Predicting the unpredictable: critical analysis and practical implications of predictive anticipatory activity.

A recent meta-analysis of experiments from seven independent laboratories (n = 26) indicates that the human body can apparently detect randomly delivered stimuli occurring 1-10 s in the future (Mossbridge etal., 2012). The key observation in these studies is that human physiology appears to be able to distinguish between unpredictable dichotomous future stimuli, such as emotional vs. neutral images or sound vs. silence. This phenomenon has been called presentiment (as in "feeling the future"). In this paper we call it predictive anticipatory activity (PAA). The phenomenon is "predictive" because it can distinguish between upcoming stimuli; it is "anticipatory" because the physiological changes occur before a future event; and it is an "activity" because it involves changes in the cardiopulmonary, skin, and/or nervous systems. PAA is an unconscious phenomenon that seems to be a time-reversed reflection of the usual physiological response to a stimulus. It appears to resemble precognition (consciously knowing something is going to happen before it does), but PAA specifically refers to unconscious physiological reactions as opposed to conscious premonitions. Though it is possible that PAA underlies the conscious experience of precognition, experiments testing this idea have not produced clear results. The first part of this paper reviews the evidence for PAA and examines the two most difficult challenges for obtaining valid evidence for it: expectation bias and multiple analyses. The second part speculates on possible mechanisms and the theoretical implications of PAA for understanding physiology and consciousness. The third part examines potential practical applications.

A double-blind, randomized study to assess the validity of applied kinesiology (AK) as a diagnostic tool and as a nonlocal proximity effect.

PREMISE: Applied Kinesiology (AK) is a diagnostic technique widely used within the Integrative Medical community. In essence, it posits that a question can be mentally held in a person's mind, sometimes while they are holding a substance like a vitamin, or a food sample, and by measuring relative muscular weakness an answer as to whether the substance or the condition represented by the question is good for that person can be obtained. This AK is presumed to have a diagnostic capability. That being presumed, this study asks the following questions: (1) Is there a difference in muscular strength when an individual holds a substance that is inimical to life processes (a poison solution), as compared to a substance that is essential for life (normal saline)? (2) Is this effect a transaction involving input from both the person being measured and the kinesiologist doing the measurement or is it only the person being measured? (3) As an extension of question 2, is the result the same when different kinesiologists take the measurement or when no kinesiologist is involved? (4) Does belief, expectation, gender, or time cognition play a role in determining response? METHODOLOGY: To answer these questions, which would help to define the parameters of the AK process, 51 participants were tested during three trials each, first by one kinesiologist, then by another, and finally, with no kinesiologist present by grip strength indicated using a hand dynamometer. Grip strength being a self-administered AK test of relative muscular strength. For each trial, a pair of randomly numbered sealed vials, each pair in a randomly numbered plastic bag, were used as the objects of the trial. In each bag, one vial contained saline solution while the other was filled with a slightly smaller amount of saline solution to which had been added ionic hydroxylamine hydrochloride (NH3OH)(+), producing a toxic solution of 9mg/ml. Each trial consisted of a separate muscle test for each vial. All present at the trials were blind as to which vial contained the toxin. And all who prepared the vials were blind to the trials. The force used by the kinesiologists in each of their trials was measured via a pressure pad system. The hand dynamometer trials were conducted with no kinesiologist present. RESULTS: Of the 151 sets of trials, the toxic vial was identified correctly in 80 of them (53%), resulting in a one-tailed exact binomial P-value of .258. Results for two of the kinesiologists were almost exactly at chance. For the third kinesiologist, there was a one-tailed exact binomial P-value of .18 (unadjusted for multiple testing). Results for the dynamometer were also almost exactly at chance. Testing whether there was a significant difference in proportions for whom the AK test worked based on belief about whether it would work resulted in non-significant χ(2) values of 0.6 (P = .439) for the trials with one kinesiologist and 2.222 (P = .136) for the hand dynamometer trials. The final variable examined was gender. While there was no significant difference in performance for males and females for the trials of the male kinesiologist or the hand dynamometer, the combined data for the two female kinesiologists did reveal a difference. Of the 33 sessions with females, only 15 were successful (45%), while for the 18 sessions with males, 14 were successful (78%), resulting in a χ(2) statistic of 4.96, P = .026. However, given all of the χ(2) tests performed in this section, the results must be interpreted with caution because of multiple testing. Results indicate belief in whether the AK test will work was not significantly related to whether it actually did work. A χ(2) test of the relationship between time perception and correct vial choice showed no significant relationships. The χ(2) statistic for the relationship using the hand dynamometer data was 0.927, P = .629. CONCLUSION: The data in this study, particularly when seen in the larger context of a review of the literature from the AK field itself by Klinkoski and Leboeuf (1990), which considered 50 papers published between 1981 and 1987 by the International College of Applied Kinesiology, and the survey by Hall, Lewith, Brien, and Little (2008), using standard evaluation criteria [quality assessment tool for studies of diagnostic accuracy included in systematic reviews (QUADAS), Standards for Reporting of Diagnostic Studies (STARD), JADAD, and Consolidated Standards of Reporting Trials (CONSORT)], for research methodology, as well as six prior non-clinical studies by Radin (1984), Quintanar and Hill (1988), Braud (1989), Arnett et al. (1999), Ludtke (2001), and Kendler and Keating (2003), all together suggest the following: The research published by the Applied Kinesiology field itself is not to be relied upon, and in the experimental studies that do meet accepted standards of science, Applied Kinesiology has not demonstrated that it is a useful or reliable diagnostic tool upon which health decisions can be based.

Testing the Storm et al. (2010) meta-analysis using Bayesian and frequentist approaches: reply to Rouder et al. (2013).

Rouder, Morey, and Province (2013) stated that (a) the evidence-based case for psi in Storm, Tressoldi, and Di Risio's (2010) meta-analysis is supported only by a number of studies that used manual randomization, and (b) when these studies are excluded so that only investigations using automatic randomization are evaluated (and some additional studies previously omitted by Storm et al., 2010, are included), the evidence for psi is "unpersuasive." Rouder et al. used a Bayesian approach, and we adopted the same methodology, finding that our case is upheld. Because of recent updates and corrections, we reassessed the free-response databases of Storm et al. using a frequentist approach. We discuss and critique the assumptions and findings of Rouder et al.

Predictive physiological anticipation preceding seemingly unpredictable stimuli: a meta-analysis.

This meta-analysis of 26 reports published between 1978 and 2010 tests an unusual hypothesis: for stimuli of two or more types that are presented in an order designed to be unpredictable and that produce different post-stimulus physiological activity, the direction of pre-stimulus physiological activity reflects the direction of post-stimulus physiological activity, resulting in an unexplained anticipatory effect. The reports we examined used one of two paradigms: (1) randomly ordered presentations of arousing vs. neutral stimuli, or (2) guessing tasks with feedback (correct vs. incorrect). Dependent variables included: electrodermal activity, heart rate, blood volume, pupil dilation, electroencephalographic activity, and blood oxygenation level dependent (BOLD) activity. To avoid including data hand-picked from multiple different analyses, no post hoc experiments were considered. The results reveal a significant overall effect with a small effect size [fixed effect: overall ES = 0.21, 95% CI = 0.15-0.27, z = 6.9, p < 2.7 × 10(-12); random effects: overall (weighted) ES = 0.21, 95% CI = 0.13-0.29, z = 5.3, p < 5.7 × 10(-8)]. Higher quality experiments produced a quantitatively larger effect size and a greater level of significance than lower quality studies. The number of contrary unpublished reports that would be necessary to reduce the level of significance to chance (p > 0.05) was conservatively calculated to be 87 reports. We explore alternative explanations and examine the potential linkage between this unexplained anticipatory activity and other results demonstrating meaningful pre-stimulus activity preceding behaviorally relevant events. We conclude that to further examine this currently unexplained anticipatory activity, multiple replications arising from different laboratories using the same methods are necessary. The cause of this anticipatory activity, which undoubtedly lies within the realm of natural physical processes (as opposed to supernatural or paranormal ones), remains to be determined.

Evaluation of the association of menopausal status with delta and beta EEG activity during sleep.

STUDY OBJECTIVES: Women report increasing sleep difficulties during menopause, but polysomnographic measures do not detect sleep disturbances. We examined whether two spectral analysis sleep measures, delta and beta power, were related to menopausal status. DESIGN: The Study of Women's Health Across the Nation (SWAN) Sleep Study compared cross-sectionally spectral sleep measures in women in different stages of menopause. SETTING: Sleep EEG was recorded in the participants' homes with ambulatory recorders. PARTICIPANTS: A multi-ethnic cohort of premenopausal and early perimenopausal (n = 189), late perimenopausal (n = 73), and postmenopausal (n = 59) women. MEASUREMENTS: EEG power in the delta and beta frequency bands was calculated for all night NREM and all night REM sleep. Physical, medical, psychological, and socioeconomic data were collected from questionnaires and diaries. RESULTS: Beta EEG power in NREM and REM sleep in late perimenopausal and postmenopausal women exceeded that in pre- and early perimenopausal women. Neither all night delta power nor the trend in delta power across the night differed by menopausal status. In a multivariate model that controlled for the physical, demographic, behavioral, psychological, and health-related changes that accompany menopause, beta power in both NREM and REM sleep EEG was significantly related to menopausal status. The frequency of hot flashes explained part but not all of the relation of beta power to menopausal status. CONCLUSIONS: Elevated beta EEG power in late perimenopausal and postmenopausal women provides an objective measure of disturbed sleep quality in these women. Elevated beta EEG activity suggests that arousal level during sleep is higher in these women.

Must psychologists change the way they analyze their data?

Wagenmakers, Wetzels, Borsboom, and van der Maas (2011) argued that psychologists should replace the familiar "frequentist" statistical analyses of their data with bayesian analyses. To illustrate their argument, they reanalyzed a set of psi experiments published recently in this journal by Bem (2011), maintaining that, contrary to his conclusion, his data do not yield evidence in favor of the psi hypothesis. We argue that they have incorrectly selected an unrealistic prior distribution for their analysis and that a bayesian analysis using a more reasonable distribution yields strong evidence in favor of the psi hypothesis. More generally, we argue that there are advantages to bayesian analyses that merit their increased use in the future. However, as Wagenmakers et al.'s analysis inadvertently revealed, they contain hidden traps that must be better understood before being more widely substituted for the familiar frequentist analyses currently employed by most research psychologists.

Bayesian estimation of the receiver operating characteristic curve for a diagnostic test with a limit of detection in the absence of a gold standard.

The receiver operating characteristic (ROC) curve is commonly used for evaluating the discriminatory ability of a biomarker. Measurements for a diagnostic test may be subject to an analytic limit of detection leading to immeasurable or unreportable test results. Ignoring the scores that are beyond the limit of detection of a test leads to a biased assessment of its discriminatory ability, as reflected by indices such as the associated area under the curve (AUC). We propose a Bayesian approach for the estimation of the ROC curve and its AUC for a test with a limit of detection in the absence of gold standard based on assumptions of normally and gamma-distributed data. The methods are evaluated in simulation studies, and a truncated gamma model with a point mass is used to evaluate quantitative real-time polymerase chain reaction data for bovine Johne's disease (paratuberculosis). Simulations indicated that estimates of diagnostic accuracy and AUC were good even for relatively small sample sizes (n=200). Exceptions were when there was a high per cent of unquantifiable results (60 per cent) or when AUC was < or =0.6, which indicated a marked overlap between the outcomes in infected and non-infected populations.

Use of complementary and alternative medicine during the menopause transition: longitudinal results from the Study of Women's Health Across the Nation.

OBJECTIVE: This study examined whether use of complementary and alternative (CAM) therapies during the menopause transition varied by ethnicity. DESIGN: The Study of Women's Health Across the Nation is a prospective cohort study following a group of 3,302 women from five racial/ethnic groups at seven clinical sites nationwide. Using longitudinal data encompassing 6 years of follow-up, we examined trends in use of five categories of CAM (nutritional, physical, psychological, herbal, and folk) by menopause status and ethnicity. To account for potential secular trends in CAM use or availability, we also evaluated the trends in CAM use over calendar time. RESULTS: Approximately 80% of all participants had used some form of CAM at some time during the 6-year study period. White and Japanese women had the highest rates of use (60%), followed by Chinese (46%), African American (40%), and Hispanic (20%) women. Overall use of CAM therapy remained relatively stable over the study period. In general, CAM use did not seem to be strongly associated with change in menopause transition status. Use of CAM among white women did not change with transition status. Among Chinese and African American participants, we observed an increase in CAM use as women transitioned to perimenopause and a decrease in use of CAM with transition to postmenopause. Among Hispanic and Japanese women, we observed a decrease in use of CAM in early perimenopause, followed by an increase as women entered late perimenopause and a decrease as they progressed to postmenopause. Patterns of use for the five individual types of CAM varied. White women had relatively stable use of all CAM therapies through the transition. Japanese women decreased use of nutritional and psychological remedies and increased use of physical remedies as they transitioned into late perimenopause. Among African American women, use of psychological remedies increased as they progressed through menopause. CONCLUSIONS: Although CAM use did vary in some ethnic groups in relation to advancing menopause status, there was no evidence of influence of calendar time on CAM use. Patterns of CAM use during menopause are likely to be driven by personal experience, menopausal health, and access to therapies. Women's personal preferences should be taken into consideration by healthcare providers for medical decision making during menopause and throughout the aging process.

Quality of life and everyday activities in patients with primary biliary cirrhosis.

UNLABELLED: Primary biliary cirrhosis (PBC) is generally a slowly progressive disease that may lead to cirrhosis and liver failure. However, patients with PBC often suffer from a variety of symptoms long before the development of cirrhosis that include issues of daily living that have an impact on their work environment and their individual quality of life. We therefore examined multiple parameters by taking advantage of the database of our cohort of 1032 patients with PBC and 1041 matched controls. The data were obtained from patients from 23 tertiary referral centers throughout the United States and from rigorously matched controls by age, sex, ethnicity, and random-digit dialing. The data showed that patients with PBC were more likely than controls to have significant articular symptoms, a reduced ability to perform household chores, and the need for help with routine activities. Patients with PBC rated their overall activity similar or superior to that of controls; however, more of them reported limitations in their ability to carry out activities at work or at home and difficulties in everyday activities. PBC cases also more frequently reported limitations in participating in certain sports or exercises and pursuing various hobbies; however, they did not report significant limitations in social activities. In a multivariable analysis, household income, a diagnosis of systemic lupus erythematosus, limitations in work activities, a reduction in work secondary to disability, and church attendance were independently increased in PBC cases with respect to controls. CONCLUSION: Our data indicate that the quality of life of patients with PBC in the United States is generally well preserved. Nevertheless, patients with PBC suffer significantly more than controls from a variety of symptoms that are beyond the immediate impact of liver failure and affect their lifestyle, personal relationships, and work activities.

Diet and lifestyle factors associated with premenstrual symptoms in a racially diverse community sample: Study of Women's Health Across the Nation (SWAN).

AIMS: We sought to determine if the frequency of reported physical or emotional premenstrual symptoms (PMSx) was associated with (1) dietary intake of phytoestrogens, fiber, fat, or calcium, (2) consumption of alcohol or caffeine, (3) active or passive smoke exposure or lack of physical exercise, and (4) race/ethnicity or socioeconomic status. METHODS: A cross-sectional analysis was conducted of PMSx and demographic and lifestyle factors reported at baseline in the multiethnic sample of 3302 midlife women in the Study of Women's Health Across the Nation (SWAN). Stepwise multiple logistic regression analyses were performed for the overall sample and for each racial/ethnic group for each of five PMSx groupings. RESULTS: Most dietary factors were not related to PMSx. Fat intake was negatively associated with craving and bloating (adjusted odds ratio [AOR] = 0.56, p = 0.024), and fiber intake was positively associated with breast pain (AOR = 1.39, p = 0.037). Alcohol intake was negatively associated with anxiety and mood changes (AOR = 0.63, p = 0.045) and headaches (AOR = 0.50, p = 0.009). Current smoking (AOR = 1.60, p = 0.028) and passive smoke exposure (AOR = 1.56, p = 0.050) were positively associated with cramps and back pain. Symptom reporting differed significantly by race/ethnicity. PMSx were also associated with comorbidities, early perimenopausal status, depressive symptoms, and symptom sensitivity. CONCLUSION: We found little evidence to support a role for diet in PMSx reporting. However, alcohol intake was positively associated with premenstrual anxiety and mood changes, and active and passive smoke exposure was associated with a number of PMSx. Ethnic differences in symptom reporting and associations of comorbidities, early perimenopausal status, depressive symptoms, and symptom sensitivity with reported PMSx were also observed.

Cross-sectional analysis of specific complementary and alternative medicine (CAM) use by racial/ethnic group and menopausal status: the Study of Women's Health Across the Nation (SWAN).

OBJECTIVE: To examine the relationships of race/ethnicity, menopausal status, health characteristics, and symptoms with use of 21 types of complementary and alternative medicine (CAM) in midlife women. DESIGN: Cross-sectional, multiple logistic regression analyses of 2,118 women completing the sixth annual visit in the Study of Women's Health Across the Nation, a multisite, multiethnic, longitudinal study. RESULTS: More than half of women used some type of CAM. Use of most types of CAM differed significantly by race/ethnicity, except the use of ginkgo biloba and glucosamine. Significantly more African Americans at most sites and Chinese women used ginseng. Use of most types of CAM did not differ significantly by menopausal status or vasomotor symptoms, except the use of soy supplements, which was significantly greater among women who reported vasomotor symptoms. Women reporting somatic symptoms were significantly more likely to use glucosamine. Women reporting psychological symptoms were significantly more likely to use ginkgo biloba and soy supplements. The number of comorbidities, moderate or high socioeconomic status, number of healthy behaviors, symptom sensitivity, age, and dietary genistein intake were significantly positively associated with use of several types of CAM. CONCLUSIONS: The use of most types of CAM is not related to menopausal status or symptom reporting but to sociodemographic factors, comorbidities, and health behaviors. Given the large proportion of midlife women who use CAM and the potential for interactions with prescribed medications, healthcare practitioners should inquire about CAM use and be aware of which factors influence the use of different types of CAM.

Complementary and alternative medicine use among American women: findings from The National Health Interview Survey, 2002.

BACKGROUND: The prevalence of use of complementary and alternative medicine (CAM) among Americans is high, especially among women, but a national profile of women CAM users has yet to be characterized. This study identified sociodemographic, health, and lifestyle factors associated with use of various types of CAM among women in the United States and examined health conditions and reasons for use. METHODS: Data from the 2002 National Health Interview Survey (NHIS), a nationally representative sample of U.S. adults, were analyzed (n = 17,295 women). Any recent use of CAM as well as specific types of CAM (e.g., biologically based therapies) use were analyzed; prayer was considered separately. Prevalence estimates and logistic regression results were weighted, and variance estimates were adjusted for complex sample design. RESULTS: About 40% of women reported any recent CAM use. Biologically based therapies (23.8%) were the most frequently reported CAM type, followed by mind-body therapies (20.9%). User characteristics were generally similar across specific CAM types; there were some differences between women who used CAM and women who prayed for health. Women frequently reported using CAM in conjunction with conventional medicine and to treat chronic pain conditions. CONCLUSIONS: This study provides a comprehensive profile of recent CAM use among a national sample of American women, including user characteristics and reasons and conditions for use. Widespread CAM use reflects a social phenomenon of healthcare-seeking practices that can potentially inform public health strategies for health promotion and disease prevention.

Risk factors and comorbidities in primary biliary cirrhosis: a controlled interview-based study of 1032 patients.

Primary biliary cirrhosis (PBC) is an autoimmune disease of unknown etiology, often associated with other autoimmune conditions. Controlled studies have so far provided conflicting data on risk factors and comorbidity rates in PBC. We enrolled patients with PBC (n = 1032) from 23 tertiary referral centers for liver diseases in the United States and random-digit-dialed controls (n = 1041) matched for sex, age, race, and geographical location. Patients and controls were administered a modified version of the US National Health and Nutrition Examination Study (NHANES III) questionnaire by trained personnel to evaluate associations between PBC and social, demographic, personal and family medical histories, lifestyle, and reproductive factors and the rates of comorbidity in affected individuals. Data indicate that having a first-degree relative with PBC (adjusted odds ratio [AOR] 10.736; 95% confidence interval 4.227-27.268), history of urinary tract infections (AOR 1.511, 95% CI 1.192-1.915), past smoking (AOR 1.569, 95% CI 1.292-1.905), or use of hormone replacement therapies (AOR 1.548, 95% CI 1.273-1.882) were significantly associated with increased risk of PBC. The frequent use of nail polish slightly increased the risk of having PBC. Other autoimmune diseases were found in 32% of cases and 13% of controls (P<0.0001). In conclusion, environmental factors, possibly including infectious agents through urinary tract infections or chemicals contained in cigarette smoke, may induce PBC in genetically susceptible individuals. Exogenous estrogens may also contribute to explain the female predominance of the disease.

Distant intentionality and the feeling of being stared at: two meta-analyses.

Findings in parapsychology suggest an effect of distant intentionality. Two laboratory set-ups explored this topic by measuring the effect of a distant intention on psychophysiological variables. The 'Direct Mental Interaction in Living Systems' experiment investigates the effect of various intentions on the electrodermal activity of a remote subject. The 'Remote Staring' experiment examines whether gazing by an observer covaries with the electrodermal activity of the person being observed. Two meta-analyses were conducted. A small significant effect size (d =.11, p =.001) was found in 36 studies on 'direct mental interaction', while a best-evidence-synthesis of 7 studies yielded d =.05 (p =.50). In 15 remote staring studies a mean effect size of d = 0.13 (p =.01) was obtained. It is concluded that there are hints of an effect, but also a shortage of independent replications and theoretical concepts.

Distant healing intention: definitions and evolving guidelines for laboratory studies.

This paper provides definitions and a discussion of evolving guidelines for conducting research on the effects of distant healing intention (DHI) on living systems in the laboratory. We consider the relevance of DHI laboratory research to applied healing, special theoretical challenges, and other considerations that distinguish DHI research from other domains of laboratory science. Two sample protocols for investigating DHI are provided, one involving the human autonomic nervous system as the "target" of distant intention, and the other involving cell cultures. In essence, DHI differs from other alternative healing modalities because it postulates that mental intention alone can affect living systems at a distance, unbounded by the usual constraints of both space and time. This postulate challenges scientific assumptions that often go unexamined, including the nature of causality, the distinction between subjective and objective states, and the efficacy of double-blind protocols in controlling for experimenters' intentions. Previous laboratory research in this domain suggests that DHI effects warrant serious study, but most scientists and funding agencies are unaware of the evidence or the relevant literature. By following these evolving guidelines, researchers' designs and their ultimate publications will conform more closely to the quality standards expected by scientific journals, and such publications will in turn attract the attention of a broader range of scientists. This seems especially important for alternative healing research in general and for distant healing in particular; both realms enjoy broad public support but have largely eluded serious attention by mainstream science.

Functional status of patients with primary biliary cirrhosis.

OBJECTIVES: Although autoimmune diseases can have a significant impact on the quality of life, there has been a relative paucity of data with respect to the functional status of patients with primary biliary cirrhosis (PBC). METHODS: We conducted a case-control study of 182 patients ("cases") with PBC as well as 225 age- and sex-matched friend control subjects using a standardized instrument obtained from the National Health and Nutrition Examination Survey. RESULTS: In all, 126 of 182 cases (69%) and 141 of 225 friend controls (62.6%) responded to this survey, a response rate comparable to or better than in similar previous studies of such instruments. Patients with PBC had a significantly reduced functional status score compared to their controls (p < 0.001). Interestingly, a lower level of education and the presence of arthritis and hypertension were significantly associated with these lower levels of functional capabilities. These data were subjected to multivariate analysis and confirmed. Age was not associated with impaired functional status in either the patients or controls. CONCLUSIONS: Studies of this nature have potential implications for the well-being and management of patients with PBC, and focus on issues that can be addressed to help maintain functional status in this chronic disease.

The association between gravidity and primary biliary cirrhosis.

PURPOSE: Primary biliary cirrhosis is an autoimmune disease with female predominance that leads to liver failure. The goal of this study was to identify reproductive risk factors associated with this disease. METHODS: We compared 182 cases of PBC with 225 age- and sex-matched friend controls to examine the role of reproductive factors. The survey instrument was developed using standardized questions obtained from the National Health and Nutrition Examination Survey (NHANES) III. RESULTS: A total of 126/182 cases (69%) and 141/225 (62.6%) friend controls responded to the survey. More cases than controls reported ever having genitourinary infection [adjusted odds ratio (OR) = 2.12, 95% confidence interval (CI) 1.01, 4.42] among those without a personal or family history of autoimmune disease. The most notable finding was that cases reported significantly more pregnancies than controls (p = 0.008). The adjusted OR for each additional pregnancy among those without a personal or family history of autoimmune disease was 1.40 (95% CI 1.14, 1.7). More controls (24.4%) than cases (16.0%) were nulliparous. Cases reported having five or more children (16.0%) with double the frequency of controls (8.2%). CONCLUSIONS: The association reported herein, between primary biliary cirrhosis and gravidity, is particularly significant because of the overwhelming female predominance.