Perforin-dependent neurologic injury in a viral model of multiple sclerosis

In this study we demonstrate perforin-mediated cytotoxic effector function is necessary for viral clearance and may directly contribute to the development of neurologic deficits after demyelination in the Theiler's murine encephalomyelitis virus (TMEV) model of multiple sclerosis. We previously demonstrated major histocompatability complex (MHC) class I-deficient (beta2m-deficient) mice with an otherwise resistant genotype develop severe demyelination with minimal neurologic disease when chronically infected with TMEV. These studies implicate CD8(+) T cells as the pathogenic cell in the induction of neurologic disease after demyelination. To determine which effector mechanisms of CD8(+) T cells, granule exocytosis or Fas ligand expression, play a role in the development of demyelination and clinical disease, we infected perforin-deficient, lpr (Fas mutation), and gld (Fas ligand mutation) mice with TMEV. Perforin-deficient mice showed viral persistence in the CNS, chronic brain pathology, and demyelination in the spinal cord white matter. Perforin-deficient mice demonstrated severely impaired MHC class I-restricted cytotoxicity against viral epitopes, but normal MHC class II-restricted delayed-type hypersensitivity responses to virus antigen. Despite demyelination, virus-infected perforin-deficient mice showed only minimal neurologic deficits as indicated by clinical disease score, activity monitoring, and footprint analysis. Perforin- and MHC class II-deficient mice (with functional CD8(+) T cells and perforin molecules and an H-2(b) haplotype) had comparable demyelination and genotype, however, only the latter showed severe clinical disease. Gld and lpr mice demonstrated normal TMEV-specific cytotoxicity and maintained resistance to TMEV-induced demyelinating disease. These studies implicate perforin release by CD8(+) T cells as a potential mechanism by which neurologic deficits are induced after demyelination.     

Comparing risk-adjustment methods for provider profiling

Risk-adjustment and provider profiling have become common terms as the medical profession attempts to measure quality and assess value in health care. One of the areas of care most thoroughly developed in this regard is quality assessment for coronary artery bypass grafting (CABG). Because in-hospital mortality following CABG has been studied extensively, risk-adjustment mechanisms are already being used in this area for provider profiling. This study compares eight different risk-adjustment methods as applied to a CABG surgery population of 28 providers. Five of the methods use an external risk-adjustment algorithm developed in an independent population, while the other three rely on an internally developed logistic model. The purposes of this study are to: (i) create a common metric by which to display the results of these various risk-adjustment methodologies with regard to dichotomous outcomes such as in-hospital mortality, and (ii) to compare how these risk-adjustment methods quantify the 'outlier' standing of providers. Section 2 describes the data, the external and internal risk-adjustment algorithms, and eight approaches to provider profiling. Section 3 then demonstrates the results of applying these methods on a data set specifically collected for quality improvement.     

Thyroid reoperations: indications and risks

Thyroid reoperations can be technically difficult and associated with an increased risk of complications. To determine the indications for reoperations and the risk of postoperative complications with these procedures, records of 362 patients undergoing thyroidectomy by a single surgeon (R.A.P.) were reviewed. Thirty-two patients had a reoperation. The group consists of 21 women and 11 men with an average age of 55 years (range, 31-79). Twenty-four patients had 1 prior operation, and 8 patients had 2 or more. We performed 4 of the initial operations, and 28 were done by surgeons at other centers. Fourteen reoperations were done for symptomatic multinodular goiter (MNG), and 5 because of a change in the histologic diagnosis from benign to cancerous. The remainder were for further treatment of malignancy. The most common operation was completion thyroidectomy (31). In 3 patients, either unilateral or bilateral modified radical neck exploration was performed. One patient required median sternotomy. One subtotal thyroidectomy was also performed. Recurrent laryngeal nerve injury occurred in 2 patients. It resolved in 1 patient but was permanent in another, who had 3 operations for MNG. One of the 2 patients with preoperative unilateral vocal cord paralysis had return of function after removal of a substernal goiter. The other had a permanent nerve injury from the original surgery. Three patients had postoperative hypocalcemia (calcium <8.0 mg/dL). This resolved in all patients within 1 to 6 months. One patient who had a third operation for MNG had postoperative hemorrhage necessitating tracheostomy for airway control. Another patient developed a seroma that resolved within 2 months. We conclude that reoperations are indicated for both benign and malignant thyroid disease. Because they carry a higher risk of complications, every effort should be made to avoid them by performing definitive initial treatment.     

Home environment and cognitive development in the first 3 years of life: A collaborative study involving six sites and three ethnic groups in North America.

Attempted to examine the generalizability of environment/development relationships among 3 ethnic groups across the first 3 years of life. Social status did not show a consistent relationship to either quality of home environment or children's developmental status across the various groups. Results indicated a fairly consistent relationship between HOME scores and children's developmental status, although there were some ethnic and social status differences in the relationship. Measures of specific aspects of the child's home environment, such as parental responsivity and availability of stimulating play materials, were more strongly related to child developmental status than global measures of environmental quality such as SES. When the child's developmental status and early home environment were both very low, the likelihood of poor developmental outcomes was markedly increased compared with cases when only one was low. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Some social mechanics of group decision making: The distribution of opinion, polling sequence, and implications for consensus.

The 1st study extrapolated earlier findings (J. H. Davis et al; see record 1989-15329-001) that the critical 4th voter in 6-person mock juries evenly divided between guilty- and not-guilty-inclined jurors (3,3) were significantly influenced by the preceding sequence (guilty or not-guilty faction voting first) and timing of a straw poll. Results implied that both procedural variables would have an effect on jury verdict distributions, but their magnitude was surprisingly low, especially for sequence. Exp 2 focused only on sequential voting in (4,2) groups in which sequential voting by majority-minority factions first was again observed to influence critical individuals, although the effect was sharply mediated by the "leniency bias." The additional empirical parameter estimates permitted a more comprehensive exploration of probable verdict consequences. Results showed that group-level decisions, under the particular conditions studied, remained counterintuitively robust against significant social influence pressures observed at the individual level, and familiar from numerous studies of conformity and minority influence. Discussion emphasized conceptual hazards associated with inferring group-level actions from individual member behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

An architecture and protocol for communications satellite constellations regarded as multi-agent systems

This paper presents an architecture for satellites regarded as intercommunicating agents. The architecture is based upon a postmodern paradigm of artificial intelligence in which represented knowledge is regarded as text, inference procedures are regarded as social discourse and decision-making conventions, and the semantics of representations is grounded in the situated behaviour and activity of agents. A particular protocol is described for agent participation in distributed search and retrieval operations conducted as joint activities.     

A female advantage in cognitive recovery from early cerebral insult.

Gender differences in cognitive outcome were examined in children born prematurely who had incurred early cerebral lesions and in a high-risk comparison group. The boys and girls, who had suffered perinatal intracranial hemorrhage (the most common neurological insult in the preterm infant) were similar in their antenatal, perinatal, and postnatal course, as well as in their sociofamilial attributes. After statistical adjustment to account for the extent of the insult, a significant gender difference in cognitive recovery was observed in the lesion group. Girls outperformed boys by about half a standard deviation on standardized intelligence tests. No gender differences were observed in the comparison group. The implications of the results for theories and empirical findings on gender differences in vulnerability to deviation from normal development are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Differential effects of clozapine and haloperidol on dopamine receptor mRNA expression in rat striatum and cortex

The regulation of the dopamine (DA) receptors is of considerable interest, in part because treatment with antipsychotic drugs is known to upregulate striatal D2-like receptors. While previous studies have focused on the regulation of striatal DA receptors, less is known about the pharmacological regulation of cortical DA receptors. The purpose of this study was to examine the regulation of DA mRNA receptor expression in the cortex compared to the striatum following treatment with antipsychotic agents. Adult male Sprague-Dawley rats were injected daily with haloperidol (2 mg/kg/day), clozapine (20 mg/kg/day) or a control vehicle for a period of 14 days. Following treatment, brains were subjected to in situ hybridization for the mRNAs encoding the five dopamine receptors; only D1, D2, and D3 receptor mRNAs were detected in these regions. Haloperidol tended to either modestly upregulate or have no effect on dopamine receptor mRNAs detected in striatal structures, while clozapine generally downregulated these mRNAs. On the other hand, in the cortex, both drugs had striking effects on D1 and D2 mRNA levels. Cortical D1 mRNA was upregulated by haloperidol, but this effect was primarily restricted to cingulate cortex; clozapine also upregulated D1 mRNA, but primarily in parietal regions. Haloperidol downregulated D2 mRNA in the majority of cortical regions, but most dramatically in frontal and cingulate regions; clozapine typically upregulated this mRNA, but primarily in regions other than frontal and cingulate cortex. These results indicate that clozapine and haloperidol each have regionally-specific effects, and differentially regulate dopamine receptor mRNA expression in striatal and cortical regions of the rat brain.     

Exposure to violent media: The effects of songs with violent lyrics on aggressive thoughts and feelings.

Five experiments examined effects of songs with violent lyrics on aggressive thoughts and hostile feelings. Experiments 1, 3, 4 and 5 demonstrated that college students who heard a violent song felt more hostile than those who heard a similar but nonviolent song. Experiments 2-5 demonstrated a similar increase in aggressive thoughts. These effects replicated across songs and song types (e.g., rock, humorous, nonhumorous). Experiments 3-5 also demonstrated that trait hostility was positively related to state hostility but did not moderate the song lyric effects. Discussion centers on the potential role of lyric content on aggression in short-term settings, relation to catharsis and other media violence domains, development of aggressive personality, differences between long-term and short-term effects, and possible mitigating factors. (PsycINFO Database Record (c) 2010 APA, all rights reserved)