on the key enzymes activities and microbial community structures involved in wastewater treatment facilities. It was found that long-term exposure to these NPs significantly affected the microbial communities and changed the relative abundances of key functional bacteria, such as ammonia-oxidizing bacteria. Also, the gene expressions and catalytic activities of essential enzymes, such as ammonia monooxygenase, nitrite oxidoreductase, nitrate reductase, and nitrite reductase, were decreased, which finally resulted in a lower efficiency of biological nitrogen removal.

  6. Changes in renal vessels associated with long-term administration of angiotensin converting enzyme inhibitor in Zucker fatty rats

    PubMed Central

    Nakanishi, Kazushige; Nagai, Yohko; Akimoto, Tatsuo; Yamanaka, Nobuaki

    2017-01-01

    Background Recently, we showed that long-term angiotensin receptor blocker (ARB) administration induced unusual proliferative changes in smooth muscle cells (SMCs) of afferent arterioles of the kidneys of Zucker fatty rats (ZFRs). In this study, we investigated renal afferent arteriolar changes induced by the long-term administration of an angiotensin converting enzyme inhibitor (ACEI) in ZFRs. Materials and Methods Fourteen 6-week-old male ZFRs were divided into two groups (n=14): the ZFR+ACEI group (n=6) was fed a standard diet containing ACEI (Enalapril, 2 mg/kg/day), and the ZFR control group (n=8) for 12 weeks. Blood pressure and proteinuria were examined and morphological studies on kidneys were performed. Results Remarkable proliferative changes in the afferent arteriolar SMCs were frequently observed in the group given ACEI; (66.1 ± 12.9%) compared with the control group (1.77 ± 1.56%, P<0.001). Conclusions It was indicated that long-term ACEI administration induced unusual proliferative changes in SMCs in afferent arterioles of ZFRs. These changes could reduce intraglomerular pressure by narrowing the lumens of afferent arterioles, but they could cause irreversible damage to the arterioles. PMID:28260705

  7. Mineralogical impact on long-term patterns of soil nitrogen and phosphorus enzyme activities

    NASA Astrophysics Data System (ADS)

    Mikutta, Robert; Turner, Stephanie; Meyer-Stüve, Sandra; Guggenberger, Georg; Dohrmann, Reiner; Schippers, Axel

    2014-05-01

    Soil chronosequences provide a unique opportunity to study microbial activity over time in mineralogical diverse soils of different ages. The main objective of this study was to test the effect of mineralogical properties, nutrient and organic matter availability over whole soil pro-files on the abundance and activity of the microbial communities. We focused on microbio-logical processes involved in nitrogen and phosphorus cycling at the 120,000-year Franz Josef soil chronosequence. Microbial abundances (microbial biomass and total cell counts) and enzyme activities (protease, urease, aminopeptidase, and phosphatase) were determined and related to nutrient contents and mineralogical soil properties. Both, microbial abundances and enzyme activities decreased with soil depth at all sites. In the organic layers, microbial biomass and the activities of N-hydrolyzing enzymes showed their maximum at the intermediate-aged sites, corresponding to a high aboveground biomass. In contrast, the phosphatase activity increased with site age. The activities of N-hydrolyzing enzymes were positively correlated with total carbon and nitrogen contents, whereas the phosphatase activity was negatively correlated with the phosphorus content. In the mineral soil, the enzyme activities were generally low, thus reflecting the presence of strongly sorbing minerals. Sub-strate-normalized enzyme activities correlated negatively to clay content as well as poorly crystalline Al and Fe oxyhydroxides, supporting the view that the evolution of reactive sec-ondary mineral phases alters the activity of the microbial communities by constraining sub-strate availability. Our data suggest a strong mineralogical influence on nutrient cycling par-ticularly in subsoil environments.

  8. Effects of long term irrigation with polluted water and sludge amendment on some soil enzyme activities

    SciTech Connect

    Topac, F.O.; Baskaya, H.S.; Alkan, U.; Katkat, A.V.

    2008-01-15

    The objective of this study was to determine the effects of wastewater sludge-fly ash mixtures on urease, dehydrogenase, alkaline phosphatase and beta-glucosidase activities in soils. In order to evaluate the probable effects of previous soil management practices (irrigation with polluted water) on soil enzymes, two different soil samples which were similar in physical properties, but different in irrigation practice were used. The application of wastewater sludges supplemented with varying doses of fly ash increased potential enzyme activities for a short period of time (3 months) in comparison to unamended soils. However, the activity levels generally showed a decreasing trend with increasing ash ratios indicating the inhibitory effect of fly ash. The urease and dehydrogenase activities were particularly lower in soils irrigated from a polluted stream, indicating the negative effects of the previous soil management on soil microbial activity.

  9. Long-term rescue of cone photoreceptor degeneration in retinitis pigmentosa 2 (RP2)-knockout mice by gene replacement therapy

    PubMed Central

    Mookherjee, Suddhasil; Hiriyanna, Suja; Kaneshiro, Kayleigh; Li, Linjing; Li, Yichao; Li, Wei; Qian, Haohua; Li, Tiansen; Khanna, Hemant; Colosi, Peter; Swaroop, Anand; Wu, Zhijian

    2015-01-01

    Retinal neurodegenerative diseases are especially attractive targets for gene replacement therapy, which appears to be clinically effective for several monogenic diseases. X-linked forms of retinitis pigmentosa (XLRP) are relatively severe blinding disorders, resulting from progressive photoreceptor dysfunction primarily caused by mutations in RPGR or RP2 gene. With a goal to develop gene therapy for the XLRP-RP2 disease, we first performed detailed characterization of the Rp2-knockout (Rp2-KO) mice and observed early-onset cone dysfunction, which was followed by progressive cone degeneration, mimicking cone vision impairment in XLRP patients. The mice also exhibited distinct and significantly delayed falling phase of photopic b-wave of electroretinogram (ERG). Concurrently, we generated a self-complementary adeno-associated viral (AAV) vector carrying human RP2-coding sequence and demonstrated its ability to mediate stable RP2 protein expression in mouse photoreceptors. A long-term efficacy study was then conducted in Rp2-KO mice following AAV-RP2 vector administration. Preservation of cone function was achieved with a wide dose range over 18-month duration, as evidenced by photopic ERG and optomotor tests. The slower b-wave kinetics was also completely restored. Morphologically, the treatment preserved cone viability, corrected mis-trafficking of M-cone opsin and restored cone PDE6 expression. The therapeutic effect was achieved even in mice that received treatment at an advanced disease stage. The highest AAV-RP2 dose group demonstrated retinal toxicity, highlighting the importance of careful vector dosing in designing future human trials. The wide range of effective dose, a broad treatment window and long-lasting therapeutic effects should make the RP2 gene therapy attractive for clinical development. PMID:26358772

  10. Responses of absolute and specific soil enzyme activities to long term additions of organic and mineral fertilizer.

    PubMed

    Zhang, Xinyu; Dong, Wenyi; Dai, Xiaoqin; Schaeffer, Sean; Yang, Fengting; Radosevich, Mark; Xu, Lili; Liu, Xiyu; Sun, Xiaomin

    2015-12-01

    Long-term phosphorus (P) and nitrogen (N) applications may seriously affect soil microbial activity. A long-term field fertilizer application trial was established on reddish paddy soils in the subtropical region of southern China in 1998. We assessed the effects of swine manure and seven different rates or ratios of NPK fertilizer treatments on (1) the absolute and specific enzyme activities per unit of soil organic carbon (SOC) or microbial biomass carbon (MBC) involved in C, N, and P transformations and (2) their relationships with soil environmental factors and soil microbial community structures. The results showed that manure applications led to increases in the absolute and specific activities of soil β-1,4-glucosidase(βG), β-1,4-N-acetylglucosaminidase (NAG), and leucine aminopeptidase (LAP). The absolute and specific acid phosphatase (AP) activities decreased as mineral P fertilizer application rates and ratios increased. Redundancy analysis (RDA) showed that there were negative correlations between absolute and specific AP activities, pH, and total P contents, while there were positive correlations between soil absolute and specific βG, NAG, and LAP enzyme activities, and SOC and total N contents. RDA showed that the contents of actinomycete and Gram-positive bacterium PLFA biomarkers are more closely related to the absolute and specific enzyme activities than the other PLFA biomarkers (P<0.01). Our results suggest that both the absolute and specific enzyme activities could be used as sensitive soil quality indicators that provide useful linkages with the microbial community structures and environmental factors. To maintain microbial activity and to minimize environmental impacts, P should be applied as a combination of inorganic and organic forms, and total P fertilizer application rates to subtropical paddy soils should not exceed 44 kg P ha(-1) year(-1).

  11. 75 FR 53976 - Risks and Benefits of Long-Term Use of Nicotine Replacement Therapy Products; Public Workshop...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-02

    ... is known about the long-term safety of nicotine from animal studies? What is known about the long... mitigate against abuse/addiction to NRT products and against initiation of NRT products by people who...

  12. Alterations in antioxidant enzyme activities and proline content in pea leaves under long-term drought stress.

    PubMed

    Karataş, Ilhami; Öztürk, Lokman; Demir, Yavuz; Unlükara, Ali; Kurunç, Ahmet; Düzdemir, Oral

    2014-09-01

    The effects of long-term drought stress on chlorophyll, proline, protein and hydrogen peroxide (H2O2) contents, malondialdehyde (MDA) in terms of lipid peroxidation and on the changes in the activities of antioxidant enzymes such as superoxide dismutase (SOD, EC 1.15.1.1), ascorbate peroxidase (APX, EC 1.11.1.11), catalase (CAT, EC 1.11.1.6) and peroxidase (POX; EC 1.11.1.7) in the leaves of pea (Pisum sativum L.) were studied in field conditions. Chlorophyll and protein contents in leaves decreased significantly with increased drought stress. The proline content increased markedly under water deficit. MDA amounts were elevated as a result of water shortage, whereas H(2)O(2) content changed slightly in pea leaves exposed to drought stress. Drought stress markedly enhanced the activities of SOD, CAT and POX but slightly changed the activity of APX. We conclude that in field conditions, long-term water shortage increased the susceptibility to drought in peas.

  13. Long-term dry storage of an enzyme-based reagent system for ELISA in point-of-care devices.

    PubMed

    Ramachandran, Sujatha; Fu, Elain; Lutz, Barry; Yager, Paul

    2014-03-21

    Lateral flow devices are commonly used for many point-of-care (POC) applications in low-resource settings. However, they lack the sensitivity needed for many analytes relevant in the diagnosis of diseases. One approach to achieve higher sensitivity is signal amplification, which is commonly used in laboratory assays, but uses reagents that require refrigeration and inherently requires multiple assay steps not normally compatible with POC settings. Enzyme-based signal amplification, such as the one used in ELISA, could greatly improve the limit of detection if it were translated to a format compatible with POC requirements. A signal-amplified POC device not only requires the reagents to be stored in a stable form, but also requires automation of the multiple sequential steps of signal amplification protocols. Here, we describe a method for the long-term dry storage of ELISA reagents: horseradish peroxidase (HRP) conjugated antibody label and its colorimetric substrate diaminobenzidine (DAB). The HRP conjugate retained ∼80% enzymatic activity after dry storage at 45 °C for over 5 months. The DAB substrate was also stable at 45 °C and exhibited no detectable loss of activity over 3 months. These reagents were incorporated into a two-dimensional paper network (2DPN) device that automated the steps of ELISA for the detection of a malarial biomarker. These results demonstrate the potential of enzyme-based signal amplification for enhanced sensitivity in POC devices for low resource settings.

  14. Effect of short- and long-term alcohol feeding in rats on pancreatic enzyme content and enzyme secretion in isolated pancreatic lobules in vitro.

    PubMed

    Bode, C; Dürr, H K; Bode, J C

    1986-07-01

    The effect of short- and long-term ethanol intake on digestive enzyme secretion was determined in isolated pancreatic lobules of rats. Groups of male Wistar rats were fed a modified Lieber-DeCarli diet containing either 5% (w/v) of ethanol, isocaloric amounts of a liquid diet in which ethanol was substituted by starch, or solid rat chow; for 3 days, 1, 2, 4, 8 and 12 weeks. Basal and caerulein-stimulated secretion of lipase, amylase, chymotrypsin and trypsin and the enzyme content in the tissue were studied. Feeding the liquid control diet decreased the tissue content of the four enzymes as compared with the values obtained in the group receiving solid rat chow. While basal and stimulated amylase secretion was markedly reduced in the former group, the secretion pattern of the other enzymes exhibited only transient changes. Caerulein-stimulated secretion of lipase and the proteases was increased by ethanol, the effect being more pronounced during the initial phase of the experiment. Alcohol feeding stimulated the basal secretion of these enzymes only in weeks 1-4. In contrast to the other enzymes, basal and stimulated amylase secretion was not enhanced by ethanol feeding. The results suggest that the enzyme secretion of the rat pancreas is distinctly altered by chronic ethanol feeding. However, the response of the pancreatic enzymes is non-parallel, and changes with the duration of alcohol intake.

  15. Enzyme replacement therapy: conception, chaos and culmination.

    PubMed Central

    Brady, Roscoe O

    2003-01-01

    Soon after the enzymatic defects in Gaucher disease and in Niemann-Pick disease were discovered, enzyme replacement or enzyme supplementation was proposed as specific treatment for patients with these and related metabolic storage disorders. While relatively straightforward in concept, successful implementation of this approach required many years of intensive effort to bring it to fruition. Procedures were eventually developed to produce sufficient quantities of the requisite enzymes for clinical trials and to target therapeutic enzymes to lipid-storing cells. These achievements led to the development of effective enzyme replacement therapy for patients with Gaucher disease and for Fabry disease. These demonstrations provide strong incentive for the application of this strategy for the treatment of many human disorders of metabolism. PMID:12803925

  16. Digestive Enzyme Replacement Therapy: Pancreatic Enzymes and Lactase.

    PubMed

    Felicilda-Reynaldo, Rhea Faye D; Kenneally, Maria

    2016-01-01

    Maldigestion occurs when digestive enzymes are lacking to help break complex food components into absorbable nutrients within the gastrointestinal tract. Education is needed to help patients manage the intricacies of digestive enzyme replacement therapies and ensure their effectiveness in reducing symptoms of maldigestion.

  17. Immediate and long-term results of mitral valve replacement with University of Cape Town mitral valve prosthesis

    PubMed Central

    Schrire, Velva; Barnard, Christiaan N.

    1970-01-01

    We describe seven years' experience with the University of Cape Town lenticular mitral valve prosthesis in 122 patients. All the patients had severe mitral valve disease. In 98 severe mitral stenosis was present with or without incompetence and in 24 the dominant or sole lesion was mitral incompetence. Other valves, particularly the tricuspid, were also frequently affected. The disability was severe or total in almost every patient. One hundred and five patients were discharged from hospital, and in 90 per cent of these the clinical improvement was most gratifying, with the disappearance of pulmonary oedema, paroxysmal dyspnoea, angina pectoris, and congestive cardiac failure. Return to full normal activity including physical work was the rule. The hospital mortality was 14 per cent and a further 38 per cent died during the follow-up period. The major post-operative complication was systemic embolism which could occur at any time after operation. The most important factor influencing the frequency of this complication was the nature of the valve seat. A bare steel seat was associated with a 100 per cent embolism, and a significant reduction occurred when a cloth-covered seat of Dacron-velour was introduced. Anticoagulant therapy appeared to prevent large or fresh clots but had no effect on the deposition of fibrin or platelet thrombi. The only other factor of importance was the age of the patient: after the age of 50 life expectancy and trouble-free long-term survival was reduced. Images PMID:5440520

  18. Long-term changes in attitudes toward premarital sex in the United States: reexamining the role of cohort replacement.

    PubMed

    Elias, Vicky L; Fullerton, Andrew S; Simpson, Joseph M

    2015-01-01

    Attitudes toward premarital sex in the United States have changed considerably since the 1970s. However, it is unclear whether these changes are due to cohort replacement, broader changes within cohorts, or a combination of the two processes. We examined within- and between-cohort changes in attitudes toward premarital sex in the United States from 1975 to 2008 using hierarchical age-period-cohort models based on data from the General Social Survey. We used a religious plausibility structure framework to examine several possible mechanisms for within- and between-cohort variation in premarital sex attitudes over time, including changes in religious participation, marital patterns, and family structure. The results provided mixed support for our hypotheses. Attitudes toward premarital sex became more permissive over time in the United States in part because of the process of cohort replacement, but the level of permissiveness peaked with the baby boomer cohorts. This cohort effect is due in part to differences in rates of religious service attendance and educational attainment. However, the overall increase in permissive attitudes toward premarital sex is also due to period effects that are not captured by the measures included in our analyses.

  19. [Severe tricuspid insufficiency and primary carcinoid tumor of the ovary. Long term success after valve replacement. Apropos of a case].

    PubMed

    Herreman, F; Vernant, P; Cachera, J P; Monier, P

    1978-01-01

    The case is reported of carcinoid heart disease in a lady of 70 with intractable congestive cardiac failure 5 years after the removal of a primary carcinoid tumour of the ovary. The special features of primary carcinoid tumours of the ovary are recalled, with emphasis on their rarity and of the absence of liver metastases. The various features of carcinoid syndrome are recalled in the light of current knowledge of the pathogenesis. A review of the literature on cardiac involvement in primary carcinoid tumours of the ovary, amounting to 10 cases, is included. The possibility of surgical cure of the heart lesions in carcinoid tumour by a prosthetic tricuspid valve are discussed, in the light of the 6 reported cases and the present one. Our report is the first one of replacement of the valve after removal of a primary ovarien carcinoid tumour, and the excellent result has been maintained after three years.

  20. Long-Term Outcomes of Conventional Aortic Valve Replacement in High-Risk Patients: Where Do We Stand?

    PubMed Central

    Fortuna, Daniela; Contini, Giovanni Andrea; Pacini, Davide; Gabbieri, Davide; De Palma, Rossana; Gherli, Tiziano

    2016-01-01

    Purpose: The introduction of transcatheter aortic valves has focused attention on the results of conventional aortic valve surgery in high-risk patients. The aim of the study was to evaluate 5-years outcomes in this category of patients in the current surgical era. Methods: This is an observational retrospective study of 581 high-risk patients undergoing aortic valve replacement from 2008 to 2013, with a mean logistic EuroSCORE of 26.6% ± 14.6%. Data were prospectively collected in a database of Emilia-Romagna region (Italy). Results: Overall 30-day mortality was 9.3%. Stroke rate was 1.5%. At 1-, 3-, and 5-years overall mortality was 18.2%, 30.4%, and 42.2%, cardiac death rate was 3.9%, 9.2%, and 12.9%, stroke rate 2.5%, 7.7%, and 10.2%, re-operation occurrence 0.2%, 0.9% and 1.3%, and new pacemaker implantation was 2.3%, 5.1% and 7.8%. At multivariate analysis, urgency, hemodynamic instability, LVEF ≤30%, NYHA III-IV, severe chronic obstructive pulmonary disease (COPD), extra-cardiac arteriopathy, cerebrovascular disease, and creatinine >2.0 mg/dL remained independent predictors of 5-year mortality. Conclusion: The results of the current study add weight to the evidence that traditional aortic valve replacement can be performed in high-risk patients with satisfactory 5-year mortality and morbidity. Our study may help to improve decision-making in this category of high-risk patients with aortic valve disease. PMID:27645551

  1. The inherent properties of enzymes can only lead to a negative temperature response of soil C decomposition on the long-term.

    NASA Astrophysics Data System (ADS)

    Alvarez, Gaël; Fontaine, Sébastien

    2015-04-01

    More than one century after the pioneer work of Arrhenius on the temperature dependence of chemical reactions, the response of soil C decomposition to global warming remains uncertain. The majority of lab experiments, generally conducted at short term (months to years), suggest that the decomposition of soil C accelerates with temperature. In contrast, long-term (> 5 years) ecosystem warming experiments show that stimulation of soil respiration is only transitory. Moreover, studies on ecosystem C fluxes along a latitudinal gradient even suggest that, for a given amount of C fixed by the ecosystem, the decomposition flux decreases with temperature leading to higher C storage in warmer ecosystems (Giardina and Ryan, 2000; Sanderman, 2003). To understand this discrepancy between short-term and long-term temperature responses of C decomposition, we re-analysed the thermo-dependence of decomposition in a theory distinguishing enzyme-limited and substrate-limited reactions. Indeed, it is increasingly recognized that decomposition of the largest pool of soil C (humified organic C, HOC) is limited by the amount of soil (extracellular) enzymes. The substrate-limited reaction and its dependence to temperature were classically modelled with the first order kinetics dC/dt=-kC where reaction velocity k is modelled by an Arrhenius equation. The thermo-dependence of enzyme-limited reactions was studied in models where the reaction velocity depends on the specific activity of enzymes and the dynamics of enzyme pool, each of which may display distinct temperature sensitivities. The dynamics of the enzyme pool depended on (1) the inactivation of enzymes and its dependence to time and temperature and (2) the microbial production of enzymes, which is limited by the energy available to soil microorganisms. These models were analysed mathematically and through simulations using data on thermodynamics properties of enzymes (activation energies) and ecosystem C fluxes. Our results show

  2. Exercise therapy may postpone total hip replacement surgery in patients with hip osteoarthritis: a long-term follow-up of a randomised trial

    PubMed Central

    Svege, Ida; Nordsletten, Lars; Fernandes, Linda; Risberg, May Arna

    2015-01-01

    Background Exercise treatment is recommended for all patients with hip osteoarthritis (OA), but its effect on the long-term need for total hip replacement (THR) is unknown. Methods We conducted a long-term follow-up of a randomised trial investigating the efficacy of exercise therapy and patient education versus patient education only on the 6-year cumulative survival of the native hip to THR in 109 patients with symptomatic and radiographic hip OA. Results regarding the primary outcome measure of the trial, self-reported pain at 16 months follow-up, have been reported previously. Results There were no group differences at baseline. The response rate at follow-up was 94%. 22 patients in the group receiving both exercise therapy and patient education and 31 patients in the group receiving patient education only underwent THR during the follow-up period, giving a 6-year cumulative survival of the native hip of 41% and 25%, respectively (p=0.034). The HR for survival of the native hip was 0.56 (CI 0.32 to 0.96) for the exercise therapy group compared with the control group. Median time to THR was 5.4 and 3.5 years, respectively. The exercise therapy group had better self-reported hip function prior to THR or end of study, but no significant differences were found for pain and stiffness. Conclusions Our findings in this explanatory study suggest that exercise therapy in addition to patient education can reduce the need for THR by 44% in patients with hip OA. ClinicalTrials.gov number NCT00319423 (original project protocol) and NCT01338532 (additional protocol for long-term follow-up). PMID:24255546

  3. Effects of Cr(VI) long-term and low-dose action on mammalian antioxidant enzymes (an in vitro study)

    SciTech Connect

    Asatiani, N.; Sapojnikova, N.; Abuladze, M.; Kartvelishvili, T.L.; Kulikova, N.; Kiziria, E.; Namchevadze, E.; Holman, H.-Y.N.

    2003-08-01

    In order to investigate the low-dose long-term Cr(VI) action on antioxidant enzymes in cultured mammalian cells we estimated the activity of glutathione dependent antioxidant enzymes, catalase and superoxide dismutase (SOD) under various chromium concentrations in human epithelial-like L-41 cells. The long-term action of 20 mu-M causes the toxicity that results in losing of the cell viability by activating the apoptotic process, as identified by morphological analysis, the activation of caspase-3, and DNA fragmentation. The toxic chromium concentration totally destroys glutathione antioxidant system, and diminishes the activity of catalase and cytosolic Cu, ZnSOD. The non-toxic concentration (2 mu-M) causes the activation of the antioxidant defense systems, and they neutralize the oxidative impact.

  4. Cervical artificial disc replacement versus fusion in the cervical spine: a systematic review comparing long-term follow-up results from two FDA trials

    PubMed Central

    Mummaneni, Praveen V.; Amin, Beejal Y.; Wu, Jau-Ching; Brodt, Erika D.; Dettori, Joseph R.; Sasso, Rick C.

    2012-01-01

    Study design: Systematic review. Clinical question: Does single-level unconstrained, semiconstrained, or fully constrained cervical artificial disc replacement (C-ADR) improve health outcomes compared with single-level anterior cervical discectomy and fusion (ACDF) in the long-term? Methods: A systematic review was undertaken for articles published up to October 2011. Electronic databases and reference lists of key articles were searched to identify US Food and Drug Administration (FDA) studies reporting long-term (≥ 48 months) follow-up results of C-ADR compared with ACDF. Non-FDA trials and FDA trials reporting outcomes at short-term or mid-term follow-up periods were excluded. Two independent reviewers assessed the strength of evidence using the GRADE criteria and disagreements were resolved by consensus. Results: Two FDA trials reporting outcomes following C-ADR (Bryan disc, Prestige disc) versus ACDF at follow-up periods of 48 months and 60 months were found (follow-up rates are 68.7% [318/463] and 50.1% [271/541], respectively). Patients in the C-ADR group showed a higher rate of overall success, greater improvements in Neck Disability Index, neck and arm pain scores, and SF-36 PhysicalComponent Scores at long-term follow-up compared with those in the ACDF group. The rate of adjacent segment disease was less in the C-ADR group versus the ACDF group at 60 months (2.9% vs 4.9%). Normal segmental motion was maintained in the C-ADR group. Furthermore, rates of revision and supplemental fixation surgical procedures were lower in the arthroplasty group. Conclusions: C-ADR is a viable treatment option for cervical herniated disc/spondylosis with radiculopathy resulting in improved clinical outcomes, maintenance of normal segmental motion, and low rates of subsequent surgical procedures at 4 to 5 years follow-up. More studies with long-term follow-up are warranted. PMID:23236315

  5. Long Term Survivorship of a Severely Notched Femoral Stem after Replacing the Fractured Ceramic head with a Cobalt-Chromium Head

    PubMed Central

    Panagopoulos, Andreas; Tatani, Irini; Megas, Panagiotis

    2016-01-01

    Background: Although ceramic head fracture occurs infrequently today, in the event of a fracture, the resulting revision surgery can prove very challenging, since the ceramic particles lodge into the surrounding soft tissue and can cause rapid implant failure Case Presentation: A case of long term survivorship of a severed notched femoral stem after replacing the fractured femoral head with a cobalt-chromium one is reported in a 40-year old woman with hip dysplasia who underwent an uncomplicated total hip arthroplasty. The incident of ceramic femoral head fracture occurred 14 months postoperatively without reporting any significant trauma. Intraoperative findings at revision were a multifragmented femoral head and a damaged polyethylene insert along with diffuse metallosis and excessive wear of the cone of the stem. Both the stem and the acetabular component were stable. After removal of ceramic fragments, metallotic tissue excision and careful lavage of the joint, the inlay was replaced by a similar one and a cobalt-chromium femoral head was placed to the existing notched taper of the firmly incorporated stem. At the 13th year follow up examination, the patient had no pain, used no walking aids, and had normal activity with no signs of wearing or loosening in the plain x-rays. Conclusion: Despite current recommendations of using ceramic femoral heads in cases of fracture or to revise the severely damaged stems we were able to provide a long term survivorship up to 13 years postoperatively of a cobalt-chromium femoral head applied to a severe damaged stem. PMID:28217203

  6. Improvement with ongoing Enzyme Replacement Therapy in advanced late-onset Pompe disease: a case study.

    PubMed

    Case, Laura E; Koeberl, Dwight D; Young, Sarah P; Bali, Deeksha; DeArmey, Stephanie M; Mackey, Joanne; Kishnani, Priya S

    2008-12-01

    Benefits of enzyme replacement therapy with Myozyme (alglucosidase alfa), anecdotally reported in late-onset Pompe disease, range from motor and pulmonary improvement in less severely affected patients, to stabilization with minimal improvement in those with advanced disease. We report a case of a 63-year-old patient with significant morbidity who made notable motor and pulmonary function gains after two years on therapy. Thus, improvements in those with advanced disease may be possible after long-term treatment.

  7. A proposal of "core enzyme" bioindicator in long-term Pb-Zn ore pollution areas based on topsoil property analysis.

    PubMed

    Yang, JinShui; Yang, FengLong; Yang, Yang; Xing, GuanLan; Deng, ChunPing; Shen, YaTing; Luo, LiQiang; Li, BaoZhen; Yuan, HongLi

    2016-06-01

    To study the effects of long-term mining activities on the agricultural soil quality of Mengnuo town in Yunnan province, China, the heavy metal and soil enzyme activities of soil samples from 47 sites were examined. The results showed that long-term mining processes led to point source heavy metal pollution and Pb, Cd, Zn and As were the primary metal pollutants. Polyphenoloxidase was found the most sensitive soil enzyme activity and significantly correlated with almost all the metals (P < 0.05). Amylase (for C cycling), acid phosphatase (for P cycling) and catalase (for redox reaction) activities showed significantly positive correlations (P < 0.05) with Pb, Cd, Zn and As contents. The correlations between soil enzymes activities and Cd, Pb and Zn contents were verified in microcosm experiments, it was found that catalase activity had significant correlations (P < 0.05) with these three metals in short-term experiments using different soils under different conditions. Based on both field investigation and microcosm simulation analysis, oxidoreductases activities (rather than a specific enzyme activity) were suggested to be used as "core enzyme", which could simply and universally indicate the heavy metal pollution degrees of different environments. And hydrolases (for C, N, P and S recycling) could be used as a supplement to improve correlation accuracy for heavy metal indication in various polluted environments.

  8. Enzyme replacement therapy and Fabry nephropathy.

    PubMed

    Warnock, David G; Daina, Erica; Remuzzi, Giuseppe; West, Michael

    2010-02-01

    Involvement of the kidneys in Fabry disease ("nephropathy") occurs in male and female individuals. The majority of patients with progressive nephropathy will have significant proteinuria and develop progressive loss of kidney function, leading to ESRD. All too often, treating physicians may ignore "normal" serum creatinine levels or "minimal" proteinuria and fail to assess properly the severity of kidney involvement and institute appropriate management. Fabry nephropathy is treatable, even in patients with fairly advanced disease. Although the cornerstone of therapy remains enzyme replacement therapy with agalsidase, this treatment alone does not reduce urine protein excretion. Treatment with angiotensin receptor blockers or angiotensin-converting enzyme inhibitors must be added to enzyme replacement therapy to reduce urine protein excretion with the hope that this will stabilize kidney function. Kidney function, with at least estimated GFR based on serum creatinine and measurements of urinary protein, should be measured at every clinic visit, and the rate of change of the estimated GFR should be followed over time. Antiproteinuric therapy can be dosed to a prespecified urine protein target rather than a specific BP goal, with the proviso that successful therapy will usually lower the BP below the goal of 130/80 mmHg that is used for other forms of kidney disease. The overall goal for treating Fabry nephropathy is to reduce the rate of loss of GFR to -1 ml/min per 1.73 m(2)/yr, which is that seen in the normal adult population. A systematic approach is presented for reaching this goal in the individual patient.

  9. Long-term results after aortic root replacement using self-assembled valve composite grafts in patients with small aortic annulus

    PubMed Central

    Urbanski, Paul P.; Dinstak, Witold; Rents, Wilko; Heinz, Nicolas; Diegeler, Anno

    2014-01-01

    OBJECTIVES The study was aimed to evaluate operative and long-term results after complete root replacement using self-assembled valve composite grafts in patients with a small aortic annulus. METHODS Among 547 consecutive patients who received the Bentall procedure between 2000 and 2012, a total of 29 patients (61 ± 10; range 42–79 years) had an annulus of ≤20 mm (mean 19.0 ± 0.9). Patients with a native aortic valve (22) suffered from stenosis, insufficiency or mixed defect in 10, 10 and 2 cases, respectively. Among the remaining 7 patients with an artificial aortic valve, there were 3 symptomatic prosthesis–patient mismatches, 3 valve prosthesis deteriorations (1 structural and 2 none-structural) and 1 paravalvular leak. Indication for aortic root replacement was true or false aneurysm, porcelain aorta and intraoperative aortic wall injury in 17, 6 and 6 patients, respectively. RESULTS The composite graft for complete aortic root replacement was assembled using a mechanical (26) or biological (3) valve prosthesis placed inside a vascular graft with a median size of 24 (range 22–26) mm. The margin of the tube beneath the valve was anastomosed to the aortic annulus, and coronary ostia were implanted in the usual manner. The mean transvalvular gradient at discharge was 10.8 ± 3.9 mmHg and remained virtually unchanged at the follow-up completed for all patients. Early mortality was 0. During the mean follow-up of 95.8 ± 43.7 months, 2 patients died (54 and 146 months after surgery) due to pulmonary embolism and myocardial infarction, respectively. CONCLUSIONS In patients with a small aortic annulus who need complete aortic root replacement, an oversizing of the valve can be easily achieved using modified, self-assembled composite grafts. Offering excellent haemodynamic characteristics, these grafts lead to prevention of prosthesis–patient mismatch and result in very good and durable functional and clinical results. PMID:24179177

  10. Association of Patient-Reported Health Status with Long-Term Mortality after Transcatheter Aortic Valve Replacement: A Report from the STS/ACC TVT Registry™

    PubMed Central

    Arnold, Suzanne V.; Spertus, John A.; Vemulapalli, Sreekanth; Dai, Dadi; O’Brien, Sean M.; Baron, Suzanne J.; Kirtane, Ajay J.; Mack, Michael J.; Green, Philip; Reynolds, Matthew R.; Rumsfeld, John S.; Cohen, David J.

    2015-01-01

    Background Although transcatheter aortic valve replacement (TAVR) is an effective treatment for aortic stenosis, long-term mortality after TAVR remains high and challenging to predict. The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a health status measure, assessed directly from patients, that integrates two clinically relevant factors (symptoms and functional status) that may predict TAVR outcomes. Methods and Results Among 7769 patients from 286 sites in the STS-ACC TVT Registry, we examined the association between pre-procedure (baseline) patient health status, as assessed by the KCCQ, and 1-year mortality after TAVR. The KCCQ Overall Summary Score was categorized as very poor: <25, poor: 25–49, fair: 50–74, or good: ≥75. Prior to TAVR, health status was rated as very poor in 28%, poor in 38%, fair in 24%, and good in 10%. Patients with worse health status were more likely to be female and had more comorbidities and higher STS mortality risk scores. Compared with those with good health status prior to TAVR, and after adjusting for a broad range of baseline covariates, patients with very poor health status had a 2-fold increased hazard of death over the first year after TAVR (adjusted HR 2.00, 95% CI 1.58–2.54), while those with poor and fair health status had intermediate outcomes (adjusted HRs 1.54, 95% CI 1.22–1.95 and 1.20, 95% CI 0.94–1.55, respectively). Conclusions In a national, contemporary practice cohort, worse pre-procedure patient health status, as assessed by the KCCQ, was associated with greater long-term mortality after TAVR. These results support the measurement and integration of the KCCQ into mortality risk assessments for patients considering TAVR. PMID:26643740

  11. Long-term Mortality Predictors in Patients with Small Aortic Annulus Undergoing Aortic Valve Replacement with a 19- or 21-mm Bioprosthesis

    PubMed Central

    de Oliveira, Jenny Lourdes Rivas; Arnoni, Renato Tambellini; dos Santos, Magaly Arrais; Almeida, Antonio Flávio Sanchez; Issa, Mário; Arnoni, Antoninho Sanfins; Chaccur, Paulo; de Souza, Luiz Carlos Bento

    2016-01-01

    Introduction Replacement of the aortic valve in patients with a small aortic annulus is associated with increased morbidity and mortality. A prosthesis-patient mismatch is one of the main problems associated with failed valves in this patient population. Objective To evaluate the long-term mortality predictors in patients with a small aortic annulus undergoing aortic valve replacement with a bioprosthesis. Methods In this retrospective observational study, a total of 101 patients undergoing aortic valve replacement from January 2000 to December 2010 were studied. There were 81 (80.19%) women with a mean age of 52.81±18.4 years. Severe aortic stenosis was the main indication for surgery in 54 (53.4%) patients. Posterior annulus enlargement was performed in 16 (15.8%) patients. Overall, 54 (53.41%) patients underwent concomitant surgery: 28 (27.5%) underwent mitral valve replacement, and 13 (12.7%) underwent coronary artery bypass graft surgery. Results Mean valve index was 0.82±0.08 cm2/m2. Overall, 17 (16.83%) patients had a valve index lower than 0.75 cm2/m2, without statistical significance for mortality (P=0.12). The overall 10-year survival rate was 83.17%. The rate for patients who underwent isolated aortic valve replacement was 91.3% and 73.1% (P=0.02) for patients who underwent concomitant surgery. In the univariate analysis, the main predictors of mortality were preoperative ejection fraction (P=0.02; HR 0.01) and EuroSCORE II results (P=0.00000042; HR 1.13). In the multivariate analysis, the main predictors of mortality were age (P=0.01, HR 1.04) and concomitant surgery (P=0.01, HR 5.04). Those relationships were statistically significant. Conclusion A valve index of < 0.75 cm2/m2 did not affect 10-year survival. However, concomitant surgery and age significantly affected mortality. PMID:27849298

  12. Artificial-enzyme gel membrane-based biosurveillance sensor with high reproducibility and long-term storage stability.

    PubMed

    Ikeno, Shinya; Yoshida, Tetsuya; Haruyama, Tetsuya

    2009-02-01

    We propose that the most sophisticated strategy for primary biosurveillance is to exploit structural commonality through the detection of biologically relevant phosphoric substances. A novel assay, an artificial-enzyme membrane was designed and synthesized for sensor fabrication. This artificial-enzyme catalyzes the hydrolysis of the diphosphoric acid anhydride structure. This structure-selective, albeit not molecule-selective, catalytic hydrolysis was successfully coupled with amperometric detection. Since the catalytic reaction produces a dephosphorylation product (PO(4)(3-)), it can be reduced by an electrode potential of -250 mV vs. Ag/AgCl. Owing to the structural selectivity of the artificial-enzyme membrane, the sensor can detect biological phosphoric substances comprehensively that have the diphosphoric acid anhydride structure. The sensor successfully determined various biological phosphoric substances at concentrations in the micromolar (microM) to millimolar (mM) range, and it showed good functional stability and reproducibility in terms of sensor responses. This sensor was used to detect Escherichia coli lysed by heat treatment, and the response increased with increasing bacterial numbers. This unique technique for analyzing molecular commonality can be applied to the surveillance of biocontaminants, e.g. microorganisms, spores and viruses. Artificial-enzyme-based detection is a novel strategy for practical biosurveillance in the front line.

  13. The long-term outcome of uncemented Low Contact Stress total knee replacement in patients with rheumatoid arthritis: results at a mean of 22 years.

    PubMed

    Abram, S G F; Nicol, F; Hullin, M G; Spencer, S J

    2013-11-01

    We reviewed the long-term clinical and radiological results of 63 uncemented Low Contact Stress (LCS) total knee replacements (TKRs) in 47 patients with rheumatoid arthritis. The mean age of the patients at the time of surgery was 69 years (53 to 81). At a mean follow-up of 22 years (20 to 25), 12 patients were alive (17 TKRs), 27 had died (36 TKRs), and eight (ten TKRs) were lost to follow-up. Revision was necessary in seven patients (seven TKRs, 11.1%) at a mean of 12.1 years (0 to 19) after surgery. In the surviving ten patients who had not undergone revision (15 TKRs), the mean Oxford knee score was 30.2 (16 to 41) at a mean follow-up of 19.5 years (15 to 24.7) and mean active flexion was 105° (90° to 150°). The survival rate was 88.9% at 20 years (56 of 63) and the Kaplan-Meier survival estimate, without revision, was 80.2% (95% confidence interval 37 to 100) at 25 years.

  14. Long-term effects of growth hormone (GH) replacement therapy on hematopoiesis in a large cohort of children with GH deficiency.

    PubMed

    Esposito, Andrea; Capalbo, Donatella; De Martino, Lucia; Rezzuto, Martina; Di Mase, Raffaella; Pignata, Claudio; Salerno, Mariacarolina

    2016-07-01

    The aim of our prospective case-control study was to evaluate long-term effects of GH replacement therapy on erythrocytes parameters, leukocytes, and platelets numbers in a large cohort of children with isolated GH deficiency (GHD). Hemoglobin (Hb) concentration, hematocrit (Hct), mean corpuscular volume, mean corpuscular hemoglobin, red cell distribution width, number of erythrocytes, leukocytes, neutrophils, lymphocytes, monocytes and platelets, ferritin, and C-reactive protein were evaluated in 85 children with isolated GHD (10.20 ± 3.50 years) before and annually during the first 5 years of GH replacement therapy and in 85 healthy children age and sex comparable to patients during 5 years of follow-up. Compared with controls, GHD children at study entry showed lower Hb (-1.18 ± 0.87 vs. -0.40 ± 0.90 SDS, p < 0.0001), red cells number (-0.24 ± 0.81 vs. 0.25 ± 1.14 SDS, p < 0.0001), and Hct (-1.18 ± 0.86 vs. -0.68 ± 0.99 SDS, p < 0.0001). Twelve GHD patients (14 %) showed a normocytic anemia. GH therapy was associated with a significant increase in Hb, Hct, and red cells number which became all comparable to controls within the first 2 years of treatment. Moreover, hemoglobin levels normalized in all anemic GHD patients after 5 years of therapy. No difference between patients and controls was found in leukocytes and platelets numbers neither at baseline nor during the study. GHD in childhood is associated with an impairment of erythropoiesis which causes a normocytic anemia in a considerable percentage of patients. GH replacement therapy exerts a beneficial effect leading to a significant increase of erythrocytes parameters and recovery from anemia. Neither GHD nor GH replacement treatment exerts effects on leukocytes or platelets numbers.

  15. Long-Term Care

    MedlinePlus

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

  16. Intravenous enzyme replacement therapy: hospital vs home.

    PubMed

    Parini, Rossella; Pozzi, Katia; Di Mauro, Stefania; Furlan, Francesca; Rigoldi, Miriam

    Two surveys were carried out to establish the status of enzyme replacement therapy (ERT) for lysosomal storage diseases in Italy. The first was a national survey covering the regional reference centres (RRCs) for these diseases; replies disclosed that 57.7% of patients are on ERT, administered almost exclusively in hospital settings (local hospital 60.7%, RRC 34.8%, home 2.6%); Italian health service procedures do not support ERT at home. The second survey was a regional survey in Lombardy, involving 48 patients (six of whom were on ERT at home). According to 40% of the patients, hospital-based ERT is disruptive, causing loss of days at school/work, stress and family issues. The patients on home therapy did not have these problems. However, 93% of patients receiving ERT in hospital perceived the advantages of greater safety, closer monitoring and more support from health professionals and experts. A total of 55% were willing to receive ERT at home, but 33% were against it. This may be the result of a lack of experience with ERT at home in Italy, or because of different opinions between family members and physicians. As international experience shows that ERT at home saves healthcare resources and improves quality of life, the issue should be raised with Italian healthcare policy makers, who should ensure nursing support for home-based ERT.

  17. Regulation of catabolic enzymes during long-term exposure of Delftia acidovorans MC1 to chlorophenoxy herbicides.

    PubMed

    Benndorf, Dirk; Davidson, Ian; Babel, Wolfgang

    2004-04-01

    Delftia acidovorans MC1 is able to grow on chlorophenoxy herbicides such as 2,4-dichlorophenoxypropionic acid (2,4-DCPP) and 2,4-dichlorophenoxyacetic acid as sole sources of carbon and energy. High concentrations of the potentially toxic organics inhibit the productive degradation and poison the organism. To discover the target of chlorophenoxy herbicides in D. acidovorans MC1 and to recognize adaptation mechanisms, the response to chlorophenoxy acids at the level of proteins was analysed. The comparison of protein patterns after chemostatic growth on pyruvate and 2,4-DCPP facilitated the discovery of several proteins induced and repressed due to the substrate shifts. Many of the induced enzymes, for example two chlorocatechol 1,2-dioxygenases, are involved in the metabolism of 2,4-DCPP. A stronger induction of some catabolic enzymes (chlorocatechol 1,2-dioxygenase TfdC(II), chloromuconate cycloisomerase TfdD) caused by an instant increase in the concentration of 2,4-DCPP resulted in increased rates of productive detoxification and finally in resistance of the cells. Nevertheless, the decrease of the (S)-2,4-DCPP-specific 2-oxoglutarate-dependent dioxygenase in 2D gels reveals a potential bottleneck in 2,4-DCPP degradation. Well-known heat-shock proteins and oxidative-stress proteins play a minor role in adaptation, because apart from DnaK only a weak or no induction of the proteins GroEL, AhpC and SodA was observed. Moreover, the modification of elongation factor Tu (TufA), a strong decrease of asparaginase and the induction of the hypothetical periplasmic protein YceI point to additional resistance mechanisms against chlorophenoxy herbicides.

  18. Long-term feeding a plant-based diet devoid of marine ingredients strongly affects certain key metabolic enzymes in the rainbow trout liver.

    PubMed

    Véron, Vincent; Panserat, Stéphane; Le Boucher, Richard; Labbé, Laurent; Quillet, Edwige; Dupont-Nivet, Mathilde; Médale, Françoise

    2016-04-01

    Incorporation of a plant blend in the diet can affect growth parameters and metabolism in carnivorous fish. We studied for the first time the long-term (1 year) metabolic response of rainbow trout fed from first feeding with a plant-based diet totally devoid of marine ingredients. Hepatic enzymes were analyzed at enzymatic and molecular levels, at 3, 8 and 24 h after the last meal to study both the short-term effects of the last meal and long-term effects of the diet. The results were compared with those of fish fed a control diet of fish meal and fish oil. Growth, feed intake, feed efficiency and protein retention were lower in the group fed the plant-based diet. Glucokinase and pyruvate kinase activity were lower in the livers of trout fed the plant-based diet which the proportion of starch was lower than in the control diet. Glutamate dehydrogenase was induced by the plant-based diet, suggesting an imbalance of amino acids and a possible link with the lower protein retention observed. Gene expression of delta 6 desaturase was higher in fish fed the plant-based diet, probably linked to a high dietary level of linolenic acid and the absence of long-chain polyunsaturated fatty acids in vegetable oils. Hydroxymethylglutaryl-CoA synthase expression was also induced by plant-based diet because of the low rate of cholesterol in the diet. Changes in regulation mechanisms already identified through short-term nutritional experiments (<12 weeks) suggest that metabolic responses are implemented at short term and remain in the long term.

  19. Changes in Soil Carbon and Enzyme Activity As a Result of Different Long-Term Fertilization Regimes in a Greenhouse Field

    PubMed Central

    Zhang, Lili; Chen, Wei; Burger, Martin; Yang, Lijie; Gong, Ping; Wu, Zhijie

    2015-01-01

    In order to discover the advantages and disadvantages of different fertilization regimes and identify the best management practice of fertilization in greenhouse fields, soil enzyme activities involved in carbon (C) transformations, soil chemical characteristics, and crop yields were monitored after long-term (20-year) fertilization regimes, including no fertilizer (CK), 300 kg N ha-1 and 600 kg N ha-1 as urea (N1 and N2), 75 Mg ha-1 horse manure compost (M), and M with either 300 or 600 kg N ha-1 urea (MN1 and MN2). Compared with CK, fertilization increased crop yields by 31% (N2) to 69% (MN1). However, compared with CK, inorganic fertilization (especially N2) also caused soil acidification and salinization. In the N2 treatment, soil total organic carbon (TOC) decreased from 14.1±0.27 g kg-1 at the beginning of the long-term experiment in 1988 to 12.6±0.11 g kg-1 (P<0.05). Compared to CK, N1 and N2 exhibited higher soil α-galactosidase and β-galactosidase activities, but lower soil α-glucosidase and β-glucosidase activities (P<0.05), indicating that inorganic fertilization had different impacts on these C transformation enzymes. Compared with CK, the M, MN1 and MN2 treatments exhibited higher enzyme activities, soil TOC, total nitrogen, dissolved organic C, and microbial biomass C and N. The fertilization regime of the MN1 treatment was identified as optimal because it produced the highest yields and increased soil quality, ensuring sustainability. The results suggest that inorganic fertilizer alone, especially in high amounts, in greenhouse fields is detrimental to soil quality. PMID:25706998

  20. Changes in soil carbon and enzyme activity as a result of different long-term fertilization regimes in a greenhouse field.

    PubMed

    Zhang, Lili; Chen, Wei; Burger, Martin; Yang, Lijie; Gong, Ping; Wu, Zhijie

    2015-01-01

    In order to discover the advantages and disadvantages of different fertilization regimes and identify the best management practice of fertilization in greenhouse fields, soil enzyme activities involved in carbon (C) transformations, soil chemical characteristics, and crop yields were monitored after long-term (20-year) fertilization regimes, including no fertilizer (CK), 300 kg N ha-1 and 600 kg N ha-1 as urea (N1 and N2), 75 Mg ha-1 horse manure compost (M), and M with either 300 or 600 kg N ha-1 urea (MN1 and MN2). Compared with CK, fertilization increased crop yields by 31% (N2) to 69% (MN1). However, compared with CK, inorganic fertilization (especially N2) also caused soil acidification and salinization. In the N2 treatment, soil total organic carbon (TOC) decreased from 14.1±0.27 g kg-1 at the beginning of the long-term experiment in 1988 to 12.6±0.11 g kg-1 (P<0.05). Compared to CK, N1 and N2 exhibited higher soil α-galactosidase and β-galactosidase activities, but lower soil α-glucosidase and β-glucosidase activities (P<0.05), indicating that inorganic fertilization had different impacts on these C transformation enzymes. Compared with CK, the M, MN1 and MN2 treatments exhibited higher enzyme activities, soil TOC, total nitrogen, dissolved organic C, and microbial biomass C and N. The fertilization regime of the MN1 treatment was identified as optimal because it produced the highest yields and increased soil quality, ensuring sustainability. The results suggest that inorganic fertilizer alone, especially in high amounts, in greenhouse fields is detrimental to soil quality.

  1. Long-term effects of oral tea polyphenols and Lactobacillus brevis M8 on biochemical parameters, digestive enzymes, and cytokines expression in broilers.

    PubMed

    Li, Hua-li; Li, Zong-jun; Wei, Zhong-shan; Liu, Ting; Zou, Xiao-zuo; Liao, Yong; Luo, Yu

    2015-12-01

    This study investigates the long-term effects of oral tea polyphenols (TPs) and Lactobacillus brevis M8 (LB) on biochemical parameters, digestive enzymes, and cytokines expression in broilers. In experiment 1, 240 broiler chickens were selected to investigate the effects of 0.06 g/kg body weight (BW) TP and 1.0 ml/kg BW LB on broilers; in experiment 2, 180 broiler chickens were assigned randomly to three groups to investigate the effects of different dosages of TP (0.03, 0.06, and 0.09 g/kg BW) combined with 1.0 ml/kg BW LB on broilers; in experiment 3, 180 broiler chickens were assigned randomly to three groups to investigate the effects of different dosages of LB (0.5, 1.0, and 1.5 ml/kg BW) combined with 0.06 g/kg BW TP on broilers. The results showed that TP and LB affected serum biochemical parameters, and TP reduced serum cholesterol (CHO) and low-density lipoprotein cholesterol (LDL-C) abundances in a dosage-dependent manner (P<0.05) on Day 84. Meanwhile, broilers fed a diet supplemented with TP or LB had a lower intestinal lipase activity on Day 84 compared with the control group (P<0.05). Middle and high dosages of TP increased pancreatic lipase and proventriculus pepsin activities (P<0.05). Also middle and high dosages of LB significantly enhanced pancreatic lipase activity (P<0.05), while high LB supplementation inhibited intestinal trypsase (P<0.05) on Day 84. Furthermore, both TP and LB reduced intestinal cytokine expression and nuclear factor-κ B (NF-κB) mRNA level on Days 56 and 84. In conclusion, long-term treatment of TP and LB improved lipid metabolism and digestive enzymes activities, and affected intestinal inflammatory status, which may be associated with the NF-κB signal.

  2. Human growth hormone replacement in adult hypopituitary patients: long-term effects on body composition and lipid status--3-year results from the HypoCCS Database.

    PubMed

    Attanasio, Andrea F; Bates, Peter C; Ho, Ken K Y; Webb, Susan M; Ross, Richard J; Strasburger, Christian J; Bouillon, Roger; Crowe, Brenda; Selander, Keith; Valle, Domenico; Lamberts, Steven W J

    2002-04-01

    The Hypopituitary Control and Complications Study is an international surveillance study evaluating efficacy and safety of GH therapy of adult GH-deficient patients in clinical practice. The present report examined baseline data from 1,123 adult onset (AO) and 362 childhood onset (CO) patients, as well as efficacy in 242 patients who had completed 3 yr of GH treatment. At study entry, mean height, body mass index, waist to hip ratio, and lean body mass were significantly (P < 0.001 for each) lower in CO compared with AO patients. After 3 yr on GH, lean body mass was significantly increased in AO males and females and CO males but not CO females, whereas fat mass was significantly decreased in AO males only. Serum total cholesterol was decreased in females (-0.32 +/- 1.00 mmol/liter; P = 0.045) and males (-0.36 +/- 0.96 mmol/liter; P = 0.004). High-density lipoprotein (HDL) cholesterol was increased for females (0.10 +/- 0.26 mmol/liter; P = 0.026) and males (0.10 +/- 0.34 mmol/liter; P = 0.022). The low-density lipoprotein/HDL ratio was decreased in AO males (-0.93 +/- 2.00; P = 0.003), AO females (-0.65 +/- 0.74; P < 0.001), and CO females (-0.69 +/- 0.76; P = 0.038), but the decrease in CO males was not significant (-0.84 +/- 2.85; P = 0.273). In AO patients, lean body mass increase from baseline was greatest in the those younger than 40 yr old, less but still significant in the middle group (40-60 yr) and unchanged in older (>60 yr) patients; conversely, decreases in the low-density lipoprotein/HDL ratio were small and not significant in the younger patients but greater and significant in the middle and older age groups. During the 3-yr treatment, 114 (7.7%) patients discontinued, including 9 (0.6%) for tumor recurrences, 9 (0.6%) for neoplasia, and 9 (0.6%) for side effects. Therefore, these observational data showed significant long-term efficacy of adult GH replacement therapy on body composition and lipid profiles and indicate that age is an important

  3. [Effects of different long-term fertilization on the activities of enzymes related to carbon, nitrogen, and phosphorus cycles in a red soil].

    PubMed

    Fan, Miao-zhen; Yin, Chang; Fan, Fen-liang; Song, A-lin; Wang, Bo-ren; Li, Dong-chu; Liang, Yong-chao

    2015-03-01

    Using a microplate fluorimetric assay method, five fertilization treatments, i.e. no-fertilizer control (CK) , sole application of nitrogen (N), balanced application of nitrogen, phosphorus, and potassium fertilizer (NPK), application of pig manure (M), and combination of pig manure with balanced chemical fertilizer (MNPK) were selected to investigate the effects of different long-term fertilization regimes on the activity of five enzymes (β-1, 4-glucosidase, βG; cellobiohydrolase, CBH; β-1, 4-xylosidase, βX; β-1, 4-N-acetylglucosaminidase, NAG; acid phosphatase, AP) in a red soil sampled from Qiyang, Hunnan Province. The results showed that compared with CK treatment, N treatment had no impact on βG, βX, CBH, and NAG activities but reduced AP activity, while NPK, M and MNPK treatments increased the activities of all the five enzymes. Correlation analysis indicated that all the five enzyme activities were positively correlated with the content of nitrate (r=0.465-0.733) , the content of available phosphorus (r=0.612-0.947) , soil respiration (r=0.781-0.949) and crop yield (r=0.735-0.960), while βG, CBH and AP were positively correlated with pH (r= 0.707-0.809), only AP was significantly correlated with dissolvable organic carbon (r = -0.480). These results suggested that the activities of the measured enzymes could be used as indicators of red soil fertility under different fertilization regimes, but the five enzymes tested provided limited information on the degree of acidification induced by application of mineral nitrogen.

  4. Hydrogen peroxide generation and antioxidant enzyme activities in the leaves and roots of wheat cultivars subjected to long-term soil drought stress.

    PubMed

    Huseynova, Irada M; Aliyeva, Durna R; Mammadov, Alamdar Ch; Aliyev, Jalal A

    2015-08-01

    The dynamics of the activity of catalase, ascorbate peroxidase, guaiacol peroxidase, and benzidine peroxidase, as well as the level of hydrogen peroxide in the vegetative organs of durum wheat (Triticum durum Desf.) cultivars was studied under long-term soil drought conditions. It was established that hydrogen peroxide generation occurred at early stages of stress in the tolerant variety Barakatli-95, whereas in the susceptible variety Garagylchyg-2 its significant amounts were accumulated only at later stages. Garagylchyg-2 shows a larger reduction of photochemical activity of PS II in both genotypes at all stages of ontogenesis under drought stress than Barakatli-95. The highest activity of catalase which plays a leading role in the neutralization of hydrogen peroxide was observed in the leaves and roots of the drought-tolerant variety Barakatli-95. Despite the fact that the protection system also includes peroxidases, the activity of these enzymes even after synthesis of their new portions is substantially lower compared with catalase. Native PAGE electrophoresis revealed the presence of one isoform of CAT, seven isoforms of APX, three isoforms of GPO, and three isoforms of BPO in the leaves, and also three isoforms of CAT, four isoforms of APX, two isoforms of GPO, and six isoforms of BPO in the roots of wheat. One isoform of CAT was found in the roots when water supply was normal and three isoforms were observed under drought conditions. Stress associated with long-term soil drought in the roots of wheat has led to an increase in the heterogeneity due to the formation of two new sedentary forms of catalase: CAT2 and CAT3.

  5. Aggression in Replacement Grower and Finisher Gilts fed a High-Tryptophan Diet and the Effect of Long-term Human-Animal Interaction

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Aggression is a major problem for swine production as it negatively impacts the pigs’ health and welfare. Dietary approaches such as increasing tryptophan (TRP) ingestion to raise cerebral serotonin (5-HT) – a key neurotransmitter for aggression control, and long-term positive social handling have b...

  6. Long-term effects of oral tea polyphenols and Lactobacillus brevis M8 on biochemical parameters, digestive enzymes, and cytokines expression in broilers

    PubMed Central

    Li, Hua-li; Li, Zong-jun; Wei, Zhong-shan; Liu, Ting; Zou, Xiao-zuo; Liao, Yong; Luo, Yu

    2015-01-01

    This study investigates the long-term effects of oral tea polyphenols (TPs) and Lactobacillus brevis M8 (LB) on biochemical parameters, digestive enzymes, and cytokines expression in broilers. In experiment 1, 240 broiler chickens were selected to investigate the effects of 0.06 g/kg body weight (BW) TP and 1.0 ml/kg BW LB on broilers; in experiment 2, 180 broiler chickens were assigned randomly to three groups to investigate the effects of different dosages of TP (0.03, 0.06, and 0.09 g/kg BW) combined with 1.0 ml/kg BW LB on broilers; in experiment 3, 180 broiler chickens were assigned randomly to three groups to investigate the effects of different dosages of LB (0.5, 1.0, and 1.5 ml/kg BW) combined with 0.06 g/kg BW TP on broilers. The results showed that TP and LB affected serum biochemical parameters, and TP reduced serum cholesterol (CHO) and low-density lipoprotein cholesterol (LDL-C) abundances in a dosage-dependent manner (P<0.05) on Day 84. Meanwhile, broilers fed a diet supplemented with TP or LB had a lower intestinal lipase activity on Day 84 compared with the control group (P<0.05). Middle and high dosages of TP increased pancreatic lipase and proventriculus pepsin activities (P<0.05). Also middle and high dosages of LB significantly enhanced pancreatic lipase activity (P<0.05), while high LB supplementation inhibited intestinal trypsase (P<0.05) on Day 84. Furthermore, both TP and LB reduced intestinal cytokine expression and nuclear factor-κ B (NF-κB) mRNA level on Days 56 and 84. In conclusion, long-term treatment of TP and LB improved lipid metabolism and digestive enzymes activities, and affected intestinal inflammatory status, which may be associated with the NF-κB signal. PMID:26642185

  7. Induction of rhodanese, a detoxification enzyme, in livers from mice after long-term irradiation with low-dose-rate gamma-rays.

    PubMed

    Nakajima, Tetsuo; Taki, Keiko; Wang, Bing; Ono, Tetsuya; Matsumoto, Tsuneya; Oghiso, Yoichi; Tanaka, Kimio; Ichinohe, Kazuaki; Nakamura, Shingo; Tanaka, Satoshi; Nenoi, Mitsuru

    2008-11-01

    The health effects of low-dose radiation exposure are of public concern. Although molecular events in the cellular response to high-dose-rate radiation exposure have been fully investigated, effects of long-term exposure to extremely low-dose-rate radiation remain unclear. Protein expression was analyzed by two-dimensional electrophoresis in livers from mice irradiated for 485 days (22 hr/day) at low-dose-rates of 0.032 microGy/min, 0.65 microGy/min and 13 microGy/min (total doses of 21 mGy, 420 mGy and 8000 mGy, respectively). One of the proteins that showed marked changes in expression was identified as rhodanese (thiosulfate sulfurtransferase). Rhodanese expression was increased after irradiation at 0.65 microGy/min and 13 microGy/min, while its expression was not changed at 0.032 microGy/min. Rhodanese is a detoxification enzyme, probably related to the regulation of antioxidative function. However, antioxidative proteins, such as superoxide dismutase (SOD)1 (also known as Cu,Zn-SOD) and SOD2 (also known as Mn-SOD), which can be induced by high-dose-rate radiation, were not induced at any low-dose-rates tested. These findings indicate that rhodanese is a novel protein induced by low-dose-rate radiation, and further analysis could provide insight into the effects of extremely low-dose-rate radiation exposure.

  8. Long-term replacement of a mutated nonfunctional CNS gene: reversal of hypothalamic diabetes insipidus using an EIAV-based lentiviral vector expressing arginine vasopressin.

    PubMed

    Bienemann, Alison S; Martin-Rendon, Enca; Cosgrave, Anna S; Glover, Colin P J; Wong, Liang-Fong; Kingsman, Susan M; Mitrophanous, Kyriacos A; Mazarakis, Nicholas D; Uney, James B

    2003-05-01

    Due to the complexity of brain function and the difficulty in monitoring alterations in neuronal gene expression, the potential of lentiviral gene therapy vectors to treat disorders of the CNS has been difficult to fully assess. In this study, we have assessed the utility of a third-generation equine infectious anemia virus (EIAV) in the Brattleboro rat model of diabetes insipidus, in which a mutation in the arginine vasopressin (AVP) gene results in the production of nonfunctional mutant AVP precursor protein. Importantly, by using this model it is possible to monitor the success of the gene therapy treatment by noninvasive assays. Injection of an EIAV-CMV-AVP vector into the supraoptic nuclei of the hypothalamus resulted in expression of functional AVP peptide in magnocellular neurons. This was accompanied by a 100% recovery in water homeostasis as assessed by daily water intake, urine production, and urine osmolality lasting for a 1-year measurement period. These data show that a single gene defect leading to a neurological disorder can be corrected with a lentiviral-based strategy. This study highlights the potential of using viral gene therapy for the long-term treatment of disorders of the CNS.

  9. Wear paths produced by individual hip-replacement patients--a large-scale, long-term follow-up study.

    PubMed

    Bennett, D; Humphreys, L; O'Brien, S; Kelly, C; Orr, J F; Beverland, D E

    2008-08-07

    Wear particle accumulation is one of the main contributors to osteolysis and implant failure in hip replacements. Altered kinematics produce significant differences in wear rates of hip replacements in simulator studies due to varying degrees of multidirectional motion. Gait analysis data from 153 hip-replacement patients 10-years post-operation were used to model two- and three-dimensional wear paths for each patient. Wear paths were quantified in two dimensions using aspect ratios and in three dimensions using the surface areas of the wear paths, with wear-path surface area correlating poorly with aspect ratio. The average aspect ratio of the patients wear paths was 3.97 (standard deviation=1.38), ranging from 2.13 to 10.86. Sixty percent of patients displayed aspect ratios between 2.50 and 3.99. However, 13% of patients displayed wear paths with aspect ratios >5.5, which indicates reduced multidirectional motion. The majority of total hip replacement (THR) patients display gait kinematics which produce multidirectional wear paths, but a significant minority display more linear paths.

  10. Modeling chronic hepatitis B or C virus infection during antiviral therapy using an analogy to enzyme kinetics: long-term viral dynamics without rebound and oscillation.

    PubMed

    Takayanagi, Toshiaki

    2013-12-01

    The basic model for chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection during therapy enables us to analyze short-term viral kinetics. However, the model is not useful for analyzing long-term viral kinetics. Here, I suggest a new model that was obtained by introducing Michaelis-Menten kinetics into the basic model. The new model can exhibit long-term viral kinetics without rebound and oscillation, unlike the basic model. The value of the parameter K in the new model is analogous to the Michaelis constant Km and is predicted to be approximately less than 10(10)/ml.

  11. Long-term soil microbial community and enzyme activity responses to an integrated cropping-livestock system in a semi-arid region

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This study is part of a larger long-term project to develop and evaluate integrated crop and livestock systems in order to reduce dependence on underground water sources by optimizing cotton (Gossypium hirsutum) production in the Texas High Plains of U.S. Microbial communities and activities were e...

  12. Different functional recovery of the left ventricle after valve replacement for aortic regurgitation: correlation between grade of ventricular arrhythmia and long-term mortality.

    PubMed

    Noji, S; Kitamura, M; Hachida, M; Endo, M; Hashimoto, A; Koyanagi, H

    1995-05-01

    Although aortic valve replacement for aortic regurgitation relieves left ventricular volume overload, ventricular size often remains abnormal after operation, particularly in the setting of marked or prolonged preoperative left ventricular dysfunction. The aim of this study is to assess the relationship between the grade of ventricular arrhythmias before operation and the recovery of left ventricular function after aortic valve replacement. Between January 1980 and August 1993, 229 patients with pure aortic regurgitation underwent aortic valve replacement at our institution. In this group, 50 patients (21.8%) who showed left ventricular end-systolic volume index (LVESVI) of 150 ml/m2 or greater received 24-hour ambulatory electrocardiographic recordings before and after operation. According to the preoperative grade of ventricular arrhythmias, the patients were divided into three groups. Group A included 20 patients with severe and frequent ventricular premature beats (VPBs). Group B included nine patients with severe and non-frequent ventricular premature beats (VPBs). Group C included 21 patients with non-severe and non-frequent VPBs. Left ventricular end-systolic dimension (LVDs), end-diastolic dimension (LVDd) and fractional shortening (LVFS) were measured in each echocardiogram before, and one year and five years after operation. LVDd significantly decreased at one year after operation in all three groups. At one year after operation, LVDs significantly decreased in group B (42.0 +/- 7.6 mm) and group C (42.6 +/- 8.6 mm), while LVDs showed no significant change in Group A (55.4 +/- 11.1 mm). After five postoperative years, further significant decrease of LVDs was found in group C (32.4 +/- 7.1 mm).(ABSTRACT TRUNCATED AT 250 WORDS)

  13. Long term effect of curcumin in restoration of tumour suppressor p53 and phase-II antioxidant enzymes via activation of Nrf2 signalling and modulation of inflammation in prevention of cancer.

    PubMed

    Das, Laxmidhar; Vinayak, Manjula

    2015-01-01

    Inhibition of carcinogenesis may be a consequence of attenuation of oxidative stress via activation of antioxidant defence system, restoration and stabilization of tumour suppressor proteins along with modulation of inflammatory mediators. Previously we have delineated significant role of curcumin during its long term effect in regulation of glycolytic pathway and angiogenesis, which in turn results in prevention of cancer via modulation of stress activated genes. Present study was designed to investigate long term effect of curcumin in regulation of Nrf2 mediated phase-II antioxidant enzymes, tumour suppressor p53 and inflammation under oxidative tumour microenvironment in liver of T-cell lymphoma bearing mice. Inhibition of Nrf2 signalling observed during lymphoma progression, resulted in down regulation of phase II antioxidant enzymes, p53 as well as activation of inflammatory signals. Curcumin potentiated significant increase in Nrf2 activation. It restored activity of phase-II antioxidant enzymes like GST, GR, NQO1, and tumour suppressor p53 level. In addition, curcumin modulated inflammation via upregulation of TGF-β and reciprocal regulation of iNOS and COX2. The study suggests that during long term effect, curcumin leads to prevention of cancer by inducing phase-II antioxidant enzymes via activation of Nrf2 signalling, restoration of tumour suppressor p53 and modulation of inflammatory mediators like iNOS and COX2 in liver of lymphoma bearing mice.

  14. A biochemical and physicochemical comparison of two recombinant enzymes used for enzyme replacement therapies of hunter syndrome.

    PubMed

    Chung, Yo Kyung; Sohn, Young Bae; Sohn, Jong Mun; Lee, Jieun; Chang, Mi Sun; Kwun, Younghee; Kim, Chi Hwa; Lee, Jin Young; Yook, Yeon Joo; Ko, Ah-Ra; Jin, Dong-Kyu

    2014-05-01

    Mucopolysaccharidosis II (MPS II, Hunter syndrome; OMIM 309900) is an X-linked lysosomal storage disease caused by a deficiency in the enzyme iduronate-2-sulfatase (IDS), leading to accumulation of glycosaminoglycans (GAGs). For enzyme replacement therapy (ERT) of Hunter syndrome, two recombinant enzymes, idursulfase (Elaprase(®), Shire Human Genetic Therapies, Lexington, MA) and idursulfase beta (Hunterase(®), Green Cross Corporation, Yongin, Korea), are currently available in Korea. To compare the biochemical and physicochemical differences between idursulfase and idursulfase beta, we examined the formylglycine (FGly) content, specific enzyme activity, mannose-6-phosphate (M6P) content, sialic acid content, and in vitro cell uptake activity of normal human fibroblasts of these two enzymes.The FGly content, which determines the enzyme activity, of idursulfase beta was significantly higher than that of idursulfase (79.4 ± 0.9 vs. 68.1 ± 2.2 %, P < 0.001). In accordance with the FGly content, the specific enzyme activity of idursulfase beta was significantly higher than that of idursulfase (42.6 ± 1.1 vs. 27.8 ± 0.9 nmol/min/μg protein, P < 0.001). The levels of M6P and sialic acid were not significantly different (2.4 ± 0.1 vs 2.4 ± 0.3 mol/mol protein for M6P and 12.3 ± 0.7 vs. 12.4 ± 0.4 mol/mol protein for sialic acid). However, the cellular uptake activity of the normal human fibroblasts in vitro showed a significant difference (Kuptake, 5.09 ± 0.96 vs. 6.50 ± 1.28 nM protein, P = 0.017).In conclusion, idursulfase beta exhibited significantly higher specific enzyme activity than idursulfase, resulting from higher FGly content. These biochemical differences may be partly attributed to clinical efficacy. However, long-term clinical evaluations of Hunter syndrome patients treated with these two enzymes will be needed to demonstrate the clinical implications of significant difference of the enzyme activity and the FGly content.

  15. The Effects of Long-Term Feeding of Rodent Food Bars on Lipid Peroxidation And Antioxidant Enzyme Levels In Fisher Rats

    NASA Technical Reports Server (NTRS)

    Ramirez, Joel; Zirkle-Yoshida, M.; Piert, S.; Barrett, J.; Yul, D.; Dalton, B.; Girten, B.

    2001-01-01

    A specialized rodent food bar diet has been developed and utilized successfully for short-duration shuttle missions. Recent tests conducted in preparation for experiments aboard the International Space Station (ISS) indicated that long-term food bar feeding for three months induced hyperlipidemia in rats. This study examined oxidative stress status in livers of these same animals. Spectrophotometric analysis of 79 Fischer rat livers (40 female and 39 male) for lipid peroxidation (LPO) and superoxide dismutase (SOD) was conducted using Bioxytech LPO-587(TM) assay kit and SOD-525(Tm) assay kit, respectively. The treatment groups consisted of 20 male CHOW and 19 male FOOD BAR rats and 20 female CHOW and 20 female FOOD BAR rats. Statistical analysis to compare differences between groups was performed by standard analysis of variance procedures. The male FOOD BAR group LPO mean (3.6 +/- 0.2 mmol/g) was significantly (p less than or equal to 0.05) greater than that of the male CHOW group (2.1 +/-0.1 mmol/g). Moreover the female FOOD BAR group LPO mean (2.9 +/-0.1 mmol/g) was also significantly greater than the female CHOW group mean (2.2 +/-0.1 mmol/g). The mean values for SOD in both male and female groups showed no significant differences between CHOW and FOOD BAR groups. These results show that LPO levels were significantly higher in both the male and female FOOD BAR groups compared to CHOW groups and that there was no concomitant increase in SOD levels across the group. In addition, males showed a greater difference than females in terms of LPO levels. These findings suggest a need for further investigation into the use of the current food bar formulation for long-term experiments such as those planned for the ISS.

  16. Fabry disease in children and the effects of enzyme replacement treatment.

    PubMed

    Pintos-Morell, Guillem; Beck, Michael

    2009-11-01

    Fabry disease is a rare, X-linked inborn error of glycosphingolipid catabolism caused by a deficiency in the activity of the lysosomal enzyme, alpha-galactosidase A. In affected patients, the enzyme substrate, globotriaosylceramide (Gb3), accumulates in cells of various tissues and organs. Lysosomal accumulation of Gb3 begins in utero, and signs and symptoms of Fabry disease emerge in childhood and adolescence. The earliest presenting symptoms are typically neuropathic pain and gastrointestinal problems, which can have a substantial impact on health-related quality of life. Life-threatening major organ involvement is rare in young patients, but signs of kidney dysfunction (e.g., proteinuria), left ventricular hypertrophy, and stroke have been reported in children. There are two enzyme preparations for therapy: agalsidase alfa and beta. In two clinical trials of enzyme replacement therapy (ERT) with agalsidase alfa, including 37 children, boys demonstrated reductions in plasma Gb3 levels, and both boys and girls reported reductions in neuropathic pain and in the use of neuropathic pain medications. Heart rate variability, which is reduced in boys with Fabry disease, was statistically significantly improved with 6 months of agalsidase alfa treatment. In a single clinical study of agalsidase beta in children (n =16), skin Gb3 deposits and plasma Gb3 levels were reduced in boys. Differences exist in the administration and the safety profile of these two enzyme formulations. Follow-up of these cohorts and additional studies will be necessary to fully evaluate long-term efficacy of ERT in children with Fabry disease.

  17. Biomolecules damage and redox status abnormalities in Fabry patients before and during enzyme replacement therapy.

    PubMed

    Biancini, Giovana Brondani; Jacques, Carlos Eduardo; Hammerschmidt, Tatiane; de Souza, Heryk Motta; Donida, Bruna; Deon, Marion; Vairo, Filippo Pinto; Lourenço, Charles Marques; Giugliani, Roberto; Vargas, Carmen Regla

    2016-10-01

    Fabry disease (FD) is caused by deficient activity of the lysosomal enzyme α-galactosidase A. Its substrates, mainly globotriaosylceramide (Gb3), accumulate and seem to induce other pathophysiological findings of FD. Once enzyme replacement therapy (ERT) is not completely efficient on preventing disease progress in FD patients, elucidating the underlying mechanisms in FD pathophysiology is essential to the development of additional therapeutic strategies. We investigated 58 Fabry patients (23 male and 35 female) subdivided into two groups (at diagnosis and during long-term ERT) and compared them to healthy individuals. Fabry patients at diagnosis presented altered glutathione (GSH) metabolism (higher GSH levels, lower glutathione peroxidase - GPx - and normal glutathione reductase - GR - activities), higher lipid peroxidation levels (thiobarbituric acid reactive species - TBARS - and malondialdehyde - MDA), nitric oxide (NO(.)) equivalents and urinary Gb3. Fabry patients on ERT presented GSH metabolism similar to controls, although lipid peroxidation and urinary levels of NO(.) equivalents remained higher whereas Gb3 levels were lower than at diagnosis but still higher than controls. These data demonstrated that redox impairment occurs in Fabry patients before and after ERT, probably as a consequence of Gb3 accumulation, providing targets to future therapy approaches using antioxidants in combination with ERT in FD.

  18. A Newly Defined and Xeno-Free Culture Medium Supports Every-Other-Day Medium Replacement in the Generation and Long-Term Cultivation of Human Pluripotent Stem Cells

    PubMed Central

    Scotty Cadet, Jean; Shah, Kevan; Walde, Amy; Tran, Huan; Kovarcik, Don Paul; Clarke, Diana; Fellner, Thomas

    2016-01-01

    Human pluripotent stem cells (hPSCs) present an unprecedented opportunity to advance human health by offering an alternative and renewable cell resource for cellular therapeutics and regenerative medicine. The present demand for high quality hPSCs for use in both research and clinical studies underscores the need to develop technologies that will simplify the cultivation process and control variability. Here we describe the development of a robust, defined and xeno-free hPSC medium that supports reliable propagation of hPSCs and generation of human induced pluripotent stem cells (hiPSCs) from multiple somatic cell types; long-term serial subculturing of hPSCs with every-other-day (EOD) medium replacement; and banking fully characterized hPSCs. The hPSCs cultured in this medium for over 40 passages are genetically stable, retain high expression levels of the pluripotency markers TRA-1-60, TRA-1-81, Oct-3/4 and SSEA-4, and readily differentiate into ectoderm, mesoderm and endoderm. Importantly, the medium plays an integral role in establishing a cGMP-compliant process for the manufacturing of hiPSCs that can be used for generation of clinically relevant cell types for cell replacement therapy applications. PMID:27606941

  19. Application of Long-term cultured Interferon-γ Enzyme-linked Immunospot Assay for Assessing Effector and Memory T Cell Responses in Cattle

    PubMed Central

    Maggioli, Mayara F.; Palmer, Mitchell V.; Vordermeier, H. Martin; Whelan, Adam O.; Fosse, James M.; Nonnecke, Brian J.; Waters, W. Ray

    2015-01-01

    Effector and memory T cells are generated through developmental programing of naïve cells following antigen recognition. If the infection is controlled up to 95 % of the T cells generated during the expansion phase are eliminated (i.e., contraction phase) and memory T cells remain, sometimes for a lifetime. In humans, two functionally distinct subsets of memory T cells have been described based on the expression of lymph node homing receptors. Central memory T cells express C-C chemokine receptor 7 and CD45RO and are mainly located in T-cell areas of secondary lymphoid organs. Effector memory T cells express CD45RO, lack CCR7 and display receptors associated with lymphocyte homing to peripheral or inflamed tissues. Effector T cells do not express either CCR7 or CD45RO but upon encounter with antigen produce effector cytokines, such as interferon-γ. Interferon-γ release assays are used for the diagnosis of bovine and human tuberculosis and detect primarily effector and effector memory T cell responses. Central memory T cell responses by CD4+ T cells to vaccination, on the other hand, may be used to predict vaccine efficacy, as demonstrated with simian immunodeficiency virus infection of non-human primates, tuberculosis in mice, and malaria in humans. Several studies with mice and humans as well as unpublished data on cattle, have demonstrated that interferon-γ ELISPOT assays measure central memory T cell responses. With this assay, peripheral blood mononuclear cells are cultured in decreasing concentration of antigen for 10 to 14 days (long-term culture), allowing effector responses to peak and wane; facilitating central memory T cells to differentiate and expand within the culture. PMID:26275095

  20. Enzyme replacement therapy in newborn mucopolysaccharidosis IVA mice: early treatment rescues bone lesions?

    PubMed

    Tomatsu, Shunji; Montaño, Adriana M; Oikawa, Hirotaka; Dung, Vu Chi; Hashimoto, Amiko; Oguma, Toshihiro; Gutiérrez, Monica L; Takahashi, Tatsuo; Shimada, Tsutomu; Orii, Tadao; Sly, William S

    2015-02-01

    We treated mucopolysaccharidosis IVA (MPS IVA) mice to assess the effects of long-term enzyme replacement therapy (ERT) initiated at birth, since adult mice treated by ERT showed little improvement in bone pathology [1]. To conduct ERT in newborn mice, we used recombinant human N-acetylgalactosamine-6-sulfate sulfatase (GALNS) produced in a CHO cell line. First, to observe the tissue distribution pattern, a dose of 250units/g body weight was administered intravenously in MPS IVA mice at day 2 or 3. The infused enzyme was primarily recovered in the liver and spleen, with detectable activity in the bone and brain. Second, newborn ERT was conducted after a tissue distribution study. The first injection of newborn ERT was performed intravenously, the second to fourth weekly injections were intraperitoneal, and the remaining injections from 5th to 14th weeks were intravenous into the tail vein. MPS IVA mice treated with GALNS showed clearance of lysosomal storage in the liver and spleen, and sinus lining cells in bone marrow. The column structure of the growth plate was organized better than that in adult mice treated with ERT; however, hyaline and fibrous cartilage cells in the femur, spine, ligaments, discs, synovium, and periosteum still had storage materials to some extent. Heart valves were refractory to the treatment. Levels of serum keratan sulfate were kept normal in newborn ERT mice. In conclusion, the enzyme, which enters the cartilage before the cartilage cell layer becomes mature, prevents disorganization of column structure. Early treatment from birth leads to partial remission of bone pathology in MPS IVA mice.

  1. Long-term environmental stewardship.

    SciTech Connect

    Nagy, Michael David

    2010-08-01

    The purpose of this Supplemental Information Source Document is to effectively describe Long-Term Environmental Stewardship (LTES) at Sandia National Laboratories/New Mexico (SNL/NM). More specifically, this document describes the LTES and Long-Term Stewardship (LTS) Programs, distinguishes between the LTES and LTS Programs, and summarizes the current status of the Environmental Restoration (ER) Project.

  2. Long-term urethral catheterisation.

    PubMed

    Turner, Bruce; Dickens, Nicola

    This article discusses long-term urethral catheterisation, focusing on the relevant anatomy and physiology, indications for the procedure, catheter selection and catheter care. It is important that nurses have a good working knowledge of long-term catheterisation as the need for this intervention will increase with the rise in chronic health conditions and the ageing population.

  3. Presynaptic long-term plasticity

    PubMed Central

    Yang, Ying; Calakos, Nicole

    2013-01-01

    Long-term synaptic plasticity is a major cellular substrate for learning, memory, and behavioral adaptation. Although early examples of long-term synaptic plasticity described a mechanism by which postsynaptic signal transduction was potentiated, it is now apparent that there is a vast array of mechanisms for long-term synaptic plasticity that involve modifications to either or both the presynaptic terminal and postsynaptic site. In this article, we discuss current and evolving approaches to identify presynaptic mechanisms as well as discuss their limitations. We next provide examples of the diverse circuits in which presynaptic forms of long-term synaptic plasticity have been described and discuss the potential contribution this form of plasticity might add to circuit function. Finally, we examine the present evidence for the molecular pathways and cellular events underlying presynaptic long-term synaptic plasticity. PMID:24146648

  4. Enzyme replacement prevents enamel defects in hypophosphatasia mice

    PubMed Central

    Yadav, Manisha C.; de Oliveira, Rodrigo Cardoso; Foster, Brian L.; Fong, Hanson; Cory, Esther; Narisawa, Sonoko; Sah, Robert L.; Somerman, Martha; Whyte, Michael P.; Millán, José Luis

    2012-01-01

    Hypophosphatasia (HPP) is the inborn error of metabolism characterized by deficiency of alkaline phosphatase activity leading to rickets or osteomalacia and to dental defects. HPP occurs from loss-of-function mutations within the gene that encodes the tissue-nonspecific isozyme of alkaline phosphatase (TNAP). TNAP knockout (Alpl−/−, a.k.a. Akp2−/−) mice closely phenocopy infantile HPP, including the rickets, vitamin B6-responsive seizures, improper dentin mineralization, and lack of acellular cementum. Here, we report that lack of TNAP in Alpl−/− mice also causes severe enamel defects, which are preventable by enzyme replacement with mineral-targeted TNAP (ENB-0040). Immunohistochemistry was used to map the spatiotemporal expression of TNAP in the tissues of the developing enamel organ of healthy mouse molars and incisors. We found strong, stage-specific expression of TNAP in ameloblasts. In the Alpl−/− mice, histological, μCT, and scanning electron microscopy analysis showed reduced mineralization and disrupted organization of the rods and inter-rod structures in enamel of both the molars and incisors. All of these abnormalities were prevented in mice receiving from birth daily subcutaneous injections of mineral-targeting, human TNAP (sALP-FcD10, a.k.a. ENB-0040) at 8.2 mg/kg/day for up to 44 days. These data reveal an important role for TNAP in enamel mineralization, and demonstrate the efficacy of mineral-targeted TNAP to prevent enamel defects in HPP. PMID:22461224

  5. Long term complications of diabetes

    MedlinePlus

    ... medlineplus.gov/ency/patientinstructions/000327.htm Long-term complications of diabetes To use the sharing features on this page, ... other tests. All these may help you keep complications of diabetes away. You will need to check your blood ...

  6. Long-term survival of non-elderly patients with severe heart failure treated with angiotensin-converting enzyme inhibitors assessment of treatment with captopril and enalapril survival study (ACESS).

    PubMed

    Huang, Chien-Ming; Young, Mason-Shing

    2002-10-01

    The present study examined the effect of treatment with angiotensin-converting enzyme inhibitors (ACEIs) on the long-term prognosis in 119 patients with dilated cardiomyopathy (DCM). Conventional therapy was used in 29 patients and 90 patients were treated with ACEIs: 50 were taking captopril and 40 were taking enalapril; 24 were taking > or = 75 mg captopril or > or = 20 mg enalapril daily (high-dose group) and 66 patients received smaller doses (low-dose group). No significant differences between groups were detected with respect to demographics and clinical signs of congestive heart failure (CHF). During follow-up, 65 patients survived and 54 patients died: 34 patients were in group 1 and 20 patients were in the placebo group. Patients treated with ACEIs had a significantly better survival during the first to third year, but the difference was not significant between the high- and low-dose groups. Comparison of the cumulative probability of death in the enalapril and captopril groups showed a trend of significant reduction of mortality by 13% in the enalapril group (p<0.10). These data indicate that ACEIs have a beneficial effect on prolonging the short- and long-term survival in DCM patients, so it is strongly recommended that all patients with DCM should be treated with ACEIs unless contraindicated. In this study, lower doses of ACEI seemed prognostically equivalent to higher doses, and enalapril appeared to be preferable to captopril in the treatment of severe CHF. Additional prospective large studies are necessary to verify the relationship observed here between the optimal dosage as well as the duration of action of different ACEIs and their outcomes.

  7. Short-term effects on antioxidant enzymes and long-term genotoxic and carcinogenic potential of CuO nanoparticles compared to bulk CuO and ionic copper in mussels Mytilus galloprovincialis.

    PubMed

    Ruiz, Pamela; Katsumiti, Alberto; Nieto, Jose A; Bori, Jaume; Jimeno-Romero, Alba; Reip, Paul; Arostegui, Inmaculada; Orbea, Amaia; Cajaraville, Miren P

    2015-10-01

    The aim of this work was to study short-term effects on antioxidant enzyme activities and long-term genotoxic and carcinogenic potential of CuO nanoparticles (NPs) in comparison to bulk CuO and ionic copper in mussels Mytilus galloprovincialis after 21 days exposure to 10 μg Cu L(-1). Then, mussels were kept for up to 122 days in clean water. Cu accumulation depended on the form of the metal and on the exposure time. CuO NPs were localized in lysosomes of digestive cells, as confirmed by TEM and X ray microanalysis. CuO NPs, bulk CuO and ionic copper produced different effects on antioxidant enzyme activities in digestive glands, overall increasing antioxidant activities. CuO NPs significantly induced catalase and superoxide dismutase activities. Fewer effects were observed in gills. Micronuclei frequency increased significantly in mussels exposed to CuO NPs and one organism treated with CuO NPs showed disseminated neoplasia. However, transcription levels of cancer-related genes did not vary significantly. Thus, short-term exposure to CuO NPs provoked oxidative stress and genotoxicity, but further studies are needed to determine whether these early events can lead to cancer development in mussels.

  8. Taliglucerase alfa: an enzyme replacement therapy using plant cell expression technology.

    PubMed

    Grabowski, Gregory A; Golembo, Myriam; Shaaltiel, Yoseph

    2014-05-01

    Gaucher disease (GD) is a rare, genetic lysosomal storage disorder caused by functional defects of acid β-glucosidase that results in multiple organ dysfunction. Glycosylation of recombinant acid human β-glucosidase and exposure of terminal mannose residues are critical to the success of enzyme replacement therapy (ERT) for the treatment of visceral and hematologic manifestations in GD. Three commercially available ERT products for treatment of GD type 1 (GD1) include imiglucerase, velaglucerase alfa, and taliglucerase alfa. Imiglucerase and velaglucerase alfa are produced in different mammalian cell systems and require production glycosylation modifications to expose terminal α-mannose residues, which are needed for mannose receptor-mediated uptake by target macrophages. Such modifications add to production costs. Taliglucerase alfa is a plant cell-expressed acid β-glucosidase approved in the United States and other countries for ERT in adults with GD1. A plant-based expression system, using carrot root cell cultures, was developed for production of taliglucerase alfa and does not require additional processing for postproduction glycosidic modifications. Clinical trials have demonstrated that taliglucerase alfa is efficacious, with a well-established safety profile in adult, ERT-naïve patients with symptomatic GD1, and for such patients previously treated with imiglucerase. These included significant improvements in organomegaly and hematologic parameters as early as 6months, and maintenance of achieved therapeutic values in previously treated patients. Ongoing clinical trials will further characterize the long-term efficacy and safety of taliglucerase alfa in more diverse patient populations, and may help to guide clinical decisions for achieving optimal outcomes for patients with GD1.

  9. Serum-Mediated Inhibition of Enzyme Replacement Therapy in Fabry Disease.

    PubMed

    Lenders, Malte; Stypmann, Jörg; Duning, Thomas; Schmitz, Boris; Brand, Stefan-Martin; Brand, Eva

    2016-01-01

    Fabry disease (FD) is a progressive multisystemic disorder, treatable with recombinant enzyme replacement therapy (agalsidase). However, recent studies suggest an endogenous inhibition of agalsidase in patients with FD, as reported for other lysosomal storage diseases. To assess the clinical consequences of serum-mediated agalsidase inhibition in affected patients, we determined the agalsidase inhibition status of 168 patients (68 male) with FD and compared outcomes of inhibition-positive patients with those of inhibition-negative patients. The assessment included clinical events during time on agalsidase, determination of renal and cardiac function, and evaluation of FD-related symptoms. The frequency of serum-mediated agalsidase inhibition was 40% in agalsidase-treated males. Inhibition did not depend on the compound initially used (agalsidase-α or -β). Agalsidase inhibition was associated with higher lyso-globotriaosylceramide levels and worse disease severity scores in patients. Compared with agalsidase inhibition-negative men, agalsidase inhibition-positive men showed greater left ventricular mass (P=0.02) and substantially lower renal function (difference in eGFR of about -30 ml/min per 1.73 m(2); P=0.04), which was confirmed by a longitudinal 5-year retrospective analysis. Additionally, affected patients presented more often with FD-typical symptoms, such as diarrhea, fatigue, and neuropathic pain, among others. Therefore, patients with poor clinical outcome on agalsidase should be tested for agalsidase inhibition. Future studies are warranted to determine if affected patients with FD benefit from acute reduction of anti-agalsidase antibodies or long-term immune modulation therapies to suppress agalsidase inhibition and to identify mechanisms that minimize antibody generation against agalsidase.

  10. Long-term parenteral nutrition

    PubMed Central

    Ladefoged, Karin; Jarnum, Stig

    1978-01-01

    Nineteen patients (11 women and eight men) aged 20-68 received long-term parenteral nutrition, mostly at home, for six to 63 months (mean 19 months). Indications for LTPN were extensive, active Crohn's disease in three patients, intestinocutaneous fistulas in three, and short-bowel syndrome in the remaining 13 patients. Subclavian or intra-atrial (Broviac) catheters were most commonly used, for which the average life was four and seven months respectively. Complications of long-term parenteral nutrition included pneumothorax in four out of 48 subclavian vein punctures. Catheter-induced thrombosis of central veins was shown by phlebography 17 times in nine patients, and eight episodes of total occlusion occurred. Two of these patients had pulmonary infarction. Nineteen episodes of catheter sepsis occurred in 11 patients, but only one was fatal. Complications related to intestinal disease included intra-abdominal abscesses and intestinal fistulas, and disturbances of liver function. Five patients died, though in only two was death related to long-term parenteral nutrition. One of these patients died from catheter sepsis, the other had subdural haematoma possibly caused by anticoagulant treatment. Eight of the 14 surviving patients still needed parenteral nutrition. All received a disability pension, but six had an acceptable quality of life with almost normal social activities. Despite problems such as difficulties in maintaining standardised infusion programmes, it was concluded that long-term parenteral nutrition at home is practicable and consistent with an acceptable quality of life. ImagesFIG 2 PMID:98199

  11. Impact of enzyme replacement therapy and hematopoietic stem cell transplantation in patients with Morquio A syndrome

    PubMed Central

    Tomatsu, Shunji; Sawamoto, Kazuki; Alméciga-Díaz, Carlos J; Shimada, Tsutomu; Bober, Michael B; Chinen, Yasutsugu; Yabe, Hiromasa; Montaño, Adriana M; Giugliani, Roberto; Kubaski, Francyne; Yasuda, Eriko; Rodríguez-López, Alexander; Espejo-Mojica, Angela J; Sánchez, Oscar F; Mason, Robert W; Barrera, Luis A; Mackenzie, William G; Orii, Tadao

    2015-01-01

    Patients with mucopolysaccharidosis IVA (MPS IVA) can present with systemic skeletal dysplasia, leading to a need for multiple orthopedic surgical procedures, and often become wheelchair bound in their teenage years. Studies on patients with MPS IVA treated by enzyme replacement therapy (ERT) showed a sharp reduction on urinary keratan sulfate, but only modest improvement based on a 6-minute walk test and no significant improvement on a 3-minute climb-up test and lung function test compared with the placebo group, at least in the short-term. Surgical remnants from ERT-treated patients did not show reduction of storage materials in chondrocytes. The impact of ERT on bone lesions in patients with MPS IVA remains limited. ERT seems to be enhanced in a mouse model of MPS IVA by a novel form of the enzyme tagged with a bone-targeting moiety. The tagged enzyme remained in the circulation much longer than untagged native enzyme and was delivered to and retained in bone. Three-month-old MPS IVA mice treated with 23 weekly infusions of tagged enzyme showed marked clearance of the storage materials in bone, bone marrow, and heart valves. When treatment was initiated at birth, reduction of storage materials in tissues was even greater. These findings indicate that specific targeting of the enzyme to bone at an early stage may improve efficacy of ERT for MPS IVA. Recombinant N-acetylgalactosamine-6-sulfate sulfatase (GALNS) in Escherichia coli BL21 (DE3) (erGALNS) and in the methylotrophic yeast Pichia pastoris (prGALNS) has been produced as an alternative to the conventional production in Chinese hamster ovary cells. Recombinant GALNS produced in microorganisms may help to reduce the high cost of ERT and the introduction of modifications to enhance targeting. Although only a limited number of patients with MPS IVA have been treated with hematopoietic stem cell transplantation (HSCT), beneficial effects have been reported. A wheelchair-bound patient with a severe form of MPS

  12. Long-term data archiving

    SciTech Connect

    Moore, David Steven

    2009-01-01

    Long term data archiving has much value for chemists, not only to retain access to research and product development records, but also to enable new developments and new discoveries. There are some recent regulatory requirements (e.g., FDA 21 CFR Part 11), but good science and good business both benefit regardless. A particular example of the benefits of and need for long term data archiving is the management of data from spectroscopic laboratory instruments. The sheer amount of spectroscopic data is increasing at a scary rate, and the pressures to archive come from the expense to create the data (or recreate it if it is lost) as well as its high information content. The goal of long-term data archiving is to save and organize instrument data files as well as any needed meta data (such as sample ID, LIMS information, operator, date, time, instrument conditions, sample type, excitation details, environmental parameters, etc.). This editorial explores the issues involved in long-term data archiving using the example of Raman spectral databases. There are at present several such databases, including common data format libraries and proprietary libraries. However, such databases and libraries should ultimately satisfy stringent criteria for long term data archiving, including readability for long times into the future, robustness to changes in computer hardware and operating systems, and use of public domain data formats. The latter criterion implies the data format should be platform independent and the tools to create the data format should be easily and publicly obtainable or developable. Several examples of attempts at spectral libraries exist, such as the ASTM ANDI format, and the JCAMP-DX format. On the other hand, proprietary library spectra can be exchanged and manipulated using proprietary tools. As the above examples have deficiencies according to the three long term data archiving criteria, Extensible Markup Language (XML; a product of the World Wide Web

  13. Musings on genome medicine: enzyme-replacement therapy of the lysosomal storage diseases

    PubMed Central

    2009-01-01

    The lysosomal storage diseases, such as Gaucher's disease, mucopolysaccharidosis I, II and IV, Fabry's disease, and Pompe's disease, are rare inherited disorders whose symptoms result from enzyme deficiency causing lysosomal accumulation. Until effective gene-replacement therapy is developed, expensive, and at best incomplete, enzyme-replacement therapy is the only hope for sufferers of rare lysosomal storage diseases. Preventive strategies involving carrier detection should be a priority toward the successful management of these conditions. PMID:20017892

  14. Immune response to enzyme replacement therapies in lysosomal storage diseases and the role of immune tolerance induction.

    PubMed

    Kishnani, Priya S; Dickson, Patricia I; Muldowney, Laurie; Lee, Jessica J; Rosenberg, Amy; Abichandani, Rekha; Bluestone, Jeffrey A; Burton, Barbara K; Dewey, Maureen; Freitas, Alexandra; Gavin, Derek; Griebel, Donna; Hogan, Melissa; Holland, Stephen; Tanpaiboon, Pranoot; Turka, Laurence A; Utz, Jeanine J; Wang, Yow-Ming; Whitley, Chester B; Kazi, Zoheb B; Pariser, Anne R

    2016-02-01

    The US Food and Drug Administration (FDA) and National Organization for Rare Disease (NORD) convened a public workshop titled "Immune Responses to Enzyme Replacement Therapies: Role of Immune Tolerance Induction" to discuss the impact of anti-drug antibodies (ADAs) on efficacy and safety of enzyme replacement therapies (ERTs) intended to treat patients with lysosomal storage diseases (LSDs). Participants in the workshop included FDA staff, clinicians, scientists, patients, industry, and advocacy group representatives. The risks and benefits of implementing prophylactic immune tolerance induction (ITI) to reduce the potential clinical impact of antibody development were considered. Complications due to immune responses to ERT are being recognized with increasing experience and lengths of exposure to ERTs to treat several LSDs. Strategies to mitigate immune responses and to optimize therapies are needed. Discussions during the workshop resulted in the identification of knowledge gaps and future areas of research, as well as the following proposals from the participants: (1) systematic collection of longitudinal data on immunogenicity to better understand the impact of ADAs on long-term clinical outcomes; (2) development of disease-specific biomarkers and outcome measures to assess the effect of ADAs and ITI on efficacy and safety; (3) development of consistent approaches to ADA assays to allow comparisons of immunogenicity data across different products and disease groups, and to expedite reporting of results; (4) establishment of a system to widely share data on antibody titers following treatment with ERTs; (5) identification of components of the protein that are immunogenic so that triggers and components of the immune responses can be targeted in ITI; and (6) consideration of early ITI in patients who are at risk of developing clinically relevant ADA that have been demonstrated to worsen treatment outcomes.

  15. Cognitive Development in Infantile-Onset Pompe Disease Under Very Early Enzyme Replacement Therapy.

    PubMed

    Lai, Chih-Jou; Hsu, Ting-Rong; Yang, Chia-Feng; Chen, Shyi-Jou; Chuang, Ya-Chin; Niu, Dau-Ming

    2016-12-01

    Most patients with infantile-onset Pompe disease die in early infancy before beginning enzyme replacement therapy, which has made it difficult to evaluate the impact of Pompe disease on cognitive development. Patients with infantile-onset Pompe disease can survive with enzyme replacement therapy, and physicians can evaluate cognitive development in these patients. We established an effective newborn screening program with quick clinical diagnostic criteria. Cognitive and motor development were evaluated using the Bayley Scales of Infant and Toddler Development-Third Edition at 6, 12, and 24 months of age. The patients who were treated very early demonstrate normal cognitive development with no significant change in cognition during this period (P = .18 > .05). The cognitive development was positively correlated with motor development (r = 0.533, P = .011). The results indicated that very early enzyme replacement therapy could protect cognitive development in patients with infantile-onset Pompe disease up to 24 months of age.

  16. Enzyme replacement in murine mucopolysaccharidosis type VII: neuronal and glial response to beta-glucuronidase requires early initiation of enzyme replacement therapy.

    PubMed

    Vogler, C; Levy, B; Galvin, N J; Thorpe, C; Sands, M S; Barker, J E; Baty, J; Birkenmeier, E H; Sly, W S

    1999-06-01

    We have previously shown that mucopolysaccharidosis type VII (MPS VII) mice receiving six weekly injections of recombinant beta-glucuronidase from birth had improved cognitive ability and reduced central nervous system lysosomal storage. However, a single beta-glucuronidase injection at 5 wk of age did not correct neuronal storage. We define the age at which central nervous system storage in MPS VII mice becomes resistant to beta-glucuronidase therapy and determine the effect of enzyme on other tissues by comparing the histology of mice begun on therapy at various times after birth. MPS VII mice received injections on the day of birth and then weekly for 5 wk with 16,000U/g beta-glucuronidase had reduced lysosomal storage in brain. The same therapy begun on d 14 of life or thereafter failed to correct neuronal storage, even when treatment was continued for six doses. Glial responsiveness or accessibility to enzyme also depended on early treatment. In contrast, leptomeningeal, osteoblast, and retinal pigment epithelial storage reduction depended on enzyme dose rather than age at initiation of therapy. Fixed tissue macrophage storage was reduced in all treated MPS VII mice, even those receiving a single dose. These observations indicate that fixed tissue macrophages in MPS VII mice remain sensitive to enzyme replacement therapy well into adulthood although neurons are responsive or accessible to enzyme therapy early in life. Because early initiation of enzyme replacement is important to achieve a central nervous system response, these studies emphasize the importance of newborn screening for lysosomal storage diseases so that early treatment can maximize the likelihood of a favorable therapeutic response.

  17. Gene therapy/bone marrow transplantation in ADA-deficient mice: roles of enzyme-replacement therapy and cytoreduction.

    PubMed

    Carbonaro, Denise A; Jin, Xiangyang; Wang, Xingchao; Yu, Xiao-Jin; Rozengurt, Nora; Kaufman, Michael L; Wang, Xiaoyan; Gjertson, David; Zhou, Yang; Blackburn, Michael R; Kohn, Donald B

    2012-11-01

    Gene therapy (GT) for adenosine deaminase-deficient severe combined immune deficiency (ADA-SCID) can provide significant long-term benefit when patients are given nonmyeloablative conditioning and ADA enzyme-replacement therapy (ERT) is withheld before autologous transplantation of γ-retroviral vector-transduced BM CD34+ cells. To determine the contributions of conditioning and discontinuation of ERT to the therapeutic effects, we analyzed these factors in Ada gene knockout mice (Ada(-/-)). Mice were transplanted with ADA-deficient marrow transduced with an ADA-expressing γ-retroviral vector without preconditioning or after 200 cGy or 900 cGy total-body irradiation and evaluated after 4 months. In all tissues analyzed, vector copy numbers (VCNs) were 100- to 1000-fold greater in mice receiving 900 cGy compared with 200 cGy (P < .05). In mice receiving 200 cGy, VCN was similar whether ERT was stopped or given for 1 or 4 months after GT. In unconditioned mice, there was decreased survival with and without ERT, and VCN was very low to undetectable. When recipients were conditioned with 200 cGy and received transduced lineage-depleted marrow, only recipients receiving ERT (1 or 4 months) had detectable vector sequences in thymocytes. In conclusion, cytoreduction is important for the engraftment of gene-transduced HSC, and short-term ERT after GT did not diminish the capacity of gene-corrected cells to engraft and persist.

  18. Asthma Medicines: Long-Term Control

    MedlinePlus

    ... Size Email Print Share Asthma Medicines: Long-term Control Page Content Article Body Corticosteroids Synthetic versions of ... form, they are used exclusively for long-term control; they are not very effective for acute symptoms. ...

  19. Long Term Surface Salinity Measurements

    NASA Technical Reports Server (NTRS)

    Schmitt, Raymond W.; Brown, Neil L.

    2005-01-01

    Our long-term goal is to establish a reliable system for monitoring surface salinity around the global ocean. Salinity is a strong indicator of the freshwater cycle and has a great influence on upper ocean stratification. Global salinity measurements have potential to improve climate forecasts if an observation system can be developed. This project is developing a new internal field conductivity cell that can be protected from biological fouling for two years. Combined with a temperature sensor, this foul-proof cell can be deployed widely on surface drifters. A reliable in-situ network of surface salinity sensors will be an important adjunct to the salinity sensing satellite AQUARIUS to be deployed by NASA in 2009. A new internal-field conductivity cell has been developed by N Brown, along with new electronics. This sensor system has been combined with a temperature sensor to make a conductivity - temperature (UT) sensor suitable for deployment on drifters. The basic sensor concepts have been proven on a high resolution CTD. A simpler (lower cost) circuit has been built for this application. A protection mechanism for the conductivity cell that includes antifouling protection has also been designed and built. Mr. A.Walsh of our commercial partner E-Paint has designed and delivered time-release formulations of antifoulants for our application. Mr. G. Williams of partner Clearwater Instrumentation advised on power and communication issues and supplied surface drifters for testing.

  20. AB055. Long term NIV

    PubMed Central

    Siopi, Dimitra

    2016-01-01

    During the last decades, non-invasive mechanical ventilation has evolved into one of the most evidence-based areas of respiratory medicine, with many indications in acute or chronic respiratory failure. From the first application of negative pressure models during poliomyelitis epidemics to the new sophisticated positive pressure models, and the development of the “intelligent ventilators”, there has been a long time course. Undoubtedly the spur was given by better understanding of respiratory physiology during sleep and the shift of healthcare towards a chronic base. Novel randomized controlled trials (RCTs) established the use of NIV in acute respiratory failure due to exacerbations of COPD, as well as acute pulmonary edema and weaning from invasive mechanical ventilation. Long-term NIV has been used in neuromuscular diseases for many decades, first in Duchenne muscular dystrophy, and then spreading to other disorders of this category, increasing survival in inherited neuromuscular diseases. NIV should be initiated early in the course of the disease, when symptomatic nocturnal hypoventilation is detected. Combined with cough augmentation (physiotherapy, insufflation-exsufflation devices) and percutaneous gastrostomy feeding, it can delay tracheostomy and invasive ventilation. In ALS patients NIV improves the quality of life and increases survival, especially when there is no bulbar involvement. The right time to initiate ventilation in this group of patients is not well established since it is difficult to detect signs and symptom of respiratory impairment. Patients seem to benefit from an early application of NIV, and their personal decisions should always be considered before any intervention. In patients with chest wall disorders NIV—despite the fact that RCTs are lacking—has proved its value in many uncontrolled trials and numerous reports. It seems to improve the work of breathing, sleep architecture, nocturnal and daytime arterial blood gases. The

  1. Long-Term Planning in Higher Education.

    ERIC Educational Resources Information Center

    United Nations Educational, Scientific and Cultural Organization, Bangkok (Thailand). Principal Regional Office for Asia and the Pacific.

    This report presents the concepts and issues discussed at a Regional Symposium on Long-term Planning in Higher Education held in Dhaka, Bangladesh, September 21-30, 1986. Chapter 1 explores some fundamental issues about the rationale for the objectives of long-term planning. It defines long-term planning in higher education, considers its…

  2. Long Term TOA - M Data and Information

    Atmospheric Science Data Center

    2015-06-30

    A Long-Term TOA and Constrained Surface Radiation Budget Project A Long-Term TOA and Constrained Surface Readiation Budget Dataset Using Merged CERES, ... and apply the knowledge to existing data to develop long-term (nearly 30 years) consistent and calibrated data product (TOA irradiances ...

  3. Oxidative stress in patients with mucopolysaccharidosis type II before and during enzyme replacement therapy.

    PubMed

    Filippon, Letícia; Vanzin, Camila S; Biancini, Giovana B; Pereira, Izabela N; Manfredini, Vanusa; Sitta, Angela; Peralba, Maria do Carmo R; Schwartz, Ida V D; Giugliani, Roberto; Vargas, Carmen R

    2011-06-01

    Mucopolysaccharidosis type II (MPS II) is a lysosomal storage disorder caused by deficiency of the enzyme iduronate-2-sulfatase, responsible for the degradation of glycosaminoglycans dermatan and heparan sulfate. Once the generation of free radicals is involved in the pathogenesis of many diseases, including some inborn errors of metabolism, the aim of this study was to evaluate blood oxidative stress parameters in MPS II patients, before and during 6 months of enzyme replacement therapy. We found significantly increased levels of malondialdehyde and carbonyl groups in plasma as well as erythrocyte catalase activity in patients before treatment compared to the control group. Plasma sulfhydryl group content and total antioxidant status were significantly reduced before treatment, while superoxide dismutase enzyme was not altered at this time when compared to controls. During enzyme replacement therapy, there was a significant reduction in levels of malondialdehyde when compared to pretreatment. Sulfhydryl groups were significantly increased until three months of treatment in MPS II patients in comparison to pretreatment. There were no significant alterations in plasma total antioxidant status and carbonyl groups as well as in catalase and superoxide dismutase activities during treatment in relation to pretreatment. The results indicate that MPS II patients are subject to lipid and protein oxidative damage and present reduction in non-enzymatic antioxidants, suggesting a possible involvement of free radicals in the pathophysiology of this disease. Also, the results may suggest that enzyme replacement therapy seems to protect against lipid peroxidation and protein damage in these patients.

  4. Effects of enzyme replacement therapy on five patients with advanced late-onset glycogen storage disease type II: a 2-year follow-up study.

    PubMed

    Furusawa, Yoshihiko; Mori-Yoshimura, Madoka; Yamamoto, Toshiyuki; Sakamoto, Chikako; Wakita, Mizuki; Kobayashi, Yoko; Fukumoto, Yutaka; Oya, Yasushi; Fukuda, Tokiko; Sugie, Hideo; Hayashi, Yukiko K; Nishino, Ichizo; Nonaka, Ikuya; Murata, Miho

    2012-03-01

    We examined the efficacy of 2-year enzyme replacement therapy (ERT) using recombinant human α-glucosidase (GAA; Myozyme®) in five long-term ventilator-dependent adults and aged patients with advanced, late-onset glycogen storage disease type II (GSDII, also known as Pompe disease). Although all patients had advanced respiratory failure and were ventilator-dependent for more than 6 years, four showed obvious improvements in muscle strength, pulmonary function, and activities of daily living after ERT. Improvement in each parameter was more prominent in the first year than in the second year. Values in the second year were still significantly better than those at study entry and indicate stabilization in the clinical status of all patients. These results suggest that ERT continues to be effective in the second year of treatment even in patients suffering from advanced late-onset GSDII disease with severe respiratory failure.

  5. Long-term efficacy of insulin glargine after switching from NPH insulin as intensive replacement of basal insulin in Japanese diabetes mellitus. Comparison of efficacy between type 1 and type 2 diabetes (JUN-LAN Study 1.2).

    PubMed

    Kanazawa, Yoshie; Igarashi, Yasuhiro; Komiya, Koji; Sakurai, Yuko; Shimizu, Tomoaki; Fujitani, Yoshio; Tanaka, Yasushi; Watada, Hirotaka; Kawamori, Ryuzo; Hirose, Takahisa

    2007-12-01

    To assess and compare the efficacy and safety of insulin glargine as intensive replacement of basal insulin in Japanese patients with type 1 (n = 72) and type 2 (n = 46) diabetes, we switched their intensive insulin regimen from NPH plus regular or rapid-acting insulin to glargine plus bolus insulin, which included regular and rapid-acting insulin, and recorded changes in glycemic control and frequency of hypoglycemia for 18 months. The dose titration of basal and bolus insulin was based on home self-monitored blood glucose measurements and monthly HbA(1C). Mean HbA(1C) level was improved significantly at 3 months after switching to glargine plus bolus insulin regimen and these effects continued for 18 months in both type 1 and type 2 diabetes patients (HbA(1C) level: type 1: baseline 8.9 +/- 2.6%, 18 months 7.8 +/- 1.5% (p<0.05), type 2: baseline 8.2 +/- 2.6%, 18 months 7.7 +/- 1.5%. Body weight was slightly but significantly increased at 18 months only in type 2 diabetes. Total daily bolus insulin doses were not changed but basal insulin could be increased significantly after switching regimens in both types diabetes compared with baseline. The frequency of mild to moderate hypoglycemia (self-assisted episodes, blood glucose <70 mg/dl) was marginally lower with glargine but not significantly. Self-monitored fasting blood glucose level was significantly improved after switching in type 2 diabetes. Patients with the worst HbA(1C) level at baseline exhibited more than 10% improvement in HbA(1C) level after switching both type 1 and type 2 diabetes. The HbA(1C) levels of the effectively treated patients were comparable to those of ineffectively treated ones at 6 months and the same improvement was seen at 18 months. Our results suggested that insulin glargine is more effective than NPH insulin as intensive replacement of basal insulin, particularly in those Japanese patients with difficult glycemic control with NPH insulin, equally in both type 1 and type 2 diabetes.

  6. Enzyme replacement therapy for murine mucopolysaccharidosis type VII leads to improvements in behavior and auditory function.

    PubMed Central

    O'Connor, L H; Erway, L C; Vogler, C A; Sly, W S; Nicholes, A; Grubb, J; Holmberg, S W; Levy, B; Sands, M S

    1998-01-01

    Mucopolysaccharidosis type VII (MPS VII; Sly syndrome) is one of a group of lysosomal storage diseases that share many clinical features, including mental retardation and hearing loss. Lysosomal storage in neurons of the brain and the associated behavioral abnormalities characteristic of a murine model of MPS VII have not been shown to be corrected by either bone marrow transplantation or gene therapy. However, intravenous injections of recombinant beta-glucuronidase initiated at birth reduce the pathological evidence of disease in MPS VII mice. In this study we present evidence that enzyme replacement initiated at birth improved the behavioral performance and reduced hearing loss in MPS VII mice. Enzyme-treated MPS VII mice performed similarly to normal mice and significantly better than mock- treated MPS VII mice in every phase of the Morris Water Maze test. In addition, the auditory function of treated MPS VII mice was dramatically improved, and was indistinguishable from normal mice. These data indicate that some of the learning, memory, and hearing deficits can be prevented in MPS VII mice if enzyme replacement therapy is initiated early in life. These data also provide functional correlates to the biochemical and histopathological improvements observed after enzyme replacement therapy. PMID:9525982

  7. The Role of Mannosylated Enzyme and the Mannose Receptor in Enzyme Replacement Therapy

    PubMed Central

    Du, Hong; Levine, Mark; Ganesa, Chandrashekar; Witte, David P.; Cole, Edward S.; Grabowski, Gregory A.

    2005-01-01

    Lysosomal acid lipase (LAL) is the critical enzyme for the hydrolysis of triglycerides (TGs) and cholesteryl esters (CEs) in lysosomes. LAL defects cause Wolman disease (WD) and CE storage disease (CESD). An LAL null (lal−/−) mouse model closely mimics human WD/CESD, with hepatocellular, Kupffer cell and other macrophage, and adrenal cortical storage of CEs and TGs. The effect on the cellular targeting of high-mannose and complex oligosaccharide–type oligosaccharide chains was tested with human LAL expressed in Pichia pastoris (phLAL) and CHO cells (chLAL), respectively. Only chLAL was internalized by cultured fibroblasts, whereas both chLAL and phLAL were taken up by macrophage mannose receptor (MMR)–positive J774E cells. After intraperitoneal injection into lal−/− mice, phLAL and chLAL distributed to macrophages and macrophage-derived cells of various organs. chLAL was also detected in hepatocytes. Ten injections of either enzyme over 30 d into 2- and 2.5-mo-old lal−/− mice produced normalization of hepatic color, decreased liver weight (50%–58%), and diminished hepatic cholesterol and TG storage. Lipid accumulations in macrophages were diminished with either enzyme. Only chLAL cleared lipids in hepatocytes. Mice double homozygous for the LAL and MMR deficiences (lal−/−;MMR−/−) showed phLAL uptake into Kupffer cells and hepatocytes, reversal of macrophage histopathology and lipid storage in all tissues, and clearance of hepatocytes. These results implicate MMR-independent and mannose 6-phosphate receptor–independent pathways in phLAL uptake and delivery to lysosomes in vivo. In addition, these studies show specific cellular targeting and physiologic effects of differentially oligosaccharide-modified human LALs mediated by MMR and that lysosomal targeting of mannose-terminated glycoproteins occurs and storage can be eliminated effectively without MMR. PMID:16380916

  8. Effects of long-term testosterone replacement therapy, with a temporary intermission, on glycemic control of nine hypogonadal men with type 1 diabetes mellitus - a series of case reports.

    PubMed

    Saad, Farid; Yassin, Aksam; Almehmadi, Yousef; Doros, Gheorghe; Gooren, Louis

    2015-01-01

    Type 2 diabetes mellitus (T2DM) is often associated with obesity and subnormal serum testosterone (T) levels. Until 5 years ago there was no indication that men with type 1 diabetes mellitus (T1DM) had subnormal serum T. But recent studies indicate that about 10% of men with T1DM suffer from hypogonadism, as a rule aged men and men with obesity. While hypogonadal men with T2DM benefit from normalization of their serum T, this has not been investigated in men with T1DM. Nine men with T1DM, erectile dysfunction and hypogonadism (total testosterone ≤ 12 nmol/L) received testosterone replacement therapy (TRT). In seven men TRT was intermitted: one man with prostate malignancy and six men because of problems of reimbursement. Incidentally, this provided an opportunity to monitor the effects of withdrawal and of the reinstatement of TRT. In all men, glycemic control (serum glucose and HbA1c), weight, waist circumference, lipid profiles and erectile function improved upon TRT. The seven men whose TRT was intermitted showed a deterioration which improved again upon reinstatement of TRT. The data suggest that aging and obese men with T1DM might have subnormal T levels and that their glycemic control, lipid profiles and erectile function might benefit from TRT.

  9. DNA damage in leukocytes from pretreatment mucopolysaccharidosis type II patients; protective effect of enzyme replacement therapy.

    PubMed

    Filippon, Letícia; Wayhs, Carlos A Y; Atik, Diana M; Manfredini, Vanusa; Herber, Silvani; Carvalho, Clarissa G; Schwartz, Ida V D; Giugliani, Roberto; Vargas, Carmen R

    2011-04-03

    Mucopolysaccharidosis type II (MPS II) is an X-linked recessive disease caused by deficiency of the lysosomal enzyme iduronate-2-sulfatase, leading to progressive accumulation of glycosaminoglycans in nearly all cell types, tissues and organs. Enzyme replacement therapy reduces the storage of these substances in the lysosomes. Oxidative stress is related to the pathophysiology of many disorders, including inborn errors of metabolism. Oxidative damage to protein and lipid has been described in MPS types I and III. The aim of this study was to analyze DNA damage, as determined by the alkaline comet assay using silver staining, in peripheral leukocytes from MPS II patients before treatment and during the first six months of enzyme replacement therapy. We also correlated DNA damage with lipid and protein oxidative damages, analyzed by plasma malondialdehyde levels and carbonyl group content, respectively. We found a significant increase in lipid and protein damage in MPS II patients before treatment when compared to controls. Also, our results showed greater DNA damage in terms of damage index (DI) in pretreatment MPS II patients (DI=18.0 ± 2.4) when compared to controls (DI=66.0 ± 2.0). Enzyme replacement therapy led to a significant decrease in levels of malondialdehyde and DNA damage when compared to pretreatment, but did not reach control values. Significant positive correlations between DNA damage and malondialdehyde levels, as well as carbonyl group content, were observed. Our findings indicate that MPS II patients are subject to DNA damage and that enzyme replacement therapy is able to protect against this process.

  10. Intrathecal enzyme replacement therapy: Successful treatment of brain disease via the cerebrospinal fluid

    PubMed Central

    Dickson, Patricia; McEntee, Michael; Vogler, Carole; Le, Steven; Levy, Beth; Peinovich, Maryn; Hanson, Stephen; Passage, Merry; Kakkis, Emil

    2010-01-01

    Treatment of brain disease with recombinant proteins is difficult due to the blood-brain barrier. As an alternative to direct injections into the brain, we studied whether application of high concentrations of therapeutic enzymes via intrathecal (IT) injections could successfully drive uptake across the ependyma to treat brain disease. We studied IT enzyme replacement therapy with recombinant human iduronidase (rhIDU) in canine mucopolysaccharidosis I (MPS I, Hurler syndrome), a lysosomal storage disorder with brain and meningeal involvement. Monthly or quarterly IT treatment regimens with rhIDU achieved supranormal iduronidase enzyme levels in the brain, spinal cord, and spinal meninges. All regimens normalized total brain glycosaminoglycan (GAG) storage and reduced spinal meningeal GAG storage by 58–70%. The improvement in GAG storage levels persisted three months after the final IT dose. The successful use of enzyme therapy via the CSF represents a potentially useful approach for lysosomal storage disorders. PMID:17321776

  11. Long-term solar-terrestrial observations

    NASA Technical Reports Server (NTRS)

    1988-01-01

    The results of an 18-month study of the requirements for long-term monitoring and archiving of solar-terrestrial data is presented. The value of long-term solar-terrestrial observations is discussed together with parameters, associated measurements, and observational problem areas in each of the solar-terrestrial links (the sun, the interplanetary medium, the magnetosphere, and the thermosphere-ionosphere). Some recommendations are offered for coordinated planning for long-term solar-terrestrial observations.

  12. Reconstructing the Phylogenetic History of Long-Term Effective Population Size and Life-History Traits Using Patterns of Amino Acid Replacement in Mitochondrial Genomes of Mammals and Birds

    PubMed Central

    Nabholz, Benoit; Lartillot, Nicolas

    2013-01-01

    The nearly neutral theory, which proposes that most mutations are deleterious or close to neutral, predicts that the ratio of nonsynonymous over synonymous substitution rates (dN/dS), and potentially also the ratio of radical over conservative amino acid replacement rates (Kr/Kc), are negatively correlated with effective population size. Previous empirical tests, using life-history traits (LHT) such as body-size or generation-time as proxies for population size, have been consistent with these predictions. This suggests that large-scale phylogenetic reconstructions of dN/dS or Kr/Kc might reveal interesting macroevolutionary patterns in the variation in effective population size among lineages. In this work, we further develop an integrative probabilistic framework for phylogenetic covariance analysis introduced previously, so as to estimate the correlation patterns between dN/dS, Kr/Kc, and three LHT, in mitochondrial genomes of birds and mammals. Kr/Kc displays stronger and more stable correlations with LHT than does dN/dS, which we interpret as a greater robustness of Kr/Kc, compared with dN/dS, the latter being confounded by the high saturation of the synonymous substitution rate in mitochondrial genomes. The correlation of Kr/Kc with LHT was robust when controlling for the potentially confounding effects of nucleotide compositional variation between taxa. The positive correlation of the mitochondrial Kr/Kc with LHT is compatible with previous reports, and with a nearly neutral interpretation, although alternative explanations are also possible. The Kr/Kc model was finally used for reconstructing life-history evolution in birds and mammals. This analysis suggests a fairly large-bodied ancestor in both groups. In birds, life-history evolution seems to have occurred mainly through size reduction in Neoavian birds, whereas in placental mammals, body mass evolution shows disparate trends across subclades. Altogether, our work represents a further step toward a more

  13. Exercise testing in late-onset glycogen storage disease type II patients undergoing enzyme replacement therapy.

    PubMed

    Marzorati, Mauro; Porcelli, Simone; Bellistri, Giuseppe; Morandi, Lucia; Grassi, Bruno

    2012-12-01

    Enzyme replacement therapy (ERT) has recently became available for patients with glycogen storage disease type II. Previous studies have demonstrated clinical efficacy of enzyme replacement therapy, however, data on physiological variables related to exercise tolerance are scarce. Four glycogen storage disease type II late-onset patients (45 ± 6 years) performed an incremental exercise on a cycle ergometer, up to voluntary exhaustion, before (BEFORE) and after 12 months of ERT (AFTER). Peak workload, oxygen uptake, heart rate, cardiac output (by impedance cardiography) and vastus lateralis oxygenation indices (by continuous-wave near-infrared spectroscopy, NIRS) were determined. Peak workload and oxygen uptake values significantly increased during ERT (54 ± 30 vs. 63 ± 31 watt, and 17.2 ± 4.4 vs. 19.7 ± 3.5 ml/kg/min, respectively, in BEFORE vs. AFTER). On the other hand, for both peak cardiac output (12.3 ± 5.3 vs. 14.8 ± 4.5L/min) and the NIRS-determined peak skeletal muscle fractional O(2) extraction, expressed as a percentage of the maximal values during a transient limb ischemia (30 ± 39% vs. 38 ± 28%), the observed increases were not statistically significant. Our findings suggest that in glycogen storage disease type II patients enzyme replacement therapy is associated with a mild improvement of exercise tolerance. The findings need to be validated during a longer follow-up on a larger group of patients.

  14. Effect of Cross-Sex Hormonal Replacement on Antioxidant Enzymes in Rat Retroperitoneal Fat Adipocytes

    PubMed Central

    Velázquez Espejel, Rodrigo; Cabrera-Orefice, Alfredo; Uribe-Carvajal, Salvador; Pavón, Natalia

    2016-01-01

    We report the effect of cross-sex hormonal replacement on antioxidant enzymes from rat retroperitoneal fat adipocytes. Eight rats of each gender were assigned to each of the following groups: control groups were intact female or male (F and M, resp.). Experimental groups were ovariectomized F (OvxF), castrated M (CasM), OvxF plus testosterone (OvxF + T), and CasM plus estradiol (CasM + E2) groups. After sacrifice, retroperitoneal fat was dissected and processed for histology. Adipocytes were isolated and the following enzymatic activities were determined: Cu-Zn superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST), and glutathione reductase (GR). Also, glutathione (GSH) and lipid peroxidation (LPO) were measured. In OvxF, retroperitoneal fat increased and adipocytes were enlarged, while in CasM rats a decrease in retroperitoneal fat and small adipocytes are observed. The cross-sex hormonal replacement in F rats was associated with larger adipocytes and a further decreased activity of Cu-Zn SOD, CAT, GPx, GST, GR, and GSH, in addition to an increase in LPO. CasM + E2 exhibited the opposite effects showing further activation antioxidant enzymes and decreases in LPO. In conclusion, E2 deficiency favors an increase in retroperitoneal fat and large adipocytes. Cross-sex hormonal replacement in F rats aggravates the condition by inhibiting antioxidant enzymes. PMID:27630756

  15. LONG-TERM MONITORING SENSOR NETWORK

    SciTech Connect

    Stephen P. Farrington; John W. Haas; Neal Van Wyck

    2003-10-16

    Long-term monitoring (LTM) associated with subsurface contamination sites is a key element of Long Term Stewardship and Legacy Management across the Department of Energy (DOE) complex. However, both within the DOE and elsewhere, LTM is an expensive endeavor, often exceeding the costs of the remediation phase of a clean-up project. The primary contributors to LTM costs are associated with labor. Sample collection, storage, preparation, analysis, and reporting can add a significant financial burden to project expense when extended over many years. Development of unattended, in situ monitoring networks capable of providing quantitative data satisfactory to regulatory concerns has the potential to significantly reduce LTM costs. But survival and dependable operation in a difficult environment is a common obstacle to widespread use across the DOE complex or elsewhere. Deploying almost any sensor in the subsurface for extended periods of time will expose it to chemical and microbial degradation. Over the time-scales required for in situ LTM, even the most advanced sensor systems may be rendered useless. Frequent replacement or servicing (cleaning) of sensors is expensive and labor intensive, offsetting most, if not all, of the cost savings realized with unattended, in situ sensors. To enable facile, remote monitoring of contaminants and other subsurface parameters over prolonged periods, Applied Research Associates, Inc has been working to develop an advanced LTM sensor network consisting of three key elements: (1) an anti-fouling sensor chamber that can accommodate a variety of chemical and physical measurement devices based on electrochemical, optical and other techniques; (2) two rapid, cost effective, and gentle means of emplacing sensor packages either at precise locations directly in the subsurface or in pre-existing monitoring wells; and (3) a web browser-based data acquisition and control system (WebDACS) utilizing field-networked microprocessor-controlled smart

  16. Virtual Models of Long-Term Care

    ERIC Educational Resources Information Center

    Phenice, Lillian A.; Griffore, Robert J.

    2012-01-01

    Nursing homes, assisted living facilities and home-care organizations, use web sites to describe their services to potential consumers. This virtual ethnographic study developed models representing how potential consumers may understand this information using data from web sites of 69 long-term-care providers. The content of long-term-care web…

  17. Long Term Preservation of Digital Information.

    ERIC Educational Resources Information Center

    Lorie, Raymond A.

    The preservation of digital data for the long term presents a variety of challenges from technical to social and organizational. The technical challenge is to ensure that the information, generated today, can survive long term changes in storage media, devices, and data formats. This paper presents a novel approach to the problem. It distinguishes…

  18. Long-Term Nutrition: A Clinician's Guide to Successful Long-Term Enteral Access in Adults.

    PubMed

    Bechtold, Matthew L; Mir, Fazia A; Boumitri, Christine; Palmer, Lena B; Evans, David C; Kiraly, Laszlo N; Nguyen, Douglas L

    2016-09-22

    Long-term nutrition support requires long-term enteral access. To ensure the success of long-term enteral access, many factors need to be taken into consideration. This article represents a guide to placing and maintaining access in patients requiring long-term nutrition and addresses many of the common questions regarding long-term enteral access, such as indications, types of access, feeding after access placed, and recognition and treatment of potential complications. This guide will help the clinician establish and maintain access to maximize nutrition in patients requiring long-term nutrition.

  19. Paying for long-term care.

    PubMed Central

    Estes, C L; Bodenheimer, T

    1994-01-01

    Everyone agrees that insurance for long-term care is inadequate in the United States. Disagreement exists, however, on whether such insurance should be provided through the private or public sector. Private insurance generally uses the experience-rating principle that persons with higher risk of illness are charged higher premiums. For private insurance for long-term care, this principle creates a dilemma. Most policies will be purchased by the elderly; yet, because the elderly have a high risk of needing long-term care, only about 20% of them can afford the cost of premiums. A public-private partnership by which the government partially subsidizes private long-term-care insurance is unlikely to resolve this dilemma. Only a social insurance program for long-term care can provide universal, affordable, and equitable coverage. PMID:8128712

  20. Long-term Effects of Shrub Encroachment and Grazing on Soil Microbial Composition and Function

    NASA Astrophysics Data System (ADS)

    Gallery, R. E.; O'Shea, C.; Kwiecien, A.; Predick, K.; Archer, S. R.

    2014-12-01

    Drylands account for ca. 35% of terrestrial net primary productivity and thus play a significant role in global water and biogeochemical cycles. Replacement of grasses by shrubs has been widespread in these systems and has altered rates of erosion and native plant biodiversity and productivity. The net effect of these changes on biogeochemical cycling is not well understood. Projected warmer and drier conditions may further alter the function and stability of these ecosystems and soil resources through direct effects on soil microbiota and plant-microbe interactions. We quantified microbial community responses to long-term livestock grazing and shrub encroachment in a Sonoran Desert grassland. We sought to characterize tipping points where biotic controls over ecosystem processes shift from being 'grass-driven' to 'shrub-driven.' We asked: How do livestock grazing (the predominant land use in dryland ecosystems) and shrub invasion (a predominant land cover change) interact to influence microbial biomass and the relative abundance of bacteria, archaea, and fungi and their extracellular enzyme activities? Surface soil from bare-ground patches, native and invasive grass rhizospheres, and bole and canopy dripline locations in patches of mature mesquite trees in long-term grazed and long-term (70+ y) protected pastures were collected and analyzed for microbial community composition, biomass, potential exoenzyme activities, and a suite of biogeochemical characteristics. We found no differences in microbial communities or the soils associated with native vs. exotic grasses. Overall, mesquite bole patches differed from other patches in all soil characteristics except potential enzyme activity: soil temperature was significantly lower, and total carbon (C) and soil moisture were significantly higher. Potential activities were lowest for bare ground and highest at shrub dripline patches for all seven exoenzymes tested. Mean potential activities for C and phosphorous (P

  1. 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…

  2. A 24-Year Enzyme Replacement Therapy in an Adenosine-deaminase-Deficient Patient.

    PubMed

    Tartibi, Hana M; Hershfield, Michael S; Bahna, Sami L

    2016-01-01

    Severe combined immunodeficiency (SCID) is a fatal childhood disease unless immune reconstitution is performed early in life, with either hematopoietic stem cell transplantation or gene therapy. One of its subtypes is caused by adenosine deaminase (ADA) enzyme deficiency, which leads to the accumulation of toxic metabolites that impair lymphocyte development and function. With the development of polyethylene glycol-conjugated adenosine deaminase (PEG-ADA) enzyme replacement therapy, many ADA-deficient children with SCID who could not receive a hematopoietic stem cell transplantation or gene therapy survived and had longer and healthier lives. We report a 24-year course of treatment in a patient who was diagnosed with ADA deficiency at 4 months of age. The patient was treated with PEG-ADA, which was the only therapy available for him. The patient's plasma ADA level was regularly monitored and the PEG-ADA dose adjusted accordingly. This treatment has resulted in near-normalization of lymphocyte counts, and his clinical course has been associated with only minor to moderate infections. Thus far, he has had no manifestations of autoimmune or lymphoproliferative disorders. This patient is among the longest to be maintained on PEG-ADA enzyme replacement therapy.

  3. Roadmap to Long-Term Monitoring Optimization

    EPA Pesticide Factsheets

    This roadmap focuses on optimization of established long-term monitoring programs for groundwater. Tools and techniques discussed concentrate on methods for optimizing the monitoring frequency and spatial (three-dimensional) distribution of wells ...

  4. Mental Health in Long Term Care Settings.

    ERIC Educational Resources Information Center

    Shore, Herbert

    1978-01-01

    There are many ways in which long-term care facilities attempt to cope with the mental health problems of the elderly. The author reviews five factors crucial to effective care for the aged in these facilities. (Author/RK)

  5. Long-term-care legal update.

    PubMed

    Fiesta, J

    1998-04-01

    As more nurses move from the acute care setting to long-term-care and home health care, different practice issues arise. To maximize liability protection, nurses must understand the legal issues unique to each delivery system.

  6. Long-Term Care Ombudsman Program

    MedlinePlus

    ... Provided to Persons Living in Long-Term Care Facilities Program data for FY 2013 indicate that long- ... least quarterly Conducted 5,417 training sessions in facilities on such topics as residents’ rights Provided 129, ...

  7. The 2014 Long-Term Budget Outlook

    DTIC Science & Technology

    2014-07-16

    Treasury from the Federal Reserve System, customs duties, estate and gift taxes, and miscellaneous fees and fines. Actual Extended Baseline...Office’s (CBO’s) most recent analysis of the outlook for the federal budget over the long term. My statement today summarizes The 2014 Long-Term Budget...Outlook, which was released yesterday.1 Between 2009 and 2012, the federal government recorded the largest budget deficits relative to the size of

  8. Evidence-based long term care design.

    PubMed

    Calkins, Margaret P

    2009-01-01

    Research on the impact of the built environment in long-term care settings continues to grow. This article focuses on work conducted and published since 2000, when an earlier review on research on dementia and design was published. The vast majority of research that addressed neurological conditions in residents in long-term care settings (assisted living and nursing homes) relates to Alzheimer's disease and related dementias.

  9. Exercise testing in late-onset glycogen storage disease type II patients undergoing enzyme replacement therapy

    PubMed Central

    Marzorati, Mauro; Porcelli, Simone; Bellistri, Giuseppe; Morandi, Lucia; Grassi, Bruno

    2012-01-01

    Enzyme replacement therapy (ERT) has recently became available for patients with glycogen storage disease type II. Previous studies have demonstrated clinical efficacy of enzyme replacement therapy, however, data on physiological variables related to exercise tolerance are scarce. Four glycogen storage disease type II late-onset patients (45 ± 6 years) performed an incremental exercise on a cycle ergometer, up to voluntary exhaustion, before (BEFORE) and after 12 months of ERT (AFTER). Peak workload, oxygen uptake, heart rate, cardiac output (by impedance cardiography) and vastus lateralis oxygenation indices (by continuous-wave near-infrared spectroscopy, NIRS) were determined. Peak workload and oxygen uptake values significantly increased during ERT (54 ± 30 vs. 63 ± 31 watt, and 17.2 ± 4.4 vs. 19.7 ± 3.5 ml/kg/min, respectively, in BEFORE vs. AFTER). On the other hand, for both peak cardiac output (12.3 ± 5.3 vs. 14.8 ± 4.5 L/min) and the NIRS-determined peak skeletal muscle fractional O2 extraction, expressed as a percentage of the maximal values during a transient limb ischemia (30 ± 39% vs. 38 ± 28%), the observed increases were not statistically significant. Our findings suggest that in glycogen storage disease type II patients enzyme replacement therapy is associated with a mild improvement of exercise tolerance. The findings need to be validated during a longer follow-up on a larger group of patients. PMID:23182645

  10. Long Term Outcomes after Pediatric Liver Transplantation

    PubMed Central

    2013-01-01

    Long term outcomes after liver transplantation are major determinants of quality of life and of the value of this heroic treatment. As short term outcomes are excellent, our community is turning to take a harder look at long term outcomes. The purpose of this paper is to review these outcomes, and highlight proposed treatments, as well as pressing topics needing to be studied. A systemic review of the English literature was carried in PubMed, covering all papers addressing long term outcomes in pediatric liver transplant from 2000-2013. Late outcomes after pediatric liver transplant affect the liver graft in the form of chronic liver dysfunction. The causes include rejection particularly humoral rejection, but also de novo autoimmune hepatitis, and recurrent disease. The metabolic syndrome is a major factor in long term cardiovascular complication risk. Secondary infections, kidney dysfunction and malignancy remain a reality of those patients. There is growing evidence of late cognitive and executive function delays affecting daily life productivity as well as likely adherence. Finally, despite a good health status, quality of life measures are comparable to those of children with chronic diseases. Long term outcomes are the new frontier in pediatric liver transplantation. Much is needed to improve graft survival, but also to avoid systemic morbidities from long term immunosuppression. Quality of life is a new inclusive measure that will require interventions and innovative approaches respectful not only on the patients but also of their social circle. PMID:24511516

  11. Long-term symptom relief after septoplasty.

    PubMed

    Sundh, Carolina; Sunnergren, Ola

    2015-10-01

    The results for long-term symptom relief after septoplasty are contradictory in reviewed publications but the findings suggest that results are unsatisfactory. In this study, we analyzed and compared short- and long-term symptom relief after septoplasty and factors possibly associated with symptom relief. 111 patients that underwent septoplasty between 2008 and 2010 were included in the study. Medical charts were reviewed for preoperative characteristics and assessments. Data on short-term symptom relief (6 months) were retrieved from the Swedish National Quality Registry for Septoplasty; data on long-term symptom relief (34-70 months) were collected through a questionnaire. Upon the 34-70 month follow-up, 53% of the patients reported that symptoms either remained or had worsened and 83% reported nasal obstruction. Degree of symptom relief was significantly higher among patients not reporting nasal obstruction than among patients reporting nasal obstruction at long-term follow-up. The proportion of patients that reported "my symptoms are gone" declined from 53% after 6 months to 18% after 34-70 months. None of the factors taken into consideration, age at surgery, gender, follow-up time, primary operation/reoperation, history of nasal trauma, self-reported allergy, rhinometric obstruction, or same sided rhinometric, clinical and subjective nasal obstruction were associated with symptom relief. The long-term results after septoplasty are unsatisfactory. A majority of patients report that their symptoms remain after septoplasty.

  12. Long-term outcomes of autoimmune pancreatitis

    PubMed Central

    Ikeura, Tsukasa; Miyoshi, Hideaki; Shimatani, Masaaki; Uchida, Kazushige; Takaoka, Makoto; Okazaki, Kazuichi

    2016-01-01

    Autoimmune pancreatitis (AIP) has been considered a favorable-prognosis disease; however, currently, there is limited information on natural course of AIP during long-term follow-up. Recently published studies regarding the long-term outcomes of AIP has demonstrated the developments of pancreatic stone formation, exocrine insufficiency, and endocrine insufficiency are observed in 5%-41%, 34%-82%, and 38%-57% of patients having the disease. Furthermore, the incidence rate of developing pancreatic cancer ranges from 0% to 4.8% during the long-term follow-up. The event of death from AIP-related complications other than accompanying cancer is likely to be rare. During follow-up of AIP patients, careful surveillance for not only relapse of the disease but also development of complications at regular intervals is needed. PMID:27678359

  13. Highly Versatile Polyelectrolyte Complexes for Improving the Enzyme Replacement Therapy of Lysosomal Storage Disorders.

    PubMed

    Giannotti, Marina I; Abasolo, Ibane; Oliva, Mireia; Andrade, Fernanda; García-Aranda, Natalia; Melgarejo, Marta; Pulido, Daniel; Corchero, José L; Fernández, Yolanda; Villaverde, Antonio; Royo, Miriam; García-Parajo, María F; Sanz, Fausto; Schwartz, Simó

    2016-10-05

    Lysosomal storage disorders are currently treated by enzyme replacement therapy (ERT) through the direct administration of the unprotected recombinant protein to the patients. Herein we present an ionically cross-linked polyelectrolyte complex (PEC) composed of trimethyl chitosan (TMC) and α-galactosidase A (GLA), the defective enzyme in Fabry disease, with the capability of directly targeting endothelial cells by incorporating peptide ligands containing the RGD sequence. We assessed the physicochemical properties, cytotoxicity, and hemocompatibility of RGD-targeted and untargeted PECs, the uptake by endothelial cells and the intracellular activity of PECs in cell culture models of Fabry disease. Moreover, we also explored the effect of different freeze-drying procedures in the overall activity of the PECs. Our results indicate that the use of integrin-binding RGD moiety within the PEC increases their uptake and the efficacy of the GLA enzyme, while the freeze-drying allows the activity of the therapeutic protein to remain intact. Overall, these results highlight the potential of TMC-based PECs as a highly versatile and feasible drug delivery system for improving the ERT of lysosomal storage disorders.

  14. Long-term fasting in the anadromous Arctic charr is associated with downregulation of metabolic enzyme activity and upregulation of leptin A1 and SOCS expression in the liver.

    PubMed

    Jørgensen, Even Hjalmar; Martinsen, Mads; Strøm, Vidar; Hansen, Kristin Elisa Ruud; Ravuri, Chandra Sekhar; Gong, Ningping; Jobling, Malcolm

    2013-09-01

    The life strategy of the anadromous Arctic charr (Salvelinus alpinus) includes several months of voluntary fasting during overwintering in freshwater, leading to emaciation prior to seawater migration in spring. In this study we compared changes in condition, substrate utilization and liver metabolism between captive anadromous charr subjected to food deprivation during late winter and spring, and conspecifics fed in excess. In March, nine out of the 10 sampled fed fish had not eaten, indicating that they were in a voluntary anorexic state. In June, the fed fish were eating and all had higher body mass, condition factor and adiposity than in March. In fasted fish there were only small decreases in body mass, condition factor and adiposity between March and May, but all these parameters decreased markedly from May to June. The fasted fish were depleted in fat and glycogen in June, had suppressed activity of hepatic enzymes involved in lipid metabolism (G6PDH and HOAD) and seemed to rely on protein-derived glucose as a major energy source. This was associated with upregulated liver gene expression of leptin A1, leptin A2, SOCS1, SOCS2 and SOCS3, and reduced IGF-I expression. In an in vitro study with liver slices it was shown that recombinant rainbow trout leptin stimulated SOCS1 and SOCS3 expression, but not SOCS2, IGF-I or genes of enzymes involved in lipid (G6PDH) and amino acid (AspAT) metabolism. It is concluded that liver leptin interacts with SOCS in a paracrine fashion to suppress lipolytic pathways and depress metabolism when fat stores are depleted.

  15. Valuing a long-term care facility.

    PubMed

    Mellen, C M

    1992-10-01

    The business valuation industry generally uses at least one of three basic approaches to value a long-term care facility: the cost approach, sales comparison approach, or income approach. The approach that is chosen and the resulting weight that is applied to it depend largely on the circumstances involved. Because a long-term care facility is a business enterprise, more weight usually is given to the income approach which factors into the estimate of value both the tangible and intangible assets of the facility.

  16. Keratoprosthesis: a long-term review.

    PubMed Central

    Barnham, J. J.; Roper-Hall, M. J.

    1983-01-01

    A keratoprosthesis (KP), is an artificial cornea which is inserted into an opacified cornea in an attempt to restore useful vision or, less commonly, to make the eye comfortable in painful keratopathy. Results o a retrospective study of 35 patients, with 55 KP insertions, are reviewed with regard to visual acuity, length of time vision is maintained, retention time, and complication. Overall there were a number of long-term real successes, eith retention of the KP and maintenance of improved vision in eyes not amenable to conventional treatment. Careful long-term follow-up was needed, with further surgical procedures often being necessary. Images PMID:6860613

  17. Long-term outcomes after severe shock.

    PubMed

    Pratt, Cristina M; Hirshberg, Eliotte L; Jones, Jason P; Kuttler, Kathryn G; Lanspa, Michael J; Wilson, Emily L; Hopkins, Ramona O; Brown, Samuel M

    2015-02-01

    Severe shock is a life-threatening condition with very high short-term mortality. Whether the long-term outcomes among survivors of severe shock are similar to long-term outcomes of other critical illness survivors is unknown. We therefore sought to assess long-term survival and functional outcomes among 90-day survivors of severe shock and determine whether clinical predictors were associated with outcomes. Seventy-six patients who were alive 90 days after severe shock (received ≥1 μg/kg per minute of norepinephrine equivalent) were eligible for the study. We measured 3-year survival and long-term functional outcomes using the Medical Outcomes Study 36-Item Short-Form Health Survey, the EuroQOL 5-D-3L, the Hospital Anxiety and Depression Scale, the Impact of Event Scale-Revised, and an employment instrument. We also assessed the relationship between in-hospital predictors and long-term outcomes. The mean long-term survival was 5.1 years; 82% (62 of 76) of patients survived, of whom 49 were eligible for follow-up. Patients who died were older than patients who survived. Thirty-six patients completed a telephone interview a mean of 5 years after hospital admission. The patients' Physical Functioning scores were below U.S. population norms (P < 0.001), whereas mental health scores were similar to population norms. Nineteen percent of the patients had symptoms of depression, 39% had symptoms of anxiety, and 8% had symptoms of posttraumatic stress disorder. Thirty-six percent were disabled, and 17% were working full-time. Early survivors of severe shock had a high 3-year survival rate. Patients' long-term physical and psychological outcomes were similar to those reported for cohorts of less severely ill intensive care unit survivors. Anxiety and depression were relatively common, but only a few patients had symptoms of posttraumatic stress disorder. This study supports the observation that acute illness severity does not determine long-term outcomes. Even extremely

  18. [Fetal pain: immediate and long term consequences].

    PubMed

    Houfflin Debarge, Véronique; Dutriez, Isabelle; Pusniak, Benoit; Delarue, Eléonore; Storme, Laurent

    2010-06-01

    Several situations are potentially painful for fetuses, such as malformations and invasive procedures. Nociceptive pathways are known to be functional at 26 weeks. Even if it is not possible to evaluate the fetal experience of pain, it is essential to examine its immediate and long-term consequences. As early as the beginning of the second trimester, hemodynamic and hormonal responses are observed following fetal nociceptive stimulation, In experimental studies, long-term changes have been noted in the corticotrop axis, subsequent responses to pain, and behavior after perinatal nociceptive stimulation.

  19. In vivo transduction by intravenous injection of a lentiviral vector expressing human ADA into neonatal ADA gene knockout mice: a novel form of enzyme replacement therapy for ADA deficiency.

    PubMed

    Carbonaro, Denise A; Jin, Xiangyang; Petersen, Denise; Wang, Xingchao; Dorey, Fred; Kil, Ki Soo; Aldrich, Melissa; Blackburn, Michael R; Kellems, Rodney E; Kohn, Donald B

    2006-06-01

    Using a mouse model of adenosine deaminase-deficient severe combined immune deficiency syndrome (ADA-deficient SCID), we have developed a noninvasive method of gene transfer for the sustained systemic expression of human ADA as enzyme replacement therapy. The method of delivery is a human immunodeficiency virus 1-based lentiviral vector given systemically by intravenous injection on day 1 to 2 of life. In this article we characterize the biodistribution of the integrated vector, the expression levels of ADA enzyme activity in various tissues, as well as the efficacy of systemic ADA expression to correct the ADA-deficient phenotype in this mouse model. The long-term expression of enzymatically active ADA achieved by this method, primarily from transduction of liver and lung, restored immunologic function and significantly extended survival. These studies illustrate the potential for sustained in vivo production of enzymatically active ADA, as an alternative to therapy by frequent injection of exogenous ADA protein.

  20. 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.

  1. Long-Term Memory and Learning

    ERIC Educational Resources Information Center

    Crossland, John

    2011-01-01

    The English National Curriculum Programmes of Study emphasise the importance of knowledge, understanding and skills, and teachers are well versed in structuring learning in those terms. Research outcomes into how long-term memory is stored and retrieved provide support for structuring learning in this way. Four further messages are added to the…

  2. Who Recommends Long-Term Care Matters

    ERIC Educational Resources Information Center

    Kane, Robert L.; Bershadsky, Boris; Bershadsky, Julie

    2006-01-01

    Purpose: Making good consumer decisions requires having good information. This study compared long-term-care recommendations among various types of health professionals. Design and Methods: We gave randomly varied scenarios to a convenience national sample of 211 professionals from varying disciplines and work locations. For each scenario, we…

  3. Long-term lysimeter data on evapotranspiration

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Long term crop evapotranspiration (ET) data measured using large weighing lysimeters have only been gathered in a few places in the world, yet are of great importance for ground truthing of many models of plant water use, mesoscale climate, remote sensing estimation of ET, climate change and climate...

  4. Long-Term Impacts of Educational Interventions

    ERIC Educational Resources Information Center

    Deming, David James

    2010-01-01

    The school accountability movement has led to a marked increase in the use of standardized test scores to measure school and teacher productivity, yet little is known about the correlation between test score gains and improvements in long-term outcomes. In the first chapter of my dissertation, I study the impact of a school choice policy in…

  5. Long-Term Stability of Tutor Performance.

    ERIC Educational Resources Information Center

    Dolmans, Diana H. J. M.; And Others

    1996-01-01

    Examined the extent to which tutor ratings remained stable in the long term by evaluating 291 ratings of 140 tutors at Maastricht University in the Netherlands between 1992 and 1995. The results indicated that, if the aggregated score and overall judgement are used to interpret the precision of individual scores, four and two occasions,…

  6. Long-Term Stability of Social Participation

    ERIC Educational Resources Information Center

    Hyyppa, Markku T.; Maki, Juhani; Alanen, Erkki; Impivaara, Olli; Aromaa, Arpo

    2008-01-01

    The long-term stability of social participation was investigated in a representative urban population of 415 men and 579 women who had taken part in the nationwide Mini-Finland Health Survey in the years 1978-1980 and were re-examined 20 years later. Stability was assessed by means of the following tracking coefficients: kappa, proportion of…

  7. Long-term opioid therapy reconsidered.

    PubMed

    Von Korff, Michael; Kolodny, Andrew; Deyo, Richard A; Chou, Roger

    2011-09-06

    In the past 20 years, primary care physicians have greatly increased prescribing of long-term opioid therapy. However, the rise in opioid prescribing has outpaced the evidence regarding this practice. Increased opioid availability has been accompanied by an epidemic of opioid abuse and overdose. The rate of opioid addiction among patients receiving long-term opioid therapy remains unclear, but research suggests that opioid misuse is not rare. Recent studies report increased risks for serious adverse events, including fractures, cardiovascular events, and bowel obstruction, although further research on medical risks is needed. New data indicate that opioid-related risks may increase with dose. From a societal perspective, higher-dose regimens account for the majority of opioids dispensed, so cautious dosing may reduce both diversion potential and patient risks for adverse effects. Limiting long-term opioid therapy to patients for whom it provides decisive benefits could also reduce risks. Given the warning signs and knowledge gaps, greater caution and selectivity are needed in prescribing long-term opioid therapy. Until stronger evidence becomes available, clinicians should err on the side of caution when considering this treatment.

  8. Professionalism in Long-Term Care Settings

    ERIC Educational Resources Information Center

    Lubinski, Rosemary

    2006-01-01

    Speech-language pathologists who serve elders in a variety of long-term care settings have a variety of professional skills and responsibilities. Fundamental to quality service is knowledge of aging and communication changes and disorders associated with this process, institutional alternatives, and the changing nature of today's elders in…

  9. Long Term Care Aide. Course Outline.

    ERIC Educational Resources Information Center

    Wilbee, Judy

    This course outline is intended to assist the instructor in the development of a curriculum for a long-term care aide program by specifying one component of the curriculum--the objectives. These objectives, or competencies expected as outcomes for student performance on completion of the program, describe the capabilities an individual must…

  10. Evaluating Long-Term Disability Insurance Plans.

    ERIC Educational Resources Information Center

    Powell, Jan

    1992-01-01

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

  11. LONG TERM HYDROLOGICAL IMPACT ASSESSMENT (LTHIA)

    EPA Science Inventory

    LTHIA is a universal Urban Sprawl analysis tool that is available to all at no charge through the Internet. It estimates impacts on runoff, recharge and nonpoint source pollution resulting from past or proposed land use changes. It gives long-term average annual runoff for a lan...

  12. Long-term fixed income market structure

    NASA Astrophysics Data System (ADS)

    Grilli, Luca

    2004-02-01

    Long-term fixed income market securities present a strong positive correlation in daily returns. By using a metrical approach and considering “modified” time series, I show how it is possible to show a more complex structure which depends strictly on the maturity date.

  13. Long-Term Care Research and Policy

    ERIC Educational Resources Information Center

    Kemper, Peter

    2003-01-01

    This article provides a framework for understanding how long-term care (LTC) research contributes to policy, develops a typology of research contributions to policy with examples of each type, and suggests ways to ensure that contributions continue in the future. The article draws on in-depth interviews with LTC experts working at the interface…

  14. The long term characteristics of greenschist

    NASA Astrophysics Data System (ADS)

    Jang, Bo-An

    2016-04-01

    The greenschist in the Jinping II Hydropower Station in southwest China exhibits continuous creep behaviour because of the geological conditions in the region. This phenomenon illustrates the time-dependent deformation and progressive damage that occurs after excavation. In this study, the responses of greenschist to stress over time were determined in a series of laboratory tests on samples collected from the access tunnel walls at the construction site. The results showed that the greenschist presented time-dependent behaviour under long-term loading. The samples generally experienced two stages: transient creep and steady creep, but no accelerating creep. The periods of transient creep and steady creep increased with increasing stress levels. The long-term strength of the greenschist was identified based on the variation of creep strain and creep rate. The ratio of long-term strength to conventional strength was around 80% and did not vary much with confining pressures. A quantitative method for predicting the failure period of greenschist, based on analysis of the stress-strain curve, is presented and implemented. At a confining pressure of 40 MPa, greenschist was predicted to fail in 5000 days under a stress of 290 MPa and to fail in 85 days under the stress of 320 MPa, indicating that the long-term strength identified by the creep rate and creep strain is a reliable estimate.

  15. Enzyme replacement treatment in type 1 and type 3 Gaucher's disease.

    PubMed

    Bembi, B; Zanatta, M; Carrozzi, M; Baralle, F; Gornati, R; Berra, B; Agosti, E

    1994-12-17

    The development of intravenous enzyme-replacement treatment for Gaucher's disease has changed life expectancy in cases without neurological involvement (type 1). The effects in patients with neurological involvement are unknown. We treated 12 Italian patients, types 1 (9) and 3 (3), with intravenous alglucerase: 70-120 IU/kg per month for type 3 and 30-60 IU/kg per month for type 1. Maintenance infusions were biweekly in patients without neurological symptoms, whereas in one symptomatic type 3 patient, infusion was weekly. All patients improved; a resumption of growth in children with growth retardation was observed and spleen and liver reduced in size. In one type 3 patient, a bone callus formed during treatment and enabled the patient to walk. Laboratory tests showed rapid increase of haemoglobin in anaemic patients, and a slower response in patients with thrombocytopaenia. In 4 patients there was temporary hypocalcaemia immediately after the beginning of treatment. Neurological symptoms were present in 1 of the type 3 patients, and electroencephalogram was abnormal in another. After 2 years of treatment, the patient with symptoms showed an improvement of psychomotor skills and of IQ from 50 to 60. Genotype analysis showed a high frequency of the 1448C mutation (54.5%). The 9 patients carrying this allele came from Italian regions which in the past had been invaded from north Europe and Scandinavia. Enzyme replacement in Gaucher's type 1 can also be effective at low doses and even with a 2-week interval between infusions. This makes treatment cheaper, and reduces hospital stay for patients.

  16. Characterization of pre- and post-treatment pathology after enzyme replacement therapy for Pompe disease.

    PubMed

    Thurberg, Beth L; Lynch Maloney, Colleen; Vaccaro, Charles; Afonso, Kendra; Tsai, Anne Chun-Hui; Bossen, Edward; Kishnani, Priya S; O'Callaghan, Michael

    2006-12-01

    In Pompe disease, a genetic deficiency of lysosomal acid alpha-glucosidase, glycogen accumulates abnormally in the lysosomes of skeletal, cardiac and smooth muscle, and contributes to clinically progressive and debilitating muscle weakness. The present study involved 8 infantile-onset Pompe patients, treated weekly with 10 mg/kg of recombinant human acid alpha-glucosidase (rhGAA). Muscle biopsies were obtained at baseline, 12 and 52 weeks post-treatment to establish an indicator of efficacy. Several histologic strategies were employed to characterize changes in pre- and post-treatment samples, including high-resolution light microscopy and digital histomorphometry, electron microscopy, capillary density and fiber type analysis, and confocal microscopy for satellite cell activation analysis. Histomorphometric analysis was performed on muscle samples to assess glycogen depletion in response to enzyme replacement therapy (ERT). The extent of glycogen clearance varied widely among these patient samples, and correlated well with clinical outcome. Low glycogen levels, mild ultrastructural damage, a high proportion of type I fibers, and young age at baseline were all features associated with good histologic response. There was no correlation between capillary density and glycogen clearance, and activated satellite cell levels were shown to be higher in post-treatment biopsies with poor histologic responses. This histopathologic study of infantile Pompe disease provides detailed insight into the cellular progression of the disease and its response to therapy while highlighting a number of methodologies which may be employed to assess regression or progression of the associated pathology. As enzyme replacement therapy becomes more prevalent for the treatment of lysosomal storage diseases, such evaluation of post-treatment pathology will likely become a more common occurrence in the daily practice of pathologists.

  17. Cardiomyopathy and response to enzyme replacement therapy in a male mouse model for Fabry disease.

    PubMed

    Nguyen Dinh Cat, Aurelie; Escoubet, Brigitte; Agrapart, Vincent; Griol-Charhbili, Violaine; Schoeb, Trenton; Feng, Wenguang; Jaimes, Edgar; Warnock, David G; Jaisser, Frederic

    2012-01-01

    Fabry disease is an X-linked disorder of glycosphingolipid metabolism that results in progressive accumulation of neutral glycosphingolipids, (predominately globotriaosylceramide; GL-3) in lysosomes, as well as other cellular compartments and the extracellular space. Our aim was to characterize the cardiac phenotype of male knock-out mice that are deficient in alpha-galactosidase A activity, as a model for Fabry disease and test the efficacy of Enzyme Replacement Therapy with agalsidase-beta. Male mice (3-4 months of age) were characterized with awake blood pressure and heart rate measurements, cardiac echocardiography and electrocardiography measurements under light anesthesia, histological studies and molecular studies with real-time polymerase chain reaction. The Fabry knock-out mouse has bradycardia and lower blood pressure than control wild type (CB7BL/6J) mice. In Fabry knock-out mice, the cardiomyopathy associated mild hypertrophy at echography with normal systolic LV function and mild diastolic dysfunction. Premature atrial contractions were more frequent in without conduction defect. Heart weight normalized to tibial length was increased in Fabry knock-out mice. Ascending aorta dilatation was observed. Molecular studies were consistent with early stages of cardiac remodeling. A single dose of agalsidase-beta (3 mg/kg) did not affect the LV hypertrophy, function or heart rate, but did improve the mRNA signals of early cardiac remodeling. In conclusion, the alpha-galactosidase A deficient mice at 3 to 4 months of age have cardiac and vascular alterations similar to that described in early clinical stage of Fabry disease in children and adolescents. Enzyme replacement therapy affects cardiac molecular remodeling after a single dose.

  18. Workshop on long-term contraceptives.

    PubMed

    1996-01-01

    The National Population Council Secretariat (NPCS) of Ghana held a three-day workshop on long-term contraceptives in 1996 in collaboration with the Ministry of Health, the Association of Voluntary Surgical Contraception, and the Johns Hopkins Population Communication Services. The session was funded by USAID. The executive director of NPCS, Dr. Richard Turkson, said that the slow rate of contraceptive acceptance was an obstacle to population control despite political concern that rapid population growth exerted an adverse impact on the economy. Only 10% of married women were using long-term or permanent methods of contraception. The hope was voiced that the participants would devise practical and cost-effective education, information, and communication (IEC) strategies to boost the demand for long-term contraceptive methods among sexually active people in Ghana. It was essential that these strategies and activities were based on a realist assessment of the demographic and social situation of the country. The examination of case studies in cultures similar to Ghana would also offer valuable lessons. The factors that hinder the acceptance of long-term methods include misconceptions, myths, and false rumors rooted in a general lack of knowledge among the people. Participants were urged to come up with strategies to counter these problems, and service providers were encouraged to improve their knowledge about contraceptive methods and counseling skills. Male involvement in contraception was also advocated. Statistics show that most Ghanians practicing contraception were using short-term methods such as foaming tablets, pills, and condoms. However, it is necessary to shift to long-term methods such as injectables, implants, and sterilization in order to achieve significant reductions in fertility.

  19. Long-term biological investigations in space.

    PubMed

    Lotz, R G; Fuchs, H; Bertsche, U

    1975-01-01

    Missions in space within the next two decades will be of longer duration than those carried out up to the present time, and the effects of such long-term flights on biological organisms are unknown. Results of biological experiments that have been performed to date cannot be extrapolated to results in future flights because of the unknown influence of adaptation over a long period of time. Prior experiments with Axolotl, fishes, and vertebrates by our research team (in part with sounding rockets) showed that these specimens did not appear to be suitable for long-term missions on which minimization of expense, technique, and energy is required. Subsequent investigations have shown the suitability of the leech (Hirudo medicinalis), which consumes blood of mammals up to ten times its own weight (1 g) and can live more than 2 years without further food supply. Emphasis in the experiments with Hirudo medicinalis is placed on metabolic rhythm and motility. Resorption and diffusion in tissue, development, and growth under long-term effects of cosmic proton radiation and zero-gravity are other focal points. The constancy of cellular life in the mature animals is a point in favor of these specimens. We have also taken into account the synergistic effects of the space environment on the problems just mentioned. The life-support system constructed for the leech has been tested successfully in four sounding rocket flights and, on that basis, has been prepared for a long-term mission. Long-term investigations out of the terrestrial biosphere will provide us with information concerning the degree of adaptation of certain physiological and biochemical functions and as to what extent biological readjustment or repair processes can occur under the specific stress conditions of space flight.

  20. Dialysis and transplantation in Fabry disease: indications for enzyme replacement therapy.

    PubMed

    Mignani, Renzo; Feriozzi, Sandro; Schaefer, Roland M; Breunig, Frank; Oliveira, João Paulo; Ruggenenti, Piero; Sunder-Plassmann, Gere

    2010-02-01

    ESRD is a major cause of morbidity and premature mortality in Fabry disease, particularly in classically affected males. The decline of renal function in Fabry nephropathy is adversely affected by male gender, advanced chronic kidney disease (CKD), and severe proteinuria. The diagnosis of Fabry nephropathy may be missed if not specifically addressed in progressive CKD and patients have been first identified in screening programs of dialysis patients. Fabry patients have worse 3-year survival rates on dialysis as compared with nondiabetic controls. The 5-year survival rate of transplanted Fabry patients is also lower than that of controls. However, because Fabry nephropathy does not recur in the allograft and transplanted Fabry patients appear to have better overall outcomes than those maintained on dialysis, kidney transplantation should be recommended as a first choice in renal replacement therapy (RRT) for Fabry disease. Appropriately designed and powered studies are not available to answer the question whether enzyme replacement therapy (ERT) influences outcomes, the course of cardiomyopathy, events, or survival in Fabry patients on RRT. The authors are not aware of compelling indications for ERT in RRT patients because progression of cardiomyopathy was documented during ERT. Whether the excess mortality risk of Fabry patients on RRT can be prevented by ERT is unknown. Despite observational reports of symptomatic improvement, the available evidence supporting ERT for such patients is not compelling enough. To clarify this issue, studies are needed to test the effectiveness of agalsidases in preventing cardiac and cerebrovascular complications in Fabry patients with ESRD.

  1. Long-Term Monitoring Research Needs: A DOE Perspective

    NASA Astrophysics Data System (ADS)

    Moore, B.; Davis, C. B.

    2002-05-01

    The U.S. Department of Energy's Office of Environmental Management is responsible for dealing with the nation's legacy of Cold War radioactive and hazardous waste and contamination. Major efforts are underway to deal with this legacy; these are expected to last up to decades and cost up to billions of dollars at some sites. At all sites, however, active remediation must eventually cease; if hazards then remain, the site must enter into a long-term stewardship mode. In this talk we discuss aspects of long-term monitoring pertinent to DOE sites, focusing on challenges to be faced, specific goals or targets to be met, and research needs to be addressed in order to enable DOE to meet its long-term stewardship obligations. DOE LTM research needs fall into three major categories: doing what we can do now much more efficiently; doing things we cannot do now; and proving the validity of our monitoring programs. Given the enormity of the DOE obligations, it will be highly desirable to develop much more efficient monitoring paradigms. Doing so will demand developing autonomous, remote monitoring networks of in situ sensors capable of replacing (or at least supplementing to a large extent) conventional groundwater and soil gas sampling and analysis programs. The challenges involved range from basic science (e.g., inventing in situ sensors for TCE that do not demand routine maintenance) to engineering (attaining superior reliability in data reporting in remote networks) to ergonomics (developing decent ways of selecting and presenting the "right" information from the monitoring network) to regulatory affairs (presenting convincing evidence that the more efficient systems actually provide superior monitoring). We explore these challenges in some detail, focusing on the "long" in long-term monitoring as it applies to DOE sites. Monitoring system performance validation and, ultimately, regulator and stakeholder acceptance of site closure and long-term stewardship plans depend

  2. β2 Agonists Enhance the Efficacy of Simultaneous Enzyme Replacement Therapy in Murine Pompe Disease

    PubMed Central

    Koeberl, Dwight D.; Li, Songtao; Dai, Jian; Thurberg, Beth L.; Bali, Deeksha; Kishnani, Priya S.

    2011-01-01

    Enzyme replacement therapy (ERT) with recombinant human acid α-glucosidase (rhGAA) has improved clinical outcomes in patients with Pompe disease; however, the response of skeletal muscle and the central nervous system to ERT has been attenuated. The poor response of skeletal muscle to ERT has been attributed to the low abundance of the cation-independent mannose-6-phosphate receptor (CI-MPR), which mediates receptor-mediated uptake of rhGAA. Hence the ability of adjunctive therapy with β2-agonists to increase CI-MPR expression in skeletal muscle was evaluated during ERT in murine Pompe disease with regard to reversal of neuromuscular involvement. Mice with Pompe disease were treated with weekly rhGAA injections (20 mg/kg) and a selective β2-agonist, either albuterol (30 mg/l in drinking water) or low-dose clenbuterol (6 mg/l in drinking water). Biochemical correction was enhanced by β2-agonist treatment in both muscle and the cerebellum, indicating that adjunctive therapy could enhance efficacy from ERT in Pompe disease with regard to neuromuscular involvement. Intriguingly, clenbuterol slightly reduced muscle glycogen content independent of CI-MPR expression, as demonstrated in CI-MPR knockout/GAA knockout mice that were otherwise resistant to ERT. Thus, adjunctive therapy with β2 agonists might improve the efficacy of ERT in Pompe disease and possibly other lysosomal storage disorders through enhancing receptor-mediated uptake of recombinant lysosomal enzymes. PMID:22154081

  3. β2 Agonists enhance the efficacy of simultaneous enzyme replacement therapy in murine Pompe disease.

    PubMed

    Koeberl, Dwight D; Li, Songtao; Dai, Jian; Thurberg, Beth L; Bali, Deeksha; Kishnani, Priya S

    2012-02-01

    Enzyme replacement therapy (ERT) with recombinant human acid α-glucosidase (rhGAA) has improved clinical outcomes in patients with Pompe disease; however, the response of skeletal muscle and the central nervous system to ERT has been attenuated. The poor response of skeletal muscle to ERT has been attributed to the low abundance of the cation-independent mannose-6-phosphate receptor (CI-MPR), which mediates receptor-mediated uptake of rhGAA. Hence the ability of adjunctive therapy with β2-agonists to increase CI-MPR expression in skeletal muscle was evaluated during ERT in murine Pompe disease with regard to reversal of neuromuscular involvement. Mice with Pompe disease were treated with weekly rhGAA injections (20 mg/kg) and a selective β2-agonist, either albuterol (30 mg/l in drinking water) or low-dose clenbuterol (6 mg/l in drinking water). Biochemical correction was enhanced by β2-agonist treatment in both muscle and the cerebellum, indicating that adjunctive therapy could enhance efficacy from ERT in Pompe disease with regard to neuromuscular involvement. Intriguingly, clenbuterol slightly reduced muscle glycogen content independent of CI-MPR expression, as demonstrated in CI-MPR knockout/GAA knockout mice that were otherwise resistant to ERT. Thus, adjunctive therapy with β2 agonists might improve the efficacy of ERT in Pompe disease and possibly other lysosomal storage disorders through enhancing receptor-mediated uptake of recombinant lysosomal enzymes.

  4. [Neuropathic Gaucher disease treated with long enzyme replacement therapy. Two clinical cases].

    PubMed

    Correa, Cecilia

    2013-01-01

    Gaucher disease (GD) is the most common of all inherited lipid storage diseases. It is an autosomal recessive disorder portraying catabolism and cerebroside deposit in the lysosomes, which is due to a lack of glucocerebrosidase enzyme. Though GD shows a panethnic pattern of presentation, it particularly affects the Ashkenazi Jewish population. Several mutations have been defined among GD patients, and some genotypes related to neurologic affection have been described (L444P--most common mutation for neuropathic GD--188S, V394L and G377S). Lipid material storage or deposit exerts multiorganic affection. Enzyme replacement therapy (ERT) has demonstrable efficacy in reversing organic damage related to GD, though its capability to stop neurologic affection is currently under controversy and particular research. This paper portrays two GD cases of Mexican children treated with ERT at general zone hospitals of the Instituto Mexicano del Seguro Social in recent years, both of them depicting characteristic type 3 GD mutations, and comparing their clinical evolution with and without neurological features.

  5. Real-world clinical experience with long-term miglustat maintenance therapy in type 1 Gaucher disease: the ZAGAL project

    PubMed Central

    Giraldo, Pilar; Alfonso, Pilar; Atutxa, Koldo; Fernández-Galán, María A.; Barez, Abelardo; Franco, Rafael; Alonso, Dora; Martin, Alejandro; Latre, Paz; Pocovi, Miguel

    2009-01-01

    There are few published data from real-world clinical experience with miglustat (Zavesca®), an oral inhibitor of glucosylceramide synthase, in type 1 Gaucher disease. We report data from a prospective, open-label investigational study that evaluated substrate reduction therapy with miglustat 100 mg t.i.d. as a maintenance therapy in patients with Type 1 Gaucher disease who had been switched from previous enzyme replacement therapy. Long-term data on changes in organ size, blood counts, disease severity bio-markers, bone marrow infiltration, overall clinical status and safety/tolerability were analyzed from 28 patients with Type 1 Gaucher disease who were attending routine clinic visits. Assessments were performed at six, 12, 24, 36 and 48 months of therapy. Disease severity biomarkers improved up to 48 months after initiation of miglustat, while other disease parameters remained stable. Miglustat showed an acceptable profile of safety and tolerability throughout treatment. In conclusion, miglustat is an effective therapy for the long-term maintenance of patients with Type 1 Gaucher disease previously stabilized with enzyme replacement therapy. PMID:19608672

  6. Case presentation: long-term treatment.

    PubMed

    Glucksman, Myron L

    2013-01-01

    The long-term (14 years) psychodynamic psychotherapy and pharmacotherapy of a depressed, suicidal, self-mutilating female patient is described. Her diagnoses included Chronic Posttraumatic Stress Disorder, Borderline Personality Disorder, and Recurrent Major Depression. Treatment was punctuated with repeated hospitalizations for self-mutilation (cutting) and suicidal ideation. A major determinant for her psychopathology was sexual abuse by her father from ages 6 to 14. This resulted in feelings of guilt and rage that she repressed and acted out through self-mutilating and suicidal behavior. A prolonged negative transference gradually became ambivalent, then positive. This was associated with her internalization of the healing qualities of the therapeutic relationship. She also gained insight into the reasons for her need to punish herself. Her initial self-representation as unworthy and bad was transformed into perceiving herself as a worthwhile, loving person. This case illustrates the role of long-term treatment for a complex, life-threatening, psychiatric disorder.

  7. Long-term sequelae of electrical injury

    PubMed Central

    Wesner, Marni L.; Hickie, John

    2013-01-01

    Abstract Objective To summarize the current evidence-based knowledge about the long-term sequelae of injuries from electrical current. Quality of evidence MEDLINE was searched for English-language articles published in the past 20 years using the following search terms: electrical, injuries, wound, trauma, accident, sequelae, long-term, follow-up, and aftereffects. For obvious reasons, it is unethical to randomly study electrical injury in controlled clinical trials. By necessity, this topic is addressed in less-rigorous observational and retrospective work and case studies. Therefore, the strength of the literature pertaining to the long-term sequelae of electrical injury is impaired by the necessity of retrospective methods and case studies that typically describe small cohorts. Main message There are 2 possible consequences of electrical injury: the person either survives or dies. For those who survive electrical injury, the immediate consequences are usually obvious and often require extensive medical intervention. The long-term sequelae of the electrical injury might be more subtle, pervasive, and less well defined, but can include neurologic, psychological, and physical symptoms. In the field of compensation medicine, determining causation and attributing outcome to an injury that might not result in objective clinical findings becomes a considerable challenge. Conclusion The appearance of these consequences of electrical injury might be substantially delayed, with onset 1 to 5 or more years after the electrical injury. This poses a problem for patients and health care workers, making it hard to ascribe symptoms to a remote injury when they might not arise until well after the incident event. PMID:24029506

  8. Long-term course of opioid addiction.

    PubMed

    Hser, Yih-Ing; Evans, Elizabeth; Grella, Christine; Ling, Walter; Anglin, Douglas

    2015-01-01

    Opioid addiction is associated with excess mortality, morbidities, and other adverse conditions. Guided by a life-course framework, we review the literature on the long-term course of opioid addiction in terms of use trajectories, transitions, and turning points, as well as other factors that facilitate recovery from addiction. Most long-term follow-up studies are based on heroin addicts recruited from treatment settings (mostly methadone maintenance treatment), many of whom are referred by the criminal justice system. Cumulative evidence indicates that opioid addiction is a chronic disorder with frequent relapses. Longer treatment retention is associated with a greater likelihood of abstinence, whereas incarceration is negatively related to subsequent abstinence. Over the long term, the mortality rate of opioid addicts (overdose being the most common cause) is about 6 to 20 times greater than that of the general population; among those who remain alive, the prevalence of stable abstinence from opioid use is low (less than 30% after 10-30 years of observation), and many continue to use alcohol and other drugs after ceasing to use opioids. Histories of sexual or physical abuse and comorbid mental disorders are associated with the persistence of opioid use, whereas family and social support, as well as employment, facilitates recovery. Maintaining opioid abstinence for at least five years substantially increases the likelihood of future stable abstinence. Recent advances in pharmacological treatment options (buprenorphine and naltrexone) include depot formulations offering longer duration of medication; their impact on the long-term course of opioid addiction remains to be assessed.

  9. Breakthroughs in long term care design.

    PubMed

    Hiatt, L

    1991-01-01

    In summary, here is what design is trying to accomplish in long term care facilities: Functional access; Privacy as entitlement; Sensory optimization to improve vision and hearing; Reduced walking and wheeling distances that still allow people to be mobile; Effective or functional placement of space and equipment; The option of smaller scale, so neither residents nor staff feel like they are hanging out with a unit full of, perhaps 68, people all the time; Flexibility and adaptability

  10. An open-label clinical trial of agalsidase alfa enzyme replacement therapy in children with Fabry disease who are naïve to enzyme replacement therapy

    PubMed Central

    Goker-Alpan, Ozlem; Longo, Nicola; McDonald, Marie; Shankar, Suma P; Schiffmann, Raphael; Chang, Peter; Shen, Yinghua; Pano, Arian

    2016-01-01

    Background Following a drug manufacturing process change, safety/efficacy of agalsidase alfa were evaluated in enzyme replacement therapy (ERT)-naïve children with Fabry disease. Methods In an open-label, multicenter, Phase II study (HGT-REP-084; Shire), 14 children aged ≥7 years received 0.2 mg/kg agalsidase alfa every other week for 55 weeks. Primary endpoints: safety, changes in autonomic function (2-hour Holter monitoring). Secondary endpoints: estimated glomerular filtration rate, left ventricular mass index (LVMI), midwall fractional shortening, pharmacodynamic parameters, and patient-reported quality-of-life. Results Among five boys (median 10.2 [range 6.7, 14.4] years) and nine girls (14.8 [10.1, 15.9] years), eight patients experienced infusion-related adverse events (vomiting, n=4; nausea, n=3; dyspnea, n=3; chest discomfort, n=2; chills, n=2; dizziness, n=2; headache, n=2). One of these had several hypersensitivity episodes. However, no patient discontinued for safety reasons and no serious adverse events occurred. One boy developed immunoglobulin G (IgG) and neutralizing antidrug antibodies. Overall, no deterioration in cardiac function was observed in seven patients with low/abnormal SDNN (standard deviation of all filtered RR intervals; <100 ms) and no left ventricular hypertrophy: mean (SD) baseline SDNN, 81.6 (20.9) ms; mean (95% confidence interval [CI]) change from baseline to week 55, 17.4 (2.9, 31.9) ms. Changes in SDNN correlated with changes in LVMI (r=−0.975). No change occurred in secondary efficacy endpoints: mean (95% CI) change from baseline at week 55 in LVMI, 0.16 (−3.3, 3.7) g/m2.7; midwall fractional shortening, −0.62% (−2.7%, 1.5%); estimated glomerular filtration rate, 0.15 (−11.4, 11.7) mL/min/1.73 m2; urine protein, −1.8 (−6.0, 2.4) mg/dL; urine microalbumin, 0.6 (−0.5, 1.7) mg/dL; plasma globotriaosylceramide (Gb3), −5.71 (−10.8, −0.6) nmol/mL; urinary Gb3, −1,403.3 (−3,714.0, 907.4) nmol/g creatinine

  11. Electrodes for long-term esophageal electrocardiography.

    PubMed

    Niederhauser, Thomas; Haeberlin, Andreas; Marisa, Thanks; Jungo, Michael; Goette, Josef; Jacomet, Marcel; Abacherli, Roger; Vogel, Rolf

    2013-09-01

    The emerging application of long-term and high-quality ECG recording requires alternative electrodes to improve the signal quality and recording capability of surface skin electrodes. The esophageal ECG has the potential to overcome these limitations but necessitates novel recorder and lead designs. The electrode material is of particular interest, since the material has to ensure conflicting requirements like excellent biopotential recording properties and inertness. To this end, novel electrode materials like PEDOT and silver-PDMS as well as established electrode materials such as stainless steel, platinum, gold, iridium oxide, titanium nitride, and glassy carbon were investigated by long-term electrochemical impedance spectroscopy and model-based signal analysis using the derived in vitro interfacial properties in conjunction with a dedicated ECG amplifier. The results of this novel approach show that titanium nitride and iridium oxide featuring microstructured surfaces did not degrade when exposed to artificial acidic saliva. These materials provide low electrode potential drifts and insignificant signal distortion superior to surface skin electrodes making them compatible with accepted standards for ambulatory ECG. They are superior to the noble and polarizable metals such as platinum, silver, and gold that induced more signal distortions and are superior to esophageal stainless steel electrodes that corrode in artificial saliva. The study provides rigorous criteria for the selection of electrode materials for prolonged ECG recording by combining long-term in vitro electrode material properties with ECG signal quality assessment.

  12. Long term therapy of generalized anxiety disorder.

    PubMed

    Rouillon, Frédéric

    2004-04-01

    Generalized anxiety disorder (GAD) is a common (lifetime prevalence: 5.1%), recurrent condition, which often heralds other psychiatric disorders, notably depression. As by definition it is a disorder progressing over months, treatment should be designed on a long term basis. And yet, few studies have been conducted beyond the classical 6-8 weeks characterizing the acute treatment phase. This is especially true of anxiolytics, but also of antidepressants, with the exception of paroxetine and venlafaxine, which are the only drugs approved in this indication in Western countries. The efficacy of psychotherapy, notably relaxation and cognitive-behavioral therapy, is established in the treatment of GAD, but its preferred indications and possible combination with antidepressants are still to be specified. Long term, not to say very long term studies of GAD, as well as depression, will still be required in the future to improve its management and specify therapeutic modalities (combination treatment, optimal duration, continuous or intermittent therapy, choice of psychotherapeutic techniques or agents, em leader ). Early and adequately prolonged treatment should not only result in more numerous remission periods, but also in decreased frequency of co-morbidities whether depressive, addictive, or of another nature, and should also reduce the social impact of GAD.

  13. Titanium for long-term tritium storage

    SciTech Connect

    Heung, L.K.

    1994-12-01

    Due to the reduction of nuclear weapon stockpile, there will be an excess of tritium returned from the field. The excess tritium needs to be stored for future use, which might be several years away. A safe and cost effective means for long term storage of tritium is needed. Storing tritium in a solid metal tritide is preferred to storing tritium as a gas, because a metal tritide can store tritium in a compact form and the stored tritium will not be released until heat is applied to increase its temperature to several hundred degrees centigrade. Storing tritium as a tritide is safer and more cost effective than as a gas. Several candidate metal hydride materials have been evaluated for long term tritium storage. They include uranium, La-Ni-Al alloys, zirconium and titanium. The criteria used include material cost, radioactivity, stability to air, storage capacity, storage pressure, loading and unloading conditions, and helium retention. Titanium has the best combination of properties and is recommended for long term tritium storage.

  14. Infective endocarditis: determinants of long term outcome

    PubMed Central

    Netzer, R O M; Altwegg, S C; Zollinger, E; Täuber, M; Carrel, T; Seiler, C

    2002-01-01

    Objective: To evaluate predictors of long term prognosis in infective endocarditis. Design: Retrospective cohort study. Setting: Tertiary care centre. Patients: 212 consecutive patients with infective endocarditis between 1980 and 1995 Main outcome measures: Overall and cardiac mortality; event-free survival; and the following events: recurrence, need for late valve surgery, bleeding and embolic complications, cerebral dysfunction, congestive heart failure. Results: During a mean follow up period of 89 months (range 1–244 months), 56% of patients died. In 180 hospital survivors, overall and cardiac mortality amounted to 45% and 24%, respectively. By multivariate analysis, early surgical treatment, infection by streptococci, age < 55 years, absence of congestive heart failure, and > 6 symptoms or signs of endocarditis during active infection were predictive of improved overall long term survival. Independent determinants of event-free survival were infection by streptococci and age < 55 years. Event-free survival was 17% at the end of follow up both in medically–surgically treated patients and in medically treated patients. Conclusions: Long term survival following infective endocarditis is 50% after 10 years and is predicted by early surgical treatment, age < 55 years, lack of congestive heart failure, and the initial presence of more symptoms of endocarditis. PMID:12067947

  15. Enhanced response to enzyme replacement therapy in Pompe disease after the induction of immune tolerance.

    PubMed

    Sun, Baodong; Bird, Andrew; Young, Sarah P; Kishnani, Priya S; Chen, Y-T; Koeberl, Dwight D

    2007-11-01

    Pompe disease, which results from mutations in the gene encoding the glycogen-degrading lysosomal enzyme acid alpha -glucosidase (GAA) (also called "acid maltase"), causes death in early childhood related to glycogen accumulation in striated muscle and an accompanying infantile-onset cardiomyopathy. The efficacy of enzyme replacement therapy (ERT) with recombinant human GAA was demonstrated during clinical trials that prolonged subjects' overall survival, prolonged ventilator-free survival, and also improved cardiomyopathy, which led to broad-label approval by the U.S. Food and Drug Administration. Patients who lack any residual GAA expression and are deemed negative for cross-reacting immunologic material (CRIM) have a poor response to ERT. We previously showed that gene therapy with an adeno-associated virus (AAV) vector containing a liver-specific promoter elevated the GAA activity in plasma and prevented anti-GAA antibody formation in immunocompetent GAA-knockout mice for 18 wk, predicting that liver-specific expression of human GAA with the AAV vector would induce immune tolerance and enhance the efficacy of ERT. In this study, a very low number of AAV vector particles was administered before initiation of ERT, to prevent the antibody response in GAA-knockout mice. A robust antibody response was provoked in naive GAA-knockout mice by 6 wk after a challenge with human GAA and Freund's adjuvant; in contrast, administration of the AAV vector before the GAA challenge prevented the antibody response. Most compellingly, the antibody response was prevented by AAV vector administration during the 12 wk of ERT, and the efficacy of ERT was thereby enhanced. Thus, AAV vector-mediated gene therapy induced a tolerance to introduced GAA, and this strategy could enhance the efficacy of ERT in CRIM-negative patients with Pompe disease and in patients with other lysosomal storage diseases.

  16. Enhanced Response to Enzyme Replacement Therapy in Pompe Disease after the Induction of Immune Tolerance

    PubMed Central

    Sun, Baodong ; Bird, Andrew ; Young, Sarah P. ; Kishnani, Priya S. ; Chen, Y.-T. ; Koeberl, Dwight D. 

    2007-01-01

    Pompe disease, which results from mutations in the gene encoding the glycogen-degrading lysosomal enzyme acid α-glucosidase (GAA) (also called “acid maltase”), causes death in early childhood related to glycogen accumulation in striated muscle and an accompanying infantile-onset cardiomyopathy. The efficacy of enzyme replacement therapy (ERT) with recombinant human GAA was demonstrated during clinical trials that prolonged subjects’ overall survival, prolonged ventilator-free survival, and also improved cardiomyopathy, which led to broad-label approval by the U.S. Food and Drug Administration. Patients who lack any residual GAA expression and are deemed negative for cross-reacting immunologic material (CRIM) have a poor response to ERT. We previously showed that gene therapy with an adeno-associated virus (AAV) vector containing a liver-specific promoter elevated the GAA activity in plasma and prevented anti-GAA antibody formation in immunocompetent GAA-knockout mice for 18 wk, predicting that liver-specific expression of human GAA with the AAV vector would induce immune tolerance and enhance the efficacy of ERT. In this study, a very low number of AAV vector particles was administered before initiation of ERT, to prevent the antibody response in GAA-knockout mice. A robust antibody response was provoked in naive GAA-knockout mice by 6 wk after a challenge with human GAA and Freund’s adjuvant; in contrast, administration of the AAV vector before the GAA challenge prevented the antibody response. Most compellingly, the antibody response was prevented by AAV vector administration during the 12 wk of ERT, and the efficacy of ERT was thereby enhanced. Thus, AAV vector–mediated gene therapy induced a tolerance to introduced GAA, and this strategy could enhance the efficacy of ERT in CRIM-negative patients with Pompe disease and in patients with other lysosomal storage diseases. PMID:17924344

  17. Antibody-mediated enzyme replacement therapy targeting both lysosomal and cytoplasmic glycogen in Pompe disease.

    PubMed

    Yi, Haiqing; Sun, Tao; Armstrong, Dustin; Borneman, Scott; Yang, Chunyu; Austin, Stephanie; Kishnani, Priya S; Sun, Baodong

    2017-02-02

    Pompe disease is characterized by accumulation of both lysosomal and cytoplasmic glycogen primarily in skeletal and cardiac muscles. Mannose-6-phosphate receptor-mediated enzyme replacement therapy (ERT) with recombinant human acid α-glucosidase (rhGAA) targets the enzyme to lysosomes and thus is unable to digest cytoplasmic glycogen. Studies have shown that anti-DNA antibody 3E10 penetrates living cells and delivers "cargo" proteins to the cytosol or nucleus via equilibrative nucleoside transporter ENT2. We speculate that 3E10-mediated ERT with GAA will target both lysosomal and cytoplasmic glycogen in Pompe disease. A fusion protein (FabGAA) containing a humanized Fab fragment derived from the murine 3E10 antibody and the 110 kDa human GAA precursor was constructed and produced in CHO cells. Immunostaining with an anti-Fab antibody revealed that the Fab signals did not co-localize with the lysosomal marker LAMP2 in cultured L6 myoblasts or Pompe patient fibroblasts after incubation with FabGAA. Western blot with an anti-GAA antibody showed presence of the 150 kDa full-length FabGAA in the cell lysates, in addition to the 95- and 76 kDa processed forms of GAA that were also seen in the rhGAA-treated cells. Blocking of mannose-6-phosphate receptor with mannose-6-phosphate markedly reduced the 95- and the 76 kDa forms but not the 150 kDa form. In GAA-KO mice, FabGAA achieved similar treatment efficacy as rhGAA at an equal molar dose in reducing tissue glycogen contents. Our data suggest that FabGAA retains the ability of rhGAA to treat lysosomal glycogen accumulation and has the beneficial potential over rhGAA to reduce cytoplasmic glycogen storage in Pompe disease.

  18. A beta-blocker, propranolol, decreases the efficacy from enzyme replacement therapy in Pompe disease

    PubMed Central

    Han, Sang-oh; Pope, Rand; Li, Songtao; Kishnani, Priya S.; Steet, Richard; Koeberl, Dwight D.

    2015-01-01

    Enzyme replacement therapy (ERT) with recombinant human acid α-glucosidase (rhGAA) fails to completely reverse muscle weakness in Pompe disease. β2-agonists enhanced ERT by increasing receptor-mediated uptake of rhGAA in skeletal muscles. Purpose To test the hypothesis that a β-blocker might reduce the efficacy of ERT, because the action of β-blockers opposes those of β2-agonists. Methods Mice with Pompe disease were treated with propranolol (a β-blocker) or clenbuterol in combination with ERT, or with ERT alone. Results Propranolol-treated mice had decreased weight gain (p<0.01), in comparison with clenbuterol-treated mice. Left ventricular mass was decreased (and comparable to wild-type) in ERT only and clenbuterol-treated groups of mice, and unchanged in propranolol-treated mice. GAA activity increased following either clenbuterol or propranolol in skeletal muscles. However, muscle glycogen was reduced only in clenbuterol-treated mice, not in propranolol-treated mice. Cell-based experiments confirmed that propranolol reduces uptake of rhGAA into Pompe fibroblasts and also demonstrated that the drug induces intracellular accumulation of glycoproteins at higher doses. Conclusion Propranolol, a commonly prescribed β-blocker, increased left ventricular mass and decreased glycogen clearance in skeletal muscle following ERT. β-blockers might therefore decrease the efficacy from ERT in patients with Pompe disease. PMID:26454691

  19. Enzyme replacement therapy for treating mucopolysaccharidosis type IVA (Morquio A syndrome): effect and limitations

    PubMed Central

    Tomatsu, Shunji; Sawamoto, Kazuki; Shimada, Tsutomu; Bober, Michael B.; Kubaski, Francyne; Yasuda, Eriko; Mason, Robert W.; Khan, Shaukat; Alméciga-Díaz, Carlos J.; Barrera, Luis A.; Mackenzie, William G.

    2015-01-01

    Introduction Following a Phase III, randomized, double-blind, placebo (PBO)-controlled, multinational study in subjects with mucopolysaccharidosis IVA (MPS IVA), enzyme replacement therapy (ERT) of elosulfase alfa has been approved in several countries. The study was designed to evaluate safety and efficacy of elosulfase alfa in patients with MPS IVA aged 5 years and older. Areas covered Outcomes of clinical trials for MPS IVA have been described. Subjects received either 2.0 mg/kg/week, 2.0 mg/kg/every other week, or PBO, for 24 weeks. The primary endpoint was the change from baseline 6-min walk test (6MWT) distance compared to PBO. The 6MWT results improved in patients receiving 2 mg/kg weekly compared to PBO. The every other week regimen resulted in walk distances comparable to PBO. There was no change from baseline in the 3 Min Stair Climb Test in both treatment groups. Following completion of the initial study, patients, who continued to receive elosulfase alfa 2 mg/kg weekly (QW) for another 48 weeks (for a total of up to 72-week exposure), did not show additional improvement on 6MWT. Expert opinion We suggest that ERT is a therapeutic option for MPS IVA, providing a modest effect and the majority of the effects are seen in the soft tissues. PMID:26973801

  20. Reduced glucosylceramide in the mouse model of Fabry disease: correction by successful enzyme replacement therapy.

    PubMed

    Quinta, Rui; Rodrigues, Daniel; Assunção, Marisa; Macedo, Maria Fatima; Azevedo, Olga; Cunha, Damião; Oliveira, Pedro; Sá Miranda, Maria Clara

    2014-02-15

    Fabry disease is an X-linked lysosomal storage disease (LSD) caused by deficient activity of α-Galactosidase A (α-Gal A). As a result, glycosphingolipids, mainly globotriaosylceramide (Gb3), progressively accumulate in body fluids and tissues. Studies aiming at the identification of secondary lipid alterations in Fabry disease may be potentially useful for the monitorization of the response to enzyme replacement therapy (ERT) and development of future therapies. The focus of this study was to evaluate if α-Gal A deficiency has an effect on two key groups of molecules of sphingolipids metabolism: glucosylceramides (GlucCers) and ceramides (Cers). Studies performed in a mouse model of Fabry disease showed reduced level of GlucCer and normal level of Cer in plasma, liver, spleen, kidney and heart. Moreover, analysis of GlucCer isoforms in Fabry knockout mice showed that GlucCer isoforms are unequally reduced in different tissues of these animals. ERT had a specific effect on the liver's GlucCer levels of Fabry knockout mice, increasing hepatic GlucCer to the levels observed in wild type mice. In contrast to Fabry knockout mice, plasma of Fabry patients had normal GlucCer and Cer but an increased GlucCer/Cer ratio. This alteration showed a positive correlation with plasma globotriaosylsphingosine (lyso-Gb3) concentration. In conclusion, this work reveals novel secondary lipid imbalances caused by α-Gal A deficiency.

  1. Continuous infusion of enzyme replacement therapy is inferior to weekly infusions in MPS I dogs

    PubMed Central

    Passage, M.B.; Krieger, A.W.; Peinovich, M.C.; Lester, T.; Le, S.Q.; Dickson, P.I.; Kakkis, E.D.

    2010-01-01

    Summary Intravenous enzyme replacement therapy with recombinant human α-l-iduronidase (rhIDU) is used weekly to treat mucopolysaccharidosis (MPS) I. We tested continuous administration of rhIDU at two dosing levels (0.58 mg/kg/week and 2 mg/kg/week) in MPS I dogs, and compared the efficacy of continuous to the clinically-used 0.58 mg/kg weekly three-hour infusion. Peak plasma concentrations of rhIDU were much higher in weekly-treated dogs (mean 256 units/ml) than steady-state concentrations in dogs treated with continuous infusion (mean 1.97 units/ml at 0.58 mg/kg/week; 10.1 units/ml at 2 mg/kg/week). Dogs receiving continuous IV rhIDU, even at a higher (2 mg/kg/week) dose, had consistently lower iduronidase levels in tissues than dogs receiving a weekly (0.58 mg/kg/week) dose. GAG storage was also less improved by continuous intravenous infusion. Adverse events were similar in all dosing groups. We found that continuous administration of 2 mg/kg/week rhIDU to MPS I dogs was insufficient to achieve GAG storage reduction comparable to 0.58 mg/kg weekly dosing. PMID:19562502

  2. Progress in Enzyme Replacement Therapy in Glycogen Storage Disease Type II

    PubMed Central

    Semplicini, Claudio; Tonin, Paola; Filosto, Massimiliano; Pegoraro, Elena; Sorarù, Gianni; Fanin, Marina

    2009-01-01

    Glycogen storage disease type II (GSDII) is an autosomal recessive lysosomal disorder caused by mutations in the gene encoding alpha-glucosidase (GAA). The disease can be clinically classified into three types: a severe infantile form, a juvenile and an adultonset form. Cases with juvenile or adult onset GSDII mimic limb-girdle muscular dystrophy or polymyositis and are often characterized by respiratory involvement. GSDII patients are diagnosed by biochemical assay and by molecular characterization of the GAA gene. Ascertaining a natural history of patients with heterogeneous late-onset GSDII is useful for evaluating their progressive functional disability. A significant decline is observed over the years in skeletal and respiratory muscle function. Enzyme replacement therapy (ERT) has provided encouraging results in the infantile form. It is not yet known if ERT is effective in late-onset GSDII. We examined a series of 11 patients before and after ERT evaluating muscle strength by MRC, timed and graded functional tests, 6-minute walk test (6MWT), respiratory function by spirometric parameters and quality of life. We observed a partial improvement during a prolonged follow-up from 3 to 18 months. The use of different clinical parameters in the proposed protocol seems crucial to determine the efficacy of ERT, since not all late-onset patients respond similarly to ERT. PMID:21179524

  3. Deleterious effects of interruption followed by reintroduction of enzyme replacement therapy on a lysosomal storage disorder.

    PubMed

    Schneider, Ana Paula; Matte, Ursula; Pasqualim, Gabriela; Tavares, Angela Maria Vicente; Mayer, Fabiana Quoos; Martinelli, Barbara; Ribas, Graziela; Vargas, Carmen Regla; Giugliani, Roberto; Baldo, Guilherme

    2016-10-01

    Temporary interruption of enzyme replacement therapy (ERT) in patients with different lysosomal storage disorders may happen for different reasons (adverse reactions, issues with reimbursement, logistic difficulties, and so forth), and the impact of the interruption is still uncertain. In the present work, we studied the effects of the interruption of intravenous ERT (Laronidase, Genzyme) followed by its reintroduction in mice with the prototypical lysosomal storage disorder mucopolysaccharidosis type I, comparing to mice receiving continuous treatment, untreated mucopolysaccharidosis type I mice, and normal mice. In the animals which treatment was temporarily interrupted, we observed clear benefits of treatment in several organs (liver, lung, heart, kidney, and testis) after reintroduction, but a worsening in the thickness of the aortic wall was detected. Furthermore, these mice had just partial improvements in behavioral tests, suggesting some deterioration in the brain function. Despite worsening is some disease aspects, urinary glycosaminoglycans levels did not increase during interruption, which indicates that this biomarker commonly used to monitor treatment in patients should not be used alone to assess treatment efficacy. The deterioration observed was not caused by the development of serum antienzyme antibodies. All together our results suggest that temporary ERT interruption leads to deterioration of function in some organs and should be avoided whenever possible.

  4. Enzyme replacement therapy from birth in a feline model of mucopolysaccharidosis type VI.

    PubMed Central

    Crawley, A C; Niedzielski, K H; Isaac, E L; Davey, R C; Byers, S; Hopwood, J J

    1997-01-01

    We report evidence of a dose responsive effect of enzyme replacement therapy in mucopolysaccharidosis type VI cats from birth, at the clinical, biochemical, and histopathological level. Cats treated with weekly, intravenous recombinant human N-acetylgalactosamine-4-sulfatase at 1 and 5 mg/kg, were heavier, more flexible, had greatly reduced or no spinal cord compression, and had almost normal urinary glycosaminoglycan levels. There was near normalization or complete reversal of lysosomal storage in heart valve, aorta, skin, dura, liver, and brain perivascular cells. No reduction in lysosomal vacuolation was observed in cartilage or cornea; however, articular cartilage was thinner and external ear pinnae were larger in some treated cats. Degenerative joint changes were not obviously delayed in treated cats. Skeletal pathology was reduced, with more normalized bone dimensions and with more uniform bone density and trabecular pattern clearly visible on radiographs by 5 to 6 mo; however, differences between 1 and 5 mg/kg dose rates were not clearly distinguishable. At a dose of 0.2 mg/kg, disease was not significantly altered in the majority of parameters examined. Lysosomal storage was present in all tissues examined in the midterm mucopolysaccharidosis type VI fetus and increased rapidly in extent and severity from birth. PMID:9045867

  5. Long-Term Wind Power Variability

    SciTech Connect

    Wan, Y. H.

    2012-01-01

    The National Renewable Energy Laboratory started collecting wind power data from large commercial wind power plants (WPPs) in southwest Minnesota with dedicated dataloggers and communication links in the spring of 2000. Over the years, additional WPPs in other areas were added to and removed from the data collection effort. The longest data stream of actual wind plant output is more than 10 years. The resulting data have been used to analyze wind power fluctuations, frequency distribution of changes, the effects of spatial diversity, and wind power ancillary services. This report uses the multi-year wind power data to examine long-term wind power variability.

  6. Transverse dimension and long-term stability.

    PubMed

    Vanarsdall, R L

    1999-09-01

    This article emphasizes the critical importance of the skeletal differential between the width of the maxilla and the width of the mandible. Undiagnosed transverse discrepancy leads to adverse periodontal response, unstable dental camouflage, and less than optimal dentofacial esthetics. Hundreds of adult retreatment patients corrected for significant maxillary transverse deficiency using surgically assisted maxillary expansion (similar to osseous distraction) has produced excellent stability. Eliciting tooth movement for children (orthopedics, lip bumper, Cetlin plate) in all three planes of space by muscles, eruption, and growth, develops the broader arch form (without the mechanical forces of fixed or removable appliances) and has also demonstrated impressive long term stability.

  7. Long-term management of prolactinomas.

    PubMed

    Schlechte, Janet A

    2007-08-01

    Prolactinomas are a frequent cause of gonadal dysfunction and infertility, especially in young women. The regulation of prolactin secretion and the efficacy of dopamine agonists in the therapy of prolactinomas are well established. The current challenges in management of prolactinomas are related to follow-up after successful therapy. Issues and questions to be addressed in this approach to long-term management of prolactinomas include the frequency of radiographic monitoring, effect of pregnancy and menopause, safety of estrogen in women taking oral contraceptives, and the potential for discontinuation of dopamine agonist therapy.

  8. Human Behaviour in Long-Term Missions

    NASA Technical Reports Server (NTRS)

    1997-01-01

    In this session, Session WP1, the discussion focuses on the following topics: Psychological Support for International Space Station Mission; Psycho-social Training for Man in Space; Study of the Physiological Adaptation of the Crew During A 135-Day Space Simulation; Interpersonal Relationships in Space Simulation, The Long-Term Bed Rest in Head-Down Tilt Position; Psychological Adaptation in Groups of Varying Sizes and Environments; Deviance Among Expeditioners, Defining the Off-Nominal Act in Space and Polar Field Analogs; Getting Effective Sleep in the Space-Station Environment; Human Sleep and Circadian Rhythms are Altered During Spaceflight; and Methodological Approach to Study of Cosmonauts Errors and Its Instrumental Support.

  9. Performance considerations in long-term spaceflight

    NASA Technical Reports Server (NTRS)

    Akins, F. R.

    1979-01-01

    Maintenance of skilled performance during extended space flight is of critical importance to both the health and safety of crew members and to the overall success of mission goals. An examination of long term effects and performance requirements is therefore a factor of immense importance to the planning of future missions. Factors that were investigated include: definition of performance categories to be investigated; methods for assessing and predicting performance levels; in-flight factors which can affect performance; and factors pertinent to the maintenance of skilled performance.

  10. Long term efficacy of a pen injector.

    PubMed

    Dinneen, S F; Cronin, C C; O'Sullivan, D J

    1991-09-01

    We assessed the long term efficacy of Novopen as a form of insulin administration. Records were obtained on 48 patients who were treated with Novopen between January '86 and October '88. Six patients were excluded due to insufficient data. The study group of 42 patients comprised 22 females and 20 males of average age 33 years (range 17-66). Mean Hb.A1 rose from 10.6% to 12.1% after Novopen therapy, a rise of 14.1%. This rise is both clinically and statistically significant (p less than 0.001; 99% confidence limits 0.59-2.78). Increases in weight and insulin dose were also noted, but did not reach statistical significance. The majority of patients felt Novopen was superior to twice daily insulin in terms of ease of administration (81%) and flexibility of lifestyle (95%), and all who were using Novopen wished to continue with it. More than 50% of patients admitted to altering their dietary habits while using Novopen. Despite continuing patient satisfaction with this form of insulin administration, its long-term use may be associated with sub-optimal metabolic control.

  11. Sleep facilitates long-term face adaptation.

    PubMed

    Ditye, Thomas; Javadi, Amir Homayoun; Carbon, Claus-Christian; Walsh, Vincent

    2013-10-22

    Adaptation is an automatic neural mechanism supporting the optimization of visual processing on the basis of previous experiences. While the short-term effects of adaptation on behaviour and physiology have been studied extensively, perceptual long-term changes associated with adaptation are still poorly understood. Here, we show that the integration of adaptation-dependent long-term shifts in neural function is facilitated by sleep. Perceptual shifts induced by adaptation to a distorted image of a famous person were larger in a group of participants who had slept (experiment 1) or merely napped for 90 min (experiment 2) during the interval between adaptation and test compared with controls who stayed awake. Participants' individual rapid eye movement sleep duration predicted the size of post-sleep behavioural adaptation effects. Our data suggest that sleep prevented decay of adaptation in a way that is qualitatively different from the effects of reduced visual interference known as 'storage'. In the light of the well-established link between sleep and memory consolidation, our findings link the perceptual mechanisms of sensory adaptation--which are usually not considered to play a relevant role in mnemonic processes--with learning and memory, and at the same time reveal a new function of sleep in cognition.

  12. Sleep facilitates long-term face adaptation

    PubMed Central

    Ditye, Thomas; Javadi, Amir Homayoun; Carbon, Claus-Christian; Walsh, Vincent

    2013-01-01

    Adaptation is an automatic neural mechanism supporting the optimization of visual processing on the basis of previous experiences. While the short-term effects of adaptation on behaviour and physiology have been studied extensively, perceptual long-term changes associated with adaptation are still poorly understood. Here, we show that the integration of adaptation-dependent long-term shifts in neural function is facilitated by sleep. Perceptual shifts induced by adaptation to a distorted image of a famous person were larger in a group of participants who had slept (experiment 1) or merely napped for 90 min (experiment 2) during the interval between adaptation and test compared with controls who stayed awake. Participants' individual rapid eye movement sleep duration predicted the size of post-sleep behavioural adaptation effects. Our data suggest that sleep prevented decay of adaptation in a way that is qualitatively different from the effects of reduced visual interference known as ‘storage’. In the light of the well-established link between sleep and memory consolidation, our findings link the perceptual mechanisms of sensory adaptation—which are usually not considered to play a relevant role in mnemonic processes—with learning and memory, and at the same time reveal a new function of sleep in cognition. PMID:23986109

  13. Climate Predictability and Long Term Memory

    NASA Astrophysics Data System (ADS)

    Zhu, X.; Blender, R.; Fraedrich, K.; Liu, Z.

    2010-09-01

    The benefit of climate Long Term Memory (LTM) for long term prediction is assessed using data from a millennium control simulation with the atmosphere ocean general circulation model ECHAM5/MPIOM. The forecast skills are evaluated for surface temperature time series at individual grid points. LTM is characterised by the Hurst exponent in the power-law scaling of the fluctuation function which is determined by detrended fluctuation analysis (DFA). LTM with a Hurst exponent close to 0.9 occurs mainly in high latitude oceans, which are also characterized by high potential predictability. Climate predictability is diagnosed in terms of potentially predictable variance fractions. Explicit prediction experiments for various time steps are conducted on a grid point basis using an auto-correlation (AR1) predictor: in regions with LTM, prediction skills are beyond that expected from red noise persistence; exceptions occur in some areas in the southern oceans and over the northern hemisphere continents. Extending the predictability analysis to the fully forced simulation shows large improvement in prediction skills.

  14. Craniopharyngioma in Children: Long-term Outcomes

    PubMed Central

    STEINBOK, Paul

    2015-01-01

    The survival rate for childhood craniopharyngioma has been improving, with more long-term survivors. Unfortunately it is rare for the patient to be normal, either from the disease itself or from the effects of treatment. Long-term survivors of childhood craniopharyngioma suffer a number of impairments, which include visual loss, endocrinopathy, hypothalamic dysfunction, cerebrovascular problems, neurologic and neurocognitive dysfunction. Pituitary insufficiency is present in almost 100%. Visual and hypothalamic dysfunction is common. There is a high risk of metabolic syndrome and increased risk of cerebrovascular disease, including stroke and Moyamoya syndrome. Cognitive, psychosocial, and emotional problems are prevalent. Finally, there is a higher risk of premature death among survivors of craniopharyngioma, and often this is not from tumor recurrence. It is important to consider craniopharyngioma as a chronic disease. There is no perfect treatment. The treatment has to be tailored to the individual patient to minimize dysfunction caused by tumor and treatments. So “cure” of the tumor does not mean a normal patient. The management of the patient and family needs multidisciplinary evaluation and should involve ophthalmology, endocrinology, neurosurgery, oncology, and psychology. Furthermore, it is also important to address emotional issues and social integration. PMID:26345668

  15. Long-Term Care Policy: Singapore's Experience.

    PubMed

    Chin, Chee Wei Winston; Phua, Kai-Hong

    2016-01-01

    Singapore, like many developed countries, is facing the challenge of a rapidly aging population and the increasing need to provide long-term care (LTC) services for elderly in the community. The Singapore government's philosophy on care for the elderly is that the family should be the first line of support, and it has relied on voluntary welfare organizations (VWOs) or charities for the bulk of LTC service provision. For LTC financing, it has emphasized the principles of co-payment and targeting of state support to the low-income population through means-tested government subsidies. It has also instituted ElderShield, a national severe disability insurance scheme. This paper discusses some of the challenges facing LTC policy in Singapore, particularly the presence of perverse financial incentives for hospitalization, the pitfalls of over-reliance on VWOs, and the challenges facing informal family caregivers. It discusses the role of private LTC insurance in LTC financing, bearing in mind demand- and supply-side failures that have plagued the private LTC insurance market. It suggests the need for more standardized needs assessment and portable LTC benefits, with reference to the Japanese Long-Term Care Insurance program, and also discusses the need to provide more support to informal family caregivers.

  16. Long term perfusion system supporting adipogenesis

    PubMed Central

    Abbott, Rosalyn D.; Raja, Waseem K.; Wang, Rebecca Y.; Stinson, Jordan A.; Glettig, Dean L.; Burke, Kelly A.; Kaplan, David L.

    2015-01-01

    Adipose tissue engineered models are needed to enhance our understanding of disease mechanisms and for soft tissue regenerative strategies. Perfusion systems generate more physiologically relevant and sustainable adipose tissue models, however adipocytes have unique properties that make culturing them in a perfusion environment challenging. In this paper we describe the methods involved in the development of two perfusion culture systems (2D and 3D) to test their applicability for long term in vitro adipogenic cultures. It was hypothesized that a silk protein biomaterial scaffold would provide a 3D framework, in combination with perfusion flow, to generate a more physiologically relevant sustainable adipose tissue engineered model than 2D cell culture. Consistent with other studies evaluating 2D and 3D culture systems for adipogenesis we found that both systems successfully model adipogensis, however 3D culture systems were more robust, providing the mechanical structure required to contain the large, fragile adipocytes that were lost in 2D perfused culture systems. 3D perfusion also stimulated greater lipogenesis and lipolysis and resulted in decreased secretion of LDH compared to 2D perfusion. Regardless of culture configuration (2D or 3D) greater glycerol was secreted with the increased nutritional supply provided by perfusion of fresh media. These results are promising for adipose tissue engineering applications including long term cultures for studying disease mechanisms and regenerative approaches, where both acute (days to weeks) and chronic (weeks to months) cultivation are critical for useful insight. PMID:25843606

  17. Long-term experience with indapamide.

    PubMed

    Beling, S; Vukovich, R A; Neiss, E S; Zisblatt, M; Webb, E; Losi, M

    1983-07-01

    Indapamide, 2.5 mg administered once daily for periods up to 36 months, was found to be safe and effective for the long-term control of mild to moderate hypertension. The effects of hydrochlorothiazide, 50 mg, and indapamide, 2.5 mg, were studied in two randomized, double-blind, multicenter trials. Data from the two multicenter trials (20 study sites) were pooled for purposes of comparison. Significant reductions in systolic and diastolic blood pressure, with patients in both supine and standing positions, occurred in both groups within the first 8 weeks of treatment. This effect was maintained throughout the active treatment period. Success, as determined by the therapeutic success rate (percentage of patients with decreases of standing phase V diastolic blood pressure of at least 10 mm Hg or to below 90 mm Hg), occurred in 53% of the patients given hydrochlorothiazide and in 56% of the indapamide-treated patients. During the study period, the nature, frequency, and severity of adverse reactions were similar for both groups. There was no clinically significant difference between the treatment groups for the laboratory assessments. Patients who completed the multicenter trials were eligible for participation in an ongoing long-term extension study of the safety of indapamide. Data are available for periods up to 36 months and demonstrate neither augmentation of clinical or laboratory adverse effects nor any potentially harmful indicators that could be attributed to prolonged treatment.

  18. Clinical review: Long-term noninvasive ventilation

    PubMed Central

    Robert, Dominique; Argaud, Laurent

    2007-01-01

    Noninvasive positive ventilation has undergone a remarkable evolution over the past decades and is assuming an important role in the management of both acute and chronic respiratory failure. Long-term ventilatory support should be considered a standard of care to treat selected patients following an intensive care unit (ICU) stay. In this setting, appropriate use of noninvasive ventilation can be expected to improve patient outcomes, reduce ICU admission, enhance patient comfort, and increase the efficiency of health care resource utilization. Current literature indicates that noninvasive ventilation improves and stabilizes the clinical course of many patients with chronic ventilatory failure. Noninvasive ventilation also permits long-term mechanical ventilation to be an acceptable option for patients who otherwise would not have been treated if tracheostomy were the only alternative. Nevertheless, these results appear to be better in patients with neuromuscular/-parietal disorders than in chronic obstructive pulmonary disease. This clinical review will address the use of noninvasive ventilation (not including continuous positive airway pressure) mainly in diseases responsible for chronic hypoventilation (that is, restrictive disorders, including neuromuscular disease and lung disease) and incidentally in others such as obstructive sleep apnea or problems of central drive. PMID:17419882

  19. Long term changes in the polar vortices

    NASA Astrophysics Data System (ADS)

    Braathen, Geir O.

    2015-04-01

    As the amount of halogens in the stratosphere is slowly declining and the ozone layer slowly recovers it is of interest to see how the meteorological conditions in the vortex develop over the long term since such changes might alter the foreseen ozone recovery. In conjunction with the publication of the WMO Antarctic and Arctic Ozone Bulletins, WMO has acquired the ERA Interim global reanalysis data set for several meteorological parameters. This data set goes from 1979 - present. These long time series of data can be used for several useful studies of the long term development of the polar vortices. Several "environmental indicators" for vortex change have been calculated, and a climatology, as well as trends, for these parameters will be presented. These indicators can act as yardsticks and will be useful for understanding past and future changes in the polar vortices and how these changes affect polar ozone depletion. Examples of indicators are: vortex mean temperature, vortex minimum temperature, vortex mean PV, vortex "importance" (PV*area), vortex break-up time, mean and maximum wind speed. Data for both the north and south polar vortices have been analysed at several isentropic levels from 350 to 850 K. A possible link between changes in PV and sudden stratospheric warmings will be investigated, and the results presented.

  20. Long Term Changes in the Polar Vortices

    NASA Astrophysics Data System (ADS)

    Braathen, Geir O.

    2016-04-01

    As the amount of halogens in the stratosphere is slowly declining and the ozone layer slowly recovers it is of interest to see how the meteorological conditions in the vortex develop over the long term since such changes might alter the foreseen ozone recovery. In conjunction with the publication of the WMO Antarctic and Arctic Ozone Bulletins, WMO has acquired the ERA Interim global reanalysis data set for several meteorological parameters. This data set goes from 1979 - present. These long time series of data can be used for several useful studies of the long term development of the polar vortices. Several "environmental indicators" for vortex change have been calculated, and a climatology, as well as trends, for these parameters will be presented. These indicators can act as yardsticks and will be useful for understanding past and future changes in the polar vortices and how these changes affect polar ozone depletion. Examples of indicators are: vortex mean temperature, vortex minimum temperature, vortex mean PV, vortex "importance" (PV*area), vortex break-up time, mean and maximum wind speed. Data for both the north and south polar vortices have been analysed at several isentropic levels from 350 to 850 K. A possible link between changes in PV and sudden stratospheric warmings will be investigated, and the results presented. The unusual meteorological conditions of the 2015 south polar vortex and the 2010/11 and 2015/16 north polar vortices will be compared to other recent years.

  1. Long term effects of Escherichia coli mastitis.

    PubMed

    Blum, Shlomo E; Heller, Elimelech D; Leitner, Gabriel

    2014-07-01

    Escherichia coli is one of the most frequently diagnosed causes of bovine mastitis, and is typically associated with acute, clinical mastitis. The objective of the present study was to evaluate the long term effects of intramammary infections by E. coli on milk yield and quality, especially milk coagulation. Twenty-four Israeli Holstein cows diagnosed with clinical mastitis due to intramammary infection by E. coli were used in this study. Mean lactation number, days in milk (DIM) and daily milk yield (DMY) at the time of infection was 3.3 ± 1.3, 131.7 days ± 78.6 and 45.7 L ± 8.4, respectively. DMY, milk constituents, somatic cells count (SCC), differential leukocytes count and coagulation parameters were subsequently assessed. Two patterns of inflammation were identified: 'short inflammation', characterized by <15% decrease in DMY and <30 days until return to normal (n = 5), and 'long inflammation', characterized by >15% decrease in DMY and >30 days to reach a new maximum DMY (n = 19). The estimated mean loss of marketable milk during the study was 200 L/cow for 'short inflammation' cases, and 1,500 L/cow for 'long inflammation' ones. Significant differences between 'short' and 'long inflammation' effects were found in almost all parameters studied. Long-term detrimental effects on milk quality were found regardless of clinical or bacteriological cure of affected glands.

  2. [Bone and joint problems in long-term dialysis].

    PubMed

    Brunner, F P

    1992-05-09

    Bone and joint pathology in patients undergoing long-term dialysis for end-stage renal failure is presented in the light of typical cases and a brief review of the literature. Osteomalacia with bone pain and fractures is caused mainly by aluminium overload due to enteral uptake from aluminium-containing phosphate binders. This is why calcium acetate or calcium carbonate should be used exclusively to lower enteral phosphate reabsorption. If--due to hypercalcemia--aluminium containing phosphate binders--cannot be entirely avoided, they should never be administered together with citrate (citrate-containing medication, fruit juice, etc.), which chelates aluminium and thereby massively increases enteral aluminium uptake. Secondary hyperparathyroidism with overt radiologically demonstrable bone disease develops in many patients on long-term dialysis despite efforts to maintain plasma calcium within or slightly above the upper normal range and concomitant treatment with calcitriol. Intravenous administration of relatively high-dose calcitriol or 1-alpha-OH-D3 (neither readily available at the present time), as well as the newly developed experimental vitamin D analogs such as 22-oxa-(OH)2-D3, which appear to suppress the parathyroid glands without increasing enteral calcium reabsorption, may in future reduce the high incidence of parathyroidectomy in patients on maintenance dialysis. beta 2-microglobulin amyloidosis is a new disease entity which develops in the majority of long-term dialysis patients. Apart from carpal tunnel syndrome, trigger fingers and tendon ruptures, it is associated with acute and chronic painful erosive arthropathy with joint effusions and fractures, particularly around the hip, due to cystic bone lesions where bone is replaced by nodular amyloid deposits.(ABSTRACT TRUNCATED AT 250 WORDS)

  3. Adjunctive albuterol enhances the response to enzyme replacement therapy in late-onset Pompe disease.

    PubMed

    Koeberl, Dwight D; Austin, Stephanie; Case, Laura E; Smith, Edward C; Buckley, Anne F; Young, Sarah P; Bali, Deeksha; Kishnani, Priya S

    2014-05-01

    Effective dosages for enzyme replacement therapy (ERT) in Pompe disease are much higher than for other lysosomal storage disorders, which has been attributed to low cation-independent mannose-6-phosphate receptor (CI-MPR) in skeletal muscle. We have previously demonstrated the benefit of increased CI-MPR-mediated uptake of recombinant human acid-α-glucosidase during ERT in mice with Pompe disease following addition of albuterol therapy. Currently we have completed a pilot study of albuterol in patients with late-onset Pompe disease already on ERT for >2 yr, who were not improving further. The 6-min walk test (6MWT) distance increased in all 7 subjects at wk 6 (30±13 m; P=0.002), wk 12 (34±14 m; P=0.004), and wk 24 (42±37 m; P=0.02), in comparison with baseline. Grip strength was improved significantly for both hands at wk 12. Furthermore, individual subjects reported benefits; e.g., a female patient could stand up from sitting on the floor much more easily (time for supine to standing position decreased from 30 to 11 s), and a male patient could readily swing his legs out of his van seat (hip abduction increased from 1 to 2+ on manual muscle testing). Finally, analysis of the quadriceps biopsies suggested increased CI-MPR at wk 12 (P=0.08), compared with baseline. With the exception of 1 patient who succumbed to respiratory complications of Pompe disease in the first week, only mild adverse events have been reported, including tremor, transient difficulty falling asleep, and mild urinary retention (requiring early morning voiding). Therefore, this pilot study revealed initial safety and efficacy in an open label study of adjunctive albuterol therapy in patients with late-onset Pompe disease who had been stable on ERT with no improvements noted over the previous several years.

  4. Enzyme Replacement Therapy in Mucopolysaccharidosis II Patients Under 1 Year of Age.

    PubMed

    Lampe, Christina; Atherton, Andrea; Burton, Barbara K; Descartes, Maria; Giugliani, Roberto; Horovitz, Dafne D G; Kyosen, Sandra O; Magalhães, Tatiana S P C; Martins, Ana Maria; Mendelsohn, Nancy J; Muenzer, Joseph; Smith, Laurie D

    2014-01-01

    Mucopolysaccharidosis (MPS) II, or Hunter syndrome, is a lysosomal storage disease characterized by multi-systemic involvement and a progressive clinical course. Enzyme replacement therapy with idursulfase has been approved in more than 50 countries worldwide; however, safety and efficacy data from clinical studies are currently only available for patients 1.4 years of age and older. Sibling case studies of infants with MPS I, II, and VI who initiated ERT in the first weeks or months of life have reported no new safety concerns and a more favorable clinical course for the sibling treated in infancy than for the later-treated sibling. Here we describe our experiences with a case series of eight MPS II patients for whom idursulfase treatment was initiated at under 1 year of age. The majority of the patients were diagnosed because of a family history of disease. All of the infants displayed abnormalities consistent with MPS II at diagnosis. The youngest age at treatment start was 10 days and the oldest was 6.5 months, with duration of treatment varying between 6 weeks and 5.5 years. No new safety concerns were observed, and none of the patients experienced an infusion-related reaction. All of the patients treated for more than 6 weeks showed improvements and/or stabilization of some somatic manifestations while on treatment. In some cases, caregivers made comparisons with other affected family members and reported that the early-treated patients experienced a less severe clinical course, although a lack of medical records for many family members precluded a rigorous comparison.

  5. Managing soils for long-term productivity

    PubMed Central

    Syers, J. K.

    1997-01-01

    Meeting the goal of long-term agricultural productivity requires that soil degradation be halted and reversed. Soil fertility decline is a key factor in soil degradation and is probably the major cause of declining crop yields. There is evidence that the contribution of declining soil fertility to soil degradation has been underestimated.
    Sensitivity to soil degradation is implicit in the assessment of the sustainability of land management practices, with wide recognition of the fact that soils vary in their ability to resist change and recover subsequent to stress. The concept of resilience in relation to sustainability requires further elaboration and evaluation.
    In the context of soil degradation, a decline in soil fertility is primarily interpreted as the depletion of organic matter and plant nutrients. Despite a higher turnover rate of organic matter in the tropics there is no intrinsic difference between the organic matter content of soils from tropical and temperate regions. The level of organic matter in a soil is closely related to the above and below ground inputs. In the absence of adequate organic material inputs and where cultivation is continuous, soil organic matter declines progressively. Maintaining the quantity and quality of soil organic matter should be a guiding principle in developing management practices.
    Soil microbial biomass serves as an important reservoir of nitrogen (N), phosphorus (P) and sulphur (S), and regulates the cycling of organic matter and nutrients. Because of its high turnover rate, microbial biomass reacts quickly to changes in management and is a sensitive indicator for monitoring and predicting changes in soil organic matter. Modelling techniques have been reasonably successful in predicting changes in soil organic matter with different organic material inputs, but there is little information from the tropics.
    Nutrient depletion through harvested crop components and residue removal, and by leaching and soil

  6. Long-term non-invasive ventilation in children.

    PubMed

    Amaddeo, Alessandro; Frapin, Annick; Fauroux, Brigitte

    2016-12-01

    Use of long-term non-invasive ventilation is increasing exponentially worldwide in children of all ages. The treatment entails delivery of ventilatory assistance through a non-invasive interface. Indications for use of non-invasive ventilation include conditions that affect normal respiratory balance (eg, those associated with dysfunction of the central drive or respiratory muscles) and disorders characterised by an increase in respiratory load (eg, obstructive airway or lung diseases). The type of non-invasive ventilation used depends on the pathophysiological features of the respiratory failure. For example, non-invasive ventilation will need to either replace central drive if the disorder is characterised by an abnormal central drive or substitute for the respiratory muscles if the condition is associated with respiratory muscle weakness. Non-invasive ventilation might also need to unload the respiratory muscles in case of an increase in respiratory load, as seen in upper airway obstruction and some lung diseases. Technical aspects are also important when choosing non-invasive ventilation-eg, appropriate interface and device. The great heterogeneity of disorders, age ranges of affected children, prognoses, and outcomes of patients needing long-term non-invasive ventilation underline the need for management by skilled multidisciplinary centres with technical competence in paediatric non-invasive ventilation and expertise in sleep studies and therapeutic education.

  7. Technology for long-term care.

    PubMed

    Tak, Sunghee H; Benefield, Lazelle E; Mahoney, Diane Feeney

    2010-01-01

    Severe staff shortages in long-term care (LTC) make it difficult to meet the demands of the growing aging population. Further, technology-savvy Baby Boomers are expected to reshape the current institutional environments toward gaining more freedom and control in their care and lives. Voices from business, academia, research, advocacy organizations, and government bodies suggest that innovative technological approaches are the linchpin that may prepare society to cope with these projected demands. In this article, we review the current state of aging-related technology, identify potential areas for efficacy testing on improving the quality of life of LTC residents in future research, and discuss barriers to implementation of LTC technology. Finally, we present a vision of future technology use that could transform current care practices.

  8. Long term performance of radon mitigation systems

    SciTech Connect

    Prill, R.; Fisk, W.J.

    2002-03-01

    Researchers installed radon mitigation systems in 12 houses in Spokane, Washington and Coeur d'Alene, Idaho during the heating season 1985--1986 and continued to monitor indoor radon quarterly and annually for ten years. The mitigation systems included active sub-slab ventilation, basement over-pressurization, and crawlspace isolation and ventilation. The occupants reported various operational problems with these early mitigation systems. The long-term radon measurements were essential to track the effectiveness of the mitigation systems over time. All 12 homes were visited during the second year of the study, while a second set 5 homes was visited during the fifth year to determine the cause(s) of increased radon in the homes. During these visits, the mitigation systems were inspected and measurements of system performance were made. Maintenance and modifications were performed to improve system performance in these homes.

  9. Long-term U. S. energy outlook

    SciTech Connect

    Friesen, G.

    1984-01-01

    Each year Chase Econometrics offers its clients a brief summary of the assumptions underlying the long-term energy forecast for the U.S. To illustrate the uncertainty involved in forecasting for the period to the year 2000, they choose to compare forecasts with some recent projections prepared by the Department of Energy's Office of Policy, Planning and Analysis for the annual National Energy Policy Plan supplement. Particular emphasis is placed on Scenario B, which is the mid-range reference case. As the introduction to the supplement emphasizes, the NEPP projections should not be considered a statement of the policy goals of the Reagan Administration. They represent an analysis of the possible evolution of U.S. energy markets, given current information and existing policies. The purpose of providing Scenario B as a reference case as well as Scenarios A and C as alternate cases is to show the sensitivity of oil price projections to small swings in energy demand.

  10. Withdrawal from long-term benzodiazepine treatment.

    PubMed Central

    Petursson, H; Lader, M H

    1981-01-01

    Long-term, normal-dose benzodiazepine treatment was discontinued in 16 patients who were suspected of being dependent on their medication. The withdrawal was gradual, placebo-controlled, and double-blind. All the patients experienced some form of withdrawal reaction, which ranged from anxiety and dysphoria to moderate affective and perceptual changes. Symptom ratings rose as the drugs were discontinued, but usually subsided to prewithdrawal levels over the next two to four weeks. Other features of the withdrawal included disturbance of sleep and appetite and noticeable weight loss. Electroencephalography showed appreciable reduction in fast-wave activity as the drugs were withdrawn, and an improvement in psychological performance was recorded by the Digit Symbol Substitution Test. Because of the risk of dependence on benzodiazepines these agents should probably not be given as regular daily treatment for chronic anxiety. PMID:6114776

  11. Long-term control of root growth

    DOEpatents

    Burton, Frederick G.; Cataldo, Dominic A.; Cline, John F.; Skiens, W. Eugene

    1992-05-26

    A method and system for long-term control of root growth without killing the plants bearing those roots involves incorporating a 2,6-dinitroaniline in a polymer and disposing the polymer in an area in which root control is desired. This results in controlled release of the substituted aniline herbicide over a period of many years. Herbicides of this class have the property of preventing root elongation without translocating into other parts of the plant. The herbicide may be encapsulated in the polymer or mixed with it. The polymer-herbicide mixture may be formed into pellets, sheets, pipe gaskets, pipes for carrying water, or various other forms. The invention may be applied to other protection of buried hazardous wastes, protection of underground pipes, prevention of root intrusion beneath slabs, the dwarfing of trees or shrubs and other applications. The preferred herbicide is 4-difluoromethyl-N,N-dipropyl-2,6-dinitro-aniline, commonly known as trifluralin.

  12. [Childhood liver transplantation. Long-term results].

    PubMed

    Jara, Paloma; Hierro, Loreto

    2010-05-01

    Liver transplantation allows long-term survival (10 years or more) in 75% of children receiving transplants before 2000. The risk of mortality after the first year is 4-10% in the next 10-20 years. Chronic rejection affects 6%. The need for late retransplantation is 3-5%. However, the follow-up of these patients involves the management of diverse problems in the graft (immunological, biliary, vascular) and others related to the use of immunosuppressants (renal dysfunction, lymphoproliferative syndrome). The transition from pediatric to adult care generates special needs. Adolescence and young adulthood are associated with a lack of compliance. Adult specialists should be aware of the special features of the original diagnosis and the surgical techniques used in childhood transplantation. Final quality of life is good overall but is lower than that in healthy young persons.

  13. Advanced long term cryogenic storage systems

    NASA Technical Reports Server (NTRS)

    Brown, Norman S.

    1987-01-01

    Long term, cryogenic fluid storage facilities will be required to support future space programs such as the space-based Orbital Transfer Vehicle (OTV), Telescopes, and Laser Systems. An orbital liquid oxygen/liquid hydrogen storage system with an initial capacity of approximately 200,000 lb will be required. The storage facility tank design must have the capability of fluid acquisition in microgravity and limit cryogen boiloff due to environmental heating. Cryogenic boiloff management features, minimizing Earth-to-orbit transportation costs, will include advanced thick multilayer insulation/integrated vapor cooled shield concepts, low conductance support structures, and refrigeration/reliquefaction systems. Contracted study efforts are under way to develop storage system designs, technology plans, test article hardware designs, and develop plans for ground/flight testing.

  14. [Enteral nutrition through long-term jejunostomy].

    PubMed

    Fernández, T; Neira, P; Enríquez, C

    2008-01-01

    We present the case of a female patient suffering a peritonitis episode after subtotal gastrectomy due to gastric neoplasm in relation to lesser curvature necrosis extending to the anterior esophageal wall. This an uncommon andsevere complication that made mandatory further aggressive surgery: transection of the abdominal esophagus, transection of the gastric stump, and cervical esophagostomy with creation of a jejunostomy with a needle catheter for feeding. This digestive tube access technique is generally used during major abdominal post-surgery until oral intake is reestablished. Our patient has been 187 days with this therapy since reconstruction of the GI tract was ruled out due to tumoral infiltration of the colon and tumor recurrence at the gastrohepatic omentum. To date, there has been no complication from permanence and/or long-term use of this technique.

  15. Reducing long-term reservoir performance uncertainty

    SciTech Connect

    Lippmann, M.J.

    1988-04-01

    Reservoir performance is one of the key issues that have to be addressed before going ahead with the development of a geothermal field. In order to select the type and size of the power plant and design other surface installations, it is necessary to know the characteristics of the production wells and of the produced fluids, and to predict the changes over a 10--30 year period. This is not a straightforward task, as in most cases the calculations have to be made on the basis of data collected before significant fluid volumes have been extracted from the reservoir. The paper describes the methodology used in predicting the long-term performance of hydrothermal systems, as well as DOE/GTD-sponsored research aimed at reducing the uncertainties associated with these predictions. 27 refs., 1 fig.

  16. Long-term monitoring for closed sites

    SciTech Connect

    Golchert, N.W.; Sedlet, J.; Veluri, V.R.

    1985-01-01

    A procedure is presented for planning and implementing a long-term environmental monitoring program for closed low-level radioactive waste disposal sites. The initial task in this procedure is to collect the available information on the legal/regulatory requirements, site and area characteristics, source term, pathway analysis, and prior monitoring results. This information is coupled with parameters such as half-life and retardation factors to develop a monitoring program. As examples, programs are presented for a site that has had little or no waste migration, and for sites where waste has been moved by suface water, by ground water, and by air. Sampling techniques and practices are discussed relative to how a current program would be structured and projections are made on techniques and practices expected to be available in the future. 8 refs., 2 figs.

  17. Neurotoxicity testing during long-term studies.

    PubMed

    Ivens, I

    1990-01-01

    Several tests and methods for the investigation of neurotoxicity were performed with female Wistar rats for up to 187 days. The methods were validated by testing 10 rats treated with beta,beta'-iminodipropionitrile (IDPN) and 10 control rats. Cage side observation of the animals revealed signs of altered behavior and motor dysfunction of the IDPN-treated rats. Results of a neuromuscular screen indicated changes in gait, righting reflex, grip strength and performance of the negative geotropism test. Investigation of the animals in activity monitors and on the accelerating rotarod showed changes of several parameters. The motor nerve conduction velocity, measured 6 months after the first treatment, was reduced by 6.7 meters per second in the IDPN group compared to controls. From the results of the tests it can be concluded that the methods chosen can be used during long-term studies but may be most useful for animals not older than 12 months.

  18. Long term cryogenic storage facility systems study

    NASA Technical Reports Server (NTRS)

    Schuster, John R.

    1987-01-01

    The Long Term Cryogenic Storage Facility Systems Study (LTCSFSS) is a Phase A study of a large capacity propellant depot for the space based, cryogenic orbital transfer vehicle. The study is being performed for Marshall Space Flight Center by General Dynamics Space Systems Division and has five principal objectives: (1) Definition of preliminary concept designs for four storage facility concepts; (2) Selection of preferred concepts through the application of trade studies to candidate propellant management system components; (3) Preparation of a conceptual design for an orbital storage facility; (4) Development of supporting research and technology requirements; and (5) Development of a test program to demonstrate facility performance. The initial study has been completed, and continuation activities are just getting under way to provide greater detail in key areas and accommodate changes in study guidelines and assumptions.

  19. Managing Records for the Long Term - 12363

    SciTech Connect

    Montgomery, John V.; Gueretta, Jeanie

    2012-07-01

    The U.S. Department of Energy (DOE) is responsible for managing vast amounts of information documenting historical and current operations. This information is critical to the operations of the DOE Office of Legacy Management. Managing legacy records and information is challenging in terms of accessibility and changing technology. The Office of Legacy Management is meeting these challenges by making records and information management an organizational priority. The Office of Legacy Management mission is to manage DOE post-closure responsibilities at former Cold War weapons sites to ensure the future protection of human health and the environment. These responsibilities include environmental stewardship and long-term preservation and management of operational and environmental cleanup records associated with each site. A primary organizational goal for the Office of Legacy Management is to 'Preserve, Protect, and Share Records and Information'. Managing records for long-term preservation is an important responsibility. Adequate and dedicated resources and management support are required to perform this responsibility successfully. Records tell the story of an organization and may be required to defend an organization in court, provide historical information, identify lessons learned, or provide valuable information for researchers. Loss of records or the inability to retrieve records because of poor records management processes can have serious consequences and even lead to an organisation's downfall. Organizations must invest time and resources to establish a good records management program because of its significance to the organization as a whole. The Office of Legacy Management will continue to research and apply innovative ways of doing business to ensure that the organization stays at the forefront of effective records and information management. DOE is committed to preserving records that document our nation's Cold War legacy, and the Office of Legacy

  20. Posterior urethral valves: long-term outcome.

    PubMed

    Caione, Paolo; Nappo, Simona Gerocarni

    2011-10-01

    Posterior urethral valves represent the most common cause of bladder outlet obstruction in infancy that impairs renal and bladder function. Long-term outcome of patients with previous PUV is evaluated. Patients over 18 years of age, treated from 1982 to 1995 before the age of 3 years were considered. Previous surgery, renal function, bladder activity, urinary incontinence, and fertility/sexual activity were evaluated. Clinical interview, creatinine clearance, uroflowmetry with ultrasound post-void urine residue, and self-administered questionnaire were recorded. Out of 45 identified records, 24 patients (53.3%) accepted to be enrolled (age 18-34 years, mean 23 years). The mean follow-up was 19.5 years (16-30 years). Out of the 21 excluded patients, 20 did not reply to the clinical interview and 1 died at age of 6 years. All the 24 patients had early endoscopic section of PUV; nine also received transient ureterocutaneostomy or vesicostomy. Ureteroneocystostomy was performed in five patients and ureterocystoplasty with unilateral nephrectomy in two. At follow-up chronic renal failure was detected in 13 patients (54.1%) and 9 (37.5%) had arterial hypertension. End-stage renal disease developed in five patients (20.8%): three had successful renal transplantation and two were in dialysis. Lower urinary tract symptoms were present in seven patients (29.1%). No significant fertility deficit and sexual dysfunction were observed in 23 patients, while 1 patient was azoospermic. No paternity was reported so far. Long-term outcome of patients with previously treated PUV is mandatory. Kidney, bladder, and sexual functions should be monitored till adulthood to verify any modified behaviour.

  1. Long-term dynamics of Typha populations

    USGS Publications Warehouse

    Grace, J.B.; Wetzel, R.G.

    1998-01-01

    The zonation of Typha populations in an experimental pond in Michigan was re-examined 15 years after the original sampling to gain insight into the long-term dynamics. Current distributions of Typha populations were also examined in additional experimental ponds at the site that have been maintained for 23 years. The zonation between T. latifolia and T. angustifolia in the previously studied pond 15 years after the initial sampling revealed that the density and distribution of shoots had not changed significantly. Thus, it appears that previously reported results (based on 7- year old populations) have remained consistent over time. Additional insight into the interaction between these two taxa was sought by comparing mixed and monoculture stands in five experimental ponds that have remained undisturbed for their 23-year history. The maximum depth of T. latifolia, the shallow- water species, was not significantly reduced when growing in the presence of the more flood tolerant T. angustifolia. In contrast, the minimum depth of T. angustifolia was reduced from 0 to 37 cm when in the presence of T. latifolia. When total populations were compared between monoculture and mixed stands, the average density of T. angustifolia shoots was 59.4 percent lower in mixed stands while the density of T. latifolia was 32 percent lower, with T. angustifolia most affected at shallow depths (reduced by 92 percent) and T. latifolia most affected at the deepest depths (reduced by 60 percent). These long-term observations indicate that competitive displacement between Typha taxa has remained stable over time.

  2. Long-term exposure to Myozyme results in a decrease of anti-drug antibodies in late-onset Pompe disease patients

    PubMed Central

    Masat, Elisa; Laforêt, Pascal; De Antonio, Marie; Corre, Guillaume; Perniconi, Barbara; Taouagh, Nadjib; Mariampillai, Kuberaka; Amelin, Damien; Mauhin, Wladimir; Hogrel, Jean-Yves; Caillaud, Catherine; Ronzitti, Giuseppe; Puzzo, Francesco; Kuranda, Klaudia; Colella, Pasqualina; Mallone, Roberto; Benveniste, Olivier; Mingozzi, Federico; Bassez, G.; Bedat-Millet, A. L.; Behin, A.; Eymard, B.; Leonard-Louis, S.; Stojkovic, T.; Canal, A.; Decostre, V.; Bouhour, F.; Boyer, F.; Castaing, Y.; Chapon, F.; Cintas, P.; Durieu, I.; Echaniz-Laguna, A.; Feasson, L.; Furby, A.; Hamroun, D.; Ferrer, X.; Solé, G.; Froissart, R.; Piraud, M.; Germain, D.; Benistan, K.; Guffon-Fouilhoux, N.; Journel, H.; Labauge, P.; Lacour, A.; Levy, A.; Magot, A.; Péréon, Y.; Minot-Myhié, M. -C.; Nadaj-Pakleza, A.; Nathier, C.; Orlikowski, D.; Pellegrini, N.; Petiot, P.; Praline, J.; Lofaso, F.; Prigent, H.; Dutry, A.; Renard, D.; Sacconi, S.; Desnuelle, C.; Salort-Campana, E.; Pouget, J.; Tiffreau, V.; Vincent, D.; Zagnoli, F.

    2016-01-01

    Immunogenicity of recombinant human acid-alpha glucosidase (rhGAA) in enzyme replacement therapy (ERT) is a safety and efficacy concern in the management of late-onset Pompe disease (LOPD). However, long-term effects of ERT on humoral and cellular responses to rhGAA are still poorly understood. To better understand the impact of immunogenicity of rhGAA on the efficacy of ERT, clinical data and blood samples from LOPD patients undergoing ERT for >4 years (n = 28) or untreated (n = 10) were collected and analyzed. In treated LOPD patients, anti-rhGAA antibodies peaked within the first 1000 days of ERT, while long-term exposure to rhGAA resulted in clearance of antibodies with residual production of non-neutralizing IgG. Analysis of  T cell responses to rhGAA showed detectable T cell reactivity only after in vitro restimulation. Upregulation of several cytokines and chemokines was detectable in both treated and untreated LOPD subjects, while IL2 secretion was detectable only in subjects who received ERT. These results indicate that long-term ERT in LOPD patients results in a decrease in antibody titers and residual production of non-inhibitory IgGs. Immune responses to GAA following long-term ERT do not seem to affect efficacy of ERT and are consistent with an immunomodulatory effect possibly mediated by regulatory T cells. PMID:27812025

  3. A replaceable dual-enzyme capillary microreactor using magnetic beads and its application for simultaneous detection of acetaldehyde and pyruvate.

    PubMed

    Shi, Jing; Zhao, Wenwen; Chen, Yuanfang; Guo, Liping; Yang, Li

    2012-07-01

    A novel replaceable dual-enzyme capillary microreactor was developed and evaluated using magnetic fields to immobilize the alcohol dehydrogenase (ADH)- and lactate dehydrogenase (LDH)-coated magnetic beads at desired positions in the capillary. The dual-enzyme assay was achieved by measuring the two consumption peaks of the coenzyme β-nicotinamide adenine dinucleotide (NADH), which were related to the ADH reaction and LDH reaction. The dual-enzyme capillary microreactor was constructed using magnetic beads without any modification of the inner surface of the capillary, and showed great stability and reproducibility. The electrophoretic resolution for different analytes can be easily controlled by altering the relative distance of different enzyme-coated magnetic beads. The apparent K(m) values for acetaldehyde with ADH-catalyzed reaction and for pyruvate with LDH-catalyzed reaction were determined. The detection limits for acetaldehyde and pyruvate determination are 0.01 and 0.016 mM (S/N = 3), respectively. The proposed method was successfully applied to simultaneously determine the acetaldehyde and pyruvate contents in beer samples. The results indicated that combing magnetic beads with CE is of great value to perform replaceable and controllable multienzyme capillary microreactor for investigation of a series of enzyme reactions and determination of multisubstrates.

  4. Hip Replacement

    MedlinePlus

    ... cemented and uncemented prostheses are comparable. However, more long-term data are available in the United States for hip replacements with cemented prostheses, because doctors have been using them ... period. Because it takes a long time for the natural bone to grow and ...

  5. Cost-effectiveness of enzyme replacement therapy for type 1 Gaucher disease

    PubMed Central

    2014-01-01

    Objective To evaluate the cost-effectiveness of enzyme replacement therapy (ERT) compared to standard medical care without ERT in the Dutch cohort of patients with type 1 Gaucher disease (GD I). Design Cost-effectiveness analysis was performed using a life-time state-transition model of the disease’s natural course. Transition probabilities, effectiveness data and costs were derived from retrospective data and prospective follow-up of the Dutch study cohort. Setting The tertiary referral center for Gaucher disease in the Netherlands. Participants The Dutch cohort of patients with GD I. Intervention ERT versus standard medical care without ERT in symptomatic patients. Main outcome measures Years free of end organ damage (YFEOD) (splenectomy, bone complication, malignancy, multiple complications), quality adjusted life years (QALY), and costs. Results Over an 85 year lifetime, an untreated GD I patient will generate 48.9 YFEOD and 55.86 QALYs. Starting ERT in a symptomatic patient increases the YFEOD by 12.8 years, while the number of QALYs gained increases by 6.27. The average yearly ERT medication costs range between €124,000 and €258,000 per patient. The lifetime costs of ERT starting in the symptomatic stage are €5,716,473 against €171,780 without ERT, a difference of €5,544,693. Consequently, the extra costs per additional YFEOD or per additional QALY are €434,416 and €884,994 respectively. After discounting effects by 1.5% and costs by 4% and under a reasonable scenario of ERT unit cost reduction by 25%, these incremental cost-effectiveness ratios could decrease to €149,857 and €324,812 respectively. Discussion ERT is a highly potential drug for GD I with substantial health gains. The conservatively estimated incremental cost-effectiveness ratios are substantially lower than for Pompe and Fabry disease. We suggest that the high effectiveness has contributed importantly to acceptance of reimbursement of ERT for GD I. The present study may

  6. Robotics for Long-Term Monitoring

    SciTech Connect

    Shahin, Sarkis; Duran, Celso

    2002-07-01

    While long-term monitoring and stewardship means many things to many people, DOE has defined it as The physical controls, institutions, information, and other mechanisms needed to ensure protection of people and the environment at sites where DOE has completed or plans to complete cleanup (e.g., landfill closures, remedial actions, and facility stabilization). Across the United States, there are thousands of contaminated sites with multiple contaminants released from multiple sources where contaminants have transported and commingled. The U.S. government and U.S. industry are responsible for most of the contamination and are landowners of many of these contaminated properties. These sites must be surveyed periodically for various criteria including structural deterioration, water intrusion, integrity of storage containers, atmospheric conditions, and hazardous substance release. The surveys, however, are intrusive, time-consuming, and expensive and expose survey personnel to radioactive contamination. In long-term monitoring, there's a need for an automated system that will gather and report data from sensors without costly human labor. In most cases, a SCADA (Supervisory Control and Data Acquisition) unit is used to collect and report data from a remote location. A SCADA unit consists of an embedded computer with data acquisition capabilities. The unit can be configured with various sensors placed in different areas of the site to be monitored. A system of this type is static, i.e., the sensors, once placed, cannot be moved to other locations within the site. For those applications where the number of sampling locations would require too many sensors, or where exact location of future problems is unknown, a mobile sensing platform is an ideal solution. In many facilities that undergo regular inspections, the number of video cameras and air monitors required to eliminate the need for human inspections is very large and far too costly. HCET's remote harsh

  7. Long-term Changes in Tropospheric Ozone

    NASA Astrophysics Data System (ADS)

    Oltmans, S.; Lefohn, A.; Galbally, I.; Scheel, E.; Bodeker, G.; Brunke, E.; Claude, H.; Tarasick, D.; Simmonds, P.; Anlauf, K.; Schmidlin, F.; Akagi, K.; Redondas, A.

    2006-05-01

    Tropospheric ozone measurements from a selected network of surface and ozonesonde sites are used to give a broad geographic picture of long-term variations. The picture of long-term tropospheric ozone changes is a varied one in terms of both the sign and magnitude of trends and in the possible causes for the changes. At mid latitudes of the S.H. three time series of ~20 years in length agree in showing increases that are strongest in the austral spring (August-October). Profile measurements show this increase extending through the mid troposphere but not into the highest levels of the troposphere. In the N.H. in the Arctic a period of declining ozone in the troposphere through the 1980s into the mid 1990s has reversed and the overall change is small. The decadal-scale variations in the troposphere in this region are related in part to changes in the lowermost stratosphere. At mid latitudes in the N.H., continental Europe and Japan showed significant increases in the 1970s and 1980s. Over North America rises in the 1970s are less than those seen in Europe and Japan, suggesting significant regional differences. In all three of these mid latitude, continental regions tropospheric ozone amounts appear to have leveled off or in some cases declined in the more recent decades. Over the North Atlantic three widely separated sites show significant increases since the late 1990s that may have peaked in recent years. In the N.H. tropics both the surface record and the ozonesondes in Hawaii show a significant increase in the autumn months in the most recent decade compared to earlier periods that drives the overall increase seen in the 30 year record. This appears to be related to a shift in the transport pattern during this season with more frequent flow from higher latitudes in the latest decade. The pattern of change, with the largest increases in the N.H. coming prior to the mid 1980s, suggests that increased positive radiative forcing due to tropospheric ozone was felt

  8. Long-term management of patients with urea cycle disorders.

    PubMed

    Berry, G T; Steiner, R D

    2001-01-01

    The long-term treatment of patients with urea cycle disorders (UCDs) includes diet treatment and use of specific medications. Guidelines are provided for patients with a severe phenotype. However, treatment must be tailored for each individual, especially with regard to residual enzyme function and in vivo metabolic capacity. This will be reflected in tests used for monitoring therapy that should be performed on a periodic basis. The goal of therapy is to eliminate chronic complications, a laudable but rarely attainable goal. Sick-day rules are discussed. Chronic management also includes diverse services that are essential to the success of the metabolic program. These include neurologic and developmental evaluations, feeding team evaluation and therapy, physical and occupational therapies, speech therapy, school and educational services, social service intervention, psychologic services, and genetic counseling.

  9. Enzyme replacement therapy for mucopolysaccharidosis VI: Growth and pubertal development in patients treated with recombinant human N-acetylgalactosamine 4-sulfatase

    PubMed Central

    Decker, Celeste; Yu, Zi-Fan; Giugliani, Roberto; Schwartz, Ida Vanessa D.; Guffon, Nathalie; Teles, Elisa Leão; Miranda, M. Clara Sá; Wraith, J. Edmond; Beck, Michael; Arash, Laila; Scarpa, Maurizio; Ketteridge, David; Hopwood, John J.; Plecko, Barbara; Steiner, Robert; Whitley, Chester B.; Kaplan, Paige; Swiedler, Stuart J.; Conrad, Susan; Harmatz, Paul

    2010-01-01

    Background and Methods Growth failure is characteristic of untreated mucopolysaccharidosis type VI (MPS VI: Maroteaux-Lamy syndrome). Growth was studied in fifty-six MPS VI patients (5 to 29 years old) prior to and for up to 240 weeks of weekly infusions of recombinant human arylsulfatase B (rhASB) at 1 mg/kg during Phase 1/2, Phase 2, Phase 3 or Phase 3 Extension clinical trials. Height, weight, and Tanner stage data were collected. Pooled data were analyzed to determine mean height increase by treatment week, growth impacts of pubertal status, baseline urinary GAG, and age at treatment initiation. Growth rate for approximately 2 years prior to and following treatment initiation was analyzed using longitudinal modeling. Results Mean height increased by 2.9 cm after 48 weeks and 4.3 cm after 96 weeks on enzyme replacement therapy (ERT). Growth on ERT was not correlated with baseline urinary GAG. Patients under 16 years of age showed greatest increases in height on treatment. Model results based on pooled data showed significant improvement in growth rate during 96 weeks of ERT when compared to the equivalent pretreatment time period. Delayed pubertal onset or progression was noted in 10 patients entering the clinical trials; all of whom showed progression of at least one Tanner stage during 2 years on ERT, and 6 of whom (60%) completed puberty. Conclusion Analysis of mean height by treatment week and longitudinal modeling demonstrate significant increase in height and growth rate in MPS VI patients receiving long-term ERT. This impact was greatest in patients aged below 16 years. Height increase may result from bone growth and/or reduction in joint contractures. Bone growth and resolution of delayed puberty may be related to improvements in general health, bone cell health, nutrition, endocrine gland function and reduced inflammation. PMID:20634905

  10. Enhanced efficacy of enzyme replacement therapy in Pompe disease through mannose-6-phosphate receptor expression in skeletal muscle.

    PubMed

    Koeberl, Dwight D; Luo, Xiaoyan; Sun, Baodong; McVie-Wylie, Alison; Dai, Jian; Li, Songtao; Banugaria, Suhrad G; Chen, Y-T; Bali, Deeksha S

    2011-06-01

    Enzyme replacement therapy (ERT) with acid α-glucosidase has become available for Pompe disease; however, the response of skeletal muscle, as opposed to the heart, has been attenuated. The poor response of skeletal muscle has been attributed to the low abundance of the cation-independent mannose-6-phosphate receptor (CI-MPR) in skeletal muscle compared to heart. To further understand the role of CI-MPR in Pompe disease, muscle-specific CI-MPR conditional knockout (KO) mice were crossed with GAA-KO (Pompe disease) mice. We evaluated the impact of CI-MPR-mediated uptake of GAA by evaluating ERT in CI-MPR-KO/GAA-KO (double KO) mice. The essential role of CI-MPR was emphasized by the lack of efficacy of ERT as demonstrated by markedly reduced biochemical correction of GAA deficiency and of glycogen accumulations in double KO mice, in comparison with the administration of the same therapeutic doses in GAA-KO mice. Clenbuterol, a selective β(2)-agonist, enhanced the CI-MPR expression in skeletal tissue and also increased efficacy from GAA therapy, thereby confirming the key role of CI-MPR with regard to enzyme replacement therapy in Pompe disease. Biochemical correction improved in both muscle and non-muscle tissues, indicating that therapy could be similarly enhanced in other lysosomal storage disorders. In summary, enhanced CI-MPR expression might improve the efficacy of enzyme replacement therapy in Pompe disease through enhancing receptor-mediated uptake of GAA.

  11. Enhanced Efficacy of Enzyme Replacement Therapy in Pompe Disease Through Mannose-6-Phosphate Receptor Expression in Skeletal Muscle

    PubMed Central

    Koeberl, Dwight D.; Luo, Xiaoyan; Sun, Baodong; McVie-Wylie, Alison; Dai, Jian; Li, Songtao; Banugaria, Suhrad G.; Chen, Y-T; Bali, Deeksha S.

    2011-01-01

    Enzyme replacement therapy (ERT) with acid α-glucosidase has become available for Pompe disease; however, the response of skeletal muscle, as opposed to the heart, has been attenuated. The poor response of skeletal muscle has been attributed to the low abundance of the cation-independent mannose-6-phosphate receptor (CI-MPR) in skeletal muscle compared to heart. To further understand the role of CI-MPR in Pompe disease, muscle-specific CI-MPR conditional knockout (KO) mice were crossed with GAA-KO (Pompe disease) mice. We evaluated the impact of CI-MPR-mediated uptake of GAA by evaluating ERT in CI-MPR-KO/GAA-KO (double KO) mice. The essential role of CI-MPR was emphasized by the lack of efficacy of ERT as demonstrated by markedly reduced biochemical correction of GAA deficiency and of glycogen accumulations in double KO mice, in comparison with administration of the same therapeutic doses in GAA-KO mice. Clenbuterol, a selective β2-agonist, enhanced CI-MPR expression in skeletal tissue and also increased efficacy from GAA therapy, thereby confirming the key role of CI-MPR with regard to enzyme replacement therapy in Pompe disease. Biochemical correction improved in both muscle and non-muscle tissues, indicating that therapy could be similarly enhanced in other lysosomal storage disorders. In summary, enhanced CI-MPR expression might improve the efficacy of enzyme replacement therapy in Pompe disease through enhancing receptor-mediated uptake of GAA. PMID:21397538

  12. A Distinct Urinary Biomarker Pattern Characteristic of Female Fabry Patients That Mirrors Response to Enzyme Replacement Therapy

    PubMed Central

    Kistler, Andreas D.; Siwy, Justyna; Breunig, Frank; Jeevaratnam, Praveen; Scherl, Alexander; Mullen, William; Warnock, David G.; Wanner, Christoph; Hughes, Derralynn A.; Mischak, Harald; Wüthrich, Rudolf P.; Serra, Andreas L.

    2011-01-01

    Female patients affected by Fabry disease, an X-linked lysosomal storage disorder, exhibit a wide spectrum of symptoms, which renders diagnosis, and treatment decisions challenging. No diagnostic test, other than sequencing of the alpha-galactosidase A gene, is available and no biomarker has been proven useful to screen for the disease, predict disease course and monitor response to enzyme replacement therapy. Here, we used urine proteomic analysis based on capillary electrophoresis coupled to mass spectrometry and identified a biomarker profile in adult female Fabry patients. Urine samples were taken from 35 treatment-naïve female Fabry patients and were compared to 89 age-matched healthy controls. We found a diagnostic biomarker pattern that exhibited 88.2% sensitivity and 97.8% specificity when tested in an independent validation cohort consisting of 17 treatment-naïve Fabry patients and 45 controls. The model remained highly specific when applied to additional control patients with a variety of other renal, metabolic and cardiovascular diseases. Several of the 64 identified diagnostic biomarkers showed correlations with measures of disease severity. Notably, most biomarkers responded to enzyme replacement therapy, and 8 of 11 treated patients scored negative for Fabry disease in the diagnostic model. In conclusion, we defined a urinary biomarker model that seems to be of diagnostic use for Fabry disease in female patients and may be used to monitor response to enzyme replacement therapy. PMID:21698285

  13. 22 CFR 228.12 - Long-term leases.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Long-term leases. 228.12 Section 228.12 Foreign... Transactions for USAID Financing § 228.12 Long-term leases. Any commodity obtained under a long-term lease..., a long-term lease is defined as a single lease of more than 180 days, or repetitive or...

  14. Evaluating Long-Term Care Through the Humanbecoming Lens.

    PubMed

    Hart, Judith D

    2015-10-01

    The author describes evaluating long-term care from the humanbecoming perspective. Three core ideas are presented related to dignity and living quality, and how the humanbecoming perspective can be incorporated into long-term care evaluations that make a difference to the residents, caregivers, management, and to the outcomes of long-term care. This approach from the humanbecoming perspective can enrich evaluative information, influence long-term care outcomes, and ensure human dignity for all concerned.

  15. Long-term data storage in diamond

    PubMed Central

    Dhomkar, Siddharth; Henshaw, Jacob; Jayakumar, Harishankar; Meriles, Carlos A.

    2016-01-01

    The negatively charged nitrogen vacancy (NV−) center in diamond is the focus of widespread attention for applications ranging from quantum information processing to nanoscale metrology. Although most work so far has focused on the NV− optical and spin properties, control of the charge state promises complementary opportunities. One intriguing possibility is the long-term storage of information, a notion we hereby introduce using NV-rich, type 1b diamond. As a proof of principle, we use multicolor optical microscopy to read, write, and reset arbitrary data sets with two-dimensional (2D) binary bit density comparable to present digital-video-disk (DVD) technology. Leveraging on the singular dynamics of NV− ionization, we encode information on different planes of the diamond crystal with no cross-talk, hence extending the storage capacity to three dimensions. Furthermore, we correlate the center’s charge state and the nuclear spin polarization of the nitrogen host and show that the latter is robust to a cycle of NV− ionization and recharge. In combination with super-resolution microscopy techniques, these observations provide a route toward subdiffraction NV charge control, a regime where the storage capacity could exceed present technologies. PMID:27819045

  16. Long-term predictions using natural analogues

    SciTech Connect

    Ewing, R.C.

    1995-09-01

    One of the unique and scientifically most challenging aspects of nuclear waste isolation is the extrapolation of short-term laboratory data (hours to years) to the long time periods (10{sup 3}-10{sup 5} years) required by regulatory agencies for performance assessment. The direct validation of these extrapolations is not possible, but methods must be developed to demonstrate compliance with government regulations and to satisfy the lay public that there is a demonstrable and reasonable basis for accepting the long-term extrapolations. Natural systems (e.g., {open_quotes}natural analogues{close_quotes}) provide perhaps the only means of partial {open_quotes}validation,{close_quotes} as well as data that may be used directly in the models that are used in the extrapolation. Natural systems provide data on very large spatial (nm to km) and temporal (10{sup 3}-10{sup 8} years) scales and in highly complex terranes in which unknown synergisms may affect radionuclide migration. This paper reviews the application (and most importantly, the limitations) of data from natural analogue systems to the {open_quotes}validation{close_quotes} of performance assessments.

  17. Long-term potentiation: peeling the onion.

    PubMed

    Nicoll, Roger A; Roche, Katherine W

    2013-11-01

    Since the discovery of long-term potentiation (LTP), thousands of papers have been published on this phenomenon. With this massive amount of information, it is often difficult, especially for someone not directly involved in the field, not to be overwhelmed. The goal of this review is to peel away as many layers as possible, and probe the core properties of LTP. We would argue that the many dozens of proteins that have been implicated in the phenomenon are not essential, but rather modulate, often in indirect ways, the threshold and/or magnitude of LTP. What is required is NMDA receptor activation followed by CaMKII activation. The consequence of CaMKII activation is the rapid recruitment of AMPA receptors to the synapse. This recruitment is independent of AMPA receptor subunit type, but absolutely requires an adequate pool of surface receptors. An important unresolved issue is how exactly CaMKII activation leads to modifications in the PSD to allow rapid enrichment. This article is part of the Special Issue entitled 'Glutamate Receptor-Dependent Synaptic Plasticity'.

  18. Neurological long term consequences of deep diving.

    PubMed Central

    Todnem, K; Nyland, H; Skeidsvoll, H; Svihus, R; Rinck, P; Kambestad, B K; Riise, T; Aarli, J A

    1991-01-01

    Forty commercial saturation divers, mean age 34.9 (range 24-49) years, were examined one to seven years after their last deep dive (190-500 metres of seawater). Four had by then lost their divers' licence because of neurological problems. Twenty seven (68%) had been selected by neurological examination and electroencephalography before the deep dives. The control group consisted of 100 men, mean age 34.0 (range 22-48) years. The divers reported significantly more symptoms from the nervous system. Concentration difficulties and paraesthesia in feet and hands were common. They had more abnormal neurological findings by neurological examination compatible with dysfunction in the lumbar spinal cord or roots. They also had a larger proportion of abnormal electroencephalograms than the controls. The neurological symptoms and findings were highly significantly correlated with exposure to deep diving (depth included), but even more significantly correlated to air and saturation diving and prevalence of decompression sickness. Visual evoked potentials, brainstem auditory evoked potentials, and magnetic resonance imaging of the brain did not show more abnormal findings in the divers. Four (10%) divers had had episodes of cerebral dysfunction during or after the dives; two had had seizures, one had had transitory cerebral ischaemia and one had had transitory global amnesia. It is concluded that deep diving may have a long term effect on the nervous system of the divers. PMID:2025592

  19. Transuranic waste: long-term planning

    SciTech Connect

    Young, K.C.

    1985-07-01

    Societal concerns for the safe handling and disposal of toxic waste are behind many of the regulations and the control measures in effect today. Transuranic waste, a specific category of toxic (radioactive) waste, serves as a good example of how regulations and controls impact changes in waste processing - and vice versa. As problems would arise with waste processing, changes would be instituted. These changes improved techniques for handling and disposal of transuranic waste, reduced the risk of breached containment, and were usually linked with regulatory changes. Today, however, we face a greater public awareness of and concern for toxic waste control; thus, we must anticipate potential problems and work on resolving them before they can become real problems. System safety analyses are valuable aids in long-term planning for operations involving transuranic as well as other toxic materials. Examples of specific system safety analytical methods demonstrate how problems can be anticipated and resolution initiated in a timely manner having minimal impacts upon allocation of resource and operational goals. 7 refs., 1 fig.

  20. Long-Term Consequences of Neonatal Injury

    PubMed Central

    Beggs, Simon

    2015-01-01

    The maturation of the central nervous system’s (CNS’s) sensory connectivity is driven by modality-specific sensory input in early life. For the somatosensory system, this input is the physical, tactile interaction with the environment. Nociceptive circuitry is functioning at the time of birth; however, there is still considerable organization and refinement of this circuitry that occurs postnatally, before full discrimination of tactile and noxious input is possible. This fine-tuning involves separation of tactile and nociceptive afferent input to the spinal cord’s dorsal horn and the maturation of local and descending inhibitory circuitry. Disruption of that input in early postnatal life (for example, by tissue injury or other noxious stimulus), can have a profound influence on subsequent development, and consequently the mature functioning of pain systems. In this review, the impact of neonatal surgical incision on nociceptive circuitry is discussed in terms of the underlying developmental neurobiology. The changes are complex, occurring at multiple anatomical sites within the CNS, and including both neuronal and glial cell populations. The altered sensory input from neonatal injury selectively modulates neuronal excitability within the spinal cord, disrupts inhibitory control, and primes the immune system, all of which contribute to the adverse long-term consequences of early pain exposure. PMID:26174217

  1. [Long-term stability of orthodontic treatment].

    PubMed

    Kuijpers-Jagtman, A M; Al Yami, E A; van 't Hof, M A

    2000-04-01

    Aim of this study was to assess long-term stability of orthodontic treatment in a sample of 1016 patients until 10 years postretention. Treatment outcome was measured with the PAR-index at 6 different stages. The mean age of the patients was 12.0 +/- 3.1 year at the start of treatment to 26.3 +/- 2.9 year 10 years postretention. The results show that 67% of the orthodontic treatment result, as measured with the PAR-index, was maintained 10 years postretention. The PAR-scores for the midline and the open bite remained about the same over the years. However, the scores for the lateral occlusion, overjet, reversed overjet, overbite, and contact point displacement of the upper and lower front teeth increased gradually over time. Nearly 50% of the total relapse took place the first two years after retention. The largest change was found for the position of the lower incisors. Ten years postretention their position was even worse than at the start of treatment.

  2. Long-term in vivo pineal microdialysis.

    PubMed

    Sun, Xing; Liu, Tiecheng; Deng, Jie; Borjigin, Jimo

    2003-09-01

    This study describes the development of a new technique for long-term measurement of daily 5-hydroxytryptamine (5-HT) and melatonin contents in the pineal gland of freely moving rats. The technique features a number of novel improvements over previous protocols. It allows visualization of the pineal gland for accurate targeting of the guide cannula, which minimizes bleeding; incurs no direct injury to the surrounding brain tissues; and causes no interference with the sympathetic innervation from the superior cervical ganglia. Robust releases of melatonin and indole precursors were continuously monitored quantitatively and reproducibly for more than 2 wk in the same animal. In addition, effects of pharmacological agents on in vivo pineal circadian rhythms can be studied reproducibly over time, and gene expression profiles can be correlated with physiological consequences in single animals. Using these approaches, it is found that beta-adrenergic activation leads to decreased release of 5-HT, and that increased cAMP signaling in vivo results in activation of N-acetyltransferase gene induction and melatonin production. These studies will enhance the understanding of signaling pathways that regulate pineal 5-HT and melatonin synthesis and secretion.

  3. Long-term corrosion testing plan.

    SciTech Connect

    Wall, Frederick Douglas; Brown, Neil R.

    2009-02-01

    This document describes the testing and facility requirements to support the Yucca Mountain Project long-term corrosion testing program. The purpose of this document is to describe a corrosion testing program that will (a) reduce model uncertainty and variability, (b) reduce the reliance upon overly conservative assumptions, and (c) improve model defensibility. Test matrices were developed for 17 topical areas (tasks): each matrix corresponds to a specific test activity that is a subset of the total work performed in a task. A future document will identify which of these activities are considered to be performance confirmation activities. Detailed matrices are provided for FY08, FY09 and FY10 and rough order estimates are provided for FY11-17. Criteria for the selection of appropriate test facilities were developed through a meeting of Lead Lab and DOE personnel on October 16-17, 2007. These criteria were applied to the testing activities and recommendations were made for the facility types appropriate to carry out each activity. The facility requirements for each activity were assessed and activities were identified that can not be performed with currently available facilities. Based on this assessment, a total of approximately 10,000 square feet of facility space is recommended to accommodate all future testing, given that all testing is consolidated to a single location. This report is a revision to SAND2008-4922 to address DOE comments.

  4. Long-term corrosion testing pan.

    SciTech Connect

    Wall, Frederick Douglas; Brown, Neil R.

    2008-08-01

    This document describes the testing and facility requirements to support the Yucca Mountain Project long-term corrosion testing needs. The purpose of this document is to describe a corrosion testing program that will (a) reduce model uncertainty and variability, (b) reduce the reliance upon overly conservative assumptions, and (c) improve model defensibility. Test matrices were developed for 17 topical areas (tasks): each matrix corresponds to a specific test activity that is a subset of the total work performed in a task. A future document will identify which of these activities are considered to be performance confirmation activities. Detailed matrices are provided for FY08, FY09 and FY10 and rough order estimates are provided for FY11-17. Criteria for the selection of appropriate test facilities were developed through a meeting of Lead Lab and DOE personnel on October 16-17, 2007. These criteria were applied to the testing activities and recommendations were made for the facility types appropriate to carry out each activity. The facility requirements for each activity were assessed and activities were identified that can not be performed with currently available facilities. Based on this assessment, a total of approximately 10,000 square feet of facility space is recommended to meet all future testing needs, given that all testing is consolidated to a single location. This report is a revision to SAND2007-7027 to address DOE comments and add a series of tests to address NWTRB recommendations.

  5. Long-term adequacy of metal resources

    USGS Publications Warehouse

    Singer, D.A.

    1977-01-01

    Although the earth's crust contains vast quantities of metals, extraction technologies and associated costs are inextricably bound to three fundamental geological factors - the amount of metal available in the earth's crust in each range of grades, the mineralogical form and chemical state of the metal, and the spatial distribution of the metal. The energy required to recover a given amount of metal increases substantially as grade declines. Most metal is produced from sulphide or oxide minerals, whereas most metal in the crust may be locked in the structures of the more refractory silicates. Recovery from silicate minerals could require orders of magnitude more energy than that used at present as also could exploitation of small, widely scattered or thin, deeply buried deposits. Although specific information on the fundamental factors is not available, each factor must in turn tend to further restrict exploitation. Independence of average grade and tonnage for many deposit types further reduces the availability of rock as a source of metal. In the long term, effects of these factors will be large increases in price for many metals. ?? 1977.

  6. Long-term data storage in diamond.

    PubMed

    Dhomkar, Siddharth; Henshaw, Jacob; Jayakumar, Harishankar; Meriles, Carlos A

    2016-10-01

    The negatively charged nitrogen vacancy (NV(-)) center in diamond is the focus of widespread attention for applications ranging from quantum information processing to nanoscale metrology. Although most work so far has focused on the NV(-) optical and spin properties, control of the charge state promises complementary opportunities. One intriguing possibility is the long-term storage of information, a notion we hereby introduce using NV-rich, type 1b diamond. As a proof of principle, we use multicolor optical microscopy to read, write, and reset arbitrary data sets with two-dimensional (2D) binary bit density comparable to present digital-video-disk (DVD) technology. Leveraging on the singular dynamics of NV(-) ionization, we encode information on different planes of the diamond crystal with no cross-talk, hence extending the storage capacity to three dimensions. Furthermore, we correlate the center's charge state and the nuclear spin polarization of the nitrogen host and show that the latter is robust to a cycle of NV(-) ionization and recharge. In combination with super-resolution microscopy techniques, these observations provide a route toward subdiffraction NV charge control, a regime where the storage capacity could exceed present technologies.

  7. Intermediate- and long-term earthquake prediction.

    PubMed Central

    Sykes, L R

    1996-01-01

    Progress in long- and intermediate-term earthquake prediction is reviewed emphasizing results from California. Earthquake prediction as a scientific discipline is still in its infancy. Probabilistic estimates that segments of several faults in California will be the sites of large shocks in the next 30 years are now generally accepted and widely used. Several examples are presented of changes in rates of moderate-size earthquakes and seismic moment release on time scales of a few to 30 years that occurred prior to large shocks. A distinction is made between large earthquakes that rupture the entire downdip width of the outer brittle part of the earth's crust and small shocks that do not. Large events occur quasi-periodically in time along a fault segment and happen much more often than predicted from the rates of small shocks along that segment. I am moderately optimistic about improving predictions of large events for time scales of a few to 30 years although little work of that type is currently underway in the United States. Precursory effects, like the changes in stress they reflect, should be examined from a tensorial rather than a scalar perspective. A broad pattern of increased numbers of moderate-size shocks in southern California since 1986 resembles the pattern in the 25 years before the great 1906 earthquake. Since it may be a long-term precursor to a great event on the southern San Andreas fault, that area deserves detailed intensified study. Images Fig. 1 PMID:11607658

  8. Intermediate- and long-term earthquake prediction.

    PubMed

    Sykes, L R

    1996-04-30

    Progress in long- and intermediate-term earthquake prediction is reviewed emphasizing results from California. Earthquake prediction as a scientific discipline is still in its infancy. Probabilistic estimates that segments of several faults in California will be the sites of large shocks in the next 30 years are now generally accepted and widely used. Several examples are presented of changes in rates of moderate-size earthquakes and seismic moment release on time scales of a few to 30 years that occurred prior to large shocks. A distinction is made between large earthquakes that rupture the entire downdip width of the outer brittle part of the earth's crust and small shocks that do not. Large events occur quasi-periodically in time along a fault segment and happen much more often than predicted from the rates of small shocks along that segment. I am moderately optimistic about improving predictions of large events for time scales of a few to 30 years although little work of that type is currently underway in the United States. Precursory effects, like the changes in stress they reflect, should be examined from a tensorial rather than a scalar perspective. A broad pattern of increased numbers of moderate-size shocks in southern California since 1986 resembles the pattern in the 25 years before the great 1906 earthquake. Since it may be a long-term precursor to a great event on the southern San Andreas fault, that area deserves detailed intensified study.

  9. The long-term variability of Vega

    NASA Astrophysics Data System (ADS)

    Butkovskaya, V.; Plachinda, S.; Valyavin, G.; Baklanova, D.; Lee, B.-C.

    2011-12-01

    Over the time of 60 years Vega (α Lyrae = HD 172167, A0V) has been generally accepted as a standard star in the near-infrared, optical, and ultraviolet regions. But is the spectrophotometric standard Vega really non-variable star? Researchers give very different answers to this question. We aim to search a periodicity in our results of spectropolarimetric study of Vega, namely periodic variations in equivalent width of the spectral lines and longitudinal magnetic field measurements. High-accuracy spectropolarimetric observations of Vega have been performed during 26 nights from 1997 to 2010 using the Coudé spectrograph of the 2.6-m Shain reflector at the Crimean Astrophysical Observatory (CrAO, Ukraine) and during 4 nights in 2007 and 2008 using the echelle spectrograph BOES at the Bohyunsan Optical Astronomy Observatory (BOAO, South Korea). The long-term (year-to-year) variability of Vega was confirmed. It was concluded that this variability does not have magnetic nature. The paper is dedicated to the memory of V.P. Merezhin.

  10. 3 CFR - Long-Term Gulf Coast Restoration Support Plan

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 3 The President 1 2011-01-01 2011-01-01 false Long-Term Gulf Coast Restoration Support Plan Presidential Documents Other Presidential Documents Memorandum of June 30, 2010 Long-Term Gulf Coast... help the Gulf Coast and its people recover from this tragedy. A long-term plan to restore the...

  11. The Place of Assisted Living in Long-Term Care and Related Service Systems

    ERIC Educational Resources Information Center

    Stone, Robyn I.; Reinhard, Susan C.

    2007-01-01

    Purpose: The purpose of this article is to describe how assisted living (AL) fits with other long-term-care services. Design and Methods: We analyzed the evolution of AL, including the populations served, the services offered, and federal and state policies that create various incentives or disincentives for using AL to replace other forms of care…

  12. Enhancement of Drug Delivery: Enzyme-replacement Therapy for Murine Morquio A Syndrome

    PubMed Central

    Tomatsu, Shunji; Montaño, Adriana M; Dung, Vu Chi; Ohashi, Amiko; Oikawa, Hirotaka; Oguma, Toshihiro; Orii, Tadao; Barrera, Luis; Sly, William S

    2010-01-01

    Mucopolysaccharidosis IVA (MPS IVA, Morquio A disease) is an inherited lysosomal storage disorder that features skeletal chondrodysplasia caused by deficiency of N-acetylgalactosamine-6-sulfate sulfatase (GALNS). Human GALNS was bioengineered with the N-terminus extended by the hexaglutamate sequence (E6) to improve targeting to bone (E6-GALNS). We initially assessed blood clearance and tissue distribution. Next, to assess the effectiveness of storage clearance and reversal of pathological phenotype, a dose of 250 U/g of enzyme was given weekly to Morquio A mice (adults: 12 or 24 weeks, newborn: 8 weeks). Sulfatase modifier factor 1 (SUMF1) was co-transfected to activate the enzyme fully. The E6-GALNS tagged enzyme had markedly prolonged clearance from circulation, giving over 20 times exposure time in blood, compared to untagged enzyme. The tagged enzyme was retained longer in bone, with residual enzyme activity demonstrable at 48 hours after infusion. The pathological findings in adult mice treated with tagged enzyme showed substantial clearance of the storage materials in bone, bone marrow, and heart valves, especially after 24 weekly infusions. Mice treated from the newborn period showed marked reduction of storage materials in tissues investigated. These findings indicate the feasibility of using tagged enzyme to enhance delivery and pathological effectiveness in Morquio A mice. PMID:20332769

  13. The neuronal response at extended timescales: long-term correlations without long-term memory

    PubMed Central

    Soudry, Daniel; Meir, Ron

    2014-01-01

    Long term temporal correlations frequently appear at many levels of neural activity. We show that when such correlations appear in isolated neurons, they indicate the existence of slow underlying processes and lead to explicit conditions on the dynamics of these processes. Moreover, although these slow processes can potentially store information for long times, we demonstrate that this does not imply that the neuron possesses a long memory of its input, even if these processes are bidirectionally coupled with neuronal response. We derive these results for a broad class of biophysical neuron models, and then fit a specific model to recent experiments. The model reproduces the experimental results, exhibiting long term (days-long) correlations due to the interaction between slow variables and internal fluctuations. However, its memory of the input decays on a timescale of minutes. We suggest experiments to test these predictions directly. PMID:24744724

  14. Scientific Understanding from Long Term Observations: Insights from the Long Term Ecological Research (LTER) Program

    NASA Astrophysics Data System (ADS)

    Gosz, J.

    2001-12-01

    The network dedicated to Long Term Ecological Research (LTER) in the United States has grown to 24 sites since it was formed in 1980. Long-term research and monitoring are performed on parameters thatare basic to all ecosystems and are required to understand patterns, processes, and relationship to change. Collectively, the sites in the LTER Network provide opportunities to contrast marine, coastal, and continental regions, the full range of climatic gradients existing in North America, and aquatic and terrestrial habitats in a range of ecosystem types. The combination of common core areas and long-term research and monitoring in many habitats have allowed unprecedented abilities to understand and compare complex temporal and spatial dynamics associated with issues like climate change, effects of pollution, biodiversity and landuse. For example, McMurdo Dry Valley in the Antarctic has demonstrated an increase in glacier mass since 1993 which coincides with a period of cooler than normal summers and more than average snowfall. In contrast, the Bonanza Creek and Toolik Lake sites in Alaska have recorded a warming period unprecedented in the past 200 years. Nitrogen deposition effects have been identified through long-term watershed studies on biogeochemical cycles, especially at Coweeta Hydrological Lab, Harvard Forest, and the Hubbard Brook Experimental Forest. In aquatic systems, such as the Northern Temperate Lakes site, long-term data revealed time lags in effects of invaders and disturbance on lake communities. Biological recovery from an effect such as lake acidification was shown to lag behind chemical recovery. The long-term changes documented over 2 decades have been instrumental in influencing management practices in many of the LTER areas. In Puerto Rico, the Luquillo LTER demonstrated that dams obstruct migrations of fish and freshwater shrimp and water abstraction at low flows can completely obliterate downstream migration of juveniles and damage

  15. Enhanced intracellular stability of dextran-horse radish peroxidase conjugate: an approach to enzyme replacement therapy.

    PubMed

    Mumtaz, S; Bachhawat, B K

    1992-09-15

    Horse radish peroxidase (HRP), a mannose-containing glycoprotein was covalently modified by conjugation with dextran. The rapid uptake of HRP by the liver is markedly inhibited by mannan. The uptake of dextran-HRP conjugate by the liver, though lower compared to that of the free enzyme, is also partially inhibited by mannan. Liposomes were therefore used as carriers for delivering the free and the modified HRP to the liver. The dextran-HRP conjugate showed greater stability intracellularly as compared to the free enzyme. The enhanced stability of enzymes upon their extensive glycosylation with nondegradable sugar polymers would be of importance in extending the catalytic life of therapeutically active enzymes and thereby improve their therapeutic potential for the treatment of certain enzyme deficiency disorders.

  16. Pancreatic enzyme replacement therapy for pancreatic exocrine insufficiency in the 21st century

    PubMed Central

    Trang, Tony; Chan, Johanna; Graham, David Y

    2014-01-01

    Restitution of normal fat absorption in exocrine pancreatic insufficiency remains an elusive goal. Although many patients achieve satisfactory clinical results with enzyme therapy, few experience normalization of fat absorption, and many, if not most, will require individualized therapy. Increasing the quantity of lipase administered rarely eliminates steatorrhea but increases the cost of therapy. Enteric coated enzyme microbead formulations tend to separate from nutrients in the stomach precluding coordinated emptying of enzymes and nutrients. Unprotected enzymes mix well and empty with nutrients but are inactivated at pH 4 or below. We describe approaches for improving the results of enzyme therapy including changing to, or adding, a different product, adding non-enteric coated enzymes, (e.g., giving unprotected enzymes at the start of the meal and acid-protected formulations later), use of antisecretory drugs and/or antacids, and changing the timing of enzyme administration. Because considerable lipid is emptied in the first postprandial hour, it is prudent to start therapy with enteric coated microbead prior to the meal so that some enzymes are available during that first hour. Patients with hyperacidity may benefit from adjuvant antisecretory therapy to reduce the duodenal acid load and possibly also sodium bicarbonate to prevent duodenal acidity. Comparative studies of clinical effectiveness of different formulations as well as the characteristics of dispersion, emptying, and dissolution of enteric-coated microspheres of different diameter and density are needed; many such studies have been completed but not yet made public. We discuss the history of pancreatic enzyme therapy and describe current use of modern preparations, approaches to overcoming unsatisfactory clinical responses, as well as studies needed to be able to provide reliably effective therapy. PMID:25206255

  17. Modeling maintenance of long-term potentiation in clustered synapses: long-term memory without bistability.

    PubMed

    Smolen, Paul

    2015-01-01

    Memories are stored, at least partly, as patterns of strong synapses. Given molecular turnover, how can synapses maintain strong for the years that memories can persist? Some models postulate that biochemical bistability maintains strong synapses. However, bistability should give a bimodal distribution of synaptic strength or weight, whereas current data show unimodal distributions for weights and for a correlated variable, dendritic spine volume. Thus it is important for models to simulate both unimodal distributions and long-term memory persistence. Here a model is developed that connects ongoing, competing processes of synaptic growth and weakening to stochastic processes of receptor insertion and removal in dendritic spines. The model simulates long-term (>1 yr) persistence of groups of strong synapses. A unimodal weight distribution results. For stability of this distribution it proved essential to incorporate resource competition between synapses organized into small clusters. With competition, these clusters are stable for years. These simulations concur with recent data to support the "clustered plasticity hypothesis" which suggests clusters, rather than single synaptic contacts, may be a fundamental unit for storage of long-term memory. The model makes empirical predictions and may provide a framework to investigate mechanisms maintaining the balance between synaptic plasticity and stability of memory.

  18. Modeling Maintenance of Long-Term Potentiation in Clustered Synapses: Long-Term Memory without Bistability

    PubMed Central

    Smolen, Paul

    2015-01-01

    Memories are stored, at least partly, as patterns of strong synapses. Given molecular turnover, how can synapses maintain strong for the years that memories can persist? Some models postulate that biochemical bistability maintains strong synapses. However, bistability should give a bimodal distribution of synaptic strength or weight, whereas current data show unimodal distributions for weights and for a correlated variable, dendritic spine volume. Thus it is important for models to simulate both unimodal distributions and long-term memory persistence. Here a model is developed that connects ongoing, competing processes of synaptic growth and weakening to stochastic processes of receptor insertion and removal in dendritic spines. The model simulates long-term (>1 yr) persistence of groups of strong synapses. A unimodal weight distribution results. For stability of this distribution it proved essential to incorporate resource competition between synapses organized into small clusters. With competition, these clusters are stable for years. These simulations concur with recent data to support the “clustered plasticity hypothesis” which suggests clusters, rather than single synaptic contacts, may be a fundamental unit for storage of long-term memory. The model makes empirical predictions and may provide a framework to investigate mechanisms maintaining the balance between synaptic plasticity and stability of memory. PMID:25945261

  19. LONG TERM IN SITU DISPOSAL ENGINEERING STUDY

    SciTech Connect

    ADAMS; CARLSON; BROCKMAN

    2003-07-23

    Patent application pulled per Ken Norris (FH General Counsel). The objective of this study is to devise methods, produce conceptual designs, examine and select alternatives, and estimate costs for the demonstration of long-term (300-year) in situ disposal of an existing waste disposal site. The demonstration site selected is the 216-A-24 Crib near the 200 East Area. The site contains a fission product inventory and has experienced plant, animal, and inadvertent than intrusion. Of the potential intrusive events and transport pathways at the site, potential human intrusion has been given primary consideration in barrier design. Intrusion by wind, plants, and animals has been given secondary consideration. Groundwater modeling for a number of barrier configurations has been carried out to help select a barrier that will minimize water infiltration and waste/water contact time. The estimated effective lifetime and cost of 20 barrier schemes, using a variety of materials, have been evaluated. The schemes studied include single component surface barriers, multicomponent barriers, and massively injected grout barriers. Five barriers with high estimated effective lifetimes and relatively low costs have been selected for detailed evaluation. They are basalt riprap barriers, massive soil barriers, salt basin barriers, multi-component fine/coarse barriers, and cemented basalt barriers. A variety of materials and configurations for marking the site have also been considered. A decision analysis was completed to select a barrier scheme for demonstration. The analysis indicated that the basalt riprap alternative would be the preferred choice for a full-scale demonstration. The recommended approach is to demonstrate the basalt riprap barrier at the 216-A-24 Crib as soon as possible. Methods and costs of assessing effectiveness of the demonstration are also described. Preliminary design modifications and costs for applying the five selected barrier schemes to other site types are

  20. Long term cultivation of larger benthic Foraminifera

    NASA Astrophysics Data System (ADS)

    Wöger, Julia; Eder, Wolfgang; Kinoshita, Shunichi; Antonino, Briguglio; Carles, Ferrandes-Cañadell; Hohenegger, Johann

    2015-04-01

    Benthic Foraminifera are used in a variety of applications employing numerous different methods, i.e. ecological monitoring, studying the effects of ocean acidification, reconstructing palaeo-bathymetry or investigating palaeo-salinity and palaeo-temperature to name only a few. To refine our understanding of ecological influences on larger benthic foraminiferal biology and to review inferences from field observations, culture experiments have become an indispensable tool. While culture experiments on smaller benthic foraminifera have become increasingly frequent in the past century, reports of the cultivation of symbiont bearing larger Foraminifera are rare. Generally, cultivation experiments can be divided into two groups: Culturing of populations and cultivation of single specimens allowing individual investigation. The latter differ form the former by several restrictions resulting from the need to limit individual motility without abridging microenvironmental conditions in the Foraminiferans artificial habitat, necessary to enable the individual to development as unfettered as possible. In this study we present first experiences and preliminary results of the long-term cultivation of larger benthic Foraminifera conducted at the 'Tropical Biosphere Research Station Sesoko Island, University of the Ryukyus', Japan, trying to reproduce natural conditions as closely as possible. Individuals of three species of larger benthic Foraminifera (Heterostegina depressa, Palaeonummulites venosus and Operculina complanata) have been cultured since April 2014. At the time of the general assembly the cultivation experiments will have been going on for more than one year, with the aim to investigate growth rates, longevities and reproduction strategies for comparison with results statistically inferred from application of the of the 'natural laboratory' method. The most important factor influencing foraminiferal health and development was found to be light intensity and light

  1. A security/safety survey of long term care facilities.

    PubMed

    Acorn, Jonathan R

    2010-01-01

    What are the major security/safety problems of long term care facilities? What steps are being taken by some facilities to mitigate such problems? Answers to these questions can be found in a survey of IAHSS members involved in long term care security conducted for the IAHSS Long Term Care Security Task Force. The survey, the author points out, focuses primarily on long term care facilities operated by hospitals and health systems. However, he believes, it does accurately reflect the security problems most long term facilities face, and presents valuable information on security systems and practices which should be also considered by independent and chain operated facilities.

  2. Carbapenem-resistant Escherichia coli harboring Klebsiella pneumoniae carbapenemase beta-lactamases associated with long-term care facilities.

    PubMed

    Urban, Carl; Bradford, Patricia A; Tuckman, Margareta; Segal-Maurer, Sorana; Wehbeh, Wehbeh; Grenner, Louise; Colon-Urban, Rita; Mariano, Noriel; Rahal, James J

    2008-06-01

    Nine carbapenem-resistant Escherichia coli isolates harboring Klebsiella pneumoniae carbapenemase (KPC)-2 or KPC-3 enzymes were identified in patients residing in 7 distinct long-term care facilities. Cefotaxime-hydrolyzing (CTX-M)-type beta-lactamases were also documented in 3 isolates. The identification of these enzymes in patients staying in long-term care facilities should be of great concern to all components of health care systems.

  3. Pulmonary complications after long term amiodarone treatment.

    PubMed Central

    Roca, J; Heras, M; Rodriguez-Roisin, R; Magriñà, J; Xaubet, A; Sanz, G

    1992-01-01

    BACKGROUND: Amiodarone hydrochloride is an antiarrhythmic agent useful in arrhythmias refractory to standard therapy. Although interstitial pneumonitis is known to be its most serious side effect, several aspects of amiodarone lung toxicity are still controversial. METHODS: Pulmonary side effects were examined in a sample of 61 symptomless patients (mean (SD) age 55 (7) years) who had had long term treatment with amiodarone (daily maintenance dose 400 mg), selected from 482 men attending the University of Barcelona myocardial infarction project. To allow for the confounding effects of coronary artery disease and tobacco history on lung function, 46 patients who had taken amiodarone for more than one year were matched with a control group from the same population. Subjects underwent measurement of lung volumes, arterial blood gas analysis and an incremental bicycle exercise test. RESULTS: Most lung function values were close to predicted values, though there was a small increase in resting alveolar-arterial oxygen tension difference (A-aDO2) at rest (4.8 (1.4) kPa in both groups). There were no differences in the results of forced spirometry or static lung volumes between the two groups, or in the fall in A-aDO2 from rest to exercise. There was a small difference between the amiodarone and the control group in transfer factor for carbon monoxide corrected for lung volume (KCO 1.67 (0.3) and 1.83 (0.3) mmol min-1 kPa-1 l-1 respectively) and in exercise capacity (140 (25) and 120 (30)w). Only three patients showed lung function impairment consistent with pneumonitis. No relation between lung function measures and cumulative doses of amiodarone or desethylamiodarone was found. CONCLUSIONS: The prevalence of clinically evident pulmonary side effects was 4.9%, which is lower than that reported in studies in which higher daily maintenance doses of amiodarone were given. The slightly lower KCO values and lower work load achieved by the patients taking amiodarone suggest a

  4. LOP- LONG-TERM ORBIT PREDICTOR

    NASA Technical Reports Server (NTRS)

    Kwok, J. H.

    1994-01-01

    The Long-Term Orbit Predictor (LOP) trajectory propagation program is a useful tool in lifetime analysis of orbiting spacecraft. LOP is suitable for studying planetary orbit missions with reconnaissance (flyby) and exploratory (mapping) trajectories. Sample data is included for a geosynchronous station drift cycle study, a Venus radar mapping strategy, a frozen orbit about Mars, and a repeat ground trace orbit. LOP uses the variation-of-parameters method in formulating the equations of motion. Terms involving the mean anomaly are removed from numerical integrations so that large step sizes, on the order of days, are possible. Consequently, LOP executes much faster than programs based on Cowell's method, such as the companion program ASAP (the Artificial Satellite Analysis Program, NPO-17522, also available through COSMIC). The program uses a force model with a gravity field of up to 21 by 21, lunisolar perturbation, drag, and solar radiation pressure. The input includes classical orbital elements (either mean or oscillating), orbital elements of the sun relative to the planet, reference time and dates, drag coefficients, gravitational constants, planet radius, rotation rate. The printed output contains the classical elements for each time step or event step, and additional orbital data such as true anomaly, eccentric anomaly, latitude, longitude, periapsis altitude, and the rate of change per day of certain elements. Selected output is additionally written to a plot file for postprocessing by the user. LOP is written in FORTRAN 77 for batch execution on IBM PC compatibles running MS-DOS with a minimum of 256K RAM. Recompiling the source requires the Lahey F77 v2.2 compiler. The LOP package includes examples that use LOTUS 1-2-3 for graphical displays, but any graphics software package should be able to handle the ASCII plot file. The program is available on two 5.25 inch 360K MS-DOS format diskettes. The program was written in 1986 and last updated in 1989. LOP is

  5. Use of a Modified α-N-Acetylgalactosaminidase in the Development of Enzyme Replacement Therapy for Fabry Disease

    PubMed Central

    Tajima, Youichi; Kawashima, Ikuo; Tsukimura, Takahiro; Sugawara, Kanako; Kuroda, Mayuko; Suzuki, Toshihiro; Togawa, Tadayasu; Chiba, Yasunori; Jigami, Yoshifumi; Ohno, Kazuki; Fukushige, Tomoko; Kanekura, Takuro; Itoh, Kohji; Ohashi, Toya; Sakuraba, Hitoshi

    2009-01-01

    A modified α-N-acetylgalactosaminidase (NAGA) with α-galactosidase A (GLA)-like substrate specificity was designed on the basis of structural studies and was produced in Chinese hamster ovary cells. The enzyme acquired the ability to catalyze the degradation of 4-methylumbelliferyl-α-D-galactopyranoside. It retained the original NAGA's stability in plasma and N-glycans containing many mannose 6-phosphate (M6P) residues, which are advantageous for uptake by cells via M6P receptors. There was no immunological cross-reactivity between the modified NAGA and GLA, and the modified NAGA did not react to serum from a patient with Fabry disease recurrently treated with a recombinant GLA. The enzyme cleaved globotriaosylceramide (Gb3) accumulated in cultured fibroblasts from a patient with Fabry disease. Furthermore, like recombinant GLA proteins presently used for enzyme replacement therapy (ERT) for Fabry disease, the enzyme intravenously injected into Fabry model mice prevented Gb3 storage in the liver, kidneys, and heart and improved the pathological changes in these organs. Because this modified NAGA is hardly expected to cause an allergic reaction in Fabry disease patients, it is highly promising as a new and safe enzyme for ERT for Fabry disease. PMID:19853240

  6. Enhanced Polyhydroxybutyrate Production for Long-Term Spaceflight Applications

    NASA Technical Reports Server (NTRS)

    Putman, Ryan J.; Rahman, Asif; Miller, Charles D.; Hadi, Masood Z.

    2015-01-01

    Synthetic biology holds the promise of advancing long term space fight by the production of medicine, food, materials, and energy. One such application of synthetic biology is the production of biomaterials, specifically polyhydroxyalkanoates (PHAs), using purposed organisms such as Escherichia coli. PHAs are a group of biodegradable bioplastics that are produced by a wide variety of naturally occurring microorganisms, mainly as an energy storage intermediate. PHAs have similar melting point to polypropylene and a Youngs modulus close to polystyrene. Due to limited resources and cost of transportation, large-scale extraction of biologically produced products in situ is extremely cumbersome during space flight. To that end, we are developing a secretion systems for exporting PHA from the cell in order to reduce unit operations. PHAs granules deposited inside bacteria are typically associated with proteins bound to the granule surface. Phasin, a granule bound protein, was targeted for type I secretion by fusion with HlyA signal peptide for indirect secretion of PHAs. In order to validate our secretion strategy, a green fluorescent protein (GFP) was tagged to the PHA polymerase enzyme (phaC), this three part gene cassette consists of phaA and phaB and are required for PHA production. Producing PHAs in situ during space flight or planet colonization will enable mission success by providing a valuable source of biomaterials that can have many potential applications thereby reducing resupply requirements. Biologically produced PHAs can be used in additive manufacturing such as three dimensional (3D) printing to create products that can be made on demand during space flight. After exceeding their lifetime, the PHAs could be melted and recycled back to 3D print other products. We will discuss some of our long term goals of this approach.

  7. Long-term outcome of large artificial patch aortic repair for diffuse stenosis in Williams syndrome.

    PubMed

    Sughimoto, Koichi; Takahara, Yoshiharu; Mogi, Kenji; Sakurai, Manabu; Aoki, Chikashi

    2010-10-01

    There have been only a few reports concerning the long-term results of a surgical procedure using a large artificial patch for patients with Williams syndrome. Twelve years have passed since a patient with William's syndrome underwent a surgery with a patch angioplasty for the diffuse supravalvular aortic stenosis and deformities of the neck branch arteries. The patient had a well-balanced aortic growth without stenotic or aneurysmal changes, which was confirmed during the time of the second surgery when replacing the mitral valve. This technique of using a large patch has proven to be safe for Williams syndrome patients with diffuse supravalvular aortic stenosis in the long term.

  8. Long term measurement network for FIFE

    NASA Technical Reports Server (NTRS)

    Blad, Blaine L.; Walter-Shea, Elizabeth A.; Hays, Cynthia J.

    1988-01-01

    The objectives were: to obtain selected instruments which were not standard equipment on the Portable Automated Mesometeorological (PAM) and Data Control Platform (DCP) stations; to assist in incorporation of these instruments onto the PAM and DCP stations; to help provide routine maintenance of the instruments; to conduct periodic instrument calibrations; and to repair or replace malfunctioning instruments when possible. All of the objectives were or will be met soon. All instruments and the necessary instrument stands were purchased or made and were available for inclusion on the PAM and DCP stations before the beginning of the IFC-1. Due to problems beyond control, the DCP stations experienced considerable difficulty in becoming operational. To fill some of the gaps caused by the DCP problems, Campbell CR21-X data loggers were installed and the data collected on cassette tapes. Periodic checks of all instruments were made, to maintain data quality, to make necessary adjustments in certain instruments, to replace malfunctioning instruments, and to provide instrument calibration. All instruments will be calibrated before the beginning of the 1988 growing season as soon as the weather permits access to all stations and provides conditions that are not too harsh to work in for extended periods of time.

  9. Stochastic Induction of Long-Term Potentiation and Long-Term Depression

    PubMed Central

    Antunes, G.; Roque, A. C.; Simoes-de-Souza, F. M.

    2016-01-01

    Long-term depression (LTD) and long-term potentiation (LTP) of granule-Purkinje cell synapses are persistent synaptic alterations induced by high and low rises of the intracellular calcium ion concentration ([Ca2+]), respectively. The occurrence of LTD involves the activation of a positive feedback loop formed by protein kinase C, phospholipase A2, and the extracellular signal-regulated protein kinase pathway, and its expression comprises the reduction of the population of synaptic AMPA receptors. Recently, a stochastic computational model of these signalling processes demonstrated that, in single synapses, LTD is probabilistic and bistable. Here, we expanded this model to simulate LTP, which requires protein phosphatases and the increase in the population of synaptic AMPA receptors. Our results indicated that, in single synapses, while LTD is bistable, LTP is gradual. Ca2+ induced both processes stochastically. The magnitudes of the Ca2+ signals and the states of the signalling network regulated the likelihood of LTP and LTD and defined dynamic macroscopic Ca2+ thresholds for the synaptic modifications in populations of synapses according to an inverse Bienenstock, Cooper and Munro (BCM) rule or a sigmoidal function. In conclusion, our model presents a unifying mechanism that explains the macroscopic properties of LTP and LTD from their dynamics in single synapses. PMID:27485552

  10. Long-term depression of excitatory synaptic transmission and its relationship to long-term potentiation.

    PubMed

    Artola, A; Singer, W

    1993-11-01

    In many brain areas, including the cerebellar cortex, neocortex, hippocampus, striatum and nucleus accumbens, brief activation of an excitatory pathway can produce long-term depression (LTD) of synaptic transmission. In most preparations, induction of LTD has been shown to require a minimum level of postsynaptic depolarization and a rise in the intracellular Ca2+ concentration [Ca2+]i in the postsynaptic neurone. Thus, induction conditions resemble those described for the initiation of associative long-term potentiation (LTP). However, data from structures susceptible to both LTD and LTP suggest that a stronger depolarization and a greater increase in [Ca2+]i are required to induce LTP than to initiate LTD. The source of Ca2+ appears to be less critical for the differential induction of LTP and LTD than the amplitude of the Ca2+ surge, since the activation of voltage- and ligand-gated Ca2+ conductances as well as the release from intracellular stores have all been shown to contribute to both LTD and LTP induction. LTD is induceable even at inactive synapses if [Ca2+]i is raised to the appropriate level by antidromic or heterosynaptic activation, or by raising the extracellular Ca2+ concentration [Ca2+]o. These conditions suggest a rule (called here the ABS rule) for activity-dependent synaptic modifications that differs from the classical Hebb rule and that can account for both homosynaptic LTD and LTP as well as for heterosynaptic competition and associativity.

  11. Replacing corn with pearl millet (raw and sprouted) with and without enzyme in chickens' diet.

    PubMed

    Afsharmanesh, M; Ghorbani, N; Mehdipour, Z

    2016-04-01

    An experiment was conducted to compare a commercial corn-soya bean meal diet with a pearl millet (raw and sprouted) diet containing less soya bean meal, alone or in combination with exogenous enzyme, on growth performance and ileal villus development of chicks. Two-hundred-and-forty-one-day-old male broilers (10/pen) were randomly allocated to one of the following dietary treatments: (i) a standard corn-soya bean meal control diet (CTL); (ii) a raw pearl millet-soya bean meal diet (PM); (iii) a sprouted pearl millet-soya bean meal diet (SPM); (iv) CTL + exogenous enzymes (CE); (v) PM + exogenous enzymes (PE); and (vi) SPM + exogenous enzymes (SPE) with four replicate pens/treatment. Body weight of birds at day 21 did not differ between those fed the CTL, and SPM and PE diets. In comparison with feeding broilers the CTL diet, feeding the PE and SPM diets caused significant decrease in feed intake, but with equivalent growth and feed efficiency. However, at day 21, feed conversion ratio did not differ between birds fed the CTL diet and those fed the PM, PE and SPM diets. At day 21, broilers fed the PM and PE diets had longer villi (p < 0.05) than those fed the CTL diet. At day 21, villi width was reduced (p < 0.05) by raw pearl millet supplementation than CTL diet. It is concluded that, in comparison with corn, broiler diets formulated with sprouted pearl millet or pearl millet with enzyme require less soya bean meal and can be used to improve growth performance traits and villus development.

  12. Long-term stability of GOES-8 and -9 attitude control

    NASA Astrophysics Data System (ADS)

    Carr, James L.

    1996-10-01

    An independent audit of the in-orbit behavior of the GOES-8 and GOES-9 satellites has been conducted for the NASA/GSFC. This audit utilized star and landmark observations from the GOES imager to determine long-term histories for spacecraft attitude, orbital position, and instrument internal misalignments. The paper presents results from this audit. Long-term drifts are found in the attitude histories, whereas the misalignment histories are shown to be diurnally stable. The GOES image navigation and registration system is designed to compensate for instrument internal misalignments, and both the diurnally repeatable and drift components of the attitude. Correlations between GOES-8 and GOES-9 long-term roll and pitch drifts implicate the Earth sensor as the origin of these observed drifts. This results clearly demonstrates the enhanced registration stability to be obtained with stellar inertial attitude determination replacing or supplementing Earth sensor control on future GOES missions.

  13. Long-term outcomes in idiopathic membranous nephropathy using a restrictive treatment strategy.

    PubMed

    van den Brand, Jan A J G; van Dijk, Peter R; Hofstra, Julia M; Wetzels, Jack F M

    2014-01-01

    Recently published Kidney Disease Improving Global Outcomes (KDIGO) guidelines recommend limiting the use of immunosuppressive drugs in idiopathic membranous nephropathy to patients at the highest risk of kidney failure. However, recommendations are based on natural history rather than direct assessment of a restrictive treatment strategy. Here, we describe the long-term outcomes of treating a large cohort of patients with idiopathic membranous nephropathy according to a restrictive treatment policy. We analyzed data for 254 patients who visited our outpatient clinic between 1995 and 2009. All patients were treated with angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers. Immunosuppressive therapy was recommended in cases of deteriorating renal function or untreatable nephrotic syndrome. Primary outcomes for the present study were renal replacement therapy and death. Secondary outcomes included adverse events during follow-up and remission of proteinuria. In total, 124 patients (49%) received immunosuppressive therapy, which predominantly consisted of cyclophosphamide combined with steroids. Ten-year cumulative incidence rates were 3% for renal replacement therapy and 10% for death. Partial remission rates were 39%, 70%, and 83% after 1, 3, and 5 years, respectively; complete remission rates were 5%, 24%, and 38% at 1, 3, and 5 years, respectively. A serious adverse event occurred in 23% of all patients. The most notable complications were infections (17%), leukopenia (18%), cardiovascular events (13%), and malignancies (8%). In conclusion, the use of a restrictive treatment strategy in this cohort of patients with idiopathic membranous nephropathy yielded favorable outcomes while limiting the number of patients exposed to toxic drugs. These results support current KDIGO guidelines.

  14. Partial resolution of bone lesions. A child with severe combined immunodeficiency disease and adenosine deaminase deficiency after enzyme-replacement therapy

    SciTech Connect

    Yulish, B.S.; Stern, R.C.; Polmar, S.H.

    1980-01-01

    A child with severe combined immunodeficiency disease and adenosine deaminase deficiency, with characteristic bone dysplasia, was treated with transfusions of frozen irradiated RBCs as a means of enzyme replacement. This therapy resulted in restoration of immunologic competence and partial resolution of the bone lesions. Although the natural history of these lesions without therapy is not known, enzyme-replacement therapy may have played a role in the resolution of this patient's bone lesions.

  15. Anti-BlyS antibody reduces the immune reaction against enzyme and enhances the efficacy of enzyme replacement therapy in Fabry disease model mice.

    PubMed

    Sato, Yohei; Ida, Hiroyuki; Ohashi, Toya

    2017-02-02

    Formation of antibodies against a therapeutic enzyme is an important complication during enzyme replacement therapy (ERT) for lysosomal storage diseases. Fabry disease (FD) is caused by a deficiency of alpha-galactosidase (GLA), which results in the accumulation of globotriaosylceramide (GL-3). We have shown immune tolerance induction (ITI) during ERT in FD model mice by using an anti-B lymphocyte stimulator (anti-BlyS) antibody (belimumab). A single dose of the anti-BlyS antibody temporarily lowered the percentage of B cells and IgG antibody titer against recombinant human GLA. Administration of a low maintenance dose of the anti-BlyS antibody suppressed the B cell population and immunotolerance was induced in 20% of mice, but antibody formation could not be prevented. We then increased the maintenance dose of the anti-BlyS antibody and immunotolerance was induced in 50% of mice. Therapeutic enzyme distribution and clearance of GL-3 were also enhanced by a high maintenance dose of the anti-BlyS antibody.

  16. Consider long-term care as service alternative.

    PubMed

    Loria, L S

    1987-04-01

    The increasing demand for elderly care services, pressures on inpatient average length of stay and payment levels, and potential financial rewards from providing additional services, makes long-term care look attractive to hospitals. Long-term care, however, is not for every hospital. Before deciding to establish long-term care services, management should examine how the service fits within the hospital's strategic plan. The action plan below provides guidance in evaluating a decision to use hospital facilities for long-term care. Examine how long-term care services fit within the hospital's strategic plan. Study area demographics and competitors to assess the need and supply of long-term care services. Survey the medical staff, consumers and payers to determine attitudes, perceptions and interests regarding long-term care services. Develop a facility plan that identifies areas of excess capacity that can be most easily converted into long-term care with minimal effects on hospital operations. Prepare a financial feasibility analysis of the contribution margin and return on investment attributable to long-term care services. Include an impact analysis on hospital operations. Establish a management task force to develop a detailed implementation plan including assigned individual responsibilities and related timetable. Develop an effective marketing plan designed to generate increased patient market share.

  17. Long-Term Monitoring of Global Climate Forcings and Feedbacks

    NASA Technical Reports Server (NTRS)

    Hansen, J. (Editor); Rossow, W. (Editor); Fung, I. (Editor)

    1993-01-01

    A workshop on Long-Term Monitoring of Global Climate Forcings and Feedbacks was held February 3-4, 1992, at NASA's Goddard Institute for Space Studies to discuss the measurements required to interpret long-term global temperature changes, to critique the proposed contributions of a series of small satellites (Climsat), and to identify needed complementary monitoring. The workshop concluded that long-term (several decades) of continuous monitoring of the major climate forcings and feedbacks is essential for understanding long-term climate change.

  18. Ecological consequences of long-term browning in lakes

    PubMed Central

    Williamson, Craig E.; Overholt, Erin P.; Pilla, Rachel M.; Leach, Taylor H.; Brentrup, Jennifer A.; Knoll, Lesley B.; Mette, Elizabeth M.; Moeller, Robert E.

    2015-01-01

    Increases in terrestrially-derived dissolved organic matter (DOM) have led to the browning of inland waters across regions of northeastern North America and Europe. Short-term experimental and comparative studies highlight the important ecological consequences of browning. These range from transparency-induced increases in thermal stratification and oxygen (O2) depletion to changes in pelagic food web structure and alteration of the important role of inland waters in the global carbon cycle. However, multi-decadal studies that document the net ecological consequences of long-term browning are lacking. Here we show that browning over a 27 year period in two lakes of differing transparency resulted in fundamental changes in vertical habitat gradients and food web structure, and that these responses were stronger in the more transparent lake. Surface water temperatures increased by 2–3 °C in both lakes in the absence of any changes in air temperature. Water transparency to ultraviolet (UV) radiation showed a fivefold decrease in the more transparent lake. The primary zooplankton grazers decreased, and in the more transparent lake were largely replaced by a two trophic level zooplankton community. These findings provide new insights into the net effects of the complex and contrasting mechanisms that underlie the ecosystem consequences of browning. PMID:26690504

  19. [Long-term follow-up of osteochondritis dissecans].

    PubMed

    Gudas, Rimtautas; Kunigiskis, Giedrius; Kalesinskas, Romas Jonas

    2002-01-01

    Fifty-two patients with osteochondritis dissecans lesions were evaluated after 7-25 years after excision of a partially detached (grade III) fragment or loose (grade IV) fragment from the medial femoral condyles. Average follow-up time was 17.2 (range 7-25 years). Two homogenic groups based on special inclusion criteria were formed; 31 patient was in the first and 21--in the second group. The only difference between the groups was the age; the age average in the first group was--25.6 years (range 15-35 years), and -45.2 years (range 35-55 years) in the second group. Patients were evaluated through ICRS (International Cartilage Repair Society), modified HSS and KOOS (Knee injury and osteoarthritis Outcome score) scales, and with X-rays. Evaluation with the ICRS, modified HSS and KOOS rating scales for osteochondritis dissecans revealed in 9 cases (17%) good results, 32 cases (62%)--fair, and 11 cases (21%)--failure results. Final ICRS and modified HSS evaluation showed statistically significantly better results in the younger patient group at the 21 years (p < 0.04). At an average 17.2 year follow-up X-rays and KOOS evaluation form showed initial and second-degree (according to Ahlbäck) osteoarthritis signs in the knees. The long-term results of the natural history of osteochondritis dissecans are extremely poor. Consequently, we recommend autologous osteochondral grafting for the replacement of the osteochondritis dissecans defects in the knee joint.

  20. Irradiated homologous cartilage grafts. Long-term results

    SciTech Connect

    Welling, D.B.; Maves, M.D.; Schuller, D.E.; Bardach, J.

    1988-03-01

    The use of irradiated homologous cartilage for the restoration of facial contour defects remains a controversial issue in reconstructive surgery. Both favorable and unfavorable reports can be found in the literature. Some basic research concerning the rate and mechanism of resorption has been completed but has failed to resolve the issue of the usefulness of this material in day-to-day practice. One frequently cited reference concerning the use of irradiated homologous cartilage in reconstructive surgery was coauthored by two of the present investigators ten years ago. In an effort to place this study in a long-term perspective, we examined 42 of the original 107 patients who formed the initial population base. Sixty-two of the original 145 irradiated homologous cartilage grafts have been followed up for an average of nine years, with an average resorption rate of approximately 75%. Eighteen of 24 grafts followed up from 11 to 16 years completely resorbed. In spite of complete graft resorption, some patients have maintained satisfactory facial contour with fibrous tissue replacement of the cartilage.

  1. [Developing the core competencies of long-term care professionals].

    PubMed

    Chen, Huey-Tzy; Lee, Kuang-Ting

    2012-12-01

    Longer average life expectancies and an ageing society have made long-term care an urgent and important issue in Taiwan. Although the implementation of Long-Term Care Ten-year Project four years ago has begun showing success in terms of assessing Taiwan's needs in terms of long-term care services and resources, there has been little forward progress in terms of training, recruiting and maintaining more competent professionals in the long-term care sector. This paper explores the current state of long-term care competency in Taiwan and educational strategies in place to improve the competency of long-term care professionals. Results indicate that the term geriatric competency embraces sub-competencies in direct care, communication, assessment, teamwork, cultural sensitivities and career care competencies. The term long-term care competency embraces the sub-competencies of supervision, management, information technology, resource management, and organizational skill. As a main contributor to effective long-term care, the nursing profession must employ effective strategies to develop competency-based education. Also, the profession must have an adequate supply of competent manpower to effectively respond to Taiwan's aging society.

  2. Long Term Agroecosystem Research in the southern plains

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The Southern Plains (SP) site of the Long Term Agroecosystem Research (LTAR) network is headquartered at USDA-ARS’s Grazinglands Research Laboratory (GRL) in El Reno, Oklahoma. The GRL was established in 1948. A long-term watershed and climate research program was established in the Little Washita ...

  3. Short- and Long-Term Consequences of Adolescent Work.

    ERIC Educational Resources Information Center

    Mihalic, Sharon Wofford; Elliott, Delbert

    1997-01-01

    Examines the short- and long-term consequences of working during adolescence. Responses from 1,725 adolescents reveal that the negative short-term effects are in the domains of school, family and friend bonding, beliefs, and substance use. The long-term beneficial effect is that the duration of early work helps employability in adulthood. (GR)

  4. Developmental Dyslexia and Explicit Long-Term Memory

    ERIC Educational Resources Information Center

    Menghini, Deny; Carlesimo, Giovanni Augusto; Marotta, Luigi; Finzi, Alessandra; Vicari, Stefano

    2010-01-01

    The reduced verbal long-term memory capacities often reported in dyslexics are generally interpreted as a consequence of their deficit in phonological coding. The present study was aimed at evaluating whether the learning deficit exhibited by dyslexics was restricted only to the verbal component of the long-term memory abilities or also involved…

  5. Ensuring climate information guides long-term development

    NASA Astrophysics Data System (ADS)

    Jones, Lindsey; Dougill, Andrew; Jones, Richard G.; Steynor, Anna; Watkiss, Paul; Kane, Cheikh; Koelle, Bettina; Moufouma-Okia, Wilfran; Padgham, Jon; Ranger, Nicola; Roux, Jean-Pierre; Suarez, Pablo; Tanner, Thomas; Vincent, Katharine

    2015-09-01

    Many sub-Saharan countries are failing to include climate information in long-term development planning. Ensuring climate-resilient development requires a step change in how medium- to long-term climate information is produced, communicated and utilized in sub-Saharan Africa and elsewhere.

  6. Prediction of Long Term Degradation of Insulating Materials

    DTIC Science & Technology

    2015-05-01

    Physical changes .......................................................................................................... 20 4.2 Thermal performance ...to address the enduring challenge of developing and evaluating the long-term performance of a thermal insula- tion for shelter systems that provides...properties of selected insulation ma- terials based on the differences in thermal conductivity and R-values. 3. Predict the long-term performance of selected

  7. Factors Affecting Long-Term Abstinence from Substances Use

    ERIC Educational Resources Information Center

    Elsheikh, Salah Elgaily

    2008-01-01

    Objective: The purpose of this study is to explore the attitudes of abstainers from drug use that relate to the factors leading to long-term abstinence. Materials and Methods: Cross-sectional study was carried out in Al-Amal Hospital to examine, which attitudes of abstainers related to long-term abstinence. A random survey was conducted on 62…

  8. 47 CFR 54.303 - Long term support.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... base-level of Long Term Support for 1998, the Administrator shall calculate the difference between the.... (2) To calculate Long Term Support for calendar year 1998, the Administrator shall adjust the base...; and (4) The line port costs in excess of basic analog service pursuant to § 69.130 of this...

  9. 47 CFR 54.303 - Long term support.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... base-level of Long Term Support for 1998, the Administrator shall calculate the difference between the.... (2) To calculate Long Term Support for calendar year 1998, the Administrator shall adjust the base...; and (4) The line port costs in excess of basic analog service pursuant to § 69.130 of this...

  10. Perceptions of control and long-term recovery from rape.

    PubMed

    Regehr, C; Cadell, S; Jansen, K

    1999-01-01

    The relationship between perceptions of control and symptoms of both long-term depression and post-traumatic stress was examined. Enduring beliefs of personal competence and control were found to be associated with lower rates of depression and stress and to be stronger predictors of long-term recovery than were rape-specific attributions. Implications for clinical practice are discussed.

  11. A new image for long-term care.

    PubMed

    Wager, Richard; Creelman, William

    2004-04-01

    To counter widely held negative images of long-term care, managers in the industry should implement quality-improvement initiatives that include six key strategies: Manage the expectations of residents and their families. Address customers' concerns early. Build long-term customer satisfaction. Allocate resources to achieve exceptional outcomes in key areas. Respond to adverse events with compassion. Reinforce the facility's credibility.

  12. 7 CFR 1773.44 - Long-term debt.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 12 2014-01-01 2013-01-01 true Long-term debt. 1773.44 Section 1773.44 Agriculture... (CONTINUED) POLICY ON AUDITS OF RUS BORROWERS RUS Required Audit Procedures and Documentation § 1773.44 Long-term debt. The CPA's workpapers must document that he/she: (a) Confirmed RUS, FFB, and RTB debt to...

  13. 7 CFR 1773.44 - Long-term debt.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 12 2011-01-01 2011-01-01 false Long-term debt. 1773.44 Section 1773.44 Agriculture... (CONTINUED) POLICY ON AUDITS OF RUS BORROWERS RUS Required Audit Procedures and Documentation § 1773.44 Long-term debt. The CPA's workpapers must document that he/she: (a) Confirmed RUS, FFB, and RTB debt to...

  14. The Effect of Modality on Long-Term Recognition Memory.

    ERIC Educational Resources Information Center

    Dean, Raymond S.; And Others

    1988-01-01

    The effects of visual and auditory modes of input on long-term memory were examined in two experiments, each with 40 and 80 undergraduates, respectively. In both experiments, visual stimulus attributes were a more salient dimension than were auditory features in the long-term encoding and retrieval process. (SLD)

  15. Pediatric Facial Fractures and Potential Long-Term Growth Disturbances

    PubMed Central

    Wheeler, Jonathan; Phillips, John

    2011-01-01

    Fractures of the pediatric craniofacial skeleton can be challenging to manage. The initial injury and subsequent treatment can cause long-term growth disturbances yielding problematic secondary deformities. This review considers the normal growth of the craniofacial skeleton and typical facial fracture presentations in children and discusses the potential long-term sequelae from these injuries and their management. PMID:22379506

  16. Expression, stability, and replacement of glucan-remodeling enzymes during developmental transitions in Saccharomyces cerevisiae.

    PubMed

    Rolli, Eleonora; Ragni, Enrico; de Medina-Redondo, María; Arroyo, Javier; de Aldana, Carlos R Vázquez; Popolo, Laura

    2011-05-01

    Sporulation is a developmental variation of the yeast life cycle whereby four spores are produced within a diploid cell, with proliferation resuming after germination. The GAS family of glycosylphosphatidylinositol-anchored glucan-remodeling enzymes exemplifies functional interplay between paralogous genes during the yeast life cycle. GAS1 and GAS5 are expressed in vegetative cells and repressed during sporulation while GAS2 and GAS4 exhibit a reciprocal pattern. GAS3 is weakly expressed in all the conditions and encodes an inactive protein. Although Gas1p functions in cell wall formation, we show that it persists during sporulation but is relocalized from the plasma membrane to the epiplasm in a process requiring End3p-mediated endocytosis and the Sps1 protein kinase of the p21-activated kinase family. Some Gas1p is also newly synthesized and localized to the spore membrane, but this fraction is dispensable for spore formation. By way of contrast, the Gas2-Gas4 proteins, which are essential for spore wall assembly, are rapidly degraded after spore formation. On germination, Gas1p is actively synthesized and concentrated in the growing part of the spore, which is essential for its elongation. Thus Gas1p is the primary glucan-remodeling enzyme required in vegetative growth and during reentry into the proliferative state. The dynamic interplay among Gas proteins is crucial to couple glucan remodeling with morphogenesis in developmental transitions.

  17. A perspective on long-term care for the elderly

    PubMed Central

    Scanlon, William J.

    1988-01-01

    Long-term care represents a significant burden to the approximately 7 million elderly in need, their families, and the Medicaid program. Concerns exist about access, quality, cost, and the distribution of the burden of care. In this article each area is discussed, highlighting the principal issues, identifying the unique aspects that pertain to long-term care, and exploring the implications for research and policy development. Future trends, especially the growth of the elderly population, are expected to affect significantly the provision of long-term care. The considerable uncertainty about how these trends may impact on long-term care is described, and the critical role social choice will play in shaping the future long-term care system is emphasized. PMID:10312975

  18. Environmental Management Long-Term Stewardship Transition Guidance

    SciTech Connect

    Kristofferson, Keith

    2001-11-01

    Long-term stewardship consists of those actions necessary to maintain and demonstrate continued protection of human health and the environment after the completion of facility cleanup. Long-term stewardship is administered and overseen by the U.S. Department of Energy Environmental Management Office of Science and Technology. This report describes the background of long-term stewardship and gives general guidance about considerations when ownership and/or responsibility of a site should be transferred to a long-term stewardship program. This guidance document will assist the U.S. Department of Energy in: (a) ensuring that the long-term stewardship program leads transition planning with respect to facility and site areas, and (b) describing the classes and types of criteria and data required to initiate transition for areas and sites where the facility mission has ended and cleanup is complete.

  19. The relationship between interannual and long-term cloud feedbacks

    SciTech Connect

    Zhou, Chen; Zelinka, Mark D.; Dessler, Andrew E.; Klein, Stephen A.

    2015-12-11

    The analyses of Coupled Model Intercomparison Project phase 5 simulations suggest that climate models with more positive cloud feedback in response to interannual climate fluctuations also have more positive cloud feedback in response to long-term global warming. Ensemble mean vertical profiles of cloud change in response to interannual and long-term surface warming are similar, and the ensemble mean cloud feedback is positive on both timescales. However, the average long-term cloud feedback is smaller than the interannual cloud feedback, likely due to differences in surface warming pattern on the two timescales. Low cloud cover (LCC) change in response to interannual and long-term global surface warming is found to be well correlated across models and explains over half of the covariance between interannual and long-term cloud feedback. In conclusion, the intermodel correlation of LCC across timescales likely results from model-specific sensitivities of LCC to sea surface warming.

  20. Long term survival effect of metoprolol in dilated cardiomyopathy

    PubMed Central

    Di, L; De Maria, R; Gavazzi, A; Gregori, D; Parolini, M; Sinagra, G; Salvatore, L; Longaro, F; Bernobich, E; Camerini, F

    1998-01-01

    Objective—To evaluate the additive effect of metoprolol treatment on long term incidence of fatal and non-fatal cardiac events in idiopathic dilated cardiomyopathy.
Design—586 patients with idiopathic dilated cardiomyopathy were prospectively enrolled in a multicentre registry and followed up for a mean (SD) of 52 (32) months. Metoprolol, carefully titrated to the maximum tolerated dose, was added to conventional heart failure treatment in 175 patients.
Results—Survival and transplant-free survival at seven years were significantly higher in the 175 metoprolol treated patients than in the remaining 411 on standard treatment (81% v 60%, p < 0.001, and 69% v 49%, p < 0.001, respectively). By multivariate analysis, metoprolol independently predicted survival and transplant-free survival (relative risk reduction values for all cause mortality and combined mortality or transplantation 51% (95% confidence interval 21% to 69%), p = 0.002, and 34% (5% to 53%), p = 0.01, respectively). New York Heart Association class, left ventricular end diastolic diameter, and pulmonary wedge pressure were also predictive. Seven year survival (80% v 62%, p = 0.004) and transplant-free survival (68% v 51%, p = 0.005) were significantly higher in 127 metoprolol treated cases than in 127 controls selected from the entire control cohort and appropriately matched. Metoprolol was associated with a 30% reduction in all cause mortality (7% to 48%, p = 0.015) and a 26% reduction in mortality or transplantation (7% to 41%, p = 0.009). 
Conclusions—The addition of metoprolol to standard heart failure treatment, including angiotensin converting enzyme inhibitors, was effective in the long term, reducing both all cause mortality and transplantation in patients with idiopathic dilated cardiomyopathy.

 Keywords: β blockade;  dilated cardiomyopathy;  heart failure PMID:9616339

  1. Issues in long-term protein delivery using biodegradable microparticles.

    PubMed

    Ye, Mingli; Kim, Sungwon; Park, Kinam

    2010-09-01

    Recently, a variety of bioactive protein drugs have been available in large quantities as a result of advances in biotechnology. Such availability has prompted development of long-term protein delivery systems. Biodegradable microparticulate systems have been used widely for controlled release of protein drugs for days and months. The most widely used biodegradable polymer has been poly(d,l-lactic-co-glycolic acid) (PLGA). Protein-containing microparticles are usually prepared by the water/oil/water (W/O/W) double emulsion method, and variations of this method, such as solid/oil/water (S/O/W) and water/oil/oil (W/O/O), have also been used. Other methods of preparation include spray drying, ultrasonic atomization, and electrospray methods. The important factors in developing biodegradable microparticles for protein drug delivery are protein release profile (including burst release, duration of release, and extent of release), microparticle size, protein loading, encapsulation efficiency, and bioactivity of the released protein. Many studies used albumin as a model protein, and thus, the bioactivity of the release protein has not been examined. Other studies which utilized enzymes, insulin, erythropoietin, and growth factors have suggested that the right formulation to preserve bioactivity of the loaded protein drug during the processing and storage steps is important. The protein release profiles from various microparticle formulations can be classified into four distinct categories (Types A, B, C, and D). The categories are based on the magnitude of burst release, the extent of protein release, and the protein release kinetics followed by the burst release. The protein loading (i.e., the total amount of protein loaded divided by the total weight of microparticles) in various microparticles is 6.7+/-4.6%, and it ranges from 0.5% to 20.0%. Development of clinically successful long-term protein delivery systems based on biodegradable microparticles requires

  2. The Womanly World of Long Term Care: The Plight of the Long Term Care Worker. Gray Paper.

    ERIC Educational Resources Information Center

    Older Women's League, Washington, DC.

    Long-term care workers (those who are paid to provide custodial care for long-term patients in nursing homes or at home) must care for a growing number of increasingly disabled or dependent persons. They are working for agencies and institutions under growing pressure to increase productivity. They face new training and competency requirements,…

  3. A calcineurin/AKAP complex is required for NMDA receptor-dependent long-term depression.

    PubMed

    Jurado, Sandra; Biou, Virginie; Malenka, Robert C

    2010-09-01

    AKAP79/150 is a protein scaffold that is thought to position specific kinases (protein kinase A and C) and phosphatases (calcineurin) in appropriate synaptic domains so that their activities can regulate excitatory synaptic strength. Using a viral-mediated molecular replacement strategy in rat hippocampal slices, we found that AKAP is required for NMDA receptor-dependent long-term depression solely because of its interaction with calcineurin.

  4. Intrathecal enzyme replacement therapy reverses cognitive decline in mucopolysaccharidosis type I.

    PubMed

    Nestrasil, Igor; Shapiro, Elsa; Svatkova, Alena; Dickson, Patricia; Chen, Agnes; Wakumoto, Amy; Ahmed, Alia; Stehel, Edward; McNeil, Sarah; Gravance, Curtis; Maher, Elizabeth

    2017-03-01

    Mucopolysaccharidosis type I (MPS I) is an inherited lysosomal storage disease that seriously affects the brain. Severity of neurocognitive symptoms in attenuated MPS subtype (MPS IA) broadly varies partially, due to restricted permeability of blood-brain barrier (BBB) which limits treatment effects of intravenously applied α-L-iduronidase (rhIDU) enzyme. Intrathecal (IT) rhIDU application as a possible solution to circumvent BBB improved brain outcomes in canine models; therefore, our study quantifies effects of IT rhIDU on brain structure and function in an MPS IA patient with previous progressive cognitive decline. Neuropsychological testing and MRIs were performed twice prior (baseline, at 1 year) and twice after initiating IT rhIDU (at 2nd and 3rd years). The difference between pre- and post-treatment means was evaluated as a percentage of the change. Neurocognitive performance improved particularly in memory tests and resulted in improved school performance after IT rhIDU treatment. White matter (WM) integrity improved together with an increase of WM and corpus callosum volumes. Hippocampal and gray matter volume decreased which may either parallel reduction of glycosaminoglycan storage or reflect typical longitudinal brain changes in early adulthood. In conclusion, our outcomes suggest neurological benefits of IT rhIDU compared to the intravenous administration on brain structure and function in a single MPS IA patient.© 2017 Wiley Periodicals, Inc.

  5. Long-Term Stewardship Baseline Report and Transition Guidance

    SciTech Connect

    Kristofferson, Keith

    2001-11-01

    Long-term stewardship consists of those actions necessary to maintain and demonstrate continued protection of human health and the environment after facility cleanup is complete. As the Department of Energy’s (DOE) lead laboratory for environmental management programs, the Idaho National Engineering and Environmental Laboratory (INEEL) administers DOE’s long-term stewardship science and technology efforts. The INEEL provides DOE with technical, and scientific expertise needed to oversee its long-term environmental management obligations complexwide. Long-term stewardship is administered and overseen by the Environmental Management Office of Science and Technology. The INEEL Long-Term Stewardship Program is currently developing the management structures and plans to complete INEEL-specific, long-term stewardship obligations. This guidance document (1) assists in ensuring that the program leads transition planning for the INEEL with respect to facility and site areas and (2) describes the classes and types of criteria and data required to initiate transition for areas and sites where the facility mission has ended and cleanup is complete. Additionally, this document summarizes current information on INEEL facilities, structures, and release sites likely to enter long-term stewardship at the completion of DOE’s cleanup mission. This document is not intended to function as a discrete checklist or local procedure to determine readiness to transition. It is an overarching document meant as guidance in implementing specific transition procedures. Several documents formed the foundation upon which this guidance was developed. Principal among these documents was the Long-Term Stewardship Draft Technical Baseline; A Report to Congress on Long-Term Stewardship, Volumes I and II; Infrastructure Long-Range Plan; Comprehensive Facility Land Use Plan; INEEL End-State Plan; and INEEL Institutional Plan.

  6. Space ventures and society long-term perspectives

    NASA Technical Reports Server (NTRS)

    Brown, W. M.

    1985-01-01

    A futuristic evaluation of mankind's potential long term future in space is presented. Progress in space will not be inhibited by shortages of the Earth's physical resources, since long term economic growth will be focused on ways to constrain industrial productivity by changing social values, management styles, or government competence. Future technological progress is likely to accelerate with an emphasis on international cooperation, making possible such large joint projects as lunar colonies or space stations on Mars. The long term future in space looks exceedingly bright even in relatively pessimistic scenarios. The principal driving forces will be technological progress, commercial and public-oriented satellites, space industrialization, space travel, and eventually space colonization.

  7. Medical care evaluation studies in long-term care facilities.

    PubMed

    Zimmer, J G

    1979-02-01

    This report describes the selection, design, conduct, analysis, and application of medical care evaluation studies in long-term care facilities (skilled nursing homes) in a regional program in the Rochester region of upstate New York. Eight examples are presented to highlight methodologic approaches and problems. They are classified under four general headings: Administration Audits, Diagnosis-specific Studies, Care Modality-specific Studies, and General Outcome Indicators. The implementation of results and recommendations from the studies is discussed and an application of "tracer" methodology for assessing the components of care activities in long-term facilities is described. Problems and challenges in long-term quality care are outlined.

  8. Glutathione level after long-term occupational elemental mercury exposure

    SciTech Connect

    Kobal, Alfred Bogomir Prezelj, Marija; Horvat, Milena; Krsnik, Mladen; Gibicar, Darija; Osredkar, Josko

    2008-05-15

    Many in vitro and in vivo studies have elucidated the interaction of inorganic mercury (Hg) and glutathione. However, human studies are limited. In this study, we investigated the potential effects of remote long-term intermittent occupational elemental Hg vapour (Hg{sup o}) exposure on erythrocyte glutathione levels and some antioxidative enzyme activities in ex-mercury miners in the period after exposure. The study included 49 ex-mercury miners divided into subgroups of 28 still active, Hg{sup o}-not-exposed miners and 21 elderly retired miners, and 41 controls, age-matched to the miners subgroup. The control workers were taken from 'mercury-free works'. Reduced glutathione (GSH) and oxidized disulphide glutathione (GSSG) concentrations in haemolysed erythrocytes were determined by capillary electrophoresis, while total glutathione (total GSH) and the GSH/GSSG ratio were calculated from the determined values. Catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR) activities in erythrocytes were measured using commercially available reagent kits, while urine Hg (U-Hg) concentrations were determined by cold vapour atomic absorption (CVAAS). No correlation of present U-Hg levels, GSH, GSSG, and antioxidative enzymes with remote occupational biological exposure indices were found. The mean CAT activity in miners and retired miners was significantly higher (p<0.05) than in the controls. No differences in mean GPx activity among the three groups were found, whereas the mean GR activity was significantly higher (p<0.05) in miners than in retired miners. The mean concentrations of GSH (mmol/g Hb) in miners (13.03{+-}3.71) were significantly higher (p<0.05) than in the control group (11.68{+-}2.66). No differences in mean total GSH, GSSG levels, and GSH/GSSG ratio between miners and controls were found. A positive correlation between GSSG and present U-Hg excretion (r=0.41, p=0.001) in the whole group of ex-mercury miners was observed. The

  9. Biocompatibility of Ti-alloys for long-term implantation.

    PubMed

    Abdel-Hady Gepreel, Mohamed; Niinomi, Mitsuo

    2013-04-01

    The design of new low-cost Ti-alloys with high biocompatibility for implant applications, using ubiquitous alloying elements in order to establish the strategic method for suppressing utilization of rare metals, is a challenge. To meet the demands of longer human life and implantation in younger patients, the development of novel metallic alloys for biomedical applications is aiming at providing structural materials with excellent chemical, mechanical and biological biocompatibility. It is, therefore, likely that the next generation of structural materials for replacing hard human tissue would be of those Ti-alloys that do not contain any of the cytotoxic elements, elements suspected of causing neurological disorders or elements that have allergic effect. Among the other mechanical properties, the low Young's modulus alloys have been given a special attention recently, in order to avoid the occurrence of stress shielding after implantation. Therefore, many Ti-alloys were developed consisting of biocompatible elements such as Ti, Zr, Nb, Mo, and Ta, and showed excellent mechanical properties including low Young's modulus. However, a recent attention was directed towards the development of low cost-alloys that have a minimum amount of the high melting point and high cost rare-earth elements such as Ta, Nb, Mo, and W. This comes with substituting these metals with the common low cost, low melting point and biocompatible metals such as Fe, Mn, Sn, and Si, while keeping excellent mechanical properties without deterioration. Therefore, the investigation of mechanical and biological biocompatibility of those low-cost Ti-alloys is highly recommended now lead towards commercial alloys with excellent biocompatibility for long-term implantation.

  10. Suppression of autophagy permits successful enzyme replacement therapy in a lysosomal storage disorder--murine Pompe disease.

    PubMed

    Raben, Nina; Schreiner, Cynthia; Baum, Rebecca; Takikita, Shoichi; Xu, Sengen; Xie, Tao; Myerowitz, Rachel; Komatsu, Masaaki; Van der Meulen, Jack H; Nagaraju, Kanneboyina; Ralston, Evelyn; Plotz, Paul H

    2010-11-01

    Autophagy, an intracellular system for delivering portions of cytoplasm and damaged organelles to lysosomes for degradation/recycling, plays a role in many physiological processes and is disturbed in many diseases. We recently provided evidence for the role of autophagy in Pompe disease, a lysosomal storage disorder in which acid alphaglucosidase, the enzyme involved in the breakdown of glycogen, is deficient or absent. Clinically the disease manifests as a cardiac and skeletal muscle myopathy. The current enzyme replacement therapy (ERT) clears lysosomal glycogen effectively from the heart but less so from skeletal muscle. In our Pompe model, the poor muscle response to therapy is associated with the presence of pools of autophagic debris. To clear the fibers of the autophagic debris, we have generated a Pompe model in which an autophagy gene, Atg7, is inactivated in muscle. Suppression of autophagy alone reduced the glycogen level by 50–60%. Following ERT, muscle glycogen was reduced to normal levels, an outcome not observed in Pompe mice with genetically intact autophagy. The suppression of autophagy, which has proven successful in the Pompe model, is a novel therapeutic approach that may be useful in other diseases with disturbed autophagy.

  11. Fabry disease and enzyme replacement therapy in classic patients with same mutation: different formulations--different outcome?

    PubMed

    Politei, J; Schenone, A B; Cabrera, G; Heguilen, R; Szlago, M

    2016-01-01

    We describe the results of the multidisciplinary evaluation in patients with Fabry disease and the same genetic mutation and their outcomes using different approved enzyme replacement therapy (ERT). We measured baseline data and serial results of neuropathic pain assessment and renal, cardiac and cerebrovascular functioning. Pain scale showed improvement in all male cases treated with agalsidasa beta. A mild improvement was detected in agalsidasa alfa-treated patients after 1 year with posterior increase. During the agalsidase beta shortage, two male patients were switched to agalsidasa alfa, after 1 year both cases presented an increase in scale values. Renal evolution showed a tendency toward a decrease in proteinuria in patients using agalsidase beta and worsening with agalsidase alfa. We found improvement in two females using agalsidase beta and no changes in the other cases regarding cardiac functioning. Brain magnetic resonance imaging (MRI) showed increase of white matter lesions in four patients. Improvement and stabilization in neuropathic pain, renal and cardiac functioning and brain MRI were found mainly in patients treated with agalsidase beta. Following the reported recommendations on reintroduction of agalsidase beta after the enzyme shortage, we decided to switch all patients to agalsidase beta.

  12. Suppression of autophagy permits successful enzyme replacement therapy in a lysosomal storage disorder—murine Pompe disease

    PubMed Central

    Takikita, Shoichi; Xu, Sengen; Xie, Tao; Myerowitz, Rachel; Komatsu, Masaaki; Van Der Meulen, Jack H; Nagaraju, Kanneboyina; Ralston, Evelyn; Plotz, Paul H

    2010-01-01

    Autophagy, an intracellular system for delivering portions of cytoplasm and damaged organelles to lysosomes for degradation/recycling, plays a role in many physiological processes and is disturbed in many diseases. We recently provided evidence for the role of autophagy in Pompe disease, a lysosomal storage disorder in which acid alpha-glucosidase, the enzyme involved in the breakdown of glycogen, is deficient or absent. Clinically the disease manifests as a cardiac and skeletal muscle myopathy. The current enzyme replacement therapy (ERT) clears lysosomal glycogen effectively from the heart but less so from skeletal muscle. In our Pompe model, the poor muscle response to therapy is associated with the presence of pools of autophagic debris. To clear the fibers of the autophagic debris, we have generated a Pompe model in which an autophagy gene, Atg7, is inactivated in muscle. Suppression of autophagy alone reduced the glycogen level by 50–60%. Following ERT, muscle glycogen was reduced to normal levels, an outcome not observed in Pompe mice with genetically intact autophagy. The suppression of autophagy, which has proven successful in the Pompe model, is a novel therapeutic approach that may be useful in other diseases with disturbed autophagy. PMID:20861693

  13. Enzyme replacement therapy started at birth improves outcome in difficult-to-treat organs in mucopolysaccharidosis I mice.

    PubMed

    Baldo, Guilherme; Mayer, Fabiana Q; Martinelli, Bárbara Z; de Carvalho, Talita G; Meyer, Fabiola S; de Oliveira, Patrícia G; Meurer, Luise; Tavares, Angela; Matte, Ursula; Giugliani, Roberto

    2013-05-01

    Since we previously observed that in patients with mucopolysaccharidosis (MPS) the storage of undegraded glycosaminoglycans (GAG) occurs from birth, in the present study we aimed to compare normal, untreated MPS I mice (knockout for alpha-l-iduronidase-IDUA), and MPS I mice treated with enzyme replacement therapy (ERT, Laronidase, 1.2mg/kg every 2 weeks) started from birth (ERT-neo) or from 2 months of age (ERT-ad). All mice were sacrificed at 6 months. Both treatments were equally effective in normalizing GAG levels in the viscera but had no detectable effect on the joint. Heart function was also improved with both treatments. On the other hand, mice treated from birth presented better outcomes in the difficult-to-treat aortas and heart valves. Surprisingly, both groups had improvements in behavior tests, and normalization of GAG levels in the brain and IDUA injection resulted in detectable levels of enzyme in the brain tissue 1h after administration. ERT-ad mice developed significantly more anti-IDUA-IgG antibodies, and mice that didn't develop antibodies had better performances in behavior tests, indicating that development of antibodies may reduce enzyme bioavailability. Our results suggest that ERT started from birth leads to better outcomes in the aorta and heart valves, as well as a reduction in antibody levels. Some poor vascularized organs, such as the joints, had partial or no benefit and ancillary therapies might be needed for patients. The results presented here support the idea that ERT started from birth leads to better treatment outcomes and should be considered whenever possible, a observation that gains relevance as newborn screening programs are being considered for MPS and other treatable lysosomal storage disorders.

  14. Long Term 1 Enhanced Surface Water Treatment Rule Documents

    EPA Pesticide Factsheets

    The Long Term 1 Enhanced Surface Water Treatment Rule (LT1ESWTR) builds on the requirements of the Surface Water Treatment Rule and specifies treatment requirements to address Cryptosporidium m and other microbial contaminants in public water systems.

  15. Long-term storage of bionanodevices by freezing and lyophilization.

    PubMed

    Seetharam, Raviraja; Wada, Yuuko; Ramachandran, Sujatha; Hess, Henry; Satir, Peter

    2006-09-01

    Successful long-term storage of a "smart dust" device integrating biomolecular motors and complex protein assemblies has been demonstrated using freezing or lyophilization, which implies that fabrication and application can be separated even for complex bionanodevices.

  16. Examining Long-Term Global Climate Change on the Web.

    ERIC Educational Resources Information Center

    Huntoon, Jacqueline E.; Ridky, Robert K.

    2002-01-01

    Describes a web-based, inquiry-oriented activity that enables students to examine long-term global climate change. Supports instruction in other topics such as population growth. (Contains 34 references.) (DDR)

  17. Long-term Outcomes of Childhood Onset Nephrotic Syndrome

    PubMed Central

    Hjorten, Rebecca; Anwar, Zohra; Reidy, Kimberly Jean

    2016-01-01

    There are limited studies on long-term outcomes of childhood onset nephrotic syndrome (NS). A majority of children with NS have steroid-sensitive nephrotic syndrome (SSNS). Steroid-resistant nephrotic syndrome (SRNS) is associated with a high risk of developing end-stage renal disease. Biomarkers and analysis of genetic mutations may provide new information for prognosis in SRNS. Frequently relapsing and steroid-dependent NS is associated with long-term complications, including dyslipidemia, cataracts, osteoporosis and fractures, obesity, impaired growth, and infertility. Long-term complications of SSNS are likely to be under-recognized. There remain many gaps in our knowledge of long-term outcomes of childhood NS, and further study is indicated. PMID:27252935

  18. Long-term Outcomes of Childhood Onset Nephrotic Syndrome.

    PubMed

    Hjorten, Rebecca; Anwar, Zohra; Reidy, Kimberly Jean

    2016-01-01

    There are limited studies on long-term outcomes of childhood onset nephrotic syndrome (NS). A majority of children with NS have steroid-sensitive nephrotic syndrome (SSNS). Steroid-resistant nephrotic syndrome (SRNS) is associated with a high risk of developing end-stage renal disease. Biomarkers and analysis of genetic mutations may provide new information for prognosis in SRNS. Frequently relapsing and steroid-dependent NS is associated with long-term complications, including dyslipidemia, cataracts, osteoporosis and fractures, obesity, impaired growth, and infertility. Long-term complications of SSNS are likely to be under-recognized. There remain many gaps in our knowledge of long-term outcomes of childhood NS, and further study is indicated.

  19. Long-Term Ecological Monitoring Field Sampling Plan for 2007

    SciTech Connect

    T. Haney R. VanHorn

    2007-07-31

    This field sampling plan describes the field investigations planned for the Long-Term Ecological Monitoring Project at the Idaho National Laboratory Site in 2007. This plan and the Quality Assurance Project Plan for Waste Area Groups 1, 2, 3, 4, 5, 6, 7, 10, and Removal Actions constitute the sampling and analysis plan supporting long-term ecological monitoring sampling in 2007. The data collected under this plan will become part of the long-term ecological monitoring data set that is being collected annually. The data will be used t determine the requirements for the subsequent long-term ecological monitoring. This plan guides the 2007 investigations, including sampling, quality assurance, quality control, analytical procedures, and data management. As such, this plan will help to ensure that the resulting monitoring data will be scientifically valid, defensible, and of known and acceptable quality.

  20. Long-term pharmacological treatment of generalized anxiety disorder.

    PubMed

    Mahe, V; Balogh, A

    2000-03-01

    Generalized anxiety disorder (GAD) is one of the most common anxiety disorders and has a poor prognosis, although it is often thought to be a minor complaint. This disorder has a chronic course of 5-15 years and longer. Long-term treatment with the commonly used benzodiazepines is controversial because of concerns over tolerance and dependence. We performed a thorough search of the literature for clinical trials of a duration of over 2 months conducted in patients with generalized anxiety disorder in order to identify any successful long-term treatment of this disorder. Only eight long-term reports of studies conducted in well-defined homogeneous groups of patients diagnosed with generalized anxiety disorder were found with the methodology of these studies presenting a number of limiting factors. The results are inconclusive and no reference drug could be identified. In addition, an adequate evaluation of the long-term treatment of GAD has not yet been performed.

  1. Earth's Long-Term Warming Trend, 1880-2015

    NASA Video Gallery

    This visualization illustrates Earth’s long-term warming trend, showing temperature changes from 1880 to 2015 as a rolling five-year average. Orange colors represent temperatures that are warmer th...

  2. Long-term monitoring for nanomedicine implants and drugs

    NASA Astrophysics Data System (ADS)

    Kendall, Michaela; Lynch, Iseult

    2016-03-01

    Increasing globalization means that traditional occupational epidemiological approaches may no longer apply, suggesting a need for an alternative model to assess the long-term impact of nanomaterial exposure on health.

  3. The Long Term Agroecosystem Research Network - Shared research strategy

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Agriculture faces tremendous challenges in meeting multiple societal goals, including a safe and plentiful food supply; climate change adaptation and mitigation; supplying sources of bioenergy; improving water, air, and soil quality; and maintaining biodiversity. The Long Term Agroecosystem Research...

  4. Biogeochemistry: Long-term effects of permafrost thaw

    NASA Astrophysics Data System (ADS)

    Zona, Donatella

    2016-09-01

    Carbon emissions from the Arctic tundra could increase drastically as global warming thaws permafrost. Clues now obtained about the long-term effects of such thawing on carbon dioxide emissions highlight the need for more data.

  5. Lead and Copper Rule Long-Term Revisions

    EPA Pesticide Factsheets

    The goal for the Lead and Copper Rule (LCR) Long-Term Revisions is to improve public health protection provided by the by making substantive changes based on topics that were identified in the 2004 National Review.

  6. The market for long-term care services.

    PubMed

    Grabowski, David C

    2008-01-01

    Although a large literature has established the importance of market and regulatory forces within the long-term care sector, current research in this field is limited by a series of data, measurement, and methodological issues. This paper provides a comprehensive review of these issues with an emphasis on identifying initiatives that will increase the volume and quality of long-term care research. Recommendations include: the construction of standard measures of long-term care market boundaries, the broader dissemination of market and regulatory data, the linkage of survey-based data with market measures, the encouragement of further market-based studies of noninstitutional long-term care settings, and the standardization of Medicaid cost data.

  7. Finance issue brief: long-term care insurance.

    PubMed

    Mintz, E

    1999-08-03

    States are turning their attention to long-term care insurance, spurred by a 1996 federal law and an increasingly urgent need for more options to finance the care of their rapidly growing elderly populations.

  8. Long-term care: a substantive factor in financial planning.

    PubMed

    Willis, D A

    2000-01-01

    More than 50 percent of women will enter a nursing home at some point in their lives. About one-third of men living to age 65 will also need nursing home care. Planning for long-term care is even more important since Medicare covers very little of the cost of such care. The Indiana Partnership Plan is one program designed to help fund the long-term care costs while allowing individuals protect other financial assets.

  9. Long-term effects of sludge application to land

    SciTech Connect

    Geertsema, W.S. ); Knocke, W.R.; Novak, J.T.; Dove, D. . Dept. of Civil Engineering)

    1994-11-01

    The purpose of this study was to evaluate the long-term environmental effects of applying alum sludge to land. Investigations at the original field site included soil analysis, soil water monitoring, groundwater monitoring, and analysis of tissues from pine needles. No long-term (30 months) effects were observed, and the authors conclude that alum coagulant sludges can be applied to forest lands at loading rates of at least 1.5 to 2.5% by dry weight without adverse effect.

  10. The Long-Term Behavior of Known & Suspected Novae

    NASA Astrophysics Data System (ADS)

    Pagnotta, A.

    2017-03-01

    The long-term evolution of classical novae is poorly understood. I discuss here an in-progress project designed to better understand the post-eruption behavior of novae and test the Hibernation theory of nova evolution. The project has two main parts: (1) a modern survey of Galactic nova magnitudes, and (2) construction of long-term light curves using primarily archival photographic plates.

  11. Long-term Morphological Modeling at Coastal Inlets

    DTIC Science & Technology

    2015-05-15

    The CMS consists of an integrated numerical modeling system for simulating wave, current, water levels, sediment transport and morphology change ...In order to quantify the physical effects of long-term, regional climactic changes in the environment, numerical morphodynamic models must be able...components of long-term, regional climactic changes in the environment. Numerical morphodynamic models must be able to reproduce the known generic

  12. Maintaining Engagement in Long-term Interventions with Relational Agents

    PubMed Central

    Bickmore, Timothy; Schulman, Daniel; Yin, Langxuan

    2011-01-01

    We discuss issues in designing virtual humans for applications which require long-term voluntary use, and the problem of maintaining engagement with users over time. Concepts and theories related to engagement from a variety of disciplines are reviewed. We describe a platform for conducting studies into long-term interactions between humans and virtual agents, and present the results of two longitudinal randomized controlled experiments in which the effect of manipulations of agent behavior on user engagement was assessed. PMID:21318052

  13. Fast and long term lipid droplet tracking with CARS microscopy.

    PubMed

    Jüngst, Christian; Winterhalder, Martin J; Zumbusch, Andreas

    2011-06-01

    Photobleaching of organic fluorophores commonly used in fluorescence microscopy puts a limit to the number of images which can be acquired. Label-free imaging techniques therefore offer advantages both for rapid image acquisition and for long-term observations. CARS microscopy is a label-free imaging technique offering molecule specific contrast. Here we demonstrate that CARS microscopy allows video-rate tracking of intracellular transport of lipid droplets, but also continuous long-term observation of cells over several hours.

  14. Influenza in long-term care facilities: preventable, detectable, treatable.

    PubMed

    Mossad, Sherif B

    2009-09-01

    Influenza in long-term care facilities is an ever more challenging problem. Vaccination of residents and health care workers is the most important preventive measure. Although vaccine efficacy has been questioned, the preponderance of data favors vaccination. Antiviral resistance complicates postexposure chemoprophylaxis and treatment. Factors that limit the choice of antiviral agents in this patient population include limited vaccine supplies and impaired dexterity and confusion in long-term care residents.

  15. Motivating the paraprofessional in long-term care.

    PubMed

    Vance, A; Davidhizar, R

    1997-06-01

    Motivating the paraprofessional employee in the long-term care setting is one of the biggest challenges facing health care supervisors. Unlike their counterparts in industry, whose work may produce tangible results and rewards, long-term care professionals often must face patients who show little or no change over time. Supervisors must have understanding and knowledge of motivational techniques that will involve and challenge paraprofessionals.

  16. Enzyme

    MedlinePlus

    Enzymes are complex proteins that cause a specific chemical change in all parts of the body. For ... use them. Blood clotting is another example of enzymes at work. Enzymes are needed for all body ...

  17. 3D printed cellular solid outperforms traditional stochastic foam in long-term mechanical response

    NASA Astrophysics Data System (ADS)

    Maiti, A.; Small, W.; Lewicki, J. P.; Weisgraber, T. H.; Duoss, E. B.; Chinn, S. C.; Pearson, M. A.; Spadaccini, C. M.; Maxwell, R. S.; Wilson, T. S.

    2016-04-01

    3D printing of polymeric foams by direct-ink-write is a recent technological breakthrough that enables the creation of versatile compressible solids with programmable microstructure, customizable shapes, and tunable mechanical response including negative elastic modulus. However, in many applications the success of these 3D printed materials as a viable replacement for traditional stochastic foams critically depends on their mechanical performance and micro-architectural stability while deployed under long-term mechanical strain. To predict the long-term performance of the two types of foams we employed multi-year-long accelerated aging studies under compressive strain followed by a time-temperature-superposition analysis using a minimum-arc-length-based algorithm. The resulting master curves predict superior long-term performance of the 3D printed foam in terms of two different metrics, i.e., compression set and load retention. To gain deeper understanding, we imaged the microstructure of both foams using X-ray computed tomography, and performed finite-element analysis of the mechanical response within these microstructures. This indicates a wider stress variation in the stochastic foam with points of more extreme local stress as compared to the 3D printed material, which might explain the latter’s improved long-term stability and mechanical performance.

  18. 3D printed cellular solid outperforms traditional stochastic foam in long-term mechanical response

    DOE PAGES

    Maiti, A.; Small, W.; Lewicki, J.; ...

    2016-04-27

    3D printing of polymeric foams by direct-ink-write is a recent technological breakthrough that enables the creation of versatile compressible solids with programmable microstructure, customizable shapes, and tunable mechanical response including negative elastic modulus. However, in many applications the success of these 3D printed materials as a viable replacement for traditional stochastic foams critically depends on their mechanical performance and micro-architectural stability while deployed under long-term mechanical strain. To predict the long-term performance of the two types of foams we employed multi-year-long accelerated aging studies under compressive strain followed by a time-temperature-superposition analysis using a minimum-arc-length-based algorithm. The resulting master curvesmore » predict superior long-term performance of the 3D printed foam in terms of two different metrics, i.e., compression set and load retention. To gain deeper understanding, we imaged the microstructure of both foams using X-ray computed tomography, and performed finite-element analysis of the mechanical response within these microstructures. As a result, this indicates a wider stress variation in the stochastic foam with points of more extreme local stress as compared to the 3D printed material, which might explain the latter’s improved long-term stability and mechanical performance.« less

  19. 3D printed cellular solid outperforms traditional stochastic foam in long-term mechanical response

    SciTech Connect

    Maiti, A.; Small, W.; Lewicki, J.; Weisgraber, T. H.; Duoss, E. B.; Chinn, S. C.; Pearson, M. A.; Spadaccini, C. M.; Maxwell, R. S.; Wilson, T. S.

    2016-04-27

    3D printing of polymeric foams by direct-ink-write is a recent technological breakthrough that enables the creation of versatile compressible solids with programmable microstructure, customizable shapes, and tunable mechanical response including negative elastic modulus. However, in many applications the success of these 3D printed materials as a viable replacement for traditional stochastic foams critically depends on their mechanical performance and micro-architectural stability while deployed under long-term mechanical strain. To predict the long-term performance of the two types of foams we employed multi-year-long accelerated aging studies under compressive strain followed by a time-temperature-superposition analysis using a minimum-arc-length-based algorithm. The resulting master curves predict superior long-term performance of the 3D printed foam in terms of two different metrics, i.e., compression set and load retention. To gain deeper understanding, we imaged the microstructure of both foams using X-ray computed tomography, and performed finite-element analysis of the mechanical response within these microstructures. As a result, this indicates a wider stress variation in the stochastic foam with points of more extreme local stress as compared to the 3D printed material, which might explain the latter’s improved long-term stability and mechanical performance.

  20. 3D printed cellular solid outperforms traditional stochastic foam in long-term mechanical response

    PubMed Central

    Maiti, A.; Small, W.; Lewicki, J. P.; Weisgraber, T. H.; Duoss, E. B.; Chinn, S. C.; Pearson, M. A.; Spadaccini, C. M.; Maxwell, R. S.; Wilson, T. S.

    2016-01-01

    3D printing of polymeric foams by direct-ink-write is a recent technological breakthrough that enables the creation of versatile compressible solids with programmable microstructure, customizable shapes, and tunable mechanical response including negative elastic modulus. However, in many applications the success of these 3D printed materials as a viable replacement for traditional stochastic foams critically depends on their mechanical performance and micro-architectural stability while deployed under long-term mechanical strain. To predict the long-term performance of the two types of foams we employed multi-year-long accelerated aging studies under compressive strain followed by a time-temperature-superposition analysis using a minimum-arc-length-based algorithm. The resulting master curves predict superior long-term performance of the 3D printed foam in terms of two different metrics, i.e., compression set and load retention. To gain deeper understanding, we imaged the microstructure of both foams using X-ray computed tomography, and performed finite-element analysis of the mechanical response within these microstructures. This indicates a wider stress variation in the stochastic foam with points of more extreme local stress as compared to the 3D printed material, which might explain the latter’s improved long-term stability and mechanical performance. PMID:27117858

  1. Planning long-term vegetation studies at landscape scales

    USGS Publications Warehouse

    Stohlgren, Thomas J.

    1995-01-01

    Long-term ecological research is receiving more attention now than ever before. Two recent books, Long-term Studies in Ecology: Approaches and Alternatives, edited by Gene Likens (1989), and Long-term Ecological Research: An International Perspective, edited by Paul Risser (1991), prompt the question, “Why are these books so thin?” Except for data from paleoecological, retrospective studies (see below), there are exceptionally few long-term data sets in terrestrial ecology (Strayer et al. 1986; Tilman 1989; this volume). In a sample of 749 papers published in Ecology, Tilman (1989) found that only 1.7% of the studies lasted at least five field seasons. Only one chapter in each of the review books dealt specifically with expanding both the temporal and the spatial scales of ecological research (Berkowitz et al. 1989; Magnuson et al. 1991). Judging by the growing number of landscape-scale long-term studies, however, such as the Long-Term Ecological Research (LTER) Program (Callahan 1991), the U.S. Environmental Protection Agency’s Environmental Monitoring and Assessment Program (EMAP; Palmer et al. 1991), the U.S. Army’s Land Condition-Trend Analysis (LCTA) Program (Diersing et al. 1992), and various agencies’ global change research programs (CEES 1993), there is a growing interest to expand ecological research both temporally and spatially.

  2. Long-term treatment with tetrahydrobiopterin in phenylketonuria: treatment strategies and prediction of long-term responders.

    PubMed

    Hennermann, Julia B; Roloff, Sylvia; Gebauer, Christine; Vetter, Barbara; von Arnim-Baas, Annabel; Mönch, Eberhard

    2012-11-01

    Tetrahydrobiopterin (BH4) responsive phenylketonuria has been described more than 10 years ago. However, criteria for the identification of long-term BH4 responsive patients are not yet established. 116 patients with phenylketonuria, aged 4-18 years, were screened for potential long-term BH4 responsiveness by at least two of the following criteria: positive neonatal BH4 loading test, putative BH4 responsive genotype, and/or milder phenotype. Patients had to be on permanent dietary treatment. 23 patients fulfilled these criteria and were tested for long-term BH4 responsiveness: 18/23 were long-term BH4 responsive, 5/23 were not. On long-term BH4 treatment over a period of 48 ± 27 months in a dose of 14.9 ± 3.3mg/kg/day phenylalanine tolerance was increased from 452 ± 201 mg/day to 1593 ± 647 mg/day, corresponding to a mean increase of 1141 ± 528 mg/day. Dietary phenylalanine intake was increased stepwise according to a clear defined protocol. In 8/18 patients, diet was completely liberalized; 10/18 patients still received phenylalanine-free amino acid formula with 0.63 ± 0.23 g/kg/day. The most predictive value for long-term BH4 responsiveness was the combination of pretreatment phenylalanine of < 1200 μmol/L, pretreatment phenylalanine/tyrosine ratio of <15, phenylalanine/tyrosine ratio of <15 on treatment, phenylalanine tolerance of >20mg/kg/day at age 3 years, positive neonatal BH4 loading, and at least one putative BH4 responsive mutation (p = 0.00024). Our data show that long-term BH4 responsiveness may be predicted already during neonatal period by determining maximum pretreatment phenylalanine and phenylalanine/tyrosine concentrations, neonatal BH4 loading and PAH genotype. A clear defined protocol is necessary to install long-term BH4 treatment.

  3. Nicotine uses neuron-glia communication to enhance hippocampal synaptic transmission and long-term memory.

    PubMed

    López-Hidalgo, Mónica; Salgado-Puga, Karla; Alvarado-Martínez, Reynaldo; Medina, Andrea Cristina; Prado-Alcalá, Roberto A; García-Colunga, Jesús

    2012-01-01

    Nicotine enhances synaptic transmission and facilitates long-term memory. Now it is known that bi-directional glia-neuron interactions play important roles in the physiology of the brain. However, the involvement of glial cells in the effects of nicotine has not been considered until now. In particular, the gliotransmitter D-serine, an endogenous co-agonist of NMDA receptors, enables different types of synaptic plasticity and memory in the hippocampus. Here, we report that hippocampal long-term synaptic plasticity induced by nicotine was annulled by an enzyme that degrades endogenous D-serine, or by an NMDA receptor antagonist that acts at the D-serine binding site. Accordingly, both effects of nicotine: the enhancement of synaptic transmission and facilitation of long-term memory were eliminated by impairing glial cells with fluoroacetate, and were restored with exogenous D-serine. Together, these results show that glial D-serine is essential for the long-term effects of nicotine on synaptic plasticity and memory, and they highlight the roles of glial cells as key participants in brain functions.

  4. Long-term treatment of major depressive disorder with paroxetine.

    PubMed

    Duboff, E A

    1993-12-01

    Recurrent unipolar depression is a common, but undertreated disorder. Many patients require long-term maintenance therapy, and full doses of antidepressant agents may be preferred for the prevention of relapse. We report results of a 1-year, multicenter, open-label study of paroxetine (10 to 50 mg/day) in 433 patients with major depressive disorder, with additional data from 110 patients who entered a long-term extension of the study. The primary measures of efficacy were the Hamilton Rating Scale for Depression (HAM-D) total and Clinical Global Impression (CGI) severity of illness scores. During the first 6 weeks of therapy, the mean HAM-D total declined approximately 50% (from 27.9 to 13.5), with continued improvement, at an attenuated rate, throughout the first year. At the end of 1 year, the mean HAM-D total was 6.9. Similarly, the CGI severity of illness score declined from 4.6 at baseline to 2.8 at week 6 and to 1.7 at the end of 1 year. Remission was maintained in the population that entered the long-term extension, with mean HAM-D total and CGI severity of illness scores of 6.4 and 1.8, respectively, after 2.5 years, and 4.2 and 1.3 after 4 years. The most common adverse events reported during long-term treatment with paroxetine were somnolence, nausea, headache, and sweating. Pharmacokinetic analysis showed no clear correlation between the concentrations of paroxetine in plasma and either clinical efficacy or tolerability. There was no increased drug accumulation during long-term treatment. Side effects tended to occur early during therapy; and no new side effects emerged during the long-term extension. These results suggest that paroxetine is effective and well tolerated in the long-term treatment of depression.

  5. Production of glucocerebrosidase with terminal mannose glycans for enzyme replacement therapy of Gaucher's disease using a plant cell system.

    PubMed

    Shaaltiel, Yoseph; Bartfeld, Daniel; Hashmueli, Sharon; Baum, Gideon; Brill-Almon, Einat; Galili, Gad; Dym, Orly; Boldin-Adamsky, Swetlana A; Silman, Israel; Sussman, Joel L; Futerman, Anthony H; Aviezer, David

    2007-09-01

    Gaucher's disease, a lysosomal storage disorder caused by mutations in the gene encoding glucocerebrosidase (GCD), is currently treated by enzyme replacement therapy using recombinant GCD (Cerezyme) expressed in Chinese hamster ovary (CHO) cells. As complex glycans in mammalian cells do not terminate in mannose residues, which are essential for the biological uptake of GCD via macrophage mannose receptors in human patients with Gaucher's disease, an in vitro glycan modification is required in order to expose the mannose residues on the glycans of Cerezyme. In this report, the production of a recombinant human GCD in a carrot cell suspension culture is described. The recombinant plant-derived GCD (prGCD) is targeted to the storage vacuoles, using a plant-specific C-terminal sorting signal. Notably, the recombinant human GCD expressed in the carrot cells naturally contains terminal mannose residues on its complex glycans, apparently as a result of the activity of a special vacuolar enzyme that modifies complex glycans. Hence, the plant-produced recombinant human GCD does not require exposure of mannose residues in vitro, which is a requirement for the production of Cerezyme. prGCD also displays a level of biological activity similar to that of Cerezyme produced in CHO cells, as well as a highly homologous high-resolution three-dimensional structure, determined by X-ray crystallography. A single-dose toxicity study with prGCD in mice demonstrated the absence of treatment-related adverse reactions or clinical findings, indicating the potential safety of prGCD. prGCD is currently undergoing clinical studies, and may offer a new and alternative therapeutic option for Gaucher's disease.

  6. [Reform of long-term care in the Netherlands: solidarity maintained?].

    PubMed

    van der Aa, Maartje J; Evers, Silvia M A A; Klosse, Saskia; Maarse, J A M Hans

    2014-01-01

    The reform of long-term care (LTC) in the Netherlands is a much debated topic. The reform essentially comes down to a shift in healthcare claims and a cutback. As of 1 January 2015, the Long-Term Care Act (WLZ) shall replace the Exceptional Medical Expenses Act (AWBZ). In doing so, parts of the AWBZ will shift to the Health Care Insurance Act (ZVW) and the renewed Social Support Act (WMO 2015), which will be carried out by municipalities. This is a significant change: whereas the AWBZ provides a right to care, the WMO commands delivery of tailor-made support. Care that falls under the WMO is only awarded if the capacity of persons seeking care, among others their financial resources and social network, are insufficient. Higher contributions than in the AWBZ may also be requested. These developments influence the experienced level of solidarity.

  7. 9975 SHIPPING PACKAGE PERFORMANCE OF ALTERNATE MATERIALS FOR LONG-TERM STORAGE APPLICATION

    SciTech Connect

    Skidmore, E.; Hoffman, E.; Daugherty, W.

    2010-02-24

    The Model 9975 shipping package specifies the materials of construction for its various components. With the loss of availability of material for two components (cane fiberboard overpack and Viton{reg_sign} GLT O-rings), alternate materials of construction were identified and approved for use for transport (softwood fiberboard and Viton{reg_sign} GLT-S O-rings). As these shipping packages are part of a long-term storage configuration at the Savannah River Site, additional testing is in progress to verify satisfactory long-term performance of the alternate materials under storage conditions. The test results to date can be compared to comparable results on the original materials of construction to draw preliminary conclusions on the performance of the replacement materials.

  8. Child maltreatment: pathway to chronic and long-term conditions?

    PubMed

    Taylor, Julie; Bradbury-Jones, Caroline; Lazenbatt, Anne; Soliman, Francesca

    2016-09-01

    The manifesto Start Well, Live Better by the UK Faculty of Public Health (Start Well, Live Better-A Manifesto for the Public's Health. London: UK Faculty of Public Health, 2014) sets out 12 compelling priorities for the protection of people's health. The focus of this document is preventative, calling for a comprehensive strategy to target a wide-ranging set of challenges to public health; however, it fails to mention child maltreatment and its negative impact on long-term health outcomes. In this article, we explore the long-term negative consequences of child maltreatment and how these can be conceptually aligned with four different characteristics of long-term health conditions. We suggest that situating child maltreatment within a long-term conditions framework could have significant advantages and implications for practice, policy and research, by strengthening a commitment across disciplines to apply evidence-based principles linked with policy and evaluation and recognizing the chronic effects of maltreatment to concentrate public, professional and government awareness of the extent and impact of the issue. We argue that a public health approach is the most effective way of focusing preventative efforts on the long-term sequelae of child maltreatment and to foster cooperation in promoting children's rights to grow and develop in a safe and caring environment free from violence and abuse.

  9. Characteristics of Long-Term Survivors of Epithelial Ovarian Cancer

    PubMed Central

    Cress, Rosemary D.; Chen, Yingjia S.; Morris, Cyllene R.; Petersen, Megan; Leiserowitz, Gary S.

    2015-01-01

    Objective To identify characteristics associated with long-term survival forepithelial ovarian cancer patients using the California Cancer Registry. Methods A descriptive analysis of survival of all California residents diagnosed with epithelial ovarian cancer between 1994 and 2001 was conducted using patients identified through the cancer registry with follow up through 2011. Characteristics of the patients who survived more than 10 years (long-term survivors) were compared to three other cohorts: patients who survived less than 2 years, those who survived at least 2 but no more than 5 years, and those who survived at least 5 but no more than 10 years. Results A total of 3,582 out of 11,541 (31% CI=30.2%, 31.8%) of the patients survived more than 10 years. Younger age, early stage, low-grade, and non-serous histology were significant predictors of long-term survival, but long-term survivors also included women with high-risk cancer. Conclusion Long-term survival is not unusual in patients with epithelial ovarian cancer, even in those with high-risk disease. Many of the prognostic factors are well known, but it remains to be determined why some patients with advanced stage high-grade cancers survive longer than others with the same histology. These findings are important for patient counseling. PMID:26244529

  10. Method for Water Management Considering Long-term Probabilistic Forecasts

    NASA Astrophysics Data System (ADS)

    Hwang, J.; Kang, J.; Suh, A. S.

    2015-12-01

    This research is aimed at predicting the monthly inflow of the Andong-dam basin in South Korea using long-term probabilistic forecasts to apply long-term forecasts to water management. Forecasted Cumulative Distribution Functions (CDFs) of monthly precipitation are plotted by combining the range of monthly precipitation based on proper Probability Density Function (PDF) in past data with probabilistic forecasts in each category. Ensembles of inflow are estimated by entering generated ensembles of precipitation based on the CDFs into the 'abcd' water budget model. The bias and RMSE between averages in past data and observed inflow are compared to them in forecasted ensembles. In our results, the bias and RMSE of average precipitation in the forecasted ensemble are bigger than in past data, whereas the average inflow in the forecasted ensemble is smaller than in past data. This result could be used for reference data to apply long-term forecasts to water management, because of the limit in the number of forecasted data for verification and differences between the Andong-dam basin and the forecasted regions. This research has significance by suggesting a method of applying probabilistic information in climate variables from long-term forecasts to water management in Korea. Original data of a climate model, which produces long-term probabilistic forecasts should be verified directly as input data of a water budget model in the future, so that a more scientific response in water management against uncertainty of climate change could be reached.

  11. Common Calibration Source for Monitoring Long-term Ozone Trends

    NASA Technical Reports Server (NTRS)

    Kowalewski, Matthew

    2004-01-01

    Accurate long-term satellite measurements are crucial for monitoring the recovery of the ozone layer. The slow pace of the recovery and limited lifetimes of satellite monitoring instruments demands that datasets from multiple observation systems be combined to provide the long-term accuracy needed. A fundamental component of accurately monitoring long-term trends is the calibration of these various instruments. NASA s Radiometric Calibration and Development Facility at the Goddard Space Flight Center has provided resources to minimize calibration biases between multiple instruments through the use of a common calibration source and standardized procedures traceable to national standards. The Facility s 50 cm barium sulfate integrating sphere has been used as a common calibration source for both US and international satellite instruments, including the Total Ozone Mapping Spectrometer (TOMS), Solar Backscatter Ultraviolet 2 (SBUV/2) instruments, Shuttle SBUV (SSBUV), Ozone Mapping Instrument (OMI), Global Ozone Monitoring Experiment (GOME) (ESA), Scanning Imaging SpectroMeter for Atmospheric ChartographY (SCIAMACHY) (ESA), and others. We will discuss the advantages of using a common calibration source and its effects on long-term ozone data sets. In addition, sphere calibration results from various instruments will be presented to demonstrate the accuracy of the long-term characterization of the source itself.

  12. Long-Term Stewardship Program Science and Technology Requirements

    SciTech Connect

    Joan McDonald

    2002-09-01

    Many of the United States’ hazardous and radioactively contaminated waste sites will not be sufficiently remediated to allow unrestricted land use because funding and technology limitations preclude cleanup to pristine conditions. This means that after cleanup is completed, the Department of Energy will have long-term stewardship responsibilities to monitor and safeguard more than 100 sites that still contain residual contamination. Long-term stewardship encompasses all physical and institutional controls, institutions, information, and other mechanisms required to protect human health and the environment from the hazards remaining. The Department of Energy Long-Term Stewardship National Program is in the early stages of development, so considerable planning is still required to identify all the specific roles and responsibilities, policies, and activities needed over the next few years to support the program’s mission. The Idaho National Engineering and Environmental Laboratory was tasked with leading the development of Science and Technology within the Long-Term Stewardship National Program. As part of that role, a task was undertaken to identify the existing science and technology related requirements, identify gaps and conflicts that exist, and make recommendations to the Department of Energy for future requirements related to science and technology requirements for long-term stewardship. This work is summarized in this document.

  13. Epilepsy-related long-term amnesia: anatomical perspectives.

    PubMed

    Butler, Chris; Kapur, Narinder; Zeman, Adam; Weller, Roy; Connelly, Alan

    2012-11-01

    There are few clues as to the neural basis of selective long-term amnesia. We report group and single-case data to shed light on this issue. In a group study of patients with transient epileptic amnesia, there were no significant correlations between volumetric measures of the hippocampus and indices of accelerated long-term forgetting or longer-term autobiographical memory loss. Post-mortem investigations in a patient with temporal lobe epilepsy who showed accelerated long-term forgetting, together with a degree of autobiographical memory loss, yielded evidence of neuronal loss and gliosis in regions of both the right and the left hippocampus. Neuronal loss and gliosis were more evident in anterior than posterior hippocampus. These results indicate that the unusual forms of long-term forgetting seen in some patients with temporal lobe epilepsy have no gross anatomical correlate. The findings leave open the possibilities that subtle structural damage or subtle functional disturbance, perhaps in the form of subclinical epileptiform activity, underly epilepsy-related long-term amnesia.

  14. The relationship between interannual and long-term cloud feedbacks

    DOE PAGES

    Zhou, Chen; Zelinka, Mark D.; Dessler, Andrew E.; ...

    2015-12-11

    The analyses of Coupled Model Intercomparison Project phase 5 simulations suggest that climate models with more positive cloud feedback in response to interannual climate fluctuations also have more positive cloud feedback in response to long-term global warming. Ensemble mean vertical profiles of cloud change in response to interannual and long-term surface warming are similar, and the ensemble mean cloud feedback is positive on both timescales. However, the average long-term cloud feedback is smaller than the interannual cloud feedback, likely due to differences in surface warming pattern on the two timescales. Low cloud cover (LCC) change in response to interannual andmore » long-term global surface warming is found to be well correlated across models and explains over half of the covariance between interannual and long-term cloud feedback. In conclusion, the intermodel correlation of LCC across timescales likely results from model-specific sensitivities of LCC to sea surface warming.« less

  15. An Exotic Long-Term Pattern in Stock Price Dynamics

    PubMed Central

    Wei, Jianrong; Huang, Jiping

    2012-01-01

    Background To accurately predict the movement of stock prices is always of both academic importance and practical value. So far, a lot of research has been reported to help understand the behavior of stock prices. However, some of the existing theories tend to render us the belief that the time series of stock prices are unpredictable on a long-term timescale. The question arises whether the long-term predictability exists in stock price dynamics. Methodology/Principal Findings In this work, we analyze the price reversals in the US stock market and the Chinese stock market on the basis of a renormalization method. The price reversals are divided into two types: retracements (the downward trends after upward trends) and rebounds (the upward trends after downward trends), of which the intensities are described by dimensionless quantities, and , respectively. We reveal that for both mature and emerging markets, the distribution of either retracements or rebounds shows two characteristic values, 0.335 and 0.665, both of which are robust over the long term. Conclusions/Significance The methodology presented here provides a way to quantify the stock price reversals. Our findings strongly support the existence of the long-term predictability in stock price dynamics, and may offer a hint on how to predict the long-term movement of stock prices. PMID:23284734

  16. Long-term greenhouse gas measurements from aircraft

    NASA Astrophysics Data System (ADS)

    Karion, A.; Sweeney, C.; Wolter, S.; Newberger, T.; Chen, H.; Andrews, A.; Kofler, J.; Neff, D.; Tans, P.

    2012-10-01

    In March 2009 the NOAA/ESRL/GMD Carbon Cycle and Greenhouse Gases Group collaborated with the US Coast Guard (USCG) to establish the Alaska Coast Guard (ACG) sampling site, a unique addition to NOAA's atmospheric monitoring network. This collaboration takes advantage of USCG bi-weekly Arctic Domain Awareness (ADA) flights, conducted with Hercules C-130 aircraft from March to November each year. NOAA has installed window-replacement inlet plates on two USCG C-130 aircraft and deploys a pallet with NOAA instrumentation on each ADA flight. Flights typically last 8 h and cover a very large area, traveling from Kodiak, AK in the south up to Barrow, AK in the north, and making altitude profiles near the coast as well as in the interior. NOAA instrumentation on each flight includes: a flask sampling system, a continuous CO2/CH4/CO/H2O analyzer, a continuous ozone analyzer, and an ambient temperature and humidity sensor. GPS time and location from the aircraft's navigation system are also collected. Air samples collected in flight are analyzed at NOAA/ESRL for the major greenhouse gases and a variety of halocarbons and hydrocarbons that influence climate, stratospheric ozone, and air quality. Instruments on this aircraft are designed and deployed to be able to collect air samples and data autonomously, so that NOAA personnel visit the site only for installation at the beginning of each season. We present an assessment of the cavity ring-down spectroscopy (CRDS) CO2/CH4/CO/H2O analyzer performance operating on an aircraft over a three-year period. We describe the overall system for making accurate greenhouse gas measurements using a CRDS analyzer on an aircraft with minimal operator interaction. Short and long-term stability of the CRDS analyzer over a seven-month deployment period is better than 0.15 ppm, 2 ppb, and 5 ppb for CO2, CH4, CO respectively, considering differences of on-board reference tank measurements from a laboratory calibration performed prior to

  17. Long-term fate of neural precursor cells following transplantation into developing and adult CNS.

    PubMed

    Lepore, A C; Neuhuber, B; Connors, T M; Han, S S W; Liu, Y; Daniels, M P; Rao, M S; Fischer, I

    2006-05-12

    Successful strategies for transplantation of neural precursor cells for replacement of lost or dysfunctional CNS cells require long-term survival of grafted cells and integration with the host system, potentially for the life of the recipient. It is also important to demonstrate that transplants do not result in adverse outcomes. Few studies have examined the long-term properties of transplanted neural precursor cells in the CNS, particularly in non-neurogenic regions of the adult. The aim of the present study was to extensively characterize the fate of defined populations of neural precursor cells following transplantation into the developing and adult CNS (brain and spinal cord) for up to 15 months, including integration of graft-derived neurons with the host. Specifically, we employed neuronal-restricted precursors and glial-restricted precursors, which represent neural precursor cells with lineage restrictions for neuronal and glial fate, respectively. Transplanted cells were prepared from embryonic day-13.5 fetal spinal cord of transgenic donor rats that express the marker gene human placental alkaline phosphatase to achieve stable and reliable graft tracking. We found that in both developing and adult CNS grafted cells showed long-term survival, morphological maturation, extensive distribution and differentiation into all mature CNS cell types (neurons, astrocytes and oligodendrocytes). Graft-derived neurons also formed synapses, as identified by electron microscopy, suggesting that transplanted neural precursor cells integrated with adult CNS. Furthermore, grafts did not result in any apparent deleterious outcomes. We did not detect tumor formation, cells did not localize to unwanted locations and no pronounced immune response was present at the graft sites. The long-term stability of neuronal-restricted precursors and glial-restricted precursors and the lack of adverse effects suggest that transplantation of lineage-restricted neural precursor cells can

  18. Plant-based oral delivery of β-glucocerebrosidase as an enzyme replacement therapy for Gaucher's disease.

    PubMed

    Shaaltiel, Yoseph; Gingis-Velitski, Svetlana; Tzaban, Salit; Fiks, Nadia; Tekoah, Yoram; Aviezer, David

    2015-10-01

    Gaucher's disease (GD), a lysosomal storage disorder caused by mutations in the gene encoding glucocerebrosidase (GCD), is currently treated by enzyme replacement therapy (ERT) using recombinant GCD that is administered intravenously every 2 weeks. However, intravenous administration includes discomfort or pain and might cause local and systemic infections that may lead to low patient compliance. An orally administered drug has the potential to alleviate these problems. In this study, we describe the potential use of plant cells as a vehicle for the oral delivery of recombinant human GCD (prGCD) expressed in carrot cells. The in vitro results demonstrate that the plant cells protect the recombinant protein in the gastric fluids and may enable absorption into the blood. Feeding experiments, with rat and pig as model animals, using carrot cells containing prGCD, show that active recombinant prGCD was found in the digestive tract and blood system and reached both, liver and spleen, the target organs in GD. These results demonstrate that the oral administration of proteins encapsulated in plant cells is feasible. Specifically, carrot cells containing recombinant human prGCD can be used as an oral delivery system and are a feasible alternative to intravenous administration of ERT for GD.

  19. Effect of aerobic and resistance exercise training on late-onset Pompe disease patients receiving enzyme replacement therapy.

    PubMed

    Terzis, Gerasimos; Dimopoulos, Filippos; Papadimas, George K; Papadopoulos, Constantinos; Spengos, Konstantinos; Fatouros, Ioannis; Kavouras, Stavros A; Manta, Panagiota

    2011-11-01

    Pompe disease is a rare autosomal recessive disorder characterized by the deficiency of acid α-glycosidase resulting in lysosomal accumulation of glycogen. The late-onset disease form is characterized by progressive skeletal and respiratory muscle dysfunction. In addition to the recently introduced enzyme replacement therapy (ERT), treatments such as protein-enriched diet and exercise training have been proposed, although little is known about their effectiveness on the physical condition of such patients. Aim of the present study was to investigate the effect of exercise training on muscular strength and body composition in five patients with late-onset Pompe disease receiving ERT. All subjects followed a 20 week lasting program of supervised aerobic and progressive resistance exercise training. Before and after the training period, body composition was determined with dual X-ray absorptiometry and isometric muscular strength was measured with a specialized load transducer. Functional capacity was assessed using the 6-min shuttle walk test. A significant increase in muscular strength (15-50% at various body parts, p<0.05) and 6-minute walking distance (203.8 ± 177 m before vs. 248.2 ± 184 m after, p<0.01) was observed after training, whereas total and lower extremities lean body mass did not change significantly. These results suggest that exercise training has a positive effect on muscular strength and functional capacity in patients on ERT with late-onset Pompe disease.

  20. One Year of Enzyme Replacement Therapy Reduces Globotriaosylceramide Inclusions in Podocytes in Male Adult Patients with Fabry Disease.

    PubMed

    Najafian, Behzad; Tøndel, Camilla; Svarstad, Einar; Sokolovkiy, Alexey; Smith, Kelly; Mauer, Michael

    2016-01-01

    Fabry nephropathy is associated with progressive accumulation of globotriaosylceramide (GL3) in podocytes. Reducing this GL3 burden may reduce podocyte injury. Sensitive methods to quantify podocyte GL3 content may determine whether a given strategy can benefit podocytes in Fabry disease. We developed an unbiased electron microscopic stereological method to estimate the average volume of podocytes and their GL3 inclusions in 6 paired pre- and post-enzyme replacement therapy (ERT) biopsies from 5 men with Fabry disease. Podocyte GL3 content was regularly reduced (average 73%) after 11-12 months of ERT. This was not detectable using a semi-quantitative approach. Parallel to GL3 reduction, podocytes became remarkably smaller (average 63%). These reductions in podocyte GL3 content or size were not significantly correlated with changes in foot process width (FPW). However, FPW after ERT was significantly correlated with the magnitude of the decrease in podocyte GL3 content from baseline to 11-12 months of ERT. Also podocytes exocytosed GL3 inclusions, a phenomenon correlated with their reduction in their GL3 content. Demonstrable after11-12 months, reduction in podocyte GL3 content allows for early assessment of treatment efficacy and shorter clinical trials in Fabry disease.

  1. Enzyme replacement therapy in two Japanese siblings with Fabry disease, and its effectiveness on angiokeratoma and neuropathic pain.

    PubMed

    Furujo, Mahoko; Kubo, Toshihide; Kobayashi, Masahisa; Ohashi, Toya

    2013-11-01

    Enzyme replacement therapy (ERT) for Fabry disease does not show a clear benefit in angiokeratoma. We describe two Japanese siblings with Fabry disease, who were diagnosed when angiokeratomas were found on the older sibling at the age of 13 years. Neither of the boys complained of pain, while both suffered from hypohidrosis. We evaluated the safety and efficacy of ERT with recombinant human agalsidase alfa (Replagal®, Dainippon-Sumitomo Pharma. Co., Osaka, Japan) in these siblings over a 5-year period. In both siblings, sweating was observed 3 months after the initiation of ERT, which motivated them to adhere to ERT. Pain sensation was regained after 12 to 36 months of ERT, followed by a decrease after 48 to 60 months. Angiokeratomas on the lateral side of the knee of the older sibling partially disappeared after 48 months of ERT. Although the height of both siblings at baseline was lower than the corresponding average age-related heights in the normal Japanese population, during ERT they were within, or close to, the average +1 standard deviation in the non-Fabry population. Their growth rate seemed to indicate catch-up growth. Other clinical symptoms were maintained at baseline levels. Immunoglobulin G anti-agalsidase alfa antibodies were not detected in both sibling during ERT, and no infusion-associated reaction was observed. The treatment was generally well tolerated. ERT was a safe and effective treatment for angiokeratoma and neuropathic pain for these two siblings with Fabry disease.

  2. 30 months follow-up of an early enzyme replacement therapy in a severe Morquio A patient: About one case.

    PubMed

    Do Cao, J; Wiedemann, A; Quinaux, T; Battaglia-Hsu, S F; Mainard, L; Froissart, R; Bonnemains, C; Ragot, S; Leheup, B; Journeau, P; Feillet, F

    2016-12-01

    Patients under 5 years were not evaluated in the phase-3 study for enzyme replacement therapy (ERT) in MPS IV A. Here we describe the evolution of a severe Morquio A pediatric patient who was diagnosed at 19 months old and treated by ERT at 21 months old for the next 30 months. Applying the standard ERT protocol on this very young patient appeared to reduce his urinary excretion of glycosaminoglycans (GAGs); the improvements in both the 6 minute-walk test (6MWT) and the stair climb test, however, were no different than those reported in the nature history study. Additionally, this young patient experienced many ERT-associated side effects, and as a result a specific corticosteroid protocol (1 mg/kg of betamethasone the day before and 1 h before the ERT infusion) was given to avoid adverse events. Under these treatments, the height of this patient increased during the first year of the ERT although no more height gain was observed thereafter for 18 months. However, despite of ERT, his bone deformities (including severe pectus carinatum) actually worsened and his medullar cervical spine compression showed no improvement (thus needed decompression surgery).

  3. One Year of Enzyme Replacement Therapy Reduces Globotriaosylceramide Inclusions in Podocytes in Male Adult Patients with Fabry Disease

    PubMed Central

    Najafian, Behzad; Tøndel, Camilla; Svarstad, Einar; Sokolovkiy, Alexey; Smith, Kelly; Mauer, Michael

    2016-01-01

    Fabry nephropathy is associated with progressive accumulation of globotriaosylceramide (GL3) in podocytes. Reducing this GL3 burden may reduce podocyte injury. Sensitive methods to quantify podocyte GL3 content may determine whether a given strategy can benefit podocytes in Fabry disease. We developed an unbiased electron microscopic stereological method to estimate the average volume of podocytes and their GL3 inclusions in 6 paired pre- and post-enzyme replacement therapy (ERT) biopsies from 5 men with Fabry disease. Podocyte GL3 content was regularly reduced (average 73%) after 11–12 months of ERT. This was not detectable using a semi-quantitative approach. Parallel to GL3 reduction, podocytes became remarkably smaller (average 63%). These reductions in podocyte GL3 content or size were not significantly correlated with changes in foot process width (FPW). However, FPW after ERT was significantly correlated with the magnitude of the decrease in podocyte GL3 content from baseline to 11–12 months of ERT. Also podocytes exocytosed GL3 inclusions, a phenomenon correlated with their reduction in their GL3 content. Demonstrable after11–12 months, reduction in podocyte GL3 content allows for early assessment of treatment efficacy and shorter clinical trials in Fabry disease. PMID:27081853

  4. Low-dose Gene Therapy Reduces the Frequency of Enzyme Replacement Therapy in a Mouse Model of Lysosomal Storage Disease

    PubMed Central

    Alliegro, Marialuisa; Ferla, Rita; Nusco, Edoardo; De Leonibus, Chiara; Settembre, Carmine; Auricchio, Alberto

    2016-01-01

    Enzyme replacement therapy (ERT) is the standard of care for several lysosomal storage diseases (LSDs). ERT, however, requires multiple and costly administrations and has limited efficacy. We recently showed that a single high dose administration of adeno-associated viral vector serotype 8 (AAV2/8) is at least as effective as weekly ERT in a mouse model of mucopolysaccharidosis type VI (MPS VI). However, systemic administration of high doses of AAV might result in both cell-mediated immune responses and insertional mutagenesis. Here we evaluated whether the combination of low doses of AAV2/8 with a less frequent (monthly) than canonical (weekly) ERT schedule may be as effective as the single treatments at high doses or frequent regimen. A greater reduction of both urinary glycosaminoglycans, considered a sensitive biomarker of therapeutic efficacy, and storage in the myocardium and heart valves was observed in mice receiving the combined than the single therapies. Importantly, these levels of correction were similar to those we obtained in a previous study following either high doses of AAV2/8 or weekly ERT. Our data show that low-dose gene therapy can be used as a means to rarify ERT administration, thus reducing both the risks and costs associated with either therapies. PMID:27658524

  5. Long-term management of patients with multiple sclerosis.

    PubMed

    Weightman, Cherie

    2006-07-01

    This article explores the challenges of long-term case management for patients who have multiple sclerosis (MS). Currently there is scant research into district nursing input into long-term management of patients who have MS. Until now the role of the community nurses has been confined to palliation or terminal care, focusing on the more physical manifestations of MS. The contemporary role of district nurse is going to evolve to include proactive approaches. Governmental initiatives demand proactive services, and place emphasis on self-care for patients with MS. Themes that emerge from this article relate to the pre-existing skills--such as managing patients with complex needs and the advanced assessment skills--that will be required to achieve this. What is clear is that community nurses already possess many of the prerequisite skills needed for long-term management, and they should not be daunted by this prospect.

  6. Long-term RNA persistence in postmortem contexts

    PubMed Central

    2013-01-01

    Ribonucleic acids (RNA) are generally considered fragile molecules that are readily degraded. However, there is growing documentation of long-term (from days to centuries) RNA persistence in a variety of contexts and tissue types, and as such a number of academic disciplines are beginning to exploit degraded RNA. While the reasons for its survival are not fully understood, there are several plausible mechanisms that would safeguard this molecule against degradation. However, after examining the literature available on the postmortem instability and decay mechanisms of RNA, it has become clear that limited experimental studies and no reviews offer an overview of these mechanisms. Hence in this review we outline molecular reasons for RNA surviving long-term postmortem, and provide specific examples of RNA survival in forensic, archival and archaeological contexts. A better understanding of the mechanisms of RNA decay will be crucial for developing expectations on its long-term survival. PMID:23618361

  7. Long-term multipactor discharge in multicarrier systems

    SciTech Connect

    Anza, S.; Vicente, C.; Gimeno, B.; Boria, V. E.; Armendariz, J.

    2007-08-15

    A new mechanism of long-term multipactor in multicarrier systems is studied employing both analytical and numerical methods. In particular, the investigation is focused on the impact that a realistic secondary emission yield at low energies produces on the development of long term multipactor. A novel analytical model for this interperiod charge accumulation is presented using the traditional multipactor theory for parallel plates, and approximating the multicarrier signal as a single-carrier signal modulated by a pulsed signal envelope. The analytical predictions are verified by numerical simulations for a typical rectangular waveguide. The analytical and numerical results demonstrate that the susceptibility of the system to develop a long-term multipactor discharge increases with higher values of low-energy secondary emission yield.

  8. Sexuality and Physical Intimacy in Long Term Care

    PubMed Central

    Lichtenberg, Peter A.

    2015-01-01

    Sexuality and sexual needs in older adults remains a neglected area of clinical intervention, particularly so in long term care settings. Because older adults in medical rehabilitation and long term care beds present with significant frailties, and often significant neurocognitive disorders it makes it difficult for occupational therapists and other staff to evaluate the capacity of an older adult resident to participate in sexual relationships. The current paper reviews the current literature on sexuality and aging, examines some of the clinical practices and guidelines regarding sexual expression in long term care and presents two case examples. A semi-structured interview and decision tree is presented to assist therapists in making careful and informed decisions and thereby balancing needs for protection with needs for autonomy. PMID:24354331

  9. Documenting Long-term Earth System Evolution With Satellite Observations

    NASA Astrophysics Data System (ADS)

    Kaye, J. A.; Koblinsky, C. J.; Cramer, B.; Karl, T.; Privette, J. L.

    2007-12-01

    Satellite observations play a critical role in documenting earth system evolution, both in terms of characterizing prior and current evolution of the Earth and providing a baseline against which future measurements can be compared. Given that the construction of the necessary long-term data sets requires the use of multiple instruments on multiple platforms, each of which may have their own characteristics, drifts, and degradation, this represents a significant challenge to the scientific community. Over the last 30-or so years, going back to the launch of the Nimbus 7 in 1978, earth scientists learned significant lessons about how to create accurate and stable long-term data records. Sponsoring agencies have tried to capture the lessons and use them as a basis for planning for future systems. This presentation will examine and present future approaches to maximize the quality of the long-term data records produced from earth satellites.

  10. Long-term effects of nanoparticles on nutrition and metabolism.

    PubMed

    Chen, Nan; Wang, Hui; Huang, Qing; Li, Jiang; Yan, Juan; He, Dannong; Fan, Chunhai; Song, Haiyun

    2014-09-24

    Nanoparticles have shown great potential in biological and biomedical applications due to their distinct physical and chemical properties. In the meanwhile, the biosafety of nanoparticles has also raised intense concerns worldwide. To address such concerns, great efforts have been made to examine short-term effects of nanoparticles on cell survival and proliferation. More recently, exploration of long-term effects of nanomaterials, particularly those with promising biomedical applications in vivo, has aroused significant interest. For example, gold nanoparticles (AuNPs) are generally considered non-toxic to cell growth, whereas recent studies suggest that AuNPs might have long-term effects on cellular metabolism and energy homeostasis. In this Review, recent advances in this direction are summarized. Further, possible mechanisms under which nanoparticles regulate metabolic signaling pathways, potential long-term effects on cellular anabolic or catabolic processes, and their implications in human health and metabolic disorders are discussed.

  11. [Renal side effects of long-term lithium therapy].

    PubMed

    Ibbeken, C; Becker, J U; Baumgärtel, M W

    2012-01-01

    Lithium is widely used in the treatment of bipolar disorders. Long-term administration of lithium often leads to side effects concerning the subjects: nephrology, endocrinology and surgery. This review emphasizes nephrotoxicity.Lithium treatment may disturb responsiveness to antidiuretic hormone (ADH), causing a nephrogenic diabetes insipidus. Furthermore long-term lithium therapy may trigger hyperparathyreoidism with hypercalcemia and chronic interstitial nephritis with development of microcysts. Long-term patients have an increased risk to develop impaired renal function. Lithium-induced endstage renal disease is rare. Termination of lithium treatment may decrease the risk of progression.To ensure security of lithium treatment regular controls of urine osmolarity, lithium-, creatinine- , thyroid stimulating hormone- and calcium-levels are essential. Patients with decreased renal function should be referred to a specialist early.

  12. Long-term visual tracking based on correlation filters

    NASA Astrophysics Data System (ADS)

    Wei, Quanlu; Lao, Songyang; Bai, Liang

    2017-03-01

    In order to accomplish the long term visual tracking task in complex scenes, solve problems of scale variation, appearance variation and tracking failure, a long term tracking algorithm is given based on the framework of collaborative correlation tracking. Firstly, we integrate several powerful features to boost the represent ability based on the kernel correlation filter, and extend the filter by embedding a scale factor into the kernelized matrix to handle the scale variation. Then, we use the Peak-Sidelobe Ratio to decide whether the object is tracked successfully, and a CUR filter for re-detection the object in case of tracking failure is learnt with random sampling. Corresponding experiment is performed on 17 challenging benchmark video sequences. Compared with the 8 existing state-of-the-art algorithms based on discriminative learning method, the results show that the proposed algorithm improves the tracking performance on several indexes, and is robust to complex scenes for long term visual tracking.

  13. Winning market positioning strategies for long term care facilities.

    PubMed

    Higgins, L F; Weinstein, K; Arndt, K

    1997-01-01

    The decision to develop an aggressive marketing strategy for its long term care facility has become a priority for the management of a one-hundred bed facility in the Rocky Mountain West. Financial success and lasting competitiveness require that the facility in question (Deer Haven) establish itself as the preferred provider of long term care for its target market. By performing a marketing communications audit, Deer Haven evaluated its present market position and created a strategy for solidifying and dramatizing this position. After an overview of present conditions in the industry, we offer a seven step process that provides practical guidance for positioning a long term care facility. We conclude by providing an example application.

  14. Long-term Internship through Cooperative Education with Regional Industries

    NASA Astrophysics Data System (ADS)

    Takahashi, Kenzo; Hase, Hiroyuki

    The long term internship is one of special educational programs for graduate students of Graduate School of Engineering in University of Fukui. This is a collaborative program between university and industries where selected post-graduate students are dispatched to companies for a long term and educated in real business environments. It is the final goal of the program to develop sophisticated specialists who would be able to catch the business strategy in industries and solve any problems by themselves. The program is managed in a semester (6 months) and contains 1.5 month prior education of preliminary special knowledge, ethics and secrecy, about 3 month dispatch with long-term internship, and 1.5 month post-education for complementary education and presentation. This paper presents the effect of this program which has been evolving since 2005.

  15. Viability of long-term gene therapy in the cochlea.

    PubMed

    Atkinson, Patrick J; Wise, Andrew K; Flynn, Brianna O; Nayagam, Bryony A; Richardson, Rachael T

    2014-04-22

    Gene therapy has been investigated as a way to introduce a variety of genes to treat neurological disorders. An important clinical consideration is its long-term effectiveness. This research aims to study the long-term expression and effectiveness of gene therapy in promoting spiral ganglion neuron survival after deafness. Adenoviral vectors modified to express brain derived neurotrophic factor or neurotrophin-3 were unilaterally injected into the guinea pig cochlea one week post ototoxic deafening. After six months, persistence of gene expression and significantly greater neuronal survival in neurotrophin-treated cochleae compared to the contralateral cochleae were observed. The long-term gene expression observed indicates that gene therapy is potentially viable; however the degeneration of the transduced cells as a result of the original ototoxic insult may limit clinical effectiveness. With further research aimed at transducing stable cochlear cells, gene therapy may be an efficacious way to introduce neurotrophins to promote neuronal survival after hearing loss.

  16. Stirling engine - Approach for long-term durability assessment

    NASA Astrophysics Data System (ADS)

    Tong, Michael T.; Bartolotta, Paul A.; Halford, Gary R.; Freed, Alan D.

    The approach employed by NASA Lewis for the long-term durability assessment of the Stirling engine hot-section components is summarized. The approach consists of: preliminary structural assessment; development of a viscoplastic constitutive model to accurately determine material behavior under high-temperature thermomechanical loads; an experimental program to characterize material constants for the viscoplastic constitutive model; finite-element thermal analysis and structural analysis using a viscoplastic constitutive model to obtain stress/strain/temperature at the critical location of the hot-section components for life assessment; and development of a life prediction model applicable for long-term durability assessment at high temperatures. The approach should aid in the provision of long-term structural durability and reliability of Stirling engines.

  17. Inflammatory markers in relation to long-term air pollution.

    PubMed

    Mostafavi, Nahid; Vlaanderen, Jelle; Chadeau-Hyam, Marc; Beelen, Rob; Modig, Lars; Palli, Domenico; Bergdahl, Ingvar A; Vineis, Paolo; Hoek, Gerard; Kyrtopoulos, Soterios Α; Vermeulen, Roel

    2015-08-01

    Long-term exposure to ambient air pollution can lead to chronic health effects such as cancer, cardiovascular and respiratory disease. Systemic inflammation has been hypothesized as a putative biological mechanism contributing to these adverse health effects. We evaluated the effect of long-term exposure to air pollution on blood markers of systemic inflammation. We measured a panel of 28 inflammatory markers in peripheral blood samples from 587 individuals that were biobanked as part of a prospective study. Participants were from Varese and Turin (Italy) and Umea (Sweden). Long-term air pollution estimates of nitrogen oxides (NOx) were available from the European Study of Cohorts for Air Pollution Effects (ESCAPE). Linear mixed models adjusted for potential confounders were applied to assess the association between NOx and the markers of inflammation. Long-term exposure to NOx was associated with decreased levels of interleukin (IL)-2, IL-8, IL-10 and tumor necrosis factor-α in Italy, but not in Sweden. NOx exposure levels were considerably lower in Sweden than in Italy (Sweden: median (5th, 95th percentiles) 6.65 μg/m(3) (4.8, 19.7); Italy: median (5th, 95th percentiles) 94.2 μg/m(3) (7.8, 124.5)). Combining data from Italy and Sweden we only observed a significant association between long-term exposure to NOx and decreased levels of circulating IL-8. We observed some indication for perturbations in the inflammatory markers due to long-term exposure to NOx. Effects were stronger in Italy than in Sweden, potentially reflecting the difference in air pollution levels between the two cohorts.

  18. Assessing the market for long-term care services.

    PubMed

    Rice, J A; Taylor, S

    1984-02-01

    Traditionally, long-term care services have been used by a diverse marketplace. The chronically ill, developmentally disabled, mentally ill and aging population has looked to long-term care support services as a means of physical and emotional support. Much of the time these services were housed together for the sake of efficiency. The enormous burden these services are creating on the economy, and the growing aging population, have forced the recognition that long-term care service delivery systems must change. Alternate programming for long-term care services that reach out into the community and into individual homes is becoming an attractive approach to meeting the growing demands of the marketplace. Home health, specialized housing and creative funding mechanisms such as HMOs, are examples of initiatives undertaken by healthcare organizations that view diversification as a vehicle for survival. Market research techniques that have been used in other industries are being adapted to the healthcare industry to ensure the proper mix of services that are demanded by older, more knowledgeable consumers. The programs of the future will be market driven, with the ability of the individual to pay for such services playing a significant role. The healthcare provider of today is in a position to serve the community in new ways. By becoming an integral link in the long-term care system and by developing new programs, the organization can serve as a catalyst for change. It is up to the governing bodies and managers of these facilities to become visionaries and to accept responsibility for assessing the market for long-term care services and to guide their organization into the future.

  19. Morphodynamic length scale and long term river meandering dynamics

    NASA Astrophysics Data System (ADS)

    Lanzoni, S.; Frascati, A.

    2009-12-01

    The fully nonlinear simulation of the lateral migration of meandering channels, combined with an analytical description of the linearized flow field, gives a powerful and yet computationally accessible tool to investigate short and long term evolution of alluvial rivers. In the present contribution we focus on the long term behavior of meandering rivers. This class of dynamical systems is driven by the coexistence of various intrinsically nonlinear mechanisms which determine the possible occurrence of two different morphodynamic regimes: the sub-resonant and the super-resonant regime. Investigating the full range of morphodynamic conditions, we end up with a new morphodynamic length scale associated with spatially oscillating disturbances, accounting for both curvature-forced variations in velocity and depth and alternate bars. Once normalized with this length scale, the relevant morphologic features of the simulated long term patterns (i.e. the probability density function of the local channel curvature and the geometric characteristics of the oxbow lakes) tend to collapse on two distinct behaviors, depending on the dominant morphologic regime. The long term river meandering dynamics is then investigated. The occurrence of cutoff events is a key mechanism in the dynamics of these systems. They introduce a strong source of nonlinearity in the evolution of river meandering, which strongly contributes to the formation of the complex planform patterns usually observed in nature. To detect the possible signatures of a chaotic behavior or a self-organized criticality state triggered in river meandering dynamics by the repeated occurrence of cutoffs, some robust nonlinear methodologies have been applied to both the spatial series of local curvatures and the time series of long term channel sinuosity. The temporal distribution of cutoff inter-arrivals is also investigated. The results are consistent and show that, at least from a modelling point of view, no evidence of

  20. The Challenge of Long-Term Climate Change

    NASA Astrophysics Data System (ADS)

    Hasselmann, K.; Latif, M.; Hooss, G.; Azar, C.; Edenhofer, O.; Jaeger, C. C.; Johannessen, O. M.; Kemfert, C.; Welp, M.; Wokaun, A.

    2003-12-01

    Climate policy needs to address the multidecadal to centennial time scale of climate change. Although the realization of short-term targets is an important first step, to be effective climate policies need to be conceived as long-term programs that will achieve a gradual transition to an essentially emission-free economy on the time scale of a century. This requires a considerably broader spectrum of policy measures than the primarily market-based instruments invoked for shorter term mitigation policies. A successful climate policy must consist of a dual approach focusing on both short-term targets and long-term goals.

  1. Storability Investigations of Water Long-Term Storage Evaluation

    DTIC Science & Technology

    1974-12-01

    previously for the other tankage and then descaled in a pickling solution of 33.2% HN03 , 1.6% HF, and 65.2% water at 140°F for 3 minutes. The titanium...AD/A-004 462 STORABILITY INVESTIGATIONS OF WATER LONG-TERM STORAGE EVALUATION E. M. Vander Wall, et al I Aerojet Liquid Rocket Company Prc pared for...Investigations of Water , Long-Term ,Annual Storage Evaluation 6. PERFORMING ORG. REPORT NUMBER 7. AU THOR(s) 0. CONTRACT OR GRANT NUMPEIR(.) Vander Wall, E. M

  2. Long-term stability test of a triple GEM detector

    NASA Astrophysics Data System (ADS)

    Adak, R. P.; Biswas, S.; Das, S.; Ghosal, D.; Ghosh, S. K.; Mondal, A.; Nag, D.; Nayak, T. K.; Patra, R. N.; Prasad, S. K.; Raha, S.; Sahu, P. K.; Sahu, S.; Swain, S.

    2016-10-01

    The main aim of the study is to perform the long-term stability test of gain of the single mask triple GEM detector. A simple method is used for this long-term stability test using a radioactive X-ray source with high activity. The test is continued till accumulation of charge per unit area > 12.0 mC/mm2. The details of the chamber fabrication, the test set-up, the method of measurement and the test results are presented in this paper.

  3. Metabolic bone diseases during long-term total parenteral nutrition.

    PubMed

    Acca, M; Ragno, A; Francucci, C M; D'Erasmo, E

    2007-01-01

    Long-term total parenteral nutrition (TPN) is a procedure commonly applied to patients with advanced forms of intestinal malabsorption. Among TPN complications, bone metabolic diseases, such as osteoporosis and osteomalacia, are a common finding. Initially considered to be a manifestation of aluminium toxicity which followed massive contamination with the element of the solutions used in TPN, metabolic osteopathy during TPN is currently considered a multiform syndrome, with a multifactorial pathogenesis, which may manifest itself with vague or clear clinical pictures. In this review, we analyse clinical, pathogenetic, and therapeutic aspects of the most common bone metabolic diseases in patients undergoing long-term TPN.

  4. Long-term Morbidity of Testicular Cancer Treatment.

    PubMed

    Fung, Chunkit; Fossa, Sophie D; Williams, Annalynn; Travis, Lois B

    2015-08-01

    Second malignant neoplasms, cardiovascular disease, neurotoxicity and ototoxicity, pulmonary complications, hypogonadism, and nephrotoxicity are potentially life-threatening long-term complications of testicular cancer and its therapy. This article describes the pathogenesis, risks, and management of these late effects experienced by long-term testicular cancer survivors, who are defined as individuals who are disease free 5 years or more after primary treatment. Testicular cancer survivors should follow applicable national guidelines for cancer screening and management of cardiovascular disease risk factors. In addition, health care providers should capitalize on the time of cancer diagnosis as a teachable moment to introduce and promote lifestyle changes.

  5. Long-term Outcomes in Youths with Diabetes Mellitus.

    PubMed

    White, Neil H

    2015-08-01

    In this article, the author reviews the long-term outcomes and their precursors of type 1 diabetes starting in youth. The author also contrasts the changing incidence of these long-term complications as we have moved from the pre-Diabetes Control and Complications Trial (DCCT) to the post-DCCT standard of care and reviews the emerging data related to complications in youths with type 2 diabetes. Finally, the author reviews the recent understanding related to the effects of diabetes on the brain and cognition.

  6. Human sperm chromosomes. Long-term effect of cancer treatment

    SciTech Connect

    Genesca, A.; Caballin, M.R.; Miro, R.; Benet, J.; Bonfill, X.; Egozcue, J. )

    1990-06-01

    The long-term cytogenetic effect of radio- or chemotherapy or both on male germ cells was evaluated by study of the chromosomal abnormalities in spermatozoa of four men treated for cancer 5-18 years earlier. The cytogenetic analysis of 422 sperm metaphases showed no differences in the aneuploidy rate. The incidence of structural chromosome aberrations was 14.0%, however, which is much higher than in controls. Thus, the high incidence of structurally aberrant spermatozoa observed in our long-term study indicates that antitumoral treatments affect stem-cell spermatogonia and that aberrant cells can survive germinal selection and produce abnormal spermatozoa.

  7. 42 CFR 412.536 - Special payment provisions for long-term care hospitals and satellites of long-term care...

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... hospitals and satellites of long-term care hospitals that discharged Medicare patients admitted from a hospital not located in the same building or on the same campus as the long-term care hospital or satellite... payment provisions for long-term care hospitals and satellites of long-term care hospitals that...

  8. 42 CFR 412.536 - Special payment provisions for long-term care hospitals and satellites of long-term care...

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... hospitals and satellites of long-term care hospitals that discharged Medicare patients admitted from a hospital not located in the same building or on the same campus as the long-term care hospital or satellite... payment provisions for long-term care hospitals and satellites of long-term care hospitals that...

  9. 42 CFR 412.536 - Special payment provisions for long-term care hospitals and satellites of long-term care...

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... hospitals and satellites of long-term care hospitals that discharged Medicare patients admitted from a hospital not located in the same building or on the same campus as the long-term care hospital or satellite... payment provisions for long-term care hospitals and satellites of long-term care hospitals that...

  10. 42 CFR 412.536 - Special payment provisions for long-term care hospitals and satellites of long-term care...

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... hospitals and satellites of long-term care hospitals that discharged Medicare patients admitted from a hospital not located in the same building or on the same campus as the long-term care hospital or satellite... payment provisions for long-term care hospitals and satellites of long-term care hospitals that...

  11. 42 CFR 412.536 - Special payment provisions for long-term care hospitals and satellites of long-term care...

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... hospitals and satellites of long-term care hospitals that discharged Medicare patients admitted from a hospital not located in the same building or on the same campus as the long-term care hospital or satellite... payment provisions for long-term care hospitals and satellites of long-term care hospitals that...

  12. Extended-spectrum beta-lactamases in long-term-care facilities.

    PubMed

    Nicolas-Chanoine, Marie-Hélène; Jarlier, Vincent

    2008-01-01

    Although the first reports on extended-spectrum beta-lactamase (ESBL)-producing isolates in long-term-care facilities (LTCFs) appeared 10 years ago, there are still scanty data on this topic. A long-term survey starting in 1993 by the microbial laboratories of the Assistance Publique Hopitaux de Paris and covering 21,000 beds, 7000 of them in LTCFs, indicated that the incidence of ESBL-producing isolates/1000 hospitalisation days in LTCFs increased from 0.07 in 1996 to 0.28 in 2005. Escherichia coli accounted for 80% of ESBL-positive isolates in 2005, whereas it accounted for <45% in 2001. This rise in E. coli with ESBLs reflected clonal spread, as found elsewhere, with CTX-M types now the predominant enzyme types.

  13. Enzyme replacement in a human model of mucopolysaccharidosis IVA in vitro and its biodistribution in the cartilage of wild type mice.

    PubMed

    Dvorak-Ewell, Melita; Wendt, Dan; Hague, Chuck; Christianson, Terri; Koppaka, Vish; Crippen, Danielle; Kakkis, Emil; Vellard, Michel

    2010-08-16

    Mucopolysaccharidosis IVA (MPS IVA; Morquio A syndrome) is a lysosomal storage disorder caused by deficiency of N-acetylgalactosamine-6-sulfatase (GALNS), an enzyme that degrades keratan sulfate (KS). Currently no therapy for MPS IVA is available. We produced recombinant human (rh)GALNS as a potential enzyme replacement therapy for MPS IVA. Chinese hamster ovary cells stably overexpressing GALNS and sulfatase modifying factor-1 were used to produce active ( approximately 2 U/mg) and pure (>or=97%) rhGALNS. The recombinant enzyme was phosphorylated and was dose-dependently taken up by mannose-6-phosphate receptor (K(uptake) = 2.5 nM), thereby restoring enzyme activity in MPS IVA fibroblasts. In the absence of an animal model with a skeletal phenotype, we established chondrocytes isolated from two MPS IVA patients as a disease model in vitro. MPS IVA chondrocyte GALNS activity was not detectable and the cells exhibited KS storage up to 11-fold higher than unaffected chondrocytes. MPS IVA chondrocytes internalized rhGALNS into lysosomes, resulting in normalization of enzyme activity and decrease in KS storage. rhGALNS treatment also modulated gene expression, increasing expression of chondrogenic genes Collagen II, Collagen X, Aggrecan and Sox9 and decreasing abnormal expression of Collagen I. Intravenous administration of rhGALNS resulted in biodistribution throughout all layers of the heart valve and the entire thickness of the growth plate in wild-type mice. We show that enzyme replacement therapy with recombinant human GALNS results in clearance of keratan sulfate accumulation, and that such treatment ameliorates aberrant gene expression in human chondrocytes in vitro. Penetration of the therapeutic enzyme throughout poorly vascularized, but clinically relevant tissues, including growth plate cartilage and heart valve, as well as macrophages and hepatocytes in wild-type mouse, further supports development of rhGALNS as enzyme replacement therapy for MPS IVA.

  14. Long-term outcomes of osseointegrated digital prostheses for proximal amputations.

    PubMed

    Sierakowski, A; Watts, C; Thomas, K; Elliot, D

    2011-02-01

    This paper presents outcomes after 13, 4, and 3½ years in three digital amputees treated with osseointegrated prostheses. One had prosthetic replacement of the index and middle fingers at the PIP level. The second had four fingers replaced at the PIP level, but only three prostheses were retained. The third had a thumb replacement at the MCP level. All patients scored their reconstructed hand highly in terms of appearance and frequency of use. The first and third patients rated the function of the reconstructed hand as similar to the normal hand, and this was confirmed by the Jebsen Test, but the second patient had poor function. All patients could detect pressure and vibration through their prostheses, although grip and pinch strengths were weaker in all three. All three also experienced some pain in the implanted fingers. This study identifies osseointegration as a stable long-term reconstructive option.

  15. First human treatment with investigational rhGUS enzyme replacement therapy in an advanced stage MPS VII patient.

    PubMed

    Fox, Joyce E; Volpe, Linda; Bullaro, Josephine; Kakkis, Emil D; Sly, William S

    2015-02-01

    Mucopolysaccharidosis type VII (MPS VII, Sly syndrome) is a very rare lysosomal storage disease caused by a deficiency of the enzyme β-glucuronidase (GUS), which is required for the degradation of three glycosaminoglycans (GAGs): dermatan sulfate, heparan sulfate, and chondroitin sulfate. Progressive accumulation of these GAGs in lysosomes leads to increasing dysfunction in numerous tissues and organs. Enzyme replacement therapy (ERT) has been used successfully for other MPS disorders, but there is no approved treatment for MPS VII. Here we describe the first human treatment with recombinant human GUS (rhGUS), an investigational therapy for MPS VII, in a 12-year old boy with advanced stage MPS VII. Despite a tracheostomy, nocturnal continuous positive airway pressure, and oxygen therapy, significant pulmonary restriction and obstruction led to oxygen dependence and end-tidal carbon dioxide (ETCO2) levels in the 60-80mmHg range, eventually approaching respiratory failure (ETCO2 of 100mmHg) and the need for full-time ventilation. Since no additional medical measures could improve his function, we implemented experimental ERT by infusing rhGUS at 2mg/kg over 4h every 2 weeks for 24 weeks. Safety was evaluated by standard assessments and observance for any infusion associated reactions (IARs). Urinary GAG (uGAG) levels, pulmonary function, oxygen dependence, CO2 levels, cardiac valve function, liver and spleen size, and growth velocity were assessed to evaluate response to therapy. rhGUS infusions were well tolerated. No serious adverse events (SAEs) or IARs were observed. After initiation of rhGUS infusions, the patient's uGAG excretion decreased by more than 50%. Liver and spleen size were reduced within 2 weeks of the first infusion and reached normal size by 24 weeks. Pulmonary function appeared to improve during the course of treatment based on reduced changes in ETCO2 after off-ventilator challenges and a reduced oxygen requirement. The patient regained the

  16. Interference Effects in Young Children's Long-Term Retention.

    ERIC Educational Resources Information Center

    Howe, Mark L.

    1995-01-01

    Two experiments examined the effects of interference on young children's long-term memory using paired-association recall and free recall. The results indicated that children were susceptible to interference, the locus of interference effects was at storage, and that both younger (preschool) and older (kindergarten) children experienced similar…

  17. 41 CFR 51-6.3 - Long-term procurements.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 41 Public Contracts and Property Management 1 2010-07-01 2010-07-01 true Long-term procurements. 51-6.3 Section 51-6.3 Public Contracts and Property Management Other Provisions Relating to Public... ensure stability of employment and development of job skills for persons who are blind or have...

  18. Gender-Based Violence in India: Long-Term Trends

    ERIC Educational Resources Information Center

    Simister, John; Mehta, Parnika S.

    2010-01-01

    This article examines long-term trends in Indian society regarding domestic violence between husband and wife, and attitudes to such violence. This article analyzes crime data and uses data from several Indian household surveys: "Work Attitudes and Spending" surveys (1992 to 2007); "World Values Survey" (1990, 1995, 2001, and…

  19. Going Solar Yields Long-Term Economical, Educational Benefits

    ERIC Educational Resources Information Center

    von Moos, Brian

    2009-01-01

    Going solar is not an easy decision, but a long-term investment with a potentially substantial up-front cost. While some schools have enough capital in reserve, can raise bond money, or can solicit sufficient donations, many schools rely on creative financial programs to make a solar energy system economically feasible. Thinking about going solar…

  20. The Aging Network and Managed Long-Term Care

    ERIC Educational Resources Information Center

    Polivka, Larry; Zayac, Helen

    2008-01-01

    Since the early 1980s, service providers and area agencies on aging, that is, the aging network, have developed a number of strengths as they built a community-based long-term-care system in most states. Many area agencies and providers now have the capacity to assess the needs of older persons, identify appropriate services, and administer…

  1. The aging network and managed long-term care.

    PubMed

    Polivka, Larry; Zayac, Helen

    2008-10-01

    Since the early 1980s, service providers and area agencies on aging, that is, the aging network, have developed a number of strengths as they built a community-based long-term-care system in most states. Many area agencies and providers now have the capacity to assess the needs of older persons, identify appropriate services, and administer cost-effective community programs while operating within fixed, capped budgets. They have also been able to identify and maintain roles for informal caregivers, draw on community resources through donations and the use of volunteers, and create substantial political support. In this article we argue that the aging network should draw on these strengths to develop integrated long-term-care systems designed to shift the balance of state long-term-care systems from institutional to home- and community-based services. We also argue that the nonprofit aging network, because it is made up of area agencies on aging and service providers, provides a potentially more effective framework for the integration of long-term-care resources than do proprietary managed care organizations.

  2. Psychosocial Mediators of Long-Term Abstinence Following Smoking Cessation.

    ERIC Educational Resources Information Center

    Horwitz, Michael B.; And Others

    It is well known that many smokers who quit during cessation programs relapse soon after leaving treatment. To investigate the relationship of health locus of control, social support, nonsmoking areas, and objecting to another person's smoking to relapse and long-term maintenance of nonsmoking, male (N=70) and female (N=149) subjects participated…

  3. Idaho National Laboratory Site Long-Term Stewardship Implementation Plan

    SciTech Connect

    B. E. Olaveson

    2006-07-27

    The U.S. Department of Energy has established long-term stewardship programs to protect human health and the environment at sites where residual contamination remains after site cleanup. At the Idaho National Laboratory Site, Comprehensive Environmental Response, Compensation, and Liability Act (CERLA) long-term stewardship activities performed under the aegis of regulatory agreements, the Federal Facility Agreement and Consent Order for the Idaho National Laboratory, and state and federal requirements are administered primarily under the direction of the Idaho Cleanup Project. It represents a subset of all on-going environmental activity at the Idaho National Laboratory Site. This plan provides a listing of applicable CERCLA long-term stewardship requirements and their planned and completed implementation goals. It proffers the Long-Term Stewardship Environmental Data Warehouse for Sitewide management of environmental data. This plan will be updated as needed over time, based on input from the U.S. Department of Energy, its cognizant subcontractors, and other local and regional stakeholders.

  4. Long-term priming of the meanings of ambiguous words

    ERIC Educational Resources Information Center

    Rodd, Jennifer M.; Lopez Cutrin, Belen; Kirsch, Hannah; Millar, Allesandra; Davis, Matthew H.

    2013-01-01

    Comprehension of semantically ambiguous words (e.g., "bark") is strongly influenced by the relative frequencies of their meanings, such that listeners are biased towards retrieving the most frequent meaning. These biases are often assumed to reflect a highly stable property of an individual's long-term lexical-semantic representations. We present…

  5. Long-Term Outcomes of an Urban Farming Internship Program

    ERIC Educational Resources Information Center

    Sonti, Nancy Falxa; Campbell, Lindsay K.; Johnson, Michelle L.; Daftary-Steel, Sarita

    2016-01-01

    Long-term impacts of an urban farming youth internship were evaluated in Brooklyn, New York. Alumni surveyed 1 to 9 years after program completion were enrolled in college or graduate school at higher rates than their peers and reported connections to the environment and healthy eating. Participants reported learning job skills through the…

  6. Investment in Skills Must Be for the Long Term

    ERIC Educational Resources Information Center

    Field, John

    2009-01-01

    Since the 1980s, researchers have formed a much better understanding of how unemployment scars people's lives, not just in the short term, but sometimes for years ahead. Researchers differ on the details, but no one disagrees that the negative effects are serious and long term. In the recession of the 1980s, government schemes to improve people's…

  7. Long-term nitrogen regulation of forest carbon sequestration

    NASA Astrophysics Data System (ADS)

    Yang, Y.; Luo, Y.

    2009-12-01

    It is well established that nitrogen (N) limits plant production but unclear how N regulates long-term terrestrial carbon (C) sequestration in response to rising atmospheric C dioxide (CO2)(Luo et al., 2004). Most experimental evidence on C-N interactions is primarily derived from short-term CO2 manipulative studies (e.g. Oren et al., 2001; Reich et al., 2006a), which abruptly increase C inputs into ecosystems and N demand from soil while atmospheric CO2 concentration in the real world is gradually increasing over time (Luo & Reynolds, 1999). It is essential to examine long-term N regulations of C sequestration in natural ecosystems. Here we present results of a synthesis of more than 100 studies on long-term C-N interactions during secondary succession. C significantly accumulates in plant, litter and forest floor in most studies, and in mineral soil in one-third studies during stand development. Substantial increases in C stock are tightly coupled with N accretion. The C: N ratio in plant increases with stand age in most cases, but remains relatively constant in litter, forest floor and mineral soil. Our results suggest that natural ecosystems could have the intrinsic capacity to maintain long-term C sequestration through external N accrual, high N use efficiency, and efficient internal N cycling.

  8. Long-Term Effects of Neurofeedback Treatment in Autism

    ERIC Educational Resources Information Center

    Kouijzer, Mirjam E. J.; de Moor, Jan M. H.; Gerrits, Berrie J. L.; Buitelaar, Jan K.; van Schie, Hein T.

    2009-01-01

    Previously we demonstrated significant improvement of executive functions and social behavior in children with autism spectrum disorders (ASD) treated with 40 sessions of EEG neurofeedback in a nonrandomized waiting list control group design. In this paper we extend these findings by reporting the long-term results of neurofeedback treatment in…

  9. Globalization, Women's Migration, and the Long-Term-Care Workforce

    ERIC Educational Resources Information Center

    Browne, Colette V.; Braun, Kathryn L.

    2008-01-01

    With the aging of the world's population comes the rising need for qualified direct long-term-care (DLTC) workers (i.e., those who provide personal care to frail and disabled older adults). Developed nations are increasingly turning to immigrant women to fill these needs. In this article, we examine the impact of three global trends--population…

  10. Current Perspectives on Long-term Obesity Pharmacotherapy.

    PubMed

    Wharton, Sean

    2016-04-01

    Approximately 1 in 4 adult Canadians are obese and, thus, are at an elevated risk for developing type 2 diabetes, cardiovascular disease and other conditions. Current treatment guidelines recommend that obese individuals lose 5% to 10% of their starting weights to minimize the risk factors for cardiovascular disease and reduce the risk for developing type 2 diabetes or hypertension. All obesity-management strategies involve lifestyle management, but few patients will lose a significant amount of weight and manage to keep it off over the long term using just this strategy. Bariatric surgery is associated with significant long-term weight loss but is restricted to subjects with very high body mass indices, who often wait many years to undergo the procedure. Recent breakthroughs in understanding the mechanisms underlying the development and maintenance of elevated body fat have led to the arrival of new obesity pharmacotherapies. These novel antiobesity therapies, which work by reducing energy intake or through increasing satiety, decreasing hunger, or reducing absorption of calories, may be used indefinitely once patients have demonstrated significant responses (usually defined as ≥5% weight loss) over the first 12 weeks of treatment. To date, 2 long-term obesity pharmacotherapies have been approved and are available in Canada: liraglutide and orlistat. Here, I summarize the mechanisms and clinical features of medications for long-term obesity management that are available in Canada, as well as those available in other jurisdictions or are currently in development.

  11. Annotated Bibliography of Intramural Research on Long-Term Care.

    ERIC Educational Resources Information Center

    National Center for Health Services Research and Health Care Technology Assessment (DHHS/PHS), Rockville, MD.

    As components of the National Center for Health Services Research Division of Intramural Research, the Long-Term Care Studies Program and the Aging Studies Program were established to define the problems of caring for the chronically ill and the elderly and to study the organization, financing, and delivery of health care services to these…

  12. Long-Term English Learners Writing Their Stories

    ERIC Educational Resources Information Center

    Jacobs, C. Lynn

    2008-01-01

    High school teacher C. Lynn Jacobs noted that the long-term English language learners in her class had improved in reading comprehension but still lacked writing skills. Inspired by a state humanities project, she worked with the students to publish a collection of stories and poems. Writing about their lives provided the motivation, and writing…

  13. Long term management practices influenced soil aggregation and carbon dynamics

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Soil aggregation protects soil organic C (SOC) against rapid decomposition, improves soil quality, and reduces soil erosion potential. The objectives of this study are to evaluate the effects of long-term (21 yrs.) management practices on SOC, water stable aggregate (WSA), and aggregate-associated ...

  14. Noise-Making amongst the Elderly in Long Term Care.

    ERIC Educational Resources Information Center

    Ryan, David Patrick; And Others

    1988-01-01

    Nurses in long-term care facilities indicated that about 30 percent of residents presented noise-making behavior. From descriptions, typology of noise-making was identified: purposeless and perseverative noise-making, noise-making in response to environment, noise-making to elicit response from environment, "chatterbox" noise-making,…

  15. Autonomy and Acceptance of Long-Term Care

    ERIC Educational Resources Information Center

    Hsu, Hui-Chuan; Ting, Yu-Shan; Jiang, Ting-Wen; Chien, Ming-Chih; Chien, Chih-Hsin

    2009-01-01

    This study explored the relationship between four types of autonomy (health autonomy, informational autonomy, living autonomy, and financial autonomy) and the acceptance of five types of long-term care (adult day care, respite care, assisted living, unit care, and group home) for the elderly in Taiwan. Data were collected from 167 middle-aged and…

  16. Long-Term Parental Illness and Children: Perils and Promises.

    ERIC Educational Resources Information Center

    Johnston, Mona; And Others

    1992-01-01

    Discusses effects of long-term parental illness, focusing on effects on children. Describes effects on family homeostasis and family coping mechanisms. Discusses school counselor's role in bringing about a more balanced viewpoint of power and sharing within the family. Recommends establishing a strong therapeutic bond, assessing what the child is…

  17. Rhinovirus outbreaks in long-term care facilities, Ontario, Canada.

    PubMed

    Longtin, Jean; Marchand-Austin, Alex; Winter, Anne Luise; Patel, Samir; Eshaghi, Alireza; Jamieson, Frances; Low, Donald E; Gubbay, Jonathan B

    2010-09-01

    Diagnostic difficulties may have led to underestimation of rhinovirus infections in long-term care facilities. Using surveillance data, we found that rhinovirus caused 59% (174/297) of respiratory outbreaks in these facilities during 6 months in 2009. Disease was sometimes severe. Molecular diagnostic testing can differentiate these outbreaks from other infections such as influenza.

  18. Rhinovirus Outbreaks in Long-term Care Facilities, Ontario, Canada

    PubMed Central

    Marchand-Austin, Alex; Winter, Anne-Luise; Patel, Samir; Eshaghi, Alireza; Jamieson, Frances; Low, Donald E.; Gubbay, Jonathan B.

    2010-01-01

    Diagnostic difficulties may have led to underestimation of rhinovirus infections in long-term care facilities. Using surveillance data, we found that rhinovirus caused 59% (174/297) of respiratory outbreaks in these facilities during 6 months in 2009. Disease was sometimes severe. Molecular diagnostic testing can differentiate these outbreaks from other infections such as influenza. PMID:20735934

  19. Long-Term Effects of First-Grade Multitier Intervention

    ERIC Educational Resources Information Center

    Al Otaiba, Stephanie; Kim, Young-Suk; Wanzek, Jeanne; Petscher, Yaacov; Wagner, Richard K.

    2014-01-01

    The purpose of this study was to compare the long-term effects of 2 first-grade Response to Intervention (RTI) models (Dynamic and Typical RTI) on the reading performance of students in second and third grade. Participants included 419 first-grade students (352 in second grade and 278 in third grade after attrition). Students were classified based…

  20. Long Term Effects of Drug Use on General Mental Ability.

    ERIC Educational Resources Information Center

    Stevens, Charles C.

    A private corporation conducted a study for the United States Air Force in 1973, investigating the long term effects of drug use on general mental ability. The air force personnel selected for participation in the study were 3741 known drug users and 6772 controls. Subjects received requests to sign a form allowing their high schools to release…

  1. Marketing in the long-term care continuum.

    PubMed

    Laurence, J Nathan; Kash, Bita A

    2010-04-01

    Today, long-term care facilities are composed of independent, assisted living, and skilled nursing facilities along with many variations of those themes in between. The clientele for these various types of facilities differ because of the level of care the facility provides as well as the amenities long-term care consumers are looking for. However, there many similarities and common approaches to how reaching the target audience through effective marketing activities. Knowing who the target audience is, how to reach them, and how to communicate with them will serve any facility well in this competitive market. Developing marketing strategies for long-term care settings is as important as understanding what elements of care can be marketed individually as a niche market. Determining the market base for a facility is equally crucial since the target populations differ among the three types of facilities. By reviewing current marketing articles and applying marketing practices, we have crafted some general principles for which each facility type can learn from. Finally, we will discuss the types of marketing and how they related to the spectrum of long-term care facilities.

  2. Descriptive Characteristics of Long-Term Private Practice Psychotherapy Clients.

    ERIC Educational Resources Information Center

    Koss, Mary P.

    Data from public and private sectors reveal that few persons stay in psychotherapy long enough to be classified as "long-term" clients. Those who do remain in psychotherapy for a long time are rarely studied because attention has generally been focused on terminators. Demographic, treatment, and psychometric characteristics of 64 long-term…

  3. Research on the Long-Term Effects of Child Abuse.

    ERIC Educational Resources Information Center

    Elam, George A.; Kleist, David M.

    1999-01-01

    Explores recent quantitative and qualitative studies of the long-term effects of child abuse, specifically, how abuse in childhood affects adulthood. Many studies associate various forms of abuse experienced in childhood with a wide range of psychological, behavioral, and relational problems in adulthood. Articles reviewed may inform marriage and…

  4. Long-term field studies: positive impacts and unintended consequences.

    PubMed

    Strier, Karen B

    2010-09-01

    Long-term field studies of wild primates can have far-reaching impacts that transcend their contributions to science. These impacts can benefit not only the study animals, study areas, and local human communities, but they can also have unintended, potentially negative consequences. Examples of some of the positive impacts from the Northern Muriqui Project of Caratinga, in Minas Gerais, Brazil, include contributions to conservation efforts on behalf of this critically endangered species, capacity building through the training of Brazilian students, and employment opportunities for local people through our collaboration with a locally administered NGO that is facilitating ecotourism, education, and reforestation programs. Some concerns about unintended consequences of the research include the effects of our trails and trail traffic on surrounding vegetation and other aspects of the environmental "footprints" that both long-term researchers and short-term visitors may leave. In addition, although precautions against potential health risks from routine exposure to human observers are now standard protocol, little is known about the other ways in which our long-term research presence can affect the primates' experiences or alter their perceptions of their social and ecological environments. Risk analysis, which weighs both the positive and negative impacts can provide useful perspectives for addressing the ethical considerations that can arise during long-term field studies.

  5. Security basics for long-term care facilities.

    PubMed

    Green, Martin

    2015-01-01

    The need for Long-Term Care (LTC) facilities is growing, the author reports, and along with it the need for programs to address the major security concerns of such facilities. In this article he explains how to apply the IAHSS Healthcare Security Industry Guidelines and the Design Guidelines to achieve a safer LTC facility.

  6. The Jornada Basin long term ecological research program

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Chihuahuan Desert landscapes exemplify the ecological conditions, vulnerability, and management challenges in arid and semi-arid regions around the world. The goal of the Jornada Basin Long Term Ecological Research program (JRN LTER) established in 1982 is to understand and quantify the key factors ...

  7. 26 CFR 1.460-1 - Long-term contracts.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... customer has title to, control over, or bears the risk of loss from, the property manufactured or... under a long-term contract will subject all other items in that contract to section 460. (2) Hybrid... construction activities (hybrid contract) generally must be classified as two contracts, a...

  8. 26 CFR 1.460-1 - Long-term contracts.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... customer has title to, control over, or bears the risk of loss from, the property manufactured or... under a long-term contract will subject all other items in that contract to section 460. (2) Hybrid... construction activities (hybrid contract) generally must be classified as two contracts, a...

  9. Case report: Long-term cognitive sequelae of sarin exposure.

    PubMed

    Loh, Yince; Swanberg, Margaret M; Ingram, M Victoria; Newmark, Jonathan

    2010-03-01

    The long-term sequelae of acute sarin exposure are not well understood. The largest clinical cohort resulted from the 1994 and 1995 attacks in Japan. Observers noted mostly psychiatric sequelae, with a high prevalence of post-traumatic stress disorder (PTSD). We describe neurocognitive findings that may represent sequelae of low-level sarin exposure in Iraq.

  10. Effects of Acute Exercise on Long-Term Memory

    ERIC Educational Resources Information Center

    Labban, Jeffrey D.; Etnier, Jennifer L.

    2011-01-01

    In this study, we tested the effect of acute exercise on long-term memory, specifically the timing of exercise relative to the memory challenge. We assessed memory via paragraph recall, in which participants listened to two paragraphs (exposure) and recounted them following a 35-min delay. Participants (n = 48) were randomly assigned to one of…

  11. Long-term Ecological Monitoring in Schools and Colleges.

    ERIC Educational Resources Information Center

    Doberski, Julian; Brodie, Iain D. S.

    1991-01-01

    The value and difficulties of long-term ecological monitoring studies undertaken in schools and colleges are reviewed. Rookeries, stream ecology, sand dune succession, fish population, and seed production and survival are presented as examples of successful studies. This is followed by a discussion of points to consider when setting up a long-term…

  12. Gender Relations, Family Relations and Long-Term Youth Unemployment.

    ERIC Educational Resources Information Center

    Jenkins, Richard; Hutson, Susan

    The relationship between long-term youth unemployment and family relationships and that between youth unemployment and courtship and marriage patterns were examined in a study conducted in two towns in South Wales. Thirty-seven young men and 26 young women between the ages of 18 and 25 who had been unemployed for 6 months or longer were…

  13. Long Term Toxicity of Cancer Treatment in Older Patients

    PubMed Central

    Shahrokni, Armin; Wu, Abraham; Carter, Jeanne; Lichtman, Stuart M.

    2016-01-01

    Synopsis With earlier cancer diagnosis among older cancer patients, the possibility of curing cancer increases. However, cancer treatment may have long lasting impact on older cancer survivors. It is vital to screen, diagnose and properly manage the long term toxicities of cancer treatment, in order to maintain quality of life of older cancer survivors PMID:26614861

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

    EPA Science Inventory

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

  15. Mathematics Learning Development: The Role of Long-Term Retrieval

    ERIC Educational Resources Information Center

    Calderón-Tena, Carlos O.; Caterino, Linda C.

    2016-01-01

    This study assessed the relation between long-term memory retrieval and mathematics calculation and mathematics problem solving achievement among elementary, middle, and high school students in nationally representative sample of US students, when controlling for fluid and crystallized intelligence, short-term memory, and processing speed. As…

  16. Suicidal Behavior in Long-Term Care Facilities.

    ERIC Educational Resources Information Center

    Osgood, Nancy J.; Brant, Barbara A.

    1990-01-01

    Surveyed administrators of 463 long-term care facilities concerning overt suicides and intentional life-threatening behaviors. Data revealed that White males were highest risk group. Refusal to eat, drink, or take medications were most common suicidal behaviors. Depression, loneliness, feelings of family rejection, and loss were significant…

  17. Dilution as a Model of Long-Term Forgetting

    ERIC Educational Resources Information Center

    Lansdale, Mark; Baguley, Thom

    2008-01-01

    This article presents a model of long term forgetting based on 3 ideas: (a) Memory for a stimulus can be described by a population of accessible traces; (b) probability of retrieval after a delay is predicted by the proportion of traces in this population that will be defined as correct if sampled; and (c) this population is diluted over time by…

  18. [Psychosocial issues of long-term cancer survivors].

    PubMed

    Weis, J; Faller, H

    2012-04-01

    Although cancer incidence rates are increasing, recent statistical studies suggest that cancer patients are showing higher cure rates as well as improved overall survival rates for most cancer locations. These advances are explained by improved strategies in early diagnoses as well as improved cancer therapies. Therefore, the number of long-term cancer survivors has also increased, but only few studies, especially within the last years, have focused on psychosocial issues of this subgroup. Some studies show that overall quality of life of long-term cancer survivors is quite high and comparable to that of the normal population. Nevertheless, a substantial percentage of former patients shows reduced quality of life and suffers from various sequelae of cancer and its treatment. This review focuses on the most common psychosocial issue of long-term survivors such as reduced psychological wellbeing, neuropsychological deficits and cancer-related fatigue syndrome. Finally, recommendations for problem-oriented interventions as well as improvement of psychosocial care of long-term survivors are given.

  19. Perceptions of Abuse in the Long-Term Care Setting.

    ERIC Educational Resources Information Center

    Gupta, D.; And Others

    Although elder abuse has received much attention in recent years, little is known about long-term care staff perceptions of active and passive abuse. Health care professionals (N=72) responsible for direct care of patients within a 275-bed skilled nursing facility completed questionnaires on elder abuse. Responses were from physicians (N=6),…

  20. 26 CFR 1.460-1 - Long-term contracts.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... earned on any hypothetical overpayment of tax, attributable to accounting for the long-term contract... taxpayer may determine the income from an exempt construction contract using any accounting method... of accounting), regardless of a taxpayer's overall method of accounting. See § 1.461-4(d)(2)(ii)...

  1. Long term agro-ecosystem research: The Southern Plains partnership

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The USDA Agricultural Research Service (ARS) is coordinating ten well-established research sites as a Long Term Agro-ecosystem Research (LTAR) Network. The goal of the LTAR is to sustain a land-based infrastructure for research, environmental management testing, and education, that enables understan...

  2. Air Force Research Laboratory’s Focused Long Term Challenges

    DTIC Science & Technology

    2008-04-01

    Air Force Research Laboratory ( AFRL ) mission is to provide support to the Air Force (AF) and the warfighters with... Air Force Research Laboratory’s Focused Long Term Challenges Leo J Rose Munitions Directorate, Air Force Research Laboratory , 101 W Eglin Blvd...This technology vision, which was born in our Air Force Research Laboratory , builds on the Air Force’s traditional kill

  3. Neural correlates of long-term intense romantic love.

    PubMed

    Acevedo, Bianca P; Aron, Arthur; Fisher, Helen E; Brown, Lucy L

    2012-02-01

    The present study examined the neural correlates of long-term intense romantic love using functional magnetic resonance imaging (fMRI). Ten women and 7 men married an average of 21.4 years underwent fMRI while viewing facial images of their partner. Control images included a highly familiar acquaintance; a close, long-term friend; and a low-familiar person. Effects specific to the intensely loved, long-term partner were found in: (i) areas of the dopamine-rich reward and basal ganglia system, such as the ventral tegmental area (VTA) and dorsal striatum, consistent with results from early-stage romantic love studies; and (ii) several regions implicated in maternal attachment, such as the globus pallidus (GP), substantia nigra, Raphe nucleus, thalamus, insular cortex, anterior cingulate and posterior cingulate. Correlations of neural activity in regions of interest with widely used questionnaires showed: (i) VTA and caudate responses correlated with romantic love scores and inclusion of other in the self; (ii) GP responses correlated with friendship-based love scores; (iii) hypothalamus and posterior hippocampus responses correlated with sexual frequency; and (iv) caudate, septum/fornix, posterior cingulate and posterior hippocampus responses correlated with obsession. Overall, results suggest that for some individuals the reward-value associated with a long-term partner may be sustained, similar to new love, but also involves brain systems implicated in attachment and pair-bonding.

  4. Long-Term Outcome in Pyridoxine-Dependent Epilepsy

    ERIC Educational Resources Information Center

    Bok, Levinus A.; Halbertsma, Feico J..; Houterman, Saskia; Wevers, Ron A.; Vreeswijk, Charlotte; Jakobs, Cornelis; Struys, Eduard; van der Hoeven, Johan H.; Sival, Deborah A.; Willemsen, Michel A.

    2012-01-01

    Aim: The long-term outcome of the Dutch pyridoxine-dependent epilepsy cohort and correlations between patient characteristics and follow-up data were retrospectively studied. Method: Fourteen patients recruited from a national reference laboratory were included (four males, 10 females, from 11 families; median age at assessment 6y; range 2y…

  5. Dying with Dementia in Long-Term Care

    ERIC Educational Resources Information Center

    Sloane, Philip D.; Zimmerman, Sheryl; Williams, Christianna S.; Hanson, Laura C.

    2008-01-01

    Purpose: To better understand the experiences and potential unmet need of persons who die in long-term care. Design and Methods: We conducted after-death interviews with staff who had cared for 422 decedents with dementia and 159 who were cognitively intact and received terminal care in U.S. nursing homes (NHs) or residential care-assisted living…

  6. Long-Term Impact of Service Learning in Environmental Studies

    ERIC Educational Resources Information Center

    MacFall, Janet

    2012-01-01

    Long-term impacts from a senior course in Environmental Studies were evaluated by a survey of program graduates (36 respondents, 50% response rate) who had participated in the course over an 8-year permiod. Each year, the Senior Seminar used a service-learning pedagogy with a different environmentally focused project ranging from web resource…

  7. The Long-Term Effects of Youth Unemployment

    ERIC Educational Resources Information Center

    Mroz, Thomas A.; Savage, Timothy H.

    2006-01-01

    Using NLSY data, we examine the long-term effects of youth unemployment on later labor market outcomes. Involuntary unemployment may yield suboptimal investments in human capital in the short run. A theoretical model of dynamic human capital investment predicts a rational "catch-up" response. Using semiparametric techniques to control for the…

  8. Treatment for childhood cancer -- long-term risks

    MedlinePlus

    ... care providers and detect any problems early. What Causes Late Effects Some cancer treatments damage healthy cells. The damage ... cells grow. Radiation therapy has a more direct effect on long-term growth ... surgery is performed, it may cause changes in the growth or function of an ...

  9. Soil quality assessment in long-term direct seed

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Producers in the Pacific Northwest are adopting direct seed farming to reduce soil erosion, improve soil quality and increase water infiltration. Some direct seed producers are concerned with reaching the yield and profit potential expected with long-term direct seed, and this may be due to soil st...

  10. The Long-Term Effects of Remedial Reading Instruction.

    ERIC Educational Resources Information Center

    Brightbill, Mary

    The long-term effects (after 3 to 5 years) of remedial reading instruction were examined. Comparison was made on reading achievement scores and on achievement ratios between a group of 16 former remedial reading clinic students, aged 12 to 20, and a matched group which did not receive remedial instruction. In addition, 45 former remedial readers…

  11. Long-Term Teacher Effects on Pupils' Learning Gains

    ERIC Educational Resources Information Center

    Bressoux, Pascal; Bianco, Maryse

    2004-01-01

    Many studies have demonstrated that a teacher has a substantial impact on how much pupils learn. However, research on the long-term effects of teachers is scarce, and the results obtained so far are inconsistent. Some studies have concluded that teacher effects are relatively permanent, while others claim that they fade away more or less rapidly…

  12. Increasing long term response by selecting for favorable minor alleles

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Long-term response of genomic selection can be improved by considering allele frequencies of selected markers or quantitative trait loci (QTLs). A previous formula to weight allele frequency of favorable minor alleles was tested, and 2 new formulas were developed. The previous formula used nonlinear...

  13. Long-Term Psychosomatic Effects of Biofeedback vs. Relaxation Training.

    ERIC Educational Resources Information Center

    Nowlis, David P.; Borzone, Ximena C.

    Differences were compared in the short-term and long-term responses of subjects with headache, insomnia, or hypertension to biofeedback training, relaxation, or a combination of both. Headache sufferers, insomniacs, and hypertensives were randomly assigned in equal numbers to biofeedback, relaxation training or a record-keeping control. Over 2…

  14. Experiences of the Long Term Stability at SLS

    SciTech Connect

    Wei, F. Q.

    2007-01-19

    The long term stability on the scale from days to a year, besides the short term stability, is one of key performance indicators of a light source. The Swiss Light Source (SLS) was installed and commissioned in 2000. It has successfully worked for more than 5 years without re-alignment of the machine. Hydrostatic Leveling System (HLS) and Horizontal Position System (HPS) have been added at supports of the storage ring (48 girders). They made evidence that the position of SLS Storage Ring (SR) is very stable on the time scale of a day, a week, a month and a year. The evidence for the long term stability is also provided by frequency of the RF cavity. The HLS is a powerful tool. The analysis of the HLS data shows that the vertical displacements, which are adjusted to correct average orbit deviations, of the SLS storage ring foundation and of the girder supports were in the range of 0.15 mm in 2003. The site, the building foundation, the mechanical supports and the temperature control are important pre-conditions to get the good long term stability. The experience gained with the long term stability at SLS is presented.

  15. Recommendations for Long Term Care in an Elderly Medicaid Population.

    ERIC Educational Resources Information Center

    Travis, Shirley S.; McAuley, William J.

    The State of Virginia has had a statewide nursing home preadmission screening program since 1977 and has made efforts to ensure appropriate placement of individuals in long term care settings. In a major effort to divert certain individuals from institutionalization, a personal care option has been provided. Using data from the Preadmission…

  16. Long-Term Sensitization Training Primes "Aplysia" for Further Learning

    ERIC Educational Resources Information Center

    Cleary, Leonard J.; Byrne, John H.; Antzoulatos, Evangelos G.; Wainwright, Marcy L.

    2006-01-01

    Repetitive, unilateral stimulation of "Aplysia" induces long-term sensitization (LTS) of ipsilaterally elicited siphon-withdrawal responses. Whereas some morphological effects of training appear only on ipsilateral sensory neurons, others appear bilaterally. We tested the possibility that contralateral morphological modifications may have…

  17. Sexuality and Aging: Implications for Long Term Care.

    ERIC Educational Resources Information Center

    Hinkley, Nancy E.

    With increasing emphasis on treating the whole person, on the maintenance of an individual's former life style, and on patients' rights, long-term care personnel need to become aware that many nursing home residents experience needs related to their sexuality. A model two-day workshop is presented wlth a focus on the following topics: (1) a broad…

  18. Children's Long-Term Memory for Autobiographical Events.

    ERIC Educational Resources Information Center

    Peterson, Carole

    2002-01-01

    Traces the origins of children's autobiographical memories, discussing research on infantile amnesia and young children's memory skills. Focuses on studies of children's long-term memory for autobiographical events that investigate delays of 1-2 years and delays of 4 years or more. Reports that a few studies have documented remarkably robust…

  19. Consolidation of Long-Term Memory: Evidence and Alternatives

    ERIC Educational Resources Information Center

    Meeter, Martijn; Murre, Jaap M. J.

    2004-01-01

    Memory loss in retrograde amnesia has long been held to be larger for recent periods than for remote periods, a pattern usually referred to as the Ribot gradient. One explanation for this gradient is consolidation of long-term memories. Several computational models of such a process have shown how consolidation can explain characteristics of…

  20. The Basics of Long-Term Debt Issuance and Management

    ERIC Educational Resources Information Center

    Van Meter, Christine M.

    2011-01-01

    Issuing long-term debt can be a complex, multifaceted process. Although the process varies by stare, typically the school business official and the district solicitor work with the financing ream, which includes a financial adviser, bond counsel, underwriter, raring agency, and possibly a bond insurance agent, paying agent, and architect.…

  1. Areas of Marital Dissatisfaction among Long-Term Couples

    ERIC Educational Resources Information Center

    Duba, Jill D.; Hughey, Aaron W.; Lara, Tracy; Burke, Monica G.

    2012-01-01

    To better understand relational dissatisfaction and duration of long-term married couples, this study surveyed 30 couples married at least 40 years with the Marital Satisfaction Inventory. Findings suggest various areas of dissatisfaction (e.g., affective communication, conflict over child rearing) and relationship among and link to other areas of…

  2. Incidental Biasing of Attention from Visual Long-Term Memory

    ERIC Educational Resources Information Center

    Fan, Judith E.; Turk-Browne, Nicholas B.

    2016-01-01

    Holding recently experienced information in mind can help us achieve our current goals. However, such immediate and direct forms of guidance from working memory are less helpful over extended delays or when other related information in long-term memory is useful for reaching these goals. Here we show that information that was encoded in the past…

  3. Effective Counseling Strategies for Supporting Long-Term Suspended Students

    ERIC Educational Resources Information Center

    Johnson, Janet L.; Sparks, Eric; Lewis, Rita G.; Niedrich, Kris; Hall, Mary; Johnson, Julie

    2006-01-01

    Long-term suspended (LTS) students are barred from the school system for lengthy periods, leaving them at risk of academic failure and vulnerable from lack of services. A program in a North Carolina public school system provided counselors to work with each LTS student. Outcome data were analyzed to determine the effectiveness of counseling…

  4. 78 FR 36449 - State Long-Term Care Ombudsman Program

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-18

    .... Functions and Responsibilities of the State Long-Term Care Ombudsman G. State Agency Responsibilities... for Aging in areas related to: 1. The roles, responsibilities and relationship of the State agency on... the individual roles and responsibilities of the Ombudsman (or representatives of the Office)...

  5. Arkansas Long Term Care Facility Nursing Assistant Training Curriculum. Revised.

    ERIC Educational Resources Information Center

    Arkansas State Dept. of Human Services, Little Rock.

    This curriculum is designed for use in developing training programs for nursing assistants who provide nursing or nursing-related services to residents in long-term care (LTC) facilities. Implementation provisions provide a general overview of the basic requirements found in Arkansas' Nursing Assistant Training Program "Rules and Regulations." The…

  6. Relating Granger causality to long-term causal effects.

    PubMed

    Smirnov, Dmitry A; Mokhov, Igor I

    2015-10-01

    In estimation of causal couplings between observed processes, it is important to characterize coupling roles at various time scales. The widely used Granger causality reflects short-term effects: it shows how strongly perturbations of a current state of one process affect near future states of another process, and it quantifies that via prediction improvement (PI) in autoregressive models. However, it is often more important to evaluate the effects of coupling on long-term statistics, e.g., to find out how strongly the presence of coupling changes the variance of a driven process as compared to an uncoupled case. No general relationships between Granger causality and such long-term effects are known. Here, we pose the problem of relating these two types of coupling characteristics, and we solve it for a class of stochastic systems. Namely, for overdamped linear oscillators, we rigorously derive that the above long-term effect is proportional to the short-term effects, with the proportionality coefficient depending on the prediction interval and relaxation times. We reveal that this coefficient is typically considerably greater than unity so that small normalized PI values may well correspond to quite large long-term effects of coupling. The applicability of the derived relationship to wider classes of systems, its limitations, and its value for further research are discussed. To give a real-world example, we analyze couplings between large-scale climatic processes related to sea surface temperature variations in equatorial Pacific and North Atlantic regions.

  7. Relating Granger causality to long-term causal effects

    NASA Astrophysics Data System (ADS)

    Smirnov, Dmitry A.; Mokhov, Igor I.

    2015-10-01

    In estimation of causal couplings between observed processes, it is important to characterize coupling roles at various time scales. The widely used Granger causality reflects short-term effects: it shows how strongly perturbations of a current state of one process affect near future states of another process, and it quantifies that via prediction improvement (PI) in autoregressive models. However, it is often more important to evaluate the effects of coupling on long-term statistics, e.g., to find out how strongly the presence of coupling changes the variance of a driven process as compared to an uncoupled case. No general relationships between Granger causality and such long-term effects are known. Here, we pose the problem of relating these two types of coupling characteristics, and we solve it for a class of stochastic systems. Namely, for overdamped linear oscillators, we rigorously derive that the above long-term effect is proportional to the short-term effects, with the proportionality coefficient depending on the prediction interval and relaxation times. We reveal that this coefficient is typically considerably greater than unity so that small normalized PI values may well correspond to quite large long-term effects of coupling. The applicability of the derived relationship to wider classes of systems, its limitations, and its value for further research are discussed. To give a real-world example, we analyze couplings between large-scale climatic processes related to sea surface temperature variations in equatorial Pacific and North Atlantic regions.

  8. Long-Term Care: Common Issues and Unknowns

    ERIC Educational Resources Information Center

    Swartz, Katherine; Miake, Naoko; Farag, Nadine

    2012-01-01

    All industrialized countries are grappling with a common problem--how to provide assistance of various kinds to their rapidly aging populations. The problem for countries searching for models of efficient and high-quality long-term care (LTC) policies is that fewer than a dozen countries have government-organized, formal LTC policies. Relatively…

  9. Long-term prognosis of depression in primary care.

    PubMed Central

    Simon, G. E.

    2000-01-01

    This article uses longitudinal data from a primary care sample to examine long-term prognosis of depression. A sample of 225 patients initiating antidepressant treatment in primary care completed assessments of clinical outcome (Hamilton Depression Rating Scale and the mood module of the Structured Clinical Interview for DSM-IIIR) 1, 3, 6, 9, 12, 18 and 24 months after initiating treatment. The proportion of patients continuing to meet criteria for major depression fell rapidly to approximately 10% and remained at approximately that level throughout follow-up. The proportion meeting criteria for remission (Hamilton Depression score of 7 or less) rose gradually to approximately 45%. Long-term prognosis (i.e. probability of remission at 6 months and beyond) was strongly related to remission status at 3 months (odds ratio 3.65; 95% confidence interval, 2.81-4.76) and only modestly related to various clinical characteristics assessed at baseline (e.g. prior history of recurrent depression, medical comorbidity, comorbid anxiety symptoms). The findings indicate that potentially modifiable risk factors influence the long-term prognosis of depression. This suggests that more systematic and effective depression treatment programmes might have an important effect on long-term course and reduce the overall burden of chronic and recurrent depression. PMID:10885162

  10. San Francisco Bay Long Term Management Strategy for Dredging

    EPA Pesticide Factsheets

    The San Francisco Bay Long Term Management Strategy (LTMS) is a cooperative effort to develop a new approach to dredging and dredged material disposal in the San Francisco Bay area. The LTMS serves as the Regional Dredging Team for the San Francisco area.

  11. Post-Learning Arousal Change and Long-Term Retention.

    ERIC Educational Resources Information Center

    Kumar, V.K.; Farley, Frank H.

    This study examined the effects on long-term retention of variations in intensity and of temporal parameters of arousal following a single learning trial in a paired-associate task. The subjects were 56 female university students. Intensity of arousal was manipulated by using two levels of white noise--75 decibels and 90 decibels sound pressure…

  12. Long-Term Adaptation to Institutionalization in Dementia Caregivers

    ERIC Educational Resources Information Center

    Gaugler, Joseph E.; Pot, Anne Margriet; Zarit, Steven H.

    2007-01-01

    Purpose: Longitudinal research in dementia has acknowledged the importance of transitions during the course of family caregiving. However, long-term adaptation to institutionalization has received little attention. This study attempts to describe caregivers' adaptation (changes in stress, well-being, and psychosocial resources) to placement up to…

  13. Long-term Toxicity of Cancer Treatment in Older Patients.

    PubMed

    Shahrokni, Armin; Wu, Abraham J; Carter, Jeanne; Lichtman, Stuart M

    2016-02-01

    With earlier cancer diagnosis among older patients with cancer, the possibility of curing cancer increases. However, cancer treatment may have a long-lasting impact on older cancer survivors. It is vital to screen, diagnose, and properly manage the long-term toxicities of cancer treatment in order to maintain the quality of life of older cancer survivors.

  14. Crystalline Concepts in Long-Term Mathematical Invention and Discovery

    ERIC Educational Resources Information Center

    Tall, David

    2011-01-01

    This paper introduces the notion of "crystalline concept" as a focal idea in long-term mathematical thinking, bringing together the geometric development of Van Hiele, process-object encapsulation, and formal axiomatic systems. Each of these is a strand in the framework of "three worlds of mathematics" with its own special characteristics, but all…

  15. Long Term Synaptic Plasticity and Learning in Neuronal Networks.

    DTIC Science & Technology

    1987-09-14

    2312/Al Al -p 1. TITLE (Include Security Classification) ’a LONG TERM SYNAPTIC PLASTICITY AND LEARNING IN NEURONAL NETWORKS 12. PERSONAL AUTHOR(S...Analysis of Simple Neuronal Networks " (2nd Annual Symposium on Networks in Brain and Computer Architecture, North Texas State University, Denton, TX

  16. Long-term results after robotically assisted coronary bypass surgery

    PubMed Central

    Ramahi, Jehad; Hasan, Faisal; Edris, Ahmad; Bartel, Thomas; Nair, Ravi; Tuzcu, Murat; Suri, Rakesh; Mihaljevic, Tomislav

    2016-01-01

    Background Robotically-assisted coronary bypass grafting (CABG) was introduced in 1998 and dedicated centers have continuously applied and developed this minimally invasive method of coronary bypass surgery. While short-term results are relatively well published, data on long-term outcome are limited. In this literature review, we assessed the outcomes after robotic CABG following the first postoperative year. Methods We searched PubMed for articles containing the terms “robotic” or “robotically assisted” and “coronary bypass”. A total of 11 papers contained long-term results. We specifically investigated survival, graft patency, freedom from angina and re-intervention, as well as freedom from major adverse cardiac and cerebrovascular events (MACCE). Results Five-year survival after robotic CABG was consistently consistently greater than 90% and graft patency between 3 and 5 years was reported to be above 90%. Fifteen percent to 26% of patients re-experienced angina at 3 to 5 years postoperatively. Long-term freedom from re-intervention reached the range and the 5-year freedom from MACCE rate was approximately 75%. Conclusions According to data in the literature, long-term results after CABG carried out with the assistance of a surgical robot appear to be in line with results achieved after conventional CABG. PMID:27942487

  17. Concept Formation Skills in Long-Term Cochlear Implant Users

    ERIC Educational Resources Information Center

    Castellanos, Irina; Kronenberger, William G.; Beer, Jessica; Colson, Bethany G.; Henning, Shirley C.; Ditmars, Allison; Pisoni, David B.

    2015-01-01

    This study investigated if a period of auditory sensory deprivation followed by degraded auditory input and related language delays affects visual concept formation skills in long-term prelingually deaf cochlear implant (CI) users. We also examined if concept formation skills are mediated or moderated by other neurocognitive domains (i.e.,…

  18. Does Head Start Yield Long-Term Benefits?

    ERIC Educational Resources Information Center

    Aughinbaugh, Alison

    2001-01-01

    Using 1997 National Longitudinal Survey of Youth data (n=7,787), the relationship between Head Start and school suspensions, grade repetition, and math achievement was examined. Estimates indicate that Head Start does not have long-term benefits, a finding compatible with studies showing that compensatory preschool programs need to be long in…

  19. Elders' Use of Informal Long-Term Care Assistance.

    ERIC Educational Resources Information Center

    Branch, Laurence G.; Jette, Alan M.

    1983-01-01

    Over 80 percent of a sample of community-living elderly were self-sufficient in performing basic activities of daily living (ADL); only 18 percent were self-sufficient in performing instrumental ADL. Most elders who use long-term care assistance relied solely on the informal support network in both instrumental (86 percent) and basic (50 percent)…

  20. Sex Differences among the Long-Term Mentally Disabled.

    ERIC Educational Resources Information Center

    Mowbray, Carol T.; Chamberlain, Philip

    1986-01-01

    Describes the experientially determined problems of long-term mentally disabled women. Reviews of 320 hospital records of patients in hospitals throughout Michigan showed significant sex differences for client age, marital status, living arrangement, diagnosis, functioning level, voluntary/involuntary status, admission information, medications,…