Fault diagnosis by refining the parameter uncertainty space of nonlinear dynamic systems

This paper deals with fault detection and isolation problems for nonlinear dynamic systems. Both problems are stated as constraint satisfaction problems (CSP) and solved using consistency techniques. The main contribution is the isolation method based on consistency techniques and uncertainty space refining of interval parameters. The major advantage of this method is that the isolation speed is fast even taking into account uncertainty in parameters, measurements, and model errors. Interval calculations bring independence from the assumption of monotony considered by several approaches for fault isolation which are based on observers. An application to a well known alcoholic fermentation process model is presented

Dynamic diagnosis based on interval analytical redundancy relations and signs of the symptoms

A model-based approach for fault diagnosis is proposed, where the fault detection is based on checking the consistencyof the Analytical Redundancy Relations (ARRs) using an interval tool. The tool takes into account the uncertainty in theparameters and the measurements using intervals. Faults are explicitly included in the model, which allows for the exploitation of additional information. This information is obtained from partial derivatives computed from the ARRs. The signs in the residuals are used to prune the candidate space when performing the fault diagnosis task. The method is illustrated using a two-tank example, in which these aspects are shown to have an impact on the diagnosis and fault discrimination, since the proposed method goes beyond the structural methods

Constraint satisfaction techniques under uncertain conditions for fault diagnosis in nonlinear dynamic systems

The speed of fault isolation is crucial for the design and reconfiguration of fault tolerant control (FTC). In this paper the fault isolation problem is stated as a constraint satisfaction problem (CSP) and solved using constraint propagation techniques. The proposed method is based on constraint satisfaction techniques and uncertainty space refining of interval parameters. In comparison with other approaches based on adaptive observers, the major advantage of the presented method is that the isolation speed is fast even taking into account uncertainty in parameters, measurements and model errors and without the monotonicity assumption. In order to illustrate the proposed approach, a case study of a nonlinear dynamic system is presented

Postmortem diagnosis of unsuspected diabetes mellitus.

Vitreous glucose, blood beta-hydroxybutyrate and glycated hemoglobin were systematically measured in a series of 500 medico-legal autopsies in order to characterize the glycemic control during the weeks preceding death and identify ketoacidosis as the cause of death in diagnosed and unsuspected diabetics. Unenhanced CT-scans, histology and toxicology were performed in all cases. 16 cases of diabetic ketoacidosis were identified based on the results of all investigations. Among those, 13 cases concerned individuals with pre-existing diagnoses of diabetes mellitus whereas 3 cases concerned individuals with undiagnosed diabetes. A recent cocaine use was observed in 2 cases. C-reactive protein, interleukin-6 and interleukin-10 were measured and proved to be increased in all cases of diabetic ketoacidosis, whereas markers of generalized, bacterial infection and sepsis were normal in most of these cases. The results of this study highlight the usefulness of systematically performing biochemistry to identify ketoacidosis in unsuspected diabetics. It also emphasizes the role of toxicology and biochemistry to support the diagnosis of diabetic ketoacidosis and delineate the pathophysiological mechanisms that may disrupt the metabolic balance and finally lead to death in diabetic individuals.

Gastrointestinal complications of post-diarrheal hemolytic uremic syndrome.

PURPOSE: Whereas gastrointestinal symptoms such as vomiting, diarrhea and abdominal pain are common in children suffering from the so-called post-diarrheal form (D+) of hemolytic uremic syndrome (HUS), more serious gastrointestinal complications are rare. We tried to define factors predictive of the severity of gastrointestinal complications post D+ HUS. METHODS: We reviewed the files of all children admitted to our hospital for D+ HUS between 1988 and 2000. We retained those cases with gastrointestinal complications and analyzed the consequences of these complications on the evolution of the children's conditions. RESULTS: Sixty-five children with D+ HUS were admitted to our hospital during this period. Sixteen children developed gastrointestinal complications involving one or more digestive organs: necrosis of the colon or ileum, hemorrhagic colitis, pancreatitis, transient diabetes, hepatic cytolysis and cholestasis, peritonitis and prolapse of the rectum. One child died. CONCLUSION: Gastrointestinal complications of D+ HUS are rare, but they can be lethal, and early surgery may sometimes prove necessary. However, we were not able to demonstrate a correlation between the severity of the gastrointestinal manifestations and the clinical or biological signs accompanying D+ HUS.

Exome sequencing of index patients with retinal dystrophies as a tool for molecular diagnosis.

BACKGROUND: Retinal dystrophies (RD) are a group of hereditary diseases that lead to debilitating visual impairment and are usually transmitted as a Mendelian trait. Pathogenic mutations can occur in any of the 100 or more disease genes identified so far, making molecular diagnosis a rather laborious process. In this work we explored the use of whole exome sequencing (WES) as a tool for identification of RD mutations, with the aim of assessing its applicability in a diagnostic context. METHODOLOGY/PRINCIPAL FINDINGS: We ascertained 12 Spanish families with seemingly recessive RD. All of the index patients underwent mutational pre-screening by chip-based sequence hybridization and resulted to be negative for known RD mutations. With the exception of one pedigree, to simulate a standard diagnostic scenario we processed by WES only the DNA from the index patient of each family, followed by in silico data analysis. We successfully identified causative mutations in patients from 10 different families, which were later verified by Sanger sequencing and co-segregation analyses. Specifically, we detected pathogenic DNA variants (∼50% novel mutations) in the genes RP1, USH2A, CNGB3, NMNAT1, CHM, and ABCA4, responsible for retinitis pigmentosa, Usher syndrome, achromatopsia, Leber congenital amaurosis, choroideremia, or recessive Stargardt/cone-rod dystrophy cases. CONCLUSIONS/SIGNIFICANCE: Despite the absence of genetic information from other family members that could help excluding nonpathogenic DNA variants, we could detect causative mutations in a variety of genes known to represent a wide spectrum of clinical phenotypes in 83% of the patients analyzed. Considering the constant drop in costs for human exome sequencing and the relative simplicity of the analyses made, this technique could represent a valuable tool for molecular diagnostics or genetic research, even in cases for which no genotypes from family members are available.

Immunoscintigraphy with antigranulocyte monoclonal antibodies for the diagnosis of septic loosening of hip prostheses.

To determine the value of immunoscintigraphy (IS) with antigranulocyte monoclonal antibodies (Mab) in the diagnosis of subacute or chronic infection of hip prostheses, we prospectively studied 57 patients (23 women and 34 men; age 29-92 years, mean 72.7 years) sent to our institution in the past 6 years for clinical suspicion of septic loosening of a hip prosthesis. Nineteen patients had bilateral prostheses and one of them was studied twice. A total of 78 prostheses were examined. All patients had three-phase bone scans followed by IS with technetium-99m antigranulocyte Mab BW 250/183. Intervals between bone scans and IS varied from 2 days to 4 weeks. Final diagnosis was assessed by culture in 48 cases (articular puncture or intraoperative sampling) and by clinical follow-up of at least 8 months in 30 cases. Twelve prostheses were considered septic and 66 non-septic. The overall sensitivity and specificity were 92% and 64% respectively for bone scans, 67% and 75% for IS and 67% and 84% for both modalities together. In three cases, IS was doubtful and the final clinical diagnosis was negative for infection. False-positive results were observed in the presence of massive loosening of the prosthesis or in association with metaplastic peri-articular bone formation. In three of the four false-negative results, infection was proven only after enrichment of the culture, and the bacterium was Staphylococcus epidermidis. In 12/33 (36%) positive bone scans IS allowed the diagnosis of infection to be excluded. Overall accuracy of both modalities together was 81% and the negative predictive value was 93%, which compares favourably with the results reported for other non-invasive methods.

Use of new biochemical plasmatic markers, plasma free and total metanephrines, for the diagnosis and follow-up of neuroblastoma in children with clinical correlation

Background: Neuroblastoma is a paediatrictumour derived from the neural crest. Biochemical diagnosis and follow up rely on quantitation of urinary catecholamines (dopamine and noradrenaline) and their metabolites vanillylmandelic acid (VMA) and homovanillic acid (HVA) (gold-standard). When combined, these analyses have a sensitivity of 95%. However, they are clearly limited by inaccuracy of urine collection in young children and normalisation of catecholamine concentrations by creatininuria. Recent development in biochemical diagnosis of pheochromocytoma, another neural crest tumour found in adults, shows that plasmatic measurement of methoxylated catecholamines called metanephrines are more sensitive and specific than other biomarkers. Moreover, a study to determine the reference intervals for metanephrines in a pediatric population has recently been completed. The aim of this work is to describe the role of metanephrines monitoring in the follow up of neuroblastoma. Method: This retrospective study included patients with neuroblastoma in whom the following parameters were determined: plasma free and total metanephrines, plasma catecholamines, 24h urinary catecholamines and metanephrines in absolute value and corrected by creatinine, VMA and HVA at the diagnosis and during treatment at the University Hospital of Lausanne (Switzerland). Eleven patients aged between the first day of life and 7 years old were followed between 2005 and 2012. Clinical outcome and biochemical concentrations of the analytes were correlated. Results: At diagnosis, plasma free and total normetanephrines and methoxytyramine have a sensitivity of 100% compared to 85% for the actual gold standard. Metanephrine remain below the upper reference limit as expected since these tumours do not produce adrenaline. The relationship between biochemical markers and clinical outcome is illustrated graphically. Plasma or urinary normetanephrine and methoxytyramine correlate better with the history of the patient than VMA and HVA, as evaluated by ordinal logistic regression. Concentrations of analytes in urine show a better correlation with clinical events when the results are corrected by creatininuria. Conclusion: Normetanephrine and methoxytyramine reflect disease history in neuroblastoma patients and could play a significant role in the follow up of this type of tumour. Formal studies in a sufficient number of patients are needed to confirm this preliminary observation.

Congenital diaphragmatic hernia : a European population-based study of epidemiology, prenatal diagnosis and mortality

Aim: To study the epidemiology and the impact of prenatal diagnosis on mortality and morbidity in infants with isolated congenital diaphragmatic hernia (CDH). Methods: Cases were identified in eight population-based registries of congenital malformations (Eurocat) in Europe. Results: A total of 183 live births were included in the study. Sixty per cent died and 67% of all deaths were during the first day of life. CDH was diagnosed prenatally in 39% of cases. Both mortality and morbidity were significantly higher for infants diagnosed prenatally compared to those diagnosed postnatally. The Apgar score was a very sensitive indicator for survival. Gestational age at birth was significantly lower for infants diagnosed prenatally compared to those diagnosed postnatally (37.6 weeks vs. 38.8 weeks, p < 0.01). At the end of follow-up, half of the survivors were leading a normal life. The most frequently reported health problems were respiratory and gastrointestinal symptoms. Conclusions: In this population-based study, mortality for infants with CDH was high (60%) and early prenatal diagnosis was a risk factor for survival. Intervention at the time of birth seems too late for the majority of newborn infants with CDH.

Prenatal diagnosis of dysmorphic syndromes by routine fetal ultrasound examination across Europe.

OBJECTIVES: Ultrasound scan in the mid-trimester of pregnancy is now a routine part of prenatal care in most European countries. The objective of this study was to evaluate the prenatal diagnosis of dysmorphic syndromes by fetal ultrasound examination. METHODS: Data from 20 registries of congenital malformations in 12 European countries were included in the study. RESULTS: There were 2454 cases with congenital heart diseases, 479 of which were recognized syndromes, including 375 chromosomal anomalies and 104 syndromes without chromosomal anomalies. Fifty-one of the 104 were detected prenatally (49.0%). One hundred and ninety-two of 1130 cases with renal anomalies were recognized syndromes, including 128 chromosomal anomalies and 64 syndromes without chromosomal anomalies; 162 of them (84.4%) were diagnosed prenatally, including 109 chromosomal anomalies and 53 non-chromosomal syndromes. Fifty-four of the 250 cases with limb defects were recognized syndromes, including 16 chromosomal syndromes and 38 syndromes without chromosomal anomalies; 21 of these 54 syndromes were diagnosed prenatally (38.9%), including 9 chromosomal syndromes. There were 243 cases of abdominal wall defects including 57 recognizable syndromes, 48 with omphalocele and 9 with gastroschisis; 48 were diagnosed prenatally (84.2%). Twenty-six of the 187 cases with diaphragmatic hernia had recognized syndromes, including 20 chromosomal aberrations and 6 syndromes without chromosomal anomalies. Twenty-two of them (84.6%) were detected prenatally. Sixty-four of 349 cases with intestinal anomalies were recognized syndromes; 24 were diagnosed prenatally (37.5%). There were 553 cases of cleft lip and palate (CL(P)) and 198 of cleft palate (CP) including 74 chromosomal anomalies and 73 recognized non-chromosomal syndromes. Prenatal diagnosis was made in 51 cases of CL(P) (53.7%) and 7 of CP (13.7%). Twenty-two of 188 anencephalic cases were syndromic and all were diagnosed prenatally. Of 290 cases with spina bifida, 18 were recognized syndromes, and of them 17 were diagnosed prenatally. All 11 syndromic encephaloceles were diagnosed prenatally. CONCLUSIONS: Around 50% of the recognized syndromes which are associated with major congenital anomalies (cardiac, renal, intestinal, limb defects, abdominal wall defects and oral clefts) can be detected prenatally by the anomaly scan. However the detection rate varies with the type of syndrome and with the different countries' policies of prenatal screening.

Intracerebellar hemorrhage caused by developmental venous anomaly, from diagnosis to treatment.

BACKGROUND: Developmental venous anomaly (DVA) is considered a benign and asymptomatic cerebrovascular malformation, and only isolated cases of symptomatic DVAs are described in the literature. Even more rarely will these symptoms come from an intraparenchymal hemorrhage caused by the DVA. METHODS AND RESULTS: We present two symptomatic DVAs by intracerebellar hemorrhage. CONCLUSION: The diagnostic steps regarding the pathophysiology of DVA hemorrhage and the treatment options are discussed.

African tick-bite fever: a new entity in the differential diagnosis of multiple eschars in travelers. Description of five cases imported from South Africa to Switzerland.

African tick-bite fever (ATBF) is a newly described spotted fever rickettsiosis that frequently presents with multiple eschars in travelers returning from sub-Saharan Africa and, to a lesser extent, from the West Indies. It is caused by the bite of an infected Amblyomma tick, whose hunting habits explain the typical presence of multiple inoculation skin lesions and the occurrence of clustered cases. The etiological agent of ATBF is Rickettsia africae, an emerging tick-borne pathogenic bacterium. We describe herein a cluster of five cases of ATBF occurring in Swiss travelers returning from South Africa. The co-incidental infections in these five patients and the presence of multiple inoculation eschars, two features pathognomonic of this rickettsial disease, suggested the diagnosis of ATBF. Indeed, the presence of at least one inoculation eschar is observed in 53-100% of cases and multiple eschars in 21-54%. Two patients presented regional lymphadenitis and one a mild local lymphangitis. Though a cutaneous rash is described in 15-46% of cases, no rash was observed in our series. ATBF was confirmed by serology. Thus, ATBF has recently emerged as one of the most important causes of flu-like illness in travelers returning from Southern Africa. The presence of one or multiple eschars of inoculation is an important clinical clue to the diagnosis. It can be confirmed by serology or by PCR of a biopsy of the eschar. Culture can also be done in reference laboratories. Dermatologists and primary care physicians should know this clinical entity, since an inexpensive and efficient treatment is available.

Small cell (neuroendocrine) carcinoma of the prostate: etiology, diagnosis, prognosis, and therapeutic implications--a retrospective study of 30 patients from the rare cancer network.

Within the framework of the Rare Cancer Network Study, we examined 30 patients suffering from small cell neuroendocrine prostate cancer, either in an early/localized or an advanced/metastatic stage. Patients were treated with cisplatin-based chemotherapy, with or without pelvic radiotherapy. Two patients with early disease achieved complete remission for a duration of 19 and 22 months. Three patients with advanced disease achieved complete remission for 6, 7, and 54 months, respectively. Twenty-five patients succumbed to massive local and/or distant failure. No patient presented with brain metastases as the initial site of relapse. Small cell neuroendocrine prostate carcinoma is a very aggressive disease with a poor prognosis, even in its localized form. Despite initial response, the common cisplatin-based chemotherapy plus radiotherapy failed to improve outcome markedly. Improvement will come from understanding the biology of the disease and integrating new targeted therapies into the treatment of this rare and aggressive tumor.