The Future of Rheumatoid Arthritis and Hand Surgery - Combining Evolutionary Pharmacology and Surgical Technique

Rheumatoid arthritis is a systemic autoimmune disease of uncertain aetiology, which is characterized primarily by synovial inflammation with secondary skeletal destructions

On the origin of innovations—the opportunity vacuum as a conceptual model for the explanation of innovation

The aim of this paper is to transfer the innovation system (IS) approach to the microeconomic level, creating a conceptual framework which helps individual actors to explain, identify, and predict the origin of innovations. Based on the ongoing discussion about the applicability of boundedly rational search and, in particular, the metaphor of an opportunity landscape, the author has developed a conceptual framework for the origin of economic innovations, structured along three dimensions. First, the adjacent possible defines a narrow space of potential first-order combinations of exiting knowledge, which is the trajectory for the new developments in technology and science. Second, the adjacent feasible defines an area of expected cost reduction which enables the exploitation of the new technologies within a threshold. Finally, the adjacent acceptable represents a small area on the current edges of socially accepted behavior, which currently only innovators embrace, but soon will reach the early majority of adopters. It is, however, the moment when all three dimensions achieve an intersecting area, when the opportunity vacuum (OV) is created. The OV is a space, which strongly attracts innovation and often creates multiple inventions at the same time emerging independently. While this model is aimed at explaining the origin of economic innovations in retrospective, it can also be applied as a framing method to anticipate future economic novelty

Structure of the core of the type III secretion system export apparatus

Export of proteins through type III secretion systems is critical for motility and virulence of many major bacterial pathogens. Three putative integral membrane proteins (FliP, FliQ, FliR) are suggested to form the core of an export gate in the inner membrane, but their structure, assembly and location within the final nanomachine remain unclear. Here, we present the cryoelectron microscopy structure of the Salmonella Typhimurium FliP–FliQ–FliR complex at 4.2 Å. None of the subunits adopt canonical integral membrane protein topologies, and common helix-turn-helix structural elements allow them to form a helical assembly with 5:4:1 stoichiometry. Fitting of the structure into reconstructions of intact secretion systems, combined with cross-linking, localize the export gate as a core component of the periplasmic portion of the machinery. This study thereby identifies the export gate as a key element of the secretion channel and implies that it primes the helical architecture of the components assembling downstream

Metastatic paraplegia: care management characteristics within a rehabilitation center.

International audienceStudy design:Retrospective study.Objectives:To determine the potential impact of rehabilitation care on associated symptoms and functional improvements of paraplegic patients with metastatic spinal cord compression.Setting:CMN Propara, Montpellier (France).Measures:Demographics, Functional Independence Measure (FIM), Frankel Modified Score and Visual Analog Scale (VAS) for pain, intercurrent adverse medical events and neurological outcome, duration of stay, survival time, rehospitalization in a non-Spinal Cord Injury unit, number of contracts defining the patients rehabilitation goals, number of contracts defining the patients duration of stay within the rehabilitation center.Results:We reviewed the charts of 26 patients. The initial neurological profile was paraplegia or paraparesis for 24 patients and quadriparesis for 2 patients. Regarding functional improvements: four patients demonstrated a poor functional evolution, five patients showed no functional improvements or very slight improvements and all the other patients showed an increase in their overall functional aptitudes. At the end of the stay, 14 patients were urinary independent. Our study reports 52 rehospitalizations in an another unit and 101 outpatient visits during their rehabilitation stay in a physical medicine and rehabilitation (PM&R) center. For the 14 patients who were deceased at the time of data collection, the median survival rate post-paraplegia was 12.7 months. A total of 12 of the 14 patients spent more than a third of their remaining survival time in a rehabilitation center.Discussion:Compared to the patients' life expectancy, their stay in a rehabilitation center is too long and prevents them from spending time with family and loved ones. The occurrence rate of the associated symptoms is high because of both cancer-related disorders and neurological disorders caused by the spinal cord lesion. PM&R professionals are faced with patients affected by chronic pain and fatigue as well as frequent rehospitalizations, short stays and outpatient stays, in the primary oncology unit. This study focuses on the need to privilege the patients' comfort over their functional rehabilitation.Spinal Cord advance online publication, 10 June 2008; doi:10.1038/sc.2008.75