On stress intensities induced by direct resistance heating

The temperature field and mode I stress intensity caused by resistance heating are calculated for a model problem. The results indicate that, for a constant far-field electric current, the stress intensity is proportional to the crack length to the power 5/2. Consequently, the effect of localized heating becomes especially important as the crack length increases and may, if ignored, cause significant errors during the more severe thermal fatigue tests that utilize direct resistance heating.

---

Résumé On calcule pour un problème de modélisation le champ de température et l'intensité de contrainte de Mode I provoqué par un chauffage par résistance. Les résultats indiquent que, pour un courant électrique constant appliqué, l'intensité de contraintes est proportionnelle à la longueur d'une fissure à la puissance 5/2.En conséquence, l'effet d'un chauffage local devient spécialement important lorsqu'on augmente la longueur de fissure, et peut, s'il est ignoré, induire des erreurs graves au cours d'essais de fatigue thermique de sévérité accrue qui recourent au chauffage direct par effect Joule.

     

A trinucleotide deletion in the transthyretin gene (delta V 122) in a kindred with familial amyloidotic polyneuropathy

A 63-year-old white man of Ecuadorian origin had a subarachnoid hemorrhage at age 57 followed by numbness and paresthesia in his lower extremities. He subsequently developed sexual impotence, alternating constipation and diarrhea, urinary frequency, and difficulty in walking. Rectal biopsy revealed amyloid deposits immunohistochemically reactive with antitransthyretin antisera. Direct DNA sequencing of the transthyretin gene of the patient showed a trinucleotide deletion in exon 4. This deletion resulted in the loss of one of two valines at position 121 or 122. DNA analysis on 11 family members at risk revealed four mutant gene carriers. Plasma transthyretin levels in the mutant gene carriers measured by nephelometry were very low. Peptide sequence analysis revealed that most of plasma transthyretin was normal with only a small amount of variant protein. This is the first report of a DNA deletion in the transthyretin gene. We speculate that the loss of valine in the carboxyl terminal region of the transthyretin monomer alters stability of the tetrameric protein, which leads to rapid clearance from the plasma and amyloid deposition in the tissue.     

Apolipoprotein B and AI distributions in the United States, 1988-1991: results of the National Health and Nutrition Examination Survey III (NHANES III)

Serum apolipoproteins (apo) B and AI were measured in a probability sample of the noninstitutionalized US civilian population, ages > or = 4 years, which included non-Hispanic whites, non-Hispanic blacks, and Mexican-Americans. Apo B concentrations were the same in males and females, lower in black males than in other males, low in childhood (approximately 0.80 g/L) and increasing to approximately 1.2 g/L in adults, and higher in younger women on hormones. Apo AI was higher in females than males, higher in blacks than in others, remained constant from childhood to adulthood (approximately 1.35 g/L) in males, but increased with age (approximately 1.30 g/L to approximately 1.55 g/L) in females, and was higher in women taking hormones. These are the first national probability estimates of apo B and apo AI in the US and are referable to the WHO-IFCC First International Reference Materials for apo AI and B.     

Meta-analysis for the evaluation of potential surrogate markers

We describe a meta-analysis approach for the evaluation of a potential surrogate marker. Surrogate markers are useful in helping to identify therapeutic mechanisms of action and disease pathogenesis, and for selecting therapies to take forward from phase II to phase III clinical trials. They have also become increasingly important for regulatory purposes by providing a basis for preliminary approval of drugs pending clinical outcome studies. Methodology for evaluating surrogate markers has focused on determining the difference in the effects of two treatments on clinical outcome in an individual clinical trial, and then estimating the proportion of this difference explained by the treatment's effects on the potential marker. Studies are, however, frequently underpowered or cease before they accumulate sufficient evidence to draw strong conclusions about the value of a potential surrogate marker using this approach, and there are also some technical difficulties with the approach. Consideration of the association between the difference in treatment effects on the clinical outcome and the difference in treatment effects on the potential marker over a range of trials provides an alternative means to evaluate a potential marker. We describe a meta-analysis approach using Bayesian methods to model this association. Importantly, this approach enables one to obtain prediction intervals for the true difference in clinical outcome for a given estimated treatment difference in the effect on the potential marker. We illustrate the methodology by applying it to results from studies of the AIDS Clinical Trials Group to assess the value of CD4 T-lymphocyte cell count as a potential surrogate marker for the treatment effects on the development of AIDS or death.