On improved volatility modelling by fitting skewness in ARCH models.

We study ARCH/GARCH effects under possible deviation from normality. Since skewness is the principal cause for deviations from normality in many practical applications, e.g. finance, we study in particular skewness. We propose robust tests for normality both for NoVaS and modified NoVaS transformed and original data. Such an approach is not applicable for EGARCH, but applicable for GARCH-GJR models. A novel test procedure is proposed for the skewness in autoregressive conditional volatility models. The power of the tests is investigated with various underlying models. Applications with financial data show the applicability and the capabilities of the proposed testing procedure.

Formulating the alginate-polyornithine biocapsule for prolonged stability: evaluation of composition and manufacturing technique.

Alginate encapsulation is one of the most widely used techniques for introducing cell-based therapeutics into the body. Numerous encapsulation methodologies exist, utilizing a variety of alginates, purification technologies, and unique polycationic membrane components. The stability of a conventional alginate formulation encapsulated using a commercially available technique and apparatus has been characterized extensively. The current study employs an encapsulation protocol and ultra-pure alginate pioneered at the University of Perugia. The enhanced microcapsules were produced, characterized, and implanted into the brain, peritoneal cavity, and subcutaneous space of Long-Evans rats. After 14, 28, 60, 90, 120, and 180 or 215 days, capsules were explanted and the surface was analyzed using Fourier-transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). Image analysis was carried out to measure changes in diameter and wall thickness. FTIR peak analysis and surface morphology from SEM indicated that the enhanced encapsulation technique and formulation produced a stable biocapsule capable of survival in all sites, including the harsh peritoneal environment, for at least 215 days. Preimplant analysis showed a marked increase in the structural integrity of the enhanced formulation with improved elasticity and burst strength compared with the baseline formulation, which remained stable for less than 60 days. The enhanced microcapsule composition showed advantages in physical strength and longevity, indicating that small changes in encapsulation methodologies and materials selection can dramatically impact the stability and longevity of alginate microcapsules and their contents.

Discovery and development of flecainide.

The flecainide discovery and development process started in 1966 with the broad goal of investigating the effects of fluorine substitution in potential drug molecules. The overall process evolved slowly. The original goals of the project were translated into the 3 major phases: (1) the synthesis and evaluation of 2 major chemical series through the efforts of chemists who incorporated fluorine atoms into new compounds; (2) a change in focus from local anesthetic programs to the antiarrhythmic project through the efforts and advisement of pharmacologists; and (3) commitment to a flecainide development plan culminating in the new drug application for approval of flecainide in the suppression and prevention of ventricular arrhythmias.

A novel specific binding site for homophthalazines in the rat brain.

The specific binding sites of a homophthalazine, girisopam, in rat brain have been localized by qualitative and quantitative autoradiography. This substance exerts strong anxiolytic and antipsychotic effects both in rodents and in humans. High labeling was present in all major components of the extrapyramidal system, such as the caudate-putamen, globus pallidus, subthalamic nucleus, substantia nigra, and the extrapyramidal portion of the accumbens nucleus and the olfactory tubercle, while specific labeling was not seen in any other brain areas including the cerebral cortex, thalamus, cerebellum or brainstem areas. This novel distribution of girisopam is consistent with its antipsychotic effect and anxiolytic properties and may provide a morphological basis for further studies to elucidate the mechanisms of action of homophthalazines in the central nervous system.

Primary Sjögren's syndrome with secondary hyperparathyroidism.

The case history of a 43-year-old woman with primary Sjögren's syndrome is presented: in 1970, xerostomia and keratoconjunctivitis sicca; in 1980, arthritis; in 1982, chronic tubulointerstitial nephritis with renal tubular acidosis and vasopressin-resistant hyposthenuria. The renal function gradually deteriorated. Chronic atrophic gastritis with vitamin B12 deficiency and chronic duodenitis with diminished disaccharidase activity in the mucosa were also diagnosed. From 1985, repeated multiple fractures of the ribs occurred, with secondary hyperparathyroidism in the background. The renal and intestinal involvement suggests that, besides the elevated parathyroid hormone level, an acquired vitamin D deficiency plays a pathogenetic role in severe osteopenia. The patient is being treated at present by haemodialysis, and subtotal parathyroidectomy and renal transplantation are planned.

Efforts to incorporate social justice perspectives into a family training program.

This paper describes the efforts of the faculty of the Family Institute of New Jersey in recent years to develop a collaborative family training program that takes into account issues of gender, race, culture, class, and sexual orientation. We have come to realize how strongly traditional approaches have been skewed in the direction of the dominant culture--white, male, heterosexist, and prioritizing the needs and experience of the middle and upper classes. We have attempted to modify our teaching, supervision, reading lists, and overall training approach to challenge trainees and ourselves to move toward broader, strength-based, and equity-based multicultural perspectives in our training. We describe our vision, how we incorporate it into our program structure, and a few of our training initiatives.

An epidemiological study of salt miners in diesel and nondiesel mines.

A cross-sectional study of 5 NaCl mines and 259 miners addressed the following questions: 1) Is there an association of increased respiratory symptoms, radiographic findings, and reduced pulmonary function with exposure to nitrogen dioxide (NO2) and/or respirable particulate (RP) among these miners? 2) Is there increased morbidity of these miners compared to other working populations? Personal samples of NO2 and respirable particulate for jobs in each mine were used to estimate cumulative exposure. NO2 is used as a surrogate measure of diesel exposure. Cough was associated with age and smoking, dyspnea with age; neither symptom was associated with exposure (years worked, estimated cumulative NO2 or RP exposure). Phlegm was associated with age, smoking, and exposure. Reduced pulmonary function (FVC, FEV1, peak, flow, FEF50, FEF75) showed no association with exposure. There was one case of small rounded and one case of small irregular opacities; pneumoconiosis was not analyzed further. Compared to underground coal miners, above ground coal miners, potash miners, and nonmining workers, the study population after adjustment for age and smoking generally showed no increased prevalence of cough, phlegm, dyspnea, or obstruction (FEV1/FVC less than 0.7). Obstruction in younger salt miners and phlegm in older salt miners was elevated compared to nonmining workers. Mean predicted pulmonary function was reduced 2-4% for FEV1 and FVC, 7-13% for FEF50, and 18-22% for FEF75 below all comparison populations.

A comparative analysis of computational motif-detection methods.

The detection of motifs within and among families of protein sequences can provide useful information regarding the function, structure and evolution of a protein. With the increasing number of computer programs available for motif detection, a comparative evaluation of the programs from a biological perspective is warranted. This study uses a set of 20 reverse transcriptase (RT) protein sequences to test and compare the ability of 7 different computational methods to locate the ordered-series-of-motifs that are well characterized in the RT sequences. The results provide insight to biologists as to the usage, value, and reliability of the numerous methods available.

An assay for serum vitamin-B12 and for intrinsic factor antibody type I by means of hog intrinsic factor.

A method of assay for the circulating intrinsic factor antibody type I (IFA1) and for the serum vitamin-B12 level by the use of hog intrinsic factor has been developed. The results, the sources of error being taken into consideration, are in agreement with the values obtained by the generally accepted methods of ARDEMAN--CHANARIN for IFA1 and of WIDE--KILLANDER for the serum vitamin-B12 level. Parallel with the increase in the frequency of circulating IFA1, the serum vitamin-B12 level was found to decline in normal individuals as well as in patients with atrophic gastritis or pernicious anaemia. The method is suitable for the assessment of vitamin-B12 deficiency and lends itself to screening of patients tending to pernicious anaemia.

Antinuclear factor, smooth and striated muscle antibodies in Duchenne-type muscular dystrophy.

Antinuclear factors and antibodies to smooth and striated muscle were studied by the indirect immune fluorescence method in the sera of 19 children suffering from progressive muscular dystrophy. In 47% of the patients antinuclear factor positivity, in 65% anti smooth muscle antibody positivity, and in 26% antistriated muscle antibody positivity was found. Antibody to striated muscle was present in patients with serious advanced dystrophy and in patients unable to walk, while anti-smooth muscle antibody occurred in less serious cases, too. On the basis of the results, it is concluded that in genetically determined progressive muscular dystrophy a secondary autoimmune process develops owing to the degeneration of muscles as the disease progresses.

Laser-nephelometric detection of soluble immune complexes.

A new method for the detection of soluble immune complexes has been worked out by combining the polyethylene glycol (PEG) precipitation method with laser nephelometry. Experiences achieved by measurements on in vitro immune complexes are presented. The method was found suitable for the detection of immune complexes development in vivo. The optimum concentration of PEG was found to be 3.51%. Results were compared to those achieved by the traditional PEG precipitation technique in 88 cases. The laser nephelometric method was found to be more sensitive and is recommended for use in clinical laboratories.

Low Identity, Low Similarity Protein Sequences: Independent Modeling of the Ordered-Series-of-Motifs and Motif-Intervening-Regions.

We present a strategy for generating a multiple alignment from a hidden Markov model (HMM) for low identity, low similarity protein sequences. In this approach the ordered-series-of-motifs and the motif-intervening-regions are independently modeled. We also provide a measure of multiple alignment goodness called the stability function to compared one alignment to another. This strategy provides a more robust HMM representing highly divergent sequence data.

Primary Sjögren's syndrome from the viewpoint of an internal physician.

The characteristics of primary Sjögren's syndrome are described on the basis of the follow-up of 65 patients with extraglandular symptoms at the onset and during the disease. The mean age of the patients at onset was 41.8 years and at the time of definite diagnosis was 45.8 years. Articular (32 cases), lacrimal (30 cases) and salivary (30 cases) manifestations were the most frequent initial symptoms. In only 22 of the 65 patients could Sjögren's syndrome be diagnosed at the onset. In most cases, the articular symptoms observed observed in 56 patients during the course corresponded to true polyarthritis, as verified by joint scintigraphy. Most frequently the wrists and ankles were affected. Chronic atrophic gastritis was found in 35 patients. In the young patients (13 cases), both the antrum and the corpus were affected more frequently than in the controls. In middle-aged patients (21 cases), atrophy of the antrum, and in the elderly (10 cases) atrophy of the corpus was more frequent than in the controls. All three types of chronic atrophic gastritis occurred in the disease. The decreased gastric acid secretion was characteristic of types A and AB gastritis, but the hypergastrinaemia only of type A. It was verified that chronic duodenitis and jejunitis occur in the disease. The pancreatic lesions were mild. Renal involvement was detected in 15 patients, vascular symptoms in 22 and lower-airway changes in 21. The variety of the different symptoms proved that primary Sjögren's syndrome can involve many organs.

Types of atrophic gastritis in patients with primary Sjögren's syndrome.

Histological examination of the gastric mucosa was performed in 44 patients with primary Sjögren's syndrome with extraglandular symptoms (mean age 51.9, range 22-76). Biopsy specimens were taken from each of three separate regions: the antrum, the corpus, and the transitional zone between the antrum and the corpus. The incidence of chronic atrophic gastritis was considerably higher in patients with Sjögren's syndrome than in the controls. In the young patients with Sjögren's syndrome atrophic lesions were more common both in the antrum and in the corpus than in the control group. In middle aged patients, however, only the antrum, and in the elderly only the corpus, was much more commonly affected than in the controls. All three types of chronic atrophic gastritis occurred in patients with Sjögren's syndrome. Decreased gastric acid secretion was associated mainly with atrophic gastritis of types A and AB, whereas hypergastrinaemia occurred almost exclusively in gastritis of type A.