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PubMed2004

Latent variable discovery in classification models.

The naive Bayes model makes the often unrealistic assumption that the feature variables are mutually independent given the class variable. We interpret a violation of this assumption as an indication of the presence of latent variables, and we show how latent variables can be detected. Latent variable discovery is interesting, especially for medical applications, because it can lead to a better understanding of application domains. It can also improve classification accuracy and boost user confidence in classification models.

Algorithms↗

PubMed2004

Using literature and data to learn Bayesian networks as clinical models of ovarian tumors.

Thanks to its increasing availability, electronic literature has become a potential source of information for the development of complex Bayesian networks (BN), when human expertise is missing or data is scarce or contains much noise. This opportunity raises the question of how to integrate information from free-text resources with statistical data in learning Bayesian networks. Firstly, we report on the collection of prior information resources in the ovarian cancer domain, which includes "kernel" annotations of the domain variables. We introduce methods based on the annotations and literature to derive informative pairwise dependency measures, which are derived from the statistical cooccurrence of the names of the variables, from the similarity of the "kernel" descriptions of the variables and from a combined method. We perform wide-scale evaluation of these text-based dependency scores against an expert reference and against data scores (the mutual information (MI) and a Bayesian score). Next, we transform the text-based dependency measures into informative text-based priors for Bayesian network structures. Finally, we report the benefit of such informative text-based priors on the performance of a Bayesian network for the classification of ovarian tumors from clinical data.

Artificial Intelligence↗

PubMed2003

Carotid atherosclerosis in chronic renal failure-the central role of increased plaque burden.

Studies on carotid artery atherosclerosis have been performed in order to understand the high risk for cardiovascular disease in chronic renal failure (CRF). The purpose of this study was to evaluate the extent and nature of carotid artery atherosclerosis in patients with CRF. Of the 135 patients with CRF (52 +/- 11 years), 58 had moderate to severe predialysis CRF (PR), 36 were on dialysis treatment (DI), and 41 were renal transplant recipients (TR). In addition, 58 control subjects (CO) were examined. Common carotid artery intima-media thickness (IMT), plaque prevalence, plaque score, and stiffness index beta were determined. Furthermore, plaque calcification and internal carotid artery stenoses were classified. Plaque prevalence (PR 64%, DI 61%, TR 51%, CO 28%; P < 0.001) and plaque score (PR 3.3 +/- 4.3, DI 3.0 +/- 3.4, TR 2.5 +/- 3.2, CO 0.8 +/- 1.7 mm; P < 0.001) were significantly greater in the CRF patient groups compared to the controls, whereas no difference in IMT was noted between the study groups. The prevalences of plaque calcification and internal carotid artery stenoses were higher among the CRF patient groups. In addition, the stiffness index beta was higher in the CRF patient groups. The present study shows that the characteristic alterations of the carotid arteries in CRF include increased plaque burden, calcification and increased arterial stiffness.

Adult↗

PubMed2004

Epicardial coronary artery constriction to cold pressor test is predictive of cardiovascular events in hypertensive patients with angiographically normal coronary arteries and without other major coronary risk factor.

Epicardial coronary endothelial dysfunction independently predicts cardiovascular events in patients with coronary risk factors. This study was designed to evaluate outcome of hypertensive patients on the basis of their epicardial coronary function assessed by cold pressor test (CPT). Control subjects (n = 68, 48.8 +/- 7.6 years) and hypertensive patients (n = 83, 51.3 +/- 7.9 years) with angiographically normal coronary arteries and without other major coronary risk factor underwent epicardial coronary reactivity assessment to CPT using quantitative angiography. Cardiovascular events were recorded with a mean follow-up of 115 months (range 84-132). In control subjects, dilation occurred in 88.2%, no change in 11.8% (mean diameter change: +14.6 +/- 9.3%). In hypertensive patients, dilation occurred in 13.3%, no change in 25.3% (mean diameter change for both: +10.9 +/- 11.2%), and constriction in 61.4% (mean diameter change: -12.7 +/- 3.4%). Endothelium-independent dilation was normal in control subjects and hypertensive patients. In control subjects, there were three cardiovascular events in two subjects (2.9%). In hypertensive patients, there were 17 cardiovascular events in 12 patients (14.5%, P < 0.01 versus control subjects), with 15 cardiovascular events in the 10/51 patients (19.6%) with coronary artery constriction, and two cardiovascular events in the 2/32 patients (6.3%) with no change or dilation (P < 0.05). In conclusion, in hypertensive patients with angiographically normal coronary arteries and without other major coronary risk factors, epicardial coronary artery dysfunction assessed by the cold pressor test is predictive of long-term cardiovascular events.

Adult↗

PubMed2004

Inflammation, infection, and aortic valve sclerosis; Insights from the Olmsted County (Minnesota) population.

Atherosclerosis-related mechanisms, including inflammation and possibly infection, are likely to be involved in the pathogenesis of calcific aortic valve disease. The purpose of this study was to examine whether systemic inflammatory markers and Chlamydia pneumoniae seropositivity are associated with aortic valve sclerosis (AVS) in a sample of the general population. Transesophageal echocardiography was performed in 381 subjects (median age: 67 years, range: 51-101; 52% men), a sample of the adult population in Olmsted County, Minnesota. The associations between systemic inflammatory markers (blood counts, including white blood cells differential counts, fibrinogen, and high-sensitivity C-reactive protein [hs-CRP]), C. pneumoniae immunoglobulin G (IgG) antibody titers, and AVS were examined. AVS was present in 140 subjects (37% of the population). After adjustment for age, sex, and smoking status: (1). hs-CRP was associated with AVS (odds ratio: 1.20 per two-fold increase in hs-CRP; 95% confidence interval: 1.01-1.43; P = 0.04) but this association was not significant after adjustment for additional risk factors for AVS, including body mass index (P = 0.52). (2). Blood counts and fibrinogen were not associated with AVS (P-values >0.30). (3). C. pneumoniae IgG antibody titers (low [1:16-1:32], intermediate [1:64-1:128], or high [>or=1:256] titers, compared with titers <1:16) were not associated with AVS (P = 0.21). In conclusion, hs-CRP is weakly associated with AVS, an association that is not independent of other AVS risk factors. Blood counts, fibrinogen, and C. pneumoniae seropositivity are not associated with AVS. These findings suggest that other non-inflammatory non-infectious mechanisms are likely to have a role in the pathogenesis of calcific aortic valve disease.

Age Distribution↗

PubMed2006

Cardiovascular disease and cognitive performance in middle-aged and elderly men.

BACKGROUND: Decline of cognitive function with age may be due, in part, to atherosclerotic changes. The aim of the present study was to determine the relative contribution of cardiovascular disease (CVD) to cognitive functioning in middle-aged and elderly men. METHODS: In a cross-sectional study, cognitive tests were administered to 400 independently living men aged 40-80 years. Compound scores were calculated for memory function, processing capacity/speed, and executive function. The MMSE was used as a measure of global cognitive function. Carotid intima-media thickness, pulse wave velocity and ankle brachial blood pressure index were assessed as measures of sub-clinical CVD. The adjusted association of sub-clinical and prevalent CVD with neuropsychological test scores in the total group and in subgroups was assessed by linear regression analysis. RESULTS: Increased IMT was associated with lower scores on memory performance, and increased PWV was associated with lower scores on processing capacity and executive functioning. Compared with subjects with no CVD, both sub-clinical and prevalent cardiovascular diseases were related to a lower memory performance, beta's (95% CI) were -0.45 (-0.83, -0.07) and -0.45 (-0.84, 0.01), respectively. These associations were present in both middle-aged and elderly men. Furthermore, we observed that for subjects who had sub-clinical or prevalent cardiovascular disease the distribution of MMSE-scores was shifted toward lower values; the distributions were statistically different (p=0.003). CONCLUSIONS: The results of this study support a relation of sub-clinical CVD with cognitive functioning in middle-aged and elderly men. These results suggest that actions to prevent cognitive decline by preventing atherosclerosis should be taken before middle age.

Adult↗

PubMed2004

Passage of murine scrapie prion protein across the mouse vascular blood-brain barrier.

Prions are the infectious agents associated with transmissible spongiform encephalopathies and are composed mainly of a misfolded form of the endogenous prion protein. Prion protein must enter the brain to produce disease. Previous work has emphasized various mechanisms which partially bypass the blood-brain barrier (BBB). Here, we used the brain perfusion method to directly assess the ability of mouse scrapie protein (PrP(SC)) to cross the mouse BBB independent of the influences of neural pathways or circulating immune cells. We found that PrP(SC) oligomers rapidly crossed the BBB without disrupting it with a unidirectional influx rate of about 4.4microl/g-min. HPLC and capillary depletion confirmed that PrP(SC) crossed the entire width of the capillary wall to enter brain parenchyma. PrP(SC) also entered the cerebrospinal fluid (CSF) compartment. These results show that a prion protein can cross the intact BBB to enter both the parenchymal and CSF compartments of the brain.

Animals↗

PubMed2005

Association of the -112A>C polymorphism of the uncoupling protein 1 gene with insulin resistance in Japanese individuals with type 2 diabetes.

The -112A>C polymorphism (rs10011540) of the gene for uncoupling protein 1 (UCP1) has been associated with type 2 diabetes mellitus in Japanese individuals. The aim of the present study was to investigate the effects of this polymorphism, as well as the well-known -3826A>G polymorphism (rs1800592), on clinical characteristics of type 2 diabetes. We determined the genotypes of the two polymorphisms in 93 Japanese patients with type 2 diabetes. Intramyocellular lipid content and hepatic lipid content (HLC) were measured by magnetic resonance spectroscopy. No significant differences in age, sex, BMI, or HbA1c level were detected between type 2 diabetic patients with the -112C allele and those without it. However, homeostasis model assessment for insulin resistance (p=0.0089) and HLC (p=0.012) was significantly greater in patients with the -112C allele. We did not detect an association of the -3826A>G polymorphism (rs1800592) of UCP1 gene with any measured parameters. These results suggest that insulin resistance caused by the -112C allele influences the susceptibility to type 2 diabetes.

Age Distribution↗

PubMedDate not supplied

Automated analysis of mature red blood cells and reticulocytes in SS and SC disease.

Phenotypic expression of sickle cell disease (SCD) is highly variable. We investigated red blood cells (RBCs) and reticulocytes using a laser light scattering method (ADVIA120, Bayer Diagnostics, Tarrytown, NY) in a series of patients with either sickle cell anemia (SS) or compound SC heterozygosity (SC), both groups with or without alpha thalassemia. Results were compared with those of a series of patients without hematological disease. Known data were consistently confirmed, namely heterogeneity in cell volume and hemoglobin (Hb) concentration, as well as the premature exit of "stress" reticulocytes from the bone marrow, mostly in SS patients. Specific changes were observed during maturation, including decreases in macrocytic and hypodense cells. Simultaneous viewing of the indices of the different RBC populations provided information on erythropoietic maturation by a rapid, reproducible, and cost-effective method.

Anemia, Sickle Cell↗

PubMed2005

The evolution of synthetic oral drug properties.

An analysis of the properties of 1791 synthetic, oral drugs approved and/or marketed since 1937 demonstrates that the median molecular weight of oral drugs has increased substantially over the past 60 years. Fewer than 5% of approved/marketed oral drugs have more than 4-H bond donors and just 2% have MW>500 and >3 H-bond donors.

Administration, Oral↗

PubMed2006

Clinical trials and the response rate illusion.

Clinical trial outcome data can be presented and analyzed as mean change scores or as response rates. These two methods of presenting the data can lead to divergent conclusions. This article explores the reasons for the apparently divergent outcomes produced by these methods and considers their implications for the analysis and reportage of clinical trial data. It is shown that relatively small differences in improvement scores can produce relatively large differences in expected response rates. This is because differences in response rates do not indicate differences in the number of people who have improved; they indicate differences in the number of people whose degree of improvement has pushed them over a specified criterion. Therefore, patients classified as non-responders may have shown substantial and clinically significant improvement, and these are the patients who are most likely to become responders when given medication. Response rates based on continuous data do not add information, and they can create an illusion of clinical effectiveness.

Antidepressive Agents↗

PubMed2004

Concentrations and specific loads of polycyclic musks in sewage sludge originating from a monitoring network in Switzerland.

Polycyclic musks (HHCB, AHTN, ADBI, AHDI, ATII) and a metabolite of HHCB (HHCB-lactone) were analyzed in sewage sludge samples within the framework of a monitoring network in Switzerland. Mean values in stabilised sludge from 16 wastewater treatment plants were 20.3 mg/kg d.m. for HHCB, 7.3 mg/kg d.m. for AHTN and 1.8 mg/kg d.m. for HHCB-lactone, respectively. Contents of ADBI, AHDI and ATII were between 0.1 and 1.8 g/kg d.m. The results show that polycyclic musks origin mainly from private households and that loads from craft industry, industry and atmospheric deposition are negligible. The technology of wastewater treatment and sludge processing seems to be of minor importance for degradation processes of polycyclic musks. The calculated input in wastewater of polycyclic musks is lower by a factor of 5-7 than the estimates based on use volumes. This discrepancy might be explained by degradation processes, other emission pathways than wastewater or inappropriate estimation of production volumes.

Environmental Monitoring↗

PubMed2006

Error bounds for data-driven models of dynamical systems.

This work provides a technique for estimating error bounds about the predictions of data-driven models of dynamical systems. The bootstrap technique is applied to predictions from a set of dynamical system models, rather than from the time-series data, to estimate the reliability (in the form of prediction intervals) for each prediction. The technique is illustrated using human core temperature data, modeled by a hybrid (autoregressive plus first principles) approach. The temperature prediction intervals obtained are in agreement with those from the Camp-Meidell inequality. Moreover, as expected, the prediction intervals increase with the prediction horizon, time-series data variability, and model inaccuracy.

Algorithms↗

PubMed2006

Automatic segmentation and recognition of anatomical lung structures from high-resolution chest CT images.

This paper describes a fully automated segmentation and recognition scheme, which is designed to recognize lung anatomical structures in the human chest by segmenting the different chest internal organ and tissue regions sequentially from high-resolution chest CT images. A sequential region-splitting process is used to segment lungs, airway of bronchus, lung lobes and fissures based on the anatomical structures and statistical intensity distributions in CT images. The performance of our scheme is evaluated by segmenting lung structures from high-resolution multi-slice chest CT images from 44 patients; the validity of our method was proved by preliminary experimental results.

Humans↗

PubMedDate not supplied

Comorbidity of obsessive-compulsive disorder and attention-deficit/hyperactivity disorder in referred children and adolescents.

OBJECTIVE: The aim of this study was to explore whether comorbid attention-deficit/hyperactivity disorder (ADHD) affects the clinical expression and outcome of obsessive-compulsive disorder (OCD) in a clinical sample. METHOD: A consecutive series of 94 children and adolescents (mean age, 13.6 +/- 2.8 years) with current diagnosis of OCD were included in the study. Twenty-four (25.5%) patients were diagnosed as having a comorbid ADHD. Subjects with OCD plus ADHD were compared with subjects with OCD but without ADHD. RESULTS: Comorbid ADHD with OCD was significantly associated with a higher rate of males, an earlier onset of OCD, a greater psychosocial impairment, and a heavier comorbidity, namely, with bipolar disorder, tic disorder, and oppositional defiant disorder/conduct disorder. Phenomenology of obsessions and compulsions and outcome were not affected by ADHD comorbidity. CONCLUSIONS: A screening for ADHD should be performed in patients with OCD, as these patients and their parents are frequently not aware that the impairment may be partly due to a comorbid ADHD.

Adolescent↗

PubMedDate not supplied

Daily evaluation of macroaspiration in the critically ill post-trauma patient.

BACKGROUND: Although critically ill trauma patients represent a high-risk population for macroaspiration, studies of trauma patients have not been explored. The study aims were to quantify rate and associated risks of macroaspiration and explore the pattern of antibiotic use and incidence of aspiration pneumonia within this patient group. METHODS: Consecutive trauma patients admitted to the intensive care unit (ICU) were prospectively observed for development of macroaspiration and subsequent aspiration pneumonia. Daily monitoring included chart review, laboratory and radiography results, and nurse inquiries for witnessed macroaspiration events. RESULTS: Seven of 60 patients included experienced a clinically confirmed macroaspiration event (11.7%). The incidence of pneumonia was similar, regardless of macroaspiration occurrence (28.6%: macroaspiration cases vs 17.0%: controls, p > or = 0.05). Patients with macroaspiration required a longer duration of mechanical ventilation (15 vs 9.5 days, p = 0.021) and intensive care unit stay (28 vs 7 days, p = 0.015). Paralytic agent utilization was associated with an increased risk for aspiration (p = 0.045). CONCLUSIONS: The incidence of macroaspiration within a critically ill trauma population may be less frequent compared with studies performed in other patient populations. Although macroaspiration was associated with a longer duration of mechanical ventilation and intensive care unit stay, this condition may not be associated with an increased rate of pulmonary infection.

Adult↗

PubMed2004

Depressive mood after a cardiac event: gender inequality and participation in rehabilitation programme.

BACKGROUND: Depressive mood after a cardiac event is common with serious consequences for the patient. AIMS: To compare gender in depressive mood during the first year after a cardiac event and to evaluate the effect of participating in a multidimensional secondary prevention program on depressive mood. METHODS: 166 men and 54 women, <73 years, consecutively answered a questionnaire concerning depressive mood at 2 weeks, 6 weeks, 5 months and 1 year after discharge after a cardiac event. At 2 weeks, each patient met a nurse, and was informed about the disease and received individual support about lifestyle changes. Of those invited to participate in a secondary prevention program, 127 patients accepted, and 93 declined participation. RESULTS: At each of the four follow-ups, women had significantly higher depression scores than men. Depressive mood in both women and men was significantly reduced at 6 weeks. Thereafter, it increased to the 2-week level in women and to above the 2-week level in men. No differences were seen in patients participating or not in secondary prevention programs. CONCLUSION: Women had higher depressive mood scores than men and secondary prevention programs failed to improve depressive mood in both women and men.

Angioplasty, Balloon, Coronary↗

PubMed2004

Effect of short-term exposure to low levels of gaseous pollutants on chronic obstructive pulmonary disease hospitalizations.

We examined the associations between gaseous pollutants and hospitalization for chronic obstructive pulmonary diseases (COPD) among elderly people living in Vancouver, British Columbia, Canada, a city in which ambient air pollution levels are relatively low. We regressed the logarithm of daily counts of acute COPD hospitalization during the 5-year period from 1994 to 1998 on the daily mean levels of each pollutant, after accounting for seasonal and subseasonal fluctuations, non-Poisson dispersion, and weather variables. Nitrogen dioxide and carbon monoxide were significantly associated with hospitalization for COPD, and the magnitude of effects was increased slightly with increasing days of exposure averaging, with the relative risk for a 7-day average being 1.11 (95%CI: 1.04, 1.20) and 1.08 (1.02, 1.13) for nitrogen dioxide and carbon monoxide, respectively. There was no significant association between either sulfur dioxide or ozone and COPD hospitalization. The combined relative risk for all four gaseous pollutants on COPD hospitalization was 1.21. The effects of gaseous pollutants on COPD hospitalization were not significant after adjustment for PM(10), although its inclusion did not have a marked effect on the point estimates for relative risks. Nitrogen dioxide has a significant impact on COPD hospitalization. Further studies are needed to separate the effects of single pollutants from the combined effects of the complex mixture of air pollutants in urban atmospheres.

Aged↗