Reinforcer Pathology: The Behavioral Economics of Abuse Liability Testing.

Understanding the abuse liability of novel drugs is critical to understanding the risk these new compounds pose to society. Behavioral economics, the integration of psychology and economics, can be used to predict abuse liability of novel substances. Here, we describe the behavioral economic concept of reinforcer pathology and how it may predict the use of novel drugs in existing drug-users and initiation of use in the drug-naive.

Does impulsivity change rate dependently following stimulant administration? A translational selective review and re-analysis.

RATIONALE: Rate dependence refers to an orderly relationship between a baseline measure of behavior and the change in that behavior following an intervention. The most frequently observed rate-dependent effect is an inverse relationship between the baseline rate of behavior and response rates following an intervention. A previous report of rate dependence in delay discounting suggests that the discounting of delayed reinforcers, and perhaps, other impulsivity measures, may change rate dependently following acute and chronic administration of potentially therapeutic medications in both preclinical and clinical studies. OBJECTIVE: The aim of the current paper was to review the effects of stimulants on delay discounting and other impulsivity tasks. METHODS: All studies identified from the literature were required to include (1) an objective measure of impulsivity; (2) administration of amphetamine, methylphenidate, or modafinil; (3) presentation of a pre- and postdrug administration impulsivity measure; and (4) the report of individual drug effects or results in groups split by baseline or vehicle impulsivity. Twenty-five research reports were then reanalyzed for evidence consistent with rate dependence. RESULTS: Of the total possible instances, 67 % produced results consistent with rate dependence. Specifically, 72, 45, and 80 % of the data sets were consistent with rate dependence following amphetamine, methylphenidate, and modafinil administration, respectively. CONCLUSIONS: These results suggest that rate dependence is a more robust phenomenon than reported in the literature. Impulsivity studies should consider this quantitative signature as a process to determine the effects of variables and as a potential prognostic tool to evaluate the effectiveness of future interventions.

Int6 regulates both proteasomal degradation and translation initiation and is critical for proper formation of acini by human mammary epithelium.

INT6/EIF3E has been implicated in breast tumorigenesis, but its functional activities remain poorly defined. We found that, repressing INT6 expression induced transformed properties in normal human mammary epithelium (MCF10A); in contrast, Int6 silencing induced apoptosis in HeLa cells. As in fission yeast, Int6 in human cells was required for assembly of active proteasomes. A reverse-phase protein array screen identified SRC3/AIB1 as one oncoprotein the level and stability of which increased when Int6 was silenced in MCF10A cells. Our data further show that Int6 binds SRC3 and its ubiquitin ligase Fbw7, thus perhaps mediating the interaction between SRC3-Fbw7 and proteasomes. Consistent with this, Int6 silencing did not increase SRC3 levels in HeLa cells, which have low Fbw7 levels. It is surprising that, however, polyubiquitylated proteins do not accumulate or may even decrease in Int6-silenced cells that contain defective proteasomes. Considering that decreased ubiquitin might explain this observation and that Int6 might control ubiquitin levels in its role as a subunit of eIF3 (eukaryote translation initiation factor 3), we found that silencing Int6 reduced monoubiquitin protein levels, which correlated with a shift of ubiquitin mRNAs from larger polysomes to non-translating ribosomes. In contrast, levels of many housekeeping proteins did not change. This apparent reduction in the translation of ubiquitin genes correlated with a modest reduction in protein synthesis rate and formation of large polysomes. To further determine whether Int6 can selectively control translation, we analyzed translation of different 5'-untranslated region reporters and found that indeed, loss of Int6 had differential effects on these reporters. Together the data suggest that Int6 depletion blocks ubiquitin-dependent proteolysis by decreasing both ubiquitin levels and the assembly of functional proteasome machinery, leading to accumulation of oncoproteins, such as SRC3 that can transform mammary epithelium. Our data also raise the possibility that Int6 can further fine-tune protein levels by selectively controlling translation of specific mRNAs.

Multiple Oral Re-reading treatment for alexia: The parts may be greater than the whole.

This study examines the reasons for the success of Multiple Oral Re-reading (MOR; Moyer, 1979), a non-invasive, easily administered alexia treatment that has been reported in the literature and is currently in clinical use. The treatment consists of reading text passages aloud multiple times a day. Findings that MOR improves reading speed on practised as well as novel text have been inconsistent, making MOR's role in the rehabilitation of alexia unclear. We hypothesised that MOR's treatment mechanism works through repetition of high frequency words (i.e., bottom-up processing). We designed and controlled our text passages to test the hypothesis that participants would not improve on all novel text but would improve on text that includes a critical mass of the words contained in the passages they were re-reading. We further hypothesised that the improvement would be at the level of their specific alexic deficit. We tested four participants with phonological alexia and two with pure alexia during 8 weeks of MOR treatment. Contrary to the conclusions of previous studies, our results indicate that improvements in top-down processing cannot explain generalisation in MOR and that much of the improvement in reading is through repetition of the practised words. However, most patients also showed improvement when specific phrases were re-used in novel passages, indicating that practice of difficult words in context may be crucial to reading improvement.

Intrasellar paraganglioma: a case report and review of the literature.

Intrasellar paragangliomas are very rare lesions with only six previous cases described in the literature. We present a further case of intrasellar paraganglioma. The patient was a 52 yr-old man who developed two transient ischemic attacks. A CT scan showed an intra- and supra-sellar expanding lesion, which was regarded as a possible non-functioning pituitary macro-adenoma. Removal of the lesion was accomplished by transsphenoidal surgery. Histological examination was diagnostic of a paraganglioma. We review the literature and discuss pathological features and possible pathogenesis of sellar and parasellar paragangliomas, underlining the necessity to consider paraganglioma in the differential diagnosis of sellar lesions.

Hospice and a university integrate systems through a nurse liaison position.

In many ways, acute hospital care and hospice care are two very different health care modalities based on two very different philosophies. Acute hospital care is primarily curative in nature, and of course, hospice is palliative care. This major philosophical difference renders understanding, appreciation, and relinquishing care to each other difficult, and at times impossible. Collaboration between the two is fraught with barriers and, therefore, requires facilitation. The initiation of this hospice nurse liaison program required vision and risk taking as well as understanding and appreciation of the contributions of both acute care and hospice care. The outcomes of patient and staff satisfaction, decreased length of stays, increased appropriate hospice referrals, decreased costs, and increased communication and collaboration between the hospital and hospices validate the worthiness of the program.

An examination of the decline in employment-based health insurance between 1988 and 1993.

This paper identifies factors associated with the decline in employment-based health insurance between 1988 and 1993. The contribution of these factors in explaining the decrease in employment-based health coverage over the period is explored using regression-based decomposition analysis. Our results indicate that decreased percentages of employers sponsoring health insurance plans, reductions in real wages, a trend toward using part-time workers, a decline in unionization, and the movement of workers across industry sectors account for 24% to 51% of the decline in employment-based health insurance coverage between 1988 and 1993.

Glucocorticoid reduction of bronchial epithelial inflammation during cardiopulmonary bypass.

Tumor necrosis factor-alpha (TNF-alpha) is released in inflammatory lung conditions, raising airway nitric oxide (NO) concentrations through the cytokine-mediated induction of nitric oxide synthase (NOS). Cardiopulmonary bypass (CPB) creates an inflammatory state, characterized by the release of TNF-alpha, that may result in lung injury following CPB. This study measured plasma levels of TNF-alpha and interleukin-6 (IL-6) as well as airway NO concentrations during CPB, and the effect of methylprednisolone (MPSS) on the levels of these inflammatory products. Twenty adult males scheduled for coronary artery bypass grafting (CABG) were anesthetized and randomized to a group given MPSS at 1 gm intravenously 5 min before CPB (Group S) or a group not given MPSS (Group N). Plasma levels of TNF-alpha and IL-6 were measured by enzyme-linked immunosorbent assay (ELISA) and the airway NO concentration by chemiluminescence. TNF-alpha was significantly (p < 0.05) increased at 30 min after the termination of CPB, while IL-6 was significantly (p < 0.05) increased at 50 min into CPB and 30 min after the end of CPB in Group N as compared with controls in the same group and with Group S at the same time intervals. A group of 10 patients undergoing repair of infrarenal aortic aneurysms, which served as a control group for plasma levels of TNF-alpha, showed no significant changes in TNF-alpha concentrations at any time during aneurysm repair. Airway NO increased significantly (p < 0.01) in Group N as compared with Group S at 5, 20, 35, and 50 min of CPB.(ABSTRACT TRUNCATED AT 250 WORDS)

Prediction of maximum voluntary ventilation (MVV) in African-American adolescent girls.

The purposes of the present study were to: 1) develop original equations to predict maximum voluntary ventilation (MVV) in African-American adolescent girls; and 2) determine the validity of existing MVV prediction equations for use in African-American subjects by comparing predicted MVV values in the literature with actual MVV values obtained in this study. Forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and 12 second MVV were measured with a clinical respirometer (Spirometrics model 2451) in 93 African-American adolescent girls (13.5 +/- 1.0 years). Age (r = 0.29), height (r = 0.38), FEV1 (r = 0.52), and FVC (r = 0.48) were significantly (P < 0.01) correlated with MVV. Multiple regression analysis was used to develop equations to predict MVV with age, height, and FEV1 as predictor variables. Using Mallow's Cp criterion, age-FEV1 and FEV1 equations appeared to be the most accurate predictors of MVV. When MVV was regressed on FEV1 in a non-intercept model, the result was the commonly cited equation MVV = 35.0 x FEV1. Thus, the previously established relationship between FEV1 and MVV can be extended to African-American adolescent girls. Comparison of predicted MVV values calculated from other published equations with our subjects' actual values indicated that equations using age and/or height as predictors did not accurately predict MVV in our subjects.

Long-term care and the private insurance market.

Increased life expectancy and the aging of the baby boom generation will bring rapid growth in the number of people at risk of needing long-term care (LTC). This Issue Brief provides an overview of the current LTC financing and delivery system in the United States, focusing on private-sector initiatives to meet the United States' LTC needs. It discusses private-sector plan design--particularly employment-based plan design--providing an in-depth look at the dramatic changes taking place in the private-sector LTC market since its inception in the early and mid 1980s. Aside from informal care provided in the community, the current system of financing LTC depends largely on the Medicaid program and individual financing. Issues confronting this system include spiraling costs associated with LTC services that may threaten beneficiaries' access to care. Other issues include the potential depletion of personal assets and a bias toward institutionalization (which may not always provide the most cost-effective or desired type of care available). Many leaders regard private long-term care insurance (LTCI) as a way to increase access to financing and as a potential alternative to Medicaid and out-of-pocket financing. By the end of 1993, a total of 3.4 million private-sector LTCI policies had been sold, up from approximately 815,000 in 1987. While the majority of these plans were sold to individuals or through group associations, employment-based plans accounted for a significant proportion of this growth. Premiums for LTCI vary substantially based on age and plan design. Insurers generally attempt to set premiums such that they will remain level over the insured's lifetime. However, because little LTC claims insurance experience yet exists, the actuarial basis for developing premiums and statutory reserves is limited. Several bills over the last three Congresses have been introduced to address the issue of LTC. However, due to cost implications and lack of consensus regarding the optimum overall structure required to finance and deliver care, broad legislation to expand coverage--particularly public coverage--is not likely in the near term.

Sources of health insurance and characteristics of the uninsured: analysis of the March 1994 Current Population Survey.

This Issue Brief provides summary data on the insured and uninsured populations in the nation and in each state and is based on EBRI analysis of the March 1994 supplement to the Current Population Survey (CPS). It discusses the way health protection has changed for the insured, how the states rank in health insurance protection, and the characteristics most closely related to whether or not an individual is likely to have health insurance protection. The March 1994 CPS represents 1993 data--the most recent data available. Forty-three percent of nonelderly respondents indicating they were noncitizens were uninsured in 1993, compared with 16.4 percent of citizens. Among all nonelderly uninsured, 15.1 percent were noncitizens. In six states a higher proportion of the total uninsured were noncitizens than in the nation as a whole. These states include California (37.8 percent), New York (26.6 percent), Florida (21.7 percent), New Jersey (20.8 percent), Illinois (19.9 percent), and Texas (17.8 percent). The CPS contained data regarding citizenship for the first time in its March 1994 survey and does not allow for the determination of legal status of noncitizens. Eighty-two percent of nonelderly Americans and 99 percent of elderly Americans (aged 65 and over)--or 215.7 million individuals--were covered by either public or private health insurance in 1993. In 1993, 18.1 percent of the nonelderly population--or 40.9 million people--were not covered by health insurance, up from 17.8 percent and 39.8 million in 1992. However, the margin of error in 1993 at the 95 percent confidence level is 0.4 percent and 765 thousand. Thus, the percentage of uninsured in 1993 ranged from 17.7 percent to 18.5 percent, and the number of uninsured ranged from 40.1 million to 41.7 million. Children accounted for the largest proportion of the increase in the number of uninsured between 1992 and 1993. Sixteen percent of all children--or 11.1 million children--were not covered by private health insurance and were either ineligible or did not receive publicly financed medical assistance in 1993, up from 15.1 percent and 10.2 million in 1992.

Observed levels of elementary and middle school children's physical activity during physical education classes.

BACKGROUND: The benefits of childhood physical activity include fitness, weight control, and exercise habits that may carry over into adulthood. School physical education is the primary program responsible for training the nation's youth to be physically active and national objectives call for students to be engaged in moderate-to-vigorous physical activity at least 50% of class time. The purpose of this study was to determine through systematic observation in a regional sample of elementary and middle schools the amount of moderate-to-vigorous physical activity students obtain during physical education classes. METHODS: Twenty elementary schools and 7 middle schools were randomly sampled from the 355 elementary schools and 117 middle schools in the 20 school districts in Harris County, Texas. In addition, 9 elementary and 6 middle schools that were identified as having excellent physical education programs were sampled purposively to provide a comparison. Seven systematic observations of student's physical activity were conducted during physical education in each school. RESULTS: The average moderate-to-vigorous physical activity in the randomly selected elementary schools was 8.6%, significantly less (P < 0.05) than for the randomly selected middle schools (16.1%) or for the comparison elementary schools (20.6%) and middle schools (24.0%). CONCLUSIONS: The average amount of physical activity observed in this regional sample of schools was less than the estimated national average of 27% and far less than the national recommendation calling for a minimum of 50%.

Employment-based health benefits: analysis of the April 1993 Current Population Survey.

The April 1993 CPS differs from the March 1993 CPS in a number of respects. The April 1993 CPS supplement surveys only workers, whereas the March CPS examines the noncash benefits received by all Americans. The April CPS asks workers about health coverage in the week in which the questions were fielded, whereas the March CPS asks about coverage in the preceding year. In April 1993, there were 112.5 million civilian American workers between the ages of 18 and 64 with jobs. Eighty-two million (73 percent) of them worked for an employer that sponsored a health insurance plan, and 65 million (58 percent of all workers) participated in their employer's health plan. About one-third of workers at firms with fewer than 10 employees had employers who offer health benefits; about one-quarter of all of the workers in these firms participated in their employer's plan. Conversely, 94 percent of workers at firms with more than 1,000 employees had an employer who sponsored health benefits, and over 77 percent of these workers participated in their employer's plan. There are 16.5 million American workers whose employers sponsored health benefits but who did not participate in these benefits. Over one-half of these workers (8.5 million) chose not to be covered. Another 36 percent of these workers (5.9 million) did not participate because they were ineligible or denied coverage. Over 66 percent of the ineligible workers did not participate because they were part-time, contract, or temporary workers. Another 26 percent had not yet completed a probationary period. Among the reasons that those who chose not to participate in their employer's coverage, the vast majority (75 percent) stated they were covered by another health care plan. Twenty-nine percent stated that they chose not to purchase coverage because it was too costly or that they did not need or want the coverage. In 1993, there were 16.7 million workers with no health insurance coverage. The vast majority of these workers (95 percent) were employed by private employers. Sixty-six percent of the workers with no health insurance coverage were self-employed or worked for firms with fewer than 100 employees.

Who are the medically uninsured in the United States?

The Employee Benefit Research Institute (EBRI) analysis of the March 1993 Current Population Survey revealed that 38.9 million Americans had no private or public health insurance during 1992. This number was up some 2.3 million over that for 1991, an increase larger than was experienced from 1989 through 1991. The proportion of the total population without such insurance also steadily increased, rising from 14.3 percent in 1989 to 15.4 percent in 1992. In 1992, 38.5 million nonelderly Americans, or 17.4 percent of those under age 65, had no health insurance, up 4.1 million since 1989. A primary reason for the rising number of the nonelderly uninsureds was a decline in health coverage among individuals (and their families) working for small firms. Among the total U.S. population, close to 59 percent received employment-based coverage. Of the remainder, Medicare accounted for just over 13 percent of the coverage, Medicaid for just over 11 percent and individually purchased private sources other than an employer or union for almost 12 percent. The New England region had the lowest proportion of medically uninsureds (almost 12 percent) and the West South Central the highest (over 25 percent). By state, Hawaii and Connecticut reported the lowest percentage of medically uninsureds, whereas Nevada, Oklahoma, Louisiana and Texas reported the highest proportions in 1992.

Neurologic complications after high-dose chemotherapy and autologous bone marrow transplantation for Hodgkin's disease.

We analyzed 168 consecutive patients with Hodgkin's disease who were treated at the University of Nebraska Medical Center between 1985 and 1990 with high-dose chemotherapy followed by autologous bone marrow transplantation (BMT) or peripheral stem-cell transplantation (PSCT), and describe their neurologic complications. All these patients had relapsed or had failed to achieve a remission with initial chemotherapy. Early complications, defined as those occurring during the first 6 weeks following the transplantation, occurred in 65 patients (39%) and included encephalopathy, seizures, psychiatric symptoms, and cerebral hemorrhage; these were mild and reversible in 47 and fatal in 18 patients. The major cause of these early neurologic complications was pulmonary failure. Late neurologic complications, defined as those occurring 6 weeks after the BMT or PSCT was performed, occurred in 21% of patients and included encephalopathy, peripheral neuropathy, cerebral hemorrhage, and spinal cord compression. Serious nervous system complications following autologous BMT or PSCT for Hodgkin's disease are less frequent than those following allogeneic BMT and are usually a result of injury to other organ systems.

Characteristics of the part-time work force. Analysis of the March 1993 Current Population Survey.

The purpose of this Issue Brief is to present a comprehensive description of part-time work and part-time workers. The report describes trends in part-time employment; characteristics of part-time workers; health, pension, and other benefits available to part-time workers; and the advantages and disadvantages of part-time work to employers and employees. The report also identifies public policy issues stemming from the increase in the number of part-time workers. The number of part-time workers increased from 10.8 million to 20.7 million between 1969 and 1993, an increase of 91.7 percent, representing 24.6 percent of the growth in the work force. Full-time employment rose 51.4 percent, from 59.2 million to 89.6 million, representing 75.4 percent of new entrants. While the part-time work force increased 91.7 percent between 1969 and 1993, growth as a proportion of the total work force has been minimal, rising from 15.5 percent in 1969 to 18.8 percent in 1993, a 3.3 percentage point increase over this 24-year period. Voluntary part-time workers represented 70.6 percent of all part-time workers in 1993, compared with the 29.4 percent classifying themselves as involuntary part-time workers. Between 1969 and 1993, the voluntary part-time work force grew from 9.0 million to 14.6 million, an average annual increase of 2.0 percent. The involuntary part-time work force increased from 1.8 million to 6.1 million, an average annual increase of 5.2 percent. Of the 28.9 million part-time workers in 1992, 71 percent received health insurance from one or more private sources. More than one-half (52 percent) received coverage through an employment-based plan, and 19 percent through another private source. By comparison, 81 percent of full-time workers received coverage from a private source: 73 percent through an employment-based plan and 8 percent from another private source. Just over one in five, or 21 percent, of part-time workers were uninsured; 16 percent of full-time workers were without health insurance. While the likelihood of a part-time worker being uninsured is 5 percentage points higher than for full-time workers, there are more full-time workers uninsured (16.4 million full-time workers were uninsured in 1992, compared with 5.9 million part-time workers).(ABSTRACT TRUNCATED AT 400 WORDS)