Oral abstracts 1: SpondyloarthropathiesO1. Detecting axial spondyloarthritis amongst primary care back pain referrals

Background: Inflammatory back pain (IBP) is an early feature of ankylosing spondylitis (AS) and its detection offers the prospect of early diagnosis of AS. However, since back pain is very common but only a very small minority of back pain sufferers have ASpA or AS, screening of back pain sufferers for AS is problematic. In early disease radiographs are often normal so that fulfilment of diagnostic criteria for AS is impossible though a diagnosis of axial SpA can be made if MRI evidence of sacroiliitis is present. This pilot study was designed to indicate whether a cost-effective pick up rate for ASpA/early AS could be achieved by identifying adults with IBP stratified on the basis of age. Methods: Patients aged between 18 and 45 years who were referred to a hospital physiotherapy service with back pain of more than 3 months duration were assessed for IBP. All were asked to complete a questionnaire based on the Berlin IBP criteria. Those who fulfilled IBP criteria were also asked to complete a second short questionnaire enquiring about SpA comorbidities, to have a blood test for HLA-B27 and CRP level and to undergo an MRI scan of the sacroiliac joints. This was a limited scan, using STIR, diffusion-weighted, T1 and T2 sequences of the sacroiliac joints to minimize time in the scanner and cost. The study was funded by a research grant from Abbott Laboratories Ltd. Results: 50 sequential patients agreed to participate in the study and completed the IBP questionnaire. Of these 27 (54%) fulfilled criteria for IBP. Of these, 2 patients reported a history of an SpA comorbidity - 1 psoriasis; 1 ulcerative colitis - and 3 reported a family history of an SpA comorbidity - 2 psoriasis; 1 Crohn's disease. 4 were HLA-B27 positive, though results were not available for 7. Two patients had marginally raised CRP levels (6, 10 -NR ≤ 5). 19 agreed to undergo MRI scanning of the sacroiliac joints and lumbar spine; 4 scans were abnormal, showing evidence of bilateral sacroiliitis on STIR sequences. In all cases the changes met ASAS criteria but were limited. Of these 4 patients 3 were HLA-B27 positive but none gave a personal or family history of an SpA-associated comorbidity and all had normal CRP levels. Conclusions: This was a pilot study yielding only limited conclusions. However, it is clear that: Screening of patients referred for physiotherapy for IBP is straightforward, inexpensive and quick. It appears that IBP is more prevalent in young adults than overall population data suggest so that targeting this population may be efficient. IBP questionnaires could be administered routinely during a physiotherapy assessment. HLA-B27 testing in this group of patients with IBP is a suitable screening tool. The sacroiliac joint changes identified were mild and their prognostic significance is not yet clear so that the value of early screening needs further evaluation. Disclosure statement: C.H. received research funding for this study from Abbott. A.K. received research funding for this study, and speaker and consultancy fees, from Abbott. All other authors have declared no conflicts of interes

Three-Dimensional Culture for Monoclonal Antibody Production by Hybridoma Cells Immobilized in Macroporous Gel Particles

Cell proliferation and long-term production of monoclonal antibody IgG(2b) by M2139 hybridoma cells immobilized in macroporous gel particles (MGPs) in packed-bed reactor were studied for a period of 60 days. The MGPs were made of supermacroporous gels produced in frozen conditions from crosslinked polyacrylamide and modified with gelatin which were housed in special plastic carriers (7 x 9 mm(2)). Cells were trapped in the interior part of MGPs by attaching to the void space of the gel matrix as three-dimensional (3D) cultivation using gelatin as a substrate layer. Optimizing productivity by hybridoma cell relies on understanding regulation of antibody production. In this study, the behavior of M2139 cells in two-dimensional cultures on multiwell plate surfaces was also investigated. The effect of three different medium such as basal medium Dulbecco's modified Eagle's medium (D-MEM) containing L-glutamine or L-glutamine + 2 mM alpha-ketoglutarate or L-alanyl-glutamine (GlutaMAX (TM) ) was studied prior to its use in 3D cultivation. The kinetics of cell growth in basal medium containing L-glutamine + alpha-ketoglutarate was similar to cells grown on Gluta- MAX containing medium, whereas D-MEM containing L-glutamine showed lower productivity. With the maximal viable cell density (6.85 x 10(6) cells mL(-1)) and highest specific mAb production rate (3.9 mu g mL(-1) 10(-4) viable cell day(-1)), D-MEM-GlutaMAX was further selected for 3D cultivation. Cells in MGPs were able to grow and secrete antibody for 30 days in packed-bed batch reactor, before a fresh medium reservoir was replaced. After being supplied with fresh medium, cells again showed continuous growth for another 30 days with mAb production efficiency of 50%. These results demonstrate that MGPs can be used efficiently as supporting carrier for long-term monoclonal antibody production

Automated Synthesis of Distributed Controllers

Synthesis is a particularly challenging problem for concurrent programs. At the same time it is a very promising approach, since concurrent programs are difficult to get right, or to analyze with traditional verification techniques. This paper gives an introduction to distributed synthesis in the setting of Mazurkiewicz traces, and its applications to decentralized runtime monitoring. 1 Context Modern computing systems are increasingly distributed and heterogeneous. Software needs to be able to exploit these advances, providing means for applications to be more performant. Traditional concurrent programming paradigms, as in Java, are based on threads, shared-memory, and locking mechanisms that guard access to common data. More recent paradigms like the reactive programming model of Erlang [4] and Scala [35,36] replace shared memory by asynchronous message passing, where sending a message is non-blocking. In all these concurrent frameworks, writing reliable software is a serious challenge. Programmers tend to think about code mostly in a sequential way, and it is hard to grasp all possible schedulings of events in a concurrent execution. For similar reasons, verification and analysis of concurrent programs is a difficult task. Testing, which is still the main method for error detection in software, has low coverage for concurrent programs. The reason is that bugs in such programs are difficult to reproduce: they may happen under very specific thread schedules and the likelihood of taking such corner-case schedules is very low. Automated verification, such as model-checking and other traditional exploration techniques, can handle very limited instances of concurrent programs, mostly because of the very large number of possible states and of possible interleavings of executions. Formal analysis of programs requires as a prerequisite a clean mathematical model for programs. Verification of sequential programs starts usually with an abstraction step -- reducing the value domains of variables to finite domains, viewing conditional branching as non-determinism, etc. Another major simplification consists in disallowing recursion. This leads to a very robust computational model, namely finite-state automata and regular languages. Regular languages of words (and trees) are particularly well understood notions. The deep connections between logic and automata revealed by the foundational work of B\"uchi, Rabin, and others, are the main ingredients in automata-based verification .Comment: ICALP 2015, Jul 2015, Kyoto, Japa