Showing papers by "University of Alberta published in 2008"

DrugBank: a knowledgebase for drugs, drug actions and drug targets

Abstract: DrugBank is a richly annotated resource that combines detailed drug data with comprehensive drug target and drug action information. Since its first release in 2006, DrugBank has been widely used to facilitate in silico drug target discovery, drug design, drug docking or screening, drug metabolism prediction, drug interaction prediction and general pharmaceutical education. The latest version of DrugBank (release 2.0) has been expanded significantly over the previous release. With approximately 4900 drug entries, it now contains 60% more FDA-approved small molecule and biotech drugs including 10% more 'experimental' drugs. Significantly, more protein target data has also been added to the database, with the latest version of DrugBank containing three times as many non-redundant protein or drug target sequences as before (1565 versus 524). Each DrugCard entry now contains more than 100 data fields with half of the information being devoted to drug/chemical data and the other half devoted to pharmacological, pharmacogenomic and molecular biological data. A number of new data fields, including food-drug interactions, drug-drug interactions and experimental ADME data have been added in response to numerous user requests. DrugBank has also significantly improved the power and simplicity of its structure query and text query searches. DrugBank is available at http://www.drugbank.ca.

Prevalence and clinical implications of sarcopenic obesity in patients with solid tumours of the respiratory and gastrointestinal tracts: a population-based study.

Abstract: Summary Background Emerging evidence on body composition suggests that sarcopenic obesity (obesity with depleted muscle mass) might be predictive of morbidity and mortality in non-malignant disease and also of toxicity to chemotherapy. We aimed to assess the prevalence and clinical implications of sarcopenic obesity in patients with cancer. Methods Between Jan 13, 2004, and Jan 19, 2007, 2115 patients with solid tumours of the respiratory or gastrointestinal tract from a cancer treatment centre serving northern Alberta, Canada, were identified. Available lumbar CT images of the obese patients were analysed for total skeletal muscle cross-sectional area; these values were also used to estimate total body fat-free mass (FFM). Findings Of the 2115 patients initially identified, 325 (15%) were classified as obese (body-mass index [BMI] ≥30). Of these obese patients, 250 had CT images that met the criteria for analysis. The remaining 75 patients were recorded as without assessable scans. Obese patients had a wide range of muscle mass. Sex-specific cut-offs that defined a significant association between low muscle mass with mortality were ascertained by optimum stratification analysis: 38 (15%) of 250 patients who had assessable CT images that met the criteria for analysis were below these cut-offs and were classified as having sarcopenia. Sarcopenic obesity was associated with poorer functional status compared with obese patients who did not have sarcopenia (p=0·009), and was an independent predictor of survival (hazard ratio [HR] 4·2 [95% CI 2·4–7·2], p r 2 =0·37). Assuming that FFM represents the volume of distribution of many cytotoxic chemotherapy drugs, we estimated that individual variation in FFM could account for up to three-times variation in effective volume of distribution for chemotherapy administered per unit body-surface area, in this population. Interpretation This study provides evidence of the great variability of body composition in patients with cancer and links body composition, especially sarcopenic obesity, to clinical implications such as functional status, survival, and potentially, chemotherapy toxicity. Funding Canadian Institutes of Health Research (Ottawa, ON, Canada), Alberta Cancer Board (Edmonton, AB, Canada), and Translational Research Training in Cancer (Edmonton, AB, Canada).

Analyzing linguistic data : a practical introduction to statistics using R

Abstract: Statistical analysis is a useful skill for linguists and psycholinguists, allowing them to understand the quantitative structure of their data This textbook provides a straightforward introduction to the statistical analysis of language Designed for linguists with a non-mathematical background, it clearly introduces the basic principles and methods of statistical analysis, using 'R', the leading computational statistics programme The reader is guided step-by-step through a range of real data sets, allowing them to analyse acoustic data, construct grammatical trees for a variety of languages, quantify register variation in corpus linguistics, and measure experimental data using state-of-the-art models The visualization of data plays a key role, both in the initial stages of data exploration and later on when the reader is encouraged to criticize various models Containing over 40 exercises with model answers, this book will be welcomed by all linguists wishing to learn more about working with and presenting quantitative data

Progress in carbon dioxide separation and capture: a review.

Abstract: This article reviews the progress made in CO2 separation and capture research and engineering. Various technologies, such as absorption, adsorption, and membrane separation, are thoroughly discussed. New concepts such as chemical-looping combustion and hydrate-based separation are also introduced briefly. Future directions are suggested. Sequestration methods, such as forestation, ocean fertilization and mineral carbonation techniques are also covered. Underground injection and direct ocean dump are not covered.

Structural variation of chromosomes in autism spectrum disorder.

Abstract: Structural variation (copy number variation [CNV] including deletion and duplication, translocation, inversion) of chromosomes has been identified in some individuals with autism spectrum disorder (ASD), but the full etiologic role is unknown. We performed genome-wide assessment for structural abnormalities in 427 unrelated ASD cases via single-nucleotide polymorphism microarrays and karyotyping. With microarrays, we discovered 277 unbalanced CNVs in 44% of ASD families not present in 500 controls (and re-examined in another 1152 controls). Karyotyping detected additional balanced changes. Although most variants were inherited, we found a total of 27 cases with de novo alterations, and in three (11%) of these individuals, two or more new variants were observed. De novo CNVs were found in ∼7% and ∼2% of idiopathic families having one child, or two or more ASD siblings, respectively. We also detected 13 loci with recurrent/overlapping CNV in unrelated cases, and at these sites, deletions and duplications affecting the same gene(s) in different individuals and sometimes in asymptomatic carriers were also found. Notwithstanding complexities, our results further implicate the SHANK3-NLGN4-NRXN1 postsynaptic density genes and also identify novel loci at DPP6-DPP10-PCDH9 (synapse complex), ANKRD11, DPYD, PTCHD1, 15q24, among others, for a role in ASD susceptibility. Our most compelling result discovered CNV at 16p11.2 (p = 0.002) (with characteristics of a genomic disorder) at ∼1% frequency. Some of the ASD regions were also common to mental retardation loci. Structural variants were found in sufficiently high frequency influencing ASD to suggest that cytogenetic and microarray analyses be considered in routine clinical workup.

Paracrine factors of mesenchymal stem cells recruit macrophages and endothelial lineage cells and enhance wound healing.

Abstract: Bone marrow derived mesenchymal stem cells (BM-MSCs) have been shown to enhance wound healing; however, the mechanisms involved are barely understood. In this study, we examined paracrine factors released by BM-MSCs and their effects on the cells participating in wound healing compared to those released by dermal fibroblasts. Analyses of BM-MSCs with Real-Time PCR and of BM-MSC-conditioned medium by antibody-based protein array and ELISA indicated that BM-MSCs secreted distinctively different cytokines and chemokines, such as greater amounts of VEGF-alpha, IGF-1, EGF, keratinocyte growth factor, angiopoietin-1, stromal derived factor-1, macrophage inflammatory protein-1alpha and beta and erythropoietin, compared to dermal fibroblasts. These molecules are known to be important in normal wound healing. BM-MSC-conditioned medium significantly enhanced migration of macrophages, keratinocytes and endothelial cells and proliferation of keratinocytes and endothelial cells compared to fibroblast-conditioned medium. Moreover, in a mouse model of excisional wound healing, where concentrated BM-MSC-conditioned medium was applied, accelerated wound healing occurred compared to administration of pre-conditioned or fibroblast-conditioned medium. Analysis of cell suspensions derived from the wound by FACS showed that wounds treated with BM-MSC-conditioned medium had increased proportions of CD4/80-positive macrophages and Flk-1-, CD34- or c-kit-positive endothelial (progenitor) cells compared to wounds treated with pre-conditioned medium or fibroblast-conditioned medium. Consistent with the above findings, immunohistochemical analysis of wound sections showed that wounds treated with BM-MSC-conditioned medium had increased abundance of macrophages. Our results suggest that factors released by BM-MSCs recruit macrophages and endothelial lineage cells into the wound thus enhancing wound healing.

Eutrophication of lakes cannot be controlled by reducing nitrogen input: Results of a 37-year whole-ecosystem experiment

Abstract: Lake 227, a small lake in the Precambrian Shield at the Experimental Lakes Area (ELA), has been fertilized for 37 years with constant annual inputs of phosphorus and decreasing inputs of nitrogen to test the theory that controlling nitrogen inputs can control eutrophication. For the final 16 years (1990-2005), the lake was fertilized with phosphorus alone. Reducing nitrogen inputs increasingly favored nitrogen-fixing cyanobacteria as a response by the phytoplankton community to extreme seasonal nitrogen limitation. Nitrogen fixation was sufficient to allow biomass to continue to be produced in proportion to phosphorus, and the lake remained highly eutrophic, despite showing indications of extreme nitrogen limitation seasonally. To reduce eutrophication, the focus of management must be on decreasing inputs of phosphorus.

The status of the world's land and marine mammals: diversity, threat, and knowledge

Abstract: Knowledge of mammalian diversity is still surprisingly disparate, both regionally and taxonomically. Here, we present a comprehensive assessment of the conservation status and distribution of the world's mammals. Data, compiled by 1700+ experts, cover all 5487 species, including marine mammals. Global macroecological patterns are very different for land and marine species but suggest common mechanisms driving diversity and endemism across systems. Compared with land species, threat levels are higher among marine mammals, driven by different processes (accidental mortality and pollution, rather than habitat loss), and are spatially distinct (peaking in northern oceans, rather than in Southeast Asia). Marine mammals are also disproportionately poorly known. These data are made freely available to support further scientific developments and conservation action.

The CGView Server: a comparative genomics tool for circular genomes

Abstract: The CGView Server generates graphical maps of circular genomes that show sequence features, base composition plots, analysis results and sequence similarity plots. Sequences can be supplied in raw, FASTA, GenBank or EMBL format. Additional feature or analysis information can be submitted in the form of GFF (General Feature Format) files. The server uses BLAST to compare the primary sequence to up to three comparison genomes or sequence sets. The BLAST results and feature information are converted to a graphical map showing the entire sequence, or an expanded and more detailed view of a region of interest. Several options are included to control which types of features are displayed and how the features are drawn. The CGView Server can be used to visualize features associated with any bacterial, plasmid, chloroplast or mitochondrial genome, and can aid in the identification of conserved genome segments, instances of horizontal gene transfer, and differences in gene copy number. Because a collection of sequences can be used in place of a comparison genome, maps can also be used to visualize regions of a known genome covered by newly obtained sequence reads. The CGView Server can be accessed at http://stothard.afns.ualberta.ca/cgview_server/

The diploid genome sequence of an Asian individual.

Abstract: Here we present the first diploid genome sequence of an Asian individual. The genome was sequenced to 36-fold average coverage using massively parallel sequencing technology. We aligned the short reads onto the NCBI human reference genome to 99.97% coverage, and guided by the reference genome, we used uniquely mapped reads to assemble a high-quality consensus sequence for 92% of the Asian individual's genome. We identified approximately 3 million single-nucleotide polymorphisms (SNPs) inside this region, of which 13.6% were not in the dbSNP database. Genotyping analysis showed that SNP identification had high accuracy and consistency, indicating the high sequence quality of this assembly. We also carried out heterozygote phasing and haplotype prediction against HapMap CHB and JPT haplotypes (Chinese and Japanese, respectively), sequence comparison with the two available individual genomes (J. D. Watson and J. C. Venter), and structural variation identification. These variations were considered for their potential biological impact. Our sequence data and analyses demonstrate the potential usefulness of next-generation sequencing technologies for personal genomics.

Effects of alteplase beyond 3 h after stroke in the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET): a placebo-controlled randomised trial.

Abstract: Summary Background Whether intravenous tissue plasminogen activator (alteplase) is effective beyond 3 h after onset of acute ischaemic stroke is unclear. We aimed to test whether alteplase given 3–6 h after stroke onset promotes reperfusion and attenuates infarct growth in patients who have a mismatch in perfusion-weighted MRI (PWI) and diffusion-weighted MRI (DWI). Methods We prospectively and randomly assigned 101 patients to receive alteplase or placebo 3–6 h after onset of ischaemic stroke. PWI and DWI were done before and 3–5 days after therapy, with T2-weighted MRI at around day 90. The primary endpoint was infarct growth between baseline DWI and the day 90 T2 lesion in mismatch patients. Major secondary endpoints were reperfusion, good neurological outcome, and good functional outcome. Patients, caregivers, and investigators were unaware of treatment allocations. Primary analysis was per protocol. This study is registered with ClinicalTrials.gov, number NCT00238537. Findings We randomly assigned 52 patients to alteplase and 49 patients to placebo. Mean age was 71·6 years, and median score on the National Institutes of Health stroke scale was 13. 85 of 99 (86%) patients had mismatch of PWI and DWI. The geometric mean infarct growth (exponential of the mean log of relative growth) was 1·24 with alteplase and 1·78 with placebo (ratio 0·69, 95% CI 0·38–1·28; Student's t test p=0·239); the median relative infarct growth was 1·18 with alteplase and 1·79 with placebo (ratio 0·66, 0·36–0·92; Wilcoxon's test p=0·054). Reperfusion was more common with alteplase than with placebo and was associated with less infarct growth (p=0·001), better neurological outcome (p Interpretation Alteplase was non-significantly associated with lower infarct growth and significantly associated with increased reperfusion in patients who had mismatch. Because reperfusion was associated with improved clinical outcomes, phase III trials beyond 3 h after treatment are warranted. Funding National Health and Medical Research Council, Australia; National Stroke Foundation, Australia; Heart Foundation of Australia.

The burden and determinants of neck pain in the general population: results of the Bone and Joint Decade 2000-2010 Task Force on Neck Pain and Its Associated Disorders.

Abstract: STUDY DESIGN: Best evidence synthesis. OBJECTIVE: To undertake a best evidence synthesis of the published evidence on the burden and determinants of neck pain and its associated disorders in the general population. SUMMARY OF BACKGROUND DATA: The evidence on burden and determinants of neck has not previously been summarized. METHODS: The Bone and Joint Decade 2000-2010 Task Force on Neck Pain and Its Associated Disorders performed a systematic search and critical review of literature published between 1980 and 2006 to assemble the best evidence on neck pain. Studies meeting criteria for scientific validity were included in a best evidence synthesis. RESULTS: We identified 469 studies on burden and determinants of neck pain, and judged 249 to be scientifically admissible; 101 articles related to the burden and determinants of neck pain in the general population. Incidence ranged from 0.055 per 1000 person years (disc herniation with radiculopathy) to 213 per 1000 persons (self-reported neck pain). Incidence of neck injuries during competitive sports ranged from 0.02 to 21 per 1000 exposures. The 12-month prevalence of pain typically ranged between 30% and 50%; the 12-month prevalence of activity-limiting pain was 1.7% to 11.5%. Neck pain was more prevalent among women and prevalence peaked in middle age. Risk factors for neck pain included genetics, poor psychological health, and exposure to tobacco. Disc degeneration was not identified as a risk factor. The use of sporting gear (helmets, face shields) to prevent other types of injury was not associated with increased neck injuries in bicycling, hockey, or skiing. CONCLUSION: Neck pain is common. Nonmodifiable risk factors for neck pain included age, gender, and genetics. Modifiable factors included smoking, exposure to tobacco, and psychological health. Disc degeneration was not identified as a risk factor. Future research should concentrate on longitudinal designs exploring preventive strategies and modifiable risk factors for neck pain. Language: en

Eosinophils: Biological Properties and Role in Health and Disease

Abstract: Eosinophils are pleiotropic multifunctional leukocytes involved in initiation and propagation of diverse inflammatory responses, as well as modulators of innate and adaptive immunity. In this review, the biology of eosinophils is summarized, focusing on transcriptional regulation of eosinophil differentiation, characterization of the growing properties of eosinophil granule proteins, surface proteins and pleiotropic mediators, and molecular mechanisms of eosinophil degranulation. New views on the role of eosinophils in homeostatic function are examined, including developmental biology and innate and adaptive immunity (as well as their interaction with mast cells and T cells) and their proposed role in disease processes including infections, asthma, and gastrointestinal disorders. Finally, strategies for targeted therapeutic intervention in eosinophil-mediated mucosal diseases are conceptualized.

Perspectives on China's outward foreign direct investment

Abstract: Recent economic data reveal that, at the infant stage, China's outward foreign direct investment (FDI) is biased towards tax havens and Southeast Asian countries and are mostly conducted by state-controlled enterprises with government sanctioned monopoly status. Further examination of China's savings rate, corporate ownership structures, and bank-dominated capital allocation suggests that, although a surge in China's outward FDI might be economically sensible, the most active players have incentives to conduct excessive outward FDI while capital constraints limit players that most likely have value-creating FDI opportunities. We then discuss plausible firm-level justifications for China's outward FDI, its importance, and promising avenues for further research.

Reducing Uncertainties About the Effects of Chemoradiotherapy for Cervical Cancer: A Systematic Review and Meta-Analysis of Individual Patient Data From 18 Randomized Trials

Abstract: Background After a 1999 National Cancer Institute (NCI) clinical alert was issued, chemoradiotherapy has become widely used in treating women with cervical cancer. Two subsequent systematic reviews found that interpretation of the benefits was complicated, and some important clinical questions were unanswered. Patients and Methods We initiated a meta-analysis seeking updated individual patient data from all randomized trials to assess the effect of chemoradiotherapy on all outcomes. We prespecified analyses to investigate whether the effect of chemoradiotherapy differed by trial or patient characteristics. Results On the basis of 13 trials that compared chemoradiotherapy versus the same radiotherapy, there was a 6% improvement in 5-year survival with chemoradiotherapy (hazard ratio [HR] = 0.81, P <.001). A larger survival benefit was seen for the two trials in which chemotherapy was administered after chemoradiotherapy. There was a significant survival benefit for both the group of trials that used platinum-based (HR = 0.83, P = .017) and non-platinum-based (HR = 0.77, P <.009) chemoradiotherapy, but no evidence of a difference in the size of the benefit by radiotherapy or chemotherapy dose or scheduling was seen. Chemoradiotherapy also reduced local and distant recurrence and progression and improved disease-free survival. There was a suggestion of a difference in the size of the survival benefit with tumor stage, but not across other patient subgroups. Acute hematologic and GI toxicity was increased with chemoradiotherapy, but data were too sparse for an analysis of late toxicity. Conclusion These results endorse the recommendations of the NCI alert, but also demonstrate their applicability to all women and a benefit of non-platinum-based chemoradiotherapy. Furthermore, although these results suggest an additional benefit from adjuvant chemotherapy, this requires testing in randomized trials.

Scales to assess the quality of randomized controlled trials: a systematic review.

Abstract: Background and Purpose: The methodological quality of randomized controlled trials (RCTs) is commonly evaluated in order to assess the risk of biased estimates of treatment effects. The purpose of this systematic review was to identify scales used to evaluate the methodological quality of RCTs in health care research and summarize the content, construction, development, and psychometric properties of these scales. Methods: Extensive electronic database searches, along with a manual search, were performed. Results: One hundred five relevant studies were identified. They accounted for 21 scales and their modifications. The majority of scales had not been rigorously developed or tested for validity and reliability. The Jadad Scale presented the best validity and reliability evidence; however, its validity for physical therapy trials has not been supported. Discussion and Conclusion: Many scales are used to evaluate the methodological quality of RCTs, but most of these scales have not been adequately developed and have not been adequately tested for validity and reliability. A valid and reliable scale for the assessment of the methodological quality of physical therapy trials needs to be developed.

Assessing Validity of ICD-9-CM and ICD-10 Administrative Data in Recording Clinical Conditions in a Unique Dually Coded Database

Abstract: The World Health Organization adopted the first version of the International Classification of Diseases (ICD) in 1900 to internationally monitor and compare mortality statistics and causes of death. Since then, the classification has been revised periodically to accommodate new knowledge of disease and health. The sixth revision, published in 1949, was more radical than the previous five revisions because this edition made it possible to record information from patient charts to compile morbidity statistics. Subsequent revisions were made in 1958 (7th Edition), in 1968 (8th Edition), and in 1979 (9th Edition). The United States modified ICD-9 by specifying many categories and extending coding rubrics to describe the clinical picture in more detail. These modifications resulted in the publication of ICD-9 Clinical Modification (ICD-9-CM) in 1979 for coding diagnoses in patient charts (Commission on Professional and Hospital Activities 1986). The latest version, ICD-10, was introduced in 1992 (World Health Organization 1992). The major differences between the ICD-10 and ICD-9-CM coding systems are: (1) the tabular list in ICD-10 has 21 categories of disease compared with 19 categories in ICD-9-CM and the category of diseases of the nervous system and sense organs in ICD-9-CM is divided into three categories in ICD-10, including diseases of the nervous system, diseases of the eye and adnexa, and diseases of the ear and mastoid process; and (2) the codes in ICD-10 are alphanumeric while codes in ICD-9-CM are numeric. Each code in ICD-10 starts with a letter (i.e., A–Z), followed by two numeric digits, a decimal, and a digit (e.g., acute bronchiolitis due to respiratory syncytial virus is J21.0). In contrast, codes in ICD-9-CM begin with three digit numbers (i.e., 001–999), that are followed by a decimal and up to two digits (e.g., acute bronchiolitis due to respiratory syncytial virus is 466.11). Canada, Australia, Germany, and other countries have enhanced ICD-10 by adding more specific codes and released country-specific ICD-10 versions, such as ICD-10-Canada (ICD-10-CA; Canadian Institute for Health Information 2003). However, ICD-10-CA has maintained its comparability with ICD-10. The basic ICD-10 structure, scope, content, and definition of existing codes are not altered in ICD-10-CA. This means that none of the ICD-10 codes are relocated or deleted. ICD-10-CA mainly extends code character levels, from third and fourth levels of ICD-10 to fourth, fifth, or sixth character levels (e.g., from I15.0 for renovascular hypertension to I15.00 for benign renovascular hypertension and I15.01 for malignant renovascular hypertension). A few additions of third- and fourth-level codes were also included in ICD-10-CA in a manner consistent with the existing classification. All of these additional codes are indicated with red maple leaf symbols in ICD-10-CA coding manuals. To continuously study the health care system and investigate or monitor population health status with ICD-10 data, it is imperative to assess errors that could occur in the process of creating administrative data due to the introduction of the new coding system, ICD-10. We conducted this study to evaluate the validity of ICD-10 administrative hospital discharge data and to determine whether there were improvements in the validity compared with the validity of ICD-9-CM data. To achieve this aim, we reviewed randomly selected charts coded using ICD-10 at four Canadian teaching hospitals, determined the presence or absence of recorded conditions, and then separately recoded the same charts using ICD-9-CM. Then we assessed the agreement between originally coded ICD-10 administrative and chart review data, and the recoded ICD-9-CM administrative data and chart review data for recording the same conditions. This permitted us to compare the accuracy of ICD-10 data relative to the chart review data, with the accuracy of ICD-9-CM data relative to the chart review data for these conditions.

Relation Between Red Blood Cell Distribution Width and Cardiovascular Event Rate in People With Coronary Disease

Abstract: Background— Higher levels of red blood cell distribution width (RDW) may be associated with adverse outcomes in patients with heart failure. We examined the association between RDW and the risk of all-cause mortality and adverse cardiovascular outcomes in a population of people with coronary disease who were free of heart failure at baseline. Methods and Results— We performed a post hoc analysis of data from the Cholesterol and Recurrent Events study. Baseline RDW was measured in 4111 participants who were randomized to receive pravastatin 40 mg daily or placebo and followed for a median of 59.7 months. We used Cox proportional hazards models to examine the association between RDW and adverse clinical outcomes. During nearly 60 months of follow-up, 376 participants died. A significant association was noted between baseline RDW level and the adjusted risk of all-cause mortality (hazard ratio per percent increase in RDW, 1.14; 95% confidence interval, 1.05 to 1.24). After categorization based on quartile of...

A comparative analysis of the efficiency of change metrics and static code attributes for defect prediction

Abstract: In this paper we present a comparative analysis of the predictive power of two different sets of metrics for defect prediction. We choose one set of product related and one set of process related software metrics and use them for classifying Java files of the Eclipse project as defective respective defect-free. Classification models are built using three common machine learners: logistic regression, naive Bayes, and decision trees. To allow different costs for prediction errors we perform cost-sensitive classification, which proves to be very successful: >75% percentage of correctly classified files, a recall of >80%, and a false positive rate <30%. Results indicate that for the Eclipse data, process metrics are more efficient defect predictors than code metrics.

Course and Prognostic Factors for Neck Pain in Whiplash-Associated Disorders (WAD) : Results of the Bone and Joint Decade 2000-2010 Task Force on Neck Pain and Its Associated Disorders

Abstract: STUDY DESIGN: Best evidence synthesis. OBJECTIVE: To perform a best evidence synthesis on the course and prognostic factors for neck pain and its associated disorders in Grades I-III whiplash-associated disorders (WAD). SUMMARY OF BACKGROUND DATA: Knowledge of the course of recovery of WAD guides expectations for recovery. Identifying prognostic factors assists in planning management and intervention strategies and effective compensation policies to decrease the burden of WAD. METHODS: The Bone and Joint Decade 2000-2010 Task Force on Neck Pain and its Associated Disorders (Neck Pain Task Force) conducted a critical review of the literature published between 1980 and 2006 to assemble the best evidence on neck pain and its associated disorders. Studies meeting criteria for scientific validity were included in a best evidence synthesis. RESULTS: We found 226 articles related to course and prognostic factors in neck pain and its associated disorders. After a critical review, 70 (31%) were accepted on scientific merit; 47 of these studies related to course and prognostic factors in WAD. The evidence suggests that approximately 50% of those with WAD will report neck pain symptoms 1 year after their injuries. Greater initial pain, more symptoms, and greater initial disability predicted slower recovery. Few factors related to the collision itself (for example, direction of the collision, headrest type) were prognostic; however, postinjury psychological factors such as passive coping style, depressed mood, and fear of movement were prognostic for slower or less complete recovery. There is also preliminary evidence that the prevailing compensation system is prognostic for recovery in WAD. CONCLUSION: The Neck Pain Task Force undertook a best evidence synthesis to establish a baseline of the current best evidence on the course and prognosis for WAD. Recovery of WAD seems to be multifactorial. Language: en

Institutional rationality and practice variation: New directions in the institutional analysis of practice

Abstract: In this paper, I highlight how popular understandings of neoinstitutionalism as a theory of isomorphism need to be revised as institutionalists have shifted attention towards the study of organizational heterogeneity. As part of this shift, old emphases on arational mimicry and stability have been replaced with new emphases on institutional rationality and ongoing struggle and change. I discuss these new directions and the implications for the study of accounting practice. I argue that given recent efforts by institutionalists to account for actors and practice diversity, there is an important opportunity for dialogue with practice theorists, such as those drawing on Actor Network Theory, and the creation of a more comprehensive approach to the study of practice that attends to both institutional and micro-processual dynamics.

Facilitated PCI in patients with ST-elevation myocardial infarction.

Abstract: In this international, double-blind, placebo-controlled study, we randomly assigned patients with ST-segment elevation myocardial infarction who presented 6 hours or less after the onset of symptoms to receive combination-facilitated PCI, abciximabfacilitated PCI, or primary PCI. All patients received unfractionated heparin or enoxaparin before PCI and a 12-hour infusion of abciximab after PCI. The primary end point was the composite of death from all causes, ventricular fibrillation occurring more than 48 hours after randomization, cardiogenic shock, and congestive heart failure during the first 90 days after randomization. Results A total of 2452 patients were randomly assigned to a treatment group. Significantly more patients had early ST-segment resolution with combination-facilitated PCI (43.9%) than with abciximab-facilitated PCI (33.1%) or primary PCI (31.0%; P = 0.01 and P = 0.003, respectively). The primary end point occurred in 9.8%, 10.5%, and 10.7% of the patients in the combination-facilitated PCI group, abciximab-facilitated PCI group, and primary-PCI group, respectively (P = 0.55); 90-day mortality rates were 5.2%, 5.5%, and 4.5%, respectively (P = 0.49). Conclusions Neither facilitation of PCI with reteplase plus abciximab nor facilitation with abciximab alone significantly improved the clinical outcomes, as compared with abciximab given at the time of PCI, in patients with ST-segment elevation myocardial infarction. (ClinicalTrials.gov number, NCT00046228.)