Showing papers by "University of Alberta published in 2005"

Coding algorithms for defining comorbidities in ICD-9-CM and ICD-10 administrative data.

Abstract: Objectives:Implementation of the International Statistical Classification of Disease and Related Health Problems, 10th Revision (ICD-10) coding system presents challenges for using administrative data. Recognizing this, we conducted a multistep process to develop ICD-10 coding algorithms to define C

Acute Renal Failure in Critically Ill Patients: A Multinational, Multicenter Study

Abstract: ContextAlthough acute renal failure (ARF) is believed to be common in the setting of critical illness and is associated with a high risk of death, little is known about its epidemiology and outcome or how these vary in different regions of the world.ObjectivesTo determine the period prevalence of ARF in intensive care unit (ICU) patients in multiple countries; to characterize differences in etiology, illness severity, and clinical practice; and to determine the impact of these differences on patient outcomes.Design, Setting, and PatientsProspective observational study of ICU patients who either were treated with renal replacement therapy (RRT) or fulfilled at least 1 of the predefined criteria for ARF from September 2000 to December 2001 at 54 hospitals in 23 countries.Main Outcome MeasuresOccurrence of ARF, factors contributing to etiology, illness severity, treatment, need for renal support after hospital discharge, and hospital mortality.ResultsOf 29 269 critically ill patients admitted during the study period, 1738 (5.7%; 95% confidence interval [CI], 5.5%-6.0%) had ARF during their ICU stay, including 1260 who were treated with RRT. The most common contributing factor to ARF was septic shock (47.5%; 95% CI, 45.2%-49.5%). Approximately 30% of patients had preadmission renal dysfunction. Overall hospital mortality was 60.3% (95% CI, 58.0%-62.6%). Dialysis dependence at hospital discharge was 13.8% (95% CI, 11.2%-16.3%) for survivors. Independent risk factors for hospital mortality included use of vasopressors (odds ratio [OR], 1.95; 95% CI, 1.50-2.55; P<.001), mechanical ventilation (OR, 2.11; 95% CI, 1.58-2.82; P<.001), septic shock (OR, 1.36; 95% CI, 1.03-1.79; P = .03), cardiogenic shock (OR, 1.41; 95% CI, 1.05-1.90; P = .02), and hepatorenal syndrome (OR, 1.87; 95% CI, 1.07-3.28; P = .03).ConclusionIn this multinational study, the period prevalence of ARF requiring RRT in the ICU was between 5% and 6% and was associated with a high hospital mortality rate.

Vinorelbine plus Cisplatin vs. Observation in Resected Non–Small-Cell Lung Cancer

Abstract: background We undertook to determine whether adjuvant vinorelbine plus cisplatin prolongs overall survival among patients with completely resected early-stage non–small-cell lung cancer. methods We randomly assigned patients with completely resected stage IB or stage II non–smallcell lung cancer to vinorelbine plus cisplatin or to observation. The primary end point was overall survival; principal secondary end points were recurrence-free survival and the toxicity and safety of the regimen. results A total of 482 patients underwent randomization to vinorelbine plus cisplatin (242 patients) or observation (240); 45 percent of the patients had pathological stage IB disease and 55 percent had stage II, and all had an Eastern Cooperative Oncology Group performance status score of 0 or 1. In both groups, the median age was 61 years, 65 percent were men, and 53 percent had adenocarcinomas. Chemotherapy caused neutropenia in 88 percent of patients (including grade 3 febrile neutropenia in 7 percent) and death from toxic effects in two patients (0.8 percent). Nonhematologic toxic effects of chemotherapy were fatigue (81 percent of patients), nausea (80 percent), anorexia (55 percent), vomiting (48 percent), neuropathy (48 percent), and constipation (47 percent), but severe (grade 3 or greater) toxic effects were uncommon (<10 percent). Overall survival was significantly prolonged in the chemotherapy group as compared with the observation group (94 vs. 73 months; hazard ratio for death, 0.69; P=0.04), as was relapse-free survival (not reached vs. 46.7 months; hazard ratio for recurrence, 0.60; P<0.001). Five-year survival rates were 69 percent and 54 percent, respectively (P=0.03). conclusions Adjuvant vinorelbine plus cisplatin has an acceptable level of toxicity and prolongs disease-free and overall survival among patients with completely resected early-stage non–small-cell lung cancer.

Corporate Governance, Economic Entrenchment, and Growth

Abstract: Outside the United States and the United Kingdom, large corporations usually have controlling owners, who are usually very wealthy families. Pyramidal control structures, cross shareholding, and super-voting rights let such families control corporations without making a commensurate capital investment. In many countries, a few such families end up controlling considerable proportions of their countries’ economies. Three points emerge. First, at the firm level, these ownership structures, because they vest dominant control rights with families who often have little real capital invested, permit a range of agency problems and hence resource misallocation. If a few families control large swaths of an economy, such corporate governance problems can attain macroeconomic importance—affecting rates of innovation, economywide resource allocation, and economic growth. If political influence depends on what one controls, rather than what one owns, the controlling owners of pyramids have greatly amplified political influence relative to their actual wealth. This influence can distort public policy regarding property rights protection, capital markets, and other institutions. We denote this phenomenon economic entrenchment, and posit a relationship between the distribution of corporate control and institutional development that generates and preserves economic entrenchment as one possible equilibrium. The literature suggests key determinants of economic entrenchment, but has many gaps where further work exploring the political economy importance of the distribution of corporate control is needed.

Mobile genetic elements: the agents of open source evolution.

Abstract: Horizontal genomics is a new field in prokaryotic biology that is focused on the analysis of DNA sequences in prokaryotic chromosomes that seem to have originated from other prokaryotes or eukaryotes. However, it is equally important to understand the agents that effect DNA movement: plasmids, bacteriophages and transposons. Although these agents occur in all prokaryotes, comprehensive genomics of the prokaryotic mobile gene pool or 'mobilome' lags behind other genomics initiatives owing to challenges that are distinct from cellular chromosomal analysis. Recent work shows promise of improved mobile genetic element (MGE) genomics and consequent opportunities to take advantage - and avoid the dangers - of these 'natural genetic engineers'. This review describes MGEs, their properties that are important in horizontal gene transfer, and current opportunities to advance MGE genomics.

Randomized trial to determine the effect of nebivolol on mortality and cardiovascular hospital admission in elderly patients with heart failure (SENIORS)

Abstract: Aims Large randomized trials have shown that beta-blockers reduce mortality and hospital admissions in patients with heart failure. The effects of beta-blockers in elderly patients with a broad range of left ventricular ejection fraction are uncertain. The SENIORS study was performed to assess effects of the beta-blocker, nebivolol, in patients ≥70 years, regardless of ejection fraction. Methods and results We randomly assigned 2128 patients aged ≥70 years with a history of heart failure (hospital admission for heart failure within the previous year or known ejection fraction ≤35%), 1067 to nebivolol (titrated from 1.25 mg once daily to 10 mg once daily), and 1061 to placebo. The primary outcome was a composite of all cause mortality or cardiovascular hospital admission (time to first event). Analysis was by intention to treat. Mean duration of follow-up was 21 months. Mean age was 76 years (SD 4.7), 37% were female, mean ejection fraction was 36% (with 35% having ejection fraction >35%), and 68% had a prior history of coronary heart disease. The mean maintenance dose of nebivolol was 7.7 mg and of placebo 8.5 mg. The primary outcome occurred in 332 patients (31.1%) on nebivolol compared with 375 (35.3%) on placebo [hazard ratio (HR) 0.86, 95% CI 0.74–0.99; P =0.039]. There was no significant influence of age, gender, or ejection fraction on the effect of nebivolol on the primary outcome. Death (all causes) occurred in 169 (15.8%) on nebivolol and 192 (18.1%) on placebo (HR 0.88, 95% CI 0.71–1.08; P =0.21). Conclusion Nebivolol, a beta-blocker with vasodilating properties, is an effective and well-tolerated treatment for heart failure in the elderly.

Spatial Analysis A Guide for Ecologists

Abstract: Preface 1. Spatial concepts and notions 2. Ecological and spatial processes 3. Points, lines and graphs 4. Spatial analysis of complete point location data 5. Contiguous units analysis 6. Spatial analysis of sample data 7. Spatial relationship and multiscale analysis 8. Spatial autocorrelation and inferential tests 9. Spatial partitioning: spatial clusters and boundary detection 10. Spatial diversity analysis 11. Spatio-temporal analysis 12. Closing comments and future directions References Index.

US valuation of the EQ-5D health states: development and testing of the D1 valuation model.

Abstract: Purpose: The EQ-5D is a brief, multiattribute, preference-based health status measure. This article describes the development of a statistical model for generating US population-based EQ-5D preference weights. Methods: A multistage probability sample was selected from the US adult civilian noninstitutional population. Respondents valued 13 of 243 EQ-5D health states using the time trade-off (TTO) method. Data for 12 states were used in econometric modeling. The TTO valuations were linearly transformed to lie on the interval 1, 1. Methods were investigated to account for interaction effects caused by having problems in multiple EQ-5D dimensions. Several alternative model specifications (eg, pooled least squares, random effects) also were considered. A modified split-sample approach was used to evaluate the predictive accuracy of the models. All statistical analyses took into account the clustering and disproportionate selection probabilities inherent in our sampling design. Results: Our D1 model for the EQ-5D included ordinal terms to capture the effect of departures from perfect health as well as interaction effects. A random effects specification of the D1 model yielded a good fit for the observed TTO data, with an overall R 2 of 0.38, a mean absolute error of 0.025, and 7 prediction errors exceeding 0.05 in absolute magnitude. Conclusions: The D1 model best predicts the values for observed health states. The resulting preference weight estimates represent a significant enhancement of the EQ-5D’s utility for health status assessment and economic analysis in the US.

Evolution of binary black-hole spacetimes.

Abstract: We describe early success in the evolution of binary black-hole spacetimes with a numerical code based on a generalization of harmonic coordinates. Indications are that with sufficient resolution this scheme is capable of evolving binary systems for enough time to extract information about the orbit, merger, and gravitational waves emitted during the event. As an example we show results from the evolution of a binary composed of two equal mass, nonspinning black holes, through a single plunge orbit, merger, and ringdown. The resultant black hole is estimated to be a Kerr black hole with angular momentum parameter a[approximate]0.70. At present, lack of resolution far from the binary prevents an accurate estimate of the energy emitted, though a rough calculation suggests on the order of 5% of the initial rest mass of the system is radiated as gravitational waves during the final orbit and ringdown.

Wolves influence elk movements: behavior shapes a trophic cascade in yellowstone national park

Abstract: A trophic cascade recently has been reported among wolves, elk, and aspen on the northern winter range of Yellowstone National Park, Wyoming, USA, but the mechanisms of indirect interactions within this food chain have yet to be established. We investigated whether the observed trophic cascade might have a behavioral basis by exploring environmental factors influencing the movements of 13 female elk equipped with GPS radio collars. We developed a simple statistical approach that can unveil the concurrent influence of several environmental features on animal movements. Paths of elk traveling on their winter range were broken down into steps, which correspond to the straight-line segment between successive locations at 5-hour intervals. Each observed step was paired with 200 random steps having the same starting point, but differing in length and/or direction. Comparisons between the characteristics of observed and random steps using conditional logistic regression were used to model environmental features influencing movement patterns. We found that elk movements were influenced by multiple factors, such as the distance from roads, the presence of a steep slope along the step, and the cover type in which they ended. The influence of cover type on elk movements depended on the spatial distribution of wolves across the northern winter range of the park. In low wolf-use areas, the relative preference for end point locations of steps followed: aspen stands > open areas > conifer forests. As the risks of wolf encounter increased, the preference of elk for aspen stands gradually decreased, and selection became strongest for steps ending in conifer forests in high wolf-use areas. Our study clarifies the behavioral mechanisms involved in the trophic cascade of Yellowstone's wolf-elk-aspen system: elk respond to wolves on their winter range by a shift in habitat selection, which leads to local reductions in the use of aspen by elk.

Edge Influence on Forest Structure and Composition in Fragmented Landscapes

Abstract: Although forest edges have been studied extensively as an important consequence of fragmenta- tion, a unifying theory of edge influence has yet to be developed. Our objective was to take steps toward the development of such a theory by (1) synthesizing the current knowledge of patterns of forest structure and composition at anthropogenically created forest edges, (2) developing hypotheses about the magnitude and distance of edge influence that consider the ecological processes influencing these patterns, and (3) identifying needs for future research. We compiled data from 44 published studies on edge influence on forest structure and composition in boreal, temperate, and tropical forests. Abiotic and biotic gradients near created forest edges generate a set of primary responses to edge creation. Indirect effects from these primary responses and the original edge gradient perpetuate edge influence, leading to secondary responses. Further changes in veg- etation affect the edge environment, resulting in ongoing edge dynamics. We suggest that the magnitude and distance of edge influence are a direct function of the contrast in structure and composition between adjacent communities on either side of the edge. Local factors such as climate, edge characteristics, stand attributes, and biotic factors affect patch contrast. Regional factors define the context within which to assess the ecological significance of edge influence (the degree to which the edge habitat differs from interior forest habitat). Our hypotheses will help predict edge influence on structure and composition in forested ecosystems, an important consideration for conservation. For future research on forest edges in fragmented landscapes, we encourage the testing of our hypotheses, the use of standardized methodology, complete descriptions of study sites, studies on other types of edges, synthesis of edge influence on different components of the ecosystem, and investigations of edges in a landscape context.

Meta-Analysis: Secondary Prevention Programs for Patients with Coronary Artery Disease

Abstract: The authors reviewed 63 randomized trials that measured the effect of adding an exercise program to secondary cardiac prevention programs. Programs that promoted exercise reduced all-cause mortalit...

An Examination of Differences between Organizational Legitimacy and Organizational Reputation

Abstract: Organizational legitimacy and organizational reputation have similar antecedents, social construction processes and consequences. Nonetheless, an improved understanding of relationships between legitimacy and reputation requires that differences between the two be specified and clarified. Our examination of past research indicates that legitimacy emphasizes the social acceptance resulting from adherence to social norms and expectations whereas reputation emphasizes comparisons among organizations. We empirically examine two antecedents of the financial, regulatory, and public dimensions of legitimacy and reputation in a population of US commercial banks. We find that isomorphism improves legitimacy, but its effects on reputation depend on the bank's reputation. Moreover, higher financial performance increases reputation, but does not increase the legitimacy of high performing banks.

An Examination of Differences Between Organizational Legitimacy and Organizational Reputation

Abstract: Organizational legitimacy and organizational reputation have similar antecedents, social construction processes and consequences. Nonetheless, an improved understanding of relationships between legitimacy and reputation requires that differences between the two be specified and clarified. Our examination of past research indicates that legitimacy emphasizes the social acceptance resulting from adherence to social norms and expectations whereas reputation emphasizes comparisons among organizations. We empirically examine two antecedents of the financial, regulatory, and public dimensions of legitimacy and reputation in a population of US commercial banks. We find that isomorphism improves legitimacy, but its effects on reputation depend on the bank's reputation. Moreover, higher financial performance increases reputation, but does not increase the legitimacy of high performing banks.

A new method for stabilization of networked control systems with random delays

Abstract: We consider the stabilization problem for a class of networked control systems in the discrete-time domain with random delays. The sensor-to-controller and controller-to-actuator delays are modeled as two Markov chains, and the resulting closed-loop systems are jump linear systems with two modes. The necessary and sufficient conditions on the existence of stabilizing controllers are established. It is shown that state-feedback gains are mode-dependent. An iterative linear matrix inequality (LMI) approach is employed to calculate the state-feedback gains.

Relation Between Serum Phosphate Level and Cardiovascular Event Rate in People With Coronary Disease

Abstract: Background— Higher levels of serum phosphate are associated with adverse cardiovascular outcomes, especially in the setting of overt hyperphosphatemia. Given the biological importance of phosphorus, it is plausible that higher levels of serum phosphate within the normal range may also be associated with adverse outcomes. Methods and Results— We performed a post hoc analysis of data from the Cholesterol And Recurrent Events (CARE) study. Baseline serum phosphate levels were measured in 4127 fasting participants who were randomized to receive pravastatin 40 mg daily or placebo and followed up for a median of 59.7 months. We used Cox proportional-hazards models to examine the association between serum phosphate and adverse clinical outcomes after adjustment for potential confounders. During nearly 60 months of follow-up, 375 participants died. A significant association was noted between baseline serum phosphate level and the age-, race-, and sex-adjusted risk of all-cause death (hazard ratio per 1 mg/dL, 1.2...

Second Language Accent and Pronunciation Teaching: A Research- Based Approach.

Abstract: Empirical studies are essential to improving our understanding of the relationship between accent and pronunciation teaching. However, the study of pronunciation has been marginalized within the field of applied linguistics. As a result, teachers are often left to rely on their own intuitions with little direction. Although some instructors can successfully assist their students under these conditions, many others are reluctant to teach pronunciation. In this article we call for more research to enhance our knowledge of the nature of foreign accents and their effects on communication. Research of this type has much to offer to teachers and students in terms of helping them to set learning goals, identifying appropriate pedagogical priorities for the classroom, and determining the most effective approaches to teaching. We discuss these possibilities within a framework in which mutual intelligibility is the primary consideration, although social ramifications of accent must also be taken into account. We describe several problem areas and identify some misconceptions about pronunciation instruction. In addition, we make suggestions for future research that would address intelligibility, functional load, computer-assisted language learning, and the role of the listener. Finally, we recommend greater collaboration between researchers and practitioners, such that more classroomrelevant research is undertaken.

Trafficking of Normal Stem Cells and Metastasis of Cancer Stem Cells Involve Similar Mechanisms: Pivotal Role of the SDF-1–CXCR4 Axis

Abstract: The alpha-chemokine stromal-derived factor (SDF)-1 and the G-protein-coupled seven-span transmembrane receptor CXCR4 axis regulates the trafficking of various cell types. In this review, we present the concept that the SDF-1-CXCR4 axis is a master regulator of trafficking of both normal and cancer stem cells. Supporting this is growing evidence that SDF-1 plays a pivotal role in the regulation of trafficking of normal hematopoietic stem cells (HSCs) and their homing/retention in bone marrow. Moreover, functional CXCR4 is also expressed on nonhematopoietic tissue-committed stem/progenitor cells (TCSCs); hence, the SDF-1-CXCR4 axis emerges as a pivotal regulator of trafficking of various types of stem cells in the body. Furthermore, because most if not all malignancies originate in the stem/progenitor cell compartment, cancer stem cells also express CXCR4 on their surface and, as a result, the SDF-1-CXCR4 axis is also involved in directing their trafficking/metastasis to organs that highly express SDF-1 (e.g., lymph nodes, lungs, liver, and bones). Hence, we postulate that the metastasis of cancer stem cells and trafficking of normal stem cells involve similar mechanisms, and we discuss here the common molecular mechanisms involved in these processes. Finally, the responsiveness of CXCR4+ normal and malignant stem cells to an SDF-1 gradient may be regulated positively/primed by several small molecules related to inflammation which enhance incorporation of CXCR4 into membrane lipid rafts, or may be inhibited/blocked by small CXCR4 antagonist peptides. Consequently, strategies aimed at modulating the SDF-1-CXCR4 axis could have important clinical applications both in regenerative medicine to deliver normal stem cells to the tissues/organs and in clinical hematology/oncology to inhibit metastasis of cancer stem cells.

Circular genome visualization and exploration using CGView

Abstract: Summary: CGView (Circular Genome Viewer) is a Java application and library for generating high-quality, zoomable maps of circular genomes. It converts XML or tab-delimited input into a graphical map (PNG, JPG or Scalable Vector Graphics format), complete with sequence features, labels, legends and footnotes. In addition to the default full view map, the program can generate a series of hyperlinked maps showing expanded views. The linked maps can be explored using any Web browser, allowing rapid genome browsing and facilitating data sharing. Availability: CGView (the standalone application, library or applet), sample input, sample maps and documentation can be obtained from http://wishart.biology.ualberta.ca/cgview/ Contact: david.wishart@ualberta.ca

Prime role for an insulin epitope in the development of type 1 diabetes in NOD mice.

Abstract: A fundamental question about the pathogenesis of spontaneous autoimmune diabetes is whether there are primary autoantigens. For type 1 diabetes it is clear that multiple islet molecules are the target of autoimmunity in man and animal models. It is not clear whether any of the target molecules are essential for the destruction of islet beta cells. Here we show that the proinsulin/insulin molecules have a sequence that is a primary target of the autoimmunity that causes diabetes of the non-obese diabetic (NOD) mouse. We created insulin 1 and insulin 2 gene knockouts combined with a mutated proinsulin transgene (in which residue 16 on the B chain was changed to alanine) in NOD mice. This mutation abrogated the T-cell stimulation of a series of the major insulin autoreactive NOD T-cell clones. Female mice with only the altered insulin did not develop insulin autoantibodies, insulitis or autoimmune diabetes, in contrast with mice containing at least one copy of the native insulin gene. We suggest that proinsulin is a primary autoantigen of the NOD mouse, and speculate that organ-restricted autoimmune disorders with marked major histocompatibility complex (MHC) restriction of disease are likely to have specific primary autoantigens.

Microvesicles derived from activated platelets induce metastasis and angiogenesis in lung cancer.

Abstract: The role of platelets in tumor progression and metastasis has been recognized but the mechanism of their action remains unclear. Five human lung cancer cell lines (A549, CRL 2066, CRL 2062, HTB 183, HTB 177) and a murine Lewis lung carcinoma (LCC) cell line (for an in vivo model of metastasis) were used to investigate how platelet-derived microvesicles (PMV), which are circular fragments shed from the surface membranes of activated platelets, and exosomes released from platelet alpha-granules, could contribute to metastatic spread. We found that PMV transferred the platelet-derived integrin CD41 to most of the lung cancer cell lines tested and stimulated the phosphorylation of mitogen-activated protein kinase p42/44 and serine/threonine kinase as well as the expression of membrane type 1-matrix metalloproteinase (MT1-MMP). PMV chemoattracted 4 of the 5 cell lines, with the highly metastatic A549 cells exhibiting the strongest response. In A549 cells, PMV were shown to stimulate proliferation, upregulate cyclin D2 expression and increase trans-Matrigel chemoinvasion. Furthermore, in these cells, PMV stimulated mRNA expression for angiogenic factors such as MMP-9, vascular endothelial growth factor, interleukin-8 and hepatocyte growth factor, as well as adhesion to fibrinogen and human umbilical vein endothelial cells. Intravenous injection of murine PMV-covered LLC cells into syngeneic mice resulted in significantly more metastatic foci in their lungs and LLC cells in bone marrow than in control animals injected with LCC cells not covered with PMV. Based on these findings, we suggest that PMV play an important role in tumor progression/metastasis and angiogenesis in lung cancer.

Natural history and pathophysiology of Q fever

Abstract: Q fever is a zoonosis caused by Coxiella burnetii. Infection with C burnetii can be acute or chronic, and exhibits a wide spectrum of clinical manifestations. The extreme infectivity of the bacterium results in large outbreaks and makes it a potential bioweapon. In the past decade, the complete genome sequencing of C burnetii, the exploration of bacterial interactions with the host, and the description of the natural history of the disease in human beings and in experimental models have all added to our knowledge about this fascinating disease. Advances in understanding the pathophysiology and natural history of Q fever are reviewed.

Controlled Physical Activity Trials in Cancer Survivors: A Systematic Review and Meta-analysis

Abstract: Background: Approximately 9.8 million cancer survivors are alive in the United States today. Enthusiasm for prescribing physical activity for cancer survivors depends on evidence regarding whether physical activity during or after completion of treatment results in improved outcomes such as cardiorespiratory fitness, fatigue, symptoms, quality of life, mental health, or change in body size. Methods: A systematic qualitative and quantitative review of the English language scientific literature identified controlled trials of physical activity interventions in cancer survivors during and after treatment. Data from 32 studies were abstracted, weighted mean effect sizes (WMES) were calculated from the 22 high-quality studies, and a systematic level of evidence criteria was applied to evaluate 25 outcomes. Results: There was qualitative and quantitative evidence of a small to moderate effect of physical activity interventions on cardiorespiratory fitness (WMES = 0.51 and 0.65 during and after treatment respectively, P < 0.01), physiologic outcomes and symptoms during treatment (WMES = 0.28, P < 0.01 and 0.39, P < 0.01, respectively), and vigor posttreatment (WMES = 0.83, P = 0.04). Physical activity was well tolerated in cancer survivors during and after treatment, but the available literature does not allow conclusions to be drawn regarding adverse events from participation. Conclusions: Physical activity improves cardiorespiratory fitness during and after cancer treatment, symptoms and physiologic effects during treatment, and vigor posttreatment. Additional physical activity intervention studies are needed to more firmly establish the range and magnitude of positive effects of physical activity among cancer survivors. (Cancer Epidemiol Biomarkers Prev 2005;14(7):1588 – 95)

Neuronal variability: noise or part of the signal?

Abstract: Sensory, motor and cortical neurons fire impulses or spikes at a regular, but slowly declining, rate in response to a constant current stimulus. Yet, the intervals between spikes often vary randomly during behaviour. Is this variation an unavoidable effect of generating spikes by sensory or synaptic processes ('neural noise') or is it an important part of the 'signal' that is transmitted to other neurons? Here, we mainly discuss this question in relation to sensory and motor processes, as the signals are best identified in such systems, although we also touch on central processes.