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We investigated racial variation in glycemic control (glycated hemoglobin A1c [HbA1c]) with fracture risk in geriatric patients with diabetes. Compared to an HbA1c of 7.0-7.9% [53-63 mmol/mol], HbA1c ≥9.0% [≥75 mmol/mol] was associated with increased fracture risk among Blacks and those of Unknown race only. This increase was attenuated in Blacks after accounting for the relative frequency of patient-provider interaction.

We investigated racial variation in glycemic control (glycated hemoglobin A1c [HbA1c]) with fracture risk in geriatric patients with diabetes. Compared to an HbA1c of 7.0–7.9% [53–63 mmol/mol], HbA1c ≥9.0% [≥75 mmol/mol] was associated with increased fracture risk among Blacks and those of Unknown race only. This increase was attenuated in Blacks after accounting for the relative frequency of patient-provider interaction.

The Schoolwide Positive Behavior Intervention Support model (SWPBIS) continues to gain widespread use across schools in the United States and abroad. Despite its widespread implementation, little research has examined factors that influence its sustainability. Informed by Rogers's diffusion theory, this study examined school personnel's perceptions of the attributes of SWPBIS that predict its sustainability. These attributes include relative advantage, compatibility, complexity, trialability, and observability. Participants were school personnel employed in schools implementing SWPBIS. Results indicated that the relative advantage and observability of SWPBIS may predict its sustainability. These results led to some important implications for practitioners involved in the implementation of the SWPBIS. Limitations and recommendations for future research are also provided.

The current article describes the evaluation of a service-based learning model as part of a special education course focused on secondary programming for students with disabilities. A total of 42 preservice teachers and 21 high school juniors and seniors with disabilities actively participated in the service learning project at a local high school. Preservice teachers conducted a transition assessment, developed and implemented lesson plans for postsecondary skill development with a high school student, presented their results to local high school personnel, and completed a self-assessment of their level of confidence in transition education for secondary students. Overall, preservice teachers reported confidence in transition planning and in designing and delivering instructional opportunities based on assessment of high school students’ transition needs. Moreover, the preservice teachers met the course learning standards by working directly with high school students. Barriers and recommendations for personnel preparation and research are discussed.

Problem behavior can be reduced through choice making and use of preferred instructional activities. However, the opportunity to choose does not imply students are more engaged with instructional activities. The purpose of this study was to evaluate the effects of differential consequences on the on-task behavior of students within the context of teacher versus student selection of instructional activities. Students were exposed to two contingencies (i.e., escape + differential attention vs. escape + physical proximity) across two stimulus events (i.e., teacher vs. student choice of preferred instructional activities) using an alternating-treatments design within an A-B-A-B design. Choice of instructional activities increased on-task behavior during student-choice conditions compared to the teacher-choice conditions, but only when differential attention was provided. Differential attention was also more effective than physical proximity at increasing on-task behavior. Implications for practice and future research are discussed.

Aim To investigate, with extended follow-up, cause-specific mortality among low-income Black and White Americans with Type 2 diabetes who have similar socio-economic status. Methods Black and White Americans aged 40–79 years with Type 2 diabetes (n = 12 498) were recruited from community health centres as part of the Southern Community Cohort Study. Multivariable Cox analysis was used to estimate mortality hazard ratios and 95% CIs for subsequent cause-specific mortality, based on both underlying and contributing causes of death. Results During the follow-up (median 5.9 years), 13.3% of the study population died. The leading causes of death in each race were ischaemic heart disease, respiratory disorders, cancer, renal failure and heart failure; however, Blacks were at a lower risk of dying from ischaemic heart disease (hazard ratio 0.70, 95% CI 0.54–0.91) or respiratory disorders (hazard ratio 0.70, 0.53–0.92) than Whites but had higher or similar mortality attributable to renal failure (hazard ratio 1.57, 95% CI 1.02–2.40), heart failure (hazard ratio 1.47, 95% CI 0.98–2.19) and cancer (hazard ratio 0.87, 95% CI 0.62–1.22). Risk factors for each cause of death were generally similar in each race. Conclusions These findings suggest that the leading causes of death and their risk factors are largely similar among Black and White Americans with diabetes. For the two leading causes of death in each race, however, ischaemic heart disease and respiratory disorders, the magnitude of risk is lower among Black Americans and contributes to their higher survival rates.

We investigated the contribution of cytochrome P450 (CYP) 1B1 to hypertension and its pathogenesis by examining the effect of its selective inhibitor, 2,4,3',5'-tetramethoxystilbene (TMS), in spontaneously hypertensive rats (SHR).Blood pressure (BP) was measured bi-weekly. Starting at 8 weeks, TMS (600 μg/kg, i.p.) or its vehicle was injected daily. At 14 weeks, samples were collected for measurement.TMS reversed increased BP in SHR (207 ± 7 vs. 129 ± 2 mmHg) without altering BP in Wistar-Kyoto rats. Increased CYP1B1 activity in SHR was inhibited by TMS (RLU: aorta, 5.4 ± 0.7 vs. 3.7 ± 0.7; heart, 6.0 ± 0.8 vs. 3.4 ± 0.4; kidney, 411 ± 45 vs. 246 ± 10). Increased vascular reactivity, cardiovascular hypertrophy, endothelial and renal dysfunction, cardiac and renal fibrosis in SHR were minimized by TMS. Increased production of reactive oxygen species and NADPH oxidase activity in SHR, were diminished by TMS. In SHR, TMS reduced increased plasma levels of nitrite/nitrate (46.4 ± 5.0 vs. 28.1 ± 4.1 μM), hydrogen-peroxide (36.0 ± 3.7 vs. 14.1 ± 3.8 μM), and thiobarbituric acid reactive substances (6.9 ± 1.0 vs. 3.4 ± 1.5 μM). Increased plasma levels of pro-inflammatory cytokines and catecholamines, and cardiac activity of extracellular signal-regulated kinase, p38 mitogen-activated protein kinase, c-Src tyrosine kinase, and protein kinase B in SHR were also inhibited by TMS.These data suggests that increased oxidative stress generated by CYP1B1 contributes to hypertension, increased cytokine production and sympathetic activity, and associated pathophysiological changes in SHR. CYP1B1 could be a novel target for developing drugs to treat hypertension and its pathogenesis.

There has been considerable emphasis on indirect functional behavior assessments in school settings. However, little research has evaluated the reliability of these methods to identify behavioral function. One indirect measure, the Questions About Behavioral Function (QABF) scale, has yet to be extensively studied in school settings, though psychometric evidence suggests it is a viable assessment of the functions of a variety of problem behaviors for persons diagnosed with intellectual and/or developmental disabilities. The purpose of this study was to examine the reliability of the QABF when completed by teachers and paraprofessionals in a school setting with children diagnosed with a variety of disabilities. Overall, results suggested that when used in a school setting without support from examiners familiar with behavior analysis or the QABF, the measure demonstrated poor inter-rater reliability and internal consistency. Factors that may have contributed to this outcome are discussed, including suggestions for future research using indirect assessments in school settings.

Deleting the tailless (TLX) gene in mice produces a highly aggressive phenotype yet to be characterized in terms of heterozygous animals or neurotransmitter mechanisms. We sought to establish pharmacological control over aggression and study the role of serotonin (5-HT)(2A/C) receptors in mediating changes in aggression. We analyzed aggression in mice heterozygous (+/-) or homozygous (-/-) for the TLX gene and wild-types (+/+) using a resident-intruder paradigm. No +/+ mice were aggressive, 36% of +/- TLX and 100% of -/- TLX mice showed aggression. Dose-effect functions were established for clozapine (0.1-1.5mg/kg, ip), ketanserin (0.3-1.25 mg/kg, ip), and (±)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane [(±)DOI] (0.5-2.0 mg/kg, ip). Injecting clozapine decreased the frequency and duration of attacks for +/- TLX and -/- TLX mice. Clozapine did not decrease grooming in either +/- TLX or -/- TLX mice but may have increased locomotion for -/- TLX mice. Injecting ketanserin, a 5-HT(2A/C) receptor antagonist, produced differential decreases in frequency and latency to aggression between genotypes and corresponding increases in locomotor behavior. Injecting (±)DOI, a 5-HT(2A/C) receptor agonist, increased the frequency and duration of attacks, decreased the latency to attacks, and decreased locomotion in +/- and -/- TLX mice. Results of the current study suggest aggression displayed by TLX null and heterozygous mice involves 5-HT(2A/C) receptors.

OBJECTIVE To determine if long-term mortality rates in early-onset insulin-treated diabetes differ by race among adults of similar socioeconomic status. RESEARCH DESIGN AND METHODS A total of 391 (299 African Americans, 92 whites) mostly low-income adults 40–79 years of age with insulin-treated diabetes diagnosed before 30 years of age were recruited from community health centers in the southeast U.S. Cox models were used to estimate hazard ratios (HRs) of all-cause mortality among African Americans compared with whites. Additionally, standardized mortality ratios (SMRs) were used to compare the mortality experience of the individuals with diabetes with both national and general community health center sex- and race-specific population norms. RESULTS Mean age at diabetes diagnosis and cohort entry, respectively, was 21 and 50 years in African Americans and 19 and 51 years in whites. During an average of 6.7 years of follow-up, 29% of African Americans and 35% of whites died. In multivariable analysis, no significant mortality difference was observed among African Americans compared with whites (HR 0.83 [95% CI 0.53–1.30]; P = 0.51). Compared with the race-specific U.S. general population, SMRs for those with diabetes were 5.7 in African Americans and 11.7 in whites. However, when compared with the same source population (i.e., the community health center population), SMRs were 3.5 and 3.7 in African Americans and whites, respectively. CONCLUSIONS Elevated mortality persists in men and women with long duration of early-onset insulin-treated diabetes, but given survival to 40 years of age and similarly low economic status and access to health care, our data do not suggest a racial disparity in mortality.

Off-task behaviors are often maintained by escape from instructional activities. However, attention is typically inseparable from escape-related consequences imposed by teachers. Testing consequent conditions separately in a typical functional analysis in these instances could lead to inconclusive results. Therefore, it may be important to manipulate both positive and negative reinforcement contingencies simultaneously to parse out possible attention versus escape functions. The purpose of this study was to evaluate an escape condition combined with two contingent attention conditions for off-task behavior in a 4-year-old preschool girl. Data from the escape and the escape + directives conditions did not conclusively demonstrate attention was a maintaining variable for off-task behavior. However, there was a differentiated effect of providing escape + differential attention + engagement stimuli when compared to the escape + physical proximity during the academic demand. Thus, academic demand may have served as a setting event for off-task behavior, but the behavior occurred more frequently when escape + physical proximity was provided during the activity. Contrastingly, adding escape + differential attention + engagement stimuli during the academic demand appeared to compete with the value of escape for off-task behavior. Implications for assessing multiple functions of problem behavior and designing effective treatment packages by practitioners are discussed.

Law enforcement agencies stress that public reporting of terror-related crime is the predominant means for disrupting these actions. However, schools may be unprepared because the majority of the populace may not understand the threat of suspicious materials or what to do when they are found on school grounds. The purpose of this study was to systematically teach preschool children to identify and report suspicious packages across three experiments. In the first experiment, we used multiple exemplar training to teach children to identify the characteristics of safe and unsafe packages. In the second experiment, we taught participants to identify the locations where packages should be considered unsafe. Finally, in the third experiment, we used behavioral skills training to teach participants to avoid touching unsafe packages, leave the area where they were located, and report their discovery to an adult. Results suggest the participants quickly developed these skills. Implications for safety skills in young school children are discussed.

Advances in gene–environment interaction research have revealed genes that are associated with aggression. However, little is known about parent perceptions of genetic screening for behavioral symptoms like aggression as opposed to diagnosing disabilities. These perceptions may influence future research endeavors involving genetic linkage studies to behavior, including proactive approaches for parents to avoid events leading to aggression. The purpose of this study was to solicit the perspectives of parents who have children with autism about screening for genes associated with aggression, compared to responses from those who have children without disabilities and those planning to have children. Parents of children with autism were more likely to support screening and the use of the results to seek treatment if necessary. Results are discussed in the context of surveillance screening and systematic early intervention for behavioral symptoms related to autism. The results may provide insight for clincians, researchers, policymakers, and advocacy groups related to diagnosing and treating aggression in people with autism.

OBJECTIVE To estimate mortality rates and risk factors for mortality in a low-socioeconomic status (SES) population of African Americans and whites with diabetes. RESEARCH DESIGN AND METHODS We determined mortality among African Americans and whites aged 40–79 years with (n = 12,498) and without (n = 49,914) diabetes at entry into a cohort of participants recruited from government-funded community health centers. Multivariable Cox analysis was used to estimate mortality hazard ratios (HRs) (95% CI) among those with versus those without diabetes and among those with diabetes according to patient characteristics. RESULTS During follow-up (mean 5.9 years), 13.5% of those with and 7.3% of those without diabetes died. All-cause mortality risk was higher among those with versus without diabetes for both African Americans (HR 1.84 [95% CI 1.71–1.99]) and whites (1.80 [1.58–2.04]), although among those with diabetes, mortality was lower among African Americans than whites (0.78 [0.69–0.87]). Mortality risk increased with duration of diabetes and was greater among patients on insulin therapy and reporting histories of cardiovascular disease (CVD), hypertension, and stroke. The HRs associated with these multiple risk factors tended to be similar by sex and race, with the exception of a differentially higher impact of prevalent CVD on mortality among African Americans (interaction P value = 0.03), despite a lower baseline prevalence of CVD. CONCLUSIONS In this population with similarly low SES and access to health care, strong and generally similar predictors of mortality were identified for African Americans and whites with diabetes, with African Americans at a moderately but significantly lower mortality risk.

School-Wide Positive Behaviour Support (SWPBS) is increasingly becoming a popular approach to managing challenging behaviour in schools. However, several issues still have to be addressed facilitate successful implementation of this approach in schools. One of these issues pertains to the appropriateness of the different measures used to determine the efficacy of the approach. Because many schools are using indirect measures to assess the effects of SWPBS implementation, determining which measures more accurately reflect the effectiveness of the SWPBS components may increase the effectiveness of school measurement systems. The purpose of this study was to examine the measures used in evaluating the efficacy of positive behaviour support. The paper discusses the strengths and weaknesses of outcome measures regarding problem behaviour, prosocial behaviour, and implementation fidelity.

OBJECTIVE In young-onset diabetes, insulin therapy status is a rough marker of diabetes type. We describe the mortality experience of a low-income, predominantly minority population with diabetes diagnosed before age 30 years, stratified by insulin therapy. RESEARCH DESIGN AND METHODS A total of 1,098 adults aged 40–79 years (median 49) diagnosed with diabetes before age 30 years and 49,914 without diabetes were recruited from community health centers. Individuals with diabetes were categorized by insulin therapy at baseline: group A, insulin therapy only; group B, insulin therapy and an oral hypoglycemic agent; and group C, no insulin therapy. Cox models were used to compute hazard ratios (HRs) and 95% CI for cause-specific mortality based on both underlying and contributing causes of death from death certificates. RESULTS During follow-up (mean 3.9 years), 15.0, 12.5, and 7.3% of groups A, B, and C, respectively, and 4.6% without diabetes died. Compared with individuals without diabetes, HRs (CI) for all-cause mortality were 4.3 (3.4–5.6), 4.2 (2.8–6.3), and 2.0 (1.4–2.8) in groups A, B, and C, respectively. The leading cause of death was renal failure (end-stage renal disease [ESRD]) in group A, ESRD and coronary artery disease (CAD) in group B, and CAD in group C and individuals without diabetes. HRs for these conditions were at least twice as high as the HRs for all-cause mortality, reaching 17.3 (10.2–29.3), 17.9 (8.3–38.7), and 5.1 (2.3–11.7) in groups A, B, and C, respectively, for ESRD. CONCLUSIONS Excess mortality persists among people with young-onset diabetes of long duration, with ESRD and CAD as the leading contributors to mortality.

The use of SWPBS has increased quite rapidly across schools. This is happening against a backdrop of enthusiasm among policymakers, researchers and practitioners about the use of evidence-based practices in school settings. As SWPBS continues to attract the interest of school personnel it is necessary to look at this approach and examine its evidence base. This study was an attempt to extend previous work to that effect. Like previous efforts, this study demonstrated that although SWPBS has become quite popular, the evidence base may still be classified as promising. Research on SWPBS has to address many methodological limitations to strengthen its evidence base.

A thermal preference task was used to assess the effects of sleep deprivation on nociceptive behavior using hot and cool stimuli. The thermal preference apparatus allowed male rats to move freely from a hot thermal plate (44.7 °C) to an adjacent plate at neutral (33.5 °C) or cold temperatures (1.3–11 °C). Investigators recorded occupancy on the colder side, frequency of movements between the 2 compartments, and first escape latency from the cold side. Parametric analysis of thermal preference indicated that behavioral allocation was related to temperature ranges previously associated with activation of thermal nociceptors. A 50% occupancy rate was determined from a stimulus–response function identifying 1.3 °C vs. 44.7 °C as optimal temperatures. This temperature combination was then used to test the effects of sleep deprivation for 48 h using the pedestal-over-water method on response allocation to the 2 temperature zones. Sleep deprivation decreased time spent on the cooled plate. Cumulative occupancy indicated differential effects for sleep deprivation with the rats preferring to remain on the hot side vs. the cold side, suggesting that sleep deprivation increased the nociceptive properties of the cold stimulus.

Research on aggression over the past two decades has focused on gene–environment interaction models to explain the relative contribution of each to this behavioral phenotype in various clinical populations. Recent investigations suggest a link between aggression in people with intellectual disabilities the functionality of the serotonin transporter. The aims in this study were to examine the possible association of the STin2 and/or the 5-HTTLPR serotonin transporter polymorphisms in adult males with and without intellectual disabilities, and to examine the association of these polymorphisms with aggression in people with intellectual disabilities. DNA samples and behavioral records were obtained from adult males with intellectual disabilities, distinguished only by the presence or absence of aggression. No association was found between either transporter polymorphism for aggression. However, the long 5-HTTLPR allele, and not the short allele or the heterozygous state, was associated with the severity of aggression. The association with aggression appears to be genetically complex, suggesting there may be other genes, interactions between genes, and/or environmental relations occasioning aggression in people with intellectual disabilities.

A functional polymorphism in the promoter of the gene encoding monoamine oxidase A has been associated with problem behavior in various populations. We examined the association of MAOA alleles in adult males with intellectual/developmental disabilities with and without established histories of problem behavior. These data were compared with a gender, ethnicity, and age-matched contrast sample. About 43% (15/35) of adults with intellectual/developmental disabilities and problem behavior possessed the low-efficiency version of the MAOA gene. In comparison, 20% (7/35) of adults with intellectual/developmental disabilities and no problem behavior and 20% (7/35) of the contrast group had the short-allele MAOA polymorphism. Therefore, a common variant in the MAOA gene may be associated with problem behavior in adults with intellectual/developmental disabilities.

Elderly patients with diabetes are at increased fracture risk. Although long exposure to hyperglycemia may increase fracture risk via adverse effects on bone metabolism, tight glycemic control may increase risk via trauma subsequent to hypoglycemia. We tested the prospective relationship between glycemic control and fracture risk in 10,572 elderly patients (age ≥65) with diabetes.Geriatric patients with diabetes were drawn from Vanderbilt University Medical Center's Electronic Health Record. Baseline was defined as age at first HbA1c after the latter of age 65 or ICD 9 code for diabetes. Cox analysis was used to test the relationship of updated mean HbA1c (average HbA1c over follow-up) with time to first fracture since baseline. HbA1c was categorized as follows:6.5% [48mmol/mol]; 6.5-6.9% [48-52mmol/mol]; 7-7.9% [53-63mmol/mol]; 8-8.9% [64-74 mmol-mol]; ≥9% [≥75mmol/mol]. The number of BMI measurements was used as a surrogate for relative frequency of outpatient visits, i.e. patient-provider contacts.During follow-up, there were 949 fracture events. HbA1c demonstrated a cubic relationship with fracture risk (p0.05). In analyses accounting for age, sex, race, and number of BMI measures (a surrogate for patient-provider interaction), compared to an HbA1c of 7-7.9%, HRs (95% CIs) were: HbA1c6.5% HR=0.97 (0.82-1.14), 6.5-6.9% HR=0.80 (0.66-0.97), 8-8.9% HR=1.13 (0.92-1.40), ≥9% HR=1.19 (0.93-1.54).An HbA1c of 6.5-6.9% is associated with the lowest risk of fracture in elderly patients with diabetes. Risk associated with an HbA1c ≥9% may be a marker of infrequent patient-provider interaction.

Purpose Radiation oncology (RO) residency applicants commonly use Internet resources for information on residency programs. The purpose of this study is to assess the accessibility, availability, and quality of online information for RO graduate medical education. Methods and materials Accessibility of online information was determined by surveying databases for RO residency programs within the Fellowship Residency Electronic Interactive Data Access System (FREIDA) of the American Medical Association, the Accreditation Council for Graduate Medical Education (ACGME), and Google search. As of June 30, 2015, websites were assessed for presence, accessibility, and overall content availability based on a 55-item list of desired features based on 13 program features important to previously surveyed applicants. Quality scoring of available content was performed based on previously published Likert scale variables deemed desirable to RO applicants. Quality score labels were given based on percentage of desired information presented. Results FREIDA and ACGME databases listed 89% and 98% of program websites, respectively, but only 56% and 52% of links routed to a RO department-specific website, respectively. Google search obtained websites for 98% of programs and 95% of links routed to RO department-specific websites. The majority of websites had program descriptions (98%) and information on staff. However, resident information was more limited (total number [42%], education [47%], previous residents [28%], positions available [35%], contact information [13%]). Based on quality scoring, program websites contained only 47% of desired information on average. Only 13% of programs had superior websites containing 80% or more of desired information. Conclusions Compared with Google, the FREIDA and ACGME program databases provide limited access to RO residency websites. The overall information availability and quality of information within RO residency websites varies widely. Applicants and programs may benefit from improved content accessibility and quality from US RO program websites in the residency application process.

REM sleep deprivation (REMSD) has been shown to increase rates of negatively reinforced operant behavior, but not operant responding maintained by positive reinforcement. The reason for this differential effect is currently unknown. We hypothesize that REMSD can increase sensitivity to noxious stimuli. In the present study, we sought to determine if REMSD was associated with a change in response to noxious heat (i.e., altered nociceptive sensitivity). Two groups of rats, aged 6 and 22 months, were subjected to hotplate algesia testing at two different temperatures (44 and 52 degrees C). Initially, baseline numbers of responses and total response time were obtained at 44 degrees C. Animals then were exposed to 48 h of REMSD or control conditions. The frequency and duration of hindpaw responses (licking and guarding) increased for young animals only after REMSD and none of the control conditions. Old rats showed increased duration of nocifensive responding after REMSD and tank control conditions without a change in the number of responses at 44 degrees C. Latency to first nocifensive response was significantly longer in the 44 degrees C hotplate tests, but decreased to levels observed throughout the 52 degrees C hotplate tests following REMSD and TC conditions. These findings suggest that REMSD increases nociceptive sensitivity under conditions of sustained, selective C nociceptor activation (42 degrees C), but not under conditions of phasic A-delta activation (52 degrees C). The findings also indicate that age can be a significant variable in REMSD studies.

Important findings are often a balance between the rigor of the experimental design and innovativeness of the experimental question. One broad topic area that has received a great deal of discussion, but little empirical study, is the evaluation of educational systems. Experimental designs that permit the analysis of practices used by state education agencies, local education agencies, and schools have the potential for yielding socially significant findings that could improve education. In this article we discuss the use of nonconcurrent multiple baseline designs as an option for studying the activities and effects of educational programs. Nonconcurrent multiple baseline designs stagger the timing of baseline-to-intervention changes across various entities, but the baselines and intervention phases are not contemporaneous across each of the tiers. Although considered less rigorous than concurrent multiple baseline designs, nonconcurrent designs have a degree of flexibility that may allow for their use in studying complex social contexts, such as educational settings, that might otherwise go unanalyzed.

REM sleep deprivation (REMSD) has been shown to increase rates of free-operant avoidance responding. Depletion of 5-hydroxytryptamine (5-HT, serotonin) levels produces similar effects on responding. We studied whether the pharmacological activation of the 5-HT1A receptor would produce effects on avoidance responding similar to REMSD and depleted 5-HT levels. Rats were trained to lever press on a free-operant avoidance task. Dose-effect functions were established for 8-OH-DPAT (a 5-HT1A receptor agonist) (0.1–1.0 mg/kg) and WAY 100635 (a 5-HT1A receptor antagonist) (0.1–1.0 mg/kg). Rats were then exposed to REMSD (48 h) or equivalent control conditions, and then administered 8-OH-DPAT (0.6 mg/kg) and/or WAY 100635 (0.025–0.1 mg/kg). Injections of 8-OH-DPAT increased rates of avoidance responding in a dose-dependent manner, while WAY 100635 did not alter responding. The effect of 8-OH-DPAT was antagonized by pre-injection of WAY 100635. REMSD and injections of 8-OH-DPAT increased rates of avoidance responding and the effects of both manipulations were reversed by pre-injection of WAY 100635. Activation of the 5-HT1A receptor may be a mechanism by which REMSD increases rates of free-operant avoidance responding.

Deleting the tailless (TLX) gene in mice produces a highly aggressive phenotype yet to be characterized in terms of heterozygous animals or neurotransmitter mechanisms. We sought to establish pharmacological control over aggression and study the role of serotonin (5-HT)(2A/C) receptors in mediating changes in aggression. We analyzed aggression in mice heterozygous (+/-) or homozygous (-/-) for the TLX gene and wild-types (+/+) using a resident-intruder paradigm. No +/+ mice were aggressive, 36% of +/- TLX and 100% of -/- TLX mice showed aggression. Dose-effect functions were established for clozapine (0.1-1.5mg/kg, ip), ketanserin (0.3-1.25 mg/kg, ip), and (±)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane [(±)DOI] (0.5-2.0 mg/kg, ip). Injecting clozapine decreased the frequency and duration of attacks for +/- TLX and -/- TLX mice. Clozapine did not decrease grooming in either +/- TLX or -/- TLX mice but may have increased locomotion for -/- TLX mice. Injecting ketanserin, a 5-HT(2A/C) receptor antagonist, produced differential decreases in frequency and latency to aggression between genotypes and corresponding increases in locomotor behavior. Injecting (±)DOI, a 5-HT(2A/C) receptor agonist, increased the frequency and duration of attacks, decreased the latency to attacks, and decreased locomotion in +/- and -/- TLX mice. Results of the current study suggest aggression displayed by TLX null and heterozygous mice involves 5-HT(2A/C) receptors.

The psychological study of human stereotypic behavior disorder began in the 1960s. Stereotypic behaviors encompass a broad range of response topographies and are emitted for a variety of reasons. Most investigators consider stereotypic behaviors to be voluntary actions repeated over long periods of time, remaining impervious to environmental changes, and developmentally inappropriate. Because stereotypic behavior can interfere with learning and persist across a variety of contexts, several treatment approaches have been developed to reduce stereotypy. This chapter reviews diagnostic features and evidence-based treatments for stereotypic behaviors in people with intellectual/developmental disabilities. Treatments are further classified as function-based or non-function-based according to the criteria set forth by the Task Force on Promotion and Dissemination of Psychological Procedure (1995). Results of this review suggest that only recently have investigators used functional assessment strategies for identifying events maintaining stereotypy. Nonetheless, several treatment strategies have been well-established as long as they are implemented with fidelity and sustained over time. Furthermore, treatment strategies can be tailored to individuals and/or combined in a variety of ways to attenuate stereotypic responding. Well-established function-based treatments for stereotypy include enriched environment, differential reinforcement, and sensory extinction. Well-established non-function-based treatments include exercise, self-monitoring, overcorrection, and response restriction. Inhibitory stimulus control is possibly efficacious for reducing stereotypy. Keywords: stereotypy; enrichment; reinforcement; extinction; exercise; restriction

Good health significantly improves a person's quality of life. However, people with intellectual disabilities disproportionately have more health problems than the general population. Further complicating the matter is that people with more severe disabilities often cannot verbalize health complications they are experiencing, which leads to health problems being undiagnosed and untreated. It is plausible these conditions can interact with reinforcement contingencies to maintain problem behavior because of the increased incidence of health problems among people with intellectual disabilities. This paper reviews common health problems influencing problem behavior and reinforcement processes. A clear implication of this review is the need for comprehensive functional assessments of problem behavior involving behavior analysts and health professionals.

From an applied behavior-analytic perspective, aggression in people with intellectual disabilities is mostly maintained by social reinforcement consequences. However, nonsocial consequences have also been identified in functional assessments on aggression. Behaviors producing their own reinforcement have been labeled "automatic" or "nonsocial" in the behavior-analytic literature, a label that bares a striking resemblance to biobehavioral explanations of reward-seeking behaviors. Biobehavioral studies have revealed that aggression activates the same endogenous brain mechanisms as primary reinforcers like food. Therefore, integrating brain-environment explanations would result in a better understanding of the functional mechanisms associated with nonsocial aggression. The purpose of this paper was to explore aggression as a reinforcing consequence for reinforcement-seeking behaviors in people with intellectual disabilities. First, the literature establishing aggression as reinforcement for arbitrary responding will be reviewed. Next, the reward-related biological process associated with aggression was described. Finally, the paper discusses what might be done to assess and treat aggression maintained by nonsocial reinforcement.

There is evidence suggesting aggression may be a positive reinforcer in many species. However, only a few studies have examined the characteristics of aggression as a positive reinforcer in mice. Four types of reinforcement schedules were examined in the current experiment using male Swiss CFW albino mice in a resident-intruder model of aggression as a positive reinforcer. A nose poke response on an operant conditioning panel was reinforced under fixed-ratio (FR 8), fixed-interval (FI 5-min), progressive ratio (PR 2), or differential reinforcement of low rate behavior reinforcement schedules (DRL 40-s and DRL 80-s). In the FR conditions, nose pokes were maintained by aggression and extinguished when the aggression contingency was removed. There were long postreinforcement pauses followed by bursts of responses with short interresponse times (IRTs). In the FI conditions, nose pokes were maintained by aggression, occurred more frequently as the interval elapsed, and extinguished when the contingency was removed. In the PR conditions, nose pokes were maintained by aggression, postreinforcement pauses increased as the ratio requirement increased, and responding was extinguished when the aggression contingency was removed. In the DRL conditions, the nose poke rate decreased, while the proportional distributions of IRTs and postreinforcement pauses shifted toward longer durations as the DRL interval increased. However, most responses occurred before the minimum IRT interval elapsed, suggesting weak temporal control of behavior. Overall, the findings suggest aggression can be a positive reinforcer for nose poke responses in mice on ratio- and time-based reinforcement schedules.

We analyzed the effects of four conventional antiepileptic drugs (AEDs) - carbamazepine (CBZ), ethosuximide (ETH), phenytoin (PHT), and valproate (VPA) - on operant behavior maintained by negative or positive reinforcement contingencies. Rats were trained to lever press on a free-operant avoidance schedule or variable-interval (VI) schedule of appetitive reinforcement. Dose-effect functions were separately established on each reinforcement contingency for CBZ (12.5-100 mg/kg), ETH (25-200 mg/kg), PHT (12.5-50 mg/kg), and VPA (50-400 mg/kg). CBZ and PHT reduced responding on free-operant avoidance and VI appetitive reinforcement tasks, with positively reinforced behavior reduced at lower drug dosages than negatively reinforced responding. ETH and VPA reduced responding on the VI appetitive reinforcement task, but did not alter behavior maintained on the free-operant avoidance schedule. Our results suggest that conventional AEDs vary in their effect on operant behavior, depending on the type of reinforcement process maintaining responding.

The management of hypercalcemia of malignancy (HCM) is difficult if the underlying neoplasm cannot be treated successfully. The overexpression of parathyroid hormone-related protein (PTHrP) by various neoplasms is a common mechanism of HCM and usually is a premorbid event. Current pharmacologic measures to control HCM are directed more toward inhibiting the action rather than inhibiting the secretion of PTHrP. The somatostatin congeners are a novel class of drugs that can inhibit some excessive hormonal states. In this report, the authors summarize an observation made using lanreotide, an investigational somatostatin congener, in treating a patient with a neuroendocrine neoplasm. Lanreotide administration resulted in normalizing the serum calcium levels while decreasing plasma PTHrP concentrations. The chronic administration of lanreotide produced a stable radiographic response and controlled the HCM without adverse side effects. The somatostatin congeners potentially offer another therapeutic modality in managing HCM.

Two experiments were conducted to test the effect of a room with sensory equipment, or Snoezelen room, on the stereotypic behavior and engagement of adults with profound mental retardation. In Experiment 1, participants were observed in their living room before and after attending the Snoezelen room. Results showed that there tended to be a reduction in stereotypy and increase in engagement when participants went from their living room to the Snoezelen room, and a return of these behaviors to pre-Snoezelen levels in the living room. Positive effects in the Snoezelen room did not carryover to the living room. In Experiment 2, the living and Snoezelen rooms were compared to an outdoor activity condition with the same participants and target behaviors. Results showed that the outdoor condition was superior, the Snoezelen condition intermediate, and the living room least effective in their impact on stereotypic behavior and engagement. Conceptualizations regarding factors that maintain stereotypic behavior and engagement were discussed in the context of the three experimental conditions.

The effects of hypercalcemia on the heart and the resulting alterations of the electrocardiogram are well established. However, there are only rare reports of arrhythmias caused by hypercalcemia in primary hyperparathyroidism. This article describes a case of severe hypercalcemia secondary to hyperparathyroidism causing tachy-brady syndrome.

Variation in the distribution of dietary nitrogen among the different amino acids is one factor that can modify the calorie equivalent per weight of amino acid or protein. This is important to consider when experimental diets with different amino acid compositions are compared and when indirect calorimetry is used to determine substrate oxidation rates. We developed a computer program to compute the energy content, oxygen equivalent, and respiratory quotient for arbitrary mixtures of amino acids and representative carbohydrates and fats. The calorie content of individual free amino acids was calculated by correction of the heat of combustion for the incomplete oxidation of amino acids characteristic of humans. Although these computations were presented before, we not report the limit of applicability of published values and the availability of the computer program to do these calculations.

The effects of insulin-induced hypoglycemia (IIH) on leucine kinetics (mumol.kg-1.min-1) and interorgan flow of amino acids (AA) were examined in 2 groups of 18-h fasted conscious dogs. Insulin was infused at 5 mU.kg-1.min-1 for 3 h. IIH (40 +/- 5 mg/dl) resulted in a drop in plasma leucine (114 +/- 10 to 64 +/- 9 microM) and leucine rate of appearance (Ra) (3.1 +/- 0.1 to 2.4 +/- 0.2) within 1 h but gradually increased (P less than 0.05) to 145 +/- 30 microM and 3.8 +/- 0.5 by 3 h. Leucine oxidative rate of disposal (Rd) increased from 0.44 +/- 0.08 to 1.02 +/- 0.35 (P less than 0.01), and nonoxidative Rd dropped initially but was near basal levels by 3 h. When euglycemia was maintained, there was sustained drop in plasma leucine from 122 +/- 12 to 42 +/- 6 mumol/l, leucine Ra from 3.1 +/- 0.4 to 1.8 +/- 0.2, oxidative Rd from 0.36 +/- 0.03 to 0.22 +/- 0.04, and nonoxidative Rd from 2.75 +/- 0.4 to 1.6 +/- 0.2 (all P less than 0.01). IIH was associated with a significant net release of leucine (and other AA) across the gut (0.04 +/- 0.05 to 1.86 +/- 0.30 mumol.kg-1.min-1; P less than 0.05). In the group with euglycemia there was no significant change in the gut balance of leucine. We conclude that IIH is associated with a proteolytic response and that the gut is the major contributor to this response.

Patients with acute exacerbation of chronic obstructive pulmonary disease (COPD) frequently report a history of theophylline use prior to arrival in the emergency department. The reliability of using this history to guide aminophylline therapy is, however, unclear. The authors studied patients with an acute exacerbation of COPD to determine the relation between the initial theophylline level and the medication history. Seventy-nine patients with a mean age of 64.3 years were entered into the study. The average theophylline level was 10.8 micrograms/mL. Forty-seven percent of the patients had subtherapeutic levels, 46% had therapeutic levels, and 7% had toxic levels. There were weak although statistically significant correlations between the theophylline level and the interval since the last theophylline dose (r = -.40, P less than .001), as well as with the last recorded outpatient theophylline level (r = .45, P less than .001). However, the theophylline level could not be predicted accurately in a number of patients. The authors conclude, because the prediction rule was often inaccurate, aminophylline therapy in patients with acute exacerbation of COPD should be based on direct measurement of the serum theophylline level.

The development of diabetic ketoacidosis is an unusual complication of a glucagon-secreting pancreatic islet cell neoplasm, with only four reported cases in the literature. In this article, the authors report on a 46-year-old woman with a glucagonoma cosecreting pancreatic polypeptide, somatostatin, and serotonin diagnosed 8 months before the onset of diabetic ketoacidosis. She was treated with hydration, insulin, and octreotide, with improvement in her clinical course and a decrease in the glucagon, pancreatic polypeptide, and chromogranin A plasma levels. With the addition of weekly 5-FU, she has maintained a partial radiographic response and has had no further episodes of diabetic ketoacidosis for a 4.5-year period. Diabetic ketoacidosis can develop in the presence of a glucagonoma, and the pathophysiology remains unknown.

Retrospective analysis of the rapid adrenocorticotropic hormone (ACTH) test in a large adult population shows a marked interdependence of the basal cortisol concentration, peak cortisol concentration, and increase in cortisol concentration. Repetition of the rapid ACTH test in the same patient does not improve diagnostic accuracy. A significant number of falsely abnormal rapid ACTH test results were observed (in comparison to continuous ACTH infusion as a reference test). This supports the use of the rapid ACTH test as a screening test, but not as a diagnostic test for adrenocortical failure. It is proposed that a peak cortisol level greater than or equal to 20 micrograms/dl (550 nmol/liter) is a sufficient single criterion for normal adrenal function as assessed by the rapid ACTH test.

Determination of amino acids by reversed-phase chromatography of the adduct with orthophthalaldehyde and a thiol is rapid and sensitive. The major recognized adverse feature of this method is the instability of the reaction product, which requires precise control of reaction timing and chromatographic parameters for reliable quantitative application. We report another source of major variability: reagent instability. Deterioration of reagent was noted as low peak heights and peak broadening and was predictable if the premixed reagent was left at room temperature. Restoration of sharp chromatograms was accomplished by addition of mercaptoethanol or sodium metabisulfite. Reagent which was chromatographically inert contained minimal free thiol by direct assay. Free thiol disappearance was markedly slowed by addition of a chelating agent. Excess mercaptoethanol was deleterious. We conclude that reagent deterioration represents oxidation of the thiol, may be reversed by rereduction with minimal thiol or bisulfite, and may be minimized by inclusion of a metal chelator in the reagent.