Search

We present a new method for model-based mutation-driven test case generation. Mutants are generated by making small syntactical modifications to the model or source code of the system under test. A test case kills a mutant if the behavior of the mutant deviates from the original system when running the test. In this work, we use hyperproperties-which allow to express relations between multiple executions-to formalize different notions of killing for both deterministic as well as non-deterministic models. The resulting hyperproperties are universal in the sense that they apply to arbitrary reactive models and mutants. Moreover, an off-the-shelf model checking tool for hyperproperties can be used to generate test cases. Furthermore, we propose solutions to overcome the limitations of current model checking tools via a model transformation and a bounded SMT encoding. We evaluate our approach on a number of models expressed in two different modeling languages by generating tests using a state-of-the-art mutation testing tool., (© The Author(s) 2021.)

Craig's interpolation theorem has numerous applications in model checking, automated reasoning, and synthesis. There is a variety of interpolation systems which derive interpolants from refutation proofs; these systems are ad-hoc and rigid in the sense that they provide exactly one interpolant for a given proof. In previous work, we introduced a parametrised interpolation system which subsumes existing interpolation methods for propositional resolution proofs and enables the systematic variation of the logical strength and the elimination of non-essential variables in interpolants. In this paper, we generalise this system to propositional hyper-resolution proofs as well as clausal proofs. The latter are generated by contemporary SAT solvers. Finally, we show that, when applied to local (or split) proofs, our extension generalises two existing interpolation systems for first-order logic and relates them in logical strength.

Many software model checkers only detect counterexamples with deep loops after exploring numerous spurious and increasingly longer counterexamples. We propose a technique that aims at eliminating this weakness by constructing auxiliary paths that represent the effect of a range of loop iterations. Unlike acceleration, which captures the exact effect of arbitrarily many loop iterations, these auxiliary paths may under-approximate the behaviour of the loops. In return, the approximation is sound with respect to the bit-vector semantics of programs. Our approach supports arbitrary conditions and assignments to arrays in the loop body, but may as a result introduce quantified conditionals. To reduce the resulting performance penalty, we present two quantifier elimination techniques specially geared towards our application. Loop under-approximation can be combined with a broad range of verification techniques. We paired our techniques with lazy abstraction and bounded model checking, and evaluated the resulting tool on a number of buffer overflow benchmarks, demonstrating its ability to efficiently detect deep counterexamples in C programs that manipulate arrays.

We describe a patient who was assigned female at birth because of genital ambiguity without performing further diagnostic procedures and presented at the age of 13-1/2 years because of her strong desire to change her legal sex. Karyotype was 46,XY; clinical, endocrinological, radiological and surgical work-up revealed hypergonadotropic hypogonadism and mixed gonadal dysgenesis. Gender identity reversal was performed after extensive psychological testing and adaptation of living circumstances resulting in a successful integration as a male with normal psychological and social functioning. In several surgical procedures, the streak gonad, the nonfunctional testis, and the rudimentary uterus were removed, and a penis was reconstructed from a penisoid with chorda and hypospadias. Our patient supports the idea that gender identity is imprinted prenatally by hitherto poorly understood mechanisms and that sex assignment in infants with ambiguous genitalia needs careful consideration of not solely endocrinological and anatomical data.

A boy, 2 years old, developed a HUS after a pneumonitis. He was treated with Heparin, salicylates and recurrent peritoneal dialysis and recovered slowly. The course of the disease was complicated by myocarditis, gastric hemorrhage and severe neurologic disturbances. 7 days after unset of hemolysis a cold agglutinin titer of 1:256 was detected. This fact arises the question whether infection with Mycoplasma pneumoniae and the presence of cold agglutinins in serum could be involved in the development of HUS. The possibility of a viral etiology for this disease is discussed.

Meteorism is a nonspecific symptom and it is difficult to exclude organic causes. In one of our patients, a 6 years old girl, the accumulation of gas had caused changes of the normal abdominal situs. Finally psychogenic aerophagia could be detected by exact analysis of the case history and the daily rhythm of meteorism. The situation within the family could be revealed as trigger mechanism and there an successful therapy was started.

40 children with clinical diagnosis of bronchial asthma aged 8--14 years, 39 with allergic disposition, were investigated. Acute therapeutic and protective effect on frequency of asthmatic attacks, pulmonary auscultation and lung function (FEV1, PF, FVC) by application of Fenoterol and Ipratropium as combination aerosol were registered. Over a period of 4 weeks we could reduce the frequency of attacks nearly to the half. 10 and 20 minutes after aerosol application we showed a good improvement of pulmonary ventilation. Only on children with severe asthma bronchiale an exclusive treatment with Berodual seems to be of modest protective effect.

This report describes the results of a systematic development screening of high risk infants in a provincial district over a period of three and a half years. Criteria for neurological research during the first year of life and organizing problems are presented. Low frequency of medical care during pregnancy seems to be a main factor predetermining cerebral palsy and multiple disabilities. An optimal transport system seems to be a supporting factor for the prevention of such motoric and mental derangements, especially in children, who initially show no pulmonary or cardiac problems.

Among the various types of hepatic ductular atresias, there is a group of patients with a definable syndrome of malformations: typical physiognomy, malformation of pulmonary arteries, mental retardation and disturbed growth of body and genitals. This syndrome has been defined only in the last two years by Watson et al. (1973) and Allagille et al. (1975). A detailed description of a boy with this combination of malformations is given. Additionally he has aplasia of the right kidney. A second patient out of 4, which we found in our cardiologic department, has hypoblasia of one kidney, too. The prognosis of the liver disease in these patients seems to be better than in other children with biliary atresia.

Long term hemodialysis and kidney transplantation has proved to be a very efficient method in the treatment of renal failure in childhood. Accordingly, the number of children treated by dialysis and transplantation in Europe is still increasing. At this time more than 1250 have been treated. As a result of recent studies, one to two children under the age of 15 years per one million population per one year reach the terminal stage of renal insufficiency. We performed our own informative study in 1975 to estimate the needs for dialysis facilities in Austria. Our results are in line with those of other projects. In view of the special childhood problems (growth, puberty, psychological problems, schooling etc.) there is a need for specialized pediatric centers which should include the facilities for nephrologic out- and in-patient treatment, a dialysis team consisting of a pediatrician, pediatric nurses, teacher, child psychologist, dietician and social worker. These enormous investments in apparature, personnel and organization are justified by the good results of survival and the reasonably normal life these children can lead.

A ten year old boy with parents of Rumanian and Turkish origin suffered from metaphyseal chondrodysplasia (McKusick type) with typical radiological changes of the metaphyseal endplates. Microscopic examination of his hair revealed only slight diminution of its thickness, and signs of increased brittleness. Because of Hirschsprung's disease resection of colon was performed. No immunologic changes were found.

The rare X-ray finding of urinary bladder wall calcifications in a newborn is reported. The newborn suffered from micturition disturbance caused by urethral valves, bilateral hydroureter and bilateral hydronephrosis. No possible definite cause for the calcification of the bladder wall could be found. The calcifications could never be detected by X-ray after the age of 5 months.

In adults, luteinizing hormone (LH) and follicle stimulating hormone (FSH) are secreted in a pulsatile manner. Prior to puberty gonadotropin (GN) levels are low and show only small fluctuations. The following investigation was performed to elucidate the type of GN secretion in infants. LH and FSH were determined every 30 min over a period of 8 h in three different groups: Group 1:2 male and 2 female adults; Groups 2:2 male and 2 female prepubertal children; Group 3:3 male and 3 female infants, aged 6-12 weeks. Group 1 showed a clear pulsatile secretion of LH (4.5-23.5 mIU/ml [range]) and FSH (6.9-16.0 mIU/ml). Group 2 demonstrated a rather constant secretion of LH (less than 1.5-2.3 mIU/ml) and FSH (1.6-4.9 mIU/ml). Group 3: In male infants pulsatile secretion of LH (3.6-34.7 mIU/ml)--and to a lesser degree of FSH (1.8-4.6 mIU/ml)--were found. In female infants the pulsatile secretion of FSH (6.5-22.7 mIU/ml) was more pronounced than that of LH (less than 1.5-4.7 mIU/ml). The secretory pattern in early infancy is of a pulsatile type.

Two boys with presumably congenital cystic changes in the lungs are described. In one child multiple cystic deformations led to acute symptoms of severe respiratory distress necessitating urgent resection of the right middle and upper lobes. The other boy had a large thick-walled cyst in the left upper lobe causing no distress whatsoever. This patient was observed for more than 6 years before operation. Multiple vascular anomalies and anastomoses were revealed during surgery. Both cases are presented in detail and the completely different clinical course is outlined. Only when careful supervision of intrapulmonary cystic changes is guaranteed can operation be postponed for longer than 6 months. Pulmonary cysts may lead to emergency procedures. They are always a potential source of serious complications such as rupture or infection. When no tendency for regression can be discovered surgical removal is indicated. Conservative treatment will not influence the course. Differential diagnosis is discussed briefly.

One particular form of an anorectal malformation--the anterior perineal anus--is frequently overlooked in the neonate period because defecation is easy at this age. However, with the change of diet, this malformation as a rule leads to chronic constipation. The lateral view at the beginning of an irrigoscopy usually shows a characteristic picture of a horizontal caudal limitation of the rectum, a dorsal pouch, a beakshaped fistula and an elevation of the anorectal transition. These findings contribute essentially to the clinical diagnosis and permit early operation.

Alport's syndrome is a hereditary nephropathy with grave prognostic consequences. The occurrence of this disease is probably more frequent than was assumed until now - many cases are not immediately recognized as such. It is possible to make a clinical diagnosis from detailed family histories and through careful examinations of family members including audiometric tests. In the early stages of the disease children merely have recurrent macro- or microhematuria. Renal functional tests are normal and there is general well-being of the patient. Whereas the biopsy specimens examined by light microscopy show non-specific alterations, those examined under the electronmicroscope already show specific defects of the basement membrane. Our studies lead us to believe that these morphologic findings correspond with changes of the basement membrane, detectable by immunochemical investigations. 6 of 12 patients have been biopsied in recent time and the above cited typical changes of the basement membrane could be demonstrated. Therefore these investigations are recommended in Alport's syndrome.

Up until now 39 cases of combined Klippel-Trénaunay syndrome and Sturge-Weber syndrome have been described. Here follows the report of a girl, now 4 years of age, displaying a full combination of these syndromes. Only a small part of the body surface is not covered with naevi teleangiectatici laterales. The patient has clear hypertrophy of the left cheek and of the left lower extremity, less noticeable on the left upper extremity. For therapeutic reasons the left side of the head and the left lower extremity were thoroughly angiographically examined--this revealed typical abnormalities. The vessel-alteration of the lower extremity are not extremely far developed and arteriovenous fistulas on a large scale are also absent. This allows us to dismiss the F.P. Weber syndrome on the one hand, while it explains the absence of complications of the Klippel-Trénaunay syndrome, as described in literature, on the other. The significance of the alterations of lymph nodes in this disease, which we are the first to describe, is at present not fully clear. The cerebral attacks have until now showed only a temporary response to medication.

Seven cases of the most severe form of tuberculous meningitis, in which a midbrain syndrome developed, are reported. Three different types of progress were observed. Exudative inflammation and cerebral edema dominated in the first group, causing the rapid development of the acute midbrain syndrome, which may turn into a bulbar syndrome. In the second group the development of the midbrain was delayed and an apallic syndrome followed. The morphological examination disclosed local diencephalic and midbrain lesions caused by herniation and specific vasculitis and vascular compression. The third group showed disintegration of cortical function as a result of parenchymal lesions, apart from local midbrain symptoms which never fully intensified into the midbrain syndrome. Observation of the progress of the disease proved that late diagnosis and delayed therapy were decisive in cases of the most severe form of tuberculous meningitis.

During the past 2 years 7 children received kidneys from cadaveric donors. 2 transplants had to be removed because of irreversible chronic rejection and 1 recipient died on the 4th day after surgery. The remaining 4 recipients are doing well. In the evaluation of the results special emphasis is placed on the normalization of growth and puberty. The difficulties of psychosocial rehabilitation are stressed.

Potter-syndrome with agenesia of the kidneys and typical face is only one variation of the big group of renofacial dysplasia. Among our patients which are under treatment because of malformations of the urinary tract very often we see children with dysplastic faces or malformed ears. Therefore vice versa patients with alterations of ears and face should be exactly investigated to exclude urinary tract malformations.

Alpha-1-antitrypsin was determined in children with glomerular diseases by means of a quantitative radial immunodiffusion method. The concentration of this inhibiting protein has been found to be very low during relapses. An attempt has been made to correlate this finding with the clinical picture and the presumed underlying pathological mechanism. The loss of this inhibitor due to proteinuria is one of the explanations, in concurrence with the findings of other authors. The second explanation lies in the consumption of the inhibitor protein as a consequence of the reaction with liberated proteolytic enzymes.

Besides classical achondroplasia various severe osteochondrodysplastic disorders have been differentiated in recent years. Their most important features include obligatory perinatal mortality, severe dystrophy of the thorax and shortening of tubular bones. Additionally some of these syndromes present visceral malformations, cleft-lip, and malformations of the genitals. A detailed case report of a patient is given. Various features: dystrophy of the thorax, micromelia, postaxial polydactyly, metaphyseal dysplasia, malformations of the great vessels, and polcystic kidney suggest the classification as short rib-polydactyly syndrome, type Saldino-Noonan.

The serum and urine levels of alpha-2-macroglobulin (alpha2-MG) was determined in 33 children with glomerular diseases and in 26 healthy control children. Healthy children showed a minimum level of 275 mg% and maximum level of 337 mg%, with a mean concentration of 301 mg% and a standard deviation of 13 mg%. No alpha2-MG was detected in the urine. Steroid-treated patients with idiopathic nephrotic syndrome displayed elevated inhibitor levels of up to 490 mg%. This might be a direct result of steroid therapy or a consequence of reactively-increased protein synthesis in response to the renal protein loss. In all these patients the urine was found to be alpha2-MG-negative, irrespective of the presence or absence of proteinuria. In the miscellaneous group of glomerulopathies without the nephrotic syndrome, serum levels of alpha2-MG were shown to be normal. The urinary concentrations of alpha2-MG were related to the activity of the disease. alpha2-MG determination in serum and urine seems to be a tool for differential diagnosis and prognosis in some cases of glomerular disease.

Alport's syndrome is defined by the combination of hereditary nephropathy and neurosensory deafness, and is diagnosed from the family history combined with renal electron microscopy. Immunoelectrophoresis of the urine of 8 of 12 children suspected of Alport's syndrome showed a precipitation line moving into the beta-zone, applying an antiglomerular basement membrane antibody derived from an immunised rabbit. All patients who showed the typical pattern of Alport's syndrome on renal electron microscopy were among the 8 cases whose urine gave this immunoelectrophoresis pattern. Additionally, 5 of the mothers of the 8 children excreted the same antigen in their urine. The urine of 30 healthy children and of 10 patients with the idiopathic nephrotic syndrome did not show the presence of this antigen. This characteristic sign of Alport's syndrome may therefore be useful for its detection.

The prolonged use of a salt restricted infant formula (1.9 mEq Na/kg/day and 1,4 mEq C1/kg/day) in a child with undiagnosed cystic fibrosis led to a life threatening metabolic disturbance. The main features were hypochloraemic alkalosis due to massive loss of electrolytes in the sweat. Urinary electrolyte excretion, however, had been lowered to a minimum due to aldosteron induced reabsorption. Plasma aldosterone levels were initially high, but returned to normal after addition of salt to the feeds. Prior to admission a sweat test had been negative. The patient clearly demonstrates the unique metabolic feature of cystic fibrosis of the ability to retain electrolytes in the tubulus and at the same time the inability of the sweat glands to reabsorb sodium and chloride. Contrary to present experience severe prolonged salt restriction is believed to be able to diminish sweat electrolytes to subpathological values.