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Background and aims: Alagille syndrome (ALGS) is a multisystem disorder, characterized by cholestasis. Existing outcome data are largely derived from tertiary centers, and real-world data are lacking. This study aimed to elucidate the natural history of liver disease in a contemporary, international cohort of children with ALGS. Approach and results: This was a multicenter retrospective study of children with a clinically and/or genetically confirmed ALGS diagnosis, born between January 1997 and August 2019. Native liver survival (NLS) and event-free survival rates were assessed. Cox models were constructed to identify early biochemical predictors of clinically evident portal hypertension (CEPH) and NLS. In total, 1433 children (57% male) from 67 centers in 29 countries were included. The 10 and 18-year NLS rates were 54.4% and 40.3%. By 10 and 18 years, 51.5% and 66.0% of children with ALGS experienced >= 1 adverse liver-related event (CEPH, transplant, or death). Children (>6 and <= 12 months) with median total bilirubin (TB) levels between >= 5.0 and <10.0 mg/dl had a 4.1-fold (95% confidence interval [CI], 1.6-10.8), and those >= 10.0 mg/dl had an 8.0-fold (95% CI, 3.4-18.4) increased risk of developing CEPH compared with those 10.0 mg/dl were associated with a 4.8 (95% CI, 2.4-9.7) and 15.6 (95% CI, 8.7-28.2) increased risk of transplantation relative to <5.0 mg/dl. Median TB <5.0 mg/dl were associated with higher NLS rates relative to >= 5.0 mg/dl, with 79% reaching adulthood with native liver (p < 0.001). Conclusions: in this large international cohort of ALGS, only 40.3% of children reach adulthood with their native liver. A TB <5.0 mg/dl between 6 and 12 months of age is associated with better hepatic outcomes. These thresholds provide clinicians with an objective tool to assist with clinical decision-making and in the evaluation of therapies., This study received funding support from the following agencies: The Alagille Syndrome Alliance, Mirum Pharmaceuticals Inc. and Albireo Pharma, Inc. who provided unrestricted educational grants to the Hospital for Sick Children (SickKids Foundation). The study sponsors were not involved in the conduct of the research study or preparation of the manuscript.

PSR J0922+0638 (B0919+06) shows unexplained anomalous variations in the on-pulse phase, where the pulse appears to episodically move to an earlier longitude for a few tens of rotations before reverting to the usual phase for approximately several hundred to more than a thousand rotations. These events, where the pulse moves in phase by up to 5°, have been previously detected in observations from~300 to 2000 MHz.We present simultaneous observations from the Effelsberg 100-m radio telescope at 1350MHz and the Bornim (Potsdam) station of the LOw Frequency ARray at 150 MHz. Our observations present the first evidence for an absence of the anomalous phase-shifting behaviour at 150 MHz. Instead, the observed intensity at the usual pulse-phase typically decreases, often showing a pseudo-nulling feature corresponding to the times when phase shifts are observed at 1350 MHz. The presence of weak emission at the usual pulse-phase supports the theory that these shifts may result from processes similar to the 'profile-absorption' expected to operate for PSR J0814+7429 (B0809+74). A possible mechanism for this could be intrinsic variations of the emission within the pulsar's beam combined with absorption by expanding shells of electrons in the line of sight.

Background: An imbalance of tryptophan metabolites plays a role in the pathophysiology of schizophrenia. Also cytokines seem to be involved and are able to enhance the tryptophan metabolism. In this study the impact of cytokines, tryptophan metabolites and antipsychotics was evaluated in schizophrenic patients/ healthy controls and correlated with the psychopathology of schizophrenia. Subjects and methods: This study investigated 12 patients with schizophrenia and 24 matched controls. Peripheral blood mononuclear cell cultures were stimulated in vitro with lipopolysaccharide (LPS) or polyinosine-polycytidylic acid (poly I:C) and different antipsychotics (quetiapine, risperidone, haloperidole and clozapine) were added. The cytokines IL-4, IL-10, IFN-γ and tryptophan metabolites were analysed. Symptom severity was assessed using the positive and negative syndrome scale (PANSS). Results: Peripheral mononuclear cells of schizophrenia patients showed a reduced IFN-γ response to LPS (p=0.008). When quetiapine and risperidone were added this imbalance between patients and controls disappeared. Tryptophan levels were significantly lower in patients’ cells cultures when the cells were stimulated with LPS (p=0.029). A group effect for lower levels in the patients’ cell culture was evaluated for tryptophan and kynurenine (p=0.043; p=0.05). In addition, high tryptophan levels correlated with low PANSS negative scores in patients and higher kynurenine levels resulted in higher PANSS positive scores. Conclusions: Only two atypical antipsychotics were identified to reverse the imbalanced cytokine levels in schizophrenia. The low concentrations of tryptophan and kynurenine in these patients could be a sign of a fast degradation of tryptophan – yet tryptophan metabolites could not be changed by any of the investigated antipsychotics.

Angiosperms, http://name.umdl.umich.edu/IC-HERB00IC-X-1645411%5DMICH-V-1645411, https://quod.lib.umich.edu/cgi/i/image/api/thumb/herb00ic/1645411/MICH-V-1645411/!250,250, The University of Michigan Library provides access to these materials for educational and research purposes. Some materials may be protected by copyright. If you decide to use any of these materials, you are responsible for making your own legal assessment and securing any necessary permission. If you have questions about the collection, please contact the Herbarium professional staff: herb-dlps-help@umich.edu. If you have concerns about the inclusion of an item in this collection, please contact Library Information Technology: libraryit-info@umich.edu., https://www.lib.umich.edu/about-us/policies/copyright-policy

Theater program of "Me and Juliet" by Rodgers and Hammerstein. This performance ran from January 9-February 28, 1959. Performers: Gail Gordon/Pat Williams as Jeanie, C. Ronald O'Neal as George, Nolan D. Bell Sr. as Sidney, Charles M. Pearson as Herbie, Bobbie M. Brown as Chris, Sherrie Farris as Grace, Mary Ann Zavela as Mildred, Barbara Bowman as Helen, Franklin G. Johnson as Bob, Robert Guillaume/William Snider as Larry, Al Fann/William F. Gilbert as Mac, Mary Ickes/Suzy Mintz as Monica, Leroy Strawder as Ruby, Henry Finney/John Senger as Charlie, Marion Ewing/Norma Powell as Lily, Benjamin Turner/J. Herbert Kerr Jr. as Jim, Gloria Schwarz as Susie, Calvin Thomas as Mr. Harrison, Beverly Gittleman/Thomasena Davis as Miss Davenport, Gloria Schwarz as Hilda, Gail Gordon/Pat Williams as Marcia, Carolyn Price/Beverly Todd as Betty, Paul Lubera as Buzz, Beverly Gittleman as Sadie, Mary Ickes as Lady with Gardenia, Barbara Bowman as Drunken Woman. Dancers: Angela Berry, Paul Lubera, Sonja Kay, Herbert Kerr, Ronald O'Neal, Alvin Reed, Gloria Schwarz, Benjamin Turner, Gwen Whitley, and Betty Lou Palivoda.