969 resultados para Chronic Low-level Exposure


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Study Design. Quiet stance on supporting bases with different lengths and with different visual inputs were tested in 24 study participants with chronic low back pain (LBP) and 24 matched control subjects. Objectives. To evaluate postural adjustment strategies and visual dependence associated with LBP. Summary of Background Data. Various studies have identified balance impairments in patients with chronic LBP, with many possible causes suggested. Recent evidence indicates that study participants with LBP have impaired trunk muscle control, which may compromise the control of trunk and hip movement during postural adjustments ( e. g., hip strategy). As balance on a short base emphasizes the utilization of the hip strategy for balance control, we hypothesized that patients with LBP might have difficulties standing on short bases. Methods. Subjects stood on either flat surface or short base with different visual inputs. A task was counted as successful if balance was maintained for 70 seconds during bilateral stance and 30 seconds during unilateral stance. The number of successful tasks, horizontal shear force, and center-of-pressure motion were evaluated. Results. The hip strategy was reduced with increased visual dependence in study participants with LBP. The failure rate was more than 4 times that of the controls in the bilateral standing task on short base with eyes closed. Analysis of center-of-pressure motion also showed that they have inability to initiate and control a hip strategy. Conclusions. The inability to control a hip strategy indicates a deficit of postural control and is hypothesized to result from altered muscle control and proprioceptive impairment.

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A systematic review of the literature on the effectiveness of physical interventions for lateral epicondylalgia ( tennis elbow) was carried out. Seventy six randomised controlled trials were identified, 28 of which satisfied the minimum criteria for meta-analysis. The evidence suggests that extracorporeal shock wave therapy is not beneficial in the treatment of tennis elbow. There is a lack of evidence for the long term benefit of physical interventions in general. However, further research with long term follow up into manipulation and exercise as treatments is indicated.

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The present study examined accumulation of the metal toxins cadmium (Cd) and lead (Pb) in relation to the abundance of cytochrome P450 4F2 (CYP4F2), CYP2E1 and concentrations of zinc and copper in liver and kidney samples using immunoblotting coupled with metal analysis. The post mortem liver and kidney cortex samples were from 23 males and 8 females aged 3-89 years. All were Caucasians who had not been exposed to metals in the workplace. Average kidney cortex Cd load of 17.4 mu g/g w.w. was 17 times greater than average liver Cd load (1.1 mu g/g w.w.). In contrast, average kidney cortex Ph load of 0.09 mu g/g w.w. was two times lower than liver Pb load of 0.19 mu g/g w.w. Average Zn and Cu concentrations in the kidney cortex samples were 67% and 33% lower than those in the liver. Liver and kidney Cd loads, but not liver or kidney Ph loads, correlated positively with donors' age. After controlling for liver Cd load, an inverse correlation was seen between Zn and age (partial r = -0.39, P = 0.02), suggesting reduction in liver Zn levels in old age. Liver CYP2E1 protein abundance correlated with age-adjusted Cd load (partial r = 0.37, P = 0.02) whereas kidney CYP4172 protein abundance showed a positive correlation with age-adjusted Cd loads (partial r = 0.40, P = 0.02). These findings suggest that Cd may be an inducer of renal CYP4172 and hepatic CYP2E1 and that increased renal CYP4172 expression may implicate in Cd-linked renal tubular dysfunction and high blood pressure, involving CYP4F2-dependent arachidonic acid metabolism. (c) 2005 Elsevier Ireland Ltd. All rights reserved.

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In recognition of a central role of the kidney in long-term blood pressure control, we undertook an in-depth analysis of the relationship between blood pressure and kidney damage caused by environmental exposure to the common pollutants cadmium and lead. The subjects were 200 healthy Thais, 16 and 60 years of age (100 female non-smokers, 53 male non-smokers, and 47 male smokers). None of these subjects had been exposed to Cd or Pb in the workplace and their urinary Cd concentrations ranged from 0.4 to 37 nM, whereas their urinary Pb concentrations ranged from 0.1 to 30 nM. The prevalence of high blood pressure was 2%, 8% and 19%, respectively in subjects with low, average and high Cd-burden (linear trend chi(2) = 6.4, P = 0.01). Multiple regression analysis revealed a significant positive association between Cd-burden and blood pressure in male nonsmokers (adjusted beta = 0.31, P = 0.02) and an inverse association between blood pressure and urinary Pb excretion rate in male smokers (adjusted beta = -0.38, P = 0.005). Associations between Cd-burden and nephropathies were evidenced by increases in urinary excretion of beta 2-microglobutin (P = 0.02) and N-acetyl-beta-D-glucosaminidase (P = 0.005) in subjects with high Cd-burden, compared with the subjects with average Cd-burden. In addition, an association between Cd-related nephropathy and high blood pressure was evidenced by a 20% increase in the prevalence of high blood pressure in people with NAG-uria (linear trend chi(2) = 4.3, P = 0.04). Our present study provides first evidence for a possible link between renal tubular damage and dysfunction caused by environmental Cd exposure and increased risk of high blood pressure. (c) 2005 Elsevier Ireland Ltd. All rights reserved.

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Although breathing perturbs balance, in healthy individuals little sway is detected in ground reaction forces because small movements of the spine and lower limbs compensate for the postural disturbance. When people have chronic low back pain (LBP), sway at the ground is increased, possibly as a result of reduced compensatory motion of the trunk. The aim of this study was to determine whether postural compensation for breathing is reduced during experimentally induced pain. Subjects stood on a force plate with eyes open, eyes closed, and while breathing with hypercapnoea before and after injection of hypertonic saline into the right lumbar longissimus muscle to induce LBP. Motion of the lumbar spine, pelvis, and lower limbs was measured with four inclinometers fixed over bony landmarks. During experimental pain, motion of the trunk in association with breathing was reduced. However, despite this reduction in motion, there was no increase in postural sway with breathing. These data suggest that increased body sway with breathing in people with chronic LBP is not simply because of reduced trunk movement, but instead, indicates changes in coordination by the central nervous system that are not replicated by experimental nociceptor stimulation.

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The development of colorectal cancer is a major complication for patients with chronic idiopathic colitis. Colitis-associated tumours tend to occur at a younger age and be more aggressive than sporadic colorectal cancers. While we have previously associated the presence of tumour-infiltrating lymphocytes (TILs) and increased apoptosis in sporadic colorectal cancer with high-level microsatellite instability and improved prognosis, little is known of the relationship between these variables in colitis-associated colorectal cancer. The aim of this study was to correlate TILs and tumour cell apoptosis in colitis-associated neoplasms stratified according to microsatellite instability. Twenty tumour and 11 dysplastic samples resected from 21 patients with long-standing colitis were analysed for microsatellite instability at 10 microsatellite markers. TIL distribution (CD3, CD8) and function (granzyme B) were quantified by immunohistochemistry. Neoplastic cell apoptosis was assessed using the M30 CytoDEATH antibody. These findings were compared with 40 microsatellite stable (MSS) sporadic colorectal cancers previously evaluated for TILs and neoplastic apoptosis. Low-level microsatellite instability was found in 1/20 colitis-associated tumours. All other colitis-associated lesions were designated MSS. CD3(+) and CD8(+) TIL counts were significantly higher in colitis-associated lesions compared with NISS sporadic colorectal cancer (p < 0.0001, p = 0.001 respectively). Despite their higher TIL density, colitis-associated tumours were more likely to present late (Dukes' stage C or D) (P = 0.02). Functionally, colitis-associated TILs demonstrated significantly less granzyme B expression compared to sporadic cancers (p = 0.002). The level of tumour cell apoptosis was similar between the two groups (sporadic, 1.53%; colitis cancers, 1.45%). In conclusion, NISS colitis-associated tumours have a higher prevalence of CD3(+)/CD8(+) TILs but no associated increase in tumour cell killing by apoptosis. Unlike cytotoxic T cells in sporadic colorectal cancer, TILs do not appear to enhance the prognosis of colitis-associated colorectal cancer. This may be related to an impairment of granzyme B expression within these lesions. Copyright (c) 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

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Cadmium (Cd) is a metal toxin of continuing worldwide concern. Daily intake of Cd, albeit in small quantities, is associated with a number of adverse health effects which are attributable to distinct pathological changes in a variety of tissues and organs. In the present review, we focus on its renal tubular effects in people who have been exposed environmentally to Cd at levels below the provisional tolerable intake level set for the toxin. We highlight the data linking such low-level Cd intake with tubular injury, altered abundance of cytochromes P450 (CYPs) in the kidney and an expression of a hypertensive phenotype. We provide updated knowledge on renal and vascular effects of the eicosanoids 20-hydroxyeicosatetraenoic acid (20-HETE) and eicosatrienoic acids (EETs), which are biologically active metabolites from arachidonate metabolism mediated by certain CYPs in the kidney. We note the ability of Cd to elicit oxidative stress and to alter metal homeostasis notably of zinc which may lead to augmentation of the defense mechanisms involving induction of the antioxidant enzyme heme oxygenase-1 (HO-1) and the metal binding protein metallothionein (MT) in the kidney. We hypothesize that renal Cd accumulation triggers the host responses mediated by HO-I and MT in an attempt to protect the kidney against injurious oxidative stress and to resist a rise in blood pressure levels. This hypothesis predicts that individuals with less active HO-1 (caused by the HO-1 genetic polymorphisms) are more likely to have renal injury and express a hypertensive phenotype following chronic ingestion of low-level Cd, compared with those having more active HO-1. Future analytical and molecular epidemiologic research should pave the way to the utility of induction of heme oxygenases together with dietary antioxidants in reducing the risk of kidney injury and hypertension in susceptible people.

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Aims: Identification of a gene for self-protection from the antibiotic-producing plant pathogen Xanthomonas albilineans, and functional testing by heterologous expression. Methods and Results: Albicidin antibiotics and phytotoxins are potent inhibitors of prokaryote DNA replication. A resistance gene (albF) isolated by shotgun cloning from the X. albilineans albicidin-biosynthesis region encodes a protein with typical features of DHA14 drug efflux pumps. Low-level expression of albF in Escherichia coli increased the MIC of albicidin 3000-fold, without affecting tsx-mediated albicidin uptake into the periplasm or resistance to other tested antibiotics. Bioinformatic analysis indicates more similarity to proteins involved in self-protection in polyketide-antibiotic-producing actinomycetes than to multi-drug resistance pumps in other Gram-negative bacteria. A complex promoter region may co-regulate albF with genes for hydrolases likely to be involved in albicidin activation or self-protection. Conclusions: AlbF is the first apparent single-component antibiotic-specific efflux pump from a Gram-negative antibiotic producer. It shows extraordinary efficiency as measured by resistance level conferred upon heterologous expression. Significance and Impact of the Study: Development of the clinical potential of albicidins as potent bactericidial antibiotics against diverse bacteria has been limited because of low yields in culture. Expression of albF with recently described albicidin-biosynthesis genes may enable large-scale production. Because albicidins are X. albilineans pathogenicity factors, interference with AlbF function is also an opportunity for control of the associated plant disease.

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Study Design. Experimental study of muscle changes after lumbar spinal injury. Objectives. To investigate effects of intervertebral disc and nerve root lesions on cross-sectional area, histology and chemistry of porcine lumbar multifidus. Summary of Background Data. The multifidus cross-sectional area is reduced in acute and chronic low back pain. Although chronic changes are widespread, acute changes at 1 segment are identified within days of injury. It is uncertain whether changes precede or follow injury, or what is the mechanism. Methods. The multifidus cross-sectional area was measured in 21 pigs from L1 to S1 with ultrasound before and 3 or 6 days after lesions: incision into L3 - L4 disc, medial branch transection of the L3 dorsal ramus, and a sham procedure. Samples from L3 to L5 were studied histologically and chemically. Results. The multifidus cross-sectional area was reduced at L4 ipsilateral to disc lesion but at L4 - L6 after nerve lesion. There was no change after sham or on the opposite side. Water and lactate were reduced bilaterally after disc lesion and ipsilateral to nerve lesion. Histology revealed enlargement of adipocytes and clustering of myofibers at multiple levels after disc and nerve lesions. Conclusions. These data resolve the controversy that the multifidus cross-sectional area reduces rapidly after lumbar injury. Changes after disc lesion affect 1 level with a different distribution to denervation. Such changes may be due to disuse following reflex inhibitory mechanisms.

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The proliferation of data throughout the strategic, tactical and operational areas within many organisations, has provided a need for the decision maker to be presented with structured information that is appropriate for achieving allocated tasks. However, despite this abundance of data, managers at all levels in the organisation commonly encounter a condition of ‘information overload’, that results in a paucity of the correct information. Specifically, this thesis will focus upon the tactical domain within the organisation and the information needs of management who reside at this level. In doing so, it will argue that the link between decision making at the tactical level in the organisation, and low-level transaction processing data, should be through a common object model that used a framework based upon knowledge leveraged from co-ordination theory. In order to achieve this, the Co-ordinated Business Object Model (CBOM) was created. Detailing a two-tier framework, the first tier models data based upon four interactive object models, namely, processes, activities, resources and actors. The second tier analyses the data captured by the four object models, and returns information that can be used to support tactical decision making. In addition, the Co-ordinated Business Object Support System (CBOSS), is a prototype tool that has been developed in order to both support the CBOM implementation, and to also demonstrate the functionality of the CBOM as a modelling approach for supporting tactical management decision making. Containing a graphical user interface, the system’s functionality allows the user to create and explore alternative implementations of an identified tactical level process. In order to validate the CBOM, three verification tests have been completed. The results provide evidence that the CBOM framework helps bridge the gap between low level transaction data, and the information that is used to support tactical level decision making.

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Non-steroidal anti-inflammatory drugs (NSAIDs) cause peptic ulcer disease, but whether they interact with Helicobacter pylori to promote damage is controversial. Moreover, the reported induction of apoptosis in gastric cells by H. pylori lipopolysaccharide (LPS) (10-9 g /ml) contrasts with studies showing low immunological potency of this LPS. Therefore, the effects of LPS from H. pylori NCTC 11637 and Escherichia coli 0111:B4 on apoptosis in a primary culture of guinea-pig gastric mucous cells were investigated in the presence and absence of the NSAID, ibuprofen. Cell loss was estimated by a crystal violet assay, and apoptosis determined from caspase activity and from condensation and fragmentation of nuclei. Exposure to E. coli LPS for 24 h caused cell loss and enhanced apoptotic activity at concentrations ≥ 10-9 g/ml, but similar effects were only obtained with H. pylori LPS at concentrations ≥10-6 g/ml. Although ibuprofen (250 μM) caused cell loss and apoptosis, addition of either E. coli or H. pylori LPSs further enhanced these effects. In conclusion, LPS and ibuprofen interact to enhance gastric cell loss and apoptosis. In such interactions, E. coli LPS is more potent than that of H. pylori. The low potency of H. pylori LPS may contribute to a chronic low-grade gastritis that can be enhanced by the use of NSAIDs. © W. S. Maney & Son Ltd.

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In this paper a new method for image retrieval using high level color semantic features is proposed. It is based on extraction of low level color characteristics and their conversion into high level semantic features using Johannes Itten theory of color, Dempster-Shafer theory of evidence and fuzzy production rules.

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Petri Nets are a formal, graphical and executable modeling technique for the specification and analysis of concurrent and distributed systems and have been widely applied in computer science and many other engineering disciplines. Low level Petri nets are simple and useful for modeling control flows but not powerful enough to define data and system functionality. High level Petri nets (HLPNs) have been developed to support data and functionality definitions, such as using complex structured data as tokens and algebraic expressions as transition formulas. Compared to low level Petri nets, HLPNs result in compact system models that are easier to be understood. Therefore, HLPNs are more useful in modeling complex systems. ^ There are two issues in using HLPNs—modeling and analysis. Modeling concerns the abstracting and representing the systems under consideration using HLPNs, and analysis deals with effective ways study the behaviors and properties of the resulting HLPN models. In this dissertation, several modeling and analysis techniques for HLPNs are studied, which are integrated into a framework that is supported by a tool. ^ For modeling, this framework integrates two formal languages: a type of HLPNs called Predicate Transition Net (PrT Net) is used to model a system's behavior and a first-order linear time temporal logic (FOLTL) to specify the system's properties. The main contribution of this dissertation with regard to modeling is to develop a software tool to support the formal modeling capabilities in this framework. ^ For analysis, this framework combines three complementary techniques, simulation, explicit state model checking and bounded model checking (BMC). Simulation is a straightforward and speedy method, but only covers some execution paths in a HLPN model. Explicit state model checking covers all the execution paths but suffers from the state explosion problem. BMC is a tradeoff as it provides a certain level of coverage while more efficient than explicit state model checking. The main contribution of this dissertation with regard to analysis is adapting BMC to analyze HLPN models and integrating the three complementary analysis techniques in a software tool to support the formal analysis capabilities in this framework. ^ The SAMTools developed for this framework in this dissertation integrates three tools: PIPE+ for HLPNs behavioral modeling and simulation, SAMAT for hierarchical structural modeling and property specification, and PIPE+Verifier for behavioral verification.^

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This study aims to bring reflection on the legitimacy crisis of the Brazilian representative democracy, which results in non-attendance of fundamental rights, regarding legal and social facts in light of the existing constitutional order and seeking solutions in more democratic procedures and in a more humane, critical, democratic and collaborative education. It has been an issue for some time the understanding that the authorities do not meet the basic needs of Brazilian citizens - the only way to make them autonomous and sufficiently able to conduct their lives in a competitive and globalized labor market. Such situation only worsened - as illustrated by the social movements in mid-2013 - when people took to the streets, showing a noticeable dissatisfaction with public services in general, and some other groups presenting specific complaints in those events. To find solutions or at least suggestions for the reflection of the problem found, a current approach to public authorities was necessary attempting to reveal how the constitutional order authorizes their operation and how - in fact - they act. In this endeavour, the legitimacy of power was discussed, involving the analysis of its origin, to whom it belongs and the legitimacy of deficit situations, concluding that it is only justified as it gets more democratic influence, with greater participation of people in its deliberations and decisions, with its plurality and complexity. Research carried out by official institutions was necessary to have evidence of the low level of social development of the country and the nonattendance of minimum basic rights, as well as exposure to various acts and omissions which show that all public authorities do not legitimately represent the people's interests. The competence of the Supreme Court to establish the broader scope of the remuneration policy in the public service received proper attention, presenting itself as an effective means to promote the reduction of the remuneration and structural inequality in public service and contributing to better care of fundamental rights. Also, considerations were made about the Decree 8243/2014, which established the National Policy for Social Participation (NPSP) and the National System of Social Participation (NSSP) and took other measures with the suggestion of its expansion into the legislative and judiciary powers as a way to legitimize the Brazilian democracy, considering its current stage. In conclusion, it is presented the idea expressed by the most influential and modern pedagogical trends for the creation of a participatory, solidary, non-hierarchical and critical culture since the childhood stage. This idea focuses on the resolution of questions addressed to the common good, which considers the complexity and the existing pluralism in society with a view to constant knowledge update. Knowledge update is in turn dynamic and requires such action, instilling - for the future generations - the idea that the creation of a more participatory and collaborative democracy is needed to reduce social inequality as a way to legitimize and promote social welfare, with the implementation of a policy devoted to meet the minimum fundamental rights to ensure dignity to the population.

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Integrating information from multiple sources is a crucial function of the brain. Examples of such integration include multiple stimuli of different modalties, such as visual and auditory, multiple stimuli of the same modality, such as auditory and auditory, and integrating stimuli from the sensory organs (i.e. ears) with stimuli delivered from brain-machine interfaces.

The overall aim of this body of work is to empirically examine stimulus integration in these three domains to inform our broader understanding of how and when the brain combines information from multiple sources.

First, I examine visually-guided auditory, a problem with implications for the general problem in learning of how the brain determines what lesson to learn (and what lessons not to learn). For example, sound localization is a behavior that is partially learned with the aid of vision. This process requires correctly matching a visual location to that of a sound. This is an intrinsically circular problem when sound location is itself uncertain and the visual scene is rife with possible visual matches. Here, we develop a simple paradigm using visual guidance of sound localization to gain insight into how the brain confronts this type of circularity. We tested two competing hypotheses. 1: The brain guides sound location learning based on the synchrony or simultaneity of auditory-visual stimuli, potentially involving a Hebbian associative mechanism. 2: The brain uses a ‘guess and check’ heuristic in which visual feedback that is obtained after an eye movement to a sound alters future performance, perhaps by recruiting the brain’s reward-related circuitry. We assessed the effects of exposure to visual stimuli spatially mismatched from sounds on performance of an interleaved auditory-only saccade task. We found that when humans and monkeys were provided the visual stimulus asynchronously with the sound but as feedback to an auditory-guided saccade, they shifted their subsequent auditory-only performance toward the direction of the visual cue by 1.3-1.7 degrees, or 22-28% of the original 6 degree visual-auditory mismatch. In contrast when the visual stimulus was presented synchronously with the sound but extinguished too quickly to provide this feedback, there was little change in subsequent auditory-only performance. Our results suggest that the outcome of our own actions is vital to localizing sounds correctly. Contrary to previous expectations, visual calibration of auditory space does not appear to require visual-auditory associations based on synchrony/simultaneity.

My next line of research examines how electrical stimulation of the inferior colliculus influences perception of sounds in a nonhuman primate. The central nucleus of the inferior colliculus is the major ascending relay of auditory information before it reaches the forebrain, and thus an ideal target for understanding low-level information processing prior to the forebrain, as almost all auditory signals pass through the central nucleus of the inferior colliculus before reaching the forebrain. Thus, the inferior colliculus is the ideal structure to examine to understand the format of the inputs into the forebrain and, by extension, the processing of auditory scenes that occurs in the brainstem. Therefore, the inferior colliculus was an attractive target for understanding stimulus integration in the ascending auditory pathway.

Moreover, understanding the relationship between the auditory selectivity of neurons and their contribution to perception is critical to the design of effective auditory brain prosthetics. These prosthetics seek to mimic natural activity patterns to achieve desired perceptual outcomes. We measured the contribution of inferior colliculus (IC) sites to perception using combined recording and electrical stimulation. Monkeys performed a frequency-based discrimination task, reporting whether a probe sound was higher or lower in frequency than a reference sound. Stimulation pulses were paired with the probe sound on 50% of trials (0.5-80 µA, 100-300 Hz, n=172 IC locations in 3 rhesus monkeys). Electrical stimulation tended to bias the animals’ judgments in a fashion that was coarsely but significantly correlated with the best frequency of the stimulation site in comparison to the reference frequency employed in the task. Although there was considerable variability in the effects of stimulation (including impairments in performance and shifts in performance away from the direction predicted based on the site’s response properties), the results indicate that stimulation of the IC can evoke percepts correlated with the frequency tuning properties of the IC. Consistent with the implications of recent human studies, the main avenue for improvement for the auditory midbrain implant suggested by our findings is to increase the number and spatial extent of electrodes, to increase the size of the region that can be electrically activated and provide a greater range of evoked percepts.

My next line of research employs a frequency-tagging approach to examine the extent to which multiple sound sources are combined (or segregated) in the nonhuman primate inferior colliculus. In the single-sound case, most inferior colliculus neurons respond and entrain to sounds in a very broad region of space, and many are entirely spatially insensitive, so it is unknown how the neurons will respond to a situation with more than one sound. I use multiple AM stimuli of different frequencies, which the inferior colliculus represents using a spike timing code. This allows me to measure spike timing in the inferior colliculus to determine which sound source is responsible for neural activity in an auditory scene containing multiple sounds. Using this approach, I find that the same neurons that are tuned to broad regions of space in the single sound condition become dramatically more selective in the dual sound condition, preferentially entraining spikes to stimuli from a smaller region of space. I will examine the possibility that there may be a conceptual linkage between this finding and the finding of receptive field shifts in the visual system.

In chapter 5, I will comment on these findings more generally, compare them to existing theoretical models, and discuss what these results tell us about processing in the central nervous system in a multi-stimulus situation. My results suggest that the brain is flexible in its processing and can adapt its integration schema to fit the available cues and the demands of the task.