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ABSTRACTCobalamin C (CblC) disease is the most common inborn error of cobalamin metabolism and recent data has indicated a higher prevalence among children of Hispanic heritage in particular. The purpose of this study was to (a) describe the neuropsychological characteristics of a pilot sample of Hispanic children with CblC disease and (b) explore potential differences in outcome based on underlying genetic mutation(s) and biochemical levels. Six Hispanic children (ages 2–10) diagnosed with CblC disease through newborn screening (NBS) underwent neuropsychological evaluation with a bilingual examiner. Biochemical levels and underlying mutation(s) were obtained through medical records. The overall sample performed below normative expectations across neuropsychological domains, including general cognition, adaptive functioning, language ability, and visual-motor integration. Underlying mutations and associative clinical phenotypes were found to significantly predict general cognitive abilities, while plasma methionine and Hcy at the time of diagnosis were significantly correlated with language outcomes. Despite limited sample size, results indicate that Hispanic children with CblC disease detected through NBS and treated early experience neuropsychological deficits even when treated with current standard treatments. However, consistent with prior research in non-Hispanic children with CblC disease, underlying mutations and early biochemical levels may predict better outcomes in this population as well.

A total of 126 scoliosis patients admitted to the hospital were screened for concomitant cervical pathologies.

Study Design: A total of 126 scoliosis patients admitted to the hospital were screened for concomitant cervical pathologies. Objectives: To investigate the prevalence of cervical spine pathologies and the clinical relevance of magnetic resonance imaging (MRI) in the evaluation of patients with neuromuscular, congenital, syndromic, and idiopathic scoliosis. Background Summary: With the development of MRI, upper neural axis abnormalities such as syringomyelia and Chiari malformation are increasingly being found in patients with scoliosis, but no report in the literature describes other pathologies in the cervical area seen concomitant with different scoliosis types. Methods: A total of 126 consecutive patients who were classified as having neuromuscular, congenital, syndromic, and idiopathic scoliosis were retrospectively evaluated. Data regarding cervical neural axis abnormalities obtained from the MRI studies were analyzed and classified into each type of scoliosis group. Results: A total of 126 patients with scoliosis were evaluated for hindbrain and cervical spine anomalies. Patients were divided into 4 groups regarding the type of scoliosis. The cervical spine of all patients was evaluated with MRI and other radiologic methods when needed. The most frequently seen pathology was syringomyelia. Other pathologies found included congenital vertebral anomalies, Chiari malformation, arachnoid cyst, atlanto-axial dissociation, split cord, posterior vertebral fusion, vertebral hypoplasia, neurenteric cyst,myelomalacia, dermoid cyst, and decrease in craniovertebral angle. Cervical pathologies were most frequently seen in neuromuscular scoliosis, followed by congenital and syndromic groups. Conclusions: Cervical spinal pathologies vary according to the type of scoliosis. The number of cervical spinal pathologies diagnosed in idiopathic scoliosis patients was least compared with neuromuscular and syndromic groups. The most common pathology was syringomyelia, followed by congenital vertebral anomalies and cerebral tonsillar hernia. Preoperative MRI scan provides vital information regarding cervical spinal pathologies encountered in scoliosis patients.

Mitochondrial DNA (mtDNA) depletion syndrome is a relatively novel cause of hepatic dysfunction in the pediatric population. It is caused by mutations in either mtDNA or nuclear DNA (nDNA) that result in a quantitative reduction in mtDNA and, in turn, dysfunctional oxidative phosphorylation. In infants, it results in the hepatocerebral phenotype, characterized by hyperbilirubinemia, coagulopathy, lactic acidosis, hypoglycemia, lethargy, encephalopathy, developmental delay, and hypotonia. Three infants diagnosed with mtDNA depletion syndrome at The Children's Hospital of Philadelphia were identified, and their clinical presentation, disease course, and histologic and ultrastructural features of liver samples (pre- and postmortem) were characterized. While a different mutant gene was identified in each child, they all showed clinical evidence of metabolic dysfunction soon after birth and expired by 1 year of age. Steatosis, cholestasis, and cytoplasmic crowding by atypical mitochondria were consistent pathologic liver findings. Other findings included hepatocyte hypereosinophilia, fibrosis, and hemosiderosis. This analysis provides insight into the important clinical signs/symptoms and histopathologic and ultrastructural features of mtDNA depletion syndrome in infants and young children. Knowledge of these characteristics will facilitate early recognition and appropriate treatment of this rare disorder. Additionally, ultrastructural evaluation of liver samples by electron microscopy is an important diagnostic component of hepatic dysfunction caused by metabolic abnormalities. This type of analysis should be routinely employed in the setting of unexplained cholestasis, especially when accompanied by steatosis and hepatocyte hypereosinophilia.

Purpose: Isobutyryl-CoA dehydrogenase deficiency is a defect in valine metabolism and was first reported in a child with cardiomyopathy, anemia, and secondary carnitine deficiency. We identified 13 isobutyryl-CoA dehydrogenase–deficient patients through newborn screening due to an elevation of C4-acylcarnitine in dried blood spots. Because C4-acylcarnitine represents both isobutyryl- and butyrylcarnitine, elevations are not specific for isobutyryl-CoA dehydrogenase deficiency but are also observed in short-chain acyl-CoA dehydrogenase deficiency. To delineate the correct diagnosis, we have developed a follow-up algorithm for abnormal C4-acylcarnitine newborn screening results based on the comparison of biomarkers for both conditions.Methods: Fibroblast cultures were established from infants with C4-acylcarnitine elevations, and the analysis of in vitro acylcarnitine profiles provided confirmation of either isobutyryl-CoA dehydrogenase or short-chain acyl-CoA dehydrogenase deficiency. Isobutyryl-CoA dehydrogenase deficiency was further confirmed by molecular genetic analysis of the gene encoding isobutyryl-CoA dehydrogenase (ACAD8). Plasma acylcarnitines, urine acylglycines, organic acids, and urine acylcarnitine results were compared between isobutyryl-CoA dehydrogenase– and short-chain acyl-CoA dehydrogenase–deficient patients.Results: Quantification of C4-acylcarnitine in plasma and urine as well as ethylmalonic acid in urine allows the differentiation of isobutyryl-CoA dehydrogenase–deficient from short-chain acyl-CoA dehydrogenase–deficient cases. In nine unrelated patients with isobutyryl-CoA dehydrogenase deficiency, 10 missense mutations were identified in ACAD8. To date, 10 of the 13 isobutyryl-CoA dehydrogenase–deficient patients remain asymptomatic, two were lost to follow-up, and one patient required frequent hospitalizations due to emesis and dehydration but is developing normally at 5 years of age.Conclusion: Although the natural history of isobutyryl-CoA dehydrogenase deficiency must be further defined, we have developed an algorithm for rapid laboratory evaluation of neonates with an isolated elevation of C4-acylcarnitine identified through newborn screening.

Abstract. The stator field-oriented sensorless vector control method is receiving wide attention from the standpoints of being sensorless and less dependent on the motor parameters. However, this method has a problem at low speeds because actual stator voltage does not coincide with the corresponding reference voltage owing to the quantization error in the controller, the discrete-time process, the forward voltage drop of switching devices, and the dead time of the inverter. In this study, an artificial neural network-based voltage compensator is proposed to reduce the voltage error between the reference and the actual voltages. The proposed method was performed on an experimental system and the results were found to be excellent.

The computational burden related to model-based predictive control (MBPC) of constrained nonlinear systems hampers its real-time application. To avoid this, input-output feedback linearisation (IOFL) techniques are used to linearise the process model over a wide operating range. The resulting linear model is then integrated in a linear MBPC scheme allowing for standard linear control techniques to be applied. However, the process input constraints become nonlinearly related with the optimisation variable due to the state-dependent nonlinear feedback law. In this paper a new method to IOFL of general multivariable discrete-time systems is proposed. By adopting an approximate IOFL based on a suitable linear model approximation, a new linear and state dependent input mapping is obtained which further enables the MBPC solution to be found through a single quadratic programming optimisation. The performance of this new technique is compared with other well-known schemes for the control of a Van der Vusse chemical reaction taking place in a CSTR.

There is a need for efficient modeling strategies which quickly lead to reliable mathematical models that can be applied for design and optimization of (bio)-chemical processes. The serial gray box modeling strategy is potentially very efficient because no detailed knowledge is needed to construct the white box part of the model and because covenient black box modeling techniques like neural networks can be used for the black box part of the model. This paper shows for a typical biochemical conversion how the serial gray box modeling strategy can be applied efficiently to obtain a model with good frequency extrapolation properties. Models with good frequency extrapolation properties can be applied under dynamic conditions that were not present during the identification experiments. For a given application domain of a model, this property can be used to considerably reduce the number of identification experiments. The serial gray box modeling strategy is demonstrated to be successful for the modeling of the enzymatic conversion of penicillin G In the concentration range of 10–100 mM and temperature range of 298–335 K. Frequency extrapolation is shown by using only constant temperatures in the (batch) identification experiments, while the model can be used reliable with varying temperatures during the (batch) validation experiments. No reliable frequency extrapolation properties could be obtained for a black box model, and for a more knowledge-driven white box model reliable frequency extrapolation properties could only be obtained by incorporating more knowledge in the model. © 1999 John Wiley & Sons, Inc. Biotechnol Bioeng 62: 666–680, 1999.

Die vorliegende Studie zeigt erstmals in Deutschland für eine unselektierte Bevölkerungsgruppe Älterer (n = 214) die Behandlungserfolge bzw. Folgen von proximalen Femurfrakturen auf. Die Inzidenz der Frakturen lag bei dieser Altersgruppe bei 636,9/100 000 Einwohner, 31,8% der Frakturen ereigneten sich bei Heimbewohnern. Das durchschnittliche Alter lag bei 82,4 Jahren, 84% der Betroffenen waren weiblich. Als Vorerkrankungen wurden besonders häufig neurodegenerative und zerebrovaskuläre Erkrankungen diagnostiziert. Bei der kognitiven Testung hatten 53,6% erhebliche Einschränkungen (MMSE < 21 Punkte), 11,2% litten an einem Parkinsonsyndrom, 16,8% hatten ein neurologisches Defizit nach Schlaganfall. Als Indikatoren für die Ergebnisqualität (Outcome) wurden Mortalität, Mobilität, Umzug in ein Heim und Schmerzen bewertet. Nach sechs Monaten waren 17,6% der Patienten verstorben, besonders betroffen waren Heimbewohner (29,9%). Von den Überlebenden der gesamten Gruppe konnten 76,1% wieder gehen (Heimbewohner 48,9%), 58,5% konnten zumindest in Begleitung das Haus verlassen (Heimbewohner 26,5%). Unabhängig beim Ankleiden waren 54,6% der Überlebenden (Heimbewohner 26,5%). Schmerzfrei waren 36,9% der Untersuchten, über ständige und gleichzeitig starke Schmerzen berichteten 10,2% der Befragten. Von den Bewohnern von Privathaushalten mußten 19,0% in ein Heim umziehen. Die Untersuchung zeigt ein erhebliches Ausmaß an funktionellen und sozialen Einbußen nach Hüftfrakturen. Zukünftige Therapiemodifikationen sollten an fallgruppenadjustierten Standards überprüft werden. Es scheint möglich, durch eine Intensivierung und Stratifizierung der perioperativen Behandlung und Rehabilitation eine Verbesserung der Mobilität und des Selbstvertrauens zu erreichen. Objective: to examine mortality, mobility, pain, institutionalization rates six month after hip fractures. Design: observational study, non-selected consecutive patients, time-set protocol. Setting: urban area (population n = 116,5000), five hospitals. Participants: hip fracture patients (n = 214), age 65 + years (mean 82.4 years). Measurements: age, gender, prefracture status, operative procedures, complications, comorbidity, cognition (MMSE), depression (GDS), fear of falling, ADL (Barthel) and mobility and pain status (SAHFE protocol). Results: the incidence for this age group was 636.9/100,000, 31.8% were institutionalized elderly. 84% of the patients were female. Pre-existing comorbidity showed a high prevalence of neurodegenerative (cognitive deficits 53.6%, Parkinson's disease/syndrome 11.2%) and cerebrovascular diseases (16.8%). Six month postfracture, the mortality was 17.6%. From those surviving 76.2% did walk indoors, 58.5% did also walk outdoors. Independent to dress were 54.6%. Severe pain was reported by 10.2%, whereas 36.9% described no pain. The institutionalization rate at six month was 19.0%. Conclusions: the study showed considerable mortality, a significant loss in function and social disintegration. Considerable differences were observed for subgroups of patients. Future treatment should focus on risk stratification and include postdischarge training programs. Moreover, preventive strategies should be implemented for high risk groups, such as ambulating patients with a history of stroke. Parkinson's disease and syndrome, dementia and nursing home residents.

In this paper, we prove that a simple system for a subsystem Ψ of the complex root system Φ can always be chosen as a subset of the positive system Φ+of Φ. Furthermore, we show that a set of distinguished coset representatives can be found for every reflection subgroup of the complex reflection groups. The corresponding results for real crystallographic root systems and their reflection groups (i.e., Weyl groups) are well known (see [9]).

In the serial gray box modeling strategy, generally available knowledge, represented in the macroscopic balance, is combined naturally with neural networks, which are powerful and convenient tools to model the inaccurately known terms in the macroscopic balance. This article shows, for a typical biochemical conversion, that in the serial gray box modeling strategy the identification data only have to cover the input-output space of the inaccurately known term in the macroscopic balances and that the accurately known terms can be used to achieve reliable extrapolation. The strategy is demonstrated successfully on the modeling of the enzymatic (repeated) batch conversion of penicillin G, for which real-time results are presented. Compared with a more data-driven black box strategy, the serial gray box strategy leads to models with reliable extrapolation properties, so that with the same number of identification experiments the model can be applied to a much wider range of different conditions. Compared to a more knowledge-driven white box strategy, the serial gray box model structure is only based on readily available or easily obtainable knowledge, so that the development time of serial gray box models still may be short in a situation where there is no detailed knowledge of the system available. © 1997 John Wiley & Sons, Inc. Biotechnol Bioeng 53: 549–566, 1997.

There is no convincing evidence that endothelial cell seeding of prosthetic grafts in humans confers any of the advantages seen in animals. However, partial endothelial coverage might exert a subtle effect not detectable with indirect end points such as patency or scintigraphy. This study examined seeded cell function by measuring fibrinolytic and platelet activation markers in patients receiving seeded and control prosthetic grafts. Thirty-two patients were randomly assigned to seeded (n=15) and control (n=17) groups. Preoperatively and 3, 6, and 12 months postoperatively, plasma levels of fibrinopeptide A (FPA), Bβ1–42 fragment, cross-linked fibrin degradation products (XL-FDP), thromboxane A2 (TXA2), platelet factor 4 (PF4), and β-thromboglobulin (ßTG) were measured. Patients with seeded grafts had significantly lower levels of FPA at 6 and 12 months (p <0.05) and a significant overall group effect (p <0.05). These patients also tended to have higher levels of XL-FDP (p <0.1). No other significant differences were seen. The lower rate of conversion of fibrinogen to fibrin and the trend toward increased fibrinolysis seen in seeded grafts may be due to the metabolic effects of viable retained seeded cells. Although comparable platelet activation indicates that endo-thelial coverage remains limited, seeding may exert an antithrombotic influence at the graft surface.