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.     

No evidence for a correlation between behaviour and the size of the Y chromosome

Y chromosome variation has been studied in three groups of Norwegian males: 35 boys from an adolescent psychiatric hospital; 45 men from a hospital for hard-to-manage or dangerous, psychotic men; and 26 boys from two ordinary school classes.
Y chromosomes with 1, 2, and 3 brightly fluorescing bands were found in all three groups. One boy carried a Y with no bands. The mean values of the Yf/Yq ratio were not significantly different in the three groups (Yf is the length of the distal, brightly fluorescing part of Yq). Two cases of XY/XYY mosaicism were found among the psychotic men.
The study shows that the human species is polymorphic with regard to the size of the Y chromosome, i. e. the number of fluorescent bands in the long arm. No phenotypical manifestation of this polymorphism, particuIarly as regards behaviour, was found.     

Recent advances in cellular immunology: implications for immunity to cancer

Basic immunologists, animal experimenters and clinicians came together earlier this year to discuss insights into, and applications of, cellular immunity to cancer. Major questions critical to the further evaluation and exploitation of the cellular immune response to cancer were explored. It was clear from this conference that there has been a move beyond phenomenology to reductionistic approaches to understanding immune events, raising hopes that the specificity of the T-cell response might be applied to the problem of human cancer.     

Pharmacologic specificity of tolerance to caffeine-induced stimulation of locomotor activity

The pharmacologic specificity of tolerance to caffeine-induced stimulation of locomotor activity was studied in adult male rats that were given access to either caffeine solution (0.5 or 1.0 mg/ml) or plain water for 10 min every 6 h on a chronic daily basis; daily caffeine intake averaged 41 and 62 mg/kg, respectively. Dose-effect curves were determined for behavioral stimulant and depressant drugs in control and caffeine-treated groups. Drugs were injected IP and locomotor activity was measured for 30 min beginning 35 min later. Rats tolerant to stimulation of locomotor activity by caffeine were also tolerant to theophylline and 7-(2-chloroethyl)theophylline, but not to any of six nonxanthine stimulants, including cocaine, methylphenidate, and d-amphetamine. The adenosine analogs, R(–)-N⁶-2-(phenylisopropyl)adenosine(R(–)-PIA) and 5-(N-ethyl)carboxamidoadenosine (NECA), decreased locomotor activity of control and caffeine-treated (0.5 mg/ml) rats; dose-effect curves in rats consuming caffeine chronically were displaced to the right of the control curves by 10-fold for R(–)-PIA and 100-fold for NECA. Dose-effect curves for the nonadenosine behavioral depressants chlorpromazine and diazepam were unchanged by chronic treatment with caffeine, but the curve for pentobarbital, which is thought to inhibit adenosine receptor binding, was shifted to the right by a factor of 3. Rats withdrawn from chronic caffeine for 24 h were still completely tolerant to caffeine-induced stimulation of locomotor activity. Dose-effect curves for R(–)-PIA and d-amphetamine in rats withdrawn from chronic caffeine for 24 h were not different from curves in control animals. These results indicate that tolerance to caffeine-induced stimulation of locomotor activity is specific to the methylxanthine class of stimulants and is not a property of nonxanthine psychomotor stimulants. Furthermore, the adenosine-antagonist activity of caffeine remains evident even in rats completely tolerant to the stimulant effect of caffeine. These results provide no support for the view that caffeine tolerance is due to enhanced sensitivity of central adenosine systems.A preliminary report of this work appeared in The Pharmacologist (28:140, 1986)     

Rectal and brain temperatures in ethanol intoxicated mice

The organometal neurotoxin trimethyltin (TMT), induces impaired learning and memory for various tasks. However, administration is also associated with other non-specific behavioral changes which may be responsible for effects on conditioned behaviors. To determine if TMT treatment causes a specific learning impairment, three experiments were done using variations of a delay of reinforcement autoshaping task in which rats learn to associate the presentation and retraction of a lever with the delivery of a food pellet reinforcer. No significant effects of TMT treatment were found with a short (4 s) delay of reinforcement, indicating that rats were motivated and had the sensorimotor capacity for learning. When the delay was increased to 6 s, 3.0 or 6.0 mg TMT/kg produced dose-related reductions in behaviors directed towards the lever. Performance of a group given 7.5 mg TMT/kg, while still impaired relative to controls, appeared to be better than the performance of groups given lower doses. This paradoxical effect was investigated with a latent inhibition paradigm, in which rats were pre-exposed to the Skinner boxes for several sessions without delivery of food reinforcement. Control rats showed retardation of autoshaping when food reinforcement was subsequently introduced. Rats given 7.5 mg TMT/kg exhibited elevated levels of lever responding during pre-exposure and autoshaping sessions. The results indicate that 7.5 mg TMT/kg produces learning impairments which are confounded by hyperreactivity to the environment and an inability to suppress behavior toward irrelevant stimuli. In contrast, low doses of TMT cause learning impairments which are not confounded by hyperreactivity, and may prove to be useful models for studying specific associational dysfunctions.     

Markers of Intestinal Permeability Are Rapidly Improved by Alcohol Withdrawal in Patients with Alcohol-Related Liver Disease

Changes in intestinal microbiome and barrier function are critical in the development of alcohol-related liver disease (ALD). Here, we determined the effects of a one-week alcohol withdrawal on parameters of intestinal barrier function in heavy drinkers with ALD in comparison to healthy non-drinkers (controls). In serum samples of 17 controls (m = 10/f = 7) and 37 age-matched ALD patients (m = 26/f = 11) undergoing a one-week alcohol withdrawal, markers of liver health and intestinal barrier function were assessed. Liver damage, e.g., fibrosis and hepatic steatosis, were assessed using FibroScan. Before alcohol withdrawal, markers of liver damage, lipopolysaccharide binding protein (LBP) and overall TLR4/TLR2 ligands in serum were significantly higher in ALD patients than in controls, whereas intestinal fatty acid binding protein (I-FABP) and zonulin protein concentrations in serum were lower. All parameters, with the exception of LBP, were significantly improved after alcohol withdrawal; however, not to the level of controls. Our data suggest that one-week of abstinence improves markers of intestinal barrier function and liver health in ALD patients.     

Physiological responses in sons of alcoholics

Researchers have differentiated sons of alcoholics (SOA's) from sons of nonalcoholics (non-SOA's) on various measures of physiological activity that appear to be related to the SOA's increased vulnerability to developing alcohol problems. This article summarizes major findings in the literature and discusses the implications of risk-related physiological characteristics for the future development of alcohol problems. SOA's tend to show signs of physiological activity associated with anxiety states, such as increased heart rate in response to stressful stimuli. Studies also demonstrate that SOA's differ greatly from non-SOA's in their response to alcohol. Drinking alcohol dramatically reduces SOAs' reactivity to both stressful and nonstressful stimuli. Additionally, SOA's appear to be less sensitive to alcohol's intoxicating and impairing effects. However, studies also suggest that some SOA's may experience more of alcohol's rewarding effects for a brief period after drinking. Increased stress-dampening and reduced responsiveness to alcohol's negative effects also appear to predict the development of future alcohol problems and may reflect important vulnerabilities in SOA's.     

Phase I-II study of gamma interferon and 5-fluorouracil for patients with metastatic renal cell carcinoma

We have completed a phase I/II trial to evaluate the toxicity and efficacy of the combination of gamma interferon and 5-fluorouracil in metastatic renal cell carcinoma. Gamma interferon was administered at a weekly dose of 100 micrograms. 5-fluorouracil was given as a 5 day continuous infusion days 1-5 of each 21 day cycle. In the phase I portion of the trial, the gamma interferon dose was held constant, while the 5-fluorouracil was escalated from 500 to 800 mg/m2/day. Serum neopterin and beta 2 microglobulin were measured prior to and 48 hours after each dose of gamma interferon for the first six weeks of treatment. Dose limiting toxicity was not encountered in the phase I part of the trial; therefore the phase II study was initiated at the 800 mg/m2/day dose of 5-fluorouracil. No responses were seen among 34 patients treated on the phase II trial. Forty-six percent of patients experienced disease stabilization and the remainder progressed through treatment. In the phase I trial, increments in neopterin and beta 2 microglobulin levels differed significantly between patients treated with lower and higher doses of 5-fluorouracil. We conclude that the addition of 5-fluorouracil to gamma interferon does not appear to enhance the cytokines clinical activity. Incremental increases in macrophage activation markers with escalating 5-fluorouracil doses suggests a role for 5-fluorouracil beyond its usual proposed cytotoxic activity and warrants further investigation into potential immunologic effects of this drug.