Subcortical loops through the basal ganglia and the cerebellum form computationally powerful distributed processing modules (DPMs). This paper relates the computational features of a DPM's loop through the basal ganglia to experimental results for two kinds of natural action selection. First, functional imaging during a serial order recall task was used to study human brain activity during the selection of sequential actions from working memory. Second, microelectrode recordings from monkeys trained in a step-tracking task were used to study the natural selection of corrective submovements. Our DPM-based model assisted in the interpretation of puzzling data from both of these experiments. We come to posit that the many loops through the basal ganglia each regulate the embodiment of pattern formation in a given area of cerebral cortex. This operation serves to instantiate different kinds of action (or thought) mediated by different areas of cerebral cortex. We then use our findings to formulate a model of the aetiology of schizophrenia.

The recent increase in reports of drug-facilitated sexual assaults has caused alarm in the general public and prompted forensic toxicologists from across North America to address the toxicological issues surrounding this matter. The authors have developed recommendations and guidelines to inform law enforcement, medical, and scientific personnel of the requirements for performing successful toxicological examinations in cases of drug-facilitated rape.

We investigated the effects of acute starvation on mitogen-induced T-cell activation and Th1/Th2 cytokine responses in rheumatoid arthritis (RA) patients. Ten RA patients with active disease underwent a 7-day fast followed by a 2-week refeeding period. Immunological, hormonal, laboratory and clinical evaluations were carried out on days 0, 7 and 21. Using flow cytometry, mitogen-stimulated T-cell activation was assessed in fresh heparinised blood via analysis of CD69 expression. Production of Th1 (interferon-gamma) and Th2 (interleukin-4, IL-4) cytokines was also assessed by ELISA. The 7-day fast significantly decreased the erythrocyte sedimentation rate, C-reactive protein level, joint count, morning stiffness, body weight, CD4+ and CD8+ counts and CD69+ expression on mitogen stimulated CD4+ lymphocytes. A significant increase in mitogen-induced IL-4 production after fasting was found. The fast markedly reduced serum leptin and insulin-like growth factor-1 concentrations. No significant differences occurred in serum cortisol or prolactin before and after fasting. Decreases in CD4+ lymphocyte activation during fasting correlated with decreases in body weight. Our results suggest that the clinical and laboratory improvements in fasting RA patients may be attributed to decreased CD4+ T-cell activation and an increase in the number and/or function of IL-4-producing Th2 cells. Factors associated with loss of body weight during acute starvation appear to have an inhibitory effect on CD4+ lymphocyte activation.

An ecosystem-based approach to bivalve aquaculture management is a strategy for the integration of aquaculture within the wider ecosystem, including human aspects, in such a way that it promotes sustainable development, equity, and resilience of ecosystems. Given the linkage between social and ecological systems, marine regulators require an ecosystem-based decision framework that structures and integrates the relationships between these systems and facilitates communication of aquaculture-environment interactions and policy-related developments and decisions. The Drivers-Pressures-State Change-Impact-Response (DPSIR) management framework incorporates the connectivity between human and ecological issues and would permit available performance indicators to be identified and organized in a manner that facilitates different regulatory needs. Suitable performance indicators and modeling approaches, which are used to assess DPSIR framework components, are reviewed with a focus on the key environmental issues associated with bivalve farming. Indicator selection criteria are provided to facilitate constraining the number of indicators within the management framework. It is recommended that an ecosystem-based approach for bivalve aquaculture be based on a tiered indicator monitoring system that is structured on the principle that increased environmental risk requires increased monitoring effort. More than 1 threshold for each indicator would permit implementation of predetermined impact prevention and mitigation measures prior to reaching an unacceptable ecological state. We provide an example of a tiered monitoring program that would communicate knowledge to decision-makers on ecosystem State Change and Impact components of the DPSIR framework.KEY WORDS: Bivalve aquaculture management · Ecosystem-based approach · DPSIR framework · Indicators · Thresholds · Benthic effects · Pelagic effects · Social-ecological systems Resale or republication not permitted without written consent of the publisher

OBJECTIVETo study the effects of long-term oral benfotiamine supplementation on peripheral nerve function and soluble inflammatory markers in patients with type 1 diabetes.RESEARCH DESIGN AND METHODSThe study randomly assigned 67 patients with type 1 diabetes to receive 24-month benfotiamine (300 mg/day) or placebo supplementation. Peripheral nerve function and levels of soluble inflammatory variables were assessed at baseline and at 24 months.RESULTSFifty-nine patients completed the study. Marked increases in whole-blood concentrations of thiamine and thiamine diphosphate were found in the benfotiamine group (both P < 0.001 vs. placebo). However, no significant differences in changes in peripheral nerve function or soluble inflammatory biomarkers were observed between the groups.CONCLUSIONSOur findings suggest that high-dose benfotiamine (300 mg/day) supplementation over 24 months has no significant effects upon peripheral nerve function or soluble markers of inflammation in patients with type 1 diabetes.