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We present the requirements, design, and evaluation of the cryogenic continuously rotating half-wave plate (CHWP) for the Simons Observatory (SO). SO is a cosmic microwave background polarization experiment at Parque Astronómico de Atacama in northern Chile that covers a wide range of angular scales using both small (⌀0.42 m) and large (⌀6 m) aperture telescopes. In particular, the small aperture telescopes (SATs) focus on large angular scales for primordial B-mode polarization. To this end, the SATs employ a CHWP to modulate the polarization of the incident light at 8 Hz, suppressing atmospheric 1/f noise and mitigating systematic uncertainties that would otherwise arise due to the differential response of detectors sensitive to orthogonal polarizations. The CHWP consists of a 505 mm diameter achromatic sapphire HWP and a cryogenic rotation mechanism, both of which are cooled down to ∼50 K to reduce detector thermal loading. Under normal operation, the HWP is suspended by a superconducting magnetic bearing and rotates with a constant 2 Hz frequency, controlled by an electromagnetic synchronous motor. We find that the number of superconductors and the number of magnets that make up the superconducting magnetic bearing are important design parameters, especially for the rotation mechanism's vibration performance. The rotation angle is detected through an angular encoder with a noise level of 0.07 μrad s. During a cooldown process, the rotor is held in place by a grip-and-release mechanism that serves as both an alignment device and a thermal path. In this paper, we provide an overview of the SO SAT CHWP: its requirements, hardware design, and laboratory performance.

We present measurements of the radial profiles of the mass and galaxy number density around Sunyaev–Zel’dovich (SZ)-selected clusters using both weak lensing and galaxy counts. The clusters are selected from the Atacama Cosmology Telescope Data Release 5 and the galaxies from the Dark Energy Survey Year 3 data set. With signal-to-noise ratio of 62 (45) for galaxy (weak lensing) profiles over scales of about 0.2–20 h-1 Mpc, these are the highest precision measurements for SZ-selected clusters to date. Because SZ selection closely approximates mass selection, these measurements enable several tests of theoretical models of the mass and light distribution around clusters. Our main findings are: (1) The splashback feature is detected at a consistent location in both the mass and galaxy profiles and its location is consistent with predictions of cold dark matter N-body simulations. (2) The full mass profile is also consistent with the simulations. (3) The shapes of the galaxy and lensing profiles are remarkably similar for our sample over the entire range of scales, from well inside the cluster halo to the quasilinear regime. We measure the dependence of the profile shapes on the galaxy sample, redshift, and cluster mass. We extend the Diemer & Kravtsov model for the cluster profiles to the linear regime using perturbation theory and show that it provides a good match to the measured profiles. We also compare the measured profiles to predictions of the standard halo model and simulations that include hydrodynamics. Applications of these results to cluster mass estimation, cosmology, and astrophysics are discussed.

We present measurements of the average thermal Sunyaev Zel’dovich (tSZ) effect from optically selected galaxy groups and clusters at high signal-to-noise (up to ) and estimate their baryon content within a radius aperture. Sources from the Sloan Digital Sky Survey Baryon Oscillation Spectroscopic Survey DR15 catalog overlap with 3,700 sq deg of sky observed by the Atacama Cosmology Telescope (ACT) from 2008 to 2018 at 150 and 98 GHz (ACT DR5), and 2,089 sq deg of internal linear combination component-separated maps combining ACT and Planck data (ACT DR4). The corresponding optical depths , which depend on the baryon content of the halos, are estimated using results from cosmological hydrodynamic simulations assuming an active galactic nuclei feedback radiative cooling model. We estimate the mean mass of the halos in multiple luminosity bins, and compare the tSZ-based estimates to theoretical predictions of the baryon content for a Navarro-Frenk-White profile. We do the same for estimates extracted from fits to pairwise baryon momentum measurements of the kinematic Sunyaev-Zel’dovich effect (kSZ) for the same dataset obtained in a companion paper. We find that the estimates from the tSZ measurements in this work and the kSZ measurements in the companion paper agree within for two out of the three disjoint luminosity bins studied, while they differ by in the highest luminosity bin. The optical depth estimates account for one-third to all of the theoretically predicted baryon content in the halos across luminosity bins. Potential systematic uncertainties are discussed. The tSZ and kSZ measurements provide a step toward empirical Compton- relationships to provide new tests of cluster formation and evolution models.

We present a detection of the pairwise kinematic Sunyaev-Zeldovich (kSZ) effect using Atacama Cosmology Telescope (ACT) and Planck CMB observations in combination with Luminous Red Galaxy samples from the Sloan Digital Sky Survey (SDSS) DR15 catalog. Results are obtained using three ACT CMB maps: co-added 150 and 98 GHz maps, combining observations from 2008-2018 (ACT DR5), which overlap with SDSS DR15 over 3,700 sq. deg., and a component-separated map using night-time only observations from 2014-2015 (ACT DR4), overlapping with SDSS DR15 over 2,089 sq. deg. Comparisons of the results from these three maps provide consistency checks in relation to potential frequency-dependent foreground contamination. A total of 343,647 galaxies are used as tracers to identify and locate galaxy groups and clusters from which the kSZ signal is extracted using aperture photometry. We consider the impact of various aperture photometry assumptions and covariance estimation methods on the signal extraction. Theoretical predictions of the pairwise velocities are used to obtain best-fit, mass-averaged, optical depth estimates for each of five luminosity-selected tracer samples. A comparison of the kSZ-derived optical depth measurements obtained here to those derived from the thermal SZ effect for the same sample is presented in a companion paper.

Two recent large data releases for the Atacama Cosmology Telescope (ACT), called DR4 and DR5, are available for public access. These data include temperature and polarization maps that cover nearly half the sky at arcminute resolution in three frequency bands; lensing maps and component-separated maps covering ~2100 deg2 of sky; derived power spectra and cosmological likelihoods; a catalog of over 4000 galaxy clusters; and supporting ancillary products including beam functions and masks. The data and products are described in a suite of ACT papers; here we provide a summary. In order to facilitate ease of access to these data, we present a set of Jupyter IPython notebooks developed to introduce users to DR4, DR5, and the tools needed to analyze these data. The data products (excluding simulations) and the set of notebooks are publicly available on the NASA Legacy Archive for Microwave Background Data Analysis; simulation products are available on the National Energy Research Scientific Computing Center.

The thermal and kinematic Sunyaev-Zel'dovich effects (tSZ, kSZ) probe the thermodynamic properties of the circumgalactic and intracluster medium (CGM and ICM) of galaxies, groups, and clusters, since they are proportional, respectively, to the integrated electron pressure and momentum along the line of sight. We present constraints on the gas thermodynamics of CMASS (constant stellar mass) galaxies in the Baryon Oscillation Spectroscopic Survey using new measurements of the kSZ and tSZ signals obtained in a companion paper [Schaan et al.]. Combining kSZ and tSZ measurements, we measure within our model the amplitude of energy injection ϵM⋆c2, where M⋆ is the stellar mass, to be ϵ=(40±9)×10-6, and the amplitude of the nonthermal pressure profile to be αNth

The scattering of cosmic microwave background (CMB) photons off the free-electron gas in galaxies and clusters leaves detectable imprints on high resolution CMB maps: the thermal and kinematic Sunyaev-Zel'dovich effects (tSZ and kSZ respectively). We use combined microwave maps from the Atacama Cosmology Telescope DR5 and Planck in combination with the CMASS (mean redshift ⟨z

We present a catalog of 4195 optically confirmed Sunyaev–Zel’dovich (SZ) selected galaxy clusters detected with signal-to-noise ratio >4 in 13,211 deg2 of sky surveyed by the Atacama Cosmology Telescope (ACT). Cluster candidates were selected by applying a multifrequency matched filter to 98 and 150 GHz maps constructed from ACT observations obtained from 2008 to 2018 and confirmed using deep, wide-area optical surveys. The clusters span the redshift range 0.04 < z < 1.91 (median z = 0.52). The catalog contains 222 z > 1 clusters, and a total of 868 systems are new discoveries. Assuming an SZ signal versus mass-scaling relation calibrated from X-ray observations, the sample has a 90% completeness mass limit of M500c > 3.8 × 1014 Me, evaluated at z = 0.5, for clusters detected at signal-to-noise ratio >5 in maps filtered at an angular scale of 2 4. The survey has a large overlap with deep optical weak-lensing surveys that are being used to calibrate the SZ signal mass-scaling relation, such as the Dark Energy Survey (4566 deg2), the Hyper Suprime-Cam Subaru Strategic Program (469 deg2), and the Kilo Degree Survey (825 deg2). We highlight some noteworthy objects in the sample, including potentially projected systems, clusters with strong lensing features, clusters with active central galaxies or star formation, and systems of multiple clusters that may be physically associated. The cluster catalog will be a useful resource for future cosmological analyses and studying the evolution of the intracluster medium and galaxies in massive clusters over the past 10 Gyr.

We construct cosmic microwave background lensing mass maps using data from the 2014 and 2015 seasons of observations with the Atacama Cosmology Telescope (ACT). These maps cover 2100 square degrees of sky and overlap with a wide variety of optical surveys. The maps are signal dominated on large scales and have fidelity such that their correlation with the cosmic infrared background is clearly visible by eye. We also create lensing maps with thermal Sunyaev-Zel'dovich contamination removed using a novel cleaning procedure that only slightly degrades the lensing signal-to-noise ratio. The cross-spectrum between the cleaned lensing map and the BOSS CMASS galaxy sample is detected at 10σ significance, with an amplitude of A = 1.02 ± 0.10 relative to the Planck best-fitting Lambda cold dark matter cosmological model with fiducial linear galaxy bias. Our measurement lays the foundation for lensing cross-correlation science with current ACT data and beyond.

We use gravitational lensing of the cosmic microwave background (CMB) to measure the mass of the most distant blindly selected sample of galaxy clusters on which a lensing measurement has been performed to date. In CMB data from the the Atacama Cosmology Telescope and the Planck satellite, we detect the stacked lensing effect from 677 near-infrared-selected galaxy clusters from the Massive and Distant Clusters of WISE Survey (MaDCoWS), which have a mean redshift of zñ = 1.08. There are currently no representative optical weak lensing measurements of clusters that match the distance and average mass of this sample. We detect the lensing signal with a significance of 4.2s. We model the signal with a halo model framework to find the mean mass of the population from which these clusters are drawn. Assuming that the clusters follow Navarro–Frenk–White (NFW) density profiles, we infer a mean mass of M500cñ = (1.7 + 0.4) ´ 1014 M*. We consider systematic uncertainties from cluster redshift errors, centering errors, and the shape of the NFW profile. These are all smaller than 30% of our reported uncertainty. This work highlights the potential of CMB lensing to enable cosmological constraints from the abundance of distant clusters populating ever larger volumes of the observable universe, beyond the capabilities of optical weak lensing measurements.

Optimal analyses of many signals in the cosmic microwave background (CMB) require map-level extraction of individual components in the microwave sky, rather than measurements at the power spectrum level alone. To date, nearly all map-level component separation in CMB analyses has been performed exclusively using satellite data. In this paper, we implement a component separation method based on the internal linear combination (ILC) approach which we have designed to optimally account for the anisotropic noise (in the 2D Fourier domain) often found in ground-based CMB experiments. Using this method, we combine multifrequency data from the Planck satellite and the Atacama Cosmology Telescope Polarimeter (ACTPol) to construct the first wide-area (≈2100 sq. deg.), arcminute-resolution component-separated maps of the CMB temperature anisotropy and the thermal Sunyaev-Zel'dovich (tSZ) effect sourced by the inverse-Compton scattering of CMB photons off hot, ionized gas. Our ILC pipeline allows for explicit deprojection of various contaminating signals, including a modified blackbody approximation of the cosmic infrared background (CIB) spectral energy distribution. The cleaned CMB maps will be a useful resource for CMB lensing reconstruction, kinematic SZ cross-correlations, and primordial non-Gaussianity studies. The tSZ maps will be used to study the pressure profiles of galaxies, groups, and clusters through cross-correlations with halo catalogs, with dust contamination controlled via CIB deprojection. The data products described in this paper are available on LAMBDA.

We present a new measurement of the kinematic Sunyaev-Zel'dovich effect using data from the Atacama Cosmology Telescope (ACT) and the Baryon Oscillation Spectroscopic Survey (BOSS). Using 600 square degrees of overlapping sky area, we evaluate the mean pairwise baryon momentum associated with the positions of 50,000 bright galaxies in the BOSS DR11 Large Scale Structure catalog. A non-zero signal arises from the large-scale motions of halos containing the sample galaxies. The data fits an analytical signal model well, with the optical depth to microwave photon scattering as a free parameter determining the overall signal amplitude. We estimate the covariance matrix of the mean pairwise momentum as a function of galaxy separation, using microwave sky simulations, jackknife evaluation, and bootstrap estimates. The most conservative simulation-based errors give signal-to-noise estimates between 3.6 and 4.1 for varying galaxy luminosity cuts. We discuss how the other error determinations can lead to higher signal-to-noise values, and consider the impact of several possible systematic errors. Estimates of the optical depth from the average thermal Sunyaev-Zel'dovich signal at the sample galaxy positions are broadly consistent with those obtained from the mean pairwise momentum signal.

We present a new measurement of the kinematic Sunyaev-Zel'dovich effect using data from the Atacama Cosmology Telescope (ACT) and the Baryon Oscillation Spectroscopic Survey (BOSS). Using 600 square degrees of overlapping sky area, we evaluate the mean pairwise baryon momentum associated with the positions of 50,000 bright galaxies in the BOSS DR11 Large Scale Structure catalog. A non-zero signal arises from the large-scale motions of halos containing the sample galaxies. The data fits an analytical signal model well, with the optical depth to microwave photon scattering as a free parameter determining the overall signal amplitude. We estimate the covariance matrix of the mean pairwise momentum as a function of galaxy separation, using microwave sky simulations, jackknife evaluation, and bootstrap estimates. The most conservative simulation-based errors give signal-to-noise estimates between 3.6 and 4.1 for varying galaxy luminosity cuts. We discuss how the other error determinations can lead to higher signal-to-noise values, and consider the impact of several possible systematic errors. Estimates of the optical depth from the average thermal Sunyaev-Zel'dovich signal at the sample galaxy positions are broadly consistent with those obtained from the mean pairwise momentum signal.

Refractive optical elements are widely used in millimeter and sub-millimeter (sub-mm) astronomical telescopes. High-resistivity silicon is an excellent material for dielectric lenses given its low loss tangent, high thermal conductivity, and high index of refraction. The high index of refraction of silicon causes a large Fresnel reflectance at the vacuum-silicon interface (up to 30%), which can be reduced with an anti-reflection (AR) coating. In this work, we report techniques for efficiently AR coating silicon at sub-mm wavelengths using deep reactive ion etching (DRIE) and bonding the coated silicon to another silicon optic. Silicon wafers of 100 mm diameter (1 mm thick) were coated and bonded using the silicon direct bonding technique at high temperature (1100°C). No glue is used in this process. Optical tests using a Fourier transform spectrometer show sub-percent reflections for a single-layer DRIE AR coating designed for use at 320 μm on a single wafer. Cryogenic (10 K) measurements of a bonded pair of AR-coated wafers also reached sub-percent reflections. A prototype two-layer DRIE AR coating to reduce reflections and increase bandwidth is presented, and plans for extending this approach are discussed.

A determination of histamine in urine by selected ion monitoring, using (15N2)histamine as internal standard, is described. Three different ionization methods were used, chemical ionization with ammonia as reactant gas offering the highest sensitivity (detection limit 40 fmol of histamine on column). The 24 h urinary excretions of 10 normal adults ranged from 142-1100 nmol (mean 321 nmol). Patients with an anaphylactoid reaction and patients with mastocytosis showed above normal values.

The determination of sulphate in plasma is described, making use of reversed-phase high-performance liquid chromatography with ultraviolet detection. The concentration of inorganic sulphate determined in plasma of twenty healthy volunteers was 0.307 +/- 0.092 mmol/l (mean +/- S.D.). In one stable chronic dialysis patient the kinetics of plasma sulphate removal were monitored during and after one single pass dialysis. In addition, plasma sulphate concentrations were determined in three stable chronic dialysis patients during a consecutive scheme of two single pass dialyses, five Redy dialyses and three single pass dialyses. As expected, plasma sulphate accumulates in plasma to a high steady-state level under Redy dialysis, whereas during single pass dialysis sulphate is efficiently removed.

By means of capillary gas chromatography urine samples of patients with cerebrotendinous xanthomatosis (CTX) were investigated before and during treatment by oral administration of chenodeoxycholic acid. The occurrence of various conjugated bile alcohols, presumably glucuronides, was demonstrated, the major compound being 5 beta-cholestane-3 alpha, 7 alpha, 12 alpha, 23 xi, 25-pentol. In the bile acid fraction norcholic acid and hydroxycholic acid were shown to be present in considerable amounts. In this way the presence of CTX can be demonstrated conclusively. After chenodeoxycholic acid therapy the excretion of both abnormal bile acids as well as of bile alcohols rapidly decreased within a few weeks, showing the effectiveness of the treatment. By early discovery and subsequent therapy it may be possible to prevent the onset of the detrimental symptoms such as mental deficiency, caused by the accumulation of cholestanol and cholesterol in CTX patients.

A procedure is described for the simultaneous determination of cholic acid and chenodeoxycholic acid pool sizes and fractional turnover rates. After oral administration of known amounts of 11,12-dideuterated chenodeoxycholic acid and 2,2,4,4-tetradeuterated cholic acid, the ratios of chenodeoxycholic acid-D2/chenodeoxycholic acid and cholic acid-D4/cholic acid are measured in consecutive serum samples, after which fractional turnover rates and pool sizes of chenodeoxycholic acid and cholic acid are determined arithmetically. In 7 healthy volunteers pool sizes for chenodeoxycholic acid and cholic acid were 22.9 +/- 7.8 and 24.1 +/- 11.7 mumol/kg, respectively. The corresponding values for the fractional turnover rates were 0.23 +/- 0.10 and 0.29 +/- 0.12/day. After oral administration of the labelled bile acids in capsule, the obtained pool sizes were significantly higher than after administration in a bicarbonate solution. Bile acid kinetics were also performed in a patient suffering from a cholesterol synthesis deficiency and in a patient very likely suffering from a bile acid synthesis deficiency. Furthermore, the kinetics of the intestinal absorption and hepatic clearance of unconjugated bile acids have been investigated in 2 healthy subjects.

This study gives a review of the results obtained from biochemical investigations of 20 patients in The Netherlands suffering from cerebrotendinous xanthomatosis, an inborn error of metabolism in bile acid synthesis. Diagnosis can best be established by determining the excretion of urinary bile alcohols, in particular 5 beta-cholestane-3 alpha, 7 alpha, 12 alpha,23,25-pentol, in urine by means of capillary gas chromatography. Measurement of serum cholestanol levels or serum cholestanol/cholesterol ratios, commonly used for establishing cerebrotendinous xanthomatosis, are not reliable. The effectiveness of the different therapies, i.e. administration of bile acids, can be evaluated by monitoring the urinary excretion of bile alcohols. From such investigations it was concluded that cholic acid especially, but also chenodeoxycholic acid are the therapies of choice for the treatment of cerebrotendinous xanthomatosis. All patients, until now diagnosed in The Netherlands were not discovered before the third or fourth decade of life because the characteristic signs only then become manifest clearly. Unfortunately, because sterol storage is almost irreversible, therapy only results in minor improvements of the patient's condition. Therefore early detection of the presence of cerebrotendinous xanthomatosis is desirable so that treatment can start before extensive storage of sterols is a fact. We developed some laboratory assays with the purpose of early detection. One consists of the detection of cerebrotendinous xanthomatosis carriers by subjecting them to oral cholestyramine administration and monitoring the urinary excretion of the bile alcohol 5 beta-cholestane-3 alpha,7 alpha,12 alpha,23,25-pentol before and after treatment. Secondly, a relatively simple screening test for cerebrotendinous xanthomatosis was developed based on an enzymatic assay of 7 alpha-hydroxylated steroids in urine. After suitable modification this assay in principle allows the screening of large populations for the existence of cerebrotendinous xanthomatosis and thus to detect the disease at an earlier stage of life.

The clinical features and additional investigations of 20 Dutch patients suffering from cerebrotendinous xanthomatosis (CTX), an inborn error of metabolism in bile acid synthesis, are described. The onset was in the second or third decade. The clinical picture at the time of examination consisted of a combination of two or more of the following signs: cataract, xanthoma of a tendon, mental deterioration, pyramidal tract signs, cerebellar signs and epilepsy. Mental retardation was reported in patients. CT-scanning showed cerebellar hypodensity in 8 out of 16 patients but this feature did not correlate well with cerebellar signs. The EEG was abnormal in all but one patient. Treatment with chenodeoxycholic acid resulted in a normalization of EEG and biochemical abnormalities but not of the clinical signs. Cholic acid was equally effective but had much less side effects. The importance of a diagnosis in early life is stressed as well as the examination of clinically unaffected heterozygous relatives.

In patients who had undergone orthotopic liver transplantation, malabsorption of prednisolone or increased metabolism of prednisolone was suspected. In order to rule out this possibility, urinary prednisolone, and some of its metabolites, viz prednisone and 6 beta-hydroxyprednisolone, were determined by means of a gas chromatographic assay. To evaluate this assay aliquots of a pooled urine from several of our patients were analysed in multiplicate (n = 10). Mean prednisone, prednisolone and 6 beta-hydroxyprednisolone concentrations of 1.9 mg/l, 6.3 mg/l and 4.1 mg/l, respectively, were found with the following respective day-to-day coefficients of variation: 12.3%, 5.2% and 5.3%. Amounts of prednisolone metabolites excreted in the urine of these patients were correlated with the ingested daily dose of prednisolone. It was concluded that overall absorption of prednisolone in these patients was adequate and not influenced by shortage of bile acids in the gastro-intestinal tract, or by steatorrhoea, both caused by external bile drainage. In addition there was no evidence for increased metabolism of prednisolone.

Patients suffering from cerebrotendinous xanthomatosis, an inborn error of metabolism in bile acid synthesis, excrete excessive amounts of 23-hydroxylated bile alcohols, 23-norcholic acid and 23-hydroxycholic acid into urine. In this study the configuration of this excreted 23-hydroxycholic acid was established as (23R)-hydroxycholic acid. Urine samples of two treated patients, receiving chenodeoxycholic acid, were investigated to see whether this administered bile acid was partly converted into 23-hydroxychenodeoxycholic acid. One patient was treated with ursodeoxycholic acid for 1 month and subsequently with chenodeoxycholic acid, and the urinary excretion of both (23R)-hydroxychenodeoxycholic acid and (23R)-hydroxyursodeoxycholic acid were followed. Indeed, all three patients excreted (23R)-hydroxylated chenodeoxycholic acid during oral treatment with chenodeoxycholic acid, and the patient treated with ursodeoxycholic acid excreted (23R)-hydroxylated ursodeoxycholic acid. During treatment with chenodeoxycholic acid the excretion of (23R)-hydroxychenodeoxycholic acid increases at first and later on decreases markedly. These findings suggest increased (23R)-hydroxylase activity in patients suffering from cerebrotendinous xanthomatosis, acting both on endogenously synthesized bile alcohols and on exogenously administered bile acids; during continuation of chenodeoxycholic acid treatment in an effective dose (750 mg/day) this enzyme activity gradually disappears.

Altered bile acid metabolism has been claimed to play a role in the etiology of benign recurrent intrahepatic cholestasis (BRIC). Therefore, we studied bile acid metabolism in detail in 10 patients with this syndrome. Pool sizes of both primary bile acids were estimated simultaneously, using deuterated cholic acid and chenodeoxycholic acid. The pool sizes of cholic acid and chenodeoxycholic acid, expressed in micromoles per kilogram body weight, were significantly contracted in BRIC patients during a cholestasis-free period: 8.0 +/- 4.2 and 11.7 +/- 4.7, respectively, versus 24.1 +/- 11.7 and 22.9 +/- 7.8 in controls. Fractional turnover rates (per day) for cholic acid and chenodeoxycholic acid were increased: 0.70 +/- 0.29 and 0.58 +/- 0.27, respectively, versus 0.29 +/- 0.12 and 0.23 +/- 0.10 in controls. Bile acid pool composition expressed as percentages in BRIC patients was cholic acid 34 +/- 17, chenodeoxycholic acid 38 +/- 9, deoxycholic acid 27 +/- 18, and lithocholic acid 1 +/- 1, with a glycine to taurine conjugation ratio of 6.7 +/- 4.9. Corresponding values for 32 controls were cholic acid 57 +/- 13, chenodeoxycholic acid 29 +/- 9, deoxycholic acid 14 +/- 9, and lithocholic acid less than 1, with a glycine to taurine conjugation ratio of 2.4 +/- 1.3. Fecal bile acid loss, in micromoles per kilogram body weight per day, was 11.2 +/- 9.0 in BRIC patients compared with 2.8 +/- 1.4 in controls. The serum 7 alpha-hydroxycholesterol level (nanomoles per liter) was significantly increased in BRIC patients: 326 +/- 179 versus 171 +/- 90 in controls. These results suggest that in BRIC patients spillover of bile acids into the colon occurs, which leads to increased fecal bile acid loss and a reduced bile acid pool size. Increased serum 7 alpha-hydroxycholesterol is probably indicative of an accelerated bile acid synthesis rate due to increased activity of cholesterol 7 alpha-hydroxylase, the enzyme catalyzing the first step in the major pathway of bile acid synthesis. The results of our study suggest that in BRIC patients a contracted bile acid pool increases the susceptibility of the liver for cholestatic agents.