Ustekinumab as Induction and Maintenance Therapy for Crohn’s Disease

BACKGROUND Ustekinumab, a monoclonal antibody to the p40 subunit of interleukin-12 and inter-leukin-23, was evaluated as an intravenous induction therapy in two populations with moderately to severely active Crohn’s disease. Ustekinumab was also evaluated as subcutaneous maintenance therapy. METHODS We randomly assigned patients to receive a single intravenous dose of ustekinumab (either 130 mg or approximately 6 mg per kilogram of body weight) or placebo in two induction trials. The UNITI-1 trial included 741 patients who met the criteria for primary or secondary nonresponse to tumor necrosis factor (TNF) antagonists or had unacceptable side effects. The UNITI-2 trial included 628 patients in whom conventional therapy failed or unacceptable side effects occurred. Patients who completed these induction trials then participated in IM-UNITI, in which the 397 patients who had a response to ustekinumab were randomly assigned to receive subcutaneous maintenance injections of 90 mg of ustekinumab (either every 8 weeks or every 12 weeks) or placebo. The primary end point for the induction trials was a clinical response at week 6 (defined as a decrease from baseline in the Crohn’s Disease Activity Index [CDAI] score of ≥100 points or a CDAI score <150). The primary end point for the maintenance trial was remission at week 44 (CDAI score <150). RESULTS The rates of response at week 6 among patients receiving intravenous ustekinumab at a dose of either 130 mg or approximately 6 mg per kilogram were significantly higher than the rates among patients receiving placebo (in UNITI-1, 34.3%, 33.7%, and 21.5%, respectively, with P≤0.003 for both comparisons with placebo; in UNITI-2, 51.7%, 55.5%, and 28.7%, respectively, with P<0.001 for both doses). In the groups receiving maintenance doses of ustekinumab every 8 weeks or every 12 weeks, 53.1% and 48.8%, respectively, were in remission at week 44, as compared with 35.9% of those receiving placebo (P = 0.005 and P = 0.04, respectively). Within each trial, adverse-event rates were similar among treatment groups. CONCLUSIONS Among patients with moderately to severely active Crohn’s disease, those receiving intravenous ustekinumab had a significantly higher rate of response than did those receiving placebo. Subcutaneous ustekinumab maintained remission in patients who had a clinical response to induction therapy. (Funded by Janssen Research and Development; ClinicalTrials.gov numbers, NCT01369329, NCT01369342, and NCT01369355.

HOMEOMORPHISMS OF UNIMODAL INVERSE LIMIT SPACES WITH A NON-RECURRENT CRITICAL POINT

Abstract. Let T be a tent map with the slope strictly between 2 and 2. Suppose that the critical point of T is not recurrent. Let K denote the inverse limit space obtained by using T repeatedly as the bonding map. We prove that every homeomorphism of K to itself is isotopic to some power of the natural shift homeomorphism. 1

The Orange Tuff : a Late Pleistocene tephra-fall deposit emplaced by a VEI 5 silicic Plinian eruption in West Java, Indonesia

A VEI 5 dacite eruption emplaced the Orange Tuff about between 34.3 cal kBP and 17.2 cal kBP. Gunung Salak is the unit’s source and the Orange Tuff represents the most recent such eruption from any of the volcanoes southwest of Bogor, Indonesia. The Orange Tuff is the region’s first such documented tephra-fall deposit whose characteristics and phenocryst geochemistry make it readily identifiable over at least 1250 km2. Magnetite compositions and temperature and fO2 estimates inferred from Fe-Ti oxide compositions are particularly useful for identifying the unit. Deposit characteristics suggest that the eruption lasted 1–11 h with mass eruption rates of 1.0–8.3 × 108 kg/s and a column height of 31–40 km. The eruption’s column height and the deposit’s 2.5–11 km3 volume suggest that the unit was dispersed over a much wider area than mapped. The unit is a marker bed throughout its mapped distribution and has potential to be applied over a much broader area as a regional marker bed. The large population and infrastructure proximal to Salak suggest that the unit should be considered in hazards assessments despite its age and the lack of subsequent similar eruptions.Published versio

Geologic Map of the Wickenburg 7.5' Quadrangle, Maricopa and Yavapai County, Arizona

This geologic map is one of a series of four 7 ½’ quadrangle maps (AZGS DGM-131 through 134; Wickenburg, Sam Powell Peak, Flores, and Vulture Peak) in the Wickenburg area. New surficial mapping was conducted throughout the 4-quadrangle mapping area and bedrock mapping was compiled from existing geologic maps. Together, these maps include detailed surficial mapping of alluvium from the Date Creek, Weaver, Wickenburg, and Vulture Mountains as well as ancestral deposits of the Hassayampa River. The relationships between relict and modern alluvial fan and Hassayampa River deposits and their positions relative to pre-existing bedrock topography presents a glimpse into the arrival and development of the modern Hassayampa River system. The Wickenburg 7 ½' Quadrangle straddles the boundary between southern Yavapai and northern Maricopa County and includes the towns of Wickenburg and Morristown, AZ. US Highway 60 passes through the quadrangle from SE to NW. The Hassayampa River flows southeast along the highway separating the Vulture Mountains to the southwest and Wickenburg Mountains to the east. The Vulture Mountains are part of a rugged terrain of dissected bedrock hills and valleys in contrast with the extensive alluvial piedmont emanating from the Wickenburg Mountains. Tributaries from both areas drain into the Hassayampa River, where incision has exposed axial basin-fill deposits overlain by ancestral Hassayampa River deposits. Bedrock pediment, hills, and inselbergs consist of Proterozoic metamorphic and igneous rocks, Cretaceous igneous intrusions, and extensive Neogene (Miocene) volcanic and hypabyssal, and associated terrestrial rocks.Documents in the AZGS Documents Repository collection are made available by the Arizona Geological Survey (AZGS) and the University Libraries at the University of Arizona. For more information about items in this collection, please contact [email protected]