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PubMed2005

Why revelations have occurred on mountains? Linking mystical experiences and cognitive neuroscience.

The fundamental revelations to the founders of the three monotheistic religions, among many other revelation experiences, had occurred on a mountain. These three revelation experiences share many phenomenological components like feeling and hearing a presence, seeing a figure, seeing lights, and feeling of fear. In addition, similar experiences have been reported by non-mystic contemporary mountaineers. The similarities between these revelations on mountains and their appearance in contemporary mountaineers suggest that exposure to altitude might affect functional and neural mechanisms, thus facilitating the experience of a revelation. Different functions relying on brain areas such as the temporo-parietal junction and the prefrontal cortex have been suggested to be altered in altitude. Moreover, acute and chronic hypoxia significantly affect the temporo-parietal junction and the prefrontal cortex and both areas have also been linked to altered own body perceptions and mystical experiences. Prolonged stay at high altitudes, especially in social deprivation, may also lead to prefrontal lobe dysfunctions such as low resistance to stress and loss of inhibition. Based on these phenomenological, functional, and neural findings we suggest that exposure to altitudes might contribute to the induction of revelation experiences and might further our understanding of the mountain metaphor in religion. Mystical and religious experiences are important not only to the mystic himself, but also to many followers, as it was indeed with respect to the leaders of the three monotheistic religions. Yet, concerning its subjective character, mystical experiences are almost never accessible to the scholars interested in examining them. The tools of cognitive neuroscience make it possible to approach religious and mystical experiences not only by the semantical analysis of texts, but also by approaching similar experiences in healthy subjects during prolonged stays at high altitude and/or in cognitive paradigms. Cognitive neurosciences, in turn, might profit from the research of mysticism in their endeavor to further our understanding of mechanisms of corporeal awareness and self consciousness.

Acclimatization↗
PubMed1976

Postcastration retention of sexual behaviour in the male BDF1 mouse: the role of experience.

Male BDF1 mice (the F1 progeny of a cross between C57BL/6 females with DBA/2 males) show a remarkable retention of sexual behaviour following castration. Two experiments were conducted to describe in detail the postcastration copulatory performance of the BDF1 male mouse and to determine to what extent such performance is influenced by experience prior to castration. Experiment I found that castration leads to significant increases in the number of mounts and intromissions needed to reach ejaculation, and to a significant increase in ejaculation latency. Experiment II found that although precastrational sexual experience is not essential for the performance of the ejaculatory reflex after castration, it does influence the frequency of its occurrence. Furthermore, type of post-weaning social experience influenced the display of ejaculatory behaviour by non-experienced castrates, as those with female social experience were superior to those with social experience with males or no social experience. The interactions of experience, hormones and genotype in the control of sexual behaviour in the BDF1 male are discussed.

Animals↗
PubMed2003

Nursing experience in Iran.

The aim of this study was to describe Iranian registered nurses' experience of nursing, and to discuss some of the sociocultural viewpoints that are relevant for such experience. Data were collected by asking 75 registered nurses (RNs) to write statements about their nursing experience. Written descriptions were analyzed by an interpretative phenomenological method. Four different themes emerged: (i) task-oriented nursing experience; (ii) caring-oriented nursing experience; (iii) altruism-oriented nursing experience; and (iv) difficulties experienced. Some participants explained nursing experience by describing a series of daily routine tasks. Others described experience by emphasizing how nursing was a caring profession, and some described their nursing experience from an altruistic viewpoint. Furthermore, the participants described nursing experience based on the relevant problems that they faced in everyday professional life. They expressed difficulties relating to work settings and also problems that were related to the sociocultural view of nursing in society. The nurses in general were dissatisfied with their work and this made them seriously consider leaving the nursing profession. The findings have implications for nursing management and education. These suggestions might enable changes that could effectively improve the status of nursing in Iran. An holistic approach is necessary to integrate these implications into a nursing system, both in practice and in education, for improving conditions that will facilitate a higher development of nursing in Iran.

Adult↗
PubMed2006

Retrieval experience in prospective memory: strategic monitoring and spontaneous retrieval.

According to the multi-process model of prospective memory (McDaniel & Einstein, 2000), performance in a prospective memory task may be due to spontaneous retrieval processes or due to strategic monitoring. Spontaneous retrieval is typically accompanied by a pop up experience and strategic monitoring by a search experience. In this study we report two experiments with young adults in which we systematically investigated whether retrieval experience differed across experimental conditions. In Experiment 1 some prospective memory targets were preceded by associated primes. We expected that presenting primes would enhance performance by an automatic activation of the intention and hence lead to an increase in pop up experiences. In Experiment 2 half of the participants received instructions containing information about the specific context in which the prospective memory task would occur, whereas the other half of the participants received no such information. We expected that specific context instructions would enhance performance by legitimate anticipation of the prospective memory task and hence would lead to an increase in search experiences. The results confirmed these expectations. They indicate that the assessment of retrieval experience can provide valuable insights into the processes underlying prospective memory performance. They also suggest that retrieval experience can vary systematically across experimental situations as predicted by the multi-process model.

Adult↗
PubMed2004

Increased ethanol drinking after repeated chronic ethanol exposure and withdrawal experience in C57BL/6 mice.

BACKGROUND: The development of dependence may have significant motivational consequences regarding continued use and abuse of ethanol. We have developed a mouse model of ethanol dependence and repeated withdrawals that demonstrates sensitization of seizures and other symptoms of withdrawal. It is unclear whether such experience influences ethanol drinking behavior. The present series of experiments were designed to examine whether repeated cycles of chronic ethanol exposure and withdrawal has an impact on subsequent motivation to voluntarily self-administer ethanol. METHODS: With the use of a modified sucrose-fading procedure, adult male C57BL/6J mice were trained to drink 15% (v/v) ethanol in a limited access procedure (2 hr/day). The animals were not food or water deprived at any time during the experiments. Once stable baseline intake was established, mice were exposed to four cycles of 16 hr of ethanol vapor (or air) in inhalation chambers separated by 8-hr periods of withdrawal. At 32 hr after the last cycle of ethanol exposure, all mice were tested for ethanol intake under limited access conditions for 5 consecutive days. The animals then received a second series of chronic ethanol exposure and withdrawal followed by another 5-day test period for ethanol drinking. RESULTS: Stable daily baseline intake was established in mice that drank 15% ethanol combined with 5% sucrose (experiment 1), 15% ethanol alone (experiment 2), 5% sucrose alone (experiment 3), or 15% ethanol when presented as a choice with water (experiment 4). After repeated cycles of chronic ethanol exposure and withdrawal experience, consumption of ethanol solutions increased over baseline levels and in comparison with control (air-exposed) groups. However, sucrose consumption did not change in mice that were trained to drink 5% sucrose. The increase in ethanol consumption after chronic ethanol exposure and withdrawal experience resulted in a significant increase in resultant blood ethanol levels. CONCLUSIONS: Once the positive reinforcing properties of ethanol were established, chronic ethanol exposure and withdrawal experience resulted in a significant increase in voluntary ethanol drinking that yielded a >2-fold increase in resultant blood ethanol levels. This increase in ethanol intake occurred whether ethanol was presented in combination with sucrose, alone (unadulterated), or as a choice with tap water. Furthermore, this effect seems to be selective for ethanol in that animals that were trained to drink a sucrose solution did not exhibit a change in their intake after similar chronic ethanol exposure. As such, this model may be useful in studying the mechanisms and conditions in which chronic ethanol treatment influences motivation to resume drinking after a period of abstinence (relapse).

Alcohol Drinking↗
PubMed1987

Deformation analyses in cell and developmental biology. Part II--Mechanical experiments on cells.

This study employs the finite element approach developed in Part I to analyze mechanical experiments on cells. It views cells as axisymmetric membrane structures containing a body of incompressible material, and models the mechanical contact between a cell and the loading apparatus by a contact algorithm. Since the method is valid for analyzing axisymmetric shell-like bodies with arbitrary shapes, it treates various mechanical experiments on cells in a unified manner. For demonstration purposes, three commonly used mechanical experiments on cells are considered; the compression experiment; the suction (micropipette aspiration) experiment; and the magnetic particle experiment. Based on an estimate of the mechanical property data for unfertilized sea urchin eggs, this analysis method predicts the responses for all three experiments using the same assumptions and approximations. This parallel treatment gives a broad basis for data correlation with experiments. The method also provides insights into mechanical experiments not offered by other approximate methods. For example, it gives the distributions of tensions and stretches on the cell cortex, and suggests the role of friction in the suction experiment.

Animals↗
PubMed2002

Adverse childhood experiences, alcoholic parents, and later risk of alcoholism and depression.

OBJECTIVE: The study examined how growing up with alcoholic parents and having adverse childhood experiences are related to the risk of alcoholism and depression in adulthood. METHODS: In this retrospective cohort study, 9,346 adults who visited a primary care clinic of a large health maintenance organization completed a survey about nine adverse childhood experiences: experiencing childhood emotional, physical, and sexual abuse; witnessing domestic violence; parental separation or divorce; and growing up with drug-abusing, mentally ill, suicidal, or criminal household members. The associations between parental alcohol abuse, the adverse experiences, and alcoholism and depression in adulthood were assessed by logistic regression analyses. RESULTS: The risk of having had all nine of the adverse childhood experiences was significantly greater among the 20 percent of respondents who reported parental alcohol abuse. The number of adverse experiences had a graded relationship to alcoholism and depression in adulthood, independent of parental alcohol abuse. The prevalence of alcoholism was higher among persons who reported parental alcohol abuse, no matter how many adverse experiences they reported. The association between parental alcohol abuse and depression was accounted for by the higher risk of having adverse childhood experiences in alcoholic families. CONCLUSIONS: Children in alcoholic households are more likely to have adverse experiences. The risk of alcoholism and depression in adulthood increases as the number of reported adverse experiences increases regardless of parental alcohol abuse. Depression among adult children of alcoholics appears to be largely, if not solely, due to the greater likelihood of having had adverse childhood experiences in a home with alcohol-abusing parents.

Adult↗
PubMed1998

Peak and nadir experiences and their consequences described by pediatric oncology nurses.

Pediatric oncology nurses experience role-related stressors, some of which are inherent to the speciality, and their consequences. Despite these difficulties, nurses continue in the specialty. One variable that helps to explain their continued commitment is "meaning", or what pediatric oncology nurses find to be most significant and satisfying in their roles. One technique for determining meaning in a role is to inquire about the peak (significant and positive) and nadir (significant and negative) role-related experiences and the consequences of both kinds of experiences. The purpose of this study was to identify the peak and nadir experiences of pediatric oncology nurses and the short- and long-term consequences of those experiences. Using an interview format that consisted of four open-ended questions and a convenience sampling plan, five nurses interviewed 26 nurses from one pediatric cancer center and 38 nurses from a national sample. The interviewers completed an initial training session on interviewing and repeated that training two more times during data collection. Written or taped oral consent was obtained at the time of each interview. Using a content analytical technique (Krippendorff, 1980), four nurses independently coded each interview. Agreement ratings ranged from 75% to 100% per coded theme for an overall agreement level of 92%. Training for the coding process occurred initially and periodically throughout the analysis period. Fifteen different themes for peak experiences were identified, the majority of which reflect the nurses' experience with patients dying, or with patients recovering and living normal lives, or with the close relationships that develop between nurses and patients. Multiple short- and long-term consequences were identified and included changes in (1) values (becoming less judgmental), (2) behaviors (giving more empathic care), and (3) perspective (accepting limitations of care). Twenty-three different nadir themes were identified. A shared characteristic of several of these themes is the nurses' regret over a perceived inadequacy in handling a situation. Another common element is witnessing patient suffering and feeling unable to adequately relieve the suffering or provide comfort to the patient. The short-term consequences of nadir experiences tend to be negative and include guilt, anger, or dread. The long-term consequences tend to be positive and similar to the long-term consequences of peak experiences. Study findings indicate that pediatric oncology nurses do find meaning in their roles and that those who continue in the speciality are able to experience positive long-term consequences. Study findings will be used to develop a new scale to measure role-related meaning and to develop interventions designed to assist nurses in finding meaning in their roles even during particularly stressful periods.

Adult↗
PubMed2005

Sleep paralysis as spiritual experience.

This article presents an overview of the sleep paralysis experience from both a cultural and a historical perspective. The robust, complex phenomenological pattern that represents the subjective experience of sleep paralysis is documented and illustrated. Examples are given showing that, for a majority of subjects, sleep paralysis is taken to be a kind of spiritual experience. This is, in part, because of the very common perception of a non-physical 'threatening presence' that is part of the event. Examples from various cultures, including mainstream contemporary America which has no widely known tradition about sleep paralysis, are used to show that the complex pattern and spiritual interpretation are not dependent on cultural models or prior learning. This is dramatically contrary to conventional explanations of apparently 'direct' spiritual experiences, explanations that are summed up as the 'Cultural Source Hypothesis.' This aspect of sleep paralysis was not recognized through most of the twentieth century. The article examines the way that conventional modern views of spiritual experience, combined with medical ideas that labeled 'direct' spiritual experiences as psychopathological, and mainstream religious views of such experiences as heretical if not pathological, suppressed the report and discussion of these experiences in modern society. These views have resulted in confusion in the scientific literature on sleep paralysis with regard to its prevalence and core features. The article also places sleep paralysis in the context of other 'direct' spiritual experiences and offers an 'Experiential Theory' of cross-culturally distributed spiritual experiences.

Affect↗
PubMedDate not supplied

Shared decision making and the experience of partnership in primary care.

PURPOSE: Communication has been researched either as a set of behaviors or as a facet of the patient-physician relationship, often leading to conflicting results. To determine the relationship between these perspectives, we examined shared decision making (SDM) and the subjective experience of partnership for patients and physicians in primary care. METHODS: From a convenience sample of experienced primary care physicians in 3 clinics, we recruited a stratified sample of 18 English- or Spanish-speaking patients. Direct observation of visits was followed by videotape-triggered stimulated recall sessions with patients and physicians. We coded decision moments for objective evidence of SDM, using a structured instrument. We classified patients' and physicians' subjective experience of partnership as positive or negative by a consensus analysis of stimulated recall sessions. We combined results from these 2 analyses to generate 4 archetypes of engagements and used grounded theory to identify themes associated with each archetype. RESULTS: The 18 visits yielded 125 decisions, 62 (50%) of which demonstrated SDM. Eighty-two decisions were discussed in stimulated recall and available for combined analysis, resulting in 4 archetypes of engagement in decision making: full engagement (SDM present, subjective experience positive)--22%; simulated engagement (SDM present, subjective experience negative)--38%; assumed engagement (SDM absent, subjective experience positive)--21%; and nonengagement (SDM absent, subjective experience negative)--19%. Thematic analysis revealed that both relationship factors (eg, trust, power) and communication behavior influenced subjective experience of partnership. CONCLUSIONS: Combining direct observation and assessment of the subjective experience of partnership suggests that communication behavior does not ensure an experience of collaboration, and a positive subjective experience of partnership does not reflect full communication. Attempts to enhance patient-physician partnership must attend to both effective communication style and affective relationship dynamics.

Adult↗
PubMed2002

Radiosurgery for residual or recurrent nonfunctioning pituitary adenoma.

OBJECT: Nonfunctioning pituitary adenomas comprise approximately 30% of all pituitary tumors. The purpose of this retrospective study is to evaluate the efficacy and role of gamma knife radiosurgery (GKS) in the management of residual or recurrent nonfunctioning pituitary adenomas. METHODS: A review was conducted of the data obtained in 42 patients who underwent adjuvant GKS at the University of Pittsburgh between 1987 and 2001. Prior treatments included transsphenoidal resection, craniotomy and resection, or conventional radiotherapy. Endocrinological, ophthalmological, and radiological responses were evaluated. The duration of follow-up review varied from 6 to 102 months (mean 31.2 months). Fifteen patients were observed for more than 40 months. The mean radiation dose to the tumor margin was 16 Gy. Conformal radiosurgery planning was used to restrict the dose to the optic nerve and chiasm. Tumor control after GKS was achieved in 100% of patients with microadenomas and 97% of patients with macroadenomas. Gamma knife radiosurgery was equally effective in controlling adenomas with cavernous sinus invasion and suprasellar extension. No patient developed a new endocrinological deficiency following GKS. One patient's tumor enlarged with an associated decline in visual function. Another patient experienced a deterioration of visual fields despite a decrease in tumor size. CONCLUSIONS: Gamma knife radiosurgery can achieve tumor control in virtually all residual or recurrent nonfunctioning pituitary adenomas. Dose sparing facilitates tumor management even when the adenoma is close to the optic apparatus or invades the cavernous sinus.

Adenoma↗
PubMed1997

Relationship between nutritional intake and dental caries experience of junior high students.

This study was designed to investigate the relationship between nutritional intake and caries experience of junior high school students. The sample consisted of 295 boys and 356 girls in Kangwha county. Dependent variables were total caries experience, occlusal surface caries experience, smooth surface caries experience and DMFS score (Decayed, Missing, Filling Tooth Surface score). Independent variables such as pit and fissure retentiveness of first molars, oral hygiene status, intraoral acidogenicity were also measured by dentists. Other independent variables such as toothbrushing habits, socioeconomic conditions, between-meal eating habits, and daily nutritional intake were determined during an interview. Univariate and multivariate analysis was performed to evaluate how nutritional intake influences caries experience. The results were as follows: 1. The most influential factor on dental caries experience was pit and fissure retentiveness. 2. Dietary fiber and potassium were the significant nutritional factors on total caries experience and occlusal caries experience, and niacin was the significant nutritional factor on smooth surface caries. 3. DMFS score was positively associated with the daily amount of carbohydrate and niacin intake, and negatively associated with total energy intake. The above results suggested that pit and fissure retentiveness was the most influential factor on caries experience. However, in this study, the intake of potassium and niacin was identified to influence the caries experience in addition to confirming the well-known relationship between fiber and carbohydrate intake.

Adolescent↗
PubMed2003

Aha! Insight experience correlates with solution activation in the right hemisphere.

In one experiment, we tested for an association between semantic activation in the right hemisphere (RH) and left hemisphere (LH) and the Aha! experience when people recognize solutions to insight-like problems. The compound remote associate problems used in this experiment sometimes evoke an Aha! experience and sometimes do not. On each trial, participants (N = 44) attempted to solve these problems and, after 7 sec, named a target word, made a solution decision, and rated their insight experience of recognizing the solution. As in prior studies, the participants demonstrated more solution priming for solutions presented to the left visual field-RH (lvf-RH) than for solutions presented to the right visual field-LH (rvf-LH). As was predicted, following unsolved problems the participants showed greater priming for solutions that they rated as evoking an insight experience on the subsequent solution decision than for solutions that did not evoke an insight experience. This association was stronger for solutions presented to the lvf-RH than for those presented to the rvf-LH. These results tie the subjective experience of insight to an objective measure--semantic priming--and suggest that people have an Aha! experience in part because they already had semantic activation that could lead them to recognize the solution quickly. We believe semantic activation in both hemispheres cooperatively contributes to problem solving, but weak solution activation that contributes to the Aha! experience is more likely to occur in the RH than in the LH.

Brain↗
PubMed1991

Summary of biological spaceflight experiments with cells.

Numerous biological experiments with cells have been conducted in space, and the importance of these experiments and this area of study is continually becoming evident. This contribution is a compilation of available information about spaceflight experiments with cells for the purpose of providing a single source of information for those interested in space gravitational cell biology. Experiments focused on a study of the effects of gravity and its absence on cells, cell function, and basic cellular processes have been included. Experiments include those involving viruses, bacteriophage, unicellular organisms, lower fungi, and animal and plant cell and tissue cultures, but exclude experiments with cells that were carried on a flight as part of a whole organism and later removed for study, and experiments with fertilized eggs. In addition, experiments in biotechnology, in which the microgravity environment is employed to study cell purification, cell fusion, protein crystallization, and similar processes, have not been included. Spaceflight experiments conducted by scientists from the U.S., U.S.S.R., and other countries and flown onboard sounding rockets (TEXUS, MAXUS, Consort), biosatellites (Biosatellite II, Cosmos), and various crewed spacecraft including the space shuttle (STS) and Soyuz, and space stations (Salyut, Mir) have been included, as well as high altitude balloon flights. Balloon flights are not spaceflights but can and are used as controls for the effects of space radiation, since organisms carried on balloons may be exposed to some of the same radiation as those taken into space, yet continue to be exposed to Earth's gravitational force. Parabolic flights on aircraft during which periods of microgravity of less than a minute are achieved have arbitrarily been excluded, because even though numerous experiments have been conducted, few results have been published.

Animals↗
PubMed2000

Clinical Experiences Are Not Predictive of Outcomes on the NATABOC Examination.

OBJECTIVE: To determine the efficacy of the National Athletic Trainers' Association Board of Certification (NATABOC) clinical experience requirements and individual student characteristics to predict candidate outcomes on the NATABOC certification examination. DESIGN AND SETTING: For all subjects, we gathered survey information and examination scores. The survey information included age, sex, route to certification, previous athletic training and allied health experience, and clinical education experiences. SUBJECTS: A total of 269 subjects, 22.25% of all first-time candidates for the June and November 1993 NATABOC examinations, were included in this study. MEASUREMENTS: Data were analyzed for standard descriptive statistics and parametric linear regression and correlational relationships. RESULTS: Total clinical hours, high-risk sport experiences, and previous athletic training experience were not predictive of examination outcomes. Although our results indicated a relationship between previous allied health experience and both outcome on the written section of the examination and age and outcome on the oral/practical section, these characteristics also were not predictive of examination outcomes. CONCLUSIONS: Gaining clinical experience hours in excess of 400 hours beyond the 800-or 1500-hour requirement may yield no greater benefit for an entry-level professional than less time. The quality, rather than the quantity, of clinical experiences should be evaluated. More emphasis should be placed on the achievement of an entry level of clinical competency, rather than on total hour collection. Also, because high-risk sport experiences did not predict outcomes on the NATABOC examination, the emphasis of clinical education should be on students' receiving a more structured clinical experience, in which they are progressively required to assume greater responsibilities integrating both cognitive and psychomotor skills, while working under the supervision of a certified athletic trainer.

Journal Article↗
PubMed1990

[On the pain experience of the tooth caused by placement of initial archwire].

Twenty nine patients completed a pain index card for the first 14 days following placement of an archwire. The index card divided the day into morning, afternoon and evening sessions and the patients were asked to score on a 0-3 basis of the severity of discomfort caused to the teeth (score 0: no discomfort, score 1: discomfort, score 2: mild pain, score 3: severe pain). Results were as follows: 1) All patients suffered discomfort and/or pain following placement of an archwire (discomfort: 10.3%, mild pain: 72.4%, severe pain: 17.2%). 2) There was no significant difference in the pain experience among the three age groups (under 12, 13 to 19 and over 20 years of age). 3) There was statistically significant difference in the pain experience between the sexes. 4) There was no significant difference in the pain experience among the four kinds of archwires (0.0175" braided wire, 0.012" stainless steel wire, 0.016" and 0.016" x 0.022" nickel titanium alloy wire). 5) The discomfort experience was observed in 37.9% and the mild pain experience was in 3.4% of the cases immediately after placement of the archwire. 6) The pain experience was observed in 62.1% of the cases by the end of the day. In 20.7% the pain experience was observed the next day and the pain experience was observed after 2 days in 3.4%. 7) In the severe pain group, the mean value of the pain experience was 4.4 days and that of the discomfort experience was 8.2 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMedDate not supplied

The statistical analysis of cancer inhibition/promotion experiments.

The purpose of this paper is to address the very important problem of accurate statistical analysis of certain types of cancer inhibition/promotion (IP) experiments. These experiments are routinely used by the National Cancer Institute to test the effects of potential chemopreventative agents. The statistical analysis is difficult since there is Type I censoring. In the IP experiments under investigation, laboratory animals (rats) are injected with a single dose of either a direct or indirect acting carcinogen. In the mammary tumor system, animals in the control group generally develop 5-7 tumors and typical experiments are usually terminated after 4-6 months. Animals are sacrificed at the end of the experiment and all observed tumors are confirmed. The two most common response variables are the number of observed tumors per animal and the rate of tumor development. The difficulty in analyzing these experiments occurs because experiments are terminated before all induced tumors have been observed. Fewer observed tumors in one group compared to another could be the result of a decreased number of induced tumors, a decrease in growth rate, or a combination of both. It is essential for the experimenter to distinguish between these two different biological actions. Present statistical techniques do not account for this confounding and since they rely primarily on nonparametric procedures, do not present an accurate description of potential IP agents. In this paper we introduce a parametric procedure that explicitly acknowledges the confounding present in experiments of this nature. The analysis is based on the comparison of the mean number of tumors per group (lambda) and the mean time to tumor appearance (mu). A longer mean time to development is believed to indicate a slower tumor growth rate. Hypothesis tests are developed to determine if there is an overall experiment effect, to isolate which groups are contributing to an observed experiment effect, and to isolate factors (tumor number and/or growth rate) contributing to an observed group difference. Confidence regions for (lambda, mu) are also generated. This analysis leads to a better understanding of how potential IP agents function.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1993

The reverse experiment in two-stage skin carcinogenesis. It cannot be genuinely performed, but when approximated, it is not innocuous.

One of the main assumptions of the two-stage theory of skin carcinogenesis is that the reverse experiment (promotion before initiation) is innocuous and that this in itself proves that there is a qualitative difference between the biological effects of initiators and promoters. However, almost all previous experiments in two-stage carcinogenesis have been arranged to justify the theory. Therefore, in order to test the theory scientifically, a series of experiments was set up comparing the tumor crop in classical two-stage and in reverse experiments. In most, a small, single dose of DMBA (200 or 100 nmol) was applied topically before or after a long-term course of 17 or 10 nmol TPA, but in one series, DMBA in larger doses (4,000 or 8,000 nmol) was given intraperitoneally. In another experiment two topical applications of 17 nmol TPA were given before or after a long-term course of very small doses (10 nmol) of DMBA applied twice a week. DMBA and TPA were generally applied in acetone. The results were statistically analyzed either from the start of the experiment, or from the time of DMBA application. A total of 736 mice were used, and they were studied once a week for papilloma and carcinoma development. No difference between classical and reverse experiments could be found as regards the carcinoma crops. For tumorigenesis (mostly papillomas) it was generally found that the reverse experiment was not innocuous, but produced a larger tumor crop than that produced by either DMBA or TPA alone. The two substances showed a reciprocal enhancing effect, which was sometimes weak, sometimes additive, and sometimes even synergistic, and was statistically most significant when the results were assessed from the time of DMBA application. Although the reverse experiment was not in any way innocuous it always resulted in a lower tumor crop than the classical sequence of DMBA followed by a course of TPA treatment. However, the lower tumor crop in the reverse experiment cannot be used to prove a qualitative difference between initiators and promoters. A course of TPA treatment alters the skin considerably, producing epidermal hyperplasia, an increased rate of cell proliferation, chronic inflammation and many other changes. A topical application of DMBA to such an altered skin is likely to have a considerably reduced tumorigenic effect. A 20-week resting period after TPA treatment seems to increase the effect of a final DMBA application, probably because part of the induced resistance is removed again.(ABSTRACT TRUNCATED AT 400 WORDS)

9,10-Dimethyl-1,2-benzanthracene↗