Regular and anomalous extraordinary optical transmission at the THz-gap.

In this paper Anomalous Extraordinary Transmission (ET) is reported for s-polarization of low loss doubly periodic subwavelength hole arrays patterned on polypropylene (PP) substrates by conventional contact photolithography at the so-called THz-gap (1-10 THz). The unexpected enhanced transmittance for s-polarization (i.e. without spoof plasmons) was previously numerically demonstrated in subwavelength slits arrays. However, subsequently no experimental work has been devoted to this unexpected Extraordinary Transmission neither in subwavelength slits nor in subwavelength holes. Here, numerical study and experimental results of the Anomalous ET and the symmetric and antisymmetric transmittance modes associated with the already well-known p-polarization ET are shown alongside a systematically analysis of the frequency peaks as a function of hole size for both incident polarizations.

Polypropylene-substrate-based SRR- and CSRR- metasurfaces for submillimeter waves.

In this paper it is presented the fabrication of low loss millimeter wave metamaterials based on patterning on polypropylene substrates by conventional contact photolitography. We study numerically and experimentally the transmission and reflection properties of two dimensional arrays of split ring resonators (SRRs), or metasurfaces, and their complementary structure (CSRRs) for co- and cross-polarization excitations up to submillimeter frequencies under normal incidence conditions. The obtained results suggest the possibility of scaling them at terahertz frequencies based on this substrate where other lossy substrates degrade the resonators quality. Left-handed metamaterials derived from these SRRs and CSRRs metasurfaces could be feasible.

Performance assessment for radiologists interpreting screening mammography.

When interpreting screening mammograms radiologists decide whether suspicious abnormalities exist that warrant the recall of the patient for further testing. Previous work has found significant differences in interpretation among radiologists; their false-positive and false-negative rates have been shown to vary widely. Performance assessments of individual radiologists have been mandated by the U.S. government, but concern exists about the adequacy of current assessment techniques. We use hierarchical modelling techniques to infer about interpretive performance of individual radiologists in screening mammography. While doing this we account for differences due to patient mix and radiologist attributes (for instance, years of experience or interpretive volume). We model at the mammogram level, and then use these models to assess radiologist performance. Our approach is demonstrated with data from mammography registries and radiologist surveys. For each mammogram, the registries record whether or not the woman was found to have breast cancer within one year of the mammogram; this criterion is used to determine whether the recall decision was correct. We model the false-positive rate and the false-negative rate separately using logistic regression on patient risk factors and radiologist random effects. The radiologist random effects are, in turn, regressed on radiologist attributes such as the number of years in practice. Using these Bayesian hierarchical models we examine several radiologist performance metrics. The first is the difference between the false-positive or false-negative rate of a particular radiologist and that of a hypothetical 'standard' radiologist with the same attributes and the same patient mix. A second metric predicts the performance of each radiologist on hypothetical mammography exams with particular combinations of patient risk factors (which we characterize as 'typical', 'high-risk', or 'low-risk'). The second metric can be used to compare one radiologist to another, while the first metric addresses how the radiologist is performing compared to an appropriate standard. Interval estimates are given for the metrics, thereby addressing uncertainty. The particular novelty in our contribution is to estimate multiple performance rates (sensitivity and specificity). One can even estimate a continuum of performance rates such as a performance curve or ROC curve using our models and we describe how this may be done. In addition to assessing radiologists in the original data set, we also show how to infer about the performance of a new radiologist with new case mix, new outcome data, and new attributes without having to refit the model.

On the change of support problem for spatio-temporal data.

In practice, spatial data are sometimes collected at points (i.e. point-referenced data) and at other times are associated with areal units (i.e. block data). The change of support problem is concerned with inference about the values of a variable at points or blocks different from those at which it has been observed. In the context of block data which can be sensibly viewed as averaging over point data, we propose a unifying approach for prediction from points to points, points to blocks, blocks to points, and blocks to blocks. The approach includes fully Bayesian kriging. We also extend our approach to the the case of spatio-temporal data, wherein a judicious specification of spatio-temporal association enables manageable computation. Exemplification of the static spatial case is provided using a dataset of point-level ozone measurements in the Atlanta, Georgia metropolitan area. The dynamic spatial case is illustrated using a temporally extended version of this dataset, enabling comparison at the common time point.*To whom correspondence should be addressed.

Predicting the cumulative risk of false-positive mammograms.

BACKGROUND: The cumulative risk of a false-positive mammogram can be substantial. We studied which variables affect the chance of a false-positive mammogram and estimated cumulative risks over nine sequential mammograms. METHODS: We used medical records of 2227 randomly selected women who were 40-69 years of age on July 1, 1983, and had at least one screening mammogram. We used a Bayesian discrete hazard regression model developed for this study to test the effect of patient and radiologic variables on a first false-positive screening and to calculate cumulative risks of a false-positive mammogram. RESULTS: Of 9747 screening mammograms, 6. 5% were false-positive; 23.8% of women experienced at least one false-positive result. After nine mammograms, the risk of a false-positive mammogram was 43.1% (95% confidence interval [CI] = 36.6%-53.6%). Risk ratios decreased with increasing age and increased with number of breast biopsies, family history of breast cancer, estrogen use, time between screenings, no comparison with previous mammograms, and the radiologist's tendency to call mammograms abnormal. For a woman with highest-risk variables, the estimated risk for a false-positive mammogram at the first and by the ninth mammogram was 98.1% (95% CI = 69.3%-100%) and 100% (95% CI = 99.9%-100%), respectively. A woman with lowest-risk variables had estimated risks of 0.7% (95% CI = 0.2%-1.9%) and 4.6% (95% CI = 1. 1%-12.5%), respectively. CONCLUSIONS: The cumulative risk of a false-positive mammogram over time varies substantially, depending on a woman's own risk profile and on several factors related to radiologic screening. By the ninth mammogram, the risk can be as low as 5% for women with low-risk variables and as high as 100% for women with multiple high-risk factors.

Active intestinal chloride secretion in human carriers of cystic fibrosis mutations: an evaluation of the hypothesis that heterozygotes have subnormal active intestinal chloride secretion.

To explain the very high frequency of cystic fibrosis (CF) mutations in most populations of European descent, it has been proposed that CF heterozygotes have a survival advantage when infected with Vibrio cholerae or Escherichia coli, the toxins of which induce diarrhea by stimulation of active intestinal chloride secretion. Two assumptions underlie this hypothesis: (1) chloride conductance by the CF transmembrane conductance regulator (CFTR) is the rate-limiting step for active intestinal chloride secretion at all levels of expression, from approximately zero in patients with CF to normal levels in people who are not carriers of a mutation; and (2) heterozygotes have smaller amounts of functional intestinal CFTR than do people who are not carriers, and heterozygotes therefore secrete less chloride when exposed to secretagogues. The authors used an intestinal perfusion technique to measure in vivo basal and prostaglandin-stimulated jejunal chloride secretion in normal subjects, CF heterozygotes, and patients with CF. Patients with CF had essentially no active chloride secretion in the basal state, and secretion was not stimulated by a prostaglandin analogue. However, CF heterozygotes secreted chloride at the same rate as did people without a CF mutation. If heterozygotes are assumed to have less-than-normal intestinal CFTR function, these results mean that CFTR expression is not rate limiting for active chloride secretion in heterozygotes. The results do not support the theory that the very high frequency of CF mutations is due to a survival advantage that is conferred on heterozygotes who contract diarrheal illnesses mediated by intestinal hypersecretion of chloride.

Modelling the cumulative risk for a false-positive under repeated screening events.

Screening examinations are widely utilized in detecting the presence of medical disorders, for instance, screening mammograms and clinical breast examinations for detection of breast cancer. Such procedures are invaluable in enabling early treatment but produce the possibilities of false-positive and false-negative diagnoses. Focusing on false-positive results, with increasing number of screening events, it is clear that the risk of a false-positive increases. The objective of this paper is to quantify the cumulative risk associated with repeated screening. We provide a very general framework within which to investigate this risk, both at the population and the individual level. The latter allows incorporation of evolving patient medical history to permit individualized assessment of risk. We model cumulative risk in terms of the number of screening events until first false-positive. We develop models which are essentially familiar actuarial models for life table data adding a Cox regression to enable individual level modelling. Because it offers several advantages, we employ a Bayesian inference framework and apply our modelling to the analysis of 9773 screening mammograms collected from 2227 women at an HMO serving nearly 300000 adults in and around Boston, MA.

Spatial modelling of multinomial data with latent structure: an application to geographical mapping of human gene and haplotype frequencies.

We develop hierarchical models for spatial multinomial data with missing categories, to analyse a database of HLA-A and -B gene and haplotype frequencies from Papua New Guinea, with a highly variable number of samples per spatial unit. The spatial structure of the multinomial data is incorporated by adopting conditional autoregressive (CAR) priors for the random effects, reflecting extra-multinomial variation. Different spatial structures are investigated, and covariate effects are evaluated using a novel model selection criterion. Tables and maps reveal strong spatial association and the importance of altitude, a covariate anticipated to be significant in explaining genetic variation. Our approach can be used in identifying associations with environmental factors, linguistic or epidemiological patterns and hence potential causes of genetic diversity (population movements, natural selection, stochastic effects).

Adult health status of women with histories of childhood abuse and neglect.

PURPOSE: Several recent studies have found associations between childhood maltreatment and adverse adult health outcomes. However, methodologic problems with accurate case determination, appropriate sample selection, and predominant focus on sexual abuse have limited the generalizability of these findings. SUBJECTS AND METHODS: We administered a survey to 1,225 women who were randomly selected from the membership of a large, staff model health maintenance organization in Seattle, Washington. We compared women with and without histories of childhood maltreatment experiences with respect to differences in physical health status, functional disability, numbers and types of self-reported health risk behaviors, common physical symptoms, and physician-coded ICD-9 diagnoses. RESULTS: A history of childhood maltreatment was significantly associated with several adverse physical health outcomes. Maltreatment status was associated with perceived poorer overall health (ES = 0.31), greater physical (ES = 0.23) and emotional (ES = 0.37) functional disability, increased numbers of distressing physical symptoms (ES = 0.52), and a greater number of health risk behaviors (ES = 0.34). Women with multiple types of maltreatment showed the greatest health decrements for both self-reported symptoms (r = 0.31) and physician coded diagnoses (r = 0.12). CONCLUSIONS: Women with childhood maltreatment have a wide range of adverse physical health outcomes.

Costs of health care use by women HMO members with a history of childhood abuse and neglect.

BACKGROUND: Early childhood maltreatment has been associated with adverse adult health outcomes, but little is known about the magnitude of adult health care use and costs that accompany maltreatment. We examined differences in annual health care use and costs in women with and without histories of childhood sexual, emotional, or physical abuse or neglect. METHODS: A random sample of 1225 women members of a health maintenance organization completed a 22-page questionnaire inquiring into childhood maltreatment experiences as measured by the Childhood Trauma Questionnaire. Health care costs and use data were obtained from the automated cost-accounting system of the health maintenance organization, including total costs, outpatient and primary care costs, and emergency department visits. RESULTS: Women who reported any abuse or neglect had median annual health care costs that were $97 (95% confidence interval, $0.47-$188.26) greater than women who did not report maltreatment. Women who reported sexual abuse had median annual health care costs that were $245 (95% confidence interval, $132.32-$381.93) greater than costs among women who did not report abuse. Women with sexual abuse histories had significantly higher primary care and outpatient costs and more frequent emergency department visits than women without these histories. CONCLUSION: Although the absolute cost differences per year per woman were relatively modest, the large number of women in the population with these experiences suggests that the total costs to society are substantial.

Exposure of human peripheral blood mononuclear cells (PBMC) to hydrostatic pressure increases their proliferative response to phytohemagglutinin A (PHA) and anti-CD3 antibody.

In the present study we show that a brief exposure of human PBMC to hydrostatic pressure (HyP) increased their proliferative response to PHA and anti-CD3 antibody, assessed by DNA synthesis. The effect of HyP was most prominent at 400 atmospheres of HyP followed by 600 and 200 atmospheres. At any pressure level, the highest effect of HyP was noted when employing PHA and anti-CD3 antibody at 10(-2) dilution. When PBMC were exposed to 400 atmospheres HyP, maximal effect was achieved at 20 minutes of exposure. The highest effect of HyP on DNA synthesis was noted at 48 and 72 hours of incubation with PHA, when exposing cells to pressure for 20 minutes at 400 atmospheres. Exposure of PBMC under similar conditions for 40 minutes, caused an increase in DNA synthesis only at 48 hours incubation with PHA. These results demonstrate that exposure of human PBMC to HyP increases their proliferative response to different polyclonal activators. The possible mechanisms involved in this phenomenon are discussed.

Human tumor cells, modified by a novel pressure/crosslinking methodology, promote autologous lymphocyte proliferation and modulate cytokine secretion.

Hydrostatic pressure (P) combined with membrane protein crosslinking (CL) by adenosine dialdehyde (AdA) can render tumor cells immunogenic. We have recently shown that PCL treatment of murine tumor cells augmented the presentation of MHC-restricted tumor-associated antigens and enhanced cell-mediated immunity. In cancer patients inoculated with autologous PCL-modified tumor cells, a significant delayed-type hypersensitivity response was elicited. Since the balance between cell-mediated immunity and humoral immunity is reciprocally controlled by immunoregulatory cytokines, we have examined the proliferative response and cytokine secretion pattern in cultures of human peripheral blood mononuclear cells (PBMC) stimulated by autologous PCL-modified and unmodified tumor cells. These tumor cells were obtained from freshly resected tumor tissue of 16 patients with colon (8), lung (4) and renal (4) carcinomas. The results demonstrated that PCL-modified tumor cells promoted an increase in PBMC proliferation in 5 out of 8 (63%), 1 out of 4 (25%) and 4 out of 4 (100%) colon, lung and renal cell carcinomas. Fourteen of the above cultures were also analyzed for the secretion of interleukin-10 and interferon-gamma. Overall, a substantial decrease in IL-10 secretion was detected in 9 out of 14 (64%) cultures while a reciprocal increase in interferon-gamma secretion was noted in 8 out of 14 (57%) cultures. Our results confirmed that PCL-modified human tumor cells of different etiologies can modulate the pattern of cytokines released from stimulated autologous lymphocytes. Such a procedure could prove valuable in the production of autologous tumor vaccines.

Approaches for optimal sequential decision analysis in clinical trials.

Unlike traditional approaches, Bayesian methods enable formal combination of expert opinion and objective information into interim and final analyses of clinical trial data. However, most previous Bayesian approaches have based the stopping decision on the posterior probability content of one or more regions of the parameter space, thus implicitly determining a loss and decision structure. In this paper, we offer a fully Bayesian approach to this problem, specifying not only the likelihood and prior distributions but appropriate loss functions as well. At each data monitoring point, we enumerate the available decisions and investigate the use of backward induction, implemented via Monte Carlo methods, to choose the optimal course of action. We then present a forward sampling algorithm that substantially eases the analytic and computational burdens associated with backward induction, offering the possibility of fully Bayesian optimal sequential monitoring for previously untenable numbers of interim looks. We show that forward sampling can always identify the optimal sequential strategy in the case of a one-parameter exponential family with a conjugate prior and monotone loss functions as well as the best member of a certain class of strategies when backward induction is infeasible. Finally, we illustrate and compare the forward and backward approaches using data from a recent AIDS clinical trial.

Human respiratory syncytial virus produces prolonged alterations of neural control in airways of developing ferrets.

A dysfunction of pathways that normally cause contraction or relaxation of airways has been proposed to explain heightened levels of responsiveness produced by various insults to the airway. For example, we previously reported (4) that infection of cotton rats with the human respiratory syncytial virus (HRSV) leads to a significant decrease in an airway's nonadrenergic noncholinergic inhibitory (NANCi) response shortly after the infection. In the present study we addressed the more chronic effects of HRSV infection on airway function in young ferrets during a period of rapid somatic growth. Animals 1 wk old received HRSV or uninfected cell culture medium intranasally. In vitro studies of airway function were performed on tracheal smooth muscle (TSM) segments at 4, 8, and 24 wk of age. To evaluate neurally mediated contractile responses, frequency-response curves to electrical field stimulation (EFS) were performed with results expressed in terms of the frequency causing 50% of the maximal contractile response (ES50). In addition, contractile responses of TSM to methacholine (MCh) were also assessed with results expressed as the concentration needed to produce 50% of the maximal contractile response (EC50). To gauge NANCi responses, TSM was contracted with neurokinin A in the presence of atropine, propranolol, and indomethacin. Relaxant responses to EFS were assessed at frequencies from 5 to 30 Hz, with results expressed as mean percent relaxation. We found increased contractile responses to EFS in infected animals compared with that in the control group in both 4- and 8-wk old animals (p = 0.001 and p = 0.008, respectively). This difference had resolved by 24 wk of age. There was no difference in TSM responses to MCh between the groups at any age. Although there were no NANCi responses in 4-wk-old ferrets from either group, NANCi responses were significantly decreased in 8-wk-old ferrets previously infected with HRSV in the first week of life (p = 0.0001). A significant difference persisted (p = 0.008), albeit to a lesser degree, at 24 wk of age. These findings demonstrate that HRSV produces prolonged alterations of TSM function in ferret airways in vitro.

Effect of aspiration of milk on mechanisms of neural control in the airways of developing rabbits.

We studied the effects of recurrent aspiration of milk on neural control of airways in young developing rabbits. Beginning at 1 week of age, rabbits received 0.5 ml/kg of whole milk or sterile physiologic saline intranasally while under light methoxyflourane anesthesia 5 days a week for a period of 3 weeks. At 4 and 8 weeks of age, in vitro studies of contractile and relaxant responses of tracheal smooth muscle (TSM) segments were evaluated. To assess the neurally mediated contractile responses, frequency response curves to electrical field stimulation (EFS) were performed with results expressed in terms of frequency of EFS causing 50% of the maximal contractile response (ES50) values. In addition, the contractile responsiveness of TSM to methacholine (MCh) as reflected by the concentration causing 50% of the maximal contractile response (EC50) values was also determined to evaluate the underlying cholinergic reactivity of this segment of airway. To assess nonadrenergic noncholinergic inhibitory (NANCi) responses, experiments were performed on TSM contracted with neurokinin A in the presence of atropine, propranolol, and indomethacin. EFS was delivered to the contracted tissue at stimulation frequencies ranging from 5 to 30 Hz with results expressed as mean percent relaxation. Recurrent aspiration of milk but not saline increased EFS-induced contractile responses, as shown by significantly lower ES50 values compared with the control group: P = 0.02 and P = 0.001 at 4 and 8 weeks of age, respectively. TSM responsiveness to MCh was no different between the two groups, suggesting that alterations in prejunctional mechanisms of neural control were most likely responsible for the increased contractile response to EFS. The NANCi responses were significantly decreased by milk aspiration at both 4 and 8 weeks of age, with the abnormalities less pronounced at the later time point. These findings demonstrate that repeated aspiration of milk leads to abnormal mechanisms of neural control within airways of developing rabbits. While aspiration of milk altered both contractile and relaxant responses to EFS, the former abnormalities became more pronounced with time while the latter appeared to be resolving. These observations suggest that injury to an airway early in development does not necessarily resolve with time but may persist, with functional abnormalities becoming more pronounced even after the airway insult has ceased.

The relationship of current psychiatric disorder to functional disability and distress in patients with inflammatory bowel disease.

Although prior theories about psychiatric disorders causing inflammatory bowel disease (IBD) have largely been discredited, these same disorders have at times been associated with functional gastrointestinal symptoms such as those found in irritable bowel syndrome. Since functional gastrointestinal symptoms can also occur in patients with organic pathology, we hypothesized that a current psychiatric disorder might amplify or produce additional gastrointestinal symptoms in patients with organic gastrointestinal diseases such as IBD, leading to additive functional disability and decreased quality of life. This pilot study evaluated a sequential sample of 40 IBD patients using the NIMH Diagnostic Interview Schedule, structured interviews for functional gastrointestinal symptoms, and prior episodes of emotional, physical, and sexual abuse as well as self-report measures of personality and disability. We compared IBD patients with and without a current psychiatric disorder while controlling for disease severity. Eight patients with major depression were treated with antidepressants. Patients with a current psychiatric disorder had significantly higher 1) mean number of lifetime psychiatric diagnoses, 2) prevalence rates of prior sexual and physical victimization, and, 3) mean numbers of both gastrointestinal and other medically unexplained symptoms despite no differences in severity of IBD. Significant and trend level differences were apparent on several measures of functional disability. A regression analysis showed that number of psychiatric diagnoses, number of functional gastrointestinal symptoms, and dissociation scale scores significantly discriminated the groups. Treatment of current major depression decreased functional disability despite no objective changes in gastrointestinal disease severity. It was concluded that the presence of a current psychiatric disorder appears to alter the perception of disease severity in patients with IBD. Nonrecognition of the psychiatric disorder may lead to unnecessary and aggressive interventions for IBD patients such as medication changes, invasive testing, or surgery. The presence of a current psychiatric illness also appears to be associated with increased functional disability. Psychiatric evaluation and treatment, therefore, have an important role in the ongoing management of IBD patients with distressing gastrointestinal symptoms not directly attributable to their IBD.

Chronic pelvic pain and gynecological symptoms in women with irritable bowel syndrome.

Chronic pelvic pain and irritable bowel syndrome are common disorders, yet very little is known about their comorbidity. As part of an epidemiological study of patients with irritable bowel syndrome or irritable bowel disease we inquired about a history of chronic pelvic pain and related gynecological problems, and hypothesized that distress associated with either of these conditions was additive in women with both syndromes. A medically trained interviewer evaluated a sequential sample of 60 women with irritable bowel syndrome and 26 women with inflammatory bowel disease in an urban gastroenterology clinic using the National Institute of Mental Health Diagnostic Interview Schedule, the Briere Child Maltreatment Interview (emotional, physical and sexual abuse), and a structured interview to elicit a lifetime history of chronic pelvic pain that was distinct from the history of bowel distress. Chronic pelvic pain was reported in 21 (35.0%) of the irritable bowel syndrome patients vs. 4 (13.8%) of the inflammatory bowel disease group (p < 0.05). Compared to women with irritable bowel syndrome alone, those with both irritable bowel syndrome and chronic pelvic pain were significantly more likely to have a lifetime history of dysthymic disorder, current and lifetime panic disorder, somatization disorder, childhood sexual abuse and hysterectomy. Logistic regression showed that mean number of somatization symptoms was the best predictor of a history of both irritable bowel syndrome and chronic pelvic pain compared either to inflammatory bowel disease or irritable bowel syndrome alone. Many women with irritable bowel syndrome may have a history of chronic pelvic pain as well. The high rates of psychopathology associated with irritable bowel syndrome and chronic pelvic pain independently are even higher in women with both syndromes, and women who present with either irritable bowel syndrome or chronic pelvic pain should probably be evaluated for both disorders.

Surface projection of murine major histocompatibility determinants induced by hydrostatic pressure and cytokines.

Augmentation of surface presentation of the major histocompatibility complex (MHC) is a leading trend for preparation of tumor vaccines. Exposure of weakly immunogenic tumor cells, such as murine B16 melanoma, to hydrostatic pressure (P) in the presence of the membrane-impermeable protein crosslinker (CL) 2',3'-adenosine dialdehyde, was previously shown to induce a substantial increase in surface presentation of MHC molecules. When B-16 melanoma cells, used here as a model, were first treated for 72 h with interferon-gamma or tumor necrosis factor-alpha at concentrations of 10 and 100 units/ml, respectively, followed by application of pressure and cross-linking (PCL), the surface presentation of H2b molecules increased by 40% compared to treatment with cytokines alone, and by up to 1,700% when compared to treatment with PCL alone. Neither P nor CL alone enhanced the MHC presentation when cells were pretreated with these cytokines. The changes in MHC observed after the cytokine treatment were transient and decayed within several hours. However, the changes induced by the sequential treatment with cytokines and PCL were sustained for at least 96 h post-PCL which is of prime importance for immunogenic expression. A series of analogous experiments in the presence of cycloheximide indicated that approximately 50% of the observed PCL-induced increase in MHC projection originates from protein synthesis while the other 50% corresponds to passive translocation of MHC compartments. B16 melanoma cells, modified by the sequential treatment of cytokines and PCL, proved to be substantially more immunogenic by an in vitro sensitization assay than cells treated by either one of these treatments alone. These results may provide a guideline for the preparation of tumor vaccines which could be applied in immunotherapy treatment of cancer.

Psychiatric diagnoses, sexual and physical victimization, and disability in patients with irritable bowel syndrome or inflammatory bowel disease.

We compared 71 patients with irritable bowel syndrome (IBS) and 40 patients with inflammatory bowel disease (IBD) using structured interviews for psychiatric, gastrointestinal and sexual/physical victimization histories, as well as self-reported measures of personality, functional disability and dissociation. IBS patients had significantly higher lifetime prevalence rates of major depression, current panic disorder, and childhood sexual abuse. Despite the absence of organic pathology, IBS patients had significantly higher numbers of medically unexplained physical symptoms and disability ratings equal to, or greater than, those of patients with severe organic gastrointestinal disease.