The Simons Observatory (SO) is a new cosmic microwave background experiment being built on Cerro Toco in Chile, due to begin observations in the early 2020s. We describe the scientific goals of the experiment, motivate the design, and forecast its performance. SO will measure the temperature and polarization anisotropy of the cosmic microwave background in six frequency bands centered at: 27, 39, 93, 145, 225 and 280 GHz. The initial configuration of SO will have three small-aperture 0.5-m telescopes and one large-aperture 6-m telescope, with a total of 60,000 cryogenic bolometers. Our key science goals are to characterize the primordial perturbations, measure the number of relativistic species and the mass of neutrinos, test for deviations from a cosmological constant, improve our understanding of galaxy evolution, and constrain the duration of reionization. The small aperture telescopes will target the largest angular scales observable from Chile, mapping ≈ 10% of the sky to a white noise level of 2 µK-arcmin in combined 93 and 145 GHz bands, to measure the primordial tensor-to-scalar ratio, r, at a target level of σ(r) = 0.003. The large aperture telescope will map ≈ 40% of the sky at arcminute angular resolution to an expected white noise level of 6 µK-arcmin in combined 93 and 145 GHz bands, overlapping with the majority of the Large Synoptic Survey Telescope sky region and partially with the Dark Energy Spectroscopic Instrument. With up to an order of magnitude lower polarization noise than maps from the Planck satellite, the high-resolution sky maps will constrain cosmological parameters derived from the damping tail, gravitational lensing of the microwave background, the primordial bispectrum, and the thermal and kinematic Sunyaev-Zel'dovich effects, and will aid in delensing the large-angle polarization signal to measure the tensorto-scalar ratio. The survey will also provide a legacy catalog of 16,000 galaxy clusters and more than 20,000 extragalactic sources a .

Interstitial nephritis due to BK polyomavirus occurred in 2.5% of patients receiving renal transplants at our center since 1996. Polyomavirus infection can cause transplant dysfunction and graft loss, but progression of the infection can frequently be abrogated with alterations in immunosuppressive therapy. Both renal biopsy and EM of urine samples are useful in the diagnosis and monitoring of polyomavirus infections.

Focal segmental glomerulosclerosis (FSGS) is a histological lesion with many causes including inherited genetic defects with significant proteinuria being the predominant clinical finding at presentation. Mutations in COL4A3 and COL4A4 are known to cause Alport syndrome, thin basement membrane nephropathy, and to result in pathognomonic glomerular basement membrane findings. Secondary FSGS is known to develop in classic Alport Syndrome at later stages of the disease. Here, we present seven families with rare or novel variants in COL4A3 or COL4A4 (six with single and one with two heterozygous variants) from a cohort of 70 families with a diagnosis of hereditary FSGS. The predominant clinical findings at diagnosis were proteinuria associated with hematuria. In all seven families, there were individuals with nephrotic range proteinuria with histologic features of FSGS by light microscopy. In one family, electron microscopy showed thin glomerular basement membrane, but four other families had variable findings inconsistent with classical Alport nephritis. There was no recurrence of disease after kidney transplantation. Families with COL4A3 and COL4A4 variants that segregated with disease represent 10% of our cohort. Thus, COL4A3 and COL4A4 variants should be considered in the interpretation of next-generation sequencing data from such patients. Furthermore, this study illustrates the power of molecular genetic diagnostics in the clarification of renal phenotypes.

Serum concentrations of 3,3',5'-triiodothyronine (reverse T3, rT3) were measured in adult patients with several systemic illnesses whose serum total and/or free T3 were low, serum total T4 was low or normal, and free T4 was either normal or elevated. The mean serum rT3 was 76, 46, and 77 ng per 100 ml in patients with hepatic cirrhosis, chronic renal failure, and acute febrile illnesses, respectively; the values in patients with hepatic cirrhosis and acute febrile illness were significantly higher than, and values in patients with renal failure did not differ significantly from, the mean serum rT3 (41 ng per 100 ml) in normal subjects. The mean serum rT3 in another group of patients from Calcutta, India, who had severe protein calorie malnutrition (PCM), was 53 ng per 100 ml; it was significantly higher than the corresponding value, 22 ng per 100 ml, in the same patients after feeding treatment. Mean serum rT3 in patients with systemic illnesses was not so high as that (151 ng per 100 ml) in the normal newborn, who also has low serum T3 and normal or high T4. High serum rT3 in patients with systemic illness could not be attributed to increased serum protein binding of rT3; whenever studied, the dialyzable fraction of rT3 was not decreased but actually increased. The mean serum-free rT3 was 450,207, and 366 pg per 100 per 100 ml in patients with hepatic cirrhosis, chronic renal failure, and acute febrile illnesses, respectively; each of these values was significantly higher than the corresponding value, 98 pg per 100 ml, in normal subjects. The mean serum free rT3, 516 pg per 100 ml, in newborn cord sera was similar to that in patients with hepatic cirrhosis but was higher than that observed in patients with chronic renal failure and acute febrile illnesses. High serum rT3 and low serum T3 in patients with PCM improved to normal or towards normal after feeding treatment. Since the peripheral metabolism of T4 is normally the predominant source of T3 as well as rT3 in man, our data, demonstrating reciprocal changes in serum rT3 and T3 and no consistent change in serum T4, suggest that body metabolism of T4 may be so altered in systemic illness that the conversion of T4 to rT3 may be increased while that to T3 is decreased. The mechanism or the biological significance of such a diversion of T4, from the normally occurring conversion to highly potent T3, to the generation of poorly calorigenic rT3 in systemic illness, is not clear at this time. The data in patients with PCM demonstrate, however, that such a change in the metabolism of T4 can be reversible.

This trial failed to demonstrate substantial benefit of a centralized system to provide standardized, telephone follow-up for postoperative patients with colorectal cancer. Future interventions could investigate a more tailored approach.

The incidence, predictors and clinical significance of acute renal failure (ARF) after lung transplantation are not well described. We retrospectively collected data on 296 patients transplanted at our center be-

An accurate blood‐based RAS mutation assay to determine eligibility of metastatic colorectal cancer (mCRC) patients for anti‐EGFR therapy would benefit clinical practice by better informing decisions to administer treatment independent of tissue availability. The objective of this study was to determine the level of concordance between plasma and tissue RAS mutation status in patients with mCRC to gauge whether blood‐based RAS mutation testing is a viable alternative to standard‐of‐care RAS tumor testing. RAS testing was performed on plasma samples from newly diagnosed metastatic patients, or from recurrent mCRC patients using the highly sensitive digital PCR technology, BEAMing (beads, emulsions, amplification, and magnetics), and compared with DNA sequencing data of respective FFPE (formalin‐fixed paraffin‐embedded) tumor samples. Discordant tissue RAS results were re‐examined by BEAMing, if possible. The prevalence of RAS mutations detected in plasma (51%) vs. tumor (53%) was similar, in accord with the known prevalence of RAS mutations observed in mCRC patient populations. The positive agreement between plasma and tumor RAS results was 90.4% (47/52), the negative agreement was 93.5% (43/46), and the overall agreement (concordance) was 91.8% (90/98). The high concordance of plasma and tissue results demonstrates that blood‐based RAS mutation testing is a viable alternative to tissue‐based RAS testing.

We conclude that AHR, when diagnosed early and treated aggressively with PP and IVIG, carries a short-term prognosis that is similar to ACR.