Establishing criteria for sexual consent capacity.

Assessment of sexual consent capacity of individuals with mental retardation is a complex problem. A struggle exists between promoting rights and protection from harm when these impairments interfere with the ability to make informed decisions. We examined the consensus of psychologists on specific criteria for sexual consent capacity. Randomly selected doctoral level members (N = 305) of the American Psychological Association completed a questionnaire regarding their opinions about various components of human sexuality. A factor analysis of individual items revealed five factors: Consequences of Sexual Activity, Essential Sexual Knowledge, Unessential Sexual Knowledge, Safety for Self and Others, and Basic Safety Skills. Generally, the factor structure identified basic sexual knowledge, knowledge of the consequences of sexual behavior, and abilities related to self-protection as integral to sexual consent capacity.

Combustion products of 1,3-butadiene are cytotoxic and genotoxic to human bronchial epithelial cells.

Adverse health effects of airborne toxicants, especially small respirable particles and their associated adsorbed chemicals, are of growing concern to health professionals, governmental agencies, and the general public. Areas rich in petrochemical processing facilities (e.g., eastern Texas and southern California) chronically have poor air quality. Atmospheric releases of products of incomplete combustion (e.g., soot) from these facilities are not subject to rigorous regulatory enforcement. Although soot can include respirable particles and carcinogens, the toxicologic and epidemiologic consequences of exposure to environmentally relevant complex soots have not been well investigated. Here we continue our physico-chemical analysis of butadiene soot and report effects of exposure to this soot on putative targets, normal human bronchial epithelial (NHBE) cells. We examined organic extracts of butadiene soot by gas chromatography-mass spectrometry (GC-MS), probe distillation MS, and liquid chromatography (LC)-MS-MS. Hundreds of aromatic hydrocarbons and polycyclic aromatic hydrocarbons with molecular mass as high as 1,000 atomic mass units were detected, including known and suspected human carcinogens (e.g., benzo(a)pyrene). Butadiene soot particles also had strong, solid-state free-radical character in electron spin resonance analysis. Spin-trapping studies indicated that fresh butadiene soot in a buffered aqueous solution containing dimethylsulfoxide (DMSO) oxidized the DMSO, leading to CH(3)* radical formation. Butadiene soot DMSO extract (BSDE)-exposed NHBE cells displayed extranuclear fluorescence within 4 hr of exposure. BSDE was cytotoxic to > 20% of the cells at 72 hr. Morphologic alterations, including cell swelling and membrane blebbing, were apparent within 24 hr of exposure. These alterations are characteristic of oncosis, an ischemia-induced form of cell death. BSDE treatment also produced significant genotoxicity, as indicated by binucleated cell formation. The combination of moderate cytotoxicity and genotoxicity, as occurred here, can be pro-carcinogenic.

Social interaction interventions for youth with severe disabilities should emphasize interdependence.

An emphasis on independence may be limiting the outcomes achieved by social interaction research. Given the lack of correlation between intellectual or adaptive functioning level and meaningful social outcomes for people with severe disabilities, a focus on increasing skills as a mechanism for increasing social outcomes seems misplaced (or, at least, inefficient). It is argued here that a more productive route for researchers to follow will be to emphasize interdependence. Implications of such a focus will change where interventions are implemented, curricular foci, and the types of instructional strategies used to improve the social life of youth with severe disabilities. MRDD Research Reviews 7:122-127, 2001.

Experimental analyses of gene-brain-behavior relations: some notes on their application.

The fields of genetics and neuroscience are yielding findings useful in understanding complex behavior-environment relations. We believe that these developments in interdisciplinary basic research are of interest to applied behavior analysts because of the long history of basic findings being used by the readership of the Journal of Applied Behavior Analysis to improve everyday human activities. An awareness of contemporary developments in a range of basic research disciplines may facilitate the systematic replication of those functional relations in applied settings. In this context, we selectively review papers published in the Journal of the Experimental Analysis of Behavior and other basic research journals that relate to gene-brain-behavior relations.

Effects of sleep deprivation on free-operant avoidance.

Two studies examined effects of sleep deprivation on free-operant avoidance by rats. In Experiment 1, a 5-s shock-shock (SS) interval and 20-s response-shock (RS) interval produced baseline performances, which were reestablished after each experimental manipulation. Once baselines were established, animals were exposed to 24, 48, or 96 hr of sleep deprivation and equivalent periods of home cage and food restriction as a control condition. Compared to baseline, sleep deprivation increased response rates by increasing the proportion of brief interresponse times (IRTs); response rates changed little in the control conditions. Percentage of shocks avoided did not systematically change across conditions. In Experiment 2, the RS interval was manipulated (10, 20, and 40 s), while the SS interval (5 s) and level of sleep deprivation (48 hr) were held constant. Across RS intervals, sleep deprivation increased response rates via a shift toward brief IRTs. In addition, sleep deprivation increased the percentage of shocks avoided as an inverse function of RS intervals.

Analyzing the multiple functions of stereotypical behavior for students with autism: implications for assessment and treatment.

We studied behavioral functions associated with stereotypical responses for students with autism. In Study 1, analogue functional analyses (attention, demand, no-attention, and recreation conditions) were conducted for 5 students. Results suggested that stereotypy was multiply determined or occurred across all assessment conditions. For 2 students, stereotypy was associated with positive and negative reinforcement and the absence of environmental stimulation. For 2 other students, stereotypy occurred at high levels across all experimental conditions. For the 5th student, stereotypy was associated with negative reinforcement and the absence of environmental stimulation. In Study 2, the stereotypy of 1 student was further analyzed on a function-by-function basis. Within a concurrent-schedules procedure, alternative responses were taught to the student using functional communication training. The results of Study 2 showed that similar topographies of stereotypy, based on qualitatively different reinforcers, were reduced only when differential reinforcement contingencies for alternative forms of communication were implemented for specific response-reinforcer relations. Our results suggest that the causes of stereotypy for students with autism are complex and that the presumed association between response topography and behavioral function may be less important than previously realized.

A correlation of APC and c-myc mRNA levels in lung cancer cell lines.

One of the functions of adenomatous polyposis coli (APC) in colorectal cancers is regulation of c-myc gene expression. However, the role of APC in lung cancers has not been elucidated. In the present study, the levels of APC and c-myc mRNA were determined in one strain of normal human bronchial epithelial (NHBE) cells, an SV-40-immortalized non-tumorigenic human bronchial epithelial cell line (BEAS-2B), 13 non-small cell lung cancer cell lines, and 4 small cell lung cancer cell lines. To establish a relationship between c-Myc and APC, we determined the ratio of c-myc and APC mRNA levels in different lung cancer cell lines. Out of 19 lung cancer cell lines, we found that 13 exhibited c-myc/APC mRNA ratio of more than two. Among the cell lines CaLu-3, NCI-H82, A427 and SW900 showed a very low level of APC mRNA and a high level of c-myc mRNA. The ratio of c-myc/APC mRNA in these cell lines was 48, 127, 325 and 708, respectively. The results of these analyses revealed an inverse relationship between APC and c-myc mRNA levels, suggesting that APC may regulate c-myc expression in lung cancer cells in a manner analogous to its role in colon cancer.

Promoting generalized social interactions using puppets and script training in an integrated preschool. A single-case study using multiple baseline design.

Puppet script training was used to teach the social skills of greeting, responding to conversations, and initiating conversations to a preschool child with visual impairments. Susie and four peers without disabilities were taught social skills utilizing puppets enacting sociodramatic scripts within group training sessions. Training sessions were immediately followed by free-play activities among peers without disabilities to assess skill generalization. A single-case study using a multiple-baseline design demonstrated that the intervention increased performance of social skills during recess with peers. Results demonstrated that Susie learned the target behaviors and generalized their use to free-play activities with her peers.

Overexpression of hMTH1 mRNA: a molecular marker of oxidative stress in lung cancer cells.

Human MutT homologue (hMTH1) mRNA was overexpressed in SV-40-transformed non-tumorigenic human bronchial epithelial cells (BEAS-2B cells) and in 11 out of 12 human lung cancer cell lines relative to normal human bronchial epithelial cells. Expression levels of hMTH1 mRNA were inversely proportional to cellular levels of 8-oxo-deoxyguanosine. Together, these results suggest that hMTH1 gene expression may represent a molecular marker of oxidative stress that could ultimately be used to elucidate the temporal relationships between oxidative stress, genomic instability and the development of lung cancer.

Academic effects of providing peer support in general education classrooms on students without disabilities.

We studied the academic effects on peers without disabilities of serving as peer supports for students with disabilities in general education classrooms. Three peers were studied using a range of indicators, including academic engagement, coursework performance, and social validity assessments. Peers assisting a student with disabilities via curricular adaptation, assignment completion, and social facilitation constituted the multicomponent independent variable. We used withdrawal or multiple baseline designs to demonstrate positive benefits for peers for all measures used. In addition, follow-up data for 2 peers indicated that the positive changes associated with serving as a peer support were maintained for up to 2 months. Our results are discussed in relation to the possible academic and social effects of providing peer supports in general education classrooms for students with and without disabilities.

Deletion and differential expression of p16INK4a in mouse lung tumors.

Recent allelotyping of chemical-induced lung tumors in hybrid mice has detected loss of heterozygosity on chromosome 4 in a region involving the interferon-alpha (IFN-alpha gene cluster that is syntenic to human chromosome 9p21-22, the location of the p16INK4a (p16) and p15INK4b (p15) tumor suppressor genes. The purpose of the current investigation was to characterize the expression of p16 and p15 in lung tumors and tumor-derived cell lines induced in A/J mice by exposure to the tobacco-specific nitrosamine, 4-methylnitrosamino-1-(3-pyridyl)-1-butanone (NNK). Expression of p16 and p15 was detected in all primary lung tumors; however, levels of expression of p16 differed by up to 15-fold between tumors. This is the first study to note a marked difference in the expression of the p16 gene in primary lung tumors. The apparent low levels of expression seen in approximately half of the tumors was not attributed to deletion, mutation or methylation of the p16 gene. Conversely, the high levels of p16 expression were not the result of effects on the retinoblastoma gene (Rb) or cyclin D1 proteins but most likely in response to a dysfunction elsewhere within this pathway. In contrast to the detection of p16 expression in primary tumors, this gene was deleted in all four cell lines. Three of four cell lines also showed loss of the p15 gene. Mapping of these homozygous deletions on chromosome 4 revealed that the p16 gene resides near the D4MIT77 marker, which is located approximately 12 cM proximal to the IFN-alpha gene cluster, thereby implicating the p16 gene as one of the targets within the allelic deletions detected previously in primary lung tumors from hybrid mice.

Radon and lung carcinogenesis: mutability of p53 codons 249 and 250 to 238Pu alpha-particles in human bronchial epithelial cells.

Radon-222, a decay product of uranium-238 and a source of high linear energy transfer (LET) alpha-particles, has been implicated in the increased risk of lung cancer in uranium miners as well as non-miners. p53 mutation spectrum studies of radon-associated lung cancer have failed to show any specific mutational hot spot with the exception of a single study in which 31% of squamous cell and large cell lung cancers from uranium miners showed a p53 codon 249 AGGarg --> ATGmet mutation. Although the results of laboratory studies indicate that double-strand breaks and deletions are the principal genetic alterations caused by alpha-particles, uncertainty still prevails in the description of DNA damage in radon-associated human lung cancer. In the present study, we have evaluated the mutability of p53 codons 249 and 250 to alpha-particles in normal human bronchial epithelial (NHBE) cells using a highly sensitive genotypic mutation assay. Exposure of NHBE cells to a total dose of 4 Gy (equivalent to approximately 1460 working level months in uranium mining) of high LET alpha-radiation induced codon 249 AGG --> AAG transitions and codon 250 CCC --> ACC transversions with absolute mutation frequencies of 3.6 x 10(-7) and 3.8 x 10(-7) respectively. This mutation spectrum is consistent with our previous report of radon-associated human lung cancer.

Induction of genomic instability in normal human bronchial epithelial cells by 238Pu alpha-particles.

Pulmonary deposition of alpha-particle-emitting radon daughters is estimated to account for 10% of all lung cancer deaths in the USA. However, the nature and timing of early (preneoplastic) genetic alterations in radon-associated lung cancer are still relatively uncertain. The purpose of this investigation was to determine whether genomic instability occurs after exposure of cultured normal human bronchial epithelial cells to six equal, fractionated doses of alpha-particles (total doses 2-4 Gy). Two weeks after the final exposure, foci of phenotypically altered cells (PACs) were detected in 0, 63 and 77% of control, low and high dose cultures respectively. Of these, 18% exhibited extended life spans relative to unexposed controls. Elevated frequencies of binucleated cells (BNCs), a marker of genomic instability, were observed in 60 and 38% of the PAC cultures from the low and high dose groups respectively. The micronucleus assay also showed evidence of genomic instability in 40 and 38% of PAC cultures from the low dose and high dose groups respectively. No changes in microsatellite length, another marker of genomic instability, were detected in any of the PAC samples with the 28 markers used for this assay. However, one PAC (L2) showed a hemizygous deletion at 9p13.3. Another PAC (H9), which exhibited the highest frequency of cells containing micronuclei (MN), exhibited a hemizygous deletion at 7q31.3. Each loss may represent a stable mutation that resulted either directly from irradiation or later in progeny of exposed cells because of alpha-particle-induced genomic instability. The fact that elevated levels of BNCs and MN were present in the progeny many generations after irradiation indicates that the genetic alterations detected with these two markers were not a direct consequence of radiation exposure, but of resulting genomic instability, which may be an early change after exposure to alpha-particles.

Sleep deprivation, allergy symptoms, and negatively reinforced problem behavior.

We studied the relation between the presence versus the absence of sleep deprivation or allergy symptoms and the rate and function of problem behavior. Three students whose problem behavior was negatively reinforced by escape form instruction were studied across several weeks using analogue functional analyses. Our results indicated that the extraexperimental events were associated with (a) termination of instruction functioning as a negative reinforcer, (b) increased rates of negatively reinforced problem behavior, or (c) increased rates of problem behavior across all conditions.

Particle clearance and histopathology in lungs of F344/N rats and B6C3F1 mice inhaling nickel oxide or nickel sulfate.

The goals of this study were to (1) determine the effects of repeated inhalation of relatively insoluble nickel oxide (NiO) and highly soluble nickel sulfate hexahydrate (NiSO4.6H2O) on lung particle clearance, (2) investigate the effects of repeated inhalation of NiO or NiSO4 on the pulmonary clearance of subsequently inhaled 85Sr-labeled microspheres, (3) correlate the observed effects on clearance with accumulated Ni lung burden and associated pathological changes in the lung, and (4) compare responses in F344 rats and B6C3F1 mice. Male F344/N rats and B6C3F1 mice were exposed whole-body to either NiO or NiSO4.6H2O 6 hr/day, 5 days/week for up to 6 months. NiO exposure concentrations were 0, 0.62, and 2.5 mg NiO/m3 for rats and 0, 1.25, and 5.0 mg NiO/m3 for mice. NiSO4.6H2O exposure concentrations were 0, 0.12, and 0.5 mg NiSO4.6H2O/m3 for rats and 0, 0.25, and 1.0 mg NiSO4.6H2O/m3 for mice. After 2 and 6 months of whole-body exposure, groups of rats and mice were acutely exposed nose-only to 63NiO (NiO-exposed animals only), 63NiSO4.6H2O (NiSO4.6H2O-exposed animals only), or to 85Sr-labeled polystyrene latex (PSL) microspheres (both NiO- and NiSO4.6H2O-exposed animals) to evaluate lung clearance. In addition, groups of rats and mice were euthanized after 2 and 6 months of exposure and at 2 and 4 months after the whole-body exposures were completed to evaluate histopathological changes in the left lung and to quantitate Ni in the right lung. Repeated inhalation of NiO results in accumulation of Ni in lungs of both rats and mice, but to a greater extent in lungs of rats. During the 4 months after the end of the whole-body exposures, some clearance of the accumulated Ni burden occurred from the lungs of rats and mice exposed to the lower, but not the higher NiO exposure concentrations. Clearance of acutely inhaled 63NiO was also impaired in both rats and mice, with the extent of impairment related to both exposure concentration and duration. However, the clearance of acutely inhaled 85Sr PSL microspheres was not impaired. The repeated inhalation of NiO resulted in alveolar macrophage (AM) hyperplasia with accumulation of NiO particles in both rats and mice, chronic alveolitis in rats, and interstitial pneumonia in mice. These lesions persisted throughout the 4-month recovery period after the NiO whole-body exposures were terminated. In contrast, repeated inhalation of NiSO4.6H2O did not result in accumulation of Ni in lungs of either rats or mice and did not affect the clearance of 63NiSO4.6H2O inhaled after either 2 or 6 months of NiSO4.6H2O exposure. Clearance of the 85Sr-labeled microspheres was significantly impaired only in rats exposed to the microspheres after 2 months of exposure to NiSO4.6H2O. Histopathological changes in rats were qualitatively similar to those seen in NiO-exposed rats. Only minimal histopathological changes were observed in NiSO4.6H2O-exposed mice. These results suggest that repeated inhalation of NiO at levels resulting in AM hyperplasia and alveolitis may impair clearance of subsequently inhaled NiO. The potential effects of repeated inhalation of soluble NiSO4.6H2O on the clearance of subsequently inhaled poorly soluble particles are less clear.

Comparing interspersed requests and social comments as antecedents for increasing student compliance.

Two students were alternately presented with interspersed high-compliance requests and social comments as antecedents to low-compliance requests. An initial comparison demonstrated similar positive effects on compliance for interspersed requests and social comments. A second analysis indicated that the effectiveness of social comments for increasing compliance was related to the time interval between social comments and low-compliance requests.

Functional analysis and treatment of eye poking.

In four studies we analyzed the eye poking of a youth with profound disabilities. In Study 1, a functional analysis showed that eye poking occurred during the no-attention condition, but not during demand, attention or recreation conditions. The analysis did not identify socially mediated variables involved in the maintenance of eye poking; rather, eye poking may have been maintained by consequences produced directly by the response. In Study 2 we had the student wear goggles to prevent potential reinforcement from finger-eye contact. The results of Study 2 indicated that eye-poking attempts were reduced when the student wore goggles. We then tested in Study 3 the effects of two alternative topographies of stimulation. Study 3 demonstrated that eye poking was reduced when a video game was provided as a competing source of visual stimulation, and that music was less effective in reducing eye poking. In Study 4, a contingency analysis using the video game was conducted in an attempt to (a) reduce the frequency of eye poking and (b) study whether the video game functioned as a reinforcer. The results of Study 4 demonstrated substantive reductions in the frequency of eye poking, and suggested that the video game served as a reinforcer.

Nodality effects during equivalence class formation: An extension to sight-word reading and concept development.

Three students with moderate disabilities were taught to read and match-to-sample sight words comprising stimulus sets based upon the four food groups. We taught students conditional discriminations within four four-member sets using a single-sample/four-comparison procedure. Students were taught A-B, B-C, and C-D conditional discriminations for each of the four potential stimulus classes. Subsequent probes tested for relations based upon symmetry and one-node and two-node transitivity. The performances for all students indicated that symmetric relations emerged before one-node transitive relations, and that one-node transitive relations emerged before two-node transitive relations. These results are consistent with a pattern of responding, referred to as a "nodality effect," in which relations with fewer nodes are demonstrated prior to the demonstration of relations with a greater number of nodes. These results extend this area of research to sight-word reading for students with moderate disabilities.

Manipulating antecedent conditions to alter the stimulus control of problem behavior.

In a three-phase study, antecedent conditions involving instructor's task demands and social comments were evaluated for 3 students with severe disabilities who emitted problem behavior. The results of a descriptive analysis (Phase 1) demonstrated that task demands served as antecedents for problem behavior, and social comments were generally associated with increased levels of positive social affect. In a subsequent experimental analysis (Phase 2), an instructor emitted high rates of social comments and gradually faded in task demands across sessions. The results of Phase 2 showed initial reductions in problem behavior to near-zero levels from the onset of intervention, with the successful reintroduction of task demands for all students. Phase 3 replicated the procedures of Phase 1. The results demonstrated that for 2 students, task demands no longer served as antecedents to problem behavior. The outcomes from two social validity assessments indicated that substantial improvements were perceived in student behavior and that the independent variable was a socially acceptable means of reducing problem behavior.