Showing papers by "McMaster University published in 2001"

GradientBased Learning Applied to Document Recognition

Abstract: Multilayer Neural Networks trained with the backpropagation algorithm constitute the best example of a successful Gradient-Based Learning technique. Given an appropriate network architecture, Gradient-Based Learning algorithms can be used to synthesize a complex decision surface that can classify high-dimensional patterns such as handwritten characters, with minimal preprocessing. This paper reviews various methods applied to handwritten character recognition and compares them on a standard handwritten digit recognition task. Convolutional Neural Networks, that are specifically designed to deal with the variability of 2D shapes, are shown to outperform all other techniques. Real-life document recognition systems are composed of multiple modules including field extraction, segmentation, recognition, and language modeling. A new learning paradigm, called Graph Transformer Networks (GTN), allows such multi-module systems to be trained globally using Gradient-Based methods so as to minimize an overall performance measure. Two systems for on-line handwriting recognition are described. Experiments demonstrate the advantage of global training, and the flexibility of Graph Transformer Networks. A Graph Transformer Network for reading bank check is also described. It uses Convolutional Neural Network character recognizers combined with global training techniques to provides record accuracy on business and personal checks. It is deployed commercially and reads several million checks per day.

Albuminuria and risk of cardiovascular events, death, and heart failure in diabetic and nondiabetic individuals

Abstract: ContextMicroalbuminuria is a risk factor for cardiovascular (CV) events. The relationship between the degree of albuminuria and CV risk is unclear.ObjectivesTo estimate the risk of CV events in high-risk individuals with diabetes mellitus (DM) and without DM who have microalbuminuria and to determine whether levels of albuminuria below the microalbuminuria threshold increase CV risk.DesignThe Heart Outcomes Prevention Evaluation study, a cohort study conducted between 1994 and 1999 with a median 4.5 years of follow-up.SettingCommunity and academic practices in North and South America and Europe.ParticipantsIndividuals aged 55 years or more with a history of CV disease (n = 5545) or DM and at least 1 CV risk factor (n = 3498) and a baseline urine albumin/creatinine ratio (ACR) measurement.Main Outcome MeasuresCardiovascular events (myocardial infarction, stroke, or CV death); all-cause death; and hospitalization for congestive heart failure.ResultsMicroalbuminuria was detected in 1140 (32.6%) of those with DM and 823 (14.8%) of those without DM at baseline. Microalbuminuria increased the adjusted relative risk (RR) of major CV events (RR, 1.83; 95% confidence interval [CI], 1.64-2.05), all-cause death (RR, 2.09; 95% CI, 1.84-2.38), and hospitalization for congestive heart failure (RR, 3.23; 95% CI, 2.54-4.10). Similar RRs were seen for participants with or without DM, even after adjusting for other CV risk factors (eg, the adjusted RR of the primary aggregate end point was 1.97 [95% CI, 1.68-2.31] in those with DM and 1.61 [95% CI, 1.36-1.90] in those without DM).Compared with the lowest quartile of ACR (<0.22 mg/mmol), the RRs of the primary aggregate end point in the second quartile (ie, ACR range, 0.22-0.57 mg/mmol) was 1.11 (95% CI, 0.95-1.30); third quartile, 1.38 (95% CI, 1.19-1.60; ACR range, 0.58-1.62 mg/mmol); and fourth quartile, 1.97 (95% CI, 1.73-2.25; ACR range, >1.62 mg/mmol) (P for trend <.001, even after excluding those with microalbuminuria). For every 0.4-mg/mmol increase in ACR level, the adjusted hazard of major CV events increased by 5.9% (95% CI, 4.9%-7.0%).ConclusionsOur results indicate that any degree of albuminuria is a risk factor for CV events in individuals with or without DM; the risk increases with the ACR, starting well below the microalbuminuria cutoff. Screening for albuminuria identifies people at high risk for CV events.

Effect of risedronate on the risk of hip fracture in elderly women. Hip Intervention Program Study Group.

Abstract: Background Risedronate increases bone mineral density in elderly women, but whether it prevents hip fracture is not known. Methods We studied 5445 women 70 to 79 years old who had osteoporosis (indicated by a T score for bone mineral density at the femoral neck that was more than 4 SD below the mean peak value in young adults [–4] or lower than –3 plus a nonskeletal risk factor for hip fracture, such as poor gait or a propensity to fall) and 3886 women at least 80 years old who had at least one nonskeletal risk factor for hip fracture or low bone mineral density at the femoral neck (T score, lower than –4 or lower than –3 plus a hip-axis length of 11.1 cm or greater). The women were randomly assigned to receive treatment with oral risedronate (2.5 or 5.0 mg daily) or placebo for three years. The primary end point was the occurrence of hip fracture. Results Overall, the incidence of hip fracture among all the women assigned to risedronate was 2.8 percent, as compared with 3.9 percent among those assigned t...

Stress Hyperglycemia and Prognosis of Stroke in Nondiabetic and Diabetic Patients A Systematic Overview

Abstract: Background and Purpose “Stress” hyperglycemia may be associated with increased mortality and poor recovery in diabetic and nondiabetic patients after stroke. A systematic review and meta-analysis of the literature relating acute poststroke glucose levels to the subsequent course were done to summarize and quantify this relationship. Methods A comprehensive literature search was done for cohort studies reporting mortality and/or functional recovery after stroke in relation to admission glucose level. Relative risks in hyperglycemic compared with normoglycemic patients with and without diabetes were calculated and meta-analyzed when possible. Results Thirty-two studies were identified; relative risks for prespecified outcomes were reported or could be calculated in 26 studies. After stroke of either subtype (ischemic or hemorrhagic), the unadjusted relative risk of in-hospital or 30-day mortality associated with admission glucose level >6 to 8 mmol/L (108 to 144 mg/dL) was 3.07 (95% CI, 2.50 to 3.79) in non...

Assessing knowledge assets: a review of the models used to measure intellectual capital

Abstract: This paper reviews the literature pertaining to the assessment of knowledge assets. Since knowledge assets are at the crux of sustainable competitive advantage, the burgeoning field of intellectual capital is an exciting area for both researchers and practitioners. Unfortunately, the measurement of such intangible assets is difficult. A variety of models have surfaced in an attempt to measure IC and this paper aims to highlight their strengths, weaknesses and operationalizations.

The mass function of dark matter haloes

Abstract: We combine data from a number of N-body simulations to predict the abundance of dark haloes in cold dark matter (CDM) universes over more than four orders of magnitude in mass. A comparison of different simulations suggests that the dominant uncertainty in our results is systematic and is smaller than 10–30 per cent at all masses, depending on the halo definition used. In particular, our 'Hubble volume' simulations of τCDM and ΛCDM cosmologies allow the abundance of massive clusters to be predicted with uncertainties well below those expected in all currently planned observational surveys. We show that for a range of CDM cosmologies and for a suitable halo definition, the simulated mass function is almost independent of epoch, of cosmological parameters and of the initial power spectrum when expressed in appropriate variables. This universality is of exactly the kind predicted by the familiar Press–Schechter model, although this model predicts a mass function shape that differs from our numerical results, overestimating the abundance of 'typical' haloes and underestimating that of massive systems.

The composite genome of the legume symbiont Sinorhizobium meliloti.

Abstract: The scarcity of usable nitrogen frequently limits plant growth. A tight metabolic association with rhizobial bacteria allows legumes to obtain nitrogen compounds by bacterial reduction of dinitrogen (N2) to ammonium (NH4+). We present here the annotated DNA sequence of the alpha-proteobacterium Sinorhizobium meliloti, the symbiont of alfalfa. The tripartite 6.7-megabase (Mb) genome comprises a 3.65-Mb chromosome, and 1.35-Mb pSymA and 1.68-Mb pSymB megaplasmids. Genome sequence analysis indicates that all three elements contribute, in varying degrees, to symbiosis and reveals how this genome may have emerged during evolution. The genome sequence will be useful in understanding the dynamics of interkingdom associations and of life in soil environments.

A comparison of methods to detect publication bias in meta-analysis.

Abstract: Meta-analyses are subject to bias for many of reasons, including publication bias. Asymmetry in a funnel plot of study size against treatment effect is often used to identify such bias. We compare the performance of three simple methods of testing for bias: the rank correlation method; a simple linear regression of the standardized estimate of treatment effect on the precision of the estimate; and a regression of the treatment effect on sample size. The tests are applied to simulated meta-analyses in the presence and absence of publication bias. Both one-sided and two-sided censoring of studies based on statistical significance was used. The results indicate that none of the tests performs consistently well. Test performance varied with the magnitude of the true treatment effect, distribution of study size and whether a one- or two-tailed significance test was employed. Overall, the power of the tests was low when the number of studies per meta-analysis was close to that often observed in practice. Tests that showed the highest power also had type I error rates higher than the nominal level. Based on the empirical type I error rates, a regression of treatment effect on sample size, weighted by the inverse of the variance of the logit of the pooled proportion (using the marginal total) is the preferred method.

Managing organizational knowledge by diagnosing intellectual capital: framing and advancing the state of the field

Abstract: Since organizational knowledge is at the crux of sustainable competitive advantage, the burgeoning field of intellectual capital is an exciting area for both researchers and practitioners. Intellectual capital is conceptualized from numerous disciplines making the field a mosaic of perspectives. Accountants are interested in how to measure it on the balance sheet, information technologists want to codify it on systems, sociologists want to balance power with it, psychologists want to develop minds because of it, human resource managers want to calculate an ROI on it, and training and development officers want to make sure that they can build it. The following article represents a comprehensive literature review from a variety of managerial disciplines. In addition to highlighting the research to date, avenues for future pursuit are also offered.

Relative Contribution of Residual Renal Function and Peritoneal Clearance to Adequacy of Dialysis: A Reanalysis of the CANUSA Study

Abstract: Studies of the adequacy of peritoneal dialysis and recommendations have assumed that renal and peritoneal clearances are comparable and therefore additive. The CANUSA data were reanalyzed in an effort to address this assumption. Among the 680 patients in the original CANUSA study, 601 had all of the variables of interest for this report. Adequacy of dialysis was estimated from GFR (mean of renal urea and creatinine clearance) and from peritoneal creatinine clearance. The Cox proportional-hazards model was used to evaluate the time-dependent association of these independent variables with patient survival. For each 5 L/wk per 1.73 m(2) increment in GFR, there was a 12% decrease in the relative risk (RR) of death (RR, 0.88; 95% confidence interval [CI], 0.83 to 0.94) but no association with peritoneal creatinine clearance (RR, 1.00; 95% CI, 0.90 to 1.10). Estimates of fluid removal (24-h urine volume, net peritoneal ultrafiltration, and total fluid removal) then were added to the Cox model. For a 250-ml increment in urine volume, there was a 36% decrease in the RR of death (RR, 0.64; 95% CI, 0.51 to 0.80). The association of patient survival with GFR disappeared (RR, 0.99; 95% CI, 0.94 to 1.04). However, neither net peritoneal ultrafiltration nor total fluid removal was associated with patient survival. Although these results may be explained partly, statistically, by less variability in peritoneal clearance than in GFR, the latter seems to be physiologically more important than the former. The assumption of equivalence of peritoneal and renal clearances is not supported by these data. Recommendations for adequate peritoneal dialysis need to be reevaluated in light of these observations.

Continuity and Discontinuity of Behavioral Inhibition and Exuberance: Psychophysiological and Behavioral Influences across the First Four Years of Life.

Abstract: Four-month-old infants were screened (N = 433) for temperamental patterns thought to predict behavioral inhibition, including motor reactivity and the expression of negative affect. Those selected (N = 153) were assessed at multiple age points across the first 4 years of life for behavioral signs of inhibition as well as psychophysiological markers of frontal electroencephalogram (EEG) asymmetry. Four-month temperament was modestly predictive of behavioral inhibition over the first 2 years of life and of behavioral reticence at age 4. Those infants who remained continuously inhibited displayed right frontal EEG asymmetry as early as 9 months of age while those who changed from inhibited to noninhibited did not. Change in behavioral inhibition was related to experience of nonparental care. A second group of infants, selected at 4 months of age for patterns of behavior thought to predict temperamental exuberance, displayed a high degree of continuity over time in these behaviors.

Geometrically frustrated magnetic materials

Abstract: The current state of efforts to understand the phenomenon of geometric magnetic frustration is described in the context of several key materials. All are transition metal oxides which crystallize with magnetic lattices which are geometrically or topologically prone to frustration such as those based on triangles or tetrahedra which share corners, edges or faces. These include the anhydrous alums, jarosites, pyrochlores, spinels, magnetoplumbites, garnets, ordered NaCl and other structure types. Special attention is paid to materials which do not undergo long range ordering at the lowest temperatures but instead form exotic ground states such as spin glasses, spin liquids and spin ices, and to S = 1/2 based materials.

Effects of ramipril and vitamin E on atherosclerosis: the study to evaluate carotid ultrasound changes in patients treated with ramipril and vitamin E (SECURE).

Abstract: Background—Activation of the renin-angiotensin-aldosterone system and oxidative modification of LDL cholesterol play important roles in atherosclerosis The Study to Evaluate Carotid Ultrasound changes in patients treated with Ramipril and vitamin E (SECURE), a substudy of the Heart Outcomes Prevention Evaluation (HOPE) trial, was a prospective, double-blind, 3×2 factorial design trial that evaluated the effects of long-term treatment with the angiotensin-converting enzyme inhibitor ramipril and vitamin E on atherosclerosis progression in high-risk patients Methods and Results—A total of 732 patients ≥55 years of age who had vascular disease or diabetes and at least one other risk factor and who did not have heart failure or a low left ventricular ejection fraction were randomly assigned to receive ramipril 25 mg/d or 10 mg/d and vitamin E (RRR-α-tocopheryl acetate) 400 IU/d or their matching placebos Average follow-up was 45 years Atherosclerosis progression was evaluated by B-mode carotid ultrasoun

ICOS is essential for effective T-helper-cell responses.

Abstract: The outcome of T-cell responses after T-cell encounter with specific antigens is modulated by co-stimulatory signals, which are required for both lymphocyte activation and development of adaptive immunity1,2,3. ICOS4,5, an inducible co-stimulator with homology to CD28, is expressed on activated, but not resting T cells, and shows T-cell co-stimulatory function in vitro. ICOS binds specifically to its counter-receptor B7RP-1 (refs 5,6,7), but not to B7-1 or B7-2. Here we provide in vivo genetic evidence that ICOS delivers a co-stimulatory signal that is essential both for efficient interaction between T and B cells and for normal antibody responses to T-cell-dependent antigens. To determine the physiological function of ICOS, we generated and characterized gene-targeted ICOS-deficient mice. In vivo, a lack of ICOS results in severely deficient T-cell-dependent B-cell responses. Germinal centre formation is impaired and immunoglobulin class switching, including production of allergy-mediating IgE, is defective. ICOS-deficient T cells primed in in vivo and restimulated in vitro with specific antigen produce only low levels of interleukin-4, but remain fully competent to produce interferon-γ.

The Health Utilities Index (HUI) system for assessing health-related quality of life in clinical studies.

Abstract: This paper reviews the Health Utilities Index (HUI? systems as means to describe health status and obtain utility scores reflecting health-related quality of life (HRQoL). The HUI Mark 2 (HUI2) and Mark 3 (HUI3) classification and scoring systems are described. The methods used to estimate multiattribute utility functions for HUI2 and HUI3 are reviewed. The use of HUI in clinical studies for a wide variety of conditions in a large number of countries is illustrated. HUI provides a comprehensive description of the health status of subjects in clinical studies. HUI has been shown to be a reliable, responsive and valid measure in a wide variety of clinical studies. Utility scores provide an overall assessment of the HRQoL of patients. Utility scores are also useful in cost-utility analyses and related studies. General population norm data are available. The widespread use of HUI facilitates the interpretation of results and permits comparisons. HUI is a useful tool for assessing health status and HRQoL in cl...

Low dose inhaled budesonide and formoterol in mild persistent asthma: the OPTIMA randomized trial.

Abstract: The optimal treatment for mild asthma is uncertain. We assessed the effects of adding a long-acting inhaled beta-agonist, formoterol, to low doses of an inhaled corticosteroid, budesonide, for 1 yr in subjects with mild asthma, receiving no or only a small dose of inhaled corticosteroid. The 698 corticosteroid free patients (Group A) were assigned to twice daily treatment with 100 microg budesonide, 100 microg budesonide plus 4.5 microg formoterol, or placebo. The 1,272 corticosteroid-treated patients (Group B) were assigned to twice daily treatment with 100 microg budesonide, 100 microg budesonide plus 4.5 microg formoterol, 200 microg budesonide, or 200 microg budesonide plus 4.5 microg formoterol. The main outcome variables were time to the first severe asthma exacerbation and poorly controlled asthma days. In Group A, budesonide alone reduced the risk for severe exacerbations by 60% and poorly controlled days by 48%; adding formoterol increased lung function with no change in other end points. By contrast, in Group B, adding formoterol reduced the risk for the first severe exacerbation and for poorly controlled days by 43 and 30%, respectively. Thus, in corticosteroid-free patients, low dose inhaled budesonide alone reduced severe exacerbations and improved asthma control, and in patients already receiving inhaled corticosteroid, adding formoterol was more effective than doubling the corticosteroid dose.

Homocysteine-induced endoplasmic reticulum stress causes dysregulation of the cholesterol and triglyceride biosynthetic pathways

Abstract: Hepatic steatosis is common in patients having severe hyperhomocysteinemia due to deficiency for cystathionine beta-synthase. However, the mechanism by which homocysteine promotes the development and progression of hepatic steatosis is unknown. We report here that homocysteine-induced endoplasmic reticulum (ER) stress activates both the unfolded protein response and the sterol regulatory element-binding proteins (SREBPs) in cultured human hepatocytes as well as vascular endothelial and aortic smooth muscle cells. Activation of the SREBPs is associated with increased expression of genes responsible for cholesterol/triglyceride biosynthesis and uptake and with intracellular accumulation of cholesterol. Homocysteine-induced gene expression was inhibited by overexpression of the ER chaperone, GRP78/BiP, thus demonstrating a direct role of ER stress in the activation of cholesterol/triglyceride biosynthesis. Consistent with these in vitro findings, cholesterol and triglycerides were significantly elevated in the livers, but not plasmas, of mice having diet-induced hyperhomocysteinemia. This effect was not due to impaired hepatic export of lipids because secretion of VLDL-triglyceride was increased in hyperhomocysteinemic mice. These findings suggest a mechanism by which homocysteine-induced ER stress causes dysregulation of the endogenous sterol response pathway, leading to increased hepatic biosynthesis and uptake of cholesterol and triglycerides. Furthermore, this mechanism likely explains the development and progression of hepatic steatosis and possibly atherosclerotic lesions observed in hyperhomocysteinemia.

Transient expression of IL-1beta induces acute lung injury and chronic repair leading to pulmonary fibrosis.

Abstract: IL-1beta is one of a family of proinflammatory cytokines thought to be involved in many acute and chronic diseases. Although it is considered to participate in wound repair, no major role has been attributed to IL-1beta in tissue fibrosis. We used adenoviral gene transfer to transiently overexpress IL-1beta in rat lungs after intratracheal administration. The high expression of IL-1beta in the first week after injection was accompanied by local increase of the proinflammatory cytokines IL-6 and TNF-alpha and a vigorous acute inflammatory tissue response with evidence of tissue injury. The profibrotic cytokines PDGF and TGF-beta1 were increased in lung fluid samples 1 week after peak expression of IL-1beta. Although PDGF returned to baseline in the third week, TGF-beta1 showed increased concentrations in bronchoalveolar lavage fluid for up to 60 days. This was associated with severe progressive tissue fibrosis in the lung, as shown by the presence of myofibroblasts, fibroblast foci, and significant extracellular accumulations of collagen and fibronectin. These data directly demonstrate how acute tissue injury in the lung, initiated by a highly proinflammatory cytokine, IL-1beta, converts to progressive fibrotic changes. IL-1beta should be considered a valid target for therapeutic intervention in diseases associated with fibrosis and tissue remodeling.

Portfolio management for new product development: results of an industry practices study

Abstract: Portfolio management for product innovation – picking the right set of development projects – is critical to new product success. This article reports on the new product portfolio practices and performance of a large sample of firms in North America. Reasons why portfolio management is important are identified, followed by the relative popularity of the different portfolio techniques: financial methods are first, followed by business strategy methods, bubble diagrams and scoring models. Next, how the various portfolio methods fare in terms of six performance metrics is probed. Financial methods, although the most popular and rigorous, yield the worst results overall, while top performing firms rely more on non-financial approaches – strategic and scoring methods. The details of how some of these more popular methods are employed by firms to rate and rank development projects are also provided. Finally, managerial implications, including suggestions for making portfolio management more effective in industry, are outlined.

Long-Term Effects of Indomethacin Prophylaxis in Extremely-Low-Birth-Weight Infants

Abstract: Background The prophylactic administration of indomethacin reduces the frequency of patent ductus arteriosus and severe intraventricular hemorrhage in very-low-birth-weight infants (those with birth weights below 1500 g). Whether prophylaxis with indomethacin confers any long-term benefits that outweigh the risks of drug-induced reductions in renal, intestinal, and cerebral blood flow is not known. Methods Soon after they were born, we randomly assigned 1202 infants with birth weights of 500 to 999 g (extremely low birth weight) to receive either indomethacin (0.1 mg per kilogram of body weight) or placebo intravenously once daily for three days. The primary outcome was a composite of death, cerebral palsy, cognitive delay, deafness, and blindness at a corrected age of 18 months. Secondary long-term outcomes were hydrocephalus necessitating the placement of a shunt, seizure disorder, and microcephaly within the same time frame. Secondary short-term outcomes were patent ductus arteriosus, pulmonary hemorrh...

Neural and Adaptive Systems: Fundamentals Through Simulations

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Intention-to-treat principle

Abstract: In deciding if a treatment is likely to work in an individual patient, clinicians need to know the effect of the intervention in patients who take the treatment as prescribed. However, participants in clinical trials may not adhere to the protocol, or clinicians may recommend withdrawal of the study

Two-year effects of alendronate on bone mineral density and vertebral fracture in patients receiving glucocorticoids: a randomized, double-blind, placebo-controlled extension trial.

Abstract: OBJECTIVE: To evaluate the continued efficacy and safety of alendronate (ALN) for up to 2 years in patients receiving glucocorticoids. METHODS: This is a 12-month extension of a previously completed 1-year trial of daily ALN, performed to evaluate the effects of ALN over a total of 2 years in 66 men and 142 women continuing to receive at least 7.5 mg of prednisone or equivalent daily. All patients received supplemental calcium and vitamin D. The primary end point was the mean percentage change in lumbar spine bone mineral density (BMD) from baseline to 24 months. Other outcomes included changes in hip and total body BMD, biochemical markers of bone turnover, radiographic joint damage of the hands, and vertebral fracture incidence. RESULTS: The mean (+/-SEM) lumbar spine BMD increased by 2.8 +/- 0.6%, 3.9 +/- 0.7%, and 3.7 +/- 0.6%, respectively, in the groups that received 5 mg, 10 mg, and 2.5/10 mg of ALN daily (P < or = 0.001) and decreased by -0.8 +/- 0.6% in the placebo group (P not significant) over 24 months. In patients receiving any dose of ALN, BMD was increased at the trochanter (P < or = 0.05) and maintained at the femoral neck. Total body BMD was increased in patients receiving 5 or 10 mg ALN (P < or = 0.01). These 2 dose levels of ALN were more effective than placebo at all sites (P < or = 0.05). Bone turnover markers (N-telopeptides of type I collagen and bone-specific alkaline phosphatase) decreased 60% and 25%, respectively, during treatment with ALN (P < or = 0.05). There were fewer patients with new vertebral fractures in the ALN group versus the placebo group (0.7% versus 6.8%; P = 0.026). The safety profile was similar between treatment groups. CONCLUSION: Alendronate is an effective, well-tolerated therapy for the prevention and treatment of glucocorticoid-induced osteoporosis, with sustained treatment advantages for up to 2 years.

Epidural analgesia reduces postoperative myocardial infarction: a meta-analysis.

Abstract: Postoperative cardiac morbidity and mortality continue to pose considerable risks to surgical patients. Postoperative epidural analgesia is considered to have beneficial effects on cardiac outcomes. The use in high-risk cardiac patients remains controversial. No study has shown that postoperative ep