The "first generation" of endovascular stent-grafts for patients with aneurysms of the descending thoracic aorta

OBJECTIVE: Our goal was to determine whether endovascular stent-grafting is feasible and effective for patients with aneurysms of the descending thoracic aorta. METHODS: Starting in July 1992, we conducted a prospective, uncontrolled clinical trial in 103 patients (mean age 69 years [range 34-89 years]) who underwent endovascular treatment of aneurysms of the descending thoracic aorta using a custom-fabricated, self-expanding stent-graft device. Follow-up was 100% complete and averaged 22 months. Sixty-two patients (60%) were judged not to be reasonable candidates for a conventional "open" surgical procedure. RESULTS: Complete thrombosis of the aneurysm was ultimately achieved in 86 (83%) patients. The early mortality rate was 9% +/- 3% (+/- 70% CL). Multivariable analysis revealed that myocardial infarction or stroke was linked with a higher likelihood of early death (P = .001). Early serious complications included paraplegia in 3% +/- 2% and stroke in 7% +/- 3%. Actuarial survival estimates at 1 year and 2 years were 81% +/- 4% and 73% +/- 5% (+/- 1 SE), respectively; being judged not to be a surgical candidate portended a higher probability of death (P = .003). According to the intent-to-treat principle, "treatment failure" (including all late sudden unexplained deaths) occurred in 38 patients; 53% +/- 10% of patients were free from treatment failure at 3.7 years. Stent-graft related complications occurred commonly and were linked with several anatomic, technical, and patient-related risk factors. CONCLUSIONS: This 5-year clinical trial involving use of a "first generation" device indicates that endovascular stent-grafting of descending thoracic aortic aneurysms is feasible with acceptable medium-term results. More refined, commercially developed devices available today offer less traumatic and more precise stent-graft deployment; these major technical advantages, coupled with important lessons we have learned over time and better patient selection, should be associated with more salutary clinical results in the future.     

Tennessee's failed managed care program for mental health and substance abuse services

In July 1996, Tennessee initiated a managed mental health and substance abuse program called TennCare Partners. This publicly funded "carve-out" experiment started chaotically and soon deteriorated into a crisis. Many patients did not receive care or lost continuity of care, and the traditional "safety net" mental health system nearly disintegrated. This qualitative case study sought to ascertain the impact of the TennCare Partners program. It points out that the program's difficulties stemmed directly from a flawed design that spread funds previously earmarked for severely mentally ill patients across the entire Medicaid population. States contemplating similar reforms should strive to protect vulnerable patients by risk-adjusting capitation payments and by focusing resources on care for severely mentally ill persons. States should also minimize program complexity and ensure the accountability of managed care networks for their patients' behavioral health care needs.     

Induction of apoptosis in cardiac myocytes by an A3 adenosine receptor agonist

The effects of the selective adenosine (ADO) A3 receptor agonist IB-MECA (N6-(3-iodobenzyl)adenosine-5'-N-methylcarboxamide) on cultured newborn rat cardiomyocytes were examined in comparison with ADO, the ADO A1 receptor-selective agonist R-PIA (N6-R-phenylisopropyladenosine), or the ADO A3 selective antagonist MRS 1191 (3-ethyl-5-benzyl-2-methyl-6-phenyl-4-phenylethynyl-1, 4-(+/-)-dihydropyridine-3,5 dicarboxylate), using digital image analysis of Feulgen-stained nuclei. At high concentration, IB-MECA (>/=10 microM ) and ADO (200 microM) induced apoptosis; however, R-PIA or MRS 1191 did not have any detectable effects on cardiac cells. In addition, DNA breaks in cardiomyocytes undergoing apoptosis following treatment by IB-MECA were identified in situ using the nick end labeling of DNA ("TUNEL"-like) assay. In the presence of >/=10 microM IB-MECA, disorder in the contraction waves appeared, and a decrease in the frequency of beats was observed. Analysis with light microscopy revealed that the number of contracting cells decreased in a concentration-dependent manner. The A3 receptor agonist IB-MECA caused an increase in intracellular free calcium concentration ([Ca2+]i). The drug produced a rapid rise followed by a sustained increase in [Ca2+]i, which lasted for 40-60 s. Finally, cessation of beating and Ca2+ transients were observed. Full recovery of contractile activity and rhythmical Ca2+ transients were observed 15-20 min after IB-MECA treatment. The induction of apoptosis in the cardiocytes by IB-MECA led to the appearance of features of apoptotic nuclei: the onset of condensation, compacting, and margination of nuclear chromatin. These effects were accompanied by the disintegration of the structural framework of the nucleus and nuclear breakdown. The results suggest that activation of the A3 adenosine receptor may participate in the process of apoptosis in cardiomyocytes.     

Human immunodeficiency virus infection, Part II

The acceptance of highly active antiretroviral therapy (HAART) among patients and health care providers has had a dramatic impact on the epidemiology and clinical characteristics of many opportunistic infections associated with human immunodeficiency virus (HIV). Previously intractable opportunistic infections and syndromes are now far less common. In addition, effective antibiotic prophylactic therapies have had a profound impact on the risk of patients developing particular infections and on the incidence of these infections overall. Most notable among these are Pneumocystis carinii, disseminated Mycobacterium avium complex, tuberculosis, and toxoplasmosis. Nevertheless, infections continue to cause significant morbidity and mortality among patients who are infected with HIV. The role of HAART in many clinical situations is unquestioned. Compelling data from clinical trials support the use of these therapies during pregnancy to prevent perinatal transmission of HIV. HAART is also recommended for health care workers who have had a "significant" exposure to the blood of an HIV-infected patient. Both of these situations are discussed in detail in this article. In addition, although more controversial, increasing evidence supports the use of HAART during the acute HIV seroconversion syndrome. An "immune reconstitution syndrome" has been newly described for patients in the early phases of treatment with HAART who develop tuberculosis, M avium complex, and cytomegalovirus disease. Accumulating data support the use of hydroxyurea, an agent with a long history in the field of myeloproliferative disorders, for the treatment of HIV. Newer agents, particularly abacavir and adefovir dipivoxil, are available through expanded access protocols, and their roles are being defined and clarified.     

Pain threshold values during periodontal probing: assessment of maxillary incisor and molar sites

Probing pain threshold (PPT) assessments were conducted in the facial and oral sulci of maxillary central incisors and first molars of 10 periodontally healthy adults. All subjects were systemically healthy, free of pain, and reported no current medication usage. A computer-linked electronic probe, modified to deliver steadily increasing forces up to 200 grams, was used to collect the data. The system contained a subject operated "off-switch" which, upon activation, signaled the computer to record the subject's PPT. Assessments of each subject's PPTs were conducted on 3 separate occasions at 7-day intervals. Results indicated that the facial sulci of the incisors were the most pain sensitive. They displayed a mean PPT of 50.9 +/- 26.6 grams. The oral sulci of the incisors exhibited a mean PPT of 76.5 +/- 45.2 grams. Facial and oral sulci of the molars evidenced mean PPT values of 102.6 +/- 52.1 grams and 113.5 +/- 51.3 grams, respectively. These data suggest that sulci associated with incisor teeth are nearly twice as pain sensitive as sulci associated with molar teeth. In addition, facial sulci are significantly more pain sensitive than oral sulci. Data did not indicate a visit effect nor a side-of-mouth effect on PPT values.     

Dynamic digital photorefractive memory for optoelectronic neural network learning modules

Neural network modules based on page-oriented dynamic digital photorefractive memory are described. The modules can implement two different interconnection organizations, fan-out and fan-in, depending on their target network applications. Neural network learning is realized by the real-time memory update of dynamic digital photorefractive memory. Physical separation of subvolumes in the page-oriented photorefractive memory architecture contributes to the low cross talk and high diffraction efficiency of the stored interconnection weights. Digitally encoded interconnection weights ensure high accuracy, providing superior neural network system scalability. Module scalability and feedforward throughput have been investigated based on photorefractive memory geometry and the photodetector power requirements. The following four approaches to extend module scalability are discussed: partial optical summation, semiparallel feedforward operation, time partitioning, and interconnection matrix partitioning. Learning capabilities of the system are investigated in terms of required interconnection primitives for implementing learning processes and three memory-update schemes. The experimental results of Perceptron learning network implementation with 900 input neurons with digital 6-bit accuracy are reported.     

Primate vocalizations during social separation and aggression: effects of alcohol and benzodiazepines

The most common group of squirrel monkey vocalizations, peeps, are emitted during different social situations including social separation, affiliative interactions, feeding and aggressive confrontations. The present experiments investigated whether peeps and other vocalizations emitted during different social contexts are pharmacologically altered in a similar manner. First, vocalizations were characterized during (1) social separation in juveniles, and (2) "resident-intruder" aggressive confrontations between dominant monkeys from different social groups. Then, the effects of alcohol (EtOH) and the benzodiazepine chlordiazepoxide (CDP) on vocalizations during social separation and during aggression were examined. Isolated juveniles emitted only one type of call, the isolation peep. Resident monkeys primarily emitted peeps, but also emitted cackles, chucks, noisy calls and pulsed calls. Aggressive peeps were similar in structure and frequency (kHz) to isolation peeps, but were shorter in duration. At the same doses, both CDP (0.3-3 mg/kg) and EtOH (0.1-1.0 g/kg) reduced explosive motor behaviors and isolation peeps in juvenile monkeys during social separation and increased threat displays and aggression peeps in resident monkeys during confrontations with an intruder monkey from a different social group. Thus, similarly structured vocalizations that were emitted during social separation and aggression were very sensitive to EtOH and CDP, but the social context determined the direction and magnitude of effects.     

Animal and plant cell lysates share a conserved chaperone system that assembles the glucocorticoid receptor into a functional heterocomplex with hsp90

The hormone-binding domain of the glucocorticoid receptor must be bound to heat shock protein (hsp) 90 for it to have a high-affinity steroid-binding conformation. Cell-free assembly of a glucocorticoid receptor-hsp90 heterocomplex is brought about in reticulocyte lysate by a preformed protein-folding complex containing hsp90, hsp70, and other proteins [Hutchison, K.A., Dittmar, K. D., & Pratt, W.B. (1994) J. Biol. Chem. 269, 27894-27899]. In this "foldosome" system, hsp70 is required for assembly of the receptor-hsp90 complex and concomitant activation of steroid-binding activity [Hutchison, K.A., Dittmar, K.D., Czar, M.J., & Pratt, W.B. (1994) J. Biol. Chem. 269, 22157-22161]. All previous experiments involving cell-free assembly of both receptor-hsp90 and protein kinase-hsp90 heterocomplexes have been carried out with the protein-folding system in rabbit reticulocyte lysate. In this work, we show that concentrated lysates of receptor-free mouse (L cells) and insect (Sf9) cells and also a plant (wheat germ) lysate fold the immunopurified glucocorticoid receptor into a functional (i.e., steroid binding) heterocomplex with hsp90. Receptor heterocomplex formation in animal lysates and in the plant lysate are not identical in that the dynamics of complex assembly are different, but both systems produce a functional complex that binds steroid. Also, in contrast to animal and insect complexes, receptor-plant hsp90 complexes are not stabilized by molybdate. When added to the other lysate, purified plant and animal hsp90s show partial complementarity, in that a receptor-hsp90 complex is formed but the receptor is not converted to the steroid-binding conformation. When added to rabbit reticulocyte lysate that has been depleted of endogenous hsp70, purified wheat germ and mouse hsp70's are equally active in promoting both assembly of receptor-hsp90 heterocomplexes and conversion of receptor to the steroid-binding conformation. Thus, hsp70 from the plant kingdom has conserved the ability to interact functionally with chaperone proteins of the animal kingdom to cooperate in protein folding as evidenced by formation of a functional receptor-hsp90 heterocomplex.     

Fast kernel conditional density estimation: A dual-tree Monte Carlo approach

We describe a fast, data-driven bandwidth selection procedure for kernel conditional density estimation (KCDE). Specifically, we give a Monte Carlo dual-tree algorithm for efficient, error-controlled approximation of a cross-validated likelihood objective. While exact evaluation of this objective has an unscalable O(n²) computational cost, our method is practical and shows speedup factors as high as 286,000 when applied to real multivariate datasets containing up to one million points. In absolute terms, computation times are reduced from months to minutes. This enables applications at much greater scale than previously possible. The core idea in our method is to first derive a standard deterministic dual-tree approximation, whose loose deterministic bounds we then replace with tight, probabilistic Monte Carlo bounds. The resulting Monte Carlo dual-tree algorithm exhibits strong error control and high speedup across a broad range of datasets several orders of magnitude greater in size than those reported in previous work. The cost of this high acceleration is the loss of the formal error guarantee of the deterministic dual-tree framework; however, our experiments show that error is still amply controlled by our Monte Carlo algorithm, and the many-order-of-magnitude speedups are worth this sacrifice in the large-data case, where cross-validated bandwidth selection for KCDE would otherwise be impractical.     

On properties not inherited by monoids from their Schützenberger groups

We give an example of a monoid with finitely many left and right ideals, all of whose Schützenberger groups are presentable by finite complete rewriting systems, and so each have finite derivation type, but such that the monoid itself does not have finite derivation type, and therefore does not admit a presentation by a finite complete rewriting system. The example also serves as a counterexample to several other natural questions regarding complete rewriting systems and finite derivation type. Specifically it allows us to construct two finitely generated monoids M and N with isometric Cayley graphs, where N has finite derivation type (respectively, admits a presentation by a finite complete rewriting system) but M does not. This contrasts with the case of finitely generated groups for which finite derivation type is known to be a quasi-isometry invariant. The same example is also used to show that neither of these two properties is preserved under finite Green index extensions.