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We report new near-infrared and mm-wave observational data on a selection of massive Galactic molecular clumps (part of the CHaMP sample) and their associated young star clusters. The clumps show, for the first time in a "dense gas tracer", a significant correlation between HCO+ line emission from cold molecular gas and Br{\gamma} line emission of associated nebulae. This correlation arises in the HCO+ line's brightness, not its linewidth. In contrast, the correlation between the N2H+ line emission and Br{\gamma} is weak or absent. The HCO+/N2H+ line ratio also varies widely from clump to clump: bright HCO+ emission tends to be more closely associated with Br{\gamma} nebulosity, while bright N2H+ emission tends to avoid areas that are bright in Br{\gamma}. Both molecular species show correlations of weak significance with infrared H2 v=1-0 and v=2-1 line emission, in or near the clumps. The H2 emission line ratio is consistent with fluorescent excitation in most of the clumps, although thermal excitation is seen in a few clumps. We interpret these trends as evidence for evolution in the gas conditions due to the effects of ongoing star formation in the clumps, in particular, the importance of UV radiation from massive YSOs as the driving agent that heats the molecular gas and alters its chemistry. This suggests that some traditional dense gas tracers of molecular clouds do not sample a homogeneous population of clumps, i.e., that the HCO+ brightness in particular is directly related to the heating and disruption of cold gas by massive young stars, whereas the N2H+ better samples gas not yet affected by this process. We therefore suggest that the HCO+-N2H+-Br{\gamma} relationship is a useful diagnostic of a molecular clump's progress in forming massive stars.
COPD and idiopathic pulmonary fibrosis (IPF) together represent a considerable unmet medical need, and advances in their treatment lag well behind those of other chronic conditions. Both diseases involve maladaptive repair mechanisms leading to progressive and irreversible damage. However, our understanding of the complex underlying disease mechanisms is incomplete; with current diagnostic approaches, COPD and IPF are often discovered at an advanced stage and existing definitions of COPD and IPF can be misleading. To halt or reverse disease progression and achieve lung regeneration, there is a need for earlier identification and treatment of these diseases. A precision medicine approach to treatment is also important, involving the recognition of disease subtypes, or endotypes, according to underlying disease mechanisms, rather than the current “one-size-fits-all” approach. This review is based on discussions at a meeting involving 38 leading global experts in chronic lung disease mechanisms, and describes advances in the understanding of the pathology and molecular mechanisms of COPD and IPF to identify potential targets for reversing disease degeneration and promoting tissue repair and lung regeneration. We also discuss limitations of existing disease measures, technical advances in understanding disease pathology, and novel methods for targeted drug delivery.
Summary Traditionally, the diagnosis of significant coronary atherosclerotic disease has relied on angiographic techniques. Both histologic analyses and, more recently, intravascular ultrasonography techniques have revealed that a significant atherosclerotic plaque load may be present in epicardial coronary arteries without significant luminal narrowing, consistent with compensatory vessel enlargement or remodeling. In patients with coronary atherosclerosis, more limited structural changes are present in the smaller resistance arterioles, whereas a decrease in luminal area with an increase in wall thickness and perivascular fibrosis are the characteristic structural changes observed in resistance arteries in the presence of systemic hypertension. Further, functional changes, such as impairment of endothelium-mediated vasodilation, are present in epicardial and resistance vessels of patients with coronary atherosclerosis and may influence the progression of this disease and development of ischemic syndromes. The introduction of two-dimensional intravascular and Doppler ultrasonography enables us to study in vivo these morphologic and functional changes. In this article, the knowledge acquired in humans on the mechanisms and clinical relevance of vascular remodeling with the use of these two ultrasonography-based techniques is reviewed. The possibility of using pharmacologic interventions to improve or normalize the vascular response to endothelium-dependent and independent vascular interventions is discussed, with special attention to the efficacy of the inhibition of the angiotensin-converting enzyme.
