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Line Intensity Mapping (LIM) is a new observational technique that uses low-resolution observations of line emission to efficiently trace the large-scale structure of the Universe out to high redshift. Common mm/sub-mm emission lines are accessible from ground-based observatories, and the requirements on the detectors for LIM at mm-wavelengths are well matched to the capabilities of large-format arrays of superconducting sensors. We describe the development of an R = 300 on-chip superconducting filter-bank spectrometer covering the 120--180 GHz band optimized for future mm-LIM experiments, focusing on SPT-SLIM, a pathfinder LIM instrument for the South Pole Telescope. Radiation is coupled from the telescope optical system to the spectrometer chip via an array of feedhorn-coupled orthomode transducers. Superconducting microstrip transmission lines then carry the signal to an array of channelizing half-wavelength resonators, and the output of each spectral channel is sensed by a lumped element kinetic inductance detector (leKID). Key areas of development include incorporating new low-loss dielectrics to improve both the achievable spectral resolution and optical efficiency and development of a robust fabrication process to create a galvanic connection between ultra-pure superconducting thin-films to realize multi-material (hybrid) leKIDs. We provide an overview of the spectrometer design, fabrication process, and prototype devices., 7 pages, 7 figures, presented at 2022 Applied Superconductivity Conference

MUSCAT is a new large-format 1.1 mm continuum camera for local and extra-galactic astronomy currently being installed at the 50 m Large Millimetre Telescope Alfonso Serrano, LMT. The focal plane is populated with 1458 feedhorn coupled Aluminium LEKIDs, cooled to 130 mk, and read out with 6 frequency division multiplexed RF readout chains, each with a 500 MHz bandwidth. The nominal mux ratio is $$\sim$$ ∼ 250 resonators per chain with an average spacing of 2 MHz between resonators. In each RF chain, the multiplexed waveform generation/decomposition is performed with the BLAST-TNG firmware on a ROACH2 FPGA board with a MUSIC DAC/ADC. The quadrature modulated IF signals are mixed to and from the LEKID readout band on a custom card that houses IQ mixers, a programmable synthesizer, and additional programmable input and output gain control and filtering. Within the cryostat, the RF signals are attenuated prior to reaching the focal plane array and then amplified at 4K. A novel software system controls all the programmable hardware and handles instructions from the LMT instrument control system to record and store observation data, as well as performing automated resonator retuning and providing results of quick look analysis to the telescope operators. In this paper, we present the detailed design and in-lab performance of the cryogenic and room temperature electronics, and the software control system.

We present the design and science goals of SPT-3G+, a new camera for the South Pole Telescope, which will consist of a dense array of 34100 kinetic inductance detectors measuring the cosmic microwave background (CMB) at 220 GHz, 285 GHz, and 345 GHz. The SPT-3G+ dataset will enable new constraints on the process of reionization, including measurements of the patchy kinematic Sunyaev-Zeldovich effect and improved constraints on the optical depth due to reionization. At the same time, it will serve as a pathfinder for the detection of Rayleigh scattering, which could allow future CMB surveys to constrain cosmological parameters better than from the primary CMB alone. In addition, the combined, multi-band SPT-3G and SPT-3G+ survey data will have several synergies that enhance the original SPT-3G survey, including: extending the redshift-reach of SZ cluster surveys to $z > 2$; understanding the relationship between magnetic fields and star formation in our Galaxy; improved characterization of the impact of dust on inflationary B-mode searches; and characterizing astrophysical transients at the boundary between mm and sub-mm wavelengths. Finally, the modular design of the SPT-3G+ camera allows it to serve as an on-sky demonstrator for new detector technologies employing microwave readout, such as the on-chip spectrometers that we expect to deploy during the SPT-3G+ survey. In this paper, we describe the science goals of the project and the key technology developments that enable its powerful yet compact design., 26 pages, 9 figures, to appear in the proceedings of SPIE Astronomical Telescopes and Instrumentation 2022

The BICEP3 Polarimeter is a small aperture, refracting telescope, dedicated to the observation of the Cosmic Microwave Background (CMB) at 95GHz. It is designed to target degree angular scale polarization patterns, in particular the very-much-sought-after primordial B-mode signal, which is a unique signature of cosmic inflation. The polarized signal from the sky is reconstructed by differencing co-localized, orthogonally polarized superconducting Transition Edge Sensor (TES) bolometers. In this work, we present absolute measurements of the polarization response of the detectors for more than $\sim 800$ functioning detector pairs of the BICEP3 experiment, out of a total of $\sim 1000$. We use a specifically designed Rotating Polarized Source (RPS) to measure the polarization response at multiple source and telescope boresight rotation angles, to fully map the response over 360 degrees. We present here polarization properties extracted from on-site calibration data taken in January 2022. A similar calibration campaign was performed in 2018, but we found that our constraint was dominated by systematics on the level of $\sim0.5^\circ$. After a number of improvements to the calibration set-up, we are now able to report a significantly lower level of systematic contamination. In the future, such precise measurements will be used to constrain physics beyond the standard cosmological model, namely cosmic birefringence., Submitted to: SPIE Astronomical Telescopes + Instrumentation (AS22)

Superconducting on-chip filter-banks provide a scalable, space saving solution to create imaging spectrometers at millimetre and sub-millimetre wavelengths. We present an easy to realise, lithographed superconducting filter design with a high tolerance to fabrication error. Using a capacitively coupled $\lambda/2$ microstrip resonator to define a narrow ($\lambda/\Delta\lambda = 300$) spectral pass band, the filtered output of a given spectrometer channel directly connects to a Lumped Element Kinetic Inductance Detector (LEKID). We show the tolerance analysis of our design, demonstrating $, Comment: 8 pages, 5 figures. Pre-print for proceedings for the Journal of Low Temperature Physics, 19th Low Temperature Detectors Conference (LTD19)

Background Iron deficiency anemia (IDA) is a prevalent yet underdiagnosed condition with a significant impact on quality of life. Oral iron supplementation is often poorly tolerated or yields inadequate response, requiring the use of intravenous iron (IVI) in some patients. Administration of certain IVI preparations has been associated with decreases in serum phosphate levels and clinically significant hypophosphatemia, which has been reported to lead to adverse events including serious fatigue and osteomalacia. Objective The purpose of this study was to systematically assess the prevalence, clinical consequences, and reporting of treatment-emergent hypophosphatemia within literature investigating IVI therapies marketed in the United States (US). Methods A systematic literature review (SLR) was conducted using the PubMed database to identify publications reporting serum phosphate levels or rates of hypophosphatemia within adult IDA patient populations receiving current US-marketed IVIs. Results The SLR yielded 511 unique publications, with 40 records meeting the final inclusion criteria. Most studies did not report phosphate monitoring methodology or an explicit definition of hypophosphatemia. Hypophosphatemia rates ranged from 0.0% to 92.1% for ferric carboxymaltose (FCM), 0.0% to 40.0% for iron sucrose, 0.4% for ferumoxytol, and 0.0% for low-molecular-weight (LMW) iron dextran. Randomized controlled studies described hypophosphatemia as "asymptomatic" or did not report on other associated sequelae. Eleven case reports detailed treatment-emergent hypophosphatemia in patients treated with FCM. Patients with acute hypophosphatemia primarily developed severe fatigue; those with repeated FCM dosing developed chronic hypophosphatemia associated with osteomalacia and bone deformities. Conclusion Studies analyzed in this SLR reported a range of hypophosphatemia rates, with the highest consistently seen in patients treated with FCM. Across the clinical literature, there appeared to be minimal standardization of phosphate monitoring and definitions of hypophosphatemia. Although multiple cases have documented serious clinical consequences of hypophosphatemia associated with certain IVIs, current trials neither consistently nor adequately assess the frequency and severity of treatment-emergent hypophosphatemia and may underestimate its prevalence.

We report on the design and performance of the Bicep3 instrument and its first three-year data set collected from 2016 to 2018. Bicep3 is a 52 cm aperture refracting telescope designed to observe the polarization of the cosmic microwave background (CMB) on degree angular scales at 95 GHz. It started science observation at the South Pole in 2016 with 2400 antenna-coupled transition-edge sensor bolometers. The receiver first demonstrated new technologies such as large-diameter alumina optics, Zotefoam infrared filters, and flux-activated SQUIDs, allowing ∼10× higher optical throughput compared to the Keck design. Bicep3 achieved instrument noise equivalent temperatures of 9.2, 6.8, and 7.1 μ K CMB s and reached Stokes Q and U map depths of 5.9, 4.4, and 4.4 μK arcmin in 2016, 2017, and 2018, respectively. The combined three-year data set achieved a polarization map depth of 2.8 μK arcmin over an effective area of 585 square degrees, which is the deepest CMB polarization map made to date at 95 GHz.

The South Pole Telescope Summertime Line Intensity Mapper (SPT-SLIM) is a pathfinder experiment that will demonstrate the use of on-chip filter-bank spectrometers for mm-wave line intensity mapping (LIM). The SPT-SLIM focal plane consists of 18 dual-polarization R=300 filter-bank spectrometers covering 120-180 GHz, coupled to aluminum kinetic inductance detectors. A compact cryostat holds the detectors at 100 mK and performs observations without removing the SPT-3G receiver. SPT-SLIM will be deployed to the 10-m South Pole Telescope for observations during the 2023-24 austral summer. We discuss the overall instrument design, expected detector performance and sensitivity to the LIM signal from CO at 0.5 < z < 2. The technology and observational techniques demonstrated by SPT-SLIM will enable next-generation LIM experiments that constrain cosmology beyond the redshift reach of galaxy surveys., 7 pages, 4 figures. Submitted to the Journal of Low Temperature Physics (Proceedings of the 19th International Workshop on Low Temperature Detectors)

The quantum efficiency and mean transverse energy of electrons emitted from a cathode determine the quality of beams generated from photoinjectors. The nitrogen-incorporated ultrananocrystalline diamond, (N)UNCD, is a new class of robust semiconductor photocathodes, which has been considered in photoinjectors for high peak current extraction. In this work, we measure the spectral response in quantum efficiency, photoemission energy spectra, and mean transverse energy of the (N)UNCD photocathode using a photoemission electron microscope. The observed quantum efficiency was comparable to that of copper photocathodes. Photoemission spectra showed the evidence of scattering of electrons before emission. This relaxation of electrons due to scattering is also observed in the spectral response of the mean transverse energy. The mean transverse energy is limited to [Formula: see text] meV at the threshold. We attribute this to the physical and chemical roughness of the (N)UNCD photocathode and, hence, smoother films will be required to further reduce the mean transverse energy obtained from the (N)UNCD photocathode.

The Summertime Line Intensity Mapper (SLIM) is a mm-wave line-intensity mapping (mm-LIM) experiment for the South Pole Telescope (SPT). The goal of SPT-SLIM is to serve as a technical and scientific pathfinder for the demonstration of the suitability and in-field performance of multi-pixel superconducting filterbank spectrometers for future mm-LIM experiments. Scheduled to deploy in the 2023-24 austral summer, the SPT-SLIM focal plane will include 18 dual-polarization pixels, each coupled to an $R = \lambda/\Delta\lambda$ = 300 thin- film microstrip filterbank spectrometer that spans the 2 mm atmospheric window (120-180 GHz). Each individual spectral channel feeds a microstrip-coupled lumped-element kinetic inductance detector, which provides the highly multiplexed readout for the 10k detectors needed for SPT-SLIM. Here we present an overview of the preliminary design of key aspects of the SPT-SLIM the focal plane array, a description of the detector architecture and predicted performance, and initial test results that will be used to inform the final design of the SPT- SLIM spectrometer array., Comment: Submitted to special issue of JLTP (proceedings of LTD19)

International audience; We present results from an analysis of all data taken by the BICEP2, Keck Array, and BICEP3 CMB polarization experiments up to and including the 2018 observing season. We add additional Keck Array observations at 220 GHz and BICEP3 observations at 95 GHz to the previous 95/150/220 GHz dataset. The Q/U maps now reach depths of 2.8, 2.8, and 8.8 μKCMB arcmin at 95, 150, and 220 GHz, respectively, over an effective area of ≈600 square degrees at 95 GHz and ≈400 square degrees at 150 and 220 GHz. The 220 GHz maps now achieve a signal-to-noise ratio on polarized dust emission exceeding that of Planck at 353 GHz. We take auto- and cross-spectra between these maps and publicly available WMAP and Planck maps at frequencies from 23 to 353 GHz and evaluate the joint likelihood of the spectra versus a multicomponent model of lensed ΛCDM+r+dust+synchrotron+noise. The foreground model has seven parameters, and no longer requires a prior on the frequency spectral index of the dust emission taken from measurements on other regions of the sky. This model is an adequate description of the data at the current noise levels. The likelihood analysis yields the constraint r0.05<0.036 at 95% confidence. Running maximum likelihood search on simulations we obtain unbiased results and find that σ(r)=0.009. These are the strongest constraints to date on primordial gravitational waves.

Objective: Hypoactive sexual desire disorder (HSDD) in women has been viewed inaccurately by some in the medical and payer community as analogous to erectile dysfunction (ED) in men. This literature review aims to highlight the distinctions between HSDD and ED.Methods: Two systematic literature searches were conducted on the epidemiology, symptomatology and biopsychosocial outcomes of HSDD and ED. Studies published since 2007 were considered for HSDD; studies published since 2012 were considered for ED.Results: HSDD in women is primarily a central nervous system condition related to neuroendocrine factors, whereby neural pathways that regulate sexual excitation and/or inhibition appear to be involved. A combination of organic and psychogenic factors often contributes to ED. HSDD and ED are associated with similar psychological and interpersonal consequences, but affect different phases of the sexual response model (desire versus arousal) and have different pathophysiologies, therefore requiring different treatment and outcome paradigms. ED is measured by objective, physiological responses (erection and sexual function), but quantitative assessments for HSDD are more difficult because loss of desire with associated distress has to be assessed. Outcome measures used to assess ED, such as the number of satisfying sexual events, are far less informative as an endpoint for randomized clinical trials of treatments for HSDD.Conclusions: HSDD and ED are distinct conditions affecting different phases of the sexual response model, and thus require clear and unique clinical characterization and adequate communication between the health care professional and patient for appropriate diagnosis, management and treatment.

Background Iron deficiency anemia (IDA) is a prevalent yet underdiagnosed condition with a significant impact on quality of life. Oral iron supplementation is often poorly tolerated or yields inadequate response, requiring the use of intravenous iron (IVI) in some patients. Administration of certain IVI preparations has been associated with decreases in serum phosphate levels and clinically significant hypophosphatemia, which has been reported to lead to adverse events including serious fatigue and osteomalacia. Objective The purpose of this study was to systematically assess the prevalence, clinical consequences, and reporting of treatment-emergent hypophosphatemia within literature investigating IVI therapies marketed in the United States (US). Methods A systematic literature review (SLR) was conducted using the PubMed database to identify publications reporting serum phosphate levels or rates of hypophosphatemia within adult IDA patient populations receiving current US-marketed IVIs. Results The SLR yielded 511 unique publications, with 40 records meeting the final inclusion criteria. Most studies did not report phosphate monitoring methodology or an explicit definition of hypophosphatemia. Hypophosphatemia rates ranged from 0.0% to 92.1% for ferric carboxymaltose (FCM), 0.0% to 40.0% for iron sucrose, 0.4% for ferumoxytol, and 0.0% for low-molecular-weight (LMW) iron dextran. Randomized controlled studies described hypophosphatemia as “asymptomatic” or did not report on other associated sequelae. Eleven case reports detailed treatment-emergent hypophosphatemia in patients treated with FCM. Patients with acute hypophosphatemia primarily developed severe fatigue; those with repeated FCM dosing developed chronic hypophosphatemia associated with osteomalacia and bone deformities. Conclusion Studies analyzed in this SLR reported a range of hypophosphatemia rates, with the highest consistently seen in patients treated with FCM. Across the clinical literature, there appeared to be minimal standardization of phosphate monitoring and definitions of hypophosphatemia. Although multiple cases have documented serious clinical consequences of hypophosphatemia associated with certain IVIs, current trials neither consistently nor adequately assess the frequency and severity of treatment-emergent hypophosphatemia and may underestimate its prevalence.

Line intensity mapping (LIM) is emerging as a powerful technique to map the cosmic large-scale structure and to probe cosmology over a wide range of redshifts and spatial scales. We perform Fisher forecasts to determine the optimal design of wide-field ground-based mm-wavelength LIM surveys for constraining properties of neutrinos and light relics. We consider measuring the auto-power spectra of several CO rotational lines (from J=2-1 to J=6-5) and the [CII] fine-structure line in the redshift range of $0.25, Comment: v2 matches the published article, with number of spectrometer-hours in caption of table 3 edited

Objective To evaluate the association between exposure to oral corticosteroids and future healthcare resource utilization and costs for patients with systemic lupus erythematosus. Methods Adults diagnosed with systemic lupus erythematosus (index date) between 1 January 2008 and 30 June 2013 and naive to oral corticosteroids with continuous health plan enrollment for ≥6 months pre- and ≥5 years post-index were identified from a large health plan claims database. Per-patient monthly average daily dose of oral corticosteroids (prednisone or its equivalent) was calculated for the first 2 years post-index to categorize patients into four steroid exposure cohorts: low (≤5 mg/day), medium (6–20 mg/day), high (>20 mg/day) and no steroids. Differences in healthcare resource utilization and total healthcare costs during the third year post-index across corticosteroid exposure cohorts were modeled with adjustment for baseline characteristics. Results The study included 18,618 systemic lupus erythematosus patients (163 high dose, 1127 medium dose, 6717 low dose and 10,611 no steroids). Compared to low-dose corticosteroid users, high-dose corticosteroid users were more likely to have emergency room visits (39.3% vs. 29.7%; p = 0.0085) and to be hospitalized (21.5% vs. 12.3%; p = 0.0005). After adjustment for baseline characteristics, they also had significantly greater average annual total healthcare costs (US$60,366 vs. US$18,777; p Conclusion Long-term high-dose oral corticosteroid use was associated with significantly greater future healthcare resource utilization and costs. Judicious reduction in daily steroid dose may decrease the imminent economic burden associated with high-dose steroid use in systemic lupus erythematosus.

BICEP Array is a degree-scale Cosmic Microwave Background (CMB) experiment that will search for primordial B-mode polarization while constraining Galactic foregrounds. BICEP Array will be comprised of four receivers to cover a broad frequency range with channels at 30/40, 95, 150 and 220/270 GHz. The first low-frequency receiver will map synchrotron emission at 30 and 40 GHz and will deploy to the South Pole at the end of 2019. In this paper, we give an overview of the BICEP Array science and instrument, with a focus on the detector module. We designed corrugations in the metal frame of the module to suppress unwanted interactions with the antenna-coupled detectors that would otherwise deform the beams of edge pixels. This design reduces the residual beam systematics and temperature-to-polarization leakage due to beam steering and shape mismatch between polarized beam pairs. We report on the simulated performance of single- and wide-band corrugations designed to minimize these effects. Our optimized design alleviates beam differential ellipticity caused by the metal frame to about 7% over 57% bandwidth (25 to 45 GHz), which is close to the level due the bare antenna itself without a metal frame. Initial laboratory measurements are also presented., 12 pages and 14 figures

BICEP3 is a 520mm aperture on-axis refracting telescope observing the polarization of the cosmic microwave background (CMB) at 95GHz in search of the B-mode signal originating from inflationary gravitational waves. BICEP3's focal plane is populated with modularized tiles of antenna-coupled transition edge sensor (TES) bolometers. BICEP3 was deployed to the South Pole during 2014-15 austral summer and has been operational since. During the 2016-17 austral summer, we implemented changes to optical elements that lead to better noise performance. We discuss this upgrade and show the performance of BICEP3 at its full mapping speed from the 2017 and 2018 observing seasons. BICEP3 achieves an order-of-magnitude improvement in mapping speed compared to a Keck 95GHz receiver. We demonstrate $6.6\mu K\sqrt{s}$ noise performance of the BICEP3 receiver., Comment: 12 pages, 9 figures, Published in Proc. SPIE. Presented at SPIE Astronomical Telescopes and Instrumentation Conference 10708: Millimeter, Submillimeter, and Far-Infrared Detectors and Instrumentation for Astronomy XI, June 2018

Summary Congenital haemophilia is an inherited bleeding disorder typically diagnosed at birth or shortly thereafter. Haemophilia imposes a significant burden on patients and their caregivers. The aim of the study was to quantify the overall burden of haemophilia on caregivers in the USA using a novel disease-specific questionnaire and the previously validated CarerQol. Targeted literature review and a previous survey conducted by the authors was used to develop an online questionnaire with six burden domains of interest to caregivers (emotional stress, financial, sacrifice, medical management, child's pain and transportation) and several visual analogue scales (VAS). Content validity of the questionnaire was confirmed by three haemophilia caregivers. The study sample consisted of caregivers of children with haemophilia identified via a previously developed opt-in research database. Descriptive statistics were employed for demographic and clinical characteristics; a generalized linear model (GLM) was used to identify factors influencing caregiver burden. A total of 310 caregivers completed the survey (45.5% response rate). Most of the participating caregivers were mothers of a child with haemophilia (88%), between 35 and 44 years of age (48%), and with a college education or a postgraduate degree (63%). ‘Child's pain’ was identified as the most burdensome domain to caregivers (median score = 3.50 out of 5), followed by ‘emotional stress’ (2.67), ‘financial’ (2.40), ‘transportation’ (2.33), ‘sacrifice’ (2.17) and ‘medical management’ (2.00) domains. Although higher income exhibited a protective effect, episodes of bleeds, current presence of an inhibitor and lower caregiver productivity in the past month negatively affected caregiver burden per GLM results. Training and educational programs should potentially be developed to address caregiver burden.

The surface epithelium of 28 gallbladders removed during elective cholecystectomies and pathology collection was studied ultrastructurally. Focusing on 10 of the 28 cases that were diagnosed as cholecystitis, we found that the epithelium displayed numerous apical mucous granules and bulging apical apices. Mucous granule changes included 1) hyperproduction of secretory granules of neutral type containing an electron-dense proteinaceous spherule, similar to that described in other mucus-producing glands of the digestive system, and 2) production of anionic, osmiophilic secretory mucus. Other alterations of the surface epithelial cells included the production of bizarre surface appendages resembling primitive cilia without axoneme and epithelial excrescences.

In view of the lack of sufficient data regarding the morphology of the cystic duct and the extensive focus on the gallbladder, a preliminary examination of the cystic duct response to female sex steroid treatment was conducted to follow up a detailed ultrastructural study of the gallbladder epithelial response to a similar treatment. As observed in the gallbladder epithelium, the cystic duct epithelial cells of nulliparous Syrian hamsters demonstrate morphologic changes in response to female sex steroid treatment. Control (C) cystic duct epithelial cells are covered by short microvilli and each cell appears to exhibit a single vestigial cilium. Estrogen (E)- and estrogen + medroxyprogesterone (E + MP)-treatments induce differential duct cell morphologic changes. These changes are the result of steroid treatments in the significant decreasing sequence E > E + MP > C for nuclear volume, indentations and perinuclear lysosomal/lipofuscin bodies. Moreover E + MP-treatment results in larger cytoplasmic volume and more sloughing of apical cell excrescences than following E treatment. It is suggested that, similar to that in the gallbladder, the action of progestin is paramount in favoring cytoplasmic morphological changes in the cystic duct which, along with the alteration of mucus, cell sloughing, decreased bile acids and motility could also participate in the gallstone nucleation process as they are brought into the gallbladder with the incoming bile flow.

Ovariectomized Syrian hamsters treated by female sex steroids during a 1-month period show gallbladder surface epithelial changes in the fundic area consistent with apical bulging and decapitations of the epithelial cells. These events were detected in the infundibulum and the fundic or body regions of estrogen- and estrogen + progesterone-treated hamsters. In control hamsters, these events were restricted to the region in the vicinity of the bile duct. Following steroid treatment, intraluminal deposits detected resembled Ca-bilirubinate deposits described in previous studies while decapitations are similar to endometrial epithelium changes associated with hormonal physiological changes or treatments. Moreover some small electrondense deposits are comparable to those found in human cholesterol gallstones. This report indicates that, besides an alteration in bile composition, cell fragments originating from the surface epithelium of the bile duct and/or of the gallbladder mucosal epithelium could participate in gallstone nucleation.

To evaluate the efficacy of an interventional regime to reduce the perinatal mode of transmission of human immunodeficiency virus (HIV).Prospective.Perinatal HIV clinic at a university affiliated maternity hospital.After adequate counseling, consenting HIV positive women were offered perinatal intervention: (i) administration of 400 mg of zidovudine (AZT) per day for the last 6 weeks of the antenatal period; (ii) delivery by elective Caesarian section before rupture of membrances; (iii) oral AZT powder in the dose of 8 mg per kilogram daily to the infant for the first 6 weeks of life; and (iv) avoidance of breast milk. The infants were scheduled for regular follow-up for at least 18 months. A definitive diagnosis of infectivity in the infant was ascertained by two positive enzyme-linked immunosorbent assays (ELISA) at the age of 9 months and between 15 to 18 months.Of the 107 mother-infant pairs enrolled, 22 infants were lost to follow-up, 15 were under 18 months of age at the time of this analysis and 2 infants died without a diagnosis. Of the remaining 68 infants followed up, 4 tested HIV positive at 18 months. Of the 229 women-infant pairs who did not receive perinatal intervention, 55 infants followed up to 15-18 months were found to be infected.This interventional strategy significantly reduced the mother to child transmission of HIV. However, the results need to be substantiated by larger studies.

This report reviews previously published studies from our laboratory and shows some recent morphological data obtained with scanning and transmission electron microscopy regarding gallstone formation and alteration of the gallbladder epithelium in the Syrian hamster model. Both male and female hamsters were treated with female sex steroids (estradiol alone, estradiol and medroxyprogesterone, medroxyprogesterone alone) during one month. The results show that the Syrian hamster is a good model to study bile changes, gallbladder structure changes, including gallstone formation, and the regulation of cholesterol metabolism at the molecular level. Arguments in favor of this animal model are presented and, during gallstone formation, epithelial cell changes, anionic mucus secretion, and formation of gallbladder luminal deposits can be demonstrated. Recent molecular biology observations related to the effect of female sex steroids on liver cholesterol 7 alpha-hydroxylase (CYP7) gene suggest that progestin alone or primed by estrogen down regulates CYP7 transcription and activity. In addition, progesterone in cell culture systems has been shown to enhance intracellular accumulation of free cholesterol by increasing its uptake and synthesis and by decreasing its esterification by inhibiting the activity of acylcoenzyme A: cholesterol acyltransferase. Non-esterified cholesterol is free to migrate to the extracellular spaces and may contribute to nucleation within the bile. It is suggested that these effects of progesterone on cholesterol metabolism combined with the CYP7 gene down regulation, physical changes in the mucus and the hypomotility of the gallbladder and biliary ducts result in hypersaturation of cholesterol in the bile which favors gallstone formation.

The primary objective of this research project was to study the role of sex steroids in the pathogenesis of cholelithiasis using the Syrian hamster as a model. In addition to the morphological examination of the gallbladder epithelium, we thought it imperative to observe the changes induced in the biliary tract in response to the sex steroid treatment. This report focuses on the morphological changes induced in the liver. The hamsters were randomly divided into 4 groups, control (C), estrogen-treated (E), estrogen and medroxyprogesterone-treated (E+MP), and medroxyprogesterone-treated (MP) groups. The E group hepatocytes demonstrated proliferation of the smooth endoplasmic reticulum, lipofuscin-like granules, aggregates of glycogen rosettes, and dense bodies. Lipid droplets in the hepatocyte cytoplasm as well as the nuclei were detected in this group. E+MP combined treatment induced an exacerbation of all the changes observed in the E group, furthermore, there appeared to be a disruption of the hepatic parenchymal architecture. The MP-treated group also exhibited the architectural changes observed in the E+MP group, but also showed sinusoidal dilation. In response to MP alone, the fatty changes in the liver appeared to be accentuated. A striking feature induced in response to MP treatment, was a focal area suggestive of adenomatous changes.

Light (LM), transmission (TEM), and scanning (SEM) electron microscopy were used to characterize morphological changes induced in the gallbladder epithelium of female Syrian hamsters in response to one-month estradiol alone (E) and estradiol with medroxyprogesterone (E + MP) treatments. TEM data were correlated with the SEM observations. Compared with control (C), E- and E + MP-treated hamsters showed significant decreases in body weight, while the liver and gallbladder, and uterus weights increased. Moreover, E treatment induced some subcellular changes (microvilli, nucleus, mitochondria, RER, glycogen, abundant apical granules). The E + MP treatment appeared to exacerbate these similar changes and, in addition, induced apical excrescences and cell shedding. Both E and E + MP gallbladders showed luminal micelles, cellular debris and crystalliths associated with mucus. Simultaneously, an increased acidification of the mucoid content of the apical granules was noticed.

Scanning (SEM), and transmission (TEM) electron microscopy were used and correlated to morphologically characterize changes induced in the gallbladder epithelium of female Syrian hamster in response to treatments with estradiol (E) alone, and estradiol with medroxyprogesterone (E + MP). Compared with control (C), the E- and E + MP-treated groups demonstrated alterations in the serum lipid profile as well as significantly decreased body weights. The liver with gallbladder weights, as well as the uterus weights, were significantly increased. Two-month E and E + MP treatment groups exhibited increased number of anionically charged apical granules, and luminal mucoid elements. Contrastingly, the three-month treatment groups demonstrated larger and more gallstone-like deposits as compared to the C and two-month E and E + MP groups. This report presents a comprehensive overview of our previous and current data, including that of other investigators in relation to the various factors and parameters involved in the cholelithiatic process.

This report is a cytometric study of the female Syrian hamster gallbladder epithelium following 1-, 2-, and 3-month administration of female sex steroids. Nulliparous, multiparous, young, old and pregnant hamsters were used in this study. A 1 month treatment with estrogen alone significantly increases the nuclear volume of the gallbladder epithelial cells, while E + P treatment significantly affects the nuclear volume only after a 2 month treatment. On the other hand, E + P and P treatments significantly increase the cell volumes as compared to the E-treated groups, this effect is most striking following the 1 month period. Prolonged sex steroid treatment (2 and 3 month) does not appear to influence the gallbladder epithelial cell and nuclear volumes as dramatically as that observed following the 1 month treatment. The nulliparous, progesterone-treated hamsters appear to have a greater cytoplasmic volume than the multiparous group and this is substantiated by the bulging apices and the luminal cellular excrescences observed with scanning and transmission electron microscopy. These observations are similar to those reported in ovariectomized hamsters (Gilloteaux et al., 1992). Further, the gallbladder epithelial cells and nuclei of the older female hamsters demonstrate an accentuated response to a 1 month sex steroid treatment as compared to the younger hamsters for the same treatment duration. These results enable us to hypothesize that changes induced by a short term sex steroid treatment participate in the gallstone nucleation process, while longer duration of the treatments contribute to progressive enlargement and accumulation of gallbladder calculi.

All the intact female Syrian hamsters treated with medroxyprogesterone (MP) for a one-month period, without dietary manipulation, display gallbladder surface epithelial changes, and intraluminal deposits. These changes include excrescences in various stages, bulging, and extrusion of material from the epithelial cells. The most striking scanning electron microscopic observations are the dramatic events, comparable to apocrine-like secretory events observed in another related study using oophorectomized hamsters. Since the hamster gallbladder does not possess mucous goblet cells, it appears that this phenomenon could be a response to the MP treatment, thus providing a larger amount of mucous product than usual with cellular material, in addition to the possible alteration in the quality of the bile following this treatment. As a result of MP treatment, intraluminal deposits were also confirmed by using light and transmission electron microscopy. In control hamsters these events were not observed, however, small blebs outlining surface epithelial cells are seen. The results in this report complement the previous studies using the male and oophorectomized Syrian hamster model subjected to similar experimental conditions. © 1993 Wiley-Liss, Inc.