An official American thoracic society workshop report: Translational research in rare respiratory diseases

Rare respiratory diseases (RRDs) are a heterogeneous group of disorders that collectively represent a significant health care burden. In recent years, strong advocacy and policy initiatives have led to advances in the implementation of research and clinical care for rare diseases. The development of specialized centers and research networks has facilitated support for affected individuals as well as emerging programs in basic, translational, and clinical research. In selected RRDs, subsequent gains in knowledge have informed the development of targeted therapies and effective diagnostic tests, but many gaps persist. There was therefore a desire to identify the elements contributing to an effective translational research program in RRDs. To this end, a workshop was convened in October 2015 with a focus on the implementation of effective transnational research networks and collaborations aimed at developing novel diagnostic and therapeutic tools. Key elements included an emphasis on molecular pathogenesis, the continuing engagement of patient advocacy groups and policy makers, the effective use of preclinical models in the translational research pipeline, and the detailed phenotyping of patient cohorts. During the course of the workshop, current logistical and knowledge gapswere identified, and new solutions or opportunities were highlighted

Anesthetic management of a patient with a double inferior vena cava and pulmonary alveolar proteinosis who underwent bilateral living-donor lobar lung transplantation.

A 43-year-old woman with pulmonary fibrosis secondary to pulmonary alveolar proteinosis was scheduled to undergo lung transplantation. Before the lung transplantation, she had undergone multiple whole-lung lavage procedures on extracorporeal circulation (ECC), which had caused scarring of the right femoral subcutaneous tissues. Preoperative examination revealed a double inferior vena cava (IVC) with interiliac communication, and the left IVC ended at the left renal vein. Surgical exposure of the right femoral vessels was performed immediately after anesthetic induction for emergent vascular access to establish an ECC. Cardiopulmonary collapse did not occur and the ECC was not required until lung resection. The lung transplantation was completed uneventfully. Congenital IVC anomaly is rare, but may make cannulation through the femoral vein difficult. Scarring of the subcutaneous tissue could result in a difficult "percutaneous" approach to the vessels. Evaluation of the vascular anatomy related to the establishment of an ECC is important before lung transplantation

Efficient in vivo catheter-based pericardial gene transfer mediated by adenoviral vectors

Adenoviral vectors are promising agents for a number of in vivo gene therapy applications including diseases of the heart and coronary vessels. Efficient intravascular gene transfer to specific sites has been achieved in occluded vessels, but otherwise is hampered by the effect of blood flow on localized vector uptake in the vessel wall. An alternative delivery approach to coronary arteries is the expression of diffusible gene products into the pericardial space surrounding the heart and coronary arteries. However, in vivo pericardial access is comparatively difficult and has been limited to surgical approaches. We hypothesized that efficient adenovirus-mediated gene expression in pericardial lining mesothelium could be achieved by transmyocardial vector delivery to the pericardium. To evaluate this concept, a hollow, helical-tipped penetrating catheter was used to deliver vector-containing fluid directly into the intrapericardial space. The catheter was introduced percutaneously in anesthetized mongrel dogs, advanced into the right ventricle, and the tip passed through the apical right ventricular myocardium under direct radiographic visualization until the open end of the catheter tip resided in the intrapericardial space. Adenoviral vectors expressing either nuclear-localizing beta-galactosidase, cytoplasmic luciferase, or secreted human alpha 1AT reporters (Av1nBg, Av1Lu, or Av1Aa, respectively) were instilled through the catheter into the intrapericardial space. Three days later the animals were sacrificed and reporter gene expression was evaluated in pericardium, epicardium, and multiple other tissues. In animals receiving Av1nBg, beta-galactosidase activity was evident in most of the pericardial lining endothelium, up to 100% in many areas. In animals receiving Av1Lu, luciferase reporter activity was abundant in pericardial tissues, but near-background levels were observed in other organs. In animals receiving Av1Aa, human alpha 1AT was abundant (16-29 mg/ml) in pericardial fluid, but was undetectable in serum. All animals tolerated the procedure well with no electrocardiographic changes and no clinical sequelae. These observations demonstrate highly efficient adenovirus vector delivery and gene transfer and expression in the pericardium and support the feasibility of localized gene therapy via catheter-based pericardial approaches. We suggest that the pericardial sac may serve as a sustained-release protein delivery system for the generation of desired gene products or their metabolites for diffusion into the epicardial region

Don’t touch me, I’m fine: Robot autonomy using an artificial innate immune system

Abstract. A model for integration of low-level responses to damage, potential damage and component failure in robots is presented. This model draws on the notion of inflammation and introduces an extensible, sub-symbolic mechanism for modulating high-level behaviour using the notion of artificial inflammation. Preliminary results obtained via simulation are presented and demonstrate the potential benefits of such a scheme. Additionally the system maps the robot’s physiological state-space, which is defined in terms of the levels and sources of inflammatory response. This is achieved using Kohonen’s Self-Organizing Map algorithm to arrange the states experienced during the lifetime of the robot. The future use of this map for diagnosis and localization of faults and for the generation of specific high-level remediation behaviour is also discussed