Furosemide, a chloride cotransport inhibitor, reversibly blocked synchronized burst discharges in hippocampal slices without reducing the pyramidal cell response to single electrical stimuli. Images of the intrinsic optical signal acquired during these slice experiments indicated that furosemide coincidentally blocked changes in extracellular space. In urethane-anesthetized rats, systemically injected furosemide blocked kainic acid-induced electrical discharges recorded from cortex. These results suggest that (i) neuronal synchronization involved in epileptiform activity can be dissociated from synaptic excitability; (ii) nonsynaptic mechanisms, possibly associated with furosemide-sensitive cell volume regulation, may be critical for synchronization of neuronal activity; and (iii) agents that affect extracellular volume may have clinical utility as antiepileptic drugs.
In some neuro-developmental disorders, the combined effect of intellectual disability and atypicalities of social cognition may put individuals at increased vulnerability in their social environment. The neurodevelopmental disorders Williams syndrome, characterised by 'hypersociability', and autism spectrum disorders, characterised by 'social withdrawal', are at two extremes of atypical social functioning in humans. In this article, we use Williams syndrome and autism spectrum disorders as exemplars to demonstrate how atypicalities of social cognition may contribute to social vulnerability in these populations. The lives of individuals with both these disorders are marred by an increased risk of social isolation, bullying, unsteady relationships, employment difficulties and abuse. While different behavioural interventions have been tried to improve social functioning in these populations, there has been great variability in their success. Finally, we discuss different issues regarding social independence of these individuals; including employment, safety and decision making.
Abstract-The hazard assessment of pulp and paper effluents in the aquatic environment is a complex task. Hundreds of individual compounds in pulping effluents and site-specific differences in processes, effluent treatment, and receiving ecosystems hinder hazard assessment. As a result, it is difficult to relate environmental effects with specific contaminants. Conventional parameters such as organic and nutrient loadings, solids deposition, and color complicate efforts to define chemical toxicants by causing environmental impacts at community and population levels. Reproduction is the most sensitive, consistent, and relevant end point tested to date in the laboratory, in mesocosms and experimental streams, and in field situations near some pulping discharges. Despite the application of a wide range of within-organism measurements, only the induction of mixed-function oxidase activities has been associated with exposure to particular effluent compounds in field situations. No complete mechanism of toxic action has been demonstrated that connects contaminant exposure, within-organism responses, whole-organism effects, and effects at the population and the community levels. Hazard assessments of pulping effluents require multidisciplinary efforts that integrate chemical, toxicological, and biological data at several organizational levels. Tiered or stepwise assessments are recommended that first clarify what adverse effects have occurred and then attempt to identify the responsible contaminants.
Summary Life‐cycle assessment (LCA) is a technique for systematically analyzing a product from cradle‐to‐grave, that is, from resource extraction through manufacture and use to disposal. LCA is a mixed or hybrid analytical system. An inventory phase analyzes system inputs of energy and materials along with outputs of emissions and wastes throughout life cycle, usually as quantitative mass loadings. An impact assessment phase then examines these loadings in light of potential environmental issues using a mixed spectrum of qualitative and quantitative methods. The constraints imposed by inventory's loss of spatial, temporal, dose‐response, and threshold information raise concerns about the accuracy of impact assessment. The degree of constraint varies widely according to the environmental issue in question and models used to extrapolate the inventory data. LCA results may have limited value in two areas: (I) local and/ortransient biophysical processes and (2) issues involving biological parameters, such as biodiversity, habitat alteration, and toxicity. The end result is that impact assessment does not measure actual effects or impacts, nor does it calculate the likelihood of an effect or risk Rather, LCA impact assessment results are largely directional environmental indicaton. The accuracy and usefulness of indicators need to be assessed individually and in a circumstance‐specific manner prior to decision making. This limits LCAs usefulness as the sole basis for comprehensive assessments and the comparisons of alternatives. In conclusion, LCA may identify potential issues from a systemwide perspective, but more‐focused assessments using other analytical techniques are often necessary to resolve the issues.
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