Deformation mechanisms leading to auxetic behaviour in the α-cristobalite and α-quartz structures of both silica and germania.

Analytical expressions have been developed in which the elastic behaviour of the α-quartz and α-cristobalite molecular tetrahedral frameworks of both silica and germania are modelled by rotation, or dilation or concurrent rotation and dilation of the tetrahedra. Rotation and dilation of the tetrahedra both produce negative Poisson's ratios (auxetic behaviour), whereas both positive and negative values are possible when these mechanisms act concurrently. Concurrent rotation and dilation of the tetrahedra reproduces with remarkable accuracy both the positive and negative ν(31) Poisson's ratios observed for silica α-quartz and α-cristobalite, respectively, when loaded in the x(3) direction. A parametric fit of the concurrent model to the germania α-quartz experimental ν(31) Poisson's ratio is used to predict ν(31) for germania α-cristobalite, for which no experimental value exists. This is predicted to be +0.007. Strain-dependent ν(31) trends, due to concurrent rotation and dilation in the silica structures, are in broad agreement with those predicted from pair-potential calculations, although significant differences do occur in the absolute values. With the model of concurrent dilation and rotation of the tetrahedra we predict that an alternative uniaxial stress (σ(3))-induced phase exists for both silica, α-quartz and α-cristobalite, and germania, α-cristobalite, having geometries in reasonable agreement with ß-quartz and idealized ß-cristobalite, respectively.

The criminalization of adults with mental illness (Part 1).

In Part 1 of "The Criminalization of Adults with Mental Illness," we have identified the major factors contributing to the criminalization of the mentally ill as being deinstitutionalization (and the related underfunded, under-coordinated recommendations of the Joint Commission on Mental Illness in 1961), the sometimes overly restrictive legal protections, and states' implementation of usually underfunded Medicaid managed care programs. Subsequent papers will describe and discuss Tennessee statistics relative to criminalization of the mentally ill (Part 2) and will introduce methods for preventing criminalization of mentally ill adults and the maintenance of mentally ill individuals who have committed minor crimes in their respective communities.

Mediating denials of pharmaceutical services: an alternative to traditional appeals.

The effectiveness of mediation as a primary tool to resolve pharmaceutical service denials by managed care is discussed. A three-month prospective randomized trial of 48 medical appeal cases involving prescription drugs was conducted by Tennessee's Department of Health. Patients whose prescription claims were denied by the state's Medicaid managed care program and whose appeals were deemed medically unnecessary by one of two independent reviewers were randomly assigned to either a standard procedure group or a mediation group. Appeals assigned to the standard procedure group were immediately referred for administrative hearing. In the mediation group, the independent reviewer assigned to the case contacted the patient's care provider, discussed the case, and recommended an alternative drug. The care provider either accepted the suggested compromise, concluding the appeals process, or declined the suggestion, allowing the appeal to go to hearing. Reviewers recorded the amount of time they spent on each appeal. The mediation did not substantially increase the time the reviewers spent on each case (mean +/- S.D. minutes, 15.83+/-7.89 mediation versus 12.26+/-6.96 standard procedure). The mean number of appealed drugs was also similar between groups (1.46+/-0.78 mediation versus 1.35+/-0.89 standard procedure). Only 21% of appealed cases went to hearings in the mediation group, while 80% did in the standard procedure group. The average cost to the state for employing mediation ($142.92+/-$186.77) was significantly lower than the average cost incurred by using standard procedures ($355.75+/-$175.43). Mediation is an effective and efficient tool for resolving patients' appeals of denied pharmaceutical services.

Cognitive and functional recovery at 6 and 12 months post-TBI.

Outcome studies examining recovery from traumatic brain injury (TBI) often fail to provide a clear understanding of the time course of cognitive, emotional, and behavioural recovery. The present study represents an effort to prospectively study individuals with TBI at fixed intervals, specifically 6 and 12 months post-injury with a window of +/- 1 month. Seventy-two individuals with new-onset TBI underwent neuropsychological evaluation and clinical interview at 6 and 12 months post-injury. Results revealed significant improvements in cognitive abilities, including memory, processing speed, language abilities, and constructional skills. There were significant gains in community integration and involvement in productive activities, but limitations in driving activities remained. Although individuals with mild-moderate TBI performed better than individuals with severe TBI, both groups demonstrated equivalent rates of recovery across domains. The results of this study provide important information regarding the time course of TBI recovery.

Decreased memory performance in healthy humans induced by stress-level cortisol treatment.

BACKGROUND: Glucocorticoids (GCs) can regulate hippocampal metabolism, physiologic functions, and memory. Despite evidence of memory decreases during pharmacological GC treatment, and correlations between memory and cortisol levels in certain disease conditions, it remains unclear whether exposure to the endogenous GC cortisol at levels seen during physical and psychological stress in humans can inhibit memory performance in otherwise healthy individuals. METHODS: Randomized, double-blind, placebo-controlled comparison of 2 fixed oral doses of cortisol (40 mg/d and 160 mg/d using split doses to approximate circadian rhythm) given for 4 days to matched groups of healthy subjects (n = 51). Lower-dose treatment approximated cortisol exposure during mild stress, whereas the higher dose approximated cortisol exposure during major stress. Cognitive testing and plasma sampling were done at baseline, after 1 and 4 days of treatment, and after a 6-day washout period, hypothesizing dose-dependent decreases in verbal declarative memory. RESULTS: Cortisol treatment at the higher dose produced reversible decreases in verbal declarative memory without effects on nonverbal memory, sustained or selective attention, or executive function. A significant interaction between time and treatment condition for paragraph recall was explained by treatment-induced differences in performance after 4 treatment days, with lower immediate and delayed recall performance during higher-dose cortisol treatment compared with lower-dose treatment and placebo. CONCLUSIONS: Several days of exposure to cortisol at doses and plasma concentrations associated with physical and psychological stress in humans can-similar to pharmacological GC treatment-reversibly decrease specific elements of memory performance in otherwise healthy individuals.

Immunization with soluble BDC 2.5 T cell receptor-immunoglobulin chimeric protein:antibody specificity and protection of nonobese diabetic mice against adoptive transfer of diabetes by maternal immunization.

The BDC 2.5 T cell clone is specific for pancreatic beta-cell antigen presented by I-Ag7, and greatly accelerates diabetes when injected into 10-21-d-old nonobese diabetic (NOD) mice. The BDC 2.5 T cell receptor (TCR) has been solubilized as a TCR-IgG1 chimeric protein. All NOD mice immunized against BDC 2.5 TCR-IgG1 produced antibodies recognizing TCR C alpha/C beta epitopes that were inaccessible on the T cell surface. 56% of the mice produced antibodies against the BDC 2.5 clonotype that specifically blocked antigen activation of BDC 2.5 cells. We have used the adoptive transfer model of diabetes to demonstrate that maternal immunization with soluble TCR protects young mice from diabetes induced by the BDC 2.5 T cell clone.

Memory improvement following induced hyperinsulinemia in Alzheimer's disease.

Dementia of the Alzheimer type (DAT) is accompanied by disruption in glucose regulation and utilization that may contribute to its characteristic memory impairment. Increasing glucose availability by raising plasma glucose improves memory in patients with DAT. Such memory improvement is associated with a secondary elevation in plasma insulin levels, raising the question of whether improvement is due to changes in insulin levels, independent of hyperglycemia. Distributions of insulin receptors in the hippocampus and insulin-mediated increases in glucose utilization in entorhinal cortex provide potential mechanisms for such improvement. We show that raising plasma insulin through intravenous infusion while keeping plasma glucose at a fasting baseline level produces striking memory enhancement for patients with DAT. Previous findings of hyperglycemic memory enhancement were also replicated. Patients with DAT also showed abnormal plasma levels of glucoregulatory hormones and metabolites at baseline and during metabolic manipulations. Our findings suggest that neuroendocrine factors play an important role in the pathophysiology of DAT.

Complementation of snf1, a mutation affecting global regulation of carbon metabolism in yeast, by a plant protein kinase cDNA.

A cDNA, cRKIN1, encoding a putative homologue of the yeast (Saccharomyces cerevisiae) SNF1-encoded protein-serine/threonine kinase, has been isolated from a library prepared from rye endosperm mRNA. Northern blot analysis demonstrated the presence of cRKIN1-related transcripts in developing endosperms but not in shoots, and Southern blot analysis showed the presence of a small gene family. SNF1 plays a central role in carbon catabolite repression in yeast and expression of the RKIN1 sequence in yeast snf1 mutants restored SNF1 function. This suggests that the RKIN1 protein has a role in the control of carbon metabolism in endosperms of rye.

Interstitial radiation therapeutic techniques at Mount Vernon Hospital.

Retrospective analysis of 56 cases of carcinoma on the lateral border of the anterior two thirds of the tongue treated at Mount Vernon Hospital using radium needle implant alone yielded 5-year actuarial survivals of 75.3 per cent in 25 T1N0 cases and 81.8 per cent in 25 T2N0 cases. Five-year actuarial local recurrence of 17.5 per cent was recorded in the T1 group and 35 per cent in the T2 group. Local recurrences were attributed to failure of the implant to encompass extensions of the tumour along the lateral border or into the musculature of the tongue. Five-year actuarial local recurrence of 66.2 per cent was recorded in 18 patients with carcinoma of the breast treated by radium needle implant alone; 4 of these 9 local recurrences occurred at some distance from the treated area and could not be classed as marginal recurrences. A preliminary investigation carried out in 1981 indicated that significant improvements in source distribution, particularly at poorly accessible sites, could be achieved using afterloading techniques. In addition the use of 192Ir as a source could result in improvements in staff protection.

Evidence for functional endothelial cell damage in early diabetic retinopathy.

Two aspects of endothelial cell function were examined in two matched groups of male insulin-dependent diabetics, six with background retinopathy and seven without retinopathy. Leakage of fluorescein from the retinal capillaries was estimated by vitreous fluorophotometry. In addition, factors VIII/von Willebrand (vWF) and VIII-related antigen (VIII-RAG), which are synthesized by the endothelial cells, were measured, together with VIII-antihaemophilic factor (VIII-AHF). The patients without retinopathy had normal leakage of fluorescein in the macula (mean +/- SEM: 1.10 +/- 0.10 g X 10(-8)/ml) and the posterior vitreous (0.45 +/- 0.11 g X 10(-8)/ml), and normal circulating levels of vWF (123% of a normal reference plasma +/- 18%), VIII-RAG (137 +/- 14%) and VIII-AHF (112 +/- 18%). In contrast, the patients with background retinopathy showed higher leakage of fluorescein in the macula (6.34 +/- 1.74 g X 10(-8)/ml; p less than 0.01), and the posterior vitreous (3.09 +/- 0.94 g X 10(-8)/ml; p less than 0.02), as well as increased levels of vWF (177 +/- 16%; p less than 0.05). There was a trend towards increased VIII-RAG (195 +/- 24%; p less than 0.1), but not VIII-AHF (126 +/- 13%). Alterations of endothelial cell function thus accompany the development of retinopathy. It cannot be said from the present study whether these alterations also precede the appearance of retinopathy.

Vitreous fluorophotometry.

Vitreous fluorophotometry is as yet in its early phase of development, where probably many of the readings obtained represent artefacts. It is, however, a potentially exciting and useful clinical research tool which may indicate early changes in blood-retinal barrier function and which enables studies of fluid dynamics in the eye. Before it can be used extensively, more work on the development of reliable, uniformly acceptable equipment is necessary.