Familial melanoma and pancreatic cancer.
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Data Interpretation, Statistical↗
Biomedical subjects
R G Thomas
Publications and source records attributed to R G Thomas.
Genetic studies in Alzheimer's disease with an NACP/alpha-synuclein polymorphism.
The non-Abeta component of Alzheimer's disease amyloid (NAC) is copurified with amyloid from the brain tissue of Alzheimer's disease victims and is immunohistochemically localized to amyloid fibrils. NAC is a hydrophobic peptide fragment from the NAC precursor protein (NACP/alpha-synuclein) that is localized to presynaptic terminals. We used a polymorphic dinucleotide repeat sequence in a genomic clone of NACP for genetic association and linkage studies. Screening of Alzheimer's disease families failed to establish linkage between NACP and Alzheimer's disease. Nevertheless, one of the NACP polymorphisms (NACP allele 2) was shown to have significant association with healthy elderly control individuals with apolipoprotein E risk. This may indicate a possible protective function of the allele.
Aged↗
Substance-dependent inpatients who accept smoking treatment.
Delineating the characteristics of substance-dependent inpatients who are interested in receiving smoking treatment is critical to developing effective recruitment strategies and interventions for this population. Thus, this study comprehensively assessed and compared substance-dependent inpatients who accepted (n = 75) versus refused (n = 25) a stop-smoking treatment. Univariate analyses found treatment acceptors were younger, more addicted to nicotine, had more smoking-related health problems, had more positive attitudes about quitting smoking, and had more positive attitudes about the relationship between smoking cessation and drug/alcohol sobriety (e.g., believed cessation would positively impact sobriety). Logistic regression revealed that believing inpatient treatment was the best time to quit smoking was the primary factor associated with accepting treatment. Aside from their attitudes about the relationship between smoking cessation and sobriety, substance abusers who accepted smoking treatment appeared similar (e.g., in demographics, smoking behaviors) to nonabusers described in previous studies.
Adult↗
ApoE and CYP2D6 polymorphism with and without parkinsonism-dementia complex in the people of Chamorro, guam.
Parkinsonism-dementia complex (PDC), a neurodegenerative disorder in the Chamorro, Guam population, has been epidemiologically ascribed to the ingestion of the neurotoxin cycasin. This disease is characterized neuropathologically by the presence of abundant neurofibrillary tangles (NFTs). We analyzed a genetic risk factor of Alzheimer's disease (AD), apolipoprotein E, hypothesized to be linked to NFT formation, and a genetic risk factor of Parkinson's disease (PD), CYP2D6 mutation, linked to slower metabolism of exogenous toxins, in Chamorro, Guam individuals with and without PDC. The representation of the G-to-C mutation in exon 9 of the CYP2D6 gene was higher in Chamorro and Filipino than in Caucasian individuals, but this mutant allele had similar high frequencies in both PDC patients and healthy Chamorro individuals. We found no alleles of these genes associated with AD or PD to be overrepresented among those with PDC.
Adult↗
Comment on soft tissue profile by Dr. Polk.
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Beauty↗
Apolipoprotein-epsilon4 and head trauma: Synergistic or additive risks?
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Aged↗
Baggage handling postures and the design of conveyors.
The main purpose of this study was to determine the height, angle and velocity of conveyors for baggage handling at Schiphol Airport. These variables have a great influence on the postures and workload of baggage handlers. One hundred and seven healthy male baggage handlers participated in a test, during which a regular baggage handling task was simulated with a mock-up. Eighteen combinations of heights, angles and velocities were tested. Data on postures were collected with the aid of task recording and analysis on computer (TRAC). The minimal volume of open space under the conveyor was determined with light cells that scored the positions of legs and feet of the subjects. In addition, opinions from the baggage handlers were gathered with a questionnaire, immediately after the test. Finally the number of selection errors made and the number of bags that fell off the conveyor were noted, to make sure that ergonomics improvements did not reduce the quality of baggage handling. On the basis of these three information sources, alternative conveyor dimensions were recommended, which are expected to improve the working conditions of the baggage handlers, without any reduction in the quality of work.
Journal Article↗
Prospective study of hospitalization for asthma. A preliminary risk factor model.
We conducted an exploratory analysis of several prospectively obtained objective measures of disease activity to derive a predictive model of hospitalization for asthma among 310 adults, ages 18 to 50 yr, with moderate to severe asthma. Baseline characteristics associated with increased risk of hospitalization in the succeeding year include (1) prior year hospitalization, (2) moderate or severe respiratory impairment, (3) a medication regimen consistent with severe asthma, (4) a history of significant systemic steroid use, (5) maximum overnight PEF variability > 40%, and (6) mean evening PEF < 60% of predicted (relative risk = 6.5, 6.9, 8.1, 3.7, 3.0, and 3.2, respectively). Recursive partitioning analysis, depicted as a "classification tree," provided a more sensitive (94%) and specific (68%) multivariate description of the data set than either logistic regression (87 and 48%, respectively) or a simple additive risk model (46 and 93%, respectively). Patients with very high (> 50%), moderately elevated (10 to 15%), and very low (< 5%) risk of hospitalization were identified on the basis of particular combinations of prior hospitalization history, level of respiratory impairment, and medication regimen. Overnight variability and mean evening PEF measured at home over a 2-wk period proved less informative for risk stratification than respiratory impairment determined once at baseline by office spirometry. The findings warrant replication and extension in other populations with the goal of developing decision rules for risk stratification and effective interventions for risk reduction.
Adult↗
Application of neural networks to the classification of giant cell arteritis.
OBJECTIVE: Neural networks are a group of computer-based pattern recognition methods that have recently been applied to clinical diagnosis and classification. In this study, we applied one type of neural network, the backpropagation network, to the diagnostic classification of giant cell arteritis (GCA). METHODS: The analysis was performed on the 807 cases in the vasculitis database of the American College of Rheumatology. Classification was based on the 8 clinical criteria previously used for classification of this data set: 1) age > or = 50 years, 2) new localized headache, 3) temporal artery tenderness or decrease in temporal artery pulse, 4) polymyalgia rheumatica, 5) abnormal result on artery biopsy, 6) erythrocyte sedimentation rate > or = 50 mm/hour, 7) scalp tenderness or nodules, and 8) claudication of the jaw, of the tongue, or on swallowing. To avoid overtraining, network training was terminated when the generalization error reached a minimum. True cross-validation classification rates were obtained. RESULTS: Neural networks correctly classified 94.4% of the GCA cases (n = 214) and 91.9% of the other vasculitis cases (n = 593). In comparison, classification trees correctly classified 91.6% of the GCA cases and 93.4% of the other vasculitis cases. Neural nets and classification trees were compared by receiver operating characteristic (ROC) analysis. The ROC curves for the two methods crossed, indicating that the better classification method depended on the choice of decision threshold. At a decision threshold that gave equal costs to percentage increases in false-positive and false-negative results, the methods were not significantly different in their performance (P = 0.45). CONCLUSION: Neural networks are a potentially useful method for developing diagnostic classification rules from clinical data.
Diagnosis, Computer-Assisted↗
Does peak inspiratory flow contribute to setting VO2max? A test of symmorphosis.
Symmorphosis predicts that animal design is optimized in such a way that structure 'statisfies but does not exceed' functional requirements. To provide one test of this hypothesis, we examined peak inspiratory flow and its relation to maximum oxygen uptake in humans. We measured maximal forced (peak) inspiratory flow (VImax) and maximum oxygen uptake (VO2max) via cycle ergometry in well trained (VO2max > 65 ml O2.kg-1.min-1) and untrained (VO2max < 45 ml O2.kg-1.min-1) male subjects. Tests of VImax and peak oxygen uptake (VO2peak) were made while the subjects were breathing through inspiratory orifices differing in area. VImax varied as an identical function of orifice diameter in both groups of subjects. However, VO2peak was more sensitive to decreasing orifice diameter in trained endurance athletes than it was in untrained individuals. The diameter of the largest orifice that caused a reduction in oxygen uptake was over two times larger for trained than for untrained subjects, corresponding to about a four-fold difference in resistance at any flow rate. These results suggest that the structures setting VImax (airway resistance and inspiratory muscle strength) are not matched to oxygen demand (VO2max) in humans. While these structures seem to be 'over-built' and hence do not likely contribute to setting the limits to aerobic performance in most humans, they may be among the primary limiting factors in the most elite endurance athletes.
Adaptation, Physiological↗
Drug and alcohol abuse inpatients' attitudes about smoking cessation.
Attitudes about quitting cigarette smoking were assessed at admission to a substance abuse treatment program for homeless veterans. The majority were interested in quitting smoking, believed that inpatient drug/alcohol treatment was the best time to quit, and that quitting would not threaten their sobriety. Using cluster analysis, four subgroups of inpatients with different levels of interest, confidence, and motivation regarding quitting smoking were identified. Our inpatients' positive attitudes about quitting smoking stand in contrast with previously reported attitudes of many health professionals, and suggest that inpatient treatment could be an opportune time to provide stop-smoking interventions. Findings also suggest that different treatment approaches may be needed for subgroups of inpatients with varying attitudes about quitting.
Adult↗
Exercise performance of mammals: an allometric perspective.
We have examined aerobic exercise performance among the mammals with particular attention to the constraints that body size places on all aspects of muscle biomechanics, aerobic energetics, tissue oxygen diffusion, cardiovascular oxygen delivery, and pulmonary oxygen uptake. Several body-size-dependent patterns emerge that seemingly govern aerobic performance in mammals, with the caveat that at any given body size there is a range of aerobic capacities, the result of natural selection operating on the size-dependent "default values" of structure and function. Among these default values, the following apparent functional clusters surface: 1. In general, concentrations and pressures (e.g., of proteins and gases) are roughly independent of body size. Inspiratory and expiratory ventilation pressures, blood pressure and the partial pressures of O2 and CO2 in lungs, blood, and tissues do not vary with body size. Likewise, concentrations of hemoglobin, myoglobin, and hematocrit are independent of body size. 2. Most volumes and capacities scale linearly with body size (i.e., as a constant function of body mass). In addition to heart, lung, and total blood volumes, important examples relevant to exercise performance are the diffusing capacities for oxygen in the lung and, apparently, in the tissues. 3. Finally, most time-dependent variables related to oxygen delivery scale allometrically with body mass; they are of shorter duration in small animals than in large ones. Biological rates, for example, Vmax of working muscle, heart and respiratory rates, and transit times of blood through the muscles and lungs, all vary roughly as the -1/5 to -1/4 power of body mass.
Animals↗
Peer review of on-scene air medical triage in Connecticut.
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Air Ambulances↗
Correlation between radiological and pathological diagnosis of silicosis: an autopsy population based study.
The radiological findings for the profusion of rounded opacities were compared to pathological findings for parenchymal silicosis in 557 gold miners who had, on average, 2.7 years between the radiological and pathological examination. Three readers read the radiographs, and ILO category 1/1 or more was defined as a positive diagnosis of silicosis. The sensitivity values were 0.393, 0.371, and 0.236, and the specificity values were 0.987, 0.965, and 0.978, for the three readers, respectively. The sensitivity of the readers improved with increasing degree of autopsy silicosis, but a large proportion of those with a moderate and marked degree of silicosis were not diagnosed radiologically. The diagnostic sensitivity of the radiological test could be improved by using category 0/1 as a cutoff point for workers exposed to a high average concentration of respirable silica dust. The diagnostic specificity of radiology could be improved by using category 1/0 or 1/1 as a cutoff point for a positive diagnosis for workers exposed to a low average concentration of respirable silica dust.
Autopsy↗
A controlled trial of two forms of self-management education for adults with asthma.
PURPOSE: Excess morbidity and mortality due to asthma, aggravated by demonstrably poor patient self-management practices, suggest the need for formal patient education programs. Individual and group asthma education programs were developed and evaluated to determine their cognitive, behavioral, and clinical effects. PATIENTS AND METHODS: We compared changes in asthma symptoms, utilization of medical services, knowledge about asthma, metered-dose inhaler (MDI) technique, and self-management behaviors for 323 adult Kaiser Permanente patients with moderate to severe asthma who were randomly assigned to small-group education, individual teaching, or 1 of 2 control conditions--an information (workbook) control or usual control (no formal asthma education). Data were collected from patients by questionnaire, diary, and physical examination at enrollment and at 5 months and 1 year after intervention. Medical record data on these patients were abstracted for a total 3-year period, from 1 year before to 2 years after enrollment. RESULTS: Compared with the usual control, the self-management education programs were associated with significant improvements in control of asthma symptoms (reduced "bother" due to asthma and increased symptom-free days), MDI technique, and environmental control practices. Small-group education also was associated with significant improvements in physician evaluation of the patients' asthma status and in patients' level of physical activity. For both group and individual education recipients, improvement in MDI technique was positively correlated with improved control of symptoms; however, the degree of improvement in symptoms was greater than that which could be accounted for on the basis of improvement in MDI technique alone. The time course over which changes occurred in the various outcome measures suggests the mechanism by which education resulted in improvement in the patient's status. Significant improvements in MDI technique and environmental control practices were manifest immediately following education (5-month follow-up) and at the 1-year follow-up. Significant improvements in symptom measures were not apparent until the 1-year follow-up. The rate of utilization of medical care for acute exacerbations decreased between baseline and the 2-year follow-up period, but this decrease did not differ significantly among treatment conditions. However, there was a trend toward greater reduction in patients receiving small-group education. An ad hoc finding of a significant difference favoring small-group education between the baseline and the second follow-up year acute visit rates was observed. This result must be regarded as tentative, since it is not clear that unambiguous statistical significance is attained in the light of multiplicity issues. However, this trend is consistent with the antecedent benefits of the small-group education, and appears to warrant further investigation. CONCLUSIONS: Carefully designed asthma education programs for adults can improve patients' understanding of their condition and its treatment and increase their motivation and confidence that the condition can be controlled, thereby increasing their adherence to the treatment regimen and management of symptoms, and, in turn, improving control of symptoms. Both small-group education and individual education were associated with significant benefits, but the group program was simpler to administer, better received by patients and educators, and more cost-effective. The results show promise for improving clinical outcomes, through well-designed educational programs, for patients with asthma and other chronic health problems.
Acute Disease↗
Trimethoprim-sulfamethoxazole prophylaxis in granulocytopenic patients with acute leukemia: evaluation of serum antibiotic levels in a randomized, double-blind, placebo-controlled Department of Veterans Affairs Cooperative Study.
Despite widespread use of trimethoprim-sulfamethoxazole (TMP-SMZ) for prophylaxis in neutropenic patients, questions remain regarding its efficacy, toxicity, the risk of selection of resistant isolates, and the relation of its activity to selective decolonization vs. the attainment of direct inhibitory levels within blood and tissues. We evaluated the effect of TMP-SMZ (160/800 mg orally every 12 hours) in 42 adult granulocytopenic patients (< 100 absolute neutrophils/mm3, mean duration 13.3 days) undergoing chemotherapy for acute leukemia at 11 participating Veterans Administration Medical Centers in a randomized, double-blind, placebo-controlled trial. No significant differences in survival, frequency of bacteremia, overall infections, use of systemic antimicrobial therapy, or adverse effects, including myelosuppression, were observed between patients receiving TMP-SMZ vs. those receiving placebo. All patients acquired trimethoprim-resistant organisms. Concentrations of trimethoprim in serum were significantly lower before febrile episodes than when patients were afebrile. These results suggest that the purported activity of TMP-SMZ may be related to the serum concentration achieved. Moreover, the results highlight the need for additional study of the value of antibiotic prophylaxis in neutropenic patients.
Acute Disease↗
Association of silicosis, lung dysfunction, and emphysema in gold miners.
BACKGROUND: In an earlier study of gold miners men with silicosis were found to have abnormal lung function, including airflow obstruction and reduced diffusing capacity. In a follow up study a sample of these men was examined by computed tomography to determine whether emphysema accounted for these abnormalities, which are associated with silicosis in this working population. METHODS: A sample of 70 men from a cohort of older gold miners with and without silicosis who had worked underground for a mean period of 29 years was examined by computed tomography to determine whether each man had emphysema. In addition, each man had lung function tests and routine chest radiography (125 kV). RESULTS: A total of 48 men had emphysema on examination by computed tomography. On the basis of the results in a chest radiograph 55 of the men had silicosis. Emphysema was related to silicosis, being present in five of the 15 men without silicosis and in 43 of the 55 with silicosis. Diffuse emphysema was apparent in two men without silicosis (14%) and in 25 men with silicosis (45%). The proportion of men with diffuse emphysema increased from 14% in those with International Labour Organisation category 0 nodule profusion to 46% in those with category 1, 48% in those with category 2, and 67% in those with category 3. Emphysema was also related to smoking: eight of the 18 who had never smoked and 40 of the 52 smokers had emphysema. All of those who had never smoked and had emphysema had silicosis with category 2/2 or greater nodule profusion. Lung function tests showed changes associated with silicosis that could be explained by the associated emphysema. CONCLUSIONS: In this population emphysema occurred in association with silicosis and accounted for the abnormalities in lung function associated with silicosis.
Gold↗
Overtraining in neural networks that interpret clinical data.
Backpropagation neural networks are a computer-based pattern-recognition method that has been applied to the interpretation of clinical data. Unlike rule-based pattern recognition, backpropagation networks learn by being repetitively trained with examples of the patterns to be differentiated. We describe and analyze the phenomenon of overtraining in backpropagation networks. Overtraining refers to the reduction in generalization ability that can occur as networks are trained. The clinical application we used was the differentiation of giant cell arteritis (GCA) from other forms of vasculitis (OTH) based on results for 807 patients (593 OTH, 214 GCA) and eight clinical predictor variables. The 807 cases were randomly assigned to either a training set with 404 cases or to a cross-validation set with the remaining 403 cases. The cross-validation set was used to monitor generalization during training. Results were obtained for eight networks, each derived from a different random assignment of the 807 cases. Training error monotonically decreased during training. In contrast, the cross-validation error usually reached a minimum early in training while the training error was still decreasing. Training beyond the minimum cross-validation error was associated with an increased cross-validation error. The shape of the cross-validation error curve and the point during training corresponding to the minimum cross-validation error varied with the composition of the data sets and the training conditions. The study indicates that training error is not a reliable indicator of a network's ability to generalize. To find the point during training when a network generalizes best, one must monitor cross-validation error separately.
Bias↗