Functional connectivity studies of patients with auditory verbal hallucinations

Functional connectivity (FC) studies of brain mechanisms leading to auditory verbal hallucinations (AVHs) utilizing functional magnetic resonance imaging (fMRI) data are reviewed. Initial FC studies utilized fMRI data collected during performance of various tasks, which suggested frontotemporal disconnection and/or source-monitoring disturbances. Later FC studies have utilized resting (no-task) fMRI data. These studies have produced a mixed picture of disconnection and hyperconnectivity involving different pathways associated with AVHs. Results of our most recent FC study of AVHs are reviewed in detail. This study suggests that the core mechanism producing AVHs involves not a single pathway, but a more complex functional loop. Components of this loop include Wernicke's area and its right homologue, the left inferior frontal cortex, and the putamen. It is noteworthy that the putamen appears to play a critical role in the generation of spontaneous language, and in determining whether auditory stimuli are registered consciously as percepts. Excessive functional coordination linking this region with the Wernicke's seed region in patients with schizophrenia could, therefore, generate an overabundance of potentially conscious language representations. In our model, intact FC in the other two legs of corticostriatal loop (Wernicke's with left IFG, and left IFG with putamen) appeared to allow hyperconnectivity linking the putamen and Wernicke's area (common to schizophrenia overall) to be expressed as conscious hallucinations of speech. Recommendations for future studies are discussed, including inclusion of multiple methodologies applied to the same subjects in order to compare and contrast different mechanistic hypotheses, utilizing EEG to better parse time-course of neural synchronization leading to AVHs, and ascertaining experiential subtypes of AVHs that may reflect distinct mechanisms

Two-photon imaging of cancer cell extravasation in live mice

Abstract MDA-MB-231 breast cancer cells were engineered to express cytoplasmic paxillin-GFP and nuclear H2B-mCherry. In order to image extravasation, the cancer cells were injected in the blood stream of nude mice. Using 2-photon excitation microscopy we can simultaneously excite the two probes and also visualize the autofluorescence of tissues. A skin flap was opened to visualize blood vessels and recognize the position of the cancer cells. Two-photon imaging showed that after an initial phase in which the cells are non-adherent, some cells spread on the internal surface of the capillaries. Days later some cells started to appear on the external side of the capillary. The extravasated cells extend very long protrusions into the tissue. The goal was to determine if at the end of the long protrusion, if it is possible to observe the formation of focal adhesions by imaging paxillin-GFP. Preliminary results show that when cells start to adhere to the blood vessel wall they form focal adhesions as determined by the characteristic elongated features observed in the paxillin-GFP channel. New approaches will allow the tracking of the tip of the protrusion to determine if focal adhesions are forming there as the cells extravasate. This is important in establishing the mechanism of cell extravasation and migration in tissues. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1412. doi:10.1158/1538-7445.AM2011-141

The Benefits of the SBI Program: Perceptions of Former Students

This study focuses on an evaluation of former students' perceptions of the skills gained when serving as a consultant on an SBI case.  The SBI course was compared to the capstone (Policy) course in an effort to determine the effectiveness of  the SBI course in enhancing specific skills in the students.By comparison, students found the Policy course to be more effective in developing analytical skills and to be more useful in their careers than the SBI course. On the other hand, the SBI course was perceived to be more effective in developing  interpersonal skills and  operational skills than the Policy course. The SBI course was found to be effective in developing analytical skills, operational skills, and interpersonal skills. Students also recommended the SBI course for other business students and found the course to be useful to them in their careers.

The Relation between Substance Use and Medication Adherence among HIV Positive Substance Users in Residential Treatment

Poor medication adherence is problematic among HIV positive, low-income African-American substance users. Substance use has been shown to be associated with poor medication adherence, though we do not know the mechanism that underlies this relationship. Lack of positive environmental rewards and the propensity to discount delayed rewards may be possible mechanisms to explain this relationship. Using baseline data from a randomized controlled trial, we examined the relationships between substance use and medication adherence, testing both environmental rewards and delay discounting as independent mediators. There was a main effect of substance use on adherence, such that high frequency of substance use predicted poor adherence. There was also a main effect of environmental rewards on adherence, such that a lack of environmental reinforcement predicted poor adherence. This study shed light on the processes that contribute to low adherence, namely substance use and lack of environmental contingencies, and suggests important targets for intervention

Enzymatic treatment of organic micropollutants in municipal wastewater: treatment conditions and reaction kinetics

Organic micropollutants enter natural waters via treated municipal wastewater discharges, threatening aquatic ecosystems and exposing humans to trace levels of these diverse chemicals through downstream drinking water supplies. Both of these concerns would be addressed simultaneously if micropollutants, which are often recalcitrant to conventional treatment processes, were removed in municipal wastewater treatment plants. Thus, the ultimate goal of this research was to advance the development of a sustainable and cost-effective enzymatic treatment process that oxidizes organic micropollutants in municipal wastewater. The enzymatic treatment process studied, laccase-catalyzed oxidation, involves the oxidation of mediator compounds by the enzyme laccase, generating mediator free radicals that can oxidize target micropollutants. The influences of key treatment conditions (pH, enzyme activity, mediator concentration, wastewater organic content) on the efficacy of the treatment process were evaluated, and the reaction kinetics of enzymatic treatment were investigated. The results demonstrated that enzymatic treatment can transform environmentally relevant concentrations of two representative micropollutants, oxybenzone and sulfamethoxazole, in a primary effluent wastewater matrix under realistic treatment conditions. Experiments with a set of structurally related chlorophenolic target compounds revealed several impacts of target compound structure on the kinetics and mechanisms of the laccase-mediator-target compound reactions. The electronic properties of the target compounds, their acid-base speciation, and steric hindrance to coupling reactions by substitution of the aromatic ring were found to influence their relative reactivities and reaction mechanisms with the free radicals generated by the laccase-mediator system. A kinetic model of the reactions between the enzyme laccase, the mediator acetosyringone, and the chlorophenolic target compounds was developed and fit the experimental data quite well despite the complexity and non-linearity of the system. This model indicated that the rate limiting step was the oxidation of the mediator by the enzyme. The relative rate constants for the reactions of the resulting mediator radical represent the distribution of the radicals among several possible reaction pathways. Although still in its early stages of development, the results of this research indicate that enzymatic treatment could one day be implemented in wastewater treatment plants for the mitigation of micropollutant release into the environment.Civil, Architectural, and Environmental Engineerin