Theory of Star Formation

We review current understanding of star formation, outlining an overall theoretical framework and the observations that motivate it. A conception of star formation has emerged in which turbulence plays a dual role, both creating overdensities to initiate gravitational contraction or collapse, and countering the effects of gravity in these overdense regions. The key dynamical processes involved in star formation -- turbulence, magnetic fields, and self-gravity -- are highly nonlinear and multidimensional. Physical arguments are used to identify and explain the features and scalings involved in star formation, and results from numerical simulations are used to quantify these effects. We divide star formation into large-scale and small-scale regimes and review each in turn. Large scales range from galaxies to giant molecular clouds (GMCs) and their substructures. Important problems include how GMCs form and evolve, what determines the star formation rate (SFR), and what determines the initial mass function (IMF). Small scales range from dense cores to the protostellar systems they beget. We discuss formation of both low- and high-mass stars, including ongoing accretion. The development of winds and outflows is increasingly well understood, as are the mechanisms governing angular momentum transport in disks. Although outstanding questions remain, the framework is now in place to build a comprehensive theory of star formation that will be tested by the next generation of telescopes.Comment: 120 pages, to appear in ARAA. No changes from v1 text; permission statement adde

Structural Basis for Metal Sensing by CnrX

International audienceCnrX is the metal sensor and signal modulator of the three-protein transmembrane signal transduction complex CnrYXH of Cupriavidus metallidurans CH34 that is involved in the setup of cobalt and nickel resistance. We have determined the atomic structure of the soluble domain of CnrX in its Ni-bound, Co-bound, or Zn-bound form. Ni and Co ions elicit a biological response, while the Zn-bound form is inactive. The structures presented here reveal the topology of intraprotomer and interprotomer interactions and the ability of metal-binding sites to fine-tune the packing of CnrX dimer as a function of the bound metal. These data suggest an allosteric mechanism to explain how the complex is switched on and how the signal is modulated by Ni or Co binding. These results provide clues to propose a model for signal propagation through the membrane in the complex

A double-blind, randomized, saline-controlled study of the efficacy and safety of co-administered intra-articular injections of Tr14 and Ze14 for treatment of painful osteoarthritis of the knee: The MOZArT trial

Osteoarthritis of the knee is a prevalent and painful condition increasing with age. The aim of this, the first well-controlled randomized controlled trial, was to evaluate the efficacy and safety of co-administered Traumeel11Traumeel and Zeel are registered trade names of Biologische Heilmittel Heel GmbH, Germany. (Tr14) and Zeel1 (Ze14) in patients with knee osteoarthritis (OA) experiencing moderate-to-severe pain. This was a double-blind, multi-center, randomized, saline-controlled trial. Eligible patients meeting the American College of Rheumatology criteria for knee OA were randomized to 3, weekly intra-articular Tr14/Ze14 (n=119) or saline (n=113) injections. Primary efficacy endpoint was knee pain change from baseline (day 1) to end-of-study visit (day 99), as measured by the WOMAC Pain Subscore. Secondary endpoints included measures of WOMAC OA Index total and subscores, 50-foot walk test, and patient (PGA) and physician (PhGA) global assessments. Safety was assessed by vital signs, treated knee examinations, adverse events (AEs), and concomitant medications use. Effect sizes were calculated post hoc for consistency with published meta-analyses of standard-of-care treatments. 232 patients were randomized with no significant baseline differences. For the primary endpoint Tr14/Ze14 was significantly superior to saline (−32.0 vs. −25.5; p=0.0383, 95% CI for difference: −12.40, −0.35). WOMAC and 50-foot walk pain measures showed statistically significant efficacy for pain relief over study days 15–99 (except Day 29). Safety profile showed no serious adverse events related to the treatment. PhGA indicated significant improvement for Tr14/Ze14 on Days 29, 71 and Day 85. In this study, intra-articular Tr14/Ze14 provided significant pain relief compared to saline-control throughout the observation period. Treatment effect sizes were clinically relevant, since these were comparable to those reported for standard-of-care treatments. The safety profile was benign

Trajectories of oral medication adherence in youth with inflammatory bowel disease

Objective: To examine longitudinal trajectories of oral thiopurine adherence over a 180-day interval in a sample of youth with inflammatory bowel disease (IBD) and to identify the role of disease activity, length of time since diagnosis, and regimen complexity in predicting adherence trajectory class membership. Method: Participants included 96 adolescents (M age = 14.32 years) with IBD. Oral medication adherence was assessed via MEMS Track Caps (i.e., an electronic monitor that allows for real-time assessment of adherence) for 6 months, after which time devices were collected and data were downloaded. Medical record reviews provided information about participants’ disease activity, length of time since diagnosis, and regimen complexity (including both medications and supplements) at the time of study enrollment. Results: Two distinct adherence trajectory classes emerged: Group 1 represented those with consistently near-perfect adherence, whereas Group 2 represented those with mild nonadherence that increased with time. Complexity of medication regimen emerged as the only predictor of trajectory class, with adolescents whose regimen involved more than 1 daily medication administration time being more likely to be classified in Group 2 (i.e., the consistently near-perfect adherence group) than those whose regimen involved only 1 daily medication administration time. Conclusions: Distinct classes of adherence trajectories in pediatric IBD can be identified with longitudinal data collection approaches; however, disease and regimen factors offered limited value in predicting adherence trajectory class. Future research should utilize longitudinal conceptualizations of adherence and examine alternative predictors of declining adherence over time