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Showing papers by "University of Calgary published in 2006"


Journal ArticleDOI
TL;DR: A model of mindfulness is proposed, in an effort to elucidate potential mechanisms to explain how mindfulness affects positive change and potential implications and future directions for the empirical study of mechanisms involved in mindfulness are addressed.
Abstract: Recently, the psychological construct mindfulness has received a great deal of attention. The majority of research has focused on clinical studies to evaluate the efficacy of mindfulness-based interventions. This line of research has led to promising data suggesting mindfulness-based interventions are effective for treatment of both psychological and physical symptoms. However, an equally important direction for future research is to investigate questions concerning mechanisms of action underlying mindfulness-based interventions. This theoretical paper proposes a model of mindfulness, in an effort to elucidate potential mechanisms to explain how mindfulness affects positive change. Potential implications and future directions for the empirical study of mechanisms involved in mindfulness are addressed.

2,895 citations


Journal ArticleDOI
TL;DR: In this article, eleven coupled climate-carbon cycle models were used to study the coupling between climate change and the carbon cycle. But, there was still a large uncertainty on the magnitude of these sensitivities.
Abstract: Eleven coupled climate–carbon cycle models used a common protocol to study the coupling between climate change and the carbon cycle. The models were forced by historical emissions and the Intergovernmental Panel on Climate Change (IPCC) Special Report on Emissions Scenarios (SRES) A2 anthropogenic emissions of CO2 for the 1850–2100 time period. For each model, two simulations were performed in order to isolate the impact of climate change on the land and ocean carbon cycle, and therefore the climate feedback on the atmospheric CO2 concentration growth rate. There was unanimous agreement among the models that future climate change will reduce the efficiency of the earth system to absorb the anthropogenic carbon perturbation. A larger fraction of anthropogenic CO2 will stay airborne if climate change is accounted for. By the end of the twenty-first century, this additional CO2 varied between 20 and 200 ppm for the two extreme models, the majority of the models lying between 50 and 100 ppm. The higher CO2 levels led to an additional climate warming ranging between 0.1° and 1.5°C. All models simulated a negative sensitivity for both the land and the ocean carbon cycle to future climate. However, there was still a large uncertainty on the magnitude of these sensitivities. Eight models attributed most of the changes to the land, while three attributed it to the ocean. Also, a majority of the models located the reduction of land carbon uptake in the Tropics. However, the attribution of the land sensitivity to changes in net primary productivity versus changes in respiration is still subject to debate; no consensus emerged among the models.

2,630 citations


Journal ArticleDOI
TL;DR: Improved outcomes for severely burned patients have been attributed to medical advances in fluid resuscitation, nutritional support, pulmonary and burn wound care, and infection control practices.
Abstract: Burns are one of the most common and devastating forms of trauma. Patients with serious thermal injury require immediate specialized care in order to minimize morbidity and mortality. Significant thermal injuries induce a state of immunosuppression that predisposes burn patients to infectious complications. A current summary of the classifications of burn wound infections, including their diagnosis, treatment, and prevention, is given. Early excision of the eschar has substantially decreased the incidence of invasive burn wound infection and secondary sepsis, but most deaths in severely burn-injured patients are still due to burn wound sepsis or complications due to inhalation injury. Burn patients are also at risk for developing sepsis secondary to pneumonia, catheter-related infections, and suppurative thrombophlebitis. The introduction of silver-impregnated devices (e.g., central lines and Foley urinary catheters) may reduce the incidence of nosocomial infections due to prolonged placement of these devices. Improved outcomes for severely burned patients have been attributed to medical advances in fluid resuscitation, nutritional support, pulmonary and burn wound care, and infection control practices.

1,627 citations


Journal ArticleDOI
TL;DR: Adalimumab was superior to placebo for induction of remission in patients with moderate to severe Crohn's disease naive to anti-TNF therapy and was well tolerated.

1,579 citations


Journal ArticleDOI
TL;DR: Among more severely depressed patients, behavioral activation was comparable to antidepressant medication, and both significantly outperformed cognitive therapy, and the implications of current treatment guidelines and dissemination are discussed.
Abstract: Antidepressant medication is considered the current standard for severe depression, and cognitive therapy is the most widely investigated psychosocial treatment for depression. However, not all patients want to take medication, and cognitive therapy has not demonstrated consistent efficacy across trials. Moreover, dismantling designs have suggested that behavioral components may account for the efficacy of cognitive therapy. The present study tested the efficacy of behavioral activation by comparing it with cognitive therapy and antidepressant medication in a randomized placebo-controlled design in adults with major depressive disorder (N = 241). In addition, it examined the importance of initial severity as a moderator of treatment outcome. Among more severely depressed patients, behavioral activation was comparable to antidepressant medication, and both significantly outperformed cognitive therapy. The implications of these findings for the evaluation of current treatment guidelines and dissemination are discussed.

1,447 citations


Journal ArticleDOI
TL;DR: In patients with suspected pulmonary embolism, multidetector CTA-CTV has a higher diagnostic sensitivity than does CTA alone, with similar specificity, and additional testing is necessary when the clinical probability is inconsistent with the imaging results.
Abstract: BACKGROUND The accuracy of multidetector computed tomographic angiography (CTA) for the diagnosis of acute pulmonary embolism has not been determined conclusively. METHODS The Prospective Investigation of Pulmonary Embolism Diagnosis II trial was a prospective, multicenter investigation of the accuracy of multidetector CTA alone and combined with venous-phase imaging (CTA-CTV) for the diagnosis of acute pulmonary embolism. We used a composite reference test to confirm or rule out the diagnosis of pulmonary embolism. RESULTS Among 824 patients with a reference diagnosis and a completed CT study, CTA was inconclusive in 51 because of poor image quality. Excluding such inconclusive studies, the sensitivity of CTA was 83 percent and the specificity was 96 percent. Positive predictive values were 96 percent with a concordantly high or low probability on clinical assessment, 92 percent with an intermediate probability on clinical assessment, and nondiagnostic if clinical probability was discordant. CTA-CTV was inconclusive in 87 of 824 patients because the image quality of either CTA or CTV was poor. The sensitivity of CTA-CTV for pulmonary embolism was 90 percent, and specificity was 95 percent. CTA-CTV was also nondiagnostic with a discordant clinical probability. CONCLUSIONS In patients with suspected pulmonary embolism, multidetector CTA-CTV has a higher diagnostic sensitivity than does CTA alone, with similar specificity. The predictive value of either CTA or CTA-CTV is high with a concordant clinical assessment, but additional testing is necessary when the clinical probability is inconsistent with the imaging results.

1,374 citations


Journal ArticleDOI
TL;DR: Data from this study support a model in which Sun proteins tether nesprins in the ONM via interactions spanning the PNS, and form a complex that links the nucleoskeleton and cytoskeleton (the LINC complex).
Abstract: The nuclear envelope defines the barrier between the nucleus and cytoplasm and features inner and outer membranes separated by a perinuclear space (PNS). The inner nuclear membrane contains specific integral proteins that include Sun1 and Sun2. Although the outer nuclear membrane (ONM) is continuous with the endoplasmic reticulum, it is nevertheless enriched in several integral membrane proteins, including nesprin 2 Giant (nesp2G), an 800-kD protein featuring an NH2-terminal actin-binding domain. A recent study (Padmakumar, V.C., T. Libotte, W. Lu, H. Zaim, S. Abraham, A.A. Noegel, J. Gotzmann, R. Foisner, and I. Karakesisoglou. 2005. J. Cell Sci. 118:3419–3430) has shown that localization of nesp2G to the ONM is dependent upon an interaction with Sun1. In this study, we confirm and extend these results by demonstrating that both Sun1 and Sun2 contribute to nesp2G localization. Codepletion of both of these proteins in HeLa cells leads to the loss of ONM-associated nesp2G, as does overexpression of the Sun1 lumenal domain. Both treatments result in the expansion of the PNS. These data, together with those of Padmakumar et al. (2005), support a model in which Sun proteins tether nesprins in the ONM via interactions spanning the PNS. In this way, Sun proteins and nesprins form a complex that links the nucleoskeleton and cytoskeleton (the LINC complex).

1,168 citations


Journal ArticleDOI
TL;DR: A self-report mindfulness measure, the Toronto Mindfulness Scale (TMS), developed and validated is a promising measure of the mindfulness state with good psychometric properties and predictive of treatment outcome.
Abstract: In this study, the authors both developed and validated a self-report mindfulness measure, the Toronto Mindfulness Scale (TMS). In Study 1, participants were individuals with and without meditation experience. Results showed good internal consistency and two factors, Curiosity and Decentering. Most of the expected relationships with other constructs were as expected. The TMS scores increased with increasing mindfulness meditation experience. In Study 2, criterion and incremental validity of the TMS were investigated on a group of individuals participating in 8-week mindfulness-based stress reduction programs. Results showed that TMS scores increased following treatment, and Decentering scores predicted improvements in clinical outcome. Thus, the TMS is a promising measure of the mindfulness state with good psychometric properties and predictive of treatment outcome.

1,126 citations


Journal ArticleDOI
TL;DR: A consensus report was needed that addresses the rapid progress in this emerging field and details how the specific study of resolution of acute inflammation provides leads for novel anti‐inflammatory therapeutics, as well as defines the terms and key components of interest in the resolution process within tissues as appreciated today.
Abstract: A recent focus meeting on Controlling Acute Inflammation was held in London, April 27-28, 2006, organized by D.W. Gilroy and S.D. Brain for the British Pharmacology Society. We concluded at the meeting that a consensus report was needed that addresses the rapid progress in this emerging field and details how the specific study of resolution of acute inflammation provides leads for novel anti-inflammatory therapeutics, as well as defines the terms and key components of interest in the resolution process within tissues as appreciated today. The inflammatory response protects the body against infection and injury but can itself become dysregulated with deleterious consequences to the host. It is now evident that endogenous biochemical pathways activated during defense reactions can counter-regulate inflammation and promote resolution. Hence, resolution is an active rather than a passive process, as once believed, which now promises novel approaches for the treatment of inflammation-associated diseases based on endogenous agonists of resolution.

1,037 citations


Journal ArticleDOI
TL;DR: Evidence is provided that the short-term, combined effects of tryptophan deprivation and tryPTophan catabolites result in GCN2 kinase-dependent down-regulation of the TCR ζ-chain in murine CD8+ T cells.
Abstract: Tryptophan catabolism is a tolerogenic effector system in regulatory T cell function, yet the general mechanisms whereby tryptophan catabolism affects T cell responses remain unclear. We provide evidence that the short-term, combined effects of tryptophan deprivation and tryptophan catabolites result in GCN2 kinase-dependent down-regulation of the TCR zeta-chain in murine CD8+ T cells. TCR zeta down-regulation can be demonstrated in vivo and is associated with an impaired cytotoxic effector function in vitro. The longer-term effects of tryptophan catabolism include the emergence of a regulatory phenotype in naive CD4+CD25- T cells via TGF-beta induction of the forkhead transcription factor Foxp3. Such converted cells appear to be CD25+, CD69-, CD45RBlow, CD62L+, CTLA-4+, BTLAlow and GITR+, and are capable of effective control of diabetogenic T cells when transferred in vivo. Thus, both tryptophan starvation and tryptophan catabolites contribute to establishing a regulatory environment affecting CD8+ as well as CD4+ T cell function, and not only is tryptophan catabolism an effector mechanism of tolerance, but it also results in GCN2-dependent generation of autoimmune-preventive regulatory T cells.

984 citations


Journal ArticleDOI
TL;DR: The Lupus Survival Study Group data are reviewed and particularly the data from the State University of New York Health Science Center at Brooklyn, NY is reviewed.
Abstract: Objective. To examine mortality rates in the largest systemic lupus erythematosus (SLE) cohort ever assembled. Methods. Our sample was a multisite international SLE cohort (23 centers, 9,547 patients). Deaths were ascertained by vital statistics registry linkage. Standardized mortality ratio (SMR; ratio of deaths observed to deaths expected) estimates were calculated for-all deaths and by cause. The effects of sex, age, SLE duration, race, and calendar-year periods were determined. Results. The overall SMR was 2.4 (95% confidence interval 2.3-2.5). Particularly high mortality was seen for circulatory disease, infections, renal disease, non-Hodgkin's lymphoma, and lung cancer. The highest SMR estimates were seen in patient groups characterized by female sex, younger age, SLE duration < 1 year, or black/African American race. There was a dramatic decrease in total SMR estimates across calendar-year periods, which was demonstrable for specific causes including death due to infections and death due to renal disorders. However, the SMR due to circulatory diseases tended to increase slightly from the 1970s to the year 2001. Conclusion. Our data from a very large multicenter international cohort emphasize what has been demonstrated previously in smaller samples. These results highlight the increased mortality rate in SLE patients compared with the general population, and they suggest particular risk associated with female sex, younger age, shorter SLE duration, and black/African American race. The risk for certain types of deaths, primarily related to lupus activity (such as renal disease), has decreased over time, while the risk for deaths due to circulatory disease does not appear to have diminished. (Less)

Journal ArticleDOI
TL;DR: The goal of this synthesis research study was to develop best practice recommendations based on a systematic approach to finding, selecting and critically appraising programmes addressing prevention and treatment of childhood obesity and related risk of chronic diseases.
Abstract: Childhood obesity is a global epidemic and rising trends in overweight and obesity are apparent in both developed and developing countries. Available estimates for the period between the 1980s and 1990s show the prevalence of overweight and obesity in children increased by a magnitude of two to five times in developed countries (e.g. from 11% to over 30% in boys in Canada), and up to almost four times in developing countries (e.g. from 4% to 14% in Brazil). The goal of this synthesis research study was to develop best practice recommendations based on a systematic approach to finding, selecting and critically appraising programmes addressing prevention and treatment of childhood obesity and related risk of chronic diseases. An international panel of experts in areas of relevance to obesity provided guidance for the study. This synthesis research encompassed a comprehensive search of medical/academic and grey literature and the Internet covering the years 1982-2003. The appraisal approach developed to identify best practice was unique, in that it considered not only methodological rigour, but also population health, immigrant health and programme development/evaluation perspectives in the assessment. Scores were generated based on pre-determined criteria with programmes scoring in the top tertile of the scoring range in any one of the four appraisal categories included for further examination. The synthesis process included identification of gaps and an analysis and summary of programme development and programme effectiveness to enable conclusions to be drawn and recommendations to be made. The results from the library database searches (13,158 hits), the Internet search and key informant surveys were reduced to a review of 982 reports of which 500 were selected for critical appraisal. In total 158 articles, representing 147 programmes, were included for further analysis. The majority of reports were included based on high appraisal scores in programme development and evaluation with limited numbers eligible based on scores in other categories of appraisal. While no single programme emerged as a model of best practice, synthesis of included programmes provided rich information on elements that represent innovative rather than best practice under particular circumstances that are dynamic (changing according to population subgroups, age, ethnicity, setting, leadership, etc.). Thus the findings of this synthesis review identifies areas for action, opportunities for programme development and research priorities to inform the development of best practice recommendations that will reduce obesity and chronic disease risk in children and youth. A lack of programming to address the particular needs of subgroups of children and youth emerged in this review. Although immigrants new to developed countries may be more vulnerable to the obesogenic environment, no programmes were identified that specifically targeted their potentially specialized needs (e.g. different food supply in a new country). Children 0-6 years of age and males represented other population subgroups where obesity prevention programmes and evidence of effectiveness were limited. These gaps are of concern because (i) the pre-school years may be a critical period for obesity prevention as indicated by the association of the adiposity rebound and obesity in later years; and (ii) although the growing prevalence of obesity affects males and females equally; males may be more vulnerable to associated health risks such as cardiovascular disease. Other gaps in knowledge identified during synthesis include a limited number of interventions in home and community settings and a lack of upstream population-based interventions. The shortage of programmes in community and home settings limits our understanding of the effectiveness of interventions in these environments, while the lack of upstream investment indicates an opportunity to develop more upstream and population-focused interventions to balance and extend the current emphasis on individual-based programmes. The evidence reviewed indicates that current programmes lead to short-term improvements in outcomes relating to obesity and chronic disease prevention with no adverse effects noted. This supports the continuation and further development of programmes currently directed at children and youth, as further evidence for best practice accumulates. In this synthesis, schools were found to be a critical setting for programming where health status indicators, such as body composition, chronic disease risk factors and fitness, can all be positively impacted. Engagement in physical activity emerged as a critical intervention in obesity prevention and reduction programmes. While many programmes in the review had the potential to integrate chronic disease prevention, few did; therefore efforts could be directed towards better integration of chronic disease prevention programmes to minimize duplication and optimize resources. Programmes require sustained long-term resources to facilitate comprehensive evaluation that will ascertain if long-term impact such as sustained normal weight is maintained. Furthermore, involving stakeholders in programme design, implementation and evaluation could be crucial to the success of interventions, helping to ensure that needs are met. A number of methodological issues related to the assessment of obesity intervention and prevention programmes were identified and offer insight into how research protocols can be enhanced to strengthen evidence for obesity interventions. Further research is required to understand the merits of the various forms in which interventions (singly and in combination) are delivered and in which circumstances they are effective. There is a critical need for the development of consistent indicators to ensure that comparisons of programme outcomes can be made to better inform best practice.

Journal ArticleDOI
Qiang Li1
TL;DR: In this paper, a survey study of 264 students from three junior high schools was conducted to investigate the nature and the extent of adolescences' experience of cyberbullying, and they found that cyber bullying was pervasive in adolescents' experience.
Abstract: This study investigates the nature and the extent of adolescences’ experience of cyberbullying. A survey study of 264 students from three junior high schools was conducted. In this article, ‘cyberb...

Journal ArticleDOI
TL;DR: In this review, the structures of a number of different Trp- and Arg-rich antimicrobial peptides are examined and some of the major mechanistic studies are presented.

Journal ArticleDOI
TL;DR: The technique is validated against a traditional "spectral binning" analysis on the basis of sensitivity to water suppression, relaxation effects, and NMR spectral acquisition times using PCA pattern recognition analysis.
Abstract: Extracting meaningful information from complex spectroscopic data of metabolite mixtures is an area of active research in the emerging field of “metabolomics”, which combines metabolism, spectroscopy, and multivariate statistical analysis (pattern recognition) methods. Chemometric analysis and comparison of 1H NMR1 spectra is commonly hampered by intersample peak position and line width variation due to matrix effects (pH, ionic strength, etc.). Here a novel method for mixture analysis is presented, defined as “targeted profiling”. Individual NMR resonances of interest are mathematically modeled from pure compound spectra. This database is then interrogated to identify and quantify metabolites in complex spectra of mixtures, such as biofluids. The technique is validated against a traditional “spectral binning” analysis on the basis of sensitivity to water suppression (presaturation, NOESY-presaturation, WET, and CPMG), relaxation effects, and NMR spectral acquisition times (3, 4, 5, and 6 s/scan) using PC...


Journal ArticleDOI
24 Mar 2006-Science
TL;DR: The authors' simulated climate matches paleoclimatic observations of past warming, and the combination of physically based climate and ice-sheet modeling with ice-core constraints indicate that the Greenland Ice Sheet and other circum-Arctic ice fields likely contributed 2.2 to 3.4 meters of sea-level rise during the Last Interglaciation.
Abstract: In the future, Arctic warming and the melting of polar glaciers will be considerable, but the magnitude of both is uncertain. We used a global climate model, a dynamic ice sheet model, and paleoclimatic data to evaluate Northern Hemisphere high-latitude warming and its impact on Arctic icefields during the Last Interglaciation. Our simulated climate matches paleoclimatic observations of past warming, and the combination of physically based climate and ice-sheet modeling with ice-core constraints indicate that the Greenland Ice Sheet and other circum-Arctic ice fields likely contributed 2.2 to 3.4 meters of sea-level rise during the Last Interglaciation.

Journal ArticleDOI
TL;DR: Two-photon laser-scanning microscopy is used to analyze lymph node priming of diabetogenic T cells and to delineate the mechanisms of Treg cell control of autoimmunity in vivo, supporting the idea that dendritic cells are central to T Reg cell function in vivo.
Abstract: The in vivo mechanism of regulatory T cell (Treg cell) function in controlling autoimmunity remains controversial. Here we have used two-photon laser-scanning microscopy to analyze lymph node priming of diabetogenic T cells and to delineate the mechanisms of Treg cell control of autoimmunity in vivo. Islet antigen–specific CD4+CD25− T helper cells (TH cells) and Treg cells swarmed and arrested in the presence of autoantigens. These TH cell activities were progressively inhibited in the presence of increasing numbers of Treg cells. There were no detectable stable associations between Treg and TH cells during active suppression. In contrast, Treg cells directly interacted with dendritic cells bearing islet antigen. Such persistent Treg cell–dendritic cell contacts preceded the inhibition of TH cell activation by dendritic cells, supporting the idea that dendritic cells are central to Treg cell function in vivo.

Journal ArticleDOI
TL;DR: It is shown that the nature of interactions through quorum-sensing chemicals does not simply involve cooperative signals, but entails other interactions such as cues and chemical manipulations that might have a role in conflicts within and between species.
Abstract: Individual bacteria can alter their behaviour through chemical interactions between organisms in microbial communities - this is generally referred to as quorum sensing. Frequently, these interactions are interpreted in terms of communication to mediate coordinated, multicellular behaviour. We show that the nature of interactions through quorum-sensing chemicals does not simply involve cooperative signals, but entails other interactions such as cues and chemical manipulations. These signals might have a role in conflicts within and between species. The nature of the chemical interaction is important to take into account when studying why and how bacteria react to the chemical substances that are produced by other bacteria.

Journal ArticleDOI
TL;DR: A library of transcriptional fusions of gfp to each of about 2,000 different promoters in E. coli K12, covering the great majority of the promoters in the organism, can serve as a tool for accurate, high-resolution analysis of transcription networks in livingE.
Abstract: E. coli is widely used for systems biology research; there exists a need, however, for tools that can be used to accurately and comprehensively measure expression dynamics in individual living cells. To address this we present a library of transcriptional fusions of gfp to each of about 2,000 different promoters in E. coli K12, covering the great majority of the promoters in the organism. Each promoter fusion is expressed from a low-copy plasmid. We demonstrate that this library can be used to obtain highly accurate dynamic measurements of promoter activity on a genomic scale, in a glucose-lactose diauxic shift experiment. The library allowed detection of about 80 previously uncharacterized transcription units in E. coli, including putative internal promoters within previously known operons, such as the lac operon. This library can serve as a tool for accurate, high-resolution analysis of transcription networks in living E. coli cells.

Proceedings ArticleDOI
11 Sep 2006
TL;DR: This work considers two unsupervised clustering algorithms, namely K-Means and DBSCAN, that have previously not been used for network traffic classification and evaluates these two algorithms and compares them to the previously used AutoClass algorithm, using empirical Internet traces.
Abstract: Classification of network traffic using port-based or payload-based analysis is becoming increasingly difficult with many peer-to-peer (P2P) applications using dynamic port numbers, masquerading techniques, and encryption to avoid detection. An alternative approach is to classify traffic by exploiting the distinctive characteristics of applications when they communicate on a network. We pursue this latter approach and demonstrate how cluster analysis can be used to effectively identify groups of traffic that are similar using only transport layer statistics. Our work considers two unsupervised clustering algorithms, namely K-Means and DBSCAN, that have previously not been used for network traffic classification. We evaluate these two algorithms and compare them to the previously used AutoClass algorithm, using empirical Internet traces. The experimental results show that both K-Means and DBSCAN work very well and much more quickly then AutoClass. Our results indicate that although DBSCAN has lower accuracy compared to K-Means and AutoClass, DBSCAN produces better clusters.

Journal ArticleDOI
TL;DR: A survey of the current efforts in mechanical micro-machining research and applications, especially for micromilling operations, can be found in this paper, where the authors suggest areas from macro-milling that should be examined and researched for application to the improvement of micro-mechanical cutting processes.
Abstract: The miniaturization of machine components is perceived by many as a requirement for the future technological development of a broad spectrum of products. Miniature components can provide smaller footprints, lower power consumption and higher heat transfer, since their surface-to-volume ratio is very high. To create these components, micro-meso-scale fabrication using miniaturized mechanical material removal processes has a unique advantage in creating 3D components using a variety of engineering materials. The motivation for micro-mechanical cutting stems from the translation of the knowledge obtained from the macro-machining domain to the micro-domain. However, there are challenges and limitations to micro-machining, and simple scaling cannot be used to model the phenomena of micro-machining operations. This paper surveys the current efforts in mechanical micro-machining research and applications, especially for micro-milling operations, and suggests areas from macro-machining that should be examined and researched for application to the improvement of micro-machining processes.

Journal ArticleDOI
TL;DR: For patients with AO and AOA, PCVplus RT does not prolong survival, and longer progression-free survival after PCV plus RT is associated with significant toxicity.
Abstract: Purpose Anaplastic oligodendroglioma (AO) and anaplastic oligoastrocytoma (AOA) are treated with surgery and radiotherapy (RT) at diagnosis, but they also respond to procarbazine, lomustine, and vincristine (PCV), raising the possibility that early chemotherapy will improve survival. Furthermore, better outcomes in AO have been associated with 1p and 19q allelic loss. Patients and Methods Patients with AO and AOA were randomly assigned to PCV chemotherapy followed by RT versus postoperative RT alone. The primary end point was overall survival. The status of 1p and 19q alleles was assessed by fluorescence in situ hybridization. Results Two hundred eighty-nine eligible patients were randomly assigned to either PCV plus RT (n = 147) or RT alone (n = 142). At progression, 80% of patients randomly assigned to RT had chemotherapy. With 3-year follow-up on most patients, the median survival times were similar (4.9 years after PCV plus RT v 4.7 years after RT alone; hazard ratio [HR] = 0.90; 95% CI, 0.66 to 1.24;...

Journal ArticleDOI
TL;DR: In this paper, the authors examined the level and characteristics of demand for long-distance wine tourism among wine consumers located far from wine regions and found that highly motivated, long distance wine tourists prefer destinations offering a wide range of cultural and outdoor attractions.

Journal ArticleDOI
TL;DR: In vivo results clearly delineate two fundamentally different molecular mechanisms for LFA-1 and Mac-1 in vivo, i.e., LFA–1–dependent adhesion followed by Mac- 1–dependent crawling, and both steps ultimately contribute to efficient emigration out of the vasculature.
Abstract: The prevailing view is that the beta2-integrins Mac-1 (alphaMbeta2, CD11b/CD18) and LFA-1 (alphaLbeta2, CD11a/CD18) serve similar biological functions, namely adhesion, in the leukocyte recruitment cascade. Using real-time and time-lapse intravital video-microscopy and confocal microscopy within inflamed microvessels, we systematically evaluated the function of Mac-1 and LFA-1 in the recruitment paradigm. The chemokine macrophage inflammatory protein-2 induced equivalent amounts of adhesion in wild-type and Mac-1-/- mice but very little adhesion in LFA-1-/- mice. Time-lapse video-microscopy within the postcapillary venules revealed that immediately upon adhesion, there is significant intraluminal crawling of all neutrophils to distant emigration sites in wild-type mice. In dramatic contrast, very few Mac-1-/- neutrophils crawled with a 10-fold decrease in displacement and a 95% reduction in velocity. Therefore, Mac-1-/- neutrophils initiated transmigration closer to the initial site of adhesion, which in turn led to delayed transmigration due to movement through nonoptimal emigration sites. Interestingly, the few LFA-1-/- cells that did adhere crawled similarly to wild-type neutrophils. Intercellular adhesion molecule-1 but not intercellular adhesion molecule-2 mediated the Mac-1-dependent crawling. These in vivo results clearly delineate two fundamentally different molecular mechanisms for LFA-1 and Mac-1 in vivo, i.e., LFA-1-dependent adhesion followed by Mac-1-dependent crawling, and both steps ultimately contribute to efficient emigration out of the vasculature.

Journal ArticleDOI
TL;DR: A computer simulation model is created that reproduces, within the standard error, the divergence angles measured in Arabidopsis seedlings and the effects of selected experimental manipulations, and offers a plausible link between molecular mechanisms of morphogenesis and the geometry of phyllotaxis.
Abstract: A striking phenomenon unique to the kingdom of plants is the regular arrangement of lateral organs around a central axis, known as phyllotaxis. Recent molecular-genetic experiments indicate that active transport of the plant hormone auxin is the key process regulating phyllotaxis. A conceptual model based on these experiments, introduced by Reinhardt et al. [Reinhardt, D., Pesce, E. R., Stieger, P., Mandel, T., Baltensperger, K., et al. (2003) Nature 426, 255-260], provides an intuitively plausible interpretation of the data, but raises questions of whether the proposed mechanism is, in fact, capable of producing the observed temporal and spatial patterns, is robust, can start de novo, and can account for phyllotactic transitions, such as the frequently observed transition from decussate to spiral phyllotaxis. To answer these questions, we created a computer simulation model based on data described previously or in this paper and reasonable hypotheses. The model reproduces, within the standard error, the divergence angles measured in Arabidopsis seedlings and the effects of selected experimental manipulations. It also reproduces distichous, decussate, and tricussate patterns. The model thus offers a plausible link between molecular mechanisms of morphogenesis and the geometry of phyllotaxis.

Journal ArticleDOI
TL;DR: In this paper, a temporal motivational theory (TMT) is proposed, which is consistent with the major findings from many other investigations, including psychobiology and behaviorism, and the potential implications of TMT are numerous, affecting our understanding on a wide range of topics, including group behavior, job design, stock market behavior, and goal setting.
Abstract: Progress toward understanding human behavior has been hindered by discipline-bound theories, dividing our efforts. Fortunately, these separate endeavors are converging and can be effectively integrated. Focusing on the fundamental features of picoeconomics, expectancy theory, cumulative prospect theory, and need theory, we construct a temporal motivational theory (TMT). TMT appears consistent with the major findings from many other investigations, including psychobiology and behaviorism. The potential implications of TMT are numerous, affecting our understanding on a wide range of topics, including group behavior, job design, stock market behavior, and goal setting.

Journal ArticleDOI
TL;DR: The only established dietary risk is a high caloric intake, and Protective factors include diets containing fibre, vegetable protein, nuts, calcium, vitamin C, coffee and alcohol, plus physical activity.
Abstract: Gallstone disease is common: >700,000 cholecystectomies and costs of approximately 6.5 billion dollars annually in the U.S. The burden of disease is epidemic in American Indians (60-70%); a corresponding decrease occurs in Hispanics of mixed Indian origin. Ten to fifteen per cent of white adults in developed countries harbour gallstones. Frequency is further reduced in Black Americans, East Asia and sub-Saharan Africa. In developed countries, cholesterol gallstones predominate; 15% are black pigment. East Asians develop brown pigment stones in bile ducts, associated with biliary infection or parasites, or in intrahepatic ducts (hepatolithiasis). Certain risk factors for gallstones are immutable: female gender, increasing age and ethnicity/family (genetic traits). Others are modifiable: obesity, the metabolic syndrome, rapid weight loss, certain diseases (cirrhosis, Crohn's disease) and gallbladder stasis (from spinal cord injury or drugs like somatostatin). The only established dietary risk is a high caloric intake. Protective factors include diets containing fibre, vegetable protein, nuts, calcium, vitamin C, coffee and alcohol, plus physical activity.

Journal ArticleDOI
TL;DR: Multiple imputation is the most accurate method for dealing with missing data in most of the missind data scenarios the authors assessed for the Zung Self-reported Depression scale.
Abstract: Missing data present a challenge to many research projects. The problem is often pronounced in studies utilizing self-report scales, and literature addressing different strategies for dealing with missing data in such circumstances is scarce. The objective of this study was to compare six different imputation techniques for dealing with missing data in the Zung Self-reported Depression scale (SDS). 1580 participants from a surgical outcomes study completed the SDS. The SDS is a 20 question scale that respondents complete by circling a value of 1 to 4 for each question. The sum of the responses is calculated and respondents are classified as exhibiting depressive symptoms when their total score is over 40. Missing values were simulated by randomly selecting questions whose values were then deleted (a missing completely at random simulation). Additionally, a missing at random and missing not at random simulation were completed. Six imputation methods were then considered; 1) multiple imputation, 2) single regression, 3) individual mean, 4) overall mean, 5) participant's preceding response, and 6) random selection of a value from 1 to 4. For each method, the imputed mean SDS score and standard deviation were compared to the population statistics. The Spearman correlation coefficient, percent misclassified and the Kappa statistic were also calculated. When 10% of values are missing, all the imputation methods except random selection produce Kappa statistics greater than 0.80 indicating 'near perfect' agreement. MI produces the most valid imputed values with a high Kappa statistic (0.89), although both single regression and individual mean imputation also produced favorable results. As the percent of missing information increased to 30%, or when unbalanced missing data were introduced, MI maintained a high Kappa statistic. The individual mean and single regression method produced Kappas in the 'substantial agreement' range (0.76 and 0.74 respectively). Multiple imputation is the most accurate method for dealing with missing data in most of the missind data scenarios we assessed for the SDS. Imputing the individual's mean is also an appropriate and simple method for dealing with missing data that may be more interpretable to the majority of medical readers. Researchers should consider conducting methodological assessments such as this one when confronted with missing data. The optimal method should balance validity, ease of interpretability for readers, and analysis expertise of the research team.

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TL;DR: Lateral ankle sprains in sports are the main cause of ligamentous posttraumatic ankle osteoarthritis and correlate with varus malalignment.
Abstract: BackgroundAnkle sprains are the most common injuries in sports and recreational activities.HypothesisAnkle osteoarthritis can be caused by ankle ligament lesions. Latency time between injury and osteoarthritis is influenced by the type and side of the injured ligaments. The side of the ligamentous lesion correlates with the hindfoot alignment.Study DesignCase series; Level of evidence, 4.MethodsOf a cohort of 247 patients with ankle arthritis, we reviewed data from 30 patients (33 ankles; mean age, 58.6 years) with ligamentous end-stage ankle osteoarthritis. The patients were evaluated etiologically, clinically, and radiologically.ResultsEtiologic analysis: 55% had a ligamentous lesion from sports injuries (soccer, 33%); 85% injured the lateral ankle ligaments, and 15% injured the medial and medial-lateral ligaments. The mean latency time between injury and osteoarthritis was 34.3 years. The survivorship rate for single severe ankle sprains was worse than that for chronic recurrent ligamentous lesions (me...