WorldWideScience

Sample records for purine-pyrimidine metabolism inborn errors

  1. Inborn Errors of Metabolism

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    2007164 Diagnosis, treatment and long-term following up of 223 patients with hyperphenylalaninemia detected by neonatal screening programs. YE Jun(叶军), et al. Xinhua Hosp, Shanghai Jiaotong Univ Med Sch, Shanghai Instit Pediatr Res, Shanghai 200092. Chin J Prev Med 2007;41(3);189-192. Objective To investigate the incidence of hyperphenylalaninemia (HPA) caused by different etiologic factors in China and the relationship between the phenylalanine and mental development of patients with HPAs who were diagnosed by neonatal screening and early treated. Methods Two hundred and twenty-three patients with HPA detected by neonatal screening programs were refered to us at the age of (41±27) days after birth. The differential diagnosis was performed by BH4 (20 mg/kg) loading test, urinary pterin analysis and dihydropteridine reductase (DHPR) activity determination respectively. The control of phenylalanine (Phe) metabolism, growth and mental development were evaluated in all treated patients. Related gene mutation analysis was performed in some patients. Results One hundred and twenty nine of 223 patients (57.8%) were diagnosed as phenylalanine hydroxylase deficiency (PAHD), 64 patients (28.7%) as BH4 responsive PAHD, 30 patients (13.5%) as 6-pyruvoyl tetrahydropterin synthase deficiency (PTSD). One hundred and forty-nine patients were followed at age of 4 m-22 y in our clinic. The 136 of 149 patients were treated according to different etiology at the age of 1.6 m(0.5~3.5 m) after birth. Thirteen patients were followed up without the need for treatment. All patients had normal growth development. One hundred and eight (79.4%) of 136 treated patients had normal mental development. The negative correlation(r=-0.439, P<0.01) between IQ and average Phe levels were observed in 58 patients. Twenty-eight patients were able to go to primary school or even university. Nine kinds of PTS gene mutations were found in 9 cases with PTSD, among which 286G→A and 259C→T were most

  2. Cardiac manifestations of inborn errors of metabolism.

    NARCIS (Netherlands)

    Evangeliou, A.; Papadopoulou-Legbelou, K.; Daphnis, E.; Ganotakis, E.; Vavouranakis, I.; Michailidou, H.; Hitoglou-Makedou, A.; Nicolaidou, P.; Wevers, R.A.; Varlamis, G.

    2007-01-01

    AIM: The aim of the study was to investigate the frequency and type of cardiac manifestations in a defined group of patients with inborn errors of metabolism. This paper also explores the key role of cardiac manifestations in the diagnosis of inborn errors of metabolism in daily practice. METHODS: O

  3. Inborn errors of metabolism underlying primary immunodeficiencies.

    Science.gov (United States)

    Parvaneh, Nima; Quartier, Pierre; Rostami, Parastoo; Casanova, Jean-Laurent; de Lonlay, Pascale

    2014-10-01

    A number of inborn errors of metabolism (IEM) have been shown to result in predominantly immunologic phenotypes, manifesting in part as inborn errors of immunity. These phenotypes are mostly caused by defects that affect the (i) quality or quantity of essential structural building blocks (e.g., nucleic acids, and amino acids), (ii) cellular energy economy (e.g., glucose metabolism), (iii) post-translational protein modification (e.g., glycosylation) or (iv) mitochondrial function. Presenting as multisystemic defects, they also affect innate or adaptive immunity, or both, and display various types of immune dysregulation. Specific and potentially curative therapies are available for some of these diseases, whereas targeted treatments capable of inducing clinical remission are available for others. We will herein review the pathogenesis, diagnosis, and treatment of primary immunodeficiencies (PIDs) due to underlying metabolic disorders.

  4. Inborn errors of cytoplasmic triglyceride metabolism.

    Science.gov (United States)

    Wu, Jiang Wei; Yang, Hao; Wang, Shu Pei; Soni, Krishnakant G; Brunel-Guitton, Catherine; Mitchell, Grant A

    2015-01-01

    Triglyceride (TG) synthesis, storage, and degradation together constitute cytoplasmic TG metabolism (CTGM). CTGM is mostly studied in adipocytes, where starting from glycerol-3-phosphate and fatty acyl (FA)-coenzyme A (CoA), TGs are synthesized then stored in cytoplasmic lipid droplets. TG hydrolysis proceeds sequentially, producing FAs and glycerol. Several reactions of CTGM can be catalyzed by more than one enzyme, creating great potential for complex tissue-specific physiology. In adipose tissue, CTGM provides FA as a systemic energy source during fasting and is related to obesity. Inborn errors and mouse models have demonstrated the importance of CTGM for non-adipose tissues, including skeletal muscle, myocardium and liver, because steatosis and dysfunction can occur. We discuss known inborn errors of CTGM, including deficiencies of: AGPAT2 (a form of generalized lipodystrophy), LPIN1 (childhood rhabdomyolysis), LPIN2 (an inflammatory condition, Majeed syndrome, described elsewhere in this issue), DGAT1 (protein loosing enteropathy), perilipin 1 (partial lipodystrophy), CGI-58 (gene ABHD5, neutral lipid storage disease (NLSD) with ichthyosis and "Jordan's anomaly" of vacuolated polymorphonuclear leukocytes), adipose triglyceride lipase (ATGL, gene PNPLA2, NLSD with myopathy, cardiomyopathy and Jordan's anomaly), hormone-sensitive lipase (HSL, gene LIPE, hypertriglyceridemia, and insulin resistance). Two inborn errors of glycerol metabolism are known: glycerol kinase (GK, causing pseudohypertriglyceridemia) and glycerol-3-phosphate dehydrogenase (GPD1, childhood hepatic steatosis). Mouse models often resemble human phenotypes but may diverge markedly. Inborn errors have been described for less than one-third of CTGM enzymes, and new phenotypes may yet be identified.

  5. Inborn errors of metabolism: a clinical overview

    Directory of Open Access Journals (Sweden)

    Ana Maria Martins

    1999-11-01

    Full Text Available CONTEXT: Inborn errors of metabolism cause hereditary metabolic diseases (HMD and classically they result from the lack of activity of one or more specific enzymes or defects in the transportation of proteins. OBJECTIVES: A clinical review of inborn errors of metabolism (IEM to give a practical approach to the physician with figures and tables to help in understanding the more common groups of these disorders. DATA SOURCE: A systematic review of the clinical and biochemical basis of IEM in the literature, especially considering the last ten years and a classic textbook (Scriver CR et al, 1995. SELECTION OF STUDIES: A selection of 108 references about IEM by experts in the subject was made. Clinical cases are presented with the peculiar symptoms of various diseases. DATA SYNTHESIS: IEM are frequently misdiagnosed because the general practitioner, or pediatrician in the neonatal or intensive care units, does not think about this diagnosis until the more common cause have been ruled out. This review includes inheritance patterns and clinical and laboratory findings of the more common IEM diseases within a clinical classification that give a general idea about these disorders. A summary of treatment types for metabolic inherited diseases is given. CONCLUSIONS: IEM are not rare diseases, unlike previous thinking about them, and IEM patients form part of the clientele in emergency rooms at general hospitals and in intensive care units. They are also to be found in neurological, pediatric, obstetrics, surgical and psychiatric clinics seeking diagnoses, prognoses and therapeutic or supportive treatment.

  6. Screening for Inborn Errors of Metabolism

    Directory of Open Access Journals (Sweden)

    F.A. Elshaari

    2013-09-01

    Full Text Available Inborn errors of metabolism (IEM are a heterogeneous group of monogenic diseases that affect the metabolic pathways. The detection of IEM relies on a high index of clinical suspicion and co-ordinated access to specialized laboratory services. Biochemical analysis forms the basis of the final confirmed diagnosis in several of these disorders. The investigations fall into four main categories1.General metabolic screening tests2.Specific metabolite assays3.Enzyme studies4.DNA analysis The first approach to the diagnosis is by a multi-component analysis of body fluids in clinically selected patients, referred to as metabolic screening tests. These include simple chemical tests in the urine, blood glucose, acid-base profile, lactate, ammonia and liver function tests. The results of these tests can help to suggest known groups of metabolic disorders so that specific metabolites such as amino acids, organic acids, etc. can be estimated. However, not all IEM needs the approach of general screening. Lysosomal, peroxisomal, thyroid and adrenal disorders are suspected mainly on clinical grounds and pertinent diagnostic tests can be performed. The final diagnosis relies on the demonstration of the specific enzyme defect, which can be further confirmed by DNA studies.

  7. Inborn errors of creatine metabolism and epilepsy.

    Science.gov (United States)

    Leuzzi, Vincenzo; Mastrangelo, Mario; Battini, Roberta; Cioni, Giovanni

    2013-02-01

    Creatine metabolism disorders include guanidinoacetate methyltransferase (GAMT) deficiency, arginine:glycine amidinotransferase (AGAT) deficiency, and the creatine transporter (CT1-encoded by SLC6A8 gene) deficiency. Epilepsy is one of the main symptoms in GAMT and CT1 deficiency, whereas the occurrence of febrile convulsions in infancy is a relatively common presenting symptom in all the three above-mentioned diseases. GAMT deficiency results in a severe early onset epileptic encephalopathy with development arrest, neurologic deterioration, drug-resistant seizures, movement disorders, mental disability, and autistic-like behavior. In this disorder, epilepsy and associated abnormalities on electroencephalography (EEG) are more responsive to substitutive treatment with creatine monohydrate than to conventional antiepileptic drugs. AGAT deficiency is mainly characterized by mental retardation and severe language disorder without epilepsy. In CT1 deficiency epilepsy is generally less severe than in GAMT deficiency. All creatine disorders can be investigated through measurement of creatine metabolites in body fluids, brain proton magnetic resonance spectroscopy ((1) H-MRS), and molecular genetic techniques. Blood guanidinoacetic acid (GAA) assessment and brain H-MRS examination should be part of diagnostic workup for all patients presenting with epileptic encephalopathy of unknown origin. In girls with learning and/or intellectual disabilities with or without epilepsy, SLC6A8 gene assessment should be part of the diagnostic procedures. The aims of this review are the following: (1) to describe the electroclinical features of epilepsy occurring in inborn errors of creatine metabolism; and (2) to delineate the metabolic alterations associated with GAMT, AGAT, and CT1 deficiency and the role of a substitutive therapeutic approach on their clinical and electroencephalographic epileptic patterns. Wiley Periodicals, Inc. © 2012 International League Against Epilepsy.

  8. Infant with cardiomyopathy: When to suspect inborn errors of metabolism?

    Institute of Scientific and Technical Information of China (English)

    Stephanie; L; Byers; Can; Ficicioglu

    2014-01-01

    Inborn errors of metabolism are identified in 5%-26% of infants and children with cardiomyopathy. Although fatty acid oxidation disorders, lysosomal and glycogen storage disorders and organic acidurias are well-known to be associated with cardiomyopathies, emerging reports suggest that mitochondrial dysfunction and congenital disorders of glycosylation may also account for a proportion of cardiomyopathies. This review article clarifies when primary care physicians and cardiologists should suspect inborn errors of metabolism in a patient with cardiomyopathy, and refer the patient to a metabolic specialist for a further metabolic work up, with specific discussions of “red flags” which should prompt additional evaluation.

  9. Inborn errors of metabolism revealed by organic acid profile analysis ...

    African Journals Online (AJOL)

    Objective: To determine the prevalence and types of inborn errors of amino ... of a metabolic disorder were studied, their ages ranged from 3 days to 12 years. ... cases (54 %), glutaric aciduria type I 3cases (13 %), phenylketonuria 2 cases (9 ...

  10. Ophthalmologic findings in patients with inborn errors of metabolism

    Directory of Open Access Journals (Sweden)

    Guevara Márquez Yamel Carolina

    2014-07-01

    Full Text Available In patient with inborn errors of metabolism (IEM, the presence of characteristic findings in ophthalmic assessment are important for the diagnosis. The presence of cataracts, cherry-red spot, corneal opacities, corneal crystals, lens dislocation, gyrate atrophy, etc., are some of the ocular abnormalities present in certain IEM. The role of the ophthalmologist in the evaluation of patients with IEM is essential. We describe the most frequent ocular findings in patients with different IEM, which are a diagnostic aid for ophthalmologists and pediatricians.

  11. Inborn Errors of Intermediary Metabolism in Critically Ill Mexican Newborns

    Directory of Open Access Journals (Sweden)

    Ibarra-González Isabel MSc

    2014-04-01

    Full Text Available Inborn errors of intermediary metabolism (IEiM are complex diseases with high clinical heterogeneity, and some patients who have severe enzyme deficiencies or are subjected to stress (catabolism/infections actually decompensate in the neonatal period. In this study, we performed metabolic tests on 2025 newborns in Mexico admitted to 35 neonatal intensive care units or emergency wards (NICUs/EWs over a 6-year period, in whom a metabolic disorder was clinically suspected. Of these 2025 newborns with sickness, 11 had IEiM, revealing a prevalence of 1:184. Clinical characteristics and outcomes of the newborns with confirmed IEiM are shown. Of these 11 patients, 4 had isolated methylmalonic acidemia, 3 had maple syrup urine disease, 2 had urea cycle disorders, 1 had 3-hydroxy-3-methylglutaric acidemia, and 1 had isovaleric acidemia. During the first week of life (average 3 days, all of these newborns presented with impaired alertness, hypotonia, feeding difficulties, and vomiting along with metabolic acidosis and hyperammonemia. Of the 11 newborns with IEiM, 7 died, leading to a mortality rate of 64%. In conclusion, the differential diagnosis of newborns admitted to the NICU/EW must include IEiM, requiring systematic screening of this population.

  12. In vivo enzyme activity in inborn errors of metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Thompson, G.N.; Walter, J.H.; Leonard, J.V.; Halliday, D. (Clinical Research Centre, Harrow (England))

    1990-08-01

    Low-dose continuous infusions of (2H5)phenylalanine, (1-13C)propionate, and (1-13C)leucine were used to quantitate phenylalanine hydroxylation in phenylketonuria (PKU, four subjects), propionate oxidation in methylmalonic acidaemia (MMA, four subjects), and propionic acidaemia (PA, four subjects) and leucine oxidation in maple syrup urine disease (MSUD, four subjects). In vivo enzyme activity in PKU, MMA, and PA subjects was similar to or in excess of that in adult controls (range of phenylalanine hydroxylation in PKU, 3.7 to 6.5 mumol/kg/h, control 3.2 to 7.9, n = 7; propionate oxidation in MMA, 15.2 to 64.8 mumol/kg/h, and in PA, 11.1 to 36.0, control 5.1 to 19.0, n = 5). By contrast, in vivo leucine oxidation was undetectable in three of the four MSUD subjects (less than 0.5 mumol/kg/h) and negligible in the remaining subject (2 mumol/kg/h, control 10.4 to 15.7, n = 6). These results suggest that significant substrate removal can be achieved in some inborn metabolic errors either through stimulation of residual enzyme activity in defective enzyme systems or by activation of alternate metabolic pathways. Both possibilities almost certainly depend on gross elevation of substrate concentrations. By contrast, only minimal in vivo oxidation of leucine appears possible in MSUD.

  13. Cultural aspects in the management of inborn errors of metabolism.

    Science.gov (United States)

    Stockler, Sylvia; Moeslinger, Dorothea; Herle, Marion; Wimmer, Banu; Ipsiroglu, Osman S

    2012-11-01

    European Health Care Systems have not yet accommodated both previous and current migration waves. Children from immigrant families, especially children with chronic conditions, are particularly affected from the shortcomings in medical care. One condition, phenylketonuria (PKU), is an inborn error of metabolism (IEM) which results in intellectual disability unless treated with a lifelong phenylalanine (Phe) restricted diet. In our PKU clinic, patients from families who previously had emmigrated from the geographic area of Turkey to Austria, exhibited worse blood Phe control and cognitive development than comparable patients from native Austrian families. Using structured and semi-structured interviews, questionnaires, and illness narratives, we identified language, psychosocial, economic, educational and cultural barriers as factors influencing adherence to treatment. Our findings led us to conclude that access to interpreter services, exploration of the socio-cultural background and of family ecology, as well as bi-directional communication and medical decision making according to the "best interest of the child" principle, may improve outcomes in patients requiring complex treatment and care.

  14. Inborn errors of metabolism in Latin America: challenges and opportunities.

    Science.gov (United States)

    Giugliani, Roberto

    2010-10-01

    Latin America includes more than 40 countries and possessions, and its population of 570 million has an important representation of the three main human races. The area is experiencing an economic improvement, progressively bringing the inborn errors of metabolism (IEM) to a higher level among health priorities. Challenges to the progress of the IEM field include the huge disparities, the high prevalence of malnutrition and infections, the co-existence of very different models of public health services, the unstable socio-economic and political conditions, and the difficulties in integrating the countries. However, a rapidly changing social and economic environment is presenting many opportunities to the IEM field, like the improvements in infrastructure, the concentration of the population in urban areas, the continuous growth of neonatal screening, the use of filter paper samples, the availability of internet communication, and the interest in IEM by the new population medical genetics discipline. Analyzing this picture, several proposals are presented, such as the development of activities of provision of health services, education and research as an integrated package, the increase in training of human resources, the expansion of access to diagnostic tests, and the use the neonatal screening framework to expand the provision of services. In a continent with few IEM centers, there is a major need for such groups to work in collaboration, complementing each other's capabilities, providing training of human resources, and developing joint projects. The integration of these groups into a large transnational network of reference centers would be a major task for the coming years.

  15. Identification and characterization of an inborn error of metabolism caused by dihydrofolate reductase deficiency

    NARCIS (Netherlands)

    Banka, S.; Blom, H.J.; Walter, J.; Aziz, M.; Urquhart, J.; Clouthier, C.M.; Rice, G.I.; Brouwer, A.P.M. de; Hilton, E.; Vassallo, G.; Will, A.; Smith, D.E.; Smulders, Y.M.; Wevers, R.A.; Steinfeld, R.; Heales, S.; Crow, Y.J.; Pelletier, J.N.; Jones, S.; Newman, W.G.

    2011-01-01

    Dihydrofolate reductase (DHFR) is a critical enzyme in folate metabolism and an important target of antineoplastic, antimicrobial, and antiinflammatory drugs. We describe three individuals from two families with a recessive inborn error of metabolism, characterized by megaloblastic anemia and/or

  16. NMR spectroscopy of aminoacylase 1 deficiency, a novel inborn error of metabolism.

    NARCIS (Netherlands)

    Engelke, U.F.H.; Sass, J.O.; Coster, R.N. van; Gerlo, E.; Olbrich, H.; Krywawych, S.; Calvin, J.; Hart, C.; Omran, H.; Wevers, R.A.

    2008-01-01

    Aminoacylase 1 deficiency is a novel inborn error of metabolism. The clinical significance of the deficiency is under discussion, as well as the possible consequences of the defect for brain metabolism and function. This study includes the five originally published cases as well as three novel ones.

  17. Inborn Errors of Fructose Metabolism. What Can We Learn from Them?

    Science.gov (United States)

    Tran, Christel

    2017-04-03

    Fructose is one of the main sweetening agents in the human diet and its ingestion is increasing globally. Dietary sugar has particular effects on those whose capacity to metabolize fructose is limited. If intolerance to carbohydrates is a frequent finding in children, inborn errors of carbohydrate metabolism are rare conditions. Three inborn errors are known in the pathway of fructose metabolism; (1) essential or benign fructosuria due to fructokinase deficiency; (2) hereditary fructose intolerance; and (3) fructose-1,6-bisphosphatase deficiency. In this review the focus is set on the description of the clinical symptoms and biochemical anomalies in the three inborn errors of metabolism. The potential toxic effects of fructose in healthy humans also are discussed. Studies conducted in patients with inborn errors of fructose metabolism helped to understand fructose metabolism and its potential toxicity in healthy human. Influence of fructose on the glycolytic pathway and on purine catabolism is the cause of hypoglycemia, lactic acidosis and hyperuricemia. The discovery that fructose-mediated generation of uric acid may have a causal role in diabetes and obesity provided new understandings into pathogenesis for these frequent diseases.

  18. Research Challenges in Central Nervous System Manifestations of Inborn Errors of Metabolism

    Science.gov (United States)

    Dickson, P.I.; Pariser, A.R.; Groft, S. C.; Ishihara, R.W.; McNeil, D.E.; Tagle, D.; Griebel, D.J.; Kaler, S.G.; Mink, J.W.; Shapiro, E.G.; Bjoraker, K.J.; Krivitzky, L.; Provenzale, J.M.; Gropman, A.; Orchard, P.; Raymond, G.; Cohen, B.H.; Steiner, R.D.; Goldkind, S. F.; Nelson, R. M.; Kakkis, E.; Patterson, M.C.

    2010-01-01

    The Research Challenges in CNS Manifestations of Inborn Errors of Metabolism workshop was designed to address challenges in translating potential therapies for these rare disorders, and to highlight novel therapeutic strategies and innovative approaches to CNS delivery, assessment of effects and directions for the future in the treatment of these diseases. Therapies for the brain in inborn errors represent some of the greatest challenges to translational research due to the special properties of the brain, and of inborn errors themselves. This review covers the proceedings of this workshop as submitted by participants. Scientific, ethical and regulatory issues are discussed, along with ways to measure outcomes and the conduct of clinical trials. Participants included regulatory and funding agencies, clinicians, scientists, industry and advocacy groups. PMID:21176882

  19. Inborn errors of metabolism in the biosynthesis and remodelling of phospholipids

    NARCIS (Netherlands)

    Wortmann, S.B.; Espeel, M.; Almeida, L.; Reimer, A.; Bosboom, D.G.; Roels, F.; Brouwer, A.P.M. de; Wevers, R.A.

    2015-01-01

    Since the proposal to define a separate subgroup of inborn errors of metabolism involved in the biosynthesis and remodelling of phospholipids, sphingolipids and long chain fatty acids in 2013, this group is rapidly expanding. This review focuses on the disorders involved in the biosynthesis of phosp

  20. Redox signalling and mitochondrial stress responses; lessons from inborn errors of metabolism

    DEFF Research Database (Denmark)

    Olsen, Rikke K J; Cornelius, Nanna; Gregersen, Niels

    2015-01-01

    Mitochondria play a key role in overall cell physiology and health by integrating cellular metabolism with cellular defense and repair mechanisms in response to physiological or environmental changes or stresses. In fact, dysregulation of mitochondrial stress responses and its consequences...... and directions that can be tested experimentally and used in the design of future new approaches for pre-symptomatic diagnosis and prognosis and perhaps more effective treatments of inborn errors of metabolism....

  1. Body composition in young adults with inborn errors of protein metabolism--a pilot study.

    Science.gov (United States)

    Wilcox, G; Strauss, B J G; Francis, D E M; Upton, H; Boneh, A

    2005-01-01

    The natural history of inborn errors of protein metabolism and the long-term effects of prescribed semisynthetic therapeutic diets are largely unknown. We assessed body composition, measuring body-fat mass and distribution, fat-free mass, total body protein, total body potassium, bone density and skeletal muscle mass, in young adults (age > 18 years; 6 female, 5 male) with inborn errors of protein metabolism maintained on long-term low-protein diets, compared with controls. Female patients were significantly shorter (159.4 cm vs 169.2 cm, p = 0.013) and had higher BMI (25.3 vs 22.0 kg/m2, p metabolic syndrome and cardiovascular disease in this population.

  2. Inborn errors of metabolism in children referred with Reye's Syndrome: a changing pattern

    Energy Technology Data Exchange (ETDEWEB)

    Rowe, P.C.; Valle, D.; Brusilow, S.W.

    1988-12-02

    Genetic disorders were identified infrequently among children presenting Reye's syndrome in the past. During a two-year period, the authors evaluated four consecutive patients referred for intensive care of Reye's syndrome. A standard investigation for inborn errors of metabolism revealed that two patients had enzymatic defects of fatty acid oxidation, and the other two had partial deficiencies of ornithine transcarbamoylase. None had experienced a previous episode of Reye's syndrome, and three of the four had been entirely healthy in the past. Their experience suggests that as the incidence of Reye's syndrome has decreased, patients with its clinical features are not more likely to have manageable inborn errors of metabolism (eg, disorders of ureagenesis, ketogenesis, and branched-chain amino acids).

  3. Report: Human biochemical genetics: an insight into inborn errors of metabolism

    Institute of Scientific and Technical Information of China (English)

    YU Chunli; SCOTT C. Ronald

    2006-01-01

    Inborn errors of metabolism (IEM) include a broad spectrum of defects of various gene products that affect intermediary metabolism in the body. Studying the molecular and biochemical mechanisms of those inherited disorder, systematically summarizing the disease phenotype and natural history, providing diagnostic rationale and methodology and treatment strategy comprise the context of human biochemical genetics. This session focused on: (1) manifestations of representative metabolic disorders; (2) the emergent technology and application of newborn screening of metabolic disorders using tandem mass spectrometry; (3) principles of managing IEM; (4) the concept of carrier testing aiming prevention. Early detection of patients with IEM allows early intervention and more options for treatment.

  4. Inborn errors of metabolism for the diagnostic radiologist

    Energy Technology Data Exchange (ETDEWEB)

    Hendriksz, Chris J. [Birmingham Children' s Hospital NHS Foundation Trust, Department of Clinical Inherited Metabolic Disorders, Birmingham (United Kingdom)

    2009-03-15

    Inherited metabolic disorders are becoming more important with the increasing availability of diagnostic methods and therapies for these conditions. The radiologist has become an important link in making the diagnosis or collaborating with the specialist centre to diagnose these disorders and monitor effects of therapy. The modes of presentation, disease-specific groups, classic radiological features and investigations are explored in this article to try and give the general radiologist some crucial background knowledge. The following presentations are covered: acute intoxication, hypoglycaemia, developmental delay and storage features. Specific groups of disorders covered are the abnormalities of intermediary metabolism, disorders of fatty acid oxidation and ketogenesis, mitochondrial disorders, lysosomal storage disorders, and, briefly, other groups such as peroxisomal disorders, disorders of glycosylation, and creatine synthesis disorders. New advances and the demands for monitoring are also briefly explored. (orig.)

  5. An insight into the biochemistry of inborn errors of metabolism for a clinical neurologist

    Directory of Open Access Journals (Sweden)

    Christopher Rita

    2008-01-01

    Full Text Available Neurological dysfunction is an important manifestation of inherited metabolic disorders. Although these are more common in childhood, adult onset forms with a different clinical presentation are often encountered. Recent advances in the diagnosis and treatment of these conditions have substantially improved the outcome in many of these conditions. This makes it essential that the practicing physician be familiar with the clinical presentation and diagnosis of these disorders. For the evaluation of a patient with a possible inborn error of metabolism, simple screening tests may aid in the diagnosis and provide direction for more comprehensive laboratory analysis. In this review, we present a practical approach to diagnosis of neurometabolic disorders. Establishing a specific diagnosis in these disorders will enable the clinician in offering a definitive long-term treatment, prognosis and genetic counselling.

  6. NMR spectroscopy of aminoacylase 1 deficiency, a novel inborn error of metabolism.

    Science.gov (United States)

    Engelke, Udo F H; Sass, Jörn Oliver; Van Coster, Rudy N; Gerlo, Erik; Olbrich, Heike; Krywawych, Stefan; Calvin, Jacqui; Hart, Claire; Omran, Heymut; Wevers, Ron A

    2008-02-01

    Aminoacylase 1 deficiency is a novel inborn error of metabolism. The clinical significance of the deficiency is under discussion, as well as the possible consequences of the defect for brain metabolism and function. This study includes the five originally published cases as well as three novel ones. NMR spectroscopy of urine, serum and cerebrospinal fluid has been used to study these patients. A typical profile with 11 accumulating N-acetylated amino acids was observed in urine from the patients. The concentration of most of the accumulating metabolites is typically 100-500 micromol/mmol creatinine. Two additional minor N-acetylated metabolites remain unidentified. The concentrations of the accumulating metabolites are amino acids in the cerebrospinal fluid from one patient. Our data define aminoacylase 1 deficiency at the metabolite level providing a specific urinary profile of accumulating N-acetylated amino acids.

  7. Essential polyunsaturated fatty acids in plasma and erythrocytes of children with inborn errors of amino acid metabolism.

    NARCIS (Netherlands)

    Vlaardingerbroek, H.; Hornstra, G.; Koning, T.J.; Smeitink, J.A.M.; Bakker, H.D.; Klerk, H. de; Rubio-Gozalbo, M.E.

    2006-01-01

    Essential fatty acids (EFAs), and their longer-chain more-unsaturated derivatives (LCPUFAs) in particular, are essential for normal growth and cognitive development during childhood. Children with inborn errors of amino acid metabolism represent a risk population for a reduced LCPUFA status because

  8. Inborn Errors of Metabolism: the metabolome is our world. Presidential address for the 11th International Congress of Inborn Errors of Metabolism (ICIEM).

    Science.gov (United States)

    McCabe, Edward R B

    2010-05-01

    Thank you for honoring me by allowing me to serve as president of the 11th International Congress of Inborn Errors of Metabolism (ICIEM). The science brought by the IEM community to the Congress was quite impressive and demonstrated the quality of research within this community. In this address, I will consider briefly the history of IEMs to determine how we have arrived where we are, and will spend more time ascertaining our place in the current biomedical community and our role in determining the future of personalized medicine. In the 1950s-1970s new tools were added to expand our ability to interrogate the metabolome and the result was an explosive increase in the number of IEMs. This set the stage for expanded newborn screening (NBS) by tandem mass spectrometry (MS/MS) to identify these patients and to intervene pre-symptomatically. The complexity of the metabolome has led us to utilize the mathematical algorithms of systems biology to reduce high dimensionality data to low dimensionality output. However, the metabolome does not exist in isolation and we must learn how to integrate the metabolome with other xomics. The metabolome is our world and the IEM community has much to share with the broader xomics communities by integrating what we have learned with the other xomics communities. They are seeking access to the metabolome as a closer measure of phenotype, and we are already extremely comfortable and competent in the metabolomic space. But we should not be insular in our occupation of this space. NBS should be the model for personalized medicine, because it is already functioning as testing system for predictive, preventive and personalized care. We have been working in the area of NBS for nearly a half century and have many lessons learned that will be valuable to the practitioners of personalized medicine - lessons that they should not have to rediscover. We must embrace the international IEM community to meet population trends and to improve the care

  9. Uric acid, an important screening tool to detect inborn errors of metabolism: a case series.

    Science.gov (United States)

    Jasinge, Eresha; Kularatnam, Grace Angeline Malarnangai; Dilanthi, Hewa Warawitage; Vidanapathirana, Dinesha Maduri; Jayasena, Kandana Liyanage Subhashinie Priyadarshika Kapilani Menike; Chandrasiri, Nambage Dona Priyani Dhammika; Indika, Neluwa Liyanage Ruwan; Ratnayake, Pyara Dilani; Gunasekara, Vindya Nandani; Fairbanks, Lynette Dianne; Stiburkova, Blanka

    2017-09-06

    Uric acid is the metabolic end product of purine metabolism in humans. Altered serum and urine uric acid level (both above and below the reference ranges) is an indispensable marker in detecting rare inborn errors of metabolism. We describe different case scenarios of 4 Sri Lankan patients related to abnormal uric acid levels in blood and urine. CASE 1: A one-and-half-year-old boy was investigated for haematuria and a calculus in the bladder. Xanthine crystals were seen in microscopic examination of urine sediment. Low uric acid concentrations in serum and low urinary fractional excretion of uric acid associated with high urinary excretion of xanthine and hypoxanthine were compatible with xanthine oxidase deficiency. CASE 2: An 8-month-old boy presented with intractable seizures, feeding difficulties, screaming episodes, microcephaly, facial dysmorphism and severe neuro developmental delay. Low uric acid level in serum, low fractional excretion of uric acid and radiological findings were consistent with possible molybdenum cofactor deficiency. Diagnosis was confirmed by elevated levels of xanthine, hypoxanthine and sulfocysteine levels in urine. CASE 3: A 3-year-10-month-old boy presented with global developmental delay, failure to thrive, dystonia and self-destructive behaviour. High uric acid levels in serum, increased fractional excretion of uric acid and absent hypoxanthine-guanine phosphoribosyltransferase enzyme level confirmed the diagnosis of Lesch-Nyhan syndrome. CASE 4: A 9-year-old boy was investigated for lower abdominal pain, gross haematuria and right renal calculus. Low uric acid level in serum and increased fractional excretion of uric acid pointed towards hereditary renal hypouricaemia which was confirmed by genetic studies. Abnormal uric acid level in blood and urine is a valuable tool in screening for clinical conditions related to derangement of the nucleic acid metabolic pathway.

  10. Inborn errors of metabolism in the biosynthesis and remodelling of phospholipids.

    Science.gov (United States)

    Wortmann, Saskia B; Espeel, Marc; Almeida, Ligia; Reimer, Annette; Bosboom, Dennis; Roels, Frank; de Brouwer, Arjan P M; Wevers, Ron A

    2015-01-01

    Since the proposal to define a separate subgroup of inborn errors of metabolism involved in the biosynthesis and remodelling of phospholipids, sphingolipids and long chain fatty acids in 2013, this group is rapidly expanding. This review focuses on the disorders involved in the biosynthesis of phospholipids. Phospholipids are involved in uncountable cellular processes, e.g. as structural components of membranes, by taking part in vesicle and mitochondrial fusion and fission or signal transduction. Here we provide an overview on both pathophysiology and the extremely heterogeneous clinical presentations of the disorders reported so far (Sengers syndrome (due to mutations in AGK), MEGDEL syndrome (or SERAC defect, SERAC1), Barth syndrome (or TAZ defect, TAZ), congenital muscular dystrophy due to CHKB deficiency (CHKB). Boucher-Neuhäuser/Gordon Holmes syndrome (PNPLA6), PHARC syndrome (ABHD12), hereditary spastic paraplegia type 28, 54 and 56 (HSP28, DDHD1; HSP54, DDHD2; HSP56, CYP2U1), Lenz Majewski syndrome (PTDSS1), spondylometaphyseal dysplasia with cone-rod dystrophy (PCYT1A), atypical haemolytic-uremic syndrome due to DGKE deficiency (DGKE).

  11. The potential of exosomes in diagnosis and treatment of inborn errors of metabolism.

    Science.gov (United States)

    van Balkom, Bas W M; van Doorn, Jaap; Verhoeven-Duif, Nanda M; Verhaar, Marianne C

    2014-07-01

    Extracellular vesicles, in particular exosomes, have gained much attention as potent mediators of intercellular signaling. Exosomes are 50-130 nm intraluminal vesicles of multivesicular bodies (MVB) that are secreted into the extracellular environment upon fusion of MVB with the plasma membrane. Current research on exosomes focuses on their biogenesis, including specific sorting mechanisms, their potential to transfer proteins and RNA from their cells of origin to target cells, specific methods of vesicle isolation, and their possible application as diagnostic and therapeutic devices. Exosomes are vesicles of endocytic origin that contain a portion of the cytoplasm. Their molecular components represent the composition and thereby the physiological state of the cells from which they originate. In this review, we recapitulate the discovery of exosomes and the subsequent expansion of exosome research into a variety of different areas of interest, with a specific focus on how exosomes could prove to be invaluable for both diagnostic and therapeutic applications within the research field of inborn errors of metabolism.

  12. Neonatal screening for inborn errors of metabolism: cost, yield and outcome.

    Science.gov (United States)

    Pollitt, R J; Green, A; McCabe, C J; Booth, A; Cooper, N J; Leonard, J V; Nicholl, J; Nicholson, P; Tunaley, J R; Virdi, N K

    1997-01-01

    OBJECTIVES. To systematically review the literature on inborn errors of metabolism, neonatal screening technology and screening programmes in order to analyse the costs and benefits of introducing screening based on tandem mass-spectrometry (tandem MS) for a wide range of disorders of amino acid and organic acid metabolism in the UK. To evaluate screening for cystic fibrosis, Duchenne muscular dystrophy and other disorders which are tested on an individual basis. HOW THE RESEARCH WAS CONDUCTED. Systematic searches were carried out of the literature on inborn errors of metabolism, neonatal screening programmes, tandem MS-based neonatal screening technology, economic evaluations of neonatal screening programmes and psychological aspects of neonatal screening. Background material on the biology of inherited metabolic disease, the basic philosophy, and the history and current status of the UK screening programme was also collected. Relevant papers in the grey literature and recent publications were identified by hand-searching. Each paper was graded. For each disease an aggregate grade for the state of knowledge in six key areas was awarded. Additional data were prospectively collected on activity and costs in UK neonatal screening laboratories, and expert clinical opinion on current treatment modalities and outcomes. These data were used to construct a decision-analysis model of neonatal screening technologies, comparing tandem MS with the existing phenylketonuria screening methods. This model determined the cost per additional case identified and, for each disease, the additional treatment costs per case, and the cost per life-year saved. All costs and benefits were discounted at 6% per annum. One-way sensitivity analysis was performed showing the effect of varying the discount rate, the incidence rate of each disorder, the number of neonates screened and the cost of tandem MS, on the cost per life-year gained. RESEARCH FINDINGS. The UK screening programmes for

  13. Errores innatos del metabolismo de las purinas y otras enfermedades relacionadas Inborn purine metabolism errors and other related diseases

    Directory of Open Access Journals (Sweden)

    Jiovanna Contreras Roura

    2012-06-01

    Full Text Available Los errores innatos en el metabolismo de las purinas son trastornos hereditarios complejos de gran impacto clínico, que presentan síntomas variables de acuerdo con el tipo de enfermedad. Pueden presentarse problemas renales de origen desconocido, retardo mental con manifestaciones neurológicas, retardo del crecimiento, infecciones recurrentes, automutilación, inmunodeficiencias, anemia hemolítica inexplicable, artritis gotosa, historia familiar, consanguinidad y reacciones adversas a fármacos que son análogos de las purinas. Las investigaciones de estas enfermedades comienzan generalmente con la cuantificación del ácido úrico en suero y en orina, por ser el producto final del metabolismo de las purinas en humanos. La dieta y el consumo de medicamentos, entre otras condiciones patológicas, fisiológicas y clínicas, también pueden modificar los niveles de este compuesto. Esta revisión pretende divulgar información de los errores innatos en el metabolismo de las purinas, y facilitar la interpretación de los niveles del ácido úrico y otros marcadores bioquímicos útiles en el diagnóstico de estas enfermedades. Se incluyen tablas que relacionan estas enfermedades con los niveles de excreción de ácido úrico y otros marcadores bioquímicos, las enzimas alteradas, los síntomas clínicos, el modo de herencia y, en algunos casos, el tratamiento propuesto. Este trabajo nos permite afirmar que las variaciones en los niveles del ácido úrico y la presencia de otros marcadores bioquímicos en orina, constituyen una herramienta importante en la pesquisa de algunos errores innatos en el metabolismo de las purinas, así como de otras condiciones patológicas relacionadas.Inborn purine metabolism errors are complex inherited disorders of great clinical impact that present with variable symptoms according to the type of disease. It might occur renal problems of unknown origin, metal retardation with neurological manifestations, retarded

  14. Incidence of Inborn Errors of Metabolism by Expanded Newborn Screening in a Mexican Hospital

    Directory of Open Access Journals (Sweden)

    Consuelo Cantú-Reyna MD

    2016-09-01

    Full Text Available Newborn screening for the detection of inborn errors of metabolism (IEM, endocrinopathies, hemoglobinopathies, and other disorders is a public health initiative aimed at identifying specific diseases in a timely manner. Mexico initiated newborn screening in 1973, but the national incidence of this group of diseases is unknown or uncertain due to the lack of large sample sizes of expanded newborn screening (ENS programs and lack of related publications. The incidence of a specific group of IEM, endocrinopathies, hemoglobinopathies, and other disorders in newborns was obtained from a Mexican hospital. These newborns were part of a comprehensive ENS program at Ginequito (a private hospital in Mexico, from January 2012 to August 2014. The retrospective study included the examination of 10 000 newborns’ results obtained from the ENS program (comprising the possible detection of more than 50 screened disorders. The findings were the following: 34 newborns were confirmed with an IEM, endocrinopathies, hemoglobinopathies, or other disorders and 68 were identified as carriers. Consequently, the estimated global incidence for those disorders was 3.4 in 1000 newborns; and the carrier prevalence was 6.8 in 1000. Moreover, a 0.04% false-positive rate was unveiled as soon as diagnostic testing revealed negative results. The most frequent diagnosis was glucose-6-phosphate dehydrogenase deficiency; and in the case of carriers, it was hemoglobinopathies. The benefit of the ENS is clear as it offers prompt treatment on the basis of an early diagnosis including proper genetic counseling. Furthermore, these results provide a good estimation of the frequencies of different forms of newborn IEM, endocrinopathies, hemoglobinopathies, and other disorders at Ginequito.

  15. Garrod's fourth inborn error of metabolism solved by the identification of mutations causing pentosuria.

    Science.gov (United States)

    Pierce, Sarah B; Spurrell, Cailyn H; Mandell, Jessica B; Lee, Ming K; Zeligson, Sharon; Bereman, Michael S; Stray, Sunday M; Fokstuen, Siv; MacCoss, Michael J; Levy-Lahad, Ephrat; King, Mary-Claire; Motulsky, Arno G

    2011-11-01

    Pentosuria is one of four conditions hypothesized by Archibald Garrod in 1908 to be inborn errors of metabolism. Mutations responsible for the other three conditions (albinism, alkaptonuria, and cystinuria) have been identified, but the mutations responsible for pentosuria remained unknown. Pentosuria, which affects almost exclusively individuals of Ashkenazi Jewish ancestry, is characterized by high levels of the pentose sugar L-xylulose in blood and urine and deficiency of the enzyme L-xylulose reductase. The condition is autosomal-recessive and completely clinically benign, but in the early and mid-20th century attracted attention because it was often confused with diabetes mellitus and inappropriately treated with insulin. Persons with pentosuria were identified from records of Margaret Lasker, who studied the condition in the 1930s to 1960s. In the DCXR gene encoding L-xylulose reductase, we identified two mutations, DCXR c.583ΔC and DCXR c.52(+1)G > A, each predicted to lead to loss of enzyme activity. Of nine unrelated living pentosuric subjects, six were homozygous for DCXR c.583ΔC, one was homozygous for DCXR c.52(+1)G > A, and two were compound heterozygous for the two mutant alleles. L-xylulose reductase was not detectable in protein lysates from subjects' cells and high levels of xylulose were detected in their sera, confirming the relationship between the DCXR genotypes and the pentosuric phenotype. The combined frequency of the two mutant DCXR alleles in 1,067 Ashkenazi Jewish controls was 0.0173, suggesting a pentosuria frequency of approximately one in 3,300 in this population. Haplotype analysis indicated that the DCXR c.52(+1)G > A mutation arose more recently than the DCXR c.583ΔC mutation.

  16. Analysis of inborn errors of metabolism:disease spectrum for expanded newborn screening in Hong Kong

    Institute of Scientific and Technical Information of China (English)

    Han-Chih Hencher Lee; Wai-Kwan Siu; Sammy Pak-Lam Chen; Chun-Yiu Law; Morris Hok-Leung Tai; Sidney Tam; Albert Yan-Wo Chan; Chloe Miu Mak; Ching-Wan Lam; Yuet-Ping Yuen; Angel On-Kei Chan; Chi-Chung Shek; Tak-Shing Siu; Chi-Kong Lai; Chor-Kwan Ching

    2011-01-01

    Background Data of classical inborn errors of metabolism (IEM) of amino acids,organic acids and fatty acid oxidation are largely lacking in Hong Kong,where mass spectrometry-based expanded newborn screening for IEM has not been initiated. The current study aimed to evaluate the approximate incidence,spectrum and other characteristics of classical IEM in Hong Kong,which would be important in developing an expanded newborn screening program for the local area.Methods The laboratory records of plasma amino acids,plasma acylcarnitines and urine organic acids analyses from year 2005 to 2009 inclusive in three regional chemical pathology laboratories providing biochemical and genetic diagnostic services for IEM were retrospectively reviewed.Results Among the cohort,43 patients were diagnosed of IEM,including 30 cases (69%) of amino acidemias(predominantly citrin deficiency,hyperphenylalaninemia due to 6-pyruvoyl-tetrahydropterin synthase deficiency and tyrosinemia type Ⅰ),5 cases (12%) of organic acidemias (predominantly holocarboxylase synthetase deficiency) and 8cases (19%) of fatty acid oxidation defects (predominantly carnitine-acylcarnitine translocase deficiency). The incidence of classical IEM in Hong Kong was roughly estimated to be at least 1 case per 4122 lives births,or 0.243 cases per 1000live births. This incidence is similar to those reported worldwide,including the mainland of China. The estimated incidence of hyperphenylalaninemia was 1 in 29 542 live births.Conclusions Our data indicate that it is indisputable for the introduction of expanded newborn screening program in Hong Kong. Since Hong Kong is a metropolitan city,a comprehensive expanded newborn screening program and referral system should be available to serve the neonates born in the area.

  17. Incidence of Inborn Errors of Metabolism by Expanded Newborn Screening in a Mexican Hospital

    Directory of Open Access Journals (Sweden)

    Consuelo Cantú-Reyna MD

    2016-09-01

    Full Text Available Newborn screening for the detection of inborn errors of metabolism (IEM, endocrinopathies, hemoglobinopathies, and other disorders is a public health initiative aimed at identifying specific diseases in a timely manner. Mexico initiated newborn screening in 1973, but the national incidence of this group of diseases is unknown or uncertain due to the lack of large sample sizes of expanded newborn screening (ENS programs and lack of related publications. The incidence of a specific group of IEM, endocrinopathies, hemoglobinopathies, and other disorders in newborns was obtained from a Mexican hospital. These newborns were part of a comprehensive ENS program at Ginequito (a private hospital in Mexico, from January 2012 to August 2014. The retrospective study included the examination of 10 000 newborns’ results obtained from the ENS program (comprising the possible detection of more than 50 screened disorders. The findings were the following: 34 newborns were confirmed with an IEM, endocrinopathies, hemoglobinopathies, or other disorders and 68 were identified as carriers. Consequently, the estimated global incidence for those disorders was 3.4 in 1000 newborns; and the carrier prevalence was 6.8 in 1000. Moreover, a 0.04% false-positive rate was unveiled as soon as diagnostic testing revealed negative results. The most frequent diagnosis was glucose-6-phosphate dehydrogenase deficiency; and in the case of carriers, it was hemoglobinopathies. The benefit of the ENS is clear as it offers prompt treatment on the basis of an early diagnosis including proper genetic counseling. Furthermore, these results provide a good estimation of the frequencies of different forms of newborn IEM, endocrinopathies, hemoglobinopathies, and other disorders at Ginequito.

  18. Living donor liver transplantation for inborn errors of metabolism - An underutilized resource in the United States.

    Science.gov (United States)

    Pham, Thomas A; Enns, Gregory M; Esquivel, Carlos O

    2016-09-01

    Inborn metabolic diseases of the liver can be life-threatening disorders that cause debilitating and permanent neurological damage. Symptoms may manifest as early as the neonatal period. Liver transplant replaces the enzymatically deficient liver, allowing for metabolism of toxic metabolites. LDLT for metabolic disorders is rarely performed in the United States as compared to countries such as Japan, where they report >2000 cases performed within the past two decades. Patient and graft survival is comparable to that of the United States, where most of the studies are based on deceased donors. No living donor complications were observed, suggesting that LDLT is as safe and effective as deceased donor transplants performed in the USA. Increased utilization of living donors in the USA will allow for early transplantation to prevent permanent neurological damage in those with severe disease. Pediatric transplant centers should consider utilizing living donors when feasible for children with metabolic disorders of the liver.

  19. Rare inborn errors of metabolism with movement disorders : a case study to evaluate the impact upon quality of life and adaptive functioning

    NARCIS (Netherlands)

    Eggink, Hendriekje; Kuiper, Anouk; Peall, Kathryn J.; Contarino, Maria Fiorella; Bosch, Annet M.; Post, Bart; Sival, Deborah A.; Tijssen, Marina A. J.; de Koning, Tom J.

    2014-01-01

    Background: Inborn errors of metabolism (IEM) form an important cause of movement disorders in children. The impact of metabolic diseases and concordant movement disorders upon children's health-related quality of life (HRQOL) and its physical and psychosocial domains of functioning has never been

  20. ECHS1 mutations in Leigh disease: a new inborn error of metabolism affecting valine metabolism.

    Science.gov (United States)

    Peters, Heidi; Buck, Nicole; Wanders, Ronald; Ruiter, Jos; Waterham, Hans; Koster, Janet; Yaplito-Lee, Joy; Ferdinandusse, Sacha; Pitt, James

    2014-11-01

    Two siblings with fatal Leigh disease had increased excretion of S-(2-carboxypropyl)cysteine and several other metabolites that are features of 3-hydroxyisobutyryl-CoA hydrolase (HIBCH) deficiency, a rare defect in the valine catabolic pathway associated with Leigh-like disease. However, this diagnosis was excluded by HIBCH sequencing and normal enzyme activity. In contrast to HIBCH deficiency, the excretion of 3-hydroxyisobutyryl-carnitine was normal in the children, suggesting deficiency of short-chain enoyl-CoA hydratase (ECHS1 gene). This mitochondrial enzyme is active in several metabolic pathways involving fatty acids and amino acids, including valine, and is immediately upstream of HIBCH in the valine pathway. Both children were compound heterozygous for a c.473C > A (p.A158D) missense mutation and a c.414+3G>C splicing mutation in ECHS1. ECHS1 activity was markedly decreased in cultured fibroblasts from both siblings, ECHS1 protein was undetectable by immunoblot analysis and transfection of patient cells with wild-type ECHS1 rescued ECHS1 activity. The highly reactive metabolites methacrylyl-CoA and acryloyl-CoA accumulate in deficiencies of both ECHS1 and HIBCH and are probably responsible for the brain pathology in both disorders. Deficiency of ECHS1 or HIBCH should be considered in children with Leigh disease. Urine metabolite testing can detect and distinguish between these two disorders.

  1. Vaccination coverage of patients with inborn errors of metabolism and the attitudes of their parents towards vaccines.

    Science.gov (United States)

    Cerutti, Marta; De Lonlay, Pascale; Menni, Francesca; Parini, Rossella; Principi, Nicola; Esposito, Susanna

    2015-11-27

    To evaluate vaccination coverage of children and adolescents with inborn errors of metabolism (IEMs) and the attitudes of their parents towards vaccination, the vaccination status of 128 patients with IEM and 128 age- and gender-matched healthy controls was established by consulting the official vaccination chart. In children with IEMs, compared with healthy controls, low vaccination rates and/or delays in administration were observed for pneumococcal conjugate, meningococcus C, measles, mumps, rubella, diphtheria-tetanus-pertussis-inactivated polio, Bacillus Calmette-Guerin, and influenza vaccines. Among the parents of IEM patients, vaccine schedule compliance was primarily driven by the doctors at the hospital's reference centres; among the parents of the healthy controls, compliance was driven by the primary care paediatricians. These results show that IEM patients demonstrate sub-optimal vaccination coverage. Further studies of the different vaccines in each IEM disorder and educational programmes aimed at physicians and parents to increase immunization coverage in these patients are urgently needed.

  2. Achieving the "triple aim" for inborn errors of metabolism: a review of challenges to outcomes research and presentation of a new practice-based evidence framework.

    Science.gov (United States)

    Potter, Beth K; Chakraborty, Pranesh; Kronick, Jonathan B; Wilson, Kumanan; Coyle, Doug; Feigenbaum, Annette; Geraghty, Michael T; Karaceper, Maria D; Little, Julian; Mhanni, Aizeddin; Mitchell, John J; Siriwardena, Komudi; Wilson, Brenda J; Syrowatka, Ania

    2013-06-01

    Across all areas of health care, decision makers are in pursuit of what Berwick and colleagues have called the "triple aim": improving patient experiences with care, improving health outcomes, and managing health system impacts. This is challenging in a rare disease context, as exemplified by inborn errors of metabolism. There is a need for evaluative outcomes research to support effective and appropriate care for inborn errors of metabolism. We suggest that such research should consider interventions at both the level of the health system (e.g., early detection through newborn screening, programs to provide access to treatments) and the level of individual patient care (e.g., orphan drugs, medical foods). We have developed a practice-based evidence framework to guide outcomes research for inborn errors of metabolism. Focusing on outcomes across the triple aim, this framework integrates three priority themes: tailoring care in the context of clinical heterogeneity; a shift from "urgent care" to "opportunity for improvement"; and the need to evaluate the comparative effectiveness of emerging and established therapies. Guided by the framework, a new Canadian research network has been established to generate knowledge that will inform the design and delivery of health services for patients with inborn errors of metabolism and other rare diseases.

  3. HPLC analysis for the clinical-biochemical diagnosis of inborn errors of metabolism of purines and pyrimidines.

    Science.gov (United States)

    Lazzarino, Giuseppe; Amorini, Angela Maria; Di Pietro, Valentina; Tavazzi, Barbara

    2011-01-01

    The determination of purines and pyrimidines in biofluids is useful for the clinical-biochemical characterization of acute and chronic pathological states that induce transient or permanent alterations of metabolism. In particular, the diagnosis of several inborn errors of metabolism (IEMs) is accomplished by the analysis of circulating and excreted purines and pyrimidines. It is certainly advantageous to simultaneously determine the full purine and pyrimidine profile, as well as to quantify other compounds of relevance (e.g., organic acids, amino acids, sugars) in various metabolic hereditary diseases, in order to screen for a large number of IEMs using a reliable and sensitive analytical method characterized by mild to moderate costs. Toward this end, we have developed an ion-pairing HPLC method with diode array detection for the synchronous separation of several purines and pyrimidines. This method also allows the quantification of additional compounds such as N-acetylated amino acids and dicarboxylic acids, the concentrations of which are profoundly altered in different IEMs. The application of the method in the analysis of biological samples from patients with suspected purine and pyrimidine disorders is presented to illustrate its applicability for the clinical-biochemical diagnosis of IEM.

  4. The significance of opthalmologic evaluation in the early diagnosis of inborn errors of metabolism: the Cretan experience

    Directory of Open Access Journals (Sweden)

    Lionis Christos

    2002-04-01

    Full Text Available Abstract Background The Inborn Errors of Metabolism (IEM are far from the rare systemic diseases that mainly affect the neural tissue. There are very few written reports on ocular findings in subjects with IEM, thus it was interesting to study the frequency of ocular findings in the studied population and explore their contribution to the early diagnosis of IEM. Methods Our study involved the evaluation of IEM suspected cases, which had been identified in a rural population in Crete, Greece. Over a period of 3 years, 125 patients, who fulfilled the inclusion criteria of this study, were examined. Analytical physical examination, detailed laboratory investigation as well as a thorough ocular examination were made. Results A diagnosis of IEM was established in 23 of the 125 patients (18.4%. Ten (43.5% of the diagnosed IEM had ocular findings, while 8 of them (34.8% had findings which were specific for the diagnosed diseases. One patient diagnosed with glycogenosis type 1b presented a rare finding. Of the 102 non-diagnosed patients, 53 (51.96 % presented various ophthalmic findings, some of which could be related to a metabolic disease and therefore may be very helpful in the future. Conclusions The ocular investigation can be extremely useful for raising the suspicion and the establishment of an early diagnosis of IEM. It could also add new findings related to these diseases. The early management of the ocular symptoms can improve the quality of life to these patients.

  5. Clinical characteristics of adult patients with inborn errors of metabolism in Spain: A review of 500 cases from university hospitals

    Directory of Open Access Journals (Sweden)

    J. Pérez-López

    2017-03-01

    Full Text Available Patients with inborn errors of metabolism (IEMs have become an emerging and challenging group in the adult healthcare system whose needs should be known in order to implement appropriate policies and to adapt adult clinical departments. We aimed to analyze the clinical characteristics of adult patients with IEMs who attend the most important Spanish hospitals caring for these conditions. A cohort study was conducted in 500 patients, categorized by metabolic subtype according to pathophysiological classification. The most prevalent group of IEMs was amino acid disorders, with 108 (21.6% patients diagnosed with phenylketonuria. Lysosomal storage disorders were the second group, in which 32 (6.4% and 25 (5% patients had Fabry disease and Gaucher disease respectively. The great clinical heterogeneity, the significant delay in diagnosis after symptom onset, the existence of some degree of physical dependence in a great number of patients, the need for a multidisciplinary and coordinated approach, and the lack of specific drug treatment are common features in this group of conditions.

  6. Long-term survival and late deaths after hematopoietic cell transplantation for primary immunodeficiency diseases and inborn errors of metabolism.

    Science.gov (United States)

    Eapen, Mary; Ahn, Kwang Woo; Orchard, Paul J; Cowan, Morton J; Davies, Stella M; Fasth, Anders; Hassebroek, Anna; Ayas, Mouhab; Bonfim, Carmem; O'Brien, Tracey A; Gross, Thomas G; Horwitz, Mitchell; Horwitz, Edwin; Kapoor, Neena; Kurtzberg, Joanne; Majhail, Navneet; Ringden, Olle; Szabolcs, Paul; Veys, Paul; Baker, K Scott

    2012-09-01

    It is uncertain whether late mortality rates after hematopoietic cell transplantation for severe combined immunodeficiency (SCID), non-SCID primary immunodeficiency diseases (non-SCID PIDD), and inborn errors of metabolism (IEM) return to rates observed in the general population, matched for age, sex, and nationality. We studied patients with SCID (n = 201), non-SCID PIDD (n = 405), and IEM (n = 348) who survived for at least 2 years after transplantation with normal T cell function (SCID) or >95% donor chimerism (non-SCID PIDD and IEM). Importantly, mortality rate was significantly higher in these patients compared with the general population for several years after transplantation. The rate decreased toward the normal rate in patients with SCID and non-SCID PIDD beyond 6 years after transplantation, but not in patients with IEM. Active chronic graft-versus-host disease at 2 years was associated with increased risk of late mortality for all diseases (hazard ratio [HR], 1.87; P = .05). In addition, late mortality was higher in patients with non-SCID PIDD who received T cell-depleted grafts (HR 4.16; P = .007) and in patients with IEM who received unrelated donor grafts (HR, 2.72; P = .03) or mismatched related donor grafts (HR, 3.76; P = .01). The finding of higher mortality rates in these long-term survivors for many years after transplantation confirms the need for long-term surveillance.

  7. Omics-Based Strategies in Precision Medicine: Toward a Paradigm Shift in Inborn Errors of Metabolism Investigations

    Directory of Open Access Journals (Sweden)

    Abdellah Tebani

    2016-09-01

    Full Text Available The rise of technologies that simultaneously measure thousands of data points represents the heart of systems biology. These technologies have had a huge impact on the discovery of next-generation diagnostics, biomarkers, and drugs in the precision medicine era. Systems biology aims to achieve systemic exploration of complex interactions in biological systems. Driven by high-throughput omics technologies and the computational surge, it enables multi-scale and insightful overviews of cells, organisms, and populations. Precision medicine capitalizes on these conceptual and technological advancements and stands on two main pillars: data generation and data modeling. High-throughput omics technologies allow the retrieval of comprehensive and holistic biological information, whereas computational capabilities enable high-dimensional data modeling and, therefore, accessible and user-friendly visualization. Furthermore, bioinformatics has enabled comprehensive multi-omics and clinical data integration for insightful interpretation. Despite their promise, the translation of these technologies into clinically actionable tools has been slow. In this review, we present state-of-the-art multi-omics data analysis strategies in a clinical context. The challenges of omics-based biomarker translation are discussed. Perspectives regarding the use of multi-omics approaches for inborn errors of metabolism (IEM are presented by introducing a new paradigm shift in addressing IEM investigations in the post-genomic era.

  8. Inborn Errors of Metabolism in the United Arab Emirates: Disorders Detected by Newborn Screening (2011-2014).

    Science.gov (United States)

    Al-Jasmi, Fatma A; Al-Shamsi, Aisha; Hertecant, Jozef L; Al-Hamad, Sania M; Souid, Abdul-Kader

    2016-01-01

    This study reports on the inborn errors of metabolism (IEM) detected by our national newborn screening between 2011 and 2014. One hundred fourteen patients (55 UAE citizens and 59 residents) were diagnosed during this period. The program was most comprehensive (tested 29 IEM) and universally applied in 2013, giving an incidence of 1 in 1,787 citizens. This relatively high prevalence resulted from the frequent consanguineous marriages (81.5%) among affected families. The following eight disorders accounted for 80% of the entities: biotinidase deficiency (14 of 55), phenylketonuria (11 of 55), 3-methylcrotonyl glycinuria (9 of 55), medium-chain acyl-CoA dehydrogenase deficiency (4 of 55), argininosuccinic aciduria, glutaric aciduria type 1, glutaric aciduria type 2, and methylmalonyl-CoA mutase deficiency (2 of 55 each). Mutation analysis was performed in 48 (87%) of the 55 patients, and 33 distinct mutations were identified. Twenty-nine (88%) mutations were clinically significant and, thus, could be included in our premarital screening. Most mutations were homozygous, except for the biotinidase deficiency. The BTD mutations c.1207T>G (found in citizens) and c.424C>A (found in Somalians) were associated with undetectable biotinidase activity. Thus, the high prevalence of IEM in our region is amenable to newborn and premarital screening, which is expected to halt most of these diseases.

  9. Neonatal Screening for Inborn Errors of Metabolism in Shanghai%上海地区遗传代谢病的新生儿筛查

    Institute of Scientific and Technical Information of China (English)

    顾学范; 叶军; 韩连书

    2009-01-01

    Objectives Inborn errors of metabolism (IEM) has a diverse spectrum and different incidence in different countries, the early diagnosis at presymptomatic stage is imperative to benefic patient from sequelae. Phenylke-tonuria (PKU) / hyperphenylalaninemia (HPA) is the most common metabolism disorder in Shanghai as well as in other regions. The study is to further clarify the incidence of inborn errors of metabolism among newborn in Shanghai. Methods The dried blood spot specimens were collected from near 90 local maternity and children's hospitals or general hospitals in Shanghai. PKU/HPA screening was carried out by fluorometric method. Neonatal screening using tandem mass spectrometry was performed in one of the study centers, Xinhua neonatal screening center. Results A total of 815 160 cases were screened from 2001 - 2007 in Shanghai, the incidence of PKU/HPA was 1 : 12 351. The tetrahydrobiopterin deficiency was 12.9% among hyperphenylalaninemia patients. According to the 116 000 neonatal samples data detected by tandem mass spectrometry, 20 cases were confirmed diagnosis, including 6 kinds diseases, it was PKU/HPA, maple syrup urine disease, methylmalonicacidemia, propionic acidemia, 3-methylcrotonyl-CoA carboxylase defection, and short chain aeyl-CoA dehydrogenase deficiency. Conclusions The pilot study shown that inborn errors of metabolism neonatal screen-ing using tandem mass was 1 : 5 800 in Shanghai, PKU/HPA was the most common disease. It is expected that the expansion of newborn screening using tandem mass spectrometry could be further considered and further improving inborn errors of metabolism preventive services in Shanghai.

  10. Evidence for Treatable Inborn Errors of Metabolism in a Cohort of 187 Greek Patients with Autism Spectrum Disorder (ASD

    Directory of Open Access Journals (Sweden)

    Martha eSpilioti

    2013-12-01

    Full Text Available We screened for the presence of inborn errors of metabolism (IEM in 187 children (105 males; 82 females, ages 4 -14 years old who presented with confirmed features of ASD. Twelve patients (7% manifested increased 3-hydroxyisovaleric acid (3-OH-IVA excretion in urine, and minor to significant improvement in autistic features was observed in seven patients following supplementation with biotin. Five diagnoses included: Lesch Nyhan syndrome (2, succinic semialdehyde dehydrogenase (SSADH deficiency (2 and phenylketonuria (1 (2.7%. Additional metabolic disturbances suggestive of IEMs included two patients whose increased urine 3-OH-IVA was accompanied by elevated methylcitrate and lactate in sera, and 30 patients that showed abnormal glucose-loading tests. In the latter group, 16/30 patients manifested increased sera beta hydroxybutyrate (b-OH-b production and 18/30 had a paradoxical increase of sera lactate. Six patients with elevated b-OH-b in sera showed improved autistic features following implementation of a ketogenic diet. Five patients showed decreased serum ketone body production with glucose loading. Twelve of 187 patients demonstrated nonspecific MRI pathology, while 25/187 had abnormal EEG findings. Finally, family history was positive for 22/187 patients (1st or 2nd degree relative with comparable symptomatology and consanguinity was documented for 12/187 patients. Our data provide evidence for a new biomarker (3-OH-IVA and novel treatment approaches in ASD patients.Concise 1 sentence take-home message: Detailed metabolic screening in a Greek cohort of autismspectrum disorder (ASD patients revealed biomarkers (urine 3-hydroxyisovaleric acid and serum b-OH-b in 7% (13/187 of patients for whom biotin supplementation or institution of a ketogenic diet resulted in mild to significant clinical improvement in autistic features.

  11. Selective screening of 650 high risk Iranian patients for detection of inborn error of metabolism

    Directory of Open Access Journals (Sweden)

    Narges Pishva

    2015-02-01

    Full Text Available Objective: Although metabolic diseases individually are rare ,but overall have an incidence of 1/2000 and can cause devastating and irreversible effect if not diagnosed early and treated promptly. selective screening is an acceptable method for detection of these multi presentation diseases.Method: using panel neonatal screening for detection of metabolic diseases in 650 high risk Iranian patients in Fars province. The following clinical features were used as inclusion criteria for investigation of the patients.Lethargy, poor feeding ,persistent vomiting, cholestasis, intractable seizure ,decreased level of consciousness ,persistent hypoglycemia, unexplained acid base disturbance and unexplained neonatal death.Result: Organic acidemia with 40 cases (42% was the most frequent disorder diagnosed in our high risk populations, followed by disorder of galactose metabolism(30%, 15 patient had classic galactosemia(GALT

  12. Selective screening of 650 high risk Iranian patients for detection of inborn error of metabolism

    Directory of Open Access Journals (Sweden)

    Narges Pishva

    2015-02-01

    Full Text Available Objective: Although metabolic diseases individually are rare ,but overall have an incidence of 1/2000 and can cause devastating and irreversible effect if not diagnosed early and treated promptly. selective screening is an acceptable method for detection of these multi presentation diseases. Method: using panel neonatal screening for detection of metabolic diseases in 650 high risk Iranian patients in Fars province. The following clinical features were used as inclusion criteria for investigation of the patients. Lethargy, poor feeding ,persistent vomiting, cholestasis, intractable seizure ,decreased level of consciousness ,persistent hypoglycemia, unexplained acid base disturbance and unexplained neonatal death. Result: Organic acidemia with 40 cases (42% was the most frequent disorder diagnosed in our high risk populations, followed by disorder of galactose metabolism(30%, 15 patient had classic galactosemia(GALT

  13. Diagnosing inborn errors of lipid metabolism with proton nuclear magnetic resonance spectroscopy.

    NARCIS (Netherlands)

    Oostendorp, M. van; Engelke, U.F.H.; Willemsen, M.A.A.P.; Wevers, R.A.

    2006-01-01

    BACKGROUND: Many severe diseases are caused by defects in lipid metabolism. As a result, patients often accumulate unusual lipids in their blood and tissues, and proper identification of these lipids is essential for correct diagnosis. In this study, we investigated the potential use of proton

  14. From genome to phenome-Simple inborn errors of metabolism as complex traits

    NARCIS (Netherlands)

    Touw, C M L; Derks, T G J; Bakker, B M; Groen, A K; Smit, G P A; Reijngoud, D J

    2014-01-01

    Sporadically, patients with a proven defect in either mFAO or OXPHOS are described presenting with a metabolic profile and clinical phenotype expressing concurrent defects in both pathways. Biochemical linkages between both processes are tight. Therefore, it is striking that concurrent dysfunction o

  15. [GASTROSTOMY POSITIVELY AFFECTS NUTRITIONAL STATUS AND DIMINISHES HOSPITAL DAYS IN PATIENTS WITH INBORN ERRORS OF METABOLISM].

    Science.gov (United States)

    Guillén-López, Sara; Vela-Amieva, Marcela; Juárez-Cruz, Merit Valeria; González-Zamora, José Francisco; Monroy-Santoyo, Susana; Belmont-Martínez, Leticia

    2015-07-01

    Introducción: el tratamiento nutricional de los pacientes con errores innatos del metabolismo (EIM) implica el uso permanente de fórmulas modificadas en aminoácidos cuyas características organolépticas pueden dificultar su aceptación por vía oral. Estos pacientes pueden tener alteraciones gastrointestinales y requieren el uso constante de medicamentos, lo cual complica la adherencia al tratamiento, comprometiéndose con ello su estado nutricional y el control de la enfermedad. La gastrostomía es una alternativa para facilitar la alimentación y el tratamiento, pero existen controversias sobre su uso. Objetivo: comparar el estado nutricional y la duración de las hospitalizaciones antes y después de la realización de la gastrostomía en un grupo de pacientes con EIM. Métodos: análisis retrospectivo de datos antropométricos, número de internamientos por descompensación metabólica y su duración en pacientes pediátricos con EIM antes y después de la gastrostomía. Resultados: se analizaron 16 niños; 40% con defectos del propionato, 25% con alteraciones del ciclo de la urea y 35% con otros EIM. Después de la gastrostomía, la proporción de pacientes eutróficos aumentó del 6 al 56% y la desnutrición disminuyó del 94 al 44%. Después de la gastrostomía, la duración de los periodos hospitalarios disminuyó significativamente de 425 a 131 días (p = 0.011); el número de internamientos disminuyó de 33 antes de la intervención a 17, sin embargo, esta diferencia no tuvo significación estadística. Conclusión: en esta muestra, la gastrostomía mejoró el estado nutricional en 56% de los pacientes con EIM, y redujo significativamente los días de hospitalización por descompensación metabólica.

  16. Inborn errors of metabolism

    Science.gov (United States)

    ... A few of them are: Fructose intolerance Galactosemia Maple sugar urine disease (MSUD) Phenylketonuria (PKU) Newborn screening ... Updated by: Chad Haldeman-Englert, MD, FACMG, Wake Forest School of Medicine, Department of Pediatrics, Section on ...

  17. Use of amplitude integrated electroencephalography (aEEG) in patients with inborn errors of metabolism - a new tool for the metabolic geneticist.

    Science.gov (United States)

    Theda, Christiane

    2010-01-01

    Patients with metabolic disorders often, especially as newborns, present with encephalopathy and seizures, frequently requiring intensive care during metabolic crises. Cerebral function monitoring using amplitude integrated electroencephalography (aEEG) can be utilized to supplement clinical assessment and other monitoring already in use in the intensive care setting. In this technique, a one or two-channel EEG tracing is obtained, processed, compressed and displayed. Use of aEEG is well established in evaluation and treatment of newborns with hypoxic ischemic encephalopathy. The basis of aEEG interpretation is the recognition of patterns which have been defined for different degrees of encephalopathy. Seizures are identified on the compressed tracing in combination with analysis of the corresponding raw EEG tracing. This review discusses the experience, although limited at this time, with use of aEEG in infants with inborn errors of metabolism. Through an international collaborative, the International Registry for Cerebral Function Monitoring in Patients with Genetics Disorders and Brain Malformations, aEEG tracings of patients with inborn errors of metabolism were collected. The features of 25 traces are included in this review. This collection includes patients with hyperammonemia (HA, n=4), disorders of energy metabolism (DEM, n=9), disorders of amino and organic acid metabolism (DAOAM, n=7), and peroxisomal disorders (PD, n=5). Fifteen of 25 patients demonstrated encephalopathic changes, including patients with HA, DEM and DAOAM, but not PD. In 15 of 25 patients seizure potentials were identified. In HA, DEM, and DAOAM both encephalopathy and seizures may coincide, while in peroxisomal disorders seizures were seen without background patterns indicating encephalopathy, likely due to neuronal migration defects as the underlying cause. The current experience with the use of aEEG in these patients, while limited, indicates that cerebral function monitoring

  18. An Economic Evaluation of Neonatal Screening for Inborn Errors of Metabolism Using Tandem Mass Spectrometry in Thailand.

    Directory of Open Access Journals (Sweden)

    Kittiphong Thiboonboon

    Full Text Available Inborn errors of metabolism (IEM are a rare group of genetic diseases which can lead to several serious long-term complications in newborns. In order to address these issues as early as possible, a process called tandem mass spectrometry (MS/MS can be used as it allows for rapid and simultaneous detection of the diseases. This analysis was performed to determine whether newborn screening by MS/MS is cost-effective in Thailand.A cost-utility analysis comprising a decision-tree and Markov model was used to estimate the cost in Thai baht (THB and health outcomes in life-years (LYs and quality-adjusted life year (QALYs presented as an incremental cost-effectiveness ratio (ICER. The results were also adjusted to international dollars (I$ using purchasing power parities (PPP (1 I$ = 17.79 THB for the year 2013. The comparisons were between 1 an expanded neonatal screening programme using MS/MS screening for six prioritised diseases: phenylketonuria (PKU; isovaleric acidemia (IVA; methylmalonic acidemia (MMA; propionic acidemia (PA; maple syrup urine disease (MSUD; and multiple carboxylase deficiency (MCD; and 2 the current practice that is existing PKU screening. A comparison of the outcome and cost of treatment before and after clinical presentations were also analysed to illustrate the potential benefit of early treatment for affected children. A budget impact analysis was conducted to illustrate the cost of implementing the programme for 10 years.The ICER of neonatal screening using MS/MS amounted to 1,043,331 THB per QALY gained (58,647 I$ per QALY gained. The potential benefits of early detection compared with late detection yielded significant results for PKU, IVA, MSUD, and MCD patients. The budget impact analysis indicated that the implementation cost of the programme was expected at approximately 2,700 million THB (152 million I$ over 10 years.At the current ceiling threshold, neonatal screening using MS/MS in the Thai context is not cost

  19. Inborn errors of ketogenesis and ketone body utilization.

    Science.gov (United States)

    Sass, Jörn Oliver

    2012-01-01

    Ketone bodies acetoacetate and 3-hydroxy-n-butyric acid are metabolites derived from fatty acids and ketogenic amino acids such as leucine. They are mainly produced in the liver via reactions catalyzed by the ketogenic enzymes mitochondrial 3-hydroxy-3-methylglutary-coenzyme A synthase and 3-hydroxy-3-methylglutary-coenzyme A lyase. After prolonged starvation, ketone bodies can provide up to two-thirds of the brain's energy requirements. The rate-limiting enzyme of ketone body utilization (ketolysis) is succinyl-coenzyme A:3-oxoacid coenzyme A transferase. The subsequent step of ketolysis is catalyzed by 2-methylactoacetyl-coenzyme A thiolase, which is also involved in isoleucine catabolism. Inborn errors of metabolism affecting those four enzymes are presented and discussed in the context of differential diagnoses. While disorders of ketogenesis can present with hypoketotic hypoglycemia, inborn errors of ketolysis are characterized by metabolic decompensations with ketoacidosis. If those diseases are considered early and appropriate treatment is initiated without delay, patients with inborn errors of ketone body metabolism often have a good clinical outcome.

  20. Risk factors and birth prevalence of birth defects and inborn errors of ...

    African Journals Online (AJOL)

    The principal BD as per the International Classification of Diseases-10 (ICD-10) ... On the other hand, consanguinity and low birth weight were associated with ... Key words: Birth defects, inborn errors of metabolism, newborn, Saudi Arabia ...

  1. Diagnosis and therapeutic monitoring of inborn errors of creatine metabolism and transport using liquid chromatography-tandem mass spectrometry in urine, plasma and CSF.

    Science.gov (United States)

    Haas, Dorothea; Gan-Schreier, Hongying; Langhans, Claus-Dieter; Anninos, Alexandros; Haege, Gisela; Burgard, Peter; Schulze, Andreas; Hoffmann, Georg F; Okun, Jürgen G

    2014-03-15

    Biochemical detection of inborn errors of creatine metabolism or transport relies on the analysis of three main metabolites in biological fluids: guanidinoacetate (GAA), creatine (CT) and creatinine (CTN). Unspecific clinical presentation of the diseases might be the cause that only few patients have been diagnosed so far. We describe a LC-MS/MS method allowing fast and reliable diagnosis by simultaneous quantification of GAA, CT and CTN in urine, plasma and cerebrospinal fluid (CSF) and established reference values for each material. For quantification deuterated stable isotopes of each analyte were used as internal standards. GAA, CT and CTN were separated by reversed-phase HPLC. The characterization was carried out by scanning the ions of each compound by negative ion tandem mass spectrometry. Butylation is needed to achieve sufficient signal intensity for GAA and CT but it is not useful for analyzing CTN. The assay is linear in a broad range of analyte concentrations usually found in urine, plasma and CSF. Comparison of the "traditional" cation-exchange chromatography and LC-MS/MS showed proportional differences but linear relationships between the two methods. The described method is characterized by high speed and linearity over large concentration ranges comparable to other published LC-MS methods but with higher sensitivity for GAA and CT. In addition, we present the largest reference group ever published for guanidino compounds in all relevant body fluids. Therefore this method is applicable for high-throughput approaches for diagnosis and follow-up of inborn errors of creatine metabolism and transport.

  2. Living with an inborn error of metabolism detected by newborn screening-parents' perspectives on child development and impact on family life.

    Science.gov (United States)

    Gramer, Gwendolyn; Haege, Gisela; Glahn, Esther M; Hoffmann, Georg F; Lindner, Martin; Burgard, Peter

    2014-03-01

    Newborn screening for inborn errors of metabolism is regarded as highly successful by health professionals. Little is known about parents' perspectives on child development and social impact on families. Parents of 187 patients with metabolic disorders detected by newborn screening rated child development, perceived burdens on child and family, and future expectations on a questionnaire with standardized answers. Parental ratings were compared with standardized psychometric test results. Regression analysis was performed to identify factors associated with extent of perceived burden. In 26.2% of patients, parents perceived delays in global development and/or specific developmental domains (physical, social, intellectual, language). Parents expected normal future development in 95.7%, and an independent adult life for their child in 94.6%. Comparison with psychometric test results showed that parents of children with cognitive impairments tended to overrate their child's abilities. Mild/medium burden posed on the family (child) by the metabolic disorder was stated by 56.1% (48.9%) of parents, severe/very severe burden by 19.3% (8.6%). One third of families reported financial burden due to the metabolic disorder. Dietary treatment and diagnoses with risk for metabolic decompensation despite treatment were associated with higher perceived burden for the family. Disorders rated as potentially very burdensome by experts were not rated accordingly by parents, demonstrating different perspectives of professionals and parents. Although newborn screening leads to favourable physical and cognitive outcome, living with a metabolic disorder may cause considerable stress on patients and families, emphasizing the need for comprehensive multidisciplinary care including psychological and social support.

  3. Automated Screening for Three Inborn Metabolic Disorders: A Pilot Study

    Directory of Open Access Journals (Sweden)

    Kavitha S

    2006-12-01

    Full Text Available Background: Inborn metabolic disorders (IMDs form a large group of rare, but often serious, metabolic disorders. Aims: Our objective was to construct a decision tree, based on classification algorithm for the data on three metabolic disorders, enabling us to take decisions on the screening and clinical diagnosis of a patient. Settings and Design: A non-incremental concept learning classification algorithm was applied to a set of patient data and the procedure followed to obtain a decision on a patient’s disorder. Materials and Methods: Initially a training set containing 13 cases was investigated for three inborn errors of metabolism. Results: A total of thirty test cases were investigated for the three inborn errors of metabolism. The program identified 10 cases with galactosemia, another 10 cases with fructosemia and the remaining 10 with propionic acidemia. The program successfully identified all the 30 cases. Conclusions: This kind of decision support systems can help the healthcare delivery personnel immensely for early screening of IMDs.

  4. Rare inborn errors of metabolism with movement disorders: a case study to evaluate the impact upon quality of life and adaptive functioning.

    Science.gov (United States)

    Eggink, Hendriekje; Kuiper, Anouk; Peall, Kathryn J; Contarino, Maria Fiorella; Bosch, Annet M; Post, Bart; Sival, Deborah A; Tijssen, Marina A J; de Koning, Tom J

    2014-11-26

    Inborn errors of metabolism (IEM) form an important cause of movement disorders in children. The impact of metabolic diseases and concordant movement disorders upon children's health-related quality of life (HRQOL) and its physical and psychosocial domains of functioning has never been investigated. We therefore conducted a case study on the HRQOL and development of adaptive functioning in children with an IEM and a movement disorder. Children with co-existent IEM and movement disorders were recruited from paediatric outpatient clinics. We systematically collected clinical data and videotaped examinations. The movement disorders were diagnosed by a panel of specialists. The Pediatric Quality of Life Inventory 4.0 and the Vineland Adaptive Behavior Scale were used to assess the HRQOL and adaptive functioning, respectively. We recruited 24 children (10 boys, mean age 7y 5 m). Six types of movement disorders were recognised by the expert panel, most frequently dystonia (16/24), myoclonus (7/24) and ataxia (6/24). Mean HRQOL (49.63, SD 21.78) was significantly lower than for other chronic disorders in childhood (e.g. malignancy, diabetes mellitus, rheumatic disease, psychiatric disorders; p adaptive functioning, most evident in their activities of daily living (51.92%, SD 27.34). Delay in adaptive functioning had a significant impact upon HRQOL (p = 0.018). A broad spectrum of movement disorders was seen in patients with IEM, although only five were receiving treatment. The overall HRQOL in this population is significantly reduced. Delay in adaptive functioning, most frequently seen in relation to activities of daily living, and the severity of the movement disorder contribute to this lower HRQOL. We plead for a greater awareness of movement disorders and that specialists should be asked to diagnose and treat these wherever possible.

  5. Mutations in THAP11 cause an inborn error of cobalamin metabolism and developmental abnormalities

    DEFF Research Database (Denmark)

    Quintana, Anita M; Yu, Hung-Chun; Brebner, Alison

    2017-01-01

    CblX (MIM309541) is an X-linked recessive disorder characterized by defects in cobalamin (vitamin B12) metabolism and other developmental defects. Mutations in HCFC1, a transcriptional co-regulator which interacts with multiple transcription factors, have been associated with cblX. HCFC1 regulates...

  6. Expanding research to provide an evidence base for nutritional interventions for the management of inborn errors of metabolism☆

    OpenAIRE

    Camp, Kathryn M; Lloyd-Puryear, Michele A.; Yao, Lynne; Groft, Stephen C.; Parisi, Melissa A.; Mulberg, Andrew; Gopal-Srivastava, Rashmi; Cederbaum, Stephen; Enns, Gregory M.; Ershow, Abby G.; Frazier, Dianne M.; Gohagan, John; Harding, Cary; Howell, R. Rodney; Regan, Karen

    2013-01-01

    A trans-National Institutes of Health initiative, Nutrition and Dietary Supplement Interventions for Inborn Errors of Metabolism (NDSI-IEM), was launched in 2010 to identify gaps in knowledge regarding the safety and utility of nutritional interventions for the management of inborn errors of metabolism (IEM) that need to be filled with evidence-based research. IEM include inherited biochemical disorders in which specific enzyme defects interfere with the normal metabolism of exogenous (dietar...

  7. AB152. Inborn errors of metabolism spectrum in symptomatic children of north India: 5-year prospective data from tertiary care centre

    Science.gov (United States)

    Kumar, Somesh; Lomash, Avinash; Varughese, Bijo; Bidhan, Sourabh; Khalil, Sumaira; Polipalli, Sunil K.; Kapoor, Seema

    2015-01-01

    Background Children with high suspicion of IEM is a more effective screening strategy in a resource limited country like India. We present a prospective analysis of symptomatic children with red flag signs suggestive of IEM referred for analysis by LCMSMS. This study investigated the spectrum of IEM in symptomatic children over a period of 5 years (1st June 2010 to May 31st 2015). Methods A total of 3,250 symptomatic children for IEM were screened. Dried blood spots were collected and processed by MS/MS (API-2000 & 3200 Qtrap), using a non derivatized kit, analysed by R-4 Stork algorithm. Results A total of 3,250 children, 1,803 boys (56.34%), 1,397 girls (43.66%) with a median age of 20.8 months (range, 0.04-148.2 months) were screened. The 125 were diagnosed with an inborn error of metabolism, with a detection rate of 3.90%. Of these, 78 (62.40%) were males and 47 (38.60%) were females with a median age of 6.55 months. Clinical variation among the patients were unexplained encephalopathy, seizures, convulsions, delayed milestones with global developmental delay, persistent metabolic acidosis with increase anion GAP. The commonest group was amino acid disorders affecting 61 (48.8%) with phenylketonuria (n=5), hyperphenylalaninemia (n=4), maple syrup urine disease (n=8), hypermethioninemia (n=3), hyperglycemia (n=14), tyrosinemia (n=5), classic neonatal onset citrullinemia (n=4), 3 with hyperornithinemia, 10 with rasied alanine (as a secondary indicator), 3 with argininemia and 2 with remethylation defect. Organic acidemias 37 (29.60%) were methylmalonic academia (n=15), malonic aciduria (n=3), propionic aciduria (n=5), glutaric academia type I (n=5) and with 3-Methyl crotonyl-CoA carboxylase deficiency (n=9). Fatty acids disorders were seen in 27 (21.60%) children with medium-chain acyl-CoA dehydrogenase deficiency being the commonest (n=5), and very-long chain acyl-CoA dehydrogenase deficiency (n=2), carnitine palmitoyl-transferase Ia deficiency (n=12), carnitine

  8. A new chemical diagnostic method for inborn errors of metabolism by mass spectrometry-rapid, practical, and simultaneous urinary metabolites analysis.

    Science.gov (United States)

    Matsumoto, I; Kuhara, T

    1996-01-01

    In most developed countries, neonatal mass screening programs for the early diagnosis of inborn errors of metabolism (IEM) have been implemented and have been found to be effective for the prevention or significant reduction of clinical symptoms such as mental retardation. These programs rely primarily on simple bacterial inhibition assays (the "Guthrie tests"). We developed a new method for screening IEM using GC/MS, which enables accurate chemical diagnoses through urinary analyses with a simple practical procedure. The urine sample preparation for GC/MS takes one hour for one sample or three hours for a batch of 30 samples (will be fully automated shortly), and the following GC/MS measurement is completed within 15 min per sample. This method allows the simultaneous analyses of amino acids, organic acids, sugars, sugar alcohols, sugar acids, and nucleic acid bases. Therefore, a large number of metabolic disorders can be simultaneously tested by this chemical diagnostic procedure. This method is quite comprehensive and different from conventional GC/MS organic acidemia screening procedures, which are not well-suited to detect metabolic disorders except organic acidurias. Sample preparation includes urease treatment, deproteinization, and derivatization. The method has also been applied to neonate urine specimens that are absorbed into filter paper. The air-dried samples were mailed to the analytical laboratory and eluted with water. The eluate (0.1 mL) was incubated with urease, followed by deproteinization with alcohol, evaporation to dryness of the supernatant, and trimethylsilylation; the samples were applied to GC/MS. A pilot study of the application of this diagnostic procedure to the neonatal mass screening of 22 disorders was started in Japan on February 1, 1995 in cooperation with four medical institutes. This program is supported by the Japanese Society for Biomedical Mass Spectrometry and the Japanese Mass Screening Society. The initial twenty

  9. Los errores congénitos del metabolismo como enfermedades raras con un planteamiento global específico Inborn errors of metabolism as rare diseases with a specific global situation

    Directory of Open Access Journals (Sweden)

    P. Sanjurjo

    2008-01-01

    result in the alteration of a protein. Depending on this protein’s function - whether as an enzyme, a hormone, a receiver-transporter of a cellular membrane or forming part of a cellular organelle (lysosome, peroxysome - different groups of diseases emerge, which cause the most outstanding characteristic of inborn errors of metabolism (IEM: their clinical heterogeneity. The majority of these diseases are autosomal recessive, with a limited number of asymptomatic carriers, but there are also those ruled by an autonomous, dominant character inheritance or linked to the X chromosome. Taken individually, CMDs are highly infrequent, but taken as a whole CMDs (of which over 500 have been described to date can affect 1/500 of the newborn. A common characteristic of many CMDs is the possibility of dietary treatment and treatment with enzymatic replacement. For essentially didactic purposes the following groups should be considered: CMDs of the intermediary metabolism (whose types are intoxication and energy deficit, CMDs of cellular organelles, complex CMDs due to cycle alterations and others. A summary is presented of the clinical, diagnostic and therapeutic aspects of one disease of each type of those previously described: hyperphenylalaninemias, deficiencies of the mitochondrial oxidative phosphorilation (OXPHOS and lysosomal storage diseases.

  10. The inborn errors of mitochondrial fatty acid oxidation.

    Science.gov (United States)

    Vianey-Liaud, C; Divry, P; Gregersen, N; Mathieu, M

    1987-01-01

    To date, seven inborn errors of mitochondrial fatty acid oxidation have been identified. A total of about 100 patients in the world have been reported. Clinically the beta-oxidation defects are more often characterized by episodic hypoglycaemia leading to a coma mimicking Reye's syndrome. The hypoglycaemia is non-ketotic since the synthesis of ketone bodies is deficient. Periods of decompensation occur when carbohydrate supply is poor, e.g. prolonged fasting, vomiting, or increased caloric requirements, as and when lipid stores are used. Defects in beta-oxidation have also been reported to be one cause of sudden infant death syndrome. The diagnosis of these inborn errors is by biochemical investigation since where symptoms suggest such a defect, the precise aetiology cannot be assessed. The biochemical diagnosis is based firstly on identification of abnormal plasma and of urinary metabolites during acute attacks. Derivatives of the omega-oxidation and omega-1-oxidation of medium chain fatty acids have been identified, as well as acylglycine and acylcarnitine conjugates. These metabolites are nearly always absent when patients are in good clinical condition. Secondly, the diagnosis must be based on the identification of the enzymatic defects: this involves global assays which allow a localization of the 'level' of the defect (i.e. the oxidation of long, medium or short chain fatty acids) and specific measurement of enzyme activities (acyl-CoA dehydrogenases and electron carriers: ETF and ETF-DH). The diagnosis of these disorders is of prime importance because of the severity of the clinical symptoms. These can be prevented, in some cases, by an appropriate diet (a high carbohydrate, low fat diet, sometimes supplemented with L-carnitine). In other cases, genetic counselling can be offered.

  11. Long-chain polyunsaturated fatty acid concentration in patients with inborn errors of metabolism Concentración de ácidos grasos poliinsaturados de cadena larga en pacientes con errores innatos del metabolismo

    Directory of Open Access Journals (Sweden)

    M.ª A. Vilaseca

    2011-02-01

    Full Text Available Introduction: Long-chain polyunsaturated fatty acid (LCPUFA can be provided by diet (fatty fish, eggs, viscera and human milk or synthetised from essential fatty acids linoleic and α-linolenic acids through the microsomal pathway. However, endogenous LCPUFA synthesis is rather low, especially for docosahexaenoic (DHA, and seems insufficient to achieve normal DHA values in individuals devoid of preformed dietary supply. Inborn errors of metabolism (IEMs are therefore diseases with a special risk for LCPUFA deficient status. Aim: Our aim was to evaluate LCPUFA status in 132 patients with different IEMs. Methods: We performed a cross-sectional study of plasma and erythrocyte LCPUFA composition of 63 patients with IEMs treated with protein-restricted diets compared with data from 69 patients with IEMs on protein-unrestricted diets, and 43 own reference values. Results: Erythrocyte and plasma DHA and arachidonic acid concentrations were significantly decreased in patients treated with protein-restriction compared with those on protein-unrestricted diets and with our reference values (p Introducción: Los ácidos grasos poliinsaturados de cadena larga (LCPUFA pueden ser suministrados por la dieta o sintetizados a partir de los ácidos grasos esenciales, linoleico y α-linolénico. La síntesis endógena de LCPUFA es escasa, especialmente la de ácido docosahe-xaenoico (DHA, e insuficiente para alcanzar los valores normales de DHA en individuos que carecen de un suministro dietético de dichos ácidos preformados. Por ello, los errores innatos del metabolismo (IEM son enfermedades con riesgo especial de deficiencia de LCPUFAs. Objetivos: Evaluar el estado de LCPUFA en 132 pacientes con diferentes IEMs. Métodos: Estudio transversal de LCPUFA en plasma y eritrocitos de 63 pacientes con IEMs tratados con dieta restringida en proteínas comparados con 69 pacientes con IEMs con una dieta libre y 43 valores de referencia. Resultados: Las concentraciones de

  12. Purine and pyrimidine metabolism.

    Science.gov (United States)

    Zöllner, N

    1982-09-01

    The pathways of purine biosynthesis and degradation have been elucidated during the last 30 years; the regulation of the mechanisms involved is not yet fully understood, particularly with respect to quantitative aspects. Research into inborn errors of purine metabolism has provided valuable insights into purine synthesis and salvage pathways. Nutrition experiments using purine-free formula diets and supplements with defined purine sources permit precise descriptions of the influence of various dietary purines on uric acid formation. Supplements of dietary purines produce dose-proportional increases in plasma uric acid concentrations, uric acid pool size and renal uric acid excretion. The magnitude of these increases depends on the type of purine compound administered, which may limit the value of food tables for human dietetics. Purine content of food must be related not only to weight but also to energy and to protein, particularly if new foodstuffs or a vegetarian diet are ingested. Dietary purines appear to influence the biosynthesis of pyrimidines. In contrast to dietary purines, pyrimidines in the diet, if administered as nucleosides or nucleotides, are utilized in animals for the synthesis of nucleic acids. Much further work is necessary for a better understanding of the inter-relationships of purine and pyrimidine metabolism.

  13. Enfermedades metabólicas en el periodo neonatal con presentación neurológica Inborn errors of metabolism with neurological manifestations in the neonatal period

    Directory of Open Access Journals (Sweden)

    Jaume Campistol

    2007-01-01

    mejorar la precocidad diagnóstica y terapéutica, especialmente con cofactores para reducir la morbimortalidad.Congenital metabolic diseases are considered as rare diseases because of their low incidence and their clinical symptoms at onset. Sometimes they can just begin in the neonatal period. Their progressive knowledge and the availability of specific and sensitive biochemical procedures allow us to diagnose many congenital metabolic diseases, which were not recognized some years ago. We reviewed the 52 patients with congenital metabolic diseases diagnosed during the last 25 years in our centre, evaluating the clinical presentation, neurological symptoms, complementary exams and clinical evolution. The mean age at onset of symptoms was 5 days and the mean age at diagnosis was 88 days of age. We considered a first group of 36 patients with inborn errors of intermediary metabolism, in whom hypotonia, weight loss and seizures are the main symptoms. The second group was composed of 8 patients with defective energy metabolism, who showed abnormal respiratory rhythm and hypotonia. Finally, we considered 8 patients with diseases of the complex molecules, who presented with hypotonia and cataracts as common symptoms at onset. The more common neurological symptoms in this period were hypotonia (60%, sensorial deficit (35% and refractory seizures (23%. The complementary laboratory tests in the first phases of the diseases allowed us to suspect a congenital metabolic disease especially among intermediary and energy defects. EEG and CSF samples were important to diagnose some inborn errors of intermediary metabolism. In the first steps, the neuroimaging was less orientative, even if it allow the exclusion of other diseases. More than half of the patients with inborn errors of metabolism with onset in the neonatal period died within the first two years of life. It is really important to suspect these diseases in the neonatal period so as to achieve an early diagnosis and prompt

  14. Poly purine.pyrimidine sequences upstream of the beta-galactosidase gene affect gene expression in Saccharomyces cerevisiae

    Directory of Open Access Journals (Sweden)

    Brahmachari Samir K

    2001-10-01

    Full Text Available Abstract Background Poly purine.pyrimidine sequences have the potential to adopt intramolecular triplex structures and are overrepresented upstream of genes in eukaryotes. These sequences may regulate gene expression by modulating the interaction of transcription factors with DNA sequences upstream of genes. Results A poly purine.pyrimidine sequence with the potential to adopt an intramolecular triplex DNA structure was designed. The sequence was inserted within a nucleosome positioned upstream of the β-galactosidase gene in yeast, Saccharomyces cerevisiae, between the cycl promoter and gal 10Upstream Activating Sequences (UASg. Upon derepression with galactose, β-galactosidase gene expression is reduced 12-fold in cells carrying single copy poly purine.pyrimidine sequences. This reduction in expression is correlated with reduced transcription. Furthermore, we show that plasmids carrying a poly purine.pyrimidine sequence are not specifically lost from yeast cells. Conclusion We propose that a poly purine.pyrimidine sequence upstream of a gene affects transcription. Plasmids carrying this sequence are not specifically lost from cells and thus no additional effort is needed for the replication of these sequences in eukaryotic cells.

  15. Diagnosis of inborn errors of metabolism using tandem mass spectrometry and gas chromatography mass spectrometry%串联质谱联合气相色谱-质谱检测遗传性代谢病

    Institute of Scientific and Technical Information of China (English)

    韩连书; 叶军; 邱文娟; 高晓岚; 王瑜; 金晶; 顾学范

    2008-01-01

    Objective To investigate the effects of tandem mass spectrometry (MS/MS) combined with gas chromatography mass spectrometry (GC-MS) in the diagnosis of inborn errors of metabolism in children. Methods Amino acids and acylcarnitines in the dry blood filter papers were tested by MS/MS, and the organic acid profiles in urea were tested by GC-MS among 4981 children suspected to be with inborn errors of metabolism from more than 100 hospitals in China. A few pediatric patients underwent analysis of activity of enzyme and gene mutation analysis too. Results 319 of the 4981 children (6.4%) were diagnosed as with 24 kinds of diseases: 155 of the 319 cases (48.6%) with 8 kinds of amino acid diseases (97 with hyperphenylalaninemia, 14 with maple syrup urine disease 13 with ornithine transcarbamylase deficiency, 13 with citrullinemia type Ⅱ, 10 with tyrosinemia type Ⅰ , 5 with citrullinemia type Ⅰ ,2 with homocystinuria, and 1 with arginasemia) ; 150 of the 319 cases (47.0%) were diagnosed as with 10 kinds of organic acidemias (81 with methylmalonic acidemia, 17 with propionic acidemia, 17 with multiple CoA carboxylase deficiency, 11 with glutaric acidemia type Ⅱ, 8 with isovaleric acidemia, 6 with β-keto thiolase deficiency, 5 with 3-methylcrotonyl-CoA carboxylase deficiency, and 3 with 3-hydroxy-3-methylglutaryl-CoA lyase deficiency) ; 14 cases (4.4%) were diagnosed as with 6 kinds of fatty acid disorders (5 with medium chain acyl-CoA dehydrogenase deficiency, 3 with very long chain acyl CoA dehydrogenase deficiency, 2 with short chain acyl-CoA dehydrogenase deficiency, 2 with multiple acyl-CoA dehydrogenase deficiency, 1 with carnitine palmitoyl transferase type Ⅱ , and 1 with carnitine palmitoyl transferase type Ⅰ ). Conclusion MS/MS is specific for amino acid diseases and fatty acid disorders. GC-MS is specific for detect organic acidemias. And the diagnoses of part of amino acid diseases need the combination of both methods.%目的 应用串联质谱检测

  16. Inborn Error of Metabolism (IEM) screening in Singapore by electrospray ionization-tandem mass spectrometry (ESI/MS/MS): An 8 year journey from pilot to current program.

    Science.gov (United States)

    Lim, J S; Tan, E S; John, C M; Poh, S; Yeo, S J; Ang, J S M; Adakalaisamy, P; Rozalli, R A; Hart, C; Tan, E T H; Ranieri, E; Rajadurai, V S; Cleary, M A; Goh, D L M

    2014-01-01

    IEM screening by ESI/MS/MS was introduced in Singapore in 2006. There were two phases; a pilot study followed by implementation of the current program. The pilot study was over a 4 year period. During the pilot study, a total of 61,313 newborns were screened, and 20 cases of IEM were diagnosed (detection rate of 1:3065; positive predictive value (PPV) of 11%). Regular self-review, participation in external quality assessment and the Region 4 Genetic collaborative programs (http://www.region4genetics.org/) had led to the robust development of our current NBS MS/MS program. Overall, from July 2006 to April 2014, we screened a total of 177,267 newborns. The mean age at the time of sampling was 47.9h. Transportation of samples to the testing laboratory averaged 0.92 day. Upon receipt of sample, the NBS result was available within 1.64 days and within 3.8 days if a second tier test was required. Using absolute cut-off values in place of the initial 99th percentile reference range for the analyte markers and the introduction of two 2nd tier tests (MMA and Succinylacetone) had significantly reduced the high recall rate from an initial 1.5% during the period 2006-07 to 0.12% in 2013. The NBS MS/MS program was supported by a centralized confirmatory/diagnostic testing laboratory and a rapid response team of metabolic specialists. The detection rate was 1: 3165 (1:2727 if maternal conditions were also included). There were 23 newborns affected with organic acidemias (incidence: 1:6565), 23 with fatty acid oxidation disorders (incidence: 1:6565), and 10 with amino acidopathies (incidence 1:17,726). The performance metrics for the screening test were acceptable (sensitivity: 95.59%, specificity: 99.85%, PPV: 20%, FPR: 0.15). Participation in the NBS MS/MS program by hospitals was voluntary, and in 2013, the uptake rate was 71% of the annual births. We hope that newborn screening by MS/MS will become a standard of care for all babies in Singapore.

  17. Stroke-like episodes caused by inborn errors of metabolism in childhood%以脑卒中样发作为主要表现的儿童遗传代谢病

    Institute of Scientific and Technical Information of China (English)

    王昕; 杨健; 李尔珍; 王立文

    2011-01-01

    Objective To make a better understanding of the stroke-like episodes caused by inborn errors of metabolism in childhood. Methods Using a retrospective method, clinical and biochemical characteristics were reviewed and analyzed in five cases of children who suffered from stroke like episodes and were diagnosed with inherited metabolic disease. Results Five patients consisted of 4 males and 1 female. Their onset ages were 10 -~ 13 years old. Two cases had homocysteinemia; three cases were diagnosed or highly suspected with mitochondrial encephaiopathy with lactic acidosis and stroke-like spells (MELAS). Two homocysteinemia patients had acute onsets, manifested as movement disorders or unconsciousness, with normal growth and mental development. Two patients with ME LAS or highly suspected MELAS, had acute onsets, with prolonged course, manifested as movement disorders, seizures, vision loss, personality change etc. Growth retardation and mental regression were common in the patients with MELAS. Serum homocysteine concentration was higher in the patients with homocysteinemia than in normal controls, MELAS patients had lacLlc acid em] a and m.] tochondnai gene MELAS A3243G mutation; riomocysteinemia patients showed mult] pie lacunar in-farction ana bilateral basal ganglia infarction in MRL MELAS patients were special with posterior dominated grey matter lesions in MM. Conclusions Lots of diseases can cause childhood stroke-like episodes, inborn metabolic errors are one of them. When a sudden stroke happened, homocysteinemia should be one of the considerations; when such thing happened in a growth retarded child with gray iriatter lesions in posterior head region, the possibility of MELAS should be pay attention to.%目的 提高对遗传代谢性疾病所致儿童卒中样发作的认识.方法采用回顾性方法,对5例确诊为儿童遗传代谢病引发率中样发作患儿的临床表现、生化特点以及诊疗情况进行分析.结果 5例患儿中4男、1

  18. beta-Ureidopropionase deficiency: an inborn error of pyrimidine degradation associated with neurological abnormalities.

    NARCIS (Netherlands)

    Kuilenburg, A.B.P. van; Meinsma, R.; Beke, E.; Assmann, B.; Ribes, A.; Lorente, I.; Busch, R.; Mayatepek, E.; Abeling, N.G.G.M.; Cruchten, A.C. van; Stroomer, A.E.; Lenthe, H. van; Zoetekouw, L.; Kulik, W.; Hoffmann, G.F.; Voit, T.; Wevers, R.A.; Rutsch, F.; Gennip, A.H. van

    2004-01-01

    beta-Ureidopropionase deficiency is an inborn error of the pyrimidine degradation pathway, affecting the cleavage of N-carbamyl-beta-alanine and N-carbamyl-beta-aminoisobutyric acid. In this study, we report the elucidation of the genetic basis underlying a beta-ureidopropionase deficiency in four p

  19. Minireview on Glutamine Synthetase Deficiency, an Ultra-Rare Inborn Error of Amino Acid Biosynthesis.

    Science.gov (United States)

    Spodenkiewicz, Marta; Diez-Fernandez, Carmen; Rüfenacht, Véronique; Gemperle-Britschgi, Corinne; Häberle, Johannes

    2016-10-19

    Glutamine synthetase (GS) is a cytosolic enzyme that produces glutamine, the most abundant free amino acid in the human body. Glutamine is a major substrate for various metabolic pathways, and is thus an important factor for the functioning of many organs; therefore, deficiency of glutamine due to a defect in GS is incompatible with normal life. Mutations in the human GLUL gene (encoding for GS) can cause an ultra-rare recessive inborn error of metabolism-congenital glutamine synthetase deficiency. This disease was reported until now in only three unrelated patients, all of whom suffered from neonatal onset severe epileptic encephalopathy. The hallmark of GS deficiency in these patients was decreased levels of glutamine in body fluids, associated with chronic hyperammonemia. This review aims at recapitulating the clinical history of the three known patients with congenital GS deficiency and summarizes the findings from studies done along with the work-up of these patients. It is the aim of this paper to convince the reader that (i) this disorder is possibly underdiagnosed, since decreased concentrations of metabolites do not receive the attention they deserve; and (ii) early detection of GS deficiency may help to improve the outcome of patients who could be treated early with metabolites that are lacking in this condition.

  20. Study of clinic etiologies about newborn infants with high risk of inborn error of metabolism%高危新生儿遗传代谢病临床病因学分析

    Institute of Scientific and Technical Information of China (English)

    庄太凤; 马建荣; 温春玲; 邢继伟; 张巍; 杨艳玲

    2011-01-01

    Objective To investigate the clinic etiologies about newborn infants with high risk of inborn error of metabolism ( IEM) in NICU. Methods We did a urine organic acid analysis about 100 newhom infants with high risk of IEM by GC/MS. At the same time . blood routine , liver and renal function , blood lactic acid, blood pyruvic acid , β-hydroxyhutyric acid ,blood ammonia and serum homocysteine were determined. There were 24 patients diagnosed IEM by analysis results among the 100 cases. After 1 or 2 courses of treatment to the 24 patients , we did follow-up examination. Results There were 12 cases confirmed with IEM in the 24 patients ,including 2 patients with propionic acidemia ( PA) ,2 with tyrosinemia,2 with homocystinemia , 1 with methylmalonic aciduria ( MMA) ,1 with glutaric acidosis type Ⅱ ( GAⅡ) ,1 with congenital lactose intolerance,1 with hypermethioninemia ,1 with β-ketothiolase deficiency and 1 with ornithine carbamoyltransferase deficiency ( OCTD). Those diseases were autosomal recessive inheritance . There were different clinical features in 12 IEM cases ,including 3 patients with blood vessel pathological changes ( microthrombus engendered and encephalon parenchyma haemo -rrhage),2 with eclampsia ,2 with recurred metabolic acidosis ,1 with sudden death,1 with recurred hypoglycemia,1 with obstinated diarrhoea ,1 with jaundice correlated with inheritance and 1 with severe pneumonia. In the crises of the 12 IEM patients , 100% patients showed hyperammonemia, 83% metabolic acidosis and pyruvemia , 67% nephridium impaired , 50% with liver impaired ,42% with blood impaired. Conclusions The newbom infants with high risk of IEM had complicated etiologies . The neonates' IEM spectrum were amplification by new technique ( eg. GC/MS ). The amplification of IEM spectrum would show more etiologies of newborn and help diagnosis and treatment .%目的 初步研究新生儿重症监护室(NICU)先天性遗传代谢病(IEM)高危新

  1. Minireview on Glutamine Synthetase Deficiency, an Ultra-Rare Inborn Error of Amino Acid Biosynthesis

    Directory of Open Access Journals (Sweden)

    Marta Spodenkiewicz

    2016-10-01

    Full Text Available Glutamine synthetase (GS is a cytosolic enzyme that produces glutamine, the most abundant free amino acid in the human body. Glutamine is a major substrate for various metabolic pathways, and is thus an important factor for the functioning of many organs; therefore, deficiency of glutamine due to a defect in GS is incompatible with normal life. Mutations in the human GLUL gene (encoding for GS can cause an ultra-rare recessive inborn error of metabolism—congenital glutamine synthetase deficiency. This disease was reported until now in only three unrelated patients, all of whom suffered from neonatal onset severe epileptic encephalopathy. The hallmark of GS deficiency in these patients was decreased levels of glutamine in body fluids, associated with chronic hyperammonemia. This review aims at recapitulating the clinical history of the three known patients with congenital GS deficiency and summarizes the findings from studies done along with the work-up of these patients. It is the aim of this paper to convince the reader that (i this disorder is possibly underdiagnosed, since decreased concentrations of metabolites do not receive the attention they deserve; and (ii early detection of GS deficiency may help to improve the outcome of patients who could be treated early with metabolites that are lacking in this condition.

  2. Modeling congenital disease and inborn errors of development in Drosophila melanogaster

    OpenAIRE

    2016-01-01

    Fly models that faithfully recapitulate various aspects of human disease and human health-related biology are being used for research into disease diagnosis and prevention. Established and new genetic strategies in Drosophila have yielded numerous substantial successes in modeling congenital disorders or inborn errors of human development, as well as neurodegenerative disease and cancer. Moreover, although our ability to generate sequence datasets continues to outpace our ability to analyze t...

  3. Modeling congenital disease and inborn errors of development in Drosophila melanogaster

    OpenAIRE

    2016-01-01

    ABSTRACT Fly models that faithfully recapitulate various aspects of human disease and human health-related biology are being used for research into disease diagnosis and prevention. Established and new genetic strategies in Drosophila have yielded numerous substantial successes in modeling congenital disorders or inborn errors of human development, as well as neurodegenerative disease and cancer. Moreover, although our ability to generate sequence datasets continues to outpace our ability to ...

  4. Inborn Errors of Long-Chain Fatty Acid β-Oxidation Link Neural Stem Cell Self-Renewal to Autism

    Directory of Open Access Journals (Sweden)

    Zhigang Xie

    2016-02-01

    Full Text Available Inborn errors of metabolism (IEMs occur with high incidence in human populations. Especially prevalent among these are inborn deficiencies in fatty acid β-oxidation (FAO, which are clinically associated with developmental neuropsychiatric disorders, including autism. We now report that neural stem cell (NSC-autonomous insufficiencies in the activity of TMLHE (an autism risk factor that supports long-chain FAO by catalyzing carnitine biosynthesis, of CPT1A (an enzyme required for long-chain FAO transport into mitochondria, or of fatty acid mobilization from lipid droplets reduced NSC pools in the mouse embryonic neocortex. Lineage tracing experiments demonstrated that reduced flux through the FAO pathway potentiated NSC symmetric differentiating divisions at the expense of self-renewing stem cell division modes. The collective data reveal a key role for FAO in controlling NSC-to-IPC transition in the mammalian embryonic brain and suggest NSC self renewal as a cellular mechanism underlying the association between IEMs and autism.

  5. An Attempt to Determine the Prevalence of Two Inborn Errors of Primary Bile Acid Synthesis : Results of a European survey

    NARCIS (Netherlands)

    Zöhrer, Evelyn; Fischler, Björn; D'Antiga, Lorenzo; Debray, Dominique; Dezsofi, Antal; Haas, Dorothea; Hadzic, Nedim; Jacquemin, Emmanuel; Lamireau, Thierry; Maggiore, Giuseppe; McKiernan, Pat J; Calvo, Pier Luigi; Verkade, Henkjan J; Hierro, Loreto; McLin, Valerie; Baumann, Ulrich; Gonzales, Emmanuel

    2017-01-01

    OBJECTIVE: Inborn errors of primary bile acid (BA) synthesis are genetic cholestatic disorders leading to accumulation of atypical BA with deficiency of normal BA. Unless treated with primary BA, chronic liver disease usually progresses to cirrhosis and liver failure before adulthood. We sought to d

  6. [A rare inborn error of intracellular processing of cobalamine presenting with microcephalus and megaloblastic anemia: a report of 3 children].

    Science.gov (United States)

    Müller, P; Horneff, G; Hennermann, J B

    2007-01-01

    Defects of methionine synthase or methionine synthase reductase result in an impaired remethylation of homocysteine to methionine. Patients present with megaloblastic anemia, failure to thrive and various neurological manifestations including mental retardation, cerebral atrophy, muscular hypotonia or hypertonia, ataxia, seizures, nystagmus and visual disturbances. We report on three children (two girls, one boy), aged 3.5-7.5 years, who presented with severe megaloblastic anemia, micro-cephalus and partly nystagmus (2/3) due to a rare inborn error of remethylation. Methionine synthase reductase deficiency, cblE type of homocystinuria (OMIM 236270), is a rare autosomal recessive inherited disorder described only in 14 patients worldwide. Metabolic hallmarks of the disease are hyperhomocysteinemia (median 98 micromol/l, normal range megaloblastic anemia. Measurements of homocysteine and methionine in plasma as well as methylmalonic acid in urine is required for confirming the diagnosis. Early treatment im-proves the outcome, although mental disability may not be prevented. Treatment has a positive impact on megaloblastic anemia but only slight effect on hyperhomocysteinemia. The long-term cardiovascular risk of hyperhomocysteinemia in cblE deficient patients is not known yet.

  7. Modeling congenital disease and inborn errors of development in Drosophila melanogaster

    Directory of Open Access Journals (Sweden)

    Matthew J. Moulton

    2016-03-01

    Full Text Available Fly models that faithfully recapitulate various aspects of human disease and human health-related biology are being used for research into disease diagnosis and prevention. Established and new genetic strategies in Drosophila have yielded numerous substantial successes in modeling congenital disorders or inborn errors of human development, as well as neurodegenerative disease and cancer. Moreover, although our ability to generate sequence datasets continues to outpace our ability to analyze these datasets, the development of high-throughput analysis platforms in Drosophila has provided access through the bottleneck in the identification of disease gene candidates. In this Review, we describe both the traditional and newer methods that are facilitating the incorporation of Drosophila into the human disease discovery process, with a focus on the models that have enhanced our understanding of human developmental disorders and congenital disease. Enviable features of the Drosophila experimental system, which make it particularly useful in facilitating the much anticipated move from genotype to phenotype (understanding and predicting phenotypes directly from the primary DNA sequence, include its genetic tractability, the low cost for high-throughput discovery, and a genome and underlying biology that are highly evolutionarily conserved. In embracing the fly in the human disease-gene discovery process, we can expect to speed up and reduce the cost of this process, allowing experimental scales that are not feasible and/or would be too costly in higher eukaryotes.

  8. Modeling congenital disease and inborn errors of development in Drosophila melanogaster.

    Science.gov (United States)

    Moulton, Matthew J; Letsou, Anthea

    2016-03-01

    Fly models that faithfully recapitulate various aspects of human disease and human health-related biology are being used for research into disease diagnosis and prevention. Established and new genetic strategies in Drosophila have yielded numerous substantial successes in modeling congenital disorders or inborn errors of human development, as well as neurodegenerative disease and cancer. Moreover, although our ability to generate sequence datasets continues to outpace our ability to analyze these datasets, the development of high-throughput analysis platforms in Drosophila has provided access through the bottleneck in the identification of disease gene candidates. In this Review, we describe both the traditional and newer methods that are facilitating the incorporation of Drosophila into the human disease discovery process, with a focus on the models that have enhanced our understanding of human developmental disorders and congenital disease. Enviable features of the Drosophila experimental system, which make it particularly useful in facilitating the much anticipated move from genotype to phenotype (understanding and predicting phenotypes directly from the primary DNA sequence), include its genetic tractability, the low cost for high-throughput discovery, and a genome and underlying biology that are highly evolutionarily conserved. In embracing the fly in the human disease-gene discovery process, we can expect to speed up and reduce the cost of this process, allowing experimental scales that are not feasible and/or would be too costly in higher eukaryotes.

  9. PNPO deficiency: an under diagnosed inborn error of pyridoxine metabolism.

    NARCIS (Netherlands)

    Khayat, M.; Korman, S.H.; Frankel, P.; Weintraub, Z.; Hershckowitz, S.; Sheffer, V.F.; Elisha, M. Ben; Wevers, R.A.; Falik-Zaccai, T.C.

    2008-01-01

    The rare autosomal recessive disorder pyridoxine 5'-phosphate oxidase (PNPO) deficiency is a recently described cause of neonatal and infantile seizures. Clinical evaluation, and biochemical and genetic testing, were performed on a neonate with intractable seizures who did not respond to anticonvuls

  10. PNPO deficiency: an under diagnosed inborn error of pyridoxine metabolism.

    Science.gov (United States)

    Khayat, Morad; Korman, Stanley H; Frankel, Pnina; Weintraub, Zalman; Hershckowitz, Sylvia; Sheffer, Vered Fleisher; Ben Elisha, Mordechai; Wevers, Ronald A; Falik-Zaccai, Tzipora C

    2008-08-01

    The rare autosomal recessive disorder pyridoxine 5'-phosphate oxidase (PNPO) deficiency is a recently described cause of neonatal and infantile seizures. Clinical evaluation, and biochemical and genetic testing, were performed on a neonate with intractable seizures who did not respond to anticonvulsant drugs and pyridoxine. Sequencing of the PNPO gene revealed a novel homozygous c.284G>A transition in exon 3, resulting in arginine to histidine substitution and reduced activity of the PNPO mutant to 18% relative to the wild type. This finding enabled molecular prenatal diagnosis in a subsequent pregnancy, accurate genetic counseling in the large inbred family, and population screening.

  11. PNPO deficiency: an under diagnosed inborn error of pyridoxine metabolism.

    NARCIS (Netherlands)

    Khayat, M.; Korman, S.H.; Frankel, P.; Weintraub, Z.; Hershckowitz, S.; Sheffer, V.F.; Elisha, M. Ben; Wevers, R.A.; Falik-Zaccai, T.C.

    2008-01-01

    The rare autosomal recessive disorder pyridoxine 5'-phosphate oxidase (PNPO) deficiency is a recently described cause of neonatal and infantile seizures. Clinical evaluation, and biochemical and genetic testing, were performed on a neonate with intractable seizures who did not respond to

  12. Secondary disorders of glycosylation in inborn errors of fructose metabolism.

    Science.gov (United States)

    Quintana, E; Sturiale, L; Montero, R; Andrade, F; Fernandez, C; Couce, M L; Barone, R; Aldamiz-Echevarria, L; Ribes, A; Artuch, R; Briones, P

    2009-12-01

    Adamowicz and colleagues raised the alert in 2007 about patients with atypical hereditary fructose intolerance (HFI) primarily misdiagnosed as CDG Ix. We describe a girl with neonatal hypertonia, facial trismus, absent swallowing and coughing reflexes, gastro-oesophageal reflux and sporadically elevated Krebs cycle metabolites and lactate. At 14 months microcephaly and hepatomegaly were noted, with hypertransaminasaemia but normal blood coagulation, glucose, phosphate, and absent urinary reducing substances. Neurological impairment persisted. Because of hepatic and neurological abnormalities with developmental delay, Tf IEF was performed and showed a severe type 1 pattern, resulting in a wrong diagnosis of CDG. Subsequently, an aversion to fruits suggested HFI, confirmed by the finding of ALDOB mutations (p.A150P/p.N335K). The girl improved with fructose-free diet, but liver cirrhosis led to hepatic transplantation. She is now 7 years old with good evolution; facial trismus and hypertonia reversed, but microcephaly persists. Transferrin MALDI-TOF MS characterization revealed underoccupation of glycosylation sites and glycan abnormalities, which reversed with dietary treatment. High maternal fructose concentrations might have caused neonatal abnormalities. Although in our patient's mother there is no fructose accumulation at present, it is possible that increased ingestion of fruits and vegetables during pregnancy, together with her heterozygosity, caused an accumulation of fructose that finally affected the fetus. We also describe slightly abnormal transferrin isoelectric focusing and MALDI-TOF MS patterns of intact transferrin and N-glycans in a fructose-1,6-bisphosphatase (FBP1)-deficient patient. While HFI is a well-known cause of secondary CDG, we found no reports of abnormal transferrin isoelectric focusing patterns in FBP1 deficiency and we introduce this condition as a possible secondary cause for altered transferrin isoelectric focusing.

  13. Stem Cell Transplant for Inborn Errors of Metabolism

    Science.gov (United States)

    2012-11-06

    Adrenoleukodystrophy; Metachromatic Leukodystrophy; Globoid Cell Leukodystrophy; Gaucher's Disease; Fucosidosis; Wolman Disease; Niemann-Pick Disease; Batten Disease; GM1 Gangliosidosis; Tay Sachs Disease; Sandhoff Disease

  14. Hematopoietic Stem Cell Transplantation (HCT) for Inborn Errors of Metabolism

    Science.gov (United States)

    2012-11-06

    Hurler's Syndrome; Maroteaux-Lamy Syndrome; Sly Syndrome; Alpha Mannosidosis; Fucosidosis; Aspartylglucosaminuria; Sphingolipidoses; Krabbe Disease; Wolman's Disease; Niemann-Pick Disease Type B; Niemann-Pick Disease, Type C

  15. Aminoacylase I deficiency: a novel inborn error of metabolism.

    NARCIS (Netherlands)

    Coster, R. van; Gerlo, E.A.; Giardina, T.G.; Engelke, U.F.H.; Smet, J.E.; Praeter, C.M. de; Meersschaut, V.A.; Meirleir, L. de; Seneca, S.; Devreese, B.; Leroy, J.G.; Herga, S.; Perrier, J.P.; Wevers, R.A.; Lissens, W.

    2005-01-01

    This is the first report of a patient with aminoacylase I deficiency. High amounts of N-acetylated amino acids were detected by gas chromatography-mass spectrometry in the urine, including the derivatives of serine, glutamic acid, alanine, methionine, glycine, and smaller amounts of threonine, leuci

  16. Metabolism

    Science.gov (United States)

    ... a particular food provides to the body. A chocolate bar has more calories than an apple, so ... acid phenylalanine, needed for normal growth and protein production). Inborn errors of metabolism can sometimes lead to ...

  17. Living with inborn errors of cholesterol biosynthesis: lessons from adult patients.

    Science.gov (United States)

    Cardoso, M L; Barbosa, M; Serra, D; Martins, E; Fortuna, A; Reis-Lima, M; Bandeira, A; Balreira, A; Marques, F

    2014-02-01

    In the last decades, nine inherited errors of the distal part of cholesterol biosynthesis have been recognized. Affected patients present complex malformation syndromes involving different organs and systems with variable degrees of severity. We report on the phenotype evolution of three patients with enzymatic defects at three distinct steps of such pathway: Smith-Lemli-Opitz syndrome, X-linked dominant chondrodysplasia punctata type 2 and congenital hemidysplasia with ichthyosiform erythroderma and limb defects syndrome. The patients' natural history, from childhood to adulthood, is thoroughly described in order to contribute for a better knowledge of these diseases. Our ultimate goals are to contribute for a better characterization of the long-term course of these metabolic disorders and for the recognition of such diseases in older patients.

  18. Selective screening of inborn errors of metabolism by using the tandem mass spectrometry:pilot study of 552 children at high risk%串联质谱技术选择性筛查遗传代谢病高危患儿552例初步分析

    Institute of Scientific and Technical Information of China (English)

    娄燕; 尹娜; 陈凤琴; 程亚颖; 徐丽瑾; 戴方; 宋晓涛

    2011-01-01

    目的 应用串联质谱(tandem mass spectrometry,MS/MS)技术进行遗传代谢病(IEM)高危儿筛查,初步了解我国IEM的发病种类和阳性率,为其有效防治提供科学依据.方法 利用MS/MS技术对在河北省石家庄市8所省、市级医院就医的552例可疑IEM患儿的血液样本进行IEM筛查.结果 发现阳性患儿64例,阳性率为11.6%.其中甲基丙二酸血症或丙酸血症33例,苯丙酮尿症2例,肉碱棕桐酞转移酶缺乏I型3例,长链酞基辅酶A脱氢酶缺乏症1例,中链酸基辅酶A脱氢酶缺乏症2例,枫糖尿症6例,短链酸基辅酶A脱氢酶缺乏症2例,戊二酸血症I型2例,异戊酸血症2例,同型肤氨酸尿症2例,肉碱缺乏症4例,酪氨酸血症1例,精氨酸境拍酸尿症1例,瓜氨酸血症2例,精氨酸血症1例.结论 MS/MS技术是筛查诊断IEM的有效工具.%Objective To study the application of tandem mass spectrometry (MS/MS) in the selective screening of inborn errors of metabolism (IEM) in high risk children and to understand the positive rate and types of IEM.Methods MS/MS was used to examine 552 blood samples from high risk cases of IEM who came from 8 hospitals in Shijiazhuang,Hebei Province.Results Sixty-four children ( 11.6% ) were confirmed with IEM by the MS/MS, including 33 cases of methylmalonic acidemia or propionic acidemias, 2 cases of phenylketonuria, 3 cases of carnitine palmotoyl transferase Ⅰ deficiency, 1 case of long-chain acyl-CoA dehydrogenase deficiency, 2 cases of medium-chain acyl-CoA dehydrogenase deficiency, 6 cases of maple syrup urine disease, 2 cases of short-chain acyl-CoA dehydrogenase deficiency, 2 cases of glutaric acidemia type Ⅰ, 2 cases of isovaleric acidemia, 2 cases of homocystinuria, 4 cases of carnitine deficiency, 1 case of tyrosinemia, 1 case of argininosuccinic aciduria, 2 cases of citrullinemia and 1 case of argininemia.Conclusions MS/MS can be used to screen and classify IEM.

  19. Inborn errors of the Krebs cycle: a group of unusual mitochondrial diseases in human.

    Science.gov (United States)

    Rustin, P; Bourgeron, T; Parfait, B; Chretien, D; Munnich, A; Rötig, A

    1997-08-22

    Krebs cycle disorders constitute a group of rare human diseases which present an amazing complexity considering our current knowledge on the Krebs cycle function and biogenesis. Acting as a turntable of cell metabolism, it is ubiquitously distributed in the organism and its enzyme components encoded by supposedly typical house-keeping genes. However, the investigation of patients presenting specific defects of Krebs cycle enzymes, resulting from deleterious mutations of the considered genes, leads to reconsider this simple envision by revealing organ-specific impairments, mostly affecting neuromuscular system. This often leaves aside organs the metabolism of which strongly depends on mitochondrial energy metabolism as well, such as heart, kidney or liver. Additionally, in some patients, a complex pattern of tissue-specific enzyme defect was also observed. The lack of functional additional copies of Krebs cycle genes suggests that the complex expression pattern should be ascribed to tissue-specific regulations of transcriptional and/or translational activities, together with a variable cell adaptability to Krebs cycle functional defects.

  20. Textbook Errors & Misconceptions in Biology: Cell Metabolism.

    Science.gov (United States)

    Storey, Richard D.

    1991-01-01

    The idea that errors and misconceptions in biology textbooks are often slow to be discovered and corrected is discussed. Selected errors, misconceptions, and topics of confusion about cell metabolism are described. Fermentation, respiration, Krebs cycle, pentose phosphate pathway, uniformity of catabolism, and metabolic pathways as models are…

  1. Textbook Errors & Misconceptions in Biology: Cell Metabolism.

    Science.gov (United States)

    Storey, Richard D.

    1991-01-01

    The idea that errors and misconceptions in biology textbooks are often slow to be discovered and corrected is discussed. Selected errors, misconceptions, and topics of confusion about cell metabolism are described. Fermentation, respiration, Krebs cycle, pentose phosphate pathway, uniformity of catabolism, and metabolic pathways as models are…

  2. One Carbon Metabolism, Fetal Growth and Long Term Consequences

    OpenAIRE

    2013-01-01

    One carbon metabolism, or methyl transfer, is critical for metabolism in all cells, is involved in the synthesis of purines, pyrimidines, in the methylation of numerous substrates, proteins, DNA and RNA, and in the expression of a number of genes. Serine is the primary endogenous methyl donor to the one carbon pool. Perturbations in methyl transfer due to nutrient and hormonal changes can have profound effect on cell function, growth and proliferation. It is postulated that at critical stages...

  3. Selective screening in neonates suspected to have inborn errors of metabolism

    Directory of Open Access Journals (Sweden)

    Rabah M. Shawky

    2015-04-01

    Conclusion: IEM represent a high percent (32.5% of neonates who had sepsis like symptoms, and when diagnosed, patients showed marked improvement after therapy. IEM should be considered in differential diagnosis of the sick neonates, and investigations, and management should be started rapidly to decrease morbidity, and mortality till nationwide screen for IEM is applied in Egypt.

  4. Importance of national and international registries of inborn errors of metabolism

    Directory of Open Access Journals (Sweden)

    Roberto Giugliani

    2014-07-01

    Full Text Available In the subject of rare diseases, experience and knowledge is limited. With a rare disease registry, longitudinal data can be added to increase information of them and to improve the quality of medical care and the patient outcome. Registries, unlike randomized controlled trials, provide a source of real-time information to develop guidelines for monitoring and to support patient management. Registries are essential to show the real situation of rare diseases and to establish management goals in order to address the unmet needs of the patients.

  5. Alpha-ketoadipic aciduria, a new inborn error of lysine metabolism; biochemical studies

    NARCIS (Netherlands)

    Przyrembel, Hildegard; Bachmann, Dorothea; Lombeck, Ingrid; Becker, K.; Wendel, U.; Wadman, S.K.; Bremer, H.J.

    1975-01-01

    Investigation of a psychomotorically retarded girl showed excretion of abnormal amounts of alpha-ketoadipic acid, alpha-hydroxyadipic acid, alpha-aminoadipic acid, 1,2-butenedicarboxylic acid and elevation of plasma alpha-aminoadipic acid levels. The identity of these metabolites was established by

  6. Inborn errors in metabolism and 4-boronophenylalanine-fructose-based boron neutron capture therapy.

    Science.gov (United States)

    Laakso, Juha; Ruokonen, Inkeri; Lapatto, Risto; Kallio, Merja

    2003-11-01

    Infusions of boronophenylalanine-fructose complex (BPA-F), at doses up to 900 mg/kg of BPA and 860 mg/kg of fructose, have been used to deliver boron to cancer tissue for boron neutron capture therapy (BNCT). In patients with phenylketonuria (PKU), phenylalanine accumulates, which is harmful in the long run. PKU has been an exclusion criterion for BPA-F-mediated BNCT. Fructose is harmful to individuals with hereditary fructose intolerance (HFI) in amounts currently used in BNCT. The harmful effects are mediated through induction of hypoglycemia and acidosis, which may lead to irreversible organ damage or even death. Consequently, HFI should be added as an exclusion criterion for BNCT if fructose-containing solutions are used in boron carriers. Non-HFI subjects may also develop symptoms, such as gastrointestinal pain, if the fructose infusion rate is high. We therefore recommend monitoring of glucose levels and correcting possible hypoglycemia promptly. Except for some populations with extremely low PKU prevalence, HFI and PKU prevalences are similar, approximately 1 or 2 per 20,000.

  7. Mutations in ACY1, the gene encoding aminoacylase 1, cause a novel inborn error of metabolism.

    NARCIS (Netherlands)

    Sass, J.O.; Mohr, V.; Olbrich, H.; Engelke, U.F.H.; Horvath, J.; Fliegauf, M.; Loges, N.T.; Schweitzer-Krantz, S.; Moebus, R.; Weiler, P.; Kispert, A.; Superti-Furga, A.; Wevers, R.A.; Omran, H.

    2006-01-01

    N-terminal acetylation of proteins is a widespread and highly conserved process. Aminoacylase 1 (ACY1; EC 3.5.14) is the most abundant of the aminoacylases, a class of enzymes involved in hydrolysis of N-acetylated proteins. Here, we present four children with genetic deficiency of ACY1. They were

  8. Mutations in ACY1, the gene encoding aminoacylase 1, cause a novel inborn error of metabolism.

    NARCIS (Netherlands)

    Sass, J.O.; Mohr, V.; Olbrich, H.; Engelke, U.F.H.; Horvath, J.; Fliegauf, M.; Loges, N.T.; Schweitzer-Krantz, S.; Moebus, R.; Weiler, P.; Kispert, A.; Superti-Furga, A.; Wevers, R.A.; Omran, H.

    2006-01-01

    N-terminal acetylation of proteins is a widespread and highly conserved process. Aminoacylase 1 (ACY1; EC 3.5.14) is the most abundant of the aminoacylases, a class of enzymes involved in hydrolysis of N-acetylated proteins. Here, we present four children with genetic deficiency of ACY1. They were i

  9. Congenital metabolic diseases: Diagnosis and treatment

    Energy Technology Data Exchange (ETDEWEB)

    Wapnir, R.A.

    1985-01-01

    This book contains eight parts, each consisting of several papers. The part titles are: The Heritage of Sir Archibald Garrod; New Approaches to the Diagnosis and Treatment of Genetic Disease; Achievements, New Trends, and Policies in the Detection of Inborn Errors of Metabolism; Disorders of Amino Acid Metabolism; Diseases of Energy Metabolism; Problems of Abnormal Storage Diseases; Inherited Diseases of Membrane Transport and Receptors; and Inborn Errors of Purine Metabolism and Urea Synthesis.

  10. Fat and Sugar Metabolism During Exercise in Patients With Metabolic Myopathy

    Science.gov (United States)

    2017-08-31

    Metabolism, Inborn Errors; Lipid Metabolism, Inborn Errors; Carbohydrate Metabolism, Inborn Errors; Long-Chain 3-Hydroxyacyl-CoA Dehydrogenase Deficiency; Glycogenin-1 Deficiency (Glycogen Storage Disease Type XV); Carnitine Palmitoyl Transferase 2 Deficiency; VLCAD Deficiency; Medium-chain Acyl-CoA Dehydrogenase Deficiency; Multiple Acyl-CoA Dehydrogenase Deficiency; Carnitine Transporter Deficiency; Neutral Lipid Storage Disease; Glycogen Storage Disease Type II; Glycogen Storage Disease Type III; Glycogen Storage Disease Type IV; Glycogen Storage Disease Type V; Muscle Phosphofructokinase Deficiency; Phosphoglucomutase 1 Deficiency; Phosphoglycerate Mutase Deficiency; Phosphoglycerate Kinase Deficiency; Phosphorylase Kinase Deficiency; Beta Enolase Deficiency; Lactate Dehydrogenase Deficiency; Glycogen Synthase Deficiency

  11. Exploration and comparison of inborn capacity of aerobic and anaerobic metabolisms of Saccharomyces cerevisiae for microbial electrical current production

    Science.gov (United States)

    Mao, Longfei; Verwoerd, Wynand S

    2013-01-01

    Saccharomyces cerevisiae possesses numerous advantageous biological features, such as being robust, easily handled, mostly non-pathogenic and having high catabolic rates, etc., which can be considered as merits for being used as a promising biocatalyst in microbial fuel cells (MFCs) for electricity generation. Previous studies have developed efficient MFC configurations to convert metabolic electron shuttles, such as cytoplasmic NADH, into usable electric current. However, no studies have elucidated the maximum potential of S. cerevisiae for current output and the underlying metabolic pathways, resulting from the interaction of thousands of reactions inside the cell during MFC operation. To address these two key issues, this study used in silico metabolic engineering techniques, flux balance analysis (FBA), and flux variability analysis with target flux minimization (FATMIN), to model the metabolic perturbation of S. cerevisiae under the MFC-energy extraction. The FBA results showed that, in the cytoplasmic NADH-dependent mediated electron transfer (MET) mode, S. cerevisiae had a potential to produce currents at up to 5.781 A/gDW for the anaerobic and 6.193 A/gDW for the aerobic environments. The FATMIN results showed that the aerobic and anaerobic metabolisms are resilient, relying on six and five contributing reactions respectively for high current production. Two reactions, catalyzed by glutamate dehydrogenase (NAD) (EC 1.4.1.3) and methylene tetrahydrofolate dehydrogenase (NAD) (EC 1.5.1.5), were shared in both current-production modes and contributed to over 80% of the identified maximum current outputs. It is also shown that the NADH regeneration was much less energy costly than biomass production rate. Taken together, our finding suggests that S. cerevisiae should receive more research effort for MFC electricity production. PMID:23969939

  12. Inborn anemias in mice

    Energy Technology Data Exchange (ETDEWEB)

    Bernstein, S.E.; Barker, J.E.; Russell, E.S.

    1981-06-01

    hereditary anemias of mice have been the chief objects of investigation. At present under study are four macrocytic anemias, five hemolytic anemias, nonhemolytic microcytic anemia, transitory siderocytic anemia, sex-linked iron-transport anemia, an ..cap alpha..-thalassemia, and a new target-cell anemia. Each of these blood dyscrasias is caused by the action of a unique mutant gene, which determines the structure of different intracellular molecules, and thus controls a different metabolic process. Thus our wide range of different hereditary anemias has considerable potential for uncovering many different aspects of hemopoietic homeostatic mechanisms in the mouse. Each anemia is studied through: (a) characterization of peripheral blood values, (b) determinations of radiosensitivity under a variety of conditions, (c) measurements of iron metabolism and heme synthesis, (d) histological and biochemical study of blood-forming tissue, (e) functional tests of the stem cell component, (f) examination of responses to erythroid stimuli, and (g) transplantation of tissue between individuals of differently affected genotypes.

  13. Cystinuria: an inborn cause of urolithiasis

    Directory of Open Access Journals (Sweden)

    Eggermann Thomas

    2012-04-01

    Full Text Available Abstract Cystinuria (OMIM 220100 is an inborn congenital disorder characterised by a defective cystine metabolism resulting in the formation of cystine stones. Among the heterogeneous group of kidney stone diseases, cystinuria is the only disorder which is exclusively caused by gene mutations. So far, two genes responsible for cystinuria have been identified: SLC3A1 (chromosome 2p21 encodes the heavy subunit rBAT of a renal b0,+ transporter while SLC7A9 (chromosome 19q12 encodes its interacting light subunit b0,+AT. Mutations in SLC3A1 are generally associated with an autosomal-recessive mode of inheritance whereas SLC7A9 variants result in a broad clinical variability even within the same family. The detection rate for mutations in these genes is larger than 85%, but it is influenced by the ethnic origin of a patient and the pathophysiological significance of the mutations. In addition to isolated cystinuria, patients suffering from the hypotonia-cystinuria syndrome have been reported carrying deletions including at least the SLC3A1 and the PREPL genes in 2p21. By extensive molecular screening studies in large cohort of patients a broad spectrum of mutations could be identified, several of these variants were functionally analysed and thereby allowed insights in the pathology of the disease as well as in the renal trafficking of cystine and the dibasic amino acids. In our review we will summarize the current knowledge on the physiological and the genetic basis of cystinuria as an inborn cause of kidney stones, and the application of this knowledge in genetic testing strategies.

  14. Fifteen years experience: Egyptian metabolic lab

    Directory of Open Access Journals (Sweden)

    Ekram M. Fateen

    2014-10-01

    Conclusion: This study illustrates the experience of the reference metabolic lab in Egypt over 15 years. The lab began metabolic disorder screening by using simple diagnostic techniques like thin layer chromatography and colored tests in urine which by time updated and upgraded the methods to diagnose a wide range of disorders. This study shows the most common diagnosed inherited inborn errors of metabolism among the Egyptian population.

  15. Metabolic investigations prevent liver transplantation in two young children with citrullinemia type I

    NARCIS (Netherlands)

    de Groot, Martijn J.; Cuppen, Marcel; Eling, Marc; Verheijen, Frans W.; Rings, Edmond H. H. M.; Reijngoud, Dirk-Jan; de Vries, Maaike M. C.; van Spronsen, Francjan J.

    2010-01-01

    Acute liver failure may be caused by a variety of disorders including inborn errors of metabolism. In those cases, rapid metabolic investigations and adequate treatment may avoid the need for liver transplantation. We report two patients who presented with acute liver failure and were referred to ou

  16. Metabolic investigations prevent liver transplantation in two young children with citrullinemia type I

    NARCIS (Netherlands)

    M.J. de Groot (Martijn); M. Cuppen (Marcel); M. Eling (Marc); F.W. Verheijen (Frans); E.H.H.M. Rings (Edmond); D.J. Reijngoud; M.M.C. de Vries (Maaike); F.J. van Spronsen (Francjan)

    2010-01-01

    textabstractAcute liver failure may be caused by a variety of disorders including inborn errors of metabolism. In those cases, rapid metabolic investigations and adequate treatment may avoid the need for liver transplantation. We report two patients who presented with acute liver failure and were re

  17. Adherence Issues in Inherited Metabolic Disorders Treated by Low Natural Protein Diets

    NARCIS (Netherlands)

    MacDonald, A.; van Rijn, M.; Feillet, F.; Lund, A. M.; Bernstein, L.; Bosch, A. M.; Gizewska, M.; van Spronsen, F. J.

    2012-01-01

    Common inborn errors of metabolism treated by low natural protein diets [amino acid (AA) disorders, organic acidemias and urea cycle disorders] are responsible for a collection of diverse clinical symptoms, each condition presenting at different ages with variable severity. Precursor-free or essenti

  18. The metabolism of vitamin B6 in relation to genetic disease

    NARCIS (Netherlands)

    Albersen, M.

    2013-01-01

    Over the past years, interest in vitamin B6 has increased, since its essential role in the brain has been recognized and specific inborn errors of metabolism resulting in functional vitamin B6 deficiency have been identified. Patients suffering from vitamin B6 deficiency present with epilepsy and, f

  19. Relevance of the Human Genome Project to inherited metabolic disease.

    Science.gov (United States)

    Burn, J

    1994-01-01

    The Human Genome Project is an international effort to identify the complete structure of the human genome. HUGO, the Human Genome Organization, facilitates international cooperation and exchange of information while the Genome Data Base will act as the on-line information retrieval and storage system for the huge amount of information being accumulated. The clinical register MIM (Mendelian Inheritance in Man) established by Victor McKusick is now an on-line resource that will allow biochemists working with inborn errors of metabolism to access the rapidly expanding body of knowledge. Biochemical and molecular genetics are complementary and should draw together to find solutions to the academic and clinical problems posed by inborn errors of metabolism.

  20. Selective screening in neonates suspected to have inborn errors of ...

    African Journals Online (AJOL)

    Rabah M. Shawky

    2015-02-16

    Feb 16, 2015 ... specificity over existing methods, and its suitability for cost- effective multidisease ... clinical examination, laboratory investigations including com- plete blood count ... Analysis of data was performed using standard computer pro- .... suspected obstructed labor, the 2nd was a female who had hypo activity ...

  1. Rare inborn errors associated with chronic hepatitis B virus infection

    DEFF Research Database (Denmark)

    Zhao, Qiang; Peng, Liang; Huang, Weijun

    2012-01-01

    Chronic hepatitis B (CHB) is a major global health issue. The role of rare genetic variants in CHB has not been elucidated. We aimed to identify rare allelic variants predisposing to CHB. We performed exome sequencing in 50 CHB patients who had no identifiable risk factors for CHB and 40 controls...... who were healthy and hepatitis B surface antibody-positive, but had never received hepatitis B vaccination. We selected six rare variant alleles and followed up their association with disease status by Sanger sequencing in a case-control study comprising 1,728 CHB patients and 1,636 healthy controls....... The latter had either not been immunized with hepatitis B vaccine or had uncertain vaccination status. Our results showed that transmembrane protein 2 p.Ser1254Asn, interferon alpha 2 p.Ala120Thr, its regulator NLR family member X1 p.Arg707Cys, and complement component 2 p.Glu318Asp were associated with CHB...

  2. Oligo-carrageenan kappa increases NADPH, ascorbate and glutathione syntheses and TRR/TRX activities enhancing photosynthesis, basal metabolism, and growth in Eucalyptus trees

    Directory of Open Access Journals (Sweden)

    Alberto eGonzález

    2014-10-01

    Full Text Available In order to analyze the effect of OC kappa in redox status, photosynthesis, basal metabolism and growth in Eucalyptus globulus, trees were treated with water (control, with OC kappa at 1 mg mL-1, or treated with inhibitors of NAD(PH, ascorbate (ASC and glutathione (GSH syntheses and thioredoxin reductase (TRR activity, CHS-828, lycorine, buthionine sulfoximine (BSO and auranofin, respectively, and with OC kappa, and cultivated for 4 months. Treatment with OC kappa induced an increase in NADPH, ASC, and GSH syntheses, TRR and thioredoxin (TRX activities, photosynthesis, growth and activities of basal metabolism enzymes such as rubisco, glutamine synthetase (GlnS, adenosine 5´-phosphosulfate reductase (APR, involved in C, N and S assimilation, respectively, Krebs cycle and purine/pyrimidine synthesis enzymes. Treatment with inhibitors and OC kappa showed that increases in ASC, GSH and TRR/TRX enhanced NADPH synthesis, increases in NADPH and TRR/TRX enhanced ASC and GSH syntheses, and only the increase in NADPH enhanced TRR/TRX activities. In addition, the increase in NADPH, ASC, GSH and TRR/TRX enhanced photosynthesis and growth. Moreover, the increase in NADPH, ASC and TRR/TRX enhanced activities of rubisco, Krebs cycle and purine/pyrimidine synthesis enzymes, the increase in GSH, NADPH, and TRR/TRX enhanced APR activity, and the increase in NADPH and TRR/TRX enhanced GlnS activity. Thus, OC kappa increases NADPH, ASC and GSH syntheses leading to a more reducing redox status, the increase in NADPH, ASC, GSH syntheses and TRR/TRX activities are cross-talking events leading to activation of photosynthesis, basal metabolism and growth in Eucalyptus trees.

  3. Errors associated with metabolic control analysis. Application Of Monte-Carlo simulation of experimental data.

    Science.gov (United States)

    Ainscow, E K; Brand, M D

    1998-09-21

    The errors associated with experimental application of metabolic control analysis are difficult to assess. In this paper, we give examples where Monte-Carlo simulations of published experimental data are used in error analysis. Data was simulated according to the mean and error obtained from experimental measurements and the simulated data was used to calculate control coefficients. Repeating the simulation 500 times allowed an estimate to be made of the error implicit in the calculated control coefficients. In the first example, state 4 respiration of isolated mitochondria, Monte-Carlo simulations based on the system elasticities were performed. The simulations gave error estimates similar to the values reported within the original paper and those derived from a sensitivity analysis of the elasticities. This demonstrated the validity of the method. In the second example, state 3 respiration of isolated mitochondria, Monte-Carlo simulations were based on measurements of intermediates and fluxes. A key feature of this simulation was that the distribution of the simulated control coefficients did not follow a normal distribution, despite simulation of the original data being based on normal distributions. Consequently, the error calculated using simulation was greater and more realistic than the error calculated directly by averaging the original results. The Monte-Carlo simulations are also demonstrated to be useful in experimental design. The individual data points that should be repeated in order to reduce the error in the control coefficients can be highlighted.

  4. An impaired respiratory electron chain triggers down-regulation of the energy metabolism and de-ubiquitination of solute carrier amino acid transporters

    OpenAIRE

    Aretz, I.; Hardt, C.; Wittig, I.; Meierhofer, D.

    2016-01-01

    Hundreds of genes have been associated with respiratory chain disease (RCD), the most common inborn error of metabolism so far. Elimination of the respiratory electron chain by depleting the entire mitochondrial DNA (mtDNA, rho0 cells) has therefore one of the most severe impacts on the energy metabolism in eukaryotic cells. In this study, proteomic data sets including the post transcriptional modifications (PTMs) phosphorylation and ubiquitination were integrated with metabolomic data sets a...

  5. Kaposi Sarcoma of Childhood: Inborn or Acquired Immunodeficiency to Oncogenic HHV-8.

    Science.gov (United States)

    Jackson, Carolyn C; Dickson, Mark A; Sadjadi, Mahan; Gessain, Antoine; Abel, Laurent; Jouanguy, Emmanuelle; Casanova, Jean-Laurent

    2016-03-01

    Kaposi sarcoma (KS) is an endothelial malignancy caused by human herpes virus-8 (HHV-8) infection. The epidemic and iatrogenic forms of childhood KS result from a profound and acquired T cell deficiency. Recent studies have shown that classic KS of childhood can result from rare single-gene inborn errors of immunity, with mutations in WAS, IFNGR1, STIM1, and TNFRSF4. The pathogenesis of the endemic form of childhood KS has remained elusive. We review childhood KS pathogenesis and its relationship to inherited and acquired immunodeficiency to oncogenic HHV-8.

  6. Metabolic and mitochondrial disorders associated with epilepsy in children with autism spectrum disorder.

    Science.gov (United States)

    Frye, Richard E

    2015-06-01

    Autism spectrum disorder (ASD) affects a significant number of individuals in the United States, with the prevalence continuing to grow. A significant proportion of individuals with ASD have comorbid medical conditions such as epilepsy. In fact, treatment-resistant epilepsy appears to have a higher prevalence in children with ASD than in children without ASD, suggesting that current antiepileptic treatments may be suboptimal in controlling seizures in many individuals with ASD. Many individuals with ASD also appear to have underlying metabolic conditions. Metabolic conditions such as mitochondrial disease and dysfunction and abnormalities in cerebral folate metabolism may affect a substantial number of children with ASD, while other metabolic conditions that have been associated with ASD such as disorders of creatine, cholesterol, pyridoxine, biotin, carnitine, γ-aminobutyric acid, purine, pyrimidine, and amino acid metabolism and urea cycle disorders have also been associated with ASD without the prevalence clearly known. Interestingly, all of these metabolic conditions have been associated with epilepsy in children with ASD. The identification and treatment of these disorders could improve the underlying metabolic derangements and potentially improve behavior and seizure frequency and/or severity in these individuals. This paper provides an overview of these metabolic disorders in the context of ASD and discusses their characteristics, diagnostic testing, and treatment with concentration on mitochondrial disorders. To this end, this paper aims to help optimize the diagnosis and treatment of children with ASD and epilepsy. This article is part of a Special Issue entitled "Autism and Epilepsy".

  7. Electrospray ionisation mass spectrometry: principles and clinical applications.

    Science.gov (United States)

    Ho, C S; Lam, C W K; Chan, M H M; Cheung, R C K; Law, L K; Lit, L C W; Ng, K F; Suen, M W M; Tai, H L

    2003-01-01

    This mini-review provides a general understanding of electrospray ionisation mass spectrometry (ESI-MS) which has become an increasingly important technique in the clinical laboratory for structural study or quantitative measurement of metabolites in a complex biological sample. The first part of the review explains the electrospray ionisation process, design of mass spectrometers with separation capability, characteristics of the mass spectrum, and practical considerations in quantitative analysis. The second part then focuses on some clinical applications. The capability of ESI-tandem-MS in measuring bio-molecules sharing similar molecular structures makes it particularly useful in screening for inborn errors of amino acid, fatty acid, purine, pyrimidine metabolism and diagnosis of galactosaemia and peroxisomal disorders. Electrospray ionisation is also efficient in generating cluster ions for structural elucidation of macromolecules. This has fostered a new and improved approach (vs electrophoresis) for identification and quantification of haemoglobin variants. With the understanding of glycohaemoglobin structure, an IFCC reference method for glycohaemoglobin assay has been established using ESI-MS. It represents a significant advancement for the standardisation of HbA1c in diabetic monitoring. With its other applications such as in therapeutic drug monitoring, ESI-MS will continue to exert an important influence in the future development and organisation of the clinical laboratory service.

  8. The Application of the GM (1,1) Metabolism Model to Error Data Processing of NC Machine Tools

    Institute of Scientific and Technical Information of China (English)

    LIAO De-gang; XIONG Xiao-hong

    2003-01-01

    This paper applied the gray system theory to error data processing of NC machine tools ac cording to the characteristic. It presented the gray metabolism model of error data processing. The test method for the model needs less capacity. Practice proved that the method is simple, calculation is easy, and results are exact.

  9. Novel quantitative metabolomic approach for the study of stress responses of plant root metabolism.

    Science.gov (United States)

    Li, Kefeng; Wang, Xu; Pidatala, Venkataramana R; Chang, Chi-Peng; Cao, Xiaohong

    2014-12-01

    Quantitative metabolomics (qMetabolomics) is a powerful tool for understanding the intricate metabolic processes involved in plant abiotic stress responses. qMetabolomics is hindered by the limited coverage and high cost of isotopically labeled standards. In this study, we first selected 271 metabolites which might play important roles in abiotic stress responses as the targets and established a comprehensive LC-MS/MS based qMetabolomic method. We then developed a novel metabolic labeling method using E. coli-Saccharomyces cerevisiae two-step cultivation for the production of uniformly (13)C-labeled metabolites as internal standards. Finally, we applied the developed qMetabolomic method to investigate the influence of Pb stress on maize root metabolism. The absolute concentration of 226 metabolites in maize roots was accurately quantified in a single run within 30 min. Our study also revealed that glycolysis, purine, pyrimidine, and phospholipids were the main metabolic pathways in maize roots involved in Pb stress response. To our knowledge, this is the most comprehensive qMetabolomic method for plant metabolomics thus far. We developed a simple and inexpensive metabolic labeling method which dramatically expanded the availability of uniformly (13)C labeled metabolites. Our findings also provided new insights of maize metabolic responses to Pb stress.

  10. Prospective audit of perinatal mortality among inborn babies in a ...

    African Journals Online (AJOL)

    2010-05-05

    May 5, 2010 ... inborn babies in a tertiary health center in Lagos,. Nigeria. EN Ekure .... The inclusion criteria for this study were birth weight of at least 500 g and/or a .... Table 4: Wigglesworth classification of perinatal deaths. Birth weight (g).

  11. Identification of errors introduced during high throughput sequencing of the T cell receptor repertoire

    Directory of Open Access Journals (Sweden)

    Cheng Cheng

    2011-02-01

    Full Text Available Abstract Background Recent advances in massively parallel sequencing have increased the depth at which T cell receptor (TCR repertoires can be probed by >3log10, allowing for saturation sequencing of immune repertoires. The resolution of this sequencing is dependent on its accuracy, and direct assessments of the errors formed during high throughput repertoire analyses are limited. Results We analyzed 3 monoclonal TCR from TCR transgenic, Rag-/- mice using Illumina® sequencing. A total of 27 sequencing reactions were performed for each TCR using a trifurcating design in which samples were divided into 3 at significant processing junctures. More than 20 million complementarity determining region (CDR 3 sequences were analyzed. Filtering for lower quality sequences diminished but did not eliminate sequence errors, which occurred within 1-6% of sequences. Erroneous sequences were pre-dominantly of correct length and contained single nucleotide substitutions. Rates of specific substitutions varied dramatically in a position-dependent manner. Four substitutions, all purine-pyrimidine transversions, predominated. Solid phase amplification and sequencing rather than liquid sample amplification and preparation appeared to be the primary sources of error. Analysis of polyclonal repertoires demonstrated the impact of error accumulation on data parameters. Conclusions Caution is needed in interpreting repertoire data due to potential contamination with mis-sequence reads. However, a high association of errors with phred score, high relatedness of erroneous sequences with the parental sequence, dominance of specific nt substitutions, and skewed ratio of forward to reverse reads among erroneous sequences indicate approaches to filter erroneous sequences from repertoire data sets.

  12. Metabolic Causes of Epileptic Encephalopathy

    Directory of Open Access Journals (Sweden)

    Joe Yuezhou Yu

    2013-01-01

    Full Text Available Epileptic encephalopathy can be induced by inborn metabolic defects that may be rare individually but in aggregate represent a substantial clinical portion of child neurology. These may present with various epilepsy phenotypes including refractory neonatal seizures, early myoclonic encephalopathy, early infantile epileptic encephalopathy, infantile spasms, and generalized epilepsies which in particular include myoclonic seizures. There are varying degrees of treatability, but the outcome if untreated can often be catastrophic. The importance of early recognition cannot be overemphasized. This paper provides an overview of inborn metabolic errors associated with persistent brain disturbances due to highly active clinical or electrographic ictal activity. Selected diseases are organized by the defective molecule or mechanism and categorized as small molecule disorders (involving amino and organic acids, fatty acids, neurotransmitters, urea cycle, vitamers and cofactors, and mitochondria and large molecule disorders (including lysosomal storage disorders, peroxisomal disorders, glycosylation disorders, and leukodystrophies. Details including key clinical features, salient electrophysiological and neuroradiological findings, biochemical findings, and treatment options are summarized for prominent disorders in each category.

  13. [Copper metabolism and genetic disorders].

    Science.gov (United States)

    Shimizu, Norikazu

    2016-07-01

    Copper is one of essential trace elements. Copper deficiency lead to growth and developmental failure and/or neurological dysfunction. However, excess copper is also problems for human life. There are two disorders of inborn error of copper metabolism, Menkes disease and Wilson disease. Menkes disease is an X linked recessive disorder with copper deficiency and Wilson disease is an autosomal recessive disorder with copper accumulation. These both disorders result from the defective functioning of copper transport P-type ATPase, ATP7A of Menkes disease and ATP7B of Wilson disease. In this paper, the author describes about copper metabolism of human, and clinical feature, diagnosis and treatment of Menkes disease and Wilson disease.

  14. Metabolic encephalopathy in Egyptian children.

    Science.gov (United States)

    Hindawy, A; Gouda, A; El-Ayyadi, A; Megahed, H; Bazaraa, H

    2007-01-01

    Fatty Acid Oxidation disorders represent an expanding group of inborn errors of metabolism. Clinical manifestations include episodic encephalopathy, hypoketotic hypoglycemia, Reye like episodes, hepatic, muscular, cardiac affection and sudden death. Analysis of urinary organic acids and plasma fatty acids of 44 clinically suspected patients by Gas Chromatography Mass spectrometry revealed 4 cases of Medium chain acyl-CoA dehydrogenase deficiency (MCADD), 3 cases of Very long chain acyl-CoA dehydrogenase deficiency, 9 cases of multiple defects of acyl-CoA dehydrogenation in addition to 3 patients with other metabolic disorders. Timely detection of these disorders including screening for MCADD can have a favorable impact on the outcome of these patients (Tab. 11, Fig. 3, Ref. 24) Full Text (Free, PDF).

  15. Medical aspects of ketone body metabolism.

    Science.gov (United States)

    Mitchell, G A; Kassovska-Bratinova, S; Boukaftane, Y; Robert, M F; Wang, S P; Ashmarina, L; Lambert, M; Lapierre, P; Potier, E

    1995-06-01

    Ketone bodies are produced in the liver, mainly from the oxidation of fatty acids, and are exported to peripheral tissues for use as an energy source. They are particularly important for the brain, which has no other substantial non-glucose-derived energy source. The 2 main ketone bodies are 3-hydroxybutyrate (3HB) and acetoacetate (AcAc). Biochemically, abnormalities of ketone body metabolism can present in 3 fashions: ketosis, hypoketotic hypoglycemia, and abnormalities of the 3HB/AcAc ratio. Normally, the presence of ketosis implies 2 things: that lipid energy metabolism has been activated and that the entire pathway of lipid degradation is intact. In rare patients, ketosis reflects an inability to utilize ketone bodies. Ketosis is normal during fasting, after prolonged exercise, and when a high-fat diet is consumed. During the neonatal period, infancy and pregnancy, times at which lipid energy metabolism is particularly active, ketosis develops readily. Pathologic causes of ketosis include diabetes, ketotic hypoglycemia of childhood, corticosteroid or growth hormone deficiency, intoxication with alcohol or salicylates, and several inborn errors of metabolism. The absence of ketosis in a patient with hypoglycemia is abnormal and suggests the diagnosis of either hyperinsulinism or an inborn error of fat energy metabolism. An abnormal elevation of the 3HB/AcAc ratio usually implies a non-oxidized state of the hepatocyte mitochondrial matrix resulting from hypoxia-ischemia or other causes. We summarize the differential diagnosis of abnormalities of ketone body metabolism, as well as pertinent recent advances in research.

  16. Genetic analysis in inherited metabolic disorders--from diagnosis to treatment. Own experience, current state of knowledge and perspectives.

    Science.gov (United States)

    Wertheim-Tysarowska, Katarzyna; Gos, Monika; Sykut-Cegielska, Jolanta; Bal, Jerzy

    2015-01-01

    Inherited metabolic disorders, also referred to as inborn errors of metabolism (IEM), are a group of congenital disorders caused by mutation in genomic or mitochondrial DNA. IEM are mostly rare disorders with incidence ranging from 1/50,000-1/150,000), however in total IEM may affect even 1/1000 people. A particular mutation affects specific protein or enzyme that improper function leads to alterations in specific metabolic pathway. Inborn errors of metabolism are monogenic disorders that can be inherited in autosomal recessive manner or, less frequently, in autosomal dominant or X-linked patterns. Some exceptions to Mendelian rules of inheritance have also been described. Vast majority of mutations responsible for IEM are small DNA changes affecting single or several nucleotides, although larger rearrangements were also identified. Therefore, the methods used for the identification of pathogenic mutations are mainly based on molecular techniques, preferably on Sanger sequencing. Moreover, the next generation sequencing technique seems to be another prospective method that can be successfully implemented for the diagnosis of inborn errors of metabolism. The identification of the genetic defect underlying the disease is not only indispensable for genetic counseling, but also might be necessary to apply appropriate treatment to the patient. Therapeutic strategies for IEM are continuously elaborated and tested (eg. enzyme replacement therapy, specific cells or organ transplantation or gene therapy, both in vivo and ex vivo) and have already been implemented for several disorders. In this article we present current knowledge about various aspects of IEM on the basis of our own experience and literature review.

  17. Metabolomics and systems pharmacology: why and how to model the human metabolic network for drug discovery☆

    Science.gov (United States)

    Kell, Douglas B.; Goodacre, Royston

    2014-01-01

    Metabolism represents the ‘sharp end’ of systems biology, because changes in metabolite concentrations are necessarily amplified relative to changes in the transcriptome, proteome and enzyme activities, which can be modulated by drugs. To understand such behaviour, we therefore need (and increasingly have) reliable consensus (community) models of the human metabolic network that include the important transporters. Small molecule ‘drug’ transporters are in fact metabolite transporters, because drugs bear structural similarities to metabolites known from the network reconstructions and from measurements of the metabolome. Recon2 represents the present state-of-the-art human metabolic network reconstruction; it can predict inter alia: (i) the effects of inborn errors of metabolism; (ii) which metabolites are exometabolites, and (iii) how metabolism varies between tissues and cellular compartments. However, even these qualitative network models are not yet complete. As our understanding improves so do we recognise more clearly the need for a systems (poly)pharmacology. PMID:23892182

  18. The application of tandem mass spectrometry to neonatal screening for inherited disorders of intermediary metabolism.

    Science.gov (United States)

    Chace, Donald H; Kalas, Theodore A; Naylor, Edwin W

    2002-01-01

    This review is intended to serve as a practical guide for geneticists to current applications of tandem mass spectrometry to newborn screening. By making dried-blood spot analysis more sensitive, specific, reliable, and inclusive, tandem mass spectrometry has improved the newborn detection of inborn errors of metabolism. Its innate ability to detect and quantify multiple analytes from one prepared blood specimen in a single analysis permits broad recognition of amino acid, fatty acid, and organic acid disorders. An increasing number of newborn screening programs are either utilizing or conducting pilot studies with tandem mass spectrometry. It is therefore imperative that the genetics community be familiar with tandem mass spectrometric newborn screening.

  19. Free radical scavenging activity and comparative metabolic profiling of in vitro cultured and field grown Withania somnifera roots.

    Directory of Open Access Journals (Sweden)

    Kalaiselvi Senthil

    Full Text Available Free radical scavenging activity (FRSA, total phenolic content (TPC, and total flavonoid content (TFC of in vitro cultured and field grown Withania somnifera (Ashwagandha roots were investigated. Withanolides analysis and comprehensive metabolic profiling between 100% methanol extracts of in vitro and field grown root tissues was performed using high performance thin layer chromatography (HPTLC and gas chromatography-mass spectrometry (GC-MS, respectively. Significantly higher levels of FRSA, TPC, and TFC were observed in in-vitro cultured roots compared with field grown samples. In addition, 30 day-cultured in vitro root samples (1 MIR exhibited a significantly higher FRSA (IC50 81.01 μg/mL, TPC (118.91 mg GAE/g, and TFC (32.68 mg CE/g compared with those in 45 day-cultured samples (1.5 MIR. Total of 29 metabolites were identified in in vitro cultured and field grown roots by GC-MS analysis. The metabolites included alcohols, organic acids, purine, pyrimidine, sugars, and putrescine. Vanillic acid was only observed in the in vitro cultured root samples, and higher level of the vanillic acid was observed in 1 MIR when compared to 1.5 MIR. Therefore, it is suggested that 1 MIR might serve as an alternative to field grown roots for the development of medicinal and functional food products.

  20. Free radical scavenging activity and comparative metabolic profiling of in vitro cultured and field grown Withania somnifera roots.

    Science.gov (United States)

    Senthil, Kalaiselvi; Thirugnanasambantham, Pankajavalli; Oh, Taek Joo; Kim, So Hyun; Choi, Hyung Kyoon

    2015-01-01

    Free radical scavenging activity (FRSA), total phenolic content (TPC), and total flavonoid content (TFC) of in vitro cultured and field grown Withania somnifera (Ashwagandha) roots were investigated. Withanolides analysis and comprehensive metabolic profiling between 100% methanol extracts of in vitro and field grown root tissues was performed using high performance thin layer chromatography (HPTLC) and gas chromatography-mass spectrometry (GC-MS), respectively. Significantly higher levels of FRSA, TPC, and TFC were observed in in-vitro cultured roots compared with field grown samples. In addition, 30 day-cultured in vitro root samples (1 MIR) exhibited a significantly higher FRSA (IC50 81.01 μg/mL), TPC (118.91 mg GAE/g), and TFC (32.68 mg CE/g) compared with those in 45 day-cultured samples (1.5 MIR). Total of 29 metabolites were identified in in vitro cultured and field grown roots by GC-MS analysis. The metabolites included alcohols, organic acids, purine, pyrimidine, sugars, and putrescine. Vanillic acid was only observed in the in vitro cultured root samples, and higher level of the vanillic acid was observed in 1 MIR when compared to 1.5 MIR. Therefore, it is suggested that 1 MIR might serve as an alternative to field grown roots for the development of medicinal and functional food products.

  1. Metabolic dysregulation in monogenic disorders and cancer - finding method in madness.

    Science.gov (United States)

    Erez, Ayelet; DeBerardinis, Ralph J

    2015-07-01

    Cancer is a prime example of a disease process in which carcinogenic and metabolic changes are intertwined to promote cell survival and growth. One approach to unravel this complex relationship is by studying rare, monogenic disorders caused by mutations in genes encoding metabolic enzymes or regulators. There are hundreds of these diseases, most of which manifest in childhood and are collectively termed 'inborn errors of metabolism' (IEMs). Several IEMs demonstrate the consequences of chronic, systemic loss of a particular metabolic activity that can result in malignancy. In this Opinion article, we present a conceptual categorization of IEMs associated with cancer and discuss how assessment of these rare diseases might inform us about the biological foundations of common types of cancer and opportunities for cancer diagnosis and therapy.

  2. [PULMONARY COMPLICATIONS IN CHILDREN, OPERATED ON FOR INBORN HEART FAILURES IN THE ARTIFICIAL BLOOD CIRCULATION ENVIRONMENT].

    Science.gov (United States)

    Moshkivska, L V; Nastenko, E A; Golovenko, O S; Lazoryshynets, V V

    2015-11-01

    The risk factors of pulmonary complications occurrence were analyzed in children, operated on for inborn heart failures in atrificial blood circulation environment. Pulmonary complications rate and the risk factors of their occurrence were analyzed.

  3. Inborn anemias in mice: (Annual report, 1980-1981)

    Energy Technology Data Exchange (ETDEWEB)

    Bernstein, S.E.

    1981-07-02

    The basic purpose of this study is the delineation and exploitation of inborn anemias of the laboratory mouse, carried out by utilization of genetically homogeneous stocks segregating only for anemia-producing genes; by physiological and histological descriptions of each condition at all stages in the life history; by determination of tissue sites of primary gene action through tissue culture studies, tissue transplantation and parabiosis experiments; by analysis of reactions of normal and anemic mice to a variety of stressful stimuli, including x-irradiation, hypoxia, and toxic chemicals, and by biochemical comparisons between tissues, especially erythrocytes and hemopoietic cells of normal vs each type of anemic mouse. At present 16 single-locus anemias are known in the mouse, plus one with multifactorial inheritance (the autoimmune hemolytic anemia of NZB inbred mice). Of these, six are maintained only by the Jackson Laboratory, and two others have but one additional source. Effects of anemia-producing mutant alleles of these loci (an; f; ja; ha; Hba/sup th/; mk; nb; Sl and Sl/sup d/; sla; sph; and W, W/sup v/, W/sup J/ and 10 other putative W-alleles) are currently under investigation at the Jackson Laboratory. 15 refs.

  4. Human Metabolic Enzymes Deficiency: A Genetic Mutation Based Approach

    Science.gov (United States)

    Chaturvedi, Swati; Singh, Ashok K.; Maity, Siddhartha; Sarkar, Srimanta

    2016-01-01

    One of the extreme challenges in biology is to ameliorate the understanding of the mechanisms which emphasize metabolic enzyme deficiency (MED) and how these pretend to have influence on human health. However, it has been manifested that MED could be either inherited as inborn error of metabolism (IEM) or acquired, which carries a high risk of interrupted biochemical reactions. Enzyme deficiency results in accumulation of toxic compounds that may disrupt normal organ functions and cause failure in producing crucial biological compounds and other intermediates. The MED related disorders cover widespread clinical presentations and can involve almost any organ system. To sum up the causal factors of almost all the MED-associated disorders, we decided to embark on a less traveled but nonetheless relevant direction, by focusing our attention on associated gene family products, regulation of their expression, genetic mutation, and mutation types. In addition, the review also outlines the clinical presentations as well as diagnostic and therapeutic approaches. PMID:27051561

  5. Metabolic pathways of lung inflammation revealed by high-resolution metabolomics (HRM) of H1N1 influenza virus infection in mice.

    Science.gov (United States)

    Chandler, Joshua D; Hu, Xin; Ko, Eun-Ju; Park, Soojin; Lee, Young-Tae; Orr, Michael; Fernandes, Jolyn; Uppal, Karan; Kang, Sang-Moo; Jones, Dean P; Go, Young-Mi

    2016-11-01

    Influenza is a significant health concern worldwide. Viral infection induces local and systemic activation of the immune system causing attendant changes in metabolism. High-resolution metabolomics (HRM) uses advanced mass spectrometry and computational methods to measure thousands of metabolites inclusive of most metabolic pathways. We used HRM to identify metabolic pathways and clusters of association related to inflammatory cytokines in lungs of mice with H1N1 influenza virus infection. Infected mice showed progressive weight loss, decreased lung function, and severe lung inflammation with elevated cytokines [interleukin (IL)-1β, IL-6, IL-10, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ] and increased oxidative stress via cysteine oxidation. HRM showed prominent effects of influenza virus infection on tryptophan and other amino acids, and widespread effects on pathways including purines, pyrimidines, fatty acids, and glycerophospholipids. A metabolome-wide association study (MWAS) of the aforementioned inflammatory cytokines was used to determine the relationship of metabolic responses to inflammation during infection. This cytokine-MWAS (cMWAS) showed that metabolic associations consisted of distinct and shared clusters of 396 metabolites highly correlated with inflammatory cytokines. Strong negative associations of selected glycosphingolipid, linoleate, and tryptophan metabolites with IFN-γ contrasted strong positive associations of glycosphingolipid and bile acid metabolites with IL-1β, TNF-α, and IL-10. Anti-inflammatory cytokine IL-10 had strong positive associations with vitamin D, purine, and vitamin E metabolism. The detailed metabolic interactions with cytokines indicate that targeted metabolic interventions may be useful during life-threatening crises related to severe acute infection and inflammation. Copyright © 2016 the American Physiological Society.

  6. Chronic mucocutaneous candidiasis disease associated with inborn errors of IL-17 immunity

    Science.gov (United States)

    Okada, Satoshi; Puel, Anne; Casanova, Jean-Laurent; Kobayashi, Masao

    2016-01-01

    Chronic mucocutaneous candidiasis (CMC) is characterized by recurrent or persistent infections affecting the nails, skin and oral and genital mucosae caused by Candida spp., mainly Candida albicans. CMC is an infectious phenotype in patients with inherited or acquired T-cell deficiency. Patients with autosomal-dominant (AD) hyper IgE syndrome (HIES), AD signal transducer and activator of transcription 1 (STAT1) gain-of-function, autosomal-recessive (AR) deficiencies in interleukin (IL)-12 receptor β1 (IL-12Rβ1), IL-12p40, caspase recruitment domain-containing protein 9 (CARD9) or retinoic acid-related orphan receptor γT (RORγT) or AR autoimmune polyendocrinopathy–candidiasis–ectodermal dystrophy (APECED) develop CMC as a major infectious phenotype that is categorized as Syndromic CMC. In contrast, CMC disease (CMCD) is typically defined as CMC in patients in the absence of any other prominent clinical signs. This definition is not strict; thus, CMCD is currently used to refer to patients presenting with CMC as the main clinical phenotype. The etiology of CMCD is not related to genes that cause severe combined immunodeficiency or combined immunodeficiency, nor to genes responsible for Syndromic CMC. Four genetic etiologies, AR IL-17 receptor A, IL-17 receptor C and ACT1 deficiencies, and AD IL-17F deficiency, are reported to underlie CMCD. Each of these gene defects directly has an impact on IL-17 signaling, suggesting their nonredundant role in host mucosal immunity to Candida. Here, we review current knowledge focusing on IL-17 signaling and the genetic etiologies responsible for, and associated with, CMC. PMID:28090315

  7. Inborn errors in RNA polymerase III underlie severe varicella zoster virus infections

    DEFF Research Database (Denmark)

    Ogunjimi, Benson; Zhang, Shen-Ying; Sørensen, Katrine Biehl

    2017-01-01

    Varicella zoster virus (VZV) typically causes chickenpox upon primary infection. In rare cases, VZV can give rise to life-threatening disease in otherwise healthy people, but the immunological basis for this remains unexplained. We report 4 cases of acute severe VZV infection affecting the centra...

  8. Newborn screening of inherited metabolic disorders by tandem mass spectrometry: past, present and future

    Directory of Open Access Journals (Sweden)

    G. Scaturro

    2013-04-01

    Full Text Available Inborn errors of metabolism are inherited biochemical disorders caused by lack of a functional enzyme, transmembrane transporter, or similar protein, which then results in blockage of the corresponding metabolic pathway. Taken individually, inborn errors of metabolism are rare. However, as a group these diseases are relatively frequent and they may account for most of neonatal mortality and need of health resources. The detection of genetic metabolic disorders should occur in a pre-symptomatic phase. Recently, the introduction of the tandem mass spectrometric methods for metabolite analysis has changed our ability to detect intermediates of metabolism in smaller samples and provides the means to detect a large number of metabolic disorders in a single analytical run. Screening panels now include a large number of disorders that may not meet all the criteria that have been used as a reference for years. The rationale behind inclusion or exclusion of a respective disorder is difficult to understand in most cases and it may impose an ethical dilemma. The current organization is an important tool of secondary preventive medicine, essential for children’s healthcare, but the strong inhomogeneity of the regional models of screening applied today create in the Italian neonatal population macroscopic differences with regards to healthcare, which is in effect mainly diversified by the newborn’s place of birth, in possible violation of the universal criterion of the equality of all citizens. Carefully weighed arguments are urgently needed since patient organizations, opinion leaders and politicians are pressing to proceed with expansion of neonatal population screening.

  9. Metabolism

    Science.gov (United States)

    ... Surgery? Choosing the Right Sport for You Shyness Metabolism KidsHealth > For Teens > Metabolism Print A A A ... food through a process called metabolism. What Is Metabolism? Metabolism (pronounced: meh-TAB-uh-lih-zem) is ...

  10. UCB Transplant of Inherited Metabolic Diseases With Administration of Intrathecal UCB Derived Oligodendrocyte-Like Cells

    Science.gov (United States)

    2017-06-27

    Adrenoleukodystrophy; Batten Disease; Mucopolysaccharidosis II; Leukodystrophy, Globoid Cell; Leukodystrophy, Metachromatic; Neimann Pick Disease; Pelizaeus-Merzbacher Disease; Sandhoff Disease; Tay-Sachs Disease; Brain Diseases, Metabolic, Inborn; Alpha-Mannosidosis; Sanfilippo Mucopolysaccharidoses

  11. Metabolic changes associated with methionine stress sensitivity in MDA-MB-468 breast cancer cells.

    Science.gov (United States)

    Borrego, Stacey L; Fahrmann, Johannes; Datta, Rupsa; Stringari, Chiara; Grapov, Dmitry; Zeller, Michael; Chen, Yumay; Wang, Ping; Baldi, Pierre; Gratton, Enrico; Fiehn, Oliver; Kaiser, Peter

    2016-01-01

    The majority of cancer cells have a unique metabolic requirement for methionine that is not observed in normal, non-tumorigenic cells. This phenotype is described as "methionine dependence" or "methionine stress sensitivity" in which cancer cells are unable to proliferate when methionine has been replaced with its metabolic precursor, homocysteine, in cell culture growth media. We focus on the metabolic response to methionine stress in the triple negative breast cancer cell line MDA-MB-468 and its methionine insensitive derivative cell line MDA-MB-468res-R8. Using a variety of techniques including fluorescence lifetime imaging microscopy (FLIM) and extracellular flux assays, we identified a metabolic down-regulation of oxidative phosphorylation in both MDA-MB-468 and MDA-MB-468res-R8 cell types when cultured in homocysteine media. Untargeted metabolomics was performed by way of gas chromatography/time-of-flight mass spectrometry on both cell types cultured in homocysteine media over a period of 2 to 24 h. We determined unique metabolic responses between the two cell lines in specific pathways including methionine salvage, purine/pyrimidine synthesis, and the tricarboxylic acid cycle. Stable isotope tracer studies using deuterium-labeled homocysteine indicated a redirection of homocysteine metabolism toward the transsulfuration pathway and glutathione synthesis. This data corroborates with increased glutathione levels concomitant with increased levels of oxidized glutathione. Redirection of homocysteine flux resulted in reduced generation of methionine from homocysteine particularly in MDA-MB-468 cells. Consequently, synthesis of the important one-carbon donor S-adenosylmethionine (SAM) was decreased, perturbing the SAM to S-adenosylhomocysteine ratio in MDA-MB-468 cells, which is an indicator of the cellular methylation potential. This study indicates a differential metabolic response between the methionine sensitive MDA-MB-468 cells and the methionine insensitive

  12. Errores innatos del metabolismo: Enfermedades lisosomales

    Directory of Open Access Journals (Sweden)

    Caridad Menéndez Saínz

    2002-03-01

    Full Text Available Dentro de los errores innatos del metabolismo se encuentran las enfermedades de almacenamiento lisosomal o enzimopatías lisosomales, las cuáles se caracterizan por un déficit enzimático específico, la excreción de metabolitos por la orina y la acumulación de los compuestos no degradados en diferentes órganos y tejidos que ocasionan la disfución de éstos. Tienen un patrón de herencia autosómico recesivo, excepto para la enfermedad de Fabry y la enfermedad de Hunter en las que el patrón de herencia está ligado al cromosoma X. Estas enfermedades tienen una baja incidencia en general, aunque hay poblaciones donde algunas de ellas tienen una alta incidencia. Su importancia radica en la magnitud que representan como problema de salud, por la pobre calidad de vida de esos pacientes, así como su fallecimiento prematuro, motivo por el cual hay que evitar los nacimientos de nuevos niños afectados.Among the metabolism inborn errors, there are the lysosomal storage diseases or lysosomal enzymopathies that are characterized by an specific enzymatic deficiency, excretion of metabollites in urine and accumulation of non-degraded compounds in various organs and tissues causing their dysfunction. These diseases have a recessive autosomal heredity, except for Fabry´s disease and Hunter’s disease in which the pattern of heredity is chromosome X-linked. These diseases have a low incidence in general although there are populations where they show a high incidence. Their importance lies in what they represent as a health problem because of the poor quality of life of these patients and their early death, therefore, it is necessary to prevent the birth of new infants affected with these diseases.

  13. Adherence issues in inherited metabolic disorders treated by low natural protein diets

    DEFF Research Database (Denmark)

    MaCdonald, A; van Rijn, M; Feillet, F

    2012-01-01

    Common inborn errors of metabolism treated by low natural protein diets [amino acid (AA) disorders, organic acidemias and urea cycle disorders] are responsible for a collection of diverse clinical symptoms, each condition presenting at different ages with variable severity. Precursor......-free or essential L-AAs are important in all these conditions. Optimal long-term outcome depends on early diagnosis and good metabolic control, but because of the rarity and severity of conditions, randomized controlled trials are scarce. In all of these disorders, it is commonly described that dietary adherence...... on their neuropsychological profile. There are little data about their ability to self-manage their own diet or the success of any formal educational programs that may have been implemented. Trials conducted in non-phenylketonuria (PKU) patients are rare, and the development of specialist L-AAs for non-PKU AA disorders has...

  14. MR diffusion imaging and MR spectroscopy of maple syrup urine disease during acute metabolic decompensation

    Energy Technology Data Exchange (ETDEWEB)

    Jan, Wajanat; Wang, Zhiyue J. [Department of Radiology, University of Pennsylvania School of Medicine, Children' s Hospital of Philadelphia, Pennsylvania (United States); Zimmerman, Robert A. [Department of Radiology, University of Pennsylvania School of Medicine, Children' s Hospital of Philadelphia, Pennsylvania (United States); Department of Radiology, Children' s Hospital of Philadelphia, 34th Street and Civic Center Boulevard, PA 19104, Philadelphia (United States); Berry, Gerard T.; Kaplan, Paige B.; Kaye, Edward M. [Department of Pediatrics, University of Pennsylvania School of Medicine, The Children' s Hospital of Philadelphia, Philadelphia, Pennsylvania (United States)

    2003-06-01

    Maple syrup urine disease (MSUD) is an inborn error of amino acid metabolism, which affects the brain tissue resulting in impairment or death if untreated. Imaging studies have shown reversible brain edema during acute metabolic decompensation. The purpose of this paper is to describe the diffusion-weighted imaging (DWI) and spectroscopy findings during metabolic decompensation and to assess the value of these findings in the prediction of patient outcome. Six patients with the diagnosis of MSUD underwent conventional MR imaging with DWI during acute presentation with metabolic decompensation. Spectroscopy with long TE was performed in four of the six patients. Follow-up examinations were performed after clinical and metabolic recovery. DWI demonstrated marked restriction of proton diffusion compatible with cytotoxic or intramyelinic sheath edema in the brainstem, basal ganglia, thalami, cerebellar and periventricular white matter and the cerebral cortex. This was accompanied by the presence of an abnormal branched-chain amino acids (BCAA) and branched-chain alpha-keto acids (BCKA) peak at 0.9 ppm as well as elevated lactate on proton spectroscopy in all four patients. The changes in all six patients were reversed with treatment without evidence of volume loss or persistent tissue damage. The presence of cytotoxic or intramyelinic edema as evidenced by restricted water diffusion on DWI, with the presence of lactate on spectroscopy, could imply imminent cell death. However, in the context of metabolic decompensation in MSUD, it appears that changes in cell osmolarity and metabolism can reverse completely after metabolic correction. (orig.)

  15. Metabolic consequences of mitochondrial coenzyme A deficiency in patients with PANK2 mutations.

    Science.gov (United States)

    Leoni, Valerio; Strittmatter, Laura; Zorzi, Giovanna; Zibordi, Federica; Dusi, Sabrina; Garavaglia, Barbara; Venco, Paola; Caccia, Claudio; Souza, Amanda L; Deik, Amy; Clish, Clary B; Rimoldi, Marco; Ciusani, Emilio; Bertini, Enrico; Nardocci, Nardo; Mootha, Vamsi K; Tiranti, Valeria

    2012-03-01

    Pantothenate kinase-associated neurodegeneration (PKAN) is a rare, inborn error of metabolism characterized by iron accumulation in the basal ganglia and by the presence of dystonia, dysarthria, and retinal degeneration. Mutations in pantothenate kinase 2 (PANK2), the rate-limiting enzyme in mitochondrial coenzyme A biosynthesis, represent the most common genetic cause of this disorder. How mutations in this core metabolic enzyme give rise to such a broad clinical spectrum of pathology remains a mystery. To systematically explore its pathogenesis, we performed global metabolic profiling on plasma from a cohort of 14 genetically defined patients and 18 controls. Notably, lactate is elevated in PKAN patients, suggesting dysfunctional mitochondrial metabolism. As predicted, but never previously reported, pantothenate levels are higher in patients with premature stop mutations in PANK2. Global metabolic profiling and follow-up studies in patient-derived fibroblasts also reveal defects in bile acid conjugation and lipid metabolism, pathways that require coenzyme A. These findings raise a novel therapeutic hypothesis, namely, that dietary fats and bile acid supplements may hold potential as disease-modifying interventions. Our study illustrates the value of metabolic profiling as a tool for systematically exploring the biochemical basis of inherited metabolic diseases.

  16. Inborn anemias in mice: (Annual report, 1981-1982)

    Energy Technology Data Exchange (ETDEWEB)

    Bernstein, S.E.

    1982-07-19

    Hereditary anemias of mice are the chief objects of investigation, specificially four macrocytic anemias, 3 types of hemolytic anemia, nonhemolytic microcytic anemia, transitory siderocytic anemia, sex-linked iron-transport anemia, the autoimmune hemolytic anemia of NZB mice, an ..cap alpha..-thalassemia and a new hypochromic anemia with hemochromatosis. New types of anemia may be analyzed as new mutations appear. Three new mutations have been identified during the past 18 months. These anemias are studied through characterization of peripheral blood values, determinations of radiosensitivity under a variety of conditions, measurements of iron metabolism and heme synthesis, study of normal and abnormal erythrocyte membrane proteins, histological and biochemical characterization of blood-forming tissue, functional tests of the stem-cell component, examination of responses to erythroid stimuli, and transplantation of tissue and parabiosis between individuals of differently affected genotypes. 31 refs.

  17. Inborn and experience-dependent models of categorical brain organization. A position paper.

    Science.gov (United States)

    Gainotti, Guido

    2015-01-01

    The present review aims to summarize the debate in contemporary neuroscience between inborn and experience-dependent models of conceptual representations that goes back to the description of category-specific semantic disorders for biological and artifact categories. Experience-dependent models suggest that categorical disorders are the by-product of the differential weighting of different sources of knowledge in the representation of biological and artifact categories. These models maintain that semantic disorders are not really category-specific, because they do not respect the boundaries between different categories. They also argue that the brain structures which are disrupted in a given type of category-specific semantic disorder should correspond to the areas of convergence of the sensory-motor information which play a major role in the construction of that category. Furthermore, they provide a simple interpretation of gender-related categorical effects and are supported by studies assessing the importance of prior experience in the cortical representation of objects On the other hand, inborn models maintain that category-specific semantic disorders reflect the disruption of innate brain networks, which are shaped by natural selection to allow rapid identification of objects that are very relevant for survival. From the empirical point of view, these models are mainly supported by observations of blind subjects, which suggest that visual experience is not necessary for the emergence of category-specificity in the ventral stream of visual processing. The weight of the data supporting experience-dependent and inborn models is thoroughly discussed, stressing the fact observations made in blind subjects are still the subject of intense debate. It is concluded that at the present state of knowledge it is not possible to choose between experience-dependent and inborn models of conceptual representations.

  18. A Neurological Enigma: The Inborn Numerical Competence of Humans and Animals

    Science.gov (United States)

    Gross, Hans J.

    2012-03-01

    "Subitizing" means our ability to recognize and memorize object numbers precisely under conditions where counting is impossible. This is an inborn archaic process which was named after the Latin "subito" = suddenly, immediately, indicating that the objects in question are presented to test persons only for the fraction of a second in order to prevent counting. Sequential counting, however, is an outstanding cultural achievement of mankind and means to count "1, 2, 3, 4, 5, 6, 7, 8 ..." without a limit. In contrast to inborn "subitizing", counting has to be trained, beginning in our early childhood with the help of our fingers. For humans we know since 140 years that we can "subitize" only up to 4 objects correctly and that mistakes occur from 5 objects on. Similar results have been obtained for a number of non-human vertebrates from salamanders to pigeons and dolphins. To our surprise, we have detected this inborn numerical competence for the first time in case of an invertebrate, the honeybee which recognizes and memorizes 3 to 4 objects under rigorous test conditions. This common ability of humans and honeybees to "subitize" up to 4 objects correctly and the miraculous but rare ability of persons with Savant syndrome to "subitize" more than hundred objects precisely raises a number of intriguing questions concerning the evolution and the significance of this biological enigma.

  19. Metabolism

    Science.gov (United States)

    ... Are More Common in People With Type 1 Diabetes Metabolic Syndrome Your Child's Weight Healthy Eating Endocrine System Blood Test: Basic Metabolic Panel (BMP) Activity: Endocrine System Growth Disorders Diabetes Center Thyroid Disorders Your Endocrine System Movie: Endocrine ...

  20. Metabolism

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    2008255 Serum adiponectin level declines in the elderly with metabolic syndrome.WU Xiaoyan(吴晓琰),et al.Dept Geriatr,Huashan Hosp,Fudan UnivShanghai200040.Chin J Geriatr2008;27(3):164-167.Objective To investigate the correlation between ser-um adiponectin level and metabolic syndrome in the elderly·Methods Sixty-one subjects with metabolic syndrome and140age matched subjects without metabolic

  1. Newborn screening of inherited metabolic diseases by tandem mass spectrometry%串联质谱仪在新生儿遗传代谢病筛查中的应用

    Institute of Scientific and Technical Information of China (English)

    Chun-li YU; 顾学范

    2006-01-01

    Application of TMS technology in newborn screening has resulted in major expansion of disorder panel for metabolic diseases in recent years. This automated, multiplex testing methodology detects multiple analytes from single analysis of one blood spot, which leads to detection of 30-35 disorders of amino acids, organic acids, and fatty acids metabolism. The early identification of persons affected with inborn errors of metabolism has led to unexpected discoveries related to the natural history of the disorder or options for therapy. This article summarized (1) the basic principles of this technology and methodology. (2) Current status of application of this methodology in the United States, European countries and in China. (3) The positive impacts on the public health and advances in medical genetics. Finally (4) Challenges, issues and possible solutions. The purpose of this article aimed at introducing new technology and exploring the possibilities of implementing into developing countries where medical genetics is not developed and foreseeing the possible problems and obstacles.

  2. A RARE CASE OF INHERITED METABOLIC DISORDER CAUSING MACROCEPHALYGLUTARIC ACIDURIA TYPE 1

    Directory of Open Access Journals (Sweden)

    Prafulla Kumar Dash

    2017-03-01

    Full Text Available BACKGROUND Glutaric aciduria type 1 is an inborn error of metabolism characterised by deficiency or defect of mitochondrial DNA-mediated enzyme, glutaryl-coenzyme A dehydrogenase. Deficiency of glutaryl-coenzyme A dehydrogenase leads to accumulation of glutaric acid in brain which affects operculisation during foetal brain development. Central nervous system is affected early because of its high energy demand. It causes macrocephaly despite significant brain atrophy and has characteristic imaging findings which helps in its diagnosis. It can be treated with suitable dietary supplementation and amino acid restriction, thereby necessitating its early detection. We are presenting a case of Glutaric Aciduria Type 1 in a male child who presented with macrocephaly and movement abnormalities.

  3. New insights into the metabolic and nutritional determinants of severe combined immunodeficiency

    Science.gov (United States)

    Field, Martha S; Kamynina, Elena; Watkins, David; Rosenblatt, David S; Stover, Patrick J

    2015-01-01

    Human mutations in MTHFD1 have recently been identified in patients with severe combined immunodeficiency (SCID). SCID results from inborn errors of metabolism that cause impaired T- and B-cell proliferation and function. One of the most common causes of SCID is adenosine deaminase (ADA) deficiency, which ultimately inhibits DNA synthesis and cell division. MTHFD1 has been shown to translocate to the nucleus during S-phase of the cell cycle; this localization is critical for synthesis of thymidyate (dTMP or the “T” base in DNA) and subsequent progression through the cell cycle and cell proliferation. Identification of MTHFD1 mutations that are associated with SCID highlights the potential importance of adequate dTMP synthesis in the etiology of SCID. PMID:27123375

  4. Secondary psychosis induced by metabolic disorders

    Directory of Open Access Journals (Sweden)

    Olivier eBonnot

    2015-05-01

    Full Text Available Metabolic disorders are not well recognized by psychiatrists as a possible source of secondary psychoses. Inborn errors of metabolism (IEMs are not frequent. Although, their prompt diagnosis may lead to suitable treatments. IEMs are well known to paediatricians, in particular for their most serious forms, having an early expression most of the time. Recent years discoveries have unveiled later expression forms, and sometimes, very discreet first physical signs. There is a growing body of evidence that supports the hypothesis that IEMs can manifest as atypical psychiatric symptoms, even in the absence of clear neurological symptoms. In the present review, we propose a detailed overview at schizophrenia-like and autism-like symptoms that can lead practitioners to bear in mind an IEM. Other psychiatric manifestations are also found, as behavioral., cognitive, learning and mood disorders. However, they are less frequent. Ensuring an accurate IEM diagnosis, in front of these psychiatric symptoms should be a priority, in order to grant suitable and valuable treatment for these pathologies.

  5. Computational Modeling of Human Metabolism and Its Application to Systems Biomedicine.

    Science.gov (United States)

    Aurich, Maike K; Thiele, Ines

    2016-01-01

    Modern high-throughput techniques offer immense opportunities to investigate whole-systems behavior, such as those underlying human diseases. However, the complexity of the data presents challenges in interpretation, and new avenues are needed to address the complexity of both diseases and data. Constraint-based modeling is one formalism applied in systems biology. It relies on a genome-scale reconstruction that captures extensive biochemical knowledge regarding an organism. The human genome-scale metabolic reconstruction is increasingly used to understand normal cellular and disease states because metabolism is an important factor in many human diseases. The application of human genome-scale reconstruction ranges from mere querying of the model as a knowledge base to studies that take advantage of the model's topology and, most notably, to functional predictions based on cell- and condition-specific metabolic models built based on omics data.An increasing number and diversity of biomedical questions are being addressed using constraint-based modeling and metabolic models. One of the most successful biomedical applications to date is cancer metabolism, but constraint-based modeling also holds great potential for inborn errors of metabolism or obesity. In addition, it offers great prospects for individualized approaches to diagnostics and the design of disease prevention and intervention strategies. Metabolic models support this endeavor by providing easy access to complex high-throughput datasets. Personalized metabolic models have been introduced. Finally, constraint-based modeling can be used to model whole-body metabolism, which will enable the elucidation of metabolic interactions between organs and disturbances of these interactions as either causes or consequence of metabolic diseases. This chapter introduces constraint-based modeling and describes some of its contributions to systems biomedicine.

  6. Neonatal seizures: the overlap between diagnosis of metabolic disorders and structural abnormalities. Case report

    Directory of Open Access Journals (Sweden)

    Freitas Alessandra

    2003-01-01

    Full Text Available Inborn metabolic errors (IME and cortical developmental malformations are uncommon etiologies of neonatal seizures, however they may represent treatable causes of refractory epilepsy and for this reason must be considered as possible etiological factors. This case report aims to demonstrate the importance of neuroimaging studies in one patient with neonatal seizures, even when there are clues pointing to a metabolic disorder. CASE REPORT: A previously healthy 14 day-old child started presenting reiterated focal motor seizures (FMS which evolved to status epilepticus. Exams showed high serum levels of ammonia and no other abnormalities. A metabolic investigation was conducted with normal results. During follow-up, the patient presented developmental delay and left side hemiparesia. Seizures remained controlled with anti-epileptic drugs for four months, followed by relapse with repetitive FMS on the left side. Temporary improvement was obtained with anti-epileptic drug adjustment. At the age of 6 months, during a new episode of status epilepticus, high ammonia levels were detected. Other metabolic exams remained normal. The child was referred to a video-electroencephalographic monitoring and continuous epileptiform discharges were recorded over the right parasagittal and midline regions, with predominance over the posterior quadrant. A new neuroimaging study was performed and displayed a malformation of cortical development. Our case illustrates that because newborns are prone to present metabolic disarrangement, an unbalance such as hyperammonemia may be a consequence of acute events and conduct to a misdiagnosis of IME.

  7. Protein homeostasis disorders of key enzymes of amino acids metabolism: mutation-induced protein kinetic destabilization and new therapeutic strategies.

    Science.gov (United States)

    Pey, Angel L

    2013-12-01

    Many inborn errors of amino acids metabolism are caused by single point mutations affecting the ability of proteins to fold properly (i.e., protein homeostasis), thus leading to enzyme loss-of-function. Mutations may affect protein homeostasis by altering intrinsic physical properties of the polypeptide (folding thermodynamics, and rates of folding/unfolding/misfolding) as well as the interaction of partially folded states with elements of the protein homeostasis network (such as molecular chaperones and proteolytic machineries). Understanding these mutational effects on protein homeostasis is required to develop new therapeutic strategies aimed to target specific features of the mutant polypeptide. Here, I review recent work in three different diseases of protein homeostasis associated to inborn errors of amino acids metabolism: phenylketonuria, inherited homocystinuria and primary hyperoxaluria type I. These three different genetic disorders involve proteins operating in different cell organelles and displaying different structural complexities. Mutations often decrease protein kinetic stability of the native state (i.e., its half-life for irreversible denaturation), which can be studied using simple kinetic models amenable to biophysical and biochemical characterization. Natural ligands and pharmacological chaperones are shown to stabilize mutant enzymes, thus supporting their therapeutic application to overcome protein kinetic destabilization. The role of molecular chaperones in protein folding and misfolding is also discussed as well as their potential pharmacological modulation as promising new therapeutic approaches. Since current available treatments for these diseases are either burdening or only successful in a fraction of patients, alternative treatments must be considered covering studies from protein structure and biophysics to studies in animal models and patients.

  8. METABOLISM

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    Objective: To determine the allele frequencies of genetic variants 373 Ala→Pro and 451 Arg→Gln of cholesteryl ester transfer protein (CETP) and to explore their potential impacts on serum lipid metabolism. Methods: The genotypes in CETP codon 373 and 451 in 91 German healthy students and 409 an-

  9. Atrial myocyte function and Ca2+ handling is associated with inborn aerobic capacity.

    Directory of Open Access Journals (Sweden)

    Anne Berit Johnsen

    Full Text Available Although high aerobic capacity is associated with effective cardiac function, the effect of aerobic capacity on atrial function, especially in terms of cellular mechanisms, is not known. We aimed to investigate whether rats with low inborn maximal oxygen uptake (VO2 max had impaired atrial myocyte contractile function when compared to rats with high inborn VO2 max.Atrial myocyte function was depressed in Low Capacity Runners (LCR relative to High Capacity Runners (HCR which was associated with impaired Ca(2+ handling. Fractional shortening was 52% lower at 2 Hz and 60% lower at 5 Hz stimulation while time to 50% relengthening was 43% prolonged and 55% prolonged, respectively. Differences in Ca(2+ amplitude and diastolic Ca(2+ level were observed at 5 Hz stimulation where Ca(2+ amplitude was 70% lower and diastolic Ca(2+ level was 11% higher in LCR rats. Prolonged time to 50% Ca(2+ decay was associated with reduced sarcoplasmic reticulum (SR Ca(2+ ATPase function in LCR (39%. Na(+/Ca(2+ exchanger activity was comparable between the groups. Diastolic SR Ca(2+ leak was increased by 109%. This could be partly explained by increased ryanodine receptors phosphorylation at the Ca(2+-calmodulin-dependent protein kinase-II specific Ser-2814 site in LCR rats. T-tubules were present in 68% of HCR cells whereas only 33% LCR cells had these structures. In HCR, the significantly higher numbers of cells with T-tubules were combined with greater numbers of myocytes where Ca(2+ release in the cell occurred simultaneously in central and peripheral regions, giving rise to faster and more spatial homogenous Ca(2+-signal onset.This data demonstrates that contrasting for low or high aerobic capacity leads to diverse functional and structural remodelling of atrial myocytes, with impaired contractile function in LCR compared to HCR rats.

  10. Investigating host-pathogen behavior and their interaction using genome-scale metabolic network models.

    Science.gov (United States)

    Sadhukhan, Priyanka P; Raghunathan, Anu

    2014-01-01

    Genome Scale Metabolic Modeling methods represent one way to compute whole cell function starting from the genome sequence of an organism and contribute towards understanding and predicting the genotype-phenotype relationship. About 80 models spanning all the kingdoms of life from archaea to eukaryotes have been built till date and used to interrogate cell phenotype under varying conditions. These models have been used to not only understand the flux distribution in evolutionary conserved pathways like glycolysis and the Krebs cycle but also in applications ranging from value added product formation in Escherichia coli to predicting inborn errors of Homo sapiens metabolism. This chapter describes a protocol that delineates the process of genome scale metabolic modeling for analysing host-pathogen behavior and interaction using flux balance analysis (FBA). The steps discussed in the process include (1) reconstruction of a metabolic network from the genome sequence, (2) its representation in a precise mathematical framework, (3) its translation to a model, and (4) the analysis using linear algebra and optimization. The methods for biological interpretations of computed cell phenotypes in the context of individual host and pathogen models and their integration are also discussed.

  11. Endocrine manifestations related to inherited metabolic diseases in adults

    Directory of Open Access Journals (Sweden)

    Vantyghem Marie-Christine

    2012-01-01

    Full Text Available Abstract Most inborn errors of metabolism (IEM are recessive, genetically transmitted diseases and are classified into 3 main groups according to their mechanisms: cellular intoxication, energy deficiency, and defects of complex molecules. They can be associated with endocrine manifestations, which may be complications from a previously diagnosed IEM of childhood onset. More rarely, endocrinopathies can signal an IEM in adulthood, which should be suspected when an endocrine disorder is associated with multisystemic involvement (neurological, muscular, hepatic features, etc.. IEM can affect all glands, but diabetes mellitus, thyroid dysfunction and hypogonadism are the most frequent disorders. A single IEM can present with multiple endocrine dysfunctions, especially those involving energy deficiency (respiratory chain defects, and metal (hemochromatosis and storage disorders (cystinosis. Non-autoimmune diabetes mellitus, thyroid dysfunction and/or goiter and sometimes hypoparathyroidism should steer the diagnosis towards a respiratory chain defect. Hypogonadotropic hypogonadism is frequent in haemochromatosis (often associated with diabetes, whereas primary hypogonadism is reported in Alström disease and cystinosis (both associated with diabetes, the latter also with thyroid dysfunction and galactosemia. Hypogonadism is also frequent in X-linked adrenoleukodystrophy (with adrenal failure, congenital disorders of glycosylation, and Fabry and glycogen storage diseases (along with thyroid dysfunction in the first 3 and diabetes in the last. This is a new and growing field and is not yet very well recognized in adulthood despite its consequences on growth, bone metabolism and fertility. For this reason, physicians managing adult patients should be aware of these diagnoses.

  12. Pelizaeus-Merzbacher disease: an X-linked neurologic disorder of myelin metabolism with a novel mutation in the gene encoding proteolipid protein.

    Science.gov (United States)

    Gencic, S; Abuelo, D; Ambler, M; Hudson, L D

    1989-01-01

    The nosology of the inborn errors of myelin metabolism has been stymied by the lack of molecular genetic analysis. Historically, Pelizaeus-Merzbacher disease has encompassed a host of neurologic disorders that present with a deficit of myelin, the membrane elaborated by glial cells that encircles and successively enwraps axons. We describe here a Pelizaeus-Merzbacher pedigree of the classical type, with X-linked inheritance, a typical clinical progression, and a pathologic loss of myelinating cells and myelin in the central nervous system. To discriminate variants of Pelizaeus-Merzbacher disease, a set of oligonucleotide primers was constructed to polymerase-chain-reaction (PCR) amplify and sequence the gene encoding proteolipid protein (PLP), a structural protein that comprises half of the protein of the myelin sheath. The PLP gene in one of two affected males and the carrier mother of this family exhibited a single base difference in the more than 2 kb of the PLP gene sequenced, a C----T transition that would create a serine substitution for proline at the carboxy end of the protein. Our results delineate the clinical features of Pelizaeus-Merzbacher disease, define the possible molecular pathology of this dysmyelinating disorder, and address the molecular classification of inborn errors of myelin metabolism. Patients with the classical form (type I) and the more severely affected, connatal variant of Pelizaeus-Merzbacher disease (type II) would be predicted to display mutation at the PLP locus. The other variants (types III-VI), which have sometimes been categorized as Pelizaeus-Merzbacher disease, may represent mutations in genes encoding other structural myelin proteins or proteins critical to myelination. Images Figure 2 Figure 3 Figure 5 Figure 6 PMID:2773936

  13. Avaliação antropométrica de pacientes com suspeita de erros inatos do metabolismo Anthropometric evaluation of patients with suspected innate errors of metabolism

    Directory of Open Access Journals (Sweden)

    Francilia de Kássia Brito-Silva

    2012-09-01

    Full Text Available OBJETIVOS: avaliar antropometricamente os pacientes com suspeita de erros inatos do metabolismo (EIM e descrever a prevalência de distúrbios nutricionais (desnutrição, sobrepeso e obesidade. MÉTODOS: foram avaliados 55 pacientes de 0 a 10 anos, de acordo com os índices antropométricos (A/I, P/I E P/A e IMC/I, no laboratório de erros inatos do metabolismo (LEIM da Universidade Federal do Pará, através de balança e antropômetro. Os dados foram coletados a partir da ficha de atendimento do LEIM. Para o diagnóstico nutricional foram utilizados os programas Anthro e Anthro Plus e o programa SPSS para a análise estatística. RESULTADOS: os pacientes atendidos pertenciam, na maioria, a faixa etária de sete meses a nove anos. Os principais sintomas foram atraso no desenvolvimento neuropsicomotor e infecções frequentes. Quanto ao estado nutricional, foi observado déficit de 23,7% no indicador de peso para idade, déficit de 50,9% no indicador de altura para idade, excesso de peso e obesidade de 15,4% para peso para altura, e 25,1% para índice de massa corporal para idade. CONCLUSÕES: os pacientes apresentaram estado nutricional inadequados, o qual na ausência de diagnóstico de EIM, os fatores envolvidos devem ser mais bem averiguados.OBJECTIVES: to provide an anthropometric evaluation of patients suspected of having innate errors of metabolism (IEMs and report the prevalence of nutritional disorders (malnutrition, overweight and obesity. METHODS: fifty-five patients aged between 0 and 10 years were evaluated for anthropometric indices (H/A, W/A and W/H and BMI/A, in the innate errors of metabolism laboratory (LEIM of the Federal University of Pará, using scales and an anthropometer. The data were collected using an LEIM form. Nutritional diagnosis was carried out using the Anthro and Anthro Plus programs and the SPSS statistics package. RESULTS: the patients attended were mostly aged between seven months and nine years. The main

  14. In-Born Radio Frequency Identification Devices for Safeguards Use at Gas-Centrifuge Enrichment Plants

    Energy Technology Data Exchange (ETDEWEB)

    Ward,R.; Rosenthal,M.

    2009-07-12

    Global expansion of nuclear power has made the need for improved safeguards measures at Gas Centrifuge Enrichment Plants (GCEPs) imperative. One technology under consideration for safeguards applications is Radio Frequency Identification Devices (RFIDs). RFIDs have the potential to increase IAEA inspector"s efficiency and effectiveness either by reducing the number of inspection visits necessary or by reducing inspection effort at those visits. This study assesses the use of RFIDs as an integral component of the "Option 4" safeguards approach developed by Bruce Moran, U.S. Nuclear Regulatory Commission (NRC), for a model GCEP [1]. A previous analysis of RFIDs was conducted by Jae Jo, Brookhaven National Laboratory (BNL), which evaluated the effectiveness of an RFID tag applied by the facility operator [2]. This paper presents a similar evaluation carried out in the framework of Jo’s paper, but it is predicated on the assumption that the RFID tag is applied by the manufacturer at the birth of the cylinder, rather than by the operator. Relevant diversion scenarios are examined to determine if RFIDs increase the effectiveness and/ or efficiency of safeguards in these scenarios. Conclusions on the benefits offered to inspectors by using in-born RFID tagging are presented.

  15. Analytical estimates of efficiency of attractor neural networks with inborn connections

    Directory of Open Access Journals (Sweden)

    Solovyeva Ksenia

    2016-01-01

    Full Text Available The analysis is restricted to the features of neural networks endowed to the latter by the inborn (not learned connections. We study attractor neural networks in which for almost all operation time the activity resides in close vicinity of a relatively small number of attractor states. The number of the latter, M, is proportional to the number of neurons in the neural network, N, while the total number of the states in it is 2N. The unified procedure of growth/fabrication of neural networks with sets of all attractor states with dimensionality d=0 and d=1, based on model molecular markers, is studied in detail. The specificity of the networks (d=0 or d=1 depends on topology (i.e., the set of distances between elements which can be provided to the set of molecular markers by their physical nature. The neural networks parameters estimates and trade-offs for them in attractor neural networks are calculated analytically. The proposed mechanisms reveal simple and efficient ways of implementation in artificial as well as in natural neural networks of multiplexity, i.e. of using activity of single neurons in representation of multiple values of the variables, which are operated by the neural systems. It is discussed how the neuronal multiplexity provides efficient and reliable ways of performing functional operations in the neural systems.

  16. Acute metabolic decompensation due to influenza in a mouse model of ornithine transcarbamylase deficiency

    Directory of Open Access Journals (Sweden)

    Peter J. McGuire

    2014-02-01

    types of inborn errors of metabolism.

  17. State of the art. Four easy pieces: interconnections between tissue injury, intermediary metabolism, autoimmunity, and chronic degeneration.

    Science.gov (United States)

    Steinman, Lawrence

    2006-08-01

    Four questions are posed: (1) Can tissue damage itself provoke autoimmunity? (2) Can genetic mutations of key structures produce tissue pathology and thus provoke autoimmunity? (3) Can acute immune damage produce tissue degeneration without further hallmarks of an immune response? (4) Can intermediary metabolism modulate immune damage to tissues? Four answers are given: (1) Tissue injury itself may lead to autoimmunity. Both innate and adaptive immunity may arise as a response to tissue injury, and the immune attack can further damage tissue. (2) Genetic mutations can lead to an immune response indistinguishable from autoimmunity, exemplified from Duchenne's Muscular Dystrophy and X-linked adrenoleukodystrophy. (3) Chronic immune damage may lead to tissue degeneration, with or without further hallmarks of an immune response. Variations on this theme, including inverse scenarios, are also possible: Inborn errors of metabolism may lead to tissue damage that may provoke an adaptive and or innate immune response. The immune response might further damage tissue. (4) Finally, perturbations of intermediary metabolism may modulate the immune response, controlling the extent of immune-mediated damage. Examples are taken from perturbations in the cholesterol pathway that influence the characteristics of the immune response, and with tryptophan metabolites that modulate autoimmunity and graft rejection. Inflammatory, degenerative, and autoimmune neurological disease will be discussed in terms of their implications for pathogenic mechanisms underlying chronic obstructive pulmonary disease.

  18. Biotin deprivation impairs mitochondrial structure and function and has implications for inherited metabolic disorders.

    Science.gov (United States)

    Ochoa-Ruiz, Estefanía; Díaz-Ruiz, Rodrigo; Hernández-Vázquez, Alaín de J; Ibarra-González, Isabel; Ortiz-Plata, Alma; Rembao, Daniel; Ortega-Cuéllar, Daniel; Viollet, Benoit; Uribe-Carvajal, Salvador; Corella, José Ahmed; Velázquez-Arellano, Antonio

    2015-11-01

    Certain inborn errors of metabolism result from deficiencies in biotin containing enzymes. These disorders are mimicked by dietary absence or insufficiency of biotin, ATP deficit being a major effect,whose responsible mechanisms have not been thoroughly studied. Here we show that in rats and cultured cells it is the result of reduced TCA cycle flow, partly due to deficient anaplerotic biotin-dependent pyruvate carboxylase. This is accompanied by diminished flow through the electron transport chain, augmented by deficient cytochrome c oxidase (complex IV) activity with decreased cytochromes and reduced oxidative phosphorylation. There was also severe mitochondrial damage accompanied by decrease of mitochondria, associated with toxic levels of propionyl CoA as shown by carnitine supplementation studies, which explains the apparently paradoxical mitochondrial diminution in the face of the energy sensor AMPK activation, known to induce mitochondria biogenesis. This idea was supported by experiments on AMPK knockout mouse embryonic fibroblasts (MEFs). The multifactorial ATP deficit also provides a plausible basis for the cardiomyopathy in patients with propionic acidemia, and other diseases.Additionally, systemic inflammation concomitant to the toxic state might explain our findings of enhanced IL-6, STAT3 and HIF-1α, associated with an increase of mitophagic BNIP3 and PINK proteins, which may further increase mitophagy. Together our results imply core mechanisms of energy deficit in several inherited metabolic disorders.

  19. Tyrosine impairs enzymes of energy metabolism in cerebral cortex of rats.

    Science.gov (United States)

    de Andrade, Rodrigo Binkowski; Gemelli, Tanise; Rojas, Denise Bertin; Funchal, Cláudia; Dutra-Filho, Carlos Severo; Wannmacher, Clovis Milton Duval

    2012-05-01

    Tyrosine levels are abnormally elevated in tissues and physiological fluids of patients with inborn errors of tyrosine catabolism, especially in tyrosinemia type II, which is caused by deficiency of tyrosine aminotransferase and provokes eyes, skin, and central nervous system disturbances. Considering that the mechanisms of brain damage in these disorders are poorly known, in this study, we investigated the in vivo and in vitro effects of tyrosine on some parameters of energy metabolism in cerebral cortex of 14-day-old Wistar rats. We observed that 2 mM tyrosine inhibited in vitro the pyruvate kinase (PK) activity and that this inhibition was prevented by 1 mM reduced glutathione with 30, 60, and 90 min of preincubation. Moreover, administration of tyrosine methyl ester (TME) (0.5 mg/g of body weight) decreased the activity of PK and this reduction was prevented by pre-treatment with creatine (Cr). On the other hand, tyrosine did not alter adenylate kinase (AK) activity in vitro, but administration of TME enhanced AK activity not prevented by Cr pre-treatment. Finally, TME administration decreased the activity of CK from cytosolic and mitochondrial fractions and this diminution was prevented by Cr pre-treatment. The results suggest that tyrosine alters essential sulfhydryl groups necessary for CK and PK functions, possibly through oxidative stress. In case this also occurs in the patients, it is possible that energy metabolism alterations may contribute, along with other mechanisms, to the neurological dysfunction of hypertyrosinemias.

  20. Acute administration of l-tyrosine alters energetic metabolism of hippocampus and striatum of infant rats.

    Science.gov (United States)

    Ramos, Andrea C; Ferreira, Gabriela K; Carvalho-Silva, Milena; Furlanetto, Camila B; Gonçalves, Cinara L; Ferreira, Gustavo C; Schuck, Patrícia F; Streck, Emilio L

    2013-08-01

    Tyrosinemia type II is an inborn error of metabolism caused by mutations in the gene that encodes tyrosine aminotransferase, which leads to increased blood tyrosine levels. Considering that tyrosine levels are highly elevated in fluids of patients with tyrosinemia type II, and that previous studies demonstrated significant alterations in brain energy metabolism of young rats caused by l-tyrosine, the present study aimed to evaluate the effect of acute administration of l-tyrosine on the activities of citrate synthase, malate dehydrogenase, succinate dehydrogenase, and mitochondrial respiratory chain complexes I, II, II-III, and IV in posterior cortex, hippocampus, and striatum of infant rats. Wistar rats (10 days old) were killed 1h after a single intraperitoneal injection of tyrosine (500 mg/kg) or saline. The activities of energy metabolism enzymes were evaluated in brain of rats. Our results demonstrated that acute administration of l-tyrosine inhibited the activity of citrate synthase activity in striatum and increased the activities of malate dehydrogenase and succinate dehydrogenase in hippocampus. On the other hand, these enzymes were not affected in posterior cortex. The activities of complex I and complex II were inhibited by acute administration of l-tyrosine in striatum. On the other hand, the acute administration of l-tyrosine increased the activity of activity of complex II-III in hippocampus. Complex IV was not affected by acute administration of l-tyrosine in infant rats. Our results indicate an alteration in the energy metabolism in hippocampus and striatum of infant rats after acute administration of l-tyrosine. If the same effects occur in the brain of the patients, it is possible that energy metabolism impairment may be contribute to possible damage in memory and cognitive processes in patients with tyrosinemia type II.

  1. Application of the back-error propagation artificial neural network (BPANN) on genetic variants in the PPAR-γ and RXR-α gene and risk of metabolic syndrome in a Chinese Han population.

    Science.gov (United States)

    Zhao, Xu; Xu, Kang; Shi, Hui; Cheng, Jinluo; Ma, Jianhua; Gao, Yanqin; Li, Qian; Ye, Xinhua; Lu, Ying; Yu, Xiaofang; Du, Juan; Du, Wencong; Ye, Qing; Zhou, Ling

    2014-03-01

    This study was aimed to explore the associations between the combined effects of several polymorphisms in the PPAR-γ and RXR-α gene and environmental factors with the risk of metabolic syndrome by back-error propagation artificial neural network (BPANN). We established the model based on data gathered from metabolic syndrome patients (n = 1012) and normal controls (n = 1069) by BPANN. Mean impact value (MIV) for each input variable was calculated and the sequence of factors was sorted according to their absolute MIVs. Generalized multifactor dimensionality reduction (GMDR) confirmed a joint effect of PPAR-γ and RXR-α based on the results from BPANN. By BPANN analysis, the sequences according to the importance of metabolic syndrome risk factors were in the order of body mass index (BMI), serum adiponectin, rs4240711, gender, rs4842194, family history of type 2 diabetes, rs2920502, physical activity, alcohol drinking, rs3856806, family history of hypertension, rs1045570, rs6537944, age, rs17817276, family history of hyperlipidemia, smoking, rs1801282 and rs3132291. However, no polymorphism was statistically significant in multiple logistic regression analysis. After controlling for environmental factors, A1, A2, B1 and B2 (rs4240711, rs4842194, rs2920502 and rs3856806) models were the best models (cross-validation consistency 10/10, P = 0.0107) with the GMDR method. In conclusion, the interaction of the PPAR-γ and RXR-α gene could play a role in susceptibility to metabolic syndrome. A more realistic model is obtained by using BPANN to screen out determinants of diseases of multiple etiologies like metabolic syndrome.

  2. On the Gate of Life Be the Inborn Origin%论命门为先天之本

    Institute of Scientific and Technical Information of China (English)

    储全根

    2001-01-01

    针对明代医家李中梓提出并影响至今的“肾为先天之本”说提出质疑,认为“肾为先天之本”论实乃李氏对其他医家研究成果的否定和抹杀,带来了中医理论的诸多矛盾和问题。肾脏作为后天脏器,不应视作先天之本。《难经》所倡导而明代医家又着力阐发的命门概念有丰富的内涵,应当确定其先天之本的重要地位,这不仅解决了中医理论上的一些矛盾,且确为完善理论所必需,并可拓展今后中医基础研究的思路和空间。%The theory of “Kidney is the inborn origin of the body”whose influence has existed even to this day advocated by Li Zhongzi,the medical scientist in Ming Dynasty is questioned in this article.The author holds that Li's theory is actually the negation of the achievements in medical research gained by the other medical scientists in chinese history and it also brings about various contradictions and problems in the theory of Traditional Chinese Medicine.As the postnatal organs of the body,kidney itself cannot be regarded as the inborn origin.The concept of gate of life advocated in The book of The Classcic on Difficulty and elucidated by the medical scientists in Ming Dynasty with great efforts contains rich connotation and its important position as the real inborn origin of the body should be detined.By do so,some contradictions in the theory of Traditional Chinese Medicine can be solved and hence,the theory is necessarily improved,and meanwhile,the method and scope of thinking in the research of the fundamental theory of Traditional Chinese Medicine can also be developed and widened.

  3. Refractive Errors

    Science.gov (United States)

    ... does the eye focus light? In order to see clearly, light rays from an object must focus onto the ... The refractive errors are: myopia, hyperopia and astigmatism [See figures 2 and 3]. What is hyperopia (farsightedness)? Hyperopia occurs when light rays focus behind the retina (because the eye ...

  4. Medication Errors

    Science.gov (United States)

    ... Proprietary Names (PDF - 146KB) Draft Guidance for Industry: Best Practices in Developing Proprietary Names for Drugs (PDF - 279KB) ... or (301) 796-3400 druginfo@fda.hhs.gov Human Drug ... in Medication Errors Resources for You Agency for Healthcare Research and Quality: ...

  5. Metabolic encephalopathy and lipid storage myopathy associated with a presumptive mitochondrial fatty acid oxidation defect in a dog

    Directory of Open Access Journals (Sweden)

    Vanessa R Biegen

    2015-11-01

    Full Text Available A 1-year-old spayed female Shih Tzu presented for episodic abnormalities of posture and mentation. Neurologic examination was consistent with a bilaterally symmetric multifocal encephalopathy. The dog had a waxing-and-waning hyperlactemia and hypoglycemia. Magnetic resonance imaging revealed bilaterally symmetric cavitated lesions of the caudate nuclei with less severe abnormalities in the cerebellar nuclei. Empirical therapy was unsuccessful and the patient was euthanized. Post-mortem histopathology revealed bilaterally symmetric necrotic lesions of the caudate and cerebellar nuclei and multi-organ lipid accumulation, including a lipid storage myopathy. Malonic aciduria and ketonuria were found on urinary organic acid screen. Plasma acylcarnitine analysis suggested a fatty acid oxidation defect. Fatty acid oxidation disorders are inborn errors of metabolism documented in humans, but poorly described in dogs. Although neurologic signs have been described in humans with this group of diseases, descriptions of advanced imaging and histopathology are severely lacking. This report suggests that abnormalities of fatty acid metabolism may cause severe, bilateral gray matter necrosis and lipid accumulation in multiple organs including the skeletal muscles, liver, and kidneys. Veterinarians should be aware that fatty acid oxidation disorders, although potentially fatal, may be treatable. A timely definitive diagnosis is essential in guiding therapy.

  6. On the origin of 3-methylglutaconic acid in disorders of mitochondrial energy metabolism.

    Science.gov (United States)

    Ikon, Nikita; Ryan, Robert O

    2016-09-01

    3-methylglutaconic acid (3MGA)-uria occurs in numerous inborn errors of metabolism (IEM) associated with compromised mitochondrial energy metabolism. This organic acid arises from thioester cleavage of 3-methylglutaconyl CoA (3MG CoA), an intermediate in leucine catabolism. In individuals harboring mutations in 3MG CoA hydratase (i.e., primary 3MGA-uria), dietary leucine is the source of 3MGA. In secondary 3MGA-uria, however, no leucine metabolism defects have been reported. While others have suggested 3MGA arises from aberrant isoprenoid shunting from cytosol to mitochondria, an alternative route posits that 3MG CoA arises in three steps from mitochondrial acetyl CoA. Support for this biosynthetic route in IEMs is seen by its regulated occurrence in microorganisms. The fungus, Ustilago maydis, the myxobacterium, Myxococcus xanthus and the marine cyanobacterium, Lyngbya majuscule, generate 3MG CoA (or acyl carrier protein derivative) in the biosynthesis of iron chelating siderophores, iso-odd chain fatty acids and polyketide/nonribosomal peptide products, respectively. The existence of this biosynthetic machinery in these organisms supports a model wherein, under conditions of mitochondrial dysfunction, accumulation of acetyl CoA in the inner mitochondrial space as a result of inefficient fuel utilization drives de novo synthesis of 3MG CoA. Since humans lack the downstream biosynthetic capability of the organisms mentioned above, as 3MG CoA levels rise, thioester hydrolysis yields 3MGA, which is excreted in urine as unspent fuel. Understanding the metabolic origins of 3MGA may increase its utility as a biomarker.

  7. Inborn anemias in mice. Progress report, 1 August 1979-15 July 1980

    Energy Technology Data Exchange (ETDEWEB)

    Bernstein, S.E.; Russell, E.S.

    1980-08-01

    Four macrocytic anemias, four hemolytic anemias, nonhemolytic microcytic anemia, transitory siderocytic anemia, sex-linked iron-transport anemia, an ..cap alpha..-thalassemia, and a new target-cell anemia are under investigation in mice. Each of these blood dyscrasias is caused by the action of a unique mutant gene, which determines the structure of different intracellular molecules, and thus controls a different metabolic process. Thus the wide range of different hereditary anemias has considerable potential for uncovering many different aspects of hemopoietic homeostatic mechanisms in the mouse. Each anemia is studied through: (a) characterization of peripheral blood values; (b) determinations of radiosensitivity under a variety of conditions; (c) measurements of iron metabolism and heme synthesis; (d) histological and biochemical study of blood-forming tissue; (e) functional tests of the stem cell component; (f) examination of responses to erythroid stimuli; and (g) transplantation of tissue between individuals of differently affected genotypes.

  8. Medication Errors - A Review

    OpenAIRE

    Vinay BC; Nikhitha MK; Patel Sunil B

    2015-01-01

    In this present review article, regarding medication errors its definition, medication error problem, types of medication errors, common causes of medication errors, monitoring medication errors, consequences of medication errors, prevention of medication error and managing medication errors have been explained neatly and legibly with proper tables which is easy to understand.

  9. Medication Errors - A Review

    OpenAIRE

    Vinay BC; Nikhitha MK; Patel Sunil B

    2015-01-01

    In this present review article, regarding medication errors its definition, medication error problem, types of medication errors, common causes of medication errors, monitoring medication errors, consequences of medication errors, prevention of medication error and managing medication errors have been explained neatly and legibly with proper tables which is easy to understand.

  10. Inborn anemias in mice. Progress report, 1 May 1977--31 July 1978

    Energy Technology Data Exchange (ETDEWEB)

    Bernstein, S.E.; Russell, E.S.

    1978-08-01

    Hereditary anemias of mice have been the chief objects of investigation. At present under study are four macrocytic anemias, four hemolytic anemias, nonhemolytic microcytic anemia, transitory siderocytic anemia, sex-linked iron-transport anemia, and the autoimmune hemolytic anemia of NZB. Each of these blood dyscrasias is caused by the action of a unique mutant gene, which determines the structure of different intracellular molecules, and thus controls a different metabolic process. Thus our wide range of different hereditary anemias has considerable potential for uncovering many different aspects of hemopoietic homeostatic mechanisms in the mouse. Each anemia is studied through: characterization of peripheral blood values, determinations of radiosensitivity under a variety of conditions, measurements of iron metabolism and heme synthesis, histological and biochemical study of blood-forming tissue, functional tests of the stem cell component, examination of responses to erythroid stimuli, and transplantation of tissue between individuals of differently affected genotypes. Considerable effort is devoted to perfection of hematologic, cell culture, and transplant methods to make these techniques useful in dealing with special problems associated with abnormal function.

  11. Olfactory guidance of nipple attachment and suckling in kittens of the domestic cat: Inborn and learned responses.

    Science.gov (United States)

    Raihani, Gina; González, Daniel; Arteaga, Lourdes; Hudson, Robyn

    2009-12-01

    In 60 kittens (11 litters) from free-ranging domestic cats we investigated the role of chemical cues in facilitating nipple attachment and suckling during the first month of postnatal life when kittens are totally dependent on the mother's milk. Kittens were tested both together and individually on sedated females in different reproductive states. We found (1) that newborn kittens with no suckling experience responded to the ventrum of lactating but not to the ventrum of nonlactating females with search behavior and attached to nipples within minutes; (2) that even in older kittens, nipple attachment depended on females' reproductive state, with virtually no attachments on nonreproducing females, some on pregnant females, the greatest number on early-lactating females, followed by a decline on late-lactating females; and (3) that kittens could locate their particular, most used nipple on their mother but not on a female of similar lactational age, even after eye opening. We suggest that kittens respond from birth with efficient nipple-search behavior to inborn olfactory cues on the mother's ventrum, that emission of these is under hormonal control, but that kittens also quickly learn olfactory cues specific to their own mother and to their own particular nipples.

  12. Hypoglycaemia related to inherited metabolic diseases in adults

    Directory of Open Access Journals (Sweden)

    Douillard Claire

    2012-05-01

    Full Text Available Abstract In non-diabetic adult patients, hypoglycaemia may be related to drugs, critical illness, cortisol or glucagon insufficiency, non-islet cell tumour, insulinoma, or it may be surreptitious. Nevertheless, some hypoglycaemic episodes remain unexplained, and inborn errors of metabolism (IEM should be considered, particularly in cases of multisystemic involvement. In children, IEM are considered a differential diagnosis in cases of hypoglycaemia. In adulthood, IEM-related hypoglycaemia can persist in a previously diagnosed childhood disease. Hypoglycaemia may sometimes be a presenting sign of the IEM. Short stature, hepatomegaly, hypogonadism, dysmorphia or muscular symptoms are signs suggestive of IEM-related hypoglycaemia. In both adults and children, hypoglycaemia can be clinically classified according to its timing. Postprandial hypoglycaemia can be an indicator of either endogenous hyperinsulinism linked to non-insulinoma pancreatogenic hypoglycaemia syndrome (NIPHS, unknown incidence in adults or very rarely, inherited fructose intolerance. Glucokinase-activating mutations (one family are the only genetic disorder responsible for NIPH in adults that has been clearly identified so far. Exercise-induced hyperinsulinism is linked to an activating mutation of the monocarboxylate transporter 1 (one family. Fasting hypoglycaemia may be caused by IEM that were already diagnosed in childhood and persist into adulthood: glycogen storage disease (GSD type I, III, 0, VI and IX; glucose transporter 2 deficiency; fatty acid oxidation; ketogenesis disorders; and gluconeogenesis disorders. Fasting hypoglycaemia in adulthood can also be a rare presenting sign of an IEM, especially in GSD type III, fatty acid oxidation [medium-chain acyl-CoA dehydrogenase (MCAD, ketogenesis disorders (3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA lyase deficiency, and gluconeogenesis disorders (fructose-1,6-biphosphatase deficiency].

  13. Biochemical, metabolic, and behavioral characteristics of immature chronic hyperphenylalanemic rats

    Science.gov (United States)

    Dienel, Gerald A.; Cruz, Nancy F.

    2015-01-01

    Phenylketonuria and hyperphenylalanemia are inborn errors in metabolism of phenylalanine arising from defects in steps to convert phenylalanine to tyrosine. Phe accumulation causes severe mental retardation that can be prevented by timely identification of affected individuals and their placement on a Phe-restricted diet. In spite of many studies in patients and animal models, the basis for acquisition of mental retardation during the critical period of brain development is not adequately understood. All animal models for human disease have advantages and limitations, and characteristics common to different models are most likely to correspond to the disorder. This study established similar levels of Phe exposure in developing rats between 3 and 16 days of age using three models to produce chronic hyperphenylalanemia, and identified changes in brain amino acid levels common to all models that persist for ~16h of each day. In a representative model, local rates of glucose utilization (CMRglc) were determined at 25–27 days of age, and only selective changes that appeared to depend on Phe exposure were observed. CMRglc was reduced in frontal cortex and thalamus and increased in hippocampus and globus pallidus. Behavioral testing to evaluate neuromuscular competence revealed poor performance in chronically-hyperphenylalanemic rats that persisted for at least three weeks after cessation of Phe injections and did not occur with mild or acute hyperphenylalanemia. Thus, the abnormal amino acid environment, including hyperglycinemia, in developing rat brain is associated with selective regional changes in glucose utilization and behavioral abnormalities that are not readily reversed after they are acquired. PMID:26224289

  14. Co-administration of creatine plus pyruvate prevents the effects of phenylalanine administration to female rats during pregnancy and lactation on enzymes activity of energy metabolism in cerebral cortex and hippocampus of the offspring.

    Science.gov (United States)

    Bortoluzzi, Vanessa Trindade; de Franceschi, Itiane Diehl; Rieger, Elenara; Wannmacher, Clóvis Milton Duval

    2014-08-01

    Phenylketonuria (PKU) is the most frequent inborn error of metabolism. It is caused by deficiency in the activity of phenylalanine hydroxylase, leading to accumulation of phenylalanine and its metabolites. Untreated maternal PKU or hyperphenylalaninemia may result in nonphenylketonuric offspring with low birth weight and neonatal sequelae, especially microcephaly and intellectual disability. The mechanisms underlying the neuropathology of brain injury in maternal PKU syndrome are poorly understood. In the present study, we evaluated the possible preventive effect of the co-administration of creatine plus pyruvate on the effects elicited by phenylalanine administration to female Wistar rats during pregnancy and lactation on some enzymes involved in the phosphoryltransfer network in the brain cortex and hippocampus of the offspring at 21 days of age. Phenylalanine administration provoked diminution of body, brain cortex an hippocampus weight and decrease of adenylate kinase, mitochondrial and cytosolic creatine kinase activities. Co-administration of creatine plus pyruvate was effective in the prevention of those alterations provoked by phenylalanine, suggesting that altered energy metabolism may be important in the pathophysiology of maternal PKU. If these alterations also occur in maternal PKU, it is possible that pyruvate and creatine supplementation to the phenylalanine-restricted diet might be beneficial to phenylketonuric mothers.

  15. [Survey in hospitals. Nursing errors, error culture and error management].

    Science.gov (United States)

    Habermann, Monika; Cramer, Henning

    2010-09-01

    Knowledge on errors is important to design safe nursing practice and its framework. This article presents results of a survey on this topic, including data of a representative sample of 724 nurses from 30 German hospitals. Participants predominantly remembered medication errors. Structural and organizational factors were rated as most important causes of errors. Reporting rates were considered low; this was explained by organizational barriers. Nurses in large part expressed having suffered from mental problems after error events. Nurses' perception focussing on medication errors seems to be influenced by current discussions which are mainly medication-related. This priority should be revised. Hospitals' risk management should concentrate on organizational deficits and positive error cultures. Decision makers are requested to tackle structural problems such as staff shortage.

  16. Inborn anemias in mice. Comprehensive progress report to accompany twenty-first renewal proposal, 1 May 1973--30 April 1976

    Energy Technology Data Exchange (ETDEWEB)

    Russell, E.S.; Bernstein, S.E.

    1976-05-01

    Progress is reported on the delineation of inborn anemias of the laboratory mouse, carried out by preparation of genetically homogeneous stocks segregating only for anemia-producing genes; by descriptions of each condition at all stages in the life history; by determination of tissue-sites of primary gene action through transplantation and parabiosis experiments; by analysis of reactions of normal and anemic mice to a variety of stressful stimuli, including x-irradiation and hypoxia; and by histological and biochemical study of normal vs. abnormal blood-forming tissue. At present 12 single-gene induced anemias are known in the mouse, plus one with multifactorial inheritance.

  17. Temperature-mediated phase transformation, pore geometry and pore hysteresis transformation of borohydride derived in-born porous zirconium hydroxide nanopowders

    Science.gov (United States)

    Nayak, Nadiya B.; Nayak, Bibhuti B.

    2016-05-01

    Development of in-born porous nature of zirconium hydroxide nanopowders through a facile hydrogen (H2) gas-bubbles assisted borohydride synthesis route using sodium borohydride (NaBH4) and novel information on the temperature-mediated phase transformation, pore geometry as well as pore hysteresis transformation of in-born porous zirconium hydroxide nanopowders with the help of X-ray diffraction (XRD), Brunauer-Emmett-Teller (BET) isotherm and Transmission Electron Microscopy (TEM) images are the main theme of this research work. Without any surfactants or pore forming agents, the borohydride derived amorphous nature of porous powders was stable up to 500 °C and then the seed crystals start to develop within the loose amorphous matrix and trapping the inter-particulate voids, which led to develop the porous nature of tetragonal zirconium oxide at 600 °C and further sustain this porous nature as well as tetragonal phase of zirconium oxide up to 800 °C. The novel hydrogen (H2) gas-bubbles assisted borohydride synthesis route led to develop thermally stable porous zirconium hydroxide/oxide nanopowders with an adequate pore size, pore volume, and surface area and thus these porous materials are further suggested for promising use in different areas of applications.

  18. Sequence Classification: 890773 [

    Lifescience Database Archive (English)

    Full Text Available oline as sole nitrogen source; deficiency of the human homolog causes HPII, an autosomal recessive inborn error of metabolism; Put2p || http://www.ncbi.nlm.nih.gov/protein/6321826 ...

  19. Hyperhomocysteinemia: genetic determinants and selected mouse models

    National Research Council Canada - National Science Library

    Gilfix, Brian M

    2003-01-01

    .... Although severe hyperhomocysteinemia is found in a number of inborn errors of metabolism, mild hyperhomocysteinemia is of concern because of its prevalence in the general population and its effect...

  20. Neonatal lactic acidosis, complex I/IV deficiency, and fetal cerebral disruption

    NARCIS (Netherlands)

    van Straaten, HLM; van Tintelen, JP; Trijbels, JMF; van den Heuvel, LP; Troost, D; Rozemuller, JM; Duran, M; de Vries, LS; Schuelke, M; Barth, PG

    2005-01-01

    Cerebral developmental abnormalities occur in various inborn errors of metabolism including peroxisomal deficiencies, pyruvate dehydrogenase complex deficiency and others. Associations with abnormalities of the respiratory chain are rare. Here we report male and female siblings with microcephaly, a

  1. Lesch-Nyhan Syndrome: Disorder of Self-mutilating Behavior

    National Research Council Canada - National Science Library

    Jathar, Prasad; Panse, Amey M; Jathar, Madhura; Gawali, Pritesh N

    2016-01-01

    Lesch-Nyhan syndrome (LNS), a rare inborn error of metabolism, is characterized by self-injurious behavior, which results in partial or total destruction of oral and perioral tissues and/ or fingers...

  2. Disease: H01197 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available iciency is a recessive inborn error of metabolism characterized by megaloblastic anemia and cerebral folate ...2012) PMID:21388369 (description, gene, drug) Wijesekara N Dihydrofolate reductase mutations-associated megaloblastic anemia

  3. CAD mutations and uridine-responsive epileptic encephalopathy

    NARCIS (Netherlands)

    Koch, J.; Mayr, J.A.; Alhaddad, B.; Rauscher, C.; Bierau, J.; Kovacs-Nagy, R.; Coene, K.L.M.; Bader, I.; Holzhacker, M.; Prokisch, H.; Venselaar, H.; Wevers, R.A.; Distelmaier, F.; Polster, T.; Leiz, S.; Betzler, C.; Strom, T.M.; Sperl, W.; Meitinger, T.; Wortmann, S.B.; Haack, T.B.

    2017-01-01

    Unexplained global developmental delay and epilepsy in childhood pose a major socioeconomic burden. Progress in defining the molecular bases does not often translate into effective treatment. Notable exceptions include certain inborn errors of metabolism amenable to dietary intervention. CAD encodes

  4. Genetics Home Reference: congenital sucrase-isomaltase deficiency

    Science.gov (United States)

    ... down into glucose and another simple sugar called fructose, and maltose is broken down into two glucose ... Encyclopedia: Abdominal bloating MedlinePlus Encyclopedia: Inborn errors of metabolism MedlinePlus Encyclopedia: Malabsorption General Information from MedlinePlus (5 ...

  5. The Acute Temporary Peritoneal Dialysis in Neonates: A Five-Year Experience

    Directory of Open Access Journals (Sweden)

    Seyedeh Fatemeh Khatami

    2015-06-01

    Conclusion: PD is an effective treatment for seriously ill newborns with life-threatening conditions such as acute renal failure or certain inborn errors of metabolism. However, mortality rate remains high due to the severity of underlying diseases and comorbidities.

  6. Evaluation of quality of life in PKU before and after introducing tetrahydrobiopterin (BH4) : A prospective multi-center cohort study

    NARCIS (Netherlands)

    Demirdas, Serwet; Maurice-Stam, Heleen; Boelen, Carolien C. A.; Hofstede, Floris C.; Janssen, Mirian C. H.; Langendonk, Janneke G.; Mulder, Margot F.; Rubio-Gozalbo, M. Estela; van Spronsen, FrancJan; de Vries, Maaike; Grootenhuis, Martha A.; Bosch, Annet M.

    2013-01-01

    Background: Phenylketonuria (PKU) is a rare inborn error of metabolism caused by phenylalanine hydroxylase enzyme (PAH) deficiency. Treatment constitutes a strict Phe restricted diet with unpalatable amino acid supplements. Residual PAH activity enhancement with its cofactor tetrahydrobiopterin (BH4

  7. Evaluation of quality of life in PKU before and after introducing tetrahydrobiopterin (BH4) : A prospective multi-center cohort study

    NARCIS (Netherlands)

    Demirdas, Serwet; Maurice-Stam, Heleen; Boelen, Carolien C. A.; Hofstede, Floris C.; Janssen, Mirian C. H.; Langendonk, Janneke G.; Mulder, Margot F.; Rubio-Gozalbo, M. Estela; van Spronsen, FrancJan; de Vries, Maaike; Grootenhuis, Martha A.; Bosch, Annet M.

    2013-01-01

    Background: Phenylketonuria (PKU) is a rare inborn error of metabolism caused by phenylalanine hydroxylase enzyme (PAH) deficiency. Treatment constitutes a strict Phe restricted diet with unpalatable amino acid supplements. Residual PAH activity enhancement with its cofactor tetrahydrobiopterin (BH4

  8. Disease: H01032 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available -acetylglutamate is the absolutely required allosteric activator of the first urea cycle enzyme carbamoylpho...S) deficiency is a rare inborn error of metabolism affecting ammonia detoxification in the urea cycle. The N

  9. 34 CFR 303.16 - Infants and toddlers with disabilities.

    Science.gov (United States)

    2010-07-01

    ..., including fetal alcohol syndrome; and severe attachment disorders. Note 2: With respect to paragraph (b) of... conditions include chromosomal abnormalities; genetic or congenital disorders; severe sensory impairments, including hearing and vision; inborn errors of metabolism; disorders reflecting disturbance of...

  10. Generalized Gaussian Error Calculus

    CERN Document Server

    Grabe, Michael

    2010-01-01

    For the first time in 200 years Generalized Gaussian Error Calculus addresses a rigorous, complete and self-consistent revision of the Gaussian error calculus. Since experimentalists realized that measurements in general are burdened by unknown systematic errors, the classical, widespread used evaluation procedures scrutinizing the consequences of random errors alone turned out to be obsolete. As a matter of course, the error calculus to-be, treating random and unknown systematic errors side by side, should ensure the consistency and traceability of physical units, physical constants and physical quantities at large. The generalized Gaussian error calculus considers unknown systematic errors to spawn biased estimators. Beyond, random errors are asked to conform to the idea of what the author calls well-defined measuring conditions. The approach features the properties of a building kit: any overall uncertainty turns out to be the sum of a contribution due to random errors, to be taken from a confidence inter...

  11. Classification of Spreadsheet Errors

    OpenAIRE

    Rajalingham, Kamalasen; Chadwick, David R.; Knight, Brian

    2008-01-01

    This paper describes a framework for a systematic classification of spreadsheet errors. This classification or taxonomy of errors is aimed at facilitating analysis and comprehension of the different types of spreadsheet errors. The taxonomy is an outcome of an investigation of the widespread problem of spreadsheet errors and an analysis of specific types of these errors. This paper contains a description of the various elements and categories of the classification and is supported by appropri...

  12. Glucide metabolism disorders (excluding glycogen myopathies).

    Science.gov (United States)

    Klepper, Joerg

    2013-01-01

    Glucide metabolism comprises pathways for transport, intermediate metabolism, utilization, and storage of carbohydrates. Defects affect multiple organs and present as systemic diseases. Neurological symptoms result from hypoglycemia, lactic acidosis, or inadequate storage of complex glucide molecules in neurological tissues. In glycogen storage disorders hypoglycemia indicates hepatic involvement, weakness and muscle cramps muscle involvement. Hypoglycemia is also the leading neurological symptom in disorders of gluconeogenesis. Disorders of galactose and fructose metabolism are rare, detectable by neonatal screening, and manifest following dietary intake of these sugars. Rare defects within the pentose metabolism constitute a new area of inborn metabolic disorders and may present with neurological symptoms. Treatment of these disorders involves the avoidance of fasting, dietary treatment eliminating specific carbohydrates, and enzyme replacement therapy in individual glycogen storage diseases.GLUT1 deficiency syndrome, a specific disorder of glucose transport into brain, results in global developmental delay, early-onset epilepsy, and a complex movement disorder. Treatment with a high-fat, low-carbohydrate ketogenic diet provides ketones as an alternative fuel to the brain and restores brain energy metabolism. Recently paroxysmal exertion-induced dyskinesia and stomatin-deficient cryohydrocytosis have been identified as an allelic disorder to GLUT1 deficiency equally responding to a ketogenic diet. Copyright © 2013 Elsevier B.V. All rights reserved.

  13. Gene transfer for inherited metabolic disorders of the liver: immunological challenges.

    Science.gov (United States)

    Gordts, Stephanie C; Van Craeyveld, Eline; Jacobs, Frank; De Geest, Bart

    2011-01-01

    Hepatocytes are a key target for gene transfer directed at correction of inborn errors of metabolism. The theoretical potential of hepatocyte-directed gene transfer contrasts with the hurdles for clinical translation of this technology. Innate immune responses following gene transfer are initiated by recognition of pathogen-associated molecular patterns by pattern recognition receptors like Toll-like receptors. Adaptive immune responses may constitute the most significant hurdle for efficient gene transfer. Besides the challenge imposed by adaptive immune responses against the vector and the potential problem of pre-existing immunity, immune responses against the transgene product may also constitute an obstacle. The liver is a tolerogenic organ. Naive T cells encounter liver antigens initially in the liver, rather than in lymphoid tissue. Lymph nodes and the spleen are anatomical compartments that provide a particular microarchitecture and microenvironment for the induction of immunity. In contrast, antigen presentation in the liver takes place in a completely different microarchitecture and microenvironment. This is a key aspect of the hepatic adaptive immune tolerance induction. Consistent with the tolerogenic nature of the liver microenvironment, the risk of antibody formation against the transgene product may be limited in the setting of hepatocyte-directed gene transfer and specifically by restricting transgene expression to hepatocytes by use of hepatocyte-specific expression cassettes. However, it is unclear to which extent animal experimental data following gene transfer predict immune responses in humans. Extrapolations from animals to humans are required but should be performed with sufficient insight into the dramatic species differences of the immune system.

  14. Vaccines are not associated with metabolic events in children with urea cycle disorders.

    Science.gov (United States)

    Morgan, Thomas M; Schlegel, Cameron; Edwards, Kathryn M; Welch-Burke, Teresa; Zhu, Yuwei; Sparks, Robert; Summar, Marshall

    2011-05-01

    Despite the success of childhood immunizations in prevention of infectious diseases, questions remain about the safety of vaccines in medically fragile children with inborn errors of metabolism such as urea cycle disorders (UCDs). Patients with UCDs are subject to hyperammonemic episodes (HAEs) after infection, fever, or other stressors. We sought to assess the risk of HAEs that required urgent care or hospitalization after routine vaccinations in pediatric patients with underlying UCDs. This was a retrospective investigation of vaccine safety in children with UCDs within the longitudinal Rare Diseases Clinical Research Consortium for UCD. Postvaccination exposure periods were defined as 7 or 21 days after any immunization. The association of vaccines and HAEs was modeled by using conditional Poisson regression, adjusting for age, and using a self-controlled case series method including all patients with ≥1 HAE and with any vaccine exposure. The study enrolled 169 children younger than 18 years. Of these children, 74 had records of at least 1 HAE and at least 1 vaccination. With adjustment for age, there was no increase in relative incidence of HAEs in either the 7-day (1.31 [95% confidence interval (CI): 0.80-2.13]) or 21-day (1.05 [95% CI: 0.74-1.47]) exposure period after vaccination compared with HAEs outside of the vaccination periods. No vaccine type was associated with significantly more HAEs. We found no statistically significant association between childhood immunizations and HAEs in children with UCDs. The results support the safety of immunization in this medically vulnerable population.

  15. Reducing medication errors.

    Science.gov (United States)

    Nute, Christine

    2014-11-25

    Most nurses are involved in medicines management, which is integral to promoting patient safety. Medicines management is prone to errors, which depending on the error can cause patient injury, increased hospital stay and significant legal expenses. This article describes a new approach to help minimise drug errors within healthcare settings where medications are prescribed, dispensed or administered. The acronym DRAINS, which considers all aspects of medicines management before administration, was devised to reduce medication errors on a cardiothoracic intensive care unit.

  16. Demand Forecasting Errors

    OpenAIRE

    Mackie, Peter; Nellthorp, John; Laird, James

    2005-01-01

    Demand forecasts form a key input to the economic appraisal. As such any errors present within the demand forecasts will undermine the reliability of the economic appraisal. The minimization of demand forecasting errors is therefore important in the delivery of a robust appraisal. This issue is addressed in this note by introducing the key issues, and error types present within demand fore...

  17. When errors are rewarding

    NARCIS (Netherlands)

    Bruijn, E.R.A. de; Lange, F.P. de; Cramon, D.Y. von; Ullsperger, M.

    2009-01-01

    For social beings like humans, detecting one's own and others' errors is essential for efficient goal-directed behavior. Although one's own errors are always negative events, errors from other persons may be negative or positive depending on the social context. We used neuroimaging to disentangle br

  18. Efficacy and outcome of expanded newborn screening for metabolic diseases - Report of 10 years from South-West Germany *

    Directory of Open Access Journals (Sweden)

    Mengel Eugen

    2011-06-01

    Full Text Available Abstract Background National newborn screening programmes based on tandem-mass spectrometry (MS/MS and other newborn screening (NBS technologies show a substantial variation in number and types of disorders included in the screening panel. Once established, these methods offer the opportunity to extend newborn screening panels without significant investment and cost. However, systematic evaluations of newborn screening programmes are rare, most often only describing parts of the whole process from taking blood samples to long-term evaluation of outcome. Methods In a prospective single screening centre observational study 373 cases with confirmed diagnosis of a metabolic disorder from a total cohort of 1,084,195 neonates screened in one newborn screening laboratory between January 1, 1999, and June 30, 2009 and subsequently treated and monitored in five specialised centres for inborn errors of metabolism were examined. Process times for taking screening samples, obtaining results, initiating diagnostic confirmation and starting treatment as well as the outcome variables metabolic decompensations, clinical status, and intellectual development at a mean age of 3.3 years were evaluated. Results Optimal outcome is achieved especially for the large subgroup of patients with medium-chain acyl-CoA dehydrogenase deficiency. Kaplan-Meier-analysis revealed disorder related patterns of decompensation. Urea cycle disorders, organic acid disorders, and amino acid disorders show an early high and continuous risk, medium-chain acyl-CoA dehydrogenase deficiency a continuous but much lower risk for decompensation, other fatty acid oxidation disorders an intermediate risk increasing towards the end of the first year. Clinical symptoms seem inevitable in a small subgroup of patients with very early disease onset. Later decompensation can not be completely prevented despite pre-symptomatic start of treatment. Metabolic decompensation does not necessarily result in

  19. Systematic error revisited

    Energy Technology Data Exchange (ETDEWEB)

    Glosup, J.G.; Axelrod, M.C.

    1996-08-05

    The American National Standards Institute (ANSI) defines systematic error as An error which remains constant over replicative measurements. It would seem from the ANSI definition that a systematic error is not really an error at all; it is merely a failure to calibrate the measurement system properly because if error is constant why not simply correct for it? Yet systematic errors undoubtedly exist, and they differ in some fundamental way from the kind of errors we call random. Early papers by Eisenhart and by Youden discussed systematic versus random error with regard to measurements in the physical sciences, but not in a fundamental way, and the distinction remains clouded by controversy. The lack of a general agreement on definitions has led to a plethora of different and often confusing methods on how to quantify the total uncertainty of a measurement that incorporates both its systematic and random errors. Some assert that systematic error should be treated by non- statistical methods. We disagree with this approach, and we provide basic definitions based on entropy concepts, and a statistical methodology for combining errors and making statements of total measurement of uncertainty. We illustrate our methods with radiometric assay data.

  20. Genetic and bibliographic information: ASAH1 [GenLibi

    Lifescience Database Archive (English)

    Full Text Available matosis (MeSH); Lysosomal Storage Diseases (MeSH) Nervous System Diseases (C10) > Central Nervous System Diseases... (C10.228) > Brain Diseases (C10.228.140) > Brain Diseases, Metabolic (C10.228.140.163) > Brain Diseases..., Metabolic, Inborn (C10.228.140.163.100) > Lysosomal Storage Diseases, Nervous ...s (C10.228.140.163.100.435.825.250) Congenital, Hereditary, and Neonatal Diseases and Abnormalities (C16) > Genetic Diseases..., Inborn (C16.320) > Metabolism, Inborn Errors (C16.320.565) > Brain Diseases

  1. Probabilistic quantum error correction

    CERN Document Server

    Fern, J; Fern, Jesse; Terilla, John

    2002-01-01

    There are well known necessary and sufficient conditions for a quantum code to correct a set of errors. We study weaker conditions under which a quantum code may correct errors with probabilities that may be less than one. We work with stabilizer codes and as an application study how the nine qubit code, the seven qubit code, and the five qubit code perform when there are errors on more than one qubit. As a second application, we discuss the concept of syndrome quality and use it to suggest a way that quantum error correction can be practically improved.

  2. Inborn anemias in mice. Progress report to accompany twenty-first renewal proposal, 1 May 1975--30 April 1976

    Energy Technology Data Exchange (ETDEWEB)

    Russell, E.S.; Bernstein, S.E.

    1976-05-15

    Progress is reported on studies on hereditary anemias of mice. At present under study are four macrocytic anemias, four hemolytic anemias, nonhemolytic microcytic anemia, transitory siderocytic anemia, sex-linked iron-transport anemia, and the autoimmune hemolytic anemia of NZB. Each of these blood dyscrasias is caused by the action of a unique mutant gene, each of which determines the structure of different intracellular molecules, and thus controls a different metabolic process. Thus our wide range of different hereditary anemias has considerable potential for uncovering many different aspects of hemopoietic homeostatic mechanisms in the mouse.

  3. Correction for quadrature errors

    DEFF Research Database (Denmark)

    Netterstrøm, A.; Christensen, Erik Lintz

    1994-01-01

    In high bandwidth radar systems it is necessary to use quadrature devices to convert the signal to/from baseband. Practical problems make it difficult to implement a perfect quadrature system. Channel imbalance and quadrature phase errors in the transmitter and the receiver result in error signal...

  4. ERRORS AND CORRECTION

    Institute of Scientific and Technical Information of China (English)

    1998-01-01

    To err is human . Since the 1960s, most second language teachers or language theorists have regarded errors as natural and inevitable in the language learning process . Instead of regarding them as terrible and disappointing, teachers have come to realize their value. This paper will consider these values, analyze some errors and propose some effective correction techniques.

  5. ERROR AND ERROR CORRECTION AT ELEMENTARY LEVEL

    Institute of Scientific and Technical Information of China (English)

    1994-01-01

    Introduction Errors are unavoidable in language learning, however, to a great extent, teachers in most middle schools in China regard errors as undesirable, a sign of failure in language learning. Most middle schools are still using the grammar-translation method which aims at encouraging students to read scientific works and enjoy literary works. The other goals of this method are to gain a greater understanding of the first language and to improve the students’ ability to cope with difficult subjects and materials, i.e. to develop the students’ minds. The practical purpose of using this method is to help learners pass the annual entrance examination. "To achieve these goals, the students must first learn grammar and vocabulary,... Grammar is taught deductively by means of long and elaborate explanations... students learn the rules of the language rather than its use." (Tang Lixing, 1983:11-12)

  6. Errors on errors - Estimating cosmological parameter covariance

    CERN Document Server

    Joachimi, Benjamin

    2014-01-01

    Current and forthcoming cosmological data analyses share the challenge of huge datasets alongside increasingly tight requirements on the precision and accuracy of extracted cosmological parameters. The community is becoming increasingly aware that these requirements not only apply to the central values of parameters but, equally important, also to the error bars. Due to non-linear effects in the astrophysics, the instrument, and the analysis pipeline, data covariance matrices are usually not well known a priori and need to be estimated from the data itself, or from suites of large simulations. In either case, the finite number of realisations available to determine data covariances introduces significant biases and additional variance in the errors on cosmological parameters in a standard likelihood analysis. Here, we review recent work on quantifying these biases and additional variances and discuss approaches to remedy these effects.

  7. Proofreading for word errors.

    Science.gov (United States)

    Pilotti, Maura; Chodorow, Martin; Agpawa, Ian; Krajniak, Marta; Mahamane, Salif

    2012-04-01

    Proofreading (i.e., reading text for the purpose of detecting and correcting typographical errors) is viewed as a component of the activity of revising text and thus is a necessary (albeit not sufficient) procedural step for enhancing the quality of a written product. The purpose of the present research was to test competing accounts of word-error detection which predict factors that may influence reading and proofreading differently. Word errors, which change a word into another word (e.g., from --> form), were selected for examination because they are unlikely to be detected by automatic spell-checking functions. Consequently, their detection still rests mostly in the hands of the human proofreader. Findings highlighted the weaknesses of existing accounts of proofreading and identified factors, such as length and frequency of the error in the English language relative to frequency of the correct word, which might play a key role in detection of word errors.

  8. Uncorrected refractive errors

    Directory of Open Access Journals (Sweden)

    Kovin S Naidoo

    2012-01-01

    Full Text Available Global estimates indicate that more than 2.3 billion people in the world suffer from poor vision due to refractive error; of which 670 million people are considered visually impaired because they do not have access to corrective treatment. Refractive errors, if uncorrected, results in an impaired quality of life for millions of people worldwide, irrespective of their age, sex and ethnicity. Over the past decade, a series of studies using a survey methodology, referred to as Refractive Error Study in Children (RESC, were performed in populations with different ethnic origins and cultural settings. These studies confirmed that the prevalence of uncorrected refractive errors is considerably high for children in low-and-middle-income countries. Furthermore, uncorrected refractive error has been noted to have extensive social and economic impacts, such as limiting educational and employment opportunities of economically active persons, healthy individuals and communities. The key public health challenges presented by uncorrected refractive errors, the leading cause of vision impairment across the world, require urgent attention. To address these issues, it is critical to focus on the development of human resources and sustainable methods of service delivery. This paper discusses three core pillars to addressing the challenges posed by uncorrected refractive errors: Human Resource (HR Development, Service Development and Social Entrepreneurship.

  9. Uncorrected refractive errors.

    Science.gov (United States)

    Naidoo, Kovin S; Jaggernath, Jyoti

    2012-01-01

    Global estimates indicate that more than 2.3 billion people in the world suffer from poor vision due to refractive error; of which 670 million people are considered visually impaired because they do not have access to corrective treatment. Refractive errors, if uncorrected, results in an impaired quality of life for millions of people worldwide, irrespective of their age, sex and ethnicity. Over the past decade, a series of studies using a survey methodology, referred to as Refractive Error Study in Children (RESC), were performed in populations with different ethnic origins and cultural settings. These studies confirmed that the prevalence of uncorrected refractive errors is considerably high for children in low-and-middle-income countries. Furthermore, uncorrected refractive error has been noted to have extensive social and economic impacts, such as limiting educational and employment opportunities of economically active persons, healthy individuals and communities. The key public health challenges presented by uncorrected refractive errors, the leading cause of vision impairment across the world, require urgent attention. To address these issues, it is critical to focus on the development of human resources and sustainable methods of service delivery. This paper discusses three core pillars to addressing the challenges posed by uncorrected refractive errors: Human Resource (HR) Development, Service Development and Social Entrepreneurship.

  10. Errors in Radiologic Reporting

    Directory of Open Access Journals (Sweden)

    Esmaeel Shokrollahi

    2010-05-01

    Full Text Available Given that the report is a professional document and bears the associated responsibilities, all of the radiologist's errors appear in it, either directly or indirectly. It is not easy to distinguish and classify the mistakes made when a report is prepared, because in most cases the errors are complex and attributable to more than one cause and because many errors depend on the individual radiologists' professional, behavioral and psychological traits."nIn fact, anyone can make a mistake, but some radiologists make more mistakes, and some types of mistakes are predictable to some extent."nReporting errors can be categorized differently:"nUniversal vs. individual"nHuman related vs. system related"nPerceptive vs. cognitive errors"n1. Descriptive "n2. Interpretative "n3. Decision related Perceptive errors"n1. False positive "n2. False negative"n Nonidentification "n Erroneous identification "nCognitive errors "n Knowledge-based"n Psychological  

  11. Errors in neuroradiology.

    Science.gov (United States)

    Caranci, Ferdinando; Tedeschi, Enrico; Leone, Giuseppe; Reginelli, Alfonso; Gatta, Gianluca; Pinto, Antonio; Squillaci, Ettore; Briganti, Francesco; Brunese, Luca

    2015-09-01

    Approximately 4 % of radiologic interpretation in daily practice contains errors and discrepancies that should occur in 2-20 % of reports. Fortunately, most of them are minor degree errors, or if serious, are found and corrected with sufficient promptness; obviously, diagnostic errors become critical when misinterpretation or misidentification should significantly delay medical or surgical treatments. Errors can be summarized into four main categories: observer errors, errors in interpretation, failure to suggest the next appropriate procedure, failure to communicate in a timely and a clinically appropriate manner. Misdiagnosis/misinterpretation percentage should rise up in emergency setting and in the first moments of the learning curve, as in residency. Para-physiological and pathological pitfalls in neuroradiology include calcification and brain stones, pseudofractures, and enlargement of subarachnoid or epidural spaces, ventricular system abnormalities, vascular system abnormalities, intracranial lesions or pseudolesions, and finally neuroradiological emergencies. In order to minimize the possibility of error, it is important to be aware of various presentations of pathology, obtain clinical information, know current practice guidelines, review after interpreting a diagnostic study, suggest follow-up studies when appropriate, communicate significant abnormal findings appropriately and in a timely fashion directly with the treatment team.

  12. Inpatients’ medical prescription errors

    Directory of Open Access Journals (Sweden)

    Aline Melo Santos Silva

    2009-09-01

    Full Text Available Objective: To identify and quantify the most frequent prescription errors in inpatients’ medical prescriptions. Methods: A survey of prescription errors was performed in the inpatients’ medical prescriptions, from July 2008 to May 2009 for eight hours a day. Rresults: At total of 3,931 prescriptions was analyzed and 362 (9.2% prescription errors were found, which involved the healthcare team as a whole. Among the 16 types of errors detected in prescription, the most frequent occurrences were lack of information, such as dose (66 cases, 18.2% and administration route (26 cases, 7.2%; 45 cases (12.4% of wrong transcriptions to the information system; 30 cases (8.3% of duplicate drugs; doses higher than recommended (24 events, 6.6% and 29 cases (8.0% of prescriptions with indication but not specifying allergy. Cconclusion: Medication errors are a reality at hospitals. All healthcare professionals are responsible for the identification and prevention of these errors, each one in his/her own area. The pharmacist is an essential professional in the drug therapy process. All hospital organizations need a pharmacist team responsible for medical prescription analyses before preparation, dispensation and administration of drugs to inpatients. This study showed that the pharmacist improves the inpatient’s safety and success of prescribed therapy.

  13. Web-based newborn screening system for metabolic diseases: machine learning versus clinicians.

    Science.gov (United States)

    Chen, Wei-Hsin; Hsieh, Sheau-Ling; Hsu, Kai-Ping; Chen, Han-Ping; Su, Xing-Yu; Tseng, Yi-Ju; Chien, Yin-Hsiu; Hwu, Wuh-Liang; Lai, Feipei

    2013-05-23

    A hospital information system (HIS) that integrates screening data and interpretation of the data is routinely requested by hospitals and parents. However, the accuracy of disease classification may be low because of the disease characteristics and the analytes used for classification. The objective of this study is to describe a system that enhanced the neonatal screening system of the Newborn Screening Center at the National Taiwan University Hospital. The system was designed and deployed according to a service-oriented architecture (SOA) framework under the Web services .NET environment. The system consists of sample collection, testing, diagnosis, evaluation, treatment, and follow-up services among collaborating hospitals. To improve the accuracy of newborn screening, machine learning and optimal feature selection mechanisms were investigated for screening newborns for inborn errors of metabolism. The framework of the Newborn Screening Hospital Information System (NSHIS) used the embedded Health Level Seven (HL7) standards for data exchanges among heterogeneous platforms integrated by Web services in the C# language. In this study, machine learning classification was used to predict phenylketonuria (PKU), hypermethioninemia, and 3-methylcrotonyl-CoA-carboxylase (3-MCC) deficiency. The classification methods used 347,312 newborn dried blood samples collected at the Center between 2006 and 2011. Of these, 220 newborns had values over the diagnostic cutoffs (positive cases) and 1557 had values that were over the screening cutoffs but did not meet the diagnostic cutoffs (suspected cases). The original 35 analytes and the manifested features were ranked based on F score, then combinations of the top 20 ranked features were selected as input features to support vector machine (SVM) classifiers to obtain optimal feature sets. These feature sets were tested using 5-fold cross-validation and optimal models were generated. The datasets collected in year 2011 were used as

  14. Error monitoring in musicians

    Directory of Open Access Journals (Sweden)

    Clemens eMaidhof

    2013-07-01

    Full Text Available To err is human, and hence even professional musicians make errors occasionally during their performances. This paper summarizes recent work investigating error monitoring in musicians, i.e. the processes and their neural correlates associated with the monitoring of ongoing actions and the detection of deviations from intended sounds. EEG Studies reported an early component of the event-related potential (ERP occurring before the onsets of pitch errors. This component, which can be altered in musicians with focal dystonia, likely reflects processes of error detection and/or error compensation, i.e. attempts to cancel the undesired sensory consequence (a wrong tone a musician is about to perceive. Thus, auditory feedback seems not to be a prerequisite for error detection, consistent with previous behavioral results. In contrast, when auditory feedback is externally manipulated and thus unexpected, motor performance can be severely distorted, although not all feedback alterations result in performance impairments. Recent studies investigating the neural correlates of feedback processing showed that unexpected feedback elicits an ERP component after note onsets, which shows larger amplitudes during music performance than during mere perception of the same musical sequences. Hence, these results stress the role of motor actions for the processing of auditory information. Furthermore, recent methodological advances like the combination of 3D motion capture techniques with EEG will be discussed. Such combinations of different measures can potentially help to disentangle the roles of different feedback types such as proprioceptive and auditory feedback, and in general to derive at a better understanding of the complex interactions between the motor and auditory domain during error monitoring. Finally, outstanding questions and future directions in this context will be discussed.

  15. Smoothing error pitfalls

    Science.gov (United States)

    von Clarmann, T.

    2014-09-01

    The difference due to the content of a priori information between a constrained retrieval and the true atmospheric state is usually represented by a diagnostic quantity called smoothing error. In this paper it is shown that, regardless of the usefulness of the smoothing error as a diagnostic tool in its own right, the concept of the smoothing error as a component of the retrieval error budget is questionable because it is not compliant with Gaussian error propagation. The reason for this is that the smoothing error does not represent the expected deviation of the retrieval from the true state but the expected deviation of the retrieval from the atmospheric state sampled on an arbitrary grid, which is itself a smoothed representation of the true state; in other words, to characterize the full loss of information with respect to the true atmosphere, the effect of the representation of the atmospheric state on a finite grid also needs to be considered. The idea of a sufficiently fine sampling of this reference atmospheric state is problematic because atmospheric variability occurs on all scales, implying that there is no limit beyond which the sampling is fine enough. Even the idealization of infinitesimally fine sampling of the reference state does not help, because the smoothing error is applied to quantities which are only defined in a statistical sense, which implies that a finite volume of sufficient spatial extent is needed to meaningfully discuss temperature or concentration. Smoothing differences, however, which play a role when measurements are compared, are still a useful quantity if the covariance matrix involved has been evaluated on the comparison grid rather than resulting from interpolation and if the averaging kernel matrices have been evaluated on a grid fine enough to capture all atmospheric variations that the instruments are sensitive to. This is, under the assumptions stated, because the undefined component of the smoothing error, which is the

  16. Learning from Errors

    Directory of Open Access Journals (Sweden)

    MA. Lendita Kryeziu

    2015-06-01

    Full Text Available “Errare humanum est”, a well known and widespread Latin proverb which states that: to err is human, and that people make mistakes all the time. However, what counts is that people must learn from mistakes. On these grounds Steve Jobs stated: “Sometimes when you innovate, you make mistakes. It is best to admit them quickly, and get on with improving your other innovations.” Similarly, in learning new language, learners make mistakes, thus it is important to accept them, learn from them, discover the reason why they make them, improve and move on. The significance of studying errors is described by Corder as: “There have always been two justifications proposed for the study of learners' errors: the pedagogical justification, namely that a good understanding of the nature of error is necessary before a systematic means of eradicating them could be found, and the theoretical justification, which claims that a study of learners' errors is part of the systematic study of the learners' language which is itself necessary to an understanding of the process of second language acquisition” (Corder, 1982; 1. Thus the importance and the aim of this paper is analyzing errors in the process of second language acquisition and the way we teachers can benefit from mistakes to help students improve themselves while giving the proper feedback.

  17. Error Correction in Classroom

    Institute of Scientific and Technical Information of China (English)

    Dr. Grace Zhang

    2000-01-01

    Error correction is an important issue in foreign language acquisition. This paper investigates how students feel about the way in which error correction should take place in a Chinese-as-a foreign-language classroom, based on empirical data of a large scale. The study shows that there is a general consensus that error correction is necessary. In terms of correction strategy, the students preferred a combination of direct and indirect corrections, or a direct only correction. The former choice indicates that students would be happy to take either so long as the correction gets done.Most students didn't mind peer correcting provided it is conducted in a constructive way. More than halfofthe students would feel uncomfortable ifthe same error they make in class is corrected consecutively more than three times. Taking these findings into consideration, we may want to cncourage peer correcting, use a combination of correction strategies (direct only if suitable) and do it in a non-threatening and sensitive way. It is hoped that this study would contribute to the effectiveness of error correction in a Chinese language classroom and it may also have a wider implication on other languages.

  18. Prediction of potential antimalarial targets of artemisinin based on protein information from whole genome of Plasmodium falciparum

    Institute of Scientific and Technical Information of China (English)

    HAN LiPing; HUANG Qiang; NAN Peng; ZHONG Yang

    2009-01-01

    On the basis of the genomic data and protein pathway information about Plasmodium falciparum clone 3D7 from the NCBI taxonomy database and the KEGG database,eight key protein enzymes in the signal pathways were selected to perform molecular docking with artemisinin.The binding modes obtained from the molecular docking suggested that purine nucleoside phosphorylase (pfPNP),peptide deformylase (pfPDF),and ribose 5-phosphate isomerase (pfRpiA) may be involved in the antimalarial mode of action of artemisinin.Artemisinin exhibited its antimalarial activity probably by interfering with the metabolic pathways of purine,pyrimidine,methionine,glyoxylate and dicarboxylate,or pentose phosphate.

  19. Errors in Neonatology

    Directory of Open Access Journals (Sweden)

    Antonio Boldrini

    2013-06-01

    Full Text Available Introduction: Danger and errors are inherent in human activities. In medical practice errors can lean to adverse events for patients. Mass media echo the whole scenario. Methods: We reviewed recent published papers in PubMed database to focus on the evidence and management of errors in medical practice in general and in Neonatology in particular. We compared the results of the literature with our specific experience in Nina Simulation Centre (Pisa, Italy. Results: In Neonatology the main error domains are: medication and total parenteral nutrition, resuscitation and respiratory care, invasive procedures, nosocomial infections, patient identification, diagnostics. Risk factors include patients’ size, prematurity, vulnerability and underlying disease conditions but also multidisciplinary teams, working conditions providing fatigue, a large variety of treatment and investigative modalities needed. Discussion and Conclusions: In our opinion, it is hardly possible to change the human beings but it is likely possible to change the conditions under they work. Voluntary errors report systems can help in preventing adverse events. Education and re-training by means of simulation can be an effective strategy too. In Pisa (Italy Nina (ceNtro di FormazIone e SimulazioNe NeonAtale is a simulation center that offers the possibility of a continuous retraining for technical and non-technical skills to optimize neonatological care strategies. Furthermore, we have been working on a novel skill trainer for mechanical ventilation (MEchatronic REspiratory System SImulator for Neonatal Applications, MERESSINA. Finally, in our opinion national health policy indirectly influences risk for errors. Proceedings of the 9th International Workshop on Neonatology · Cagliari (Italy · October 23rd-26th, 2013 · Learned lessons, changing practice and cutting-edge research

  20. Error Free Software

    Science.gov (United States)

    1985-01-01

    A mathematical theory for development of "higher order" software to catch computer mistakes resulted from a Johnson Space Center contract for Apollo spacecraft navigation. Two women who were involved in the project formed Higher Order Software, Inc. to develop and market the system of error analysis and correction. They designed software which is logically error-free, which, in one instance, was found to increase productivity by 600%. USE.IT defines its objectives using AXES -- a user can write in English and the system converts to computer languages. It is employed by several large corporations.

  1. LIBERTARISMO & ERROR CATEGORIAL

    Directory of Open Access Journals (Sweden)

    Carlos G. Patarroyo G.

    2009-01-01

    Full Text Available En este artículo se ofrece una defensa del libertarismo frente a dos acusaciones según las cuales éste comete un error categorial. Para ello, se utiliza la filosofía de Gilbert Ryle como herramienta para explicar las razones que fundamentan estas acusaciones y para mostrar por qué, pese a que ciertas versiones del libertarismo que acuden a la causalidad de agentes o al dualismo cartesiano cometen estos errores, un libertarismo que busque en el indeterminismo fisicalista la base de la posibilidad de la libertad humana no necesariamente puede ser acusado de incurrir en ellos.

  2. Metabolic acidosis

    Science.gov (United States)

    Acidosis - metabolic ... Metabolic acidosis occurs when the body produces too much acid. It can also occur when the kidneys are not ... the body. There are several types of metabolic acidosis. Diabetic acidosis develops when acidic substances, known as ...

  3. Metabolic neuropathies

    Science.gov (United States)

    Neuropathy - metabolic ... can be caused by many different things. Metabolic neuropathy may be caused by: A problem with the ... one of the most common causes of metabolic neuropathies. People who are at the highest risk for ...

  4. TCA Cycle Defects and Cancer: When Metabolism Tunes Redox State

    Directory of Open Access Journals (Sweden)

    Simone Cardaci

    2012-01-01

    Full Text Available Inborn defects of the tricarboxylic acid (TCA cycle enzymes have been known for more than twenty years. Until recently, only recessive mutations were described which, although resulted in severe multisystem syndromes, did not predispose to cancer onset. In the last ten years, a causal role in carcinogenesis has been documented for inherited and acquired alterations in three TCA cycle enzymes, succinate dehydrogenase (SDH, fumarate hydratase (FH, and isocitrate dehydrogenase (IDH, pointing towards metabolic alterations as the underlying hallmark of cancer. This paper summarizes the neoplastic alterations of the TCA cycle enzymes focusing on the generation of pseudohypoxic phenotype and the alteration of epigenetic homeostasis as the main tumor-promoting effects of the TCA cycle affecting defects. Moreover, we debate on the ability of these mutations to affect cellular redox state and to promote carcinogenesis by impacting on redox biology.

  5. Orwell's Instructive Errors

    Science.gov (United States)

    Julian, Liam

    2009-01-01

    In this article, the author talks about George Orwell, his instructive errors, and the manner in which Orwell pierced worthless theory, faced facts and defended decency (with fluctuating success), and largely ignored the tradition of accumulated wisdom that has rendered him a timeless teacher--one whose inadvertent lessons, while infrequently…

  6. Challenge and Error: Critical Events and Attention-Related Errors

    Science.gov (United States)

    Cheyne, James Allan; Carriere, Jonathan S. A.; Solman, Grayden J. F.; Smilek, Daniel

    2011-01-01

    Attention lapses resulting from reactivity to task challenges and their consequences constitute a pervasive factor affecting everyday performance errors and accidents. A bidirectional model of attention lapses (error [image omitted] attention-lapse: Cheyne, Solman, Carriere, & Smilek, 2009) argues that errors beget errors by generating attention…

  7. Patient error: a preliminary taxonomy.

    NARCIS (Netherlands)

    Buetow, S.; Kiata, L.; Liew, T.; Kenealy, T.; Dovey, S.; Elwyn, G.

    2009-01-01

    PURPOSE: Current research on errors in health care focuses almost exclusively on system and clinician error. It tends to exclude how patients may create errors that influence their health. We aimed to identify the types of errors that patients can contribute and help manage, especially in primary ca

  8. Automatic Error Analysis Using Intervals

    Science.gov (United States)

    Rothwell, E. J.; Cloud, M. J.

    2012-01-01

    A technique for automatic error analysis using interval mathematics is introduced. A comparison to standard error propagation methods shows that in cases involving complicated formulas, the interval approach gives comparable error estimates with much less effort. Several examples are considered, and numerical errors are computed using the INTLAB…

  9. Imagery of Errors in Typing

    Science.gov (United States)

    Rieger, Martina; Martinez, Fanny; Wenke, Dorit

    2011-01-01

    Using a typing task we investigated whether insufficient imagination of errors and error corrections is related to duration differences between execution and imagination. In Experiment 1 spontaneous error imagination was investigated, whereas in Experiment 2 participants were specifically instructed to imagine errors. Further, in Experiment 2 we…

  10. Error bars in experimental biology.

    Science.gov (United States)

    Cumming, Geoff; Fidler, Fiona; Vaux, David L

    2007-04-09

    Error bars commonly appear in figures in publications, but experimental biologists are often unsure how they should be used and interpreted. In this article we illustrate some basic features of error bars and explain how they can help communicate data and assist correct interpretation. Error bars may show confidence intervals, standard errors, standard deviations, or other quantities. Different types of error bars give quite different information, and so figure legends must make clear what error bars represent. We suggest eight simple rules to assist with effective use and interpretation of error bars.

  11. Video Error Correction Using Steganography

    Directory of Open Access Journals (Sweden)

    Robie David L

    2002-01-01

    Full Text Available The transmission of any data is always subject to corruption due to errors, but video transmission, because of its real time nature must deal with these errors without retransmission of the corrupted data. The error can be handled using forward error correction in the encoder or error concealment techniques in the decoder. This MPEG-2 compliant codec uses data hiding to transmit error correction information and several error concealment techniques in the decoder. The decoder resynchronizes more quickly with fewer errors than traditional resynchronization techniques. It also allows for perfect recovery of differentially encoded DCT-DC components and motion vectors. This provides for a much higher quality picture in an error-prone environment while creating an almost imperceptible degradation of the picture in an error-free environment.

  12. Error-Free Software

    Science.gov (United States)

    1989-01-01

    001 is an integrated tool suited for automatically developing ultra reliable models, simulations and software systems. Developed and marketed by Hamilton Technologies, Inc. (HTI), it has been applied in engineering, manufacturing, banking and software tools development. The software provides the ability to simplify the complex. A system developed with 001 can be a prototype or fully developed with production quality code. It is free of interface errors, consistent, logically complete and has no data or control flow errors. Systems can be designed, developed and maintained with maximum productivity. Margaret Hamilton, President of Hamilton Technologies, also directed the research and development of USE.IT, an earlier product which was the first computer aided software engineering product in the industry to concentrate on automatically supporting the development of an ultrareliable system throughout its life cycle. Both products originated in NASA technology developed under a Johnson Space Center contract.

  13. Kupffer cells modulate hepatic fatty acid oxidation during infection with PR8 influenza.

    Science.gov (United States)

    Tarasenko, Tatyana N; Singh, Larry N; Chatterji-Len, Milani; Zerfas, Patricia M; Cusmano-Ozog, Kristina; McGuire, Peter J

    2015-11-01

    In response to infection, patients with inborn errors of metabolism may develop a functional deterioration termed metabolic decompensation. The biochemical hallmarks of this disruption of metabolic homeostasis are disease specific and may include acidosis, hyperammonemia or hypoglycemia. In a model system previously published by our group, we noted that during influenza infection, mice displayed a depression in hepatic mitochondrial enzymes involved in nitrogen metabolism. Based on these findings, we hypothesized that this normal adaptation may extend to other metabolic pathways, and as such, may impact various inborn errors of metabolism. Since the liver is a critical organ in inborn errors of metabolism, we carried out untargeted metabolomic profiling of livers using mass spectrometry in C57Bl/6 mice infected with influenza to characterize metabolic adaptation. Pathway analysis of metabolomic data revealed reductions in CoA synthesis, and long chain fatty acyl CoA and carnitine species. These metabolic adaptations coincided with a depression in hepatic long chain β-oxidation mRNA and protein. To our surprise, the metabolic changes observed occurred in conjunction with a hepatic innate immune response, as demonstrated by transcriptional profiling and flow cytometry. By employing an immunomodulation strategy to deplete Kupffer cells, we were able to improve the expression of multiple genes involved in β-oxidation. Based on these findings, we are the first to suggest that the role of the liver as an immunologic organ is central in the pathophysiology of hepatic metabolic decompensation in inborn errors of metabolism due to respiratory viral infection.

  14. A Characterization of Prediction Errors

    OpenAIRE

    Meek, Christopher

    2016-01-01

    Understanding prediction errors and determining how to fix them is critical to building effective predictive systems. In this paper, we delineate four types of prediction errors and demonstrate that these four types characterize all prediction errors. In addition, we describe potential remedies and tools that can be used to reduce the uncertainty when trying to determine the source of a prediction error and when trying to take action to remove a prediction errors.

  15. Error Analysis and Its Implication

    Institute of Scientific and Technical Information of China (English)

    崔蕾

    2007-01-01

    Error analysis is the important theory and approach for exploring the mental process of language learner in SLA. Its major contribution is pointing out that intralingual errors are the main reason of the errors during language learning. Researchers' exploration and description of the errors will not only promote the bidirectional study of Error Analysis as both theory and approach, but also give the implication to second language learning.

  16. Error bars in experimental biology

    OpenAIRE

    2007-01-01

    Error bars commonly appear in figures in publications, but experimental biologists are often unsure how they should be used and interpreted. In this article we illustrate some basic features of error bars and explain how they can help communicate data and assist correct interpretation. Error bars may show confidence intervals, standard errors, standard deviations, or other quantities. Different types of error bars give quite different information, and so figure legends must make clear what er...

  17. Diagnostic errors in pediatric radiology

    Energy Technology Data Exchange (ETDEWEB)

    Taylor, George A.; Voss, Stephan D. [Children' s Hospital Boston, Department of Radiology, Harvard Medical School, Boston, MA (United States); Melvin, Patrice R. [Children' s Hospital Boston, The Program for Patient Safety and Quality, Boston, MA (United States); Graham, Dionne A. [Children' s Hospital Boston, The Program for Patient Safety and Quality, Boston, MA (United States); Harvard Medical School, The Department of Pediatrics, Boston, MA (United States)

    2011-03-15

    Little information is known about the frequency, types and causes of diagnostic errors in imaging children. Our goals were to describe the patterns and potential etiologies of diagnostic error in our subspecialty. We reviewed 265 cases with clinically significant diagnostic errors identified during a 10-year period. Errors were defined as a diagnosis that was delayed, wrong or missed; they were classified as perceptual, cognitive, system-related or unavoidable; and they were evaluated by imaging modality and level of training of the physician involved. We identified 484 specific errors in the 265 cases reviewed (mean:1.8 errors/case). Most discrepancies involved staff (45.5%). Two hundred fifty-eight individual cognitive errors were identified in 151 cases (mean = 1.7 errors/case). Of these, 83 cases (55%) had additional perceptual or system-related errors. One hundred sixty-five perceptual errors were identified in 165 cases. Of these, 68 cases (41%) also had cognitive or system-related errors. Fifty-four system-related errors were identified in 46 cases (mean = 1.2 errors/case) of which all were multi-factorial. Seven cases were unavoidable. Our study defines a taxonomy of diagnostic errors in a large academic pediatric radiology practice and suggests that most are multi-factorial in etiology. Further study is needed to define effective strategies for improvement. (orig.)

  18. Improved synthesis of glycine, taurine and sulfate conjugated bile acids as reference compounds and internal standards for ESI-MS/MS urinary profiling of inborn errors of bile acid synthesis.

    Science.gov (United States)

    Donazzolo, Elena; Gucciardi, Antonina; Mazzier, Daniela; Peggion, Cristina; Pirillo, Paola; Naturale, Mauro; Moretto, Alessandro; Giordano, Giuseppe

    2017-04-01

    Bile acid synthesis defects are rare genetic disorders characterized by a failure to produce normal bile acids (BAs), and by an accumulation of unusual and intermediary cholanoids. Measurements of cholanoids in urine samples by mass spectrometry are a gold standard for the diagnosis of these diseases. In this work improved methods for the chemical synthesis of 30 BAs conjugated with glycine, taurine and sulfate were developed. Diethyl phosphorocyanidate (DEPC) and diphenyl phosphoryl azide (DPPA) were used as coupling reagents for glycine and taurine conjugation. Sulfated BAs were obtained by sulfur trioxide-triethylamine complex (SO3-TEA) as sulfating agent and thereafter conjugated with glycine and taurine. All products were characterized by NMR, IR spectroscopy and high resolution mass spectrometry (HRMS). The use of these compounds as internal standards allows an improved accuracy of both identification and quantification of urinary bile acids. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Transient Error Data Analysis.

    Science.gov (United States)

    1979-05-01

    Analysis is 3.2 Graphical Data Analysis 16 3.3 General Statistics and Confidence Intervals 1" 3.4 Goodness of Fit Test 15 4. Conclusions 31 Acknowledgements...MTTF per System Technology Mechanism Processor Processor MT IE . CMUA PDP-10, ECL Parity 44 hrs. 800-1600 hrs. 0.03-0.06 Cm* LSI-1 1, NMOS Diagnostics...OF BAD TIME ERRORS: 6 TOTAL NUMBER OF ENTRIES FOR ALL INPUT FILESs 18445 TIME SPAN: 1542 HRS., FROM: 17-Feb-79 5:3:11 TO: 18-1Mj-79 11:30:99

  20. Minimum Error Entropy Classification

    CERN Document Server

    Marques de Sá, Joaquim P; Santos, Jorge M F; Alexandre, Luís A

    2013-01-01

    This book explains the minimum error entropy (MEE) concept applied to data classification machines. Theoretical results on the inner workings of the MEE concept, in its application to solving a variety of classification problems, are presented in the wider realm of risk functionals. Researchers and practitioners also find in the book a detailed presentation of practical data classifiers using MEE. These include multi‐layer perceptrons, recurrent neural networks, complexvalued neural networks, modular neural networks, and decision trees. A clustering algorithm using a MEE‐like concept is also presented. Examples, tests, evaluation experiments and comparison with similar machines using classic approaches, complement the descriptions.

  1. Analytics for Metabolic Engineering.

    Science.gov (United States)

    Petzold, Christopher J; Chan, Leanne Jade G; Nhan, Melissa; Adams, Paul D

    2015-01-01

    Realizing the promise of metabolic engineering has been slowed by challenges related to moving beyond proof-of-concept examples to robust and economically viable systems. Key to advancing metabolic engineering beyond trial-and-error research is access to parts with well-defined performance metrics that can be readily applied in vastly different contexts with predictable effects. As the field now stands, research depends greatly on analytical tools that assay target molecules, transcripts, proteins, and metabolites across different hosts and pathways. Screening technologies yield specific information for many thousands of strain variants, while deep omics analysis provides a systems-level view of the cell factory. Efforts focused on a combination of these analyses yield quantitative information of dynamic processes between parts and the host chassis that drive the next engineering steps. Overall, the data generated from these types of assays aid better decision-making at the design and strain construction stages to speed progress in metabolic engineering research.

  2. Error Analysis and Propagation in Metabolomics Data Analysis.

    Science.gov (United States)

    Moseley, Hunter N B

    2013-01-01

    Error analysis plays a fundamental role in describing the uncertainty in experimental results. It has several fundamental uses in metabolomics including experimental design, quality control of experiments, the selection of appropriate statistical methods, and the determination of uncertainty in results. Furthermore, the importance of error analysis has grown with the increasing number, complexity, and heterogeneity of measurements characteristic of 'omics research. The increase in data complexity is particularly problematic for metabolomics, which has more heterogeneity than other omics technologies due to the much wider range of molecular entities detected and measured. This review introduces the fundamental concepts of error analysis as they apply to a wide range of metabolomics experimental designs and it discusses current methodologies for determining the propagation of uncertainty in appropriate metabolomics data analysis. These methodologies include analytical derivation and approximation techniques, Monte Carlo error analysis, and error analysis in metabolic inverse problems. Current limitations of each methodology with respect to metabolomics data analysis are also discussed.

  3. Errors in CT colonography.

    Science.gov (United States)

    Trilisky, Igor; Ward, Emily; Dachman, Abraham H

    2015-10-01

    CT colonography (CTC) is a colorectal cancer screening modality which is becoming more widely implemented and has shown polyp detection rates comparable to those of optical colonoscopy. CTC has the potential to improve population screening rates due to its minimal invasiveness, no sedation requirement, potential for reduced cathartic examination, faster patient throughput, and cost-effectiveness. Proper implementation of a CTC screening program requires careful attention to numerous factors, including patient preparation prior to the examination, the technical aspects of image acquisition, and post-processing of the acquired data. A CTC workstation with dedicated software is required with integrated CTC-specific display features. Many workstations include computer-aided detection software which is designed to decrease errors of detection by detecting and displaying polyp-candidates to the reader for evaluation. There are several pitfalls which may result in false-negative and false-positive reader interpretation. We present an overview of the potential errors in CTC and a systematic approach to avoid them.

  4. Error Analysis in Mathematics Education.

    Science.gov (United States)

    Rittner, Max

    1982-01-01

    The article reviews the development of mathematics error analysis as a means of diagnosing students' cognitive reasoning. Errors specific to addition, subtraction, multiplication, and division are described, and suggestions for remediation are provided. (CL)

  5. Payment Error Rate Measurement (PERM)

    Data.gov (United States)

    U.S. Department of Health & Human Services — The PERM program measures improper payments in Medicaid and CHIP and produces error rates for each program. The error rates are based on reviews of the...

  6. Error bounds for set inclusions

    Institute of Scientific and Technical Information of China (English)

    ZHENG; Xiyin(郑喜印)

    2003-01-01

    A variant of Robinson-Ursescu Theorem is given in normed spaces. Several error bound theorems for convex inclusions are proved and in particular a positive answer to Li and Singer's conjecture is given under weaker assumption than the assumption required in their conjecture. Perturbation error bounds are also studied. As applications, we study error bounds for convex inequality systems.

  7. Uncertainty quantification and error analysis

    Energy Technology Data Exchange (ETDEWEB)

    Higdon, Dave M [Los Alamos National Laboratory; Anderson, Mark C [Los Alamos National Laboratory; Habib, Salman [Los Alamos National Laboratory; Klein, Richard [Los Alamos National Laboratory; Berliner, Mark [OHIO STATE UNIV.; Covey, Curt [LLNL; Ghattas, Omar [UNIV OF TEXAS; Graziani, Carlo [UNIV OF CHICAGO; Seager, Mark [LLNL; Sefcik, Joseph [LLNL; Stark, Philip [UC/BERKELEY; Stewart, James [SNL

    2010-01-01

    UQ studies all sources of error and uncertainty, including: systematic and stochastic measurement error; ignorance; limitations of theoretical models; limitations of numerical representations of those models; limitations on the accuracy and reliability of computations, approximations, and algorithms; and human error. A more precise definition for UQ is suggested below.

  8. Feature Referenced Error Correction Apparatus.

    Science.gov (United States)

    A feature referenced error correction apparatus utilizing the multiple images of the interstage level image format to compensate for positional...images and by the generation of an error correction signal in response to the sub-frame registration errors. (Author)

  9. Errors in causal inference: an organizational schema for systematic error and random error.

    Science.gov (United States)

    Suzuki, Etsuji; Tsuda, Toshihide; Mitsuhashi, Toshiharu; Mansournia, Mohammad Ali; Yamamoto, Eiji

    2016-11-01

    To provide an organizational schema for systematic error and random error in estimating causal measures, aimed at clarifying the concept of errors from the perspective of causal inference. We propose to divide systematic error into structural error and analytic error. With regard to random error, our schema shows its four major sources: nondeterministic counterfactuals, sampling variability, a mechanism that generates exposure events and measurement variability. Structural error is defined from the perspective of counterfactual reasoning and divided into nonexchangeability bias (which comprises confounding bias and selection bias) and measurement bias. Directed acyclic graphs are useful to illustrate this kind of error. Nonexchangeability bias implies a lack of "exchangeability" between the selected exposed and unexposed groups. A lack of exchangeability is not a primary concern of measurement bias, justifying its separation from confounding bias and selection bias. Many forms of analytic errors result from the small-sample properties of the estimator used and vanish asymptotically. Analytic error also results from wrong (misspecified) statistical models and inappropriate statistical methods. Our organizational schema is helpful for understanding the relationship between systematic error and random error from a previously less investigated aspect, enabling us to better understand the relationship between accuracy, validity, and precision. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Metabolic Panel

    Science.gov (United States)

    ... basic metabolic panel (BMP) and comprehensive metabolic panel (CMP). The BMP checks your blood sugar, calcium, and ... as creatinine to check your kidney function. The CMP includes all of those tests, as well as ...

  11. Metabolic Disorders

    Science.gov (United States)

    ... as your liver, muscles, and body fat. A metabolic disorder occurs when abnormal chemical reactions in your body ... that produce the energy. You can develop a metabolic disorder when some organs, such as your liver or ...

  12. Metabolic Syndrome

    Science.gov (United States)

    Metabolic syndrome is a group of conditions that put you at risk for heart disease and diabetes. These ... doctors agree on the definition or cause of metabolic syndrome. The cause might be insulin resistance. Insulin is ...

  13. Firewall Configuration Errors Revisited

    CERN Document Server

    Wool, Avishai

    2009-01-01

    The first quantitative evaluation of the quality of corporate firewall configurations appeared in 2004, based on Check Point FireWall-1 rule-sets. In general that survey indicated that corporate firewalls were often enforcing poorly written rule-sets, containing many mistakes. The goal of this work is to revisit the first survey. The current study is much larger. Moreover, for the first time, the study includes configurations from two major vendors. The study also introduce a novel "Firewall Complexity" (FC) measure, that applies to both types of firewalls. The findings of the current study indeed validate the 2004 study's main observations: firewalls are (still) poorly configured, and a rule-set's complexity is (still) positively correlated with the number of detected risk items. Thus we can conclude that, for well-configured firewalls, ``small is (still) beautiful''. However, unlike the 2004 study, we see no significant indication that later software versions have fewer errors (for both vendors).

  14. Beta systems error analysis

    Science.gov (United States)

    1984-01-01

    The atmospheric backscatter coefficient, beta, measured with an airborne CO Laser Doppler Velocimeter (LDV) system operating in a continuous wave, focussed model is discussed. The Single Particle Mode (SPM) algorithm, was developed from concept through analysis of an extensive amount of data obtained with the system on board a NASA aircraft. The SPM algorithm is intended to be employed in situations where one particle at a time appears in the sensitive volume of the LDV. In addition to giving the backscatter coefficient, the SPM algorithm also produces as intermediate results the aerosol density and the aerosol backscatter cross section distribution. A second method, which measures only the atmospheric backscatter coefficient, is called the Volume Mode (VM) and was simultaneously employed. The results of these two methods differed by slightly less than an order of magnitude. The measurement uncertainties or other errors in the results of the two methods are examined.

  15. Catalytic quantum error correction

    CERN Document Server

    Brun, T; Hsieh, M H; Brun, Todd; Devetak, Igor; Hsieh, Min-Hsiu

    2006-01-01

    We develop the theory of entanglement-assisted quantum error correcting (EAQEC) codes, a generalization of the stabilizer formalism to the setting in which the sender and receiver have access to pre-shared entanglement. Conventional stabilizer codes are equivalent to dual-containing symplectic codes. In contrast, EAQEC codes do not require the dual-containing condition, which greatly simplifies their construction. We show how any quaternary classical code can be made into a EAQEC code. In particular, efficient modern codes, like LDPC codes, which attain the Shannon capacity, can be made into EAQEC codes attaining the hashing bound. In a quantum computation setting, EAQEC codes give rise to catalytic quantum codes which maintain a region of inherited noiseless qubits. We also give an alternative construction of EAQEC codes by making classical entanglement assisted codes coherent.

  16. Experimental repetitive quantum error correction.

    Science.gov (United States)

    Schindler, Philipp; Barreiro, Julio T; Monz, Thomas; Nebendahl, Volckmar; Nigg, Daniel; Chwalla, Michael; Hennrich, Markus; Blatt, Rainer

    2011-05-27

    The computational potential of a quantum processor can only be unleashed if errors during a quantum computation can be controlled and corrected for. Quantum error correction works if imperfections of quantum gate operations and measurements are below a certain threshold and corrections can be applied repeatedly. We implement multiple quantum error correction cycles for phase-flip errors on qubits encoded with trapped ions. Errors are corrected by a quantum-feedback algorithm using high-fidelity gate operations and a reset technique for the auxiliary qubits. Up to three consecutive correction cycles are realized, and the behavior of the algorithm for different noise environments is analyzed.

  17. Register file soft error recovery

    Science.gov (United States)

    Fleischer, Bruce M.; Fox, Thomas W.; Wait, Charles D.; Muff, Adam J.; Watson, III, Alfred T.

    2013-10-15

    Register file soft error recovery including a system that includes a first register file and a second register file that mirrors the first register file. The system also includes an arithmetic pipeline for receiving data read from the first register file, and error detection circuitry to detect whether the data read from the first register file includes corrupted data. The system further includes error recovery circuitry to insert an error recovery instruction into the arithmetic pipeline in response to detecting the corrupted data. The inserted error recovery instruction replaces the corrupted data in the first register file with a copy of the data from the second register file.

  18. Controlling errors in unidosis carts

    Directory of Open Access Journals (Sweden)

    Inmaculada Díaz Fernández

    2010-01-01

    Full Text Available Objective: To identify errors in the unidosis system carts. Method: For two months, the Pharmacy Service controlled medication either returned or missing from the unidosis carts both in the pharmacy and in the wards. Results: Uncorrected unidosis carts show a 0.9% of medication errors (264 versus 0.6% (154 which appeared in unidosis carts previously revised. In carts not revised, the error is 70.83% and mainly caused when setting up unidosis carts. The rest are due to a lack of stock or unavailability (21.6%, errors in the transcription of medical orders (6.81% or that the boxes had not been emptied previously (0.76%. The errors found in the units correspond to errors in the transcription of the treatment (3.46%, non-receipt of the unidosis copy (23.14%, the patient did not take the medication (14.36%or was discharged without medication (12.77%, was not provided by nurses (14.09%, was withdrawn from the stocks of the unit (14.62%, and errors of the pharmacy service (17.56% . Conclusions: It is concluded the need to redress unidosis carts and a computerized prescription system to avoid errors in transcription.Discussion: A high percentage of medication errors is caused by human error. If unidosis carts are overlooked before sent to hospitalization units, the error diminishes to 0.3%.

  19. Prediction of discretization error using the error transport equation

    Science.gov (United States)

    Celik, Ismail B.; Parsons, Don Roscoe

    2017-06-01

    This study focuses on an approach to quantify the discretization error associated with numerical solutions of partial differential equations by solving an error transport equation (ETE). The goal is to develop a method that can be used to adequately predict the discretization error using the numerical solution on only one grid/mesh. The primary problem associated with solving the ETE is the formulation of the error source term which is required for accurately predicting the transport of the error. In this study, a novel approach is considered which involves fitting the numerical solution with a series of locally smooth curves and then blending them together with a weighted spline approach. The result is a continuously differentiable analytic expression that can be used to determine the error source term. Once the source term has been developed, the ETE can easily be solved using the same solver that is used to obtain the original numerical solution. The new methodology is applied to the two-dimensional Navier-Stokes equations in the laminar flow regime. A simple unsteady flow case is also considered. The discretization error predictions based on the methodology presented in this study are in good agreement with the 'true error'. While in most cases the error predictions are not quite as accurate as those from Richardson extrapolation, the results are reasonable and only require one numerical grid. The current results indicate that there is much promise going forward with the newly developed error source term evaluation technique and the ETE.

  20. Prioritising interventions against medication errors

    DEFF Research Database (Denmark)

    Lisby, Marianne; Pape-Larsen, Louise; Sørensen, Ann Lykkegaard

    2011-01-01

    Abstract Authors: Lisby M, Larsen LP, Soerensen AL, Nielsen LP, Mainz J Title: Prioritising interventions against medication errors – the importance of a definition Objective: To develop and test a restricted definition of medication errors across health care settings in Denmark Methods: Medication...... errors constitute a major quality and safety problem in modern healthcare. However, far from all are clinically important. The prevalence of medication errors ranges from 2-75% indicating a global problem in defining and measuring these [1]. New cut-of levels focusing the clinical impact of medication...... errors are therefore needed. Development of definition: A definition of medication errors including an index of error types for each stage in the medication process was developed from existing terminology and through a modified Delphi-process in 2008. The Delphi panel consisted of 25 interdisciplinary...

  1. [Metabolic syndrome].

    Science.gov (United States)

    Mitsuishi, Masanori; Miyashita, Kazutoshi; Itoh, Hiroshi

    2009-02-01

    Metabolic syndrome, which is consisted of hypertension, dyslipidemia and impaired glucose tolerance, is one of the most significant lifestyle-related disorders that lead to cardiovascular diseases. Among many upstream factors that are related to metabolic syndrome, obesity, especially visceral obesity, plays an essential role in its pathogenesis. In recent studies, possible mechanisms which connect obesity to metabolic syndrome have been elucidated, such as inflammation, abnormal secretion of adipokines and mitochondrial dysfunction. In this review, we focus on the relationship between obesity and metabolic syndrome; and illustrate how visceral obesity contributes to, and how the treatments for obesity act on metabolic syndrome.

  2. Improved Error Thresholds for Measurement-Free Error Correction

    Science.gov (United States)

    Crow, Daniel; Joynt, Robert; Saffman, M.

    2016-09-01

    Motivated by limitations and capabilities of neutral atom qubits, we examine whether measurement-free error correction can produce practical error thresholds. We show that this can be achieved by extracting redundant syndrome information, giving our procedure extra fault tolerance and eliminating the need for ancilla verification. The procedure is particularly favorable when multiqubit gates are available for the correction step. Simulations of the bit-flip, Bacon-Shor, and Steane codes indicate that coherent error correction can produce threshold error rates that are on the order of 10-3 to 10-4—comparable with or better than measurement-based values, and much better than previous results for other coherent error correction schemes. This indicates that coherent error correction is worthy of serious consideration for achieving protected logical qubits.

  3. PREVENTABLE ERRORS: NEVER EVENTS

    Directory of Open Access Journals (Sweden)

    Narra Gopal

    2014-07-01

    Full Text Available Operation or any invasive procedure is a stressful event involving risks and complications. We should be able to offer a guarantee that the right procedure will be done on right person in the right place on their body. “Never events” are definable. These are the avoidable and preventable events. The people affected from consequences of surgical mistakes ranged from temporary injury in 60%, permanent injury in 33% and death in 7%”.World Health Organization (WHO [1] has earlier said that over seven million people across the globe suffer from preventable surgical injuries every year, a million of them even dying during or immediately after the surgery? The UN body quantified the number of surgeries taking place every year globally 234 million. It said surgeries had become common, with one in every 25 people undergoing it at any given time. 50% never events are preventable. Evidence suggests up to one in ten hospital admissions results in an adverse incident. This incident rate is not acceptable in other industries. In order to move towards a more acceptable level of safety, we need to understand how and why things go wrong and have to build a reliable system of working. With this system even though complete prevention may not be possible but we can reduce the error percentage2. To change present concept towards patient, first we have to change and replace the word patient with medical customer. Then our outlook also changes, we will be more careful towards our customers.

  4. Comparison of analytical error and sampling error for contaminated soil.

    Science.gov (United States)

    Gustavsson, Björn; Luthbom, Karin; Lagerkvist, Anders

    2006-11-16

    Investigation of soil from contaminated sites requires several sample handling steps that, most likely, will induce uncertainties in the sample. The theory of sampling describes seven sampling errors that can be calculated, estimated or discussed in order to get an idea of the size of the sampling uncertainties. With the aim of comparing the size of the analytical error to the total sampling error, these seven errors were applied, estimated and discussed, to a case study of a contaminated site. The manageable errors were summarized, showing a range of three orders of magnitudes between the examples. The comparisons show that the quotient between the total sampling error and the analytical error is larger than 20 in most calculation examples. Exceptions were samples taken in hot spots, where some components of the total sampling error get small and the analytical error gets large in comparison. Low concentration of contaminant, small extracted sample size and large particles in the sample contribute to the extent of uncertainty.

  5. The Usability-Error Ontology

    DEFF Research Database (Denmark)

    2013-01-01

    ability to do systematic reviews and meta-analyses. In an effort to support improved and more interoperable data capture regarding Usability Errors, we have created the Usability Error Ontology (UEO) as a classification method for representing knowledge regarding Usability Errors. We expect the UEO...... in patients coming to harm. Often the root cause analysis of these adverse events can be traced back to Usability Errors in the Health Information Technology (HIT) or its interaction with users. Interoperability of the documentation of HIT related Usability Errors in a consistent fashion can improve our...... will grow over time to support an increasing number of HIT system types. In this manuscript, we present this Ontology of Usability Error Types and specifically address Computerized Physician Order Entry (CPOE), Electronic Health Records (EHR) and Revenue Cycle HIT systems....

  6. Nested Quantum Error Correction Codes

    CERN Document Server

    Wang, Zhuo; Fan, Hen; Vedral, Vlatko

    2009-01-01

    The theory of quantum error correction was established more than a decade ago as the primary tool for fighting decoherence in quantum information processing. Although great progress has already been made in this field, limited methods are available in constructing new quantum error correction codes from old codes. Here we exhibit a simple and general method to construct new quantum error correction codes by nesting certain quantum codes together. The problem of finding long quantum error correction codes is reduced to that of searching several short length quantum codes with certain properties. Our method works for all length and all distance codes, and is quite efficient to construct optimal or near optimal codes. Two main known methods in constructing new codes from old codes in quantum error-correction theory, the concatenating and pasting, can be understood in the framework of nested quantum error correction codes.

  7. Processor register error correction management

    Science.gov (United States)

    Bose, Pradip; Cher, Chen-Yong; Gupta, Meeta S.

    2016-12-27

    Processor register protection management is disclosed. In embodiments, a method of processor register protection management can include determining a sensitive logical register for executable code generated by a compiler, generating an error-correction table identifying the sensitive logical register, and storing the error-correction table in a memory accessible by a processor. The processor can be configured to generate a duplicate register of the sensitive logical register identified by the error-correction table.

  8. Is Menkes Syndrome a Copper Storage Disorder

    DEFF Research Database (Denmark)

    Heydorn, Kaj; Damsgaard, Else; Horn, N.

    1978-01-01

    Menkes disease, which is transmitted as an X-linked, recessive trait, has been disclosed as an inborn error of Cu metabolism. The clinical symptoms are thought to be caused by defective metabolic functions due to a general body deficiency of Cu. It was recently demonstrated that Menkes disease is...

  9. [Hereditary fructose intolerance (author's transl)].

    Science.gov (United States)

    Thanner, F

    1977-07-01

    Hereditary fructose intolerance (HFI) is the most important disturbance in human fructose metabolism. This paper deals with the present knowledge of biochemistry and pathophysiology of this inborn error of metabolism, which is often wrongly diagnosed and gives a detailed description of diagnostic and therapeutic procedures.

  10. The value of plasma vitamin B6 profiles in early onset epileptic encephalopathies

    NARCIS (Netherlands)

    Mathis, Déborah; Abela, Lucia; Albersen, Monique; Bürer, Céline; Crowther, Lisa; Beese, Karin; Hartmann, Hans; Bok, Levinus A; Struys, Eduard; Papuc, Sorina M; Rauch, Anita; Hersberger, Martin; Verhoeven-Duif, Nanda M; Plecko, Barbara

    2016-01-01

    BACKGROUND: Recent decades have unravelled the molecular background of a number of inborn errors of metabolism (IEM) causing vitamin B6-dependent epilepsy. As these defects interfere with vitamin B6 metabolism by different mechanisms, the plasma vitamin B6 profile can give important clues for furthe

  11. The Usability-Error Ontology

    DEFF Research Database (Denmark)

    2013-01-01

    ability to do systematic reviews and meta-analyses. In an effort to support improved and more interoperable data capture regarding Usability Errors, we have created the Usability Error Ontology (UEO) as a classification method for representing knowledge regarding Usability Errors. We expect the UEO...... will grow over time to support an increasing number of HIT system types. In this manuscript, we present this Ontology of Usability Error Types and specifically address Computerized Physician Order Entry (CPOE), Electronic Health Records (EHR) and Revenue Cycle HIT systems....

  12. Anxiety and Error Monitoring: Increased Error Sensitivity or Altered Expectations?

    Science.gov (United States)

    Compton, Rebecca J.; Carp, Joshua; Chaddock, Laura; Fineman, Stephanie L.; Quandt, Lorna C.; Ratliff, Jeffrey B.

    2007-01-01

    This study tested the prediction that the error-related negativity (ERN), a physiological measure of error monitoring, would be enhanced in anxious individuals, particularly in conditions with threatening cues. Participants made gender judgments about faces whose expressions were either happy, angry, or neutral. Replicating prior studies, midline…

  13. Measurement Error and Equating Error in Power Analysis

    Science.gov (United States)

    Phillips, Gary W.; Jiang, Tao

    2016-01-01

    Power analysis is a fundamental prerequisite for conducting scientific research. Without power analysis the researcher has no way of knowing whether the sample size is large enough to detect the effect he or she is looking for. This paper demonstrates how psychometric factors such as measurement error and equating error affect the power of…

  14. Nucleotide Metabolism

    DEFF Research Database (Denmark)

    Martinussen, Jan; Willemoës, M.; Kilstrup, Mogens

    2011-01-01

    Metabolic pathways are connected through their utilization of nucleotides as supplier of energy, allosteric effectors, and their role in activation of intermediates. Therefore, any attempt to exploit a given living organism in a biotechnological process will have an impact on nucleotide metabolism....... The aim of this article is to provide knowledge of nucleotide metabolism and its regulation to facilitate interpretation of data arising from genetics, proteomics, and transcriptomics in connection with biotechnological processes and beyond....

  15. Nucleotide Metabolism

    DEFF Research Database (Denmark)

    Martinussen, Jan; Willemoës, M.; Kilstrup, Mogens

    2011-01-01

    Metabolic pathways are connected through their utilization of nucleotides as supplier of energy, allosteric effectors, and their role in activation of intermediates. Therefore, any attempt to exploit a given living organism in a biotechnological process will have an impact on nucleotide metabolism....... The aim of this article is to provide knowledge of nucleotide metabolism and its regulation to facilitate interpretation of data arising from genetics, proteomics, and transcriptomics in connection with biotechnological processes and beyond....

  16. Error begat error: design error analysis and prevention in social infrastructure projects.

    Science.gov (United States)

    Love, Peter E D; Lopez, Robert; Edwards, David J; Goh, Yang M

    2012-09-01

    Design errors contribute significantly to cost and schedule growth in social infrastructure projects and to engineering failures, which can result in accidents and loss of life. Despite considerable research that has addressed their error causation in construction projects they still remain prevalent. This paper identifies the underlying conditions that contribute to design errors in social infrastructure projects (e.g. hospitals, education, law and order type buildings). A systemic model of error causation is propagated and subsequently used to develop a learning framework for design error prevention. The research suggests that a multitude of strategies should be adopted in congruence to prevent design errors from occurring and so ensure that safety and project performance are ameliorated.

  17. Spatial frequency domain error budget

    Energy Technology Data Exchange (ETDEWEB)

    Hauschildt, H; Krulewich, D

    1998-08-27

    The aim of this paper is to describe a methodology for designing and characterizing machines used to manufacture or inspect parts with spatial-frequency-based specifications. At Lawrence Livermore National Laboratory, one of our responsibilities is to design or select the appropriate machine tools to produce advanced optical and weapons systems. Recently, many of the component tolerances for these systems have been specified in terms of the spatial frequency content of residual errors on the surface. We typically use an error budget as a sensitivity analysis tool to ensure that the parts manufactured by a machine will meet the specified component tolerances. Error budgets provide the formalism whereby we account for all sources of uncertainty in a process, and sum them to arrive at a net prediction of how "precisely" a manufactured component can meet a target specification. Using the error budget, we are able to minimize risk during initial stages by ensuring that the machine will produce components that meet specifications before the machine is actually built or purchased. However, the current error budgeting procedure provides no formal mechanism for designing machines that can produce parts with spatial-frequency-based specifications. The output from the current error budgeting procedure is a single number estimating the net worst case or RMS error on the work piece. This procedure has limited ability to differentiate between low spatial frequency form errors versus high frequency surface finish errors. Therefore the current error budgeting procedure can lead us to reject a machine that is adequate or accept a machine that is inadequate. This paper will describe a new error budgeting methodology to aid in the design and characterization of machines used to manufacture or inspect parts with spatial-frequency-based specifications. The output from this new procedure is the continuous spatial frequency content of errors that result on a machined part. If the machine

  18. Reducing errors in emergency surgery.

    Science.gov (United States)

    Watters, David A K; Truskett, Philip G

    2013-06-01

    Errors are to be expected in health care. Adverse events occur in around 10% of surgical patients and may be even more common in emergency surgery. There is little formal teaching on surgical error in surgical education and training programmes despite their frequency. This paper reviews surgical error and provides a classification system, to facilitate learning. The approach and language used to enable teaching about surgical error was developed through a review of key literature and consensus by the founding faculty of the Management of Surgical Emergencies course, currently delivered by General Surgeons Australia. Errors may be classified as being the result of commission, omission or inition. An error of inition is a failure of effort or will and is a failure of professionalism. The risk of error can be minimized by good situational awareness, matching perception to reality, and, during treatment, reassessing the patient, team and plan. It is important to recognize and acknowledge an error when it occurs and then to respond appropriately. The response will involve rectifying the error where possible but also disclosing, reporting and reviewing at a system level all the root causes. This should be done without shaming or blaming. However, the individual surgeon still needs to reflect on their own contribution and performance. A classification of surgical error has been developed that promotes understanding of how the error was generated, and utilizes a language that encourages reflection, reporting and response by surgeons and their teams. © 2013 The Authors. ANZ Journal of Surgery © 2013 Royal Australasian College of Surgeons.

  19. Error Analysis in English Language Learning

    Institute of Scientific and Technical Information of China (English)

    杜文婷

    2009-01-01

    Errors in English language learning are usually classified into interlingual errors and intralin-gual errors, having a clear knowledge of the causes of the errors will help students learn better English.

  20. Error Analysis And Second Language Acquisition

    Institute of Scientific and Technical Information of China (English)

    王惠丽

    2016-01-01

    Based on the theories of error and error analysis, the article is trying to explore the effect of error and error analysis on SLA. Thus give some advice to the language teachers and language learners.

  1. Quantifying error distributions in crowding.

    Science.gov (United States)

    Hanus, Deborah; Vul, Edward

    2013-03-22

    When multiple objects are in close proximity, observers have difficulty identifying them individually. Two classes of theories aim to account for this crowding phenomenon: spatial pooling and spatial substitution. Variations of these accounts predict different patterns of errors in crowded displays. Here we aim to characterize the kinds of errors that people make during crowding by comparing a number of error models across three experiments in which we manipulate flanker spacing, display eccentricity, and precueing duration. We find that both spatial intrusions and individual letter confusions play a considerable role in errors. Moreover, we find no evidence that a naïve pooling model that predicts errors based on a nonadditive combination of target and flankers explains errors better than an independent intrusion model (indeed, in our data, an independent intrusion model is slightly, but significantly, better). Finally, we find that manipulating trial difficulty in any way (spacing, eccentricity, or precueing) produces homogenous changes in error distributions. Together, these results provide quantitative baselines for predictive models of crowding errors, suggest that pooling and spatial substitution models are difficult to tease apart, and imply that manipulations of crowding all influence a common mechanism that impacts subject performance.

  2. Discretization error of Stochastic Integrals

    CERN Document Server

    Fukasawa, Masaaki

    2010-01-01

    Asymptotic error distribution for approximation of a stochastic integral with respect to continuous semimartingale by Riemann sum with general stochastic partition is studied. Effective discretization schemes of which asymptotic conditional mean-squared error attains a lower bound are constructed. Two applications are given; efficient delta hedging strategies with transaction costs and effective discretization schemes for the Euler-Maruyama approximation are constructed.

  3. Dual Processing and Diagnostic Errors

    Science.gov (United States)

    Norman, Geoff

    2009-01-01

    In this paper, I review evidence from two theories in psychology relevant to diagnosis and diagnostic errors. "Dual Process" theories of thinking, frequently mentioned with respect to diagnostic error, propose that categorization decisions can be made with either a fast, unconscious, contextual process called System 1 or a slow, analytical,…

  4. Barriers to medical error reporting

    Directory of Open Access Journals (Sweden)

    Jalal Poorolajal

    2015-01-01

    Full Text Available Background: This study was conducted to explore the prevalence of medical error underreporting and associated barriers. Methods: This cross-sectional study was performed from September to December 2012. Five hospitals, affiliated with Hamadan University of Medical Sciences, in Hamedan,Iran were investigated. A self-administered questionnaire was used for data collection. Participants consisted of physicians, nurses, midwives, residents, interns, and staffs of radiology and laboratory departments. Results: Overall, 50.26% of subjects had committed but not reported medical errors. The main reasons mentioned for underreporting were lack of effective medical error reporting system (60.0%, lack of proper reporting form (51.8%, lack of peer supporting a person who has committed an error (56.0%, and lack of personal attention to the importance of medical errors (62.9%. The rate of committing medical errors was higher in men (71.4%, age of 50-40 years (67.6%, less-experienced personnel (58.7%, educational level of MSc (87.5%, and staff of radiology department (88.9%. Conclusions: This study outlined the main barriers to reporting medical errors and associated factors that may be helpful for healthcare organizations in improving medical error reporting as an essential component for patient safety enhancement.

  5. Onorbit IMU alignment error budget

    Science.gov (United States)

    Corson, R. W.

    1980-01-01

    The Star Tracker, Crew Optical Alignment Sight (COAS), and Inertial Measurement Unit (IMU) from a complex navigation system with a multitude of error sources were combined. A complete list of the system errors is presented. The errors were combined in a rational way to yield an estimate of the IMU alignment accuracy for STS-1. The expected standard deviation in the IMU alignment error for STS-1 type alignments was determined to be 72 arc seconds per axis for star tracker alignments and 188 arc seconds per axis for COAS alignments. These estimates are based on current knowledge of the star tracker, COAS, IMU, and navigation base error specifications, and were partially verified by preliminary Monte Carlo analysis.

  6. Measurement Error Models in Astronomy

    CERN Document Server

    Kelly, Brandon C

    2011-01-01

    I discuss the effects of measurement error on regression and density estimation. I review the statistical methods that have been developed to correct for measurement error that are most popular in astronomical data analysis, discussing their advantages and disadvantages. I describe functional models for accounting for measurement error in regression, with emphasis on the methods of moments approach and the modified loss function approach. I then describe structural models for accounting for measurement error in regression and density estimation, with emphasis on maximum-likelihood and Bayesian methods. As an example of a Bayesian application, I analyze an astronomical data set subject to large measurement errors and a non-linear dependence between the response and covariate. I conclude with some directions for future research.

  7. Binary Error Correcting Network Codes

    CERN Document Server

    Wang, Qiwen; Li, Shuo-Yen Robert

    2011-01-01

    We consider network coding for networks experiencing worst-case bit-flip errors, and argue that this is a reasonable model for highly dynamic wireless network transmissions. We demonstrate that in this setup prior network error-correcting schemes can be arbitrarily far from achieving the optimal network throughput. We propose a new metric for errors under this model. Using this metric, we prove a new Hamming-type upper bound on the network capacity. We also show a commensurate lower bound based on GV-type codes that can be used for error-correction. The codes used to attain the lower bound are non-coherent (do not require prior knowledge of network topology). The end-to-end nature of our design enables our codes to be overlaid on classical distributed random linear network codes. Further, we free internal nodes from having to implement potentially computationally intensive link-by-link error-correction.

  8. Error Propagation in the Hypercycle

    CERN Document Server

    Campos, P R A; Stadler, P F

    1999-01-01

    We study analytically the steady-state regime of a network of n error-prone self-replicating templates forming an asymmetric hypercycle and its error tail. We show that the existence of a master template with a higher non-catalyzed self-replicative productivity, a, than the error tail ensures the stability of chains in which merror tail is guaranteed for catalytic coupling strengths (K) of order of a. We find that the hypercycle becomes more stable than the chains only for K of order of a2. Furthermore, we show that the minimal replication accuracy per template needed to maintain the hypercycle, the so-called error threshold, vanishes like sqrt(n/K) for large K and n<=4.

  9. FPU-Supported Running Error Analysis

    OpenAIRE

    T. Zahradnický; R. Lórencz

    2010-01-01

    A-posteriori forward rounding error analyses tend to give sharper error estimates than a-priori ones, as they use actual data quantities. One of such a-posteriori analysis – running error analysis – uses expressions consisting of two parts; one generates the error and the other propagates input errors to the output. This paper suggests replacing the error generating term with an FPU-extracted rounding error estimate, which produces a sharper error bound.

  10. Metabolic acidosis.

    Science.gov (United States)

    Lim, Salim

    2007-01-01

    Acute metabolic acidosis is frequently encountered in critically ill patients. Metabolic acidosis can occur as a result of either the accumulation of endogenous acids that consumes bicarbonate (high anion gap metabolic acidosis) or loss of bicarbonate from the gastrointestinal tract or the kidney (hyperchloremic or normal anion gap metabolic acidosis). The cause of high anion gap metabolic acidosis includes lactic acidosis, ketoacidosis, renal failure and intoxication with ethylene glycol, methanol, salicylate and less commonly with pyroglutamic acid (5-oxoproline), propylene glycole or djenkol bean (gjenkolism). The most common causes of hyperchloremic metabolic acidosis are gastrointestinal bicarbonate loss, renal tubular acidosis, drugs-induced hyperkalemia, early renal failure and administration of acids. The appropriate treatment of acute metabolic acidosis, in particular organic form of acidosis such as lactic acidosis, has been very controversial. The only effective treatment for organic acidosis is cessation of acid production via improvement of tissue oxygenation. Treatment of acute organic acidosis with sodium bicarbonate failed to reduce the morbidity and mortality despite improvement in acid-base parameters. Further studies are required to determine the optimal treatment strategies for acute metabolic acidosis.

  11. A summary of NICU fat emulsion medication errors and nursing services: data from MEDMARX.

    Science.gov (United States)

    Hicks, Rodney W; Becker, Shawn C; Chuo, John

    2007-12-01

    Intralipid infusions remain a critical part of ensuring adequate nutritional supplement and growth in premature and term infants. Managing intralipid therapy requires great care to prevent metabolic and physiological side effects. The authors sought to systematically study medication errors associated with intralipid administration in the neonatal intensive care unit (NICU). A descriptive quantitative and qualitative analysis incorporating secondary data was used. Medication error data were drawn from 54 institutions that voluntarily participated with MEDMARX, a national, Internet-accessible medication error reporting program owned and operated by the United States Pharmacopeia. These errors were associated with NICUs, and each medication error record identified nursing staff as making the initial error. A total of 257 errors were reviewed, with 3.9% resulting in harm. The mean age of the neonate was 7 days, and more errors occurred on Mondays than any other day of the week. Errors disproportionately occurred between 6 pm and midnight, with a significant difference between errors near 7 am and 7 pm (P = .002). Wrong dose errors occurred in 69% of the sample. Nearly one quarter of the errors resulted from misprogramming infusion devices (either pumps or syringes). Qualitative findings revealed that many of the errors were the result of the nurse's misinterpretation of the modes (ie, time, volume, or rate) on the infusion device or by not recognizing the decimal point on the device's display panel. Several errors involved switching the rate of infusion with total parenteral nutrition and that of intralipids. Voluntary medication error reporting offers valuable insights into intralipid errors occurring in NICUs. Secondary analysis is an ethical, economic means of studying the occurrence of such errors. MEDMARX data suggest that some of the serious errors are the result of complex care and equipment needed for these vulnerable infants.

  12. Metabolic encephalopathies.

    Science.gov (United States)

    Angel, Michael J; Young, G Bryan

    2011-11-01

    Kinnier Wilson coined the term metabolic encephalopathy to describe a clinical state of global cerebral dysfunction induced by systemic stress that can vary in clinical presentation from mild executive dysfunction to deep coma with decerebrate posturing; the causes are numerous. Some mechanisms by which cerebral dysfunction occurs in metabolic encephalopathies include focal or global cerebral edema, alterations in transmitter function, the accumulation of uncleared toxic metabolites, postcapillary venule vasogenic edema, and energy failure. This article focuses on common causes of metabolic encephalopathy, and reviews common causes, clinical presentations and, where relevant, management.

  13. Quantile Regression With Measurement Error

    KAUST Repository

    Wei, Ying

    2009-08-27

    Regression quantiles can be substantially biased when the covariates are measured with error. In this paper we propose a new method that produces consistent linear quantile estimation in the presence of covariate measurement error. The method corrects the measurement error induced bias by constructing joint estimating equations that simultaneously hold for all the quantile levels. An iterative EM-type estimation algorithm to obtain the solutions to such joint estimation equations is provided. The finite sample performance of the proposed method is investigated in a simulation study, and compared to the standard regression calibration approach. Finally, we apply our methodology to part of the National Collaborative Perinatal Project growth data, a longitudinal study with an unusual measurement error structure. © 2009 American Statistical Association.

  14. The uncorrected refractive error challenge

    Directory of Open Access Journals (Sweden)

    Kovin Naidoo

    2016-11-01

    Full Text Available Refractive error affects people of all ages, socio-economic status and ethnic groups. The most recent statistics estimate that, worldwide, 32.4 million people are blind and 191 million people have vision impairment. Vision impairment has been defined based on distance visual acuity only, and uncorrected distance refractive error (mainly myopia is the single biggest cause of worldwide vision impairment. However, when we also consider near visual impairment, it is clear that even more people are affected. From research it was estimated that the number of people with vision impairment due to uncorrected distance refractive error was 107.8 million,1 and the number of people affected by uncorrected near refractive error was 517 million, giving a total of 624.8 million people.

  15. Numerical optimization with computational errors

    CERN Document Server

    Zaslavski, Alexander J

    2016-01-01

    This book studies the approximate solutions of optimization problems in the presence of computational errors. A number of results are presented on the convergence behavior of algorithms in a Hilbert space; these algorithms are examined taking into account computational errors. The author illustrates that algorithms generate a good approximate solution, if computational errors are bounded from above by a small positive constant. Known computational errors are examined with the aim of determining an approximate solution. Researchers and students interested in the optimization theory and its applications will find this book instructive and informative. This monograph contains 16 chapters; including a chapters devoted to the subgradient projection algorithm, the mirror descent algorithm, gradient projection algorithm, the Weiszfelds method, constrained convex minimization problems, the convergence of a proximal point method in a Hilbert space, the continuous subgradient method, penalty methods and Newton’s meth...

  16. Error Analysis in Mathematics Education.

    Science.gov (United States)

    Radatz, Hendrik

    1979-01-01

    Five types of errors in an information-processing classification are discussed: language difficulties; difficulties in obtaining spatial information; deficient mastery of prerequisite skills, facts, and concepts; incorrect associations; and application of irrelevant rules. (MP)

  17. Comprehensive Error Rate Testing (CERT)

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Centers for Medicare and Medicaid Services (CMS) implemented the Comprehensive Error Rate Testing (CERT) program to measure improper payments in the Medicare...

  18. Aging transition by random errors

    Science.gov (United States)

    Sun, Zhongkui; Ma, Ning; Xu, Wei

    2017-02-01

    In this paper, the effects of random errors on the oscillating behaviors have been studied theoretically and numerically in a prototypical coupled nonlinear oscillator. Two kinds of noises have been employed respectively to represent the measurement errors accompanied with the parameter specifying the distance from a Hopf bifurcation in the Stuart-Landau model. It has been demonstrated that when the random errors are uniform random noise, the change of the noise intensity can effectively increase the robustness of the system. While the random errors are normal random noise, the increasing of variance can also enhance the robustness of the system under certain conditions that the probability of aging transition occurs reaches a certain threshold. The opposite conclusion is obtained when the probability is less than the threshold. These findings provide an alternative candidate to control the critical value of aging transition in coupled oscillator system, which is composed of the active oscillators and inactive oscillators in practice.

  19. Aging transition by random errors

    Science.gov (United States)

    Sun, Zhongkui; Ma, Ning; Xu, Wei

    2017-01-01

    In this paper, the effects of random errors on the oscillating behaviors have been studied theoretically and numerically in a prototypical coupled nonlinear oscillator. Two kinds of noises have been employed respectively to represent the measurement errors accompanied with the parameter specifying the distance from a Hopf bifurcation in the Stuart-Landau model. It has been demonstrated that when the random errors are uniform random noise, the change of the noise intensity can effectively increase the robustness of the system. While the random errors are normal random noise, the increasing of variance can also enhance the robustness of the system under certain conditions that the probability of aging transition occurs reaches a certain threshold. The opposite conclusion is obtained when the probability is less than the threshold. These findings provide an alternative candidate to control the critical value of aging transition in coupled oscillator system, which is composed of the active oscillators and inactive oscillators in practice. PMID:28198430

  20. Metabolic Syndrome

    Science.gov (United States)

    ... hypertension, hypertriglyceridemia, insulin resistance syndrome, low HDL cholesterol, Metabolic Syndrome, overweight, syndrome x, type 2 diabetes Family Health, Kids and Teens, Men, Women January 2005 Copyright © American Academy of Family PhysiciansThis ...

  1. Error correcting coding for OTN

    DEFF Research Database (Denmark)

    Justesen, Jørn; Larsen, Knud J.; Pedersen, Lars A.

    2010-01-01

    Forward error correction codes for 100 Gb/s optical transmission are currently receiving much attention from transport network operators and technology providers. We discuss the performance of hard decision decoding using product type codes that cover a single OTN frame or a small number...... of such frames. In particular we argue that a three-error correcting BCH is the best choice for the component code in such systems....

  2. Errors in Chemical Sensor Measurements

    Directory of Open Access Journals (Sweden)

    Artur Dybko

    2001-06-01

    Full Text Available Various types of errors during the measurements of ion-selective electrodes, ionsensitive field effect transistors, and fibre optic chemical sensors are described. The errors were divided according to their nature and place of origin into chemical, instrumental and non-chemical. The influence of interfering ions, leakage of the membrane components, liquid junction potential as well as sensor wiring, ambient light and temperature is presented.

  3. Metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Gogia Atul

    2006-02-01

    Full Text Available The Metabolic syndrome is a widely prevalent and multi-factorial disorder. The syndrome has been given several names, including- the metabolic syndrome, the insulin resistance syndrome, the plurimetabolic syndrome, and the deadly quartet. With the formulation of NCEP/ATP III guidelines, some uniformity and standardization has occurred in the definition of metabolic syndrome and has been very useful for epidemiological purposes. The mechanisms underlying the metabolic syndrome are not fully known; however resistance to insulin stimulated glucose uptake seems to modify biochemical responses in a way that predisposes to metabolic risk factors. The clinical relevance of the metabolic syndrome is related to its role in the development of cardiovascular disease. Management of the metabolic syndrome involves patient-education and intervention at various levels. Weight reduction is one of the main stays of treatment. In this article we comprehensively discuss this syndrome- the epidemiology, pathogenesis, clinical relevance and management. The need to do a comprehensive review of this particular syndrome has arisen in view of the ever increasing incidence of this entitiy. Soon, metabolic syndrome will overtake cigarette smoking as the number one risk factor for heart disease among the US population. Hardly any issue of any primary care medical journal can be opened without encountering an article on type 2 diabetes, dyslipidemia or hypertension. It is rare to see type 2 diabetes, dyslipidemia, obesity or hypertension in isolation. Insulin resistance and resulting hyperinsulinemia have been implicated in the development of glucose intolerance (and progression to type 2 diabetes, hypertriglyceridemia, hypertension, polycystic ovary yndrome, hypercoagulability and vascular inflammation, as well as the eventual development of atherosclerotic cardiovascular disease manifested as myocardial infarction, stroke and myriad end organ diseases. Conversely

  4. Lipid Metabolism

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    2008393 Effects of angiotensin Ⅱ type 1 receptor blocker on triglyceride metabolism in the liver: experiment with Zucker fatty rats. RAN Jianmin(冉建民), et al. Dept Endocrinol, Guangzhou Red Cross Hosp, 4th Hosp Med Coll, Jinan Univ, Guangzhou 510220. Natl Med J China 2008;88(22):1557-1561. Objective To investigate the effects of angiotensin receptor blocker (ARB) on triglyceride (TG) metabolism and mechanism thereof.

  5. Error image aware content restoration

    Science.gov (United States)

    Choi, Sungwoo; Lee, Moonsik; Jung, Byunghee

    2015-12-01

    As the resolution of TV significantly increased, content consumers have become increasingly sensitive to the subtlest defect in TV contents. This rising standard in quality demanded by consumers has posed a new challenge in today's context where the tape-based process has transitioned to the file-based process: the transition necessitated digitalizing old archives, a process which inevitably produces errors such as disordered pixel blocks, scattered white noise, or totally missing pixels. Unsurprisingly, detecting and fixing such errors require a substantial amount of time and human labor to meet the standard demanded by today's consumers. In this paper, we introduce a novel, automated error restoration algorithm which can be applied to different types of classic errors by utilizing adjacent images while preserving the undamaged parts of an error image as much as possible. We tested our method to error images detected from our quality check system in KBS(Korean Broadcasting System) video archive. We are also implementing the algorithm as a plugin of well-known NLE(Non-linear editing system), which is a familiar tool for quality control agent.

  6. Quantum error correction for beginners.

    Science.gov (United States)

    Devitt, Simon J; Munro, William J; Nemoto, Kae

    2013-07-01

    Quantum error correction (QEC) and fault-tolerant quantum computation represent one of the most vital theoretical aspects of quantum information processing. It was well known from the early developments of this exciting field that the fragility of coherent quantum systems would be a catastrophic obstacle to the development of large-scale quantum computers. The introduction of quantum error correction in 1995 showed that active techniques could be employed to mitigate this fatal problem. However, quantum error correction and fault-tolerant computation is now a much larger field and many new codes, techniques, and methodologies have been developed to implement error correction for large-scale quantum algorithms. In response, we have attempted to summarize the basic aspects of quantum error correction and fault-tolerance, not as a detailed guide, but rather as a basic introduction. The development in this area has been so pronounced that many in the field of quantum information, specifically researchers who are new to quantum information or people focused on the many other important issues in quantum computation, have found it difficult to keep up with the general formalisms and methodologies employed in this area. Rather than introducing these concepts from a rigorous mathematical and computer science framework, we instead examine error correction and fault-tolerance largely through detailed examples, which are more relevant to experimentalists today and in the near future.

  7. Dominant modes via model error

    Science.gov (United States)

    Yousuff, A.; Breida, M.

    1992-01-01

    Obtaining a reduced model of a stable mechanical system with proportional damping is considered. Such systems can be conveniently represented in modal coordinates. Two popular schemes, the modal cost analysis and the balancing method, offer simple means of identifying dominant modes for retention in the reduced model. The dominance is measured via the modal costs in the case of modal cost analysis and via the singular values of the Gramian-product in the case of balancing. Though these measures do not exactly reflect the more appropriate model error, which is the H2 norm of the output-error between the full and the reduced models, they do lead to simple computations. Normally, the model error is computed after the reduced model is obtained, since it is believed that, in general, the model error cannot be easily computed a priori. The authors point out that the model error can also be calculated a priori, just as easily as the above measures. Hence, the model error itself can be used to determine the dominant modes. Moreover, the simplicity of the computations does not presume any special properties of the system, such as small damping, orthogonal symmetry, etc.

  8. Analytics for metabolic engineering

    Directory of Open Access Journals (Sweden)

    Christopher J Petzold

    2015-09-01

    Full Text Available Realizing the promise of metabolic engineering has been slowed by challenges related to moving beyond proof-of-concept examples to robust and economically viable systems. Key to advancing metabolic engineering beyond trial-and-error research is access to parts with well-defined performance metrics that can be readily applied in vastly different contexts with predictable effects. As the field now stands, research depends greatly on analytical tools that assay target molecules, transcripts, proteins, and metabolites across different hosts and pathways. Screening technologies yield specific information for many thousands of strain variants while deep omics analysis provide a systems-level view of the cell factory. Efforts focused on a combination of these analyses yield quantitative information of dynamic processes between parts and the host chassis that drive the next engineering steps. Overall, the data generated from these types of assays aid better decision-making at the design and strain construction stages to speed progress in metabolic engineering research.

  9. Analytics for Metabolic Engineering

    Science.gov (United States)

    Petzold, Christopher J.; Chan, Leanne Jade G.; Nhan, Melissa; Adams, Paul D.

    2015-01-01

    Realizing the promise of metabolic engineering has been slowed by challenges related to moving beyond proof-of-concept examples to robust and economically viable systems. Key to advancing metabolic engineering beyond trial-and-error research is access to parts with well-defined performance metrics that can be readily applied in vastly different contexts with predictable effects. As the field now stands, research depends greatly on analytical tools that assay target molecules, transcripts, proteins, and metabolites across different hosts and pathways. Screening technologies yield specific information for many thousands of strain variants, while deep omics analysis provides a systems-level view of the cell factory. Efforts focused on a combination of these analyses yield quantitative information of dynamic processes between parts and the host chassis that drive the next engineering steps. Overall, the data generated from these types of assays aid better decision-making at the design and strain construction stages to speed progress in metabolic engineering research. PMID:26442249

  10. Harmless error analysis: How do judges respond to confession errors?

    Science.gov (United States)

    Wallace, D Brian; Kassin, Saul M

    2012-04-01

    In Arizona v. Fulminante (1991), the U.S. Supreme Court opened the door for appellate judges to conduct a harmless error analysis of erroneously admitted, coerced confessions. In this study, 132 judges from three states read a murder case summary, evaluated the defendant's guilt, assessed the voluntariness of his confession, and responded to implicit and explicit measures of harmless error. Results indicated that judges found a high-pressure confession to be coerced and hence improperly admitted into evidence. As in studies with mock jurors, however, the improper confession significantly increased their conviction rate in the absence of other evidence. On the harmless error measures, judges successfully overruled the confession when required to do so, indicating that they are capable of this analysis.

  11. Explaining errors in children's questions.

    Science.gov (United States)

    Rowland, Caroline F

    2007-07-01

    The ability to explain the occurrence of errors in children's speech is an essential component of successful theories of language acquisition. The present study tested some generativist and constructivist predictions about error on the questions produced by ten English-learning children between 2 and 5 years of age. The analyses demonstrated that, as predicted by some generativist theories [e.g. Santelmann, L., Berk, S., Austin, J., Somashekar, S. & Lust. B. (2002). Continuity and development in the acquisition of inversion in yes/no questions: dissociating movement and inflection, Journal of Child Language, 29, 813-842], questions with auxiliary DO attracted higher error rates than those with modal auxiliaries. However, in wh-questions, questions with modals and DO attracted equally high error rates, and these findings could not be explained in terms of problems forming questions with why or negated auxiliaries. It was concluded that the data might be better explained in terms of a constructivist account that suggests that entrenched item-based constructions may be protected from error in children's speech, and that errors occur when children resort to other operations to produce questions [e.g. Dabrowska, E. (2000). From formula to schema: the acquisition of English questions. Cognitive Liguistics, 11, 83-102; Rowland, C. F. & Pine, J. M. (2000). Subject-auxiliary inversion errors and wh-question acquisition: What children do know? Journal of Child Language, 27, 157-181; Tomasello, M. (2003). Constructing a language: A usage-based theory of language acquisition. Cambridge, MA: Harvard University Press]. However, further work on constructivist theory development is required to allow researchers to make predictions about the nature of these operations.

  12. Pauli Exchange Errors in Quantum Computation

    CERN Document Server

    Ruskai, M B

    2000-01-01

    We argue that a physically reasonable model of fault-tolerant computation requires the ability to correct a type of two-qubit error which we call Pauli exchange errors as well as one qubit errors. We give an explicit 9-qubit code which can handle both Pauli exchange errors and all one-bit errors.

  13. Metabolic Syndrome (For Parents)

    Science.gov (United States)

    ... Old Feeding Your 1- to 2-Year-Old Metabolic Syndrome KidsHealth > For Parents > Metabolic Syndrome A A A ... this is a condition called metabolic syndrome . About Metabolic Syndrome Not to be confused with metabolic disease (which ...

  14. Inborn anemias in mice. Comprehensive progress report, 1 August 1979-1 June 1982, to accompany twenty-seventh renewal proposal

    Energy Technology Data Exchange (ETDEWEB)

    Bernstein, S.E.; Russell, E.S.; Barker, J.E.

    1982-07-01

    Hereditary anemias of mice have been investigated including four macrocytic anemias, three hemolytic anemias, nonhemolytic microcytic anemia, transitory siderocytic anemia, sex-linked iron-transport anemia, an ..cap alpha..-thalassemia, and a new target-cell anemia. Each of these blood dyscrasias is caused by the action of a unique mutant gene, which determines the structure of different intracellular molecules controlling a different metabolic process. Thus the wide range of different hereditary anemias has considerable potential for uncovering many different aspects of hemopoietic homeostatic mechanisms in the mouse and by extension to man from an understanding of mammalian mechanisms utilized in the control of erythropoiesis. Each of the different anemias is studied through: (a) biochemical and biophysical characterization of peripheral blood cells; (b) determinations of cellular and organismic radiosensitivity under a variety of conditions; (c) measurements of iron metabolism and heme biosynthesis; (d) morphological and biochemical study of blood-forming tissue; (e) functional tests of the stem cell component; (f) examination of responses to erythroid stimuli and inhibitors; and (g) physiological complementation analysis via transplantation of tissue between individuals of differently affected genotypes.

  15. Error-associated behaviors and error rates for robotic geology

    Science.gov (United States)

    Anderson, Robert C.; Thomas, Geb; Wagner, Jacob; Glasgow, Justin

    2004-01-01

    This study explores human error as a function of the decision-making process. One of many models for human decision-making is Rasmussen's decision ladder [9]. The decision ladder identifies the multiple tasks and states of knowledge involved in decision-making. The tasks and states of knowledge can be classified by the level of cognitive effort required to make the decision, leading to the skill, rule, and knowledge taxonomy (Rasmussen, 1987). Skill based decisions require the least cognitive effort and knowledge based decisions require the greatest cognitive effort. Errors can occur at any of the cognitive levels.

  16. Error-associated behaviors and error rates for robotic geology

    Science.gov (United States)

    Anderson, Robert C.; Thomas, Geb; Wagner, Jacob; Glasgow, Justin

    2004-01-01

    This study explores human error as a function of the decision-making process. One of many models for human decision-making is Rasmussen's decision ladder [9]. The decision ladder identifies the multiple tasks and states of knowledge involved in decision-making. The tasks and states of knowledge can be classified by the level of cognitive effort required to make the decision, leading to the skill, rule, and knowledge taxonomy (Rasmussen, 1987). Skill based decisions require the least cognitive effort and knowledge based decisions require the greatest cognitive effort. Errors can occur at any of the cognitive levels.

  17. POSITION ERROR IN STATION-KEEPING SATELLITE

    Science.gov (United States)

    of an error in satellite orientation and the sun being in a plane other than the equatorial plane may result in errors in position determination. The nature of the errors involved is described and their magnitudes estimated.

  18. Orbit IMU alignment: Error analysis

    Science.gov (United States)

    Corson, R. W.

    1980-01-01

    A comprehensive accuracy analysis of orbit inertial measurement unit (IMU) alignments using the shuttle star trackers was completed and the results are presented. Monte Carlo techniques were used in a computer simulation of the IMU alignment hardware and software systems to: (1) determine the expected Space Transportation System 1 Flight (STS-1) manual mode IMU alignment accuracy; (2) investigate the accuracy of alignments in later shuttle flights when the automatic mode of star acquisition may be used; and (3) verify that an analytical model previously used for estimating the alignment error is a valid model. The analysis results do not differ significantly from expectations. The standard deviation in the IMU alignment error for STS-1 alignments was determined to the 68 arc seconds per axis. This corresponds to a 99.7% probability that the magnitude of the total alignment error is less than 258 arc seconds.

  19. Negligence, genuine error, and litigation

    Directory of Open Access Journals (Sweden)

    Sohn DH

    2013-02-01

    Full Text Available David H SohnDepartment of Orthopedic Surgery, University of Toledo Medical Center, Toledo, OH, USAAbstract: Not all medical injuries are the result of negligence. In fact, most medical injuries are the result either of the inherent risk in the practice of medicine, or due to system errors, which cannot be prevented simply through fear of disciplinary action. This paper will discuss the differences between adverse events, negligence, and system errors; the current medical malpractice tort system in the United States; and review current and future solutions, including medical malpractice reform, alternative dispute resolution, health courts, and no-fault compensation systems. The current political environment favors investigation of non-cap tort reform remedies; investment into more rational oversight systems, such as health courts or no-fault systems may reap both quantitative and qualitative benefits for a less costly and safer health system.Keywords: medical malpractice, tort reform, no fault compensation, alternative dispute resolution, system errors

  20. Large errors and severe conditions

    CERN Document Server

    Smith, D L; Van Wormer, L A

    2002-01-01

    Physical parameters that can assume real-number values over a continuous range are generally represented by inherently positive random variables. However, if the uncertainties in these parameters are significant (large errors), conventional means of representing and manipulating the associated variables can lead to erroneous results. Instead, all analyses involving them must be conducted in a probabilistic framework. Several issues must be considered: First, non-linear functional relations between primary and derived variables may lead to significant 'error amplification' (severe conditions). Second, the commonly used normal (Gaussian) probability distribution must be replaced by a more appropriate function that avoids the occurrence of negative sampling results. Third, both primary random variables and those derived through well-defined functions must be dealt with entirely in terms of their probability distributions. Parameter 'values' and 'errors' should be interpreted as specific moments of these probabil...

  1. Redundant measurements for controlling errors

    Energy Technology Data Exchange (ETDEWEB)

    Ehinger, M. H.; Crawford, J. M.; Madeen, M. L.

    1979-07-01

    Current federal regulations for nuclear materials control require consideration of operating data as part of the quality control program and limits of error propagation. Recent work at the BNFP has revealed that operating data are subject to a number of measurement problems which are very difficult to detect and even more difficult to correct in a timely manner. Thus error estimates based on operational data reflect those problems. During the FY 1978 and FY 1979 R and D demonstration runs at the BNFP, redundant measurement techniques were shown to be effective in detecting these problems to allow corrective action. The net effect is a reduction in measurement errors and a significant increase in measurement sensitivity. Results show that normal operation process control measurements, in conjunction with routine accountability measurements, are sensitive problem indicators when incorporated in a redundant measurement program.

  2. Toward a cognitive taxonomy of medical errors.

    OpenAIRE

    Zhang, Jiajie; Patel, Vimla L.; Johnson, Todd R.; Shortliffe, Edward H.

    2002-01-01

    One critical step in addressing and resolving the problems associated with human errors is the development of a cognitive taxonomy of such errors. In the case of errors, such a taxonomy may be developed (1) to categorize all types of errors along cognitive dimensions, (2) to associate each type of error with a specific underlying cognitive mechanism, (3) to explain why, and even predict when and where, a specific error will occur, and (4) to generate intervention strategies for each type of e...

  3. Robust Quantum Error Correction via Convex Optimization

    CERN Document Server

    Kosut, R L; Lidar, D A

    2007-01-01

    Quantum error correction procedures have traditionally been developed for specific error models, and are not robust against uncertainty in the errors. Using a semidefinite program optimization approach we find high fidelity quantum error correction procedures which present robust encoding and recovery effective against significant uncertainty in the error system. We present numerical examples for 3, 5, and 7-qubit codes. Our approach requires as input a description of the error channel, which can be provided via quantum process tomography.

  4. Errors depending on costs in sample surveys

    OpenAIRE

    Marella, Daniela

    2007-01-01

    "This paper presents a total survey error model that simultaneously treats sampling error, nonresponse error and measurement error. The main aim for developing the model is to determine the optimal allocation of the available resources for the total survey error reduction. More precisely, the paper is concerned with obtaining the best possible accuracy in survey estimate through an overall economic balance between sampling and nonsampling error." (author's abstract)

  5. Error-tolerant Tree Matching

    CERN Document Server

    Oflazer, K

    1996-01-01

    This paper presents an efficient algorithm for retrieving from a database of trees, all trees that match a given query tree approximately, that is, within a certain error tolerance. It has natural language processing applications in searching for matches in example-based translation systems, and retrieval from lexical databases containing entries of complex feature structures. The algorithm has been implemented on SparcStations, and for large randomly generated synthetic tree databases (some having tens of thousands of trees) it can associatively search for trees with a small error, in a matter of tenths of a second to few seconds.

  6. Immediate error correction process following sleep deprivation

    National Research Council Canada - National Science Library

    HSIEH, SHULAN; CHENG, I‐CHEN; TSAI, LING‐LING

    2007-01-01

    ...) participated in this study. Participants performed a modified letter flanker task and were instructed to make immediate error corrections on detecting performance errors. Event‐related potentials (ERPs...

  7. Metabolic syndrome

    Institute of Scientific and Technical Information of China (English)

    Charles Shaeffer

    2004-01-01

    @@ The emergence of cardiac disease as the number one world-wide cause of death justifies efforts to identify individuals at higher risk for preventive therapy. The metabolic syndrome, originally described by Reaven, 1 has been associated with higher cardiovascular disease risk. 2 Type Ⅱ diabetes is also a frequent sequela. 3

  8. The error of our ways

    Science.gov (United States)

    Swartz, Clifford E.

    1999-10-01

    In Victorian literature it was usually some poor female who came to see the error of her ways. How prescient of her! How I wish that all writers of manuscripts for The Physics Teacher would come to similar recognition of this centerpiece of measurement. For, Brothers and Sisters, we all err.

  9. Measurement error in geometric morphometrics.

    Science.gov (United States)

    Fruciano, Carmelo

    2016-06-01

    Geometric morphometrics-a set of methods for the statistical analysis of shape once saluted as a revolutionary advancement in the analysis of morphology -is now mature and routinely used in ecology and evolution. However, a factor often disregarded in empirical studies is the presence and the extent of measurement error. This is potentially a very serious issue because random measurement error can inflate the amount of variance and, since many statistical analyses are based on the amount of "explained" relative to "residual" variance, can result in loss of statistical power. On the other hand, systematic bias can affect statistical analyses by biasing the results (i.e. variation due to bias is incorporated in the analysis and treated as biologically-meaningful variation). Here, I briefly review common sources of error in geometric morphometrics. I then review the most commonly used methods to measure and account for both random and non-random measurement error, providing a worked example using a real dataset.

  10. Finding errors in big data

    NARCIS (Netherlands)

    Puts, Marco; Daas, Piet; de Waal, A.G.

    No data source is perfect. Mistakes inevitably creep in. Spotting errors is hard enough when dealing with survey responses from several thousand people, but the difficulty is multiplied hugely when that mysterious beast Big Data comes into play. Statistics Netherlands is about to publish its first

  11. Having Fun with Error Analysis

    Science.gov (United States)

    Siegel, Peter

    2007-01-01

    We present a fun activity that can be used to introduce students to error analysis: the M&M game. Students are told to estimate the number of individual candies plus uncertainty in a bag of M&M's. The winner is the group whose estimate brackets the actual number with the smallest uncertainty. The exercise produces enthusiastic discussions and…

  12. Typical errors of ESP users

    Science.gov (United States)

    Eremina, Svetlana V.; Korneva, Anna A.

    2004-07-01

    The paper presents analysis of the errors made by ESP (English for specific purposes) users which have been considered as typical. They occur as a result of misuse of resources of English grammar and tend to resist. Their origin and places of occurrence have also been discussed.

  13. Theory of Test Translation Error

    Science.gov (United States)

    Solano-Flores, Guillermo; Backhoff, Eduardo; Contreras-Nino, Luis Angel

    2009-01-01

    In this article, we present a theory of test translation whose intent is to provide the conceptual foundation for effective, systematic work in the process of test translation and test translation review. According to the theory, translation error is multidimensional; it is not simply the consequence of defective translation but an inevitable fact…

  14. A brief history of error.

    Science.gov (United States)

    Murray, Andrew W

    2011-10-03

    The spindle checkpoint monitors chromosome alignment on the mitotic and meiotic spindle. When the checkpoint detects errors, it arrests progress of the cell cycle while it attempts to correct the mistakes. This perspective will present a brief history summarizing what we know about the checkpoint, and a list of questions we must answer before we understand it.

  15. Error processing in Huntington's disease.

    Directory of Open Access Journals (Sweden)

    Christian Beste

    Full Text Available BACKGROUND: Huntington's disease (HD is a genetic disorder expressed by a degeneration of the basal ganglia inter alia accompanied with dopaminergic alterations. These dopaminergic alterations are related to genetic factors i.e., CAG-repeat expansion. The error (related negativity (Ne/ERN, a cognitive event-related potential related to performance monitoring, is generated in the anterior cingulate cortex (ACC and supposed to depend on the dopaminergic system. The Ne is reduced in Parkinson's Disease (PD. Due to a dopaminergic deficit in HD, a reduction of the Ne is also likely. Furthermore it is assumed that movement dysfunction emerges as a consequence of dysfunctional error-feedback processing. Since dopaminergic alterations are related to the CAG-repeat, a Ne reduction may furthermore also be related to the genetic disease load. METHODOLOGY/PRINCIPLE FINDINGS: We assessed the error negativity (Ne in a speeded reaction task under consideration of the underlying genetic abnormalities. HD patients showed a specific reduction in the Ne, which suggests impaired error processing in these patients. Furthermore, the Ne was closely related to CAG-repeat expansion. CONCLUSIONS/SIGNIFICANCE: The reduction of the Ne is likely to be an effect of the dopaminergic pathology. The result resembles findings in Parkinson's Disease. As such the Ne might be a measure for the integrity of striatal dopaminergic output function. The relation to the CAG-repeat expansion indicates that the Ne could serve as a gene-associated "cognitive" biomarker in HD.

  16. Learner Corpora without Error Tagging

    Directory of Open Access Journals (Sweden)

    Rastelli, Stefano

    2009-01-01

    Full Text Available The article explores the possibility of adopting a form-to-function perspective when annotating learner corpora in order to get deeper insights about systematic features of interlanguage. A split between forms and functions (or categories is desirable in order to avoid the "comparative fallacy" and because – especially in basic varieties – forms may precede functions (e.g., what resembles to a "noun" might have a different function or a function may show up in unexpected forms. In the computer-aided error analysis tradition, all items produced by learners are traced to a grid of error tags which is based on the categories of the target language. Differently, we believe it is possible to record and make retrievable both words and sequence of characters independently from their functional-grammatical label in the target language. For this purpose at the University of Pavia we adapted a probabilistic POS tagger designed for L1 on L2 data. Despite the criticism that this operation can raise, we found that it is better to work with "virtual categories" rather than with errors. The article outlines the theoretical background of the project and shows some examples in which some potential of SLA-oriented (non error-based tagging will be possibly made clearer.

  17. Input/output error analyzer

    Science.gov (United States)

    Vaughan, E. T.

    1977-01-01

    Program aids in equipment assessment. Independent assembly-language utility program is designed to operate under level 27 or 31 of EXEC 8 Operating System. It scans user-selected portions of system log file, whether located on tape or mass storage, and searches for and processes 1/0 error (type 6) entries.

  18. Amplify Errors to Minimize Them

    Science.gov (United States)

    Stewart, Maria Shine

    2009-01-01

    In this article, the author offers her experience of modeling mistakes and writing spontaneously in the computer classroom to get students' attention and elicit their editorial response. She describes how she taught her class about major sentence errors--comma splices, run-ons, and fragments--through her Sentence Meditation exercise, a rendition…

  19. Toward a cognitive taxonomy of medical errors.

    Science.gov (United States)

    Zhang, Jiajie; Patel, Vimla L; Johnson, Todd R; Shortliffe, Edward H

    2002-01-01

    One critical step in addressing and resolving the problems associated with human errors is the development of a cognitive taxonomy of such errors. In the case of errors, such a taxonomy may be developed (1) to categorize all types of errors along cognitive dimensions, (2) to associate each type of error with a specific underlying cognitive mechanism, (3) to explain why, and even predict when and where, a specific error will occur, and (4) to generate intervention strategies for each type of error. Based on Reason's (1992) definition of human errors and Norman's (1986) cognitive theory of human action, we have developed a preliminary action-based cognitive taxonomy of errors that largely satisfies these four criteria in the domain of medicine. We discuss initial steps for applying this taxonomy to develop an online medical error reporting system that not only categorizes errors but also identifies problems and generates solutions.

  20. Error and its meaning in forensic science.

    Science.gov (United States)

    Christensen, Angi M; Crowder, Christian M; Ousley, Stephen D; Houck, Max M

    2014-01-01

    The discussion of "error" has gained momentum in forensic science in the wake of the Daubert guidelines and has intensified with the National Academy of Sciences' Report. Error has many different meanings, and too often, forensic practitioners themselves as well as the courts misunderstand scientific error and statistical error rates, often confusing them with practitioner error (or mistakes). Here, we present an overview of these concepts as they pertain to forensic science applications, discussing the difference between practitioner error (including mistakes), instrument error, statistical error, and method error. We urge forensic practitioners to ensure that potential sources of error and method limitations are understood and clearly communicated and advocate that the legal community be informed regarding the differences between interobserver errors, uncertainty, variation, and mistakes.

  1. Analytical method for coupled transmission error of helical gear system with machining errors, assembly errors and tooth modifications

    Science.gov (United States)

    Lin, Tengjiao; He, Zeyin

    2017-07-01

    We present a method for analyzing the transmission error of helical gear system with errors. First a finite element method is used for modeling gear transmission system with machining errors, assembly errors, modifications and the static transmission error is obtained. Then the bending-torsional-axial coupling dynamic model of the transmission system based on the lumped mass method is established and the dynamic transmission error of gear transmission system is calculated, which provides error excitation data for the analysis and control of vibration and noise of gear system.

  2. Microanalysis of gene expression in cultured cells

    NARCIS (Netherlands)

    E. van der Veer (Eveliene)

    1982-01-01

    textabstractIn this thesis two aspects of gene expression in cultured cells have been studied: the heterogeneity in gene expression in relation with the development and application of microchemical techniques for the prenatal diagnosis of inborn errors of metabolism and the possibility of inducing g

  3. Bismi Renai Tuhuiar/icisis, an Uncommniy diagnosed

    African Journals Online (AJOL)

    scores and birth weight were unknown. Physical ex- ... percent increase) following rehydration At discharge eight days later, weight was 2.55kg. He was g read- mitted two days after discharge with a day history of recurrent diarrhoea,,4 percent weight loss and clini- .... eral inborn errors of metabolism (IEM) presenting in.

  4. Clinical profile and molecular characterization of Galactosemia in Brazil: identification of seven novel mutations

    OpenAIRE

    Garcia, Daniel F.; Camelo Junior, Jose S.; Molfetta, Greice A; Turcato, Marlene; Souza, Carolina F. M.; Porta, Gilda; Carlos E. Steiner; Silva Junior, Wilson A

    2016-01-01

    Abstract Background Classical Galactosemia (CG) is an inborn error of galactose metabolism caused by the deficiency of the galactose-1-phosphate uridyltransferase enzyme. It is transmitted as an autosomal recessive disease and is typically characterized by neonatal galactose intolerance, with complications ranging from neonatal jaundice and liver failure to late complications, such as motor and reproductive dysfunctions. Galactosemia is ...

  5. In vivo neuroprotective effect of L-carnitine against oxidative stress in maple syrup urine disease

    NARCIS (Netherlands)

    Mescka, Caroline; Moraes, Tarsila; Rosa, Andrea; Mazzola, Priscila; Piccoli, Bruna; Jacques, Carlos; Dalazen, Giovana; Coelho, Juliana; Cortes, Marcelo; Terra, Melaine; Regla Vargas, Carmen; Dutra-Filho, Carlos S

    2011-01-01

    Maple syrup urine disease (MSUD) is an autosomal recessive inborn error of metabolism caused by deficiency of the activity of the mitochondrial enzyme complex branched-chain α-keto acid dehydrogenase (BCKAD) leading to accumulation of the branched-chain amino acids (BCAA) leucine, isoleucine and val

  6. Liver transplantation in glycogen storage disease type I

    NARCIS (Netherlands)

    Boers, Susanna J. B.; Visser, Gepke; Smit, Peter G. P. A.; Fuchs, Sabine A.

    2014-01-01

    Glycogen storage disease type I (GSDI), an inborn error of carbohydrate metabolism, is caused by defects in the glucose-6-transporter/glucose-6-phosphatase complex, which is essential in glucose homeostasis. Two types exist, GSDIa and GSDIb, each caused by different defects in the complex. GSDIa is

  7. D-glyceric aciduria is caused by genetic deficiency of D-glycerate kinase (GLYCTK)

    DEFF Research Database (Denmark)

    Sass, Jörn Oliver; Fischer, Kathleen; Wang, Raymond;

    2010-01-01

    D-glyceric aciduria is a rare inborn error of serine and fructose metabolism that was first described in 1974. Most affected individuals have presented with neurological symptoms. The molecular basis of D-glyceric aciduria is largely unknown; possible causes that have been discussed are deficienc...

  8. Revised proposal for the prevention of low bone mass in patients with classic galactosemia.

    NARCIS (Netherlands)

    van Erven, Britt; Römers, Myrna M M; Rubio-Gozalbo, M Estela

    2014-01-01

    Decreased bone mass is frequently encountered in classic galactosemia, an inborn error of galactose metabolism. This decrease is most prominent in adults, but is already seen in prepubertal children with increased risk of osteoporosis and fractures later in life. Therefore, bone health in patients w

  9. Gastrointestinal Disorders in Children with Neurodevelopmental Disabilities

    Science.gov (United States)

    Sullivan, Peter B.

    2008-01-01

    Children with neurodevelopmental disabilities such as cerebral palsy (CP), spina bifida, or inborn errors of metabolism frequently have associated gastrointestinal problems. These include oral motor dysfunction leading to feeding difficulties, risk of aspiration, prolonged feeding times, and malnutrition with its attendant physical compromise.…

  10. Favorable outcome in a newborn with molybdenum cofactor type A deficiency treated with cPMP

    NARCIS (Netherlands)

    Hitzert, Marrit M; Bos, Arend F; Bergman, Klasien A.; Veldman, Alex; Schwarz, Guenter; Santamaria-Araujo, José Angel; Heiner-Fokkema, Rebecca; Sival, Deborah A; Lunsing, Roelineke J; Arjune, Sita; Kosterink, Jos G W; van Spronsen, FrancJan

    2012-01-01

    Molybdenum cofactor deficiency (MoCD) is a lethal autosomal recessive inborn error of metabolism with devastating neurologic manifestations. Currently, experimental treatment with cyclic pyranopterin monophosphate (cPMP) is available for patients with MoCD type A caused by a mutation in the MOCS-1 g

  11. Newborn Screening: National Library of Medicine Literature Search, January 1980 through March 1987. No. 87-2.

    Science.gov (United States)

    Patrias, Karen

    This bibliography, prepared by the National Library of Medicine through a literature search of its online databases, covers all aspects of newborn screening. It includes references to screening for: inborn errors of metabolism, such as phenylketonuria and galactosemia; hemoglobinopathies, particularly sickle cell disease; congenital hypothyroidism…

  12. The molecular basis of Dutch infantile nephropathic cystinosis.

    NARCIS (Netherlands)

    Heil, S.G.; Levtchenko, E.N.; Monnens, L.A.H.; Trijbels, J.M.F.; Put, N.M.J. van der; Blom, H.J.

    2001-01-01

    Infantile nephropathic cystinosis, an inborn error of metabolism with an autosomal recessive inheritance pattern, is characterized by lysosomal storage of the amino acid cystine due to an impaired transport of cystine out of the lysosomes. Initial clinical features consist of the renal Fanconi syndr

  13. Viral symbiosis and the holobiontic nature of the human genome.

    Science.gov (United States)

    Ryan, Francis Patrick

    2016-01-01

    The human genome is a holobiontic union of the mammalian nuclear genome, the mitochondrial genome and large numbers of endogenized retroviral genomes. This article defines and explores this symbiogenetic pattern of evolution, looking at the implications for human genetics, epigenetics, embryogenesis, physiology and the pathogenesis of inborn errors of metabolism and many other diseases.

  14. Effects of β-alanine administration on selected parameters of oxidative stress and phosphoryltransfer network in cerebral cortex and cerebellum of rats

    NARCIS (Netherlands)

    Gemelli, Tanise; de Andrade, Rodrigo Binkowski; Rojas, Denise Bertin; Bonorino, Nariélle Ferner; Mazzola, Priscila Nicolao; Tortorelli, Lucas Silva; Funchal, Cláudia; Filho, Carlos Severo Dutra; Wannmacher, Clovis Milton Duval

    2013-01-01

    β-Alanine is a β-amino acid derivative of the degradation of pyrimidine uracil and precursor of the oxidative substrate acetyl-coenzyme A (acetyl-CoA). The accumulation of β-alanine occurs in β-alaninemia, an inborn error of metabolism. Patients with β-alaninemia may develop neurological abnormaliti

  15. The G22A Polymorphism of the ADA Gene and Susceptibility to Autism Spectrum Disorders

    Science.gov (United States)

    Hettinger, Joe A.; Liu, Xudong; Holden, Jeanette Jeltje Anne

    2008-01-01

    Inborn errors of purine metabolism have been implicated as a cause for some cases of autism. This hypothesis is supported by the finding of decreased adenosine deaminase (ADA) activity in the sera of some children with autism and reports of an association of the A allele of the ADA G22A (Asp8Asn) polymorphism in individuals with autism of…

  16. Defining the phenotype and diagnostic considerations in adults with congenital disorders of N-linked glycosylation

    NARCIS (Netherlands)

    Wolthuis, D.F.; Janssen, M.C; Cassiman, D.; Lefeber, D.J.; Morava-Kozicz, E.

    2014-01-01

    Congenital disorders of N-glycosylation (CDG) form a rapidly growing group of more than 20 inborn errors of metabolism. Most patients are identified at the pediatric age with multisystem disease. There is no systematic review on the long-term outcome and clinical presentation in adult patients. Here

  17. D-glyceric aciduria is caused by genetic deficiency of D-glycerate kinase (GLYCTK)

    DEFF Research Database (Denmark)

    Sass, Jörn Oliver; Fischer, Kathleen; Wang, Raymond

    2010-01-01

    D-glyceric aciduria is a rare inborn error of serine and fructose metabolism that was first described in 1974. Most affected individuals have presented with neurological symptoms. The molecular basis of D-glyceric aciduria is largely unknown; possible causes that have been discussed...

  18. Biomarker for Glycogen Storage Diseases

    Science.gov (United States)

    2017-07-03

    Fructose Metabolism, Inborn Errors; Glycogen Storage Disease; Glycogen Storage Disease Type I; Glycogen Storage Disease Type II; Glycogen Storage Disease Type III; Glycogen Storage Disease Type IV; Glycogen Storage Disease Type V; Glycogen Storage Disease Type VI; Glycogen Storage Disease Type VII; Glycogen Storage Disease Type VIII

  19. Hereditary fructose intolerance and alpha(1) antitrypsin deficiency.

    Science.gov (United States)

    Hillebrand, G; Schneppenheim, R; Oldigs, H D; Santer, R

    2000-07-01

    A patient with coexisting hereditary fructose intolerance (HFI) and alpha(1) antitrypsin deficiency (alpha(1)ATD) is described. Protease inhibitor typing was not conclusive, presumably because of impaired N-glycosylation secondary to HFI. The case underlines the diagnostic role of molecular genetic techniques in inborn errors of metabolism.

  20. Gastrointestinal Disorders in Children with Neurodevelopmental Disabilities

    Science.gov (United States)

    Sullivan, Peter B.

    2008-01-01

    Children with neurodevelopmental disabilities such as cerebral palsy (CP), spina bifida, or inborn errors of metabolism frequently have associated gastrointestinal problems. These include oral motor dysfunction leading to feeding difficulties, risk of aspiration, prolonged feeding times, and malnutrition with its attendant physical compromise.…

  1. Clinical and radiological picture of alcaptonuria and ochronosis

    Energy Technology Data Exchange (ETDEWEB)

    Guhl, B.; Moedder, B.; Guhl, C.

    1981-06-01

    Three observations of ochronosis are presented. The clinical and radiological findings were typical. Ochronosis is a rare disease due to an inborn error of metabolism. During the first decades of life the only sign is usually alcaptonuria. In elderly patients ochronosis may develope. The treatment is symptomatic.

  2. Megaloblastic anemia--a rare cause.

    Science.gov (United States)

    Debnath, Sanjib Kr; Aggarwal, Anju; Mittal, Hema

    2011-10-01

    A 2- year- old boy presented with non responsive megaloblastic anemia, growth failure and developmental delay. Blood levels of B(12), folic acid and iron were normal. Tandem mass spectroscopy for common inborn errors of metabolism did not reveal any abnormality. There was an increased excretion of orotic acid in urine. The authors report this as a rare cause of megaloblastic anemia.

  3. Homocystinuria: A rare condition presenting as stroke and megaloblastic anemia.

    Science.gov (United States)

    Bhardwaj, Parveen; Sharma, Ravi; Sharma, Minoo

    2010-07-01

    Homocystinuria is an inborn error of amino acid metabolism in which homocystine accumulates in the blood and produces a slowly evolving clinical syndrome. We are presenting a case of a 4-year-old female child who presented to us with stroke and also had megaloblastic anemia. She was diagnosed as having homocystinuria type-1, and she responded to treatment.

  4. Tandem Mass Neonatal Screening in Taiwan—Report from One Center

    Directory of Open Access Journals (Sweden)

    Hsiang-Po Huang

    2006-01-01

    Conclusion: We found that MS/MS neonatal screening was valuable in the early diagnosis of severe and treatable inborn errors of metabolism such as organic acidemias and urea cycle disorders. It also detected less severe disorders that required only observation.

  5. Timelines of the “free-particle” and “fixed-particle” models of stone-formation: theoretical and experimental investigations

    NARCIS (Netherlands)

    Kok, D.J.; W.P.A. Boellaard; Y. Ridwan (Yanto); Levchenko, V.A.

    2017-01-01

    textabstractTwo major theories on renal stone formation will be reviewed, the “free-particle” and “fixed-particle” mechanisms. These theories combine data on intrinsic factors (inborn metabolic errors), extrinsic factors (diet), renal cell responses and the physico-chemistry and biochemistry of urin

  6. A common mutation, R208X, identified in Vietnamese patients with mitochondrial acetoacetyl-CoA thiolase (T2) deficiency

    NARCIS (Netherlands)

    Fukao, Toshiyuki; Hoan Thi Nguyen, [No Value; Nhan Thu Nguyen, [No Value; Dung Chi Vu, [No Value; Ngoc Thi Bich Can, [No Value; Anh Thi Van Pham, [No Value; Khanh Ngoc Nguyen, [No Value; Kobayashi, Hironori; Hasegawa, Yuki; Thao Phuong Bui, [No Value; Niezen-Koning, Kary E.; Wanders, Ronald J. A.; de Koning, Tom; Liem Thanh Nguyen, [No Value; Yamaguchi, Seiji; Kondo, Naomi

    2010-01-01

    Mitochondrial acetoacetyl-CoA thiolase (12) deficiency is an inborn error of metabolism affecting isoleucine catabolism and ketone body utilization. This disorder is clinically characterized by intermittent keto-acidotic episodes with no clinical symptoms between episodes. In general, 12 gene mutati

  7. OMEGA-3 LONG-CHAIN POLYUNSATURATED FATTY ACIDS IN OLDER CHILDREN

    Science.gov (United States)

    Phenylketonuria (PKU), the most prevalent inborn error of metabolism, is usually secondary to low hepatic activity of phenylalanine hydroxylase, the enzyme that catalyzes conversion of phenylalanine to tyrosine. Growth and development of infants and children with PKU who are managed by mandatory n...

  8. Phenylketonuria : a 21(st) century perspective

    NARCIS (Netherlands)

    Blau, Nenad; van Spronsen, Francjan J.; Levy, Harvey L.

    2010-01-01

    Phenylketonuria is the most prevalent disorder caused by an inborn error in aminoacid metabolism. It results from mutations in the phenylalanine hydroxylase gene. Phenotypes can vary from a very mild increase in blood phenylalanine concentrations to a severe classic phenotype with pronounced hyperph

  9. Autism in patients with propionic acidemia

    NARCIS (Netherlands)

    Witters, P.; Debbold, E.; Crivelly, K.; Kerckhove, K. Vande; Corthouts, K.; Debbold, B.; Andersson, H.; Vannieuwenborg, L.; Geuens, S.; Baumgartner, M.; Kozicz, L.T.; Settles, L.; Morava, E.

    2016-01-01

    Certain inborn errors of metabolism have been suggested to increase the risk of autistic behavior. In an animal model, propionic acid ingestion triggered abnormal behavior resembling autism. So far only a few cases were reported with propionic acidemia and autistic features. From a series of twelve

  10. Neurological images in phenylketonuria (PKU

    Directory of Open Access Journals (Sweden)

    Juan Francisco Cabello

    2014-07-01

    Full Text Available Phenylketonuria is an inborn error of metabolism that causes structural abnormalities in the white matter of the brain. In untreated patients demyelization can be observed, and there is evidence of intramyelin edema even in some treated patients. Imaging studies especially magnetic resonance imaging are useful for the study of patients with phenylketonuria, but their benefit as monitoring tools is controversial.

  11. Phenylketonuria: central nervous system and microbiome interaction

    Directory of Open Access Journals (Sweden)

    Demian Arturo Herrera Morban

    2017-06-01

    Full Text Available Phenylketonuria (PKU is an autosomal recessive inborn error of metabolism characterized by increased phenylalanine (Phe levels causing an inadequate neurodevelopment; the treatment of PKU is a Phe-restricting diet, and as such it can modulate the intestinal microbiome of the individual, generating central nervous system secondary disturbances that, added to the baseline disturbance, can influence the outcome of the disease.

  12. Space Saving Statistics: An Introduction to Constant Error, Variable Error, and Absolute Error.

    Science.gov (United States)

    Guth, David

    1990-01-01

    Article discusses research on orientation and mobility (O&M) for individuals with visual impairments, examining constant, variable, and absolute error (descriptive statistics that quantify fundamentally different characteristics of distributions of spatially directed behavior). It illustrates the statistics with examples, noting their…

  13. Discretization vs. Rounding Error in Euler's Method

    Science.gov (United States)

    Borges, Carlos F.

    2011-01-01

    Euler's method for solving initial value problems is an excellent vehicle for observing the relationship between discretization error and rounding error in numerical computation. Reductions in stepsize, in order to decrease discretization error, necessarily increase the number of steps and so introduce additional rounding error. The problem is…

  14. Discretization vs. Rounding Error in Euler's Method

    Science.gov (United States)

    Borges, Carlos F.

    2011-01-01

    Euler's method for solving initial value problems is an excellent vehicle for observing the relationship between discretization error and rounding error in numerical computation. Reductions in stepsize, in order to decrease discretization error, necessarily increase the number of steps and so introduce additional rounding error. The problem is…

  15. Correction of errors in power measurements

    DEFF Research Database (Denmark)

    Pedersen, Knud Ole Helgesen

    1998-01-01

    Small errors in voltage and current measuring transformers cause inaccuracies in power measurements.In this report correction factors are derived to compensate for such errors.......Small errors in voltage and current measuring transformers cause inaccuracies in power measurements.In this report correction factors are derived to compensate for such errors....

  16. Error Analysis of Band Matrix Method

    OpenAIRE

    Taniguchi, Takeo; Soga, Akira

    1984-01-01

    Numerical error in the solution of the band matrix method based on the elimination method in single precision is investigated theoretically and experimentally, and the behaviour of the truncation error and the roundoff error is clarified. Some important suggestions for the useful application of the band solver are proposed by using the results of above error analysis.

  17. Error Correction in Oral Classroom English Teaching

    Science.gov (United States)

    Jing, Huang; Xiaodong, Hao; Yu, Liu

    2016-01-01

    As is known to all, errors are inevitable in the process of language learning for Chinese students. Should we ignore students' errors in learning English? In common with other questions, different people hold different opinions. All teachers agree that errors students make in written English are not allowed. For the errors students make in oral…

  18. 5 CFR 1601.34 - Error correction.

    Science.gov (United States)

    2010-01-01

    ... 5 Administrative Personnel 3 2010-01-01 2010-01-01 false Error correction. 1601.34 Section 1601.34... Contribution Allocations and Interfund Transfer Requests § 1601.34 Error correction. Errors in processing... in the wrong investment fund, will be corrected in accordance with the error correction...

  19. STRUCTURED BACKWARD ERRORS FOR STRUCTURED KKT SYSTEMS

    Institute of Scientific and Technical Information of China (English)

    Xin-xiu Li; Xin-guo Liu

    2004-01-01

    In this paper we study structured backward errors for some structured KKT systems.Normwise structured backward errors for structured KKT systems are defined, and computable formulae of the structured backward errors are obtained. Simple numerical examples show that the structured backward errors may be much larger than the unstructured ones in some cases.

  20. Metabolic Syndrome

    Directory of Open Access Journals (Sweden)

    Sevil Ikinci

    2010-10-01

    Full Text Available Metabolic Syndrome is a combination of risk factors including common etiopathogenesis. These risk factors play different roles in occurence of atherosclerotic diseases, type 2 diabetes, and cancers. Although a compromise can not be achieved on differential diagnosis for MS, the existence of any three criterias enable to diagnose MS. These are abdominal obesity, dislipidemia (hypertrigliceridemia, hypercholesterolemia, and reduced high density lipoprotein hypertension, and elevated fasting blood glucose. According to the results of Metabolic Syndrome Research (METSAR, the overall prevalence of MS in Turkey is 34%; in females 40%, and in males it is 28%. As a result of “Western” diet, and increased frequency of obesity, MS is observed in children and in adolescents both in the world and in Turkey. Resulting in chronic diseases, it is thought that the syndrome can be prevented by healthy lifestyle behaviours. [TAF Prev Med Bull 2010; 9(5.000: 535-540

  1. Managing human error in aviation.

    Science.gov (United States)

    Helmreich, R L

    1997-05-01

    Crew resource management (CRM) programs were developed to address team and leadership aspects of piloting modern airplanes. The goal is to reduce errors through team work. Human factors research and social, cognitive, and organizational psychology are used to develop programs tailored for individual airlines. Flight crews study accident case histories, group dynamics, and human error. Simulators provide pilots with the opportunity to solve complex flight problems. CRM in the simulator is called line-oriented flight training (LOFT). In automated cockpits CRM promotes the idea of automation as a crew member. Cultural aspects of aviation include professional, business, and national culture. The aviation CRM model has been adapted for training surgeons and operating room staff in human factors.

  2. Robot learning and error correction

    Science.gov (United States)

    Friedman, L.

    1977-01-01

    A model of robot learning is described that associates previously unknown perceptions with the sensed known consequences of robot actions. For these actions, both the categories of outcomes and the corresponding sensory patterns are incorporated in a knowledge base by the system designer. Thus the robot is able to predict the outcome of an action and compare the expectation with the experience. New knowledge about what to expect in the world may then be incorporated by the robot in a pre-existing structure whether it detects accordance or discrepancy between a predicted consequence and experience. Errors committed during plan execution are detected by the same type of comparison process and learning may be applied to avoiding the errors.

  3. Manson’s triple error

    Directory of Open Access Journals (Sweden)

    Delaporte F.

    2008-09-01

    Full Text Available The author discusses the significance, implications and limitations of Manson’s work. How did Patrick Manson resolve some of the major problems raised by the filarial worm life cycle? The Amoy physician showed that circulating embryos could only leave the blood via the percutaneous route, thereby requiring a bloodsucking insect. The discovery of a new autonomous, airborne, active host undoubtedly had a considerable impact on the history of parasitology, but the way in which Manson formulated and solved the problem of the transfer of filarial worms from the body of the mosquito to man resulted in failure. This article shows how the epistemological transformation operated by Manson was indissociably related to a series of errors and how a major breakthrough can be the result of a series of false proposals and, consequently, that the history of truth often involves a history of error.

  4. What is Metabolic Syndrome?

    Science.gov (United States)

    ... from the NHLBI on Twitter. What Is Metabolic Syndrome? Metabolic syndrome is the name for a group of ... that may play a role in causing metabolic syndrome. Outlook Metabolic syndrome is becoming more common due to a ...

  5. Offset Error Compensation in Roundness Measurement

    Institute of Scientific and Technical Information of China (English)

    朱喜林; 史俊; 李晓梅

    2004-01-01

    This paper analyses three causes of offset error in roundness measurement and presents corresponding compensation methods.The causes of offset error include excursion error resulting from the deflection of the sensor's line of measurement from the rotational center in measurement (datum center), eccentricity error resulting from the variance between the workpiece's geometrical center and the rotational center, and tilt error resulting from the tilt between the workpiece's geometrical axes and the rotational centerline.

  6. FAKTOR PENYEBAB MEDICATION ERROR DI INSTALASI RAWAT DARURAT FACTORS AFFECTING MEDICATION ERRORS AT EMERGENCY UNIT

    OpenAIRE

    2014-01-01

    Background: Incident of medication errors is an importantindicator in patient safety and medication error is most commonmedical errors. However, most of medication errors can beprevented and efforts to reduce such errors are available.Due to high number of medications errors in the emergencyunit, understanding of the causes is important for designingsuccessful intervention. This research aims to identify typesand causes of medication errors.Method: Qualitative study was used and data were col...

  7. Error-resilient DNA computation

    Energy Technology Data Exchange (ETDEWEB)

    Karp, R.M.; Kenyon, C.; Waarts, O. [Univ. of California, Berkeley, CA (United States)

    1996-12-31

    The DNA model of computation, with test tubes of DNA molecules encoding bit sequences, is based on three primitives, Extract-A-Bit, which splits a test tube into two test tubes according to the value of a particular bit x, Merge-Two-Tubes and Detect-Emptiness. Perfect operations can test the satisfiability of any boolean formula in linear time. However, in reality the Extract operation is faulty; it misclassifies a certain proportion of the strands. We consider the following problem: given an algorithm based on perfect Extract, Merge and Detect operations, convert it to one that works correctly with high probability when the Extract operation is faulty. The fundamental problem in such a conversion is to construct a sequence of faulty Extracts and perfect Merges that simulates a highly reliable Extract operation. We first determine (up to a small constant factor) the minimum number of faulty Extract operations inherently required to simulate a highly reliable Extract operation. We then go on to derive a general method for converting any algorithm based on error-free operations to an error-resilient one, and give optimal error-resilient algorithms for realizing simple n-variable boolean functions such as Conjunction, Disjunction and Parity.

  8. Enfermedades metabólicas de aparición en la edad adulta Adult-onset metabolic diseases

    Directory of Open Access Journals (Sweden)

    A. García Ribes

    2008-01-01

    Full Text Available Los errores congénitos del metabolismo (ECM pueden debutar en la adolescencia y en la edad adulta. Aunque es difícil aportar datos exactos de prevalencia ya que existen escasos estudios al respecto, incluso considerándolos poco frecuentes, la importancia de su detección radica en las posibilidades terapéuticas y de consejo genético familiar. La principal sintomatología de los ECM del adulto es la neurológica, seguida de la hepática. Se puede establecer dos modos básicos de debut. Uno es el agudo, normalmente en forma de alteración del nivel de conciencia, letargia, coma de etiología desconocida en un paciente previamente sano (déficits del ciclo de la urea, trastornos de la remetilación de la homocisteína y porfirias son aquí las causas más frecuentes. Por otra parte está la sintomatología crónica, insidiosa, a menudo progresiva, en la que suele haber cuadros clínicos complejos, y más raramente un síntoma aislado de manera persistente (la enfermedad de Wilson, enfermedades mitocondriales, lisosomales, la enfermedad de Refsum y las glucogenosis son algunos ejemplos en este grupo. Es de especial importancia conocer las formas de debut agudo, que suelen ser situaciones de extrema urgencia, en las que una conducta adecuada puede evitar el fallecimiento del paciente. En este caso, exámenes sencillos de laboratorio como la determinación del amonio, homocisteína, lactato, acilcarnitinas, aminoácidos, ácidos orgánicos y porfirinas, pueden orientar el diagnóstico y permiten iniciar un tratamiento intensivo. En este capítulo se pretende realizar un enfoque práctico, abordando las características generales y claves clínicas de sospecha de los ECM más habituales en el adulto.Inborn errors of metabolism (IEM can have their onset in adolescence or in adulthood. Although it is difficult to contribute exact data on prevalence -because there are few studies in this respect, and IEM are regarded as infrequent- their detection is

  9. Metabolismo do cálcio na fenilcetonúria Calcium metabolism in phenilke

    Directory of Open Access Journals (Sweden)

    Fabiana Ferreira Martins

    2009-06-01

    Full Text Available A Fenilcetonúria é um erro inato do metabolismo do aminoácido fenilalanina. O tratamento é essencialmente dietético e envolve uma restrição severa no consumo de alimentos contendo aminoácido fenilalanina. Embora a alimentação seja complementada com fórmulas a fim de suprir as necessidades de vitaminas, minerais e aminoácidos essenciais, carências nutricionais ainda ocorrem. Isto se deve, principalmente, à restrição de fontes protéicas, que acarreta deficiência na ingestão de diversos nutrientes, dentre eles o cálcio. O cálcio possui importante relação com a formação mineral óssea. Estudos recentes demonstram que portadores de fenilcetonúria apresentam freqüentemente osteopenia e fraturas, sendo a maior incidência em crianças acima de 8 anos de idade. O rápido aumento da estatura, a dieta deficiente em cálcio e níveis de aminoácido fenilalanina elevados têm sido descritos como os principais fatores para a aquisição de massa óssea inadequada. A suplementação de cálcio em crianças saudáveis mostrou um efeito positivo sobre a aquisição de massa óssea na fase da pré-puberdade. Assim, torna-se relevante compreender a necessidade da suplementação de cálcio em pacientes fenilcetonúria, a fim de favorecer o desenvolvimento ósseo esperado.Phenylketonuria is an inborn error of the metabolism of the amino acid phenylalanine. The treatment is essentially dietetic and involves a severe restriction in the consumption of foods containing aminoacid phenylalanine. Although the diet is complemented with supplements in order to meet the vitamin, mineral and essential amino acid requirements, nutritional deficiencies still occur. This is mainly due to restricting the consumption of protein sources, which results in low intake of several nutrients, including calcium. Calcium is strongly related to bone mineral formation. Recent studies have demonstrated that patients with phenylketonuria often present osteopenia and

  10. Righting errors in writing errors: the Wing and Baddeley (1980) spelling error corpus revisited.

    Science.gov (United States)

    Wing, Alan M; Baddeley, Alan D

    2009-03-01

    We present a new analysis of our previously published corpus of handwriting errors (slips) using the proportional allocation algorithm of Machtynger and Shallice (2009). As previously, the proportion of slips is greater in the middle of the word than at the ends, however, in contrast to before, the proportion is greater at the end than at the beginning of the word. The findings are consistent with the hypothesis of memory effects in a graphemic output buffer.

  11. Effects of Listening Conditions, Error Types, and Ensemble Textures on Error Detection Skills

    Science.gov (United States)

    Waggoner, Dori T.

    2011-01-01

    This study was designed with three main purposes: (a) to investigate the effects of two listening conditions on error detection accuracy, (b) to compare error detection responses for rhythm errors and pitch errors, and (c) to examine the influences of texture on error detection accuracy. Undergraduate music education students (N = 18) listened to…

  12. Aperçu des maladies neurométaboliques chez l'adulte

    OpenAIRE

    Mochel, Fanny

    2015-01-01

    International audience; Introduction : Inborn errors of metabolism (IEM) are traditionally defined by enzymatic deficiencies or defects in proteins involved in cellular metabolism. Historically discovered and characterized in children, a growing number of IEM are described in adults, and especially in the field of neurology. In daily practice, it is important to recognize emergency situations as well as neurodegenerative diseases for which a metabolic disease is likely, especially when therap...

  13. SENSITIVE ERROR ANALYSIS OF CHAOS SYNCHRONIZATION

    Institute of Scientific and Technical Information of China (English)

    HUANG XIAN-GAO; XU JIAN-XUE; HUANG WEI; L(U) ZE-JUN

    2001-01-01

    We study the synchronizing sensitive errors of chaotic systems for adding other signals to the synchronizing signal.Based on the model of the Henon map masking, we examine the cause of the sensitive errors of chaos synchronization.The modulation ratio and the mean square error are defined to measure the synchronizing sensitive errors by quality.Numerical simulation results of the synchronizing sensitive errors are given for masking direct current, sinusoidal and speech signals, separately. Finally, we give the mean square error curves of chaos synchronizing sensitivity and threedimensional phase plots of the drive system and the response system for masking the three kinds of signals.

  14. Error signals driving locomotor adaptation

    DEFF Research Database (Denmark)

    Choi, Julia T; Jensen, Peter; Nielsen, Jens Bo

    2016-01-01

    perturbations. Forces were applied to the ankle joint during the early swing phase using an electrohydraulic ankle-foot orthosis. Repetitive 80 Hz electrical stimulation was applied to disrupt cutaneous feedback from the superficial peroneal nerve (foot dorsum) and medial plantar nerve (foot sole) during...... anaesthesia (n = 5) instead of repetitive nerve stimulation. Foot anaesthesia reduced ankle adaptation to external force perturbations during walking. Our results suggest that cutaneous input plays a role in force perception, and may contribute to the 'error' signal involved in driving walking adaptation when...

  15. (Errors in statistical tests3

    Directory of Open Access Journals (Sweden)

    Kaufman Jay S

    2008-07-01

    Full Text Available Abstract In 2004, Garcia-Berthou and Alcaraz published "Incongruence between test statistics and P values in medical papers," a critique of statistical errors that received a tremendous amount of attention. One of their observations was that the final reported digit of p-values in articles published in the journal Nature departed substantially from the uniform distribution that they suggested should be expected. In 2006, Jeng critiqued that critique, observing that the statistical analysis of those terminal digits had been based on comparing the actual distribution to a uniform continuous distribution, when digits obviously are discretely distributed. Jeng corrected the calculation and reported statistics that did not so clearly support the claim of a digit preference. However delightful it may be to read a critique of statistical errors in a critique of statistical errors, we nevertheless found several aspects of the whole exchange to be quite troubling, prompting our own meta-critique of the analysis. The previous discussion emphasized statistical significance testing. But there are various reasons to expect departure from the uniform distribution in terminal digits of p-values, so that simply rejecting the null hypothesis is not terribly informative. Much more importantly, Jeng found that the original p-value of 0.043 should have been 0.086, and suggested this represented an important difference because it was on the other side of 0.05. Among the most widely reiterated (though often ignored tenets of modern quantitative research methods is that we should not treat statistical significance as a bright line test of whether we have observed a phenomenon. Moreover, it sends the wrong message about the role of statistics to suggest that a result should be dismissed because of limited statistical precision when it is so easy to gather more data. In response to these limitations, we gathered more data to improve the statistical precision, and

  16. Topological Quantum Computation and Error Correction by Biological Cells

    CERN Document Server

    Lofthouse, J T

    2005-01-01

    A Topological examination of phospholipid dynamics in the Far from Equilibrium state has demonstrated that metabolically active cells use waste heat to generate spatially patterned membrane flows by forced convection and shear. This paper explains the resemblance between this nonlinear membrane model and Witten Kitaev type Topological Quantum Computation systems, and demonstrates how this self-organising membrane enables biological cells to circumvent the decoherence problem, perform error correction procedures, and produce classical level output as shielded current flow through cytoskeletal protein conduit. Cellular outputs are shown to be Turing compatible as they are determined by computable in principle hydromagnetic fluid flows, and importantly, are Adaptive from an Evolutionary perspective.

  17. Errors associated with outpatient computerized prescribing systems

    Science.gov (United States)

    Rothschild, Jeffrey M; Salzberg, Claudia; Keohane, Carol A; Zigmont, Katherine; Devita, Jim; Gandhi, Tejal K; Dalal, Anuj K; Bates, David W; Poon, Eric G

    2011-01-01

    Objective To report the frequency, types, and causes of errors associated with outpatient computer-generated prescriptions, and to develop a framework to classify these errors to determine which strategies have greatest potential for preventing them. Materials and methods This is a retrospective cohort study of 3850 computer-generated prescriptions received by a commercial outpatient pharmacy chain across three states over 4 weeks in 2008. A clinician panel reviewed the prescriptions using a previously described method to identify and classify medication errors. Primary outcomes were the incidence of medication errors; potential adverse drug events, defined as errors with potential for harm; and rate of prescribing errors by error type and by prescribing system. Results Of 3850 prescriptions, 452 (11.7%) contained 466 total errors, of which 163 (35.0%) were considered potential adverse drug events. Error rates varied by computerized prescribing system, from 5.1% to 37.5%. The most common error was omitted information (60.7% of all errors). Discussion About one in 10 computer-generated prescriptions included at least one error, of which a third had potential for harm. This is consistent with the literature on manual handwritten prescription error rates. The number, type, and severity of errors varied by computerized prescribing system, suggesting that some systems may be better at preventing errors than others. Conclusions Implementing a computerized prescribing system without comprehensive functionality and processes in place to ensure meaningful system use does not decrease medication errors. The authors offer targeted recommendations on improving computerized prescribing systems to prevent errors. PMID:21715428

  18. Error detection and reduction in blood banking.

    Science.gov (United States)

    Motschman, T L; Moore, S B

    1996-12-01

    Error management plays a major role in facility process improvement efforts. By detecting and reducing errors, quality and, therefore, patient care improve. It begins with a strong organizational foundation of management attitude with clear, consistent employee direction and appropriate physical facilities. Clearly defined critical processes, critical activities, and SOPs act as the framework for operations as well as active quality monitoring. To assure that personnel can detect an report errors they must be trained in both operational duties and error management practices. Use of simulated/intentional errors and incorporation of error detection into competency assessment keeps employees practiced, confident, and diminishes fear of the unknown. Personnel can clearly see that errors are indeed used as opportunities for process improvement and not for punishment. The facility must have a clearly defined and consistently used definition for reportable errors. Reportable errors should include those errors with potentially harmful outcomes as well as those errors that are "upstream," and thus further away from the outcome. A well-written error report consists of who, what, when, where, why/how, and follow-up to the error. Before correction can occur, an investigation to determine the underlying cause of the error should be undertaken. Obviously, the best corrective action is prevention. Correction can occur at five different levels; however, only three of these levels are directed at prevention. Prevention requires a method to collect and analyze data concerning errors. In the authors' facility a functional error classification method and a quality system-based classification have been useful. An active method to search for problems uncovers them further upstream, before they can have disastrous outcomes. In the continual quest for improving processes, an error management program is itself a process that needs improvement, and we must strive to always close the circle

  19. Antenna motion errors in bistatic SAR imagery

    Science.gov (United States)

    Wang, Ling; Yazıcı, Birsen; Cagri Yanik, H.

    2015-06-01

    Antenna trajectory or motion errors are pervasive in synthetic aperture radar (SAR) imaging. Motion errors typically result in smearing and positioning errors in SAR images. Understanding the relationship between the trajectory errors and position errors in reconstructed images is essential in forming focused SAR images. Existing studies on the effect of antenna motion errors are limited to certain geometries, trajectory error models or monostatic SAR configuration. In this paper, we present an analysis of position errors in bistatic SAR imagery due to antenna motion errors. Bistatic SAR imagery is becoming increasingly important in the context of passive imaging and multi-sensor imaging. Our analysis provides an explicit quantitative relationship between the trajectory errors and the positioning errors in bistatic SAR images. The analysis is applicable to arbitrary trajectory errors and arbitrary imaging geometries including wide apertures and large scenes. We present extensive numerical simulations to validate the analysis and to illustrate the results in commonly used bistatic configurations and certain trajectory error models.

  20. Medication errors: hospital pharmacist perspective.

    Science.gov (United States)

    Guchelaar, Henk-Jan; Colen, Hadewig B B; Kalmeijer, Mathijs D; Hudson, Patrick T W; Teepe-Twiss, Irene M

    2005-01-01

    In recent years medication error has justly received considerable attention, as it causes substantial mortality, morbidity and additional healthcare costs. Risk assessment models, adapted from commercial aviation and the oil and gas industries, are currently being developed for use in clinical pharmacy. The hospital pharmacist is best placed to oversee the quality of the entire drug distribution chain, from prescribing, drug choice, dispensing and preparation to the administration of drugs, and can fulfil a vital role in improving medication safety. Most elements of the drug distribution chain can be optimised; however, because comparative intervention studies are scarce, there is little scientific evidence available demonstrating improvements in medication safety through such interventions. Possible interventions aimed at reducing medication errors, such as developing methods for detection of patients with increased risk of adverse drug events, performing risk assessment in clinical pharmacy and optimising the drug distribution chain are discussed. Moreover, the specific role of the clinical pharmacist in improving medication safety is highlighted, both at an organisational level and in individual patient care.

  1. Cosine tuning minimizes motor errors.

    Science.gov (United States)

    Todorov, Emanuel

    2002-06-01

    Cosine tuning is ubiquitous in the motor system, yet a satisfying explanation of its origin is lacking. Here we argue that cosine tuning minimizes expected errors in force production, which makes it a natural choice for activating muscles and neurons in the final stages of motor processing. Our results are based on the empirically observed scaling of neuromotor noise, whose standard deviation is a linear function of the mean. Such scaling predicts a reduction of net force errors when redundant actuators pull in the same direction. We confirm this prediction by comparing forces produced with one versus two hands and generalize it across directions. Under the resulting neuromotor noise model, we prove that the optimal activation profile is a (possibly truncated) cosine--for arbitrary dimensionality of the workspace, distribution of force directions, correlated or uncorrelated noise, with or without a separate cocontraction command. The model predicts a negative force bias, truncated cosine tuning at low muscle cocontraction levels, and misalignment of preferred directions and lines of action for nonuniform muscle distributions. All predictions are supported by experimental data.

  2. Field errors in hybrid insertion devices

    Energy Technology Data Exchange (ETDEWEB)

    Schlueter, R.D. [Lawrence Berkeley Lab., CA (United States)

    1995-02-01

    Hybrid magnet theory as applied to the error analyses used in the design of Advanced Light Source (ALS) insertion devices is reviewed. Sources of field errors in hybrid insertion devices are discussed.

  3. Medical errors: legal and ethical responses.

    Science.gov (United States)

    Dickens, B M

    2003-04-01

    Liability to err is a human, often unavoidable, characteristic. Errors can be classified as skill-based, rule-based, knowledge-based and other errors, such as of judgment. In law, a key distinction is between negligent and non-negligent errors. To describe a mistake as an error of clinical judgment is legally ambiguous, since an error that a physician might have made when acting with ordinary care and the professional skill the physician claims, is not deemed negligent in law. If errors prejudice patients' recovery from treatment and/or future care, in physical or psychological ways, it is legally and ethically required that they be informed of them in appropriate time. Senior colleagues, facility administrators and others such as medical licensing authorities should be informed of serious forms of error, so that preventive education and strategies can be designed. Errors for which clinicians may be legally liable may originate in systemically defective institutional administration.

  4. Experimental demonstration of topological error correction.

    Science.gov (United States)

    Yao, Xing-Can; Wang, Tian-Xiong; Chen, Hao-Ze; Gao, Wei-Bo; Fowler, Austin G; Raussendorf, Robert; Chen, Zeng-Bing; Liu, Nai-Le; Lu, Chao-Yang; Deng, You-Jin; Chen, Yu-Ao; Pan, Jian-Wei

    2012-02-22

    Scalable quantum computing can be achieved only if quantum bits are manipulated in a fault-tolerant fashion. Topological error correction--a method that combines topological quantum computation with quantum error correction--has the highest known tolerable error rate for a local architecture. The technique makes use of cluster states with topological properties and requires only nearest-neighbour interactions. Here we report the experimental demonstration of topological error correction with an eight-photon cluster state. We show that a correlation can be protected against a single error on any quantum bit. Also, when all quantum bits are simultaneously subjected to errors with equal probability, the effective error rate can be significantly reduced. Our work demonstrates the viability of topological error correction for fault-tolerant quantum information processing.

  5. Game Design Principles based on Human Error

    Directory of Open Access Journals (Sweden)

    Guilherme Zaffari

    2016-03-01

    Full Text Available This paper displays the result of the authors’ research regarding to the incorporation of Human Error, through design principles, to video game design. In a general way, designers must consider Human Error factors throughout video game interface development; however, when related to its core design, adaptations are in need, since challenge is an important factor for fun and under the perspective of Human Error, challenge can be considered as a flaw in the system. The research utilized Human Error classifications, data triangulation via predictive human error analysis, and the expanded flow theory to allow the design of a set of principles in order to match the design of playful challenges with the principles of Human Error. From the results, it was possible to conclude that the application of Human Error in game design has a positive effect on player experience, allowing it to interact only with errors associated with the intended aesthetics of the game.

  6. L’errore nel laboratorio di Microbiologia

    Directory of Open Access Journals (Sweden)

    Paolo Lanzafame

    2006-03-01

    Full Text Available Error management plays one of the most important roles in facility process improvement efforts. By detecting and reducing errors quality and patient care improve. The records of errors was analysed over a period of 6 months and another was used to study the potential bias in the registrations.The percentage of errors detected was 0,17% (normalised 1720 ppm and the errors in the pre-analytical phase was the largest part.The major rate of errors was generated by the peripheral centres which send only sometimes the microbiology tests and don’t know well the specific procedures to collect and storage biological samples.The errors in the management of laboratory supplies were reported too. The conclusion is that improving operators training, in particular concerning samples collection and storage, is very important and that an affective system of error detection should be employed to determine the causes and the best corrective action should be applied.

  7. An Error Analysis on TFL Learners’ Writings

    Directory of Open Access Journals (Sweden)

    Arif ÇERÇİ

    2016-12-01

    Full Text Available The main purpose of the present study is to identify and represent TFL learners’ writing errors through error analysis. All the learners started learning Turkish as foreign language with A1 (beginner level and completed the process by taking C1 (advanced certificate in TÖMER at Gaziantep University. The data of the present study were collected from 14 students’ writings in proficiency exams for each level. The data were grouped as grammatical, syntactic, spelling, punctuation, and word choice errors. The ratio and categorical distributions of identified errors were analyzed through error analysis. The data were analyzed through statistical procedures in an effort to determine whether error types differ according to the levels of the students. The errors in this study are limited to the linguistic and intralingual developmental errors

  8. Error Propagation in a System Model

    Science.gov (United States)

    Schloegel, Kirk (Inventor); Bhatt, Devesh (Inventor); Oglesby, David V. (Inventor); Madl, Gabor (Inventor)

    2015-01-01

    Embodiments of the present subject matter can enable the analysis of signal value errors for system models. In an example, signal value errors can be propagated through the functional blocks of a system model to analyze possible effects as the signal value errors impact incident functional blocks. This propagation of the errors can be applicable to many models of computation including avionics models, synchronous data flow, and Kahn process networks.

  9. Experimental demonstration of topological error correction

    OpenAIRE

    2012-01-01

    Scalable quantum computing can only be achieved if qubits are manipulated fault-tolerantly. Topological error correction - a novel method which combines topological quantum computing and quantum error correction - possesses the highest known tolerable error rate for a local architecture. This scheme makes use of cluster states with topological properties and requires only nearest-neighbour interactions. Here we report the first experimental demonstration of topological error correction with a...

  10. Sampling error of observation impact statistics

    OpenAIRE

    Kim, Sung-Min; Kim, Hyun Mee

    2014-01-01

    An observation impact is an estimate of the forecast error reduction by assimilating observations with numerical model forecasts. This study compares the sampling errors of the observation impact statistics (OBIS) of July 2011 and January 2012 using two methods. One method uses the random error under the assumption that the samples are independent, and the other method uses the error with lag correlation under the assumption that the samples are correlated with each other. The OBIS are obtain...

  11. Acoustic Evidence for Phonologically Mismatched Speech Errors

    Science.gov (United States)

    Gormley, Andrea

    2015-01-01

    Speech errors are generally said to accommodate to their new phonological context. This accommodation has been validated by several transcription studies. The transcription methodology is not the best choice for detecting errors at this level, however, as this type of error can be difficult to perceive. This paper presents an acoustic analysis of…

  12. Medication errors: the importance of safe dispensing.

    NARCIS (Netherlands)

    Cheung, K.C.; Bouvy, M.L.; Smet, P.A.G.M. de

    2009-01-01

    1. Although rates of dispensing errors are generally low, further improvements in pharmacy distribution systems are still important because pharmacies dispense such high volumes of medications that even a low error rate can translate into a large number of errors. 2. From the perspective of pharmacy

  13. Understanding EFL Students' Errors in Writing

    Science.gov (United States)

    Phuket, Pimpisa Rattanadilok Na; Othman, Normah Binti

    2015-01-01

    Writing is the most difficult skill in English, so most EFL students tend to make errors in writing. In assisting the learners to successfully acquire writing skill, the analysis of errors and the understanding of their sources are necessary. This study attempts to explore the major sources of errors occurred in the writing of EFL students. It…

  14. Error Analysis of Quadrature Rules. Classroom Notes

    Science.gov (United States)

    Glaister, P.

    2004-01-01

    Approaches to the determination of the error in numerical quadrature rules are discussed and compared. This article considers the problem of the determination of errors in numerical quadrature rules, taking Simpson's rule as the principal example. It suggests an approach based on truncation error analysis of numerical schemes for differential…

  15. Error Analysis in Mathematics. Technical Report #1012

    Science.gov (United States)

    Lai, Cheng-Fei

    2012-01-01

    Error analysis is a method commonly used to identify the cause of student errors when they make consistent mistakes. It is a process of reviewing a student's work and then looking for patterns of misunderstanding. Errors in mathematics can be factual, procedural, or conceptual, and may occur for a number of reasons. Reasons why students make…

  16. Error Analysis and the EFL Classroom Teaching

    Science.gov (United States)

    Xie, Fang; Jiang, Xue-mei

    2007-01-01

    This paper makes a study of error analysis and its implementation in the EFL (English as Foreign Language) classroom teaching. It starts by giving a systematic review of the concepts and theories concerning EA (Error Analysis), the various reasons causing errors are comprehensively explored. The author proposes that teachers should employ…

  17. Human Error Mechanisms in Complex Work Environments

    DEFF Research Database (Denmark)

    Rasmussen, Jens

    1988-01-01

    will account for most of the action errors observed. In addition, error mechanisms appear to be intimately related to the development of high skill and know-how in a complex work context. This relationship between errors and human adaptation is discussed in detail for individuals and organisations...

  18. Errors and Uncertainty in Physics Measurement.

    Science.gov (United States)

    Blasiak, Wladyslaw

    1983-01-01

    Classifies errors as either systematic or blunder and uncertainties as either systematic or random. Discusses use of error/uncertainty analysis in direct/indirect measurement, describing the process of planning experiments to ensure lowest possible uncertainty. Also considers appropriate level of error analysis for high school physics students'…

  19. Measurement error in a single regressor

    NARCIS (Netherlands)

    Meijer, H.J.; Wansbeek, T.J.

    2000-01-01

    For the setting of multiple regression with measurement error in a single regressor, we present some very simple formulas to assess the result that one may expect when correcting for measurement error. It is shown where the corrected estimated regression coefficients and the error variance may lie,

  20. Jonas Olson's Evidence for Moral Error Theory

    NARCIS (Netherlands)

    Evers, Daan

    2016-01-01

    Jonas Olson defends a moral error theory in (2014). I first argue that Olson is not justified in believing the error theory as opposed to moral nonnaturalism in his own opinion. I then argue that Olson is not justified in believing the error theory as opposed to moral contextualism either (although

  1. AWARENESS OF DE NTISTS ABOUT MEDICATION ERRORS

    Directory of Open Access Journals (Sweden)

    Sangeetha

    2014-01-01

    Full Text Available OBJECTIVE: To assess the awareness of medication errors among dentists. METHODS: Medication errors are the most common single preventable cause o f adverse events in medication practice. We conducted a survey with a sample of sixty dentists. Among them 30 were general dentists (BDS and 30 were dental specialists (MDS. Questionnaires were distributed to them with questions regarding medication erro rs and they were asked to fill up the questionnaire. Data was collected and subjected to statistical analysis using Fisher exact and Chi square test. RESULTS: In our study, sixty percent of general dentists and 76.7% of dental specialists were aware about the components of medication error. Overall 66.7% of the respondents in each group marked wrong duration as the dispensing error. Almost thirty percent of the general dentists and 56.7% of the dental specialists felt that technologic advances could accompl ish diverse task in reducing medication errors. This was of suggestive statistical significance with a P value of 0.069. CONCLUSION: Medication errors compromise patient confidence in the health - care system and increase health - care costs. Overall, the dent al specialists were more knowledgeable than the general dentists about the Medication errors. KEY WORDS: Medication errors; Dosing error; Prevention of errors; Adverse drug events; Prescribing errors; Medical errors.

  2. Error-Compensated Integrate and Hold

    Science.gov (United States)

    Matlin, M.

    1984-01-01

    Differencing circuit cancels error caused by switching transistors capacitance. In integrate and hold circuit using JFET switch, gate-to-source capacitance causes error in output voltage. Differential connection cancels out error. Applications in systems where very low voltages sampled or many integrate-and -hold cycles before circuit is reset.

  3. Jonas Olson's Evidence for Moral Error Theory

    NARCIS (Netherlands)

    Evers, Daan

    2016-01-01

    Jonas Olson defends a moral error theory in (2014). I first argue that Olson is not justified in believing the error theory as opposed to moral nonnaturalism in his own opinion. I then argue that Olson is not justified in believing the error theory as opposed to moral contextualism either (although

  4. Human Errors and Bridge Management Systems

    DEFF Research Database (Denmark)

    Thoft-Christensen, Palle; Nowak, A. S.

    Human errors are divided in two groups. The first group contains human errors, which effect the reliability directly. The second group contains human errors, which will not directly effect the reliability of the structure. The methodology used to estimate so-called reliability distributions on ba...

  5. The Problematic of Second Language Errors

    Science.gov (United States)

    Hamid, M. Obaidul; Doan, Linh Dieu

    2014-01-01

    The significance of errors in explicating Second Language Acquisition (SLA) processes led to the growth of error analysis in the 1970s which has since maintained its prominence in English as a second/foreign language (L2) research. However, one problem with this research is errors are often taken for granted, without problematising them and their…

  6. Error estimate for Doo-Sabin surfaces

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Based on a general bound on the distance error between a uniform Doo-Sabin surface and its control polyhedron, an exponential error bound independent of the subdivision process is presented in this paper. Using the exponential bound, one can predict the depth of recursive subdivision of the Doo-Sabin surface within any user-specified error tolerance.

  7. Medication errors: the importance of safe dispensing.

    NARCIS (Netherlands)

    Cheung, K.C.; Bouvy, M.L.; Smet, P.A.G.M. de

    2009-01-01

    1. Although rates of dispensing errors are generally low, further improvements in pharmacy distribution systems are still important because pharmacies dispense such high volumes of medications that even a low error rate can translate into a large number of errors. 2. From the perspective of pharmacy

  8. Preventing statistical errors in scientific journals.

    NARCIS (Netherlands)

    Nuijten, M.B.

    2016-01-01

    There is evidence for a high prevalence of statistical reporting errors in psychology and other scientific fields. These errors display a systematic preference for statistically significant results, distorting the scientific literature. There are several possible causes for this systematic error pre

  9. Quantum error-correction failure distributions: Comparison of coherent and stochastic error models

    Science.gov (United States)

    Barnes, Jeff P.; Trout, Colin J.; Lucarelli, Dennis; Clader, B. D.

    2017-06-01

    We compare failure distributions of quantum error correction circuits for stochastic errors and coherent errors. We utilize a fully coherent simulation of a fault-tolerant quantum error correcting circuit for a d =3 Steane and surface code. We find that the output distributions are markedly different for the two error models, showing that no simple mapping between the two error models exists. Coherent errors create very broad and heavy-tailed failure distributions. This suggests that they are susceptible to outlier events and that mean statistics, such as pseudothreshold estimates, may not provide the key figure of merit. This provides further statistical insight into why coherent errors can be so harmful for quantum error correction. These output probability distributions may also provide a useful metric that can be utilized when optimizing quantum error correcting codes and decoding procedures for purely coherent errors.

  10. Correlated measurement error hampers association network inference.

    Science.gov (United States)

    Kaduk, Mateusz; Hoefsloot, Huub C J; Vis, Daniel J; Reijmers, Theo; van der Greef, Jan; Smilde, Age K; Hendriks, Margriet M W B

    2014-09-01

    Modern chromatography-based metabolomics measurements generate large amounts of data in the form of abundances of metabolites. An increasingly popular way of representing and analyzing such data is by means of association networks. Ideally, such a network can be interpreted in terms of the underlying biology. A property of chromatography-based metabolomics data is that the measurement error structure is complex: apart from the usual (random) instrumental error there is also correlated measurement error. This is intrinsic to the way the samples are prepared and the analyses are performed and cannot be avoided. The impact of correlated measurement errors on (partial) correlation networks can be large and is not always predictable. The interplay between relative amounts of uncorrelated measurement error, correlated measurement error and biological variation defines this impact. Using chromatography-based time-resolved lipidomics data obtained from a human intervention study we show how partial correlation based association networks are influenced by correlated measurement error. We show how the effect of correlated measurement error on partial correlations is different for direct and indirect associations. For direct associations the correlated measurement error usually has no negative effect on the results, while for indirect associations, depending on the relative size of the correlated measurement error, results can become unreliable. The aim of this paper is to generate awareness of the existence of correlated measurement errors and their influence on association networks. Time series lipidomics data is used for this purpose, as it makes it possible to visually distinguish the correlated measurement error from a biological response. Underestimating the phenomenon of correlated measurement error will result in the suggestion of biologically meaningful results that in reality rest solely on complicated error structures. Using proper experimental designs that allow

  11. Model error estimation in ensemble data assimilation

    Directory of Open Access Journals (Sweden)

    S. Gillijns

    2007-01-01

    Full Text Available A new methodology is proposed to estimate and account for systematic model error in linear filtering as well as in nonlinear ensemble based filtering. Our results extend the work of Dee and Todling (2000 on constant bias errors to time-varying model errors. In contrast to existing methodologies, the new filter can also deal with the case where no dynamical model for the systematic error is available. In the latter case, the applicability is limited by a matrix rank condition which has to be satisfied in order for the filter to exist. The performance of the filter developed in this paper is limited by the availability and the accuracy of observations and by the variance of the stochastic model error component. The effect of these aspects on the estimation accuracy is investigated in several numerical experiments using the Lorenz (1996 model. Experimental results indicate that the availability of a dynamical model for the systematic error significantly reduces the variance of the model error estimates, but has only minor effect on the estimates of the system state. The filter is able to estimate additive model error of any type, provided that the rank condition is satisfied and that the stochastic errors and measurement errors are significantly smaller than the systematic errors. The results of this study are encouraging. However, it remains to be seen how the filter performs in more realistic applications.

  12. Analysis of errors in forensic science

    Directory of Open Access Journals (Sweden)

    Mingxiao Du

    2017-01-01

    Full Text Available Reliability of expert testimony is one of the foundations of judicial justice. Both expert bias and scientific errors affect the reliability of expert opinion, which in turn affects the trustworthiness of the findings of fact in legal proceedings. Expert bias can be eliminated by replacing experts; however, it may be more difficult to eliminate scientific errors. From the perspective of statistics, errors in operation of forensic science include systematic errors, random errors, and gross errors. In general, process repetition and abiding by the standard ISO/IEC:17025: 2005, general requirements for the competence of testing and calibration laboratories, during operation are common measures used to reduce errors that originate from experts and equipment, respectively. For example, to reduce gross errors, the laboratory can ensure that a test is repeated several times by different experts. In applying for forensic principles and methods, the Federal Rules of Evidence 702 mandate that judges consider factors such as peer review, to ensure the reliability of the expert testimony. As the scientific principles and methods may not undergo professional review by specialists in a certain field, peer review serves as an exclusive standard. This study also examines two types of statistical errors. As false-positive errors involve a higher possibility of an unfair decision-making, they should receive more attention than false-negative errors.

  13. Errors in quantum tomography: diagnosing systematic versus statistical errors

    Science.gov (United States)

    Langford, Nathan K.

    2013-03-01

    A prime goal of quantum tomography is to provide quantitatively rigorous characterization of quantum systems, be they states, processes or measurements, particularly for the purposes of trouble-shooting and benchmarking experiments in quantum information science. A range of techniques exist to enable the calculation of errors, such as Monte-Carlo simulations, but their quantitative value is arguably fundamentally flawed without an equally rigorous way of authenticating the quality of a reconstruction to ensure it provides a reasonable representation of the data, given the known noise sources. A key motivation for developing such a tool is to enable experimentalists to rigorously diagnose the presence of technical noise in their tomographic data. In this work, I explore the performance of the chi-squared goodness-of-fit test statistic as a measure of reconstruction quality. I show that its behaviour deviates noticeably from expectations for states lying near the boundaries of physical state space, severely undermining its usefulness as a quantitative tool precisely in the region which is of most interest in quantum information processing tasks. I suggest a simple, heuristic approach to compensate for these effects and present numerical simulations showing that this approach provides substantially improved performance.

  14. Impact of Measurement Error on Synchrophasor Applications

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Yilu [Univ. of Tennessee, Knoxville, TN (United States); Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Gracia, Jose R. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Ewing, Paul D. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Zhao, Jiecheng [Univ. of Tennessee, Knoxville, TN (United States); Tan, Jin [Univ. of Tennessee, Knoxville, TN (United States); Wu, Ling [Univ. of Tennessee, Knoxville, TN (United States); Zhan, Lingwei [Univ. of Tennessee, Knoxville, TN (United States)

    2015-07-01

    Phasor measurement units (PMUs), a type of synchrophasor, are powerful diagnostic tools that can help avert catastrophic failures in the power grid. Because of this, PMU measurement errors are particularly worrisome. This report examines the internal and external factors contributing to PMU phase angle and frequency measurement errors and gives a reasonable explanation for them. It also analyzes the impact of those measurement errors on several synchrophasor applications: event location detection, oscillation detection, islanding detection, and dynamic line rating. The primary finding is that dynamic line rating is more likely to be influenced by measurement error. Other findings include the possibility of reporting nonoscillatory activity as an oscillation as the result of error, failing to detect oscillations submerged by error, and the unlikely impact of error on event location and islanding detection.

  15. Adjoint Error Estimation for Linear Advection

    Energy Technology Data Exchange (ETDEWEB)

    Connors, J M; Banks, J W; Hittinger, J A; Woodward, C S

    2011-03-30

    An a posteriori error formula is described when a statistical measurement of the solution to a hyperbolic conservation law in 1D is estimated by finite volume approximations. This is accomplished using adjoint error estimation. In contrast to previously studied methods, the adjoint problem is divorced from the finite volume method used to approximate the forward solution variables. An exact error formula and computable error estimate are derived based on an abstractly defined approximation of the adjoint solution. This framework allows the error to be computed to an arbitrary accuracy given a sufficiently well resolved approximation of the adjoint solution. The accuracy of the computable error estimate provably satisfies an a priori error bound for sufficiently smooth solutions of the forward and adjoint problems. The theory does not currently account for discontinuities. Computational examples are provided that show support of the theory for smooth solutions. The application to problems with discontinuities is also investigated computationally.

  16. On the Combination Procedure of Correlated Errors

    CERN Document Server

    Erler, Jens

    2015-01-01

    When averages of different experimental determinations of the same quantity are computed, each with statistical and systematic error components, then frequently the statistical and systematic components of the combined error are quoted explicitly. These are important pieces of information since statistical errors scale differently and often more favorably with the sample size than most systematical or theoretical errors. In this communication we describe a transparent procedure by which the statistical and systematic error components of the combination uncertainty can be obtained. We develop a general method and derive a general formula for the case of Gaussian errors with or without correlations. The method can easily be applied to other error distributions, as well. For the case of two measurements, we also define disparity and misalignment angles, and discuss their relation to the combination weight factors.

  17. On the combination procedure of correlated errors

    Energy Technology Data Exchange (ETDEWEB)

    Erler, Jens [Universidad Nacional Autonoma de Mexico, Instituto de Fisica, Mexico D.F. (Mexico)

    2015-09-15

    When averages of different experimental determinations of the same quantity are computed, each with statistical and systematic error components, then frequently the statistical and systematic components of the combined error are quoted explicitly. These are important pieces of information since statistical errors scale differently and often more favorably with the sample size than most systematical or theoretical errors. In this communication we describe a transparent procedure by which the statistical and systematic error components of the combination uncertainty can be obtained. We develop a general method and derive a general formula for the case of Gaussian errors with or without correlations. The method can easily be applied to other error distributions, as well. For the case of two measurements, we also define disparity and misalignment angles, and discuss their relation to the combination weight factors. (orig.)

  18. Advanced hardware design for error correcting codes

    CERN Document Server

    Coussy, Philippe

    2015-01-01

    This book provides thorough coverage of error correcting techniques. It includes essential basic concepts and the latest advances on key topics in design, implementation, and optimization of hardware/software systems for error correction. The book’s chapters are written by internationally recognized experts in this field. Topics include evolution of error correction techniques, industrial user needs, architectures, and design approaches for the most advanced error correcting codes (Polar Codes, Non-Binary LDPC, Product Codes, etc). This book provides access to recent results, and is suitable for graduate students and researchers of mathematics, computer science, and engineering. • Examines how to optimize the architecture of hardware design for error correcting codes; • Presents error correction codes from theory to optimized architecture for the current and the next generation standards; • Provides coverage of industrial user needs advanced error correcting techniques.

  19. Human error: A significant information security issue

    Energy Technology Data Exchange (ETDEWEB)

    Banks, W.W.

    1994-12-31

    One of the major threats to information security human error is often ignored or dismissed with statements such as {open_quotes}There is not much we can do about it.{close_quotes} This type of thinking runs counter to reality because studies have shown that, of all systems threats, human error has the highest probability of occurring and that, with professional assistance, human errors can be prevented or significantly reduced Security analysts often overlook human error as a major threat; however, other professionals such as human factors engineers are trained to deal with these probabilistic occurrences and mitigate them. In a recent study 55% of the respondents surveyed considered human error as the most important security threat. Documentation exists to show that human error was a major cause of the consequences suffered at Three Mile Island, Chernobyl, Bhopal, and the Exxon tanker, Valdez. Ironically, causes of human error can usually be quickly and easily eliminated.

  20. Radar error statistics for the space shuttle

    Science.gov (United States)

    Lear, W. M.

    1979-01-01

    Radar error statistics of C-band and S-band that are recommended for use with the groundtracking programs to process space shuttle tracking data are presented. The statistics are divided into two parts: bias error statistics, using the subscript B, and high frequency error statistics, using the subscript q. Bias errors may be slowly varying to constant. High frequency random errors (noise) are rapidly varying and may or may not be correlated from sample to sample. Bias errors were mainly due to hardware defects and to errors in correction for atmospheric refraction effects. High frequency noise was mainly due to hardware and due to atmospheric scintillation. Three types of atmospheric scintillation were identified: horizontal, vertical, and line of sight. This was the first time that horizontal and line of sight scintillations were identified.

  1. Carbohydrate Metabolism Disorders

    Science.gov (United States)

    ... you eat. Food is made up of proteins, carbohydrates, and fats. Chemicals in your digestive system (enzymes) ... metabolic disorder, something goes wrong with this process. Carbohydrate metabolism disorders are a group of metabolic disorders. ...

  2. Relationships of Measurement Error and Prediction Error in Observed-Score Regression

    Science.gov (United States)

    Moses, Tim

    2012-01-01

    The focus of this paper is assessing the impact of measurement errors on the prediction error of an observed-score regression. Measures are presented and described for decomposing the linear regression's prediction error variance into parts attributable to the true score variance and the error variances of the dependent variable and the predictor…

  3. PRS1 is a key member of the gene family encoding phosphoribosylpyrophosphate synthetase in Saccharomyces cerevisiae

    DEFF Research Database (Denmark)

    Carter, Andrew T.; Beiche, Flora; Hove-Jensen, Bjarne;

    1997-01-01

    In Saccharomyces cerevisiae the metabolite phosphoribosyl-pyrophosphate (PRPP) is required for purine, pyrimidine, tryptophan and histidine biosynthesis. Enzymes that can synthesize PRPP can be encoded by at least four genes. We have studied 5-phospho-ribosyl-1(α)-pyrophosphate synthetases (PRS......) genetically and biochemically. Each of the four genes, all of which are transcribed, has been disrupted in haploid yeast strains of each mating type and although all disruptants are able to grow on complete medium, differences in growth rate and enzyme activity suggest that disruption of PRS1 or PRS3 has...... a significant effect on cell metabolism, whereas disruption of PRS2 or PRS4 has little measurable effect. Using Western blot analysis with antisera raised against peptides derived from the non-homology region (NHR) and the N-terminal half of the PRS1 gene product it has been shown that the NHR is not removed...

  4. Cancer stem cell metabolism

    National Research Council Canada - National Science Library

    Peiris-Pagès, Maria; Martinez-Outschoorn, Ubaldo E; Pestell, Richard G; Sotgia, Federica; Lisanti, Michael P

    2016-01-01

    .... Cancer stem cells also seem to adapt their metabolism to microenvironmental changes by conveniently shifting energy production from one pathway to another, or by acquiring intermediate metabolic phenotypes...

  5. Orthogonality of inductosyn angle-measuring system error and error-separating technology

    Institute of Scientific and Technical Information of China (English)

    任顺清; 曾庆双; 王常虹

    2003-01-01

    Round inductosyn is widely used in inertial navigation test equipment, and its accuracy has significant effect on the general accuracy of the equipment. Four main errors of round inductosyn,i. e. the first-order long-period (360°) harmonic error, the second-order long-period harmonic error, the first-order short-period harmonic error and the second-order short-period harmonic error, are described, and the orthogonality of these tour kinds of errors is studied. An error separating technology is proposed to separate these four kinds of errors,and in the process of separating the short-period harmonic errors, the arrangement in the order of decimal part of the angle pitch number can be omitted. The effectiveness of the technology proposed is proved through measuring and adjusting the angular errors.

  6. Error processing network dynamics in schizophrenia.

    Science.gov (United States)

    Becerril, Karla E; Repovs, Grega; Barch, Deanna M

    2011-01-15

    Current theories of cognitive dysfunction in schizophrenia emphasize an impairment in the ability of individuals suffering from this disorder to monitor their own performance, and adjust their behavior to changing demands. Detecting an error in performance is a critical component of evaluative functions that allow the flexible adjustment of behavior to optimize outcomes. The dorsal anterior cingulate cortex (dACC) has been repeatedly implicated in error-detection and implementation of error-based behavioral adjustments. However, accurate error-detection and subsequent behavioral adjustments are unlikely to rely on a single brain region. Recent research demonstrates that regions in the anterior insula, inferior parietal lobule, anterior prefrontal cortex, thalamus, and cerebellum also show robust error-related activity, and integrate into a functional network. Despite the relevance of examining brain activity related to the processing of error information and supporting behavioral adjustments in terms of a distributed network, the contribution of regions outside the dACC to error processing remains poorly understood. To address this question, we used functional magnetic resonance imaging to examine error-related responses in 37 individuals with schizophrenia and 32 healthy controls in regions identified in the basic science literature as being involved in error processing, and determined whether their activity was related to behavioral adjustments. Our imaging results support previous findings showing that regions outside the dACC are sensitive to error commission, and demonstrated that abnormalities in brain responses to errors among individuals with schizophrenia extend beyond the dACC to almost all of the regions involved in error-related processing in controls. However, error related responses in the dACC were most predictive of behavioral adjustments in both groups. Moreover, the integration of this network of regions differed between groups, with the

  7. Embedded wavelet video coding with error concealment

    Science.gov (United States)

    Chang, Pao-Chi; Chen, Hsiao-Ching; Lu, Ta-Te

    2000-04-01

    We present an error-concealed embedded wavelet (ECEW) video coding system for transmission over Internet or wireless networks. This system consists of two types of frames: intra (I) frames and inter, or predicted (P), frames. Inter frames are constructed by the residual frames formed by variable block-size multiresolution motion estimation (MRME). Motion vectors are compressed by arithmetic coding. The image data of intra frames and residual frames are coded by error-resilient embedded zerotree wavelet (ER-EZW) coding. The ER-EZW coding partitions the wavelet coefficients into several groups and each group is coded independently. Therefore, the error propagation effect resulting from an error is only confined in a group. In EZW coding any single error may result in a totally undecodable bitstream. To further reduce the error damage, we use the error concealment at the decoding end. In intra frames, the erroneous wavelet coefficients are replaced by neighbors. In inter frames, erroneous blocks of wavelet coefficients are replaced by data from the previous frame. Simulations show that the performance of ECEW is superior to ECEW without error concealment by 7 to approximately 8 dB at the error-rate of 10-3 in intra frames. The improvement still has 2 to approximately 3 dB at a higher error-rate of 10-2 in inter frames.

  8. Regression calibration with heteroscedastic error variance.

    Science.gov (United States)

    Spiegelman, Donna; Logan, Roger; Grove, Douglas

    2011-01-01

    The problem of covariate measurement error with heteroscedastic measurement error variance is considered. Standard regression calibration assumes that the measurement error has a homoscedastic measurement error variance. An estimator is proposed to correct regression coefficients for covariate measurement error with heteroscedastic variance. Point and interval estimates are derived. Validation data containing the gold standard must be available. This estimator is a closed-form correction of the uncorrected primary regression coefficients, which may be of logistic or Cox proportional hazards model form, and is closely related to the version of regression calibration developed by Rosner et al. (1990). The primary regression model can include multiple covariates measured without error. The use of these estimators is illustrated in two data sets, one taken from occupational epidemiology (the ACE study) and one taken from nutritional epidemiology (the Nurses' Health Study). In both cases, although there was evidence of moderate heteroscedasticity, there was little difference in estimation or inference using this new procedure compared to standard regression calibration. It is shown theoretically that unless the relative risk is large or measurement error severe, standard regression calibration approximations will typically be adequate, even with moderate heteroscedasticity in the measurement error model variance. In a detailed simulation study, standard regression calibration performed either as well as or better than the new estimator. When the disease is rare and the errors normally distributed, or when measurement error is moderate, standard regression calibration remains the method of choice.

  9. Medical errors recovered by critical care nurses.

    Science.gov (United States)

    Dykes, Patricia C; Rothschild, Jeffrey M; Hurley, Ann C

    2010-05-01

    : The frequency and types of medical errors are well documented, but less is known about potential errors that were intercepted by nurses. We studied the type, frequency, and potential harm of recovered medical errors reported by critical care registered nurses (CCRNs) during the previous year. : Nurses are known to protect patients from harm. Several studies on medical errors found that there would have been more medical errors reaching the patient had not potential errors been caught earlier by nurses. : The Recovered Medical Error Inventory, a 25-item empirically derived and internally consistent (alpha =.90) list of medical errors, was posted on the Internet. Participants were recruited via e-mail and healthcare-related listservs using a nonprobability snowball sampling technique. Investigators e-mailed contacts working in hospitals or who managed healthcare-related listservs and asked the contacts to pass the link on to others with contacts in acute care settings. : During 1 year, 345 CCRNs reported that they recovered 18,578 medical errors, of which they rated 4,183 as potentially lethal. : Surveillance, clinical judgment, and interventions by CCRNs to identify, interrupt, and correct medical errors protected seriously ill patients from harm.

  10. Common errors in disease mapping

    Directory of Open Access Journals (Sweden)

    Ricardo Ocaña-Riola

    2010-05-01

    Full Text Available Many morbid-mortality atlases and small-area studies have been carried out over the last decade. However, the methods used to draw up such research, the interpretation of results and the conclusions published are often inaccurate. Often, the proliferation of this practice has led to inefficient decision-making, implementation of inappropriate health policies and negative impact on the advancement of scientific knowledge. This paper reviews the most frequent errors in the design, analysis and interpretation of small-area epidemiological studies and proposes a diagnostic evaluation test that should enable the scientific quality of published papers to be ascertained. Nine common mistakes in disease mapping methods are discussed. From this framework, and following the theory of diagnostic evaluation, a standardised test to evaluate the scientific quality of a small-area epidemiology study has been developed. Optimal quality is achieved with the maximum score (16 points, average with a score between 8 and 15 points, and low with a score of 7 or below. A systematic evaluation of scientific papers, together with an enhanced quality in future research, will contribute towards increased efficacy in epidemiological surveillance and in health planning based on the spatio-temporal analysis of ecological information.

  11. On Nautical Observation Errors Evaluation

    Directory of Open Access Journals (Sweden)

    Wlodzimierz Filipowicz

    2015-12-01

    Full Text Available Mathematical Theory of Evidence (MTE enables upgrading models and solving crucial problems in many disciplines. MTE delivers new unique opportunity once one engages possibilistic concept. Since fuzziness is widely perceived as something that enables encoding knowledge thus models build upon fuzzy platforms accepts ones skill within given field. At the same time evidence combining scheme is a mechanism enabling enrichment initial data informative context. Therefore it can be exploited in many cases where uncertainty and lack of precision prevail. In nautical applications, for example, it can be used in order to handle data feature systematic and random deflections. Theoretical background was discussed and computer application was successfully implemented in order to cope with erroneous and uncertain data. Output of the application resulted in making a fix and a posteriori evaluating its quality. It was also proven that it can be useful for calibrating measurement appliances. Unique feature of the combination scheme proven by the author in his previous paper, enables identifying measurement systematic deflection. Based on the theorem the paper aims at further exploration of practical aspects of the problem. It concentrates on reduction of hypothesis frame reduction and random along with systematic errors identifications.

  12. Medication errors in anesthesia: unacceptable or unavoidable?

    Directory of Open Access Journals (Sweden)

    Ira Dhawan

    Full Text Available Abstract Medication errors are the common causes of patient morbidity and mortality. It adds financial burden to the institution as well. Though the impact varies from no harm to serious adverse effects including death, it needs attention on priority basis since medication errors' are preventable. In today's world where people are aware and medical claims are on the hike, it is of utmost priority that we curb this issue. Individual effort to decrease medication error alone might not be successful until a change in the existing protocols and system is incorporated. Often drug errors that occur cannot be reversed. The best way to ‘treat' drug errors is to prevent them. Wrong medication (due to syringe swap, overdose (due to misunderstanding or preconception of the dose, pump misuse and dilution error, incorrect administration route, under dosing and omission are common causes of medication error that occur perioperatively. Drug omission and calculation mistakes occur commonly in ICU. Medication errors can occur perioperatively either during preparation, administration or record keeping. Numerous human and system errors can be blamed for occurrence of medication errors. The need of the hour is to stop the blame - game, accept mistakes and develop a safe and ‘just' culture in order to prevent medication errors. The newly devised systems like VEINROM, a fluid delivery system is a novel approach in preventing drug errors due to most commonly used medications in anesthesia. Similar developments along with vigilant doctors, safe workplace culture and organizational support all together can help prevent these errors.

  13. [Medication errors in anesthesia: unacceptable or unavoidable?

    Science.gov (United States)

    Dhawan, Ira; Tewari, Anurag; Sehgal, Sankalp; Sinha, Ashish Chandra

    Medication errors are the common causes of patient morbidity and mortality. It adds financial burden to the institution as well. Though the impact varies from no harm to serious adverse effects including death, it needs attention on priority basis since medication errors' are preventable. In today's world where people are aware and medical claims are on the hike, it is of utmost priority that we curb this issue. Individual effort to decrease medication error alone might not be successful until a change in the existing protocols and system is incorporated. Often drug errors that occur cannot be reversed. The best way to 'treat' drug errors is to prevent them. Wrong medication (due to syringe swap), overdose (due to misunderstanding or preconception of the dose, pump misuse and dilution error), incorrect administration route, under dosing and omission are common causes of medication error that occur perioperatively. Drug omission and calculation mistakes occur commonly in ICU. Medication errors can occur perioperatively either during preparation, administration or record keeping. Numerous human and system errors can be blamed for occurrence of medication errors. The need of the hour is to stop the blame - game, accept mistakes and develop a safe and 'just' culture in order to prevent medication errors. The newly devised systems like VEINROM, a fluid delivery system is a novel approach in preventing drug errors due to most commonly used medications in anesthesia. Similar developments along with vigilant doctors, safe workplace culture and organizational support all together can help prevent these errors. Copyright © 2016. Publicado por Elsevier Editora Ltda.

  14. Medication errors in anesthesia: unacceptable or unavoidable?

    Science.gov (United States)

    Dhawan, Ira; Tewari, Anurag; Sehgal, Sankalp; Sinha, Ashish Chandra

    Medication errors are the common causes of patient morbidity and mortality. It adds financial burden to the institution as well. Though the impact varies from no harm to serious adverse effects including death, it needs attention on priority basis since medication errors' are preventable. In today's world where people are aware and medical claims are on the hike, it is of utmost priority that we curb this issue. Individual effort to decrease medication error alone might not be successful until a change in the existing protocols and system is incorporated. Often drug errors that occur cannot be reversed. The best way to 'treat' drug errors is to prevent them. Wrong medication (due to syringe swap), overdose (due to misunderstanding or preconception of the dose, pump misuse and dilution error), incorrect administration route, under dosing and omission are common causes of medication error that occur perioperatively. Drug omission and calculation mistakes occur commonly in ICU. Medication errors can occur perioperatively either during preparation, administration or record keeping. Numerous human and system errors can be blamed for occurrence of medication errors. The need of the hour is to stop the blame - game, accept mistakes and develop a safe and 'just' culture in order to prevent medication errors. The newly devised systems like VEINROM, a fluid delivery system is a novel approach in preventing drug errors due to most commonly used medications in anesthesia. Similar developments along with vigilant doctors, safe workplace culture and organizational support all together can help prevent these errors. Copyright © 2016. Published by Elsevier Editora Ltda.

  15. Error correction maintains post-error adjustments after one night of total sleep deprivation.

    Science.gov (United States)

    Hsieh, Shulan; Tsai, Cheng-Yin; Tsai, Ling-Ling

    2009-06-01

    Previous behavioral and electrophysiologic evidence indicates that one night of total sleep deprivation (TSD) impairs error monitoring, including error detection, error correction, and posterror adjustments (PEAs). This study examined the hypothesis that error correction, manifesting as an overtly expressed self-generated performance feedback to errors, can effectively prevent TSD-induced impairment in the PEAs. Sixteen healthy right-handed adults (seven women and nine men) aged 19-23 years were instructed to respond to a target arrow flanked by four distracted arrows and to correct their errors immediately after committing errors. Task performance and electroencephalogram (EEG) data were collected after normal sleep (NS) and after one night of TSD in a counterbalanced repeated-measures design. With the demand of error correction, the participants maintained the same level of PEAs in reducing the error rate for trial N + 1 after TSD as after NS. Corrective behavior further affected the PEAs for trial N + 1 in the omission rate and response speed, which decreased and speeded up following corrected errors, particularly after TSD. These results show that error correction effectively maintains posterror reduction in both committed and omitted errors after TSD. A cerebral mechanism might be involved in the effect of error correction as EEG beta (17-24 Hz) activity was increased after erroneous responses compared to after correct responses. The practical application of error correction to increasing work safety, which can be jeopardized by repeated errors, is suggested for workers who are involved in monotonous but attention-demanding monitoring tasks.

  16. Profiling metabolic networks to study cancer metabolism.

    Science.gov (United States)

    Hiller, Karsten; Metallo, Christian M

    2013-02-01

    Cancer is a disease of unregulated cell growth and survival, and tumors reprogram biochemical pathways to aid these processes. New capabilities in the computational and bioanalytical characterization of metabolism have now emerged, facilitating the identification of unique metabolic dependencies that arise in specific cancers. By understanding the metabolic phenotype of cancers as a function of their oncogenic profiles, metabolic engineering may be applied to design synthetically lethal therapies for some tumors. This process begins with accurate measurement of metabolic fluxes. Here we review advanced methods of quantifying pathway activity and highlight specific examples where these approaches have uncovered potential opportunities for therapeutic intervention.

  17. Temporal expression-based analysis of metabolism.

    Directory of Open Access Journals (Sweden)

    Sara B Collins

    Full Text Available Metabolic flux is frequently rerouted through cellular metabolism in response to dynamic changes in the intra- and extra-cellular environment. Capturing the mechanisms underlying these metabolic transitions in quantitative and predictive models is a prominent challenge in systems biology. Progress in this regard has been made by integrating high-throughput gene expression data into genome-scale stoichiometric models of metabolism. Here, we extend previous approaches to perform a Temporal Expression-based Analysis of Metabolism (TEAM. We apply TEAM to understanding the complex metabolic dynamics of the respiratorily versatile bacterium Shewanella oneidensis grown under aerobic, lactate-limited conditions. TEAM predicts temporal metabolic flux distributions using time-series gene expression data. Increased predictive power is achieved by supplementing these data with a large reference compendium of gene expression, which allows us to take into account the unique character of the distribution of expression of each individual gene. We further propose a straightforward method for studying the sensitivity of TEAM to changes in its fundamental free threshold parameter θ, and reveal that discrete zones of distinct metabolic behavior arise as this parameter is changed. By comparing the qualitative characteristics of these zones to additional experimental data, we are able to constrain the range of θ to a small, well-defined interval. In parallel, the sensitivity analysis reveals the inherently difficult nature of dynamic metabolic flux modeling: small errors early in the simulation propagate to relatively large changes later in the simulation. We expect that handling such "history-dependent" sensitivities will be a major challenge in the future development of dynamic metabolic-modeling techniques.

  18. Metabolism disrupting chemicals and metabolic disorders.

    Science.gov (United States)

    Heindel, Jerrold J; Blumberg, Bruce; Cave, Mathew; Machtinger, Ronit; Mantovani, Alberto; Mendez, Michelle A; Nadal, Angel; Palanza, Paola; Panzica, Giancarlo; Sargis, Robert; Vandenberg, Laura N; Vom Saal, Frederick

    2017-03-01

    The recent epidemics of metabolic diseases, obesity, type 2 diabetes(T2D), liver lipid disorders and metabolic syndrome have largely been attributed to genetic background and changes in diet, exercise and aging. However, there is now considerable evidence that other environmental factors may contribute to the rapid increase in the incidence of these metabolic diseases. This review will examine changes to the incidence of obesity, T2D and non-alcoholic fatty liver disease (NAFLD), the contribution of genetics to these disorders and describe the role of the endocrine system in these metabolic disorders. It will then specifically focus on the role of endocrine disrupting chemicals (EDCs) in the etiology of obesity, T2D and NAFLD while finally integrating the information on EDCs on multiple metabolic disorders that could lead to metabolic syndrome. We will specifically examine evidence linking EDC exposures during critical periods of development with metabolic diseases that manifest later in life and across generations.

  19. Identification errors in pathology and laboratory medicine.

    Science.gov (United States)

    Valenstein, Paul N; Sirota, Ronald L

    2004-12-01

    Identification errors involve misidentification of a patient or a specimen. Either has the potential to cause patients harm. Identification errors can occur during any part of the test cycle; however, most occur in the preanalytic phase. Patient identification errors in transfusion medicine occur in 0.05% of specimens; for general laboratory specimens the rate is much higher, around 1%. Anatomic pathology, which involves multiple specimen transfers and hand-offs, may have the highest identification error rate. Certain unavoidable cognitive failures lead to identification errors. Technology, ranging from bar-coded specimen labels to radio frequency identification tags, can be incorporated into protective systems that have the potential to detect and correct human error and reduce the frequency with which patients and specimens are misidentified.

  20. Error handling strategies in multiphase inverse modeling

    Energy Technology Data Exchange (ETDEWEB)

    Finsterle, S.; Zhang, Y.

    2010-12-01

    Parameter estimation by inverse modeling involves the repeated evaluation of a function of residuals. These residuals represent both errors in the model and errors in the data. In practical applications of inverse modeling of multiphase flow and transport, the error structure of the final residuals often significantly deviates from the statistical assumptions that underlie standard maximum likelihood estimation using the least-squares method. Large random or systematic errors are likely to lead to convergence problems, biased parameter estimates, misleading uncertainty measures, or poor predictive capabilities of the calibrated model. The multiphase inverse modeling code iTOUGH2 supports strategies that identify and mitigate the impact of systematic or non-normal error structures. We discuss these approaches and provide an overview of the error handling features implemented in iTOUGH2.

  1. Beyond the answer: post-error processes.

    Science.gov (United States)

    Kleiter, G D; Schwarzenbacher, K

    1989-08-01

    When you suspect that you just gave an erroneous answer to a question you stop and rethink. Suspected errors lead to a shift in the control and content of cognitive processes. In the present experiment we investigated the influence of errors upon heart rates and response latencies. Sixty-four subjects participated in an experiment in which each subject solved a sequence of 60 verbal analogies. The results demonstrated increased latencies after errors and decelerated heart rates during the post-error period. The results were explained by a psychophysiological model in which the septo-hippocampal system functions as a control system which coordinates the priority and selection of cognitive processes. Error detection suppresses strategies which otherwise prevent looping and iterative reanalyses of old material. The inhibition is also responsible for the cardiac slowing during the post-error period.

  2. Meteorological Error Budget Using Open Source Data

    Science.gov (United States)

    2016-09-01

    VBA ) script was created that would read the model - based output and corresponding sounding data for each message type (METCM or METB3), output type...produce artillery MET error budget tables that account for expected errors when using MET model -based systems. Representatives of the US and other...nations within the North Atlantic Treaty Organization expressed a need for shareable model -based MET error budgets. Use of an openly available civilian

  3. Soft errors in modern electronic systems

    CERN Document Server

    Nicolaidis, Michael

    2010-01-01

    This book provides a comprehensive presentation of the most advanced research results and technological developments enabling understanding, qualifying and mitigating the soft errors effect in advanced electronics, including the fundamental physical mechanisms of radiation induced soft errors, the various steps that lead to a system failure, the modelling and simulation of soft error at various levels (including physical, electrical, netlist, event driven, RTL, and system level modelling and simulation), hardware fault injection, accelerated radiation testing and natural environment testing, s

  4. Analysis of Errors Encountered in Simultaneous Interpreting

    Institute of Scientific and Technical Information of China (English)

    方峥

    2015-01-01

    I.Introduction1.1 Definition of an error An error happens when the interpreter’s delivery affects the communicative impact of the speaker’s message,including semantic inaccuracies and inaccuracies of presentation.Along with the development of simultaneous interpreting,there has been a number of professional interpreters and linguists present their definitions and points of views about the errors

  5. Medication errors in anesthesia: unacceptable or unavoidable?

    OpenAIRE

    Ira Dhawan; Anurag Tewari; Sankalp Sehgal; Ashish Chandra Sinha

    2017-01-01

    Abstract Medication errors are the common causes of patient morbidity and mortality. It adds financial burden to the institution as well. Though the impact varies from no harm to serious adverse effects including death, it needs attention on priority basis since medication errors' are preventable. In today's world where people are aware and medical claims are on the hike, it is of utmost priority that we curb this issue. Individual effort to decrease medication error alone might not be succes...

  6. Group representations, error bases and quantum codes

    Energy Technology Data Exchange (ETDEWEB)

    Knill, E

    1996-01-01

    This report continues the discussion of unitary error bases and quantum codes. Nice error bases are characterized in terms of the existence of certain characters in a group. A general construction for error bases which are non-abelian over the center is given. The method for obtaining codes due to Calderbank et al. is generalized and expressed purely in representation theoretic terms. The significance of the inertia subgroup both for constructing codes and obtaining the set of transversally implementable operations is demonstrated.

  7. ERROR CORRECTION IN HIGH SPEED ARITHMETIC,

    Science.gov (United States)

    The errors due to a faulty high speed multiplier are shown to be iterative in nature. These errors are analyzed in various aspects. The arithmetic coding technique is suggested for the improvement of high speed multiplier reliability. Through a number theoretic investigation, a large class of arithmetic codes for single iterative error correction are developed. The codes are shown to have near-optimal rates and to render a simple decoding method. The implementation of these codes seems highly practical. (Author)

  8. Medication errors recovered by emergency department pharmacists.

    Science.gov (United States)

    Rothschild, Jeffrey M; Churchill, William; Erickson, Abbie; Munz, Kristin; Schuur, Jeremiah D; Salzberg, Claudia A; Lewinski, Daniel; Shane, Rita; Aazami, Roshanak; Patka, John; Jaggers, Rondell; Steffenhagen, Aaron; Rough, Steve; Bates, David W

    2010-06-01

    We assess the impact of emergency department (ED) pharmacists on reducing potentially harmful medication errors. We conducted this observational study in 4 academic EDs. Trained pharmacy residents observed a convenience sample of ED pharmacists' activities. The primary outcome was medication errors recovered by pharmacists, including errors intercepted before reaching the patient (near miss or potential adverse drug event), caught after reaching the patient but before causing harm (mitigated adverse drug event), or caught after some harm but before further or worsening harm (ameliorated adverse drug event). Pairs of physician and pharmacist reviewers confirmed recovered medication errors and assessed their potential for harm. Observers were unblinded and clinical outcomes were not evaluated. We conducted 226 observation sessions spanning 787 hours and observed pharmacists reviewing 17,320 medications ordered or administered to 6,471 patients. We identified 504 recovered medication errors, or 7.8 per 100 patients and 2.9 per 100 medications. Most of the recovered medication errors were intercepted potential adverse drug events (90.3%), with fewer mitigated adverse drug events (3.9%) and ameliorated adverse drug events (0.2%). The potential severities of the recovered errors were most often serious (47.8%) or significant (36.2%). The most common medication classes associated with recovered medication errors were antimicrobial agents (32.1%), central nervous system agents (16.2%), and anticoagulant and thrombolytic agents (14.1%). The most common error types were dosing errors, drug omission, and wrong frequency errors. ED pharmacists can identify and prevent potentially harmful medication errors. Controlled trials are necessary to determine the net costs and benefits of ED pharmacist staffing on safety, quality, and costs, especially important considerations for smaller EDs and pharmacy departments. Copyright (c) 2009 American College of Emergency Physicians

  9. Error Estimates of Theoretical Models: a Guide

    CERN Document Server

    Dobaczewski, J; Reinhard, P -G

    2014-01-01

    This guide offers suggestions/insights on uncertainty quantification of nuclear structure models. We discuss a simple approach to statistical error estimates, strategies to assess systematic errors, and show how to uncover inter-dependencies by correlation analysis. The basic concepts are illustrated through simple examples. By providing theoretical error bars on predicted quantities and using statistical methods to study correlations between observables, theory can significantly enhance the feedback between experiment and nuclear modeling.

  10. Maximum privacy without coherence, zero-error

    Science.gov (United States)

    Leung, Debbie; Yu, Nengkun

    2016-09-01

    We study the possible difference between the quantum and the private capacities of a quantum channel in the zero-error setting. For a family of channels introduced by Leung et al. [Phys. Rev. Lett. 113, 030512 (2014)], we demonstrate an extreme difference: the zero-error quantum capacity is zero, whereas the zero-error private capacity is maximum given the quantum output dimension.

  11. How social is error observation? The neural mechanisms underlying the observation of human and machine errors.

    Science.gov (United States)

    Desmet, Charlotte; Deschrijver, Eliane; Brass, Marcel

    2014-04-01

    Recently, it has been shown that the medial prefrontal cortex (MPFC) is involved in error execution as well as error observation. Based on this finding, it has been argued that recognizing each other's mistakes might rely on motor simulation. In the current functional magnetic resonance imaging (fMRI) study, we directly tested this hypothesis by investigating whether medial prefrontal activity in error observation is restricted to situations that enable simulation. To this aim, we compared brain activity related to the observation of errors that can be simulated (human errors) with brain activity related to errors that cannot be simulated (machine errors). We show that medial prefrontal activity is not only restricted to the observation of human errors but also occurs when observing errors of a machine. In addition, our data indicate that the MPFC reflects a domain general mechanism of monitoring violations of expectancies.

  12. Research on the technology for processing errors of photoelectric theodolite based on error design idea

    Science.gov (United States)

    Guo, Xiaosong; Pu, Pengcheng; Zhou, Zhaofa; Wang, Kunming

    2012-10-01

    The errors existing in photoelectric theodolite were studied according to the error design idea , that is - the correction of theodolite errors was achieved by analyzing the effect of errors actively instead of processing the data with error passively. Aiming at the shafting error, the relationship between different errors was analyzed by the error model based on coordinate transformation, and the real-time error compensation method based on the normal-reversed measuring method and levelness auto-detection was supposed. As to the eccentric error of dial, the idea of eccentric residual error was presented and its influence to measuring precision was studied, then the dynamic compensation model was build, so the influence of eccentric error of dial to measuring precision can be eliminated. For the centering deviation in the process of measuring angle, the compensation method based on the error model was supposed, in which the centering deviation was detected automatically based on computer vision. The above method based on error design idea reduced the influence to measuring result by software compensation method effectively, and improved the automation degree of azimuth angle measuring of theodolite, at the same time the precision was not depressed.

  13. Spelling Errors in University Students’ English Writing

    Institute of Scientific and Technical Information of China (English)

    王祥德; 邓兆红

    2012-01-01

      [3] Wyatt, V. An Analysis of Errors in Composition Writing[J]. ELT Journal,1973(2):177-188.%  This paper investigated the spelling errors made by university students in Hong Kong. By analyzing the spelling errors in the untimed essays and exam scripts, we found that students are prone to make more spelling mistakes in exam scripts, the same type of errors occur in both of the two kinds of texts; and their ranks of the frequency also are the same

  14. Error measuring system of rotary Inductosyn

    Science.gov (United States)

    Liu, Chengjun; Zou, Jibin; Fu, Xinghe

    2008-10-01

    The inductosyn is a kind of high-precision angle-position sensor. It has important applications in servo table, precision machine tool and other products. The precision of inductosyn is calibrated by its error. It's an important problem about the error measurement in the process of production and application of the inductosyn. At present, it mainly depends on the method of artificial measurement to obtain the error of inductosyn. Therefore, the disadvantages can't be ignored such as the high labour intensity of the operator, the occurrent error which is easy occurred and the poor repeatability, and so on. In order to solve these problems, a new automatic measurement method is put forward in this paper which based on a high precision optical dividing head. Error signal can be obtained by processing the output signal of inductosyn and optical dividing head precisely. When inductosyn rotating continuously, its zero position error can be measured dynamically, and zero error curves can be output automatically. The measuring and calculating errors caused by man-made factor can be overcome by this method, and it makes measuring process more quickly, exactly and reliably. Experiment proves that the accuracy of error measuring system is 1.1 arc-second (peak - peak value).

  15. Estimating IMU heading error from SAR images.

    Energy Technology Data Exchange (ETDEWEB)

    Doerry, Armin Walter

    2009-03-01

    Angular orientation errors of the real antenna for Synthetic Aperture Radar (SAR) will manifest as undesired illumination gradients in SAR images. These gradients can be measured, and the pointing error can be calculated. This can be done for single images, but done more robustly using multi-image methods. Several methods are provided in this report. The pointing error can then be fed back to the navigation Kalman filter to correct for problematic heading (yaw) error drift. This can mitigate the need for uncomfortable and undesired IMU alignment maneuvers such as S-turns.

  16. Beam positioning error budget in ICF driver

    CERN Document Server

    Shi Zhi Quan; Su Jing Qin

    2002-01-01

    The author presents the method of linear weight sum to beam positioning budget on the basis of ICF request on targeting, the approach of equal or unequal probability to allocate errors to each optical element. Based on the relationship between the motion of the optical components and beam position on target, the position error of the optical components was evaluated, which was referred to as the maximum range. Lots of ray trace were performed, the position error budget were modified by law of the normal distribution. An overview of position error budget of the components is provided

  17. Study of Errors among Nursing Students

    Directory of Open Access Journals (Sweden)

    Ella Koren

    2007-09-01

    Full Text Available The study of errors in the health system today is a topic of considerable interest aimed at reducing errors through analysis of the phenomenon and the conclusions reached. Errors that occur frequently among health professionals have also been observed among nursing students. True, in most cases they are actually “near errors,” but these could be a future indicator of therapeutic reality and the effect of nurses' work environment on their personal performance. There are two different approaches to such errors: (a The EPP (error prone person approach lays full responsibility at the door of the individual involved in the error, whether a student, nurse, doctor, or pharmacist. According to this approach, handling consists purely in identifying and penalizing the guilty party. (b The EPE (error prone environment approach emphasizes the environment as a primary contributory factor to errors. The environment as an abstract concept includes components and processes of interpersonal communications, work relations, human engineering, workload, pressures, technical apparatus, and new technologies. The objective of the present study was to examine the role played by factors in and components of personal performance as compared to elements and features of the environment. The study was based on both of the aforementioned approaches, which, when combined, enable a comprehensive understanding of the phenomenon of errors among the student population as well as a comparison of factors contributing to human error and to error deriving from the environment. The theoretical basis of the study was a model that combined both approaches: one focusing on the individual and his or her personal performance and the other focusing on the work environment. The findings emphasize the work environment of health professionals as an EPE. However, errors could have been avoided by means of strict adherence to practical procedures. The authors examined error events in the

  18. Error Analysis and English Language Teaching

    Institute of Scientific and Technical Information of China (English)

    Ma; Jinling

    2015-01-01

    The theory of Error Analysis is a crucial part in the research of second language acquisition and it has significant influence on exploring the pattern of English teaching.Although there are some limitations in error analysis both in theory and practice, its significant role has been proved and recognized.It is inevitable that how to scientifically treat the errors will be become more and more popular in modern English teaching.The aim of this paper is to show the importance of error analysis in English teaching and also present how well it can function in English language teaching.

  19. Error computation for adaptive finite element analysis

    CERN Document Server

    Khan, A A; Memon, I R; Ming, X Y

    2002-01-01

    The paper gives a simple numerical procedure for computations of errors generated by the discretisation process of finite element method. The procedure given is based on the ZZ error estimator which is believed to be reasonable accurate and thus can be readily implemented in any existing finite element codes. The devised procedure not only estimates the global energy norm error but also evaluates the local errors in individual elements. In the example, the given procedure is combined with an adaptive refinement procedure, which provides guidance for optimal mesh designing and allows the user to obtain a desired accuracy with a limited number of interaction. (author)

  20. The NASTRAN Error Correction Information System (ECIS)

    Science.gov (United States)

    Rosser, D. C., Jr.; Rogers, J. L., Jr.

    1975-01-01

    A data management procedure, called Error Correction Information System (ECIS), is described. The purpose of this system is to implement the rapid transmittal of error information between the NASTRAN Systems Management Office (NSMO) and the NASTRAN user community. The features of ECIS and its operational status are summarized. The mode of operation for ECIS is compared to the previous error correction procedures. It is shown how the user community can have access to error information much more rapidly when using ECIS. Flow charts and time tables characterize the convenience and time saving features of ECIS.