Showing papers by "Dalhousie University published in 2003"

Core outcome domains for chronic pain clinical trials: IMMPACT recommendations.

Abstract: Objective. To provide recommendations for the core outcome domains that should be considered by investigators conducting clinical trials of the efficacy and effectiveness of treatments for chronic pain. Development of a core set of outcome domains would facilitate comparison and pooling of d

Rapid worldwide depletion of predatory fish communities

Abstract: Serious concerns have been raised about the ecological effects of industrialized fishing1, 2, 3, spurring a United Nations resolution on restoring fisheries and marine ecosystems to healthy levels4. However, a prerequisite for restoration is a general understanding of the composition and abundance of unexploited fish communities, relative to contemporary ones. We constructed trajectories of community biomass and composition of large predatory fishes in four continental shelf and nine oceanic systems, using all available data from the beginning of exploitation. Industrialized fisheries typically reduced community biomass by 80% within 15 years of exploitation. Compensatory increases in fast-growing species were observed, but often reversed within a decade. Using a meta-analytic approach, we estimate that large predatory fish biomass today is only about 10% of pre-industrial levels. We conclude that declines of large predators in coastal regions5 have extended throughout the global ocean, with potentially serious consequences for ecosystems5, 6, 7. Our analysis suggests that management based on recent data alone may be misleading, and provides minimum estimates for unexploited communities, which could serve as the ‘missing baseline’8 needed for future restoration efforts.

Pyogenic Bacterial Infections in Humans with MyD88 Deficiency

Abstract: MyD88 is a key downstream adapter for most Toll-like receptors (TLRs) and interleukin-1 receptors (IL-1Rs). MyD88 deficiency in mice leads to susceptibility to a broad range of pathogens in experimental settings of infection. We describe a distinct situation in a natural setting of human infection. Nine children with autosomal recessive MyD88 deficiency suffered from life-threatening, often recurrent pyogenic bacterial infections, including invasive pneumococcal disease. However, these patients were otherwise healthy, with normal resistance to other microbes. Their clinical status improved with age, but not due to any cellular leakiness in MyD88 deficiency. The MyD88-dependent TLRs and IL-1Rs are therefore essential for protective immunity to a small number of pyogenic bacteria, but redundant for host defense to most natural infections.

The importance of cognitive errors in diagnosis and strategies to minimize them.

Abstract: In the area of patient safety, recent attention has focused on diagnostic error. The reduction of diagnostic error is an important goal because of its associated morbidity and potential preventability. A critical subset of diagnostic errors arises through cognitive errors, especially those a

Collapse and Conservation of Shark Populations in the Northwest Atlantic

Abstract: Overexploitation threatens the future of many large vertebrates. In the ocean, tunas and sea turtles are current conservation concerns because of this intense pressure. The status of most shark species, in contrast, remains uncertain. Using the largest data set in the Northwest Atlantic, we show rapid large declines in large coastal and oceanic shark populations. Scalloped hammerhead, white, and thresher sharks are each estimated to have declined by over 75% in the past 15 years. Closed-area models highlight priority areas for shark conservation, and the need to consider effort reallocation and site selection if marine reserves are to benefit multiple threatened species.

Neurobiology of butyrylcholinesterase.

Abstract: Butyrylcholinesterase is a serine hydrolase related to acetylcholinesterase that catalyses the hydrolysis of esters of choline, including acetylcholine. Butyrylcholinesterase has unique enzymatic properties and is widely distributed in the nervous system, pointing to its possible involvement in neural function. Here, we summarize the biochemical properties of butyrylcholinesterase and review the evidence that this enzyme has important roles in cholinergic neurotransmission and could be involved in other nervous system functions and in neurodegenerative diseases.

Genome scan meta-analysis of schizophrenia and bipolar disorder, part III: Bipolar disorder.

Abstract: Genome scans of bipolar disorder (BPD) have not produced consistent evidence for linkage. The rank-based genome scan meta-analysis (GSMA) method was applied to 18 BPD genome scan data sets in an effort to identify regions with significant support for linkage in the combined data. The two primary analyses considered available linkage data for "very narrow" (i.e., BP-I and schizoaffective disorder-BP) and "narrow" (i.e., adding BP-II disorder) disease models, with the ranks weighted for sample size. A "broad" model (i.e., adding recurrent major depression) and unweighted analyses were also performed. No region achieved genomewide statistical significance by several simulation-based criteria. The most significant P values (<.01) were observed on chromosomes 9p22.3-21.1 (very narrow), 10q11.21-22.1 (very narrow), and 14q24.1-32.12 (narrow). Nominally significant P values were observed in adjacent bins on chromosomes 9p and 18p-q, across all three disease models on chromosomes 14q and 18p-q, and across two models on chromosome 8q. Relatively few BPD pedigrees have been studied under narrow disease models relative to the schizophrenia GSMA data set, which produced more significant results. There was no overlap of the highest-ranked regions for the two disorders. The present results for the very narrow model are promising but suggest that more and larger data sets are needed. Alternatively, linkage might be detected in certain populations or subsets of pedigrees. The narrow and broad data sets had considerable power, according to simulation studies, but did not produce more highly significant evidence for linkage. We note that meta-analysis can sometimes provide support for linkage but cannot disprove linkage in any candidate region.

The future for fisheries.

Abstract: Formal analyses of long-term global marine fisheries prospects have yet to be performed, because fisheries research focuses on local, species-specific management issues. Extrapolation of present trends implies expansion of bottom fisheries into deeper waters, serious impact on biodiversity, and declining global catches, the last possibly aggravated by fuel cost increases. Examination of four scenarios, covering various societal development choices, suggests that the negative trends now besetting fisheries can be turned around, and their supporting ecosystems rebuilt, at least partly.

Reaction of Li with Alloy Thin Films Studied by In Situ AFM

Abstract: Many intermetallic materials deliver poor capacity retention when cycled vs Li Many authors have attributed this poor capacity retention to large volume expansions of the active material Here we report the volume changes of continuous and patterned films of crystalline Al, crystalline Sn, amorphous Si (a-Si), and a-Si 0 6 4 Sn 0 3 6 as they reversibly react with Li measured by in situ atomic force microscopy (AFM) Although these materials all undergo large volume expansions, the amorphous phases undergo reversible shape and volume changes The crystalline materials do not We attribute this difference to the homogeneous expansion and contraction that occurs in the amorphous materials Inhomogeneous expansion occurs in the crystalline materials due to the presence of coexisting phases with different Li concentrations Thin films of a-Si and a-Si 0 6 4 Sn 0 3 6 show good capacity retention with cycle number

Marine ecology: Spring algal bloom and larval fish survival

Abstract: The different factors that influence the prevalent decline in fish stocks are currently subject to urgent and intense scrutiny. Here we combine the use of remote-sensing satellite data with a long-term data set of haddock recruitment off the eastern continental shelf of Nova Scotia, Canada, to show that the survival of the larval fish depends on the timing of the local spring bloom of phytoplankton. This link has been suspected for more than 100 years, but its verification has had to wait for technology with sufficient spatial and temporal resolution.

Global inventory of nitrogen oxide emissions constrained by space‐based observations of NO2 columns

Abstract: [1] We use tropospheric NO2 columns from the Global Ozone Monitoring Experiment (GOME) satellite instrument to derive top-down constraints on emissions of nitrogen oxides (NOx ≡ NO + NO2), and combine these with a priori information from a bottom-up emission inventory (with error weighting) to achieve an optimized a posteriori estimate of the global distribution of surface NOx emissions. Our GOME NO2 retrieval improves on previous work by accounting for scattering and absorption of radiation by aerosols; the effect on the air mass factor (AMF) ranges from +10 to −40% depending on the region. Our AMF also includes local information on relative vertical profiles (shape factors) of NO2 from a global 3-D chemical transport model (GEOS-CHEM); assumption of a globally uniform shape factor, as in most previous retrievals, would introduce regional biases of up to 40% over industrial regions and a factor of 2 over remote regions. We derive a top-down NOx emission inventory from the GOME data by using the local GEOS-CHEM relationship between NO2 columns and NOx emissions. The resulting NOx emissions for industrial regions are aseasonal, despite large seasonal variation in NO2 columns, providing confidence in the method. Top-down errors in monthly NOx emissions are comparable with bottom-up errors over source regions. Annual global a posteriori errors are half of a priori errors. Our global a posteriori estimate for annual land surface NOx emissions (37.7 Tg N yr−1) agrees closely with the GEIA-based a priori (36.4) and with the EDGAR 3.0 bottom-up inventory (36.6), but there are significant regional differences. A posteriori NOx emissions are higher by 50–100% in the Po Valley, Tehran, and Riyadh urban areas, and by 25–35% in Japan and South Africa. Biomass burning emissions from India, central Africa, and Brazil are lower by up to 50%; soil NOx emissions are appreciably higher in the western United States, the Sahel, and southern Europe.

Meta-analysis of cod-shrimp interactions reveals top-down control in oceanic food webs

Abstract: Here we present a meta-analytic approach to analyzing population interac- tions across the North Atlantic Ocean. We assembled all available biomass time series for a well-documented predator-prey couple, Atlantic cod (Gadus morhua) and northern shrimp (Pandalus borealis), to test whether the temporal dynamics of these populations are con- sistent with the ''top-down'' or the ''bottom-up'' hypothesis. Eight out of nine regions showed inverse correlations of cod and shrimp biomass supporting the ''top-down'' view. Exceptions occurred only close to the southern range limits of both species. Random-effects meta-analysis showed that shrimp biomass was strongly negatively related to cod biomass, but not to ocean temperature in the North Atlantic Ocean. In contrast, cod biomass was positively related to ocean temperature. The strength of the cod-shrimp relationship, how- ever, declined with increasing mean temperature. These results show that changes in predator populations can have strong effects on prey populations in oceanic food webs, and that the strength of these interactions may be sensitive to changes in mean ocean temperature. This means that the effects of overfishing in the ocean cascade down to lower trophic levels, as has been shown previously for lakes and coastal seas. In order to further investigate these processes, we establish a methodological framework to analyze species interactions from time series data.

Comparison of Bayesian and Maximum Likelihood Bootstrap Measures of Phylogenetic Reliability

Abstract: Owing to the exponential growth of genome databases, phylogenetic trees are now widely used to test a variety of evolutionary hypotheses. Nevertheless, computation time burden limits the application of methods such as maximum likelihood nonparametric bootstrap to assess reliability of evolutionary trees. As an alternative, the much faster Bayesian inference of phylogeny, which expresses branch support as posterior probabilities, has been introduced. However, marked discrepancies exist between nonparametric bootstrap proportions and Bayesian posterior probabilities, leading to difficulties in the interpretation of sometimes strongly conflicting results. As an attempt to reconcile these two indices of node reliability, we apply the nonparametric bootstrap resampling procedure to the Bayesian approach. The correlation between posterior probabilities, bootstrap maximum likelihood percentages, and bootstrapped posterior probabilities was studied for eight highly diverse empirical data sets and were also investigated using experimental simulation. Our results show that the relation between posterior probabilities and bootstrapped maximum likelihood percentages is highly variable but that very strong correlations always exist when Bayesian node support is estimated on bootstrapped character matrices. Moreover, simulations corroborate empirical observations in suggesting that, being more conservative, the bootstrap approach might be less prone to strongly supporting a false phylogenetic hypothesis. Thus, apparent conflicts in topology recovered by the Bayesian approach were reduced after bootstrapping. Both posterior probabilities and bootstrap supports are of great interest to phylogeny as potential upper and lower bounds of node reliability, but they are surely not interchangeable and cannot be directly compared.

The hedgehog signaling network

Abstract: In the hedgehog signaling network, mutations result in various phenotypes, including, among others, holoprosencephaly, nevoid basal cell carcinoma syndrome, Pallister-Hall syndrome, Greig cephalopolysyndactyly, Rubinstein-Taybi syndrome, isolated basal cell carcinoma, and medulloblastoma. Active Hedgehog ligand is double lipid modified with a C-terminal cholesterol moiety and an N-terminal palmitate. Transport active Hedgehog from the signaling cell to the responding cell occurs through three mechanisms: 1). formation of multimeric Hedgehog which makes it soluble; 2). function of Dispatched in releasing the lipid-anchored protein from the signaling cell; and 3). movement across the plasma membrane of the responding cell by Tout-velu-dependent synthesis of heparan sulfate proteoglycan. In the responding cell, active Hedgehog binds to its receptor Patched, a 12-pass transmembrane protein, which frees Smoothened, an adjacent 7-pass transmembrane protein, for downstream signaling. Patched and Smoothened may shuttle oppositely between the plasma membrane and endocytic vesicles in response to active Hedgehog ligand. In downstream signaling, Cubitus interruptus (Gli proteins in vertebrates), Costal 2, Fused, and Suppressor of Fused form a tetrameric complex. Cubitus interruptus is a bifunctional transcription regulator. In the absence of active Hedgehog ligand, a truncated transcriptional repressor is generated that binds target genes and blocks their transcription. In the presence of active Hedgehog ligand, a full length transcriptional activator binds target genes and upregulates their transcription. Target genes include Wingless (Wnt gene family in vertebrates), Decapentaplegic (Bone Morphogenetic Proteins in vertebrates), and Patched. The upregulation of Patched expression, resulting in Patched protein at the cell membrane, sequesters Hedgehog and limits its spread beyond the cells in which it is produced. Thus, a balance is created by the antagonism of Hedgehog and Patched, whose relative concentrations alternate with respect to each other. Many more factors that are essential for the hedgehog signaling network are also discussed: Megalin, Rab23, Hip, GAS1, PKA, GSK3, CK1, Slimb, SAP18, and CBP.

Role modeling in physicians' professional formation: reconsidering an essential but untapped educational strategy

Abstract: Forming technically proficient, professional, and humanistic physicians for the 21st century is no easy task. Mountains of biomedical knowledge must be acquired, diagnostic competence achieved, effective communication skills developed, and a solid and applicable understanding of the practice and role of physicians in society today must be reached. The central experience for learners in this complex and challenging terrain is the "modeling of" and "learning how to be" a caregiver and health professional. Role modeling remains one crucial area where standards are elusive and where repeated negative learning experiences may adversely impact the development of professionalism in medical students and residents. The literature is mainly descriptive, defining the attributes of good role models from both learners and practitioners' perspectives. Because physicians are not "playing a role" as an actor might, but "embodying" different types of roles, the cognitive and behavioral processes associated with successfully internalizing roles (e.g., the good doctor/medical educator) are important. In this article, the authors identify foundational questions regarding role models and professional character formation; describe major social and historical reasons for inattention to character formation in new physicians; draw insights about this important area from ethics and education theory (philosophical inquiry, apprenticeship, situated learning, observational learning, reflective practice); and suggest the practical consequences of this work for faculty recruitment, affirmation, and development.

Do low-income lone mothers compromise their nutrition to feed their children?

Abstract: Background: Women who live in disadvantaged circumstances in Canada exhibit dietary intakes below recommended levels, but their children often do not. One reason for this difference may be that mothers modify their own food intake to spare their children nutritional deprivation. The objective of our study was to document whether or not low-income lone mothers compromise their own diets to feed their children. Methods: We studied 141 low-income lone mothers with at least 2 children under the age of 14 years who lived in Atlantic Canada. Women were identified through community organizations using a variety of recruitment strategies. The women were asked weekly for 1 month to recall their food intake over the previous 24 hours; they also reported their children9s ( n = 333) food intake. Mothers also completed a questionnaire about “food insecurity,” that is, a lack of access to adequate, nutritious food through socially acceptable means, during each interview. Results: Household food insecurity was reported by 78% of mothers during the study month. Mothers9 dietary intakes and the adequacy of intake were consistently poorer than their children9s intake overall and over the course of a month. The difference in adequacy of intake between mothers and children widened from Time 1, when the family had the most money to purchase food, to Time 4, when the family had the least money. The children experienced some improvement in nutritional intake at Time 3, which was possibly related to food purchases for them associated with receipt of the Child Tax Benefit Credit or the Goods and Services Tax Credit. Interpretation: Our study demonstrates that low-income lone mothers compromise their own nutritional intake in order to preserve the adequacy of their children9s diets.

Clinically important change in the visual analog scale after adequate pain control.

Abstract: Objectives: To define the minimum clinically important difference (MCID) for the visual analog scale (VAS) of pain severity by measuring the change in VAS associated with adequate pain control. Methods: The authors conducted a prospective, observational study. Adult emergency department (ED) patients with acute pain (<72 hours) were eligible. Patients rated their pain severity on a 100-mm VAS on presentation and at discharge. Patients were asked if they would accept any analgesic, then if they would accept a parenteral analgesic before treatment. At discharge, they were asked whether they had received adequate pain control. Results: The authors enrolled 143 patients (mean age, 36 years; 54% female). The mean decrease in VAS was -30.0 mm (95% confidence interval [CI] = -36.4 to -23.6) for the 116 of 143 (81%) patients with adequate pain control at discharge vs. -5.7 (95% CI = -11.2 to -0.3) for the 27 with inadequate pain control (p < 0.001). At discharge, the mean VAS was 31.3 mm for those with adequate pain control vs. 55.1 for those without. Mean VAS for the 114 of 143 patients who would accept any analgesics initially was 64.7 vs. 47.1 for the 29 reporting no analgesic need. Initially, 77 patients would accept parenteral analgesics (mean VAS = 72.5 mm). Conclusions: A mean reduction in VAS of 30.0 mm represents a clinically important difference in pain severity that corresponds to patients' perception of adequate pain control. Defining MCID based on adequate analgesic control rather than minimal detectable change may be more appropriate for future analgesic trials, when effective treatments for acute pain exist.

Time scale and other invariants of integrative mechanical behavior in living cells.

Abstract: In dealing with systems as complex as the cytoskeleton, we need organizing principles or, short of that, an empirical framework into which these systems fit. We report here unexpected invariants of cytoskeletal behavior that comprise such an empirical framework. We measured elastic and frictional moduli of a variety of cell types over a wide range of time scales and using a variety of biological interventions. In all instances elastic stresses dominated at frequencies below 300 Hz, increased only weakly with frequency, and followed a power law; no characteristic time scale was evident. Frictional stresses paralleled the elastic behavior at frequencies below 10 Hz but approached a Newtonian viscous behavior at higher frequencies. Surprisingly, all data could be collapsed onto master curves, the existence of which implies that elastic and frictional stresses share a common underlying mechanism. Taken together, these findings define an unanticipated integrative framework for studying protein interactions within the complex microenvironment of the cell body, and appear to set limits on what can be predicted about integrated mechanical behavior of the matrix based solely on cytoskeletal constituents considered in isolation. Moreover, these observations are consistent with the hypothesis that the cytoskeleton of the living cell behaves as a soft glassy material, wherein cytoskeletal proteins modulate cell mechanical properties mainly by changing an effective temperature of the cytoskeletal matrix. If so, then the effective temperature becomes an easily quantified determinant of the ability of the cytoskeleton to deform, flow, and reorganize.

Cutting edge: distinct Toll-like receptor 2 activators selectively induce different classes of mediator production from human mast cells.

Abstract: Mast cells play a critical role in host defense against bacterial infection. Murine mast cells produce cytokines in response to bacterial peptidoglycan and LPS via Toll-like receptor (TLR) TLR2- and TLR4-dependent mechanisms. The expression of TLRs by human mast cells and responses to known TLR activators was examined. Human mast cells expressed mRNA for TLR1, TLR2, and TLR6 but not TLR4. Bacterial peptidoglycan and yeast zymosan were potent inducers of GM-CSF and IL-1β and also induced substantial short-term cysteinyl leukotriene generation. In contrast, a synthetic triacylated lipopeptide induced short-term degranulation but failed to induce cysteinyl leukotriene production. The TLR4 activator Escherichia coli LPS did not induce a GM-CSF, IL-1β leukotriene, or degranulation response. These data demonstrate highly selective production of different classes of mast cell mediators in response to distinct TLR activators of potential importance to the host response to bacterial or fungal pathogens.

Topical and Peripherally Acting Analgesics

Abstract: Acute nociceptive, inflammatory, and neuropathic pain all depend to some degree on the peripheral activation of primary sensory afferent neurons. The localized peripheral administration of drugs, such as by topical application, can potentially optimize drug concentrations at the site of origin of the pain, while leading to lower systemic levels and fewer adverse systemic effects, fewer drug interactions, and no need to titrate doses into a therapeutic range compared with systemic administration. Primary sensory afferent neurons can be activated by a range of inflammatory mediators such as prostanoids, bradykinin, ATP, histamine, and serotonin, and inhibiting their actions represents a strategy for the development of analgesics. Peripheral nerve endings also express a variety of inhibitory neuroreceptors such as opioid, alpha-adrenergic, cholinergic, adenosine and cannabinoid receptors, and agonists for these receptors also represent viable targets for drug development. At present, topical and other forms of peripheral administration of nonsteroidal anti-inflammatory drugs, opioids, capsaicin, local anesthetics, and alpha-adrenoceptor agonists are being used in a variety of clinical states. There also are some clinical data on the use of topical antidepressants and glutamate receptor antagonists. There are preclinical data supporting the potential for development of local formulations of adenosine agonists, cannabinoid agonists, cholinergic ligands, cytokine antagonists, bradykinin antagonists, ATP antagonists, biogenic amine antagonists, neuropeptide antagonists, and agents that alter the availability of nerve growth factor. Given that activation of sensory neurons involves multiple mediators, combinations of agents targeting different mechanisms may be particularly useful. Topical analgesics represent a promising area for future drug development.

Eat and run? The hunger/satiation hypothesis in vertical migration: history, evidence and consequences

Abstract: The study of vertical migrations in aquatic organisms has a long and colourful history, much of it to do with the effects of changing sampling technology on our understanding of the phenomenon. However, the overwhelming majority of such studies carried out today still depend on detecting differences in vertical distribution profiles during some course of time, or acoustic echoes of migrating bands of organisms. These can not distinguish migratory activity of individual organisms, but can only assess net results of mass transfers of populations, which may integrate many individual migrations. This is an important distinction, for without knowing the actual movements of individuals it seems unlikely that we will be able to understand their causes, nor the effects of vertical migrations on the environment or on the migrators themselves. This review examines evidence for individual vertical movements gathered from 'tracers', mainly gut contents, and reviews the evidence for the hypothesis that such movements are in fact driven by hunger and satiation. The more recently appreciated vertical migrations of phytoplankters and their similarities in form and driving forces to those of zooplankton and nekton are also discussed. Finally, the role of vertical migrators in vertical fluxes of materials is discussed, along with the consequences of satiation-driven descent for such estimates.

Zeolite-Confined Nano-RuO2: A Green, Selective, and Efficient Catalyst for Aerobic Alcohol Oxidation

Abstract: The development of green, selective, and efficient catalysts, which can aerobically oxidize a variety of alcohols to their corresponding aldehydes and ketones, is of both economic and environmental significance. We report here the synthesis of a novel aerobic oxidation catalyst, a zeolite-confined nanometer-sized RuO(2) (RuO(2)-FAU), by a one-step hydrothermal method. Using the spatial constraints of the rigid zeolitic framework, we sucessfully incorporated RuO(2) nanoparticles (1.3 +/- 0.2 nm) into the supercages of faujasite zeolite. Ru K-edge X-ray absorption fine structure results indicate that the RuO(2) nanoclusters anchored in the zeolite are structurally similar to highly hydrous RuO(2); that is, there is a two-dimensional structure of independent chains, in which RuO(6) octahedra are connected together by two shared oxygen atoms. In our preliminary catalytic studies, we find that the RuO(2) nanoclusters exhibit extraordinarily high activity and selectivity in the aerobic oxidation of alcohols under mild conditions, for example, air and ambient pressure. The physically trapped RuO(2) nanoclusters cannot diffuse out of the relatively narrow channels/pores of the zeolite during the catalytic process, making the catalyst both stable and reusable.